Quinolyl propyl piperidine derivatives and their use as antibacterial agents

专利摘要:
The present invention provides that R 1 is hydrogen or a halogen atom or a hydroxy radical; Halogen may be represented when R ′ 1 is a hydrogen atom or R 1 is also a halogen atom; A quinolyl propyl piperidine derivative of formula (1) wherein R ° is a hydrogen atom. The derivative is an antimicrobial agent. Formula 1
公开号:KR20020038757A
申请号:KR1020027003547
申请日:2000-09-14
公开日:2002-05-23
发明作者:말레롱장-뤽；타바르미셸；카리장-크리스토프；에베르미셸；엘아마드유세프；미냐니세르주；비비아니파브리스
申请人:추후제출；아방티 파르마 소시에테 아노님；
IPC主号:

专利说明:

QUINOLYL PROPYL PIPERIDINE DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS}
[4] Patent application WO 99/37635 discloses antimicrobial quinolylpropylpiperidine derivatives of the formula:
[5] Chemical formula
[6]
[7] Wherein the R ₁ radical is in particular (C ₁ -C ₆ ) alkoxy, R ₂ is hydrogen, R ₃ is in the 2- or 3-position and is a thiol, halogen, alkylthio, trifluoromethyl, alkyloxycarbo (C ₁ -C ₆ ) alkyl which may be optionally substituted with 1 to 3 substituents selected from alkyl, alkylcarbonyl, alkenyloxycarbonyl, alkenylcarbonyl, hydroxyl optionally substituted with alkyl, and the like. ₄ is a -CH ₂ -R ₅ group and R ₅ is alkyl, hydroxyalkyl, alkenyl, alkynyl, tetrahydrofuryl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted heteroarylalkyl, optionally Substituted heteroaroyl and the like, n is 0 to 2, m is 1 or 2 and A and B are in particular oxygen, sulfur, sulfinyl, sulfonyl or CR ₆ R ₇ and R ₆ and R ₇ are H , Thiol, alkylthio, halo, trifluoromethyl, alkenyl, alkenylcarbonyl, hydroxyl, amino The like.
[8] European patent application EP 30044 discloses the use of quinoline derivatives corresponding to the general formula as cardiovascular agents:
[9] Chemical formula
[10]
[11] Wherein R ₁ is especially alkyloxy, AB is —CH ₂ —CH ₂ —, —CHOH—CH ₂ —, —CH ₂ —CHOH—, —CH ₂ CO— or —CO—CH ₂ —, R ₁ is H, OH or alkyloxy, R ₂ is ethyl or vinyl, R ₃ is especially alkyl, hydroxyalkyl, cycloalkyl, hydroxyl, alkenyl, alkynyl, tetrahydrofuryl, phenylalkyl, optionally substituted Diphenylalkyl, optionally substituted phenylalkenyl, optionally substituted benzoyl or benzoylalkyl, or optionally substituted heteroaroyl or heteroarylalkyl, z is H or alkyl or together with R ₃ forms a cycloalkyl radical.
[12] R ₁ is hydrogen or a halogen atom or a hydroxyl radical,
[13] R ′ ₁ may represent a halogen atom or when R ₁ is also a halogen atom,
[14] R ° is a hydrogen atom, or
[15] R ₁ and R ° together form a bond,
[16] R ′ ₁ is a hydrogen atom,
[17] R ₂ represents a carboxyl, carboxymethyl or 2-carboxyethyl radical,
[18] R ₃ is either in hydroxyl, halogen, oxo, carboxyl, alkyloxycarbonyl, alkyloxy or alkylthio or in the phenyl, phenylthio or phenylalkylthio radicals [they themselves are halogen, hydroxyl, alkyl, alkyloxy, trifluoro May carry from 1 to 4 substituents selected from methyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano, acetamido (1-4C) or amino; or a cycloalkyl or cycloalkylthio radical In which the cyclic moiety comprises 3 to 7 members, or 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally [halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, tri 5- to 6-membered aromatic heterocyclyl or hetero optionally substituted with fluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] Or an alkyl radical substituted with 1 to 3 substituents selected from cyclylthio radicals, having 1 to 6 carbon atoms, or R ₃ represents [halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, Carboxyl, alkyloxycarbonyl, cyano or amino] substituted with a phenyl radical capable of carrying 1 to 3 substituents or substituted with a cycloalkyl radical comprising 3 to 7 members or in nitrogen, oxygen or sulfur Optionally selected from 1 to 4 heteroatoms and optionally substituted with halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino A propargyl radical substituted with a 5-6 membered aromatic heterocyclyl radical, or R ₃ represents cinnamil or 4-phenabuten-3-yl Or
[19] R ₂ represents hydroxymethyl, alkyloxycarbonyl, alkyloxycarbonylmethyl or 2- (alkyloxycarbonyl) ethyl radicals (the alkyl moiety contains 1 to 6 carbon atoms)
[20] R ₃ is phenylthio capable of carrying 1 to 3 substituents [selected from halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano or amino] As a radical, as a cycloalkylthio radical (the cyclic moiety comprises from 3 to 7 members), or from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and [halogen, hydroxyl, alkyl, alkyloxy, tri Fluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] alkyl radicals (1-6 carbon atoms) substituted with 5- to 6-membered aromatic heterocyclylthio radicals optionally substituted Or R ₃ is selected from halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano or amino] Substituted with a phenyl radical capable of carrying 1 to 3 substituents or substituted with a cycloalkyl radical containing 3 to 7 members or containing 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur [halogen, hydroxyl , Alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] propargyl radicals substituted with 5- to 6-membered aromatic heterocyclyl radicals optionally substituted ,
[21] R ₄ represents an alkyl radical (including 1 to 6 carbon atoms), an alkenyl-CH ₂ -radical or alkynyl-CH ₂ -radical, wherein the alkenyl or alkynyl moiety comprises 2 to 6 carbon atoms,
[22] Alkyl radicals and moieties are linear or branched radicals and moieties thereof in the form of diastereomers or mixtures thereof, and the salts thereof have been found in the present invention to be potent antimicrobial agents and this fact is the subject of the present invention. Achieve.
[23] Alkyl radicals and moieties are straight or branched radicals and moieties and include from 1 to 3 carbon atoms (except where specifically mentioned) and when R ₁ or R ′ ₁ represent a halogen atom or R ₃ is halogen When carrying a substituent, the latter can be selected from fluorine, chlorine, bromine or iodine, preferably fluorine.
[24] In the above formula, when R ₃ carries an aromatic heterocyclyl substituent, the latter is thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, pyridyl , Pyridazinyl, pyrazinyl or pyrimidinyl, but not limited to. In addition, in the definition of R ₃ , substituted alkyl radicals carry a single cyclic radical simultaneously.
[1] The present invention relates to a quinolylpropylpiperidine derivative of formula (I) which is active as an antimicrobial agent:
[2]
[3] The invention also relates to a process for the preparation of such compounds and to compositions comprising the same.
[25] According to the invention, the product of formula 1 condenses the R ₃ chain onto the quinolylpropylpiperidine derivative of formula 2 to obtain a quinolylpropylpiperidine derivative of formula 3 And then optionally reduce the oxo radicals represented by R ″ ₁ and R ″ ′ ₁ with alcohols in which R ₁ represents hydroxyl, and optionally, a quinolylpropylpiperidine derivative in which R ₁ is a halogen atom. If you want to obtain, performing the halogenated, and optionally obtaining a corresponding quinolyl propyl piperidine derivative of halogenated by-dihydro-halogenated to forming a bond with the R ₁ and R °, or R _"1 and R "a" is _1-oxo-and di-halogenated products of the formula (3) to form a radical, R ₁ and R together _'1 is a halogen atom to give a quinolyl propyl piperidine derivative, and / or if La piperidin Dean that reduction of the protected acid in the 3-position in the form of an R _'2 radical as a hydroxymethyl radical and optionally converted to a carboxymethyl or 2-carboxyethyl radical according to a conventional method, and then, optionally, acid-protecting It can be obtained by removing radicals and optionally converting the obtained product into a salt.
[26]
[27]
[28] Wherein R ₃ and R ₄ are as defined above, R ″ ₁ and R ″ ′ ₁ represent a hydrogen atom or together form an oxo radical and R ′ ₂ is a protected carboxyl, carboxymethyl or 2-carboxyethyl radical Or alkyloxycarbonyl, alkyloxycarbonylmethyl or 2- (alkyloxycarbonyl) ethyl radicals.
[29] The process of condensing the R ₃ chain on the piperidine is advantageously carried out by acting a derivative of formula 4, the reaction being carried out in an anhydrous environment, preferably in an inert environment (for example nitrogen or argon), an amide (for example , Organic solvents such as dimethylformamide), ketones (e.g. acetone) or nitrile (e.g. acetonitrile), nitrogen organic bases (e.g. triethylamine) or inorganic bases (e.g. In the presence of a base such as alkali metal carbonate: potassium carbonate).
[30] R ₃ -X
[31] Wherein R ₃ is as defined above and X represents a halogen atom, a methylsulfonyl radical, a trifluoromethylsulfonyl radical or a p-toluenesulfonyl radical.
[32] Preferably, the reaction is carried out using derivatives wherein X is bromine or iodine atom.
[33] When R ₃ represents propargyl substituted with phenyl, cycloalkyl or heterocyclyl, it is often desirable to condense propargyl halides and then replace the chain with phenyl, cycloalkyl or heterocyclyl radicals.
[34] In this alternative, the addition of the propargyl chain is carried out using propargyl bromide, under the conditions described above for R ₃ , for example, the presence or absence of alkali metal iodides such as potassium iodide or sodium iodide Is carried out under. In the case of substitution by phenyl or heterocyclyl radicals, the reaction is carried out by the action of a halide derived from the cyclic radical to be substituted, in the presence of triethylamine, in the presence of an amide (eg dimethylformamide) or nitrile (eg For example, in anhydrous environment in a solvent such as acetonitrile) and at a reflux temperature of 20 ° C. to a solvent in the presence of a palladium salt such as, for example, tetrakis (triphenylphosphine) palladium, and first copper iodide. Is performed.
[35] In case of substitution by a cycloalkyl group, the reaction is carried out in an anhydrous environment, for example in an ether such as tetrahydrofuran, above an organolithium compound such as n-butyllithium or tert-butyllithium at a temperature of -78 to 0 ° C Actuated on the resulting propargyl derivatives followed by cycloalkanone followed by deoxygenation of the intermediate alcohols according to conventional methods.
[36] When the alkyl radical represented by R ₃ carries a carboxyl or amino substituent, the latter is either protected beforehand or released after the reaction. This operation is carried out in accordance with conventional methods that do not adversely affect the rest of the molecule, in particular by TW Greene and PGM Wuts, Protective Groups in Organic Synthesis (2nd ed.), A. Wiley-Interscience Publication (1991), or McOmie , Protective Groups in Organic Chemistry, Plenum Press (1973).
[37] The protected carboxyl radical represented by R ′ ₂ may be selected from easily hydrolyzable esters. For example methyl, benzyl or tert-butyl ester or alternatively phenylpropyl or propargyl esters. The protection of the carboxyl radicals is optionally carried out simultaneously with the reaction. In this case, the product of formula (2) used carries a R ' ₂ radical which is a carboxyl radical.
[38] Reduction of the oxo radicals into alcohols is in accordance with conventional methods which do not adversely affect the rest of the molecule, in particular for example hydrides (alkali borohydrides such as sodium borohydride, potassium borohydride, sodium tria). It is carried out by the action of a reducing agent such as cetoxyborohydride or sodium cyanoborohydride, lithium aluminum hydride or diisobutylaluminum hydride, and the reaction is preferably carried out in an inert atmosphere, In an organic solvent chlorinated solvent (e.g. dichloromethane) such as methanol, ethanol or isopropanol) or ether (e.g. tetrahydrofuran).
[39] R halogenated fluoride to produce a _'1 is a hydroxyl jitsu halogen atoms from the R derivative _{"Single-quinolyl} propyl derivatives fluoro-amino sulfur-tree (e. G., Diethylamino-sulfur trifluoride, bis (2-methoxy Reagents such as tetraalkylammonium, trialkylbenzylammonium or trialkylphenylammonium halides in the presence of ethyl) aminosulfur trifluoride (Deoxofluor ^R or morpholinosulfur trifluoride) or else in the presence of sulfur tetrafluoride Or by alkali metal halides, optionally with added crown ethers. Fluorination reactions also include sulfur fluorides (eg, morpholinosulfur trifluoride, sulfur tetrafluoride (J. Org. Chem., 40, 3808 (1975)), diethylaminosulfur trifluoride (Tetrahedron) , 44, 2875 (1988)) or bis (2-methoxyethyl) aminosulfur trifluoride (Deoxofluor ^R ). In contrast, the fluorination reaction also uses a fluorinating agent such as hexafluoropropyldiethylamine (JP 2 039 546) or N- (2-chloro-1,1,2-trifluoroethyl) diethylamine. Can be performed. If tetraalkylammonium halides are used, the latter are, for example, tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium (eg tetra (n-butyl) ammonium), tetrapentylammonium, tetracyclohexyl Ammonium, triethylmethylammonium, tributylmethylammonium or trimethylpropylammonium halide. The reaction can be carried out in an organic solvent such as a chlorinated solvent (eg dichloromethane, dichloroethane or chloroform) or in an ether (eg tetrahydrofuran or dioxane), from -78 to 40 ° C. (preferably 0 to 30 ° C.). It is advantageous to carry out the reaction in an inert environment (particularly argon or nitrogen).
[40] The reaction may also be carried out in an organic solvent such as a chlorinated solvent (eg dichloromethane or chloroform) by treatment with a halogenating agent such as thionyl chloride or phosphorus trichloride at a reflux temperature of 0 to the reaction mixture.
[41] Dehalogenation of the product of formula (3) in which R ″ ₁ and R ″ ′ ₁ together form an oxo radical to produce a quinolylpropylpiperidine derivative wherein R ₁ and R ′ ₁ are halogen atoms is subject to the above halogenation conditions. It can be performed under.
[42] The dehydrohalogenation of halogenated derivatives obtained from derivatives wherein R ₁ is hydroxyl is particularly effective at diazabicyclo [5,4,0] clouding at 20 ° C. to the reflux temperature of the reaction mixture in an aromatic organic solvent (eg toluene). It may be carried out by the deck-7-en treatment.
[43] The reduction of the acid protected in the form of R ′ ₂ radicals to the hydroxymethyl radical at the 3-position of the piperidine is carried out according to a conventional method which does not adversely affect the rest of the molecule, in particular the reduction being carried out with ether (e.g. In a solvent such as tetrahydrofuran) by the action of a hydride (for example lithium aluminum hydride or diisobutylaluminum hydride) at a temperature of 20 to 60 ° C.
[44] The conversion of hydroxymethyl radicals to carboxymethyl radicals at the 3-position of piperidine is carried out according to conventional methods, which do not adversely affect the rest of the molecule, in particular for example thionyl chloride or phosphorus trichloride or phosphorus tri The corresponding cyanomethyl derivative may be prepared by the action of a halogenating agent such as bromide followed by alkali cyanide (eg potassium cyanide or sodium cyanide) and then hydrolysis of the nitrile. Halogenation can be carried out in a chlorinated solvent (eg dichloromethane or chloroform) at 0 ° C. to the reflux temperature of the solvent.
[45] The reaction of alkali cyanide can be dimethyl sulfoxide, amide (eg dimethylformamide), ketone (eg acetone), ether such as tetrahydrofuran, or alcohol such as methanol or ethanol for example. In a solvent such as 20 ° C. to reflux temperature of the reaction mixture. Hydrolysis of the nitrile is effected according to a conventional method which does not adversely affect the rest of the molecule, in particular in methanol-based medium at hydrochloric acid at a temperature of 20 to 70 ° C., followed by saponification of the obtained ester (eg dioxane To sodium hydroxide in a mixture of water and water) or by the action of aqueous sulfuric acid directly at a temperature of from 50 to 80 ° C.
[46] The conversion of hydroxymethyl radicals to 2-carboxyethyl radicals at the 3-position of piperidine is condensed, for example, by condensation of the sodium salt of diethyl malonate, followed by acid hydrolysis in the aqueous medium of the obtained product. By halogenated derivatives prepared as described above.
[47] In order to obtain quinolylpropylpiperidine derivatives in which R ₂ is a carboxyl radical, the removal of the acid-protecting radicals is carried out according to conventional methods, in particular by acid hydrolysis or saponification of the R ′ ₂ ester. In particular, sodium hydroxide is reacted in an aqueous / organic medium, for example in an alcohol such as methanol, or in an ether such as dioxane, at 20 to the reflux temperature of the reaction mixture. Hydrolysis can also be carried out at a temperature of 20-100 ° C. in aqueous hydrochloric acid medium.
[48] The quinolylpropylpiperidine derivatives of the formula (2) wherein R ′ ₂ represents a carboxyl radical or the corresponding acid are according to or analogously to the process described in the examples below or in European patent application EP 30044 or international application WO 99/37635. It may be prepared according to or similar to the disclosed method. Intermediates of the quinolylpropylpiperidine derivatives in which R ₄ represents alkenyl-CH ₂ O- or alkynyl-CH ₂ O-, react the corresponding halogenated derivatives on the hydroxylated quinoline derivatives at the 6-position to R It can be obtained similarly to the preparation of intermediates which are _tetravalent alkyloxy.
[49] The protected 2-carboxyethyl derivative of formula (2) can be obtained according to or similarly to the method disclosed in the international application WO 99/37635, followed by hydrolysis of the nitrile and esterification of the acid obtained, or in the examples below It may be prepared according to or similar to the method described.
[50] It is understood that derivatives of formula 1, 2 or 3 or their starting intermediates may exist in cis or trans form with respect to the substituents at the 3- and 4-positions of piperidine. Derivatives of the trans batch can be obtained from derivatives of the cis batch according to or similarly to the method disclosed in the international application WO 99/37635.
[51] The quinolylpropylpiperidine derivative of Formula 1 may optionally be purified by physical methods such as crystallization or chromatography.
[52] It is also understood that when R ' ₁ is a hydrogen atom and R ₁ is hydroxyl or halogen, diastereomeric forms are present and diastereomeric forms and mixtures thereof are also within the scope of the present invention. The latter can in particular be separated off by silica chromatography or high performance liquid chromatography (HPLC).
[53] Quinolylpropylpiperidine derivatives of formula (1) can be converted to addition salts with acids by known methods. It is understood that these salts also fall within the scope of the present invention.
[54] Examples of addition salts with pharmaceutically acceptable acids include salts formed with inorganic acids (hydrochloride, hydrobromide, sulfate, nitrate or phosphate) or salts formed with organic acids (succinate, fumarate, tartrate, acetate, propionate, Maleate, citrate, methanesulfonate, ethanesulfonate, phenylsulfonate, p-toluenesulfonate, isethionate, naphthylsulfonate or camphorsulfonate, or salts formed with substituted derivatives of these compounds). Can be.
[55] Some of the quinolylpropylpiperidine of formula (I) carrying a carboxyl radical can be converted in the form of metal salts or with addition salts with nitrogen bases according to known methods. These salts also fall within the scope of the present invention. The salts are obtained by reacting a metal base of ammonia or amine (e.g. alkali or alkaline earth metal base) with the product according to the invention in a suitable solvent such as alcohol, ether or water, or by exchange reaction with a salt of an organic acid. Can be. After any concentration of the solution, the salt forms a precipitate and is separated by filtration, sedimentation or lyophilization. Examples of pharmaceutically acceptable salts include salts with alkali metals (sodium, potassium or lithium) or salts with alkaline earth metals (magnesium or calcium), ammonium salts or nitrogen bases (ethanolamine, diethanolamine, trimethylamine, triethyl Amine, methylamine, propylamine, diisopropylamine, N, N-dimethylethanolamine, benzylamine, dicyclohexylamine, N-benzyl-β-phenethylamine, N, N'-dibenzylethylenediamine, di Phenylenediamine, benzylhydrylamine, quinine, choline, arginine, lysine, leucine or dibenzylamine).
[56] Quinolylpropylpiperidine derivatives according to the invention are particularly advantageous antibacterial agents.
[57] In vitro, in the case of Gram-positive microorganisms, the quinolylpropylpiperidine derivatives according to the invention are methicillin-resistant Staphylococcus aureus AS5155 at concentrations of 0.015-4 μg / ml, and most of these are 0.06 It has been found to be active against Streptococcus pneumoniae IP53146 at a concentration of from 8 μg / ml and to enterococcus fascium ATCC19434 or H983401 at a concentration of 0.12 to 64 μg / ml, and against gram-negative microorganisms, which It has been shown to be active against Moraxella catarrhalis IPA152 at concentrations of 0.12 to 32 μg / ml; In vivo, they experimented with mice with Staphylococcus aureus IP8203 at a dose of 10 to 150 mg / kg in subcutaneous injection (CD ₅₀ ) and in some cases at a dose of 20 to 150 mg / kg by oral administration. It turned out to be active against infection.
[58] Finally, the products according to the invention are particularly advantageous due to their low toxicity. None of the products showed toxicity at doses of 100 mg / kg subcutaneously in mice (two doses).
[59] Particularly advantageous among the products of the present invention
[60] R ₁ is hydrogen or a halogen atom or a hydroxyl radical,
[61] R ′ ₁ is a hydrogen atom,
[62] R ° is a hydrogen atom,
[63] R ₁ and R ° together form a bond,
[64] R ′ ₁ is a hydrogen atom,
[65] R ₂ represents a carboxyl or carboxymethyl radical,
[66] R ₃ is in halogen, oxo, alkyloxy or alkylthio or in phenyl or phenylthio radicals (which themselves may carry 1 to 4 halogen atoms), or in cycloalkyl or cycloalkylthio radicals (cyclic moiety) Comprises 3 to 7 members), or from 5 to 6 membered aromatic heterocyclyl or heterocyclylthio radicals containing 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally substituted by halogen Nitrogen, oxygen, or propargyl radicals representing alkyl radicals (1-6 carbon atoms) substituted with one to three substituents selected, or R ₃ substituted by itself with a phenyl radical capable of carrying one to three halogen substituents; 5- to 6-membered aromatic heterocyclyl radicals containing 1 to 4 heteroatoms selected from sulfur Represents a substituted or propargyl radical, R ₃ is or indicate or when wheat,
[67] R ₂ represents a hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonylmethyl radical (the alkyl moiety contains 1 to 6 carbon atoms) and R ₃ contains 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur Or an alkyl radical substituted with 5 to 6 membered aromatic heterocyclylthio radicals having 1 to 6 carbon atoms, or R ₃ is selected from nitrogen, oxygen or sulfur and includes 5 to 4 heteroatoms including 1 to 4 heteroatoms; Represents a propargyl radical substituted with a six-membered aromatic heterocyclyl radical, R ₄ represents an alkyl radical (containing 1 to 6 carbon atoms),
[68] Alkyl radicals and moieties are quinolylpropylquinoline derivatives of formula (I) which are straight or branched chain radicals and moieties, and diastereomeric forms or mixtures thereof, and salts thereof, and more particularly advantageous among these products are the following compounds:
[69] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Acetic acid;
[70] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid;
[71] (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylsulfanyl) ethyl] piperidine-3 Acetic acid;
[72] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Acetic acid;
[73] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop- 2-ynyl] -piperidine-3-carboxylic acid.
[74] Particularly preferred are the products mentioned in the examples; The quinolipropylpiperidine derivatives below are also advantageous products.
[75] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-carboxylic acid
[76] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine-3-carboxylic acid
[77] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine-3-carboxylic acid
[78] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-carboxylic acid
[79] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-3-carboxylic acid
[80] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-3-carboxylic acid
[81] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-3-carboxylic acid
[82] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3-carboxylic acid
[83] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3-carboxylic acid
[84] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3-carboxylic acid
[85] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidine-3-carboxylic acid
[86] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-carboxylic acid
[87] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3-carboxylic acid
[88] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-carboxylic acid
[89] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-carboxylic acid
[90] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-carboxylic acid
[91] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidine-3-carboxylic acid
[92] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine-3-carboxylic acid
[93] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) butyl] piperidine-3-carboxylic acid
[94] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidine-3-carboxylic acid
[95] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3-carboxylic acid
[96] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidine-3-carboxylic acid
[97] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidine-3-carboxylic acid
[98] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidine-3-carboxylic acid
[99] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidine-3-carboxylic acid
[100] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3-carboxylic acid
[101] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidine-3-carboxylic acid
[102] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidine-3-carboxylic acid
[103] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3-carboxylic acid
[104] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidine-3-carboxylic acid
[105] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidine-3-carboxylic acid
[106] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidine-3-carboxylic acid
[107] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid
[108] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid
[109] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid
[110] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid
[111] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid
[112] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid
[113] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-carboxylic acid
[114] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-3-carboxylic acid
[115] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-3-carboxylic acid
[116] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-3-carboxylic acid
[117] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3-carboxylic acid
[118] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine-3-carboxylic acid
[119] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine-3-carboxylic acid
[120] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-3-carboxylic acid
[121] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-3-carboxylic acid
[122] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-3-carboxylic acid
[123] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-3-carboxylic acid
[124] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-3-carboxylic acid
[125] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-3-carboxylic acid
[126] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-3-carboxylic acid
[127] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-3-carboxylic acid
[128] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid
[129] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidine-3-carboxylic acid
[130] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid
[131] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] piperidine-3-carboxylic acid
[132] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-3-carboxylic acid
[133] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-3-carboxylic acid
[134] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-3-carboxylic acid
[135] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-3-carboxylic acid
[136] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-3-carboxylic acid
[137] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine-3-carboxylic acid
[138] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine-3-carboxylic acid
[139] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine-3-carboxylic acid
[140] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3-carboxylic acid
[141] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine-3-carboxylic acid
[142] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine-3-carboxylic acid
[143] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine-3-carboxylic acid
[144] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-3-carboxylic acid
[145] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-carboxylic acid
[146] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-3-carboxylic acid
[147] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine-3-carboxylic acid
[148] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-3-carboxylic acid
[149] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-3-carboxylic acid
[150] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-carboxylic acid
[151] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-carboxylic acid
[152] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-carboxylic acid
[153] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine-3-carboxylic acid
[154] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-carboxylic acid
[155] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-carboxylic acid
[156] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine-3-carboxylic acid
[157] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-carboxylic acid
[158] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-carboxylic acid
[159] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-carboxylic acid
[160] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidine-3-carboxylic acid
[161] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl] piperidine-3-carboxylic acid
[162] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-carboxylic acid
[163] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-3-carboxylic acid
[164] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-carboxylic acid
[165] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-carboxylic acid
[166] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3-carboxylic acid
[167] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3-carboxylic acid
[168] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-carboxylic acid
[169] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3-carboxylic acid
[170] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3-carboxylic acid
[171] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3-carboxylic acid
[172] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3-carboxylic acid
[173] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-3-carboxylic acid
[174] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-3-carboxylic acid
[175] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) propyl] piperidine-3-carboxylic acid
[176] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl) butyl] piperidine-3-carboxylic acid
[177] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl) thioethyl] piperidine-3-carboxylic acid
[178] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) thiopropyl] piperidine-3-carboxylic acid
[179] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) propyl] piperidine-3-carboxylic acid
[180] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl) butyl] piperidine-3-carboxylic acid
[181] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl) thioethyl] piperidine-3-carboxylic acid
[182] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) thiopropyl] piperidine-3-carboxylic acid
[183] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidine-3-carboxylic acid
[184] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl) butyl] piperidine-3-carboxylic acid
[185] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl) thioethyl] piperidine-3-carboxylic acid
[186] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thiopropyl] piperidine-3-carboxylic acid
[187] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] piperidine-3-carboxylic acid
[188] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl) butyl] piperidine-3-carboxylic acid
[189] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl) thioethyl] piperidine-3-carboxylic acid
[190] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) thiopropyl] piperidine-3-carboxylic acid
[191] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-3-carboxylic acid
[192] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-3-carboxylic acid
[193] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-3-carboxylic acid
[194] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-3-carboxylic acid
[195] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] piperidine-3-carboxylic acid
[196] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidine-3-carboxylic acid
[197] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl] piperidine-3-carboxylic acid
[198] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine-3-carboxylic acid
[199] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] piperidine-3-carboxylic acid
[200] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-3-carboxylic acid
[201] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidine-3-carboxylic acid
[202] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl] piperidine-3-carboxylic acid
[203] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3-carboxylic acid
[204] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-2-yl) butyl] piperidine-3-carboxylic acid
[205] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-2-yl) thioethyl] piperidine-3-carboxylic acid
[206] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) thiopropyl] piperidine-3-carboxylic acid
[207] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3-carboxylic acid
[208] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl) butyl] piperidine-3-carboxylic acid
[209] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl) thioethyl] piperidine-3-carboxylic acid
[210] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) thiopropyl] piperidine-3-carboxylic acid
[211] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] piperidine-3- Carboxylic acid
[212] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] piperidine-3- Carboxylic acid
[213] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thiopropyl] piperidine-3 Carboxylic acid
[214] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) propyl] piperidine-3- Carboxylic acid
[215] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazol-2-yl) butyl] piperidine-3- Carboxylic acid
[216] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) thioethyl] piperidine-3 Carboxylic acid
[217] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) thiopropyl] piperidine-3 Carboxylic acid
[218] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) propyl] piperidine-3- Carboxylic acid
[219] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazol-4-yl) butyl] piperidine-3- Carboxylic acid
[220] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimidazol-4-yl) thioethyl] piperidine-3 Carboxylic acid
[221] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) thiopropyl] piperidine-3 Carboxylic acid
[222] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) propyl] piperidine-3-carboxylic acid
[223] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazol-4-yl) butyl] piperidine-3-carboxylic acid
[224] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazol-4-yl) thioethyl] piperidine-3- Carboxylic acid
[225] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) thiopropyl] piperidine-3- Carboxylic acid
[226] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine-3-carboxylic acid
[227] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine-3-carboxylic acid
[228] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3-carboxylic acid
[229] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine-3-carboxylic acid
[230] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-3-carboxylic acid
[231] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-3-carboxylic acid
[232] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-carboxylic acid
[233] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine-3-carboxylic acid
[234] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] piperidine-3-carboxylic acid
[235] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine-3-carboxylic acid
[236] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine-3-carboxylic acid
[237] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidine-3-carboxylic acid
[238] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidine-3-carboxylic acid
[239] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperidine-3-carboxylic acid
[240] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidine-3-carboxylic acid
[241] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidine-3-carboxylic acid
[242] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidine-3-carboxylic acid
[243] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidine-3-carboxylic acid
[244] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine-3-carboxylic acid
[245] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine-3-carboxylic acid
[246] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3-carboxylic acid
[247] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine-3-carboxylic acid
[248] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine-3-carboxylic acid
[249] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine-3-carboxylic acid
[250] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidine-3-carboxylic acid
[251] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidine-3-carboxylic acid
[252] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thioethyl] piperidine-3-carboxylic acid
[253] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-carboxylic acid
[254] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-3-carboxylic acid
[255] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-3-carboxylic acid
[256] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine-3-carboxylic acid
[257] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-3-carboxylic acid
[258] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine-3-carboxylic acid
[259] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidine-3-carboxylic acid
[260] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-3-carboxylic acid
[261] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine-3-carboxylic acid
[262] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidine-3-carboxylic acid
[263] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidine-3-carboxylic acid
[264] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine-3-carboxylic acid
[265] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3-carboxylic acid
[266] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[267] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[268] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[269] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[270] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[271] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[272] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[273] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoromethyl) phenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[274] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoromethyl) phenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[275] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoromethyl) phenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[276] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[277] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[278] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[279] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[280] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[281] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop-2-ynyl] piperidine-3 Carboxylic acid
[282] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) prop-2-ynyl] piperidine-3 Carboxylic acid
[283] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) prop-2-ynyl] piperidine-3 Carboxylic acid
[284] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[285] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichlorophenyl) prop-2-ynyl] piperidine-3 Carboxylic acid
[286] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[287] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[288] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[289] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[290] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[291] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-methylphenyl) prop-2-ynyl] piperidine- 3-carboxylic acid
[292] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-carboxylic acid
[293] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-carboxylic acid
[294] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-carboxylic acid
[295] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-methoxyphenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[296] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop-2-ynyl ] Piperidine-3-carboxylic acid
[297] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) prop-2-ynyl] piperidine-3 Carboxylic acid
[298] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methylphenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[299] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[300] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[301] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[302] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[303] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[304] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[305] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) prop-2-ynyl] piperidine 3-carboxylic acid
[306] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[307] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[308] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[309] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) prop-2-ynyl] py Ferridine-3-carboxylic acid
[310] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) prop-2-ynyl] py Ferridine-3-carboxylic acid
[311] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[312] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[313] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[314] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[315] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[316] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[317] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[318] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[319] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[320] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[321] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[322] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[323] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2-ynyl] piperidine-3 Carboxylic acid
[324] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-carboxylic acid
[325] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3- Carboxylic acid
[326] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] Piperidine-3-carboxylic acid
[327] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] Piperidine-3-carboxylic acid
[328] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] Piperidine-3-carboxylic acid
[329] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] Piperidine-3-carboxylic acid
[330] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] Piperidine-3-carboxylic acid
[331] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] Piperidine-3-carboxylic acid
[332] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl ) Propyl] piperidine-3-carboxylic acid
[333] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl ) Butyl] piperidine-3-carboxylic acid
[334] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl ) Propyl] piperidine-3-carboxylic acid
[335] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl ) Butyl] piperidine-3-carboxylic acid
[336] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] pi Ferridine-3-carboxylic acid
[337] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] pi Ferridine-3-carboxylic acid
[338] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] pi Ferridine-3-carboxylic acid
[339] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] pi Ferridine-3-carboxylic acid
[340] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] pi Ferridine-3-carboxylic acid
[341] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] pi Ferridine-3-carboxylic acid
[342] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl ] Piperidine-3-carboxylic acid
[343] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl ] Piperidine-3-carboxylic acid
[344] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl ] Piperidine-3-carboxylic acid
[345] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl ] Piperidine-3-carboxylic acid
[346] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperi Dean-3-carboxylic acid
[347] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperi Dean-3-carboxylic acid
[348] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperi Dean-3-carboxylic acid
[349] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperi Dean-3-carboxylic acid
[350] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperi Dean-3-carboxylic acid
[351] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperi Dean-3-carboxylic acid
[352] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperi Dean-3-carboxylic acid
[353] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] Piperidine-3-carboxylic acid
[354] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] Piperidine-3-carboxylic acid
[355] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] Piperidine-3-carboxylic acid
[356] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] Piperidine-3-carboxylic acid
[357] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] Piperidine-3-carboxylic acid
[358] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] Piperidine-3-carboxylic acid
[359] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl ] Piperidine-3-carboxylic acid
[360] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl ] Piperidine-3-carboxylic acid
[361] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl ] Piperidine-3-carboxylic acid
[362] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl ] Piperidine-3-carboxylic acid
[363] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl ] Piperidine-3-carboxylic acid
[364] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl ] Piperidine-3-carboxylic acid
[365] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthioethyl] piperidine-3 Carboxylic acid
[366] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3 Carboxylic acid
[367] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl ] Piperidine-3-carboxylic acid
[368] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl ] Piperidine-3-carboxylic acid
[369] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl ] Piperidine-3-carboxylic acid
[370] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl ] Piperidine-3-carboxylic acid
[371] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl ] Piperidine-3-carboxylic acid
[372] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenyl Thio) ethyl] piperidine-3-carboxylic acid
[373] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[374] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenyl Thio) ethyl] piperidine-3-carboxylic acid
[375] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[376] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] Piperidine-3-carboxylic acid
[377] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] Piperidine-3-carboxylic acid
[378] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] Piperidine-3-carboxylic acid
[379] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] Piperidine-3-carboxylic acid
[380] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] Piperidine-3-carboxylic acid
[381] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] Piperidine-3-carboxylic acid
[382] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) Ethyl] piperidine-3-carboxylic acid
[383] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) Propyl] piperidine-3-carboxylic acid
[384] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) Ethyl] piperidine-3-carboxylic acid
[385] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) Propyl] piperidine-3-carboxylic acid
[386] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] pi Ferridine-3-carboxylic acid
[387] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] py Ferridine-3-carboxylic acid
[388] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] pi Ferridine-3-carboxylic acid
[389] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] py Ferridine-3-carboxylic acid
[390] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] pi Ferridine-3-carboxylic acid
[391] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] py Ferridine-3-carboxylic acid
[392] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) Ethyl] piperidine-3-carboxylic acid
[393] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) Propyl] piperidine-3-carboxylic acid
[394] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) Ethyl] piperidine-3-carboxylic acid
[395] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) Propyl] piperidine-3-carboxylic acid
[396] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) Ethyl] piperidine-3-carboxylic acid
[397] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) Propyl] piperidine-3-carboxylic acid
[398] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl ] Piperidine-3-carboxylic acid
[399] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl ] Piperidine-3-carboxylic acid
[400] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl ] Piperidine-3-carboxylic acid
[401] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl ] Piperidine-3-carboxylic acid
[402] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl ] Piperidine-3-carboxylic acid
[403] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl ] Piperidine-3-carboxylic acid
[404] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-carboxylic acid
[405] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine 3-carboxylic acid
[406] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-carboxylic acid
[407] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine 3-carboxylic acid
[408] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-carboxylic acid
[409] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine 3-carboxylic acid
[410] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine-3-carboxylic acid
[411] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 3-carboxylic acid
[412] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperi Dean-3-carboxylic acid
[413] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperi Dean-3-carboxylic acid
[414] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperi Dean-3-carboxylic acid
[415] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperi Dean-3-carboxylic acid
[416] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Dean-3-carboxylic acid
[417] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperi Dean-3-carboxylic acid
[418] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Dean-3-carboxylic acid
[419] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperi Dean-3-carboxylic acid
[420] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3 Carboxylic acid
[421] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3 Carboxylic acid
[422] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3 Carboxylic acid
[423] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3 Carboxylic acid
[424] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] pi Ferridine-3-carboxylic acid
[425] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] py Ferridine-3-carboxylic acid
[426] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] pi Ferridine-3-carboxylic acid
[427] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] py Ferridine-3-carboxylic acid
[428] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] Piperidine-3-carboxylic acid
[429] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] Piperidine-3-carboxylic acid
[430] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl ] Piperidine-3-carboxylic acid
[431] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Propyl] piperidine-3-carboxylic acid
[432] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl ) Butyl] piperidine-3-carboxylic acid
[433] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[434] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Thiopropyl] piperidine-3-carboxylic acid
[435] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Propyl] piperidine-3-carboxylic acid
[436] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl ) Butyl] piperidine-3-carboxylic acid
[437] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[438] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Thiopropyl] piperidine-3-carboxylic acid
[439] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Propyl] piperidine-3-carboxylic acid
[440] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl ) Butyl] piperidine-3-carboxylic acid
[441] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[442] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Thiopropyl] piperidine-3-carboxylic acid
[443] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Propyl] piperidine-3-carboxylic acid
[444] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl ) Butyl] piperidine-3-carboxylic acid
[445] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[446] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Thiopropyl] piperidine-3-carboxylic acid
[447] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] Piperidine-3-carboxylic acid
[448] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] Piperidine-3-carboxylic acid
[449] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl ] Piperidine-3-carboxylic acid
[450] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl ] Piperidine-3-carboxylic acid
[451] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] Piperidine-3-carboxylic acid
[452] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] Piperidine-3-carboxylic acid
[453] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl ] Piperidine-3-carboxylic acid
[454] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl ] Piperidine-3-carboxylic acid
[455] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] Piperidine-3-carboxylic acid
[456] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] Piperidine-3-carboxylic acid
[457] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl ] Piperidine-3-carboxylic acid
[458] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl ] Piperidine-3-carboxylic acid
[459] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl ) Propyl] piperidine-3-carboxylic acid
[460] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-2-yl ) Butyl] piperidine-3-carboxylic acid
[461] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[462] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl ) Thiopropyl] piperidine-3-carboxylic acid
[463] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl ) Propyl] piperidine-3-carboxylic acid
[464] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl ) Butyl] piperidine-3-carboxylic acid
[465] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl ) Thioethyl] -piperidine-3-carboxylic acid
[466] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-3- Yl) thiopropyl] -piperidine-3-carboxylic acid
[467] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) propyl] piperidine-3-carboxylic acid
[468] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1,3-thiazole- 2-yl) butyl] piperidine-3-carboxylic acid] -piperidine-3-carboxylic acid
[469] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) thiopropyl] piperidine-3-carboxylic acid
[470] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) propyl] piperidine-3-carboxylic acid
[471] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1-methylimidazole- 2-yl) butyl] piperidine-3-carboxylic acid
[472] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (1-methylimidazole- 2-yl) thioethyl] -piperidine-3-carboxylic acid
[473] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) thiopropyl] -piperidine-3-carboxylic acid
[474] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) propyl] piperidine-3-carboxylic acid
[475] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylimidazole- 4-yl) butyl] piperidine-3-carboxylic acid
[476] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylimidazole- 4-yl) thioethyl] -piperidine-3-carboxylic acid
[477] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) thiopropyl] -piperidine-3-carboxylic acid
[478] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) propyl] piperidine-3-carboxylic acid
[479] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylpyrazole-4 -Yl) butyl] piperidine-3-carboxylic acid
[480] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylpyrazole-4 -Yl) thioethyl] -piperidine-3-carboxylic acid
[481] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) thiopropyl] -piperidine-3-carboxylic acid
[482] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Propyl] piperidine-3-carboxylic acid
[483] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (oxazol-2-yl) Butyl] piperidine-3-carboxylic acid
[484] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (oxazol-2-yl) Thioethyl] piperidine-3-carboxylic acid
[485] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Thiopropyl] piperidine-3-carboxylic acid
[486] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) propyl ] Piperidine-3-carboxylic acid
[487] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-2-yl) butyl ] Piperidine-3-carboxylic acid
[488] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) thio Propyl] piperidine-3-carboxylic acid
[489] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) propyl ] Piperidine-3-carboxylic acid
[490] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-3-yl) butyl ] Piperidine-3-carboxylic acid
[491] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-3-yl) thio Ethyl] piperidine-3-carboxylic acid
[492] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) thio Propyl] piperidine-3-carboxylic acid
[493] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) propyl ] Piperidine-3-carboxylic acid
[494] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-4-yl) butyl ] Piperidine-3-carboxylic acid
[495] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [5- (pyridin-4-yl) pentyl ] Piperidine-3-carboxylic acid
[496] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-2-yl) thio Ethyl] piperidine-3-carboxylic acid
[497] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-4-yl) thio Ethyl] piperidine-3-carboxylic acid
[498] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) thio Propyl] piperidine-3-carboxylic acid
[499] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Propyl] piperidine-3-carboxylic acid
[500] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-2-yl) Butyl] piperidine-3-carboxylic acid
[501] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-2-yl) Thioethyl] piperidine-3-carboxylic acid
[502] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Thiopropyl] piperidine-3-carboxylic acid
[503] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Propyl] piperidine-3-carboxylic acid
[504] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-4-yl) Butyl] piperidine-3-carboxylic acid
[505] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-4-yl) Thioethyl] piperidine-3-carboxylic acid
[506] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Thiopropyl] piperidine-3-carboxylic acid
[507] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Propyl] piperidine-3-carboxylic acid
[508] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-5-yl) Butyl] piperidine-3-carboxylic acid
[509] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-5-yl) Thioethyl] piperidine-3-carboxylic acid
[510] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Thiopropyl] piperidine-3-carboxylic acid
[511] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) propyl ] Piperidine-3-carboxylic acid
[512] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrazin-2-yl) butyl ] Piperidine-3-carboxylic acid
[513] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrazin-2-yl) thio Ethyl] piperidine-3-carboxylic acid
[514] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) thio Propyl] piperidine-3-carboxylic acid
[515] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Propyl] piperidine-3-carboxylic acid
[516] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-3-yl) Butyl] piperidine-3-carboxylic acid
[517] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-3-yl) Thioethyl] piperidine-3-carboxylic acid
[518] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Thiopropyl] piperidine-3-carboxylic acid
[519] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Propyl] piperidine-3-carboxylic acid
[520] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-4-yl) Butyl] piperidine-3-carboxylic acid
[521] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-4-yl) Thioethyl] piperidine-3-carboxylic acid
[522] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Thiopropyl] piperidine-3-carboxylic acid
[523] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylprop-2-ynyl] Piperidine-3-carboxylic acid
[524] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[525] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[526] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[527] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[528] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[529] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[530] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[531] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[532] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2- (trifluoromethyl ) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[533] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3- (trifluoromethyl ) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[534] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-trifluoromethyl) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[535] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[536] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[537] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[538] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-difluoro Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[539] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-difluoro Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[540] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[541] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[542] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[543] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trichloro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[544] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[545] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[546] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-4-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[547] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[548] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-5-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[549] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-2-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[550] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluoro-4- Methylphenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[551] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[552] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[553] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-5- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[554] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chloro-2-meth Methoxyphenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[555] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-bis (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[556] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dimethylphenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[557] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichloro-6 -Methylphenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[558] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chlorothiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[559] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorothiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[560] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-methylthiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[561] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylthiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[562] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[563] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[564] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-3- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[565] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[566] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 4-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[567] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 5-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[568] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[569] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[570] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[571] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[572] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[573] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-5-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[574] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[575] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[576] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[577] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[578] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[579] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[580] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) pro Ph-2-inyl] piperidine-3-carboxylic acid
[581] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[582] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[583] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylpropen-2-yl] Piperidine-3-carboxylic acid
[584] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbuten-3-yl] py Ferridine-3-carboxylic acid
[585] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbutyl] piperidine-3 Carboxylic acid
[586] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenyl) propyl ] Piperidine-3-carboxylic acid
[587] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-fluorophenyl) butyl ] Piperidine-3-carboxylic acid
[588] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluorophenyl) propyl ] Piperidine-3-carboxylic acid
[589] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-fluorophenyl) butyl ] Piperidine-3-carboxylic acid
[590] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) propyl ] Piperidine-3-carboxylic acid
[591] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-fluorophenyl) butyl ] Piperidine-3-carboxylic acid
[592] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluoro Phenyl) propyl] piperidine-3-carboxylic acid
[593] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,3-difluoro Phenyl) butyl] piperidine-3-carboxylic acid
[594] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluoro Phenyl) propyl] piperidine-3-carboxylic acid
[595] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,6-difluoro Phenyl) butyl] piperidine-3-carboxylic acid
[596] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenyl) propyl] Piperidine-3-carboxylic acid
[597] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-chlorophenyl) butyl] Piperidine-3-carboxylic acid
[598] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenyl) propyl] Piperidine-3-carboxylic acid
[599] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-chlorophenyl) butyl] Piperidine-3-carboxylic acid
[600] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenyl) propyl] Piperidine-3-carboxylic acid
[601] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-chlorophenyl) butyl] Piperidine-3-carboxylic acid
[602] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-dichlorophenyl) Propyl] piperidine-3-carboxylic acid
[603] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,3-dichlorophenyl) Butyl] piperidine-3-carboxylic acid
[604] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-dichlorophenyl) Propyl] piperidine-3-carboxylic acid
[605] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,6-dichlorophenyl) Butyl] piperidine-3-carboxylic acid
[606] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenyl) propyl] py Ferridine-3-carboxylic acid
[607] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-methylphenyl) butyl] py Ferridine-3-carboxylic acid
[608] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [5- (2-methylphenyl) phenyl] pi Ferridine-3-carboxylic acid
[609] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenyl) propyl] py Ferridine-3-carboxylic acid
[610] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylphenyl) butyl] pi Ferridine-3-carboxylic acid
[611] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenyl) propyl] py Ferridine-3-carboxylic acid
[612] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-methylphenyl) butyl] py Ferridine-3-carboxylic acid
[613] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenyl) propyl ] -Piperidine-3-carboxylic acid
[614] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-methoxyphenyl) butyl ] Piperidine-3-carboxylic acid
[615] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenyl) propyl ] Piperidine-3-carboxylic acid
[616] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methoxyphenyl) butyl ] Piperidine-3-carboxylic acid
[617] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenyl) propyl ] Piperidine-3-carboxylic acid
[618] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-methoxyphenyl) butyl ] Piperidine-3-carboxylic acid
[619] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-trifluoromethylphenyl) Propyl] -piperidine-3-carboxylic acid
[620] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-trifluoromethylphenyl) Butyl] piperidine-3-carboxylic acid
[621] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-trifluoromethylphenyl) Propyl] -piperidine-3-carboxylic acid
[622] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-trifluoromethylphenyl) Butyl] piperidine-3-carboxylic acid
[623] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-trifluoromethylphenyl) Propyl] piperidine-3-carboxylic acid
[624] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-trifluoromethylphenyl) Butyl] piperidine-3-carboxylic acid
[625] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylthioethyl] piperidine- 3-carboxylic acid
[626] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylthiopropyl] piperidine- 3-carboxylic acid
[627] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenylthio) Propyl] piperidine-3-carboxylic acid
[628] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluorophenylthio) Propyl] piperidine-3-carboxylic acid
[629] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-fluorophenylthio) Ethyl] piperidine-3-carboxylic acid
[630] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-fluorophenylthio) Ethyl] piperidine-3-carboxylic acid
[631] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenylthio) Propyl] piperidine-3-carboxylic acid
[632] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3-difluoro Phenylthio) ethyl] piperidine-3-carboxylic acid
[633] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluoro Phenylthio) propyl] piperidine-3-carboxylic acid
[634] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,6-difluoro Phenylthio) ethyl] piperidine-3-carboxylic acid
[635] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluoro Phenylthio) propyl] piperidine-3-carboxylic acid
[636] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-chlorophenylthio) ethyl ] Piperidine-3-carboxylic acid
[637] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenylthio) propyl ] Piperidine-3-carboxylic acid
[638] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-chlorophenylthio) ethyl ] Piperidine-3-carboxylic acid
[639] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenylthio) propyl ] Piperidine-3-carboxylic acid
[640] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-chlorophenylthio) ethyl ] Piperidine-3-carboxylic acid
[641] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenylthio) propyl ] Piperidine-3-carboxylic acid
[642] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3-dichlorophenylthio ) Ethyl] piperidine-3-carboxylic acid
[643] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-dichlorophenylthio ) Propyl] piperidine-3-carboxylic acid
[644] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,6-dichlorophenylthio ) Ethyl] piperidine-3-carboxylic acid
[645] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-dichlorophenylthio ) Propyl] piperidine-3-carboxylic acid
[646] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methylphenylthio) ethyl] Piperidine-3-carboxylic acid
[647] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenylthio) propyl] Piperidine-3-carboxylic acid
[648] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylphenylthio) ethyl] Piperidine-3-carboxylic acid
[649] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenylthio) propyl] Piperidine-3-carboxylic acid
[650] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methylphenylthio) ethyl] Piperidine-3-carboxylic acid
[651] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenylthio) propyl] Piperidine-3-carboxylic acid
[652] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-trifluoromethylphenylthio Ethyl] -piperidine-3-carboxylic acid
[653] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-trifluoromethylphenylthio ) Propyl] -piperidine-3-carboxylic acid
[654] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-trifluoromethylphenylthio Ethyl] -piperidine-3-carboxylic acid
[655] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-trifluoromethylphenylthio ) Propyl] -piperidine-3-carboxylic acid
[656] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-trifluoromethylphenylthio Ethyl] -piperidine-3-carboxylic acid
[657] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-trifluoromethylphenylthio ) Propyl] -piperidine-3-carboxylic acid
[658] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methoxyphenylthio) Ethyl] piperidine-3-carboxylic acid
[659] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenylthio) Propyl] piperidine-3-carboxylic acid
[660] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methoxyphenylthio) Ethyl] piperidine-3-carboxylic acid
[661] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenylthio) Propyl] piperidine-3-carboxylic acid
[662] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methoxyphenylthio) Ethyl] piperidine-3-carboxylic acid
[663] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenylthio) Propyl] piperidine-3-carboxylic acid
[664] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [cyclopropylmethyl] piperidine-3- Carboxylic acid
[665] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopropyl) ethyl] piperi Dean-3-carboxylic acid
[666] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [cyclobutylmethyl] piperidine-3- Carboxylic acid
[667] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclobutyl) ethyl] piperi Dean-3-carboxylic acid
[668] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [cyclopentylmethyl] piperidine-3- Carboxylic acid
[669] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentyl) ethyl] piperi Dean-3-carboxylic acid
[670] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [cyclohexylmethyl] piperidine-3- Carboxylic acid
[671] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperi Dean-3-carboxylic acid
[672] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopropylthio) ethyl] py Ferridine-3-carboxylic acid
[673] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclopropylthio) propyl] py Ferridine-3-carboxylic acid
[674] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclobutylthio) ethyl] py Ferridine-3-carboxylic acid
[675] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclobutylthio) propyl] py Ferridine-3-carboxylic acid
[676] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] py Ferridine-3-carboxylic acid
[677] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclopentylthio) propyl] py Ferridine-3-carboxylic acid
[678] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexylthio) ethyl] py Ferridine-3-carboxylic acid
[679] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclohexylthio) propyl] py Ferridine-3-carboxylic acid
[680] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2-methylthioethyl] piperidine- 3-carboxylic acid
[681] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-methylthiopropyl] piperidine- 3-carboxylic acid
[682] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2-ethylthioethyl] piperidine- 3-carboxylic acid
[683] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-ethylthiopropyl] piperidine- 3-carboxylic acid
[684] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (n-propylthio) ethyl] Piperidine-3-carboxylic acid
[685] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (n-propylthio) propyl] Piperidine-3-carboxylic acid
[686] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (n-butylthio) ethyl] Piperidine-3-carboxylic acid
[687] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (n-butylthio) propyl] Piperidine-3-carboxylic acid
[688] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) propyl ] Piperidine-3-carboxylic acid
[689] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-2-yl) butyl ] Piperidine-3-carboxylic acid
[690] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) thio Propyl] piperidine-3-carboxylic acid
[691] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chlorothiene-2- Yl) propyl] piperidine-3-carboxylic acid
[692] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (5-chlorothiene-2- I) Butyl] piperidine-3-carboxylic acid
[693] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (5-chlorothiene-2- Yl) thioethyl] piperidine-3-carboxylic acid
[694] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chlorothiene-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[695] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorothiene-2- Yl) propyl] piperidine-3-carboxylic acid
[696] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-chlorothiene-2- I) Butyl] piperidine-3-carboxylic acid
[697] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-chlorothiene-2- Yl) thioethyl] piperidine-3-carboxylic acid
[698] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorothiene-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[699] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-methylthiene-2- Yl) propyl] piperidine-3-carboxylic acid
[700] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (5-methylthiene-2- I) Butyl] piperidine-3-carboxylic acid
[701] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (5-methylthiene-2- Yl) thioethyl] piperidine-3-carboxylic acid
[702] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-methylthiene-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[703] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylthiene-2- Yl) propyl] piperidine-3-carboxylic acid
[704] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylthiene-2- I) Butyl] piperidine-3-carboxylic acid
[705] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylthiene-2- Yl) thioethyl] piperidine-3-carboxylic acid
[706] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylthiene-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[707] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) propyl ] Piperidine-3-carboxylic acid
[708] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-3-yl) butyl ] Piperidine-3-carboxylic acid
[709] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-3-yl) thio Ethyl] piperidine-3-carboxylic acid
[710] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) thio Propyl] piperidine-3-carboxylic acid
[711] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (fur2-yl) propyl] Piperidine-3-carboxylic acid
[712] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (fur2-yl) butyl] Piperidine-3-carboxylic acid
[713] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (fur2-yl) thioethyl ] Piperidine-3-carboxylic acid
[714] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (fur2-yl) thiopropyl ] Piperidine-3-carboxylic acid
[715] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (fur3-yl) propyl] Piperidine-3-carboxylic acid
[716] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (fur3-yl) butyl] Piperidine-3-carboxylic acid
[717] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (fur3-yl) thioethyl ] Piperidine-3-carboxylic acid
[718] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (fur3-yl) thiopropyl ] Piperidine-3-carboxylic acid
[719] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) propyl] piperidine-3-carboxylic acid
[720] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1-methylpyrrole-2- I) Butyl] piperidine-3-carboxylic acid
[721] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (1-methylpyrrole-2- Yl) thioethyl] piperidine-3-carboxylic acid
[722] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) thiopropyl] -piperidine-3-carboxylic acid
[723] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) propyl] piperidine-3-carboxylic acid
[724] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1-methylpyrrole-3- I) Butyl] piperidine-3-carboxylic acid
[725] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (1-methylpyrrole-3- Yl) thioethyl] piperidine-3-carboxylic acid
[726] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-3- Yl) thiopropyl] -piperidine-3-carboxylic acid
[727] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) propyl] piperidine-3-carboxylic acid
[728] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1,3-thiazole- 2-yl) butyl] piperidine-3-carboxylic acid
[729] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (1,3-thiazole- 2-yl) thioethyl] piperidine-3-carboxylic acid
[730] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) thiopropyl] piperidine-3-carboxylic acid
[731] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) propyl] piperidine-3-carboxylic acid
[732] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (1-methylimidazole- 2-yl) butyl] piperidine-3-carboxylic acid
[733] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (1-methylimidazole- 2-yl) thioethyl] -piperidine-3-carboxylic acid
[734] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) thiopropyl] -piperidine-3-carboxylic acid
[735] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) propyl] piperidine-3-carboxylic acid
[736] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylimidazole- 4-yl) butyl] piperidine-3-carboxylic acid
[737] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylimidazole- 4-yl) thioethyl] -piperidine-3-carboxylic acid
[738] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) thiopropyl] -piperidine-3-carboxylic acid
[739] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) propyl] piperidine-3-carboxylic acid
[740] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-methylpyrazole-4 -Yl) butyl] piperidine-3-carboxylic acid
[741] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylpyrazole-4 -Yl) thioethyl] -piperidine-3-carboxylic acid
[742] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) thiopropyl] -piperidine-3-carboxylic acid
[743] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Propyl] piperidine-3-carboxylic acid
[744] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (oxazol-2-yl) Butyl] piperidine-3-carboxylic acid
[745] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (oxazol-2-yl) Thioethyl] piperidine-3-carboxylic acid
[746] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Thiopropyl] piperidine-3-carboxylic acid
[747] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) propyl ] Piperidine-3-carboxylic acid
[748] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-2-yl) butyl ] Piperidine-3-carboxylic acid
[749] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) thio Propyl] piperidine-3-carboxylic acid
[750] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) propyl ] Piperidine-3-carboxylic acid
[751] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-3-yl) butyl ] Piperidine-3-carboxylic acid
[752] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-3-yl) thio Ethyl] piperidine-3-carboxylic acid
[753] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) thio Propyl] piperidine-3-carboxylic acid
[754] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) propyl ] Piperidine-3-carboxylic acid
[755] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-4-yl) butyl ] Piperidine-3-carboxylic acid
[756] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [5- (pyridin-4-yl) pentyl ] Piperidine-3-carboxylic acid
[757] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-2-yl) thio Ethyl] piperidine-3-carboxylic acid
[758] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-4-yl) thio Ethyl] piperidine-3-carboxylic acid
[759] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) thio Propyl] piperidine-3-carboxylic acid
[760] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Propyl] piperidine-3-carboxylic acid
[761] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-2-yl) Butyl] piperidine-3-carboxylic acid
[762] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-2-yl) Thioethyl] piperidine-3-carboxylic acid
[763] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Thiopropyl] piperidine-3-carboxylic acid
[764] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Propyl] piperidine-3-carboxylic acid
[765] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-4-yl) Butyl] piperidine-3-carboxylic acid
[766] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-4-yl) Thioethyl] piperidine-3-carboxylic acid
[767] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Thiopropyl] piperidine-3-carboxylic acid
[768] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Propyl] piperidine-3-carboxylic acid
[769] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-5-yl) Butyl] piperidine-3-carboxylic acid
[770] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-5-yl) Thioethyl] piperidine-3-carboxylic acid
[771] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Thiopropyl] piperidine-3-carboxylic acid
[772] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) propyl ] Piperidine-3-carboxylic acid
[773] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrazin-2-yl) butyl ] Piperidine-3-carboxylic acid
[774] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrazin-2-yl) thio Ethyl] piperidine-3-carboxylic acid
[775] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) thio Propyl] piperidine-3-carboxylic acid
[776] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Propyl] piperidine-3-carboxylic acid
[777] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-3-yl) Butyl] piperidine-3-carboxylic acid
[778] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-3-yl) Thioethyl] piperidine-3-carboxylic acid
[779] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Thiopropyl] piperidine-3-carboxylic acid
[780] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Propyl] piperidine-3-carboxylic acid
[781] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-4-yl) Butyl] piperidine-3-carboxylic acid
[782] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-4-yl) Thioethyl] piperidine-3-carboxylic acid
[783] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Thiopropyl] piperidine-3-carboxylic acid
[784] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylprop-2-ynyl] Piperidine-3-carboxylic acid
[785] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[786] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[787] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[788] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[789] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[790] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[791] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[792] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenyl) prop- 2-ynyl] piperidine-3-carboxylic acid
[793] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2- (trifluoromethyl ) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[794] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3- (trifluoromethyl ) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[795] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4- (trifluoromethyl ) Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[796] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[797] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[798] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenyl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[799] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-difluoro Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[800] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-difluoro Phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[801] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[802] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[803] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[804] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trichloro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[805] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dichlorophenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[806] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[807] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-4-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[808] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[809] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-5-fluor Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[810] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-2-fluoro Rophenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[811] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluoro-4- Methylphenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[812] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[813] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[814] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-5- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[815] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chloro-2-meth Methoxyphenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[816] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-bis (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[817] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dimethylphenyl) Prop-2-ynyl] -piperidine-3-carboxylic acid
[818] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichloro-6 -Methylphenyl) prop-2-ynyl] -piperidine-3-carboxylic acid
[819] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chlorothiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[820] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorothiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[821] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-methylthiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[822] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylthiene-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[823] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[824] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[825] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-3- Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[826] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 2-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[827] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 4-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[828] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole- 5-yl) prop-2-ynyl] piperidine-3-carboxylic acid
[829] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[830] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[831] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) prop-2-ynyl] -piperidine-3-carboxylic acid
[832] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[833] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[834] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-5-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[835] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[836] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[837] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) prop Ph-2-inyl] piperidine-3-carboxylic acid
[838] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[839] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[840] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[841] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) pro Ph-2-inyl] piperidine-3-carboxylic acid
[842] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[843] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Prop-2-ynyl] piperidine-3-carboxylic acid
[844] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylpropen-2-yl] Piperidine-3-carboxylic acid
[845] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbuten-3-yl] py Ferridine-3-carboxylic acid
[846] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbutyl] piperidine-3-acetic acid
[847] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3-acetic acid
[848] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine-3-acetic acid
[849] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3-acetic acid
[850] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine-3-acetic acid
[851] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-acetic acid
[852] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-3-acetic acid
[853] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-3-acetic acid
[854] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-3-acetic acid
[855] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3-acetic acid
[856] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3-acetic acid
[857] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3-acetic acid
[858] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidine-3-acetic acid
[859] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-acetic acid
[860] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3-acetic acid
[861] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-acetic acid
[862] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-acetic acid
[863] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-acetic acid
[864] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidine-3-acetic acid
[865] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine-3-acetic acid
[866] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidine-3-acetic acid
[867] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidine-3-acetic acid
[868] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3-acetic acid
[869] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) phenyl] piperidine-3-acetic acid
[870] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidine-3-acetic acid
[871] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidine-3-acetic acid
[872] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidine-3-acetic acid
[873] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3-acetic acid
[874] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidine-3-acetic acid
[875] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidine-3-acetic acid
[876] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3-acetic acid
[877] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidine-3-acetic acid
[878] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidine-3-acetic acid
[879] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidine-3-acetic acid
[880] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine-3-acetic acid
[881] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidine-3-acetic acid
[882] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine-3-acetic acid
[883] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidine-3-acetic acid
[884] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidine-3-acetic acid
[885] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidine-3-acetic acid
[886] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidine-3-acetic acid
[887] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-acetic acid
[888] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-acetic acid
[889] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-3-acetic acid
[890] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine-3-acetic acid
[891] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-3-acetic acid
[892] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-3-acetic acid
[893] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3-acetic acid
[894] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine-3-acetic acid
[895] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine-3-acetic acid
[896] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-3-acetic acid
[897] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-3-acetic acid
[898] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-3-acetic acid
[899] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-3-acetic acid
[900] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-3-acetic acid
[901] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-3-acetic acid
[902] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-3-acetic acid
[903] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-3-acetic acid
[904] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3-acetic acid
[905] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidine-3-acetic acid
[906] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3-acetic acid
[907] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] piperidine-3-acetic acid
[908] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-3-acetic acid
[909] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-3-acetic acid
[910] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-3-acetic acid
[911] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-3-acetic acid
[912] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-3-acetic acid
[913] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine-3-acetic acid
[914] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine-3-acetic acid
[915] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine-3-acetic acid
[916] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3-acetic acid
[917] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine-3-acetic acid
[918] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine-3-acetic acid
[919] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine-3-acetic acid
[920] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-3-acetic acid
[921] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-acetic acid
[922] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-3-acetic acid
[923] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine-3-acetic acid
[924] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-3-acetic acid
[925] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-3-acetic acid
[926] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-acetic acid
[927] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-acetic acid
[928] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-acetic acid
[929] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine-3-acetic acid
[930] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclophenylmethyl] piperidine-3-acetic acid
[931] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-acetic acid
[932] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine-3-acetic acid
[933] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-acetic acid
[934] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-acetic acid
[935] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-acetic acid
[936] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidine-3-acetic acid
[937] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl] piperidine-3-acetic acid
[938] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid
[939] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-3-acetic acid
[940] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid
[941] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-acetic acid
[942] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-acetic acid
[943] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3-acetic acid
[944] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3-acetic acid
[945] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-acetic acid
[946] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3-acetic acid
[947] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3-acetic acid
[948] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3-acetic acid
[949] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3-acetic acid
[950] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3-acetic acid
[951] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-3-acetic acid
[952] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-3-acetic acid
[953] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-3-acetic acid
[954] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) propyl] piperidine-3-acetic acid
[955] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl) butyl] piperidine-3-acetic acid
[956] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl) thioethyl] piperidine-3-acetic acid
[957] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) thiopropyl] piperidine-3-acetic acid
[958] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) propyl] piperidine-3-acetic acid
[959] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl) butyl] piperidine-3-acetic acid
[960] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl) thioethyl] piperidine-3-acetic acid
[961] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) thiopropyl] piperidine-3-acetic acid
[962] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidine-3-acetic acid
[963] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl) butyl] piperidine-3-acetic acid
[964] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl) thioethyl] piperidine-3-acetic acid
[965] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thiopropyl] piperidine-3-acetic acid
[966] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] piperidine-3-acetic acid
[967] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl) butyl] piperidine-3-acetic acid
[968] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl) thioethyl] piperidine-3-acetic acid
[969] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) thiopropyl] piperidine-3-acetic acid
[970] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-3-acetic acid
[971] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-3-acetic acid
[972] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-3-acetic acid
[973] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-3-acetic acid
[974] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur2-yl) propyl] piperidine-3-acetic acid
[975] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur2-yl) butyl] piperidine-3-acetic acid
[976] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur2-yl) thioethyl] piperidine-3-acetic acid
[977] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur2-yl) thiopropyl] piperidine-3-acetic acid
[978] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur3-yl) propyl] piperidine-3-acetic acid
[979] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur3-yl) butyl] piperidine-3-acetic acid
[980] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur3-yl) thioethyl] piperidine-3-acetic acid
[981] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur3-yl) thiopropyl] piperidine-3-acetic acid
[982] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3-acetic acid
[983] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-2-yl) butyl] piperidine-3-acetic acid
[984] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-2-yl) thioethyl] piperidine-3-acetic acid
[985] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) thiopropyl] piperidine-3-acetic acid
[986] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3-acetic acid
[987] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl) butyl] piperidine-3-acetic acid
[988] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl) thioethyl] piperidine-3-acetic acid
[989] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) thiopropyl] piperidine-3-acetic acid
[990] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl] piperidine-3-acetic acid
[991] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thiazol-2-yl) butyl] piperidine-3-acetic acid
[992] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine-3-acetic acid
[993] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidine-3-acetic acid
[994] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) propyl] piperidine-3- Acetic acid
[995] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazol-2-yl) butyl] piperidine-3- Acetic acid
[996] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) thioethyl] piperidine-3 Acetic acid
[997] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) thiopropyl] piperidine-3 Acetic acid
[998] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) propyl] piperidine-3- Acetic acid
[999] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazol-4-yl) butyl] piperidine-3- Acetic acid
[1000] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimidazol-4-yl) thioethyl] piperidine-3 Acetic acid
[1001] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) thiopropyl] piperidine-3 Acetic acid
[1002] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) propyl] piperidine-3-acetic acid
[1003] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazol-4-yl) butyl] piperidine-3-acetic acid
[1004] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazol-4-yl) thioethyl] piperidine-3- Acetic acid
[1005] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) thiopropyl] piperidine-3- Acetic acid
[1006] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine-3-acetic acid
[1007] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine-3-acetic acid
[1008] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3-acetic acid
[1009] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine-3-acetic acid
[1010] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-3-acetic acid
[1011] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-3-acetic acid
[1012] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-acetic acid
[1013] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-acetic acid
[1014] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine-3-acetic acid
[1015] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] piperidine-3-acetic acid
[1016] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine-3-acetic acid
[1017] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine-3-acetic acid
[1018] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidine-3-acetic acid
[1019] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidine-3-acetic acid
[1020] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperidine-3-acetic acid
[1021] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidine-3-acetic acid
[1022] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidine-3-acetic acid
[1023] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidine-3-acetic acid
[1024] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidine-3-acetic acid
[1025] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine-3-acetic acid
[1026] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine-3-acetic acid
[1027] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3-acetic acid
[1028] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine-3-acetic acid
[1029] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine-3-acetic acid
[1030] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine-3-acetic acid
[1031] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidine-3-acetic acid
[1032] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidine-3-acetic acid
[1033] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thioethyl] piperidine-3-acetic acid
[1034] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-acetic acid
[1035] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-3-acetic acid
[1036] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-3-acetic acid
[1037] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine-3-acetic acid
[1038] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-3-acetic acid
[1039] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine-3-acetic acid
[1040] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidine-3-acetic acid
[1041] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-3-acetic acid
[1042] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine-3-acetic acid
[1043] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidine-3-acetic acid
[1044] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidine-3-acetic acid
[1045] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine-3-acetic acid
[1046] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3-acetic acid
[1047] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop-2-ynyl] piperidine-3-acetic acid
[1048] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1049] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1050] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1051] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1052] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1053] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1054] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1055] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1056] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1057] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoromethyl) phenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1058] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethyl) phenyl) prop-2-ynyl] piperidine -3-acetic acid
[1059] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl) phenyl) prop-2-ynyl] piperidine -3-acetic acid
[1060] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1061] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1062] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop-2-ynyl] piperidine-3- Acetic acid
[1063] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[1064] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[1065] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop-2-ynyl] piperidine-3 Acetic acid
[1066] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) prop-2-ynyl] piperidine-3 Acetic acid
[1067] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) prop-2-ynyl] piperidine-3 Acetic acid
[1068] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1069] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichlorophenyl) prop-2-ynyl] piperidine-3 Acetic acid
[1070] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1071] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1072] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1073] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1074] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1075] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-methylphenyl) prop-2-ynyl] piperidine- 3-acetic acid
[1076] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-acetic acid
[1077] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-acetic acid
[1078] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5- (trifluoromethyl) phenyl) prop-2- Inyl] piperidine-3-acetic acid
[1079] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2- (methoxyphenyl) prop-2-ynyl] pi Ferridine-3-acetic acid
[1080] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop-2-ynyl ] Piperidine-3-acetic acid
[1081] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) prop-2-ynyl] piperidine-3 Acetic acid
[1082] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methylphenyl) prop-2-ynyl] piperi Din-3-acetic acid
[1083] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1084] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) prop-2-ynyl] piperidine -3-acetic acid
[1085] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) prop-2-ynyl] piperidine -3-acetic acid
[1086] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) prop-2-ynyl] piperidine -3-acetic acid
[1087] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) prop-2-ynyl] piperidine -3-acetic acid
[1088] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1089] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpron-2-yl) prop-2-ynyl] piperidine -3-acetic acid
[1090] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) prop-2-ynyl] piperidine -3-acetic acid
[1091] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1092] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-4-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1093] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-5-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1094] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) prop-2-ynyl] py Ferridine-3-acetic acid
[1095] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyldiazol-4-yl) prop-2-ynyl] piperi Din-3-acetic acid
[1096] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-diazol-4-yl) prop-2-ynyl] piperidine -3-acetic acid
[1097] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1098] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1099] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1100] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1101] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1102] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1103] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1104] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1105] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1106] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] piperidine-3- Acetic acid
[1107] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1108] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1109] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropen-2-yl) prop-2-ynyl] piperidine- 3-acetic acid
[1110] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylbuten-3-yl) prop-2-ynyl] piperidine-3 Acetic acid
[1111] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl] piperidine-3 Acetic acid
[1112] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (phenylbutyl] piperidine-3 Acetic acid
[1113] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] Piperidine-3-acetic acid
[1114] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] Piperidine-3-acetic acid
[1115] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] Piperidine-3-acetic acid
[1116] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] Piperidine-3-acetic acid
[1117] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] Piperidine-3-acetic acid
[1118] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] Piperidine-3-acetic acid
[1119] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl ) Propyl] piperidine-3-acetic acid
[1120] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl ) Butyl] piperidine-3-acetic acid
[1121] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl ) Propyl] piperidine-3-acetic acid
[1122] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl ) Butyl] piperidine-3-acetic acid
[1123] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] pi Ferridine-3-acetic acid
[1124] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1125] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] pi Ferridine-3-acetic acid
[1126] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1127] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] pi Ferridine-3-acetic acid
[1128] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1129] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl ] Piperidine-3-acetic acid
[1130] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl ] Piperidine-3-acetic acid
[1131] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl ] Piperidine-3-acetic acid
[1132] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl ] Piperidine-3-acetic acid
[1133] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperi Din-3-acetic acid
[1134] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperi Din-3-acetic acid
[1135] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperi Din-3-acetic acid
[1136] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperi Din-3-acetic acid
[1137] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperi Din-3-acetic acid
[1138] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperi Din-3-acetic acid
[1139] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperi Din-3-acetic acid
[1140] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1141] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1142] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1143] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1144] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1145] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1146] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1147] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1148] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1149] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1150] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1151] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1152] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidine-3 Acetic acid
[1153] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3 Acetic acid
[1154] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1155] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1156] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1157] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1158] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1159] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1160] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[1161] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[1162] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[1163] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[1164] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1165] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1166] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1167] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1168] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1169] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1170] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) Ethyl] piperidine-3-acetic acid
[1171] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) Propyl] piperidine-3-acetic acid
[1172] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) Ethyl] piperidine-3-acetic acid
[1173] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) Propyl] piperidine-3-acetic acid
[1174] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] pi Ferridine-3-acetic acid
[1175] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] py Ferridine-3-acetic acid
[1176] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] pi Ferridine-3-acetic acid
[1177] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] py Ferridine-3-acetic acid
[1178] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] pi Ferridine-3-acetic acid
[1179] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] py Ferridine-3-acetic acid
[1180] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1181] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1182] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1183] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1184] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1185] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1186] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl ] Piperidine-3-acetic acid
[1187] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl ] Piperidine-3-acetic acid
[1188] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl ] Piperidine-3-acetic acid
[1189] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl ] Piperidine-3-acetic acid
[1190] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl ] Piperidine-3-acetic acid
[1191] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl ] Piperidine-3-acetic acid
[1192] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-acetic acid
[1193] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine -3-acetic acid
[1194] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-acetic acid
[1195] (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclo) ethyl] piperidine- 3-acetic acid
[1196] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclomethyl] piperidine-3-acetic acid
[1197] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine -3-acetic acid
[1198] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-acetic acid
[1199] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine -3-acetic acid
[1200] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine-3-acetic acid
[1201] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine -3-acetic acid
[1202] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperi Din-3-acetic acid
[1203] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperi Din-3-acetic acid
[1204] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperi Din-3-acetic acid
[1205] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthiopropyl] piperidine -3-acetic acid
[1206] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-3-acetic acid
[1207] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperi Din-3-acetic acid
[1208] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Din-3-acetic acid
[1209] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperi Din-3-acetic acid
[1210] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3 Acetic acid
[1211] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3 Acetic acid
[1212] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3 Acetic acid
[1213] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3 Acetic acid
[1214] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] pi Ferridine-3-acetic acid
[1215] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] py Ferridine-3-acetic acid
[1216] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] pi Ferridine-3-acetic acid
[1217] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] py Ferridine-3-acetic acid
[1218] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] Piperidine-3-acetic acid
[1219] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] Piperidine-3-acetic acid
[1220] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-3-acetic acid
[1221] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1222] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Propyl] piperidine-3-acetic acid
[1223] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl ) Butyl] piperidine-3-acetic acid
[1224] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1225] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1226] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Propyl] piperidine-3-acetic acid
[1227] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl ) Butyl] piperidine-3-acetic acid
[1228] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1229] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1230] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Propyl] piperidine-3-acetic acid
[1231] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl ) Butyl] piperidine-3-acetic acid
[1232] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1233] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1234] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Propyl] piperidine-3-acetic acid
[1235] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl ) Butyl] piperidine-3-acetic acid
[1236] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1237] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1238] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] Piperidine-3-acetic acid
[1239] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] Piperidine-3-acetic acid
[1240] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl ] Piperidine-3-acetic acid
[1241] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl ] Piperidine-3-acetic acid
[1242] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] Piperidine-3-acetic acid
[1243] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] Piperidine-3-acetic acid
[1244] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl ] Piperidine-3-acetic acid
[1245] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1246] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] Piperidine-3-acetic acid
[1247] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] Piperidine-3-acetic acid
[1248] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl ] Piperidine-3-acetic acid
[1249] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl ] Piperidine-3-acetic acid
[1250] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl ) Propyl] piperidine-3-acetic acid
[1251] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-2-yl ) Butyl] piperidine-3-acetic acid
[1252] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-2-yl ) Thioethyl] piperidine-3-acetic acid
[1253] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) thiopropyl] -1- [3- (1-methylpyrrole-2- Yl) thiopropyl] piperidine-3-acetic acid
[1254] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1255] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl ) Butyl] piperidine-3-acetic acid
[1256] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl ) Thioethyl] piperidine-3-acetic acid
[1257] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl ) Thiopropyl] piperidine-3-acetic acid
[1258] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) propyl ] Piperidine-3-acetic acid
[1259] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (diazol-2-yl) butyl ] Piperidine-3-acetic acid
[1260] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (diazol-2-yl) di Ethyl] piperidine-3-acetic acid
[1261] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) thio Propyl] piperidine-3-acetic acid
[1262] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazole-2 -Yl) propyl] piperidine-3-acetic acid
[1263] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazole-2 -Yl) butyl] piperidine-3-acetic acid
[1264] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazole-2 -Yl) thioethyl] piperidine-3-acetic acid
[1265] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazole-2 -Yl) thiopropyl] piperidine-3-acetic acid
[1266] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazole-4 -Yl) propyl] piperidine-3-acetic acid
[1267] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazole-4 -Yl) butyl] piperidine-3-acetic acid
[1268] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimidazole-4 -Yl) thioethyl] piperidine-3-acetic acid
[1269] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazole-4 -Yl) thiopropyl] piperidine-3-acetic acid
[1270] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole-4- Yl) propyl] piperidine-3-acetic acid
[1271] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazole-4- I) butyl] piperidine-3-acetic acid
[1272] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazole-4- Yl) thioethyl] piperidine-3-acetic acid
[1273] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole-4- Yl) thiopropyl] piperidine-3-acetic acid
[1274] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl ] Piperidine-3-acetic acid
[1275] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl ] Piperidine-3-acetic acid
[1276] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) thioethyl] -1- [2- (oxazol-2-yl) Thioethyl] piperidine-3-acetic acid
[1277] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thio Propyl] piperidine-3-acetic acid
[1278] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] Piperidine-3-acetic acid
[1279] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] Piperidine-3-acetic acid
[1280] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl ] Piperidine-3-acetic acid
[1281] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1282] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] Piperidine-3-acetic acid
[1283] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] Piperidine-3-acetic acid
[1284] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl ] Piperidine-3-acetic acid
[1285] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl ] Piperidine-3-acetic acid
[1286] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] Piperidine-3-acetic acid
[1287] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] Piperidine-3-acetic acid
[1288] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] Piperidine-3-acetic acid
[1289] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl ] Piperidine-3-acetic acid
[1290] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl ] Piperidine-3-acetic acid
[1291] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl ] Piperidine-3-acetic acid
[1292] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl ] Piperidine-3-acetic acid
[1293] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thio Ethyl] piperidine-3-acetic acid
[1294] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thio Propyl] piperidine-3-acetic acid
[1295] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl ] Piperidine-3-acetic acid
[1296] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl ] Piperidine-3-acetic acid
[1297] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thio Ethyl] piperidine-3-acetic acid
[1298] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thio Propyl] piperidine-3-acetic acid
[1299] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl ] Piperidine-3-acetic acid
[1300] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl ] Piperidine-3-acetic acid
[1301] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thio Ethyl] piperidine-3-acetic acid
[1302] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thio Propyl] piperidine-3-acetic acid
[1303] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] Piperidine-3-acetic acid
[1304] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] Piperidine-3-acetic acid
[1305] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl ] Piperidine-3-acetic acid
[1306] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1307] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl ] Piperidine-3-acetic acid
[1308] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl ] Piperidine-3-acetic acid
[1309] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thio Ethyl] piperidine-3-acetic acid
[1310] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thio Propyl] piperidine-3-acetic acid
[1311] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl ] Piperidine-3-acetic acid
[1312] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl ] Piperidine-3-acetic acid
[1313] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thio Ethyl] piperidine-3-acetic acid
[1314] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thio Propyl] piperidine-3-acetic acid
[1315] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop-2-ynyl] pi Ferridine-3-acetic acid
[1316] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1317] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1318] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1319] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1320] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1321] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1322] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1323] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop-2 -Inyl] piperidine-3-acetic acid
[1324] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop-2 -Inyl] piperidine-3-acetic acid
[1325] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoromethyl) Phenyl) -2-ynyl] piperidine-3-acetic acid
[1326] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoromethyl) Phenyl) -2-ynyl] piperidine-3-acetic acid
[1327] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoromethyl) Phenyl) -2-ynyl] piperidine-3-acetic acid
[1328] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) prop -2-ynyl] piperidine-3-acetic acid
[1329] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) prop -2-ynyl] piperidine-3-acetic acid
[1330] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop -2-ynyl] piperidine-3-acetic acid
[1331] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[1332] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[1333] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1334] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1335] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1336] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichloro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1337] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichlorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1338] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1339] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1340] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1341] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1342] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1343] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl Prop-2-ynyl] piperidine-3-acetic acid
[1344] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3- (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1345] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4- (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1346] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5- (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1347] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-methoxy Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1348] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluor Rhomethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1349] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1350] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6- Methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1351] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-3-acetic acid
[1352] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl Prop-2-ynyl] piperidine-3-acetic acid
[1353] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl Prop-2-ynyl] piperidine-3-acetic acid
[1354] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl Prop-2-ynyl] piperidine-3-acetic acid
[1355] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl Prop-2-ynyl] piperidine-3-acetic acid
[1356] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop -2-ynyl] piperidine-3-acetic acid
[1357] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl Prop-2-ynyl] piperidine-3-acetic acid
[1358] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl Prop-2-ynyl] piperidine-3-acetic acid
[1359] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1360] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-4-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1361] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-5-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1362] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazole-2 -Yl) prop-2-ynyl] piperidine-3-acetic acid
[1363] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazole-4 -Yl) prop-2-ynyl] piperidine-3-acetic acid
[1364] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole-4- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1365] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1366] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1367] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1368] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop -2-ynyl] piperidine-3-acetic acid
[1369] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop -2-ynyl] piperidine-3-acetic acid
[1370] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop -2-ynyl] piperidine-3-acetic acid
[1371] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1372] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1373] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1374] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop -2-ynyl] piperidine-3-acetic acid
[1375] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1376] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1377] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] py Ferridine-3-acetic acid
[1378] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperi Din-3-acetic acid
[1379] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidine-3- Acetic acid
[1380] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3- Acetic acid
[1381] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] Piperidine-3-acetic acid
[1382] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] Piperidine-3-acetic acid
[1383] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] Piperidine-3-acetic acid
[1384] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] Piperidine-3-acetic acid
[1385] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] Piperidine-3-acetic acid
[1386] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] Piperidine-3-acetic acid
[1387] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl ) Propyl] piperidine-3-acetic acid
[1388] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl ) Butyl] piperidine-3-acetic acid
[1389] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl ) Propyl] piperidine-3-acetic acid
[1390] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl ) Butyl] piperidine-3-acetic acid
[1391] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] py Ferridine-3-acetic acid
[1392] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1393] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] pi Ferridine-3-acetic acid
[1394] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1395] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] py Ferridine-3-acetic acid
[1396] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] pi Ferridine-3-acetic acid
[1397] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-chlorophenyl) propyl ] Piperidine-3-acetic acid
[1398] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-chlorophenyl) butyl ] Piperidine-3-acetic acid
[1399] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-chlorophenyl) propyl ] Piperidine-3-acetic acid
[1400] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-chlorophenyl) butyl ] Piperidine-3-acetic acid
[1401] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperi Din-3-acetic acid
[1402] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperi Din-3-acetic acid
[1403] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperi Din-3-acetic acid
[1404] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperi Din-3-acetic acid
[1405] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperi Din-3-acetic acid
[1406] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperi Din-3-acetic acid
[1407] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperi Din-3-acetic acid
[1408] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1409] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1410] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1411] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1412] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] Piperidine-3-acetic acid
[1413] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] Piperidine-3-acetic acid
[1414] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1415] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1416] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1417] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1418] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl ] Piperidine-3-acetic acid
[1419] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl ] Piperidine-3-acetic acid
[1420] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidine-3 Acetic acid
[1421] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3 Acetic acid
[1422] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1423] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1424] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1425] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1426] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl ] Piperidine-3-acetic acid
[1427] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl ] Piperidine-3-acetic acid
[1428] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[1429] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[1430] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[1431] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[1432] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1433] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1434] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1435] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1436] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] Piperidine-3-acetic acid
[1437] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] Piperidine-3-acetic acid
[1438] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-chlorophenylthio) Ethyl] piperidine-3-acetic acid
[1439] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) Propyl] piperidine-3-acetic acid
[1440] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) Ethyl] piperidine-3-acetic acid
[1441] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) Propyl] piperidine-3-acetic acid
[1442] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenolthio) ethyl] Piperidine-3-acetic acid
[1443] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenolthio) propyl] Piperidine-3-acetic acid
[1444] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenolthio) ethyl] Piperidine-3-acetic acid
[1445] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenolthio) propyl] Piperidine-3-acetic acid
[1446] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenolthio) ethyl] Piperidine-3-acetic acid
[1447] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenolthio) propyl] Piperidine-3-acetic acid
[1448] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1449] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1450] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1451] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1452] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) Ethyl] piperidine-3-acetic acid
[1453] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) Propyl] piperidine-3-acetic acid
[1454] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] pi Ferridine-3-acetic acid
[1455] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] py Ferridine-3-acetic acid
[1456] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl ] Piperidine-3-acetic acid
[1457] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl ] Piperidine-3-acetic acid
[1458] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl ] Piperidine-3-acetic acid
[1459] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl ] Piperidine-3-acetic acid
[1460] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-acetic acid
[1461] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine -3-acetic acid
[1462] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-acetic acid
[1463] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine -3-acetic acid
[1464] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclophenylmethyl] piperidine-3-acetic acid
[1465] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine -3-acetic acid
[1466] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine-3-acetic acid
[1467] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine -3-acetic acid
[1468] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperi Din-3-acetic acid
[1469] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperi Din-3-acetic acid
[1470] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperi Din-3-acetic acid
[1471] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl] piperi Din-3-acetic acid
[1472] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-3-acetic acid
[1473] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperi Din-3-acetic acid
[1474] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Din-3-acetic acid
[1475] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperi Din-3-acetic acid
[1476] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3 Acetic acid
[1477] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3 Acetic acid
[1478] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3 Acetic acid
[1479] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3 Acetic acid
[1480] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] pi Ferridine-3-acetic acid
[1481] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] py Ferridine-3-acetic acid
[1482] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] pi Ferridine-3-acetic acid
[1483] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] py Ferridine-3-acetic acid
[1484] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] Piperidine-3-acetic acid
[1485] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] Piperidine-3-acetic acid
[1486] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-3-acetic acid
[1487] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1488] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Propyl] piperidine-3-acetic acid
[1489] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl ) Butyl] piperidine-3-acetic acid
[1490] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1491] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1492] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Propyl] piperidine-3-acetic acid
[1493] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl ) Butyl] piperidine-3-acetic acid
[1494] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1495] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1496] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Propyl] piperidine-3-acetic acid
[1497] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl ) Butyl] piperidine-3-acetic acid
[1498] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1499] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1500] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Propyl] piperidine-3-acetic acid
[1501] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl ) Butyl] piperidine-3-acetic acid
[1502] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl ) Thioethyl] piperidine-3-acetic acid
[1503] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1504] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] Piperidine-3-acetic acid
[1505] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] Piperidine-3-acetic acid
[1506] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl ] Piperidine-3-acetic acid
[1507] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl ] Piperidine-3-acetic acid
[1508] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] Piperidine-3-acetic acid
[1509] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] Piperidine-3-acetic acid
[1510] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl ] Piperidine-3-acetic acid
[1511] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl ] Piperidine-3-acetic acid
[1512] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] Piperidine-3-acetic acid
[1513] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] Piperidine-3-acetic acid
[1514] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl ] Piperidine-3-acetic acid
[1515] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl ] Piperidine-3-acetic acid
[1516] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpropyl-2-yl ) Propyl] piperidine-3-acetic acid
[1517] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpropyl-2-yl ) Butyl] piperidine-3-acetic acid
[1518] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpropyl-2-yl ) Thioethyl] piperidine-3-acetic acid
[1519] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpropyl-2-yl ) Thiopropyl] piperidine-3-acetic acid
[1520] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl ) Propyl] piperidine-3-acetic acid
[1521] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl ) Butyl] piperidine-3-acetic acid
[1522] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl ) Thioethyl] piperidine-3-acetic acid
[1523] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl ) Thiopropyl] piperidine-3-acetic acid
[1524] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) propyl ] Piperidine-3-acetic acid
[1525] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (diazol-2-yl) butyl ] Piperidine-3-acetic acid
[1526] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (diazol-2-yl) thio Ethyl] piperidine-3-acetic acid
[1527] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (diazol-2-yl) thio Propyl] piperidine-3-acetic acid
[1528] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazole-2 -Yl) propyl] piperidine-3-acetic acid
[1529] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazole-2 -Yl) butyl] piperidine-3-acetic acid
[1530] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazole-2 -Yl) thioethyl] piperidine-3-acetic acid
[1531] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazole-2 -Yl) thiopropyl] piperidine-3-acetic acid
[1532] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazole-4 -Yl) propyl] piperidine-3-acetic acid
[1533] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazole-4 -Yl) butyl] piperidine-3-acetic acid
[1534] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimidazole-4 -Yl) thioethyl] piperidine-3-acetic acid
[1535] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazole-4 -Yl) thiopropyl] piperidine-3-acetic acid
[1536] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole-4- Yl) propyl] piperidine-3-acetic acid
[1537] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazole-4- I) butyl] piperidine-3-acetic acid
[1538] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazole-4- Yl) thioethyl] piperidine-3-acetic acid
[1539] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole-4- Yl) thiopropyl] piperidine-3-acetic acid
[1540] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl ] Piperidine-3-acetic acid
[1541] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl ] Piperidine-3-acetic acid
[1542] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thio Ethyl] piperidine-3-acetic acid
[1543] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thio Propyl] piperidine-3-acetic acid
[1544] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] Piperidine-3-acetic acid
[1545] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-2-yl) butyl ] Piperidine-3-acetic acid
[1546] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-2-yl) thio Ethyl] piperidine-3-acetic acid
[1547] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) thio Propyl] piperidine-3-acetic acid
[1548] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) propyl ] Piperidine-3-acetic acid
[1549] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-3-yl) butyl ] Piperidine-3-acetic acid
[1550] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-3-yl) thio Ethyl] piperidine-3-acetic acid
[1551] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) thio Propyl] piperidine-3-acetic acid
[1552] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) propyl ] Piperidine-3-acetic acid
[1553] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridin-4-yl) butyl ] Piperidine-3-acetic acid
[1554] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [5- (pyridin-4-yl) pentyl ] Piperidine-3-acetic acid
[1555] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-4-yl) thio Ethyl] piperidine-3-acetic acid
[1556] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) thio Propyl] piperidine-3-acetic acid
[1557] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Propyl] piperidine-3-acetic acid
[1558] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-2-yl) Butyl] piperidine-3-acetic acid
[1559] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-2-yl) Thioethyl] piperidine-3-acetic acid
[1560] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Thiopropyl] piperidine-3-acetic acid
[1561] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Propyl] piperidine-3-acetic acid
[1562] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-4-yl) Butyl] piperidine-3-acetic acid
[1563] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-4-yl) Thioethyl] piperidine-3-acetic acid
[1564] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Thiopropyl] piperidine-3-acetic acid
[1565] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Propyl] piperidine-3-acetic acid
[1566] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrimidin-5-yl) Butyl] piperidine-3-acetic acid
[1567] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrimidin-5-yl) Thioethyl] piperidine-3-acetic acid
[1568] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Thiopropyl] piperidine-3-acetic acid
[1569] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) propyl ] Piperidine-3-acetic acid
[1570] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrazin-2-yl) butyl ] Piperidine-3-acetic acid
[1571] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrazin-2-yl) thio Ethyl] piperidine-3-acetic acid
[1572] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) thio Propyl] piperidine-3-acetic acid
[1573] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Propyl] piperidine-3-acetic acid
[1574] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-3-yl) Butyl] piperidine-3-acetic acid
[1575] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-3-yl) Thioethyl] piperidine-3-acetic acid
[1576] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Thiopropyl] piperidine-3-acetic acid
[1577] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Propyl] piperidine-3-acetic acid
[1578] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyridazin-4-yl) Butyl] piperidine-3-acetic acid
[1579] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridazin-4-yl) Thioethyl] piperidine-3-acetic acid
[1580] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Thiopropyl] piperidine-3-acetic acid
[1581] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylprop-2-ynyl] Piperidine-3-acetic acid
[1582] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1583] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1584] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1585] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1586] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1587] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenyl) prop -2-ynyl] piperidine-3-acetic acid
[1588] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1589] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1590] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenyl) prop- 2-ynyl] piperidine-3-acetic acid
[1591] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2- (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1592] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3- (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1593] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4- (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1594] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1595] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1596] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenyl) prop Ph-2-inyl] piperidine-3-acetic acid
[1597] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-difluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1598] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-difluoro Phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1599] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-dichlorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[1600] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-dichlorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[1601] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichlorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[1602] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trichloro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1603] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dichlorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[1604] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1605] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-4-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1606] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1607] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-5-fluor Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1608] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-2-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[1609] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluoro-4- Methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1610] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1611] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1612] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-5- ( Trifluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1613] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chloro-2-meth Methoxyphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1614] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-bis (tri Fluoromethyl) phenyl) prop-2-ynyl] piperidine-3-acetic acid
[1615] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-dimethylphenyl) Prop-2-ynyl] piperidine-3-acetic acid
[1616] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-dichloro-6 -Methylphenyl) prop-2-ynyl] piperidine-3-acetic acid
[1617] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1618] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-chlorothiene-2- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1619] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorothiene-2- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1620] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (5-methylthiene-2- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1621] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylthiene-2- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1622] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1623] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-2- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1624] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylpyrrole-3- Yl) prop-2-ynyl] piperidine-3-acetic acid
[1625] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thiazol-2-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1626] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thiazol-4-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1627] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (thiazol-5-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1628] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (1-methylimidazole- 2-yl) prop-2-ynyl] piperidine-3-acetic acid
[1629] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylimidazole- 4-yl) prop-2-ynyl] piperidine-3-acetic acid
[1630] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylpyrazole-4 -Yl) prop-2-ynyl] piperidine-3-acetic acid
[1631] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-2-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1632] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-4-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1633] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (oxazol-5-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1634] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-2-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1635] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-3-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1636] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridin-4-yl) prop Ph-2-inyl] piperidine-3-acetic acid
[1637] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-2-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1638] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-4-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1639] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrimidin-5-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1640] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) pro Ph-2-inyl] piperidine-3-acetic acid
[1641] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-3-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1642] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyridazin-4-yl) Prop-2-ynyl] piperidine-3-acetic acid
[1643] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylpropen-2-yl] Piperidine-3-acetic acid
[1644] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbuten-3-yl] py Ferridine-3-acetic acid
[1645] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidin-3-yl} propane-1-ioic acid
[1646] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidin-3-yl} propane-1-ioic acid
[1647] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1648] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1649] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1650] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1651] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1652] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1653] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-3 Propyl-1-Oic Acid
[1654] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-3 Propyl-1-Oic Acid
[1655] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3 Propyl-1-Oic Acid
[1656] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3 Propyl-1-Oic Acid
[1657] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidin-3-yl} propane -1-Oiksan
[1658] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidin-3-yl} propane -1-Oiksan
[1659] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidin-3-yl} propane -1-Oiksan
[1660] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidin-3-yl} propane -1-Oiksan
[1661] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidin-3-yl} propane -1-Oiksan
[1662] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidin-3-yl} propane -1-Oiksan
[1663] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1664] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1665] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1666] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1667] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidin-3-yl} propane- 1-Oiksan
[1668] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidin-3-yl} propane- 1-Oiksan
[1669] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidin-3-yl} propane- 1-Oiksan
[1670] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidin-3-yl} propane- 1-Oiksan
[1671] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidin-3-yl} propane- 1-Oiksan
[1672] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidin-3-yl} propane- 1-Oiksan
[1673] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidin-3-yl} propane- 1-Oiksan
[1674] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1675] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1676] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1677] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1678] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1679] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1680] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1681] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1682] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1683] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1684] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1685] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1686] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidin-3-yl} propane-1-o Iksan
[1687] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidin-3-yl} propane-1-o Iksan
[1688] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1689] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1690] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1691] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1692] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1693] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1694] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine- 3-yl} propane-1-ioic acid
[1695] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine- 3-yl} propane-1-ioic acid
[1696] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine- 3-yl} propane-1-ioic acid
[1697] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine- 3-yl} propane-1-ioic acid
[1698] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidin-3-yl} Propane-1-Oric Acid
[1699] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1700] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidin-3-yl} Propane-1-Oric Acid
[1701] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1702] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidin-3-yl} Propane-1-Oric Acid
[1703] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1704] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3- Propane-1-oic acid
[1705] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidine-3- Propane-1-oic acid
[1706] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3- Propane-1-oic acid
[1707] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] piperidine-3- Propane-1-oic acid
[1708] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidin-3-yl} propane -1-Oiksan
[1709] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidin-3-yl} propane -1-Oiksan
[1710] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidin-3-yl} propane -1-Oiksan
[1711] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidin-3-yl} propane -1-Oiksan
[1712] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidin-3-yl} propane -1-Oiksan
[1713] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidin-3-yl} propane -1-Oiksan
[1714] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine-3- Propane-1-oic acid
[1715] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine-3- Propane-1-oic acid
[1716] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3- Propane-1-oic acid
[1717] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine-3- Propane-1-oic acid
[1718] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine-3- Propane-1-oic acid
[1719] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine-3- Propane-1-oic acid
[1720] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1721] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1722] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1723] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1724] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidin-3-yl } Propane-1-ioic acid
[1725] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidin-3-yl } Propane-1-ioic acid
[1726] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidin-3-yl} propane-1-ioic acid
[1727] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidin-3-yl} propane-1 Oiksan
[1728] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidin-3-yl} propane-1-ioic acid
[1729] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidin-3-yl} propane-1 Oiksan
[1730] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidin-3-yl} propane-1-ioic acid
[1731] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidin-3-yl} propane-1 Oiksan
[1732] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidin-3-yl} propane-1-ioic acid
[1733] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidin-3-yl} propane-1 Oiksan
[1734] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidin-3-yl} propane- 1-Oiksan
[1735] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidin-3-yl} propane- 1-Oiksan
[1736] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidin-3-yl} propane- 1-Oiksan
[1737] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl] piperidin-3-yl} propane- 1-Oiksan
[1738] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidin-3-yl} propane- 1-Oiksan
[1739] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidin-3-yl} propane- 1-Oiksan
[1740] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidin-3-yl} propane- 1-Oiksan
[1741] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidin-3-yl} propane- 1-Oiksan
[1742] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidin-3-yl} propane-1-o Iksan
[1743] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidin-3-yl} propane-1-o Iksan
[1744] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidin-3-yl} propane-1-o Iksan
[1745] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidin-3-yl} propane-1-o Iksan
[1746] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidin-3-yl} propane -1-Oiksan
[1747] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidin-3-yl} propane -1-Oiksan
[1748] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidin-3-yl} propane -1-Oiksan
[1749] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidin-3-yl} propane -1-Oiksan
[1750] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1751] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1752] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1753] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1754] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1755] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothien-2-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1756] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1757] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1758] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1759] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothien-2-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1760] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothien-2-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1761] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1762] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1763] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1764] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1765] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1766] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1767] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1768] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1769] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1770] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1771] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1772] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1773] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1774] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1775] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1776] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1777] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1778] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1779] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1780] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1781] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1782] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1783] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-2-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1784] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-2-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1785] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1786] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) propyl] piperidine-3 Propyl-1-Oic Acid
[1787] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole-3-yl) butyl] piperidine-3 Propyl-1-Oic Acid
[1788] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole-3-yl) thioethyl] piperidine- 3-yl} propane-1-ioic acid
[1789] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) thiopropyl] piperidine- 3-yl} propane-1-ioic acid
[1790] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1791] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thiazol-2-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1792] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1793] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1794] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) propyl] piperidine -3-yl} propane-1-ioic acid
[1795] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazol-2-yl) butyl] piperidine -3-yl} propane-1-ioic acid
[1796] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) thioethyl] piperi Din-3-yl} propane-1-ioic acid
[1797] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) thiopropyl] piperi Din-3-yl} propane-1-ioic acid
[1798] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) propyl] piperidine -3-yl} propane-1-ioic acid
[1799] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazol-4-yl) butyl] piperidine -3-yl} propane-1-ioic acid
[1800] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimidazol-4-yl) thioethyl] piperi Din-3-yl} propane-1-ioic acid
[1801] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) thiopropyl] piperi Din-3-yl} propane-1-ioic acid
[1802] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) propyl] piperidine- 3-yl} propane-1-ioic acid
[1803] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazol-4-yl) butyl] piperidine- 3-yl} propane-1-ioic acid
[1804] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazol-4-yl) thioethyl] piperidine -3-yl} propane-1-ioic acid
[1805] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) thiopropyl] piperidine -3-yl} propane-1-ioic acid
[1806] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1807] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1808] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1809] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1810] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1811] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1812] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1813] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1814] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1815] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1816] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1817] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1818] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1819] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1820] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperidin-3-yl} Propane-1-Oric Acid
[1821] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1822] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1823] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1824] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1825] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1826] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1827] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1828] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1829] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1830] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1831] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1832] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1833] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1834] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1835] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidin-3-yl} Propane-1-Oric Acid
[1836] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidin-3-yl} Propane-1-Oric Acid
[1837] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidin-3-yl } Propane-1-ioic acid
[1838] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidin-3-yl } Propane-1-ioic acid
[1839] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1840] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1841] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1842] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1843] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidin-3-yl } Propane-1-ioic acid
[1844] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidin-3-yl } Propane-1-ioic acid
[1845] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine-3- Propane-1-oic acid
[1846] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3- Propane-1-oic acid
[1847] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop-2-ynyl] piperidin-3-yl} propane -1-Oiksan
[1848] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1849] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1850] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1851] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop-2-ynyl] piperidine- 3-yl} propane-1-ioic acid
[1852] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) prop-2-ynyl] piperidine- 3-yl} propane-1-ioic acid
[1853] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) prop-2-ynyl] piperidine- 3-yl} propane-1-ioic acid
[1854] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop-2-ynyl] piperidine-3 Propyl-1-Oic Acid
[1855] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop-2-ynyl] piperidine-3 Propyl-1-Oic Acid
[1856] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop-2-ynyl] piperidine-3 Propyl-1-Oic Acid
[1857] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoromethyl) phenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1858] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoromethyl) phenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1859] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoromethyl) phenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1860] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1861] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1862] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1863] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1864] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1865] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1866] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1867] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1868] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1869] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichlorophenyl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1870] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1871] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1872] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1873] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1874] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1875] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1876] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3- (trifluoromethyl) phenyl) prop -2-ynyl] piperidin-3-yl} propane-1-ioic acid
[1877] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4- (trifluoromethyl) phenyl) prop -2-ynyl] piperidin-3-yl} propane-1-ioic acid
[1878] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5- (trifluoromethyl) phenyl) prop -2-ynyl] piperidin-3-yl} propane-1-ioic acid
[1879] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-methoxyphenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1880] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop- 2-ynyl] piperidin-3-yl} propane-1-ioic acid
[1881] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1882] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methylphenyl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1883] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1884] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothien-2-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1885] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1886] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1887] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1888] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1889] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-2-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1890] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole-3-yl) prop-2-ynyl] Piperidin-3-yl} propane-1-ioic acid
[1891] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1892] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1893] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-5-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1894] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimidazol-2-yl) prop-2- Inyl] piperidin-3-yl} propane-1-ioic acid
[1895] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) prop-2- Inyl] piperidin-3-yl} propane-1-ioic acid
[1896] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) prop-2-ynyl ] Piperidin-3-yl} propane-1-ioic acid
[1897] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1898] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1899] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1900] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1901] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1902] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1903] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1904] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1905] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1906] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[1907] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1908] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2-ynyl] piperi Din-3-yl} propane-1-ioic acid
[1909] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidine -3-yl} propane-1-ioic acid
[1910] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine -3-yl} propane-1-ioic acid
[1911] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1912] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1913] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1914] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1915] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1916] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1917] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-di Fluorophenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1918] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-di Fluorophenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1919] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-di Fluorophenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1920] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-di Fluorophenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1921] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[1922] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) Butyl] piperidin-3-yl} propane-1-ioic acid
[1923] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[1924] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) Butyl] piperidin-3-yl} propane-1-ioic acid
[1925] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[1926] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) Butyl] piperidin-3-yl} propane-1-ioic acid
[1927] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1928] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichloro Phenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1929] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichloro Phenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1930] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichloro Phenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1931] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[1932] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[1933] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl ] Piperidin-3-yl} propane-1-ioic acid
[1934] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[1935] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[1936] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[1937] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[1938] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1939] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1940] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1941] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1942] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1943] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[1944] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1945] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1946] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1947] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1948] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[1949] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[1950] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[1951] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[1952] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1953] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1954] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1955] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1956] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1957] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1958] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-di Fluorophenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1959] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-di Fluorophenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1960] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-di Fluorophenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1961] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-di Fluorophenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1962] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1963] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1964] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1965] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1966] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1967] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[1968] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichloro Phenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1969] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1970] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichloro Phenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1971] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichloro Phenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1972] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1973] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[1974] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1975] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[1976] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[1977] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[1978] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1979] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1980] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1981] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1982] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1983] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[1984] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1985] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1986] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1987] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1988] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[1989] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[1990] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine- 3-yl} propane-1-ioic acid
[1991] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[1992] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine- 3-yl} propane-1-ioic acid
[1993] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[1994] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine- 3-yl} propane-1-ioic acid
[1995] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[1996] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine- 3-yl} propane-1-ioic acid
[1997] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[1998] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[1999] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2000] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2001] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2002] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2003] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2004] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2005] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2006] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[2007] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[2008] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[2009] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[2010] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2011] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2012] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2013] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2014] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2015] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2016] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2017] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2018] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2019] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2020] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2021] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2022] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2023] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2024] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2025] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2026] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2027] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2028] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2029] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2030] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2031] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2032] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2033] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2034] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2035] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2036] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2037] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2038] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2039] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2040] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2041] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2042] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2043] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2044] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2045] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2046] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2047] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2048] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2049] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2050] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2051] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole- 3-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2052] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole- 3-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2053] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 3-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2054] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2055] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thiazole-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2056] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2057] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2058] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2059] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimida Zol-2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2060] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimida Zol-2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2061] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2062] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2063] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimida Zol-4-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2064] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimida Zol-4-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2065] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2066] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2067] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazole -4-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2068] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazole -4-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2069] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2070] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2071] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazole-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2072] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazole-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2073] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2074] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2075] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2076] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2077] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2078] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2079] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2080] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2081] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2082] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2083] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2084] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl ) Pentyl] piperidin-3-yl} propane-1-ioic acid
[2085] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2086] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2087] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2088] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2089] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2090] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2091] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Propyl] piperidin-3-yl} propane-1-ioic acid
[2092] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-4- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2093] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-4- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2094] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2095] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Propyl] piperidin-3-yl} propane-1-ioic acid
[2096] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-5- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2097] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-5- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2098] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2099] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2100] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2101] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2102] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2103] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-3- Propyl] piperidin-3-yl} propane-1-ioic acid
[2104] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazine-3- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2105] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine-3- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2106] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-3- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2107] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-4- Propyl] piperidin-3-yl} propane-1-ioic acid
[2108] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazine-4- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2109] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine-4- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2110] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-4- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2111] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop-2- Inyl] piperidin-3-yl} propane-1-ioic acid
[2112] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine -3-yl} propane-1-ioic acid
[2113] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2114] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2115] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2116] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2117] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2118] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2119] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2120] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2121] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2122] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2123] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2124] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2125] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2126] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2127] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-di Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2128] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-di Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2129] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2130] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2131] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2132] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6 -Trichlorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2133] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2134] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2135] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2136] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2137] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2138] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2139] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro- 4-methylphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2140] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2141] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2142] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2143] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2 -Methoxyphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2144] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2145] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethyl Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2146] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro -6-methylphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2147] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2148] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2149] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2150] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2151] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2152] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2153] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2154] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylphyl- 3-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2155] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2156] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2157] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2158] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2159] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2160] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2161] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2162] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2163] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2164] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2165] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2166] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2167] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2168] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2169] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2170] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2171] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-3-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2172] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2173] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidine -3-yl} propane-1-ioic acid
[2174] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine -3-yl} propane-1-ioic acid
[2175] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2176] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2177] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2178] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2179] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2180] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2181] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-di Fluorophenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2182] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-di Fluorophenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2183] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-di Fluorophenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2184] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-di Fluorophenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2185] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[2186] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) Butyl] piperidin-3-yl} propane-1-ioic acid
[2187] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[2188] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) Butyl] piperidin-3-yl} propane-1-ioic acid
[2189] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[2190] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) Propyl] piperidin-3-yl} propane-1-ioic acid
[2191] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2192] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichloro Phenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2193] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichloro Phenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2194] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichloro Phenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2195] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2196] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[2197] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl ] Piperidin-3-yl} propane-1-ioic acid
[2198] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2199] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[2200] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2201] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl ] Piperidin-3-yl} propane-1-ioic acid
[2202] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl Propyl] piperidin-3-yl} propane-1-ioic acid
[2203] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2204] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2205] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2206] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2207] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2208] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2209] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2210] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2211] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2212] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoro Methylphenyl) propyl] piperidin-3-yl} propane-1-ioic acid
[2213] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoro Methylphenyl) butyl] piperidin-3-yl} propane-1-ioic acid
[2214] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[2215] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[2216] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2217] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[2218] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2219] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[2220] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2221] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[2222] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-di Fluorophenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2223] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-di Fluorophenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2224] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-di Fluorophenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2225] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-di Fluorophenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2226] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2227] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2228] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2229] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2230] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio ) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2231] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2232] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichloro Phenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2233] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2234] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichloro Phenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2235] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichloro Phenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2236] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2237] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2238] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2239] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2240] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2241] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2242] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2243] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2244] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2245] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2246] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoro Methylphenylthio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2247] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoro Methylphenylthio) propyl] piperidin-3-yl} propane-1-ioic acid
[2248] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2249] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2250] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2251] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[2252] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenyl Thio) ethyl] piperidin-3-yl} propane-1-ioic acid
[2253] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl Thio) propyl] piperidin-3-yl} propane-1-ioic acid
[2254] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine- 3-yl} propane-1-ioic acid
[2255] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[2256] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine- 3-yl} propane-1-ioic acid
[2257] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[2258] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine- 3-yl} propane-1-ioic acid
[2259] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[2260] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidine- 3-yl} propane-1-ioic acid
[2261] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] Piperidin-3-yl} propane-1-ioic acid
[2262] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2263] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2264] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2265] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2266] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2267] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2268] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl ] Piperidin-3-yl} propane-1-ioic acid
[2269] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl ] Piperidin-3-yl} propane-1-ioic acid
[2270] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[2271] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[2272] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperi Din-3-yl} propane-1-ioic acid
[2273] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperi Din-3-yl} propane-1-ioic acid
[2274] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2275] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2276] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) Ethyl] piperidin-3-yl} propane-1-ioic acid
[2277] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) Propyl] piperidin-3-yl} propane-1-ioic acid
[2278] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2279] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2280] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2281] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2282] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2283] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-chlorothiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2284] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2285] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2286] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2287] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorothiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2288] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorothiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2289] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2290] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2291] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2292] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2293] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2294] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2295] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthiene- 2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2296] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthiene- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2297] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2298] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2299] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2300] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2301] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2302] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2303] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2304] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2305] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2306] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2307] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2308] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2309] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2310] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2311] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2312] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole- 2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2313] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2314] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2315] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrole- 3-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2316] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrrole- 3-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2317] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 3-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2318] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2319] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thiazole-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2320] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2321] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2322] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2323] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimida Zol-2-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2324] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimida Zol-2-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2325] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2326] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2327] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimida Zol-4-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2328] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylimida Zol-4-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2329] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2330] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) propyl] piperidin-3-yl} propane-1-ioic acid
[2331] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylpyrazole -4-yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2332] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylpyrazole -4-yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2333] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2334] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2335] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazole-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2336] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazole-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2337] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2338] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2339] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2340] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2341] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2342] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2343] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2344] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2345] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2346] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2347] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2348] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl ) Pentyl] piperidin-3-yl} propane-1-ioic acid
[2349] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2350] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2351] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Propyl] piperidin-3-yl} propane-1-ioic acid
[2352] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-2- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2353] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-2- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2354] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2355] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Propyl] piperidin-3-yl} propane-1-ioic acid
[2356] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-4- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2357] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-4- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2358] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2359] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Propyl] piperidin-3-yl} propane-1-ioic acid
[2360] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidine-5- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2361] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine-5- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2362] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2363] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Propyl] piperidin-3-yl} propane-1-ioic acid
[2364] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl ) Butyl] piperidin-3-yl} propane-1-ioic acid
[2365] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl ) Thioethyl] piperidin-3-yl} propane-1-ioic acid
[2366] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2367] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-3- Propyl] piperidin-3-yl} propane-1-ioic acid
[2368] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazine-3- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2369] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine-3- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2370] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-3- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2371] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-4- Propyl] piperidin-3-yl} propane-1-ioic acid
[2372] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazine-4- Yl) butyl] piperidin-3-yl} propane-1-ioic acid
[2373] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine-4- Yl) thioethyl] piperidin-3-yl} propane-1-ioic acid
[2374] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-4- Yl) thiopropyl] piperidin-3-yl} propane-1-ioic acid
[2375] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylprop-2 -Inyl] piperidin-3-yl} propane-1-ioic acid
[2376] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2377] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2378] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2379] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2380] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2381] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2382] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2383] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2384] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop P-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2385] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2386] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2387] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoro Chloromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2388] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (methoxy Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2389] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (methoxy Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2390] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (methoxy Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2391] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-di Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2392] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-di Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2393] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2394] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2395] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2396] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6 -Trichlorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2397] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2398] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2399] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2400] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2401] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2402] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2 -Fluorophenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2403] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro- 4-methylphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2404] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2405] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2406] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5 -(Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2407] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2 -Methoxyphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2408] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (Trifluoromethyl) phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2409] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethyl Phenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2410] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro -6-methylphenyl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2411] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2412] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chlorothiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2413] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2414] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2415] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthiene- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2416] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2417] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2418] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylpyrrole- 3-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2419] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2420] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2421] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2422] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methylimida Zol-2-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2423] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimida Zol-4-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2424] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazole -4-yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2425] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2426] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2427] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2428] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2429] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2430] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2431] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-2- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2432] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2433] (3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine-5- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2434] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl ) Prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2435] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-3- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2436] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine-4- Yl) prop-2-ynyl] piperidin-3-yl} propane-1-ioic acid
[2437] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidin-3-yl} propane -1-Oiksan
[2438] (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidin-3-yl} propane- 1-Oiksan
[2439] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropene-2- Piperidin-3-yl} propane-1-ioic acid
[2440] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl ] Piperidin-3-yl} propane-1-ioic acid
[2441] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropene-2- Piperidin-3-yl} propane-1-ioic acid
[2442] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl ] Piperidin-3-yl} propane-1-ioic acid
[2443] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidine
[2444] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine
[2445] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine
[2446] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine
[2447] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine
[2448] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine
[2449] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine
[2450] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine
[2451] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine
[2452] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) ethyl] piperidine
[2453] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine
[2454] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine
[2455] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine
[2456] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine
[2457] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine
[2458] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine
[2459] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine
[2460] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine
[2461] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine
[2462] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine
[2463] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine
[2464] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine
[2465] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine
[2466] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine
[2467] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine
[2468] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine
[2469] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine
[2470] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine
[2471] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine
[2472] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine
[2473] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine
[2474] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine
[2475] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine
[2476] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine
[2477] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl] piperidine
[2478] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine
[2479] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidine
[2480] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl] piperidine
[2481] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine
[2482] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidine
[2483] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine
[2484] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine
[2485] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine
[2486] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine
[2487] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine
[2488] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine
[2489] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidine
[2490] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thiopropyl] piperidine
[2491] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine
[2492] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine
[2493] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine
[2494] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine
[2495] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine
[2496] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine
[2497] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine
[2498] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine
[2499] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop-2-ynyl] piperidine
[2500] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] Piperidine
[2501] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] Piperidine
[2502] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] Piperidine
[2503] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) prop-2-ynyl] pi Ferridine
[2504] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) prop-2-ynyl] pi Ferridine
[2505] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) prop-2-ynyl] pi Ferridine
[2506] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop-2-ynyl] piperi Dean
[2507] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) prop-2-ynyl] piperi Dean
[2508] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) prop-2-ynyl] piperi Dean
[2509] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (trifluoromethyl) phenyl) prop- 2-ynyl] piperidine
[2510] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (trifluoromethyl) phenyl) prop- 2-ynyl] piperidine
[2511] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (trifluoromethyl) phenyl) prop- 2-ynyl] piperidine
[2512] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) prop-2-ynyl] Piperidine
[2513] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) prop-2-ynyl] Piperidine
[2514] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop-2-ynyl] Piperidine
[2515] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] Piperidine
[2516] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] Piperidine
[2517] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) prop-2-ynyl ] Piperidine
[2518] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) prop-2-ynyl ] Piperidine
[2519] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-5-yl) prop-2-ynyl ] Piperidine
[2520] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2-ynyl ] Piperidine
[2521] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2-ynyl ] Piperidine
[2522] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl ] Piperidine
[2523] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-ynyl] Piperidine
[2524] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] Piperidine
[2525] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2-ynyl] Piperidine
[2526] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl ] Piperidine
[2527] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] Piperidine
[2528] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2-ynyl ] Piperidine
[2529] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2-ynyl ] Piperidine
[2530] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl ] Piperidine
[2531] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl ] Piperidine
[2532] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Fluorophenylthio) ethyl] piperidine
[2533] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Fluorophenylthio) propyl] piperidine
[2534] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluorophenylthio) ethyl] piperidine
[2535] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluorophenylthio) propyl] piperidine
[2536] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Fluorophenylthio) ethyl] piperidine
[2537] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Fluorophenylthio) propyl] piperidine
[2538] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Chlorophenylthio) ethyl] piperidine
[2539] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Chlorophenylthio) propyl] piperidine
[2540] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Chlorophenylthio) ethyl] piperidine
[2541] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluorophenylthio) propyl] piperidine
[2542] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Chlorophenylthio) ethyl] piperidine
[2543] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Chlorophenylthio) propyl] piperidine
[2544] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Methylphenylthio) ethyl] piperidine
[2545] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methylphenylthio) propyl] piperidine
[2546] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Methylphenylthio) ethyl] piperidine
[2547] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methylphenylthio) propyl] piperidine
[2548] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Methylphenylthio) ethyl] piperidine
[2549] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methylphenylthio) propyl] piperidine
[2550] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Trifluoromethylphenylthio) ethyl] piperidine
[2551] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Trifluoromethylphenylthio) propyl] piperidine
[2552] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Trifluoromethylphenylthio) ethyl] piperidine
[2553] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Trifluoromethylphenylthio) propyl] piperidine
[2554] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Trifluoromethylphenylthio) ethyl] piperidine
[2555] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Trifluoromethylphenylthio) propyl] piperidine
[2556] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Methoxyphenylthio) ethyl] piperidine
[2557] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methoxyphenylthio) propyl] piperidine
[2558] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Methoxyphenylthio) ethyl] piperidine
[2559] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methoxyphenylthio) propyl] piperidine
[2560] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Methoxyphenylthio) ethyl] piperidine
[2561] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methoxyphenylthio) propyl] piperidine
[2562] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiene- 3-yl) thioethyl] piperidine
[2563] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 3-yl) thiopropyl] piperidine
[2564] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pur- 2-yl) thioethyl] piperidine
[2565] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pur- 2-yl) thiopropyl] piperidine
[2566] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pur- 3-yl) thioethyl] piperidine
[2567] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pur- 3-yl) thiopropyl] piperidine
[2568] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole -2-yl) thioethyl] piperidine
[2569] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -2-yl) thiopropyl] piperidine
[2570] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazole -2-yl) thioethyl] piperidine
[2571] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -2-yl) thiopropyl] piperidine
[2572] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 2-yl) thioethyl] piperidine
[2573] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) thiopropyl] piperidine
[2574] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 3-yl) thioethyl] piperidine
[2575] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 3-yl) thiopropyl] piperidine
[2576] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 4-yl) thioethyl] piperidine
[2577] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 4-yl) thiopropyl] piperidine
[2578] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine -2-yl) thioethyl] piperidine
[2579] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine -2-yl) thiopropyl] piperidine
[2580] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazine- 2-yl) thioethyl] piperidine
[2581] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazine- 2-yl) thiopropyl] piperidine
[2582] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine -3-yl) thioethyl] piperidine
[2583] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -3-yl) thiopropyl] piperidine
[2584] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine -4-yl) thioethyl] piperidine
[2585] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -4-yl) thiopropyl] piperidine
[2586] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop -2-ynyl] piperidine
[2587] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Fluorophenyl) prop-2-ynyl] piperidine
[2588] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluorophenyl) prop-2-ynyl] piperidine
[2589] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Fluorophenyl) prop-2-ynyl] piperidine
[2590] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Chlorophenyl) prop-2-ynyl] piperidine
[2591] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Chlorophenyl) prop-2-ynyl] piperidine
[2592] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Chlorophenyl) prop-2-ynyl] piperidine
[2593] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methylphenyl) prop-2-ynyl] piperidine
[2594] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methylphenyl) prop-2-ynyl] piperidine
[2595] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methylphenyl) prop-2-ynyl] piperidine
[2596] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2597] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2598] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- (Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2599] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methoxyphenyl) prop-2-ynyl] piperidine
[2600] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methoxyphenyl) prop-2-ynyl] piperidine
[2601] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methoxyphenyl) prop-2-ynyl] piperidine
[2602] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 2-yl) prop-2-ynyl] piperidine
[2603] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 3-yl) prop-2-ynyl] piperidine
[2604] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -2-yl) prop-2-ynyl] piperidine
[2605] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -4-yl) prop-2-ynyl] piperidine
[2606] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -5-yl) prop-2-ynyl] piperidine
[2607] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -2-yl) prop-2-ynyl] piperidine
[2608] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -4-yl) prop-2-ynyl] piperidine
[2609] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -5-yl) prop-2-ynyl] piperidine
[2610] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) prop-2-ynyl] piperidine
[2611] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 3-yl) prop-2-ynyl] piperidine
[2612] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 4-yl) prop-2-ynyl] piperidine
[2613] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine -2-yl) prop-2-ynyl] piperidine
[2614] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazine- 2-yl) prop-2-ynyl] piperidine
[2615] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -3-yl) prop-2-ynyl] piperidine
[2616] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -4-yl) prop-2-ynyl] piperidine
[2617] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl ] Piperidine
[2618] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl ] Piperidine
[2619] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Fluorophenylthio) ethyl] piperidine
[2620] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Fluorophenylthio) propyl] piperidine
[2621] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluorophenylthio) ethyl] piperidine
[2622] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluorophenylthio) propyl] piperidine
[2623] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Fluorophenylthio) ethyl] piperidine
[2624] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Fluorophenylthio) propyl] piperidine
[2625] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Chlorophenylthio) ethyl] piperidine
[2626] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Chlorophenylthio) propyl] piperidine
[2627] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Chlorophenylthio) ethyl] piperidine
[2628] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Chlorophenylthio) propyl] piperidine
[2629] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Chlorophenylthio) ethyl] piperidine
[2630] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Chlorophenylthio) propyl] piperidine
[2631] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Methylphenylthio) ethyl] piperidine
[2632] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methylphenylthio) propyl] piperidine
[2633] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Methylphenylthio) ethyl] piperidine
[2634] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methylphenylthio) propyl] piperidine
[2635] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Methylphenylthio) ethyl] piperidine
[2636] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methylphenylthio) propyl] piperidine
[2637] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Trifluoromethylphenylthio) ethyl] piperidine
[2638] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Trifluoromethylphenylthio) propyl] piperidine
[2639] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Trifluoromethylphenylthio) ethyl] piperidine
[2640] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Trifluoromethylphenylthio) propyl] piperidine
[2641] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Trifluoromethylphenylthio) ethyl] piperidine
[2642] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Trifluoromethylphenylthio) propyl] piperidine
[2643] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- Methoxyphenylthio) ethyl] piperidine
[2644] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methoxyphenylthio) propyl] piperidine
[2645] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Methoxyphenylthio) ethyl] piperidine
[2646] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methoxyphenylthio) propyl] piperidine
[2647] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4- Methoxyphenylthio) ethyl] piperidine
[2648] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methoxyphenylthio) propyl] piperidine
[2649] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiene- 3-yl) thioethyl] piperidine
[2650] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 3-yl) thiopropyl] piperidine
[2651] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pur- 2-yl) thioethyl] piperidine
[2652] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pur- 2-yl) thiopropyl] piperidine
[2653] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pur- 3-yl) thioethyl] piperidine
[2654] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pur- 3-yl) thiopropyl] piperidine
[2655] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole -2-yl) thioethyl] piperidine
[2656] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -2-yl) thiopropyl] piperidine
[2657] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazole -2-yl) thioethyl] piperidine
[2658] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -2-yl) thiopropyl] piperidine
[2659] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 2-yl) thioethyl] piperidine
[2660] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) thiopropyl] piperidine
[2661] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 3-yl) thioethyl] piperidine
[2662] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 3-yl) thiopropyl] piperidine
[2663] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 4-yl) thioethyl] piperidine
[2664] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 4-yl) thiopropyl] piperidine
[2665] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidine -2-yl) thioethyl] piperidine
[2666] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine -2-yl) thiopropyl] piperidine
[2667] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazine- 2-yl) thioethyl] piperidine
[2668] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazine- 2-yl) thiopropyl] piperidine
[2669] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine -3-yl) thioethyl] piperidine
[2670] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -3-yl) thiopropyl] piperidine
[2671] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazine -4-yl) thioethyl] piperidine
[2672] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -4-yl) thiopropyl] piperidine
[2673] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylprop -2-ynyl] piperidine
[2674] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Fluorophenyl) prop-2-ynyl] piperidine
[2675] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluorophenyl) prop-2-ynyl] piperidine
[2676] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Fluorophenyl) prop-2-ynyl] piperidine
[2677] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Chlorophenyl) prop-2-ynyl] piperidine
[2678] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Chlorophenyl) prop-2-ynyl] piperidine
[2679] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Chlorophenyl) prop-2-ynyl] piperidine
[2680] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methylphenyl) prop-2-ynyl] piperidine
[2681] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methylphenyl) prop-2-ynyl] piperidine
[2682] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methylphenyl) prop-2-ynyl] piperidine
[2683] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- (Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2684] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2685] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Trifluoromethyl) phenyl) prop-2-ynyl] piperidine
[2686] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Methoxyphenyl) prop-2-ynyl] piperidine
[2687] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Methoxyphenyl) prop-2-ynyl] piperidine
[2688] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- Methoxyphenyl) prop-2-ynyl] piperidine
[2689] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 2-yl) prop-2-ynyl] piperidine
[2690] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 3-yl) prop-2-ynyl] piperidine
[2691] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -2-yl) prop-2-ynyl] piperidine
[2692] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -4-yl) prop-2-ynyl] piperidine
[2693] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole -5-yl) prop-2-ynyl] piperidine
[2694] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -2-yl) prop-2-ynyl] piperidine
[2695] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -4-yl) prop-2-ynyl] piperidine
[2696] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazole -5-yl) prop-2-ynyl] piperidine
[2697] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) prop-2-ynyl] piperidine
[2698] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 3-yl) prop-2-ynyl] piperidine
[2699] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 4-yl) prop-2-ynyl] piperidine
[2700] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidine -2-yl) prop-2-ynyl] piperidine
[2701] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazine- 2-yl) prop-2-ynyl] piperidine
[2702] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -3-yl) prop-2-ynyl] piperidine
[2703] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine -4-yl) prop-2-ynyl] piperidine
[2704] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fluoro-4-phenylbutyl] piperidine-3-carboxylic acid
[2705] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine-3-carboxylic acid
[2706] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine-3-carboxylic acid
[2707] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-3-carboxylic acid
[2708] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine-3-carboxylic acid
[2709] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6-tetrafluorophenylthio) ethyl] piperidine 3-carboxylic acid
[2710] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) propyl] piperidine 3-carboxylic acid
[2711] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] piperidine-3- Carboxylic acid
[2712] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] piperidine-3- Carboxylic acid
[2713] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine-3-carboxylic acid
[2714] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3-carboxylic acid
[2715] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-3-carboxylic acid
[2716] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3-carboxylic acid
[2717] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-carboxylic acid
[2718] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-carboxylic acid
[2719] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] piperidine-3- Carboxylic acid
[2720] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] piperidine-3- Carboxylic acid
[2721] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylic acid
[2722] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-carboxylic acid
[2723] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine-3-carboxylic acid
[2724] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] piperidine-3-carboxylic acid
[2725] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[2726] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[2727] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[2728] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[2729] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[2730] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[2731] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluorophenyl) prop-2-ynyl] pi Ferridine-3-carboxylic acid
[2732] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano-6-fluorophenyl) prop-2-ynyl] piperidine 3-carboxylic acid
[2733] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (acetamido-5-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylic acid
[2734] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (trifluoromethoxyphenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[2735] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] py Ferridine-3-carboxylic acid
[2736] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] pi Ferridine-3-carboxylic acid
[2737] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[2738] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenyl Thio) ethyl] piperidine-3-carboxylic acid
[2739] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[2740] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6- Tetrafluorophenylthio) ethyl] piperidine-3-carboxylic acid
[2741] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6- Tetrafluorophenylthio) propyl] piperidine-3-carboxylic acid
[2742] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chloro Phenylthio) ethyl] piperidine-3-carboxylic acid
[2743] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro Phenylthio) propyl] piperidine-3-carboxylic acid
[2744] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio ) Ethyl] piperidine-3-carboxylic acid
[2745] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio ) Propyl] piperidine-3-carboxylic acid
[2746] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl ] Piperidine-3-carboxylic acid
[2747] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl ] Piperidine-3-carboxylic acid
[2748] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl ] Piperidine-3-carboxylic acid
[2749] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-2-yl ) Thioethyl] piperidine-3-carboxylic acid
[2750] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridine-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[2751] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperi Dean-3-carboxylic acid
[2752] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] py Ferridine-3-carboxylic acid
[2753] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2754] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2755] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2756] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano-6-fluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2757] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (acetamido-5-fluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2758] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (trifluoromethoxyphenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[2759] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] py Ferridine-3-carboxylic acid
[2760] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] pi Ferridine-3-carboxylic acid
[2761] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Thio) ethyl] piperidine-3-carboxylic acid
[2762] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[2763] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenyl Thio) ethyl] piperidine-3-carboxylic acid
[2764] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Thio) propyl] piperidine-3-carboxylic acid
[2765] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6- Tetrafluorophenylthio) ethyl] piperidine-3-carboxylic acid
[2766] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6- Tetrafluorophenylthio) propyl] piperidine-3-carboxylic acid
[2767] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chloro Phenylthio) ethyl] piperidine-3-carboxylic acid
[2768] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro Phenylthio) propyl] piperidine-3-carboxylic acid
[2769] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio ) Ethyl] piperidine-3-carboxylic acid
[2770] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio ) Propyl] piperidine-3-carboxylic acid
[2771] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl ] Piperidine-3-carboxylic acid
[2772] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl ] Piperidine-3-carboxylic acid
[2773] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl ] Piperidine-3-carboxylic acid
[2774] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thioethyl ] Piperidine-3-carboxylic acid
[2775] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridine-2- Yl) thioethyl] piperidine-3-carboxylic acid
[2776] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridine-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[2777] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperi Dean-3-carboxylic acid
[2778] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperi Dean-3-carboxylic acid
[2779] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] pi Ferridine-3-carboxylic acid
[2780] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] py Ferridine-3-carboxylic acid
[2781] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2782] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2783] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2784] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2785] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2786] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2787] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2788] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano-6-fluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[2789] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (acetamido-5-fluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[2790] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (trifluoromethoxyphenyl) prop -2-ynyl] piperidine-3-carboxylic acid
[2791] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-acetic acid
[2792] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] piperidine-3-acetic acid
[2793] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine-3-acetic acid
[2794] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) propyl] piperidine-3-acetic acid
[2795] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-3-acetic acid
[2796] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine-3-acetic acid
[2797] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6-tetrafluorophenylthio) ethyl] piperidine -3-acetic acid
[2798] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) propyl] piperidine -3-acetic acid
[2799] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] piperidine-3- Acetic acid
[2800] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] piperidine-3- Acetic acid
[2801] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine-3-acetic acid
[2802] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3-acetic acid
[2803] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-3-acetic acid
[2804] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3-acetic acid
[2805] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-acetic acid
[2806] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-acetic acid
[2807] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] piperidine-3- Acetic acid
[2808] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] piperidine-3- Acetic acid
[2809] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-acetic acid
[2810] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-acetic acid
[2811] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine-3-acetic acid
[2812] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] piperidine-3-acetic acid
[2813] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[2814] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[2815] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[2816] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-3-acetic acid
[2817] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-3-acetic acid
[2818] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluorophenyl) prop-2-ynyl] pi Ferridine-3-acetic acid
[2819] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano-6-fluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[2820] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (acetamido-5-fluorophenyl) prop-2-ynyl] piperi Din-3-acetic acid
[2821] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (trifluoromethoxyphenyl) prop-2-ynyl] piperidine-3- Acetic acid
[2822] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] py Ferridine-3-acetic acid
[2823] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] pi Ferridine-3-acetic acid
[2824] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[2825] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[2826] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[2827] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[2828] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6- Tetrafluorophenylthio) ethyl] piperidine-3-acetic acid
[2829] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6- Tetrafluorophenylthio) propyl] piperidine-3-acetic acid
[2830] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chloro Phenylthio) ethyl] piperidine-3-acetic acid
[2831] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro Phenylthio) propyl] piperidine-3-acetic acid
[2832] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio ) Ethyl] piperidine-3-acetic acid
[2833] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio ) Propyl] piperidine-3-acetic acid
[2834] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl ] Piperidine-3-acetic acid
[2835] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl ] Piperidine-3-acetic acid
[2836] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl ] Piperidine-3-acetic acid
[2837] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl ] Piperidine-3-acetic acid
[2838] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridine-2- Yl) thioethyl] piperidine-3-acetic acid
[2839] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridine-2- Yl) thiopropyl] piperidine-3-acetic acid
[2840] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperi Din-3-acetic acid
[2841] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperi Din-3-acetic acid
[2842] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] pi Ferridine-3-acetic acid
[2843] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] py Ferridine-3-acetic acid
[2844] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2845] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2846] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2847] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2848] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2849] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2850] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2851] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[2852] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido-5-fluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2853] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluoromethoxyphenyl) prop- 2-ynyl] piperidine-3-acetic acid
[2854] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] py Ferridine-3-acetic acid
[2855] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] pi Ferridine-3-acetic acid
[2856] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[2857] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[2858] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenyl Thio) ethyl] piperidine-3-acetic acid
[2859] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Thio) propyl] piperidine-3-acetic acid
[2860] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6- Tetrafluorophenylthio) ethyl] piperidine-3-acetic acid
[2861] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6- Tetrafluorophenylthio) propyl] piperidine-3-acetic acid
[2862] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chloro Phenylthio) ethyl] piperidine-3-acetic acid
[2863] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro Phenylthio) propyl] piperidine-3-acetic acid
[2864] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio ) Ethyl] piperidine-3-acetic acid
[2865] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio ) Propyl] piperidine-3-acetic acid
[2866] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl ] Piperidine-3-acetic acid
[2867] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl ] Piperidine-3-acetic acid
[2868] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl ] Piperidine-3-acetic acid
[2869] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl ] Piperidine-3-acetic acid
[2870] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridine-2- Yl) thioethyl] piperidine-3-acetic acid
[2871] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridine-2- Yl) thiopropyl] piperidine-3-acetic acid
[2872] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperi Din-3-acetic acid
[2873] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperi Din-3-acetic acid
[2874] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] pi Ferridine-3-acetic acid
[2875] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] py Ferridine-3-acetic acid
[2876] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2877] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2878] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2879] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2880] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2881] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2882] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro Lophenyl) prop-2-ynyl] piperidine-3-acetic acid
[2883] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluorophenyl) Prop-2-ynyl] piperidine-3-acetic acid
[2884] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido-5-fluorophenyl Prop-2-ynyl] piperidine-3-acetic acid
[2885] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluoromethoxyphenyl) prop- 2-ynyl] piperidine-3-acetic acid
[2886] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] pi Ferridine
[2887] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] py Ferridine
[2888] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] pi Ferridine
[2889] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] pi Ferridine
[2890] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6-tetrafluorophenylthio ) Ethyl] piperidine
[2891] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio ) Propyl] piperidine
[2892] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] Piperidine
[2893] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] Piperidine
[2894] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperi Dean
[2895] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperi Dean
[2896] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine
[2897] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine
[2898] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine
[2899] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine
[2900] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] Piperidine
[2901] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thiopropyl] Piperidine
[2902] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyanoheptylthio) ethyl] piperidine
[2903] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyanoheptylthio) propyl] piperidine
[2904] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine
[2905] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert-butylthio) propyl] piperidine
[2906] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2 -Inyl] piperidine
[2907] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl) prop-2 -Inyl] piperidine
[2908] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2 -Inyl] piperidine
[2909] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) prop-2 -Inyl] piperidine
[2910] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop -2-ynyl] piperidine
[2911] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop -2-ynyl] piperidine
[2912] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluorophenyl) prop -2-ynyl] piperidine
[2913] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluorophenyl) prop-2- Inyl] piperidine
[2914] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido-5-fluorophenyl) prop-2 -Inyl] piperidine
[2915] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluoromethoxyphenyl) prop-2-ynyl] pi Ferridine
[2916] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3, 5-difluorophenylthio) ethyl] piperidine
[2917] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 5-difluorophenylthio) propyl] piperidine
[2918] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2, 5-difluorophenylthio) ethyl] piperidine
[2919] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 5-difluorophenylthio) propyl] piperidine
[2920] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2, 3,4,6-tetrafluorophenylthio) ethyl] piperidine
[2921] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,4,6-tetrafluorophenylthio) propyl] piperidine
[2922] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluoro-5-chlorophenylthio) ethyl] piperidine
[2923] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluoro-5-chlorophenylthio) propyl] piperidine
[2924] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Trifluoromethoxyphenylthio) ethyl] piperidine
[2925] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Trifluoromethoxyphenylthio) propyl] piperidine
[2926] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Cyanophenylthio) ethyl] piperidine
[2927] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Cyanophenylthio) propyl] piperidine
[2928] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 2-yl) thioethyl] piperidine
[2929] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) thiopropyl] piperidine
[2930] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluoropyridin-2-yl) thioethyl] piperidine
[2931] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluoropyridin-2-yl) thiopropyl] piperidine
[2932] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyano Heptylthio) ethyl] piperidine
[2933] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano Heptylthio) propyl] piperidine
[2934] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert- Butylthio) ethyl] piperidine
[2935] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert- Butylthio) propyl] piperidine
[2936] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3-difluorophenyl) prop-2-ynyl] piperidine
[2937] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 5-difluorophenyl) prop-2-ynyl] piperidine
[2938] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 5-difluorophenyl) prop-2-ynyl] piperidine
[2939] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 6-difluorophenyl) prop-2-ynyl] piperidine
[2940] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,5-trifluorophenyl) prop-2-ynyl] piperidine
[2941] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,6-trifluorophenyl) prop-2-ynyl] piperidine
[2942] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Cyano-3-fluorophenyl) prop-2-ynyl] piperidine
[2943] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano- 6-fluorophenyl) prop-2-ynyl] piperidine
[2944] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido -5-fluorophenyl) prop-2-ynyl] piperidine
[2945] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluorome Methoxyphenyl) prop-2-ynyl] piperidine
[2946] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3, 5-difluorophenylthio) ethyl] piperidine
[2947] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 5-difluorophenylthio) propyl] piperidine
[2948] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2, 5-difluorophenylthio) ethyl] piperidine
[2949] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 5-difluorophenylthio) propyl] piperidine
[2950] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2, 3,4,6-tetrafluorophenylthio) ethyl] piperidine
[2951] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,4,6-tetrafluorophenylthio) propyl] piperidine
[2952] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluoro-5-chlorophenylthio) ethyl] piperidine
[2953] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluoro-5-chlorophenylthio) propyl] piperidine
[2954] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Trifluoromethoxyphenylthio) ethyl] piperidine
[2955] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Trifluoromethoxyphenylthio) propyl] piperidine
[2956] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Cyanophenylthio) ethyl] piperidine
[2957] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Cyanophenylthio) propyl] piperidine
[2958] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine- 2-yl) thioethyl] piperidine
[2959] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridine- 2-yl) thiopropyl] piperidine
[2960] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Fluoropyridin-2-yl) thioethyl] piperidine
[2961] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- Fluoropyridin-2-yl) thiopropyl] piperidine
[2962] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyano Phenylthio) ethyl] piperidine
[2963] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyano Phenylthio) propyl] piperidine
[2964] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert- Butylthio) ethyl] piperidine
[2965] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert- Butylthio) propyl] piperidine
[2966] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3-difluorophenyl) prop-2-ynyl] piperidine
[2967] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 5-difluorophenyl) prop-2-ynyl] piperidine
[2968] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 5-difluorophenyl) prop-2-ynyl] piperidine
[2969] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 6-difluorophenyl) prop-2-ynyl] piperidine
[2970] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,5-trifluorophenyl) prop-2-ynyl] piperidine
[2971] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2, 3,6-trifluorophenyl) prop-2-ynyl] piperidine
[2972] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Cyano-3-fluorophenyl) prop-2-ynyl] piperidine
[2973] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano- 6-fluorophenyl) prop-2-ynyl] piperidine
[2974] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido -5-fluorophenyl) prop-2-ynyl] piperidine
[2975] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluorome Methoxyphenyl) prop-2-ynyl] piperidine
[2976] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] piperidine-3- Carboxylic acid
[2977] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] piperidine-3- Carboxylic acid
[2978] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridine-2- Yl) thioethyl] piperidine-3-carboxylic acid
[2979] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridine-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[2980] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridine-2- Yl) thioethyl] piperidine-3-carboxylic acid
[2981] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridine-2- Yl) thiopropyl] piperidine-3-carboxylic acid
[2982] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] piperidine-3- Acetic acid
[2983] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] piperidine-3- Acetic acid
[2984] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridine-2- Yl) thioethyl] piperidine-3-acetic acid
[2985] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridine-2- Yl) thiopropyl] piperidine-3-acetic acid
[2986] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridine-2- Yl) thioethyl] piperidine-3-acetic acid
[2987] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridine-2- Yl) thiopropyl] piperidine-3-acetic acid
[2988] The following examples illustrate the invention but are not limited thereto.
[2989] Example 1
[2990] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylic acid
[2991] 0.2 g 3-phenylpropyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate, 3 A mixture of cm 3 of dioxane and 1 cm 3 of normal aqueous sodium hydroxide is allowed to reach 60 ° C. for 16 hours with stirring. The reaction mixture is cooled and diluted with 25 cm 3 of water and then extracted three times with 20 cm 3 of ether. The combined ether phases are washed three times with 10 cm 3 of water. The ether solution is dried over magnesium sulfate in the presence of animal charcoal, filtered through filter paper, and then mixed under reduced pressure (5 kPa) at a temperature of about 25 ° C. 0.060 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylic acid is obtained in the form of a colorless lacquer. .
[2992] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.35 to 1.95 (mt, 9H), 2.30 (wide t, J = 11 Hz, 1H), 2.38 (wide d, J = 11 Hz, 1H), 2.45 to 2.65 (mt, 3H), 2,60 (t, J = 7.5 Hz, 2H), 2.90 (unsplit peak, 1H), 2.95 to 3.15 (unsplit peak, 3H), 3.95 (s, 3H), 7.15 to 7.25 (mt, 3H), 7.25 to 7.35 (mt, 3H), 7.35 to 7.45 (mt, 2H), 7.93 (d, J = 9 Hz, 1H), 8.63 (d, J = 4.5 Hz, 1H).
[2993] 3-phenylpropyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate
[2994] 1.75 g of 0.93 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid hydrochloride solution in 20 cm 3 of dimethylformamide anhydride Potassium carbonate and then 1.15 cm 3 of 1-bromophenylpropane are added at a temperature of about 25 ° C. with stirring. The suspension is brought to a temperature of about 60 ° C. for 17 hours. After cooling, the mixture is poured into 200 cm 3 of water and extracted three times with 30 cm 3 of ether. The combined ether extracts are washed twice with 20 cm 3 of water. The ether solution is extracted with 20 cm 3 of normal aqueous hydrochloric acid and twice with 20 cm 3 of water. The combined aqueous extracts are made alkaline by the addition of solid sodium bicarbonate. The extraction is performed three times with 20 cm 3 of ether and the ether extract is washed three times with 20 cm 3 of water and then dried over potassium sulfate in the presence of 0.1 g of animal charcoal. After filtration through filter paper and concentrated under reduced pressure (5 kPa) at a temperature of about 30 ° C., 0.84 g of 3-phenylpropyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl ) -Propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate is obtained in the form of a light brown oil.
[2995] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propyl] piperidine-3-carboxylic acid hydrochloride is prepared by the following method:
[2996] 8.8 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid, while stirring, in 200 cm 3 of 5N aqueous hydrochloric acid Heated to a temperature of about 100 ° C. for 48 hours. The reaction mixture is concentrated at a temperature of about 50 ° C. under reduced pressure (5 kPa). The residue is taken up in 100 cm 3 of acetone. The mixture is concentrated at a temperature of about 60 ° C. under reduced pressure (5 kPa). This operation is repeated two more times. The residue is finally crushed until it crystallizes in 100 cm 3 of acetone. After filtration of the crystals and drying in a desiccator under reduced pressure (10 kPa), 7.2 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine- 3-carboxylic acid hydrochloride is obtained in the form of a beige solid that melts (melts with softening) at approximately 270 ° C.
[2997] (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid is obtained by the following method:
[2998] 25 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine is a mixture of 250 cm 3 carbon tetrachloride and 250 cm 3 acetonitrile Dissolved in. A 51.3 g sodium metaperiodate solution in 325 cm 3 of water is added at a temperature of about 20 ° C. with good stirring, followed by 0.27 g of ruthenium trihydrate hydrate. After addition of the reactants, a weak exotherm is maintained at about 30 ° C. for 15 minutes. The mixture is stirred at room temperature for 2 hours. The resulting suspension is filtered and the insoluble matter is washed five times with 80 cm 3 of dichloromethane. After stirring the filtrate, the organic phase is separated by sedimentation and the aqueous phase is saturated with sodium chloride and then extracted with two additional 300 cm < 3 > portions of dichloromethane. The combined organic extracts are washed with water (three times 200 cm 3), dried over magnesium sulfate, filtered through filter paper and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 23.2 g of oil are obtained, which are purified by chromatography on silica gel (particle size 20-45 μm; diameter 6.5 cm; height 30 cm) at atmospheric pressure, elution is dichloromethane / methanol (volume 97/3) Perform a mixture and collect 400-cm 3 fractions. Fractions 4 to 8 are combined and then concentrated under reduced pressure (5 kPa). 11.8 g of brown oil is obtained. The latter is dissolved in 60 cm 3 of acetonitrile and refluxed for a few minutes in the presence of 0.5 g of animal charcoal. After filtration, the obtained solution is cooled. The crystallized product is filtered off and washed twice with 10 cm 3 of acetonitrile. The solid is dried in a desiccator in the presence of potassium hydroxide (10 kPa) in vacuo. 8.8 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid is obtained in the form of a beige solid which melts at 160 ° C. .
[2999] (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine is prepared by the following method:
[3000] 18.4 cm 3 of triethylamine was stirred with 20.8 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine in 270 cm 3 of chloroform. After addition to the solution, a solution of 7.2 cm 3 of benzoyl chloride in 50 cm 3 of chloroform is added for more than 1 hour. After the mixture is stirred at a temperature of about 20 ° C. for 1 hour 30 minutes, 100 cm 3 of distilled water is added to the reaction mixture. The chloroform phase is separated by sedimentation, washed twice with 100 cm 3 of water and then dried over magnesium sulfate. After filtration through filter paper, the chloroform solution is concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 25 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine are obtained in the form of a brown oil.
[3001] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by the application of the method disclosed in patent application FR 2,354,771.
[3002] Example 2
[3003] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl)] piperidine-3 -Carboxylic acid dihydrochloride
[3004] 0.057 cm 3 of 2-iodothiophene and 1.42 cm 3 of triethylamine were added to 0.185 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) in 4 cm 3 of dimethylformamide anhydride. Propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid solution was added with stirring, followed by 0.038 g of tetrakis (triphenylphosphine) palladium and 0.019 g of cuprous iodide Add. The solution is stirred at a temperature of about 20 ° C. for 20 hours. 75 cm 3 of ethyl acetate and 75 cm 3 of water are added to the reaction mixture. After stirring the mixture, the aqueous phase is separated by sedimentation and then neutralized to pH 6 by addition of 0.1N aqueous hydrochloric acid solution. The aqueous phase is extracted with 50 cm 3 of ethyl acetate; The extract is washed twice with 75 cm 3 saturated aqueous sodium chloride solution. The organic solution is dried over magnesium sulfate, filtered and mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.090 g of yellow oil is obtained, which is purified by chromatography on silica gel (particle size 20-45 μm; diameter 1 cm; height 30 cm), which is eluted with dichloromethane / methanol (volume 92 / under nitrogen pressure of 50 kPa). 8) and 50-cm 3 fractions are collected. Fractions 12-15 were combined and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). The obtained oil is taken up in 1 cm 3 of a 4N solution of hydrochloric acid in dioxane. Concentrated under the same conditions as described above, the residue was taken up in 10 cm 3 of diethyl ether, and then filtered to obtain 0.030 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl]. -1- [3- (thien-2-yl) prop-2-ynyl)] piperidine-3-carboxylic acid dihydrochloride is collected in the form of a white solid.
[3005] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.15 to 2.10 and 3.00 to 3.65 (mts, 14H), 3.98 (s, 3H), 4.25 to 4.55 (non-divided peak) , 2H), 7.16 (dd, J = 5 and 3 Hz, 1H), 7.40 to 7.60 (mt, 4H), 7.75 (wide area d, J = 5 Hz, 1H), 7.96 (mt, 1H), 8.79 (mt, 1H) ), 10.50 to 10.70 (wide undivided peak, 1H), 12.85 to 13.15 (wide undivided peak, 1H).
[3006] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid can be prepared by the following method have:
[3007] 0.3 g of (prop-2-ynyl) (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1 in 3 cm 3 dioxane and 1.48 cm 3 N sodium hydroxide The-(prop-2-ynyl) piperidine-3-carboxylate is heated at a temperature of about 70 ° C. for 17 hours with stirring. The reaction mixture is concentrated at a temperature of about 50 ° C. under reduced pressure (5 kPa). 1.48 cm 3 of normal aqueous hydrochloric acid is added to the obtained solid residue, followed by 10 cm 3 of water. The obtained solution is extracted five times with 20 cm 3 of dichloromethane. The organic extracts are combined and then concentrated under reduced pressure (5 kPa). 0.189 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid in white foam form Get into.
[3008] (Prop-2-ynyl) (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxyl The rate can be prepared by the following method:
[3009] 0.95 g potassium carbonate, 0.835 g (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid hydro in 15 cm 3 of dimethylformamide anhydride To the solution of chloride is added followed by 0.36 cm 3 of propargyl bromide. The mixture is stirred at a temperature of about 70 ° C. under a nitrogen atmosphere for 18 hours. 100 cm 3 of ethyl acetate and 100 cm 3 of distilled water are added to the reaction mixture. The organic phase is separated by sedimentation and then washed 5 times with 40 cm 3 of water and twice with 50 cm 3 of saturated sodium chloride solution. The organic solution is dried over magnesium sulfate, filtered and mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa) to the maximum concentration. The oil obtained is purified by chromatography on silica gel (particle size 20-45 μm; diameter 2 cm; height 40 cm), which is eluted with ethyl acetate under nitrogen pressure of 50 kPa and a 50-cm 3 fraction is collected. Fractions 17-21 were combined and concentrated at 40 ° C. under reduced pressure (5 kPa). 300 g of (prop-2-ynyl) (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3 The carboxylic acid is obtained in the form of a yellow oil.
[3010] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid hydrochloride can be obtained as described in Example 1.
[3011] Example 3
[3012] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenyl-2-thio) ethyl] piperidine-3-carboxylic acid Dihydrochloride
[3013] 0.54 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- in 4 cm 3 methanol and 0.8 cm 3 5N aqueous sodium hydroxide The mixture of fluorophenylthio) -2-ethyl] piperidine-3-carboxylate is heated at 60 ° C. for 20 hours with stirring. After the solvent is mixed under reduced pressure (5 kPa) at a temperature of about 40 ° C., the obtained residue is taken up in 10 cm 3 of water and then acidified with 0.4 cm 3 of concentrated hydrochloric acid. The solution is mixed under the same conditions and the resulting residue is triturated in a dichloromethane / methanol (vol. 90/10) mixture. Insoluble material is filtered off and washed with 5 cm 3 of dichloromethane. The filtrate is dried over sodium sulfate and then concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). The residue is triturated in 10 cm 3 of diisopropyl ether and then 1 cm 3 of a 5N solution of hydrochloric acid in diisopropyl ether is added with stirring. The crystals are separated by filtration and washed twice with 5 cm 3 of diisopropyl ether. 0.45 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) -2- after drying in air Ethyl] piperidine-3-carboxylic acid dihydrochloride is obtained in the form of a pale yellow amorphous solid which melts with softening at about 140 ° C.
[3014] Infrared spectra (KBr): 3058 and 3012 cm ^-1 (aromatic CH v), 2935 and 2862 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1719 cm ^-1 (acidic C = O v), 1618, 1600, 1578, 1541 and 1496 cm ^-1 (aromatic nucleus C = C v), 1274 cm ^-1 (Acidic CO v), 1251 and 1216 cm ^-1 (ether CO v _as ), 1021 cm ^-1 (ether CO v _s + alcohol CO v), 847 cm ^-1 (4,6-disubstituted quinol CH γ ), 781 and 729 cm ^-1 (1,3-disubstituted phenyl CH γ).
[3015] Mass spectrum (EI-m / z): = 482 (M ⁺ ), 483 (M-CO ₂ ) ⁺ , 341 (MC ₇ H ₆ SF) ⁺ base peak, 297, 341 (M-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ NO ⁺ ), 128 (C ₆ H ₅ SF ⁺ ), 36 (HCl ⁺ )
[3016] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) -2-ethyl] piperidine-3- Carboxylate can be prepared by the following method:
[3017] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propyl] piperidine-3-carboxylate hydrochloride and 2-bromo-1- (3-fluorophenyl 0.55 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1, prepared in a similar manner to Example 4 except for using thioethane. -[2- (3-fluorophenylthio) -2-ethyl] piperidine-3-carboxylate is obtained in the form of a yellow viscous oil.
[3018] Infrared spectrum (CCl ₄ ): 2949 cm ⁻¹ , aliphatic CH v, 1737 cm ⁻¹ , C═O v, 1227 cm ⁻¹ , ether CO v, 845 cm ⁻¹ , quinoline CH γ.
[3019] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propyl] piperidine-3-carboxylate hydrochloride was prepared under the conditions of Example 6.
[3020] Example 4
[3021] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylic acid
[3022] 0.7 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (in 5 cm 3 of methanol added with 2.9 cm 3 of N aqueous sodium hydroxide Phenylthioethyl)] piperidine-3-carboxylate is stirred at a temperature of about 80 ° C. for 2 hours. The resulting solution is neutralized with 0.18 cm 3 of acetic acid and then mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). The residue obtained was purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3 cm; height 20 cm) at atmospheric pressure, elution was carried out with a dichloromethane / ethanol (volume 90/10) mixture and a 20-cm 3 fraction Collect it. Fractions 21 to 52 were combined and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.53 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylic acid is beige Obtained in oil form.
[3023] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.35 to 1.95 (mt, 7H), 2.28 (wide t, J = 10.5 Hz, 1H), 2.43 (wide d, J = 10.5 Hz, 1H), 2.59 (mt, 1H), 2.64 (t, J = 7 Hz, 2H), 2.77 (unsplit peak, 1H), 2.93 (unsplit peak, 1H), 3.03 (mt, 2H) , 3.13 (mt, 2H), 3.95 (s, 3H), 7.21 (tt, J = 7.5 and 2 Hz, 1H), 7.25 to 7.45 (mt, 7H), 7.93 (d, J = 9 Hz, 1H), 8.63 ( d, J = 4.5 Hz, 1H).
[3024] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylate is obtained by the following method Can be manufactured:
[3025] 1 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride and 1 g of potassium carbonate in 100 cm 3 of acetonitrile Stir at a temperature of about 20 ° C. for 20 minutes. After adding 0.61 g of 2-bromo-1-phenylthioethane, previously dissolved in 5 cm 3 of acetonitrile, the mixture is heated at a temperature of about 60 ° C. for 5 hours. After addition of 20 cm 3 of dimethylformamide and additional 0.61 g of 2-bromo-1-phenylthioethane, it is further heated for 8 h 30 min. After cooling, the reaction mixture is filtered; The resulting solution is concentrated at a temperature of about 70 ° C. under reduced pressure (5 kPa). The residue is taken up in 50 cm 3 of ethanol and concentrated again under the same conditions as above. The residue is diluted with 30 cm 3 of water and then extracted three times with 20 cm 3 of dichloromethane. The combined extracts are dried over magnesium sulfate and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 1 g of oil is obtained, which is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; height 20 cm) at atmospheric pressure, the elution being a dichloromethane / ethanol (volume 90/10) mixture And collect 25-cm 3 fractions. Fractions 15 to 26 were combined and then concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.79 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylate is yellow Obtained in the form of an oil.
[3026] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride can be prepared under the conditions of Example 6.
[3027] Example 5
[3028] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3- Carboxylic Acid Dihydrochloride
[3029] 0.5 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperi A mixture of din-3-carboxylate, 0.8 cm 3 of 5N sodium hydroxide and 5 cm 3 of methanol is stirred at 70 ° C. for 3 hours. After the obtained solution was mixed under reduced pressure (5 kPa) at a temperature of about 40 ° C., a solid residue (0.67 g) was obtained, which was taken up in 10 cm 3 of dichloromethane. The mixture is cooled to about 0 ° C. and then 1 cm 3 of a 6.3 N solution of hydrochloric acid in diisopropyl ether is added. 10 cm 3 of ethyl ether is added dropwise with stirring. After settling for 15 minutes, the suspension is filtered off and then washed twice with 5 cm 3 of dichloromethane / ethylether (volume 5/5) mixture and then twice with 5 cm 3 of ether. 0.34 g of solid was obtained, which was purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 1.5 cm; 8.5 g) under atmospheric pressure, the elution being dichloromethane / methanol (volume 80/20) Perform with mixture and collect 3-cm 3 fractions. Fractions 7 to 35 were combined and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). The obtained residue is triturated twice in 10 cm 3 of ethyl ether and then concentrated under the same conditions as above under reduced pressure. 0.14 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine 3-carboxylic acid dihydrochloride is obtained in a creamy solid form that melts with softening at about 168 ° C.
[3030] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, addition of several drops of d4-CD ₃ COOD, δ (ppm)): 1.35 to 2.30 and 2.90 to 3.65 (mts, 12H), 3.99 (s, 3H ), 4.20 to 4.50 (mt, 2H), 5.40 to 5.60 (mt, 1H), 7.25 to 7.70 (mt, 5H), 770 to 7.80 (mt, 1H), 7.99 (mt, 1H), 8.20 (d, J) = 9 Hz, 1 H), 9.01 (wide area d, J = 5 Hz, 1 H).
[3031] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3 Carboxylate
[3032] 0.15 g sodium borohydride, in portions at a temperature of about 20 ° C. under an inert atmosphere, 1.59 g methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinoline) in 25 cm 3 methanol -4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate is added to the stirred solution. The mixture is continuously stirred at a temperature of about 20 ° C. for 75 minutes. Then 15 cm 3 of distilled water is added while maintaining the same temperature. The mixture, having a milky appearance, is concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). The obtained residue was taken up in 40 cm 3 of distilled water to which 80 cm 3 of dichloromethane was added, stirred, and separated by sedimentation. The organic phase is recovered and washed once with 40 cm 3 of water and dried over magnesium sulfate. After filtration through filter paper, the solvent was mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa), followed by 1.39 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- ( 6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate is obtained in the form of a foam and in the form of an orange sticky solid.
[3033] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate is obtained by the following method Can be manufactured as:
[3034] 4.51 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2.3 g of carbonic acid in 75 cm 3 of acetone The suspension of potassium is heated at a temperature of about 58 ° C. while stirring. A solution of 2.5 cm 3 of 1-bromo-3-phenylpropane in 7.5 cm 3 of acetone is added dropwise at this temperature. The heating is extended for 19 hours. After cooling, the reaction is filtered; the cake is washed twice with 30 cm 3 of acetone. The filtrate and washings are combined and concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). 7.12 g of product are obtained in oil form, which is purified by chromatography on a column of silica gel (particle size 20-45 μm; diameter 7 cm; mass 712 g) under atmospheric pressure, the elution being chloroform / methanol / aqueous ammonia (vol. 12 / 2.25 / 0.38) mixture and collect 65-cm 3 fractions. Fractions 9-14 were combined and then concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). 6.7 g of oil are obtained, which is subjected to a second purification by chromatography on a silica gel column (particle size 20-45 μm; diameter 4.8 cm; mass 336 g) under atmospheric pressure, the elution being ethyl acetate and methanol (volume 9/1) and collect 20-cm 3 fractions. Fractions 71 to 122 are combined and then concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). 1.66 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate Obtained in the form of a brown oil.
[3035] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate can be prepared by the following method:
[3036] 19.4 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (t-butyloxocarbonyl) piperidine in 355 cm 3 methanol The solution of -3-carboxylic acid (80% content) is cooled to about -30 ° C. 7.7 cm 3 of thionyl chloride is added while stirring while maintaining a temperature between -25 and -30 ° C. After addition, the mixture is held at about −30 ° C. for 30 minutes and then returned to a temperature of about 20 ° C. After stirring for 19 hours at room temperature, the reaction mixture is concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 300 cm 3 of water to which 200 cm 3 of dichloromethane is added, followed by stirring. The organic phase is separated by sedimentation; The aqueous phase is extracted again with 200 cm 3 of dichloromethane. The aqueous phase is brought to pH 8 by the stepwise addition of solid sodium hydrogen carbonate. The obtained alkaline solution is extracted three times with 200 cm 3 of dichloromethane, and then the combined organic extracts are washed twice with 200 cm 3 of water and dried over magnesium sulfate. After filtration through filter paper, the organic solution is concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 4.51 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate are obtained in the form of a brown lacquer.
[3037] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butoxycarbonyl) piperidine-3-carboxylic acid Can be manufactured with:
[3038] Cool a solution of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine in 54 cm 3 of acetone to a temperature of about 0 ° C. Let's do it. 150 cm 3 of 3M sulfuric acid is added with stirring over 15 minutes while maintaining a temperature of 0-5 ° C. The temperature is lowered to about 0 ° C. and 32 g of sodium permanganate solution in 200 cm 3 of distilled water is added dropwise to the mixture. The reaction mixture is further stirred at a temperature of 10-15 ° C. for 45 minutes and then the temperature is raised to about 20 ° C. After stirring for 3 hours at this temperature, the reaction is cooled to a temperature of about 0 ° C. and then 160 cm 3 of 38% potassium hydroxide solution is slowly added at a temperature lower than 10 ° C. After stirring for 30 minutes at a temperature of about 10 ° C, the mixture is filtered. The cake is taken up in 300 cm 3 of water to which 15 cm 3 of 38% potassium hydroxide is added and stirred for 20 minutes. After filtration, the cake was washed twice with 200 cm 3 of distilled water, then the filtrates were combined and 24 g of di-tert-butyl dicarbonate was added. The solution is stirred at a temperature of about 20 ° C. for 15 hours. After 1 liter of ethyl acetate is added and stirred, the mixture is separated by sedimentation and the separated aqueous phase is then adjusted to pH 5 by addition of 38 cm 3 of 37% concentrated aqueous hydrochloric acid. The mixture is again extracted 5 times with 1 liter of ethyl acetate. The extracts are combined and washed twice with 1 liter of water saturated with sodium chloride. The organic solution is dried over magnesium sulfate, filtered through filter paper and concentrated at a temperature of about 40 ° C. under reduced pressure (5 kPa). 21.2 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (t-butyloxocarbonyl) piperidine-3-carboxylic acid Obtained in the form of a brown solid which melts with softening at 114 ° C.
[3039] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by the application of the method disclosed in patent application FR 2,354,771. have.
[3040] Example 6
[3041] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylic acid
[3042] 0.25 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine in 6 cm 3 of methanol The 3-carboxylate solution is added to 0.41 cm 3 of 5N aqueous sodium hydroxide and then heated under an inert atmosphere for 18 hours 30 minutes at a temperature of about 57 ° C. The mixture is cooled and then concentrated at a temperature of about 40 ° C. under reduced pressure (2 kPa). The residue is taken up in 10 cm 3 of water, acidified with 2 cm 3 of N aqueous hydrochloric acid and concentrated at a temperature of about 45 ° C. under reduced pressure (2 kPa). The obtained residue is triturated in 10 cm 3 of dichloromethane / methanol (volume 90/10) and then filtered. The obtained residue is triturated in 10 cm 3 of dichloromethane / methanol (volume 90/10) and then filtered off. Insoluble matter is washed twice with 10 cm 3 of dichloromethane. The combined organic filtrates are concentrated at a temperature of about 30 ° C. under reduced pressure (2 kPa). 0.22 g of residue is obtained, which is stirred in a mixture of 20 cm 3 of water and 15 cm 3 of dichloromethane. The aqueous phase is separated by sedimentation and then extracted three times with 10 cm 3 of dichloromethane. The aqueous phase is concentrated under reduced pressure (5 kPa) at a temperature of about 40 ° C. to dryness. The residue is triturated in 10 cm 3 of dichloromethane / methanol (volume 90/10) mixture. The insoluble material is filtered off and the cake is washed with the same mixture of 5 cm 3. The filtrate is dried over magnesium sulfate and then concentrated under the same conditions as above under reduced pressure and finally dried at a temperature of about 40 ° C. under partial pressure (13 Pa) for 2 hours. 0.11 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylic acid is weak Obtained in a solid form such as a pale yellow foam that melts with softening at 166 ° C.
[3043] Infrared spectra (KBr): 2931, 2859 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)) , 1719 cm ^-1 (acidic C = O v), 1618, 1601, 1542 and 1492 cm ^-1 (aromatic nucleus C = C v), 1275 cm ^-1 (acidic CO v), 1225 cm ^-1 (ether CO v _as ), 1022 cm ⁻¹ (ether CO v _s ), 846 cm ⁻¹ (CHγ as a 4,6-disubstituted quinol), 761 and 693 cm ⁻¹ (monosubstituted phenyl CH γ).
[3044] Mass spectrum (EI-m / z): = 442 (M ⁺ ), 398 (M-CO ₂ ) ⁺ , 327 (MC ₉ H ₇ ) ⁺ , 283, 327 (M-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ ON ⁺ ), 115 (C ₉ H ₇ ⁺ ), 44 (CO ₂ ⁺ ), 36 (HCl ⁺ Base peak)
[3045] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylate
[3046] 0.138 g of tetrakis (triphenylphosphine) -palladium, 0.041 g of triphenylphosphine and 0.070 g of cuprous iodide were dissolved in an inert atmosphere at a temperature of about 20 ° C. in 0.7 g of 12 cm 3 of acetonitrile. To a stirred solution of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate do. 0.56 g of iodobenzene is added continuously followed by 0.51 cm 3 of triethylamine. The mixture is stirred at a temperature of about 20 ° C. for 22 hours and then filtered. The cake is washed three times with 10 cm 3 of acetonitrile. The combined filtrates are added to 100 cm 3 of dichloromethane and 100 cm 3 of water and then stirred. The organic phase is separated by sedimentation and washed three times with 50 cm 3 saturated sodium chloride solution. After drying over magnesium sulfate and filtration, the organic solution was purified by chromatography on a silica gel column (particle size 40-60 μm; diameter 3 cm, 65 g) under reduced pressure (2 kPa), wherein elution was carried out with ethyl acetate. And collect 2.5-cm 3 fractions. Fractions 52 to 210 are combined and concentrated at a temperature of about 35 ° C. under reduced pressure (2 kPa). 0.64 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylate Is obtained in the form of a light brown oil.
[3047] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate is prepared by the following method can do:
[3048] 14.7 cm 3 of triethylamine was added to 10 g of methyl (3R, 4R) -4- [3- (6-methoxyquinoline-4- in 100 cm 3 of dimethylformamide anhydride under an inert atmosphere at a temperature of about 20 ° C. To a stirred solution of yl) propyl] piperidine-3-carboxylate hydrochloride followed by 45 minutes followed by 3 cm 3 of propargyl bromide diluted in 10 cm 3 of dimethylformamide anhydride. After stirring for 15 minutes at a temperature of about 20 ° C., the mixture is heated at a temperature of about 45 ° C. for 4 hours. After cooling, the reaction mixture is poured into a mixture of 250 cm 3 of ethyl acetate and 250 cm 3 of distilled water. The mixture is stirred for a few minutes and then the organic phase is separated by sedimentation. The aqueous phase is extracted twice with 250 cm 3 of ethyl acetate. The organic phases are combined, washed three times with 200 cm 3 of distilled water and then dried over magnesium sulfate. After filtration, the solvent was mixed at a temperature of about 40 ° C. under reduced pressure (2 kPa), and an oil of 7.8 g was obtained, which was subjected to a silica gel column (particle size 40-63 μm; diameter 7 cm, under argon pressure (50 kPa)). 475 g), purified by chromatography, eluting with ethyl acetate and collecting 8-cm 3 fractions. Fractions 468-612 were combined and then concentrated at a temperature of about 45 ° C. under reduced pressure (2 kPa). 4.7 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate is orange Obtained in oil form.
[3049] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride can be prepared by the following method:
[3050] 2 cm 3 of thionyl chloride was added to 4.29 g of (3R, 4R) -4- [3- (6-methoxyquinoline) in 50 cm 3 of methanol cooled to a temperature of about -30 ° C. with a cooling bath of acetone and solid carbon dioxide. -4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid is added dropwise to the stirred suspension. The resulting solution is brought to a temperature of about 20 ° C. and the reaction mixture is stirred at this temperature for 16 hours. After mixing the solution at about 40 ° C. under reduced pressure (5 kPa), the obtained residue is triturated in about 30 cm 3 of diisopropyl ether. The obtained crystals are filtered off, washed twice with 10 cm 3 of diisopropyl ether and dried in air. 4.20 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride is light yellow that melts with softening at about 140 ° C. Obtained in solid form.
[3051] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid can be prepared by the following method have:
[3052] 3 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine is dissolved in 3 cm 3 of acetone. 14.5 cm 3 of 3M sulfuric acid, previously cooled to about 5 ° C., is added to the solution, ie, a solution cooled to the same temperature with a bath of ice and acetone. A solution of 4.64 g of sodium permanganate monohydrate in 25 cm 3 of water is added to the resulting solution over 30 minutes while maintaining a temperature of 0-7 ° C. The reaction mixture is stirred at a temperature of 10-17 ° C. for 4 hours. Filter the reaction; Insoluble matter is washed twice with 10 cm 3 of water. On the one hand, an orange solution and on the other hand a black inorganic substance are obtained. The orange solution is adjusted to pH 10 by adding 4.6 g of sodium carbonate. The mixture is filtered; A solution (1) and an insoluble inorganic material (2) are obtained. The black inorganic material is stirred for 30 minutes in 20 cm 3 of water and then the pH is adjusted to 12 by adding 2 cm 3 of potassium hydroxide solution. After filtration of the mixture, a solution (3) and an insoluble inorganic substance (3) are obtained. Insoluble materials (2) and (4) are stirred for 15 minutes in 15 cm 3 of water to which 3 cm 3 of potassium hydroxide solution is added. The suspension is filtered. Obtain the solution (5). The aqueous solutions (1), (3) and (5) were combined and 2.31 g of di-tert-butyl dicarbonate were added and stirring was performed at a temperature of about 20 ° C. for 15 minutes. The mixture is extracted six times with 10 cm 3 of ethyl acetate. The combined organic phases are washed with 20 cm 3 of water and then with 20 cm 3 saturated aqueous sodium chloride solution. Dried over sodium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature of about 35 ° C., followed by 2.86 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl ] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid is obtained in the form of a beige solid which becomes grassy at 154 ° C.
[3053] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by the application of the method disclosed in patent application FR 2,354,771.
[3054] Example 7
[3055] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine-3- Carboxylic acid
[3056] 0.44 cm 3 of 5N aqueous sodium hydroxide was added to 0.28 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (2 in 10 cm 3 of methanol. -Fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate, and then the mixture is heated for 20 hours at about 57 ° C. After cooling, the solution is cooled under reduced pressure (2 kPa) Mix at a temperature of 40 ° C. 0.41 g of a residue is obtained, which is taken up in 20 cm 3 of water to which 3.5 cm 3 of 1N hydrochloric acid is added The aqueous phase is extracted five times with 15 cm 3 of dichloromethane and then the aqueous phase. The resulting residue is concentrated to dryness under a reduced pressure (5 kPa) at a temperature of about 40 ° C. The resulting residue is triturated in a 10 cm 3 dichloromethane / methanol (volume 90/10) mixture, the insoluble material is filtered off and the cake is 10 cm 3. The filtrate is dried over magnesium sulfate, then concentrated under reduced pressure (5 kPa) at a temperature of about 40 ° C. and finally concentrated (13 Pa) and dried for 2 hours at a temperature of about 40 ° C. 0.15 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( 2-Fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a solid, such as a pale yellow foam that is softened at about 154 ° C.
[3057] Infrared spectrum (KBr): 3057 cm ^-1 (aromatic CH v), 2933, 2864 cm ^-1 (CH ₂ v), 3000, 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1722 cm ^-1 (acidic C = O v), 1618, 1601, 1542 and 1493 cm ^-1 (aromatic nucleus C = C v), 1275 cm ^-1 (acidic CO v ), 1217 cm ^-1 (ether CO v _as ), 1022 cm ^-1 (ether CO v _s ), 847 cm ^-1 (4,6-disubstituted quinol CH γ), 765 cm ^-1 (ortho- Disubstituted phenyl CH γ).
[3058] Mass spectrum: (DCI) m / z = 461 MH ⁺ .
[3059] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine-3 Carboxylate
[3060] 0.041 g of tetrakis (triphenylphosphine) -palladium and 0.070 g of cuprous iodide were subjected to 0.7 g of methyl (3R, 4R) -4- in 14 cm 3 of acetonitrile at a temperature of about 20 ° C. and an inert atmosphere. To a stirred solution of [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate. 0.32 cm 3 of 1-fluoro-2-iodobenzene and 0.51 cm 3 of triethylamine are added successively. The mixture is stirred at a temperature of about 20 ° C. for 20 hours. The reaction mixture is filtered and the cake is washed three times with 10 cm 3 of acetonitrile. The combined filtrates are taken into a mixture of 100 cm 3 of dichloromethane and 100 cm 3 of water with stirring. The organic phase is separated by sedimentation, washed three times with 50 cm 3 saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated at a temperature of about 35 ° C. under reduced pressure (2 kPa). The obtained residue is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 4 cm; height 14 cm) under argon pressure (50 kPa), the elution is performed with ethyl acetate and a 2-cm 3 fraction is collected. Fractions 33 to 160 are combined and then mixed at a temperature of about 40 ° C. under reduced pressure (2 kPa). 0.56 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylate is obtained in the form of a light brown oil.
[3061] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate was prepared under the conditions of Example 6. Prepared under
[3062] Example 8
[3063] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3- Carboxylic Acid Dihydrochloride
[3064] 0.66 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (3-fluorophenyl) propionate After addition to the phen-2-ynyl] piperidine-3-carboxylate solution, the mixture is heated at a temperature of about 100 ° C. for 3 hours and additionally 3.5 cm 3 of aqueous 6N hydrochloric acid solution is added. The reaction mixture is cooled to a temperature of about 40 ° C. and then concentrated under reduced pressure (2 kPa) at a temperature of about 60 ° C. The obtained residue is taken up in 10 cm 3 of water and 8 cm 3 of dichloromethane and then separated by sedimentation. The aqueous phase is extracted twice with 6 cm 3 of dichloromethane The aqueous phase is concentrated to dryness under reduced pressure (1 kPa) at a temperature of about 50 ° C. The resulting residue is 5 cm 3 of dichloromethane / methanol (volume 90/10). ) Dissolved in the mixture and dried over sodium sulfate, and then filtered, and the solvent is evaporated at a temperature of about 40 ° C. under reduced pressure (1 kPa). Is taken up in a mixture of 2-propanol and isopropyl ether, dissolved under high temperature conditions and filtered through a filter paper The filtrate is cooled to about 25 ° C. and then mixed under reduced pressure (1 kPa) at a temperature of about 45 ° C. The residue is taken up in a 10 cm < 3 > dichloromethane / methanol (volume 90/10) mixture and concentrated again under the same conditions 0.44 g of (3R, 4R) -4- [3- (6-methoxyquinoline-4- Yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid dihydrochloride in the form of a yellow foam in which it melts with softening at a temperature of about 222 ° C. Is obtained.
[3065] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 2.15 (undivided peak, 6H), 2.35 (non-divided peak, 1H), 3.00 to 3.90 (mt, 7H) ), 4.02 (s, 3H), 4.40 (wide s, 2H), 7.25 to 7.55 (mt, 4H), 7.60 (wide s, 1H), 7.75 (dd, J = 9 and 2 Hz, 1H), 7.82 (d , J = 5 Hz, 1H), 8.27 (d, J = 9 Hz, 1H), 8.97 (d, J = 5 Hz, 1H), 11.15 to 11.45 (wide undivided peak, 1H).
[3066] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3 Carboxylate
[3067] 1.2 g of methyl in 25 cm 3 of acetonitrile at 0.07 g triphenylphosphine, 0.237 g tetrakis (triphenylphosphine) palladium and 0.12 g cuprous iodide under an inert atmosphere and at a temperature of about 20 ° C. To a stirred solution of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [rop-2-ynyl] piperidine-3-carboxylate . 0.56 cm 3 of 1-fluoro-3-iodobenzene and 0.88 cm 3 of triethylamine are added successively. After stirring for 20 hours at a temperature of about 20 ° C., the reaction mixture is filtered through celite and the cake is washed with acetonitrile. The filtrate is mixed at a temperature of about 35 ° C. under reduced pressure (2 kPa). The obtained residue is taken into a mixture of 80 cm 3 of dichloromethane and 80 cm 3 of water. After separation by sedimentation, the organic phase is washed three times with 50 cm 3 saturated sodium chloride solution. The organic solution is dried over magnesium sulfate, filtered and concentrated at a temperature of about 40 ° C. under reduced pressure (2 kPa). 1.91 g of oil are obtained, which is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3 cm; 77 g) under argon pressure (50 kPa), elution is carried out with ethyl acetate and 5-cm 3 Collect fractions. Fractions containing the expected product are combined and then mixed at a temperature of about 40 ° C. under reduced pressure (2 kPa). 1.08 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperi Dean-3-carboxylate is obtained in the form of a yellow oil.
[3068] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [rop-2-ynyl] piperidine-3-carboxylate was prepared under the conditions of Example 6. Prepared under.
[3069] Example 9
[3070] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3-carboxylic acid
[3071] 0.37 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (in 6 cm 3 of dioxane added with 1.6 cm 3 of N aqueous hydroxide Thien-2-yl) propyl] piperidine-3-carboxylate solution is stirred at a temperature of about 60 ° C. for 20 hours. After the solvent was mixed at a temperature of about 45 ° C. under reduced pressure (5 kPa), the obtained residue was washed with 20 cm 3 of ethyl ether. The ether is separated by sedimentation and then the aqueous phase is neutralized with 1.6 cm 3 of N hydrochloric acid and then extracted twice with 30 cm 3 of ethyl acetate. The combined extracts are dried over magnesium sulfate. The organic solution is mixed after filtration at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.21 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3-carboxylic acid Obtained in the form of a beige foam which melts with softening at about 60 ° C.
[3072] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.35 to 1.90 (mt, 9H), 2.29 (wide t, J = 11 Hz, 1H), 2.39 (wide d, 1 = 11 Hz, 1H), 2.45 to 2.55 (mt, 2H), 2.58 (mt, 1H), 2.83 (t, J = 8 Hz, 2H), 2.85 to 3.15 (mt, 4H), 3.95 (s, 3H), 6.88 (Broad d, J = 3 Hz, 1H), 6.95 (dd, J = 5 Hz), 7.30 to 7.45 (mt, 4H), 7.93 (d, J = 9 Hz, 1H), 8.63 (d, J = 5 Hz, 1H) .
[3073] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3-carboxylate
[3074] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 3-bromo-1- (thien-2-yl) propane A reaction similar to Example 4 was carried out except that 0.37 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3 Obtain ((thien-2-yl) propyl] piperidine-3-carboxylate in the form of a light brown gum. Mass spectrum (EI-m / z): 466 (M ⁺ ), 369 (MC ₅ H ₅ S) ⁺ , 355 (MC ₆ H ₇ S) ⁺ base peak, 294 (MC ₁₁ H ₁₀ NO) ⁺ , 186 ( C ₁₂ H ₁₂ NO ⁺ ), 97 (C ₅ H ₅ S ⁺ ).
[3075] Example 10
[3076] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthioethyl)] piperidine-3 -Carboxylic acid trihydrochloride
[3077] 0.3 g methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-yl) in 2.5 cm 3 methanol A solution of thioethyl)] piperidine-3-carboxylate and 0.44 cm 3 of 5N aqueous sodium hydroxide is heated with stirring at a temperature of about 60 ° C. for 20 hours. After cooling, the reaction mixture was mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa); The residue is taken up in 5 cm 3 of water and then oxidized by adding 1 cm 3 of 35% hydrochloric acid. The mixture is mixed under the same conditions as above, and the obtained residue is triturated in a 10 cm 3 dichloromethane / methanol (volume 90/10) mixture. 0.34 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [2- (1,3-thiazol-2-ylthioethyl)] piperi Dean-3-carboxylic acid trihydrochloride is obtained in the form of a pale yellow foam.
[3078] Infrared spectra (KBr): 3097 cm ^-1 (thiazole CH v), 3058 and 3012 cm ^-1 (aromatic CH v), 2929 and 28615 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1715 cm ^-1 (acidic C = O v), 1617, 1600, 1543 and 1496 cm ^-1 (aromatic nucleus C = C v), 1274 cm ^-1 (acidic CO v), 1250 and 1219 cm ^-1 (ether CO v _as ), 1020 cm ^-1 (ether CO v _s + alcohol CO v), 846 cm ^-1 (4, CH γ, 6-disubstituted quinol), 740 cm ⁻¹ (thiazole CH γ).
[3079] Mass spectrum (EI-m / z): = 471 (M ⁺ ), 355 (MC ₃ H ₂ NS ₂ ) ⁺ , 341 (MC ₄ H ₄ S ₂ ) ⁺ base peak, 297, 341 (M-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ NO ⁺ ), 117 (C ₃ H ₃ NS ⁺ ), 44 (CO ₂ ⁺ ).
[3080] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthioethyl)] piperidine- 3-carboxylate
[3081] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1-[(1,3-thiazole- A reaction similar to Example 4 was conducted except that 2-yl) thio] ethane was used, so that 0.31 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl ] -1- [2- (1,3-thiazol-2-ylthioethyl)] piperidine-3-carboxylate is obtained in the form of an orange lacquer.
[3082] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.30 to 1.85 (mt, 7H), 2.20 to 2.35 (mt, 1H), 2.35 (dd, J = 11 and 3 Hz , 1H), 2.50-2.85 (mt, 5H), 3.03 (t, J = 7 Hz, 2H), 3.25-3.40 (mt, 2H), 3.53 (s, 3H), 3.94 (s, 3H), 7.31 (d , J = 5 Hz, 1H), 7.35 (d, J = 2.5 Hz, 1H), 7.40 (dd, J = 9 and 2.5 Hz, 1H), 7.63 (d, J = 3.5 Hz, 1H), 7.72 (d, J = 3.5 Hz, 1H), 7.93 (d, J = 9 Hz, 1H), 8.63 (d, J = 5 Hz, 1H).
[3083] Example 11
[3084] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-carboxylic acid hydrochloride
[3085] 0.12 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3- The mixture in 1.8 cm 3 of methanol of carboxylate and 0.6 cm 3 of N aqueous sodium hydroxide is stirred at a temperature of about 60 ° C. for 20 hours. The reaction mixture is mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 5 cm 3 of water and acidified with 1 cm 3 of 2N aqueous hydrochloric acid. The mixture is again mixed under the same conditions as above and the fresh residue is triturated in a 5 cm 3 dichloromethane / methanol (vol 90/10) mixture. After filtration and the filtrate was mixed under reduced pressure (5 kPa) at a temperature of about 40 ° C., the obtained residue was triturated in 3 cm 3 of diisopropyl ether. The insoluble material is filtered off, washed twice with 1 cm 3 of diisopropyl ether and dried in air. 0.14 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-carboxylic acid Hydrochloride is obtained in the form of a beige solid which melts with softening at about 148 ° C.
[3086] Infrared spectrum (KBr): 3058 and 3013 cm ^-1 (aromatic CH v), 2934 and 2862 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1719 cm ^-1 (acid C = O v), 1618, 1600, 1541 and 1497 cm ^-1 (aromatic nucleus C = C v), 1276 cm ^-1 (acid CO v), 1251 and 1219 cm ⁻¹ (ether CO v _as ), 1022 cm ⁻¹ (ether CO v _s + alcohol CO v), 847 cm ⁻¹ (CH γ which is 4,6-disubstituted quinol), 760 cm ⁻¹ (1,2-disubstituted phenyl CH γ).
[3087] Mass spectrum (EI-m / z): = 438 (M-CO ₂ ⁺ ), 355 (MC ₆ H ₄ SF) ⁺ , 341 (MC ₇ H ₆ SF) ⁺ base peak, 297, 341 (M-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ NO ⁺ ), 128 (C ₆ H ₅ SF ⁺ ), 36 (HCl ⁺ ).
[3088] Mass spectrum (DCI): m / z = 483 (M + H) ⁺ .
[3089] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-carboxylate
[3090] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1- (2-fluorophenylthio) ethane A reaction similar to Example 4 was carried out except for using 0.17 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2 -(2-fluorophenylthio) ethyl] piperidine-3-carboxylate is obtained in the form of an orange lacquer.
[3091] Infrared spectrum (CH ₂ Cl ₂ ): 2942 cm ⁻¹ , aromatic CH v, 1727 cm ⁻¹ , C═O v, 1227 cm ⁻¹ , ether CO v, 848 cm ⁻¹ , quinoline CH γ.
[3092] Example 12
[3093] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride
[3094] 0.34 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3- 0.5 cm 3 of 5N aqueous sodium hydroxide is added to a stirred solution of 3 cm 3 methanol of carboxylate and the mixture is heated at a temperature of about 60 ° C. for 20 hours. After mixing at a temperature of about 40 ° C. under reduced pressure (5 kPa), the obtained residue is taken up in 5 cm 3 of water and then oxidized by adding 1 cm 3 of 35% hydrochloric acid. The mixture is mixed again under the same conditions as above under reduced pressure; The obtained residue is taken up in 5 cm 3 of dichloromethane / methanol (volume 90/10). The insoluble material is filtered off and the solvent is mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.35 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl] propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3-carboxylic acid Dihydrochloride is obtained in the form of a beige solid which melts with softening at about 150 ° C.
[3095] Infrared spectra (KBr): 3102 cm ^-1 (thiophene CH v), 3058-3012 cm ^-1 (aromatic CH v), 2932 and 2865 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1717 cm ^-1 (acidic C = O v), 1618, 1600, 1541 and 1496 cm ^-1 (aromatic nucleus C = C v), 1276 cm ^-1 (acidic CO v), 1250 and 1218 cm ^-1 (ether CO v _as ), 1020 cm ^-1 (ether CO v _s + alcohol CO v), 846 cm ^-1 (4, CH γ, 6-disubstituted quinol), 725 cm ⁻¹ (thiophene CH γ).
[3096] Mass spectrum (EI-m / z): 355 (MC ₄ H ₃ S ₂ ) ⁺ , 341 (MC ₅ H ₅ S ₂ ) ⁺ base peak, 297, 341 (M-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ NO ⁺ ), 115 (C ₄ H ₃ S ₂ ⁺ ).
[3097] Mass spectrum (DCI): m / z = 471 (M + H) ⁺ .
[3098] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3-carboxylate
[3099] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1- (thien-2-ylthio) ethane A reaction similar to Example 4 was carried out except that 0.34 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (Thien-2-ylthio) ethyl] piperidine-3-carboxylate is obtained in the form of a green lacquer.
[3100] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.30 to 1.90 (mt, 7H), 2.15 to 2.30 (mt, 1H), 2.35 to 2.60 (mt, 4H), 2.65 to 2.80 (mt, 2H), 3.02 (t, J = 7 Hz, 2H), 3.03 (wide t, J = 7.5 Hz, 2H), 3.54 (s, 3H), 3.95 (s, 3H), 7.06 (dd , J = 5.5 and 3.5 Hz, 1H), 7.19 (dd, J = 3.5 and 1.5 Hz, 1H), 7.32 (d, J = 4.5 Hz, 1H), 7.36 (d, J = 3 Hz, 1H), 7.42 ( dd, J = 9 and 3 Hz, 1H), 7.62 (dd, J = 5.5 and 1.5 Hz, 1H), 7.95 (d, J = 9 Hz, 1H), 8.64 (d, J = 4.5 Hz, 1H).
[3101] Example 13
[3102] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3- Carboxylic Acid Dihydrochloride
[3103] 0.51 g of methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperi The stirred solution in 15 cm 3 of methanol to which 0.86 cm 3 of 5N aqueous potassium hydroxide was added was stirred, followed by heating at a temperature of about 60 ° C. for 22 hours. The reaction mixture is mixed at about 30 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 15 cm 3 of 2-propanol to which 6 cm 3 of dichloromethane is added. 2 cm 3 of a 6N solution of hydrochloric acid in 2-propanol is poured into the resulting solution. The solvent is mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). Obtaining a solid, the solid is taken up in 15 cm 3 of 2-propanol. After 15 minutes of stirring, the insoluble material was filtered off; The cake is washed twice with 10 cm 3 of 2-propanol. The combined filtrates are concentrated at a temperature of about 30 ° C. under reduced pressure (5 kPa). 0.55 g of solid product are obtained, which are taken up in 10 cm 3 of diethyl ether. The solvent is evaporated under reduced pressure (5 kPa) at a temperature of about 40 ° C. 0.54 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine 3-carboxylic acid dihydrochloride is obtained in the form of a light brown solid which melts with softening at 116 ° C.
[3104] ¹ H NMR spectrum (600 MHz, d6- (CD ₃ ) ₂ SO, at a temperature of 373K, δ (ppm)): 1.40 to 2.30 (mt, 9H), 2.70 (mt, 2H), 2.80 to 3.70 (mts, 4H), 3.99 (s, 2H), 6.32 (wide area d, J _HF = 48 Hz, 1H), 7.15 to 7.45 (mt, 6H), 7.50 to 7.60 (mt, 2H), 8.09 (d, J = 9 Hz, 1H ), 8.82 (d, J = 5 Hz, 1 H), 10.90 to 11.40 (wide undivided peak, 1 H).
[3105] Methyl (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3 Carboxylate
[3106] 0.9 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6) at a temperature of about 20 ° C. while stirring 0.31 cm 3 of diethylaminosulfur trifluoride -Methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate is added to a solution of 5 cm 3 of dichloromethane. After 2 hours, the reaction mixture is poured into 15 cm 3 saturated aqueous sodium hydrogen carbonate solution. Extracted with 10 cm 3 of dichloromethane and twice with 5 cm 3 of dichloromethane, the organic extract was washed twice with 15 cm 3 of water, dried over magnesium sulfate, filtered and mixed under reduced pressure (5 kPa) at a temperature of about 30 ° C. do. 0.88 g of oil is obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2.5 cm; 44 g) under atmospheric pressure. Elution is performed with ethyl acetate / methanol (volume 9/1) and a 20-cm 3 fraction is collected. Fractions 5 to 10 are combined and mixed at a temperature of about 35 ° C. under reduced pressure (5 kPa). 0.57 g of methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperi Dean-3-carboxylate is obtained in the form of a yellow oil.
[3107] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3 Carboxylate was prepared under the conditions of Example 5.
[3108] Example 14
[3109] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylic acid trihydrochloride
[3110] 0.5 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl in 7.8 cm 3 of 6N hydrochloric acid ] The piperidine-3-carboxylate solution is heated at a temperature of about 100 ° C. for 2 hours with stirring. The reaction mixture was concentrated to dryness at a temperature of about 80 ° C. under reduced pressure (5 kPa), and then the obtained residue was triturated in 10 cm 3 of diisopropyl ether. The insoluble material was filtered off and dried at a temperature of about 60 ° C. under reduced pressure (13 kPa). 0.55 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylic acid Trihydrochloride is obtained as a creamy solid that melts with softening at about 165 ° C.
[3111] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 2.40 and 3.00 to 3.60 (mts, 16H), 3.62 (wide area t, J = 7.5 Hz, 2H), 4.05 (s, 3H), 7.21 (dd, J = 8 and 5 Hz, 1H), 7.43 (d, J = 8 Hz, 1H), 7.67 (wide s, 1H), 7.73 (double t, J = 8 and 1.5 Hz, 1H), 7.84 (dd, J = 9 and 2.5 Hz, 1H), 7.95 (d, J = 5 Hz, 1H), 8.45 (d, J = 9 Hz, 1H), 8.49 (wide area d, J = 5 Hz, 1H) , 9.05 (d, J = 5 Hz, 1 H), 11.25 (non-split peak, 1 H).
[3112] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylate
[3113] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1- (pyridin-2-ylthio) ethane A reaction similar to Example 4 was carried out except that 0.52 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2 -(Pyridin-2-ylthio) ethyl] piperidine-3-carboxylate is obtained in the form of a yellow oil.
[3114] Infrared spectrum (CH ₂ Cl ₂ ): 2949 cm ⁻¹ , aliphatic CH v, 1737 cm ⁻¹ , C═O v, 1227 cm ⁻¹ , ether CO v, 845 cm ⁻¹ , quinoline CH γ.
[3115] Example 15
[3116] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylic acid dihydrochloride
[3117] 0.55 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine in 8.5 cm 3 of 6N hydrochloric acid The 3-carboxylate solution is heated at a temperature of about 100 ° C. for 2 hours with stirring. After cooling, the reaction mixture was concentrated under a reduced pressure (5 kPa) at a temperature of about 80 ° C. to dryness. The obtained residue is triturated in 15 cm 3 of diisopropyl ether. After filtering off the insoluble material, the cake is washed with 10 cm 3 of diisopropyl ether. The obtained solid is dried at a temperature of about 60 ° C. under reduced pressure (13 Pa) for 2 hours. 0.51 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylic acid Dihydrochloride is obtained in the form of a beige solid which melts with softening at about 150 ° C.
[3118] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, d4-CD ₃ COOD add a few drops, at a temperature of 373K, δ (ppm)): 1.20 to 2.35 and 2.75 to 3.50 (mts, 29H) , 4.03 (s, 3H), 7.57 (mt, 1H), 7.60 to 7.75 (mt, 2H), 8.24 (d, J = 9 Hz, 1H), 8.85 (d, J = 5 Hz, 1H).
[3119] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylate
[3120] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1- (cyclohexylthio) ethane A reaction similar to Example 4 was conducted except that 0.57 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl Thio) -2-ethyl] piperidine-3-carboxylate is obtained in the form of an orange oil.
[3121] Infrared spectrum (CH ₂ Cl ₂ ): 2934 cm ⁻¹ , aliphatic CH v, 1732 cm ⁻¹ , C═O v, 1227 cm ⁻¹ , ether CO v, 848 cm ⁻¹ , quinoline CH γ.
[3122] Example 16
[3123] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-thienyl) butan-4-one] piperidine-3-carboxylic acid di Trifluoroacetate
[3124] 1.55 g of (3R, 4R) -4- [3- () in 40 cm 3 of acetone anhydride while stirring 1.76 cm 3 of 4-chloro-2′-butyrrothienone at a temperature of about 20 ° C. under inert atmosphere. 6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid ditrifluoroacetate solution is added followed by 3.86 g of potassium carbonate. The mixture is heated at a temperature of about 57 ° C. for 20 hours. After cooling the reaction mixture, the insoluble material is filtered off, then the cake is washed with 10 cm 3 of acetone and the filtrate is mixed under reduced pressure (5 kPa) at a temperature of about 40 ° C. The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4 cm; height 35 cm) at atmospheric pressure, elution is carried out with a dichloromethane / methanol (volume 90/10) mixture and a 100-cm 3 fraction Collect it. Fractions 43 to 122 are combined and then mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). An oil of 1.09 g is obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4 cm; height 35 cm) at atmospheric pressure. Elution is then carried out with a dichloromethane / methanol (volume 90/10) mixture and 100-cm 3 fractions are collected. Fractions 125 to 216 are combined and then mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). 0.48 g of oil is obtained, which is purified in the form of ditrifluoroacetate prepared from 0.1 cm 3 of trifluoroacetic acid in a mixture of 10 cm 3 of dichloromethane and 5 cm 3 of methanol. The reaction mixture was mixed (at a partial pressure of 5 kPa and at a temperature of about 40 ° C.), the obtained residue was taken up in 10 cm 3 of diethyl ether and the solid was filtered off, then 0.35 g of (3R, 4R) -4- [3- ( 6-methoxyquinolin-4-yl) propyl] -1- [4- (2-thienyl) butan-4-one] piperidine-3-carboxylic acid ditrifluoroacetate as a beige solid 90 Obtained in% Purity
[3125] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, d4-CD ₃ COOD add a few drops, at a temperature of 383 K, δ (ppm)): 1.50 to 2.25 and 2.95 to 3.55 (mts, 20H) , 3.96 (s, 3H), 7.23 (mt, 1H), 7.36 (d, J = 5 Hz, 1H), 7.40 to 7.50 (mt, 2H), 7.88 (d, J = 4 Hz, 1H), 7.92 (d, J = 5 Hz, 1H), 7.99 (d, J = 9 Hz, 1H), 8.66 (d, J = 5 Hz, 1H).
[3126] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid ditrifluoroacetate
[3127] Pure trifluoroacetic acid of 1.75 cm 3 was subjected to 1.5 g of (3R, 4R) -1- (tert-butyloxycarbonyl) -4- [3- (6 in 15 cm 3 of dichloromethane at a temperature of about 20 ° C. -Methoxy-4-quinolin-4-yl) propyl] piperidine-3-carboxylic acid is added to the stirred suspension. The resulting solution is stirred at the same temperature for 20 hours and then mixed at a temperature of about 40 ° C. under reduced pressure (5 kPa). 2.46 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid ditrifluoroacetate are obtained in the form of a brown oil.
[3128] (3R, 4R) -1- (tert-Butyloxycarbonyl) -4- [3- (6-methoxy-4-quinolin-4-yl) propyl] piperidine-3-carboxylic acid in Example 6 Prepared accordingly.
[3129] Example 17
[3130] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3-carboxylic acid dihydrochloride
[3131] 0.71 cm 3 of 5N aqueous sodium hydroxide was added to 0.46 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- Fluorophenyl) propyl] piperidine-3-carboxylate solution is added and the mixture is then heated at a temperature of about 60 ° C. for 20 hours. After cooling to a temperature of about 25 ° C., the solution is mixed at a temperature of about 40 ° C. under reduced pressure (1 kPa). 0.76 g of residue is obtained, which is taken up in 35 cm 3 of water and treated with 5.8 cm 3 of 1N hydrochloric acid. The aqueous phase is extracted five times with 10 cm 3 of dichloromethane, and the aqueous phase is mixed at a temperature of about 40 ° C under reduced pressure (1 kPa) to dryness. The obtained residue is triturated in a 10 cm 3 dichloromethane / methanol (volume 90/10) mixture. The insoluble material is filtered off and the cake is washed twice with the same mixture of 5 cm 3. The filtrate is mixed at a temperature of about 40 ° C. under reduced pressure (1 kPa). The residue is taken up in 20 cm 3 of water and the aqueous phase is extracted four times with 5 cm 3 of dichloromethane. The aqueous phase is mixed at a temperature of about 50 ° C. under reduced pressure (1 kPa) to obtain a dry phase. The obtained residue is triturated in a 5 cm 3 dichloromethane / methanol (volume 90/10) mixture. The insoluble material is filtered off and the cake is washed twice with the same mixture. The filtrate is dried over magnesium sulfate, then mixed under reduced pressure (1 kPa) at a temperature of about 40 ° C. to a dry phase and finally dried at a temperature of about 25 ° C. under partial pressure (13 Pa) for 2.5 days. 0.35 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3-carboxylic acid di Hydrochloride is obtained in a solid form such as a pale yellow foam that melts at about 194 ° C.
[3132] Infrared spectrum (KBr): 3051 to 3016 cm ^-1 (aromatic CH v), 2935 and 2869 cm ^-1 (CH ₂ v), 3000 and 2750 cm ^-1 (acidic OH v), 2800 and 1900 cm ^-1 (N ⁺ H v (tertiary amine salt + quinoline salt)), 1721 cm ^-1 (acid C = O v), 1618, 1601, 1542 and 1493 cm ^-1 (aromatic nucleus C = C v), 1276 cm ^-1 (acid CO v), 1226 cm ^-1 (ether CO v _as ), 1021 cm ^-1 (ether CO v _s ), 847 cm ^-1 (4,6-disubstituted quinoline CH γ), 764 cm ^-1 (ortho -Disubstituted phenyl CH γ).
[3133] Mass spectrum (EI-m / z): 464 (M) ⁺ , 402 (M-CO ₂ ) ⁺ , 355 (MC ₇ H ₅ F) ⁺ , 341 (MC ₈ H ₈ F) ⁺ base peak, 297 (m / z = 341-CO ₂ ) ⁺ , 186 (C ₁₂ H ₁₂ ON ⁺ ), 109 (C ₇ H ₅ F) ⁺ , 44 (CO ₂ ) ⁺ , 136 (HCl ⁺ ).
[3134] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3-carboxylate
[3135] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 3-bromo-1- (2-fluorophenyl) propane A reaction similar to that of Example 4 was conducted except that 0.47 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( 2-fluorophenyl) propyl] piperidine-3-carboxylate is obtained in the form of a pale yellow oil.
[3136] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.30 to 1.85 (mt, 9H), 2.05 to 2.35 (mt, 4H), 2.40 to 2.85 (mt, 5H), 3.03 (t, J = 7 Hz, 2H), 3.53 (s, 3H), 3.94 (s, 3H), 7.05 to 7.35 (mt, 4H), 7.32 (d, J = 5 Hz, 1H), 7.35 (d, J = 2.5 Hz, 1H), 7.40 (dd, J = 9 and 2.5 Hz, 1H), 7.93 (d, J = 9 Hz, 1H), 8.63 (d, J = 5 Hz, 1H).
[3137] Example 18
[3138] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3-carboxylic acid
[3139] 0.9 cm 3 of 5N aqueous sodium hydroxide was dissolved in 21 cm 3 of methanol in 0.58 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- To the fluorophenyl) propyl] piperidine-3-carboxylate solution, the mixture is then heated at a temperature of about 60 ° C. for 20 hours, and to the resultant is added 0.2 cm 3 of 5N aqueous sodium hydroxide. After cooling to a temperature of about 25 ° C., the solution is mixed at a temperature of about 40 ° C. under reduced pressure (1 kPa). The residue is taken up in 30 cm 3 of water and treated with 7.8 cm 3 of 1N hydrochloric acid. The aqueous phase is extracted five times with 10 cm 3 of dichloromethane, and the aqueous phase is mixed at a temperature of about 60 ° C. under reduced pressure (1 kPa) to obtain a dry phase. The obtained residue is triturated in a 10 cm 3 dichloromethane / methanol (volume 90/10) mixture. The insoluble material is filtered off and then the cake is washed twice with the same mixture of 5 cm 3. The filtrate is dried over sodium sulfate and then mixed at a temperature of about 40 ° C. under reduced pressure (1 kPa) to form a dry phase. 0.46 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3-carboxylic acid Obtained in a solid form such as a pale yellow foam that melts at about 206 ° C.
[3140] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) at a temperature of 403K): 1.35 to 2.30 and 2.75 to 3.60 (mts, 18H), 2.75 (t, J = 7.5 Hz, 2H), 3.99 (s, 3H), 7.00 (mt, 1H), 7.05 to 7.15 (mt, 2H), 7.30 to 7.40 (mt, 1H), 7.35 (d, J = 5 Hz, 1H), 7.45 (mt, 2H), 8.01 (d, J = 9 Hz, 1H), 8.67 (d, J = 5 Hz, 1H).
[3141] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3-carboxylate
[3142] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 3-bromo-1- (3-fluorophenyl) propane A reaction similar to Example 4 was carried out except that 0.58 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( 3-fluorophenyl) propyl] piperidine-3-carboxylate is obtained in the form of a dark yellow oil.
[3143] Infrared spectrum (CH ₂ Cl ₂ ): 2949 cm ⁻¹ , aliphatic CH v, 1733 cm ⁻¹ , C═O v, 1228 cm ⁻¹ , ether CO v, 848 cm ⁻¹ , quinoline CH γ.
[3144] Example 19
[3145] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3- Carboxylic acid
[3146] 3.9 cm 3 of 1N aqueous sodium hydroxide was added to 0.6 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene in 10 cm 3 of dioxane To 3--3-yl) prop-2-ynyl] piperidine-3-carboxylate solution, the mixture is then heated at a temperature of about 65 ° C. for 16 hours. After cooling the mixture, the organic phase is extracted three times with 50 cm 3 of ethyl acetate. The aqueous phase is acidified with 3.9 cm 3 of 1N hydrochloric acid. The solution was taken up in a saturated aqueous solution of 10 cm 3 of sodium bicarbonate, and then the organic phase was extracted twice with 20 cm 3 of ethyl acetate and twice with 20 cm 3 of dichloromethane, dried over sodium sulfate, filtered and then under reduced pressure (2 kPa) about 45 Concentrate at dry temperature to make it dry. 0.32 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine 3-carboxylic acid is obtained in the form of a white foam.
[3147] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 1.90 (mt, 7H), 2.43 (mt, 1H), 2.50 to 3.00 (mt, 4H), 3.04 ( Wide t, J = 7.5 Hz, 2H), 3.55 (s, 2H), 3.93 (s, 3H), 7.15 (dd, J = 5 and 1.5 Hz, 2H), 7.32 (d, J = 5 Hz, 1H), 7.35 to 7.50 (mt, 2H), 7.62 (dd, J = 5 and 3 Hz, 1H), 7.75 (dd, J = 3 and 1.5 Hz, 1H), 7.92 (d, J = 9 Hz, 1H), 8.62 (d , J = 5 Hz, 1H), from 12.00 and 13.00 (very broad undivided peak, 1H).
[3148] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3 Carboxylate
[3149] 1 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl-prop-2-ynyl] piperidine-3-carboxylate , Methyl (3R, 4R) from 0.9 g of 3-iodothiophene, 0.2 g of tetrakis (triphenylphosphine) palladium, 0.1 g of first copper iodide, 0.060 g of triphenylphosphine and 0.75 cm 3 of triethylamine Preparation of -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate The reaction is carried out as in Example 9. The residue obtained is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; column height 35 cm) at atmospheric pressure (elution is carried out with ethyl acetate to collect 40 cm 3 fractions). Fractions 18 to 49 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3 0.6 g of carboxylate are obtained in the form of a brown oil.
[3150] 3-iodothiophene is N.A. It may be prepared according to Petasis et al., Synlett., 1999, 141.
[3151] Example 20
[3152] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) prop-2-enyl] -1- (3-phenylpropyl) piperidine-3-carboxylic acid hydrochloride
[3153] 0.23 g of methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (6-methoxyquinolin-4-yl) prop-2-enyl] piperidine-3-carboxylate, A mixture of 7 cm 3 of methanol and 0.4 cm 3 of 5N aqueous sodium hydroxide is heated at 60 ° C. for 20 hours with stirring. After mixing the solvent at a temperature near 40 ° C. under reduced pressure (5 kPa), the obtained residue is taken up in 6 cm 3 of water, washed with 3 cm 3 of dichloromethane and acidified with 2 cm 3 of 1 N hydrochloric acid. The solution is mixed under the same conditions and the residue obtained is triturated in a mixture of 9 cm 3 of dichloromethane and 3 cm 3 of isopropanol. Insoluble material is filtered off and washed with 20 cm 3 of dichloromethane. The filtrate is dried over sodium sulfate and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). After drying in air, (3R, 4R) -1- (3-phenylpropyl) -4- [3- (6-methoxyquinolin-4-yl) prop-2-enyl] piperidine-3- 0.16 g of carboxylic acid hydrochloride is obtained in the form of a brown amorphous solid.
[3154] Infrared spectra (KBr): 2936 and 2857 cm ^-1 (CH ₂ ν), 2838 cm ^-1 (O-CH ₃ CH ν), 3000 and 2750 cm ^-1 (acidic OH ν), 2800 and 1900 cm ^-1 ( N ⁺ H v (tertiary amine salt + quinoline salt)), 1716 cm ^-1 (acidic C = O v), 1621, 1603, 1589, 1509 and 1473 cm ^-1 (aromatic nucleus C = C v), 1229 cm ^-1 (ether CO ν _as ), 1031 cm ^-1 (ether CO ν _s ), 969 cm ^-1 (trans CH = CH γ), 849 cm ^-1 (4,6-disubstituted quinoline CH γ).
[3155] Mass spectrum (DCI): m / z = 445 (MH ⁺ )
[3156] Methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (6-methoxyquinolin-4-yl) prop-2-enyl] piperidine-3-carboxylate
[3157] Methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (R, S) -chloro-3- (6-methoxyquinolin-4-yl) propyl] piperi in 5 cm 3 of toluene A solution of 0.25 g of din-3-carboxylate and 1.52 g of 1,8-diazabicyclo [5.4.0] undec-7-ene is brought to 110 ° C. for 4 hours. The reaction mixture is concentrated at a temperature near 50 ° C. under reduced pressure (5 kPa). The residue is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; silica mass 78.5 g) (elution is carried out with an ethyl acetate / methanol (97/3 volume) mixture under nitrogen pressure 50 kPa). 25 cm 3 fractions are collected). Fractions 71-120 were combined and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.08 g of methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (6-methoxyquinolin-4-yl) prop-2-enyl] piperidine-3-carboxylate Obtained in the form of a pale yellow lacquer.
[3158] Methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (R, S) -chloro-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3- Carboxylate can be obtained by the following method:
[3159] 0.46 cm 3 of thionyl chloride was maintained in 15 cm 3 of chloroform while maintaining the temperature at 0 ° C. To the solution of 1 g of 6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate is added dropwise. The reaction mixture is brought to a temperature near 20 ° C. under stirring over 2 hours. The reaction mixture is subsequently concentrated at a temperature near 50 ° C. under reduced pressure (5 kPa). The residue is dissolved in 30 cm 3 of distilled water, the aqueous phase is washed with 15 cm 3 of dichloromethane and basified to pH 9 with solid potassium carbonate, and finally extracted three times with 20 cm 3 of dichloromethane. The organic phases are combined, washed twice with 20 cm 3 of distilled water and then dried over magnesium sulfate. After filtration and concentration under reduced pressure (5 kPa) at a temperature near 45 ° C., methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (R, S) -chloro-3- 1.16 g of (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate are obtained in the form of a brown oil.
[3160] Methyl (3R, 4R) -1- (3-phenylpropyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Carboxylate is prepared as described in Example 5.
[3161] Example 21
[3162] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl ] Piperidine-3-carboxylic acid dihydrochloride
[3163] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- in 10 cm 3 of methanol and 1.25 cm 3 of 5 N sodium hydroxide 0.8 g of (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate is heated at a temperature near 60 ° C. for 4 hours under stirring. The reaction mixture is mixed at a temperature near 50 ° C. under reduced pressure (5 kPa). 15 cm 3 of water is added to the obtained residue, followed by 2 cm 3 of 5N aqueous hydrochloric acid. The reaction mixture is mixed again until dry. The obtained residue is triturated with a dichloromethane / methanol (90/10 volume) mixture. Sodium chloride is filtered and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature near 30 ° C. The resulting foam is triturated with ethyl ether. The solid formed is filtered off. 0.75 g of beige solid are obtained. This solid is dissolved in a mixture of 50 cm 3 of chloroform and 50 cm 3 of acetonitrile. The insoluble material is filtered and the filtrate is acidified with 20 cm 3 of 1 N hydrochloric acid solution in ether. The reaction mixture is mixed at a temperature near 30 ° C. under reduced pressure (5 kPa). The obtained residue is triturated with ethyl ether. The solid formed is filtered off and dried under vacuum. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl ] 0.7 g of piperidine-3-carboxylic acid dihydrochloride are obtained in the form of a beige solid.
[3164] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.25 to 1.90 (mt, 8H), 2.22 (mt, 2H), 2.65 to 2.90 (mt, 2H), 3.35 to 3.60 (mt, 4H), 3.91 and 3.93 (2s, 3H), 4.29 (undivided peak, 1H), 5.28 (mt, 1H); 5.50 and 5.52 (2d, J = 4.5 Hz, 1H), 7.07 (mt, 1H), 7.28 (dd, J = 4 and 1 Hz, 1H), 7.35 to 7.45 (mt, 2H), 7.50 to 7.60 (mt, 2H), 7.95 (d, J = 9 Hz, 1H), 8.71 (d, J = 5 Hz, 1H).
[3165] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) Propyl] piperidine-3-carboxylate
[3166] Under stirring, 0.16 g of sodium borohydride was added to methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6 in 20 cm 3 of methanol at a temperature below 25 ° C. -Methoxyquinolin-4-yl) propan-3-one] piperidine-3-carboxylate is added to a 1.8 g solution. The reaction mixture is stirred at room temperature for 2 hours. After mixing methanol under reduced pressure (5 kPa), the mixture is stirred with 50 cm 3 of dichloromethane and 50 cm 3 of saturated ammonium chloride solution. The organic phase is precipitated and then dried over magnesium sulfate. After filtration through paper and concentration under reduced pressure (5 kPa) at a temperature near 40 ° C., 1.6 g of product are obtained, which is subjected to silica gel column (particle size 20-45 μm; diameter 3 cm; 60 g at atmospheric pressure). Purification by chromatography on) (elution is carried out with a dichloromethane / methanol (96/4 volume) mixture to collect 10 cm 3 fractions). Collect fractions 30-45. These fractions are combined and then concentrated at approximately 40 ° C. under reduced pressure (5 kPa). Methyl (3R.4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl] piperidine-3- 1.05 g of carboxylate are obtained in the form of a mobile brown oil.
[3167] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propan-3-one] piperidine-3 Carboxylate can be prepared by the following method:
[3168] 6.44 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propan-3-one] piperidine-3-carboxylate in 100 cm 3 of acetonitrile, 2- (3- A mixture of 3.43 g of fluorophenylthio) ethyl-1-chloride, 8.85 g of potassium carbonate and 1.24 g of potassium iodide is heated at a temperature near 65 ° C. for 48 hours. After cooling, the insoluble material is filtered off. The filtrate is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The oily residue is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 6 cm; 250 g) at atmospheric pressure (elution with dichloromethane / ethyl acetate / methanol (50/50/3 volume) mixture 50 cm 3 fractions are collected). Collect fractions 19-25. These fractions are combined and then concentrated at approximately 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) -3-oxopropyl] piperidine-3 2.1 g of carboxylate are obtained in the form of a mobile brown oil. Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -3-oxopropyl] piperidine-3-carboxylate is prepared as described in Example 5.
[3169] 2- (3-fluorophenylthio) ethyl-1-chloride can be prepared by the following method:
[3170] A solution of 3.75 g of sodium hydroxide pellets in 50 cm 3 of distilled water is added dropwise to a solution of 10 g of 3-fluorothiophenol and Aliqiat 336 0.1 cm 3 in 125 cm 3 of 1,2-dichloroethane. The temperature is raised to 33 ° C. The reaction mixture is stirred at room temperature for 5 hours. The reaction mixture is settled apart. The organic phase is washed with 50 cm 3 of 0.1 N HCl and 50 cm 3 of distilled water and then dried over magnesium sulfate. After filtration through paper and concentration under reduced pressure (5 kPa) at a temperature near 40 ° C., 15 g of a residue were obtained, which was subjected to a silica gel column (particle size 20-45 μm; diameter 6 cm; 400 g at atmospheric pressure). Purification by chromatography (elution is carried out with cyclohexane to collect 100 cm 3 fractions). Collect fractions 15-40. These fractions are combined and then concentrated at approximately 40 ° C. under reduced pressure (5 kPa). 13.6 g of 2- (3-fluorophenylthio) ethyl-1-chloride are obtained in the form of a mobile colorless oil.
[3171] Example 22
[3172] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl ] Piperidine-3-carboxylic acid dihydrochloride
[3173] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- in 12 cm 3 of methanol and 1.4 cm 3 of 5 N sodium hydroxide 0.9 g of (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate is heated under stirring at a temperature near 60 ° C. for 4 hours. The reaction mixture is mixed at a temperature near 50 ° C. under reduced pressure (5 kPa). 15 cm 3 of water is added to the obtained residue, followed by 2.1 cm 3 of 5N aqueous hydrochloric acid. The reaction mixture is mixed again until dry. The residue obtained is taken in a dichloromethane / methanol (90/10 volume) mixture. Sodium chloride is filtered and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature near 30 ° C. The resulting foam is triturated with ethyl ether. The solid formed is filtered off. 0.9 g of beige solid is obtained. This solid is dissolved in a mixture of 50 cm 3 of chloroform and 50 cm 3 of acetonitrile. The insoluble material is filtered and the filtrate is acidified with 20 cm 3 of a 1 N hydrochloric acid solution in ether. The reaction mixture is mixed at a temperature near 30 ° C. under reduced pressure (5 kPa). The obtained residue is triturated with ethyl ether. The solid formed is filtered off and dried under vacuum. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl ] 0.9 g of piperidine-3-carboxylic acid dihydrochloride is obtained in the form of a beige solid.
[3174] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) with a few drops of d4-CD ₃ COOD at 600 MHz, 383 K): 1.40 to 2.25 and 2.65 to 3.65 (mts, 16H), 3.96 (s, 3 H), 6.31 (mt, J _HF = 47 Hz, 1H); 7.03 (mt, 1 H); 7.25 (mt, 2H), 7.30 to 7.45 (mt, 2H), 7.53 (mt, 1H), 7.57 (mt, 1H), 8.09 (d, J = 9 Hz, 1H), 8.82 (d, J = 5 Hz , 1H).
[3175] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) Propyl] piperidine-3-carboxylate
[3176] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) 1.7 g of propyl] piperidine-3-carboxylate is dissolved in 17 cm 3 of dichloromethane under an argon atmosphere. 0.53 cm 3 of diethylaminosulfur trifluoride is added dropwise at 20 ° C under stirring. After stirring at room temperature for 2 hours, the reaction mixture is cooled to 15 ° C. and 20 cm 3 of saturated sodium hydrogen carbonate solution is added dropwise. The organic phase is precipitated and then the aqueous phase is extracted twice with 50 cm 3 of dichloromethane. The combined organic extracts are washed twice with 50 cm 3 of distilled water and then dried over magnesium sulfate. After filtration through paper, the solution is mixed at a temperature near 30 ° C. under reduced pressure (5 kPa). 1.6 g of a brown oil is obtained, which is purified twice by chromatography on a silica gel column (particle size 24-45 μm; diameter 3 cm; 60 g) at atmospheric pressure (elution is dichloromethane / methanol (98 / 2 volumes) and a 10 cm 3 fraction is collected). For the first purification, fractions 15 to 25 are collected. For the second tablet, fractions 18-30 are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa). Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) 0.92 g of propyl] piperidine-3-carboxylate is obtained in the form of a brown oil.
[3177] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) Propyl] piperidine-3-carboxylate is obtained as described in Example 21.
[3178] Example 23
[3179] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazole-2 -Ylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride
[3180] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3 in methanol A mixture of 0.21 g of -thiazol-2-ylthio) ethyl] piperidine-3-carboxylate and 0.33 cm 3 of 5 N aqueous sodium hydroxide is heated under stirring at a temperature near 60 ° C. for 18 hours. After cooling, the reaction mixture is mixed at a temperature near 40 ° C. under reduced pressure (5 kPa); The residue is taken up in 6 cm 3 of water and then washed with 6 cm 3 of ethyl acetate. The aqueous phase is mixed at a temperature near 80 ° C. under reduced pressure (5 kPa) until dry. The residue obtained is triturated with 5 cm 3 of dichloromethane and then acidified by addition of 1 cm 3 of a 3.3 N hydrochloric acid solution in diisopropyl ether. Insoluble material is filtered off and washed twice with 3 cm 3 of a dichloromethane / methanol (90/10 volume) mixture. The filtrate is mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazole-2 0.19 g of -ylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride are obtained in the form of a beige amorphous solid which softens at approximately 75 ° C.
[3181] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) with a few drops of d4-CD ₃ COOD at 400 MHz, 373 K): 1.35 to 2.15 and 2.50 to 3.70 (mt, 16H), 3.94 (s, 3H), 5.28 (mt, 1H), 7.40 to 7.75 (mt, 5H), 7.99 (d, J = 9 Hz, 1H), 8.72 (d, J = 5 Hz, 1H).
[3182] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazole- 2-ylthio) ethyl] piperidine-3-carboxylate
[3183] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3- From thiazol-2-ylthio) ethyl] piperidine-3-carboxylate and sodium borohydride, methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6 0.17 g of -methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl] piperidine-3-carboxylate is obtained in the form of a yellow viscous oil. .
[3184] Infrared spectrum (CCl ₄ ): 3550-3150 cm ^-1 , alcohol OH ν, 2949 cm ^-1 , aliphatic CH ν, 1736 cm ^-1 , C = O ν, 1228 cm ^-1 , ether CO ν, 1031 cm ^-1 , Alcohol CO ν, 854 cm ⁻¹ , quinoline CH γ.
[3185] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl] Piperidine-3-carboxylates are methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2- ( It can be prepared similarly to Example 4 from 2-chloroethylthio) thiazole.
[3186] 2- (2-chloroethylthio) thiazole can be prepared by the following method:
[3187] 1.2 cm 3 of 1-bromo-2-chloroethane is run in a stirred solution of 1.47 g of 2-mercaptothiazole and 1.95 g of potassium carbonate in 12.5 cm 3 of dimethylformamide at a temperature near 20 ° C. The mixture is subsequently stirred at a temperature near 20 ° C. for 2 hours. Insoluble material is filtered off and washed twice with 5 cm 3 of dimethylformamide. The filtrate is run on a mixture of 50 g of crushed ice and 50 cm 3 of distilled water, then 50 cm 3 of ethyl ether is added and the mixture is stirred, followed by sedimentation. The aqueous phase is precipitated and then extracted twice with 25 cm 3 of ethyl ether. The combined ethereal phases are washed twice with 25 cm 3 of water and then dried over magnesium sulfate. After filtration through paper, the organic solution is mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). 2.11 g of 2- (2-chloroethylthio) thiazole are obtained in the form of a yellow mobile oil.
[3188] Example 24
[3189] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thiethylthio) ethyl] Piperidine-3-carboxylic acid dihydrochloride
[3190] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] A mixture of piperidine-3-carboxylate 0.45 g, methanol 3.5 cm 3 and 5 N aqueous sodium hydroxide 0.54 cm 3 is heated at a temperature near 60 ° C. for 20 hours with stirring. After mixing the solvent at a temperature near 40 ° C. under reduced pressure (5 kPa), the obtained residue is taken up in 3 cm 3 of 6N aqueous hydrochloric acid solution. The solution is mixed under the same conditions and the residue obtained is triturated with a dichloromethane / methanol (90/10 volume) mixture. Insoluble material is filtered off and washed twice with 1 cm 3 of this mixture. The filtrate is dried over sodium sulfate and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). After drying in air, (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- 0.16 g of thienylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride is obtained in the form of a beige solid which is softened at approximately 148 ° C.
[3191] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with a few drops of d4-CD ₃ COOD): 1.35 to 2.30 and 2.80 to 3.75 (mts, 16H), 3.98 and 4.00 (2s , 3H), 5.40 to 5.63 (mt, 1H), 7.05 to 7.15 (mt, 1H), 7.25 to 7.40 (mt, 1H), 7.50 to 7.80 (mt, 3H), 8.00 (mt, 1H), 8.24 (Wide) d, J = 9 Hz, 1H), 9.05 (d, J = 5 Hz, 1H).
[3192] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] Piperidine-3-carboxylate
[3193] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienyl by carrying out the reaction similar to Example 5 From thio) ethyl] piperidine-3-carboxylate and sodium borohydride, methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4 0.95 g of -yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylate is obtained in the form of an orange oil.
[3194] Infrared spectrum (CH ₂ Cl ₂ ): 3600-3150 cm ^-1 , alcohol OH ν, 2951 cm ^-1 , aliphatic CH ν, 1732 cm ^-1 , C = O ν, 1228 cm ^-1 , ether CO ν, 1031 cm ^-1 , alcohol CO ν, 847 cm ^-1 , quinoline CH γ.
[3195] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Carboxylate is methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2- (2-chloroethylthio) It can be prepared similarly to Example 4 from thiophene.
[3196] 2- (2-chloroethylthio) thiophene can be prepared by the following method:
[3197] 4.72 cm 3 of thiophene-2-thiol is run under stirring with a stirring solution of 8.25 cm 3 of 20% aqueous sodium hydroxide solution and 14.6 cm 3 of 1-bromo-2-chloroethane at a temperature near 20 ° C. The mixture is subsequently stirred at a temperature near 20 ° C. for 6 hours. 40 cm 3 of ethyl ether is subsequently added and the organic phase is washed with water and then dried over magnesium sulfate. After filtration through paper, the organic solution is mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4.5 cm; silica weight 250 g) under nitrogen pressure dropped to 50 kPa (elution is cyclohexane / ethyl acetate (95 / 5 volumes) is carried out to the mixture). 7.27 g of 2- (2-chloroethylthio) thiophene are obtained in the form of a yellow mobile oil.
[3198] Example 25
[3199] (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 -Inyl] piperidine-3-carboxylic acid dihydrochloride
[3200] 5 N aqueous sodium hydroxide 2.1 cm 3 to methyl (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1-in 15 cm 3 dioxane To a 1.3 g solution of [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is added and the solution is heated at a temperature near 60 ° C. for 16 hours. After cooling, the resulting solution is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The residue obtained was chromatographed on an amicon silica gel column (particle size 20-45 μm; diameter 4 cm; height 24 cm) under argon pressure (50 kPa) (elution was performed with chloroform, methanol and ammonia (24/12 / 1 volume) and a 30 cm 3 fraction is collected). Fractions 41 to 58 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). 1.0 g of foam is obtained, which is dissolved in 8 cm 3 of acetone. This solution is added to 5 cm 3 of a 1 N hydrochloric acid solution in ether. After stirring for 5 minutes, the solid obtained is filtered and then dried to a constant weight at a temperature near 40 ° C. under reduced pressure (2 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 820 mg of -ynyl] piperidine-3-carboxylic acid dihydrochloride are obtained in the form of a hygroscopic white solid.
[3201] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with few drops of d4-CD ₃ COOD): 1.35 to 2.30 and 2.90 to 3.65 (mts, 12H), 3.99 (s, 3H ), 4.20 to 4.50 (mt, 2H), 5.40 to 5.60 (mt, 1H), 7.25 to 7.70 (mt, 5H), 7.70 to 7.80 (mt, 1H), 7.99 (mt, 1H), 8.20 (d, J) = 9 Hz, 1H), 9.01 (broad d, J = 5 Hz, 1H).
[3202] Methyl (3R, 4R) -4- [3- (R, S) -Hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop- 2-ynyl] piperidine-3-carboxylate
[3203] 0.193 g of sodium borohydride is methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl in 30 cm 3 of methanol To a stirred solution of 2 g of prop-2-ynyl] piperidine-3-carboxylate are added in 2 fractions at a temperature near 20 ° C. under an inert atmosphere. The mixture is subsequently stirred at a temperature near 20 ° C. for 3 hours. Then 10 cm 3 of distilled water are added while maintaining the same temperature. The mixture is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 25 cm 3 of distilled water. The mixture is extracted with 150 cm 3 in total of dichloromethane. The organic phases are combined, washed three times with 30 cm 3 of water and then dried over magnesium sulfate. After filtering through the paper and then mixing the solvent under reduced pressure (5 kPa) at a temperature near 40 ° C., 1.8 g of foam were obtained, which was then subjected to an amicon silica gel column (particle size 20-45 μm; diameter at atmospheric pressure). Purification by chromatography on 3 cm; 30 cm in height (elution is carried out with ethyl acetate to collect 50 cm 3 fractions). Fractions 17 to 28 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3- (R, S) -Hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop- 1.4 g of 2-ynyl] piperidine-3-carboxylate are thus obtained in the form of a pale yellow foam.
[3204] Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine 3-carboxylate can be obtained by the following method:
[3205] 0.404 g of tetrakis (triphenylphosphine) palladium, 0.118 g of triphenylphosphine and 0.191 g of first copper iodide were methyl (3R, 4R) -4 in 40 cm 3 of acetonitrile at a temperature near 20 ° C. under an inert atmosphere. To a stirred solution of 1.97 g of-[3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate. Subsequently add 0.90 cm 3 of 3-fluoroiodobenzene, followed by 1.40 cm 3 of triethylamine. The mixture is stirred at a temperature near 20 ° C. for 15 hours and then filtered through celite. The cake is washed three times with 10 cm 3 of acetonitrile. The combined filtrates are concentrated at a temperature near 40 ° C. under reduced pressure (2 kPa). 4.3 g of oil are obtained, which are purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; height 60 cm) at atmospheric pressure (elution is carried out with ethyl acetate to yield 50 cm 3 fractions). Collected). Fractions 21 to 42 are combined and mixed at a temperature near 35 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine 2 g of -3-carboxylate are obtained in the form of a yellow oil.
[3206] Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate Can be obtained as:
[3207] 19.6 cm 3 of triethylamine is methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] pi in 150 cm 3 of anhydrous dimethylformamide at a temperature near 20 ° C under an inert atmosphere. To a stirred suspension of 15 g of ferridine-3-carboxylate dihydrochloride is added followed by 3.95 cm 3 of propargyl bromide diluted in 5 cm 3 of anhydrous dimethylformamide after 45 minutes. After stirring at a temperature near 20 ° C. for 15 minutes, the mixture is heated at a temperature near 45 ° C. for 4 hours. After cooling, the reaction mixture is poured into a mixture of 150 cm 3 of ethyl acetate and 150 cm 3 of distilled water. The mixture is stirred for several minutes and then the organic phase is settled apart. The aqueous layer is extracted twice with 150 cm 3 of ethyl acetate. The combined organic phases are washed three times with 200 cm 3 of distilled water and then dried over sodium sulfate. After filtration and mixing the solvent at a temperature near 40 ° C. under reduced pressure (2 kPa), 13.8 g of oil were obtained, which was subjected to a silica gel column (particle size 40-63 μm; diameter under argon pressure (50 kPa)). Purification by chromatography on 5 cm; 34 cm high (elution was carried out to fraction 40 with a mixture of ethyl acetate and cyclohexane (9/1 vol) followed by ethyl acetate for the next fraction, yielding a 50 cm 3 fraction. Collected). Fractions 23 to 70 are combined and then mixed at a temperature near 45 ° C. under reduced pressure (2 kPa). 8.2 g of methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate are orange Obtained in oil form.
[3208] Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate dihydrochloride can be obtained as described in Example 5. have.
[3209] Example 26
[3210] (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-3-carboxylic acid dihydrochloride
[3211] 2 cm 3 of 5 N aqueous sodium hydroxide was added to methyl (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- in 13 cm 3 of dioxane. To a solution of 1.3 g of [3- (thien-3-yl) propyl-2-ynyl] piperidine-3-carboxylate is added then the solution is heated at a temperature near 60 ° C. for 3 hours. After cooling, the resulting solution is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The obtained residue is taken up in 75 cm 3 of distilled water. The aqueous phase is washed with a total of 75 cm 3 of dichloromethane. The aqueous phase is concentrated to a volume near 10 cm 3, cooled to a temperature near 5 ° C. and then acidified to a pH near 1 with the addition of 5 N hydrochloric acid. After stirring at a temperature near 20 ° C. for 12 hours, the aqueous phase is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The obtained residue is taken up in 50 cm 3 of acetone. The resulting solution is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; height 30 cm) under argon pressure (50 kPa) (elution is a mixture of chloroform, methanol and ammonia (24 / 12/1 volume) to collect 15 cm 3 fractions). Fractions 19 to 53 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). 0.8 g of foam are obtained, which are dissolved in 7 cm 3 of dichloromethane. This solution is added to 9 cm 3 of a 1 N hydrochloric acid solution in ether. After stirring at a temperature near 20 ° C. for 5 minutes, the solid obtained is filtered off, washed with a total of 50 cm 3 of diethyl ether and then dried to a constant weight at a temperature near 40 ° C. under reduced pressure (2 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 0.92 g of -ynyl] piperidine-3-carboxylic acid dihydrochloride is obtained in the form of off-white crystals.
[3212] ¹ H NMR spectrum (400 MHz, d4-CD ₃ OD, δ (ppm)): 1.50 to 2.30 (mt, 7H), 3.06 and 3.11 (2 mts, 1H), 3.15 to 3.95 (mt, 4H), 4.03 and 4.04 (2s, 3H), 4.15 to 4.45 (mt, 2H), 5.55 and 5.66 (2 mts, 1H), 7.04 (mt, 1H), 7.37 (mt, 1H), 7.51 (d, J = 5 Hz, 1H ), 7.62 and 7.69 (2 broad s, 1H), 7.77 (dd, J = 9 and 2 Hz, 1H), 8.10 to 8.20 (mt, 2H), 8.92 and 8.94 (mt, 1H).
[3213] Methyl (3R, 4R) -4- [3- (R, S) -Hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-3-carboxylate
[3214] 0.15 g of sodium borohydride is methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) in 15 cm 3 of methanol To a stirred solution of 1.6 g of prop-2-ynyl] piperidine-3-carboxylate is added in one fraction at a temperature near 20 ° C. under an inert atmosphere. The mixture is subsequently stirred at a temperature near 25 ° C. for 2.5 h. 15 cm 3 of distilled water is then added dropwise over approximately 10 minutes while maintaining a temperature near 15 ° C. The mixture is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 20 cm 3 of distilled water. The mixture is extracted with a total of 100 cm 3 of dichloromethane. The organic phases are combined, dried over sodium sulphate and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The solid obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; height 35 cm) under argon pressure (50 kPa) (elution is a mixture of ethyl acetate and cyclohexane (8 / 2 volumes) to collect 15 cm 3 fractions). Fractions 38 to 59 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 1.3 g of -ynyl] piperidine-3-carboxylate are thus obtained in foam form.
[3215] Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine 3-carboxylate can be obtained by the following method:
[3216] 0.404 g of tetrakis (triphenylphosphine) palladium, 0.118 g of triphenylphosphine and 0.191 g of first copper iodide were methyl (3R, 4R) -4 in 40 cm 3 of acetonitrile at a temperature near 20 ° C. under an inert atmosphere. To a stirred solution of 1.97 g of-[3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate. 0.84 cm 3 of 2-iodothiophene is subsequently added followed by 1.40 cm 3 of triethylamine. The mixture is stirred at a temperature near 20 ° C. for 48 hours and then filtered through celite. The cake is washed with acetonitrile. The combined filtrates are concentrated at a temperature near 40 ° C. under reduced pressure (2 kPa). 4.2 g of oil are obtained, which are purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; height 30 cm) under argon pressure (50 kPa) (elution is carried out with ethyl acetate and cyclo 15 cm 3 fractions are collected with a mixture of hexanes (8/2 vol). Fractions 16 to 32 are combined and mixed at a temperature near 35 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine 1.6 g of 3-carboxylate are obtained in the form of an orange oil.
[3217] Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate is described in Example 25 As shown in FIG.
[3218] Example 27
[3219] (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-3-carboxylic acid monohydrochloride
[3220] 5 N aqueous sodium hydroxide 2.5 cm 3 to methyl (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- 16 cm 3 in dioxane To a solution of 1.6 g of [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate is added then the solution is heated at a temperature near 60 ° C. for 50 hours. After cooling, the resulting solution is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The obtained residue is taken up in 50 cm 3 of acetone and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3.5 cm; height 34 cm) under argon pressure (50 kPa) (elution is a mixture of chloroform, methanol and ammonia (24 / 12/1 volume) to collect 15 cm 3 fractions). Fractions 16 to 28 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (2 kPa). The solid is taken up in acetone and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). 0.72 g of foam are obtained, which are dissolved in 8 cm 3 of dichloromethane. This solution is added to 8 cm 3 of a 1 N hydrochloric acid solution in ether. After stirring at a temperature near 20 ° C. for 15 minutes, the solid obtained is filtered and then dried to a constant weight at a temperature near 40 ° C. under reduced pressure (2 kPa). (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 0.74 g of -ynyl] piperidine-3-carboxylic acid monohydrochloride are obtained in the form of off-white crystals that melt at 166 ° C.
[3221] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, temperature of 383 K, δ (ppm)): 1.68 (mt, 2H), 1.87 (mt, 1H), 1.89 (mt, 1H), 2.05 To 2.25 (mt, 3H), 3.05 to 3.45 (mt, 5H), 3.98 (s, 3H), 4.25 (limit AB, 2H), 6.31 (mt, J _HF = 16 Hz, 1H), 7.12 (dd, J) = 5 and 3.5 Hz, 1H), 7.35-7.45 (mt, 2H), 7.45-7.55 (mt, 2H), 7.64 (d, J = 5 Hz, 1H), 8.05 (d, J = 9 Hz, 1H) , 8.80 (d, J = 5 Hz, 1H).
[3222] Methyl (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-3-carboxylate
[3223] A solution of 1.14 cm 3 of sulfur diethylaminotrisulfide in 10 cm 3 of dichloromethane was added to methyl (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinoline-4 in 50 cm 3 of dichloromethane. To a solution of 3.4 g of -yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate dropwise over an inert atmosphere over approximately 15 minutes. After stirring at a temperature near 20 ° C. for 9 hours, the reaction mixture is cooled to a temperature near 10 ° C. and 60 cm 3 of saturated sodium hydrogen carbonate solution are added over approximately 15 minutes. The organic phase is precipitated and washed with a total of 300 cm 3 of distilled water. The organic phase is dried over sodium sulphate, filtered and then concentrated at a temperature near 40 ° C. under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4 cm; height 31 cm) under argon pressure (50 kPa) (elution is a mixture of ethyl acetate and cyclohexane (1 / 1 volume) to collect 15 cm 3 fractions). Fractions 34 to 65 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). The solid is taken up in acetone and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 0.74 g of 2-ynyl] piperidine-3-carboxylate are obtained in the form of a yellow oil.
[3224] Methyl (3R, 4R) -4- [3- (R, S) -Hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-3-carboxylate can be prepared as described in Example 26.
[3225] Example 28
[3226] (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 -Inyl] piperidine-3-carboxylic acid dihydrochloride
[3227] Methyl (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- in 15 cm 3 of dioxane and 2.4 cm 3 of 5N aqueous sodium hydroxide A solution of 1.48 g of [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is heated at a temperature near 60 ° C. for 17 hours. After cooling, the resulting solution is concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The obtained residue is taken up in 50 cm 3 of acetone and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2.8 cm; volume 150 cm 3) at atmospheric pressure (elution is a mixture of dichloromethane, methanol and ammonia (120/20/3 volume) 20 cm 3 fractions are collected). Fractions containing the expected product are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). The solid is taken up in 25 cm 3 of acetone and then 5 cm 3 of a 1 N hydrochloric acid solution in ether and 20 cm 3 of diethyl ether are added. After stirring at a temperature near 20 ° C. for 2 hours, the solid obtained is filtered and then dried to a constant weight at a temperature near 40 ° C. under reduced pressure (2 kPa). (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 0.6 g of -ynyl] piperidine-3-carboxylic acid dihydrochloride are obtained in the form of a solid.
[3228] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, at a temperature of 373 K, δ (ppm)): 1.55 to 1.95 (mt, 3H), 2.00 to 2.30 (mts, 4H), 3.15 to 3.50 (mt, 5H), 3.99 (s, 3H), 4.31 (limit AB, 2H), 6.38 (mt, J _HF = 47 Hz, 1H), 7.25 to 7.55 (mt, 5H), 7.55 (dd, J = 9 And 2.5 Hz, 1H), 7.60 (d, J = 5 Hz, 1H), 8.12 (d, J = 9 Hz, 1H), 8.84 (d, J = 5 Hz, 1H).
[3229] Methyl (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop- 2-ynyl] piperidine-3-carboxylate
[3230] A solution of 1.4 cm 3 of sulfur diethylaminotrisulfide in 5 cm 3 of dichloromethane was dissolved in methyl (3R, 4R) -4- [3- (R, S) -hydroxy- in 75 cm 3 of dichloromethane under inert atmosphere over approximately 15 minutes. To a temperature near 15 ° C. of 4.2 g of (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate Add dropwise to the cooled solution. After stirring at a temperature near 25 ° C. for 9 hours, 100 cm 3 of saturated sodium hydrogen carbonate solution is added while the temperature does not exceed 25 ° C. The organic phase is precipitated and washed with a total of 100 cm 3 of distilled water. The organic phase is dried over magnesium sulphate, filtered and concentrated at a temperature near 40 ° C. under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4 cm; height 42 cm) at atmospheric pressure (elution is carried out with ethyl acetate to collect 70 cm 3 fractions). Fractions 19 to 35 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (2 kPa). The solid is taken up in acetone and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop- 3.1 g of 2-ynyl] piperidine-3-carboxylate are obtained in the form of a yellow oil.
[3231] Methyl (3R, 4R) -4- [3- (R, S) -Hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop- 2-ynyl] piperidine-3-carboxylate can be prepared as described in Example 25.
[3232] Example 29
[3233] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 2-yl) prop-2-ynyl] piperidine
[3234] 4.2 cm 3 of a 20% solution of diisobutylaluminum hydride in toluene was converted to methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4 in 10 cm 3 of toluene. 0.5 g of -yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate is added to the mixture cooled to -20 ° C under stirring. Stirring is maintained at this temperature for 3 hours and then 15 cm 3 of saturated ammonium chloride solution is added, stirring is maintained for 15 minutes and then the temperature is raised to a temperature near 20 ° C. The organic phase is separated by settling, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2 cm; height 20 cm) (elution is dichloromethane under nitrogen pressure of 50 kPa, followed by a mixture of dichloromethane and methanol (95 / 5 volume) to collect 30 cm 3 fractions). Fractions 14-16 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 5 cm 3 of dichloromethane and filtered. The filtrate is concentrated under reduced pressure (2 kPa) until dry. (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene- 0.17 g of 2-yl) prop-2-ynyl] piperidine is obtained in the form of a rubber.
[3235] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.25 to 1.90 (mt, 8H), 2.22 (mt, 2H), 2.65 to 2.90 (mt, 2H), 3.35 to 3.60 (mt, 4H), 3.91 and 3.93 (2s, 3H), 4.29 (non-split peak, 1H), 5.28 (mt, 1H), 5.50 and 5.52 (2d, J = 4.5 Hz, 1H), 7.07 (mt, 1H), 7.28 (dd, J = 4 and 1 Hz, 1H), 7.35 and 7.45 (mt, 2H), 7.50 to 7.60 (mt, 2H), 7.95 (d, J = 9 Hz, 1H), 8.71 (d , J = 5 Hz, 1H).
[3236] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-thien-2-yl) prop 2-ynyl] piperidine-3-carboxylate is obtained as described in Example 26.
[3237] Example 30
[3238] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -3-hydroxymethyl-1- [2- (1, 3-thiazol-2-ylthio) ethyl] -3-piperidine
[3239] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3- From thiazol-2-ylthio) ethyl] piperidine-3-carboxylate and sodium borohydride, (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6- 0.33 g of methoxyquinolin-4-yl) propyl] -3-hydroxymethyl-1- [2- (1,3-thiazol-2-ylthio) ethyl] -3-piperidine obtained in oil form do.
[3240] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.10 to 2.20, 2.55 to 2.90 and 3.30 to 3.60 (mts, 16H), 2.60 (t, J = 6.5 Hz, 2H ), 3.93 and 3.94 (2s, 3H), 4.26 (unsplit peak, 1H), 5.27 (mt, 1H), 5.50 to 5.60 (mt, 1H), 7.35 to 7.45 (mt, 2H), 7.56 (mt, 1H) ), 7.63 (d, J = 3 Hz, 1H), 7.71 (d, J = 3 Hz, 1H), 7.95 (d, J = 9 Hz, 1H), 8.72 (d, J = 5 Hz, 1H).
[3241] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl] Piperidine-3-carboxylates are methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromine Prepared analogously to Example 4 from mother-1- (1,3-thiazol-2-ylthio) ethane.
[3242] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate is prepared as described in Example 5.
[3243] Example 31
[3244] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetic acid
[3245] 0.25 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetate in 5 cm 3 of dioxane And a mixture of 5 N aqueous sodium hydroxide 0.42 cm 3 for 9 days at a temperature near 20 ° C. The reaction mixture is concentrated at a temperature near 20 ° C. under reduced pressure (5 kPa). 0.48 g of oil are obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 1.9 cm; 28 g) at atmospheric pressure (elution is a mixture of chloroform / methanol / 28% aqueous ammonia). (12/3 / 0.5 volume) to collect 10 cm 3 fractions). Fractions 5 to 8 are combined and then mixed at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.18 g of product are obtained, which product is purified in hydrochloride form: the product is dissolved in a mixture of 5 cm 3 of diethyl ether and 1 cm 3 of acetone; 0.4 cm 3 of a 1 N hydrochloric acid solution in ether is added to the solution. The precipitate is filtered and dried for 1 hour at a temperature near 40 ° C. under reduced pressure (13 Pa). 0.13 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetic acid is a very hygroscopic creamy solid Obtained in form.
[3246] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with a few drops of d4-CD ₃ COOD): 1.30 to 2.50 and 2.75 to 3.85 (mts, 20H), 2.63 (t, J = 7.5 Hz, 2H), 3.93 (s, 3H), 7.20-7.30 (mt, 3H), 7.30 (t, J = 8 Hz, 2H), 7.38 (mt, 2H), 7.44 (dd, J = 9 and 2.5 Hz, 1H), 7.96 (d, J = 9 Hz, 1H), 8.66 (d, J = 5 Hz, 1H).
[3247] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetate
[3248] Anhydrous gaseous hydrochloric acid (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3- in 10 cm 3 of methanol Sparg in the stirred solution at a temperature near 20 ° C. of 0.3 g of acetonitrile. The mixture is subsequently diluted with 20 cm 3 of water and then poured into 15 cm 3 of saturated sodium hydrogen carbonate solution. After extracting twice with 20 cm 3 of dichloromethane, the combined extracts are washed with 25 cm 3 of water and then dried over magnesium sulfate, filtered and finally evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.27 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetate in the form of a yellow oil Obtained.
[3249] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetonitrile can be obtained by the following method Can:
[3250] 0.565 g of sodium cyanide (3R, 4R) -3-chloromethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) in 50 cm 3 of dimethyl sulfoxide To a stirring solution of 1.3 g of piperidine is added, the mixture is heated at a temperature near 60 ° C. for 20 hours. After cooling, the reaction mixture is poured into 500 cm 3 of water and then extracted twice with 200 cm 3 of diethyl ether. The combined extracts are dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2 cm; 32 g) at atmospheric pressure (elution is carried out with ethyl acetate to collect 15 cm 3 fractions). Fractions 12 to 19 are combined and then evaporated at a temperature near 40 ° C. (5 kPa). 0.34 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (phenylpropyl)] piperidine-3-acetonitrile in the form of a yellow oil Obtained.
[3251] (3R, 4R) -3-chloromethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine can be obtained by the following method :
[3252] 3.6 cm <3> of thionyl chloride (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) in 20 cm <3> of chloroform 2.9 g of ferridine is added dropwise at a temperature near 20 ° C. The mixture is heated at a temperature near 60 ° C. for 2 hours and then after cooling, it is poured into 50 cm 3 of water to which 250 g of ice is added. After separation from the chloroform phase by settling, the mixture is extracted with 100 cm 3 of dichloromethane. 5 g of sodium bicarbonate are added to the aqueous phase and then extracted twice with 200 cm 3 of dichloromethane. The organic extract is dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 1.3 g of (3R, 4R) -3-chloromethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine are obtained in the form of a brown oil .
[3253] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine oxalate is obtained by the following method Can be:
[3254] 0.25 g of (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine in 10 cm 3 of anhydrous dimethylformamide, 1-bromo-3- A mixture of 0.14 cm 3 of phenylpropane and 0.197 g of potassium carbonate is stirred for 4 hours at a temperature near 60 ° C. under a nitrogen atmosphere. 200 cm 3 of ethyl acetate is added to the reaction mixture followed by 200 cm 3 of water. The organic phase is precipitated and then washed four times with 100 cm 3 of water and once with 100 cm 3 of saturated sodium chloride solution and then dried over magnesium sulfate. After filtration and concentration under reduced pressure (5 kPa) at a temperature near 45 ° C., 0.31 g of a colorless oil is obtained, which is subjected to a silica gel column (particle size 40-63 μm; diameter 2 cm; height 20 cm). Purification by chromatography (elution is carried out with a dichloromethane / methanol (90/10 volume) mixture under nitrogen pressure 50 kPa to collect 10 cm 3 fractions). Fractions 8-12 are combined and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.243 g of 6-methoxy-4- [3- (3-hydroxymethyl-1-phenylpropyl-4-piperidyl) propyl] quinoline are obtained in the form of a colorless oil. The product is purified in the form of oxalate which is prepared in ethyl acetate. 0.243 g of (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) oxalate was melted while softening at 55 ° C It is obtained in the form of a white solid.
[3255] (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine can be obtained as described in patent application WO99 / 37635.
[3256] Example 32
[3257] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop -2-ynyl] piperidine-3-carboxylic acid
[3258] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl]-in 7.6 cm 3 of dioxane and 1.22 cm 3 of 5 N aqueous sodium hydroxide solution A solution of 0.73 g of 1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3-carboxylate is heated under stirring for 3 hours 30 minutes at a temperature near 60 ° C. After cooling to a temperature near 20 ° C., the reaction mixture is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 5 cm; silica volume 120 cm 3) under argon pressure (55 kPa) (elution is dichloromethane / methanol / acetonitrile (92 / 8/7 volumes), the mixture is first performed with 1120 cm 3). Elution is 224 cm 3 of the same mixture (but composition of 92/12/7 volumes), 224 cm 3 of the same mixture (composition of 92/16/7 volumes), 400 cm 3 of dichloromethane / methanol (50/50 volumes) mixture, finally pure Subsequently performed with 400 cm 3 of methanol. Fraction 112 cm 3 is collected and then 7 cm 3 fractions are collected. Fractions 173 to 468 are combined and then evaporated at a temperature near 35 ° C. under reduced pressure (2 kPa). A foam is obtained, which is dried for 4-5 hours at a temperature near 30 ° C. under reduced pressure (30 Pa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop 0.33 g of 2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a beige solid with a foam appearance which melts at 113-115 ° C.
[3259] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed: 1.40-1.95 and 2.30-2.95 (mts, 12H), 3.53 and 3.55 (2s, all 2H), 3.90 and 3.92 (2s, all 3H), 5.24 (mt, 1H), 5.35 to 5.65 (wide undivided peak, 1H), 7.14 (d, J = 5 Hz, 1H), 7.30 to 7.45 (mt, 2H), 7.53 and 7.55 (2d, J = 5 Hz, all 1H), 7.60 ( dd, J = 5 and 3 Hz, 1H), 7.74 (mt, 1H), 7.94 (d, J = 9.5 Hz, 1H), 8.70 (d, J = 5 Hz, 1H).
[3260] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop Ph-2-inyl] piperidine-3-carboxylate
[3261] The preparation method is methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop in 20 cm 3 of acetonitrile. From 1.2 g of 2-ynyl) piperidine-3-carboxylate, 0.067 g of triphenylphosphine, 0.227 g of tetrakis (triphenylphosphine) palladium, 0.115 g of first copper iodide and 10 cm 3 of acetonitrile, Then from methyl ethyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [from 0.84 cm 3 of triethylamine, 0.95 g of 3-iodothiophene and 5 cm 3 of acetonitrile. 3- (thien-3-yl) prop-2-ynyl] piperidine-3-carboxylate. The reaction mixture is filtered and the cake is washed with 30 cm 3 of acetonitrile. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (2 kPa). The obtained residue is taken up in 100 cm 3 of dichloromethane. The resulting organic solution is washed three times with 50 cm 3 of saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure under the same conditions as above. The residue obtained is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 4 cm; silica volume 220 cm 3) under argon pressure 55 kPa (elution is performed with ethyl acetate). A fraction of 180 cm 3 is collected and then a 10 cm 3 fraction is collected. Fractions 73 to 300 were combined and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). 0.96 g of the product are obtained, which is 0.76 g of 3-iodothiophene, 0.092 g of cuprous iodide, 0.054 g of triphenylphosphine, 0.67 cm 3 of triethylamine and 0.181 of tetrakis (triphenylphosphine) palladium g and acetonitrile at 27 cm 3 for 16 hours at a temperature near 20 ° C. The reaction mixture is filtered; The cake is washed with 30 cm 3 of acetonitrile. The filtrate is concentrated at a temperature near 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 50 cm 3 of dichloromethane; The solution is washed three times with 25 cm 3 of saturated sodium chloride solution, precipitated and separated, dried over sodium sulfate, filtered and concentrated at a temperature near 35 ° C under reduced pressure (2 kPa). 1.15 g of a residue are obtained, which are purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 4 cm; silica volume 120 cm 3) at argon pressure 55 kPa (elution is performed with ethyl acetate). do). A fraction of 110 cm 3 is collected first, followed by an 8 cm 3 fraction. Fractions 68 to 260 are combined and then concentrated at a temperature near 45 ° C. under reduced pressure (2 kPa). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop 0.73 g of p-2-ynyl] piperidine-3-carboxylate are obtained in the form of a yellow foam.
[3262] Infrared spectrum (CCl ₄ ): 3600-3200 cm ^-1 , OH ν, 2950 cm ^-1 , aliphatic CH ν, 1739 cm ^-1 , C = O ν, 1241 cm ^-1 , ether CO ν, 626 cm ^-1 , Thiophene CH γ.
[3263] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine 3-carboxylate
[3264] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate in acetonitrile 50 cm 3 2.45 g, 2.1 g potassium carbonate, 0.95 g potassium iodide and 0.6 cm 3 of propargyl bromide are stirred for 40 hours at a temperature near 20 ° C. under an inert atmosphere. After filtering the reaction mass, the filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2.5 cm; mass 50 g) (elution is carried out with ethyl acetate to collect 60 cm 3 fractions). Fractions 6-12 were combined and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3 1.35 g of carboxylate are obtained in rubber form.
[3265] Infrared spectrum (CCl ₄ ): 3600-3200 cm ^-1 , OH ν, 3311 cm ^-1 , acetylene CH ν, 2950 cm ^-1 , aliphatic CH ν, 1740 cm ^-1 , C = O ν, 1242 cm ^-1 , Ether CO ν.
[3266] 3-iodothiophene can be prepared according to N, A, Petasis et al., Synlett., 141 (1988).
[3267] Example 33
[3268] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Carboxylic Acids, Diastereomers A and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl Piperidine-3-carboxylic acid, diastereomer B
[3269] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2 dissolved in 100 cm 3 of dichloromethane 1.36 g of -thienylthio) ethyl] piperidine-3-carboxylic acid are chromatographed on a 35 cm column of 6 cm diameter packed with 700 g of silica (particle size 5-15 μm) from Daiso. Elution is carried out using a dichloromethane / methanol (92/8 volume) mixture containing 0.05% triethylamine. The flow rate is 90 cm 3 per minute and detection is carried out using ultraviolet radiation of 280 nm. This operation results in the obtaining of two diastereomers. The fraction corresponding to the first diastereomer is concentrated under reduced pressure (5 kPa) until dried at a temperature near 40 ° C. and the resulting residue is dried in an oven at a temperature near 40 ° C. under reduced pressure (13 Pa). (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- 0.28 g of carboxylic acid (diastereomer A, 0.5% dichloromethane [α] ²⁰ _D = -73.8 ° +/- 1.4) are obtained in the form of a yellow foam. The fraction corresponding to the second diastereomer is treated as above. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- 0.46 g of carboxylic acid (diastereomer B, [α] ²⁰ _D = + 71.2 ° +/- 1.2 in 0.5% dichloromethane) are obtained in the form of a yellow foam.
[3270] Diastereomer A: ¹ H NMR Spectrum (300 MHz, (CD ₃ ) ₂ SO, δ (ppm)): 1.35 to 1.75 and 1.94 (mts, 7H), 2.22 (mt, 1H), 2.36 (wide area d, J = 10.5 Hz, 1H), 2.50 to 2.65 (mt, 1H), 2.61 (t, J = 7 Hz, 2H), 2.76 (mt, 1H), 2.85 to 3.05 (mt, 1H), 2.98 (mt, 2H) ), 3.95 (s, 3H), 5.22 (mt, 1H), 5.51 (wide area d, J = 4.5 Hz, 1H), 7.07 (dd, J = 5 and 4 Hz, 1H), 7.22 (wide area d, J = 4 Hz, 1H), 7.36 (mt, 1H), 7.35-7.45 (mt, 2H), 7.64 (wide area d, J = 5 Hz, 1H), 7.95 (d, J = 9.5 Hz, 1H), 8.72 (d , J = 5 Hz, 1H).
[3271] Diastereomer B: ¹ H NMR Spectrum (300 MHz, (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 1.95 (mts, 7H), 2.22 (mt, 1H), 2.39 (wide area d, J = 10.5) Hz, 1H), 2.50-2.95 (mt, 3H), 2.60 (t, J = 7 Hz, 2H), 2.97 (mt, 2H), 3.92 (s, 3H), 5.25 (mt, 1H), 5.51 (fraction) Hal peak, 1H), 7.06 (dd, J = 5 and 3.5 Hz, 1H), 7.20 (dd, J = 3.5 and 1.5 Hz, 1H), 7.40 (mt, 2H), 7.53 (d, J = 5 Hz, 1H), 7.63 (dd, J = 5 and 1.5 Hz, 1H), 7.73 (d, J = 10 Hz, 1H), 8.70 (d, J = 5 Hz, 1H).
[3272] Example 34
[3273] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] pi Ferridine-3-carboxylic acid dihydrochloride
[3274] 1 cm 3 of aqueous 5N sodium hydroxide solution was added with methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 in 5 cm 3 methanol. To a 0.26 g solution of-[2- (tert-butylthio) ethyl] piperidine-3-carboxylate is added under stirring under an inert atmosphere. After the solution is heated to a temperature near 60 ° C. and then cooled to room temperature, the reaction mass is evaporated under reduced pressure (2.8 kPa) at a temperature near 60 ° C. The obtained residue is taken up in 5 cm 3 of distilled water and then 5 cm 3 of concentrated hydrochloric acid (d = 1.18) is added. The mixture is evaporated at a temperature near 60 ° C. under reduced pressure (2.8 kPa). The residue obtained is taken in 4 cm 3 of a dichloromethane / methanol (90/10 volume) mixture. The white precipitate obtained is filtered and washed twice with 2 cm 3 of this same mixture. The filtrate is concentrated at a temperature near 40 ° C. under reduced pressure (2.8 kPa). The product obtained is dried at a temperature near 60 ° C. under reduced pressure (16 Pa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] pi 0.29 g of ferridine-3-carboxylic acid dihydrochloride is obtained in the form of a beige solid which is softened near 169 ° C.
[3275] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) at 400 MHz, temperature 383 K). A mixture of two diastereomers is observed:
[3276] 1.34 and 1.36 (2s, all 9H), 1.40-2.35 and 2.90-3.70 (mts, 12H), 3.00 (wide t, J = 8 Hz, 2H), 3.26 (t, J = 8 Hz, 2H), 4.01 ( s, 3H), 5.40 (mt, 1H), 7.55 to 7.70 (mt, 2H), 7.82 (mt, 1H), 8.22 (d, J = 9 Hz, 1H), 8.88 (d, J = 5 Hz, 1H ), 10.90 to 11.45 (wide undivided peak, 1H).
[3277] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] Piperidine-3-carboxylate
[3278] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 in 15 cm 3 of acetonitrile and 15 cm 3 of methanol 0.717 g of carboxylate is heated with 0.43 g of 2-chloroethyl tert-butyl sulfide with stirring for 16 h at a temperature near reflux under an inert atmosphere in the presence of 0.33 g of potassium carbonate and 0.4 g of potassium iodide. After cooling the reaction mixture to a temperature near 20 ° C., the insoluble material is filtered off. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; height 35 cm) under a nitrogen pressure of 100 kPa (elution with dichloromethane / methanol (97/3 vol) mixture 35 cm 3 fractions are collected). Fractions 54 to 70 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] 0.265 g of piperidine-3-carboxylate are obtained in the form of a brown lacquer.
[3279] Infrared Spectrum ^{_{(CCl 4): 3550-3100 cm -1}} , alcoholic OH ν, 2959 cm ^-1, aliphatic ^{CHν, 1736 cm -1, C =} O ν, 1242, 1228 cm -1, ν CO ether, 1034 cm ^{- 1} , alcohol CO ν, 853 cm ⁻¹ , quinoline CH γ.
[3280] 2-chloroethyl tert-butyl sulfide can be prepared by the application of the method described in patent EP 136878.
[3281] Example 35
[3282] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Didine-3-carboxylic acid dihydrochloride
[3283] 2 cm <3> of 5N aqueous sodium hydroxide solution was dissolved in 10 cm <3> of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 To a solution of 0.48 g of-[2- (cyclopentylthio) ethyl] piperidine-3-carboxylate is added under stirring under an inert atmosphere. After heating the mixture at a temperature near 60 ° C. for 16 hours, the reaction mass is evaporated under reduced pressure (2.9 kPa) at a temperature near 60 ° C. and the residue obtained is taken in 4.3 cm 3 of distilled water with 4.3 cm 3 of 28% hydrochloric acid added. . The remaining insoluble material is filtered off and the filtrate is evaporated under the same conditions as above. The residue obtained is stirred in a dichloromethane / methanol (90/10 volume) mixture. The resulting precipitate is filtered and washed three times with 2.5 cm 3 of the same mixture. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi 0.48 g of din-3-carboxylic acid dihydrochloride is obtained in the form of a green foam which melts while softening at a temperature near 156 ° C.
[3284] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) at 400 MHz, temperature 373 K). A mixture of two diastereomers is observed:
[3285] 1.45 to 2.30 and 2.90 to 3.60 (mts, 20H), 2.98 (wide area t, J = 7.5 Hz, 2H), 3.22 (mt, 1H), 3.30 (t, J = 7.5 Hz, 2H), 4.00 (s, 3H ), 5.37 (mt, 1H), 7.50 to 7.65 (mt, 2H), 7.77 (mt, 1H), 8.17 (d, J = 9 Hz, 1H), 8.85 (d, J = 5 Hz, 1H).
[3286] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] pi Ferridine-3-carboxylate
[3287] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 in 15 cm 3 of acetonitrile and 15 cm 3 of methanol 0.717 g of carboxylate is heated with stirring with 0.439 g of 90% 2-chloroethyl cyclopentyl sulfide in the presence of 0.332 g of potassium carbonate and 0.4 g of potassium iodide for 3½ hours at a temperature near the reflux temperature under an inert atmosphere. After cooling the reaction mixture to a temperature near 20 ° C., the insoluble material is filtered off and washed with acetonitrile. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; height 45 cm) under a nitrogen pressure of 100 kPa (elution with dichloromethane / methanol (95/5 vol) mixture 35 cm 3 fractions are collected). Fractions 25 to 45 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] pi 0.48 g of ferridine-3-carboxylate is obtained in the form of a dark green lacquer.
[3288] Infrared spectrum (CCl ₄ ): 3550-3100 cm ^-1 , alcohol OH ν, 2951 cm ^-1 , aliphatic CH ν, 1736 cm ^-1 , C = O ν, 1242, 1228 cm ^-1 , ether CO ν, 1034 cm ^-1 , alcohol CO ν, 853 cm ^-1 , quinoline CH γ.
[3289] 2-chloroethyl cyclopentyl sulfide can be prepared by the application of the method described in patent application FR 2,395,260.
[3290] Example 36
[3291] (3R, 4R) -1- [2- (3-Fluolphenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid dihydrochloride
[3292] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinoline-) in 10 cm 3 of dioxane added with 0.78 cm 3 of 5 N aqueous sodium hydroxide solution A mixture of 0.48 g of 4-yl) propyl] piperidine-3-acetate is stirred at a temperature near 60 ° C. for 20 hours. After cooling to a temperature near 20 ° C., the reaction mass is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and then diluted with 10 cm 3 of water. A sufficient amount of aqueous citric acid solution is brought to pH 4. The mixture is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and the resulting residue is taken up in 70 cm 3 of water and 20 cm 3 of ethanol. The mixture is brought to pH 9 and then evaporated at a temperature near 50 ° C. under reduced pressure (5 kPa). The residue obtained is taken up in 50 cm 3 of a mixture of chloroform / methanol / 28% aqueous ammonia (12/3 / 0.5 vol) and then the inorganic salts are filtered off. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 1.2 g of product are obtained, which are purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2 cm; height 25 cm) at atmospheric pressure (elution is chloroform / methanol / 28% aqueous ammonia ( 12/3 / 0.5 volumes) to collect the first 100 cm 3 fractions, then approximately 15 cm 3 fractions). Fractions 8-18 were combined and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.31 g of the product is obtained in the form of a pale yellow foam, which is stirred with 13 cm 3 of 0.1 N aqueous hydrochloric acid at a temperature near 20 ° C. for 2 hours. After adding 5 cm 3 of dioxane and stirring for a further 2 hours at a temperature near 20 ° C., the dioxane is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The resulting solution is frozen and then lyophilized. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid dihydrochloride 0.35 g is obtained in the form of a white lyophilisate.
[3293] ¹ H NMR spectrum (400 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm) at a temperature of 383 K); 1.45 to 1.95 (mt, 8H), 2.33 (dd, J = 16 and 5.5 Hz, 1H), 2.45 to 2.60 (mt, 1H), 2.90 to 3.55 (mt, 10H), 4.00 (s, 3H), 7.06 ( Wide t, J = 8 Hz, 1H), 7.28 (d, J = 8 Hz, 2H), 7.41 (mt, 1H), 7.46 (d, J = 5 Hz, 1H), 7.48 (d, J = 2.5 Hz , 1H), 7.51 (dd, J = 9.5 and 2.5 Hz, 1H), 8.07 (d, J = 9.5 Hz, 1H), 8.72 (d, J = 5 Hz, 1H).
[3294] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate
[3295] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3- in 15 cm 3 of acetonitrile added with 1.4 g potassium carbonate and 0.15 g potassium iodide A mixture of 0.76 g of acetate and 0.42 g of 2- (3-fluorophenylthio) ethyl-1-chloride is heated with stirring for 20 hours at a temperature near 70 ° C. under an inert atmosphere. After 0.15 g of potassium iodide is added and heated for an additional 5 hours, the reaction mixture is cooled to a temperature near 20 ° C., diluted with 15 cm 3 of water and extracted twice with 20 cm 3 of ethyl acetate. The combined extracts are washed with 30 cm 3 of aqueous hydrochloric acid. The acid solution is separated and alkaline (pH 8-9) to a sufficient amount of saturated aqueous sodium hydrogen carbonate solution. The mixture is extracted twice with 30 cm 3 of ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.71 g of oil are obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2.5 cm; silica volume 120 cm 3) at atmospheric pressure (elution is dichloromethane / methanol (99/1) Volume) mixture). The fraction 500 cm 3 is collected first and then approximately 15 cm 3 fractions are collected. Fractions 10-20 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.48 g of methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate This is obtained in the form of a yellow oil.
[3296] Infrared spectrum (CH ₂ Cl ₂ ); 2934, 2861 cm ^-1 , aliphatic CH ν, 2807, 2767 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1730 cm ^-1 , ester CO ν, 1242, 1227 cm ^-1 , ether CO ν, 848 cm ^-1 , quinoline CH γ.
[3297] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate
[3298] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperi in 100 cm 3 of anhydrous methanol added with 1 cm 3 of 95% sulfuric acid A mixture of 2.8 g of din-3-acetic acid is heated with stirring for 2 hours at a temperature near the boiling point. After cooling to a temperature near 20 ° C., the reaction mass is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and 20 cm 3 of saturated aqueous sodium hydrogen carbonate solution are added to the residue obtained. The mixture is extracted four times with 20 cm 3 of dichloromethane. The combined extracts are dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 2.25 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate are obtained in the form of a brown oil.
[3299] Infrared spectrum (CH ₂ Cl ₂ ); 2954, 2865 cm ^-1 , Aliphatic CH ν, 2788 cm ^-1 , N (CH ₂ ) ₂ CH ₂ ν, 1736 cm ^-1 , Ester C = O ν, 1242, 1227 cm ^-1 , Ether CO ν, 848 cm ^-1 , quroline CH γ.
[3300] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetic acid
[3301] 1.48 g of potassium permanganate already dissolved in 45 cm 3 of distilled water, followed by 220 cm 3 of acetone in (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1-in 100 cm 3 of acetone To a solution of 2 g of (tert-butyloxycarbonyl) piperidine-3-acetaldehyde is added with stirring at a temperature near 20 ° C. under an inert atmosphere. The resulting mixture is stirred at a temperature near 20 ° C. for 2 hours and then cooled to a temperature of 0-5 ° C., followed by addition of a solution of 5 g of sodium sulfite in 150 cm 3 of water. The brown manganese dioxide precipitate is filtered through celite and the acetone is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. An amount of citric acid sufficient to result in pH 4-5 is added to the reaction mixture. The mixture is extracted twice with 100 cm 3 of ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 2.8 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetic acid are obtained in the form of a white foam. do.
[3302] Infrared spectrum (KBr); 2977, 2932, 2868 cm ^-1 , Aliphatic CH ν, 3000-2200 cm ^-1 , Acid OHν, 1734 cm ^-1 , Acid C = O ν, 1689 cm ^-1 , Carbamate C = O ν, 1391, 1365 cm ^-1 , CH ₃ δ _as , 1246 cm ^-1 , ether CO ν, 1170 cm ^-1 , carbamate CO ν, 848 cm ^-1 , quinoline CH γ.
[3303] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde
[3304] A solution of 5.6 cm 3 of dimethyl sulfoxide dissolved in 80 cm 3 of dichloromethane followed by (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinoline dissolved in 80 cm 3 of dichloromethane 4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine A solution of 13.5 g, finally a solution of 26.5 cm 3 of triethylamine dissolved in 80 cm 3 of dichloromethane was oxalyl in 80 cm 3 of dichloromethane The chloride is added to the solution cooled to a temperature near -60 ° C. of 3.5 cm 3 with continuous stirring under a nitrogen atmosphere. The resulting solution is maintained near −60 ° C. for 1 hour and then at a temperature near 20 ° C. for 3½ hours. After dilution with 150 cm 3 of dichloromethane, the reaction mixture is washed twice with 300 cm 3 of water. The organic solution separated by sedimentation is dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. 12.7 g of a brown oil are obtained, which are taken up in 400 cm 3 of diethyl ether. The resulting solution is washed twice with 300 cm 3 of water, then once with 300 cm 3 of aqueous 5% citric acid solution, and finally twice with 300 cm 3 of water. The organic solution is dried over magnesium sulfate and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 7.73 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde is a yellow viscous rubber form Is obtained.
[3305] Infrared spectrum (CCl ₄ ); 2978, 2932, 2864 cm ^-1 , aliphatic CH ν, 2717 cm ^-1 , aldehyde CHν, 1729 cm ^-1 , aldehyde C = O ν, 1694 cm ^-1 , carbamate C = O ν, 1391, 1366 cm ^-1 , CH ₃ δ _as , 1242 cm ⁻¹ , ether CO ν, 1158 cm ⁻¹ , carbamate CO ν, 844 cm ⁻¹ , quinoline CH γ.
[3306] (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine
[3307] 2 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine in 10 cm 3 of toluene and tri 0.72 cm 3 solution of ethylamine borane is stirred at a temperature near 110 ° C. under an inert atmosphere for 10 hours. The reaction mass is concentrated under reduced pressure (5 kPa) until dry at a temperature near 60 ° C. 2.1 g of orange foam are obtained, which product is dissolved in 9 cm 3 of acetone and 1.9 cm 3 of 5% aqueous hydrochloric acid is added. After the mixture is stirred at a temperature near 20 ° C. for 20 minutes, the reaction mass is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is taken as 7.5% cm 3 of tetrahydrofuran, 6.2 cm 3 of 30% aqueous sodium hydroxide solution and 7.5 cm 3 of hydrogen peroxide as a 30% aqueous solution. The mixture is heated at a temperature near reflux for 3 hours. After cooling, the reaction mixture is stirred with 30 cm 3 of chloroform at a temperature near 20 ° C. Separating the aqueous phase by settling; The organic phase is washed three times with 30 cm 3 of water and once with 20 cm 3 of saturated sodium chloride solution. After drying over magnesium sulfate, the organic solution is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 1.7 g of a tan oil is obtained, which is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; mass 60 g) at atmospheric pressure (elution is dichloromethane / methanol (95/5). Volume) and 20 cm 3 fractions are collected). Fractions 4 and 5 are combined and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine 0.95 g This is obtained in the form of an orange-yellow foam.
[3308] Infrared spectrum (KBr); 3550-3100 cm ^-1 , alcohol OH ν, 2972, 2931, 2865 cm ^-1 , aliphatic CHν, 1690 cm ^-1 , carbamate C = O ν, 1391, 1365 cm ^-1 , CH ₃ δ _as , 1244, 1228 cm ⁻¹ , ether CO v, 1158 cm ⁻¹ , carbamate CO v, 1031 cm ⁻¹ , alcohol CO v, 845 cm ⁻¹ , quinoline CH γ.
[3309] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine
[3310] 3 cm 3 of triethylamine, followed by 3.15 g of di-tert-butyl dicarbonate was added (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinyl in 50 cm 3 of dichloromethane. To a suspension of 5 g of piperidine hydrochloride is added under stirring at a temperature near 20 ° C. After 45 minutes, the resulting solution is washed twice with 30 cm 3 of water, dried over magnesium sulfate and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 6 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine are obtained in the form of a brown oil do.
[3311] Infrared spectrum (CH ₂ Cl ₂ ); 2972, 2933, 2860 cm ^-1, aliphatic CH ν, 1680 cm ^-1, carbamate C = Oν, 1391, 1365 cm -1, CH 3 δ as, 1244, 1228 cm -1, ν CO ether, 1165 cm ^{- 1} , carbamate CO ν, 845 cm ⁻¹ , quinoline CH γ.
[3312] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine hydrochloride can be obtained by the application of the method described in patent application FR 2,354,771. .
[3313] Example 37
[3314] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid dihydrochloride
[3315] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) in 8 cm 3 of dioxane in the presence of 0.5 cm 3 of 5 N aqueous sodium hydroxide solution A mixture of 0.3 g)) ethyl] piperidine-3-acetate is heated under stirring at a temperature near 60 ° C. for 20 hours. After cooling to a temperature near 20 ° C., the reaction mixture is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). A yellow foam is obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 1.6 cm; silica volume 40 cm 3) at atmospheric pressure (elution is chloroform / methanol / 28% aqueous ammonia ( 12/3 / 0.5 volumes) to collect the first 125 cm 3 fractions, then approximately 10 cm 3 fractions). Fractions 3 to 7 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.27 g of lacquer are obtained, which is taken up in 5 cm 3 of dioxane, 11 cm 3 of 0.1 N aqueous hydrochloric acid and 14 cm 3 of distilled water. Dioxane is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and the residue solution is lyophilized. 0.29 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid dihydrochloride Obtained in the form of a white lyophilisate.
[3316] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm)) at a temperature of 400 MHz, 383 K: 1.25 to 2.05 (mt, 18H), 2.33 (dd, J = 16 and 5.5 Hz, 1H) , 2.50 to 2.60 (mt, 1H), 2.83 (mt, 1H), 2.95 to 3.30 (mt, 10H), 4.00 (s, 3H), 7.45 (d, J = 5 Hz, 1H), 7.48 (d, J) = 2 Hz, 1H), 7.51 (dd, J = 9.5 and 2 Hz, 1H), 8.08 (d, J = 9.5 Hz, 1H), 8.72 (d, J = 5 Hz, 1H).
[3317] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetate
[3318] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3- in 25 cm 3 of acetonitrile added with 2.3 g of potassium carbonate and 0.55 g of potassium iodide A mixture of 1.2 g of acetate and 0.65 g of 2-chloroethyl cyclohexyl sulfide is heated with stirring for 4 hours at a temperature near 80 ° C. under an inert atmosphere. After cooling to a temperature near 20 ° C., 30 cm 3 of water is added to the reaction mixture and then extracted twice with 200 cm 3 of ethyl acetate. The combined organic extracts are washed twice with 40 cm 3 of aqueous hydrochloric acid. After sedimentation separation, the combined acid extracts are basified with saturated aqueous sodium hydrogen carbonate solution and then extracted twice with 100 cm 3 of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.80 g of a brown oil is obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 2.5 cm; silica volume 120 cm 3) at atmospheric pressure (elution is dichloromethane / methanol (99 / 1 vol) mixture was first performed to collect 250 cm 3 fractions and then to a dichloromethane / methanol (90/1 vol) mixture to collect 200 cm 3 fractions). Elution is again carried out with a dichloromethane / methanol (99/1 volume) mixture to collect approximately 10 cm 3 fractions. Fractions 10 to 33 are combined and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.30 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetate is colorless oil Obtained in form.
[3319] Infrared spectrum (CCl ₄ ); 2932, 2855 cm ^-1 , aliphatic CH ν, 2800, 2763 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1737 cm ^-1 , ester C = O ν, 1241, 1227 cm ^-1 , ether CO ν, 844 cm ^-1 , quinoline CH γ.
[3320] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate can be prepared as described in Example 36.
[3321] Example 38
[3322] (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] Piperidine-3-carboxylic acid dihydrochloride
[3323] Methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6 N aqueous hydrochloric acid in 3 cm 3 A 0.2 g solution of 2-thienylthio) ethyl] piperidine-3-carboxylate is heated under stirring at a temperature near 100 ° C. for 7 hours and then evaporated at a temperature near 50 ° C. under reduced pressure (5 kPa). The residue obtained is stirred at 10 cm 3 of diisopropyl ether. The resulting crystals are filtered off, washed twice with 5 cm 3 of diisopropyl ether and dried at a temperature near 60 ° C. under reduced pressure (13 Pa). (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] 0.22 g of piperidine-3-carboxylic acid dihydrochloride is obtained in the form of a beige solid which is softened at a temperature near 140 ° C.
[3324] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) with a few drops of d4-CD ₃ COOD at 400 MHz, 373 K). A mixture of two diastereomers is observed: 1.55-2.30 and 3.10-3.50 (mts, 15H), 3.10 (wide s, 1H), 3.98 (s, 3H), 6.31 (mt, J _HF = 48 Hz, 1H) , 7.10 (mt, 1H), 7.29 (wide area d, J = 4 Hz, 1H), 7.35-7.45 (mt, 1H), 7.45-7.60 (mt, 2H), 7.64 (wide area d, J = 5.5 Hz, 1H ), 8.06 (d, J = 9 Hz, 1H), 8.82 (d, J = 5 Hz, 1H).
[3325] Methyl (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] Piperidine-3-carboxylate
[3326] 0.16 cm 3 of diethylaminosulfur trifluoride dissolved in 2 cm 3 of dichloromethane was converted to methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy in 8 cm 3 of dichloromethane. Add 0.5 g of quinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylate to a stirred solution cooled to a temperature near 10 ° C. under an inert atmosphere. . After stirring at this temperature for 10 minutes, the mixture is brought to a temperature near 20 ° C. and stirring is continued for 18 hours. After adding 8 cm 3 of saturated aqueous sodium hydrogen carbonate solution and stirring for 15 minutes, the organic phase is precipitated and separated. The aqueous phase is extracted once with 5 cm 3 of dichloromethane and the combined organic extracts are dried over magnesium sulfate, filtered and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.5 g of a red oil is obtained, which is purified by chromatography on a silica gel column (particle size 40-63 μm; diameter 3.5 cm; silica height 35 cm) under nitrogen pressure of 100 kPa (elution is dichloromethane / methanol (97.5 / 2.5 volumes) in a mixture to collect 30 cm 3 fractions). Fractions 25 to 29 are combined and evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] 0.2 g of piperidine-3-carboxylate are obtained in the form of an orange oil.
[3327] Infrared spectrum (CCl ₄ ); 2950 cm ^-1 , aliphatic CH ν, 2804, 2767 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1737 cm ^-1 , ester C = O ν, 1243, 1229 cm ^-1 , ether CO ν, 852 cm ^-1 , quinoline CH γ.
[3328] Example 39
[3329] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3- Acetic acid dihydrochloride
[3330] 0.8 cm 3 of aqueous 5 N sodium hydroxide solution was dissolved in 10 cm 3 of dioxane in methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl To a stirred solution of 0.43 g of prop-2-ynyl] piperidine-3-acetate under an inert atmosphere. The mixture is heated at a temperature near 60 ° C. for 20 hours and then cooled to a temperature near 20 ° C., and then the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature near 45 ° C. 0.8 g of product are obtained, which is purified by chromatography on a silica gel column (particle size 20-44 μm; diameter 3 cm; silica height 30 cm) at atmospheric pressure (elution is chloroform / methanol / 28% aqueous ammonia). (12/3 / 0.5 volume) with a mixture to collect 25 cm 3 fractions). Fractions 14 to 29 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.350 g of a white solid are obtained, wherein the hydrochloride is prepared in the following manner: the resulting solid is dissolved in 5 cm 3 of dichloromethane and the resulting solution is stirred in 10 cm 3 of a 1 N hydrochloric acid solution in ether under inert atmosphere. Add. The mixture is diluted with 100 cm 3 of anhydrous ether. A white suspension is obtained, which is stirred for 3 hours at a temperature near 20 ° C. The crystals are filtered off, washed five times with 10 cm 3 of diethyl ether and then dried at a temperature near 20 ° C under partial pressure (10 Pa). (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3- 0.430 g of acetic acid dihydrochloride is obtained in the form of a white solid that softens and decomposes at around 180 ° C.
[3331] ¹ H NMR spectra (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.35 to 3.80 (mts, 16H), 4.00 (s, 3H), 4.38 and 4.43 (non-divided peak, all 2H) , 7.16 (mt, 1H), 7.46 (d, J = 3.5 Hz, 1H), 7.53 (mt, 1H), 7.64 (mt, 2H), 7.74 (d, J = 5 Hz, 1H), 8.12 (d, J = 9.5 Hz, 1H), 8.86 (undivided peak, 1H), 9.95 and 10.45 (2 broad undivided peaks, all 1H), 12.20 to 12.55 (wide undivided peak, 1H).
[3332] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3 -acetate
[3333] 0.027 g of triphenylphosphine, 0.091 g of tetrakis (triphenylphosphine) palladium, and then 0.044 g of first copper iodide were added to methyl (3R, 4R) -4- [3- (6- in 15 cm 3 of anhydrous acetonitrile. To a stirred solution of methoxyquinolin-4-yl) propyl] -1- [rop-2-ynyl] piperidine-3-acetate is added at a temperature near 20 ° C. under an inert atmosphere. After the resulting solution is stirred for 15 minutes, 0.2 cm 3 of 2-iodothiophene and 0.32 cm 3 of triethylamine are added. After stirring at a temperature near 20 ° C. for 12 hours, the reaction mixture is filtered through celite and the cake is washed five times with 10 cm 3 of acetonitrile. The combined organic extracts are evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. 1.1 g of oil are obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 4 cm; silica height 28 cm) at atmospheric pressure (elution is carried out with ethyl acetate to give 30 cm 3 fractions). Is collected). Fractions 14 to 27 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3 0.430 g of acetate are obtained in the form of a yellow viscous oil.
[3334] Infrared spectrum (CH ₂ Cl ₂ ): 2936, 2862 cm ^-1 , aliphatic CH ν, 2806, 2763 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1731 cm ^-1 , ester C = O ν, 1242, 1227 cm ⁻¹ , ether CO ν, 848 cm ⁻¹ , quinoline CH γ.
[3335] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [rop-2-ynyl] piperidine-3-acetate
[3336] 1.28 cm 3 of triethylamine, followed by 0.26 cm 3 of 97% propargyl bromide, followed by methyl (3R, 4R) -4- (3- (6-methoxyquinolin-4-yl) propyl] piperidine in 15 cm 3 of anhydrous dimethylformamide. Add 0.8 g of -3-acetate to a stirred solution at a temperature near 20 ° C. under an inert atmosphere The mixture is brought to a temperature near 45 ° C. for 6 hours and then cooled to approximately 20 ° C. After dilution with 150 cm 3 of water The mixture is extracted five times with 50 cm 3 of ethyl acetate The combined extracts are washed three times with 50 cm 3 of water, dried over magnesium sulfate, filtered and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 1 g of the residue is obtained, which is purified by chromatography on a silica gel column (particle size 20-45 μm; diameter 3 cm; silica height 27 cm) at atmospheric pressure (elution is performed with pure ethyl acetate). 50 cm 3 fractions are collected in fraction 7 Combine 10 and evaporate under reduced pressure (5 kPa) at a temperature near 40 ° C. Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [rop 0.45 g of 2-ynyl] piperidine-3-acetate are obtained in the form of a colorless viscous oil.
[3337] IR spectrum _{(CH 2 Cl 2): 3302} cm -1, acetylenic ^{CH ν, 2936, 2863 cm -1} , aliphatic ^{CH ν, 2808, 2764 cm -1} , N (CH 2) 3 CH 2 ν, 1731 cm - ¹ , ester C═O ν, 1242, 1227 cm ⁻¹ , ether CO ν, 848 cm ⁻¹ , quinoline CH γ.
[3338] Methyl (3R, 4R) -4- (3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate is prepared following the procedure described in Example 36.
[3339] Example 40
[3340] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylic acid di Hydrochloride, diastereomer A and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] Piperidine-3-carboxylic acid dihydrochloride, diastereomer B
[3341] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclo in dioxane 36 cm ³ A mixture of heptylthio) ethyl] piperidine-3-carboxylate and 2.8 cm ³ of 5N aqueous sodium hydroxide solution is heated at a temperature near 60 ° C. for 24 hours. After cooling the reaction mixture to a temperature near 20 ° C. and then concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C., the obtained residue was subjected to silica gel (particle size 20 to 45 μm; diameter 4 cm; mass 180 g). Purify by chromatography at atmospheric pressure on a column of, eluting with dichloromethane / methanol / 28% aqueous ammonia (40/5 / 0.5 vol) and collecting 50 cm ³ fractions. Three batches were obtained and evaporated at a temperature of 40 ° C. under reduced pressure (5 kPa); Batch A (0.48 g) corresponds to diastereomer A, batch B (0.6 g) corresponds to diastereomer B and batch C (0.5 g) corresponds to a mixture of two diastereomers. Batch A is purified in the following manner: after dissolving in 15 cm ³ of dichloromethane and adding to 10 cm ³ of a 1N solution of hydrochloric acid in diethyl ether, the obtained rubbery mixture is brought to a temperature near 40 ° C. under reduced pressure (5 kPa). Evaporate at The residue is taken up in 40 cm ³ of acetonitrile and 0.5N hydrochloric acid, and the resulting solution is evaporated under the same conditions described above. A white solid is obtained and the product is dried under reduced pressure (vacuum over phosphorus pentoxide, 5 kPa) for 16 hours. After stirring in diethyl ether 100 cm ³ and filtration, it is (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclo Heptylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride, 0.514 g of diastereomer A ([α] ²⁰ _D = 58.3 ° +/- 1.00, in methanol at 0.5%) are obtained in white solid form. . Treat batches B and C in the same way. Particularly batch B is (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine 0.650 g of -3-carboxylic acid dihydrochloride, diastereomer B ([a] ²⁰ _D = + 120.4 ° +/- 1.7 in methanol at 0.5%) are obtained in the form of a white solid.
[3342] Diastereomer A : ¹ H NMR Spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)):
[3343] 1.40-2.35 and 2.70-3.85 (mts, 29H), 4.01 (s, 3H), 5.50 (mt, 1H), 5.60-6.40 (wide undivided peak, 1H), 7.55 (mt, 1H), 7.75 (wide d , J = 9 Hz, 1H), 7.99 (d, J = 5 Hz, 1H), 8.30 (d, J = 9 Hz, 1H), 9.04 (d, J = 5 Hz, 1H), 10.80 (unsplit peak) , 1H).
[3344] Diastereomer B : ¹ H NMR Spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)):
[3345] 1.35 to 2.25 and 2.70 to 3.80 (mts, 29H), 4.00 (s, 3H), 5.49 and 5.55 (2 mts, 1H (all)), 5.75 to 6.20 (wide undivided peak, 1H), 7.56 and 7.62 (2 Wide s, 1H (all)), 7.71 (wide d, J = 9 Hz, 1H), 7.92 (mt, 1H), 8.24 (d, J = 9 Hz, 1H), 9.00 (d, J = 4 Hz, 1H), 10.56 (non-split peak, 1H).
[3346] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] pi Ferridine-3-carboxylate
[3347] 0.221 g of sodium borohydride in methyl (3R, 4R) -4- [3-oxo-3- (6-methoxy-quinolin-4-yl) in 20 cm ³ of methanol under inert atmosphere under stirring at a temperature near 20 ° C ) Propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate was added in portions to a mixture of 2.5 g. After addition, the mixture is stirred at a temperature near 20 ° C. for 2 hours. The reaction mixture is evaporated under reduced pressure (5 kPa) and the residue obtained is taken up in 50 cm ³ of dichloromethane and 30 cm ³ of saturated aqueous ammonium chloride solution. The precipitated separated organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C. 2.5 g of product are obtained and the product is purified by chromatography on silica gel (particle size 20-45 μm; diameter 4 cm; mass 150 g) at atmospheric pressure, elution is dichloromethane / methanol (95/5 vol) mixture 50 cm ³ fractions are collected. Fractions containing the desired product are combined and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] pi 1.95 g of ferridine-3-carboxylate are obtained in the form of a viscous oil.
[3348] Infrared spectrum (CCl ₄ ): 3500-3100 cm ^-1 , alcohol OH ν, 2930 cm ^-1 , aliphatic CH ν, 2805, 2772 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1736 cm ^-1 , ester C = O ν, 1242, 1228 cm ^-1 , ether CO ν, 1034 cm ^-1 , alcohol CO ν, 854 cm ^-1 , quinoline CH γ
[3349] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate
[3350] 3.06 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate in acetonitrile 75 cm ³ , 2-chloroethyl A mixture of 1.79 g of cycloheptyl sulfide, 5.39 g of potassium carbonate and 1.29 g of potassium iodide is heated under stirring in a nitrogen atmosphere at a temperature near 72 ° C. for 24 hours. After cooling to approximately 20 ° C., the reaction mixture is filtered through celite and the filtrate is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The residue obtained is purified by chromatography on silica gel (particle size 20-45 μm; diameter 4 cm; mass 150 g) at atmospheric pressure, elution is carried out with an ethyl acetate / methanol (95/5 vol) mixture and 50 cm ³ fractions are collected. Fractions containing the desired product are combined and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate 2.6 g are obtained in the form of a viscous oil.
[3351] Infrared spectrum (CCl ₄ ): 2930 cm ^-1 , aliphatic CH ν, 2805, 2767 cm ^-1 , N (CH ₂ ) ₃ CH ₂ ν, 1740 cm ^-1 , ester C = O ν, 1693 cm ^-1 , ketone C = O ν, 1241, 1228 cm ^-1 , ether CO ν, 850 cm ^-1 , quinoline CH γ
[3352] 2-chloroethyl cycloheptyl sulfide
[3353] 5.11 cm ³ of thienyl chloride is added dropwise to a solution of 1.74 g of 2-hydroxyethyl cycloheptyl sulfide in 30 cm ³ of chloroform at a temperature near 20 ° C. under inert atmosphere with stirring. After addition, the reaction mixture is first stirred at the same temperature for 15 minutes and then at a temperature near 60 ° C. for 1 hour. The mixture under reduced pressure (5 kPa) evaporated to dryness at a temperature of close to 40 ℃ then takes once the obtained residue was subjected to the water 2 times 50 cm ³ and then with saturated sodium hydrogen carbonate solution, 50 cm ^3. The precipitated ether solution is dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C.
[3354] Infrared spectrum (CCl ₄ ): 2930 cm ^-1 , 2855 cm ^-1 , CH ₂ ν, 1459, 1445 cm ^-1 , CH ₂ δ, 1210 cm ^-1 , C-Cl ω, 702 cm ^-1 , C-Cl ν
[3355] 2-hydroxyethyl cycloheptyl sulfide
[3356] The dimethyl formamide was 2.32 g 2-mercaptoethanol dissolved in advance in 10 cm ³ is added slowly to a stirred suspension of 60% sodium hydride in 10 cm ³ of anhydrous dimethylformamide at a temperature in the vicinity of 20 ℃ under inert atmosphere 0.91 g . After stirring for 20 minutes, 3.5 g of bromocycloheptane dissolved in 10 cm ³ of dimethylformamide is added. The reaction is terminated by stirring the reaction at a temperature near 20 占 폚 for 1 hour 30 minutes. The reaction mixture is poured into 150 cm ³ of water and 100 cm ³ of diethyl ether is added thereto. The ether phase is precipitated out and the aqueous phase is extracted once with 50 cm ³ of diethyl ether. The combined organic phases are then washed twice with 100 cm ³ of water, dried over magnesium sulfate, filtered and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 3.2 g of 2-hydroxyethyl cycloheptyl sulfide are obtained in the form of a yellow oil.
[3357] Infrared spectrum (CH ₂ Cl ₂ ): 3608, 3457 cm ^-1 , OH (glass and bond) ν, 2927, 2855 cm ^-1 , aliphatic CH ν, 1057 cm ^-1 , CO ν
[3358] Example 41
[3359] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid dihydrochloride
[3360] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine- ³ in dioxane 13 cm ³ A stirring mixture of 0.598 g of acetate and 1 cm ³ of 5N aqueous sodium hydroxide solution is heated at 60 ° C. for 20 hours in an inert atmosphere. After evaporation of the reaction mixture under reduced pressure (5 kPa) at a temperature near 50 ° C., 1 g of a yellow foam was obtained, which product was subjected to silica gel (particle size 20 to 45 μm; diameter 3 cm; silica height 21 cm) column Purification by chromatography at atmospheric pressure, elution is carried out with a mixture of chloroform / methanol / 28% aqueous ammonia (12/3 / 0.5 volume) and 50 cm ³ fractions are collected. Fractions 4 to 7 are combined and then evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.495 g of product are obtained, which are dissolved in 5 cm ³ of dichloromethane. After adding 10 cm ³ of a 1N solution of hydrochloric acid in ether, a pasty precipitate is obtained, which is diluted with 100 cm ³ of diethyl ether. The mixture is stirred at a temperature near 20 ° C. The white suspension obtained is filtered and washed three times with 30 cm ³ of diethyl ether. The resulting white solid is dried under reduced pressure (10 kPa) at a temperature near 40 ° C. until a certain weight is obtained. (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid dihydrochloride 0.55 g is obtained in the form of a white solid which melts while softening around 200 ° C.
[3361] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) at a temperature of 400 MHz, 383 K):
[3362] 1.40 to 1.95 (mt, 8H), 2.30 (dd, J = 16 and 5.5 Hz, 1H), 2.45 to 2.60 (mt, 1H), 3.00 to 3.35 (mt, 10H), 4.00 (s, 3H), 7.08 ( dd, J = 5 and 3.5 Hz, 1H), 7.28 (wide area d, J = 3.5 Hz, 1H), 7.45 to 7.55 (mt, 2H), 7.56 (dd, J = 9.5 and 3 Hz, 1H), 7.62 ( Wide area d, J = 7 Hz, 1H), 8.15 (d, J = 9.5 Hz, 1H), 8.75 (d, J = 5 Hz, 1H).
[3363] Example 41A
[3364] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl) piperidine-3-acetate
[3365] 4.06 g of potassium carbonate, followed by 1 g of potassium iodide, is placed under an inert atmosphere, in methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate 2.1 to a stirred solution of 1.15 g of 2- (2-chloroethylthio) thiophene in g and acetonitrile 50 cm ³ . The mixture is heated at 70 ° C. for 20 hours. After cooling to a temperature of about 20 ℃, then the reaction mixture was diluted with ethyl acetate, 100 cm ³ of water and 100 cm ^3. The mixture is stirred and the organic phase is precipitated and the aqueous phase is extracted twice with 50 cm ³ of ethyl acetate. The organic phases are combined and extracted three times with 50 cm ³ of IN aqueous hydrochloric acid. Combine the acid solutions and bring to pH 8 with sufficient sodium bicarbonate. The resulting oil is extracted three times with 100 cm ³ of ethyl acetate. The combined extracts are dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. 1.5 g of an orange oil are obtained, which product is chromatographed at atmospheric pressure on silica gel (particle size 20 to 45 μm; diameter 3 cm; silica height 55 cm) on column, elution is carried out with pure ethyl acetate and 50 cm ³ fractions are collected. Fractions 12 to 30 are combined and then evaporated under the same conditions as above. 0.60 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate Obtained in the form of a colorless viscous oil.
[3366] Infrared spectrum (CH ₂ Cl ₂ ): 2933, 2861 cm ⁻¹ , aliphatic CH ν, 2803, 2766 cm ⁻¹ , N (CH ₂ ) ₃ CH ₂ ν, 1730 cm ⁻¹ , ester C═O ν, 1242, 1277 cm ^-1 , ether CO ν, 847 cm ^-1 , quinoline CH γ
[3367] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate is prepared following the procedure described in Example 36.
[3368] Example 42
[3369] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ylene) piperidine-3-carboxylic acid hydrochloride
[3370] Preparation was carried out similarly to the method described in Example 32, to give (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2 -Ylene) piperidine-3-carboxylic acid hydrochloride is prepared in an off-white solid form.
[3371] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 2.40 and 2.90 to 3.90 (mts, 14H), 3.95 (mt, 2H), 4.03 (s, 3H), 6.46 (dt, J = 7.5 Hz, 1H), 6.84 (d, J = 16 Hz, 1H), 7.30-7.50 (mt, 3H), 7.53 (wide area d, J = 7.5 Hz, 2H), 7.63 (mt, 1H), 7.75 (dd, J = 9.5 and 2 Hz, 1H), 7.84 (d, J = 5.5 Hz, 1H), 8.31 (d, J = 9.5 Hz, 1H), 8.99 (d, J = 5.5 Hz, 1H), 10.93 (unsplit peak, 1H).
[3372] Example 43
[3373] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid, Diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Didine-3-carboxylic acid, diastereomer B
[3374] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy dissolved in 100 cm ³ of a dichloromethane / ethanol / tetrahydrofuran (65/15/20 volume) mixture 5 g of quinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid packed with 1,200 kg of Kromasil ^R silica (particle size 10 μm) length 35 cm, diameter Chromatography on a column of 8 cm. Elution is carried out using the same mixture as above. The flow rate is 150 cm ³ per minute for the first 30 minutes and subsequently 200 cm ³ per minute. Detection is performed using ultraviolet light at 280 nm. This operation yields two diastereomers. The first fraction is concentrated to dryness under reduced pressure (5 kPa) at a temperature around 40 ° C. A solid residue is obtained which is taken up in diethyl ether and filtered and dried at a temperature near 20 ° C. in air. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid, 1.5 g of Diastereomer A ([a] ²⁰ _D = -47.1 ° +/- 0.9 at 0.5% in dichloromethane are obtained in the form of a beige solid. The fraction corresponding to the second diastereomer is treated as above.
[3375] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid, 1.7 g of diastereomer B ([a] ²⁰ _D = + 98.7 ° +/- 1.6, in dichloromethane at 0.5%) are obtained in the form of a beige solid.
[3376] Diastereomer A : ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.10 to 2.05 (mts, 17H), 2.33 (very broad t, J = 10 Hz, 1H) , 2.45 (wide d, J = 10 Hz, 1H), 2.59 (undivided peak, 1H), 2.60 to 2.80 (mt, 5H), 2.90 (wide d, J = 10 Hz, 1H), 3.06 (wide d, J = 10 Hz, 1H), 3.96 (s, 3H), 5.22 (very wide d, J = 7 Hz, 1H), 5.40 to 5.70 (wide undivided peak, 1H), 7.30 to 7.45 (mt, 2H), 7.57 (d, J = 4.5 Hz, 1H), 7.94 (d, J = 9 Hz, 1H), 8.72 (d, J = 4.5 Hz, 1H), 12.50 to 13.40 (very broad undivided peak, 1H).
[3377] Diastereomer B : ¹ H NMR Spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.10 to 2.00 (mts, 17H), 2.33 (mt, 1H), 2.40 to 2.55 (mt, 1H), 2.57 (wide s, 1H), 2.60 to 2.80 (mt, 5H), 2.82 (mt, 1H), 2.99 (mt, 1H), 3.92 (s, 3H), 5.25 (mt, 1H), 5.40 to 5.70 (wide undivided peak, 1H), 7.35 to 7.45 (mt, 2H), 7.53 (d, J = 4.5 Hz, 1H), 7.94 (d, J = 10 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H), 12.40-13.50 (very broad undivided peak, 1H).
[3378] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Dean-3-carboxylic acid is prepared from its hydrochloride according to the following process.
[3379] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi Didine-3-carboxylic acid dihydrochloride
[3380] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi 0.4 g of din-3-carboxylate are heated in 3 cm ³ of methanol and to it are added 0.48 cm ³ of 5N aqueous sodium hydroxide solution under inert atmosphere for 16 hours. After the reaction mass was concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C., the obtained residue was taken up in 5 cm ³ of 6N hydrochloric acid and then in 2.5 cm ³ of methanol. The brown solution obtained is evaporated under the same conditions as above. The resulting residue is taken up in 5 cm ³ of diisopropyl ether, filtered and washed twice with 3 cm ³ of the same solvent. The solid obtained is dried under reduced pressure (13 Pa) at a temperature near 60 ° C. (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperi 0.37 g of din-3-carboxylic acid dihydrochloride are obtained in the form of a brown solid which is softened at around 170 ° C.
[3381] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) at 400 MHz, temperature 383 K). A mixture of two diastereomers is observed:
[3382] 1.20 to 2.25 and 2.80 to 3.40 (mts, 25H), 3.28 (t, J = 8 Hz, 2H), 4.00 (s, 3H), 5.36 (mt, 1H), 7.50 to 7.65 (mt, 2H), 7.70 ( mt, 1H), 8.13 (wide area d, J = 9 Hz, 1H), 8.81 (d, J = 5 Hz, 1H).
[3383] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] pi Ferridine-3-carboxylate
[3384] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine in 9 cm ³ of acetonitrile and 1 cm ³ of methanol A stirred mixture of 0.54 g of 3-carboxylate, 0.295 g of 2-chloroethyl cyclohexyl sulfide, 0.23 g of potassium carbonate and 0.27 g of potassium iodide is brought to a temperature near the boiling point for 20 hours under an inert atmosphere. The reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C. The residue obtained was purified by chromatography under silica gel (particle size 40-63 μm; diameter 3.5 cm; silica height 35 cm) column under 80 kPa argon pressure, and the elution was carried out with a dichloromethane / methanol (95/5 volume) mixture. 35 cm ³ fractions are collected. Fractions 23 to 40 are combined and then concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] pi 0.4 g of ferridine-3-carboxylate is obtained in the form of a brown lacquer.
[3385] Infrared spectrum (CCl ₄ ): 3600-3200 cm ^-1 , OH ν, 2932, 2854 cm ^-1 , aliphatic CH ν, 1736 cm ^-1 , C = O ν, 1242 cm ^-1 , ether CO ν
[3386] Example 44
[3387] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] py Ferridine-3-carboxylic acid, diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene -2-yl) prop-2-ynyl] piperidine-3-carboxylic acid, diastereomer B
[3388] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline) dissolved in 100 cm ³ of a dichloromethane / methanol / acetonitrile (85/8/7 volume) mixture -4-yl) propyl] -1- [3- (thienyl-2-yl) prop-2-ynyl] piperidine-3-carboxylic acid to 1,200 kg of Kromasil ^R silica (particle size 10 μm) Chromatography is performed on packed columns of 35 cm in length and 8 cm in diameter. Elution is carried out using the same mixture as above. Detection is performed using ultraviolet light at 280 nm. This operation yields two diastereomers. The first fraction is concentrated to dryness under reduced pressure (5 kPa) at a temperature around 40 ° C. A solid residue is obtained, which is dried under reduced pressure (23 Pa) at a temperature near 20 ° C. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] py 0.612 g of ferridine-3-carboxylic acid, diastereomer A ([a] ²⁰ _D = -67.5 ° +/- 1.3, in dichloromethane at 0.5%) are obtained in the form of a white foam. The fraction corresponding to the second diastereomer is treated as above.
[3389] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] py 0.596 g of ferridine-3-carboxylic acid, diastereomer B ([a] ²⁰ _D = -106.0 ° +/− 1.6, in dichloromethane at 0.5%) is obtained in the form of a white foam.
[3390] Diastereomer A : ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.40 to 1.95 (mt, 7H), 2.40 (mt, 1H), 2.50 to 2.60 (mt, 1H), 2.60 to 2.80 (mt, 2H), 2.90 (unsplit peak, 1H), 3.63 (s, 2H), 3.94 (s, 3H), 5.24 (mt, 1H), 5.52 (mt, 1H), 7.08 (dd, J = 5 and 4 Hz, 1H), 7.31 (dd, J = 4 and 1 Hz, 1H), 7.35 (d, J = 3 Hz, 1H), 7.40 (dd, J = 9 and 3 Hz, 1H ), 7.56 (d, J = 4.5 Hz, 1H), 7.59 (dd, J = 5 and 1 Hz, 1H), 7.95 (d, J = 9 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H) ).
[3391] Diastereomer B : ¹ H NMR Spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 1.95 (mt, 7H), 2.38 (mt, 1H), 2.50 to 2.75 (mt, 3H), 2.71 (non-split peak, 1H), 3.58 (s, 2H), 3.90 (s, 3H), 5.25 (mt, 1H), 5.52 (mt, 1H), 7.07 (dd, J = 5 and 3.5 Hz , 1H), 7.29 (broad d, J = 3.5 Hz, 1H), 7.30-7.45 (mt, 2H), 7.53 (d, J = 4.5 Hz, 1H), 7.58 (broad d, J = 5 Hz, 1H) , 7.94 (d, J = 10 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H).
[3392] Example 45
[3393] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl Piperidine-3-carboxylic acid
[3394] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4- in 5 cm ³ dioxane added with 5N aqueous sodium hydroxide solution 0.51 cm ³ The solution of 0.460 g of 1) propyl] -1- [2- (5-chlorothien-2-yl)] piperidine-3-carboxylate is stirred for 48 hours at a temperature near 60 ° C. After adding 1 cm ³ of 5N sodium hydroxide solution, the mixture is heated again for 72 hours at a temperature near 70 ° C. The reaction mixture was evaporated under reduced pressure (5 kPa) at a temperature near 45 ° C. and the residue obtained was then chromatographed under 40 kPa nitrogen pressure on a column of silica gel (particle size 40 to 63 μm; diameter 3 cm; silica height 27 cm) column. Purification with, elution is carried out with a dichloromethane / methanol / 28% aqueous ammonia (14/4 / 0.6 volume) mixture and 15 cm ³ fractions are collected. Fractions 7-16 are evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (chlorothien-2-yl)] 0.30 g of piperidine-3-carboxylic acid is obtained in the form of a white foam.
[3395] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed:
[3396] 1.40 to 3.10 (mts, 16H), 3.92 and 3.95 (2s, 3H (all)), 5.23 (mt, 1H), 5.50 (mt, 1H), 7.05 to 7.15 (mt, 2H), 7.30 to 7.45 (mt, 2H), 7.52 and 7.54 (2 d, J = 5 Hz, 1H (all)), 7.94 (mt, 1H), 8.70 (d, J = 5 Hz, 1H).
[3397] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothiene-2- I)] piperidine-3-carboxylate
[3398] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine in 40 cm ³ of acetonitrile and 10 cm ³ of methanol A solution of 1 g of -3-carboxylate is stirred at a temperature near 20 ° C. and then 1.16 g of potassium carbonate and 0.5 g of potassium iodide are added. 1 g of 2-chloro-5- (2-chloroethylthio) thiophene and 10 cm ³ of acetonitrile are added to the resulting suspension. The mixture is stirred at a temperature near 80 ° C. for 72 hours. The reaction mass is poured into 75 cm ³ of ethyl acetate and then washed three times with 70 cm ³ of water. The organic phase is dried over sodium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 45 ° C. The residue obtained is purified by chromatography under silica gel (particle size 20-40 μm; diameter 3.5 cm; silica height 31 cm) column under 40 kPa nitrogen pressure, elution is carried out with ethyl acetate and a 30 cm ³ fraction is collected. . Fractions 24 to 52 are combined and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (chlorothien-2-yl) ] 0.48 g of piperidine-3-carboxylate are obtained in the form of a brown oil.
[3399] Mass spectrum: (CI) m / z, 535 MH ⁺
[3400] 2-chloro-5- (2-chloroethylthio) thiophene
[3401] 28 cm ³ of 5N aqueous sodium hydroxide solution was added to a 17.9 g solution of 2-chloro-5-thiopentthiol in 30 cm ³ of 1-chloro-2-bromoethane cooled to a temperature near 5 ° C under stirring, followed by temperature Return to around 20 ° C. during which stirring is continued for 16 h. The reaction mixture is diluted with 300 cm ³ of ethyl acetate and washed three times with 150 cm ³ of water. The organic solution is dried over sodium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 45 ° C. 20.6 g of 2-chloro-5- (2-chloroethylthio) thiophene are obtained in the form of a brown oil.
[3402] Mass spectrum: DCI m / z = 535 MH ⁺
[3403] 2-chloro-5-thiopentthiol was prepared from E. Jones and M. Moodie, Tetrahedron, 1965, vol. 21, 1333-1336.
[3404] Example 46
[3405] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid
[3406] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -fluoro- in 2 cm ³ of water and 10 cm ³ of acetone A mixture of 0.4 g of 3-phenylpropyl] piperidine-3-carboxylate and 0.18 g of lithium hydroxide monohydrate was stirred at a temperature of around 20 ° C. for 3 days and then at a temperature of 40 ° C. under reduced pressure (5 kPa). Evaporate. The residue obtained is purified by chromatography under silica gel (particle size 20-45 μm; diameter 3 cm; 50 g) column under 50 kPa argon pressure, elution is carried out with a dichloromethane / methanol (95/5 volume) mixture. 910 cm ³ fractions are collected. Then eluted with a dichloromethane / methanol (90/10 volume) mixture and a 13 cm ³ fraction was collected. Fractions 47 to 69 are combined and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The evaporated residue is taken up in dichloromethane, filtered and concentrated under the same conditions as above. The product obtained is stirred for 10 min at 10 cm ³ of diisopropyl ether. The crystals are filtered off and washed once with 5 cm ³ of diisopropyl ether and 3 times with 5 cm ³ of pentane. 0.13 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid Obtained in the form of a gray solid with a melting point of 60 ° C. corresponding to one of the isomers.
[3407] ([α] ²⁰ _D = +37.5 +/- 0.9 at 0.5% in methanol)
[3408] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.45 to 3.10 (mts, 16H), 3.02 (broad t, J = 7 Hz, 2H), 4.04 (s, 3H ), 5.59 (mt, J _HF = 48 Hz, 1H), 7.32 (d, J = 4.5 Hz, 1H), 7.35 to 7.50 (mt, 7H), 7.42 (d, J = 9 Hz, 1H), 8.62 ( d, J = 4.5 Hz, 1H).
[3409] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -fluoro-3-phenylpropyl] piperidine-3 Carboxylate
[3410] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) in dichloromethane 17.7 cm ³ in a diethylaminosulfur trifluoride 0.425 cm ³ at a temperature near 20 ° C. under an inert atmosphere. Propyl] -1- [3- (R, S) -hydroxy-3-phenylpropyl] piperidine-3-carboxylate is added to 1.18 g of a stirred solution. After stirring for 3 hours, the mixture is poured into 32 cm ³ of saturated aqueous sodium hydrogen carbonate solution. Dichloromethane 15 cm ³ is added and the mixture is stirred for a further 10 minutes. After settling separation, the organic phase is separated off, and the aqueous phase is extracted three times with 10 cm ³ of dichloromethane. The combined organic extracts are washed three times with 20 cm ³ of water, dried over sodium sulphate, filtered and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 1.11 g of residue are obtained, which product is chromatographed under 50 kPa argon pressure on a silica column (particle size 20 to 45 μm; diameter 2.8 cm; silica 45 g) and the elution is ethyl acetate / methanol (98/2 Volume) and 15 cm ³ fractions are collected. Fractions 10-20 were combined and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -fluoro-3-phenylpropyl] piperidine-3 0.6 g of carboxylate are obtained in the form of a pale yellow thick oil.
[3411] Infrared spectra (CH ₂ Cl ₂ ): 2951, 1732, 1621, 1509, 1473, 1227, 1167,1031 and 848 cm ^-1
[3412] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -hydroxy-3-phenylpropyl] piperidine-3 Carboxylate can be prepared similarly to the method described in Example 1.
[3413] Example 47
[3414] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl ] Piperidine-3-carboxylic acid trihydrochloride
[3415] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine-) in 6.66 cm ³ methanol To a solution maintained at a temperature near 20 ° C. of 0.33 g of 2-ylthio) ethyl] piperidine-3-carboxylate is added 1.33 cm ³ of 5N aqueous sodium hydroxide solution under nitrogen atmosphere with stirring. The resulting solution is heated at around 60 ° C. for 16 hours. The reaction mass is evaporated to dryness at a temperature near 60 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 3.4 cm ³ of distilled water, followed by 3.43 cm ³ in 35% concentrated aqueous hydrochloric acid. A yellow solution is obtained, which is evaporated under the same conditions as above. The evaporation residue is taken up in 10 cm ³ of a dichloromethane / methanol (80/20 vol) mixture. The resulting insoluble material is filtered off and washed twice with a 2.5 cm ³ dichloromethane / methanol (90/10 volume) mixture. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-pyridin-2-ylthio) ethyl] 0.40 g of piperidine-3-carboxylic acid trihydrochloride is obtained in the form of a beige solid having a melting point of 155 ° C.
[3416] ¹ H NMR spectrum (400 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm) at a temperature of 383 K). A mixture of two diastereomers is observed:
[3417] 1.50 to 2.30 and 3.15 to 3.65 (mts, 16H), 4.00 (s, 3H), 5.38 (mt, 1H), 7.18 (wide dd, J = 8 and 5 Hz, 1H), 7.38 (d, J = 8 Hz , 1H), 7.55 to 7.65 (mt, 2H), 7.69 (t, J = 8 and 2 Hz, 1H), 7.80 (mt, 1H), 8.20 (wide area d, J = 10 Hz, 1H), 8.48 (dmt , J = 5 Hz, 1H), 8.35 (wide area d, J = 5 Hz, 1H).
[3418] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) Ethyl]] piperidine-3-carboxylate
[3419] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] pi in methanol 15 cm ³ A stirred solution of 0.77 g of ferridine-3-carboxylate is cooled to a temperature near 0 ° C. under an inert atmosphere. 0.063 g of sodium borohydride is added and after 15 minutes the temperature is returned to around 20 ° C. for 16 hours. After adding 5 cm ³ of saturated aqueous ammonium chloride solution, the mixture is stirred for 10 minutes and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The obtained residue is taken up in 10 cm ³ of a dichloromethane / methanol (95/5 volume) mixture and filtered. Insoluble material is washed twice with 5 cm ³ of the same mixture. The filtrate is evaporated under the same conditions as above. A foam is obtained, which product is purified by chromatography under silica gel (particle size 40 to 63 μm; diameter 3.5 cm; silica height 35 cm) column under 100 kPa nitrogen pressure, and the elution is dichloromethane / methanol (96/4 Volume) and a 35 cm ³ fraction is collected. After the first 50 fractions, the elution is carried out with a dichloromethane / methanol (90/10 volume) mixture. Fractions 61-90 were combined and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) 0.33 g of ethyl] piperidine-3-carboxylate are obtained in the form of a beige lacquer.
[3420] Infrared spectra (CH ₂ Cl ₂ ): 2596, 2951, 1622, 1579, 1508, 1455, 1415, 1242, 1228, 1125, 1031, 856 and 831 cm ^-1
[3421] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3 Carboxylate
[3422] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (2-chloroethyl) piperidine-3- in 20 cm ³ of acetonitrile A mixture of 1.35 g of carboxylate dihydrochloride is stirred under an inert atmosphere at a temperature near 20 ° C. 1.37 g of potassium carbonate and 0.456 g of potassium iodide are added, followed by 0.367 g of 2-mercaptopyridine and 1 cm ³ of methanol. A red suspension is obtained, which is heated at a temperature near 80 ° C. for 1 hour 30 minutes. After cooling the reaction mass to a temperature around 20 ° C., the insoluble material is filtered off and washed with acetonitrile. The filtrate is evaporated at a temperature near 40 ° C. under reduced pressure (5 kPa). The evaporation residue is purified by chromatography under silica gel (particle size 40-63 μm; diameter 3.5 cm; silica height 35 cm) column under 100 kPa nitrogen pressure and elution is carried out with an ethyl acetate / methanol (95/5 volume) mixture. 35 cm ³ fractions are collected. Fractions 19-40 were combined and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3 0.77 g of carboxylate are obtained in the form of a red viscous oil.
[3423] Infrared spectrum (CH ₂ Cl ₂ ): 2952, 2809, 1733, 1692, 1620, 1580, 1455, 1415, 1243, 1125, 1029 and 853 cm ^-1
[3424] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3 Carboxylate is prepared analogously to the method described in Example 5.
[3425] Example 48
[3426] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Acetic acid dihydrochloride, diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thi Nylthio) ethyl] piperidine-3-acetic acid, diastereomer B
[3427] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] 1.2 g of piperidine-3-acetic acid are chromatographed on a column of 35 cm in length and 6 cm in diameter packed with 700 g of Kromasil ^R silica (particle size 10 μm). Elution is carried out using a dichloromethane / ethanol / triethylamine (98/2 / 0.1 volume) mixture. The flow rate is 70 cm ³ per minute. Detection is performed using ultraviolet light at 265 nm. After several preliminary injections, the fractions corresponding to diastereomer A are collected. These fractions are concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). 0.34 g of the product are obtained, which are salted in the following way: 0.3 g of the product is taken up in 30 cm ³ of ether, filtered and dissolved in 25 cm ³ of acetone. The obtained solution is poured into 5 cm ³ of a 5N solution of hydrochloric acid in ether. After the mixture is concentrated under reduced pressure under the same conditions as above, the obtained residue is taken up in 20 cm ³ of water and the solution is lyophilized. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- 0.190 g of acetic acid dihydrochloride, diastereomer A are obtained in the form of an orange lyophilisate. During the preliminary separation of the two diastereomers, the mixture fraction is concentrated as above for reprocessing. The separation conditions are as follows:
[3428] A column of 35 cm length and 6 cm diameter packed with 700 g of Kromasil ^R silica (particle size 10 μm). Elution is carried out using a dichloromethane / acetonitrile / triethylamine (60/40/4 / 0.1 volume) mixture. The flow rate is 80 cm ³ per minute. After three preliminary injections, the fraction corresponding to diastereomer B is collected. These fractions are concentrated under the same conditions as above. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Acetic acid, 0.34 g of diastereomer B is obtained in the form of a yellow foam ([a] ²⁰ _D = +55.4 +/- 1.1 at 0.5% in dichloromethane).
[3429] Diastereomer A : ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) by addition of a few drops of d4-CD ₃ COOD at a temperature of 400 MHz, 373 K): 1.40 to 1.90 and 2.20 to 2.55 (mts, 10H), 2.95-3.35 (mt, 8H), 3.99 (s, 3H), 5.40 (mt, 1H), 7.07 (dd, J = 5.5 and 3.5 Hz, 1H), 7.27 (wide area d, J = 3.5 Hz, 1H), 7.55 to 7.65 (mt, 3H), 7.85 (d, J = 4.5 Hz, 1H), 8.17 (d, J = 9 Hz, 1H), 8.88 (d, J = 4.5 Hz, 1H) .
[3430] Diastereomer B : ¹ H NMR spectrum (250 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 2.80 (mts, 16H), 2.88 (broad t, J = 7 Hz, 2H), 3.92 (s, 3H), 5.27 (mt, 1H), 7.04 (dd, J = 5.5 and 3.5 Hz, 1H), 7.17 (dd, J = 3.5 and 1.5 Hz, 1H), 7.30 to 7.45 (mt, 2H) , 7.54 (d, J = 4.5 Hz, 1H), 7.60 (dd, J = 5.5 and 1.5 Hz, 1H), 7.94 (d, J = 9.5 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H) .
[3431] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] Piperidine-3-acetic acid
[3432] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) in 5 cm ³ of dioxane with 5N aqueous sodium hydroxide solution 0.683 cm ³ added The mixture of propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate dihydrochloride is stirred at a temperature near 60 ° C. for 20 hours. After evaporation under reduced pressure (5 kPa) at a temperature near 40 ° C., the obtained residue was purified by chromatography on atmospheric pressure on silica gel (particle size 20 to 45 μm; diameter 1 cm; silica volume 20 cm ³ ) column, Elution is carried out with a chloroform / methanol / aqueous ammonia (12/3/1 volume) mixture. Fractions 1-3 are combined and concentrated under the above conditions. The product is obtained, which is dried to constant weight at a temperature near 40 ° C. under reduced pressure (10 Pa) in an oven.
[3433] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] 0.179 g of piperidine-3-acetic acid is obtained in the form of a white foam which is a mixture of two diastereomers.
[3434] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed: 1.15-2.80 (mts, 16H), 2.88 (wide t, J = 7 Hz, 2H), 3.91 and 3.92 (2s, 3H (all)), 5.26 (non-divided peak, 1H), 7.04 (dd, J = 5.5 and 3.5 Hz, 1H), 7.16 (dd, J = 3.5 and 1 Hz, 1H), 7.30 to 7.45 (mt, 2H), 7.54 (mt, 1H), 7.60 (wide d, J = 5.5 Hz, 1H), 7.94 (d, J = 9 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H).
[3435] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] Piperidine-3-acetate dihydrochloride
[3436] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinoline-4) in 12 cm ³ of methanol, while stirring 1 drop of 5N aqueous sodium hydroxide solution and then aliquoting 0.17 g of sodium borohydride. -Yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate was added to a solution maintained at a temperature near 20 占 폚. The mixture is stirred at a temperature near 20 ° C. for 3 hours. After 10 cm ³ of water is added, methanol is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The obtained residue was extracted twice with 20 cm ³ of dichloromethane and then the combined extracts were washed twice with 30 cm ³ of water, dried over magnesium sulfate, filtered and concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). An oil is obtained, which is purified by chromatography on silica gel (particle size 20-45 μm; diameter 2.5 cm; silica volume 150 cm ³ ) at atmospheric pressure on column, elution is dichloromethane / methanol (99/1 volume) Is carried out in a mixture. Fractions 56-115 are combined and then concentrated as above. Oil is obtained and its hydrochloride is prepared as follows: The oil is dissolved in 20 cm ³ of diethyl ether and then poured into 2 cm ³ of a 1N solution of hydrochloric acid in ether. The precipitate formed is filtered and dried under reduced pressure (10 Pa) at a temperature near 40 ° C. in an oven. Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] 0.3 g of piperidine-3-acetate dihydrochloride are obtained in the form of a white solid.
[3437] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) at 400 MHz, temperature 383 K). A mixture of two diastereomers is observed:
[3438] 1.40 to 2.00 and 2.25 to 2.70 (mts, 10H (all)), 2.90 to 3.40 (unsplit peak, 4H), 3.27 (mt, 4H), 3.61 and 3.63 (2s, 3H (all)), 4.00 (s, 3H), 5.38 (mt, 1H), 7.10 (dd, J = 5 and 3.5 Hz, 1H), 7.29 (wide area d, J = 3.5 Hz, 1H), 7.55 to 7.60 (mt, 2H), 7.65 (d, J = 5 Hz, 1H), 7.76 (mt, 1H), 8.16 (d, J = 8.5 Hz, 1H), 8.85 (d, J = 4.5 Hz, 1H).
[3439] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- acetate
[3440] Methyl (3R, 4R) -4 in acetonitrile 60 cm ³ at a temperature near 20 ° C. while stirring 1.5 g of 2- (2-chloroethylthio) thiophene, 5.2 g of potassium carbonate and 2.5 g of potassium iodide To a solution of 2.8 g of-[3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate. The mixture is heated at a temperature near reflux for 20 hours and then cooled to approximately 20 ° C. 130 cm ^{3 of} water and 50 cm ³ of ethyl acetate are added to the reaction mixture. The mixture is separated by sedimentation and the organic phase is washed with 150 cm ³ of water, dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C. An oil is obtained, which is purified by chromatography on silica gel (particle size 20-45 μm; diameter 2.5 cm; silica volume 100 cm ³ ) at atmospheric pressure on column, elution is dichloromethane / methanol (95/5 volumes) Is carried out in a mixture. Fraction 30 cm ³ is collected first, then approximately 10 cm ³ fractions are collected. Fractions 1 to 4 are combined and then evaporated as described above. 2.3 g of a brown oil are obtained, the product is subjected to secondary purification by chromatography on an atmospheric pressure on silica gel (particle size 20 to 45 μm; diameter 2.5 cm; silica volume 300 cm ³ ) column and elution is dichloromethane / methanol ( 99/1 vol.) Mixture and approximately 10 cm ³ fractions are collected. Fractions 21 to 30 are combined and then concentrated under the above conditions. Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- 0.84 g of acetate is obtained in the form of a pale yellow oil.
[3441] Infrared Spectra (CH ₂ Cl ₂ ): 2937, 2806, 2765, 1731, 1693, 1620, 1505, 1243 and 849 cm ^-1
[3442] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate
[3443] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- () in 460 cm ³ of anhydrous methanol added with concentrated sulfuric acid (d = 1.83) 4.3 cm ³ A solution of 10.8 g of tert-butyloxycarbonyl) piperidine-3-acetic acid is heated at a temperature near 65 ° C. for 2 hours under stirring. After cooling to approximately 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and the resulting residue is taken up in 200 cm ³ of water and sodium hydrogencarbonate is brought to a pH of around 8-9. To be alkaline.
[3444] The mixture is extracted four times with 200 cm ³ of ethyl acetate. The aqueous phase is made basic to pH near 11 by addition of the required amount of sodium carbonate. The mixture is extracted twice with 200 cm ³ of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. 6.84 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate are obtained in the form of a brown oil.
[3445] Infrared Spectrum (CCl ₄ ): 2935, 2812, 1738, 1692, 1620, 1504, 1242, 1032 and 851 cm ^-1
[3446] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetic acid
[3447] A solution of 0.85 g of potassium permanganate in 25 cm ^{3 of} water and 120 cm ³ of acetone was subjected to (3R, 4R) -4- [3- in acetone 60 cm ³ at a temperature near 25 ° C. with stirring over approximately 1 hour. To a solution of 1.2 g of oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde is added. The mixture is stirred at the same temperature for 3 hours and then cooled to approximately 10 ° C. A solution of 5 g of sodium sulfite in 200 cm ³ of water is added to the reaction mixture and the resulting mixture is filtered through celite. Acetone of the filtrate is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and the evaporation residue is taken up in 200 cm ³ of water and washed with 200 cm ³ of diethyl ether. The aqueous phase is precipitated and separated, acidified with citric acid in the solid state to a pH around ^3-4 and extracted with 200 cm ³ of diethyl ether. The precipitated ether solution is dried over magnesium sulfate, filtered and evaporated under the above conditions. 0.74 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetic acid is yellow Obtained in solid form.
[3448] Infrared Spectrum (KBr): 2932, 2588, 1730, 1690, 1620, 1431, 1246, 1165, and 857 cm ^-1
[3449] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde
[3450] Dichloromethane 65 cm³65 cm of dichloromethane under an inert atmosphere with stirring a mixture of 13.7 g of dimethyl sulfoxide in³Oxalyl chloride 8.3 cm³The solution was gradually cooled to a solution cooled to a temperature near -60 ° C. After stirring the mixture for 15 minutes, 65 cm of dichloromethane³(3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 dissolved in 10 g of-(tert-butyloxycarbonyl) piperidine are slowly added. The mixture was stirred for 30 minutes, then dichloromethane 65 cm³61.7 cm triethylamine dissolved in³Finally dropping. The mixture is stirred for an additional 3 hours at approximately -60 ° C and then 400 cm of cold water³Pour into. After settling out the mixture, the organic phase was separated by 10% (mass 400 cm aqueous citric acid solution³Washed with and then dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. 9.95 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde Obtained in the form of a brown oil.
[3451] Infrared Spectrum (CCl ₄ ): 2932, 2720, 1729, 1694, 1430, 1244, 1164 and 850 cm ^-1
[3452] (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert -Butyloxycarbonyl) piperidine
[3453] Triethylaminoborane complex 33.4 cm ³ with (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl in toluene 500 cm ³ at a temperature near 20 ° C. under stirring. ] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine is added to a solution and then the mixture is heated at a temperature near 110 ° C. for 18 hours. After the reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature near 45 ° C., the obtained residue was taken up in 500 cm ³ of tetrahydrofuran. The resulting solution contains approximately 63 cm ³ of water added over 20 minutes, then 47.5 g of sodium perborate are added over approximately 1 hour. The mixture is stirred at a temperature near 20 ° C. for 4 hours and then 300 cm ³ of saturated ammonium chloride solution are added. The organic solution is precipitated and separated, dried over magnesium sulfate and concentrated under the same conditions as above. The residue obtained is purified by chromatography on a column of silica gel (particle size 20 to 45 μm; diameter 9 cm; silica volume 2500 cm ³ ), elution is carried out with a dichloromethane / methanol (97.5 / 2.5 volume) mixture and 1 liter Fractions are collected. Fractions 1 to 17 are separated and the elution is then carried out with a dichloromethane / methanol (95/5 volume) mixture, in which a 1 liter fraction is collected. Fractions 30 to 35 are combined and finally the elution is carried out with a dichloromethane / methanol (90/10 volume) mixture and 1 liter fraction is collected. Fractions 36-41 are combined and at the same time the fractions 30-41 are combined and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert 20 g of -butyloxycarbonyl) piperidine are obtained in oil form.
[3454] Infrared Spectra (CH ₂ Cl ₂ ): 3612, 2480, 2937, 1680, 1432, 1243, 1163 and 859 cm ^-1
[3455] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine
[3456] 162 cm ³ of triethylamine dissolved in 300 cm ³ of dichloromethane over a period of approximately 20 minutes at a temperature near 20 ° C., followed by 85 g of di-tert-butyl dicarbonate over 2 hours, dichloromethane 1700 cm ³ To a stirred solution of 126 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine in water. The mixture is stirred for 16 h at a temperature near 20 ° C. and then 400 cm ³ of water is added. The organic phase is precipitated, dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. To give a oily residue, and the product is taken up in ethyl acetate and then washed twice with 1000 cm ^3, twice with water and once with saturated aqueous citric acid solution, 200 cm ³ 250 cm ³ to 200 cm ³ water. The organic solution is dried over magnesium sulfate, filtered and concentrated under the above conditions. 148 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -3-vinylpiperidine brown Obtained in oil form.
[3457] Infrared spectra (CH ₂ Cl ₂ ): 2979, 1683, 1431, 1246, 1164 and 853 cm ^-1
[3458] (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by applying the method disclosed in patent application FR 2,354,771. .
[3459] Example 49
[3460] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Acetic acid, diastereomer A, and (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinoline-4- I) propyl] piperidine-3-acetic acid, diastereomer B
[3461] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl ] 0.7 g of piperidine-3-acetic acid is chromatographed on a column of 35 cm length and 6 cm diameter packed with 700 g of Kromasil ^R silica (particle size 10 μm). Elution is carried out using a dichloromethane / acetonitrile / methanol / triethylamine (56/40/4 / 0.5 volume) mixture. The flow rate is 70 cm ³ per minute. Detection is performed using ultraviolet light at 265 nm. Several preliminary injections lead to the separation of two diastereomers. The fraction corresponding to the first diastereomer A is concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The obtained crystal mass is dried at a temperature near 20 ° C. under reduced pressure (5 Pa) in an oven. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 0.185 g of acetic acid, diastereomer A are obtained in the form of an off-white solid ([α] ²⁰ _D = +55.9 +/- 1.2 in 0.5% in methanol). The mixture fractions are concentrated under the same conditions as described above for reprocessing. Fresh injection is performed to give a second diastereomer. Three preliminary injections make it possible to obtain the fraction corresponding to diastereomer B. These fractions are concentrated at a temperature near 40 ° C. under reduced pressure (5 kPa). The obtained crystal mass is dried at a temperature near 20 ° C. under reduced pressure (10 Pa). (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 0.200 g of acetic acid, diastereomer B are obtained in the form of an off-white solid ([α] ²⁰ _D = +41.0 +/- 1.0, in 0.5% in methanol).
[3462] Diastereomer A : ¹ H NMR Spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.15 to 1.85 and 1.95 to 2.20 (2 series of mts, 11H (all)), 2.40 to 2.60 (mt, 3H), 2.65 to 2.80 (mt, 2H), 3.08 (t, J = 7 Hz, 2H), 3.92 (s, 3H), 5.27 (mt, 1H), 5.52 (non-split peak, 1H), 6.98 (double t, J = 8.5 and 2.5 Hz, 1H), 7.10 to 7.20 (mt, 2H), 7.25 to 7.45 (mt, 3H), 7.55 (d, J = 4.5 Hz, 1H), 7.94 (d, J = 9 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3463] Diastereomer B : ¹ H NMR Spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.30 to 1.90 and 1.95 to 2.15 (2 series of mts, 10H (all)), 2.40 to 2.60 (mt, 3H), 2.75 (mt, 1H), 2.95 to 3.15 (undivided peak, 2H), 3.10 (t, J = 7 Hz, 2H), 3.93 (s, 3H), 5.28 (mt, 1H), 5.53 (d, J = 5 Hz, 1H), (double t, J = 8.5 and 2.5 Hz, 1H), 7.10 to 7.20 (mt, 2H), 7.35 (mt, 1H), 7.35 to 7.45 (mt, 2H) , 7.55 (d, J = 4.5 Hz, 1H), 7.95 (d, J = 9.5 Hz, 1H), 8.72 (d, J = 4.5 Hz, 1H), 11.00 to 12.5 (very broad undivided peak, 1H).
[3464] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl ] Piperidine-3-acetic acid
[3465] (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydride in 20 cm ³ of dioxane added with 5N aqueous sodium hydroxide 2 cm ³ A solution of 1.3 g of oxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate is heated under stirring at a temperature near 60 ° C. for 20 hours. The reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. and the residue obtained is taken up in 30 cm ³ of water and 5 cm ³ of methanol and acidified with citric acid. The solvent is evaporated under the same conditions as above and the obtained residue is then taken up in 70 cm ³ of a dichloromethane / methanol (80/20 vol) mixture. Filtering citric acid crystals; The filtrate is evaporated as above and the evaporated residue is taken up in 30 cm ³ of diethyl ether, filtered and air dried. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl ] 1.1 g of piperidine-3-acetic acid are obtained in the form of a cream solid.
[3466] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed:
[3467] 1.15 to 1.90, 2.00 to 2.25 and 2.35 to 2.90 (mts, 16H (all)), 3.13 (wide t, J = 7 Hz, 2H), 3.92 (s, 3H), 5.27 (mt, 1H), 5.54 (mt , 1H), 7.00 (double t, J = 8.5 Hz, 1H), 7.10 to 7.25 (mt, 2H), 7.30 to 7.50 (mt, 3H), 7.55 (mt, 1H), 7.94 (d, J = 9 Hz , 1H), 8.71 (d, J = 4.5 Hz, 1H), 11.50 to 13.50 (very broad undivided peak, 1H).
[3468] Example 49A
[3469] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) Propyl] piperidine-3-acetate
[3470] 0.28 g of sodium borohydride and 2 drops of 5N aqueous sodium hydroxide solution were added to methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- in 50 cm ³ of methane. 3.2 g of oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate are added to a solution maintained at a temperature in the range of 20 ° C. The mixture is stirred at a temperature near 20 ° C. for 4 hours. After adding 30 cm ³ of water, the mixture is extracted twice with 30 cm ³ of dichloromethane. The combined organic phases are washed with 60 cm ³ of water, dried over magnesium sulphate, filtered and then evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The residual oil is purified by chromatography on silica gel (particle size 20-45 μm; diameter 4 cm; silica volume 520 cm ³ ) column at atmospheric pressure, elution is carried out with a dichloromethane / methanol (99/1 volume) mixture and approx. 60 cm ³ fractions are collected. Fractions 40 to 72 are combined and evaporated under these conditions. 1.7 g of oil are obtained and its hydrochloride is prepared as follows: A solution of 0.30 g of oil in 5 cm ³ of diethyl ether is poured into 5 cm ³ of a 5N hydrochloric acid solution in ether. The gel obtained is diluted with 10 cm ³ ether and stirred at a temperature near 20 ° C. for 15 minutes and then evaporated under reduced pressure (5 kPa) at a temperature near 30 ° C. The obtained residue is dissolved in 30 cm ³ of water and lyophilized. Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) 0.26 g of propyl] piperidine-3-acetate is obtained in the form of a cream lyophilisate.
[3471] ¹ H NMR spectrum (d6- (CD ₃ ) ₂ SO, δ (ppm) by addition of a few drops of d4-CD ₃ COOD at a temperature of 400 MHz, 373 K). A mixture of two diastereomers is observed:
[3472] 1.45 to 2.00 and 2.25 to 2.60 (mts, 10H (all)), 3.05 to 3.45 (mts, 8H), 3.60 and 3.63 (2s, 3H (all)), 3.97 and 3.98 (2s, 3H (all)), 5.39 (mt, 1H), 7.03 (mt, 1H), 7.23 (mt, 2H), 7.37 (mt, 1H), 7.50 to 7.65 (mt, 2H), 7.80 (mt, 1H), 8.12 (d, J = 9.5 Hz, 1H), 8.84 (d, J = 5 Hz, 1H).
[3473] Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 -acetate
[3474] 2.26 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate, previously dissolved in 50 cm ³ of acetonitrile, is stirred At a temperature near 20 ° C., 6.91 g of potassium carbonate and 2 g of potassium iodide were then added to a solution of 4 g of 1-[(2-chloroethyl) thio] -3-fluorobenzene in 50 cm ³ of acetonitrile. do. The mixture is heated at a temperature near 70 ° C. for 18 hours. Further 0.3 g of potassium iodide is added and after further heating at a temperature near 70 ° C. for 4 hours, the reaction mass is cooled to approximately 20 ° C., then 200 cm ³ of water are added and extracted twice with 150 cm ³ of ethyl acetate. . The combined extracts are washed with 300 cm ³ of water, dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The residue obtained is purified by chromatography on silica gel (particle size 20-45 μm; diameter 5.2 cm; silica volume 950 cm ³ ) column at atmospheric pressure, elution is carried out with a dichloromethane / methanol (99/1 volume) mixture Collect approximately 6 cm ³ fractions. Fractions 24 to 36 are combined and concentrated under the above conditions. Methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 3.3 g of acetate are obtained in the form of a yellow oil.
[3475] Infrared spectra (CH ₂ Cl ₂ ): 2936, 2806, 1731, 1692, 1620, 1505, 1474,1243, 881 and 853 cm ^-1
[3476] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate was obtained in Example 48.
[3477] Example 50
[3478] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[3479] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) in 9 cm ³ of dioxane added with 1.41 cm ³ of 5N aqueous sodium hydroxide solution. Propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is stirred for 18 hours at a temperature near 60 ° C. After cooling to approximately 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. The obtained residue was purified by chromatography at a pressure of 50 kPa on a silica gel (particle size 20 to 45 μm; diameter 3.3 cm; mass 56 g), and the elution was primarily a dichloromethane / methanol (95/5 volume) mixture. To perform. Fractions 100 cm ³ are collected first, followed by 16 cm ³ fractions. Fractions 1 to 36 are separated. Elution is subsequently carried out with dichloromethane / methanol (75/25 vol). A first fraction of 200 cm ³ , a second fraction of 150 cm ³ and then a third fraction of 100 cm ³ are obtained. The latter two fractions are combined and concentrated as above. The obtained residue is taken up in dichloromethane and filtered. The filtrate is evaporated as above and the new residue obtained is triturated in 25 cm ³ of a diisopropyl ether / pentane (50/50 vol) mixture. The product to be crystallized is filtered, washed with 10 cm ³ of the same mixture and then three times with 10 cm ³ of pentane. (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl 0.53 g of) prop-2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a cream solid at a melting point of 106 ° C.
[3480] A mixture of ¹ H NMR spectra (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)) isomers is observed:
[3481] 1.40 to 1.95 (mt, 7H), 2.30 to 3.00 (mt, 5H), 3.57 and 3.59 (2s, 2H (all)), 3.90 and 3.93 (2s, 3H (all)), 5.25 (mt, 1H), 5.55 (Unsplit peak, 1H), 7.22 (mt, 2H), 7.25 to 7.45 (mt, 3H), 7.56 (mt, 1H), 7.94 (d, J = 9 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H), 12.10-12.80 (wide undivided peak, 1H).
[3482] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylate
[3483] Tetrakis (triphenylphosphine) palladium 0.138 g, cuprous iodide and 0.046 g of 1-bromo-3,5-di-methyl benzene 0.42 cm ³ fluoro, triethylamine and 9.5 cm ³ (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl] piperidine-3-carboxyl To a stirred mixture at a temperature near 20 ° C. under 0.95 g of inert atmosphere at a rate of 3. The mixture is heated for 3 hours at a temperature near 80 ° C. After cooling to approximately 20 ° C., the reaction mixture is 30 cm of ethyl acetate. ³ and water 30 cm ³ and stirred for 5 minutes, while the organic phase is precipitated and separated, the aqueous layer is extracted twice with ethyl acetate 30 cm ^{3. The} combined organic extracts are washed with water 30 cm ³ , dried over sodium sulphate and filtered. Then concentrated under reduced pressure (5 kPa) at a temperature near 40 ° C. The residue obtained was silica gel (particle size 20 to 45 μm; diameter 2.3 cm; 40 g Purification by chromatography under nitrogen pressure of 50 kPa on column and elution is carried out with pure ethyl acetate, two fractions of 100 cm ³ are collected first and then 20 cm ³ fractions are combined, fractions 8 to 40 are combined and Evaporate under conditions Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 0.967 g of 5-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate are obtained in the form of an orange foam.
[3484] Infrared Spectrum (KBr): 3424, 2948, 1734, 1618, 1586, 1432, 1242, 1122, 1028, 990 and 373 cm ^-1
[3485] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine 3-carboxylate can be prepared as described in Example 32.
[3486] Example 51
[3487] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[3488] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) in 8.8 cm ³ of dioxane added with 1.37 cm ³ of 5N aqueous sodium hydroxide solution. Propyl] -1- [3- (2,5-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is stirred for 17 hours at a temperature near 60 ° C. After cooling to approximately 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature near 40 ° C. An oil is obtained, which is purified by chromatography under silica pressure (particle size 20 to 45 μm; diameter 3 cm; 25 g) on a column under nitrogen pressure of 50 kPa, and the elution is dichloromethane / methanol (85/15 vol. ) To a mixture, first collecting 100 cm ³ of fractions and then collecting 50 cm ³ fractions. Combine fractions 3 and 4 and concentrate as above. The evaporated residue is taken up in dichloromethane and filtered.
[3489] The filtrate is concentrated as above and then the product obtained is taken by stirring at a temperature within the range of 20 ° C. for 16 h in 40 cm 3 of a pentane / diisopropyl ether (50/50 vol) mixture. The obtained crystals are filtered and washed twice with 10 cm 3 of the same mixture as above and then with 20 cm 3 of pentane. 0.392 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-di Fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a pale yellow solid that is a mixture of two diastereomers (melt at 109 ° C. temperature). ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). Two diastereomeric mixtures are observed:
[3490] 1.40-2.00 (mts, 7H), 2.30-3.00 (mt, 5H), 3.64 and 3.65 (2s, all 2H), 3.90 and 3.92 (2s, all 3H), 5.26 (non-divided peak, 1H), 5.56 (non-divided) Hal peak, 1H), 7.25 to 7.50 (mt, 5H), 7.56 (mt, 1H), 7.94 (d, J = 9 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H), 12.40 to 12.70 (ratio) Peak, 1H).
[3491] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl]-
[3492] 1- [3- (2,5-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate
[3493] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylic acid 1.1 g, triethylamine 11 cm 3, tetrakis (triphenylphosphine) palladium 0.16 cm 3, first copper iodide 0.053 g and 1-bromo A mixture of -2.5-difluorobenzene 0.47 cm 3 is stirred for 3 hours and 15 minutes under an inert atmosphere at a temperature in the range of 80 ° C. After cooling to about 20 ℃ temperature, and the reaction mixture has a 30 ㎤ water and ethyl acetate 30 ㎤ added during the stirring. While separating the organic phase, the aqueous phase is extracted twice with 30 cm 3 of ethyl acetate. The organic extracts are combined, washed three times with 25 cm 3 of water, dried over sodium sulfate and concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The product was obtained, which was purified by chromatography (eluent: ethyl acetate) on a silica gel (particle size 20-45 μm; diameter 3.3 cm; 50 g) column under 50 kPa nitrogen pressure to obtain a 300 cm 3 aliquot. Collect and then collect 30 cm 3 fractions. Fractions 7 to 22 are combined and then concentrated under the above conditions. Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro 0.91 g of phenyl) prop-2-ynyl] piperidine-3-carboxylate are obtained in the form of an off-white foam.
[3494] Infrared Spectrum (CCl ₄ ): 3614, 2950, 1738, 1622, 1497, 1249, 1163, 1033 and 873 cm ^-1
[3495] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [rop-2-ynyl] piperidine 3-carboxylate was prepared in Example 43.
[3496] Example 52
[3497] (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, Diastereomer A, and (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperi Din-3-acetic acid, diastereomer B
[3498] (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperi Kromasil 1.3 g of din-3-acetic acid^RChromatography is carried out on a column 35 cm long and 6 cm in diameter packed with 700 g of silica (particle size 10 μm). Eluate using a dichloromethane / acetonitrile / methanol / triethylamine (56/40/4 / 0.5 volume) mixture. The flow rate is 70 cm 3 / min. Detection using ultraviolet light at 265 nm. Two preliminary injections separate the two diastereomers. The first fraction, diastereomer A, is concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The evaporated residue obtained is dried in an oven under reduced pressure (10 kPa) at a temperature in the range of 20 ° C. 0.310 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Acetic acid, diastereomer A is obtained in the form of a foam with a beige color ([α] in dichloromethane at 0.5%²⁰ _D= -43.6 +/- 1.0). The second corresponding fraction, diastereomer B, is concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The evaporated residue obtained is dried in an oven under reduced pressure (10 kPa) at a temperature in the range of 20 ° C. 0.260 g (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Acetic acid, diastereomer B is obtained in the form of a beige foam ([α] in dichloromethane at 0.5%²⁰ _D= +55.4 +/- 1.0).
[3499] Diastereomer A : ¹ H NMR Spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.10 to 2.20 and 2.30 to 2.80 (mts of 2 series, all 29H), 3.93 (s, 3H) , 5.28 (wide dd, J = 7.5 and 3 Hz, 1 H), 5.30 to 5.70 (wide undivided peak, 1 H), 7.35 to 7.45 (mt, 2H), 7.56 (d, J = 4.5 Hz, 1H), 7.94 ( d, J = 9.5 Hz, 1H), 8.72 (d, J = 4.5 Hz, 1H).
[3500] Diastereomer B : ¹ H NMR Spectrum (300MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.10 to 2.10 and 2.30 to 2.80 (mts of 2 series, all 29H), 3.92 (s, 3H) , 5.27 (wide dd, J = 7.5 and 3 Hz, 1H), 5.30 to 5.75 (wide undivided peak, 1H), 7.35 to 7.45 (mt, 2H), 7.54 (d, J = 4.5 Hz, 1H), 7.94 ( d, J = 9.5 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3501] (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperi Din-3-acetic acid
[3502] (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3- (R, S)-in 35 cm 3 of dioxane while stirring 2.96 cm 3 of aqueous 5N sodium hydroxide solution at a temperature in the range of 20 ° C. To a solution of 1.9 g of hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate. The solution is heated for 16 hours at a temperature in the range of 60 ° C. Half the mixture is evaporated under reduced pressure (5 kPa) at a temperature in the range of 50 ° C. and then taken up within 50 cm 3 of acetone and redevaporated as above. After the obtained residue is taken up in 50 cm 3 of diethyl ether and concentrated as under the above conditions, the obtained yellow solid has 20 cm 3 added water and is acidified with an amount of citric acid sufficient to obtain a pH within the range 4-5. . The mixture is extracted with 50 cm 3 of dichloromethane. The organic extract is concentrated under reduced pressure (5 kPa) at a temperature in the range of 50 ° C. The evaporation residue is taken twice in 100 cm 3 of dichloromethane / methanol (90/10 volume), and the insoluble material is filtered each time after the residue is taken. The combined filtrates are concentrated as above and the obtained residue is taken up in 50 cm 3 of diethyl ether and evaporated as under the above conditions. The obtained crystals are taken up in 50 cm 3 of diethyl ether, filtered and washed twice with 50 cm 3 of diethyl ether. The product is finally dried in an oven under reduced pressure, ie 5 kPa and then 10 kPa at a temperature in the range of 60 ° C. (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid Obtained in the form of a yellow solid. ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed.
[3503] 1.00-2.95 (mts, 29H), 3.92 (s, 3H), 5.27 (mt, 1H), 5.54 (unsplit peak, 1H), 7.30-7.45 (mt, 2H), 7.55 (mt, 1H), 7.95 ( d, J = 9.5 Hz, 1H), 8.72 (d, J = 4.5 Hz, 1H), 10.80 to 11.90 (very broad undivided peak, 1H).
[3504] Example 52A
[3505] Methyl (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] piperidine -3-acetate dihydrochloride
[3506] 0.42 g of sodium borohydride was added in (3R, 4R) -1- [2- (cyclohexylthio) ethyl in 50 cm 3 (added 1 drop of 5N sodium hydroxide solution) in methanol in portions for approximately 1 hour with stirring under an inert atmosphere. 3.5 g of) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate is added to the solution cooled to a temperature within the range of 15 ° C. The mixture is stirred at this temperature for 2 hours and cooled to approximately 10 ° C. Then 10 cm 3 of water is added dropwise. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the range of 45 ° C. After adding 100 cm 3 of water to the obtained residue, the mixture is extracted twice with 100 cm 3 of ethyl acetate. The combined extracts are dried over sodium sulphate as above, filtered and concentrated. An oil was obtained, which was purified by chromatography (eluant: ethyl acetate) on a silica gel (particle size 20-45 μm; diameter 3 cm; height 35 cm) column under 50 kPa nitrogen pressure to obtain 30 cm 3 fractions. Collect. Fractions 19 to 42 are combined and then concentrated under the above conditions. 2.44 g of product are obtained and its hydrochloride is prepared in the following manner: 0.5 g of the product are dissolved in 10 cm 3 of diethyl ether and the solution is poured into 5 cm 3 of a 1N hydrochloric acid solution in ether. 10 cm 3 of ether is added and the mixture is left to work for 1 hour at a temperature in the range of 20 ° C. The mixture is filtered and the cake is washed twice with 10 cm 3 of diethyl ether and dried under reduced pressure (5 kPa) at a temperature in the range of 20 ° C and then in an oven under reduced pressure (10 kPa) at a temperature in the range of 60 ° C. Methyl (3R, 4R) -1- [2- (cyclohexylthio) ethyl) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] piperidine 0.46 g of 3-acetate dihydrochloride is obtained in the form of a pale pink solid which melts (softens) at a temperature of 80 ° C.^OneH NMR spectrum (d6- (CD at 400MHz, 383K temperature)₃)₂SO, δ (ppm)). Two diastereomeric mixtures are observed.
[3507] 1.20 to 2.05 and 2.30 to 2.65 (mts, all 20H), 2.82 (mt, 1H), 2.85 to 3.50 (wide undivided peak, 4H), 2.96 (mt, 2H), 3.19 (mt, 2H), 3.62 and 3.63 (2s, all 3H), 4.00 (s, 3H), 5.37 (mt, 1H), 7.50 to 7.65 (mt, 2H), 7.73 (unsplit peak, 1H), 8.15 (wide area d, J = 9 Hz, 1H) , 8.83 (d, J = 4.5 Hz, 1 H).
[3508] Methyl (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate
[3509] 3.9 g of acetonitrile in 50 cm 3 of acetonitrile at temperatures in the range of 20 ° C. and under an inert atmosphere with stirring 2.06 g of chloroethyl cyclohexyl sulfide, 50 cm 3 of acetonitrile, followed by 1.78 g of potassium iodide and 7.25 g of potassium carbonate To methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate solution. The mixture is heated at a temperature in the range of 80 ° C. for 18 hours. After cooling to approximately 20 ° C., the mixture has 100 cm 3 of water and 100 cm 3 of ethyl acetate added. The aqueous phase is extracted with 200 cm 3 of ethyl acetate while the organic phase is precipitated and separated. The organic extracts are combined, dried over sodium sulfate, filtered and concentrated at a temperature in the range of 45 ° C. under reduced pressure (5 kPa). Oil was obtained, and the obtained oil was purified on a column of silica gel (particle size 20-45 μm; diameter 3.5 cm; height 46 cm) under 50 kPa nitrogen pressure (eluant: dichloromethane / methanol (95/5 volume) mixture) 50 cm 3 fractions are collected. Fractions 18 to 37 are combined and concentrated as above. The product was obtained, which was purified by chromatography (eluent: ethyl acetate / cyclohexane (7/3 volume) mixture) on silica gel (particle size 20-45 μm; diameter 4 cm; height 40 cm) column under 50 kPa nitrogen pressure Collect 100 cm 3 fractions. Fractions 24 to 54 are combined and then concentrated under the same conditions as above. 3.7 g of methyl (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Acetate is obtained in the form of a brown oil.
[3510] Infrared spectra (CH ₂ Cl ₂ ): 2933, 2855, 1732, 1693, 1620, 105, 1244, 1029 and 853 cm ^-1
[3511] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate was obtained in Example 48.
[3512] Example 53
[3513] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] py Ferridine-3-acetic acid, diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene -2-yl) prop-2-ynyl] piperidine-3-acetic acid, diastereomer B
[3514] 1.2 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl Prop-2-ynyl] piperidine-3-acetic acid is chromatographed on a 35 cm long and 6 cm diameter column packed with 700 g of Kromasil ^R silica (particle size 10 μm). Eluate using a dichloromethane / nitrile acetate / methanol / triethylamine (70/15/15 / 0.05 vol) mixture. The flow rate is 90 cm 3 / min. Detection using ultraviolet light at 265 nm. Two preliminary injections separate the two diastereomers. The first fraction, diastereomer A, is concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The obtained crystals are dried in an oven under reduced pressure (10 kPa) at a temperature in the range of 20 ° C. 0.408 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2- Inyl] piperidine-3-acetic acid, diastereomer A is obtained in the form of a yellow solid ([a] ²⁰ _D = -62.9 +/- 1.3 in methanol at 0.5%). The second corresponding fraction, diastereomer B, is concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The obtained crystals are dried in an oven under reduced pressure (10 kPa) at a temperature in the range of 20 ° C. 0376 g (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl ] Piperidine-3-acetic acid, diastereomer B is obtained in the form of a yellow solid ([a] ²⁰ _D = +46.9 +/- 1.1 in methanol at 0.5%).
[3515] Diastereomer A : ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with few drops of d4-CD ₃ COOD): 1.20 to 2.00 and 2.05 to 2.50 (mts of 2 series, all 12H), 2.60 to 2.85 (mt, 2H), 3.55 (limit AB, J = 17 Hz, 2H), 3.90 (s, 3H), 5.27 (dd, J = 8 and 3 Hz, 1H), 7.04 (mt, 1H) , 7.26 (broad d, J = 4 Hz, 1H), 7.30 to 7.45 (mt, 2H), 7.52 (d, J = 5.5 Hz, 1H), 7.56 (d, J = 4.5 Hz, 1H), 7.93 (d, J = 10 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H).
[3516] Diastereomer B : ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with few drops of d4-CD ₃ COOD): 1.20 to 1.90 and 2.00 to 2.45 (mts of 2 series, all 12H), 2.60 to 2.85 (mt, 2H), 3.50 (AB, J = 17 Hz, 2H), 3.91 (s, 3H), 5.27 (dd, J = 8 and 3.5 Hz, 1H), 7.05 (dd, J = 5.5 and 4 Hz, 1H), 7.26 (wide area d, J = 4 Hz, 1H), 7.35 to 7.45 (mt, 2H), 7.50 to 7.60 (mt, 2H), 7.95 (d, J = 10 Hz, 1H), 8.71 ( d, J = 4.5 Hz, 1H).
[3517] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-3-acetic acid
[3518] 3 g of methyl- (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4-) in 50 cm 3 of dioxane (with 5 cm 3 of 5N aqueous sodium hydroxide solution) I) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate solution is heated for 17 hours with stirring under an inert atmosphere at a temperature in the range of 60 ° C. After cooling to approximately 20 ° C., the mixture is concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. and then the residue is taken up in 100 cm 3 of dichloromethane and 5 cm 3 of water. The mixture is acidified with sufficient amount of citric acid to obtain a pH 4-5 and then dried over magnesium sulfate as above, filtered and concentrated. Residual water is entrained by azeotroping in chloroform. After concentration as above, the obtained residue was chromatographed under atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 3.5 cm; silica volume 200 cm 3) (eluant: chloroform / methanol / 28% aqueous ammonia (12 /2/0.5 volume) mixture) to collect approximately 60 cm 3 fractions. Fractions containing the expected product are combined and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The obtained residue was taken up in 40 cm 3 of diethyl ether, filtered off, washed twice with 5 cm 3 of ether, dried at a temperature in the range 20 ° C. under reduced pressure (5 kPa) and then in the range 40 ° C. under reduced pressure (10 Pa). Dry in oven at temperature inside. 1.9 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl ) Prop-2-ynyl] piperidine-3-acetic acid is obtained in the form of a white solid.
[3519] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). Two diastereomeric mixtures are observed:
[3520] 1.20 to 2.45 (mts, 12H), 2.60 to 2.85 (mt, 2H), 3.48 (mt, 2H), 3.92 (s, 3H), 5.28 (mt, 1H), 7.06 (dd, J = 5.5 and 3.5 Hz, 1H), 7.27 (dd, J = 3.5 and 1 Hz, 1H), 7.30 to 7.45 (mt, 2H), 7.50 to 7.60 (mt, 2H), 7.94 (d, J = 9 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H).
[3521] Example 53A
[3522] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop Ph-2-inyl] piperidine-3-acetate
[3523] 4.0 g of methyl (3R, 4R) -4- in 65 cm 3 of methanol (added 1 drop of 5N sodium hydroxide solution) while stirring 0.317 g of sodium borohydride under an inert atmosphere at a temperature of less than 30 ° C. over approximately 40 minutes. Addition to a solution of [3-oxo-3- (6-methoxyquinolin-4-yl) propyl-1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate do. After stirring for 3 hours at a temperature in the range of 20 ° C., the mixture has 100 cm 3 of water added and then extracted four times with 50 cm 3 of dichloromethane. The extract is washed three times with 50 cm 3 of water, dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. An oil is obtained, which is purified by chromatography (eluent: ethyl acetate) under atmospheric pressure on a silica gel (particle size 20-45 μm; diameter 3.2 cm; silica volume 300 cm 3) column to collect approximately 100 cm 3 fractions. Collect fractions corresponding to the expected product. These fractions are concentrated as above. 3.5 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene-2- I) prop-2-ynyl] piperidine-3-acetic acid is obtained in the form of a yellow oil.
[3524] Infrared Spectrum (CCl ₄ ): 2939, 1739, 1622, 1509, 1434, 1241, 850 and 696 cm ^-1
[3525] Hydrochloride was prepared in the following manner: 0.5 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4) in 20 cm 3 of dichloromethane -Yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate solution while stirring with 30 cm 3 of dichloro ether (4 cm 3 in 1N of ether) Hydrochloric acid solution). After 2 hours, the white solid formed was filtered off, washed twice with 5 cm 3 of diethyl ether, in a oven at a temperature within the range of 40 ° C. under reduced pressure (10 Pa) until partial weight (5 kPa) followed by constant weight. To dry. 0.35 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiene-2- I) prop-2-ynyl] piperidine-3-acetate dihydrochloride is obtained in the form of a white solid.
[3526] Infrared Spectrum (KBr): 3278, 2932, 2524, 1730, 1619, 1601, 1427, 1248, 1021, 849 and 714 cm ^-1
[3527] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] py Ferridine-3-acetate
[3528] 0.263 g of triphenylphosphine followed by 0.85 g of terraquis (triphenylphosphine) palladium, 0.4 g of first copper iodide and 1.75 cm 3 of iodothiophene under inert atmosphere at a temperature in the range of 20 ° C. with stirring 4.3 g methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl] pi in 100 cm 3 of acetonitrile Add to the ferridine-3-acetate solution The mixture is stirred for 10 minutes and then 2.95 cm 3 of triethylamine After stirring for 48 hours at 20 ° C., the mixture is filtered through celite and insoluble The material is washed twice with 50 cm 3 of acetonitrile The filtrate is concentrated under reduced pressure (5 kPa) at a temperature within the range of 40 ° C. The concentrated residue is silica gel (particle size 20-45 μm; diameter 4.5 cm; silica volume 500 cm 3). Approximately 60 cm 3 by purification under atmospheric pressure on a column (eluant: pure ethyl acetate) Collect fractions Collect the fractions corresponding to the expected product Concentrate these fractions under these conditions 4 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinoline-4- Il) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate in the form of a yellow oil.
[3529] Infrared (CCl ₄ ): 2935, 1740, 1692, 1431, 1242, 1032, 849 and 698 cm ^-1
[3530] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl] piperidine-3-acetate
[3531] 5 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinoline-4) in 60 cm 3 of dimethylformamide was reduced under reduced pressure at a temperature in the range of 20 ° C. with stirring of 4.8 cm 3 of triethylamine. -Yl) propyl] piperidine-3-acetate solution. After stirring for 15 minutes at this temperature, 1.5 cm 3 of propargyl bromide is added over approximately 15 minutes, after 15 minutes, the mixture is heated at a temperature in the range of 45 ° C. for 4 hours. After cooling to approximately 20 ° C., the reaction mixture is poured into approximately 700 cm 3 of water and then the mixture is extracted four times with 80 cm 3 of diethyl ether. The combined extracts are washed three times with 80 cm 3 of water, dried, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The evaporation residue is purified by chromatography (eluent: pure ethyl acetate) under atmospheric pressure on a column of silicakel (particle size 20-45 μm; diameter 4 cm; silica volume 500 cm 3) to collect 60 cm 3 fractions. Fractions 9-20 are combined and then concentrated under the above conditions. 4.3 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl] piperidine-3-acetate Is obtained in the form of a yellow oil.
[3532] Infrared Spectrum (CCl ₄ ): 3311, 2936, 1739, 1692, 1620, 1431, 1242, 1032, 849, 654 and 627 cm ^-1
[3533] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate was prepared as in Example 48.
[3534] Example 54
[3535] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, Diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-3-acetic acid, diastereomer B, dihydrochloride
[3536] By the method described in Example 52, (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2 Two diastereomers of -cyclopentylthio) ethyl] piperidine-3-acetic acid were separated. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, Diastereomer B is isolated in the form of a white solid, to prepare its dihydrochloride ([a] ²⁰ _D = -89.6 +/- 1.6, in 0.5% methanol), and 3R, 4R) -4- [3- Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, diastereomer A in the form of a yellow dark oil ([Α] ²⁰ _D = +57.4 +/- 0.9, in 0.5% methanol).
[3537] Diastereomer A : ¹ H NMR Spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.15 to 2.10 and 2.25 to 2.60 (mts, all 24H), 2.70 (mt, 2H), 3.11 ( mt, 1H), 3.92 (s, 3H), 5.26 (dd, J = 8 and 4 Hz, 1H), 7.35 to 7.45 (mt, 2H), 7.54 (d, J = 4.5
[3538] Hz, 1H), 7.94 (d, J = 10 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3539] Diastereomer B : ¹ H NMR Spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.30 to 2.10, 2.15 to 2.40 and 2.65 to 3.50 (mts, all 27H), 4.00 and 4.01 (2s , All 3H), 5.50mt, 1H), 7.54 and 7.58 (2d, J = 2.5Hz, all 1H), 7.71 (very wide d, J = 9Hz, 1H), 7.96 (mt, 1H), 8.23 (very wide d, J = 9 Hz, 1H), 9.00 (very wide d, J = 4.5 Hz, 1H), 9.70 to 9.85 and 10.15 to 10.35 (2 undivided peaks, all 1H).
[3540] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-3-acetic acid
[3541] 1.6 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4) in 30 cm 3 of dioxane (with 2.6 cm 3 of 5N aqueous sodium hydroxide solution) -Yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetate dihydrochloride solution is stirred at a temperature in the range of 65 ° C. for 6 hours. After concentrating the reaction mixture at a temperature in the range of 40 ° C. under reduced pressure (5 kPa), a residue is obtained, which is taken twice in 30 cm 3 of chloroform and concentrated under these conditions. The residue was purified by chromatography on a column of silica gel (particle size 20-45 μm; diameter 3 cm; silica volume 100 cm 3) under atmospheric pressure (eluant: chloroform / methanol / 28% aqueous ammonia (12/3 / 0.5 volume) mixture) Collect 30 cm 3 fractions. Fractions containing the expected product are collected and concentrated as above. 1.5 g of a colorless lacquer are obtained, which product is taken up in 20 cm 3 of diethyl ether, filtered and washed twice with 10 cm 3 of diethyl ether. The product is dried under partial pressure (5 kPa) and then dried in an oven under reduced pressure (10 Pa) at a temperature in the range of 40 ° C. until constant weight. 1.35 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl ] Piperidine-3-acetic acid is obtained in the form of a white solid.
[3542] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). Two diastereomeric mixtures are observed:
[3543] 1.00 to 2.20 and 2.25 to 2.80 (mts, all 25H), 3.10 (mt, 2H), 3.92 (wide s, 3H), 5.26 (unsplit peak, 1H), 7.20 to 7.60 (mt, 3H), 7.93 (wide d, J = 9 Hz, 1H), 8.71 (mt, 1H).
[3544] Example 54A
[3545] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- ( cyclopentylthio) ethyl] Piperidine-3-acetate dihydrochloride
[3546] 2.5 g of methyl (3R, 4R) in 40 cm 3 of methanol (added 1 drop of 5N aqueous sodium hydroxide solution) in portions over approximately 30 minutes at a temperature of less than 30 ° C. while stirring 0.227 g of sodium borohydride under an inert atmosphere. To a mixture of -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetate. After stirring the reaction mixture for 3 hours at a temperature in the range 20 ° C., 100 cm 3 of water is added and the mixture is extracted four times with 50 cm 3 of ethyl acetate. The combined extracts are washed three times with 50 cm 3 of water, dried over magnesium sulfate, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The obtained residual oil is purified by chromatography (eluent: pure ethyl ether) under atmospheric pressure on a silicakel (particle size 20-45 μm; diameter 3.2 cm; silica volume 100 cm 3) column to collect 25 cm 3 fractions. Fractions containing the expected product are combined and then concentrated as above. 2.1 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) Ethyl] piperidine-3-acetate is obtained in the form of a pale yellow oil. Hydrochloride was prepared in the following manner: A solution of 0.5 g of the oil obtained above dissolved in 15 cm 3 of dichloromethane was poured into 4 cm 3 of 1N hydrochloric acid solution in diethyl ether with stirring. The product is precipitated and crystallized by addition of 25 cm 3 of diethyl ether. The solid is filtered off, washed twice with 10 cm 3 of ether and dried under reduced pressure (5 kPa) over potassium hydroxide and then dried in an oven under reduced pressure (10 Pa) at a temperature in the range of 40 ° C. until constant weight. 0.35 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) Ethyl] piperidine-3-acetate dihydrochloride is obtained in the form of an off-white solid.
[3547] Infrared Spectrum (KBr): 3355, 2950, 2560, 2051, 1982, 1731, 1619, 1601, 1428, 1248, 1206, 1020, 849 and 714 cm ^-1
[3548] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetate
[3549] 4.9 g methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate in 130 cm 3 of acetonitrile, 2.9 g 2 A mixture of chloroethyl cyclopentyl sulfide, 9 g potassium carbonate and 2.7 g potassium iodide is stirred for 17 hours at a temperature in the range of 65 ° C. After cooling to a temperature in the range of 20 ° C., the reaction mixture is extracted three times with 60 cm 3 of ethyl acetate with 150 cm 3 of water added. The organic extracts are combined, washed twice with 50 cm 3 [lacuna], dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at temperatures in the range of 40 ° C. An oil is obtained and the product is purified by atmospheric chromatography (eluent: pure ethyl acetate) on an silica gel (particle size 20-45 μm; diameter 4 cm; silica volume 300 cm 3) column under atmospheric pressure to collect approximately 70 cm 3 fractions. Fractions containing the expected product are collected and concentrated under the above conditions. 2.6 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3 Acetate is obtained in the form of a yellow oil.
[3550] Infrared spectrum (CCl ₄ ): 2952, 2802, 1738, 1692, 1620,
[3551] 1504, 1242, 1165, 1032, and 850 cm ^-1
[3552] Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid was obtained in Example 48.
[3553] 2-Chloroethyl cyclopentyl sulfide can be prepared by applying the method described in patent application FR 2,395,260.
[3554] Example 55
[3555] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[3556] 0.531 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4) in 5.3 cm 3 of dioxane (with 0.84 cm 3 5N aqueous sodium hydroxide solution) -Yl) propyl] -1- [3- (2,6-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is stirred for 15 hours at a temperature in the range of 60 ° C. . After cooling at a temperature in the 20 ° C. range, the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the 40 ° C. range. The residue obtained was purified by chromatography (eluant: dichloromethane / methanol (90/10 volume) mixture) on a silica gel (particle size 20-45 μm; diameter 3 cm; 20 g) column under nitrogen pressure of 50 kPa, first Collect 100 cm 3 aliquots and then collect 25 cm 3 fractions. Fractions 1-12 are combined and then concentrated as above. A foam is obtained and the product is taken for 15 minutes in 15 cm 3 of diisopropyl ether with stirring. After 15 cm 3 of pentane was added and stirred for an additional 10 minutes, the crystalline product formed was filtered off, twice with 10 cm 3 of diisopropyl ether / pentane (50/50 vol) mixture and 3 with 20 cm 3 of pentane Washed once and dried in air. 0.293 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-di Fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a cream solid that melts at 107 ° C.
[3557] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed:
[3558] 1.40 to 1.95 and 2.30 to 3.00 (mts, all 12H), 3.67 and 3.68 (2s, all 2H), 3.88 and 3.92 (2s, all 3H), 5.24 (mt, 1H), 5.55 (non-split peak, 1H), 7.22 (mt, 2H), 7.30 to 7.60 (mt, 4H), 7.39 (d, J = 9 Hz, 1H), 8.70 (mt, 1H), 12.20 to 12.80 (wide undivided peak, 1H).
[3559] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylate 1.07 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- in 10 cm 3 of triethylamine The mixture of (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate is stirred at a temperature in the range of 20 ° C. under reduced pressure for 5 minutes. 0.156 g tetrakis (triphenylphosphine) palladium, 0.051 g cuprous iodide and 0.78 g 1-bromo-2,6-difluorobenzene are added. The mixture is stirred at a temperature in the range of 80 ° C. for 3 hours 30 minutes. After cooling to approximately 20 ° C., the reaction mixture has 30 cm 3 of water and 30 cm 3 of ethyl acetate added. After stirring for 10 minutes, the mixture is sedimented and separated. After separation of the organic phase, the aqueous phase is extracted with 30 cm 3 of ethyl acetate. The organic phases are combined, washed three times with 30 cm 3 of water, dried over sodium sulfate, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The residue was purified by chromatography (eluent: pure ethyl acetate) under partial pressure of 50 kPa on a silica gel (particle size 20-45 μm; diameter 3 cm; 50 g) column, first collecting 300 cm 3 aliquots, and then 38 Collect cm 3 fractions. Fractions 6-16 are combined and concentrated as above. 0.55 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) prop] -1- [3- (2,6 -Difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is obtained in the form of a pale yellow foam.
[3560] Infrared Spectrum (CCl ₄ ): 3615, 2950, 1738, 1622, 1470, 1241, 1007, 854 and 719 cm ^-1
[3561] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine 3-carboxylate can be prepared as described in Example 32.
[3562] Example 56
[3563] (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine -3-acetic acid
[3564] 0.525 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] in 5 cm 3 dioxane while stirring 0.83 cm 3 5N aqueous sodium hydroxide solution at a temperature within the range of 20 ° C. It is injected into the -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine-3-acetate solution and then the mixture is heated at a temperature in the range of 60 ° C. for 3 hours. After cooling to approximately 20 ° C., the mixture is stirred for 3 days and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The residue obtained is taken up in 15 cm 3 of water and then the solution is extracted with 5 cm 3 of ethyl acetate. The pH of the aqueous phase is adjusted within the range 5-6 by addition of 4.1 cm 3 of 1N aqueous hydrochloric acid, followed by extraction with 30 cm 3 of dichloromethane and then with 10 cm 3 of the same solvent. The organic extracts are combined, washed twice with 5 cm 3 of water, dried over magnesium sulfate, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The residue obtained is taken up in diethyl ether and then concentrated under the same conditions as above until constant weight is obtained. 0.45 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] Piperidine-3-acetic acid is obtained in the form of a light beige solid.
[3565] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)):
[3566] 1.20 to 1.80 (mt, 7H), 2.10 to 2.35 (mt, 4H), 2.43 (dd, J = 16.5 and 10.5 Hz, 1H), 2.75 (mt, 2H), 3.05 (mt, 2H), 3.47 (s, 2H), 3.93 (s, 3H), 7.18 (mt, 2H), 7.25 to 7.35 (mt, 1H), 7.33 (d, J = 4 Hz, 1H), 7.35 to 7.45 (mt, 2H), 7.92 (d, J = 9 Hz, 1H), 8.62 (d, J = 4 Hz, 1H).
[3567] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl) piperi Din-3-acetate
[3568] 0.35 cm 3 of 1-bromo-3,5-difluorobenzene followed by 0.112 g of tetrakis (triphenylphosphine) palladium and 0.037 g of first copper iodide under an inert atmosphere at a temperature in the range of 20 ° C. 0.77 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine- in 7.7 cm 3 of triethylamine Add to a stirred mixture of 3-acetate. The suspension obtained is heated at a temperature in the range of 80 ° C. for 3 hours and then at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in 50 cm 3 of ethyl acetate in 20 cm 3 of water. After the mixture was stirred for 15 minutes, the residual insoluble material was separated by filtration through clarcel and then the filtrate was settled: the organic phase was separated and washed three times with 3 cm 3 of water and saturated aqueous sodium chloride solution, Dry over magnesium sulfate, filter and concentrate at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The oil residue obtained is purified by chromatography (eluant: dichloromethane / methanol (97/3 volume) mixture) on a silica gel (particle size 40-63μ; diameter 3 cm; 45 g) column under nitrogen pressure of 50 kPa. Collect fractions containing the expected product. These fractions are concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). 0.345 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl ] Piperidine-3-acetate is obtained in the form of a pale yellow oil.
[3569] Mass spectrum (EI): m / z = 506 M ⁺
[3570] Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-acetate was described in Example 39. It was prepared according to the method.
[3571] Example 57
[3572] (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4- Yl) propyl] piperidine-3-carboxylic acid dihydrochloride
[3573] 0.42 g of methyl (3R, 4R) -1- [2- (3,5-difluorophenylthio) in 5.5 cm 3 of methanol under inert atmosphere while stirring 1.6 cm 3 of aqueous 5N sodium hydroxide solution at a temperature in the range of 20 ° C To ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate solution. The mixture is heated at a temperature in the range of 60 ° C. for 16 h. The resulting solution is evaporated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. and then 5 cm 3 of distilled water and 2.66 cm 3 of 6N aqueous hydrochloric acid are added to the obtained residue. The mixture is heated at a temperature in the range of 60 ° C. until a homogeneous solution is obtained and the solution is subsequently evaporated under the above conditions. The residue obtained is triturated in 10 cm 3 of dichloromethane / methanol (90/10 vol) mixture and then the insoluble material obtained is filtered off and washed twice with the same mixture of 2.5 cm 3. The filtrate is concentrated under the same conditions as above. 0.465 g of (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline 4-yl) propyl] piperidine-3-carboxylic acid dihydrochloride is obtained in the form of a yellow foam which melts at 160 ° C. (decomposition).
[3574] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). A mixture of two diastereomers is observed:
[3575] 1.35 to 2.35 and 2.60 to 4.00 (mts, all 16H), 4.01 and 4.02 (2s, all 3H), 5.45 to 5.65 (mt, 1H), 7.10 (mt, 1H), 7.21 (mt, 2H), 7.50 to 7.70 (mt, 1H), 7.76 (mt, 1H), 8.00 (mt, 1H), 8.33 (mt, 1H), 9.04 (d, J = 5.5 Hz, 1H), 11.10 to 11.55 (2 undivided peak, all 1H ).
[3576] Methyl (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4 -Yl) propyl] piperidine-3-carboxylate
[3577] 0.332 g of potassium carbonate previously dissolved in 5 cm 3 of acetonitrile, followed by 0.4 g of potassium iodide, and finally 0.675 g of 1-[(2-bromoethyl) thio] -3,5-difluorobenzene 0.717 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6) in 15 cm 3 of acetonitrile and 1 cm 3 of methanol with stirring under an inert atmosphere at a temperature in the range of 20 ° C. -Methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate solution. The mixture is heated at a temperature in the range of 80 ° C. for 3 hours. After cooling to a temperature in the range of 20 ° C., the reaction mixture is filtered and the cake is washed twice with 5 cm 3 of acetonitrile. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The residue was purified by chromatography on a silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm) column under 50 kPa nitrogen pressure (eluant: dichloromethane / methanol (95/5 volume) mixture) to collect 35 cm 3 fractions do. Fractions 18 to 21 are combined and then evaporated as above. 0.47 g of methyl (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxy Quinolin-4-yl) propyl] piperidine-3-carboxylate is obtained as an orange viscous oil.
[3578] Infrared spectra (CH ₂ Cl ₂ ): 3597, 2951, 2814, 1733, 1611, 1586, 1242, 1119, 985, 877, 840 and 667 cm ^-1
[3579] 1-[(2-bromoethyl) thio] -3,5-difluorobenzene
[3580] A solution of 2.59 g sodium hydroxide pellets in 27 cm 3 distilled water followed by 0.27 cm 3 aliquot 336 (tricaprylmethylammonium chloride) was stirred under an inert atmosphere with 7.5 g 3,3 g of 7.5 g in 3,1,2-dibromoethane. To a mixture of 5-difluorothiophenol (maintained at a temperature in the range of 23 ° C.). After 15 minutes of stirring at a temperature in the range of 20 ° C., 50 cm 3 of dichloromethane is added to the mixture, and after a few minutes, the organic phase is sedimented and separated, with 25 cm 3 of water and 25 cm 3 of saturated 10% sodium chloride The solution is washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. The evaporation residue was purified by chromatography (eluent: cyclohexane) on a silica gel (particle size 40-63 μm; diameter 5 cm; height 30 cm) column under 50 kPa nitrogen pressure, first collecting 500 cm 3 fractions, then 50 cm 3 days Collect fractions. Fractions 9 to 26 were combined and then concentrated to reduced pressure (5 kPa) g at a temperature in the range of 40 ° C. 5.9 g of 1-[(2-bromoethyl) thio] -3,5-difluorobenzene are obtained in the form of a colorless liquid.
[3581] Infrared Spectrum (CCl ₄ ): 3094, 1607, 1587, 1429, 1192, 1122, 988, 876, 841 and 667 cm ^-1
[3582] 3,5-difluorothiophenols are described in Dae-Kee Kim, Jongsik Gam et al., J. Med. Chem., 1997, p.2371.
[3583] Example 58
[3584] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl ) Prop-2-ynyl] piperidine-3-carboxylic acid
[3585] 0.810 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4) in 8 cm 3 of dioxane (with 1.3 cm 3 added 5N aqueous sodium hydroxide solution) -Yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate mixture is stirred at a temperature in the range of 60 ° C. for 17 hours. After cooling to approximately 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the range of 50 ° C. The residue obtained is purified by chromatography (eluant: dichloromethane / methanol (92/8 volume) mixture) on a silica gel (particle size 20-45 μm; diameter 3 cm; weight 45 g) column under nitrogen pressure of 50 kPa. A 275 cm 3 aliquot is collected first, followed by 20 cm 3 fractions. Collect fractions 12-46. These fractions are combined and concentrated at a temperature in the range of 35 ° C. under reduced pressure (5 kPa). The obtained residue is taken up in dichloromethane and filtered. The filtrate is evaporated as above and the new residue obtained is triturated in 10 cm 3 of diisopropyl ether. The mixture is stirred at a temperature in the range of 20 ° C. for 1 hour and then left for 16 hours. The solid precipitate is separated by filtration and washed twice with 10 cm 3 of the same solvent and then twice with 10 cm 3 of pentane. 0.47 g of (3R, 4R) -4- [3- (R, S) -hydroxy -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid at 92 ° C Obtained in the form of a melting white solid.
[3586] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)): Mixture of diastereomers is observed:
[3587] 1.40-1.95 and 2.30-3.00 (2 series of mts, all 12H), 3.64 and 3.65 (2s, all 2H), 3.90 and 3.92 (2s, all 3H), 5.25 (mt, 1H), 5.52 (non-split peak, 1H), and 7.15 to 7.30 (mt, 1H), and 7.30 to 7.60 (mt, 5H), 7.93 (d, J = 10 Hz, 1H), 8.70 (d, J = 4.5 Hz, 1H), 11.90 to 12.80 ( Very broad undivided peak, 1H).
[3588] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro Phenyl) prop-2-ynyl] piperidine-3-carboxylate
[3589] 0.16 g of tetrakis (triphenylphosphine) palladium, 0.053 g of cuprous iodide and 0.47 cm 3 of 1-bromo-2,3-difluorobenzene were weighed 1.1 g of 11 g of triethylamine. Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine To a mixture of -3-carboxylate (stirring at a temperature in the range of 20 ° C. under an inert atmosphere). The mixture is heated at a temperature in the range of 80 ° C. for 3 hours 30 minutes. After cooling to approximately 20 ° C., the reaction mixture is taken up in 30 cm 3 of ethyl acetate and 30 cm 3 of water and stirred for 15 minutes. The aqueous phase is extracted three times with 30 cm 3 of ethyl acetate while the organic phase is precipitated and separated. The organic extracts are combined, washed three times with 30 cm 3 of water, dried over sodium sulfate, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The resulting residue is purified by chromatography (eluent: pure ethyl acetate) on a silica gel (particle size 20-45 μm; diameter 3 cm; 50 g) column under 50 kPa nitrogen pressure. A 300 cm 3 aliquot is collected first and then 30 cm 3 fractions are obtained. Fractions 10 to 30 are combined and evaporated under these conditions. 0.94 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3- Difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate is obtained in the form of an orange foam.
[3590] Infrared spectra (CH ₂ Cl ₂ ): 3598, 2951, 1733, 1622, 1489, 1475, 1243, 1227, 1031, 856 and 831 cm ^-1
[3591] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine 3-carboxylate can be prepared as described in Example 32.
[3592] Example 59
[3593] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid
[3594] 1.7 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline-4) in 17 cm 3 dioxane (with 2.58 cm 3 5N aqueous sodium hydroxide solution) -Yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylate for 15 hours at a temperature in the range of 60 ° C Stir. After cooling to a temperature in the range of 20 ° C., the reaction mixture is concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The obtained residue was purified by chromatography (eluent: dichloromethane / methanol (90/10 volume) mixture) on a silica gel (particle size 20-45 μm; diameter 3 cm; 50 g) column under nitrogen pressure of 50 kPa to obtain 200 cm 3 first. One fraction is then collected for 23 cm 3 fractions. Fractions 3 to 21 are combined and then concentrated as above. Foam was obtained and the product was subjected to second chromatography (eluent: dichloromethane / methanol (95/5 volume) mixture) on a silica gel (particle size 20-45 μm; diameter 3 cm; 70 g) column under nitrogen pressure of 50 kPa. Purify, first collect 250 cm 3 fractions, then 100 cm 3 fractions, and then 20 cm 3 fractions. Fractions 1 to 17 are combined and then concentrated as above. A foam is obtained and the product is taken up in dichloromethane and then in a 50/50 mixture of 20 cm 3 of diisopropyl ether and pentane. The crystalline product formed is filtered off and washed twice with 10 cm 3 of diisopropyl ether / pentane (50/50 vol) mixture and twice with 10 cm 3 of pentane and then dried in air. 0.524 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5 Trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid is obtained in the form of a cream solid that melts at approximately 97 ° C.
[3595] ¹ H NMR spectrum (300MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): Diastereomeric mixtures are observed at 50/50 ratio:
[3596] 1.40 to 2.00 (mt, 7H), 2.35 to 3.00 (mt, 5H), 3.65 and 3.66 (2s, all 2H), 3.90 and 3.92 (2s, all 3H), 5.24 (mt, 1H), 5.54 (unsplit peak) , 1H), 7.25-7.45 (mt, 3H), 7.50-7.70 (mt, 2H), 7.94 (d, J = 9.5 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3597] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate
[3598] 1.95 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (in 20 cm 3 of triethylamine The mixture of prop-2-ynyl) piperidine-3-carboxylate is stirred for 5 minutes under an inert atmosphere at a temperature in the range of 20 ° C. 0.284 g of tetrakis (triphenylphosphine) palladium, 0.094 g of cuprous iodide and 1.56 g of 1-bromo-2,3,5-trifluorobenzene are added. The mixture is stirred at a temperature in the range of 80 ° C. for 2 hours 30 minutes. After cooling to approximately 20 ° C., the reaction mixture has 60 cm 3 of water and 60 cm 3 of ethyl acetate added. After stirring for 30 minutes, the mixture is sedimented and separated. After separation of the organic phase, the aqueous phase is extracted three times with 30 cm 3 of ethyl acetate. The organic extracts are combined, washed three times with 30 cm 3 of water, dried over sodium sulfate, filtered and concentrated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The residue obtained was purified by chromatography (eluent: pure ethyl acetate) under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μm; diameter 4 cm; 80 g), first 100 cm 3 fractions followed by 20 cm 3 fractions. Collect. Fractions 23 to 27 are combined and concentrated as above. 1.3 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3, 5-Trifluorophenyl) prop-2-ynyl] pyrepidine-3-carboxylate is obtained in foam form.
[3599] Infrared Spectrum (CCl ₄ ): 2950, 1740, 1624, 1496, 1231, 1133, 861 and 845 cm ^-1
[3600] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3 (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine- 3-carboxylate can be prepared as described in Example 32.
[3601] Example 60
[3602] (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl]
[3603] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid
[3604] 1.28 g of methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinoline-4) in 25 cm 3 dioxane (with 2 cm 3 5N aqueous sodium hydroxide solution) -Yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate is stirred at a temperature in the range of 60 ° C. for 18 hours. After evaporation at a temperature in the range of 50 ° C. under reduced pressure (5 kPa), the residue is taken up in 50 cm 3 of acetone. Acetone is evaporated at a temperature in the range of 50 ° C. under reduced pressure (5 kPa). The residue is taken up in 75 cm 3 of water and 100 cm 3 of dichloromethane. Isolate the organic phase. The aqueous phase is extracted twice with 100 cm 3 of dichloromethane and then the organic extracts are combined, dried over sodium sulphate, filtered and evaporated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). The solid obtained is taken up in 50 cm 3 of diethyl ether and the resulting suspension is stirred for 48 hours at a temperature in the range of 20 ° C. The solid is filtered off, washed with a total of 75 cm 3 of diethyl ether and dried at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). 1 g of solid is obtained and the product is chromatographed on silica gel (particle size 60-200 μm; diameter 2 cm; silica height 15 cm) under 100 kPa nitrogen pressure (eluant: chloroform / methanol / aqueous ammonia (24/6 / 1 volume) mixture), and 20 cm <3> fractions are collected. Fractions containing the product are collected and evaporated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). 0.97 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio ) Ethyl] piperidine-3-acetic acid is obtained in the form of a white foam which is a mixture of two diastereomers.
[3605] ¹ H NMR spectrum (400 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm) with few drops of d4-CD3COOD). Two diastereomeric mixtures are observed at a 50/50 ratio:
[3606] 1.15 to 1.65 (mt, 5H), 1.90 to 2.60 (mt, 7H), 2.61 (mt, 2H), 2.78 (mt, 2H), 2.93 (wide area t, J = 7 Hz, 2H), 3.92 and 3.93 (2 s , All 3H), 6.36 (mt, J _HF = 48 Hz, 1H), 7.04 (dd, J = 5.5 and 3.5 Hz, 1H), 7.18 (dd, J = 3.5 and 1 Hz, 1H), 7.29 (mt, 1H) , 7.44 (mt, 1H), 7.49 (wide area d, J = 4.5 Hz, 1H), 7.59 (dd, J = 5.5 and 1 Hz, 1H), 7.98 (wide area d, J = 9 Hz, 1H), 8.77 (d, J = 4.5 Hz, 1H).
[3607] Methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl Piperidine-3-acetate
[3608] 0.62 cm 3 of diethylaminosulfur trifluoride over 1.15 g of methyl (3R, 4R) -4- [3- (R, S in 15 cm 3 of dichloromethane at a temperature in the range of 20 ° C. under an inert atmosphere over approximately 15 minutes. To a stirred mixture of) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate. . The stirring is maintained for 18 hours. After adding 30 cm <3> of saturated aqueous sodium carbonate solution, the organic phase is sedimented and separated. The aqueous phase is extracted twice with 50 cm 3 of dichloromethane and then the organic extracts are combined and washed twice with 50 cm 3 of distilled water, dried over sodium sulfate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the range of 40 ° C. Yield 1.95 g of yellow oil, which was chromatographed on a column of silica gel (particle size 20-45 μm; diameter 3 cm; silica height 40 cm) under 100 kPa nitrogen pressure (eluant: cyclohexane / ethyl acetate (3/2) Volume) mixture) to collect 80 cm 3 fractions. Fractions 32 to 64 are combined and evaporated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). 1.28 g of methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienyl Thio) ethyl] piperidine-3-acetate is obtained in the form of a colorless oil.
[3609] ¹ H NMR spectrum (300 MHz, d 6-(CD ₃ ) ₂ SO, δ (ppm)). Two diastereomeric mixtures are observed at a ratio of 60/40:
[3610] 1.10 to 1.60 (mt, 5H), 1.85 to 2.15 (mt, 6H), 2.20 to 2.80 (mt, 5H), 2.88 (wide t, J = 7 Hz, 2H), 3.53 and 3.55 (2s, all 3H), 3.93 And 3.94 (2s, all 3H), 6.40 (mt, J _HF = 48 Hz, 1H), 7.03 (dd, J = 5.5 and 3.5 Hz, 1H), 7.15 (wide area d, J = 3.5 Hz, 1H), 7.30 ( Wide d, J = 1.5 Hz, 1H), 7.46 (dd, J = 9 and 1.5 Hz, 1H), 7.49 (wide d, J = 4.5 Hz, 1H), 7.60 (dd, J = 5.5 and 1 Hz, 1H) , 7.99 (wide area d, J = 9 Hz, 1 H), 8.79 (d, J = 4.5 Hz, 1 H).
[3611] Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] Piperidine-3-acetate is prepared as described in Example 48.
[3612] Example 61
[3613] (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Acetic acid, diastereomer A
[3614] 0.5 g of methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl]-in 10 cm 3 of dioxane (with 0.77 cm 3 5N aqueous sodium hydroxide solution) 1- [2- (2-thienylthio) ethyl] piperidine-3-acetate, diastereomer A ([α] ²⁰ _D = -48 ± 3 in methanol) for 18 hours at a temperature in the range of 60 ° C Stir while. After evaporation at a temperature in the range of 50 ° C. under reduced pressure (5 kPa), 0.6 g of a solid was obtained, which was subjected to a nitrogen pressure of 100 kPa on a column of silica gel (particle size 20-45 μm; diameter 2 cm; silica height 30 cm). Chromatography (eluent: chloroform / methanol / aqueous ammonia (24/6/1 volume) mixture) is purified to collect 20 cm 3 fractions. Fractions containing product are combined and evaporated at a temperature in the range of 40 ° C. under reduced pressure (5 kPa). 0.27 g (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine 3-Acetic acid, diastereomer A is obtained in the form of a white foam ([a] ²⁰ _D = -66 ± 1.2 in methanol).
[3615] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 1.55 (mt, 5H), 1.85 to 2.20 and 2.35 to 2.60 (mts of 2 series, all 9H), 2.68 (mt, 2H), 2.89 (broad t, J = 7 Hz, 2H), 3.94 (s, 3H), 6.38 (mt, J _HF = 48 Hz, 1H), 7.05 (dd, J = 5.5 and 3.5 Hz, 1H), 7.17 (dd, J = 3.5 and 1 Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 7.45 (dd, J = 9 and 2.5 Hz, 1H), 7.51 (d, J = 4.5 Hz, 1H), 7.60 (dd, J = 5.5 and 1 Hz, 1H), 7.99 (d, J = 9 Hz, 1H), 8.78 (d, J = 4.5 Hz, 1H).
[3616] Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3 Acetate, Diastereomer A
[3617] Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3 Acetate, diastereomer B
[3618] 3.2 g of methyl (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienyl Thio) ethyl] piperidine-3-acetate is chromatographed on a 30 cm long and 8 cm diameter column packed with 1200 g of Chiralcel OD silica (particle size 20 μm). Eluate with a hexane / isopropanol (90/10 volume) mixture. The flow rate is 140 cm 3 / min. Detection with ultraviolet rays at 265 nm. After several preliminary injections, fractions corresponding to diastereomers A and B are collected. The fraction corresponding to diastereomer A is concentrated at a temperature corresponding to 40 ° C. under reduced pressure (5 kPa). 1.6 g of methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperi Dean-3-acetate, diastereomer A is obtained in concentrated oil form ([a] ²⁰ _D = -48 +/- 3 in 0.1% methanol). Fractions comprising diastereomer B are concentrated under the same conditions as above. 1.17 g of methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperi Dean-3-acetate, diastereomer B is obtained in the form of a thick oil ([α] ²⁰ _D = +82 +/- 3 in 0.1% in methanol).
[3619] Diastereomer A:
[3620] Infrared spectra (KBr): 2936, 2861, 2805, 2768, 1731, 1623, 1594, 1508, 1475, 1435, 1359, 1229, 1217, 1167, 1108, 1084, 1030, 855, 847 and 830 cm ^-1 .
[3621] Diastereomer B:
[3622] Infrared Spectrum (KBr): 2932, 2861, 2805, 2768, 1731, 1623, 1594, 1509, 1475, 1435, 1359, 1229, 1217, 1168, 1108, 1083, 1030, 855, 847 and 830 cm ^-1 .
[3623] Methyl (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl ] Piperidine-3-acetate is prepared as described in Example 60.
[3624] Example 62
[3625] (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- Acetic acid, diastereomer B
[3626] 0.5 g of methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- 0.29 g of (3R, 4R) -4- [3 using (2-thienylthio) ethyl] piperidine-3-acetate and diastereomer B ([α] ²⁰ _D = +82) as starting materials -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, diastereomer B in white foam form ([A] ²⁰ _D = +66.3 1.1).
[3627] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)): 1.20 to 1.60 (mt, 5H), 1.90 to 2.15 and 2.30 to 2.60 (mts of 2 series, all 9H), 2.68 (mt, 2H), 2.89 (broad t, J = 7 Hz, 2H), 3.95 (s, 3H), 6.38 (mt, J _HF = 48 Hz, 1H), 7.05 (dd, J = 5.5 and 3.5 Hz, 1H), 7.18 (dd, J = 3.5 and 1 Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 7.46 (dd, J = 9 and 2.5 Hz, 1H), 7.51 (d, J = 4.5 Hz, 1H), 7.61 (dd, J = 5.5 and 1 Hz, 1H), 7.99 (d, J = 9 Hz, 1H), 8.78 (d, J = 4.5 Hz, 1H).
[3628] Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3 Acetate, diastereomer B is prepared as described above in Example 61.
[3629] Example 63
[3630] (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop- 2-ynyl] piperidine-3-carboxylic acid, diastereomer A, and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, diastereomer B
[3631] 1.50 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [dissolved in 200 cm 3 of dichloromethanol Chromatography of 3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid into a 6 cm diameter 30 cm column packed with 700 g of Kromasil ^R silica (particle size 10 μm) Graphy. Eluate using a dichloromethane / acetonitrile / methanol mixture (90/5/5 volumes). The flow rate is 130 cm 3 / min and is detected by ultraviolet light at 265 nm. In this operation, after four preliminary injections, two diastereomers are obtained. The first corresponding fractions are concentrated under reduced pressure (5 kPa) until dried at a temperature in the range of 40 ° C. and the resulting residue is dried in an oven at a temperature in the range of 40 ° C. under reduced pressure (13 Pa). 1.9 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) Prop-2-ynyl] piperidine-3-carboxylic acid, diastereomer A ([a] ²⁰ _D = -50.9 ° +/- 1.4 in 0.5% in methanol) is obtained in foam form.
[3632] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)):
[3633] 1.40 to 2.00 (mt, 7H), 2.35 to 3.00 (mt, 5H), 3.66 (s, 2H), 3.92 (s, all 3H), 5.24 (mt, 1H), 5.54 (non-split peak, 1H), 7.25 To 7.45 (mt, 3H), 7.50 to 7.70 (mt, 2H), 7.94 (d, J = 9.5 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3634] The fraction corresponding to the second diastereomer is treated as above. 2.17 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) Prop-2-ynyl] piperidine-3-carboxylic acid, diastereomer B (in [α] ²⁰ _D = + 67.8 ° +/- 1.2, in 0.5% in methanol) in the form of foam is obtained.
[3635] ¹ H NMR spectrum (300 MHz, d6- (CD ₃ ) ₂ SO, δ (ppm)):
[3636] 1.40 to 2.00 (mt, 7H), 2.35 to 3.00 (mt, 5H), 3.65 (s, 2H), 3.90 (s, all 3H), 5.24 (mt, 1H), 5.54 (unsplit peak, 1H), 7.25 To 7.45 (mt, 3H), 7.50 to 7.70 (mt, 2H), 7.94 (d, J = 9.5 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H).
[3637] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-3-carboxylic acid can be prepared as described in Example 59.
[3638] The invention also provides for the at least one quinolylpropylpiperidine derivative according to the invention, optionally in salt form, in pure form or in combination with one or more compatible and pharmaceutically acceptable diluents or adjuvants. It relates to a pharmaceutical composition containing.
[3639] The compositions according to the invention can be used by oral, parenteral, topical or rectal route or in aerosol form.
[3640] As a solid composition for oral administration, tablets, pills, hard gelatin capsules, powders or granules may be used. In such compositions, the active products according to the invention, usually in the form of a combination, are mixed with one or more inert diluents or auxiliaries, for example sucrose, lactose or starch. These compositions may include materials other than diluents, for example lubricants such as magnesium stearate or controlled release coatings.
[3641] Liquid compositions for oral administration may be pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs, including inert diluents such as water or paraffin solution. Such compositions may also include substances other than diluents, for example wetting agents, sweetening agents or flavoring agents.
[3642] The composition for parenteral administration may be an emulsion or a sterile liquid. As the solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, or injectable organic esters such as ethyl oleate can be used. These compositions may also include auxiliaries, in particular wetting agents, isotonic agents, emulsifiers, dispersants and stabilizers.
[3643] Sterilization can be carried out in a number of ways, for example using a bacterial filter, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions that can be dissolved when used in sterile water or other injectable sterile media.
[3644] Topical injectable compositions can be, for example, creams, ointments, lotions or aerosols.
[3645] Compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active ingredient, excipients such as cocoa butter, semisynthetic glycerides or polyethylene glycols.
[3646] The composition may also be an aerosol. For use in liquid aerosol form, the composition may be a stable sterile liquid or solid composition that is dissolved in pyrogen-free sterile water, physiological saline or other pharmaceutically acceptable vehicle in use. For use in the form of dry aerosols for direct inhalation, the active ingredient is finely blended with a water soluble solid diluent or vehicle with a particle size of 30 to 80 μm, for example dextran, mannitol or lactose.
[3647] In the treatment of humans, the novel quinolylpropylpiperidine derivatives according to the invention are particularly useful for the treatment of infectious diseases of bacterial origin. Dosage depends on the desired effect and duration of treatment. The physician will determine the dose that is deemed most appropriate according to treatment and according to age, weight, degree of infection and other factors specific to the subject being treated. In general, the dosage is from 750 mg to 3 g of active product or from 400 mg to 1.2 g intravenously in two or three doses per day orally for adults.
[3648] The following examples illustrate the compositions according to the invention.
[3649] Example 1
[3650] Liquid compositions for parenteral use comprising the following components are prepared in accordance with conventional techniques;
[3651] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] 125 mg of piperidine-3-carboxylic acid
[3652] Enough for Glucose 2.5%
[3653] Sufficient amount for sodium hydroxide pH = 4-4.5
[3654] Sufficient quantity for 20 ml of water for injection
[3655] Example 2
[3656] Liquid compositions for parenteral use comprising the following components are prepared in accordance with conventional techniques;
[3657] (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] 125 mg of piperidine-3-acetic acid
[3658] Enough for Glucose 2.5%
[3659] Sufficient amount for sodium hydroxide pH = 4-4.5
[3660] Sufficient quantity for 20 ml of water for injection

权利要求:
Claims (11)
[1" claim-type="Currently amended] Quinolylpropylpiperidine derivatives of formula (1) in diastereomeric form or mixtures thereof, and salts thereof.
Formula 1

R ₁ is hydrogen or a halogen atom or a hydroxyl radical,
R ′ ₁ may represent a halogen atom or when R ₁ is also a halogen atom,
R ° is a hydrogen atom, or
R ₁ and R ° together form a bond,
R ′ ₁ is a hydrogen atom,
R ₂ represents a carboxyl, carboxymethyl or 2-carboxyethyl radical,
R ₃ is either in hydroxyl, halogen, oxo, carboxyl, alkyloxycarbonyl, alkyloxy or alkylthio or in the phenyl, phenylthio or phenylalkylthio radicals [they themselves are halogen, hydroxyl, alkyl, alkyloxy, trifluoro May carry from 1 to 4 substituents selected from methyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano, acetamido (1-4C) or amino; or a cycloalkyl or cycloalkylthio radical In which the cyclic moiety comprises 3 to 7 members, or 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally [halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoro Methoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] 5- to 6-membered aromatic heterocyclyl or hetero yarn optionally substituted Indicate keulril thio radical an alkyl radical substituted with one to three substituents selected from (C 1 -C 6) or, R ₃ is - halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxyl , Selected from alkyloxycarbonyl, cyano or amino] is substituted with a phenyl radical capable of carrying 1 to 3 substituents or is substituted with a cycloalkyl radical comprising 3 to 7 members or selected from nitrogen, oxygen or sulfur 5 containing 1 to 4 heteroatoms and optionally substituted with halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino Or a propargyl radical substituted with a 6 to 6 membered aromatic heterocyclyl radical, or R ₃ represents cinnamil or 4-phenabuten-3-yl. Or
R ₂ represents a hydroxymethyl, alkyloxycarbonyl, alkyloxycarbonylmethyl or 2- (alkyloxycarbonyl) ethyl radical (the alkyl moiety comprises 1 to 6 carbon atoms),
R ₃ is phenylthio capable of carrying 1 to 3 substituents [selected from halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano or amino] As a radical, as a cycloalkylthio radical (the cyclic moiety comprises from 3 to 7 members), or from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and [halogen, hydroxyl, alkyl, alkyloxy, tri Fluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] alkyl radicals (1-6 carbon atoms) substituted with 5- to 6-membered aromatic heterocyclylthio radicals optionally substituted Or R ₃ is selected from halogen, hydroxyl, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxyl, alkyloxycarbonyl, cyano or amino] Substituted with a phenyl radical capable of carrying 1 to 3 substituents or substituted with a cycloalkyl radical containing 3 to 7 members or containing 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur [halogen, hydroxyl , Alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxyl, alkyloxycarbonyl, cyano or amino] propargyl radicals substituted with 5- to 6-membered aromatic heterocyclyl radicals optionally substituted ,
R ₄ represents an alkyl radical (including 1 to 6 carbon atoms), an alkenyl-CH ₂ -radical or alkynyl-CH ₂ -radical, wherein the alkenyl or alkynyl moiety comprises 2 to 6 carbon atoms,
Alkyl radicals and moieties are straight or branched radicals and moieties and contain 1 to 4 carbon atoms except where noted.
[2" claim-type="Currently amended] The method of claim 1,
R ₁ is hydrogen or a halogen atom or a hydroxyl radical,
R ′ ₁ is a hydrogen atom,
R ° is a hydrogen atom,
R ₁ and R ° together form a bond,
R ′ ₁ is a hydrogen atom,
R ₂ represents a carboxyl or carboxymethyl radical,
R ₃ is in halogen, oxo, alkyloxy or alkylthio or in phenyl or phenylthio radicals (which themselves may carry 1 to 4 halogen atoms), or in cycloalkyl or cycloalkylthio radicals (cyclic moiety) Is a 3 to 7 member), or a 1 to 4 membered aromatic heterocyclyl or heterocyclylthio radical containing 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally substituted by halogen Or a propargyl radical or a nitrogen, oxygen or sulfur substituted with a phenyl radical which represents an alkyl radical (with 1 to 6 carbon atoms) substituted with from 3 to 3 substituents or R ₃ itself may carry 1 to 3 halogen substituents. Substitution with 5- to 6-membered aromatic heterocyclyl radicals containing 1 to 4 heteroatoms selected Represents a propargyl radical, R ₃ represents cinnamil,
R ₂ represents a hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonylmethyl radical (the alkyl moiety contains 1 to 6 carbon atoms) and R ₃ contains 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur Or an alkyl radical substituted with 5 to 6 membered aromatic heterocyclylthio radicals having 1 to 6 carbon atoms, or R ₃ is selected from nitrogen, oxygen or sulfur and includes 5 to 4 heteroatoms including 1 to 4 heteroatoms; A propargyl radical substituted with a six-membered aromatic heterocyclyl radical,
R ₄ represents an alkyl radical (containing 1 to 6 carbon atoms),
Quinolylpropylpiperidine derivatives in the form of diastereomers or mixtures thereof, characterized in that the alkyl radicals and moieties are straight or branched radicals and moieties, and salts thereof.
[3" claim-type="Currently amended] 3. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl]-according to claim 1 or 2 in the form of diastereoisomers or mixtures thereof. Quinolylpropylpiperidine derivatives characterized in that 1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, and salts thereof.
[4" claim-type="Currently amended] The compound according to claim 1 or 2, wherein (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] py Quinolylpropylpiperidine derivatives characterized in that it is ferridine-3-acetic acid, and salts thereof.
[5" claim-type="Currently amended] 3. (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl]-according to claim 1 or 2 in the form of diastereomers or mixtures thereof. Quinolylpropylpiperidine derivatives characterized in that 1- [2- (2-thienylsulfanyl) ethyl] piperidine-3-acetic acid, and salts thereof.
[6" claim-type="Currently amended] 3. (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy- according to claim 1 or 2 in the form of diastereomers or mixtures thereof. Quinolylpropylpiperidine derivatives characterized in that 3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, and salts thereof.
[7" claim-type="Currently amended] 3. (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl]-according to claim 1 or 2 in the form of diastereoisomers or mixtures thereof. Quinolylpropylpiperidine derivatives characterized in that 1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, and salts thereof.
[8" claim-type="Currently amended] The R ₃ chain defined in claim 1 is condensed onto a quinolylpropylpiperidine derivative of formula 2 to obtain a quinolylpropylpiperidine derivative of formula 3,
If desired, remove acid-protecting radicals,
If desired, the oxo radicals represented by R ″ ₁ and R ″ ′ ₁ are to be reduced with alcohols in which R ₁ represents hydroxyl, and then optionally, to obtain a quinolylpropylpiperidine derivative wherein R ₁ is a halogen atom. If halogenated, optionally, dehydrohalogenation of the corresponding halogenated derivative to give a quinolylpropylpiperidine derivative wherein R ₁ and R ° together form a bond, or R ″ ₁ and R ″ ′ ₁ Dihalogenated the product of formula 3, wherein together form an oxo radical, to obtain a quinolylpropylpiperidine derivative wherein R ₁ and R ′ ₁ are halogen atoms,
And / or optionally, the acid protected in the form of an R ′ ₂ radical at the 3-position of piperidine is reduced to a hydroxymethyl radical and optionally converted to a carboxymethyl or 2-carboxyethyl radical according to conventional methods. And then
Optionally a quinolylpropylpiperidine derivative according to claim 1, characterized by removing the acid-protecting radicals and / or optionally separating the diastereomers and optionally converting the product obtained into a salt. Manufacturing method.
Formula 2

Formula 3

In the above formula,
R ₃ and R ₄ are as defined in claim 1,
R ″ ₁ , and R ″ ′ ₁ represent a hydrogen atom or together form an oxo radical,
R ′ ₂ represents a protected carboxyl, carboxymethyl or 2-carboxyethyl radical, or an alkyloxycarbonyl, alkyloxycarbonylmethyl or 2- (alkyloxycarbonyl) ethyl radical.
[9" claim-type="Currently amended] The method according to claim 2, wherein the condensation of the R ₃ chain on the piperidine is carried out by the action of a derivative of the formula
Chemical formula
R ₃ -X
In the above formula,
R ₃ is as described above,
X represents a halogen atom, a methylsulfonyl radical, a trifluoromethylsulfonyl radical or a p-toluenesulfonyl radical.
[10" claim-type="Currently amended] The process according to claim 2 or 3, wherein when R ₃ represents propargyl substituted with phenyl, cycloalkyl or heterocyclyl, the reaction is preferably condensed with propargyl halide and then the chain is phenyl, cycloalkyl or heterocycle. Characterized in that it is substituted with a aryl radical.
[11" claim-type="Currently amended] A pharmaceutical composition comprising at least one derivative according to claim 1 in a pure state or in combination with one or more compatible and pharmaceutically acceptable diluents or adjuvants.

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引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
1999-09-17|Priority to FR9911679A

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1999-09-17|Priority to FR99/11679

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2000-09-14|Application filed by 추후제출, 아방티 파르마 소시에테 아노님

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2000-09-14|Priority to PCT/FR2000/002541

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2002-05-23|Publication of KR20020038757A

优先权:

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申请号 | 申请日 | 专利标题

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FR9911679A|FR2798656B1|1999-09-17|1999-09-17|Derivatives of quinolyl propyl piperidine, their preparation and the compositions containing them|

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FR99/11679|1999-09-17|

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PCT/FR2000/002541|WO2001025227A2|1999-09-17|2000-09-14|Quinolyl propyl piperidine derivatives and their use as antibacterial agents|