anti-infectious compounds

专利摘要:
  METHOD AND APPARATUS FOR CONVERSION OF BIDIMENSIONAL VIDEO CONTENT FOR INSERTION IN THREE-DIMENSIONAL VIDEO CONTENT.A method and apparatus are provided that convert video content from a first type of format to a second type of format so that the video content can be viewed with other video content that has the second type of video format. The method includes determining a first format of a first stream of video content (702) and determining a second format of a second stream of video content (704, 706). The method also includes converting (806, 808) the format of the second stream of video content to the format of the first stream and combining (812) the first stream of video content with the second stream of converted video content to form . In order to present the first and second streams of video content the method decodes the first combined and second converted streams of video content using the first format.
公开号:BR112012023576A2
申请号:R112012023576-1
申请日:2011-03-18
公开日:2020-09-01
发明作者:Zeasung No；Sunhee Kang；Fanny Anne Ewann；Ji Youn Nam；Thierry Christophe；Denis Philippe Cedric Fenistein；Heo Jamung；Jang Jiyeon；Jaeseung Kim；Priscille Brodin；Min Jung Seo；Young Mi Kim；Jonathan Cechetto；Heekyoung Jeon；Auguste Genovesio；Saeyeon Lee
申请人:Institut Pasteur Korea；Institut National de la Santé et de la Recherche Medicale (INSERM)；
IPC主号:

专利说明:

"It is the Invention Patent Specification Report for" ANTI-INFECTIVE COMPOSITES ", The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular tuberculosis.
Background to the Tuberculosis (TB) Invention as a disease continues to result in millions of deaths each year.
Inappropriate use of chemotherapy has led to an increasing number of drug-resistant cases.
This situation is probably worsened by the emergence of extremely resistant strains to all currently known drugs (Van Rie and Enarson, 2006). The internationally recommended TB control strategy also referred to as directly observed short-term chemotherapy (DOTS), says | v with a combination of five antibacterial agents, to be taken over a delayed period of more than six months (http: // www: who.int/tb/dots/en/). With the use of a mathematical model, taking into account the duration of treatment and dynamics of TB, the benefits of reduced treatment time were predicted to be substantial and are likely to contribute enormously to a reduced global TB burden (Salomon et al. , 2006). Current chemotherapy consists of compounds that directly target the Mycobacterium tuberculosis bacillus, either by neutralizing germinal information trails and clinical processes such as RNA polymerization and inhibition of protein synthesis or by interfering with mycobacterial specific cell envelope synthesis.
The most widely used dedicated anti-tuberculosis drugs isoniazid, ethionamide and pyrazinamide are prodrugs that first require activation. As active forms, they demonstrate inhibitory activity in a wide range of mycobacterial targets, which have not yet been fully characterized.
As for other chronic infectious diseases such as the human immunodeficiency virus, a method of mullti-therapy, including drugs that target a wide range of critical aspects of M. tuberculosis, proved to be the most successful strategy to date. this date.
It is therefore likely that a combination of current drug inhibitors, having different mechanisms of action against M. tuberculosis,
be the solution for disease control.
The most challenging methods for discovering new anti-TB drugs rely on the evaluation of active compounds that target critical aspects essential for the survival of the bacillus.
Although there is still a lack of understanding of the biological mechanisms behind the persistence of the bacillus tubercle, that is, the location and state of latent bacteria, in humans, M. tuberculosis is supposed to reside in primary granulomas under hypoxic conditions (Lenaerts et al. others, 2007) as well as hiding within various types of cells (Houben and others, 2006; Neyrolles and others,% 2006). The bacillus is mainly located within phagocytic cells, such as macrophages and dendritic cells, and it has been clearly established that. bacillus tuber adopts a different phenotype in the host macrophage phagosome, compared to growth in extracellular conditions (Rohde et al., 2007; Schnappinger et al., 2003). In infection, an inflammatory response is induced, thereby initiating recruitment of T lymphocytes that release interleukins and cytokines, which in turn activate the infected macrophages to enable the pathogen to be destroyed.
In the appropriate trigger, the host macrophage is thus able to eliminate invading bacillus.
This is also supported by the fact that the person who inhales M. tuberculosis, more than 95% percent does not develop the disease, suggesting that the response of the human host is sufficient in most cases to prevent pathogenesis induced by M. tuberculosis.
This gives rise to the hypothesis that small molecular compounds can mimic immune cell response signals and induce host cells to remove mycobacteria.
Consequently, the phenotypic cell-based assay, suitable for evaluating high productivity, which provides for the search for compounds that would prevent the multiplication of M. tuberculosis within the host macrophage (WO2010003533A2), overcoming many of the numerous and heavy steps in the past. in previous methodologies |
(Arain et al., 1996).
It was an objective of the present invention to identify effective compounds against bacterial infections, in particular compounds that would prevent the multiplication of M. tuberculosis within the host macrophage.
Description of the invention In one aspect, the present invention relates to compounds having the general formula la: o 1 (Fes
NOR la 'where mé 0o, 1,2,3ou4; * no 1,2,0U3; X, Y and Z are CH, N or N-oxide; R is, in each occurrence, independently selected from the group consisting of hydrogen, halogen, C + -C19 alkyl, C1-C3 haloalkyl, C3C; cycloalkyl, hydroxyl, oxo, -OR, -C (0) ORÍ, -C (O) RÍ, - C (OINIR) 2, -CN, -NOz -NH2 -N (R) 2, -ORHeta, -ORN ( R4) 2, - C (OINIRIRHetA, -C (OIN (RÓHetA, -C (O) HetA, -C (OIN (RIRIS (O) 2R «; - S (O) AN (R) a, -S (O ) LR , -N (RÍCIOIRÍSRI, -N (RIRÍS (OLRI, or - N (RÍIS (OLRÍ, -C (S) RÍ, arila, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; R 'is, in each occurrence, independently selected from the group consisting of hydrogen, halogen, C1-Ci19 alkyl, C3-Ci, 9 cycloalkyl, Ca-C19 alkenyl, C3-C19 cycloalkenyl, Cz- C15 alkynyl, C7-C19 haloalkyl, -OH, -ORô, Cr-C1o alkoxy, Ca-Cio cycloalkoxy, Ca-C15 cycloalkylalkoxy, Ca-Ci5s —cycloalkylalkyl, -CN, -NO>, -NHo, -N (R) 2, -C (O) Ró, -C (O0) ORÉ, -C (O) N (Ró) 2, - SRº, -S (O) Rº, -S (O) 2R5, -S (O) 2N (Rº) 2, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; R 'is, in each occurrence, independently selected from the group consisting of hydrogen. halogen, C1-C19 alkyl, C3-C19 cycloalkyl, C-C3 haloalkyl, hydroxyl, -OR $, -CN, -NO>, -NH>, -N (RÍC (O) RS, - q
C (O) Rô, -C (O0) ORS, -C (OINIRÔ) 2, -S (O) R, -S (O) 2Rô, -S (O) 2N (RÔ)>, arila, for example, phenyl, benzyl, heteroaryl, heterocyclyl, any of which is optionally substituted, or two groups of R they are connected to each other to form cyclic or heterocyclic rings of five or six members, any of which is optionally substituted; Rº is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C179 alkyl, C3-C16 cycloalkyl, Ca-C19 alkenyl, C3-C1o cycloalkenyl, C2-Ci1a alkynyl, CC haloalkyl, -C (O) R ”, -R (RINC (IOIR ', -C (O) OR', -R'WRICIOIOR, - C (OINIR) 3; -R (RIC (IOINIR) 2, -S (O) R”, -S ( O) 2R ”, -S (O) N (R”) s, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is “optionally substituted; and Rº, Rº and R are, in each occurrence , independently selected from the group consisting of hydrogen, C; -C19 alkyl, Ca-C19 cycloalkyl, CC, alkenyl, C3-C1.5 cycloalkenyl, C3-C1.5 alkynyl, Cy-C15 haloalkyl , aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted.
The term "optionally substituted" as used here is intended to indicate that a hydrogen atom attached to a member atom within a group, or several such hydrogen atoms, is replaced by a group, such as halogen including fluorine, C; -Ci5 alkyl, C; -C3 haloalkyl, C3-C7 cycloalkyl, oxo, -OH, -OR , -OC (O) Rº -CN, NO>, -N (R )>, - NIRBIC (O) RE , -RN (RICIO) RE, -C (O) Rº, -RºC (O) Rô, -C (0) OR , -RºC (0) OR *, -CIO) INIRô) 2, -REC (O) NIRE) 2, -S (O) RÊ, -S (O) 2Rº, -S (O) 2N (R)>, phenyl, benzyl, aryl, heteroaryl or heterocyclic, any of which alone is "optionally substituted" ; that is, one or more of the hydrogen atoms can be replaced by one of the groups mentioned above.
R8 is, in each occurrence, independently selected from the group consisting of hydrogen, halogen, C1-C15 alkyd, C; -C3 haloalkyl, C3-C; cycloalkyl, hydroxyl, oxo, -ORº, -C (O0) ORº, -C (O) Rº, -C (O) N (Rº) », - CN, -NO>, -NHa, -N (RY) 2 , -ORHetA, -ORN (R ) 2, -C (O) IN (RÓHetA, -C (O) HetA, -CIOINIRIRÍS (O) LR *; —-S (O) N (R% -S (O ) LR, -N (RICIOIRÍSR, - q
N (RIRÍS (O) 2Rº, or -N (RÓS (O) 2Rº, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclic, any of which is optionally substituted.
R9 is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C; alkyl optionally substituted with at least one hydroxyl or halogen; C3-C; cycloalkyl, aryl, for example, phenyl, benzyl, and heterocyclyl, any of which is optionally substituted.
In one embodiment, the present invention also relates to pharmaceutically acceptable salts of the compounds according to the present invention.
The term "alkyl" refers to a monovalent saturated, straight-chain or branched, aliphatic hydrocarbon radical having several carbon atoms in the specified range. Thus, for example, "Cr-Cs" alkyl "refers to any of the isomers of hexyl alkyl and pentyl alkyl as well as n-, iso-, sec-, and t-butyl, n- and isopropyl, ethyl and methyl .
The term "alkoxy" means a group having the formula -O-alkyl, in which an alkyl group, as defined above, is attached to the parent molecule by means of an oxygen atom. The alkyl portion of an alkoxy group may have 1 to 20 carbon atoms (ie, C; -C29 alkoxy), 1 to 12 carbon atoms (ie, C; -Ci2 alkoxy), or 1 to 6 carbon atoms (ie, C1-Cs alkoxy) Examples of suitable alkoxy groups include, but are not limited to, methoxy -O-CH; or OMe), ethoxy -OCH3CH; 3 or -OEt), t-butoxy (- OC (CH3) 3 or -OtBu) and the like , The term "alkenyl" refers to a linear or branched monovalent aliphatic hydrocarbon radical containing a carbon-carbon double bond and having several carbon atoms in the specified range. Thus, for example, " C2-Cs alkenyl "refers to all hexenyl and pentenyl isomers as well as 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl, 1-propenyl, 2-propenyl, and ethylene (or vinyl).
The term "alkynyl" refers to a monovalent straight or branched chain aliphatic hydrocarbon radical containing a carbon-carbon triple bond and having several carbon atoms in the specified range. each. Thus, for example, "C> -Cs alkynyl" refers to all hexinyl and pentynyl isomers as well as 1-butynyl, 2-butynyl, 3-butynyl, 1-propynyl, 2-propynyl, and ethynyl.
The term "alkylene" refers to a saturated, straight or branched or cyclic hydrocarbon radical having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms, 1 to 10 atoms carbon, or 1 to 6 carbon atoms. Typical alkylene radicals include, but are not limited to, methylene (-CH2-), 1,1-ethyl -CH (CH3) -), 1,2-ethyl -CHCH2-), 1,1-propill (CCH (CH2CH3) -), 1,2-propyl! (-CHXCH (CH3) -), 1,3-propyl (- CHICH; CH> 2-), 1,4-butyl CCHCHCH2CH2-), and the like. . The term "alkenylene" refers to an unsaturated, branched or linear or cyclic hydrocarbon radical having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon or alkene atoms For example, an alkenylene group can have 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 6 carbon atoms. Typical alkenylene radicals include, but are not limited to, 1,2 -etenila -CH = CH-).
The term "alkynylene" refers to an unsaturated, branched or linear or cyclic hydrocarbon radical having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different origin carbon atoms. For example, an alkynylene group can have 1 to 20 carbon atoms, 1 to 10 carbon atoms or 1 to 6 carbon atoms. Typical alkynylene radicals include, but are not limited to, acetylene (-C = C -), propargyl -CH2C = C-), and 4-pentynyl (CCH; CH; CH; C = CH-).
The term "cycloalkite", alone or in combination with any other term, refers to a group, such as optionally substituted or unsubstituted cyclic hydrocarbon, having three to eight carbon atoms, less than otherwise defined. Thus, for example, "C3-C8 cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, eciclooctyl.
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The term "haloalkyl" refers to an alkyl group, as defined. here which is replaced by at least one halogen.
Examples of straight or branched chain "haloalkyl" groups useful in the present invention include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, etbutyl independently substituted by one or more halogens.
The term "haloalkyl" should be interpreted to include such substituents, such as -CHF2, -CF3, -CH7-CH2-F, -CH7-CF3, and the like.
The term "heteroalkyl" refers to an alkyl group where one or more carbon atoms have been replaced by a hetero atom, such as, ON orS, For example, if the alkyl group carbon atom that is attached to the origin molecule is replaced by a heteroatom (for example, O, - N, or S) the resulting heteroalkyl groups are, respectively, an alkoxy group (for example, -OCH; s, etc.), an amine (for example, -NHCH; , - 7 N (CH;) 2, etc.), or thioalkyl group (e.g., -SCH ;, etc.). If a non-terminal carbon atom of the alkyl group that is not attached to the origin molecule is replaced by a heteroatom (for example, O, N, or S) and the resulting heteroalkyl groups are, respectively, an alkyl ether ( for example, -CH2CH2-0-CHs ;, etc.), alkyl amine (for example, -CHANHCH ;, - CHIAN (CH3) 2, etc.), or thioalkyl ether (for example, -CH2-S- CH;). The term "halogen" refers to fluorine, chlorine, bromine, or iodine.
The term "arylal" refers to (i) optionally substituted phenyl, (ii) 9 or 10 membered optionally substituted fused, bicyclic carbocyclic ring systems in which at least one ring is aromatic, and (iii) sys - fused carbocyclic ring, 11 to 14 membered tricyclic ring themes, optionally substituted where at least one ring is aromatic.
Suitable aryls include, for example, phenyl, biphenyl, naphthyl, tetrahydronaphthyl (tetralinyl), indenite, anthracenyl, and fluorenyl.
The term "phenyl" as used here is understood to indicate that optionally substituted or unsubstituted phenyl group.
The term "benzyl" as used herein is intended to indicate that optionally substituted or unsubstituted benzyl group.
The term "heteroaryl" refers to (1) optionally substituted 5 q and 6 membered heteroaromatic rings and (ii) 9 to 10 membered, optionally substituted, fused ring systems in which at least one ring is aromatic , in which the heteroaromatic ring or the bicyclic fused ring system contains from 1 to 4 independently selected heteroatoms from N, O, eS, where each N is optionally in the form of an oxide and each S in a non-aromatic ring is optionally S (O) or S (O)>. Suitable 5- and 6-membered heteroaromatic rings include, for example, pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thienila, furanyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isooxazole, iszoxol, thiadiazolyl.
Suitable 9 to 10-membered heterobicyclic ring systems include, for example, benzofuranyl, - indolyl, indazolyl, naphthyridinyl, isobenzofuranyl, benzopiperidinyl, benzisoxazolyl, benzoxazolyl, chromenyl, quinolinyl, isoquinolinyl, cinnolinyl, cinquinolin 7 nazolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, isoindolyl, benzodioxolyl, benzofuranyl, imidazo [1,2-a] pyridinyl, benzotriazolyl, dihydroindolyl, dihydroisoindolyl, indazolyl, indolinyl, isoindolinyl, quinolazaline
2,3-dihydrobenzofuranyl, and 2,3-dihydrobenzo-1 4-dioxinyl.
The term "heterocyclyl" refers to (i) 4 to 8 membered, saturated and unsaturated, but non-aromatic, optionally substituted monocyclic rings containing at least one carbon atom and 1 to 4 hetero atoms, (ii ) optionally substituted bicyclic ring systems containing from 1 to 6 heteroatoms, and (iii) optionally substituted tricyclic ring systems, where each ring in (ii) or (iii) is independent of fused to, or in point with the other ring or rings and each ring is saturated or unsaturated, but not aromatic, and where each heteroatom in (i), (ii), and (ii) is independently selected from N, O, and S, in that each N is optionally in the form of an oxide and each S is optionally oxidized to S (O) or S (O)>. Suitable 4- to 8-membered saturated heterocyclics include, for example, azetidinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrimidine, tetrahydrofuranil, tetrahydrofuranil, tetrahydrofuranil, - nila, diazepanila, tetrahydropyranyl, tetrahydrothiopyranyl, dioxanil, and azacycloocti-
q la. Suitable unsaturated heterocyclic rings include those that correspond to the saturated heterocyclic rings listed in the above sequence in which a single bond is replaced by a double bond. It is understood that the specific rings and ring systems suitable for use in the present invention are not limited to those listed in this and the preceding paragraphs. These rings and ring systems are merely representative. In one embodiment, the compound has the general formula lb: us mao and NT EEE
NOR Th where "0 is0,1,2,0u3; right0, 1,20u3; mean, 1,2,3or4, A is NR" !, C = O, C = S, OP (O), P = O, CH2, or a heteroaryl selected from the group consisting of NeTé rn N ç CC ed, ro, N CN bh E 4 ar o EE HIT HA HED: Weé C = O, O, S, CH2 or NR '*; R'º is a selected portion of the group consisting of í RU en, MN Ny nu air á Ç and Rº HI EQ HE nº Rude (Ra, * "= * N Sa Get OC Be E ã FR 1a E z 2 Hd HO and HA HI Ro
N N OG Ba, HC, JF AÁrºh A mm 2 nt FINGER "Oo Rd O) TN, 4 | - <NR no Hr" HO "A.
N |
R *! is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C19 alkyl, C3-C179 cycloalkyl, Ca-C10 alkenyl, C3-C1.9 cycloalkenyl, C2-C109 alkynyl, Ci-C1o haloalkyl, -OH, - OR, C1-C1 alkoxy, Ca-C1 cycloalkoxy, C3-C1 cycloalkylalkoxy, C3-C15 cyclo- —alkylalkyl, -NHa, -N (R / ) 2, -C (O) R " , -C ( O0) OR " , -C (OINIR ) 2, -S (O) R" , - S (O) aR " , -S (O) 2N (R *) 2, aryl, for example, phenyl , benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; R " Is, in each occurrence, independently selected from the group consisting of hydrogen, Ci-Ca1, alkyl, C3-C19 cycloalkyl, Ca-C1o alkenyl, C3-Ci6 cycloalkenyl, Cz-C19 alkynyl, C; -C1o haloalkyl, hydroxyl, OR ”, -C (O) R, -RA (ROC (OIR *, -C (O) JOR *, -RARMÁCIO) JOR *, -CN, - - NO2 ;, -NHz -N (RÚ) 2 , -C (OINIR to -RIRICIOINIR '*) 2, -S (O) R *, - S (O0) aR *, -S (O) 2N (R **) 2, aryl, for example, phenyl, benzyl , heteroaryl, and he- 'terocyclyl, any of which is optionally substituted; R "* is, at each occurrence, independently selected from the group consisting of hydrogen, C1-C19 alkyl, C3-C19 cycloalkyl, C-C10 alkenyl, C3 -C19 cycloalkenyl, C3-C19 alkynyl, C1-C1o haloalkyl, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclic, whichever is optionally substituted; and R ** is, in each occurrence, independently selected from the group that consists of hydrogen, C1-Cs alkyl optionally substituted with at least one hydroxyl or halogen; C3-C; ci cloalkyl, C2-C1, alkenyl, C3-C19 cycloalkenyl, C2-C1.9 alkynyl, C1-C19 haloalkyl, aryl, for example, phenyl, benzyl, heteroaryl and heterocyclyl, any of which is optionally substituted.
In another aspect, the present invention relates to compounds having one of formulas 1 to 352, as shown in table 1 and / or example 2, preferably 15, 16, 31, 32, 44, 45, 47, 49, 54- 57, 60-87, 89-103, 106, 107, 110, 111, 113, 116-135, 137-141, 143, 144, 147, 148, 152, 154, 157- 159,161-167,171-182, 184- 193, 196, 198, 199-202, 209-218, 221-227, 231, 248-260, 262-264, 267-269, 271-274, 280-293, 295-315, 317-318, 320- 321, 324, and 330 as shown in Table 1, and pharmaceutically acceptable salts | of the same. Particularly preferred are compounds having one of formulas 47, 54, 177 and 185 as shown in table 1. Their pharmaceutical activity is also shown in figure 2. Preferably, the compounds as defined above have an inhibitory activity on bacterial growth , preferably on the growth of M. tuberculose, within a host cell, preferably a macrophage, in a concentration between 1 to 20 µM, preferably less than 1 µM.
In one aspect, the present invention relates to compounds as defined above for use in the treatment of a bacterial infection, for example, tuberculosis.
- In one aspect, the present invention relates to compounds as defined above for use in the treatment of tuberculosis. In one aspect, the present invention relates to the pharmaceutical composition comprising a compound as defined above, and a pharmaceutically acceptable carrier.
In one aspect, the present invention relates to a method of treating tuberculosis, comprising applying an appropriate amount of a compound as defined above or a pharmaceutical composition as defined above, to a person in need thereof.
In one embodiment, a "suitable amount", as used here, is understood to refer to an amount in the range of 0.01 mg / kg of body weight to 1 g / kg of body weight.
The objectives of the present invention are also solved by a compound that competitively inhibits the specific binding of a compound according to the present invention. Preferably, such specific binding is with respect to a target protein of said compound according to the present invention.
The objectives of the present invention are also solved by a method of treating a bacterial infection, in particular tuberculosis comprising applying an adequate amount of a | compound whose compound is characterized by the ability to competitively inhibit the specific binding of a compound according to the present invention or the pharmaceutical composition according to the present invention, to a target protein, to a person in need of it.
Pharmaceutical composition Pharmaceutically acceptable salts Examples of pharmaceutically acceptable addition salts include, without limitation, non-toxic organic and inorganic acid addition salts, such as acetate derived from acetic acid, aconate derived from aconitic acid, ascorbate derived from acetic acid ascorbic acid, benzenesulfonate derived from benzensulfonic acid, benzoate derived from acid. benzoic acid, cinnamic acid derived from cinnamic acid, citrate derived from citric acid, embonate derived from embonic acid, enanthate derived from enanthic acid, formate derived from formic acid, fumarate derived from fumaric acid, glutamate derived from glutamic acid, glycolate derived from glycolic acid, hydrochloride derived from hydrochloric acid, hydrobromide derived from hydrobromic acid, lactate derived from lactic acid, maleate derived from maleic acid, malonate derived from malonic acid, derived malonate mandelic acid, methanesulphonic acid-derived methanesulfonate, naphthalene-2-sulfonic acid-derived naphthalene-2, nitric acid-derived nitrate, perchloric acid-derived perchlorate, phosphoric acid-derived phosphate, phthalalate-derived phthalic acid, salicylate derived from salicylic acid, sorbate derived from sorbic acid, stearate derived from stearic acid, succinate derived from acid succinic, sulfate derived from sulfuric acid, tartrate derived from tartaric acid, toluene-p-sulfonate derived from p-toluenesulfonic acid, and the like, Such salts can be formed by procedures well known and described in the art.
Other acids such as oxalic acid, which cannot be considered pharmaceutically acceptable, can be useful in the preparation of salts useful as intermediates in obtaining a chemical compound of the invention and its pharmaceutically acceptable acid addition salts. |
In another embodiment, the compounds of the invention are used in their respective free base forms in accordance with the present invention.
Metal salts of a chemical compound of the invention include alkali metal salts, such as the sodium salt of a chemical compound of the invention containing a carboxy group.
The chemical compounds of the invention can be supplied in unsolvated or solvated forms together with a pharmaceutically acceptable solvent (s) such as water, ethanol, and the like. Solvated forms can also include hydrated forms, such as the monohydrate, dihydrate, hemihydrate, trihydrate, tetrahydrate, and the like. In general, solvated forms are considered equivalent to unsolvated forms for the purposes of this invention. : Administration and Formulation The production of drugs containing the compounds of the invention, their active metabolites or isomers and salts according to the invention and their application can be carried out according to well-known pharmaceutical methods.
While the compounds of the invention, usable in accordance with the invention for use in therapy, can be administered in the form of the crude chemical compound, it is preferred to introduce the active ingredient, optionally in the form of a physiologically acceptable salt in the pharmaceutical composition together with one or more adjuvants, excipients, vehicles, buffers, thinners, and / or other usual pharmaceutical auxiliaries. Such salts of the compounds of the invention can be anhydrous or solvated.
In a preferred embodiment, the invention provides medicaments comprising a usable compound according to the invention, or a pharmaceutically acceptable salt or derivative thereof, together with one or more pharmaceutically acceptable carriers for that purpose, and, optionally, other therapeutic and / or prophylactic ingredients. The vehicle (s) must be "acceptable" in the sense of being compatible with other ingredients of the formulation and not harmful to the recipient.
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A medicament of the invention can be those suitable for oral, rectal, bronchial, nasal, topical, buccal, sublingual, transdermal, vaginal or parenteral administration (including injection, cutaneous, subcutaneous, intramuscular, intraperitoneal, intravenous, intraarterial, intracerebral, intraocular), or those in a form suitable for administration by inhalation or insufflation, including aerosol administration of powders and liquids, or sustained release systems. Suitable examples of sustained release systems include semipermeable matrices of solid hydrophobic polymers containing the compound of the invention, whose matrices may be in the form of shaped articles, for example, films or microcapsules.
The compounds usable according to the invention, together - with a conventional adjuvant, vehicle, or diluent, can thus be placed in the form of medicament and unit dosages thereof.
Such forms include solids, and in particular tablets, charged capsules, powder and pellet forms, and liquids, in particular solutions, suspensions, aqueous or non-aqueous emulsions, elixirs, and capsules loaded with them, all for use oral, suppositories for rectal administration, and sterile injectable solutions for parenteral use. Such a drug and unit dosage forms thereof may comprise conventional ingredients in conventional proportions, with or without additional active compounds or principles, and such unit dosage forms may contain any suitable effective amount of the active ingredient commensurate with the daily dosage range. intended to be employed.
The compounds usable according to the invention can be administered in a wide variety of oral and parenteral dosage forms. It will be obvious to those skilled in the art that the following dosage forms may comprise, as the active component, or one (with - usable station (s) according to the invention or a pharmaceutically acceptable salt of a usable compound (s) according to the invention.
To prepare a medicament of a usable compound according to the invention, pharmaceutically acceptable vehicles can be either solid or liquid. Solid form preparations include powders, compresses | dosages, pills, capsules, seals, suppositories, and dispersible granules. A solid vehicle can be one or more substances that can also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, compressing disintegrating agents, or an encapsulating material. In powders, the vehicle is a finely divided solid that is in a mixture with the finely divided active component. In tablets, the active component is mixed with the vehicle having the necessary bonding capacity in appropriate proportions and compacted in the desired shape and size. Suitable vehicles are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, bring. corner, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the 'formulation of the active compound with encapsulating material as a vehicle, providing a capsule in which the active component, with or without vehicles, is surrounded by a vehicle, which is thereby associated with him. Similarly, stamps or lozenges are included. Pills, powders, capsules, pills, stamps, and lozenges can be used as solid forms suitable for oral administration.
To prepare suppositories, a low melting wax, such as a mixture of fatty acid glyceride or cocoa butter, is first melted and the active component is dispersed homogeneously in it, such as by stirring. The homogeneous molten mixture is then poured into convenient sized molds, allowed to cool, and thereby solidify. Compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such vehicles as are known in the art to be appropriate. Liquid preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions. For example, liquid parenteral injection preparations can be formulated as solutions in aqueous polyethylene glycol solution.
The chemical compounds according to the present invention can | therefore, they can be formulated for parenteral administration (for example by injection, for example bolus injection or continuous infusion) and can be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added condom. The compositions can take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and can contain formulation agents, such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredient can be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization of solution, for constitution with a suitable vehicle, for example, sterile, pyrogen-free water, before use.
- Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable coloring, flavoring, stabilizing and thickening agents, as desired, Aqueous suspensions suitable for oral use can be made by dispersing the component finely divided active in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well-known suspending agents.
Also included are solid form preparations that are intended to be converted, immediately before use, into liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersing agents, thickeners, solubilizers, esimilars.
In one embodiment of the present invention, the drug is typically or systemically applied or by a combination of the two routines.
For administration, the compounds of the present invention can, in one embodiment, be administered in a formulation containing 0.001% to 70% by weight of the compound, preferably between 0.01% to 70% by weight of the compound, even more preferred between 0, 1% and 70% by weight of | compound. In one embodiment, the appropriate amount of compound administered is in the range of 0.01 mg / kg body weight to 1 g / kg body weight.
Compositions suitable for administration also include lozenges comprising the active agent in a flavored base, usually sucrose and acacia or tragacanth; lozenges comprising the active ingredient in an inert base such as gelatin and glycerol or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
Solutions or suspensions are applied directly to the nasal cavity by conventional methods, for example, with a dropper, pipette or spray. The compositions can be supplied in single or multiple doses. In the latter case of a dropper or pipette, this can be achieved by the patient by administering an appropriate, predetermined volume of: solution or suspension. In the case of a spray, this can be achieved, for example, by means of a metered atomizing spray pump.
Administration to the respiratory tract can also be achieved through an aerosol formulation in which the active ingredient is supplied in a pressurized package with a suitable propellant, such as a chlorofluorocarbon (CFC), for example, dichlorodifluoromethane, trichlorofluoro-methane, or dichlorotetrafluoroethane, carbon dioxide, or other suitable gas. The aerosol can conveniently also contain a surfactant, such as lecithin. The dose of drug can be controlled by the provision of a metered valve.
Alternatively the active ingredients can be supplied in the form of a dry powder, for example, a powder mixture of the compound in a suitable powder base, such as lactose, starch, starch derivatives, such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP). Conveniently the powdered vehicles will form a gel in the nasal cavity. The powdered composition can be presented in unit dose form, for example, in capsules or cartridges of, for example, gelatin, or blister packs from which the powder can be administered via an inhaler.
In compositions intended for administration to the respiratory tract | However, including intranasal compositions, the compound will generally have a small particle size, for example, on the order of 5 microns or less. Such a particular size can be obtained by methods known in the art, for example, by micronization. When desired, compositions adapted to provide sustained release of the active ingredient can be employed.
The pharmaceutical preparations are preferably in unit dosage forms. In such a way, the preparation is subdivided into unit doses containing appropriate amounts of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as tablets, capsules and powders packaged in vials or ampoules. In addition, the unit dosage form may be a capsule, tablet, seal, or lozenge itself, or it may be the appropriate number of any of these in packaged form. Tablets or capsules for oral administration and liquids for intravenous administration and continuous infusion are preferred compositions.
Further details on techniques for formulation and administration can be found in the latest issue of Remington's Pharmaceutical Sciences (Maack Publishing Co. Easton, Pa.).
figures and tables Reference is made to the figures and tables, in which figure 1 shows the dose response results on compound 8 (A) of the in vitro growth fluorescence assay (QUM) (B) and the intracellular growth assay ( QIM) (C). Each curve represents a separate replicated experiment, [Cpd] refers to the concentration of compound, (M) refers to the molar; Figure 2 illustrates the kinetics of inhibition and bactericidal activity of imidazopyridine compounds 47 and 54 compared to the reference compound PA-824 represented in the CFU reduction items (A) and as a time course (B). Chemical structure of positive control PA-824 (C); Figure 3 shows the in vivo efficacy of compounds 177 and 185 in a murine model of acute tuberculosis infection.
| Table 1 summarizes imidazopyridine derivatives (general scaffolding la and lb) with their inhibitory activities, where the numbers in bold refer to the compounds listed in example 2; Table 2 shows the antibacterial activity for compound 47 and compound 54 in several strains resistant to multiple drugs (MDR).
EXAMPLES The invention is now described with reference to the following examples which are intended to illustrate, not to limit the scope of the invention. Example 1: Primary sequencing of a large library of small synthetic compounds using the photon-based cell assay, ”A library of 120,000 small molecule compounds was analyzed using a validated phenotypic cell-based assay (WO '2010003533 A2). Active compounds from the primary evaluation were confirmed through dose response in the intracellular assay (QIM) and an in vitro assay (QUM), where the abbreviation "QIM" stands for Quantification of Intracellular Mycobacteria and the abbreviation "QUM" stands for Quantification of Mycobacteria growth in vitro. Compound 8 (figure 1A) demonstrated activity in both the QUM and QIM tests (figure IB and 1C respectively) and is based on general scaffolds of imidazopyridine la and lb. Compound 8, from the dose response confirmation experiments, demonstrated a minimal inhibitory concentration (MIC) or 5 yuM and 2.5 UM in the QUM and QIM assays, respectively. MIC is the minimum compound concentration required to achieve 80% inhibition of bacterial growth. Compound 8 demonstrated potent antibacterial activity and is therefore the focus of the present invention. Example 2: Derivatization of the general imidazopyridine scaffolding Imidazopyridine compounds (scaffolds la and lb; see table 1) have been derivatized, according to the methods shown below (Schemes 1-13). The resulting derivatives were examined for inhibitory activity (MIC) using the assays described above (Example 1) and the results are summarized in table 1. | NO, AS.
Ea, Aos - Se and the ariniants Shoras 5 cure note x E os E EEE a o.
Scheme 1 General procedure for the synthesis of A1 To a solution of ethyl propionylacetate (6.9 mmol) in Et20 (380 mL) was added ammonium acetate (2.07 mmol) and N- "5 bromosuccinimide (7.6 mmol) The mixture was stirred at room temperature for 6 hours.
After the reaction was completed, the reaction mixture was filtered and washed with H2 O (30 ml). The organic layer was dried over MgSO2, anhydrous and concentrated in vacuo to provide A1. General procedure for the synthesis of A2 To a solution of A1 (0.89 mmol) in EtOH (4 mL) was added 2-aminopyridine (0.89 mmol). The mixture was stirred and refluxed overnight.
After cooling, the dark residue was diluted with EtOAc (20 ml) e. saturated NaHCO3 solution (30 mL). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo.
The crude product was purified by flash column chromatography to provide ethyl A2, 2-methylimidazo [1,2-alpyridine-3-carboxylate (A2) Q OEt at 1H NMR (400 MHz, CDCl3) 5 1.28 (t, J = 7.2 Hz, 3H), 2.56 (s, 3H), 4.27 (q, J = 7.2 Hz, 2H), 6.78 (dd, Jy = 7.2 Hz, 7, 2 Hz, 1H), 7.19 (dd, J = 6.8 Hz, 6.8 Hz, 1H) 7.42 (dd, J = 8.8 Hz, 8.8 Hz, 1H), 9.12 (dd , J = 6.8 Hz, 6.8 Hz, 1H); * C NMR (100 MHz, CDC) 5 14.5, 16.7, 60.3, 112.6, 113.6, 116.9, 127.5, 127 9, 146.9, 152.8, 161 , 4. |
General procedure for the synthesis of A3 To a solution of A2 (0.31 mmol) in H20 (1.0 mL) and EtoOH (3.0 mL) was added lithium hydroxide (0.93 mmol). The mixture was stirred at room temperature overnight.
After the reaction was completed, the mixture was evaporated and 1 N HCl (10 ml) was added until pH was 4. The residual pale solid was collected by filtration and washed with H20 to provide A3. General procedure for the synthesis of A4 To a solution of A3 (0.568 mmol) in CH3Cl7 (3 mL), triethylamine (1.7 mmol), benzylamine (0.58 mmol) and 1-ethyl-3- (3) were added - dimethylaminopropyl) carbodiimide (0.84 mmol). The reaction mixture was stirred at room temperature overnight.
After the reaction was completed, the * reaction mixture was diluted with CH2Cl2 (10 ml), washed with 1 N HCl (10 ml) and NaHCO solution; saturated (10 mL). The organic layer was dried over MgSO4, anhydrous and concentrated in vacuo.
The crude product was purified by flash column chromatography to provide A4. Copy picture from p. 18 of the pdf with translation LU Ee Po and "Po 7 esa ter Nr refer 4 h NA X = CH.
The 81 B2 Scheme 2 o. 39 mecosrademos The ETA "Oo. And O and Om, R2L, 401," ERA Naz6O, PátdppNE Bom "O. Ôr * Zaoam dpiiáta Scheme 3 General procedure of B1 A solution of 4-chlorobenzonitrile (1.0 mmol!) in ethylene glycol |
(2 ml) was added to the appropriate amine (5.0 mmol). The reaction mixture was heated to 160 ° C for 12 h and then cooled to room temperature, poured into ice water, and extracted three times with EtOAc. The combined organic layers were washed with sodium chloride solution in water and dried over MgSOA4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to provide B1. 4 (Piperidin-1-yl) benzonitrile NC. * O '1H NMR (400 MHz, CDCl3) 5 1.60 - 1.68 (m, 5H), 3.30 - 3.40 (m, .10 4H), 6.83 (d, J = 9, 2Hz2H), 7.46 (d, J = 8.8 Hz, 2H). General procedure of B2 and C2 Method |: To a solution of B1 (1.0 mmol) in THF (10 mL) was added LAH at 0 “ºC. The mixture was refluxed for 1 h and then cooled to room temperature. The reaction mixture was quenched by —addition of NaHCO; saturated aqueous solution (10 mL) and extracted three times with E-tOAc. The combined organic layers were washed with a solution of: sodium chloride saturated in water and dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by means of flash column chromatography to provide B2. (4 (Piperidin-1-yl) phenyl)] methanamine “AO.
O 1H NMR (400 MHz, CDCl3) 5 1.55 - 1.59 (m, 2H), 1.68 - 1.74 (m, 4H), 3.13 (t, J = 5.6 Hz, 4H ), 3.77 (s, 2H), 6.92 (d, J = 8.4 Hz 2H), 7.19 (d, J = 8.8 Hz, 2H). Method Il: To a solution of 4-bromobenzylamine (1.0 mmol) in DME (3mL) was added the appropriate arylboronic acid (1.0 mmol), 1,1-bis (diphenylfoafino) ferrocene) -dichloropalladium (11) ( 0.03 mmol), Na2CO3 (aq. /
2.0 mmol). The mixture was stirred and heated to reflux under an N2 atmosphere. After 1 h, the mixture was cooled to room temperature, then the mixture was extracted with EtOAc, washed with sat. NaHCO3. (aq.), brine and dried over MgSO4 and filtered. After removing the solvent, the amines were obtained, which were used without purification. General C1 procedure To a solution of 4-chlorobenzonitrile (1.0 mmol) in DME (3 mL) was added the appropriate arylboronic acid (1.0 mmol), 1.1 ”- bis (diphenylphosphino) ferrocene) dichloropalladium (11 ) (0.03 mmol), Na2CO3 (aq. 2.0 mmol). The mixture was stirred and heated to reflux under an N2 atmosphere. After 1 h, the mixture was cooled to room temperature, then filtered and evaporated in vacuo. The residue was extracted with EtOAc, washed with sat. NaHCO3 (aq.), Brine and dried over MgSOA4, filtered and concentrated in The residue was purified by flash column chromatography to provide C1. 2 '(Trifluoromethyl) biphenyl-4-carbonitrile “Os 1H NMR (400 MHz, CDCl3) 5 7.30 (d, J - 7.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.54 (dd, J = 7.6, 7.6 Hz, 1H), 7.61 (dd, J = 7.2 , 7.6 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 1.6 Hz, 1H).
A FE OR AE EO,. 7 a LE LE E Esquemad4 Procedure for the synthesis of D1 A mixture of 4-fluorobenzonitrile (4.2 g, 35 mmol), piperazine (1.0 g, 12 mmol) and K2CO3 (4.8 g, 35 mmol) in DMSO (30 mL) was stirred | overnight at 120 ºC. The reaction mixture was poured onto ice and the resulting solid was filtered, washed with methanol and dried in vacuo to provide D1 as a white solid; * H NMR (400 MHz, DMSO) at 3.49 (s, 8H), 7.01 (d, J = 9.2 Hz, 4H), 7.57 (d, J = 9.2 Hz, 4H) ; LCMS (electrospray) m / z (M + H) +289.
Procedure for the synthesis of D2 To a stirred solution of D1 (0.30 g, 1.00 mmol) in THF (5 mL) was added LAH (0.24 g, 6.20 mmol) and the resulting mixture was heated reflux temperature for 3 h. The reaction mixture was quenched with water and the solid was filtered. The filtrate was extracted with MC (30 ml x 2), the organic layer was washed with NaxCO; saturated aqueous (20 mL) and concentrated in vacuo to provide D2; 1H NMR (400 MHz, CDCl3) 5 3.32 (s, 8H), 3.80 (s, 4H), 6.95 (d, J = 8.4 Hz, 4H), 7.25 (d, J = 84 Hz, 4H); LCMS '(electrospray) m / z (M) + 296.
Procedure for the synthesis of D3 To a stirred solution of D2 (0.70 9, 2.36 mmol) in MC (25 mL) was added butyryl chloride (25 ul, 0.23 mmol) and the resulting mixture was stirred for 30 min under an ice bath. After removing the ice bath, the reaction mixture was stirred for an additional 30 min. The reaction mixture. 20 was diluted with MC (20 ml), washed with saturated aqueous Na2CO3 (20 ml) and the organic layer was concentrated under reduced pressure. The crude residue was purified by column chromatography (20% MeOH in MC) to provide D3; 1H NMR (400 MHz, CDCl3) at 0.41 (t, J = 7.2 Hz, 3H), 1.00 (brs, 2H), 1.12 - 1.21 (m, 2H), 1.63 (t, J = 7.2 Hz, 2H), 2.80 (s, 8H), 3.27 (s, 2H), 3.84 (d J = 5.2Hz 2H), 5.16 (brs, 1H), 6.38 - 6.45 (m, 4H), 6.67 - 6.74 (m, 4H); LCMS (electrospray) m / z (M + H) + 367.
Procedure for the synthesis of D4 To a solution of acid (0.012 g, 0.054 mmol) in DMF (1 mL) were added triethylamine (15uL, 0.11 mmo!), D3 (0.020 g, 0.055 mmol), hydroxybenzotriazole (87 mg 0.027 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (0.016 g, 0.082 mmol) and the reaction mixture was stirred at 80 ° C overnight. The reaction mixture was cooled to -10 |
ºC, the resulting solid was filtered, washed with MC and dried in vacuo to provide DA; fa q> Amine Fes pg Nilamine o. FO - x is in
LOS RRNO SO SN: E: E2 Scheme 5 Procedure for E2 synthesis A mixture of E1 (0.32 g, 0.86 mmol), an amine (excess) and DIPEA (0.75 mL, 4.32 mmol) in ethylene glycol (4 ml) was heated to 160] ºC for 1.5 days. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL x 3). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo. The crude residue was purified by flash column chromatography (20% MeOH in MC) and then precipitated with acetonitrile to provide E2 as a white solid. E * neo, & PUROS Õ an H0.0ºC s% 2) Xylenes, Reflixo - nr W BE Ps - e "Fa s Fa DOF, õ LAH DEAD, PPhs, phthaliriide - Nidraine hydrate THE ç THF O EtOH, Reflux * Re ds a ... De no Fa as FB Scheme 6 General procedure for the synthesis of F1 To an ice-cooled solution of 4 (trifluoromethoxy) aniline (11.29 mmol) in HBF4 (50%, 22.58 mmol ) and water (2 ml) was added dropwise with a pre-cooled solution of NaNO2 (12.42 | mmol) in water (2 ml). During the addition, the temperature was carefully kept below 5 “C and the mixture The resulting mixture was allowed to stir at 0 ° C for 30 min. The diazonium salt (F1) was collected by filtration, washed with Et20, and extensively dried in vacuo. General procedure for the synthesis of F2 F1 (11.80 mmol) was added to a solution of 2-chloroacetoacetate (11.30 mmol) in pyridine (4 mL) and water (4 mL) at -5 ° C. The mixture was stirred at -5 ° C for 30 min, and the resulting precipitate was filtered and washed with cooled water. Recrystallization from Et oH / water provided F2. 2: Gloro-2- (2- (4- (trifluoromethoxylfentyl ivdrazone) (E) -ethyl acetate (F2) 3 and ota
OE 1H NMR (400 MHz, CDC13) 5 1.41 (t, J = 7.2 Hz, 3H), 4.39 (q, J = 7.2 Hz, 2H), 7.20 (d, J = 9.6 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H), 8.32 (brs, 1H) General procedure for the synthesis of F3: A mixture of F2 (9.33 mmol) , bicycles (2,2,1] hepta-2,5-diene (46.87 mmol) and Et3N (28.00 mmol) in toluene (10 mL) were stirred at 70 ° C for 1 h. The resulting mixture was cooled and filtered, the filter mass was washed with toluene, and the organic fractions were combined and evaporated.The residue was refluxed in xylenes (10 mL) for 2 h, column chromatography of the cooled reaction mixture, eluting with hexanes, first - xylenes were provided, and then another elution with ethyl acetate gave F3. 1- (4- (Trifluoromethoxy) phenyl) -1H-pyrazol-3-carboxylate (F3) O
Õ |
1H NMR (400 MHz, CDCI3) 5 1.42 (t, J = 7.2 Hz, 3H), 4.44 (q, J = 7.2 Hz, 2H), 7.00 (d, J = 2 , 4 Hz, 1H), 7.33 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 9.2 Hz, 2H), 7.91 (d, J = 2.4 Hz, 1H) General procedure for the synthesis of F4 LiA1H4 (0.67 mmol) was added to a stirred solution of F3 (0.67 mmol) in THF (5 mL) at 0 ° C, and the mixture was heated to temperature. at room temperature for 1 hr, then cooled to 0 ºC and quenched with frost.
The resulting mixture was diluted with ethyl acetate (10 ml), washed with water (10 ml) and sodium chloride solution saturated in water (10 ml). The organic layer was dried over MgSO, anhydrous, filtered and concentrated in vacuo.
The crude product was purified by flash column chromatography to provide FA. General procedure for the synthesis of F5 i DEAD (0.84 mmol) was added dropwise to a stirred and cooled (O ºC) solution of phthalimide ( 0.83 mmol), Ph3P (0.84 mmol) and F4 (0.69 mmol) in dry THF.
The cooling bath removed and stirring was continued at room temperature for 4 hr, then water (1 ml) was added.
The reaction mixture was filtered through a silica column, eluting with CHzCk.
The eluate was concentrated in vacuo and the residue was purified by flash column chromatography to provide F5. General procedure for the synthesis of F6 To a solution of F5 (0.69 mmol) in EtOH (5 mL) was added hydrazine hydrate (1.38 mmol). The reaction mixture was stirred and refluxed for 4 hr.
After cooling, the reaction mixture was evaporated and diluted with EtOAc (10 mL) and saturated NaHCO3 solution (10 mL), then washed with water-saturated sodium chloride solution (10 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo.
The raw product F6 was used for the next step without further purification. | à, sm Agr O o Toluene, reflix o | NHNH, HC!
SS o NHz 1) NaOH / MeOH, H2O, ref. Oo NDA Oo
AMORA NO RR N & 12-propanol, hot & OCcF, ocr, G2 [>] Scheme 7 General procedure for the synthesis of G1] To a solution of cyclohexane-1,3-dione (17.84 mmol) in toluene - ( 20 mL) DMF.DMA (26.75 mmol) was added. The reaction mixture was stirred and refluxed overnight. After cooling, the reaction mixture was concentrated in vacuo. The crude product G1 was used for the next step without further purification. General procedure for the synthesis of G2 To a solution of G1 (8.98 mmol) in methanol (20 mL) and water (3 mL) were added hydrochloride (4 - (trifluoromethoxy) phenyl) hydrazine B (8.98 mmol) and sodium hydroxide (8.98 mmol). The reaction mixture is heated to reflux for 2 h and concentrated in vacuo. Then to the residue were added ACOH (20 ml) and water (10 ml), and the reaction mixture was heated to 110 ºC for 2 h. At the conclusion of the reaction, the solution was concentrated in vacuo, the residue was diluted with EtOAc (20 ml) and saturated NaHCO3 solution (20 ml), then washed with sodium chloride solution saturated in water (20 ml). The organic layer was dried over anhydrous Mg-SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to provide G2. General procedure for the synthesis of G3 To a solution of G2 (2.36 mmol) in 2-propanol (5 mL) was added ammonium acetate (23.65 mmol). After complete dissolution, molecular sieves (4A, 1.0 gq) and NABH3CN (11.82 mmol) were added and | the reaction mixture was stirred and refluxed overnight.
After cooling, the reaction mixture was evaporated and diluted with EtOAc (10 ml) and saturated NaHCO3 solution (10 ml), then washed with water-saturated sodium chloride solution (10 ml). The organic layer was dried over anhydrous Mg-SO4, filtered and concentrated in vacuo.
The crude product G3 was used for the next step without further purification, ed Tm oa 2a, ss ro, SEE O DF, 00. m "m in" Scheme 8; General procedure for H1 synthesis To a solution of 4-trifluoromethoxybenzyl bromide (1.05 9, * 10 4.09mmol) in 5 ml of dry DMF was added sodium cyanide (220 mg, 4.50 mmol). The reaction was stirred for 1 h at room temperature, poured into water and extracted with ethyl acetate (2 x 20 mL). The combined layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo.
The raw product H1 was used in the next reaction without further purification.
General procedure for the synthesis of H2 To a solution of H1 (93 mg, 0.46 mmol) in EtOH was added a 50 weight% hydroxylamine solution in water (0.12 mL, 1.84 mmol). The reaction mixture was refluxed overnight.
After cooling, the mixture was concentrated in vacuo.
The crude product H2 was used in the following reaction in another purification, General procedure for the synthesis of H4 To a solution of H3 (11 mg, 0.50 mmol) in dry DMF were added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (97 mg, 0.506 mmol), 1-hydroxybenzotriazole (68 mg, 0.556 mmol). The mixture was stirred for 30 min at room temperature.
Then to the reaction mixture, a solution of C2 (108 mg, 0.48 mmol) in dry DMF was added.
The reaction mixture was stirred at 140 ° C for 2 h.
After cooling, the reaction mixture was diluted with ethyl acetate (10 ml), washed with | saturated NaHCO3 (10 mL) and sodium chloride solution saturated in water (10 mL). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo.
The crude product was purified by flash column chromatography to provide H4. O.
If water is only aorta "N" N n Rn ": E OO DU TT E" DEAR GiLeL = Ol POC, rentxo and DIPEA, CHxCk, and oCF.,. 4 6 Scheme 9 General procedure for the synthesis of | 2 To a solution of 11 (253 mg, 1.0 mmol) in EtOH was added hydrazine hydrate (0.75 mL, mmol). The reaction mixture was refluxed for 12 h.
After cooling, the resulting precipitate (D2) was filtered, washed with EtOH and dried.
General procedure for the synthesis of I3 'To a solution of 12 (96 mg, 0.402 mmol) in CH2Cl2 was added Et3N (0.057 mL, 0.406 mmol). The reaction mixture was cooled to 0 ° C and to the mixture a solution of chloro-ketyl chloride (0.035 ml, 0.442 mmol) in CH2 Cl2 was added dropwise. The reaction mixture was stirred at 0 ºC, the reaction temperature was raised to room temperature and the resulting mixture was also stirred for 30 min. To the mixture, water was added, the solution was extracted with CH2 Cl2, washed with chloride solution. water-saturated sodium.
The organic layer was dried over anhydrous MASO4 and concentrated in vacuo.
The crude product (13) was used for the next reaction without further purification.
General procedure for the synthesis of l4 13 (0.402 mmol) was placed under nitrogen and POCI3 (2 mL) was added.
The reaction mixture was refluxed for 2 h.
The mixture was res- | cooled to room temperature, poured into water and extracted with efilacetate (x 2). The combined organic layers were washed with a saturated sodium chloride solution in water, dried over anhydrous MgSO4 and concentrated in vacuo.
The crude product was purified by flash column chromatography to supply4. General procedure for the synthesis of I6 To a solution of 14 (50 mg, 0.17 mmol) in CH2Cl2 were added | 5 (50 mg, 0.20 mmol) and DIPEA (0.035 mL, 0.20 mmol). The reaction mixture was stirred overnight, the mixture was extracted with CH2 Cl2 and water, washed with water-saturated sodium chloride solution.
The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo.
The crude product was purified by flash column chromatography to provide 16. Br CN i & PdCiz (dpph), Na; CO ,; (O oil * DMEIHZO (3: 1, viv) (À OH OcF, 120ºC, 2h cf; JJ ”Scheme 10 General procedure for the synthesis of J1 '15 To a solution of 1-bromo + 4- (trifluoromethoxy) benzene (0.50 g, 2.07 mmol) in DME (6 mL) 3-cyanophenyl boronic acid (0.37 g, 2.49 mmol), 1.1 "-bis (diphenylphosphino) ferrocene) -dichloropalladium ( II) (0.046 9, 0.062 mmol) and Na2CO3 (2 mL of aqueous solution, 0.44 g, 4.14 mmol) The resulting mixture was stirred at 120 ° C for 2 hours.
After removal of organic solvent, the resulting residue was diluted with water (10 ml) and extracted with methylene chloride (10 ml x 2). The organic layer was dried over MgSO4 and concentrated in vacuo.
The resulting crude residue was purified by flash column chromatography (n-hexane: ethyl acetate = 10: 1 ratio) to provide J1, the potential - the OD: O the MD.
A. |
Scheme 11 General procedure for the synthesis of K2 and K3 A stirred suspension of K1 (0.050 g, 0.12 mmol) and NaH-CO (0.051 g, 0.60 mmol) in methylene chloride (2.0 mL) was periodinane dess-martin (0.10 g, 0.24 mmol) is added under an ice bath.
After 5 minutes, the reaction temperature was raised to room temperature and the resulting solution was stirred for 2 h.
The reaction mixture was diluted with methylene chloride (10 ml) and washed with saturated aqueous NaHCO3 solution (10 ml) and saturated sodium chloride solution in water (10 ml). The organic layer was dried over anhydrous MgSO4 and concentrated in vacuo. The resulting crude residue was purified by flash column chromatography (methylene chloride: methanol = 50: 1 ratio) to provide K2 and K3. Ph 'CN.
Oxalite chloride cn eo ”oH 4ssmin o 25 [E Lz 13 Scheme 52 General procedure for the synthesis of L2. 15 A solution of oxalyl chloride (0.43 mL, 4.94 mmol) in methylene chloride (5 mL) was cooled to -78 ° C and DMSO (0.70 mL, 9.88 mmol) was added slowly .
After 10 minutes, a solution of alcohol (0.50 g, 2.47 mmol) in methylene chloride (3 mL) was added over 10 min, and the mixture was also stirred for 15 min at -78 ° C.
Triethylamine 20 (14mL, 9.88 mmol) was added to the solution and the mixture was stirred for min and allowed to warm to 0 ° C.
After stirring was complete, the reaction mixture was diluted with methylene chloride (15 ml) and washed with aqueous Na2CO3 (15 ml). The organic layer was dried over MgSO, and concentrated in vacuo.
The resulting crude residue was purified by columnaflash chromatography (n-hexane: ethyl acetate = 5: 1 ratio) to provide L2, General procedure for the synthesis of L3 A methyltriphenylphosphonium bromide suspension (0.43 9, |
1.20 mmol) in THF (5 mL) nBuLi (2.5 M in n-hexane, 0.48 mL, 1.20 mmol) was added under an ice bath and the mixture was stirred for 30 min.
A solution of ketone compound in THF (3 ml) was added dropwise and the resulting mixture was allowed to warm to room temperature over 2h.
After completion of the reaction, the solution was diluted with methylene chloride (10 mL) and washed with NaHCO; aqueous (15 mL). The organic layer was dried over MgSO, and concentrated in vacuo.
The resulting crude residue was purified by flash column chromatography (n-hexane; ethyl acetate = 15: 1 ratio) to provide a target compound L3. LO so 1 oO Sms X "Br SO me -. Mo O = hetercarila Scheme13 General procedure for the synthesis of M2 To a solution of MI (0.050 g, 0.413 mmol) in DME (2 mL) boronic pyridine acid was added (0.017 g, 0.18 mmol), 1,1-bis (diphenitphosphine) ferrocene) -dichloropalladium (Il) (1.5 mg, 3.38 umol) and Na2CO3.15 (0.5mL aqueous solution, 0.024 g , 0.22 mmol) The resulting mixture was stirred at 120 ° C for 2h.
After removing organic solvent, the resulting residue was diluted with water (10 ml) and extracted with methylene chloride (10 ml x 2). The organic layer was dried over MgSO4 and concentrated in vacuo.
The resulting crude residue was purified by flash column chromatography (methylene chloride: methanol = 20: 1 ratio) to provide a target compound M2. 2-Methylimidazo [1,2-alpyridine-S-carboxylic acid (1) os 1H NMR (400 MHz, CD3OD) at 2.84 (s, 3H), 7.04 (dd, 7 = 1.2 Hz, 7 , 2 Hz, 1H), 7.96 (d, u = 8.8 Hz, 1H), 8.07 (dd, 7 = 1.2 Hz, 7.2 Hz, 1H), 9.65 (dJ = 72H2 , 1H). |
Ethyl 2-methyl-7-phenylimidazo [1,2-alpyridine-3-carboxylate (2 1H NMR (400 MHz, CDC13) 5 1.45 (t, J = 7.2 Hz, 3H), 2.73 ( s, 3H), 4.44 (q, J = 7.2 Hz, 2H), 7.25 (dd, J = 1.6 Hz, 7.2 Hz, 1H), 7.42 -7.51 ( m, 3H), 7.68 (d, J = 7.6 Hz, 2H), 7.80 (s, 1H), 9.32 (d, J = 7.2 Hz, 1H). 2-Methyl acid -7-phenylimidazo [1,2-a] pyridine-3-carboxylic (3) 1H NMR (400 MHz, DMSO d-6) 5 2.60 (s, 3H), 7.43 - 7.52 (m, .5H), 7.83 (s, 1H), 7.85 (s, 1H), 7.94 (s, 1H), 9.26 (d, J = 7.6 Hz, 1H) 2-Methyl- Ethyl 6-phenylimidazo [1,2-a] pyridine-3-carboxylate (4)% oe
WASN 1H NMR (400 MHz, CDCI3) at 1.41 (t, J = 7.2 Hz, 3H), 2.70 (s,: 10 3H), 4.40 (qg, J = 27.2Hz, 2H ), 7.33-7.36 (m, 1H), 7.42 (t J = 7.4 Hz, 2H), 7.56 (d, J = 7.2 Hz, 2H), 7.60 - 7.61 (m, 1H), 9.52 (s, 1H). 2-Methyl-N- (pyridin4-yl) imidazo [1,2-a] pyridine-3-carboxamide (5)
NA OQ and 7H NMR (400 MHz, CDCI3 + DMSO-d6) 5 2.72 (s, 3H), 6.89 (dd, J = 12.7.2 Hz, 1H), 7.28 -7.33 (m, 1H), 7.52 (d, y = 9.2 Hz, 1H), 7.57 (dd, J = 1.6.4.8 Hz, 2H), 8.43 (dd, J = 1.6, 4.8 Hz, 1H), 8.92 (br s, 1H), 9.11 (d, J = 6.8 Hz, 1H); LCMS (electrospray) m / z (M + H) + 253.18 2-Methyl-N- (4-phenoxyphenyl) imidazo [1,2-a] pyridine-3-carboxamide (6) and 2 rx 17H NMR (400 MHz, CDCl3) 5 2.60 (s, 3H), 6.89 (t, J = 8.0 Hz, |
3H), 6.96 (d, J = 6.8Hz, 2H), 7.02 (t, J = 7.6Hz, 1H), 7.27 (t, J = 7.6Hz, 2H), 7, 38 (t, J = 6.8Hz, 1H), 7.47 (d, J = 8.8Hz, 1H), 7.57 (d, J = 6.8Hz, 2H), 8.89 (d, J = 6.8 Hz, 1H). N- (4- (Benzyloxy) phenyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (7) | o F40-o 17H NMR (400 MHz, CDCl3) 5 2.57 (s, 3H), 4.97 (s, 2H), 6.88 - 6.91 (m, 3H), 7.19 (t J = 7.2Hz, 1H), 7.28 (t, J = 8.4Hz, 2H), 7.32 (t J = 6.8Hz, 3H), 7.43 - 7.46 (m, 3H), 8.85 (d, J = 5.6 Hz, 1H). N-Benzyl-2-methylimidazo [1,2-a] pyridine-3-carboxamide (3) O. KR LO ss Ú 7H NMR (400 MHz, CDCl3) 5 2.68 (s, 3H), 4.70 ( d, J = 5.6 Hz, 2H) 6.13 (brs, 1H), 6.91 (dd, J = 1.2 Hz, 7.2 Hz, 1H), 7.29 - 7.39 (m , 6H), 7.56 (d, J = 9.2 Hz, 1H), 9.42 (d, J = 7.2 Hz, 1H). N- (4-Fluorobenzyl) -2-methylimidazo [1.2-alpiridine-3-carboxamide (9) N F *
N 'H NMR (400 MHz, CDCl3) 5 2.67 (s, 3H), 4.66 (d, J = 6.0 Hz, - 2H), 6.11 (brs, 1H), 6.91 ( d, J = 6.8 Hz, 1H), 7.02 - 7.06 (m, 2H), 7.30 - 7.36
15. (m, 3H), 7.56 (d, J = 8.8 Hz, 1H), 9.41 (d, J = 6.8 Hz, 1H). 4 - ((2-Methylimidazo [1,2-alpyridine-3-carboxamido) methyl) methyl benzoate (10)
PO oe AND
SN * H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 3.90 (s, 3H), 4.76 (d, J = 6.0 Hz, 2H), 6.24 (brs , 1H), 6.91 - 6.95 (m, 1H), 7.32 - 7.36 (m, 1H), 7.44 (djJ = 8.4Hz, 2H) 7.56 (d, J = 9.2 Hz, 1H), 8.02 (d, J = 8.4 Hz, 2H), 9.41 (d, J = 6.8 Hz, 1H). 4 - ((2-methylimidazo [1,2-a] pyridine-3-carboxamido) methyl) benzoic acid |
(11) oH and
At TN 17H NMR (400 MHz, CD30D) at 2.64 (s, 3H), 4.69 (s, 2H), 7.03 (dd, Ju = 6.8 Hz, 6.8 Hz, 1H), 7.43 - 7.47 (m, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.53 - 7.55 (m, 1H), 8.01 (d, J = 8.4 Hz, 2H), 9.04 (d, J = 7.2 Hz, 1H). N- (A-Methoxybenzyl) - - methylimidazo [1,2-a] lpiridine-3-carboxamide (12)
O 'oMe' 1H NMR (400 MHz, CDCl3) 5 2.67 (s, 3H), 3.810 (s, 3H), 4.63 (d, J = 5.2 Hz, 2H), 6.01 (m , 1H), 6.89 - 6.94 (m, 3H), 730 - 7.35 (m, 3H), 7.56 - i 7.58 (m, 1H), 9.43 (dd, J = 0.8, 6.8 Hz, 1H). 2-Methyl-N- (pyridin-3-ylmethyl) imidazo [1 s2-alpiridine-S-carboxamide (13)% *
SN 1H NMR (400 MHz, CDCl3) 5 2.68 (s, 3H), 4.70 (d, J = 6.0 Hz, 2H), 6.30 (brs, 1H), 6.89 -, 6 , 93 (m, 1-H), 7.26 - 7.35 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 8.53 (d, J = 3.6 Hz, 1H), 8.62 (s, 1H), 9.38. (d, J = 7.2 Hz, 1H). 2-Methyl-N- (pyridin-4-ylmethyl) imidazo [1,2-a] pyridine-3-carboxamide (14)
N 1H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 4.68 (d, J = 6.0 Hz, 2H), 6.41 (brs, 1H), 6.88 -6, 92 (m, 1H), 7.25 (d, J = 4.4 Hz, 2H), 7.30 - 7.34 (m, 1H), 7.53 (d, J = 8.8 Hz, 1H ), 8.53 (d, J = 4.4 Hz, 2H), 9.35 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 17.0, 42.4, 113.6, 115.2, 116.7, 122.3, 127.5, 128.3, 145.9, 146.4, 147 , 7, 150.3, 161.9. 2-Methyl-N- (4-phenoxybenzyl) imidazo [1,2-a] pyridine-3-carboxamide (15) | oo, FO o S / N 17H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 4.67 (d, J = 5.6 Hz, 2H), 6.14 (brs, 1H), 6.92 -6.96 (m, 1H), 6.99 - 7.08 (m, 4H), 7.12 (dd, J = 6.4 Hz, 6.4 Hz, 1H), 7.31 - 7.37 (m, 5H), 7.59 (d, J = 8.8 Hz, 1H), 9.43 (d, J = 6.8 Hz, 1H). N-Biphenyl-ylmethyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (16) LOU ex * N: 17H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 4.74 (d, J = 4.0 Hz, '2H), 6.19 (brs, 1H), 6 , 91 (dd, J = 6.0 Hz, 6.0 Hz, 1H), 7.30 - 7.36 (m, 2H),, 7.41 - 7.45 (m, 5H), 7.58 (m, 4H), 9.43 (d, J = 6.8 Hz, 1H). N- (1H-Indol-5-yl)] methyl) -2-methylimidazo [1,2-a] lpiridine-3-carboxamide (17) x À Der. ot “N 7H NMR (400 MHz, CDCl3) 5 2.68 (s, 3H), 4.78 (d, J = 5.2 Hz, 2H), 6.18 (brs, 1H), 6.55 ( s, 1H), 6.98 - 7.02 (m, 1H), 7.22 - 7.24 (m, 2H),: 7.40 (s, 1H), 7.42 (s, 1H), 7.66 - 7.68 (m, 2H), 8.24 (brs, 1H), 9.47 (d, J = 7.2 Hz, 1H). N- (Cyclohexylmethyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (18) DR
O 1H NMR (400 MHz, CDCl3) 5 0.94 - 1.27 (m, 5H), 1.54 - 1.78 (m, 6H), 2.67 (s, 3H), 3.31 (t J = 6.2 Hz, 2H), 5.91 (m 1H), 6.64 (t J = 6.8 Hz, 1H), 7.24 - 7.28 (m, 1H), 7.50 ( d, JU = 9.2 Hz, 1H), 9.32 (d, J = 6.8 Hz, 1H). 4 - ((2-Methylimidazo [1,2-a] pyridine-3-carboxamido) methyl) tert-butyl piperidine-1-carboxylate (19) e. " "O. |
38/175 | 1H NMR (400 MHz, CDCl3) 5 1.87 - 1.25 (m, 2H), 1.44 (s, 9H), 1.73 - 1.82 (m, 3H), 1.97 (m, 2H), 2.70 (s, 3H), 3.40 (m, 2H), 5.92 (t J = 5.6 Hz, 1H), 6.90 (t, J = 6.8 Hz, 1H ), 7.29 -7.33 (m, 1H), 7.55 (d, J = 8.8 Hz, 1H), 9.36 (d, J = 6.8 Hz, 1H). 2-Methyl-N- (piperidin-4-ylmethyl) imidazo [1,2-a] pyridine-3-carboxamide (20) Us O: 1H NMR (400 MHz, CDCl3) 5 1.20 - 1.77 (m , 6H), 2.58 - 2.64 (m, 1H), 2.65 (s, 3H), 3.13 (d, J = 11.6 Hz, 2H), 3.34 (t J = 12 , 0 Hz, 2H), 3.68 (br s, 1H), 6.71 (m, 1H), 6.84 (t J = 6.8 Hz, 1H), 7.26 (t J = 7, 6 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 9.28 (d, J = 86.8 Hz, 1H). i 10 2-Methyl-N-phenethylimidazo [1,2-a] pyridine-3-carboxamide (21) 1 Q Ã nO
EX 'H NMR (400 MHz, CDCl3) 5 2.28 (s, 3H), 2.82 (t, J = 7.2Hz, 2H), 3.56 (t, J = 6.8Hz, 2H), 6.79 (t, J = 6.8Hz, 1H), 7.06 (t, J = 6.8Hz, 1H), 7.14 (d, J = 7.2Hz, 3H), 7.30 (t , J = 7.2 Hz, 2H), 7.33 (d, J = 6.8 Hz, 1H), 8.74 (d, = 5.6 Hz, 1H). BR 15 N- (4-Methoxyphenethyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (22)
GOT. J 1H NMR (400 MHz, CDCl3) 5 2.46 (s, 3H), 2.92 (t, J = 6.6 Hz, 2H), 3.74 (q, J = 6.4 Hz, 2H) , 3.80 (s, 3H), 6.87 - 6.92 (m, 3H), 7.18 (d, J = 8.4 Hz, 2H), 7.29 - 7.33 (m, 1H ), 7.55 (d, J = 8.8 Hz, 1H), 9.41 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) * 310.25 2-Methyl-N- (2-phenoxyethyl) imidazo [1,2-a] pyridine-3-carboxamide (23)
FO 1H NMR (400 MHz, CDCl3) 5 2.72 (s, 3H), 3.93 (q, J = 4.8 Hz, 2H), 4.19 (t, J = 5.0 Hz, 2H) , 6.33 (m, 1H), 6.90 - 9.94 (m, 3H), 6.98 (d, J = 7.4 Hz, 1H), 7.28 - 7.34 (m, 3H ), 7.57 (d, J = 9.2 Hz, 1H), 9.40 (d, J = 7.2 Hz, |
1H). N- (2- (Benzyloxy) ethyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (24) = O O Qro. 1H NMR (400 MHz, CDCl3) 3 2.66 (s, 3H), 3.68 - 3.75 (m, 4H), 4/57 (s, 2H), 6.90 (dd, J = 1, 2.6.8Hz, 1H), 7.27 - 7.34 (m, 6H), 7.57 (dd, J = 1.2, 9.2 Hz, 1H), 9.37 (dd, J = 2.0.6.8 Hz, 1H), 2- (2-Methylimidazo [1,2-a] pyridine-3-carboxamido) -3-phenylpropanoate. (S) -methyl (25) = o N o 1H NMR (400 MHz, CDCl3) 5 2.50 (s, 3H), 3.25 (dd, J = 5.6, 14.0 Hz 1H) 3, 33 (dd, J = 5.6.14.0 Hz, 1H), 5.08 -5.13 (m, 1H), 6.23 (d, J = 7.2 Hz, 1H), 6.91 (dd, J = 1.2, 6.8 Hz, 1H), 7.14 - 7.16 (m, 2H), 7.27 - 7.35 (m, 4H), 7.57 (d, J = 8.8 Hz, 1H), 9.39 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) * 338.28 i N- (2-Methylimidazo [1,2-a] pyridin-3-i1) -2-phenylacetamide (26) o Cx 1H NMR ( 400 MHz, CD30D) at 2.26 (s, 3H), 3.82 (s, 2H), 7.24 - 7.31 (m, 2H), 7.36 - 7.41 (m, 2H), 7.43 - 7.44 (m, 3H), 7.76 (d, JU = 6.8 Hz, 1H). N-Benzyl-8-chloro-2-methylimidazo [1. 12-alpyridine-3-carboxamide (27) N O
O 7H NMR (400 MHz, CDCl3) 5 2.72 (s, 3H), 4.71 (d, J = 6.0 Hz, |
2H), 6.14 (brs, 1H), 6.87 (dd, J = 7.2 Hz, 7.2 Hz, 1H), 7.32 (dd, J = 4.4 Hz, 4.4 Hz , 1H), 7.34 - 7.42 (m, 5H), 9.38 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCI3) 16.9, 29.9, 43.8, 113.1, 122.4, 126.2, 127.1, 127.9, 128.0, 129.1, 138, 1, 141.8, 145.9, 161.3. - N-Benzyl-7-chloro-2-methylimidazo [1,2-a] pyridine-3-carboxamide (28) O. RO cs or at 17H NMR (400 MHz, CDCl3) 5 2.66 (s, 3H) , 4.69 (d, J = 5.6 Hz, 2H), 6.13 (brs, 1H), 6.89 -6.91 (m, 1H), 7.29 - 7.37 (m, SH ), 7.55 (d, J = 1.6 Hz, 1H), 9.37 (d, J = 7.6 Hz, 1H). N-Benzyl-6-chloro-2-methylimidazo [1,2-a] pyridine-3-carboxamide (29) - o “ex O 17H NMR (40.0 MHz, CDCl3) 5 2.68 (s, 3H) , 4.70 (d, J = 5.6 Hz, 2H), 6.16 (brs, 1H), 7.30 -7.35 (m, 3H), 7.37 - 7.38 (m, 3H ), 7.53 (d, J = 9.2 Hz, 1H), 9.56 (d, J = 1.6 Hz, 1H). N-Benzyl-2,8-dimethylimidazo [1,2-a] pyridine-3-carboxamide (30) o
Ú N. 1H NMR (400 MHz, MeOH-d4) 5 2.55 (s, 3H), 2.63 (s, 3H), 4.63 (s 2H), 6.95 (t J = 6.8Hz, 1H) , 7.25 (d, J = 6.8Hz, 1H), 7.28 (d, J = 7.2Hz, 1H), 7.37 (t, JU = 7.2Hz, 2H), 7.42 ( d, J = 7.6 Hz, 2H), 8.87 (d, J = 6.8 Hz, 1H). N-Benzyl-2,7-dimethylimidazo [1,2-a] pyridine-3-carboxamide (31
OO 1H NMR (400 MHz, MeOH-d4) 5 2.44 (s, 3H), 2.59 (s, 3H), 4.83 (s, 2H), 6.91 (d, J = 7.2Hz , 1H), 7.28 (t, J = 7.2Hz, 1H), 7.33 (d, J = 6, AHz, 2H), 7.37 (tJ = 7.2Hz, 1H), 7.42 (d, J = 7.6 Hz, 2H), 8.92 (d, J = 7.2 Hz, 1H). N-Benzyl-2,6-dimethylimidazo [1,2-a] pyridine-3-carboxamide (32) |
S |
N 1H NMR (400 MHz, MeOH-da4) 5 2.36 (s, 3H), 2.59 (s, 3H), 4.63 (s, 2H), 7.29 (d, J = 7.6Hz , 1H), 7.31 (d, J = 1.6Hz, 1H), 7.87 (J = 7.2Hz, 3H), 7.43 (1, J = 4.8Hz, 2H), 7.46 (s, 1H), 8.83 (s, 1H). N-Benzyl-2,5-dimethylimidazo [1,2-a] pyridine-3-carboxamide (33) o
EO 1H NMR (400 MHz, MeOH-d4) 5 2.44 (s, 3H), 2.59 (s, 3H), 4.29 (s, 2H), 6.75 (d, J = 7.2Hz , 1H), 7.21 - 7.27 (m, 3H), 7.33 (t J = 6.4Hz, 2H), 7.41 (t, J = 8.8Hz, 1H), 7.49 ( s, 1H). - N-Benzyl-6-fluoro-2-methylimidazo [1,2-a] pyridine-3-carboxamide (34)
O "ot 1H NMR (400 MHz, CD30D) at 2.68 (s, 3H), 4.71 (d, J = 6.0 Hz, 2H), 7.24-7.39 (m 6H), 7 , 52 -7.56 (m, 1H), 9.48 - 9.49 (m, 1H); LCMS (ele-: trovaporization) m / z (M + H) + 284.27 N-Benzyl-7- cyano-2-methylimidazo [1 ta, Aaarpoxamias (35) so, o ”ne SAN 1H NMR (400 MHz, CDCl3) 5 1.64 (s, 3H), 4.61 (d, J = 6.0 Hz, 2H), 6.39 (brs, 1H), 6.85 (dd, J = 1.2 Hz, 5.2 Hz, 1H), 6.89 (s, 1H), 7.29 - 7.38 ( m, 5H), 8.13 (d, J = 5.6 Hz, 1H) N-Benzyl-6-cyano-2-methylimidazo [1,2-a] pyridine-3-carboxamide (36) 5º “O
SN 1H NMR (400 MHz, CD30D) 5 2.63 (s, 3H), 4.65 (s, 2H), 7.27 (t, J = 7.4 Hz, 1H), 7.35 (t J = 7.6 Hz, 2H), 7.42 (d, J = 7.6 Hz, 2H), 7.57 (dd, J |
421175 | = 0.8, 9.2 Hz, 1H), 7.85 (dd, J = 1.6, 9.2 Hz, 1H), 9.58 (m, 1H). N-Benzyl-2-methyl-7-phenylimidazo [1 SS (37) ONLY
N 'H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 4.71 (d, J = 5.6 Hz, 2H), 6.15 (brs, 1H), 7.22 (dd , J = 2.0 Hz, 7.2 Hz, 1H), 7.29 - 7.33 (m, 1H), 7.36-7.44 (m, SH), 7.47 - 7.51 ( m, 2H), 7.66 (s, 1H), 7.68 (d, J = 1.2 Hz, 1H), 7.78 (s, 1H), 9.47 (d, J = 7.2 Hz, 1H). N-Benzyl-2-methyl-6-phenylimidazo [1,2-a] pyridine-3-carboxamide (38): AO NH and TN 1H NMR (400 MHz, CDCl3) 5 2.71 (s, 3H), 4.73 (d, J = 5.6 Hz, 2H), 6.12 (m, 1H), 7.30 7.34 (m, 1H), 7.36 - 7.40 (m, 7H), 7.60 - 7.66 (m, 4H), 9/71 (s, 1H). N-Benzyl-8-fluoro-2-methylimidazo [1,2-alpyridine-3-carboxamide (39)
F '1H NMR (400 MHz, MeOH-d4) 5 2.63 (s, 3H), 4.64 (s, 2H), 6.96 - 7.01 (m, 1H), 7.21 (t, J = 6.8 Hz, 1H), 7.25 - 7.29 (m, 2H), 7.37 (t J = 7.2 Hz, 2H), 7.41 (t J = 7.6 Hz, 2H), 8.84 (d, J = 6.8 Hz, 1H). N-Benzyl - - methyl-B- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (40) = E.
IA O 1H NMR (400 MHz, MeOH-ds) 3 2.66 (s, 3H), 4.63 (s, 2H), 7.15 (t J = 6.8Hz, 1H), 7.25-7 , 28 (m, 1H), 7.37 (t, J = 8.0 Hz, 2H), 7.43 (d, J = 7.6 Hz, 2H), 7.82 (d, J = 7.2 Hz, 1H), 9.21 (d, J = 6.8 Hz, 1H). N-Benzyl-B-methoxy-2-methylimidazo [1,2-a] lpiridine-3-carboxamide (41) |
=
QTO —o 1H NMR (400 MHz, MeOH-d4) 5 2.65 (s, 3H), 3.95 (s, 2H), 4.02 (s, 3H), 6.96 (d, J = 8 , 0Hz, 1H), 7.03 (t, J = 6.8Hz, 1H), 7.23-7.26 (m, 1H), 7.29 (d, J = 5.6Hz, 2H), 7 , 34 (t, J = 6.0 Hz, 2H), 7.39 (t J = 6.4 Hz, 1H), 8.93 (d, J = 7.2 Hz2, 1H). N-Benzyl-B-cyano-2-methylimidazo [1,2-a] pyridine-3-carboxamide (42) Aro
NE IS 1H NMR (400 MHz, MeOH-d4) 5 2.67 (s, 3H), 4.65 (s, 2H), 7.17. (t J = 7.2Hz, 1H), 7.26-7.31 (m, 2H), 7.38 (t J = 7.2Hz, 2H), 744 (d, J = 8.0Hz, 2H) , 8.21 (d, J = 7.2 Hz, 1H), 9.19 (d, J = 6.8 Hz, 1H). Ú N-Benzyl-8-hydroxy-2-methylimidazo [1,2-alpyridine-3-carboxamide (43)
AXO at 1H NMR (400 MHz, MeOH-d4) 5 2.60 (s, 3H), 4.63 (s, 2H), 6.70 (d, J = 7.6Hz, 1H), 6.83 ( t, J = 6.8Hz, 1H), 7.28 (t, J = 7.2Hz, 1H), 7.40 (t, J = 8.0Hz, 3H), 7.42 (d, J = 7 , 2Hz, 2H), 8.53 (d, J = 6.0Hz, 1H). N- (Biphenyl-4-ylmethyl) -6-chloro-2-methylimidazo [1,2-a] pyridine-3-carboxamide - (4) o * N 1H NMR (400 MHz, CDCl3) 5 2.69 (s , 3H), 4.73 (d, J = 5.2 Hz, 2H), 6.18 (brs, 1H), 6.92 (d, J = 6.4 Hz, 1H), 7.36 (d , J = 7.2 Hz, 1H), 7.44 - 7.45 (m, 4H), 7.57 - 7.60 (m, 5H), 9.39 (d, J = 7.6 Hz, 1H), N- (Biphenyl-4-ylmethyl) -7-chloro-2-methylimidazo [1,2-alpyridine-3-carboxamide (45) O, "A. 1H NMR (400 MHz, CDCl3) 5 2.70 (s, 3H), 4.73 (d, J = 5.2 Hz, |
44/175 | 2H), 6.20 (brs, 1H), 7.29 -7.36 (m, 4H), 7.45 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 9 , 6 Hz, 1H), 7.57 (m, 5H), 9.56 (s, 1H) N-Benzyl-2-ethylimidazo [1 s2-alpiridine-3-carboxamide (46)
SO 1H NMR (400 MHz, CDCl3) ô 1.40 (t, J = 7.6 Hz, 3H), 1.63 (s, 3H) 2.99 (q J = 7.6 Hz, 2H), 4, 71 (d, J = 86.0 Hz, 2H), 6.09 (brs, 1H), 6.92 (dd, J = 5.6 Hz, 1H), 7.30 - 7.38 (m, 6H ), 7.60 (d, J = 9.2 Hz, 1H), 9.40 (d, J = 7.2 Hz, 1H). N- (Biphenyl-4-ylmethyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (47)
OR | and "N 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4.75 (d, J = 5.6 Hz, 2H), 6.19 (brs, 1H), 6.92 (dd, J- 6.4 Hz, 64 Hz, 1H), 7.32 (d, J = 7.6 Hz , 1H), 7.35 (d, J = 7.2 Hz, 1H), 7.45 (d, J- 8.0 Hz, 4H), 7.58 - 7.59 (m, 5H), 9 , 41 (d, J = 6.8 Hz, 1H). N-Benzyl-2-propylimidazo [1,2-a] pyridine-3-carboxamide (48) 5) .- N 1H NMR (400 MHz, CD3OD ) 5 0.93 (1, J = 7.4 Hz, 3H), 1.75 - 1.85 (m, 2H), 2.89 (t J = 7.8 Hz, 2H), 4.67 ( d, J = 5.6 Hz, 2H), 6.24 (m, 1H), 6.86 (t, J = 6.8 Hz, 1H), 7.26 - 7.36 (m, 6H), 7.54 (d, J = 8.8 Hz, 1H), 9.31 (d, J = 6.8 Hz, 1H). N- (Biphenyl-4-ylmethyl) -2-propylimidazo [1,2- a] lpiridine-3-carboxamide (49)% Nha o
N 1H NMR (400 MHz, CDCl3) 5 0.98 (t, J = 7.4 Hz, 3H), 1.80 - 1.89 (m, 2H) 2.93 (tJ = 7.8 Hz 2H), 4.73 (d, J = 5.6 Hz, 2H), 6.29 (t J = 5.2 Hz,
Í |
1H), 6.89 (dd, J = 1.2, 6.8 Hz, 1H), 7.27 - 7.37 (m, 2H), 7.42 - 7.46 (m, 4H), 7 , 56 - 7.61 (m, 5H), 9.35 (d, J = 6.8 Hz, 1H). ; LCMS (electrospray) m / z (M + H) + 370.32 N-Benzyl-2-cyclopropylimidazo] 1,2-a] pyridine-3-carboxamide (50) O
N 17H NMR (400 MHz, CD3OD) 5 1.00 - 1.03 (m, 2H), 1.14 - 1.18 (m, 2H), 2.11 - 2.15 (m, 1H), 6.91 (dd, J = 1.2, 6.8 Hz, 1H), 7.29 - 7.38 (m, 5H), 7.57 (dd, J = 0.8, 8.8 Hz, 1H), 9.49 -9.51 (m, 1H); LCMS (electrospray) m / z (M + H) + 292.23 N-Benzyl-2-isopropylimidazo [1,2-a] pyridine-3-carboxamide (51) CX
TN 1H NMR (400 MHz, CDCl3) 5 1.41 (d, J = 6.8 Hz, 6H), 3.36 - 3.32 (m, 1H), 4.71 (d, J = 5.6 Hz, 2H), 6.11 (brs, 1H), 6.88 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 7.29 (dd, J = 6.8 Hz, 6, 8 Hz, 1H), 7.31 - 7.39 (m, 5H), 7.62 (d, J = 9.2 Hz, 1H), 9.31 (d, J = 7.2 Hz, 1H) . - N- (Biphenyl-4-ylmethyl) -2-isopropylimidazo [1,2-a] pyridine-3-carboxamide (52) o LO O | OK
SN 1H NMR (400 MHz, CDCl3) 5 1.44 (d, J = 6.4 Hz, 6H), 3.34 - 3.41 (m, 1H), 4.76 (d, J = 5.6 Hz, 2H), 6.16 (brs, 1H), 6.90 (dd, J = 7.2 Hz, 7.2 Hz, 1H), 7.29 - 7.37 (m, 2H), 7, 42 - 7.47 (m, 4H), 7.60 - 7.64 (m, 5H), 9.32 (d, J = 7.2 Hz, 1H). N-Benzyl-2-phenylimidazo [1,2-a] pyridine-3-carboxamide (53) ÇA) oo 17H NMR (400 MHz, CDCl3) 5 4.50 (d, J = 5.6 Hz, 2H), 6.090 (m, |
1H), 7.14 - 7.16 (m, 2H), 7.26 - 7.32 (m, 4H), 7.36 - 7.40 (m, 4H), 7.61 - 7.63 ( m, 2H), 7.69 (d, J = 9.2 Hz, 1H), 2-Ethyl-N- (4-phenoxybenzyl) imidazo [1,2-a] pyridine-3-carboxamide (54) O. AT THE
STO WA "N 7H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.99 (a, J = 7.6 Hz, 2H) 4.67 (d, J = 5.6 Hz, 2H), 6.08 (brs, 1H), 6.89 - 6.93 (m, 1H), 7.00 (dd, J = 2.0 Hz, 8.8 Hz, 4H ), 7.08 -7.12 (m, 1H), 7.30 - 7.35 (m, 5H), 7.60 (d, J = 9.2 Hz, 1H), 9.39 (d, JU = 7.2 Hz, 1H). N- (4-tert-Butylbenzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (55) o .: CS 1H NMR (400 MHz, CDCl3) 5 1.32 (s, 9H), 1.41 (t J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 5 , 6 Hz, 2H), 6.12 (brs, 1H), 6.93 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.34 - 7.36 (m, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 9, 40 (d, J = 7.2 Hz, 1H). 2-Ethyl-N - (((1-methyl-1H-indol-5-yl) methyl) imidazo [1,2-a] pyridine-3-] carboxamide (56) O, / FSM
N 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.81 (s, 3H) , 4.79 (d, J = 5.6 Hz, 2H), 6.08 (brs, 1H), 6.48 (s, 1H), 6.92 (dd, J = 6.8 Hz, 6, 8 Hz, 1H), 7.08 (s, 1H), 7.25 (s, 1H), 7.26 - 7.34 (m, 2H), 7.60 (d, J = 8.8 Hz, 1H), 7.63 (s, 1H), 9.43 (d, J = 7.2 Hz, 1H). 2-Ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide 2 »o [ds, 1H NMR (400 MHz, CDCl3) 5 1.41 (t J = 7.6 Hz, 3H), 3.00 (q, J = |
1H), 7.14 - 7.16 (m, 2H), 7.26 - 7.32 (m, 4H), 7.36 - 7.40 (m, 4H), 7.61 - 7.63 ( m, 2H), 7.69 (d, J = 9.2 Hz, 1H), 2-Ethyl-N- (4-phenoxybenzyl) imidazo [1,2-alpiridine-3-carboxamide (54) O. NO STO
TN 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.67 (d, J = 5 , 6 Hz, 2H), 6.08 (brs, 1H), 6.89 - 6.93 (m, 1H), 7.00 (dd, J = 2.0 Hz, 8.8 Hz, 4H), 7.08 -7.12 (m, 1H), 7.30 - 7.35 (m, 5H), 7.60 (d, J = 9.2 Hz, 1H), 9.39 (d, J = 7.2 Hz, 1H). N- (4-tert-Butylbenzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (55) Ok ok "N 1H NMR (400 MHz, CDCl3) 5 1.32 (s, 9H), 1.41 (t J = 7.6 Hz, 3H), 2.99 (qg J = 7.6 Hz, 2H), 4.68 (d, J = 5.6 Hz, 2H), 6.12 ( brs, 1H), 6.93 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.34 - 7.36 ( m, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 9.40 (d, J = 7.2 Hz, 1H). 2-Ethyl-N - (((1-methyl-1H-indol-5-yl)] methyl) imidazo [1,2-a] lpyridine-3-: carboxamide (56) or 7 * H NMR ( 400 MHz, CDCI3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.81 (s, 3H), 4.79 (d, J = 5.6 Hz, 2H), 6.08 (brs, 1H), 6.48 (s, 1H), 6.92 (dd, J = 6.8 Hz, 6.8 Hz, 1H ), 7.08 (s, 1H), 7.25 (s, 1H), 7.26 - 7.34 (m, 2H), 7.60 (d, J = 8.8 Hz, 1H), 7 , 63 (s, 1H), 9.43 (d, J = 7.2 Hz, 1H). 2-Ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3- carboxamide (57) & RE e. and TN 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 3.00 (q, J = q
7.6 Hz, 2H), 4.69 (d, J = 6.0 Hz, 2H), 6.21 (brs, 1H), 6.91 (dd, J = 6.8 Hz, 6.8 Hz , 1H), 7.19 (s, 1H), 7.21 (s, 1H), 7.30 - 7.34 (m, 1H), 7.389 (s, 1H), 7.41 (s, 1H) , 7.60 (d, Jy = 9.2 Hz, 1H), 9.37 (d, J = 7.2 Hz, 1H); 18C NMR (100 MHz, CDCI3) 5 13.5, 23.7, 42.9, 113.5, 114.7, 119.3, 121.5, 121.9, 127.3, 128.3, 129 , 2 / 137.3, 146.4, 148.8, 151.1, 161.7. 2-Ethyl-N - (((1-methyl-1H-indol-6-yl)] methyl) imidazo [1,2-a] pyridine-3-carboxamide (58) FAITH "N N
SA 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.80 (s, 3H) , 4.78 (d, J = 5.6 Hz, 2H), 6.09 (brs, 1H), 6.48 (d, J = 2.8 Hz, 1H), 6.89-6.93 (m , 1H), 7.08 (d, J = 3.2 Hz, 1H), 7.23 - 7.33 (m, 3H), - 7.59 (s, 1H), 7.62 (d, J = 5.6 Hz, 1H), 9.41 (d, JU = 6.8 Hz, 1H). 2-Ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide - O x H o
SS * H NMR (400 MHz, CDCI3) 5 1.37 (t J = 7.6 Hz, 3H), 2.98 (a, JS 15 = 7.6 Hz, 2H), 3.14 (t, J = 4.8 Hz, 4H), 3.85 (t, J = 4.8 Hz, 4H), 4.61 (d J =: 5.6 Hz, 2H), 6.05 (brs, 1H), 6.88 - 6.92 (m, 3H), 7.27 - 7.33 (m, 3H), 7.59 (d, J = 8.8 Hz, 1H), 9.39 (d, J = 7.2 Hz, 1H). 2-Ethyl-N- (4-isopropoxybenzyl) imidazo [1,2-a] pyridine-3-carboxamide (60) or 1H NMR (400 MHz, CDCl3) 5 1.32 (d, J = 5.6 Hz, 6H), 1.38 (t J = 7.6Hz, 3H), 2.96 (g, J = 7.6Hz, 2H), 4.52 -4.56 (m, 1H), 4.61 (d , J = 4.8 Hz, 2H), 6.05 (brs, 1H), 6.86 - 6.92 (m, 3H), 7.26 - 7.33 (m, 3H), 7.59 ( d, J = 8.8 Hz, 1H), 9.38 (d, J = 6.4 Hz, 1H). 2-Ethyl-N- (4-isobutoxybenzyl) imidazo [1,2-a] lpiridine-3-carboxamide (61)
it's the IT'S THE
N 1H NMR (400 MHz, CDCl3) 3 1.01 (d, J = 6.8 Hz, 6H), 1.37 (LJ = 7.6 Hz, 3H), 2.05 - 2.09 (m, 1H), 2.96 (q, J = 7.6 Hz, 2H), 3.71 (d, J = 6.8 Hz, 2H), 4.62 (d, J = 5.2 Hz, 2H) , 6.06 (brs, 1H), 6.89 (dd, J = 2.4 Hz, 2H), 6.92 (dd, J = 1.2 Hz, 6.8 Hz, 1H), 7.27 - 7.34 (m, 3H), 7.59 (d, J = 8.0 Hz, 1H), 9.37 (dd J = 2.4 Hz, 6.8 Hz, 1H); 13C NMR (100 MHz, CDCI3S) 5 13.6, 19.4, 23.5, 28.4, 43.3, 53.1, 74.7, 113.4, 115.0, 116.7, 124 , 2, 127.2, 128.3, 129.2, 130.0, 146.2, 150.7, 159.0, 161.5. NBiphenyl-4-ylmethyl) -2-ethyl-6-methylimidazo [1,2-a] pyridine-3-carboxamide (62): - OS
N 7H NMR (400 MHz, MeOH-d4) 5 1.34 (t, J = 7.6Hz, 3H), 2.37 (s, 3H), 3.02 (g, J = 7.6Hz, 2H) , 4.68 (s, 2H), 7.381-7.34 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 4.8 Hz, 1H) , 7.51 (d, J = 8.8 Hz, 3H), 7.64 (t, J = 4.4 Hz, 4H), 8.78 (s, 1H). '2-Ethyl-6-methyl-N- (4-phenoxybenzyl) imidazo [1,2-a] pyridine-3-carboxamide (63)
CHAOS $ 1H NMR (400 MHz, MeOH-d4) at 1.35 (t, J = 8.0 Hz, 3H), 2.37 (s, 3H), 2.99 (q, J = 7.2 Hz, 2H ), 4.61 (s, 2H), 6.99 (d, JU = 8.8Hz, 4H), 7.12 (tl J = 7.2Hz, 1H), 7.31-7.36 (m, 3H), 7.42 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 9.2 Hz, 1H), 8.76 (s, 1H). N- (4-tert-Butylbenzyl) -2-ethyl-S-methylimidazo [1,2-a] pyridine-3-carboxamide (64)
O
QUO 'H NMR (400 MHz, MeOH-d4) 5 1.30 (t, J = 7.2Hz, 3H), 1.32 (s, 9H), 2.37 (s, 3H), 2.98 ( q, J = 8.0Hz, 2H), 4.59 (s, 2H), 7.30 (d, J = 1.6Hz, 1H), 7.34 (d, J = 8.4Hz, 2H), 7.41 (d, J = 6.8 Hz, 2H), 7.47 (d, J = 9.2 Hz2, 1H), 8.74 (s, 1H). 2-Ethyl-6-methyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide (65) o
RF Wants O 1H NMR (400 MHz, MeOH-d4) 5 1.33 (t J = 8.0 Hz, 3H), 2.36 (s,. 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.65 (s, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 9.2 Hz, 1H), 7.48 (d, J = 9.2Hz, 1H), 7.52 (d, y = 8.4Hz, 2H), 8.77 (s, 1H). 2-Ethyl-6-methyl-N (((1-methyl-1H-indol-5-yl)] methyl) imidazo] [1,2-a] pyridine-3-carboxamide (66) - o
N 1H NMR (400 MHz, MeOH-da4) 5 1.28 (t, J = 7.6 Hz, 3H), 2.36 (s, 3H), 2.95 (q, J = 7.2 Hz, 2H) , 3.80 (s, 3H), 4.71 (s, 2H), 6.42 (d, J = 2.8Hz, 1H), 7.16 (d, Ju = 3.2Hz, 1H), 7 , 26 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 9.2 Hz, 2H), 7.59 (s, 1H), 8.73 (s, 1H). 2-Ethyl-6-methyl-N - (((1-methyl-1H-indol-6-yl) methyl) imidazo [1,2-a] pyridine-3-carboxamide (67) o 2
N PA 7H NMR (400 MHz, MeOH-d4) 5 1.30 (t, J = 7.6Hz, 3H), 2.35 (s, 3H), 3.0 (q, J = 7.6Hz, 2H ), 3.80 (s, 3H), 4.75 (s, 2H), 6.41 (d, J = 3.2Hz, 1H), 7.11-7.14 (m, 2H), 7, 32 (d, J = 9.2Hz, 1H), 7.46 (d, J = 9.2Hz, 2H), 7.55 (d, J |
= 8.0 Hz, 1H), 8.74 (s, 1H). 2-Ethyl-7-methyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (68) o. RN LU o LE
SN White solid, mp 190 ºC; 1H NMR (400 MHz, MeOH-d4) 5 131 (J = 7.6 Hz, 3H), 2.43 (s, 3H), 2.98 (a, J = 7.6 Hz, 2H), 3.14 (t J = 4.8 Hz, 4H), 3.35 (s, 1H), 3.85 (t, J = 4.8 Hz, 4H), 4.53 (s, 2H), 6.90 ( d, J = 7.2 Hz, 1H), 6.98 (d, JU = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 3H), 8.83 (d, J = 7.2 Hz, 1H). 2-Ethyl-7-methyl-N- (naphthalen-2-ylmethyl) imidazo [1,2-a] lpiridine-3-carboxamide (69) -% 4 Ro White solid, mp 192 ºC; 1H NMR (400 MHz, MeOH-d4) 5 1.33 (t, J = 7.6 Hz, 3H), 2.45 (s, 3H), 3.02 (q, J = 7.6 Hz, 2H ), 4.79 (s, 2H), 6.9 (d, J = 7.2 Hz, 1H), 7.33 (s, 1H), 7.45-7.48 (m, 2H), 7 , 56 (d, J = 8.8 Hz, 1H), 7.82-7.88 (m, 4H), 8.87 (d, J = 7.2 Hz, 1H). Ú 15 6-Chloro-N- (4-chlorobenzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (70): AX ”% NH" N 1H NMR (400 MHz, CDCl3) 5 1.41 ( , J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.66 (d, J = 5.6 Hz, 2H), 6.14 (m, 1H ), 7.29 - 7.35 (m, 5H), 7.54 (dd, J = 0.8, 9.6 Hz, 1H), 9.51 (dd, J = 0.8, 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 348.14 6-Chloro-2-methyl-N- (4-phenoxybenzyl) imidazo [1,2-a] pyridine-3- carboxamide (71) |
"N 1H NMR (400 MHz, CDCl3) 3 1.41 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.67 (d, J = 5.6 Hz, 2H), 7.01 (d, J = 8.4 Hz, 4H), 7.09 - 7.13 (m, 1H), 7.30 (dd, J = 2.0, 9.6 Hz, 1H), 7.32 - 7.36 (m, 4H), 7.54 (d, J = 9.6 Hz, 1H), 9.54 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 406.23 6-Chloro-2-methyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (72) o ”k No. A | 1H NMR (400 MHz, CDCI3) 5 1.43 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.71 (d, J = 6.0 Hz, 2H), 6.415 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.31 (dd, J = 2.0 , 9.6 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 9.6 Hz, 1H), 9.54 (d, J = 2 , 0 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 398.21 - N- (4-tert-Butylbenzyl) -6-chloro-2-methylimidazo [1,2-alpiridine-3 - carboxamide (73) and FE
O 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 6.0 Hz, 2H), 6.09 (m, 1H), 7.28 - 7.31 (m, 1H), 7.32 (djJ = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 9.6 Hz, 1H), 9.54 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 370.25 6-Chloro-2-methyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (74) | OO
And the
O H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.16 (t, JU = 4.8 Hz, 4H), 3.96 (t, J = 4.8 Hz, 4H), 4.61 (d, J- 5.6 Hz, 2H), 6.92 (d, J = 8 , 8 Hz, 2H), 7.26 -7.30 (m, 3H), 7.54 (d, J = 9.6 Hz, 1H), 9.52 (d, J = 1.2 Hz, 1H ); LCMS (electrospray) m / z (M + H) + 399.30 6-Chloro-N- (d-isopropoxybenzyl) -2-methylimidazo [1,2-a] pyridine-3-carboxamide (75) Y
I '7H NMR (400 MHz, CDCl3) 5 1.34 (d, J = 6.0 Hz, 6H), 1.39 (, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 4.52 - 4.58 (m, 1H), 4.62 (d, J = 5.6 Hz, 2H), 6.03 (m, 1H), 6.89 ( d, J = 8.8 Hz, 2H), 7.27 - 7.31 (m, 3H), 7.54 (d, J = 9.6Hz, 1H), 9.53 (d, J = 1, 2Hz, 1H); LCMS (electrospray) m / z (M + H) + 372.22 6-Chloro-N- (4-isobutoxybenzyl) -2-methylimidazo (1,2-a] pyridine-3- 'carboxamide (76)
FT. “CO 1H NMR (400 MHz, CDCI3) 5 1.00 (d, J = 6.8 Hz, 6H), 1.36 (t J =
15. 7.6 Hz, 3H), 2.03 -2.09 (m, 1H), 2.93 (q, J = 7.6 Hz, 2H), 3.69 (d, J = 6.8 Hz , 2H), 4.59 (d, J = 5.68 Hz, 2H), 6.13 (t JU = 4.8 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H) , 7.24 - 7.27 (m, 3H), 7.49 (d, J = 9.6 Hz, 1H), 9.47 (d, J = 1.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 386.30 6-Chlorine-2-methyl-N - (((1-methyl-1H-indol-5-yl)] methyl) imidazo [1,2-alpiridine -3- carboxamide (77) |
The% nha Sound SN 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.81 ( s, 3H), 4.78 (d, J = 5.6 Hz, 2H), 6.07 (m, 1H), 6.48 (d, J = 3.2 Hz, 1H), 7.09 ( d, J = 2.8 Hz, 1H), 7.24 - 7.26 (m, 1H), 7.29 (dd, J = 2.0, 9.6 Hz, 1H), 7.34 (d , J = 8.4 Hz, 1H), 7.53 (d, J = 9.6 Hz, 1H), 7.63 (s, 1H), 9.54 (d J = 1.2 Hz, 1H); LOMS (electrospray) m / z (M + H) + 367.19 6-Chlorine-2-methyl-N - (((1-methyl-1H-indol-6-yl)] ethyl) imidazo [1,2-a ] pyridine-3-carboxamide (78)
WA TN 1H NMR (400 MHz, CDCl3) 5 1.36 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.80 (s, 3H ), 4.82 (d, J = 5.6 Hz, 2H), 6.13 (m, 1H), 649 (d, J = 3.2 Hz 1H) 7.08 (d, J = 2.8 Hz, 1H), 7.12 (dd, J = 1.2.8.0 Hz, 1H), 7.30 (dd, J = 2.0, 9.6 Hz, 1H), 7.34 (s, 1H ), 7.55 (d, J = 9.6 Hz, 1H), 7.63 (d, J = 8.0] Hz, 1H), 9.54 (d, J = 1.2 Hz, 1H) ; LCMS (electrospray) m / z (M + H) + 367.26 6-Chloro-2-ethyl-N- (4- (piperidin-1-i) benzyl) imidazo] 1,2-a] pyridine-3- carboxamide (79)
A o, ne. ”
N 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 1.54 - 1.60 (m, 2H), 1.69 - 1.73 (m, 4H ), 2.94 (q, J = 7.6 Hz, 2H), 3.16 (t, J = 5.14 Hz, 4H), 4.59 (d, J = 5.6 Hz, 2H), 6.00 (m, 1H), 6.93 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.29 (dd, J = 2 , 0.9.6 Hz, 1H), 7.53 (d, J = 9.6 Hz, 1H), 9.52 (djJ = 2.0Hz, 1H); LCMS (electrospray) m / z (M + H) + 397.32 6-Chloro-2-ethyl-N- (naphthalen-2-ylmethyl) imidazo [1,2-a] pyridine-3-carboxamide |
(80) “and the" AN 1H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.4 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4, 87 (a, J = 5.6 Hz, 2H), 6.19 (m, 1H), 7.31 (dd, J = 2.0, 9.6 Hz, 1H), 7.47 - 7.51 (m, 3H), 7.55 (d, J = 9.6 Hz, 1H), 7.82 - 7.85 (m, 3H), 7.87 (d / J = 84Hz, 1H), 9, 57 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 364.20 N- (Biphenyl-4-ylmethyl) -6-chloro-2-methylimidazo [1, 2-alpiridine-3-carboxamide i (81) - o SS r O “o SW" N 1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz, 3H), 3.01 ( q, J = 7.6 Hz, 2H), 4.75 (d, J = 5.6 Hz, 2H), 6.45 (m, 1H), 7.31 (dd, J = 2.0, 9, 6 Hz, 1H), 7.43 - 7.47 (m, 4H), 7.55 (d, J = 9.2 Hz, 1H), 7.58 - 7.62 (m, 4H), 9, 56. (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 390.25 6-Chloro-N - (((2'-chlorobiphenyl-4-yl)] methyl) -2-ethylimidazo [1,2-alpiridine-3- " carboxamide (82) Cc,% ah 1H NMR (400 MHz, CDCl3) 5 1.44 (t, JU = 7.6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4 , 77 (d, J = 6.0 Hz, 2H), 6.18 (m, 1H), 7.27 - 7.35 (m, 4H), 7.43 - 7.48 (m, 5H), 7.56 (d, J = 9.6 Hz, 1H), 9.56 (d, J = 2.0 Hz, 1H); LCMS (electrovaporization) m / z (M + H) + 404.26 6-Chloro-N - (((4 "-chlorobiphenyl-4yl)] methyl) -2-ethylimidazo [1,2-alpiridine-3-carboxamide (83) |
"and
N 1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz, 3H), 3.01 (q, = 7.6 Hz, 2H), 4.71 (d, J = 6 , 0 Hz, 2H), 6.13 (m, 1H), 7.31 (dd, J = 2.0, 9.6 Hz, 1H), 741 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.54 - 7.58 (m, 3H), 9.55 (d , J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 424.26 6-Chloro-2-ethyl-N - (((2'-methylbiphenyl4-iN) methyl) imidazo [1,2-a] pyridine-3-carboxamide (84). NH “" N 17H NMR (400 MHz, CDCl3) at 1.43 (t, J = 7.6 Hz, 3H), 2.27 (s, 3H), 3.02 (q, J = 7.6 Hz , 2H), 4.76 (d, J = 5.6 Hz, 2H), 6.21 (t J = 5.2 Hz, 1H), 7.20-7.28 (m, 4H), 7, 30 (dd, J = 2.0, 9.6 Hz, 1H), 7.34 (d, 1 = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 9.6 Hz, 1H), 9.55 (d, J = 2.0 Hz, Ú 1H); LCMS (electrospray) m / z (M + H) + 404.26. 6-Chloro-2-ethyl-N - (((3'-methylbiphenyl-4-yl)] methyl) imidazo [1,2-a] pyridine-3-carboxamide (85)
NH “oo 1H NMR (400 MHz, CDCl3) 5 1.43 (t J = 7.6 Hz, 3H), 242 (s, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.75 (d, J = 5.6 Hz, 2H), 6.14 (m, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.31 (dd, 7 = 2 , 0, 9.6 Hz, 1H), 7.34 (d, J = 7.2 Hz, 1H), 7.39 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 9.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 9.56 (d, J = 2 , 0 Hz, 1H); LCMS (electrospray) m / z |
(M + H) + 404.26 6-Chloro-2-ethyl-N - (((4'-methylbiphenyl-4-iI) methyl) imidazo [1,2-a] pyridine-3-carboxamide (86)
NE O 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H) , 4.74 (d, J = 5.6 Hz, 2H), 6.16 (m, 1H), 7.25 (d, J = 7.2 Hz, 2H), 7.30 (dd, J = 2.0, 9.6 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.49 (d, J. = 8.0 Hz, 2H), 7.54 (d , J = 9.6 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 9.55 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 404.26. T-M-a-Chlorotaraill. 2 feel the AI lol aline Sariguamida (87) ex. oo 1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 4.85 (d, J = 5.6 Hz, 2H), 6.12 (brs, 1H), 6.90 (dd, J = 7.6, 2.4 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.58 (d, 1H), 9.34 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 348.21 7-Chloro-2-ethyl-N- (4-hydroxybenzyl) imidazo [1,2-a] pyridine-3-carboxamide (88) al sx á h 1H NMR (400 MHz, MeOH-d4) 5 1.29 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 3.12 - 3, 15 (m, 4H), 4.52 (s, 2H), 6.76 (d, J = 8.4 Hz, 2H), 7.06 (dd, J = 7.6, 2.0 Hz, 1H ), 7.23 (d, J = 8.4 Hz, 2H), 7.58 (d, J-1.6 Hz, 1H), 8.91 (d, 4 = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 330.25 7-Chloro-2-ethyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (89) |
LEO ee ars White solid, mp 195 ºC; 1H NMR (400 MHz, MeOH-d4) 5 1.31 (t, J = 7.6 Hz, 3H), 3.00 (a, J = 7.6 Hz, 2H), 3.14 (t, J = 4.8 Hz, 4H), 3.84 (t, J = 4.8 Hz, 4H), 4.54 (s, 2H), 6.97 (d, J = 6.8 Hz, 2H), 7.07 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.59 (s, 1H), 8.93 (d, 1 = 7 , 2 Hz, 1H). 7-Chloro-2-ethyl-N- (4- (piperidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (90) x O
AND . at N 7 H NMR (400 MHz, CDCl 3) 5 1.35 (t, J = 7.6 Hz, 3H), 1.55 - 1.57. (m, 2H), 1.66 - 1.70 (m, 4H), 2.91 (q, J = 7.6 Hz, 2H), 3.42 - 3.15 (m, 4H), 4, 56 (d, J = 5.6 Hz, 2H), 6.07 (brs, 1H), 6.86 (dd, J = 7.6, 2.0 Hz, 1H), 6.90. 10 (d / J = 8.4 Hz, 2H) 7.22 (d, J = 8, A4 Hz, 2H), 7.54 (d, J] = 2.0 Hz, 1H), 9.30 (d , J = 7.6 Hz, 1H); LOMS (electrospray) m / z (M + H) + 397.32 7-Chloro-2-ethyl-N- (naphthalen-2-ylmethyl) imidazo [1,2-a] pyridine-3-carboxamide eu: and RAN H NMR (400 MHz, MeOH-d4) 5 1.32 (t J = 7.6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4.79 (s, 2H) , 7.06 (dd, J = 7.6, 2.0 Hz, 1H), 7.45 - 7.48 (m, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.82 - 7.88 (m, 4H), 8.96 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 364.20 N- (4-tert-Butylbenzyl) -7-chloro-2-ethylimidazo [1,2-a] lpiridine-3-carboxamide 192) cs er 1H NMR (400 MHz, CDCl3) 5 1.32 (s, 9H), 1.40 (t J = 7.6 Hz, |
3H), 2.96 (q, uy = 7.6 Hz, 2H), 4.67 (d, J = 5.6 Hz, 2H), 6.13 (brs, 1H), 6.90 (dd, J = 7.2, 24 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 370.25 NXBiphenyl4-ylmethyl) -7-chloro-2-ethylimidazo [1,2-a] lpiridine-3-carboxamide (23). LO er N 1H NMR (400 MHz, CDCl3) ô 1.42 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.74 (d, J = 5.6 Hz, 2H), 6.14 (brs, 1H), 6.91 (dd, J = 7.6.2.4 Hz, ”- 1H), 7.35 (m, 1H), 7.42 - 7.46 (m, 4H), 7.57 - 7.62 (m, 5H), 9.38 (d, J = 7.6 Hz 1H); 13C NMR (100 MHz, CDCl3) 5 13.4, 23.6, 31.5, 34.7, 43.4, 114.7, '115.8, 126.0, 127.5, 128.6, 133.6, 135.0, 146 , 2, 150.9, 151.6, 161.3,; LCMS (electrospray) m / z (M + H) + 390.25 - 7-Chloro-N - (((2'-chlorobiphenyl-4-yl)] methyl) -2-ethylimidazo [1,2-a] pyridine- 3- carboxamide (94) 8 Loo - ds 1H NMR (400 MHz, MeOH-d4) 5 1.32 (t, J = 7.6 Hz, 3H), 3.01 (q, i J = 7.6 Hz , 2H), 4.68 (s, 2H), 7.03 (dd, J = 7.6, 2.0 Hz, 1H), 7.29 - 7.57 (m, 9H), 8.94 ( d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 424.26 7-Chlorine-N - (((4 "-chlorobiphenyl-4-yl)] Mmethyl) -2-ethylimidazo [1,2-a] pyridine-3 - carboxamide (95) q LO and N 1H NMR (400 MHz, CDCl3) at 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.73 (s, 2H), 6.15 (brs, 1H), 6.91 (dd, J - 7.6, 2.0 Hz, 1H), 7.40 (d, J = 8.4 Hz , 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H ), 7.60 (d, J = 1.6 Hz, 1H), 9.38 (d, J = 7.2 Hz, 1H); LCMS (e- | electrovaporization) m / z (M + H) + 424.26 7-Chloro-2-ethyl-N - (((2'-methylbiphenyl-4-yl)] methyl) imidazo [1,2-a] pyridine-3-carboxamide (96)
HC% LO ss to RN 1H NMR (400 MHz, CDCl3) 5 1.46 (t, J = 7.6 Hz, 3H), 2.31 (s, 3H) 305 (q J = 7.6 Hz, 2H ), 4.79 (d, J = 5.6 Hz, 2H), 6.22 (brs, 1H), 6.95 (dd, J = 7.6, 1.6 Hz, 1H), 7.24 - 7.36 (m, 4H), 7.39 (d, J = 7.6 Hz, 2H), 7 45 (d, J = 7.6 Hz, 2H), 7.63 (d, 1H), 9.42 (d, J = 7.2 Hz, 1H); LCMS (electroplating) m / z (M + H) + 404.26. 7-Chloro-2-ethyl-N - (((3'-methylbiphenyl-4-yl)] methyl) imidazo [1,2-a] pyridine-3-carboxamide (97) CHy
FN Li 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.42 (s, i 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.74 (d, J = 5.6 Hz, 2H), 6.13 (brs, 1H), 6.91 - (dd, J = 7.6, 2.0 Hz, 1H), 7 , 18 (d, J = 8.4 Hz, 1H), 7.33 - 7.40 (m, 3H), 7 43 (d, J = 8.4 Hz, 2H), 7.58 - 7.61 (m, 3H), 9.38 (d, J = 7.6 Hz, 1H); LCMS (electrovaporization) m / z (M + H) +404,33 7-Chloro-2-ethyl-N - ((4, -methylbiphenyl-4-yl)] methyl) imidazo [1,2-a] pyridine-3-carboxamide (98) O, H LO Fe o N 'H NMR (400 MHz, CDCl8) 51.41 (t, J = 7.6 Hz, 3H), 2.40 (s, 3H), 2 , 99 (q, J = 7.6 Hz, 2H), 4.73 (s, 2H), 6.91 (dd, J = 7.6, 2.0 Hz, 1H), 7.25 (d / J = 84Hz 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.58 - |
7.60 (m, 3H), 9.38 (d, J = 7.2 Hz, 1H); LOMS (electrospray) m / z (M + H) + 404.26 N- (Biphenyl-4-ylmethyl) -6-chloro-2- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (99 )% NH and o at 1H NMR (400 MHz, CDCl3) 5 4.74 (d, J = 5.6 Hz, 2H), 6.69 (m, 1H), 7.36 (dd, J = 7.2 , 7.2 Hz, 1H), 7.43 - 7.47 (m, 5H), 7.56 (dd, J = 8.0, 8.4. Hz, 4H), 7.71 (d, J = 9.6 Hz, 1H), 9.45 (s, 1H)); LCMS (electrospray) m / z (M + H) + 430.18 à. N- (4-tert-Butylbenzyl) -S-chloro-2- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (100) o. The ”“ ota xs. a “1H NMR (400 MHz, CDCl3) 3 1.32 (s, 9H), 4.67 (d, J - 6.0 Hz, 2H), 6.63 (m, 1H), 7.30 (d , J- 8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.41 - '7.45 (m, 1H), 7.69 (d, J = 9 , 6 Hz, 1H), 9.42 (d, J = 1.2 Hz, 1H); LCMS (electrovaporization) m / z (M + H) + 410.25 N4-Bromobenzyl) -7-chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamide (101) XD
EE 1H NMR (400 MHz, CDCl3) 5 1.41 (1, J = 7.6 Hz, 3H), 2.97 (a, J = 7.6 Hz, 2H), 4.65 (d, J = 5.6 Hz, 2H), 6.09 (brs, 1H), 6.91 (dd, Ju = 7.6.2.0 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 1H) 9.35 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 394.13 7-Chloro-2-ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3- | carboxamide (102).
LO 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.70 (d, J = 5.6 Hz, 2H), 6.09 (brs, 1H), 6.91 (dd, u = 7.6, 2.0 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 1H) 9.36 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 398.28 2-Ethyl-6-fluoro-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (103) 1 'NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.71 (d, y = 6.0 Hz, 2H), 6.14 (brs, 1H), 6.91 (dd, JU = 7.6, 2.0 Hz, i 10 1H), 7.20 (d, J = 8, 0 Hz, 1H), 7.26 (m, 1H), 7.57 (d, J = 5.2 Hz, 1H), 7.59 (d, J = 5.2 Hz, 1H), 9.45 (dd, J = 5.2, 2.4 Hz, 1H); LCMS (electrospray) m / z º (M + H) + 382.15 2-Ethyl-7-methoxy-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (104 ) 1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.87 (s, 3H) , 6.06 (m, 1H), 6.61 (dd, J = 2.8, 7.6, 1H), 6.89 (d, J = 2.4 Hz, 1H), 7.21 (d , J = 8.8 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 9.24 (d, J = 7.6 Hz, 1H). 2-Ethyl-7-hydroxy-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (105) to 10
OR * H NMR (400 MHz, CDCI3 + CD30D) 5 1.21 (t J = 7.6 Hz, 3H), 2.79 (q, J = 7.6 Hz, 2H), 4.51 (q, J = 4.0 Hz, 2H), 4.74 (brs, 1H), 6.49 (dd, J = |
2.4, 7.6, 1H), 6.89 (d, J = 2.4 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 8.86 (d, Jy = 7.6 Hz, 1H). 7-Chloro-2-ethyl-N- (4- (propylamino) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (106) oO “o.
LE 1H NMR (400 MHz, CDCI3) 5 1.00 (t, J = 7.4 Hz, 3H), 1.37 (| J = 7.6 Hz, 3H), 1.60 - 1.69 (m , 2H), 2.93 (q, J = 8.0 Hz, 2H), 3.08 (t, J = 7.2 Hz, 2H), 3.69 (brs, 1H), 4.55 (d , J = 5.2 Hz, 2H), 5.96 (m, 1H), 6.80 (d, J = 8,: 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 1.2 Hz, 1H), 9.35 (d, J = 7.6 Hz, 1H). - 10 7-Chloro-2-ethyl-N- (4- (pentylamino) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (107) o Xi
LE 1H NMR (400 MHz, CDCI3) 5 0.92 (t, J = 7.0 Hz, 3H), 1.25 - 1.42 (m, 8H), 1.58 - 1.66 (m, 2H ), 2.93 (q, J = 7.6 Hz, 2H), 3.10 (t, J = 7.2 Hz, 2H), - 3.66 (brs, 1H), 4.55 (d, J = 5.2 Hz, 2H), 5.95 (m, 1H), 6.60 (d, J = 8.4, 2H), 6.89 (dd, J = 2.0.7.2 Hz , 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 1.2 Hz, 1H), 9.36 (d, JU = 7.6 Hz, 1H ). 6-Chloro-2-ethyl-N- (4- (4-methylpiperazin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (108) to OT and
N 1H NMR (400 MHz, CDCl3) at 1.39 (t, J = 7.6 Hz, 3H), 2.36 (s, 3H) 2.58 (tJ = 5.0 Hz, 4H), 2, 95 (q, J = 7.6 Hz, 2H), 3.22 (t, J = 4.8 Hz, 4H), 4.60 (d, J = 5.6 Hz, 2H), 6.93 ( d, J = 8.8 Hz, 2H), 7.26 - 7.30 (m, 3H), 7.53 (d, J = 5.6 Hz, 1H), 9.53 (d, J = 1 , 6 Hz, 1H). |
7-Chloro-2-ethyl-N- (4- [4-methylpiperazin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (109) OW-OHa
LOS No.
AR 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.35 (s, 3H), 2.57 - 2.59 (m, 4H), 2, 94 (q, J = 7.6 Hz, 2H), 3.20 - 3.23 (m, 4H), 4.59 (d dJ = 5.2 Hz 2H), 6.00 (brs, 1H), 6 , 88 - 6.94 (m, 3H), 7.27 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 2.0 Hz, 1H), 9.35 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 412.29 7-Chloro-2-ethyl-N- (4- (4-isopropylpiperazin-1-yl) benzyl) imidazo [1,2- - alpiridine -3-carboxamide (110) rs Lo - & NH Fx o. 10 "H NMR (400 MHz, CDCl3) 5 1.10 (d, J = 6.0 Hz, 6H), 1.38 (J = 7.6 Hz, 3H), 2.69 (m, 4H), 2.94 (q, J = 7.6 Hz, 2H), 3.22 (m, 4H), 4.60 (d, J = 5.6 Hz, 2H), 5.99 (m, 1H), 6.90 (dd, J = 2.0, 7.6 Hz, 1H), 6.93 (d, J- 8.4 Hz, 1H), 7.26 - 7.38 (m, 5H), 7 , 58 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H). '7-Chloro-2-ethyl-N- (4- (4-phenylpiperazin- 1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (111) | N LT
NH ok at N 'H NMR (400 MHz, DMSO-d6) 5 1.29 (t, J = 7.6 Hz, 3H), 3.00 (a, J = 7.6 Hz, 2H), 3.380 ( m, 8H), 4.48 (d, Jy = 6.0 Hz, 2H), 6.84 (t, J = 6.0 Hz, 1H), 7.01 - 7.05 (m, 4H), 7.13 (dd, J = 2.4, 7.6 Hz, 1H), 7.26 - 7.31 (m, 4H), 7.82 (d, J = 1.6 Hz, 1H), 8 , 45 (t, J = 6.0 Hz, 1H), 8.99 (d, JU = 7.6 Hz, 1H). 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -6-methoxyimidazo [1,2-alpyridine-3-carboxamide (112) | o S White solid; melting point = 173.8 ºC; 1H NMR (400 MHz, CDCl3) 5 1.389 (1, J = 7.6 Hz, 3H), 2.95 (q, J = 7.2 Hz, 2H), 3.24 - 3.27 (m, 4H ), 3.33 - 3.36 (m, 4H), 3.87 (s, 3H), 4.63 (d, J = 5.6 Hz, 2H), 6.03 (t J = 5.0 Hz, 1H), 6.91 - 7.01 (m, 6H), 7.31 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 9.6 Hz, 1H, 9 , 11 (d J = 24Hz, 1H); LCMS (electrospray) m / z (M + H) + 488 6-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1- il) benzyl) imidazo [1,2-alpyridine-3-carboxamide (113) O ”
IH 1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.96 (q, J = '7.6 Hz 2H), 3.25 - 3.27 ( m, 4H), 3.34 - 3.36 (m, 4H), 4.62 (d, J = 5.6 Hz, 2H), 6.02-6.64 (m, 1H), 6.92 - 6.95 (m, 3H), 86.97 - 7.01 (m, 3H), 7.29 (dd, J = 2.4, 9.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 9.6 Hz, 2H), 9.54 (d, J = 1.2 Hz, 2H); LCMS (electrospray) m / z (M + H) + 492.28 '2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -7-methoxyimidazo] 1,2 - alpiridine-3-carboxamide (114) Fo Ç Fo 250 ue White solid; 1H NMR (400 MHz, CDCl3); at 1.30 (t, J = 7.6 Hz, 3H), 2.84 (q, J = 7.6 Hz, 2H), 3.18 - 3.19 (m, 4H), 3.26 - 3.27 (m, 4H), 3.78 (s, 3H), 4.54 (d, J = 5.6 Hz, 2H), 6.15 (brs, 1H), 6.51 - 6.53 (m, 1H), 6.79 (s, 1H), 6.85 - 6.95 (m, 6H), 7.24 (d, J = 8.0 Hz, 2H), 9.12 (d, J = 8.0 Hz, 1H), 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -8-methoxyimidazo [1,2-alpyridine-3-carboxamide ( 115) |
OD Sa Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.34 (tl J = 7.6 Hz, 3H), 2.93 (q, J = 7.6 Hz, 2H), 3.22 - 3.27 (m; 4H), 3.29 - 3 , 34 (m, 4H), 3.99 (s, 3H), 4.60 (d, J = 5.6 Hz, 2H), 6.08 (brs, 1H), 6.58 (d, J = 7.6 Hz, 1H), 6.76 (dd, J = 7.2, 7.6 Hz, 1H), 6.89 - 6.99 (m, 6H), 7.28 (d, J = 84 Hz, 2H), 895 (d J = 7.2 Hz, 1H). T7-Chloro-2-ethyl-N - (((4 "-fluorobiphenyl-4-yl)] methyl) imidazo [1,2-a] pyridine-3-: carboxamide (116) Loo - 1H NMR (400 MHz, CDCI3 ) 5 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.73 (d, J = 5.6 Hz, 2H), 6.14 (brs, 1H), 6.91 (dd, J = 7.2.2.0 Hz, '10 1H), 7.13 (t J = 8A Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.52 - 7.56 (m, 4H), 7.60 (d, J = 2.0 Hz, 1H), 9.38 (d, JU = 7.2 Hz, 1H); LCMS (electrospray). M / z (M + H) + 408.21 N - (((4 "-tert-Butylbiphenyl-4-yl)] methyl) -7-chloro-2-ethylimidazo [1 , 2-a] pyridine-3- 'carboxamide (117) Copy picture from page 63 of the pdf * H NMR (400 MHz, CDCl3) 5 1.36 (s, 9H), 1.41 (t J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.73 (d, J = 5.6 Hz, 2H), 6.13 (brs, 1H), 6.91 ( dd, J = 7.2, 2.0 Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7, 53 (d, J- 8.4 Hz, 2H), 7.59 - 7.61 (m, 3H), 9.38 (d, JU = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 446.30 7-Chloro-2-ethyl-N - (((4 "-methoxybiphenyl-4yl)] Mmethyl) imidazo [1,2-a] lpiridine-3- carboxamide (118) FAO " LE
1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.99 (a, J = 7.6 Hz, 2H), 3.85 (s, 3H), 4.72 (d, J = 6.0 Hz, 2H), 6.12 (brs, 1H), 6.91 (dd, J = 7.2, 2.0 Hz, 1H), 6.98 (d , J = 8.8 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 1.6 Hz, 1H), 9.38 (d, J = 7.6 Hz 1H); LCMS (electrospray) m / z (M + H ) + 420.18 7-Chloro-2-ethyl-N - (((4 '- (trifluoromethoxy) biphenyl-4yl) methyl) imidazo] 1,2-alpyridine-3-carboxamide (119) q Fs 1H NMR (400 MHz , CDCI3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.75 (d, J = 86.0 Hz, 2H ), 6.15 (brs, 1H), 6.91 (dd, J = 7.6.2.0 Hz, 1H), 7.28 (d, J = 84 Hz, 2H), 7.46 (d , J = 8.4 Hz, 2H), 7.54 - 7.60 (m, 5H),. 9.38 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 474.18 7-Chloro-2-ethyl-N - (((4 '- (trifluoromethyl) biphenyl-4yl) methyl) imidazo [1,2-alpiridine-3- carboxamide (120) Ú. * o 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.76 (d, J = 6.0 Hz, 2H), 6.16 (brs, 1H), 6.92 (dd, J = 7.2.2.0 Hz,. 1H), 7.48 (d, J = 8.4 Hz , 2H), 7.60 (m, 3H), 7.70 (m, 3H), 9.38 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 458.20 6-Chlorine-N - (((4'-cyanobiphenyl-4-yl) methyl) -2-ethylimidazo] [1,2-alpiridine-3-carboxamide (121) Lo e. 1H NMR (400 MHz, CDCl3) 5 1.44 (t, J = 7.6 Hz, 3H), 3.02 (q, J = 7.2 Hz, 2H), 4.77 (d, J = 5 , 6 Hz, 2H), 6.19 (m, 1H), 7.32 (dd, J = 2.0, 9.6 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H ), 7.56 (d, J = 9.6 Hz, 1H), 7.68 (d, J = 84 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 9, 55 (d, J = 2.0 Hz, 1H). 7-Chloro-N - (((4'-cyanobiphenyl-4-yl) methyl) -2-ethylimidazo [1,2-a] pyridine-3- | carboxamide (122) u LOOP Fe
E O 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.76 (d, J = 6.0 Hz, 2H), 6.17 (brs, 1H), 6.92 (dd, J = 7.6.2.4 Hz, 1H), 7.49 (d, J = 8.0 Hz , 2H), 7.60 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 2.4 Hz, 1H) 7.68 (d, J = 8, A4Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 9.38 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 415.21 6-Chloro-2-ethyl-N - ((2 "- (trifluoromethyl) biphenyl-4-iN) methyl) imidazo [1,2-a] pyridine-3-carboxamide (123) - sna 9 NH e and 7H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz; 3H), 3.02 (q, J =. 10 7, 2 Hz, 2H), 4.78 (d, J = 5.6 Hz, 2H), 6.17 (m, 1H), 7.30 - 7.35 (m, 4H), 7.42 (d, J = 8.0 Hz, 2H), 7.48 (t, J = 8.0 Hz, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 9.56 (d, J = 1.2 Hz, 1H). I 7-Chlorine-2-ethyl-N - (((2 '- (trifluoromethyl) biphenyl-4-yl)] methyl) imidazo [1,2-BR alpiridine-3-carboxamide (124)
OO Sea 1H NMR (400 MHz, CDCI3) & 1.41 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.68 Hz, 2H), 4.77 (d, J = 5.6 Hz, 2H), 6.16 (brs, 1H), 6.92 (dd, J = 7.2, 2.4 Hz, 1H), 7.32 (d, J = 7.6 Hz , 1H), 7.34 (d, J = 84 Hz, 2H), 7.41 (d J = 8.4 Hz, 2H), 7.47 (t J = 7.6 Hz, 1H), 7, 56 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 2.4 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 9.38 ( d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) +458.27 6-Chlorine-N - (((2 "-cyanobiphenyl-4yl)] methyl) -2-ethylimidazo] 1,2-a] pyridine-3-carboxamide (125) |
NC. oO —Yn. .. * H NMR (400 MHz, CDCI8) 5 1.45 (t, J = 7.6 Hz, 3H), 3.03 (q, J = 7.6 Hz, 2H), 4.78 (d, J = 5.6 Hz, 2H), 6.18 - 6.20 (m, 1H), 7.32 (dd, J = 1.2, 7.6 Hz, 1H), 7.46 (dd, J = 7 , 6, 7.6 Hz, 1H), 7.50 - 7.55 (m, 3H), 7.57 (d, J = 8.4 Hz, 2H), 7.65 (dd, J = 7, 6, 7.6 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 9.568 (d, J = 12H2 / 1H). 7-Chloro-N - (((2'-cyanobiphenyl-4-yl)] methyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (126) | OO! E 1H NMR (400 MHz, CDCl3) 5 1.44 (t, J = 7.6 Hz, 3H), 3.02 (q, J = '7.6 Hz, 2H), 4.77 (d, J = 5.6 Hz, 2H), 6.18 (brs, 1H), 6.92 (dd, J = 7.6, 2.0 Hz, 1H), 7.47 -7.60 (m, 4H) , 7.63 - 7.65 (m, 4H), 7.77 (d, J = 7.6 Hz, 1H), 9.38 S (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 415.28 6-Chlorine-N - (((3'-cyanobiphenyl-4-yl) methyl) -2-ethylimidazo [1,2-a] pyridine-3- 'carboxamide (127) ex “oo 7H NMR (400 MHz, CDCl3) 5 1.44 (t, J = 7.6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4 , 77 (d, J = 5.6 Hz, 2H), 6.19 (m, 1H), 7.32 (dd, J = 2.0, 9.2 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.55 - 7.59 (m, 3H), 7.64 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 9.56 (d, J = 1.6 Hz, 1H). 7-Chloro-N - (((3'-cyanobiphenyl-4-yl)] methyl) -2-ethylimidazo [1,2-a] lpiridine-3-carboxamide (128) LE
* H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.76 (d, J = 6.0 Hz, 2H), 6.17 (brs, 1H), 86.92 (dd, JU = 7.2, 2.0 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.55 -7.63 (m, 5H), 7.80 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 1.6 Hz, 1H), 9, 38 (d, J = 7.2 Hz, 1H); LCMS (electrospray) mz (M + HH) +415.28 6-Chlorine-N - (((4'-chloro-2 "'- (trifluoromethyl) biphenyl-4-yl)] methyl) -2-ethylimidazo [1, 2- alpiridine-3-carboxamide (129) oO ES
O Ú 1H NMR (400 MHz, CDCI8) 5 1.44 (t, J = 7.6 Hz, 3H), 3.02 (q, J =. 7.6 Hz, 2H), 4.77 (d, J = 5.6 Hz, 2H), 6.18 (m, 1H), 7.27 (d, J = 7.6 Hz, 2H), 7.31 (d J = 7.6 Hz, 2H), 7 , 42 (d, J = 8.0 Hz, 2H), 7.52 - 7.56 (m, 2H), 7.73 (d, J = 2.0 Hz, 1H), 7.88 (s, 1H), 9.55 (d, J = 1.2 Hz, 1H). 7-Chlorine-N - (((4 "-chloro-2" - (trifluoromethyl) biphenyl-4-yl)] methyl) -2-ethylimidazo [1,2- - alpiridine-3-carboxamide (130) Fº o LO. ; H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 3.01 (q J = 7.6 Hz 2H), 4.76 (d, J = 6.0 Hz, 2H), 6.16 (brs, 1H), 6.92 (dd, J = 7.2, 2.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.53 (dd, J = 8.0, 1.6 Hz, 1H ), 7.60 (d, J = 2.0 Hz, 1H), 7.73 (d, J = 2.0 Hz, 1H), 9.38 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 492.21 G6-Chlorine-N - (((4'-cyano-2'-methylbiphenyl-4-yl) methyl) -2-ethylimidazo [1,2-a ] pyridine-3-carboxamide (131)
ON o: 1H NMR (400 MHz, CDCl3) 5 1.44 (t, J = 7.6 Hz, 3H), 2.30 (s, q
3H), 3.03 (q, J = 7.6 Hz, 2H), 4.77 (d, J = 5.6 Hz, 2H), 6.21 (t J = 5.2 Hz, 1H), 7.30 - 7.33 (m, 4H), 7.31 (d, J = 7.6 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.52 - 7 , 56 (m, 2H), 7.52 - 7.57 (m, 3H), 9.56 (d, J = 2.0 Hz, 1H). 7-Chloro-N - (((4 "-cyano-2'-methylbiphenyl-4yl) methyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (132) He, LO" o 1H NMR (400 MHz, CDCI3) to 1.43 (t, J = 7.6 Hz, 3H), 2.29 (s, 3H), 3.02 (q, J = 7.8 Hz, 2H), 4.77 ( d, J = 6.0 Hz, 2H), 6.18 (brs, 1H), 6.92. (dd, J = 7.6, 2.0 Hz, 1H), 7.380 (d, J = 8.0 Hz, 3H), 7.45 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 7.6 Hz, 1H), 7.56 (s, 1H), 7.60 (d, J = 24 Hz, 1H), 9.39 (d, J =. 10 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 429.29 7-Chlorine-N - (((2'-chloro-4 "-fluorobiphenyl-4-yl)] methyl) -2-ethylimidazo [1,2- alpiridine-3-carboxamide (133) sa LCMS (electrospray) m / z (M + H) + 442.15 and 7-Chloro-2-ethyl-N- (4- (pyridin-4-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (134) | LOS rs 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.76 (d, J = 5.6 Hz, 2H), 6.20 (brs, 1H), 6.91 (dd, J = 7.6.2.0 Hz , 1H), 7.26 - 7.51 (m, 4H), 7.61 (d, J = 2.0 Hz, 1H), 7.65 (d, J = 8.0 Hz, 2H), 8 , 65 (brs, 2H), 9.37 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) +391.20 7-Chlorine-2-ethyl-N- (4- (5-methoxypyridin-2-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (135) | FU TI "
LE 'H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 3.91 (s, 3H ), 4.74 (d, J = 5.6 Hz, 2H), 6.11 (brs, 1H), 6.91 (dd, J = 7.6.2.0 Hz, 1H), 7.28 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 1H), 7.67 (d , J = 8.8 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 84H 2H) 8.39 (d, J = 2.8 Hz, 1H), 9.38 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 421.20 N- (4- (1H-Pyrrol-2-yl) benzyl) -7-chloro-2-ethylimidazo [1,2-a] pyridine -3- carboxamide (136) 17H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.69 (m, '10 4H), 2.97 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 6.0 Hz, 2H), 6.10 (m, 1H), 6.29 - 6.32 (m, 1H), 6.53 - 6.54 (m, 1H), 6.87 - 6.88 (m, 1H), 6.91 (dd, J = 2.0.7.2 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 2.0 Hz, 1H), 8.51 (brs, 1H), 9.37 (d, J = 7.6 Hz, 1H). - 7-Chloro-2-ethyl-N- (4- (furan-2-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (137) o
NA e: 1H NMR (400 MHz, CDCI8) 5 1.40 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.70 (d, J 5.6 Hz, 2H), 6.47 - 6.48 (m, 1H), 6.53 - 6.54 (m, 1H), 6.66 (d, J = 3.2, 1H), 6.91 (dd, J = 7.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.47 (d, 1 = 1.2 Hz, 1H), 7, 60 (d, J = 1.6 Hz, 1H), 7.68 (d, J = 8.0 Hz, 2H), 9.37 (d, J-7.2 Hz2.1H). N- (4- (1H-Pyrrol-1-yl) benzyl) -7-chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamide (138) |
The e
LE 1H NMR (400 MHz, CDCI3) 5 1.41 (t J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.71 (d, J = 6 , 0 Hz, 2H), 6.12 - 6.14 (m, 1H), 6.34 - 86.36 (m, 2H), 6.92 (dd, J = 2.0, 7.6 Hz, 1H), 7.08 -7.09 (m, 2H), 7.40 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 21H), 7, 60 (d, J = 2.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 2H), 938 (d / J = 7.6 Hz, 1H). 6-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethoxy) phenoxy) piperidin-1-yl) benzyl) imidazo- [1,2-a] pyridine-3-carboxamide (139) o . to x Y00F,
OR 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 1.90 - 1.98 (m, 2H), 2.07 - 2.13 (m, 2H ), 2.96 (q, J = 7.6 Hz, 2H), 3.10 - 3.46 (m, 2H), '10 348-3.54 (m, 2H), 4.42-4, 48 (m, 1H), 3.22 (t J = 4.8 Hz, 4H), 4.61 (d, J = - 5.6 Hz, 2H), 6.00 - 6.20 (m, 1H ), 6.91 (d, J = 7.2 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.4 Hz, 1H), 7 , 26 - 7.31 (m, 3H), 7.54 (d, J = 9.6 Hz, 1H), 9.53 (d, J = 1.6 Hz, 1H), 7-Chlorine-2- ethyl-N- (4- (4- (4- (trifluoromethoxy) phenoxy) piperidin-1-. 15 ylbenzylimidazo- [1,2-a] lpyridine-3-carboxamide (140) 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 1.89 - 1.98 (m, 2H), 2.07 - 2.13 (m, 2H), 2.9.5 (q, J = 7.6 Hz, 2H), 3.09 - 3.16 (m, 2H), 3.47 - 3.53 (m, 2H), 4.42 - 4.48 (m, 1H), 3 , 22 (t, J = 4.8 Hz, 4H), 4.60 (d, J = 5.6 Hz, 2H), 5.99 - 6.01 (m, 1H), 6.88 - 6, 93 (m, 3H), 6.96 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 7.26 -7.29 (m, 2H) , 7.59 (d, J = 2.0 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H). N - (((4 "-Clorobiphenyl-4-yl)] methyl) - 2-ethylimidazo [1,2-alpyrazine-3-carboxamide (141) | o 1H NMR (400 MHz, DMSO-d6) 5 1.46 (t, J = 7.6 Hz, 3H), 3.06 (q, J = 7.6 Hz, 2H), 4.76 (d, J = 5.6 Hz, 2H), 6.23 - 6.25 (m, 1H), 741 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 8.03 (d, J = 4.4 Hz, 1H) , 9.11 (s, 1H), 9.28 (d, J = 4.8 Hz, 1H). N7-Chloro-2-ethylimidazo [1,2-a] lpiridin-3-yl) biphenyl-4-carboxamide (142) e | LO 1H NMR (400 MHz, CDCl3) 5 1.33 (t, J = 7.6 Hz, 3H), 2.75 (q, J = 7.2 Hz, 2H), 6.78 (dd, Ju = 1.2, 7.2, 1H), 6.89 (dd, J = 1.2, 7.2 Hz, 1H), 7.44: (d, J = 8.0 Hz, 2H), 7, 48 - 7.53 (m, 3H), 7.58 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.72 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 8.02 (brs, 1H),: 10 807 (d J = 8.0 Hz, 2H). 2- (Biphenyl-4-yl) -N- (7-chloro-2-ethylimidazo [1,2-a] pyridin-3-i) acetamide (143) * o; LE 1H NMR (400 MHz, DMSO-d6) 5 1.25 (t, J = 7.6 Hz, 3H), 2.62 (q, J = 7.6 Hz, 2H), 3.89 (s, 2H), 6.74 (dd, J = 2.0, 7.2 Hz, 1H), 7.00 (brs, 1H), 7.44 - 7.53 (m, 5H), 7.61 (d , J = 7.2 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H). N- (4- (4- (4- (Butiramidomethyl) phenyl) piperazin-1-i) benzyl) -7-chloro-2-ethylimidazo- [1,2-a] pyridine-3-carboxamide (144) o DUL
LE 17H NMR (400 MHz, CDCI3) 5 0.93 (t, J = 6.4 Hz, 3H), 1.37 (tl J = 6.0 Hz, 3H), 1.65 - 1.71 (m , 2H), 2.15 (t J = 6.4 Hz, 2H), 2.94 (q, J = 6.0 Hz, 2H), 3.33 (s, 8H), 4.36 (d, J = 4.4 Hz, 2H), 4.61 (d, J = 4.0 Hz, 2H), 5.59 (brs, |
1H), 6.01 (brs, 1H), 6.88 - 6.98 (m, 5H), 7.19 (d, J = 7.2 Hz, 2H), 7.29 (d, J = 7 , 2 Hz, 2H), 7.58 (s, 1H), 9.35 (d, J = 7.2 Hz, 1H); LCMS (electrospray) miz (M + H) + 573. N- (4-tert-Butylbenzyl) -2-ethyl-7- (piperazin-1-iD) imidazo [1,2-a] pyridine-3-carboxamide ( 145) xo “o 1H NMR (400 MHz, DMSO) 5 1.20 (t, J = 7.6 Hz, 3H), 1.24 (s, 9H), 2.78 - 2.80 (m, 4H ), 2.86 (q, J = 7.6 Hz, 2H), 3.13 - 3.145 (m, 4H), 4.42 (d, J = 6.0 Hz, 2H), 6.66 (d , J = 2.0 Hz, 1H), 6.86 (dd, .J = 8.0, 2.0 Hz, 1H),] 7.24 (d, J = 8.4 Hz, 2H), 7 , 32 (d, J = 87.4 Hz, 2H), 7.99 (brt, J = 6.0 Hz, 1H),. 10 8.75 (d, J = 8.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 420; MP 186.1 - 186.9 ºC. 6-Chloro-N- (4-cyanobenzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide 1 (146): AI
NH o White solid; melting point = 223 - 224 ° C; 1H NMR (400 '15 MHz, CDCl3) δ 1.45 (tJ = 7.6 Hz, 3H), 3.02 (q, J = 7.2 Hz, 2H), 4.76 (d J = 6, 0 Hz, 2H), 6.21 - 6.23 (m, 1H), 7.33 (dd, J = 2.0, 9.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 9.2 Hz, 1H), 7.67 (d, J = 8.0 Hz, 2H), 9.53 (d, J = 2.0 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 339.16 6-Chloro-2-ethyl-N- (4- (trifluoromethyl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (147) € tF,
GT “White solid; melting point = 179 - 180 ° C; 1H NMR (400 MHz, CDCl3) 5 1.44 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.77 (d J = |
6.0 Hz, 2H), 6.19 - 6.21 (m, 1H), 7.32 (dd, Jy = 2.0, 9.2 Hz, 1H), 7.50 (d, J = 8 , 4 Hz, 2H), 7.56 (d, J = 9.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 9.54 (d, J = 2.0 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 382.15 7-Chloro-2-ethyl-N- (4- (trifluoromethyl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (148) o ”% NA ch er White solid; melting point = 196.2 - 196.9 ºC; 1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.4 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.76 (d, J = - 6.4 Hz, 2H), 6.92 (dd, JU = 2.0, 7.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 9.36 (d, J = 7.6 Hz, 1H); LOMS (ele- '10 trovaporization) m / z (M + H) + 382.15 2-Ethyl-6-nitro-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-s- - carboxamide (149). OcF, dO
N 1H NMR (400 MHz, CDCl3) 5 1.37 (t J = 7.6 Hz, 3H), 349 (q, J = '7.6 Hz, 2H), 4.66 (d, JU = 6, 0 Hz, 2H), 7.19 (d, J = 7.6 Hz, 2H), 7.41 (d, J = 84: 15 Hz, 2H), 7.60 (d, J = 10.0 Hz , 1H), 7.82 (brs, 1H), 7.99 (dd, J = 10.0, 2.0 Hz, 1H), 9.11 (d, J = 1.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 409.23 2-Ethyl-7-nitro-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (150)
LO on "N 7H NMR (400 MHz, DMSO-d6) 3 1.29 (t, J = 7.6 Hz, 3H), 3.05 (q, J = 7.6 Hz, 2H), 4.57 ( d, J = 5.6 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.76 (dd, J = 7.6, 2.4 Hz, 1H), 8.56 (d, J = 2.4 Hz, 1H), 8.79 (bis, 1H), 9.06 (d, J = 8.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 409.35 2-Ethyl-N- (4- (trifluoromethoxy) benzyl) -6ftrifluoromethyl) imidazo [1,2- | alpiridine-3-carboxamide (151) of 1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz, 3H), 3.02 (a, J = 7.6 Hz, 2H), 4.71 (d , J = 5.6 Hz, 2H), 6.21 (brs, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H ), 7.48 (dd, J = 9.2, 1.2 Hz, 1H), 7.69 (d, J = 9.2 Hz, 1H) / 9.84 (d J = 1.2 Hz, 1H ); LCMS (electrospray) m / z (M + H) + 432.42 6-Bromo-2-ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide (152) u "N '1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.71 (d , J = 5.6 Hz, 2H), 6.14 (brs, 1H), 7.23 (d, J = 84 Hz, 2H),. 10 7.39-7.42 (m, 3H), 7.51 (d, J = 9.2 Hz, 1H), 9.63 (d, J = 2.0 Hz, 1H); LOMS (electrospray) m / z (M + H) + 444.12] 6,7-Dichloro-2-ethyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (153): Rom Do Ú to 1H NMR (400 MHz, CDCI3) 5 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H) 4.70 (d, J = 6.0 Hz, 2H), 6.14 (brs, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.8 Hz , 2H), 7.72 (s, 1H), 9.66 (s, 1H); LCMS (electrospray) m / z (M + H) + 432.15 6-Chloro-2-methyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] lpiridine-3-carboxamide (154)
ADE X nº “O
N White solid; melting point = 192 - 193 ° C; 1H NMR (400 |
7TT7INTS MHz, CDCI3) at 2.70 (s, 3H), 4.71 (d, J = 6.0 Hz, 2H), 6.12 - 6.14 (m, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.32 (dd, J = 2.0, 9.6 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.52 ( d, J = 9.6 Hz, 1H), 9.65 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 384.20 2-Eti-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] lpyrazine-3-carboxamide (155) OCFs a white solid; melting point = 176 - 177 ºC; 1H NMR (400: MHz, CDCI3) at 1.48 (t, J = 7.6 Hz, 3H), 3.04 (q, J = 7.6 Hz, 2H), 4.71 (d, J = 5.6 Hz, 2H), 6.26 - 6.27 (m, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.8 Hz, 10 2H) 8.02 (d, J = 4.8 Hz, 1H), 9.10 (d, J = 1.2 Hz, 1H), 9.25 (dd, J = 1.2.4, 8 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 365.12 '7T-2-Ethyl-3 ((4 (trifluoromethoxy) benzyl) carbamoyl) imidazo [1,2-alpyrazine (156). [% NH prose
A White solid; melting point = 215 - 216 ° C; 1H NMR (400 i 15 MHz, CDCl3) 5 1.43 (t J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.70 (d J = 6 , 0 Hz, 2H), 8.19 - 6.20 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H ), 7.69 (dd, J = 1.6, 5.6 Hz, 1H), 8.57 (d, J = 2.0 Hz, 1H), 9.29 (d, J = 6.0 Hz , 1 H)); LCMS (electrospray) m / z (M + H) + 381.13 6-Chloro-2-ethyl-N- (4-methoxyphenethyl) imidazo [1,2-a] pyridine-3-carboxamide (157) P
NT "o
NO |
White solid; melting point = 129 - 130 ° C; 1H NMR (400 MHz, CDCI3) at 1.25 (t, JU = 7.4 Hz, 3H), 2.72 (q, J = 7.6 Hz, 2H), 2.92 (tl J = 6, 8 Hz, 2H), 3.77 (q, J = 5.6 Hz, 2H), 3.80 (s, 3H), 5.73 - 5.74 (m, 1H), 6.89 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.0 Hz, 1H), 7.51 (dd J = 0 , 8.9.6 Hz, 1H), 9.49 (d, J = 2.0 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 358.21 6-Chloro-N- (4-chlorophenethyl) -2-ethylimidazo [1,2-a] lpiridine-3-carboxamide (158) e. "O . N White solid; melting point = 158 - 159 “ºC; 1H NMR (400 MHz, CDCl3) δ 1.28 (t J = 7.4 Hz, 3H), 2.76 (q, J -7.6 Hz, 2H), 2.96 (t J = '6, 6 Hz, 2H), 3.78 (q, J = 6.0 Hz, 2H), 5.73 - 5.74 (m, 1H), 7.20 (d, J = 8.4 Hz,. 2H ), 7.29 (d, J = 2.0 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.52 (dd, J = 2.0, 9.6 Hz , 1H), 9.48 (d, J = 1.6 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 362.16 '15 NA (4'Butiramidomethyl) biphenyl-4-yl) methyl) -7-chloro-2-ethylimidazo [1,2-. alpiridine-3-carboxamide (159)
POOH FAITH] White solid; 1H NMR (400 MHz, CDCl3); 5 0.95 (t, J = 7.2 Hz, 3H), 1.39 (t, J = 7.6 Hz, 3H), 1.64 - 1.75 (m, 2H), 2.19 ( t J = 7.2 Hz, 2H), 2.97 (q, J = 7.6 Hz, 2H), 4.48 (d, J = 5.6 Hz, 2H), 4.73 (d, J = 5.6 Hz, 2H), 5.71 (brs, 1H), 6.12 (brt, J = 5.6 Hz, 1H), 6.90 (dd, J = 2.0, 7.2 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.51 - 7.60 (m, SH), 9, 37 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 489. 7-3 - ((((4'-Chloro- [1,1 "-biphenyl] -4-yl)] methyl) carbamoyl) -2- ethylimidazo [1,2-a] pyrazine (160) | bl White solid; melting point = 238 ° C; 1H NMR (400 MHz, CDCl3) 5 1.43 (t, J = 7.6 Hz, 3H), 3 .00 (q, J = 7.6 Hz, 2H), 4.73 (d, J = 6.0 Hz, 2H), 6.21 (t, J = 4.8 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.57 (d , J = 8.4 Hz, 2H), 7.69 (dd, J = 2.0.6.4 Hz 1H) 8.56-8.57 (m, 1H), 9.31 (d, J = 6.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 407.12 6-Chloro-2-ethylimidazo [1,2-alpiridine-3-carboxylate - de - [1,1 '-bifenill4- ilmetila (161) “the
N. White solid; melting point = 122.3 - 123.0 ºC; 1H NMR (400 MHz, CDCl3) δ 1.34 (t J = 7.6 Hz, 3H), 3.13 (q, J = 7.6 Hz, 2H), 5.48 (s, 2H), 7, 34 - 7.38 (m, 2H), 7.45 (dd, J = 7.2, 8.0 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H),: 7, 57 - 7.65 (m, 5H), 9.45 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z. (M + H) + 390.20 6-Chloro-N- (4- (4- (4-chlorophenoxy) piperidin-1-i) benzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (162 ) O. the, ego DO.
N 17H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 1.94 (m, 2H), 2.06-2.10 (m, 2H), 2, 96 (q, J = 7.6 Hz, 2H), 3.09-3.14 (m, 2H), 3.15-3.52 (m, 2H), 4.43 (m, 1H), 4 , 81 (d, J = 5.6 Hz, 2H), 6.01 (brs, 1H), 6.85 (d, J = 9.2 Hz, 2H), 6.95 (d, J = 8, 8 Hz, 2H), 7.20-7.31 (m, 5H), 7.53 (d, J = 10.4 Hz, 1H) / 953 (d, J = 1.2 Hz, 1H); LOMS (electrospray) m / z (M + H) + 523.29 7-Chlorine-N- (4- (4- (4-chlorophenoxy) piperidin-1-i) benzyl) -2-ethylimidazo [1,2- alpiridine-3-carboxamide (163) | a Lo oh a ”7H NMR (400 MHz, CDCl3) 5 1.21 (t, J = 7.2 Hz, 3H), 1.91-1.96 (m, 2H), 2.06-2.11 (m, 2H), 2.96 (q, J = 7.6 Hz, 2H), 2.97-3.15 (m, 2H), 3.47- 3.52 (m, 2H), 4, 43 (m, 1H), 4.60 (d, J = 5.6 Hz, 2H), 6.00 (brs, 1H), 6.86 (d, J = 8.8 Hz, 2H), 6, 90 (dd, J = 7.6, 24 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H), 7.21- 7.28 (m, 4H), 7.58 (d , J = 1.6 Hz, 1H), 9.36 (d, J 57.6 Hz, 1H); LCMS (electrovaporization) m / z (M + H) + 523.29 6-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethyl) phenoxy) piperidin-1- - yl) benzyl ) imidazo [1,2-a] pyridine-3-carboxamide (164): LOU Ro. SO “N CF; 1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 1.94-1.99 '10 (m, 2H), 2.10-2.15 (m, 2H), 2.96 (q, J = 7.6 Hz, 2H), 3.12-3.18 (m, 2H), 3.47-3.53 (m, 2H), 4.53-4 , 57 (m, 1H), 4.61 (d, J = 5.2 Hz, 2H), 6.02 (brs, 1H), 6.96 - (d, y = 8.4 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 7.27-7.381 (m, 3H), 7.51-7.55 (m, 3H), 9.53 (d, JU = 2, 0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 557.37 Ú 7-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethyl) phenoxy) piperidin-1-ylbenzyl) imidazole [1 , 2-a] pyridine-3-carboxamide (165) POTN
N 7H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 1.94-1.98 (m, 2H), 2.09-2.11 1 (m, 2H), 2.95 (q, J = 7.6 Hz, 2H), 3.12-3.18 (m, 2H), 3.47-3.53 (m, 2H), 4.55 (m , 1H), 4.60 (d, J = 5.6 Hz, 2H), 6.00 (brs, 1H), 6.90 (dd, J = 7.6.2.0 Hz, 1H), 6 , 96 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 7.28 (djJ = 8.8 Hz 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 2.0 Hz, 1H), 9.36 (d, J = 8.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 557.37 6-Chloro-2-ethyl-N- (4- (4- [4-fluorophenoxy) piperidin-1-yl) benzyl) imidazo [1,2 - | alpiridine-3-carboxamide (166)
FO Roo Se TN 1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 1.91-1.94 (m, 2H), 2.06-2.11 ( m, 2H), 2.96 (q, J = 7.6 Hz, 2H), 3.08-3.14 (m, 2H), 3.47- 3.54 (m, 2H), 4.37 -4.39 (m, 1H), 4.61 (d, J = 5.6 Hz, 2H), 6.01 (brs, 1H), 6.86-6.89 (m, 2H), 6, 95-7.00 (m, 4H), 7.26-7.30 (m, 3H), 7.53 (d, J = 8.8 Hz, 1H), 9.53 (d, J = 1, 6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 507.31 7-Chloro-2-ethyl-N- (4 - ([4- (4-fluorophenoxy) piperidin-1-yl) benzi) imidazo [1, 2-alpiridine-3-carboxamide (167) AO N
E White solid; melting point = 138 - 139 ° C; 1H NMR (400 i 10 MHz, CDCl3) 5 1.38 (t J = 7.6 Hz, 3H), 1.88 - 1.96 (m, 2H), 2.05 - 2.12 (m, 2H) , 2.95 (q, J = 7.6 Hz, 2H), 3.08 - 3.14 (m, 2H), 3.48 -3.54 (m, 2H), 4.35 -: 4, 41 (m, 2H), 4.60 (d, J = 5.6 Hz, 2H), 5.99 - 6.01 (m, 1H), 6.86 - 6.91 (m, 3H), 6 , 91 - 7.00 (m, 4H), 7.27 (d, J = 84 Hz, 2H), 7.59 (d, J = 2.0 Hz, 1H), '9.36 (d, J = 7.6 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 507.31 2-Ethyl-N- (4- (4- (4- (trifluoromethoxy) phenoxy) piperidin-1-yl) benzyl) -6- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (168) Rs K o “O SE 7 1H NMR (400 MHz, CDCl3) 5 1.41 (t J = 7.6 Hz, 3H), 1,980-1 , 98 (m, 2H), 2.08-2.13 (m, 2H), 2.99 (q, J = 7.6 Hz, 2H), 3.10-3.15 (m, 2H), 3.47- 3.54 (m, 2H), 4.43-4.46 (m, 1H), 4.62 (d, J = 5.6 Hz, 2H), 6.05 (brs, 1H) , 6.91 (djJ = 8.4Hz, 2H), 6.96 (d, J = 8.4Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.28 (d , J = 8.4 Hz, 2H), 7.46 (dd, J = 9.2, 2.0 Hz, 1H), 7.69 (d, JU = 9.2 Hz, 1H), 9.85 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 607.56 |
7-Chloro-N- (4- (4- (cyclopentyloxymethyl) piperidin-1-yl) benzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (169)
DD% hi to RAN White solid; 1H NMR (400 MHz, CDCl3); 5 1.23 - 1.38 (m, 2H), 1.31 (t Ju = 7.6 Hz, 3H), 1.47 - 1.52 (m, 2H), 1.56 - 1.70 ( m, 7H), 1.80 - 1.83 (m, 2H), 2.64-2.70 (m, 2H), 2.87 (q, J = 7.6 Hz, 2H), 3.21 (d J = 6.8 Hz, 2H), 3.63 - 3.66 (m, 2H), 3.81 - 3.86 (m, 1H), 4.53 (d, J = 5.2 Hz , 2H), 6.07 (brt, J = 5.2 Hz, 1H), 6.82 (dd, J = 1.6, 7.2 Hz, 1H), 6.88 (d, J = 8, 4 Hz, i 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 1.6 Hz, 1H), 9.26 (d, J = 7.2 Hz, 1H); 18C NMR (100 MHz, CDCI3) 5 13.3, 23.4, 23.6, 29.3, 32.3, 36.4, 43.3, 49.6.73.7, 81.5, 114 , 5, 115.1, 115.6, 116.7, 128.1, 128.5, 128.7, 128.8, 133.4, 146.0, 151.5, 161.1. 2-Ethyl-7-nitro-N- (4- (4- (4 (trifluoromethoxy) phenoxy) piperidin-1- - iN) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (170) x À LO :! o Q LE “1H NMR (400 MHz, CDCl3) ô 1.43 (t, J = 7.6 Hz, 3H), 1.95 (m, 2H) 2.10 (m, 2H), 3.01 ( q, J = 7.6 Hz, 2H), 3.11 - 3.16 (m, 2H), 3.49-3.53 (m, 2H), 4.45 (m, 1H), 4.63 (d, J = 5.2 Hz, 2H), 6.1 1 (brs, 1H), 6.91 (d, J = 9.2 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 7.28 (d J = 8.8 Hz, 2H), 7.72 (d, J = 7.6 Hz, 1H ), 8.53 (s, 1H), 9.54 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 584.58 6-Chloro-2-ethyl-N- (4- (4- (4-fluorobenzyl) piperazin-1-i) benzyl) imidazo [1,2 - alpiridine-3-carboxamide (171) Fr [) N Ro 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 2.59 (m, |
4H), 2.95 (q, J = 7.6 Hz, 2H), 3.20 (m, 4H), 3.52 (s, 2H), 4.60 (d, J = 5.6 Hz, 2H), 6.00 (brs, 1H), 6.91 (d, J = 84 Hz, 2H), 7.01 (t / J = 8.4 Hz, 2H), 7.26 - 7.32 ( m, 5H), 7.53 (d, J = 9.6 Hz, 1H), 9.52 (d, J = 1.2 Hz, 1H); LCMS (electrovaporization) m / z (M + H) + 506.29 7-Chloro-2-ethyl-N- (4- (4- (4-fluorobenzyl) piperazin-1-yl) benzyl) imidazo [1 , 2-alpiridine-3-carboxamide (172) FO N ITQ NH
X o White solid; melting point = 141 - 142 * C; 1H NMR (400 - MHz, CDC13) 5 1.37 (t, J = 7.8 Hz, 3H), 2.59 (t, J = 4.8 Hz, 4H), 2.94 (q, J = 7.2 Hz, 2H), 3.20 (t, J = 5.0 Hz, 4H), 3.53 (s, 2H), 4.59 (d, J = 5.2 Hz, 2H), ' 10 5.98-6.00 (m, 1H), 6.88 -6.92 (m, 3H), 7.01 (dd, J = 8.8, 8.8 Hz, 2H), 7.25 - 7.27 (m, 4H), 7.31 (dd, J = 5.6, 8.0 Hz, 2H), 7.58 (d, J = 2.0 Hz, 1H), 9.36 ( d, s J = 7.6 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 506.36 6-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethoxy) benzyl) piperazin-1- 'yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (173)
TX - Yº cr,. OS - White solid; melting point = 138.1 - 138.7 ºC; 1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.60 (t, J = 5.0 Hz, 4H), 2.95 (q, J = 7 , 6 Hz, 2H), 3.21 (t, J = 5.0 Hz, 4H), 3.56 (s, 2H), 4.60 (d, J = 5.6 Hz, 2H), 6, 00 - 6.02 (m, 1H), 6.92 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.26 - 7.30 (m, 3H), 7.38 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 9.2 Hz, 1H), 9.53 (d, J = 2.0 Hz 1H ); LCMS (electrospray) m / z (M + H) + 572.40 7-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethoxy) benzyl) piperazin-1- i) benzyl) imidazo [ 1,2-a] pyridine-3-carboxamide (174) | ITQ.
N IS E, White solid; melting point = 137.1 - 137.6 ºC; 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H), 2.60 (t, J = 4.8 Hz, 4H), 2.94 (q, J = 7 , 6 Hz, 2H), 3.21 (t, J = 4.8 Hz, 4H), 3.56 (s, 2H), 4.60 (d, J = 5.6 Hz, 2H), 5, 99 - 6.00 (m, 1H), 6.88 - 6.93 (m, 3H), 7.18 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 80Hz 2H ) 7.38 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 572.40 - 6,7-Dichloro-2-ethyl-N- (4- (4- (4-fluorobenzyl) piperazin-1- i) benzyl) imidazo ( [1,2-a] iridine.3-carboxamide 175) mo ae '1H NMR (400 MHz, DMSO-d6) 5 1.24 (t, J = 7.6 Hz, 3H), 2.50' 10 ( m 4H), 2.95 (q9, J = 7.6 Hz, 2H), 3.08 (m, 4H), 3.48 (s, 2H), 4.41 (d, J = 6.0 Hz , 2H), 6.89 (d, J = 8.8 Hz, 2H), 7.14 (dd, Jy = 9.2 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H ), 7.33-7.36 (m, 2H), 8.06 (s, 1H), 8.44 (t, 1H), 9.20 (s, 1H); LCMS "(electrospray) miz (M + H) + 540.36 R 7-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-i) benzyl) imidazo [1,2 - alpiridine-3-carboxamide (176)
F oo% NH o White solid; melting point = 212 - 213 ºC 1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3 , 26 (t J = 4.8 Hz, 4H), 3.35 (t, J = 4.8 Hz, 4H), 4.62 (d, J = 5.6 Hz, 2H), 6.01 - 6.03 (m, 1H), 6.89 - 7.02 (m, 7H), 7.30 (d, J = 84 Hz, 2H), 7.59 (d, J = 2.0 Hz, 1H ), 9.37 (d J = 7.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 492.28 7-chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1- | iNbenzyl) imidazo [1, 2-a] lpiridine-3-carboxamide (177)
F oo% um 2 "N White solid; melting point = 204.4 - 206.9 ºC; 1H NMR (400 MHz, DMSO-d6) at 1.36 (t, J = 7.6 Hz, 3H) , 3.14 (q, J = 7.6 Hz, 2H), 3.54 - 3.70 (m, 8H), 4.56 (d, J = 6.0 Hz, 2H), 7.26 ( dd, J = 8.4, 8.8 Hz, 2H), 7.36 - 7.50 (m, 6H), 7.63 (dd, J = 2.4.7.8Hz, 1H), 8, 15 (d, 7 = 1.6 Hz, 1H), 9.13 (d, J = 7.2 Hz, 1H), 9.26 (t, J = 5.6 Hz, 1H). 6-Chlorine -2-ethyl-N- (4- (4- (4- (trifluoromethoxy) phenyl) piperazin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (178)
OIE O "» NH "o White solid; melting point = 206.5 - 207.0 ºC; 1H NMR (400" 10 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 3.30 - 3.40 (m, 8H), 4.63 (d, J = 5.2 Hz, 2H), 6.03 - 6 , 04 (m, 1H), 6.95 (d, J = 9.2 Hz,] 2H), 6.98 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8 , 0 Hz, 2H), 7.27 - 7.32 (m, 3H), 7.54 (d, J = 9.6 Hz, 1H), 9.53 - 9.34 (m, 1H); LCMS (electrospray) m / z (M + H) + 558.32 7-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethoxy) phenyl) piperazin-1- i) benzyl) imidazo [1 , 2-a] pyridine-3-carboxamide (179).
The EI
LB White solid; melting point = 216.3 - 217.0 ºC; 1H NMR (400 |
MHz, CDCI3) to 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.380 - 3.40 (m, 8H), 4, 62 (d, J = 5.6 Hz, 2H), 6.01 - 6.02 (m, 1H), 6.90 (dd, J = 2.0, 7.2 Hz, 1H), 6.94 (d, J = 9.2 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 7.31 (d , J = 8.8 Hz, 2H), 7.59 (d, JU = 1.6 Hz, 1H), 9.37 (d, J = 7.6 Hz 1H); LCMS (electrospray) m / z ( M + H) + 558.32 6,7-Dichloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-iN) benzyl) imidazo [1,2- a] pyridine-3 -carboxamide (180)
F o Lo at "N 1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J = - 7.6 Hz, 2H), 3, 24-3.27 (m, 4H), 3.34-3.36 (m, 4H), 4.62 (d, J = 5.6 Hz, 2H), 6.03 (brs, 1H), 6 , 91-7.02 (m, 6H), 7.30 (d, J = 8.8 Hz, 2H), 7.71 (s, 1H), 9.67 (s. 1H); LCMS (electrospray) m / z (M + H) + 526.35 2-Ethyl-N- (4- (4- (4 (trifluoromethoxy) phenyl) piperazin-1-yl) benzyl) imidazo [1,2- - alpiridine-3- carboxamide (181) ocF, Do 'NH AND
N White solid; melting point = 178 - 179 ºC; 1H NMR (400 MHz, CDCl3) 5 1.40 (t J = 7.6 Hz, 3H), 2.97 (q, J = 7.2 Hz, 2H), 3.31 - 3.38 (m, 8H), 4.63 (d, J = 5.6 Hz, 2H), 6.05 (t, J = 5.0 Hz, 1H), 6.89 - 6.99 (m, 5H), 7, 14 (d, J = 8.8 Hz, 2H), 7.29 - 7.32 (m, 3H), 7.60 (d, Jy = 9.2 Hz, 1H), 9.40 (d, J = 6.8 Hz, 1H); LCMS (electrospray) m / z (M + H) - + 524.45 6-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -N- methylimidazo [1,2-alpiridine-3-carboxamide (182) |
F Ds
DO% à White solid; melting point = 148 - 149 ° C; 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.4 Hz, 3H), 2.78 (q, J = 7.6 Hz, 2H), 2.99 (s, 3H), 3.24 - 3.27 (m, 4H), 3.33 - 3.36 (m, 4H), 4.66 (s, 2H), 6.92 - 7.02 (m, 6H), 7, 12 - 7.20 (m, 2H), 7.21 (dd, J = 2.0, 9.6 Hz, 1H), 7.52 (d, J = 9.6 Hz, 1H), 8A46 (d J = 1.6 Hz 1H); LOMS (electrospray) m / z (M + H) + 506.36 7-Chlorine-N- (4- (4 - ((difluoromethoxy) methyl) piperidin-1-yl) benzyl) -2- 'ethylimidazo [1, 2-a] pyridine-3-carboxamide (183)
F and IA,
N AOC agtg ——— t — t—— White solid; 1H NMR (400 MHz, CDCl3) 5 1.37 (t J = 7.6 Hz, '3H), 1.41 - 1.48 (m, 2H), 1.70 - 1.86 (m, 3H) , 2.72 (t, J = 12.4 Hz, 2H), 2.93 (q J = 7.6 Hz, 2H), 3.69-3.73 (m, 4H), 4.58 (d , J = 5.6 Hz, 2H), 6.00 (brs,: 1H), 6.20 (t, J = 75.2 Hz, due to F2), 6.88 (dd, J = 1.6 Hz, 7.6 Hz, 1H), 6.92 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 1.6 Hz, 1H), 9.34 (d, 'J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 477. 7-Chloro-2-ethyl-N - (((4 '- (hexanamidomethyl) biphenyl-4-yl) methyl) imidazo [1,2-alpiridine-3 -carboxamide (184) o Su oo "o
E White solid; 1H NMR (400 MHz, CDCl3); 5 0.87 (t, J = 6.8 Hz, 3H), 1.380 - 1.35 (m, 4H), 1.40 (t, J = 7.6 Hz, 3H), 1.63 - 1, 71 (m, 2H), 2.21 (t J = 7.6 Hz, 2H), 3.03 (q, J = 7.6 Hz, 2H), 447 (d, J = 5.6 Hz, 2H ), 4.72 (d, J = 6.0 Hz, 2H), 5.74 (brs, 1H), 6.99 (dd, J = 2.0.7.2 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.51-7.59 (m, 5H), 7.74 (brs, 1H), 9.32 (d, J = |
7.2 Hz, 1H); LOMS (electrospray) m / z (M + H) + 517. 6-Chloro-2-ethyl-N- (4- (4- (triluoromethoxy) phenoxy) benzyl) imidazo] 1,2-alpiridine-3-carboxamide ( 185)
FO mm MXN 6 1H NMR (400 MHz, CDCI3) 5 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J - 7.6 Hz, 2H), 4.68 (d, J = 6.0 Hz, 2H), 6.1 1 (brs, 1H), 7.00 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H ), 7.18 (d, J = 8.8 Hz, 2H), 7.30 (dd, Ju = 9.6, 2.0 Hz, 1H), 7.37 (d, J = 8.8 Hz , 2H), 7.54 (d, J = 9.2 Hz, 1H), 9.53 (d, J = 1.6 Hz,. 1H); LCMS (electrospray) m / z (M + H) + 490.17 7-Chloro-2-ethyl-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2- '10 alpiridine-3 -carboxamide (186) sq oh and õ 'White solid; melting point = 141 - 142 ° C; 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J =, 7.6 Hz, 2H), 4.68 (d, J = 5.6 Hz, 2H), 6.09 - 6.11 (m, 1H), 6.91 (dd, J = 2.0, 7.6 Hz, 1H), 6.98 - 7.02 ( m, 4H), 7.18 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 2.0 Hz, 15. 1H), 9.37 (d, J = 7.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 490.24 6-Chloro-2-ethyl-N- (4- (4-fluorophenoxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide (187) a ÇA "q DU: Tr White solid; melting point = 168 - 169 ºC; 1H NMR (400 MHz, CDCI3) 5 1.41 (t, J = 7.4 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.67 (d J = 6.0 Hz, 2H), 6.09-86.11 (m, 1H), 6.96 - 7.06 (m, 6H), 7.30 (dd, J = 2.0, 9.6 Hz, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 9.6 Hz, 1H ), 9.53 (d, J = 1.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 424.26 |
7-Chloro-2-ethyl-N- (4- (4-fluorophenoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (188)
OS% DR ah to N. White solid; melting point = 146 - 147 ° C; 1H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 4.668 (d, J = 5.6 Hz , 2H), 6.07-6.09 (m, 1H), 6.91 (dd, J = 2.2.7A4 Hz, 1H), 6.95 - 7.06 (m, 6H), 7, 33 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 2.2 Hz, 1H), 9.37 (d, J = 7.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 424.26: 6-Bromo-2-ethyl-N- (4- (4-fluorophenoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (189) at F '10 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4, 66 (d, J = 5.6 Hz, 2H), 6.09 (brs, 1H), 6.95-7.06 (m, 6H), 7.34 (d, J = 8.8 Hz, 2H ), 7.40 (dd, J = 9.6, 1.6 Hz, 1H), 7.49 (d, J = 9.6 Hz, 1H), 9.63 (d, J = 1.2 Hz , 1H); LCMS (electrospray) m / z (M + H) + 470.10 "6-Chloro-N- (4- (4-chlorophenoxy) benzyl) -2-ethylimidazo [1,2-a] lpiridine-3-carboxamide ( 190) 'o, OP QD ho White solid; melting point = 159 - 160.7 ºC; 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 2, 99 (q, J = 7.2 Hz, 2H), 4.68 (d, J = 5.6 Hz, 2H), 6.10 - 6.11 (m, 1H), 6.94 (d, J = 9.2 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 7.27 - 7.32 (m, 3H), 7.36 (d, J = 8.4 Hz , 2H), 7.55 (d, J = 9.6 Hz, 1H), 9.54 (d, J = 2.0 Hz, 1H); LOCMS (electrospray) m / z (M + H) + 440, 18 7-Chloro-N- (4- (4-chlorophenoxy) benzyl) -2-ethylimidazo [1,2-alpiridine-3-carboxamide (191) |
RS o e po White solid; melting point = 167.1 - 167.9 ºC; 1H NMR (400 MHz, CDCI3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J - 7.6 Hz, 2H), 4.67 (d, J = 5 , 6 Hz, 2H), 6.08 - 8.10 (m, 1H), 6.91 (dd, JU = 2.4, 7.6 Hz, 1H), 6.94 (d, J = 8, 8 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 9.2 Hz, 2H), 7.35 (d, J = 8.8 Hz 2H) 7.60 (d, J = 2.0 Hz, 1H), 9.37 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 440.18 2-Ethyl-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2-a] pyridine-3-. carboxamide (192)
6. ET. 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.01 (q, J = 7.6 Hz, 2H), 4.69 (d, J = 6, 0 Hz, 2H), 6.12 (brs, 1H), 6.92 (t, J = 6.8 Hz, 1H), - 7.00 (d, J = 9.2 Hz, 2H), 7, 01 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.8 Hz, 2H), 7.31-7.36 (m, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.8 Hz, 1H), 9.40 (d, J = 6.8 Hz, 1H); LCMS (electrospray) m / z (M + H) + 456.23 7-Chloro-2-ethyl-N - ((6- (4-fluorophenoxy) pyridin-3-yl)] Mmethyl) imidazo [1,2- . 15 alpiridine-3-carboxamide (193)
TO a
White solid; melting point = 167.0 - 167.6 "ºC; 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 4.64 (d, J = 6 , 0 Hz, 2H), 6.09 (t, J = 5.6 Hz, 1H), 6.90 - 6.93 (m, 2H), 7.06 - 7.11 (m, 4H), 7 , 58 (d, J = 2.0 Hz, 1H), 7.80 (dd, J = 2.8, 8.8 Hz, 1H), 8.20 (d, J = 2.0 Hz, 1H) 9.34 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 425.28 6-Chlorine-2-ethyl-N - ((6- (4- (trifluoromethoxy) phenoxy) pyridin-3-yl) methyl) imidazo] 1, 2-a] lpiridine-3-carboxamide (194) |
“Q and the white solid; melting point = 154 - 155 ºC; 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.8 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.66 (d, J = 6 , 0 Hz, 2H), 6.14 (t, J = 5.6 Hz, 1H), 6.96 (d, J = 84 Hz, 1H), 7.16 (d J = 9.2 Hz, 2H ), 7.24 (d, J = 9.2 Hz, 2H), 7.32 (dd, J = 2.0, 9.6 Hz, 1H), 7.54 (d J = 9.2 Hz, 1H ) 7.80 (dd, J = 24.8.4Hz, 1H), 8.20 (d, J = 2.4 Hz, 1H), 9.51 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 491.26 7-Chloro-2-ethyl-N - ((6- (4- (trifluoromethoxy) phenoxy) pyridin-3- i) methyl) imidazo [1, 2-a] pyridine-3-carboxamide (195). O,
ET | and SS a - White solid; 1H NMR (400 MHz, CDCI3) 5 1.41 (t J = 7.4 Hz, 3H) 2.97 (q J = 7.6 Hz, 2H), 4.66 (d, JU = 6.0 Hz , 2H), 6.14 (t J = 5.4 Hz, '1H), 6.92 (dd, J = 2.0, 7.6 Hz, 1H), 6.96 (d, J = 8, 8 Hz, 1H), 7.16 (d, J = 9.2 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H), 7.60 (d, J = 1.6 Hz , 1H), 7.79 (dd, J = 2.4, - 8.4 Hz, 1H), 8.20 (d, J = 2.0 Hz, 1H), 9.35 (d, J = 7 , 6 Hz, 1H). 4-Phenoxybenzyl (196) x 6-Chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxylate (196) x. ” "OE White solid; melting point = 123.3 - 123.8 ºC; 1H NMR (400 MHz, CDCI3) 5 1.31 (t, J = 7.4 Hz, 3H), 3.10 (q, J = 7.6 Hz, 2H), 4.67 (s, 2H), 7.02 (d, J- 8.4 Hz, 4H), 7.12 (dd, J = 7.2, 7.6 Hz , 1H), 7.34 (dd, JU = 7.2.7.6 Hz, 3H), 7.43 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 9, 6 Hz, 1H), 9.42 (d, J = 2.0 Hz 1H); LCMS (electrospray) m / z (M + H) + 407.12 6-Chlorine-2-ethyl-N- (4- (4-fluorophenoxy) benzyl) -N-methylimidazo] 1,2-a] pyridine-3-carboxamide (197) |
Ao a QD White solid; 1H NMR (400 MHz, CDCl3) 5 1.37 (t J = 7.4 Hz, 3H), 2.78 (q, J = 7.6 Hz, 2H), 3.01 (s, 3H), 4 , 70 (s, 2H), 6.94 - 7.06 (m, 6H), 7.21 - 7.26 (m, 3H), 8.47 (d, J = 9.2 Hz, 1H), 8.47 (d, J = 1.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 438.20 6-Chloro-2-ethyl-N- (4- (4- (trifluoromethoxy) phenylamino) benzyl) imidazo] 1,2-a] pyridine-3 -carboxamide (198) TO "! aq TRA, 1 1H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.64 (d, J = 5.6 Hz, 2H), 5.74 (s, 1H), 6.07 (brs, 1H), 7.04 (d, J - = 7.2 Hz , 2H), 7.06 (d, J = 7.2 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.28-7.32 (m, 3H) 7, 54 (d, J = 9.2Hz, 1H), 9.54 (d, J = 1.2 Hz, 1H); LCMS (electrovapo- rization) m / z (M + H) + 489.22 7- Chloro-2-ethyl-N- (4- (4- (trifluoromethoxy) phenylamino) benzyl) imidazo [1,2- - alpyridine-3-carboxamide (199)
NO | CPA at SN of, 1H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz 2H), 4.63 (d, J = 5.6 Hz, 2H), 5.74 (s, 1H), 6.05 (brs, 1H), 6.91 (dd, J = 7.6, 2.0 Hz, 1H), 7, 04 (d, J = 9.2 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 9.2 Hz, 2H), 7.29 ( d, J = 8.8 Hz, 2H), 7.59 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 489.22 6-Chloro-2-ethyl-N- (4- (4- (trifluoromethyl) benzyloxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide (200) |
LO O "1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 4.64 (d, J = 5.6 Hz, 2H), 5.06 (s, 2H), 6.05 (brs, 1H), 6.97 (d, J = 8.4 Hz, 2H), 7.20-7, 33 (m, SH), 7.46 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 9.2 Hz, 2H), 9.53 (d, J = 1.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 504.25 7-Chloro-2-ethyl-N- (4- (4- (trifluoromethyl) benzyloxy) benzyl) imidazo [1,2- alpiridine-3-carboxamide (201) VOTE "
A '1H NMR (400 MHz, CDCl3) 5 1.39 (t, J = 7.6 Hz, 3H), 2.95 (q, J - 7.6 Hz, 2H), 4.63 (d, J = 5.6 Hz, 2H), 5.06 (s, 2H), 6.03 (brs, 1H), 6.90 (dd, J. 10 = 7.6.2.0 Hz, 1H), 6 , 97 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.59 (d, J = '2.0 Hz, 1H), 9.36 ( d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 504.25 ”B-Chlorine-2-ethyl-N- (4- (4-fluorobenzyloxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (202) “the H LEO LO“ the 1H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H) , 4.63 (d, J = 5.6 Hz, 2H), 5.03 (s, 2H), 6.04 (brs, 1H), 6.96 (d, J = 8.8 Hz, 2H) , 7.06 (d, J = 8.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.28-7.32 (m, 3H), 7.40 ( dd, J = 8.8 Hz, 2H), 7.53 (d, J = 9.2 Hz, 1H), 9.53 (d, J = 1.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 438.20 7-Chloro-2-ethyl-N- (4- [4-fluorobenzyloxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide ( 203) | o H LEOA os a "N 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 4, 62 (d, J = 5.6 Hz, 2H), 5.03 (s, 2H), 6.02 (brs, 1H), 6.90 (dd, J = 7.6, 2.4 Hz, 1H ), 8.96 (d, J = 8.8 Hz, 2H), 7.07 (dd, J = 8.8 Hz, 2H), 7.30 (d, J - 8.8 Hz, 2H), 7.40 (dd, J = 8.8 Hz, 2H), 7.58 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H); LCMS (electrospray ) m / z (M + H) + 438.20 6-Chloro-2-ethyl-N - (((2- (4- (trifluoromethoxy) phenyl) -1H-benzo [d] imidazo! -5- iNmethyl) imidazo [1,2-a] pyridine-3-carboxamide (204)
TALS | “And NA D-oer, i 1H NMR (400 MHz, DMSO-d6) 1.26 (m, 3H), 2.97-3.03 (m, 2H), 4.65 (t, J = 6, 4 Hz, 2H), 7.24 (dd, J = 18.4, 8.0 Hz, 1H), 7.45 (d, J = 9.6.2.4 '10 Hz 1H), 7.51 -7.56 (m, 3H), 7.65-7.68 (m, 2H), 8.24-8.28 (m, 1H), 8.52-8.56. (m, 1H), 9.09-7.10 (m, 1H), 12.96 (ss, 1H); LCMS (electrospray) m / z (M + H) + 514.38 7-Chloro-2-ethyl-N - ((2- (4- (trifluoromethoxy) phenyl) -1H-benzo [d] imidazo | -5- 'iNmethyl) imidazo [1,2-a] pyridine-3-carboxamide (205): K LOS er EO sa at 1H NMR (400 MHz; CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H) , 2.97 (q, J = 7.6 Hz, 2H), 4.82 (d, J = 5.6 Hz, 2H), 6.19 (brs, 1H), 6.90 (dd, J - 7.6, 2.0 Hz, 1H), 7.30 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.50-7.52 (m, 1H), 7.59 (d J = 2.0 Hz, 1H), 7.81 (m, 1H), 8.07 (d, J = 8.8 Hz, 2H), 9.37 (d, J = 7, 6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 514.31 7-Chlorine-2-ethyl-N - ((2- (morpholinomethyl) -1H-benzo [d] imidazo] -5 - i) methyl) imidazo [1,2-a] lpyridine-3-carboxamide (206) |
TVI es: AS and CQ 'H NMR (400 MHz, DMSO-d6) 5 1.23-1.28 (m, 3H), 2.44 (m, 4H), 2.98 (q, J = 7, 6 Hz, 2H), 3.59 (m, 4H), 3.69 (s, 2H), 4.61 (ni, 2H), 86.19 (brs, 1H), 7.09 (dd, J = 9.6, 2.0 Hz, 1H), 7.18 (dd, J = 9.6, 7.2 Hz, 1H), 7.41 (m, 1H), 7.51 (m, 1H), 7.79 (d, J = 2.0 Hz, 1H), 8.52 (m, 1H), 8.96 (d, J = 7.6 Hz 1H) 9.37 (d J = 7.6 Hz , 1H), 12.27 (m, 1H); LCMS (electrospray) miz (M + H) + 453.39 6-Chloro-2-ethyl-N - ((2- (4- (trifluoromethoxy) phenyl) benzo [d] oxazol-5-. I) Dmethyl) imidazo [1,2-a] pyridine-3-carboxamide (207) o, H EN EF 008. White solid; 1H NMR (400 MHz, CDCl3); 5 1.40 (t, J = 7.6 Hz, 3H) 2.99 (q J = 7.6 Hz, 2H), 4.82 (d, J = 6.0 Hz, 2H), 6.20 (brs, 1H), 7.31 '(dd, J = 1.6 Hz, 7.6 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.42 (dd, J = 1.6 Hz, 8.4 Hz, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), - 8.29 (d, J = 8.8 Hz, 2H), 9.55 (d, J = 1.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 515, 517 (Cl isotope standard). : 15 7-Chloro-2-ethyl-N - (((2- (4- (trifluoromethoxy) phenyl) benzo [d] oxazol-5-iNmethyl) imidazo [1,2-a] pyridine-3-carboxamide (208) [) TO LO is A Def; White solid; 1H NMR (400 MHz, CDCl3); 5 1.40 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 4.82 (d, J = 6.0 Hz, 2H), 6 , 19 (brs, 1H), 6.92 (dd, J = 2.0 Hz, 7.6 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.41 (dd , J = 2.0 Hz, 84Hz, 1H) 7.59 (d, J = 8.8 Hz, 2H), 7.77 (s, 1H), 8.28 (d, Jy = 8.8 Hz, 2H), 9.38 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 515, 517 (Isotope standard C)). |
6-Chloro-N- (4- (2,6-dimethylmorpholine) benzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (209) A o to LI “od White solid; melting point = 176 - 177 “C; 1H NMR (400 MHz, CDCl3) 5 1.25 (s, 3H),), 1.27 (s, 3H), 1.39 (t J = 7.6 Hz, 3H), 2.42 (t J = 11.2H2 / 2H), 2.95 (g, J = 7.2 Hz, 2H), 3.46 (d, J = 10.4 Hz, 2H), 3.78 - 3.82 (m, 2H), 4.61 (d, J = 5.6 Hz, 2H), 6.00 - 6.02 (m, 1H), 6.91 (d, J = 8.8 Hz, 1H), 7, 26 - 7.31 (m, 3H), 7.54 (d, J = 9.2 Hz, 1H), 9.53 (d, J = 2.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 427.32. 7-Chloro-N- (4- (2,6-dimethylmorpholine) benzyl) -2-ethylimidazo [1,2-a] lpyridine-3-carboxamide (210) A,
OUTSIDE | O
N - White solid; melting point = 165 - 166 ҼC; 1H NMR (400 MHz, CDCl3) 5 1.25 (s, 3H), 1.27 (s, 3H), 1.38 (t, J = 7.6 Hz, 3H), 2.42 (t J = '11.2 Hz, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.45 (d, J = 10.4 Hz, 2H), 3.76 - 3.84 (m 2H), 4.60 (d, J = 5.5 Hz, 2H), 5.99 - 6.01 (m, 1H), 6.89 - 6.92 (m, 3H), 7.28 (d , J = 84 Hz, 2H), 7.58 (d, J = 2.0 Hz, 1H), 9.385 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 427.32 6-Chloro-2-ethyl-N- (4-pyrrolidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (211) O
N White solid; melting point = 222 - 223 ° C; 1H NMR (400 MHz, CDCl3) δ 1.38 (tJ = 7.4 Hz, 3H), 1.99 - 2.03 (m, 4H), 2.94 (q, J = 7.6 |
Hz, 2H), 3.29 (t, J = 6.6 Hz, 4H), 4.57 (d, J = 5.6 Hz, 2H), 5.95 - 5.97 (m, 1H), 6.56 (d, J = 8.4 Hz, 2H), 7.22 - 7.30 (m, 6H), 7.53 (d, J = 9.6 Hz, 1H), 9.53 (d , J = 1.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 383.24 7-Chloro-2-ethyl-N- (4- (pyrrolidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3- carboxamide (212) AD : that of pos 1H NMR (400 MHz, CDCl3) 5 1.35 - 1.42 (m, 3H), 1.93 - 1.96 (m, 2H), 1.99 - 2.02 (m, 2H ), 2.90 - 2.99 (m, 2H), 3.28 (t, J = 6.4 Hz, 2H), 3.38 (t,: J = 6.4 Hz, 2H), 4, 57 (d, J = 4.8 Hz, 2H), 5.95 - 6.02 (m, 1H), 6.56 (d, J = 84 Hz, 2H), 6.85 - 6.92 (m , 1H), 7.14 - 7.31 (m, 3H), 7.57 - 7.59 (m, 1H), 9.36 (d, S 10 J = 7.6Hz, 1H) 7-Chloro- N- (4- (5,6-dihydropyridin-1 (2H-yl) benzyl) -2-ethylimidazo [1,2- - alpyridine-3-carboxamide (213) yo) N. e. cr * N 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 2.29-2.32: (m, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.38 (t, J = 5.6 Hz, 2H), 3.68-3.72 (m, 2H),. 15 4.59 (d, J = 5.6 Hz, 2H), 5.79-5.82 (m, 1H), 5.88-5.91 (m, 1H), 5.99 (brs, 1H ), 6.88-6.93 (m, 3H), 7.27 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 1.6 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 395.35 6-Chloro-2-ethyl-N- (4 - ([4-methylpiperidin-1-yl) benzyl) imidazo [1,2-a] pyridine -3- carboxamide (214) POWDER
WA TN * H NMR (400 MHz, CDCl3) 5 0.97 (d, J = 6.4 Hz, 3H), 1.35 (m, 2H), 1.38 (t, J = 7.6 Hz, 3H), 1.53 (m, 1H), 1.72-1.76 (m, 2H), 2.66-2.73 (m, 2H), 2.95 (q, J = 7.6 Hz , 2H), 3.64-3.67 (m, 2H), 4.59 (d, J = 5.6 Hz, 2H), 5.99 (brs, 1H), 6.93 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 7.6 Hz, 2H), 7.29 (dd, J = |
9.6, 2.0 Hz, 1H), 7.53 (d, J = 9.6 Hz, 1H), 9.53 (d, J = 1.6 Hz, 1H); LCMS (e-electrovaporization) m / z (M + H) + 411.40 T7-Chloro-2-ethyl-N- (4- (4-methylpiperidin-1-yl) benzyl) imidazo] 1,2-a] pyridine-3-carboxamide (215)
VOTD and
BN 17H NMR (400 MHz, CDCl3) 5 0.97 (d, J = 6.8 Hz, 3H), 1.35 (m, 2H), 1.37 (t J = 7.6 Hz, 3H), 1.51-1.53 (m, 1H), 1.72-1.75 (m, 2H), 2.68-2.73 (m, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.64-3.67 (m, 2H), 4.59 (d, J] = 5.6 Hz, 2H),. 5.98 (brs, 1H), 6.90 (dd, J = 7.6, 24 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 2.4 Hz, 1H), 9.36 (d, J = 7.6 Hz, 1H); LCMS 7 10 (electrospray) m / z (M + H) + 411.40 6-Chloro-N- (4- (3,5-dimethylpiperidin-1-yl) benzyl) -2-ethylimidazo [1,2-alpiridine - - 3-carboxamide (216) to OQ “o
N - Pale yellow solid; melting point = 157.2 - 158.0 ° C; 1H NMR (400 MHz, CDCl3); 3 0.91 (d, J = 6.4 Hz, 6H), 1.35 (t, J = 7.6 Hz, 3H), '15 1.73-1.81 (m, 4H), 2, 16 (dd, J = 11.6, 11.6 Hz, 2H), 2.90 (q, 7.6 Hz, 2H), 3.58 - 3.61 (m, 2H), 4.56 (d , J = 5.6 Hz, 2H), 6.01 (brs, 1H), 6.90 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H ), 7.26 (dd, J = 2.0, 9.6 Hz, 1H), 7.49 (d, J = 9.6 Hz, 1H), 9.49 (d, J = 2.0 Hz , 1H); 138C NMR (100 MHz, CDCl3); 5 13.3, 19.6, 23.6, 30.9, 42.2, 43.4, 57.2, 115.4, 116.6, 117.0, 121.5, 126.3, 127 , 8, 128.2, 128.9, 144.5, 151.3, 151.4, 161.1; LCMS (electrospray) m / z (M + H) + 425, 427 (Standard C isotope). 7-Chloro-N- (4- (3.5-dimethylpiperidin-1-yl) benzyl) -2-ethylimidazo [1,2-a] lpyridine-3-carboxamide (217) | ca Pale yellow solid; melting point = 181.5 - 182.8 ºC; 1H NMR (400 MHz, CDCl3); 5 0.92 (d, J = 6.8 Hz, 6H), 1.35 (t, J = 7.6 Hz, 3H), 1.74 - 1.82 (m, 4H), 2.17 ( dd, J = 11.6, 11.6 Hz, 2H), 2.90 (q, 7.6 Hz, 2H), 3.59 - 3.62 (m, 2H), 4.57 (d, J = 5.2 Hz, 2H), 6.01 (brs, 1H), 6.87 (dd, J = 2.0, 7.6Hz, / 1H), 6.91 (d, J = 8.8Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 2.0 Hz, 1H), 9.33 (d, J = 7.6 Hz, 1H) ; 18C NMR (100 MHz, CDCl3); 5 13.4, 19.6, 23.6, 30.9, 42.2, 43.4, 57.2, 114.7, 115.1, 115.7, 116.6, 127.8, 128 , 6, 128.9, 133.6, 146.1, 151.3, 151.6, 161.1; LCMS (electrospray) m / z (M + H) + | 425, 427 (Isotope C standard)). - 10 7-Chloro-2-ethyl-N- (4- (4-hvdroxipiperidin-1-i) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (218). Pedal oh Pale yellow solid; melting point = 179.1 - 180.0 ºC; 1H: NMR (400 MHz, DMSO-d6); 5 1.22 (t, J = 7.2 Hz, 3H), 1.39 - 1.48 (m, 2H), 1.76 - 1.81 (m, 2H), 2.76 - 2.82 (m, 2H), 2.92 (q, J = 7.2 Hz, 2H), 3.46 - 3.51 - 15. (m, 2H), 3.57 - 3.62 (m, 1H) , 4.39 (d, J = 5.6 Hz, 2H), 4.64 (d, J = 4.0 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 7 , 07 (dd, J = 2.0, 7.2 Hz, 1H), 7.18 (d, J = 84 Hz, 2H), 7.77 (d, J = 2.0 Hz, 1H), 8 , 37 (t, J = 5.6 Hz, 1H), 8.93 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 413, 415 (Cl isotope standard). 2-Ethyl-6-methyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (219)
LO O "o
SN White solid; 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.2 Hz, 3H), 2.35 (s, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.15 (t, J = 4.8 Hz, 4H). 3.86 (t J = 4 Hz, 4H), 4.61 (d, J = 5.2 Hz, 2H), 6.00 (brs, 1H), 6.91 (d, J = 8.8 Hz , 2H), |
7.16 (dd, J = 2.0 Hz, 9.2 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.49 (d, J = 9.2 Hz, 1H), 9.20 (s, 1H); LCMS (electrospray) m / z (M + H) + 379, Acid 1- (4 - ((6-chloro-2-ethylimidazo [1,2-a] lpyridine-3-carboxamido) methyl) phenyl) piperidine-4 -carboxylic (220) Pp LD NH
SATAN A White solid; 1H NMR (400 MHz, DMSO-d6); 5 1.23 (t, J = 7.6 Hz, 3H), 1.57 - 1.67 (m, 2H), 1.85 - 1.89 (m, 2H), 2.34 - 2.41 (m, 1H), 2.68 - - 2.74 (m, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.58 - 3.61 (m, 2H), 4 , 41 (d, J = 5.6 Hz, 2H), 56.90 (d, Jy = 8.8 Hz, 2H), 7.20 (d, J = 8.8 Hz, 2H), 7.43 (dd, J = 2.0, 9.6 Hz, 1H), 7.64 (d, J = 9.6 Hz, 1H), 8.38 (brt, J = 5.6 Hz, 1H), 9 , 05 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z 441 (M + H) +, - N- (4- (Azepan-1-yl) benzyl) -6-chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamide (221) o, H Neca - and SN 1H NMR (400 MHz, CDCl3) 5 1.26 (t, J = 7.2 Hz, 3H), 1.38 (m, 7 4H), 1.53-1 , 56 (m, 4H), 2.95 (q, J = 7.6 Hz, 2H), 3.45 (t J = 5.6 Hz, 4H), 4.56 (d / J = 5.6 Hz , 2H), 5.97 (brs, 1H), 6.68 (d, J = 8.8 Hz, 2H), 7.21 (d J = 88 Hz, 2H), 7.28 (dd, JU = 9.6, 2.0 Hz, 2H), 7.53 (d, J = 9.6 Hz, 1H), 9.53 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z (M + H) + 411.40 N- (4- (Azepan-1-yl) benzyl) -7-chloro-2-ethylimidazo [1,2-alpiridine-3-carboxamide (222 ) 4 LO-O rs 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 1.52-1.55 (m, 4H), 1.78 (m, 4H), 2.94 (q, J = 7.6 Hz, 2H), 3.45 (t, J = 6.0 Hz, 4H), 4.56 (d, J = 5.2 Hz, 2H) , 5.95 (brs, 1H), 6.67 (d, J = 8.8 Hz, 2H), 6.89 (dd, J = 7.6, |
2.4 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 2.4 Hz, 1H), 9.36 (d, J = 7, 6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 411.40 7-Chlorine-N- (4- (3a 4-dihydro-1H-isoindol-2 (3H, 7H, 7aH) -yl) benzyl) -2- ethylimidazo [1,2-a] pyridine-3-carboxamide (223) à À DO er SN White solid; 1H NMR (400 MHz, CDCl3); at 1.36 (t, J = 7.6 Hz, 3H), 1.96 (dd, J = 4.0 Hz, 16.4 Hz, 2H), 2.25 - 2.31 (m, 2H) , 2.45 (dd, J = 5.2 Hz, 8.8 Hz, 2H), 2.92 (q, J = 7.6 Hz, 2H), 3.11 (dd, J = 5.2 Hz , 8.8 Hz, 2H), 3.39 (dd, J = 6.4 Hz, 8.8 Hz, 2H), 4.55 (d, JU = 5.2 Hz, 2H), 5.67 ( s, 2H), 5.94 S (brs, 1H), 6.51 (d, J = 8.8 Hz, 2H), 6.89 (dd, J = 2.0 Hz, 7.6 Hz, 1H ), 7.22 (d, '10 J = 8.8 Hz, 2H), 7.57 (d, J = 2.0 Hz, 1H), 9.35 (d, J = 7.6 Hz, 1H) ; LCMS (electrovaporization) m / z (M + H) + 435, 437 (Cl isotope standard). N- (4- (1H-isoindol-2 (3H, 3aH, 4H, 5H, 6H, 7H, 7aH) -yl) benzyl) -7-chloro-2-: ethylimidazo [1,2-a] pyridine-3 -carboxamide (224). 4th DO. IN White solid; 1H NMR (400 MHz, CDCl3); at 1.36 (t, 1 = 7.6 Hz, 3H) 1.40-2.03 (m, 8H), 2.29 - 2.34 (m, 2H), 2.92 (q, J = 7.2 Hz, 2H), 3.16 (dd, J = 5.2 Hz, 9.2 Hz, 2H), 3.29 (dd, J = 6.8 Hz, 8.8 Hz, 2H), 4.55 (d, J = 5.2 Hz, 2H), 5.97 (brs, 1H), 5.49 (d, J = 8.4 Hz, 2H), 6.88 (dd, J = 2 , 4 Hz, 7.6 Hz, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.56 (d, JU = 2.4 Hz, 1H), 9.33 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 437, 439 (Isotope standard C) 7-Chloro-2-ethyl-N- (4- (4,5,6,7-tetrahydro-2H-isoindo] l -2- yl) benzyl) imidazo ([1,2-alpyridine-3-carboxamide (225) a À DO ed ed RAN |
White solid; 1H NMR (400 MHz, CDCl3); 5 1.39 (t, J = 7.6 Hz, 3H), 1.74 - 1.77 (m, 4H), 2.63 (m, 4H), 2.97 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 6.0 Hz, 2H), 6.14 (brs, 1H), 6.78 (s, 2H), 6.91 (dd, J = 2.0 Hz, 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 2.0 Hz, 1H), 936 (d J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 433, 435 (C isotope standard). 6-Chloro-2-ethyl-N - ((1- [4- (trifluoromethoxy) benzyl) piperidin-4-iNmethyl) imidazo [1,2-alpiridine-3-carboxamide (226) o. % NH "q G 'ocF, i TS - White solid; melting point = 171 - 172 ºC; 1H NMR (400 MHz CDCI3) 5 1.35 -1.41 (m, 2H), 1.44 (t, J = 7.6 Hz, 3H), 1.63 - 1.72 (m,: 1H), 1.74 - 1.77 (m, 2H), 1.99 - 2.05 (m, 2H), 2.90 - 2.93 (m, 2H), 3.00 (q, J = 7.6 Hz, 2H), 3.41 (t J = 6.2 Hz, 2H), 3.51 (s, 2H), 5.89 (t, J = 5.4 Hz, 1H), - 7.15 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 2.4, 9.6 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 9.6 Hz, 1H), 9.49 (d, J = 1.6 Hz, 1H) ); LCMS (electrospray. 15 zation) m / z (M + H) +495.34 6-Chloro-2-ethyl-N - ((1- (4-fluorobenzyl) piperidin-4-yl)] methyl) imidazo [1,2-. alpiridine-3-carboxamide (227) 'Pe,% NH Roi “oh White solid; melting point = 176 - 177 ºC; 1H NMR (400 MHz, CDCl3) 5 1.33 - 1, 39 (m, 2H), 1.44 (t J = 7.6 Hz, 3H), 1.62 - 1.70 (m, 1H) 1.72-1.76 (m, 2H), 1.95 - 2.00 (m, 2H), 2.88 - 2.91 (m, 2H), 2.99 (q, J = 7.6 Hz, 2H), 3.05 (t, J = 6.4 Hz, 2H), 3.46 (s, 2H), 5.87 - 5.89 (m, 1H), 6.99 (dd, J = 84, 8.8 Hz, 2H), 7.25 - 7 , 30 (m, 3H), 7.53 (d, J = 9.6 Hz, 1H), 9.48 (d, J = 1.6 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 429.29 7-Chloro-2-ethyl-N - ((1- (4- (trifluoromethoxy) benzyl) piperidin-4- | iDmethyl) imidazo [1,2 -a] pyridine-3-carboxamide (228)
N% PX oCcF, c o N White solid; melting point = 145 - 146 ºC; 1H NMR (400 MHz, CDCl3) 5 1.33 - 1.39 (m, 2H), 1.44 (t, J = 7.6 Hz, 3H), 1.62 - 1.69 (m, 1H) , 1.72 - 1.76 (m, 2H), 1.96 - 2.02 (m, 2H), 2.88 - 2.91 (m, 2H), 2.99 (q, J = 7, 6Hz 2H), 3.41 (tJ = 6.4 Hz, 2H), 3.48 (s, 2H), 5.87 (t J = 5.4 Hz, 1H), 6.88 (dd, J = 2.0, 7.6 Hz, 1H), 7.15 (d, JU = 8.0 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 2.4 Hz, 1H), 9.31 (d, J = 7.2 Hz, 1H)); LCMS (electrospray) mz (M + H) + 495.20 6-Chloro-2-ethyl-N- (1- (4- (trifluoromethoxy) benzyl) piperidin-4-i) imidazo [1,2- '10 alpiridine-3-carboxamide (229) OO
QNTO White solid; melting point = 157 - 158 ° C; 1H NMR (400 MHz, CDCl3) 5 1.43 (t, JU = 7.6 Hz, 3H), 1.56 - 1.66 (m, 2H), 2.05 - 2.410 (m, '1H), 2.22 - 2.27 (m, 2H), 2.81 - 2.84 (m, 2H), 2.98 (q, J = 7.6 Hz, 2H), 3.53. (s, 2H), 4.08 - 4.11 (m, 1H), 5.69 - 5.71 (m, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7 , 29 (dd, J = 2.0,9.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 9.2 Hz, 1H) , 9.46 (d, J = 1.6 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 481.26 (6-Chloro-2-ethylimidazo [1,2-a] pyridin-3-i1) (4- (4- (trifluoromethoxy) benzyloxy) piperidin- 1-il)] netanone (230)
OLD “and
SN H NMR (400 MHz, CDCl3) δ 1.38 (t, J = 7.2 Hz, 3H), 1.71-1.78 (m, 2H), 1.94 (m, 2H), 2 , 78 (q J = 7.6 Hz, 2H), 3.51 (m, 2H), 3.74 (m, 1H), 3.89 (m, 2H), 4.58 (s, 2H), 7.19-7.23 (m, 3H), 7.38 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 9.6 Hz, 1H), 8.48 (s , 1H); LCMS (electrospray) m / z (M + H) + |
481.26 6-Chloro-2-ethyl-N - ((I- (4- (trifluoromethoxy) phenyl) -1H-pyraz] l-3- i) meti) imidazo [1,2-a] pyridine-3- carboxamide (231) ocF; oO O, | SW "N 1H NMR (400 MHz, CDCl3) 5 1.48 (t, J = 7.6 Hz, 3H), 3.12 (q, J = 76Hz 2H) 4.80 (d, J = -4, 8Hz, 2-H), 6.49 (d, J = 2.4 Hz, 2H), 6.69 (brs, IH), 7.29-7.33 (m, 3H), 7.55 (d , J = 9.2 Hz, 1H), 7.70 (d, J = 9.2 Hz, 2H), 7.90 (d, J = 2, A Hz, 1H), 9.56 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z. (M + H) + 464.19 T7-Chlorine-2-ethyl-N - ((1- (4- (trifluoromethoxy) phenyl) -1H -pyrazol-3- '10 ilmeti) imidazo [1,2-alpiridine-3-carboxamide (232) a [0 err RN 7H NMR (400 MHz, CDCl3) 5 1.47 (t, J = 7.6 Hz, 3H), 3.11 (q, J = '7.6 Hz, 2H), 4.79 (d, u = 5.2 Hz, 2H), 6.48 (d, J = 2.4 Hz, 2H ), 6.68 (brs, 1H), .6.91 (dd, J = 7.6, 2.0 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7, 60 (d, J = 2.0 Hz, 1H), 7.70 (d, J = 6.8 Hz, 2H), 7.90 (d, J = 2.0 Hz, 1H), 9.39 ( d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 464.19 6-Chloro-2-ethyl-N - ((1- (4- (trifluoromethyl) phenyl) -1H-pyrazol-3-yl) methyl) imidazo [1,2-a] pyridine-3-carboxamide 122 aa o .- 1H NMR (400 MHz, DMSO-d6) 5 1.29 (t, J = 7, 6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4.62 (d, J = 5.6 Hz, 2H), 6.59 (d, J = 2.8 Hz, 1H), 7.46 (dd, J = 89.2.1.6 Hz, 1H), 7.67 (d, J = 9.2 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 8.06 (d, |
J = 8.4 Hz, 2H), 8.55 (t J = 5.6 Hz, 1H), 8.62 (d, J = 2.4 Hz, 1H), 9.10 (d, J = 2 , 0 Hz, 2H); LCMS (electrospray) m / z (M + H) + 448.37 7-Chloro-2-ethyl-N - ((1- (4- (trifluoromethyl) phenyl) -1H-pyrazol-3-ylmethyl) imidazo [1 , 2-a] pyridine-3-carboxamide (25) o À No o ”and SAN 1H NMR (400 MHz, DMSO-d6) at 1.28 (t, J = 7.6 Hz, 3H), 3.02 (q, J = 7.6 Hz, 2H), 4.61 (d, J = 5.6 Hz, 2H), 6.58 (d, J = 2.8 Hz, 1H), 7.11 (dd , J = 7.6,2.0 Hz, 1H), 7.80 (d, J = 2.0 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 8.06 (d, 'J = 8.8 Hz, 2H), 8.52 (t J = 5.6 Hz, 1H), 8.61 (d, J = 2.4 Hz, 1H), 8.97 (d J =. 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 448.13 6-Chlorine-2-ethyl-N - ((1- (4-fluorophenyl) -1H-pyrazole -3-yl)] methyl) imidazo [1,2-alpyridine-3-carboxamide (235) r - [U and '1H NMR (400 MHz, CDCl3) 5 1.47 (t, J = 7.6 Hz, 3H), 3.11 (q, J. = 7.6 Hz, 2H), 4.79 (d, J = 4.8 Hz, 2H), 6.46. (D, 7 = 2.0 Hz , 1H), 6.70 (brs, 1H), 7.16 (dd, JU = 8.8 Hz, 2H), 7.30 (dd, J = 9.2, 2.0 Hz, 1H), 7 , 55 (d, J = 9.6 Hz 1H), 7.61-7.64 (m, 2H), 7.85 (d, J = 2.4 Hz, 1H), 9.56 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 398.32 7-Chlorine-2-ethyl- N - ((1- (4-fluorophenyl) -1H-pyrazol-3-yl) methyl) imidazo [1,2-alpyridine-3-carboxamide (236) and the se.
AO 'H NMR (400 MHz, CDCI3) 3 1.46 (t, J = 7.6 Hz, 3H), 3.11 (q, J = 7.6 Hz 2H), 4.78 (d, J = 4.8 Hz, 2H), 6.46 (d, J = 2.0 Hz, 1H), 6.69 (brs, |
1H), 6.91 (dd, J = 7.6, 24 Hz, 1H), 7.16 (dd, J = 8.8 Hz, 2H), 7.59-7.64 (m, 3H), 7.85 (d, J = 2.4 Hz, 1H), 9.39 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 398.14 6-Chloro-2-ethyl-N - ((1 (4- (trifluoromethoxy) phenyl) -4,5,6,7-tetrahydro- 1H-indazol-4-yl) methyl) imidazo [1,2-alpiridine-3-carboxamide 23)
DO aa ex q Coe, 'H NMR (400 MHz, CDCl3) 5 1.41 (t, J = 7.6 Hz, 3H), 1.89-1.98 (m, 3H), 2.27 (m , 1H), 2.77-2.84 (m, 2H), 2.96 (q, J = 7.6 Hz, 2H), 5.40 (m, 1H), 5.96 (d, J = 8.0 Hz, 1H), 7.29-7.34 (m, 3H), 7.54-7.58 (m, 3H), 7.70 (s, '1H), 9.54 (d, J = 1.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 504.25. 10 6-Chloro-2-ethyl-N - ((1- (4-fluorophenyl) -4,5,6,7-tetrahydro-1H-indazol-4-yl)] methyl) imidazo [1,2-alpiridine- 3-carboxamide (238) oil. The. = CT EA Dr] 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 1.88-1.97 (m, 3H), 2.26 (m, 1H ), 2.74-2.78 (m, 2H), 2.96 (q, J = 7.6 Hz, 2H), 5.40 (m,. 1H), 5.96 (d, J = 7 , 6 Hz, 1H), 7.17 (dd, J = 8.0, 8.8 Hz, 2H), 7.31 (dd, JU = 9.2, 2.0 Hz, 1H), 7.48 -7.50 (m, 2H), 7.55 (d, J = 9.2 Hz, 1H), 7.68 (s, 1H), 2:54 (d, J = 2.0 Hz, 1H) ; LOMS (electrospray) m / z (M + H) + 438.40 6-Chloro-2-ethyl-3 - ((4- (trifluoromethoxy) phenoxy) methyl) imidazo [1,2-a] pyridine 2a to ocrs O
White solid; melting point = 127 - 128 ° C; 1H NMR (400 MHz CDCl3) δ 1.34 (t J = 7.6 Hz, 3H), 2.82 (q, J- 7.6 Hz, 2H), 5.27 (s, 2H), 7, 00 (d, J = 9.2 Hz, 2H), 7.19 (d, J = 9.2 Hz, 2H), 7.53 (dd, J = 0.8, 9.2 Hz, 1H), 8.12 (dd, J = 0.8, 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 371.07 |
: N - ((6-Chloro-2-ethylimidazo ([1,2-a] pyridin-3-yl) methyl) -4- (trifluoromethoxy) aniline (240) a cr.
QT if White solid; 1H NMR (400 MHz, CDCl3) 5 1.35 (J = 7.6 Hz, 3H), 2.82 (q, J = 7.2 Hz, 2H), 3.67 (t, J = 4.6 Hz, 1H), 4.50 (d, J = 5.2 Hz, 2H, 6/72 (d J = 8.8 Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H) , 7.51 (dd, J = 2.0, 9.6 Hz, 1H), 7.51 (d, J = 9.6 Hz, 1H), 8.10 (d, J = 1.2 Hz, 1H); LOCMS (electrospray) m / z (M + H) + 370.11. N - ((6-Chloro-2-ethylimidazo [1,2-alpiridin-3-iN) methyl) -4- ( 4- (4- fluorophenyl) piperazin-1-i) aniline (241) '10
LS - will O
N White solid; melting point = 191 - 192 ° C; 1H NMR (400 'MHz, CDCl3) 5 1.85 (J = 7.6 Hz, 3H), 2.82 (q, J = 7.2 Hz, 2H), 3.22 - 3.24. (m, 4H), 3.26 - 3.28 (m, 4H), 3.40 (br s, 1H), 4.50 (s, 2H) ,. 6.75 (d, J = 8.8 Hz, 2H), 6.92 - 7.01 (m, 6H), 7.14 (dd, J = 1.6, 9.2 Hz, 1H), 7.51 (d, J = 9.6 Hz , 1H), 8.18 (d, J = 1.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 464.32 N - (((6-Chloro-2-ethylimidazo [1,2-alpiridin-3-yl)] Mmethyl) -4- (4-fluorophenoxy) aniline (242) q White solid; melting point = 148.6 - 148.8 ° C; 1H NMR (400 MHz, CDCl3) 5 1.35 (t, J = 7.4 Hz, 3H), 2.82 (q, J = 7.6 Hz, 2H), 4.50 (s, 2H), 674 (d J = 8.8 Hz, 2H), 6.90 - 7.01 (m, 6H), 7.15 (dd, J = 2.0, 9.8 Hz, 1H), 7.52 ( d, J = 9.2 Hz, 1H), 8.16 (d, J = 1.2 Hz, 1H); LCMS (electrospray) | m / z (M + H) + 396.17 S- (6-Chloro-2-ethylimidazo [1,2-a] pyridin-3-i1) -3- (4- (trifluoromethoxy) benzyl) - 1,2 .4-0xadiazole (243) N
N Pale yellow solid; melting point = 146.4 - 146.9 ° C; 1H —RMN (400 MHz, CDCI3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.22 (q, J = 7.2 Hz, 2H), 4.20 (s, 2H) , 7.21 (d, J = 8.0 Hz, 2H), 7.40 (dd, J = 2.0, 9.6 Hz, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.65 (d, J = 9.6 Hz, 1H), 8.47 (d, J = 1.2 Hz, 1H); LCMS (ele-: trovaporization) m / z (M + H) + 423.10 2- (7-Chloro-2-ethylimidazo [1,2-a] pyridin-3-1) -5 - ((4- ( 4- (triluoromethoxyphenyl) piperazin-1-yl) methyl) -1,3,4-0xadiazole (244), LS OA 'E NM Pale yellow solid; 1H NMR (400 MHz, CDCl3) 1.41 (t J =. 74 Hz, 3H), 2.83 (t, J = 4.8 Hz, 4H), 3.16 (q, J = 7.6 Hz, 2H), 3.23 (LJ = 4.8 Hz, 4H ), 4.02 (s, 2H), 6.88 (d, u = 9.2 Hz, 2H), 7.05 (dd, JU = 2.0, 9.6 Hz, 1H), '7, 10 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 1.6 Hz, 1H), 9.42 (d, JU = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 507.24 S- (6-Chloro-2-ethylimidazo [1,2-a] pyridin-3-i1) -3- (4- (4-fluorophenoxy) benzyl) - 1 , 2,4-0 xadiazole (245)
F Oo pe
NAN Yellow solid; melting point = 129.9 ºC; 1H NMR (400 MHz, CDCl3) 5 1.41 (t J = 7.8 Hz, 3H), 3.22 (q, J = 7.2 Hz, 2H), 4.16 (s, 2H), 6 , 93 -7.04 (m, 6H), 7.36-7.39 (m, 3H), 7.63 (d, Jy = 9.6 Hz, 1H), 9.48 (d, JU = 2 , 0 |
Hz, 1H); LCMS (electrospray) m / z (M + H) + 449 6-Chloro-N, 2-diethylimidazo [1,2-a] pyridine-3-carboxamide (246) If “os White solid; melting point = 176.7 ºC; 1H NMR (400 MHz, CDCIS); 5 1.29 (t, J = 7.2 Hz, 3H), 1.43 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.2 Hz 2H) 3.51 -3.57 (m, 2H), 5.79 (brs, 1H), 7.27 (dd, J = 2.4 Hz, 9.6 Hz, 1H), 7.51 (d, J = 9, 6 Hz, 1H), 9.45 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z (M + H) + 252. 6-Chlorine-2-ethyl-N-isobutylimidazo [1,2-a ENO (247) “o White solid; melting point = 162.2 ºC; 1H NMR (400 MHz,: 10 CDCI3); 51.01 (d, J = 6.8Hz, 6H), 1.45 (t J = 7.6 Hz, 3H), 1.90 - 1.97 (m , 1H), 3.01 (q, J = 7.6 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 5.86 (brs, 1H), 7.28 - ( dd, Jy = 2.0 Hz, 9.6 Hz, 1H), 7.53 (d, J = 9.6 Hz, 1H), 9.47 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 280. '7-Chloro-2-ethyl-N - (((4' (trifluoromethoxy) biphenyl-3-yl)] meti) imidazo] 1,2-alpiridine- 3-carboxamide (248) - À NH
It is cr N a White solid; melting point = 192.6 "* C; 1H NMR (400 MHz, CDCl3); 5 1.37 (t, J = 7.2 Hz, 3H), 2.95 (q, Jy = 7.2 Hz, 2H), 4.75 (d, J = 6.0 Hz, 2H), 6 , 19 (brt, J = 6.0 Hz, 1H), 6.88 (dd, J = 2.0.7.6 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H) , 7.36 (d, J = 7.6 Hz, 1H), 7.43 (dd, J = 7.2, 7.6 Hz, 1H), 7.48 - 7.59 (m, 5H), 9.33 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z 474, 476 (M + H) + (Cl isotope standard). 2-Ethyl-7-methyl-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide (249) '
STEEL% NH Fax
TN Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.33 (t J = 7.6 Hz, 3H), 2.91 (q, J = 7.6 Hz, 2H), 4.64 (d, Jy = 5.2 Hz, 2H), 6, 25 (brt, J = 5.2 Hz, 1H), 6.69 (dd, J = 1.6, 7.2 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.80 (s, 1H), 7.35 (d, J = 8.4 Hz, 2H), 9.19 (d, J = 7.2 Hz, 1H). T7-Bromo-2-ethyl-N- (4- (triluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (250)
ADS% X- NH Br N 'White solid; 1H NMR (400 MHz, CDCl3); at 1.37 (t J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 4.67 (d, J = 5.6 Hz, 2H), 6, 18 (brt, J = 5.6 Hz, "1H), 6.99 (dd, J = 1.6, 7.2 Hz, 1H), 7.19 (d, J = 8.4 Hz, 2H) , 7.38 (d, J = 84: 10 Hz 2H), 7.75 (d, J = 1.6 Hz, 1H), 9.25 (d, J = 7.2 Hz, 1H). 2-Ethyl -8-fluoro-N- (4- (trifluoromethoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (251) is OCF; PTN
It is white solid; 1H NMR (400 MHz, CDCl3); 5 1.38 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 6.0 Hz, 2H), 6 , 25 (brs, 1H), 6.79 - 6.84 (m, 1H), 7.00 (dd, J = 8.0, 9.6 Hz, 1H), 7.19 (d, J = 8 , 4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 9.16 (d, J = 6.8 Hz, 1H). 7-Chloro-2-ethyl-N - (((4'-formylbiphenyl-4-yl) methyl) imidazo] [1,2-a] pyridine-3-carboxamide (252) q o
DD% X NH and o "N White solid; 1H NMR (400 MHz, CDCl3); 5 1.40 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 4.75 (d, J = 6.0 Hz, 2H), 6.18 (brt, J = 6.0 Hz, 1H), 6.89 (dd, J - 24, 7.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 24 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7 , 73 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 8.4 Hz 2H) 9.36 (d, J = 7.6 Hz, 1H), 10.05 (s, 1H) ; 18C NMR (100 MHz, CDCI3) 5 13.4, 23.8, 43.4, 114.9, 115.9, 127.8, 128.0, 128.4, 128.7, 130.5, 133.8,: 135.5, 138.7, 139.3, 146.3, 146.7, 151.9, 161.4, 192.0 (hidden 1 aromatic carbon). 6-fluoro-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2-alpyridine-3-carboxamide (253) o ”5; F. A OCcF;
TO - White solid; melting point = 133.4 ºC; 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.6 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 5 , 6 'Hz, 2H), 6.12 - 6.14 (m, 1H), 6.98 - 7.03 (m, 4H), 7.18 (d, J = 8.8 Hz, 2H), 7.23 - 7.28 (m, 1H), 7.58 (dd, Ju = 5.2, 9.6 Hz, 1H), 9.44 - 9.46 (m, 1H); LCMS (electrospray) m / z (M + H) + 474,6-Bromo-2-ethyl-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2-alpiridine-3-carboxamide ( 254) [O Ros O. “eo,
N White solid; melting point = 152.9 ºC; 1H NMR (400 MHz, CDCl3) 5 1.42 (t, J = 7.4 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.68 (d, J = 5 , 6 Hz 2H), 6.12-6.14 (m, 1H), 6.98 - 6.03 (m, 4H), 7.18 (d, J = 8.8 Hz, 2H), |
7.37 (d, J = 8.4 Hz, 1H), 7.40 (dd, J = 2.0, 9.6 Hz, 1H), 7.50 (d, J = 9.2 Hz, 1H ), 9.63 (d, J = 1.2 Hz, 1H)); LCMS (electrospray) m / z (M + H) + 534, 536 (Br isotope standard). 2-Ethyl-6-methyl-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2-alpyridine-3-carboxamide (255) Poa Xe a
WIN Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.31 (tl J = 7.6 Hz, 3H), 2.30 (s, 3H), 2.90 (q, J = 7.6 Hz, 2H), 4.62 (d, J = 5 , 6 Hz, 2H), - 6.32 (brt, J = 5.6 Hz, 1H), 6.93 - 6.96 (m, 4H), 7.1 1-7.14 (m, 3H) , 7.31 (d, J = 8.4 Hz, 2H), 7.42 (d, 7 = 8.4 Hz, 1H), 9.11 (s, 1H); LCMS (electrospray - '10 tion) m / z470 (M + H) +. 2-Ethyl-7-methyl-N- (4- (4 (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2- 'alpyridine-3-carboxamide (256)
A% X NH A sd DCF; - AE Pale yellow solid; melting point = 133.6 ºC; 1H NMR (400 MHz, CDCl3); at 1.36 (t, J = 7.6 Hz, 3H), 2.39 (s, SH), 2.93 (q, J = 7.6 Hz, 2H) 4.65 (d, J = 5 , 6 Hz, 2H), 6.13 (btt, J = 5.6 Hz, 1H), 6.71 (dd, J = 1.6.7.2 Hz, 1H), 6.96 - 7.00 (m, 4H), 7.15 (d, J = 8.4 Hz, 2H), 7.32 - 7.37 (m, 3H), 9.23 (d, J = 7.2 Hz, 1H) ; LOMS (electrospray) m / z 470 (M + H) +. 2-Ethyl-B8-fluoro-N- (4- (4- (trifluoromethoxy) phenoxy) benzyl) imidazo [1,2-alpyridine-3-carboxamide (257) O, S / N
F Pale yellow solid; melting point = 105.6 ºC; 1H NMR (400 MHz, CDCl3); at 1.35 (t, Jy = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 4.65 (d J = |
5.6 Hz, 2H), 6.29 (brt, J = 5.6 Hz, 1H), 6.77 - 6.82 (m, 1H), 6.96 - 7.02 (m, 5H), 7.13 - 7.17 (m, 2H), 7.32 - 7.35 (m, 2H), 9.12 (dd, J = 0.8, 7.2 Hz, 1H); LCMS (electrospray) m / z 474 (M + H) +. 2-Ethyl-6-fluoro-N- (4- (4- (trifluoromethoxy) benzyloxy) benzyl) imidazo [1,2-alpyridine-3-carboxamide (258) O, OCF;
TN White solid; 1H NMR (400 MHz, CDCl3); 5 1.37 (t J = 7.2 Hz, 3H), 2.93 (q, J = 7.2 Hz, 2H), 4.62 (d, J = 5.6 Hz, 2H), 5, 06 (s, 2H), 6.06 (brt,: J = 5.6 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 7.22 - 7.26 (m, 3H), 7.29 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.47 - 7.58 (m, 1H), 9, 43 - 9.45 (m, 1H); Ú 10 LCMS (electrospray) m / z 488 (M + H) +. 6-Bromo-2-ethyl-N- (4- (4- (triluoromethoxy) benzyloxy) benzyl) imidazo [1,2- - alpiridine-3-carboxamide (259)
ADA. a - to Pv. Pale yellow solid; melting point = 189.7 ºC; 1H NMR (400 MHz, CDCl3); 5 1.36 (t, J = 7.6 Hz, 3H), 2.92 (q, J = 7.6 Hz, 2H), 4.62 (d, J = 5.6 Hz, 2H), 5, 05 (s, 2H), 6.06 (brt, J = 5.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 7.36 (dd, J = 2.0, 9.2 Hz, 1H), 7.43 - 7.49 (m , 3H), 9.60 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z 548, 550 (M + H) + (Br isotope standard). 2-Ethyl-N- (4- (4- (trifluoromethoxy) benzyloxy) benzyl) imidazo [1,2-a] lpiridine-3-carboxamide (260) o QD% ah o Se SN |
White solid; melting point = 138.7 ºC; 1H NMR (400 MHz, CDCl3); 5 1.35 (t, J = 7.6 Hz, 3H), 2.91 (q, J = 7.6 Hz, 2H), 4.60 (d, J = 5.6 Hz, 2H), 5 , 03 (s, 2H), 6.14 (brt, J = 5.6 Hz, 1H), 6.85 (ddd, J = 1.2, 7.2, 7.2 Hz, 1H), 6, 92 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.26 - 7.30 (m, 3H) 742 (d J = 8.8 Hz , 2H), 7.55 (d, J = 9.2 Hz, 1H), 9.33 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z 470 (M + H) +. 1E) -7-Chloro-2-ethyl-N- (4 - ((4- (triluoromethoxy) benzylidene) amino) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (261)
LOLITA Yº | and.
N '10 Solid not entirely white; melting point = 194 ° C; 1H NMR (400 MHz, CDCI3) at 1.42 (t, J = 7.4 Hz, 3H), 3.00 (q, J = 7.6 Hz, 2H), 4.72 (d, - J = 5.2 Hz, 2H), 6.14 (t, J = 5.2 Hz, 1H), 6.90 - 6.94 (m, 1H), 7.22 (d J = 8.0 Hz, 2H ), 7.30 - 7.35 (m, 3H), 7.42 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.8 Hz, 7 1H), 7, 94 (d, J = 8.8 Hz, 2H), 8.45 (s, 1H), 9.41 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 467, - 7-Chloro-2-ethyl-N- (4 - ((4- (trifluoromethoxy) benzyl) amino) benzyl) imidazo [1,2-alpiridine- 3-carboxamide (262) | ADA
NH e e White solid; melting point = 169.6 ºC; 1H NMR (400 MHz, CDCI3) at 1.36 (t, J = 7.6 Hz, 3H), 2.05 - 2.12 (m, 2H), 2.93 (q, J = 7.2 Hz , 2H), 4.18 (brs, 1H), 4.55 (d, J = 5.2 Hz, 2H), 5.99 - 6.01 (m, 1H), 6.60 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 8.0 Hz, 4H), 7.38 (d, J = 8, 0 Hz, 2H), 7.56 (s, 1H), 9.33 (d, y = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 503. 2-Ethyl-N- (4- (methyl (4- (trifluoromethoxy) benzyl) amino) benzyl) imidazo [1,2- | alpiridine-3-carboxamide (263) Loo o, ek Not entirely white solid; 1H NMR (400 MHz, CDCl3) 5 1.39 (t J = 7.6 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 3.03 (s, 3H), 4 , 53 (s, 2H), 4.59 (d, J = 5.6 Hz, 2H), 5.98 - 5.99 (m, 1H), 6.72 (d, J = 8.8 Hz, 2H ), 6.89 - 6.92 (m, 1H) 7.16 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.8 Hz, 1H), 7.29 -7 , 33 (m, 1H), 7.60 (d, J = 8.8 Hz, 1H), 9.39 (d, J = 6.8 Hz, 1H); LCMS (electrospray) mi / z (M + H) + 505,. 7-Chloro-2-ethyl-N- (4- (4-fluorophenoxy) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (264) xo - "F los - 10 White solid; melting point = 89.7 ºC; 1H NMR (400 MHz, CDCI3) at 1.298 (t, J = 7.6 Hz, 3H), 3.07 (q, J = 7.6 Hz, 2H), 5.37 (s, 2H), 6.93 - 7.05 (m, 7H), 7.41 (d, J - 8.8 Hz, 2H), 7.62 (d, J = 2.0 Hz, 1H), 9 , 24 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 425. 7-Chloro-2-ethyl-N- (4- (hexahydropyrrole [1,2 -a] pyrazin-2 (1H) - mpendinimidazole1 2-aleiridine-t-carsonan (265) Oo
LE White solid; melting point = 159.1 ºC; 1H NMR (400 MHz, CDCl3); 5 1.20 (t, J = 7.2 Hz, 3H), 1.85 - 1.92 (m, 2H), 2.01 - 2.03 (m, 2H), 2.17 - 2.21 (m, 2H), 2.39 - 2.58 (m, 5H), 3.14 - 3.16 (m, 2H), 3.61 (d, J = 11.6 Hz, 1H), 3, 75 (d, J = 10.0 Hz, 1H), 4.59 (d, J = 5.2 Hz, 2H), 6.01 (brs, 1H), 6.88 (dd, J = 1.6Hz , 7.2 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8A Hz, 2H), 7.56 (d, / = 1.6 Hz, 1H), 9.34 (d, J = 7.2 Hz, 1H); LCMS (electroplating) m / z (M + H) + 438. |
6-Chloro-2-ethyl-N- (4- (hexahydropyrrolo [1,2-a] pyrazin-2 (1H) -yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (266) N
OD “oh White solid; melting point = 163.0 ºC; 1H NMR (400 MHz, CDCl3); at 1.38 (t, J = 7.6 Hz, 3H), 1.47 - 1.53 (m, 2H), 1.65 - 1.85 (m, 2H), 217 (tJ = 88Hz 2H) , 2.34 -2.40 (m, 1H), 2.54 (t J = 10.8 Hz, 1H), 2.89 - 2.97 (m, 3H), 3.13 (m, 2H) , 3.61 (d, J = 12.4 Hz, 1H), 3.76 (d, J] = 10.4 Hz, 1H), 4.60 (d, J = 5.6 Hz, 2H), 6.01 (brs, 1H), 6.93 (d, J = 8.4 Hz, 2H), 7.25 - 7.29 (m, 3H), 7.52 (d, J = 9.6 Hz , 1H), 9.51 (s, 1H); LCMS (electrospray) m / z (M + H) + 438,. 10 6-Chloro-2-ethyl-N- (4- (octahydroisoquinolin-2 (1H) -i) benzyl) imidazo [1,2-alpyridine-3-carboxamide (267) - -% X di “" N 'Solid white; melting point = 141.7 ºC; 1H NMR (400 MHz,. CDCI3); 5 0.94 - 1.03 (m, 3H), 1.24 - 1.42 (m, 4H), 1, 34 (t, J = 7.2 Hz, 3H), 1.57 - 1.66 (m, 3H), 1.73 - 1.74 (m, 2H), 2.30 - 2.35 (m, 1H), 2.65 - 2.72 (m, 1H), 2.89 (g, J = 7.2 Hz, 2H), 3.48 - 3.53 (m, 1H), 3.67 - 3 , 71 (m, 1H), 4.56 (d, J = 5.6 Hz, 2H), 6.03 (brt, J = 5.6 Hz, 1H), 6.89 (d, J = 8, 4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H) 7.24 (dd, J = 2.0, 9.2 Hz, 1H), 7.48 (d, J = 9 , 2 Hz, 1H), 9.48 (d, J = 2.0 Hz, 1H); 18C NMR (100 MHz, CDCl3) 5 13.3, 23.5, 26.1, 26.5, 30, 5, 32.8, 33.0, 41.6, 41.8, 43.3, 50.3, 56.2, 115.4, 116.5, 116.9, 121.5,126,3,127,8,128, 2, 128.8, 144.5, 151.3, 151.5, 161.1; LCMS (electrospray) m / z 451, 453 (M + H) + (CI isotope standard). 2-ethyl-N- (4- (octahydroisoquinolin-2 (1H) -yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (268) | o SS a "N White solid; melting point = 174.2 ºC; 1H NMR (400 MHz, CDCl3); 3. 0.93 - 1.01 (m, 3H), 1.24 - 1.40 (m, 4H), 1.30 (t, J = 7.6 Hz, 3H), 1.56 - 1, 64 (m, 3H), 1.71 - 1.72 (m, 2H), 2.27 - 2.33 (m, 1H), 2.63 - 2.69 (m, 1H), 2.86 ( q, J = 7.6 Hz, 2H), 3.48 - 3.50 (m, 1H), 3.65 - 3.68 (m, 1H), 4.53 (d J = 5.2Hz 2H) , 6.10 (bt, J = 5.2 Hz, 1H), 6.81 (d, J = 7.2 Hz, 1H), 6.87. (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 9.25 (d, J = 7.2 Hz , 1H); 18C NMR (100 MHz, CDCl3) 5 13.3; 23.4, 26.1, 26.4, 30.5, 32.8, 33.0, - 41.6, 41.7, 43.3, 50.2, 56.1, 1 14.5, 115.1, 1 15.6, 1 16.4, 127.8, 128.4, 128.7, 133.4, 145.9, 151.4, 151.5, 161.1; LOMS (electrospray) m / z 451 '10, 453 (M + H) + (CI isotope standard). 7-Chloro-2-ethyl-N- (4- [4-oxopiperidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3- 'carboxamide (269) and ADD er RÁ Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.37 (tl J = 7.2 Hz, 3H), 2.54 (t, J = 6.6 Hz, 4H), 2.93 (q, J = 7.2 Hz, 2H), 3, 60 (t, J = 6.0 Hz, 4H), 4.61 (d, J = 5.6 Hz, 2H), 6.04 (brt, J = 5.6 Hz, 1H), 6.89 ( dd, J = 2.4, 7.6 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7, 58 (d, J = 2.4 Hz, 1H), 9.35 (d, JU = 7.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 41 1.413 (Cl isotope standard). 7-Chloro-2-ethyl-N- (4- (4-0x0-3,4-dihydropyridin-1 (2H) -i) benzyl) imidazo [1,2-alpyridine-3-carboxamide (270) qo SEO «>. ci RAN: Pale yellow solid; melting point = 201.3 - 202.8 ºC; 1H NMR (400 MHz, CDCl3); 5 1.38 (t, J = 7.6 Hz, 3H), 2.64 (t, J = 7.6 Hz, 2H), 2.95 (q, J = 7.6 Hz, 2H), 3 , 98 (t, J = 7.2 Hz, 2H), 4.66 (d, J = 5.6 Hz, 2H), 5.23 (d, J = 8.0 Hz, 1H), 6.13 (t / J = 5.6 Hz, 1H), 6.89 (dd, J = 2.4, 7.6 Hz, 1H), 7.08 (d J = 84 Hz, 2H), 7.38 ( d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 2.4 Hz, 1H), 9.34 (d, Jy = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 409, 411 (Ci isotope standard). 7-Chloro-2-ethyl-N- (4- (4-methylenepiperidin-1-yl) benzyl) imidazo [1,2-ajpiridine-: 3-carboxamide (271) AX o% X NH a N White solid; melting point = 168.3 ºC; 1H NMR (400 MHz, CDCl3B); 5 1.33 (t, J = 7.2 Hz, 3H), 2.32 - 2.34 (m, 4H), 2.89 (q, JU = 7.2 Hz, 2H), 3.23 - 3.25 (m, 4H), 4.56 (d, J = 5.2 Hz, 2H), 4.73 (s, 2H), 6.07 (brs, 1H), 6.84 (d, J = 7.2 Hz, 1H), 6.90 (d, J = 84 Hz, 2H), 7.22 (d, J = 84 Hz, 2H), '7.54 (s, 1H), 9, 29 (d, JU = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.4,
15. 23,5,34,2,43,3, 51,2, 108,5, 114,6, 115,1, 115,7, 116,7, 128,3, 128,5, 128,9, 133.5, 145.8, 146.0, 150.8, 151.5, 161.1; LCMS (electrospray) m / z 409, 411 (M + H) + (Cl isotope standard). 6-Chloro-2-ethyl-N- (4- (2-methylpiperidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (272)
The sticky pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 0.99 (d, J = 6.4 Hz, 3H), 1.32 (t J = 7.6 Hz, 3H) ', 1.55 - 1.70 (m, 4H), 1.81 - q
1.88 (m, 2H), 2.91 (q, J = 7.6 Hz, 2H), 2.92 - 2.98 (m, 1H), 3.21 - 3.26 (m, 1H) , 3.93 - 3.96 (m, 1H), 4.58 (d, J = 5.2 Hz, 2H), 6.01 (brt, J = 5.2 Hz, 1H), 6.90 ( d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 7.26 (dd, uy = 2.0, 9.2 Hz, 1H), 7, 50 (d, J = 9.2 Hz, 1H), 9.50 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz, CDC13) d13,3,13,7, 19.6, 23.6, 26.2, 31.6, 43.4, 44.6, 51.2, 115.4, 117, 0, 117.5, 121.6, 126.3, 127.9, 128.2, 128.8, 144.5, 151.1, 151.4, 161.1; LCMS (electrospray) m / z 411, 413 (M + H) + (Cl isotope standard), 7-Chloro-2-ethyl-N- (4- (2-methylpiperidin-1-i) benzyl) imidazo [1, 2-a] pyridine-3-carboxamide (273) oO:% NH cs. 7 PN White solid; melting point = 1 17.9 ºC; 1H NMR (400 MHz,. CDCI3); 5 1.00 (d, J = 6.4 Hz, 3H), 1.35 (t, J = 7.6 Hz, 3H), 1.56 - 1.69 (m, 4H), 1.75 - 1.90 (m, 2H), 2.92 (q, J = 7.6 Hz, 2H), 2.96 - 2.99 (m, 1H), 3.23 - - 3.28 (m, 1H ), 3.95 - 3.98 (m, 1H), 4.59 (d, Jy = 5.6 Hz, 2H), 6.08 (brt, J = 5.6 Hz, 1H), 6.87 (dd, J = 2.0, 7.6 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 7.23 (d, J =. 15 88Hz 2H) 7.57 ( d, J = 2.0 Hz, 1H), 9.32 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) 5 13.4, 13.7, 19.5, 23.5, 26.1, 31.6, 43.3, 44.5, 51.2, 1146,. 115.1, 115.7, 1 17.4, 127.8, 128.5, 128.8, 133.5, 146.0, 151.0, 151.5, 161.1; LCMS (electrospray) m / z 41 1, 413 (M + H) + (Isotope standard C!). 7-Chloro-N- (4- (4,4-dimethylpiperidin-1-i) benzyl) -2-ethyl-1,8a- dihydroimidazo [1,2-a] lpiridine-3-carboxamide (274)
AS & NH and ixo White solid; melting point = 121.3 "ºC; 1H NMR (400 MHz, CDCl3); 5 0.97 (s, SH), 1.34 (t, J = 7.2 Hz, 3H), 1.49 - 1.52 (m, 4H), 2.89 (q, J = 7.2 Hz, 2H), 3.15 - 3.17 (m, 4H), 4.57 (d, J = 5.2 Hz, 2H), 6.00 (btt, J = 5.2 |
Hz, 1H), 6.86 (dd, JU = 2.0, 7.6 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8 , 4 Hz, 2H), 7.56 (d, J = 2.0 Hz, 1H), 9.32 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.4, 23.5, 28.0, 29.8, 38.5, 43.4, 45.9, 1 14.7, 1 15.7, 116.4 , 127.9, 128.6, 128.9, 129.0, 183.6, 146.1, 151.5, 151.6, 161.2; LCMS (electrospray) m / z425,427 (M + H) + (Cl isotope standard). 6-Chloro-2-ethyl-N- (4- (4- (trifluoromethyl) piperidin-1-i) benzyl) imidazo [1,2-alpyridine-3-carboxamide (275)% hyas, das, - White solid ; melting point = 197.9 ºC; 1H NMR (400 MHz, CDCl3); 5 1.35 (t, J = 7.6 Hz, 3H), 1.68 - 1.82 (m, 2H), 1.94 - 1.97 (m, 2H), i 10 212-2.18 (m, 1H), 2.688 - 2.73 (m, 2H), 2.91 (q, 7 = 7.6 Hz, 2H), 3.73 - 3.77 (m, 2H), 4.58 ( d, J = 5.6 Hz, 2H), 6.04 (brt, J = 5.2 Hz, 1H), 6.91 (d J = 8.8 1 Hz, 2H), 7.25 - 7, 29 (m, 3H), 7.50 (d, J = 9.2 Hz, 1H), 9.50 (d, 7 = 1.2 Hz, 1H); LCMS (electrospray) m / z 465, 467 (M + H) + (CI isotope standard). T-Chloro-2-ethyl-N- (4- (4- (trifluoromethyl) piperidin-1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (276). o CD AA% nNh cr "N White solid; melting point = 209.4 ºC; 1H NMR (400 MHz, CDCl3); 5 1.34 (t, J = 7.6 Hz, 3H), 1.68 - 1.78 (m, 2H), 1.94 - 1.98 (m, 2H), 2.11 - 2.20 (m, 1H), 2.66 - 2.73 (m, 2H), 2, 90 (q, J = 7.6 Hz, 2H), 3.73 - 3.77 (m, 2H), 4.58 (d, J = 5.2 Hz, 2H), 6.03 (brt, J = 5.2 Hz, 1H), 6.86 (dd, JU = 2.4, 7.6Hz, 1H), 6.91 (d, J = 8.8Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.56 (d J = 2.4 Hz, 1H), 9.32 (d, J = 7.6 Hz, 1H); LCMS (electrospray) mz 465, 467 (M + H) + (Isotope standard C!). 6-Chloro-N- (4- (4,4-difluoropiperidin-1-yl) benzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (277) q
OS% .- Nha
SAN White solid; melting point = 194.2 ºC; 1H NMR (400 MHz, CDCl3); at 1.36 (t, J = 7.6 Hz, 3H), 1.98 - 2.13 (m, 4H), 2.92 (q, J = 7.6 Hz, 2H), 3.33 - 3.36 (m, 4H), 4.59 (d, J = 5.6 Hz, 2H), 6.04 (bit, J = 5.6 Hz, 1H), 6.91 - 6.95 (m , 2H), 7.25 - 7.30 (m, 3H), 7.52 (d, J = 9.6 Hz, 1H), 9.51 (d, J = 20Hz 1H); LCMS (electrospray) m / z 433, 435 (M + H) + (Isotope standard C!). 7-Chloro-N- (4- (4,4-difluoropiperidin-1-yl) benzyl) -2-ethylimidazo [1,2- º alpiridine-3-carboxamide (278)
F | LAS% X- no od e "N 'White solid; melting point = 166.3 ºC; 1H NMR (400 MHz, CDCl3); 51.34 (t J = 7.2 Hz, 3H), 2.03 - 2.12 (m, 4H), 2.90 (q, Jy = 7.2 Hz, - 2H), 3.32 - 3.35 (m, 4H), 4.58 (d, J = 5.2 Hz, 2H), 6.06 (brt, J = 5.2 Hz, 1H), 6.86 (dd, J = 2.0, 7.6 Hz, 1H), 6.91 (d, J = 8 , 4 Hz, 2H), 7.25 (d, J = 84 Hz, º 2H), 7.55 (d, J = 2.0 Hz, 1H), 9.31 (d, J = 7.6 Hz , 1H); LCMS (electrospray) m / z 433, 435 (M + H) + (Isotope standard C]). 6-Chloro-2-ethyl-N- (4- (4- (hydroxymethyl) piperidin- 1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (279) ADD
NH “od
SN Pale yellow solid; melting point = 161.1 ° C; 1H NMR (400 MHz, CDCl3); 5 1.23 - 1.41 (m, 2H), 1.33 (t, J = 7.6 Hz, 3H), 1.59 - 1.65 (m, 1H), 1.80 - 1.84 (m, 2H), 2.64 - 2.71 (m, 2H), 2.89 (q, J = 7.6 Hz, 2H), 3.50 (djJ = 6.4 Hz 2H), 3.66 -3.69 (m, 2H), 4.55 (d, J = 5.2 Hz, 2H), 6.09 (btt, J = /
5.2 Hz, 1H), 6.89 (d, J = 8.4 Hz, 2H), 7.21 (d J = 84 Hz, 2H), 7.23 (dd, J = 2.0, 9 , 2 Hz, 1H), 7.47 (d, J = 9.2 Hz, 1H), 9.45 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz, CDCIS) 5 13.3, 23.4, 28.7, 38.6, 43.3, 49.6, 67.6, 115.3, 116.8, 1 16.9, 121.5, 126.2, 128.2, 128.3, 128.8, 144.4, 151.3, 151.4, 161.1; LCMS (electrospray) m z 427.429 (M + H) + (CI isotope standard). 7-Chloro-2-ethyl-N- (4- (4- (hydroxymethyl) piperidin-1-iN) benzyl) imidazo [1,2-alpyridine-3-carboxamide (280) oH
ADS% nho White solid; melting point = 179.8 ºC; 1H NMR (400 MHz, - CDCl3); 5 1.33 (t, J = 7.6 Hz, 3H), 1.35 - 1.42 (m, 2H), 1.60 - 1.67 (m, 1H), 1.82-1.85 (m, 2H), 1.98 (brs, 1H), 2.66 - 2.73 (m, 2H), 2.91 (q, J = 7.6 Hz,. 2H), 3.52 (d , J = 6.4 Hz, 2H), 3.68 - 3.71 (m, 2H), 4.56 (d, J = 5.6 Hz, 2H), 6.04 (brt, JU = 5, 6 Hz, 1H), 6.86 (dd, J = 2.0, 7.6 Hz, 1H), 6.91 (d, J = 8.8 Hz,, 2H), 7.22 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 2.0 Hz, 1H), 9.380 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) 5 13.4, 23.5, 28.7, 38.6, 43.3, 49.7, 67.7, 1. 15 14.7,115.1, 115.7, 116.8, 128.3, 128.6, 128.8, 133.6, 146.1, 151.5, 151.6, 161.1; LCMS (electrospray) m / z 427, 429 (M + H) + (CI isotope standard). 6-Chloro-2-ethyl-N- (4- (4- (methoxymethyl) piperidin-1-iI) benzyl) imidazo ([1,2-alpyridine-3-carboxamide (281) ADD »% NH Se SN White solid ; melting point = 162.1 ºC; 1H NMR (400 MHz, CDCI3S); 5 1.34-1.57 (m, 2H), 1.36 (t, Ju = 7.6 Hz, 3H), 1 , 70 - 1.85 (m, 3H), 2.68 - 2.74 (m, 2H), 2.88 (q, J = 7.6 Hz, 2H), 3.25 (d, J = 6 , 4 Hz, 2H), 3.53 (s, 3H), 3.68 - 3.71 (m, 2H), 4.58 (d, J = 5.6 Hz, 2H), 5.98 (brt , J = 5.6 Hz, 1H), 6.92 (d, J = 8.4 Hz, 2H), 7.24 - 7.30 (m, 3H), 7.51 (d, J = 10, 0 Hz, 1H), 9.52 (d, 7 = 1.6 Hz, 1H); LCMS (electrospray) m / z 441, 443 (M + H) + (Standard | Cl isotope). 7-Chlorine-2 -ethyl-N- (4- (4- (methoxymethyl) piperidin-1-i) benzyl) imidazo [1,2-alpyridine-3-carboxamide (282) Dx with air AN White solid; melting point = 172.5 ºC; 1H NMR (400 MHz, —CDCI3); 51.33-1.43 (m, 2H), 1.35 (t J = 7.6 Hz, 3H),, 72 - 1.85 (m, 3H ), 2.67 - 2.74 (m, 2H), 2.90 (q, J = 7.6 Hz, 2H), 3.25 (d, J = 6.4 Hz, 2H), 3.35 (s, 3H), 3.68 - 3.71 (m, 2H), 4.58 (d, J = 5.2 Hz, 2H), 5.97 (brt, J = 5.2 Hz, 1H) , 1 6.88 (dd , J = 2.4, 7.6 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz,. 2H), 7.57 (d, J = 2.4 Hz, 1H), 9.34 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z2441,443 (M + H) + (CI isotope standard). 7-Chloro-2-ethyl-N- (4- (4-phenylpiperidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3- 'carboxamide (283) to O o RÁAN White solid; melting point = 164.5 ºC; 1H NMR (400 MHz, CDCl3); 5 1.36 (t, J = 7.6 Hz, 3H), 1.87 - 1.98 (m, 4H), 2.67 - 2.68 (m, 1H), 2.80-2.85 (m, 2H), 2.91 (q, J = 7.6 Hz, 2H), 3.80 - 3.83 (m, 2H), 4.59 (d, J = 5.6 Hz, 2H) , 6.01 (btt, J = 5.6 Hz, 1H), 6.87 (d, u = 7.6 Hz, 1H), 6.97 (d, JU = 8.4 Hz, 2H), 7 , 19 - 7.33 (m, 7H), 7.57 (s, 1H), 9.34 (d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.4, 23.6, 33.3, 42.6, 43.4, 50.5, 114.7, 115.1, 115.8, 116.9, 126 , 5, 127.0, 128.5, 128.6, 128.7, 128.9, 133.6, 146.1, 146.2, 151.5, 151.6, 161.2; LCMS (electrospray) m / z 473, 475 (M + H) + (Isotope pattern Cl). 6-Chloro-2-ethyl-N- (4- (4-phenylpiperidin-1-yl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (284) | the SI “the
N Pale yellow solid; melting point = 138.2 ºC; 1H NMR (400 MHz, CDCl3); 5 1.36 (1, J = 7.6 Hz, 3H), 1.84 - 1.97 (m, 4H), 2.62 - 2.69 (m, 1H), 2.79 - 2.86 (m, 2H), 2.92 (q, J = 7.6 Hz, 2H), 3.80 -3.83 (m, 2H), 4.60 (d, J = 5.2 Hz, 2H) , 6.07 (brt, J = 5.2 Hz, 1H), 6.97 (d, JU = 8.8 Hz, 2H), 7.19 - 7.33 (m 8H), 7.50 (d , J = 9.6 Hz, 1H), 9.50 (d, J = 2.0 Hz, 1H); 138C NMR (100 MHz, CDCI3) 5 13.3, 23.5, 33.3, 42.5, 43.3, 50.5, 1 15.4, 1 16.9, 1 17.0, 121, 6, 126.3, 126.4, 126.9, 128.2, 128.4, 128.6, 128.9, 144.4, 146.0, 151.3, 151.4, 161.1; LCMS (electrospray) m / z 473, 475 (M + H) + (Isotope- standard. Po Cl). 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperidine-1-yl) benzyl ) imidazo [1,2-a] pyridine-3-carboxamide (285) o
N: Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.37 (t J = - 7.6 Hz, 3H), 1.81 - 1.95 (m, 4H), 2.60 - 2.67 (m, 1H), 2.77 - 2.85 (m, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.79 - 3.82 (m, 2H), 4.61 (d, J = 5.6 Hz, 2H) , 6.02 (brs, 1H), 6.89 (ddd, J = 1.2.6.8, 6.8 Hz, 1H), 6.96 - 7.02 (m, 4H), 7.17 - 7.23 (m, 2H), 7.25 - 7.33 (m, 3H), 7.8 (d, J = 8.8 Hz, 1H), 9.39 (d, J = 6.8 Hz, 1H). 6-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperidin-1-yl) benzyl) imidazo ([1,2-alpyridine-3-carboxamide (286) GIVES LI
SEN White solid; melting point = 164.0 ºC; 1H NMR (400 MHz, CDCl3); 51.35 (t J = 7.6 Hz, 3H), 1.76 - 1.95 (m, 4H), 2.60 - 2.66 (m, 1H), q
2.78 - 2.85 (m, 2H), 2.92 (q, J = 7.6 Hz, 2H), 3.79 - 3.82 (m, 2H), 4.60 (d, J = 5.2 Hz, 2H), 6.08 (brt, J = 5.2 Hz, 1H), 6.96 - 7.01 (m, 4H), 7.17 - 7.21 (m, 2H), 7.26 - 7.29 (m, 3H), 7.51 (d, J = 9.6 Hz, 1H), 9.52 (d, J = 1.6 Hz, 1H); LCMS (electrospray) m / z 491 (M + H) +. T7-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) piperidin-1-yl) benzyl) imidazo] 1,2-alpyridine-3-carboxamide (287) OD "Xe
FAN White solid; melting point = 182.7 ºC; 1H NMR (400 MHz,: CDCl3); 5 1.35 (t, J = 7.6 Hz, 3H), 1.79 - 1.95 (m, 4H), 2.59 - 2.67 (m, 1H), 2.78 - 2.85 (m, 2H), 2.91 (q, J = 7.6 Hz, 2H), 3.79 - 3.82 (m, 2H), 4.59 (d, J = 5.6 Hz, 2H) , 6.03 (brt, J = 5.6 Hz, 1H), 6.87 (dd, y = 2.4.7.6 Hz, 1H), 6.96 -] 7.01 (m, 4H) , 7.17 - 7.21 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.57 (d J = 2.4. Hz, 1H), 9.33 ( d, J = 7.6 Hz, 1H); LCMS (electrospray) m / 2 491 (M + H) + 2-Ethyl-N- (4- (4- (4- (trifluoromethoxy) phenyl) piperidin-1-yl) benzyl) imidazo [1,2- '15 alpiridine-3-carboxamide (288) Pale yellow solid; melting point = 146.0 ºC; 1H NMR (400 MHz, CDCl3); 5 1.37 (t, Jy = 7.6 Hz, 3H), 1.81 - 1.96 (m, 4H), 2.63 - 2.69 (m, 1H), 2.79 - 2.86 (m, 2H), 2.94 (q, J = 7.6 Hz, 2H), 3.80 - 3.83 (m, 2H), 4.61 (d, 7 = 5.6 Hz, 2H) , 6.01 (brt, 7 = 5.6 Hz, 1H), 6.88 (ddd, J = 0.8, 6.8, 6.8 Hz, 1H), 6.97 (d, J = 8 , 8 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.24 - 7.33 (m, 5H), 7.58 (d, J = 8.8 Hz, 1H ), 9.39 (d, J = 6.8 Hz, 1H). 6-Chloro-2-ethyl-N- (4- (4- (4- (trifluoromethoxy) phenyl) piperidin-1-iN) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (289) |
O 'o. ST Be TN White solid; melting point = 164.0 ºC; 1H NMR (400 MHz, CDCl3); 5 1.37 (t J = 7.6 Hz, 3H), 1.81 - 1.96 (m, 4H), 2.63 - 2.70 (m, 1H), 2.79 - 2.86 ( m, 2H), 2.92 (q, Jy = 7.6 Hz, 2H), 3.80 - 3.83 (m, 2H), 4.60 (d, J = 5.2 Hz, 2H), 6.04 (brt, J = 5.2 Hz, 1H), 6.96 (d, / = 8.4 Hz, 2H), 7.14 (d, J = 84Hz 2H) 7.24-7.29 (m, 5H), 7.51 (d, J = 9.6 Hz, 1H), 9.51 (d, J = 1.6 Hz, 1H), 7-Chlorine-2-ethyl-N- (4 - (4- (4- (trifluoromethoxy) phenyl) piperidin-1- i) benzyl) imidazo [1,2-a] lpyridine-3-carboxamide (290); a A Xi or “SN White solid; 1H NMR (400 MHz, CDCl3); 5 1.36 (t, J = 7.6 Hz, 3H), 1.82-1.96 (m, 4H), 2.64 - 2.70 (m, 1H), 2.79 - 2.86 (m, 2H), 2.91 (q, J = Í 7.6 Hz, 2H), 3.80 - 3.83 (m, 2H), 4.59 (d, J = 5.36 Hz, 2H ), 6.04 (brs, 1H), 6.87 (dd, J = 1.6, 7.2 Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.24 - 7.28 (m, 4H), 7.57 (d, 7 = 1.6 Hz, 1H), 9.34 (d, J = 7.2 Hz, 1H). 6-Chloro-2-ethyl-N- (4- (4-lysopropoxymethyl) piperidin-1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (291) o THE
SS White solid; 1H NMR (400 MHz, CDCl3); 5 1.29 (d, J = 6.0 Hz, 6H), 1.46 - 1.56 (m, 2H), 1.50 (t, J = 7.6 Hz, 3H), 1.81 - 1.89 (m, 1H), 1.99 - 2.02 (m, 2H), 2.82 - 2.89 (m, 2H), 3.06 (q, J = 7.6 Hz, 2H) , 343 (d J = 6.4 Hz, 2H), 3.66 - 3.72 (m, 1H), 3.82 - 3.85 (m, 2H), 4.73 (d, J = 5, 6 Hz, 2H), 20 6.17 (brtJ = 5.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H ), |
7.40 (dd, J = 2.0, 9.2 Hz, 1H), 7.65 (d, J = 9.2 Hz, 1H), 9.65 (d, JU = 2.0 Hz, 1H ); 138C NMR (100 MHz, CDCI3) 5 13.3, 22.2, 23.6, 29.4, 36.6, 43.4, 49.7, 71.8, 73.3, 1 15.4, 1 16.8, 1 17.0, 121.5, 126.3, 128.2, 128.8, 144.5, 151.4, 151.6, 161.1 (hidden 1 aromatic carbon). 7-Chloro-2-ethyl-N- (4- (4-lysopropoxymethyl) piperidin-1-yl) benzyl) imidazo [1,2- a] pyridine-3-carboxamide (292)
N 2200 o RN White solid; 1H NMR (400 MHz, CDCl3); 5 1.14 (d, J = 6.0 Hz, 6H), 1.31 - 1.41 (m, 2H), 1.34 (t JU = 7.6 Hz, 3H), 1.66 - 1 , 73 (m, 1H), 1.84 - 1.87 (m, 2H), 2.67 - 2.74 (m, 2H), 2.90 (q, J = 7.6 Hz, 2H), 3.27 (d, J = 6.8 '10 Hz 2H), 3.50 - 3.56 (m, 1H), 3.67 - 3.70 (m, 2H), 4.57 (d, J = 5.6 Hz, 2H), 5.99 (brt, J = 5.6 Hz, 1H), 6.86 (dd, J = 2.0, 7.2 Hz, 1H), 6.91 (d , J- 8.4 Hz,, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.56 (d, J-1.6 Hz, 1H), 9.33 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.4, 22.2, 23.6, 29.4, 36.6, 43.4, 49.7, 71.8, '73.3, 114.7, 115.2, 115.8, 1 16.8, 128.2, 128.6, 128.8, 133.6, 146.1, 151.6, 151.7,161.2,. 6-Chloro-N- (4- (4- (cyclopentyloxymethyl) piperidin-1-yl) benzyl) -2-ethylimidazo [1,2-a] pyridine-3-carboxamide (293) XY nh “ed
AN White solid; 1H NMR (400 MHz, CDCl3); 5 1.28 - 1.38 (m, 2H), 1.32 (t J = 7.6 Hz, 3H), 1.46 - 1.51 (m, 2H), 1.58 - 1.66 ( m, 7H), 1.79 - 1.83 (m, 2H), 2.63-2.70 (m, 2H), 2.87 (q, J = 7.6 Hz, 2H), 3.21 (d, J = 6.4 Hz, 2H), 3.63 - 3.66 (m, 2H), 3.82 - 3.83 (m, 1H), 4.54 (d, J = 5.2 Hz, 2H), 6.08 (brt, J = 5.2 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 7.19 - 7.25 (m, 3H), 7.45 (d, J = 9.2 Hz, 1H), 9.44 (d, J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCI; 3) 5 13.2, 23.4, 23.6, 29.3, 32.3, 36.4, 43.3, 49.6, 73.7, 81.5 , 115.3, 116.6, 116.8, 121.4,126,2,128,0,128,1,128.7, 144.4, 151.3, 151.5, 161.0. q
N44- (4-Benzylpiperidin-1-yl) benzyl) -7-chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamide (294) ODDS
E NH a RAN White solid; melting point = 63.8 ºC; 1H NMR (400 MHz, CDC); 5 1.33 (t, J = 7.6 Hz, 3H), 1.37 - 1.44 (m, 2H), 1.63 - 1.70 (m, 1H), 1.72-1.76 (m 2H), 2.56 (d, J = 6.8Hz, 2H), 2.61 - 2.67 (m, 2H), 2.89 (q, J = 7.6 Hz, 2H), 3 , 63 - 3.66 (m, 2H), 4.56 (d, J = 5.2 Hz, 2H), 6.08 (brs, 1H), 6.84 - 6.87 (m, 1H), 6.89 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 7.2 Hz, 2H), 7.19 - 7.30 (m, 5H), 7.54 (d , J = 1.6 Hz, 1H), 9.29 - 9.32 (m, 1H); 13C NMR (100 MHz, CDCI3) 5 13.3, 23.5, 32.0, 37.9, 43.2, 43.3, 49.9, 1 14.6, 1 15.1, 115.7 , 116,7, '10 126,0,128,2, 128,3, 128,5, 128,8, 129,2, 133,5, 140,5, 146,0, 151,5, 151,6, 161 ,1 ; LCMS (electrospray) m / z 487, 489 (M + H) + (Cl isotope standard). . 2-Ethyl-N- (4- (4 - ((4-fluorophenoxy) methyl) piperidin-1-yl) benzyl) imidazo [1,2-alpiridine-3-carboxamide (295) O "o: White solid; melting range = 144.2 ° C; 1H NMR (400 MHz, CDCl3); 51.39 (t J = 7.2 Hz, 3H), 1.46 - 1.60 (m, 3H), 1.94 - 1 , 96 (m, 2H), 2.73 - 2.78 (m, 2H), 2.96 (q, J = 7.2 Hz, 2H), 3.73 (d, J = 12.0, 2H ), 3.80 (d, J = 6.0 Hz, 2H), 4.61 (d, J = 5.2 Hz, 2H), 5.99 (brs, 1H), 6.82 - 6.84 (m, 1H), 6.89 - 6.92 (m, 2H), 6.94 - 6.98 (m, 4H), 7.25 - 7.29 (m, 2H), 7.32 (d J = 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 7.2 Hz, 1H); LCMS (electroplating) m / z (M + H) + 487. 6-Chloro-2-ethyl-N- (4- (4 - ((4-fluorophenoxy) methyl) piperidin-1- i) benzyl) imidazo [1,2-a] lpiridine -3-carboxamide (296) Da 220 "O |
White solid; melting point = 171.0 ºC; 1H NMR (400 MHz, CDCl3); at 1.38 (t, J = 7.6 Hz, 3H), 1.50 - 1.56 (m, 2H), 1.94 - 1.96 (m, 3H), 2.72 - 2.79 (m, 2H), 2.95 (q, J = 7.6 Hz, 2H), 3.74 (d, J = 12.4 Hz, 2H), 3.80 (d, J = 5.6 Hz , 2H), 4.60 (d, J = 5.6 Hz, 2H), 6.01 (brs, 1H), 6.81 - 6.84 (m, 2H) 6.94-6.98 (m , 4H), 7.27-7.29 (m, 3H), 7.53 (d, J = 9.6 Hz, 1H), 9.52 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z (M + H) + 521. 7-Chloro-2-ethyl-N- (4- (4 - ((4-fluorophenoxy) methyl) piperidin-1- i) benzyl) imidazo [1 CD AA Oy Lo DI
E White solid; melting point = 186.5 ºC; 1H NMR (400 MHz, 10 CDCI3); 51.37 (t J = 7.6 Hz, 3H), 1.50 - 1.61 (m, 2H), 1.94 - 1.96 (m, 3H), 2.76 (t J = 10, 8 Hz, 2H), 2.98 (q, J = 7.6 Hz, 2H), 3.74 (d, J = 12.0 Hz, 2H), - 3.80 (d, J = 5.6 Hz, 2H), 4.59 (d, J = 5.6 Hz, 2H), 6.00 (brs, 1H), 6.80 -6.84 (m, 2H), 6.88 - 6.90 (m, 1H), 6.94 - 6.98 (m, 4H), 7.25-7.27 (m, 2H), 7.58 (d, 'J = 1.6 Hz, 1H), 9 , 34 (d, J = 8.0 Hz, 1H); LCMS (electrospray) m / z (MHH) +521. is 6-Chloro-2-ethyl-N- (4- (4 - ((4- (trifluoromethoxy) phenoxy) methyl) piperidin-1-iNbenzyl) imidazo [1,2-a] pyridine-3-carboxamide (298) : the ADE
SAS “et WI" N Pale yellow solid; melting point = 183.6 ºC; 1H NMR (400 MHz, CDCI3); 5 1.35 (t, J = 7.6 Hz, 3H), 1.46 - 1 , 57 (m, 2H), 1.93 - 1.96 (m, 3H) 2.72-2.78 (m, 2H), 2.91 (q, J = 7.6 Hz, 2H), 3 , 71 - 3.74 (m, 2H), 3.81 (d, 1 = 6.0 Hz, 2H), 4.58 (d, J = 5.6 Hz, 2H), 6.05 (brt, J = 5.6 Hz, 1H), 6.85 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 7.1 1 (d, J = 8.8 Hz, 2H), 7.24 - 7.28 (m, 3H), 7.50 d, J = 9.6 Hz, 1H), 9.50 (d, J = 1.2 Hz, 1H); LCMS (electrospray) m / z 587, 589 (M + H) + (Isotope standard C)). 7-Chloro-2-ethyl-N- (4- (4 - ((4- (trifluoromethoxyphenoxy ) methyl) piperidin-1- | iN) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (299) (Ç) or N,
OO cr AN White solid; melting point = 189.5 ºC; 1H NMR (400 MHz, CDCl3); 5 1.34 (t, J = 7.6 Hz, 3H), 1.46 - 1.56 (m, 2H), 1.98 - 2.02 (m, 3H), 2.71 - 2.78 (m, 2H), 2.90 (q, J = 7.6 Hz, 2H), 3.71 - 3.74 (m, 2H), 3.81 (d, J = 60Hz 2H), 4.57 (d, J = 5.2 Hz, 2H), 6.05 (btt, J = 5.2 Hz, 1H), 6.84 -6.87 (m, 3H), 6.93 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 2, 0 Hz, 1H), 9.31 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z 587, 589 (M + H) + (Cl isotope standard). "Ethyl 1- (4 - ((6-Chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamido) methyl) phenyl) piperidine-4-carboxylate (300) o A Da: Xi:
PN. White solid; 1H NMR (400 MHz, CDCl3); 5 1.23 (t, J = 7.2 Hz, 3H), 1.35 (t J = 7.2 Hz, 3H), 1.80 - 1.90 (m, 2H), 1.98 - 2 , 02 (m, 2H), 2.38 - i 2.46 (m, 1H), 2.75 - 2.82 (m, 2H), 2.91 (q, J] = 7.6 Hz, 2H ), 3.681 - 3.65 (m, 2H), 4.11 (q, J = 7.2 Hz, 2H), 4.57 (d, J = 5.6 Hz, 2H), 6.03 (brt , J = 5.6 Hz, 1H) 6.90 (d, J = 8.8 Hz, 2H), 7.23 - 7.28 (m, 3H), 7.49 (d, J = 9.6 Hz, 1H), 9.49 (d, J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.3, 14.4, 23.6, 28.1, 41.6, 43.3, 49.2, 60.6, 115.4, 116.9, 1 17.0, 121.5, 126.3, 128.2, 128.6, 128.9, 144.5, 151.2, 151.4, 161.1, 174.9. 1- (4 - ((7-Chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamido) methyl) phenyl) piperidine-4-carboxylate (301) | the o AND
LF to N White solid; 1H NMR (400 MHz, CDCl3); 5 1.21 (t J = 7.2 Hz, 3H), 1.381 (t J = 7.2 Hz, 3H), 1.77 - 1.87 (m, 2H), 1.96 - 2.00 ( m, 2H), 2.36 - 2.42 (m, 1H), 2.72 - 2.79 (m, 2H), 2.87 (q, J = 7.2 Hz, 2H), 3.58 - 3.63 (m, 2H), 4.089 (q, J = 7.2 Hz, 2H), 4.53 (d, J = 5.6 Hz, 2H), 6.12 (brt, J = 5, 6 Hz, 1H), 6.81 (dd J = 2.0.7.2 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 7.20 (d J = 8, 8 Hz, 2H), 7.51 (d, J = 2.0, 1H), 9.25 (d, JU = 7.2 Hz, 1H); 138C NMR (100 MHz, CDCI3) 5 13.3, 14.3, 23.4, 28.0, 41.0, 43.2, 49.1, 60.5, 114.5, 115.1, 115 , 6, 116.7, 128.4, 128.6, 128.8, 133.4, 146.0, 151.1, 151.5, 161.1, 174.8. '1- (4 - (((7-chloro-2-ethylimidazo [1,2-a] pyridine-3-carboxamido) methyl) phenyl) piperidine-4-carboxylic acid (302)' Oro% Nha ek a &,. White solid; * H NMR (400 MHz, DMSO-d6); 5 1.22 (t, J = 7.6 Hz, 3H), 1.57 - 1.66 (m, 2H), 1.84 - 1.88 (m, 2H), 2.29 - 2.34 (m, 1H), 2.67 - "2.73 (m, 2H), 2.92 (q, J = 7.6 Hz, 2H), 3.57 - 3.60 (m, 2H), 4 , 40 (d, J = 5.6 Hz, 2H), 5.75 (s, 1H), 6.89 (d, Jy = 8.4 Hz, 2H), 7.06 (dd, J = 1, 6, 7.6 Hz, 1H), 719 (d, J = 8, A4Hz, 2H), 7.77 (d, J = 1.6 Hz, 1H), 8.37 (brt, J = 5.6 Hz, 1H), 8.93 (d, J = 7.6 Hz, 1H). 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) imidazo] 1, 2-a] pyridine-3-carboxamide (303)
DA oO
Not
N White solid; melting point = 189.2 ºC; 1H NMR (400 MHz, CDCl3S) δ 1.40 (t J = 7.8 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 3.24 - 3.29 (m, |
2H), 3.32 - 3.36 (m, 2H), 4.63 (d, J = 5.6 Hz, 2H), 6.02 - 6.04 (m, 1H), 6.90 - 7 , 01 (m, 7H), 7.30 - 7.34 (m, 2H), 7.60 (d, J = 9.2 Hz, 1H), 9.41 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 458. 8- (Difluoromethoxy) -2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-ylbenzyl) imidazo [1,2- alpiridine-3-carboxamide (304)
DS bx NH x N OCHF, z Pale yellow; melting point = 186.3 ºC; 1H NMR (400 MHz, CDCI3) 5 1.38 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 3.24 - 3.27 (m , 4H), 3.34 - 3.36 (m, 4H), 4.63 (d, J = 5.6 Hz, 2H), 6.05 - 6.07 (m, 1H), 6.85. (dd, J = 7.2 Hz, 1H), 6.91 - 7.01 (m, 6H), 7.10 (d, J = 7.6 Hz, 2H), 7.26 (t J = 74 , 2Hz, 1H due to F2), 9.24 (d, J = 6.8 Hz, 1H); LCMS (electrospray) miz (M + H) + 524 Ú 8-Bromo-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) imidazo [1,2-. alpiridine-3-carboxamide (305) F
ROO. x N Br 7 - White solid; 1H NMR (400 MHz, CDCl3) 5 1.37 (t, J = 7.6 Hz, 3H) 3.00 (g J = 7.6 Hz, 2H), 3.23 -3.35 (m, 8H), 4 , 61 (d, J = 5.6 Hz, 2H), 6.08 (brs, 1H), 6.77 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 6.90 - 7 .00 (m, 6H), 7.29 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 7.2 Hz, 1H), 9.38 (d, J = 7, 2 Hz, IH) .; 13C MR (100 MHz, CDCI3) 5 14.1, 23.7, 43.4, 49.5, 50.6, 1 10.7, 113.3, 115.7, 115.9, 116.7, 118.4, 127.6, 129.0, 129.2, 129.4, 144.1, 148.0, 151.0, 151.5, 158.8, 161.3; LCMS (electrospray) m / z (M + H) + 538. 2-Ethyl-6-fluoro-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) imidazo [1,2-alpiridine-3-carboxamide ( 306) | F; OO
White solid; melting point = 200.9 ºC; 1H NMR (400 MHz, CDCI3) 5 1.40 (t, J = 7.8 Hz, 3H), 2.96 (q, J = 7.6 Hz, 2H), 3.24 - 3.29 (m , 2H), 3.32 - 3.36 (m, 2H), 4.62 (d, J = 5.6 Hz, 2H), 6.03 - 6.05 (m, 1H), 6.92 - 7.01 (m, 6H), 7.22 - 7.27 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.56 (dd, JU = 5.0, 98Hz 1H) 9.44-9.46 (m, 1H); LCMS (electrospray) m / z (M + H) + 476. 6-Bromo-2-ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) imidazo [1,2- alpiridine-3-carboxamide (307)
OP O, NH '"o
N] White solid; melting point = 218.1 ºC; 1H NMR (400 MHz, - CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.24 - 3.29 ( m, 2H) 3.31-3.36 (m, 2H), 4.62 (d, J = 5.6 Hz, 2H), 6.04 (t J = 5.0 Hz, 1H), 6, 92 - 7.01 (m, 6H), 7.31 (d, J = 8.8 Hz, 2H), 7.39 (dd, J = 2.0, 9.2 Hz, 1H),] 7, 49 (d, J = 9.6 Hz, 1H), 9.63 (d, / = 1.6 Hz, 1H); LCMS (electrospray) - m / z (M + H) + 536, 538 (Br isotope standard). 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -6-methylimidazo [1,2-alpyridine-3-carboxamide (308) Ff
OD% onh
WA N White solid; melting point = 187.6 * C; 1H NMR (400 MHz, CDCl3); 5 1.35 (t, J = 7.6 Hz, 3H), 2.89 (s, 3H), 2.91 (q, J = 7.6 Hz, 2H), 3.22 - 3.24 ( m, 4H), 3.31 - 3.33 (m, 4H), 4.60 (d, J = 5.2 Hz, 2H), 6.04 (bit, J = 5.2 Hz, 1H), 6.89 - 6.99 (m, 6H), 7.13 (dd, J = 1.6, 9.2 Hz, 1H), 7.28 (d, J = 8.4 Hz 2H) 7.46 (d, J = 9.2 Hz, 1H), 9.18 (s, 1H); LCMS (electrospray) m / z |
472 (M + H) +. 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -7-methylimidazo [1,2-aljpiridine-3-carboxamide (309) Dr a co Ss, White solid ; melting point = 203.7 ºC; 1H NMR (400 MHz, CDCl); 51.35 (t J = 7.6 Hz, 3H), 2.40 (s, 3H), 2.91 (q, J = 7.6 Hz, 2H), 3, 23 - 3.26 (m, 4H), 3.32 - 3.34 (m, 4H), 4.60 (d, J = 5.6 Hz, 2H), 6.02 (brt, J = 5: 6 Hz, 1H), 6.72 - 6.74 (m, 1H), 6.91 - 7.00 (m, 6H), 7.29 - 7.33 (m, 3H), 9.25 (d , J = 7.2 Hz, 1H); LCMS (electrospray) m / z 472 (M + H) +. 2-Ethyl-8-fluoro-N- (4- (4- (4-fluorophenyl) piperazin-1-i) benzyl) imidazo [1,2-alpyridine-3-carboxamide (310)
F - the% X Ne "N
F Ú Pale yellow solid; melting point = 204.1 ºC; 1H NMR (400 'MHz, CDCl3 + CD3; OD); at 1.34 (t, J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.24 - 3.26 (m, 4H), 3.33 - 3.35 (m, 4H), 4.60 (d, J = 5.6 Hz, 2H), 6.44 (brt, J = 5.6 Hz, 1H), 6.81 - 6.86 (m , 1H), 6.92 - 7.06 (m, 7H), 7.29 (d, J = 8.8 Hz, 2H) 9.08 (d, J = 6.8 Hz, 1H); LCMS (electrospray) m / z 476 (M + H) +. 7-Bromo-2-ethyl-N- (4- (4- (4-fluorophenyl) perazin-1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (311)
ADD e, NH
BS SN White solid; melting point = 214.6 “C; 1H NMR (400 MHz, CDC); 5 1.36 (t, J = 7.6 Hz, 3H), 2.92 (q, J = 7.6 Hz, 2H), 3.24 - 3.28 (m, |
4H), 3.33 - 3.35 (m, 4H), 4.60 (d, J = 5.2 Hz, 2H), 6.02 (brt, J = 5.2 Hz, 1H), 6, 91 - 7.02 (m, 7H), 7.28 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 1.6 Hz, 1H), 9.28 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z 536, 538 (M + H) + (Br isotope standard). 2-Ethyl-N- (4- (4- (4-fluorophenyl) piperazin-1-yl) benzyl) -8- (pyridin-4-iN) imidazo [1,2-a] pyridine-3-carboxamide (312 ) and ODAS "White solid; 1H NMR (400 MHz, CDCI3) at 1.40 (t J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 3.25 (t , J = 5.2 Hz, 4H), 3.34 (t, J = 5.2 Hz, 4H), 4.64 (d, J = 5.6 Hz, 2H), 6.10 (brs, 1H ), 6.91 - 7.04 (m, 7H), 7.32 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 5.2 Hz, 2H), 8.72 (d, J = 4.4 - Hz, 2H), 9.47 (d, J = 6.8 Hz, 1H); LCMS (electrospray) m / z (M + H) +
535. S 2-Ethyl-6-fluoro-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (313) oO
NH “os * White solid; melting point = 193.4 ºC; 1H NMR (400 MHz, CDCI3) 5 1.38 (t, J = 7.4 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.15 - 3.17 (m , 4H), 3.85 - 3.87 (m, 7H), 4.62 (d, J = 52 Hz, 2H), 6.00 - 6.02 (m, 1H), 6.92 (d, J = 9.6 Hz, 2H), 7.1 1 (dd, J = 2.4, 9.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 9.6 Hz, 1H), 9.10 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z (M + H) +395 2-Ethyl-7-methoxy-N- (4-morpholinobenzyl) imidazo [1,2-a] lpiridine-3-carboxamide (314) |
Do the AI
NH Meo RA White solid; 1H NMR (400 MHz, CDCl3); 5 1.33 (t, J = 7.6 Hz, 3H), 2.86 (q, J = 7.6 Hz, 2H), 3.12 - 3.14 (m, 4H), 3.80 - 3.88 (m, 4H), 3.83 (s, 3H), 4.56 (d, J = 5.6 Hz, 2H), 5.98 (brt, J = 5.6 Hz, 1H), 6.56 (dd, J = 2.4, 7.6 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H ), 7.25 (d, J = 8.8 Hz 2H), 9.19 (d, J = 7.6 Hz 1H); 188 NMR (100 MHz, CDCI3) 5 13.4, 23.5, A3.1, 49.4, 55.6, 67.0, 94.5, 107.4, 113.9, 116.0, 128 , 8, 128.9, 129.6, 148.1, 150.9, 151.0, 159.4, 161.5. 6-Bromo-2-ethyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (315) Ps
TI Br. 'Oa - 10 White solid; melting point = 228.2 ºC; 1H NMR (400 MHz, CDCl3); 5 1.38 (1, J = 7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 3.16 (t J = 4.8 Hz, 4H), 3, 86 (t, = 4.8 Hz, 4H), 4.61 (d, J = 5.6 Hz, 2H), 6.02 (brs, 1H), 6.91 (d, J = 8.8 Hz , 2H), 7.29 (d, Ju = 8.8 Hz, 2H), 7.38 (dd, J = 1.6 Hz, 9.6 Hz, - 1H), 7.48 (d, JU = 9.6 Hz, 1H), 9.61 (d, J = 0.8 Hz, 1H); LCMS (electrospray) m / z (M + H) + 443. 2-Ethyl-6-fluoro-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (316) a LO
Z oA White solid; melting point = 181.7 ºC; 1H NMR (400 MHz, CDC); 5 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 3.19 (t, J = 4.8 Hz, 4H) 3, 89 (t J = 4.8 Hz, 4H), 4.64 (d, J = 5.2 Hz, 2H), 6.02 (brs, 1H), 6.91 (d, J = 8.4 Hz, 2H), 7.26 - 7.33 (m, 3H), 7.60 (dd, J = 5.2 Hz, 5.4 Hz, 1H), 9.48 (dd, Jy = 2.4 Hz, 5.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 383. |
2-Ethyl-8-fluoro-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (317) re oo
E White solid; melting point = 197.3 ºC; 1H NMR (400 MHz, CDCl3); 5 1.39 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 3.15 - 3.17 (m, 4H) 3.85-3 , 87 (m, 4H), 4.61 (d, J = 5.6 Hz, 2H), 6.05 (brs, 1H), 6.80 - 6.85 (m, 1H), 6.92 ( d, J = 8.8 Hz, 2H), 7.00 - 7.05 (m, 1H), 7.29 (d, J = 8.8 Hz, 2H), 9.19 (dd, J = 0 , 8 Hz, 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 383. 2-Ethyl-8-methoxy-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (318) No 7 O. ST É
AND . Pale yellow solid; 1H NMR (400 MHz, CDCl3); ô 1.33 (t, J = 7.6 Hz, 3H), 2.92 (q, J = 7.6 Hz, 2H), 3.12 - 3.14 (m, 4H), 3.82 - 3.84 (m, 4H), * 3.98 (s, 3H), 4.58 (d, J = 5.6 Hz, 1H), 6.08 (brs, 1H), 6.57 (d, JU = 7.2 Hz, 1H), 6.75 (dd, J = 7.2, 7.2 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 7.26 ( d, J = 8.8 Hz, 2H) 8.93 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCI3) at 13.9, 236, 43.2, 49.3, 56.0, 67.0, 103.1, 113.0, 116.0, 120.9, 124.8 , 128.9, 129.4, 140.4, 148.2, 149.9, 150.9, 161.5. 8- (Difluoromethoxy) -2-ethyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (319) n » FO H
CS = TN OCHFz |
Not entirely white solid; melting point = 163.0 ºC; 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 2.97 (q, J = 7.6 Hz, 2H), 3.16 (t, J = 5 , 0 Hz, 4H), 3.86 (t, J = 4.8 Hz, 4H), 4.62 (d, J = 5.6 Hz, 2H), 6.03 -6.05 (m, 1H ), 6.85 (dd, J = 7.6 Hz, 2H), 6.92 (d, J = 6.8 Hz, 2H), 7.11 (d J = 76Hz, 1H), 7.26 ( t J = 74.2 Hz, 1H due to F2), 7.29 (d, J = 8.4 Hz, 2H), 9.25 (d, J = 7.2 Hz, 1H); LOMS (electrospray) m / z (M + H) + 431 8-Bromo-2-ethyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3-carboxamide (320) rs o, Ses Br White solid; 1H NMR (400 MHz, CDCl3) 5 1.36 (t, J = 7.6 Hz, 3H) 2.99 (q J = 7.6 Hz, 2H) 3.15 (t J = 4.8 Hz, 4H) , 3.85 (t J = 4.8 Hz, 4H), 4.60 (d, J = 5.2 Hz, 2H), 6.06 (brs, 1H), 6.77 (dd, J = 7 , 2 Hz, 1H), 6.90 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 2H), 7.56 (dd, J = 0.8 Hz, 7.2 Hz, 1H), 9.37 B (dd, J = 0.8 Hz, 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 445.: 2-Ethyl-N- (4-morpholinobenzyl) -6- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (321) TX: IA
NH “o" N White solid; melting point = 207.6 * C; 1H NMR (400 MHz, CDC); 5 1.37 (t J = 7.2 Hz, 3H), 2.94 (q, J = 7.2 Hz, 2H), 3.13 - 3.15 (m, 4H), 3.83 - 3.85 (m, 4H), 4.60 (d, JU = 5.2 Hz, 2H) , 6.10 (brs, 1H), 6.89 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.44 (d, J - 9.2 Hz, 1H), 7.65 (d, J = 9.2 Hz 1H) 9.82 (s 1H). 2-Ethyl-N- (4-morpholinobenzyl) -7 - (trifluoromethyl) imidazo [1 , 2-a] pyridine-s-carboxamide (322)> » FAITH
FAN nl |
White solid; melting point = 174.1 ºC; 1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 3.16 (t, J = 4 , 8 Hz, 4H), 3.86 (t, J = 4.8 Hz, 4H), 4.62 (d, J = 5.6 Hz, 2H), 6.09 - 6.11 (m, 1H ), 6.91 (d, J = 8.8 Hz, 2H), 7.07 (dd, J = 2.0, 7.6 Hz, 1H), 7.29 (d, J = 8.4 Hz , 2H) 7.88-7.90 (m, 1H), 9.50 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z (M + H) + 433 2-Ethyl-N- (4-morpholinobenzyl) -8- (trifluoromethyl) imidazo [1,2-a] pyridine-3-carboxamide (323) A. NX son and
SE SN CF; 3 White solid; melting point = 200.6 ºC; 1H NMR (400 MHz, CDC); 5 1.34 (t J = 7.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 3.14 - 3.16 (m, '4H), 3.83 - 3.86 (m, 4H), 4.60 (d, J = 5.6 Hz, 2H), 6.11 (brt, J = 5.6 Hz, 1H), 6.89 (d, J = 8 , 8 Hz, 2H), 6.93 (dd, J = 6.8, 6.8 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 6.8 Hz, 1H), 9.54 (d, J = 6.8 Hz, 1H). 7-Bromo-2-ethyl-N- (4-morpholinobenzyl) imidazo [1,2-a] pyridine-3- 7 15 carboxamide (324)
OO% ah cs and bs, Pale gray solid; melting point = 202.6 ºC; 1H NMR (400 MHz, CDCIs); 1.34 (1, J = 7.6 Hz, 3H), 2.90 (q, J = 7.6 Hz, 2H), 3.13 - 3.15 (m, 4H), 3.83 - 3 , 86 (m, 4H), 4.58 (d, J = 5.6 Hz, 2H), 6.05 (brt, J = 5.6 Hz, 1H), 6.88 (d, J = 8, 8 Hz, 2H), 6.97 (dd, J = 2.0, 7.2 Hz, 1H), 7.26 (d, J = 8.8 Hz 2H), 7.74 (d J = 2, 0 Hz, 1H), 9.25 (d, J = 7.2 Hz, 1H); 180 NMR (100 MHz, CDCIs) 5 13.4, 23.5, 43.2, 49.3, 67.0, 115.1, 116.0, 117.0, 119.1, 121.1, 128 , 5, 128.9, 129.2, 143.6, 151.0, 151.4, 161.2; LCMS (electrospray) m / z 443, 445 (M + H) + (Br isotope standard). 2-Ethyl-N- (4-morpholinobenzyl) -7- (pyridin-4-i) imidazo [1,2- | alpiridine-3-carboxamide (325) OD AND AT
SE No yellow solid; melting point = 210.1 ºC; 1H NMR (400 MHz, CDCl3); 5 1.37 (t J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.12 - 3.15 (m, 4H) 3.82-3, 85 (m, 4H), 4.60 (d, J = 5.2 Hz, 2H), 6.16 (brt, J = 5.2 Hz, 1H), 6.88 (d, J = 8.8 Hz, 2H), 7.16 (dd, J = 2.0, 7.2 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.53 (d, / = 6 , 0 Hz, 2H), 7.85 (d, J = 2.0 Hz, 1H), 8.88 (d, JU = 6.0 Hz, 2H), 9.44 (d, JU = 7.2 Hz, 1H); 18C NMR (100 MHz, CDCI3) 5 13.3, 23.6, 43.2, 49.3, 66.9, 111.8, 114.3, 115.3, 116.0, 121.2, 128 , 6, 128.9, 129.2, 136.3, 145.5, 146.1, 150.7, 151.0, 151.9, 161.2; LCMS (electrospray) m / z 442. (M + H) +, 2-Ethyl-N- (4-morpholinobenzyl) -7- (pyridin-3-i) irnidazo [1,2-a] pyridine-3- 'carboxamide (326) o! the LIA
NH Ns: '"N no Yellow solid; melting point = 208.5 ºC; 1H NMR (400 MHz, CDC); 51.36 (t J = 7.2 Hz, 3H), 2.93 (q, J = 7.2 Hz, 2H), 3.12 - 3.15 (m, 4H), 3.82 - 3.85 (m, 4H), 4.59 (d, J = 4.8 Hz, 2H) , 6.21 (brs, 1H), 6.87 (d, J = 8.4 Hz; 2H), 7.12 (d, J = 6.0 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.37 (dd, JU = 5.6, 6.0 Hz, 1H), 7.77 (brs, 1H), 7.90 (d, 1 = 7.2 Hz, 1H), 8.60 (brs, 1H), 8.88 (brs, 1H), 9.41 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) 5 13.3, 23.5, 43.2, 49.3, 66.9, 112.2, 113.8, 115.0, 1 16.0, 123.9, 128.5, 128.9, 129.3, 134 , 0, 134.2, 136.2, 146.3, 148.0, 149.6, 150.9, 151.7, 161.3; LCMS (electrospray) m / z 442 (M + H) +. 2-Ethyl-N- (4-morpholinobenzyl) -8B- (pyridin-4-yl) imidazo [1,2-a] pyridine-3- | carboxamide (327)
FLIGHT o White solid; 1H NMR (400 MHz, CDCI; 3) 5 1.40 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 3.16 (t, J = 4.8 Hz, 4H), 3.86 (t, J = 4.8 Hz, 4H), 4.63 (d, J = 5.6 Hz, 2H), 6.07 (brs, 1H), 6.92 (d, J = 8.8 Hz, 2H), 7.02 (dd, JU = 68Hz 6.8 Hz, 1H), 7.31 (d J = 8.8 Hz, 2H), 7, 54 (dd, J = 1.2 Hz, 7.2 Hz, 1H), 7.99 (d, J = 6.0 Hz, 2H), 8.72 (d, J = 5.2 Hz, 2H) , 9.47 (dd, J = 1.2 Hz, 5.6 Hz, 1H); LCMS (electrospray) m / z (M + H) + 442, 2-Ethyl-7- (4-methylpiperazin-1-yl) -N- (4-morpholinobenzyl) imidazo [1,2-alpiridine-3-carboxamide ( 328)
Xsh ck Ss. ds: | O White solid; melting point = 204.8 “C; 1H NMR (400 MHz, 'CDC); 5 1.33 (t, J = 7.6 Hz, 3H), 2.33 (s, 3H), 2.54 - 2.56 (m, 4H), 2.85 (q, J = 7.6 Hz, 2H), 3.12 - 3.15 (m, 4H), 3.27 - 3.30 (m, 4H), 3.83 - 3.85 (m, 4H), 4.57 (d, J = 5.6 Hz, 2H), 5.91 (brt, J = 5.6 Hz, 1H), 6.62 (dd, J = 244, 8.0 Hz, 1H), 6.5 (d, J = 2.4 Hz, 1H), 6.88 (d, JU = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 9.16 (d, J = 80 Hz, 1H); 13C NMR (100 MHz, CDCI3) 5 13.4, 23.6, 43.1, 46.2, 47.8, 49.4, 54.7, 67.0, 96.4, 105.9, 1 13.2, 116.0, 128.3, 128.8, 129.8, 148.5, 150.0, 150.9, 151.2, 161.7; LCMS (electrospray) m / z 463 (M + H) +. 2-Ethyl-7- (4- (4-fluorophenyl) piperazin-1-yl) - N- (4-morpholinobenzyl) imidazo [1,2-alpyridine-3-carboxamide (329) |
> »A no
DP White solid; 1H NMR (400 MHz, CDCIs); 5 1.34 (t J = 7.6 Hz, 3H), 2.87 (q, J = 7.6 Hz, 2H), 3.13 - 3.15 (m, 4H), 3.22 - 3 , 25 (m, 4H), 3.41 - 3.43 (m, 4H), 3.83 - 3.86 (m, 4H), 4.58 (d, J = 5.2 Hz, 2H), 5.99 (brt, J = 5.2 Hz, 1H), 6.67 (dd, J = 2.4, 8.0 Hz, 1H), 6.81 (d, J = 2.4 Hz, 1H ), 6.88 - 6.93 (m 4H), 6.96 (dd, J = 8.4.8.8Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 9 , 19 (d J = 8.0 Hz, 1H); LCMS (electrospray) m / z 543 (M + H) +. 2-Ethyl-7- (4-phenylpiperazin-1-yl) -N- (4- (trifluoromethyl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (330) A ”% X NH Pale yellow solid; melting point = 235.2 ºC; 1H NMR (400.10 MHz, CDC); 5 1.40 (t J = 7.2 Hz, 3H), 2.93 (q, J = 7.2 Hz, 2H), 3.34 - 3.36 (m, 4H), 3.44 - 3 , 48 (m, 4H), 4.74 (d, J = 6.0 Hz, H), 6.07 (brt, J = 6.0 Hz,. 1H), 6.70 (dd, J = 2 , 4, 7.6 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.90 (dd, J = 7.2, 7.6 Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 7.28 - 7.32 (m, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.61 (d, JU = 8.4 Hz, 2H), 9.22 (d, J = 7.6 Hz, 1H); LCMS (electrospray) m / z508 (M + H) t. 2-Ethyl-7- (4- (4-fluorobenzyl) piperazin-1-i1) -N- (4-morpholinobenzyl) imidazo [1,2-alpiridine-3-carboxamide (331) OO T. NA,
And what. White solid; melting point = 212.5 ºC; 1H NMR (400 MHz, CDCl3); 5 1.38 (t J = 7.6 Hz, 3H), 2.56 - 2.58 (m, 4H), 2.85 (q, J = 7.6 Hz, q
2H), 3.13 - 3.15 (m, 4H), 3.26 - 3.29 (m, 4H), 3.51 (s, 2H), 3.83 - 3.86 (m, 4H) , 4.57 (d, J = 5.6 Hz, 2H), 5.93 (brt, J = 5.6 Hz, 1H), 86.62 (dd, J = 2.4.7.6 Hz, 1H), 6.75 (d, J = 2.4 Hz, 1H), 6.88 (d, J = 8.8 Hz, 2H), 6.98 - 7.03 (m, 2H), 7, 26 - 7.31 (m, 4H), 9.15 (d, J = 7.6 Hz, 1H). 6-Chloro-2-ethyl-N- (4 - ((4- (morpholine-4-carbonyl) benzyl) carbamoyl) benzyl) imidazo [1,2-a] pyridine-3-carboxamide (332) oo oe Oo Solid White; 1H NMR (400 MHz, CDCI3) at 1.40 (t J = 1.6 Hz, 3H), 2.98 (q, J = 7.6 Hz, 2H), 3.72 (m, 8H), 4.65 (d, J = 6.0 Hz, 2H), 4.73 (d, J = 6.0 Hz, 2H), 6.29 (brs, 1H), 6.62 (brs, 1H), 7.31 (dd, J = 2.0 Hz, 9.6 Hz, 1H), 7.36 (s, 4H), 7.43 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 9.6 Hz, 1H), 7.80 (d, J. = 8.0 Hz, 2H), 9.49 (s, 1H); LCMS (electrospray) m / z (M + H) + 560. 7-Chloro-2-ethyl-N- (4- (morpholine-4-carbonyl) benzyl) imidazo [1,2-a] pyridine-3- ' carboxamide (333) EH,
LET. 15 White solid; 1H NMR (400 MHz, CDCI3) 5 1.42 (t, J = 7.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 3.70 - 3.71 (m , 8H), 4.72 (d, J = 6.0 Hz, 2H), 6.17 (brs, 1H), 7.31 (dd, J = 2.0 Hz, 9.2 Hz, 1H), 7.42 (s, 4H), 7.55 (dd, J = 0.8 Hz, 9.6 Hz, 1H), 9.53 (dd, J = 0.8 Hz, 2.0 Hz, 1H) .; LCMS (electrospray) m / z (M + H) + 427. 2-Ethyl-N - ((2- (4-fluorophenyl) benzo [d] oxazol-S-yl)] | methyl) imidazo [1, 2-alpiridine-3-carboxamide EA Ro. White solid; 1H NMR (400 MHz, DMSO-ds) 5 1.25 (t, J = 7.6 Hz, 3H), 2.99 (q, Jy = 7.6 Hz, 2H), 4.65 (d, J = 6.0 Hz, 2H), 6.99 (dd, J = 7.2 Hz, 1H), 7.36 (dd, J = 6.8 Hz, 1H), 7.42 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.58 '
(d, J = 9.2 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 8.23 (dd, J = 5.2 Hz , 8.8 Hz, 2H), 8.47 (t, J = 6.0 Hz, 1H), 8.97 (d, J = 6.8 Hz, 1H); LCMS (e-electrovaporization) m / z (M + H) + 415. 6-Chloro-2-ethyl-N - ((2- (4-fluorophenyl) benzo [d] oxazol-5-yl)] methyl) imidazo [1,2-alpyridine-3-carboxamide E oo.
F White solid; 1H NMR (400 MHz, DMSO-d6) 5 1.25 (t, J = 1.6 Hz, 3H), 2.99 (q, J = 7.6 Hz, 2H), 4.65 (d, J = 5.6 Hz, 2H), 7.41 - 7.46 (m, 4H), 7.64 (d, J = 9.6 Hz, 1H), 7.74 (d, J = 8.4 Hz , 1H), 7.78 (s, 1H), 8.21 - 8.25 (m, 2H), 8.54 (t, J = 5.6 Hz, 1H), 9.08 (d, J = 2.0 Hz, 1H); LCMS (electrovaporization) m / z (M + H) + 449. T7-Chloro-2-ethyl-N - ((2- (4-fluorophenyl) benzo [d] oxazol-5-i) methyl) imidazo [ 1,2-alpyridine-3-carboxamide (336) Qu Os LEO,. White solid; 1H NMR (400 MHz, DMSO-ds) 5 1.25 (t, JU = 7.2 Hz, 3H), 2.98 (q, J = 7.2 Hz, 2H), 4.64 (d, J = 5.6 Hz, 2H), 7.07 (d, J = 7.6: 15 Hz, 1H), 7.42-7.46 (m, 3H), 7.75 (d, J = 8, 4 Hz, 2H), 7.77 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 8.55 (brs, 1H), 8.96 (d, J = 7, 2 Hz, 1H); LCMS (electrospray, zation) m / z (M + H) + 449. 6-Chlorine-N- (4- (4- (4-chlorophenyl) piperidin-1-yl) benzyl) -2-ethylimidazo [1, 2- alpiridine-3-carboxamide (337) OO 2 and Pale yellow solid; 1H NMR (400 MHz, CDCIa) 5 1.39 (t, J = 7.6 Hz, 3H), 1.80 - 1.96 (m, 4H), 2.60 - 2.68 (m, 1H) , 2.92 - 2.98 (m, 4H), 2.95 (q, J = 7.6 Hz, 2H), 3.79 - 3.83 (m, 2H), 4.61 (q, J = 5.2 Hz, 2H), 5.99 - 6.01 (m, 1H), 6.90 (dd, J = 2.2.7.4 Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.26 - 7.29 (m, 4H), 7.59 (d, J = 2.0 Hz, 1H), 9.30 (d, J = 7.6 Hz 1H) LCMS (electrospray) m / z (M + H) + 507 q
7-Chloro-N- (4- (4- (4-chlorophenyl) piperidin-1-i) benzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (338) OF
LE Pale yellow solid; melting point = 177.0 ºC; 1H NMR (400 MHz, CDCl3) 5 1.40 (t, J = 7.4 Hz, 3H), 1.80 - 1.96 (m, 4H), 2.60 - 2.67 (m, 1H) 2.79-2.86 (m, 4H), 2.96 (q, J = 7.4 Hz, 2H), 3.80 - 3.83 (m, 2H), 4.62 (q, J = 5.2 Hz, 2H), 6.00 - 6.02 (m, 1H), 6.98 (dd, J = 8.8 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.26 - 7.31 (m, 4H), 7.54 (d, J = 9.6 Hz, 2H), 9.30 (d, J = 7.6 Hz, 1H). 6-Chloro-N - (((2-cyclohexylbenzo [d] oxazol-5-yl) methyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (339). AA EA O
SW N White solid; melting point = 169.7 ºC; 1H NMR (400 MHz, CDCl3) 5 1.30 - 1.44 (m, 4H), 1.59 - 1.88 (m, 8H), 2.16 (d, J = 10.8 Hz, 2H) , '2.96 (q, J = 7.6 Hz, 2H), 4.78 (d, J = 5.6 Hz, 2H), 6.19 (brs, 1H), 7.28 (d, 4 = - 1.6 Hz, 1H), 7.30 - 7.34 (m, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 9.2 Hz, 1H), 7.67 (s, 1H), 9.53 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z (M + H) + 437, T-Chlorine-N - (((2-cyclohexylbenzo [d] oxazol-5-yl)] methyl) -2-ethylimidazo [1,2-alpiridine-3 -carboxamide (340) or LOS cr EN. White solid; melting point = 163.0 ºC; 1H NMR (400 MHz, CDCl;) 51.30-1.46 (m, 6H), 1.60 - 1.73 (m, 4H), 1.86 (d, J = 13.2 Hz, 2H) , 2.15 (d, J = 13.2 Hz, 2H), 2.95 (q, J = 7.2 Hz, 2H), 4.77 (d, J = 5.6 Hz, 2H), |
6.12 (brs, 1H), 6.89 (d, J = 7.2 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8 , 0 Hz, 1H), 7.58 (s, 1H), 7.67 (s, 1H), 9.36 (d, J = 7.2 Hz, 1H),; LCMS (electrovaporization) m / z (M + H) + 437. 6-Chloro-2-ethyl-N- (4 - ([4- (4-fluorophenyl) -4-hydroxypiperidin-1-ylbenzi) imidazo [ 1,2-a] pyridine-3-carboxamide (341) o Fr White solid; melting point = 173.5 ° C; 1H NMR (400 MHz, CDC) 5 1.35 (t, J = 7.6 Hz, 3H), 1.66 (s, 1H), 1.85 (d, uy = 12.0 Hz, 2H), 2.18 - 2.26 (m, 2H), 2.91 (q, J = 7 , 6 Hz, 2H), 3.21 - 3.26 (dd, J = 10.4 Hz, 12.0 Hz, 2H), 3.58 (d, J = 1 1.6 Hz, 2H), 4 , 60 (d, J = 5.6 Hz, 2H), 86.00 (brs, 1H), 6.89 (dd J = 1.6 Hz, 7.6 Hz, 1H), 6.99 (d, J = 8.4 Hz, 2H), 7.04 (dd, JU = 8.8 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.48 (dd, J = 5 , 2 Hz, 8.8 Hz, 2H), 7.56 (d, J = 2.0 Hz, 1H), 9.35 (d, J = 7.6 Hz, 1H).; LCMS (electrospray) m / zi (M + H) + 507. 7-Chloro-2-ethyl-N- (4- (4- (4-fluorophenyl) -4-hydroxypiperidin-1-ylbenzylimidazo [1,2-a] lpiridine-3 -carboxamide (342) u H 'N. ao a - a =, F White solid; melting point = 199.0 “ºC; 1H NMR (400 MHz, CDCl3) 5 1.38 (t, J = 7.6 Hz, 3H), 1.6 (s, 1H), 1.86 (dd, J = 2.8 Hz, 14.0Hz, 2H), 2.19 - 2.26 (m, 2H), 2 , 95 (q, J = 7.6 Hz, 2H), 3.20 -3.27 (m, 2H), 3.59 (dd, J = 2.4 Hz, 10.0 Hz, 2H), 4 , 61 (d, Jy = 5.6 Hz, 2H), 6.02 (s, 1H), 6.98 - 7.06 (m 4H), 7.27 (d, J = 8.8 Hz, 2H ), 7.29 (s, 1H), 7.46 - 7.51 (m, 2H), 7.53 (s, 1H), 9.52 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z (M + H) +
507. N- (4- (4-Carbamoylpiperidin-1-yl) benzyl) -6-chloro-2-ethylimidazo [1,2-alpyridine-3-carboxamide (343) | O
ADD% onh “o
N White solid; melting point = 257.5 ºC; 1H NMR (400 MHz, DMSO-ds); 5 1.23 (t, J = 7.2 Hz, 3H), 1.57 - 1.66 (m, 2H), 1.74 - 1.76 (m, 2H), 2.19 - 245 (m , 1H), 2.59 - 2.66 (m, 2H), 2.94 (q, J = 7.2 Hz, 2H), 3.65 - 3.69 (m, 2H), 4.41 ( d, J = 6.0 Hz, 2H), 6.75 (brs, 1H), 6.90 (d, J = 8.4 Hz, 2H), 7.20 (d J = 8.4 Hz, 2H ), 7.26 (brs, 1H), 7.43 (dd, J = 2.4, 9.6 Hz, 1H), 7.67 (d, J = 9.6 Hz, 1H), 8.38 (brt, JU = 6.0 Hz, 1H), 9.06 (d, J = 2.4 Hz, 1H); LCMS (electrospray) m / z 440 (M + H) +. N- (4- (4-Carbamoylpiperidin-1-yl) benzyl) -7-chloro-2-ethylimidazo [1,2-alpyridine-3-carboxamide (344) o AD Dm '% rh - a = White solid; melting point = 244 “C; 1H NMR (400 MHz, 'DMSO-ds); 5 1.23 (t, J = 7.2 Hz, 3H), 1.56 - 1.66 (m, 2H), 1.74 - 1.76 (m, 2H),. 2.18 - 2.24 (m, 1H), 2.59 - 2.66 (m, 2H), 2.92 (q, J = 7.2 Hz, 2H), 3.65 - 3.68 ( m, 2H), 4.40 (d, J = 5.6 Hz, 2H), 6.75 (brs, 1H), 6.89 (d, Ju = 8.8 Hz, 2H), 7.07 ( dd, uy = 2.0, 7.6 Hz, 1H), 7.19 (d, Ju = 8.8 Hz, 2H), 7.25 (brs, 1H), 7.77 (dJ = 2.0Hz , 1H), 8.36 (brt, J = 5.6 Hz, 1H), 8.93 (d, Jy = 7.6 Hz, 1H); LCMS (electrospray) m / z 440 (M + H) +. 6-Chloro-N- (4- (4- (dimethylcarbamoyl) piperidin-1-yl) benzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (345) o A Dr o NH
SN |
White solid; 1H NMR (400 MHz, CDCIs); 5 1.35 (t, J = 7.6 Hz, 3H), 1.78 - 1.81 (m, 2H), 1.90 - 2.00 (m, 2H), 2.59 - 2.67 (m, 1H), 2.71 - 7.78 (m, 2H), 2.91 - 2.97 (m, 5H), 3.07 (s, 3H), 3.73 - 3.76 (m , 2H), 4.57 (d J = 5.2 Hz, 2H), 6.03 (brt, J = 5.2 Hz, 1H), 6.90 (d, J = 8.4 Hz, 2H) , 7.23 - 7.28 (m, 3H) 7.50 (d, J = 96 Hz, 1H), 9.50 (d, J = 1.2 Hz, 1H); 18C NMR (100 MHz, CDCI3) 5 13.3, 23.6, 28.4, 35.8, 37.2, 38.7, 43.3, 49.3, 1 15.4, 116.7, 117.0, 121.5, 126.3, 128.2, 128.5, 128.9, 144.5, 151.3, 151.4, 161.1, 174.7; LCMS (electrospray) m / z 468 (M + H) +. 7-Chloro-N- (4- (4- (dimethylcarbamoyl) piperidin-1-yl) benzyl) -2-ethylimidazo [1,2-alpyridine-3-carboxamide (346) o
AD x NH. cr RAN O Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.33 (tl J = '7.2 Hz, 3H), 1.77 - 1.80 (m, 2H), 1.88 - 1.99 (m, 2H), 2.58 - 2.66 (m, 1H), 2.70 - 2.77 (m, 2H), 2.89 - 2.95 (m, 5H), 3.06 (s, 3H), 3.71 - 3.74 (m , 2H),. 4.56 (d, J = 5.2 Hz, 2H), 6.07 (brs, 1H), 6.84 (dd, J = 1.6, 7.2 Hz, 1H), 6.89 (df J = 84Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 1.6 Hz, 1H), 9.30 (d, 'J = 7, 2 Hz, 1H); 138C NMR (100 MHz, CDCI3) 5 13.4, 23.5, 28.4, 35.8, 37.2, 38.7, 43.3, 49.3, 114.6, 115.1, 115 , 7, 1 16.7, 128.5, 128.6, 128.8, 133.5, 146.1, 151.2, 151.6, 161.2, 174.7; LCMS (electrospray) m / z 468 (M + H) +. 6-Chloro-2-ethyl-N- (4- (4- [4-fluorobenzyloxy) piperidin-1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (347) LI "
O to NH
TN Pale pink solid; 1H NMR (400 MHz, CDCl3); 5 1.35 (t J = 7.6 '
Hz, 3H), 1.73 - 1.82 (m, 2H), 2.00 - 2.04 (m, 2H), 2.91 - 2.98 (m, 4H), 3.50 - 3, 59 (m, 3H), 4.53 (s, 2H), 4.58 (d, J = 5.2 Hz, 2H), 6.00 (brt, JU = 5.2 Hz, 1H), 6, 91 (d, J = 8.8 Hz, 2H), 6.99 - 7.04 (m, 2H), 7.23 - 7.35 (m, 5H), 7.50 (d, J = 9, 6 Hz, 1H), 9.51 (d, J = 2.0 Hz, 1H); LCMS (electrospray) m / z 521 (MHH) + 7-Chloro-2-ethyl-N- (4- (4- (4-fluorobenzyloxy) piperidin-1-yl) benzyl) imidazo [1,2-alpiridine-3 -carboxamide (348) SO ”
QT% ni Cr No Pale pink solid; 1H NMR (400 MHz, CDCl3); 5 1.34 (t, J = 7.2 Hz, 3H), 1.73 - 1.82 (m, 2H), 1.96 - 2.07 (m, 2H), 2.91 - 2.95 (m, 4H), 3.49 - 3.59 (m, 3H), 4.52 (s, 2H), 4.56 (d, J = 5.6 Hz, 2H), 5.99 (brt, J = 5.6 Hz, 1H), '6.86 - 6.92 (m, 3H), 6.99 - 7.03 (m, 2H), 7.22 - 7.32 (m, 4H), 7.55 (d, J = 1.6 Hz, 1H), 9.32 (d, J = 7.2 Hz, 1H); LCMS (electrospray) m / z 521 (M + H) +. 6-Chloro-N- (3-chloro-4-morpholinobenzyl) -2-ethylimidazo [1,2-a] pyridine-3- '15 carboxamide (349) Do Na
SN White solid; melting point = 175.5 ºC; 1H NMR (400 MHz, CDC); 5 1.37 (tl J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 2.99 - 3.03 (m, 4H), 3.83 - 3 , 85 (m, 4H), 4.58 (d, J = 6.0 Hz, 2H), 6.45 (brt, J = 6.0 Hz, 1H), 6.99 (d, J = 8, 0 Hz, 1H), 7.21 (dd, J = 1.6, 8.0 Hz, 1H), 7.26 - 7.28 (m, 1H), 7.36 (d, J = 1.6Hz , 1H), 7.49 (d, J = 9.2 Hz, 1H), 9.47 (d, J = 0.8 Hz, 1H); 13C NMR (100 MHz, CDCI3) at 13.3, 23.7, 42.7, 51.8, 67.2, 115.1, 117.0, 120.7, 121.7, 126.3, 127 , 0, 128.4, 129.2, 130.1, 134.0, 144.6, 148.6, 151.6, 161.2; LCMS (electrospray) m / z 433 (M + H) +. 7-Chloro-N- (3-chloro-4-morpholinobenzyl) -2-ethylimidazo] 1,2-a] pyridine-3-q carboxamide (350)
LOS NX NH o cr N Pale yellow solid; 1H NMR (400 MHz, CDCI; 3); 5 1.38 (t, J = 7.6 Hz, 3H), 2.94 (q, J = 7.6 Hz, 2H), 3.02 - 3.05 (m, 4H), 3.85 - 3.87 (m, 4H), 4.59 (d, J = 5.6 Hz, 2H), 6.09 (brt, J = 5.6 Hz, 1H), 6.88 (dd, J = 2 , 0, 7.2 Hz, 1H) 7.00 (d, J = 8.0 Hz, 1H), 7.22 (dd, J = 1.6.8.0 Hz, 1H), 7.37 (d 1 = 1.6 Hz, 1H), 7.57 (d, J = 2.0 Hz, 1H), 9.32 (d, J = 7.2 Hz, 1H); 18C NMR (100. MHz, CDCIs) 5 13.4, 23.7, 42.7, 51.8, 67.3, 1 14.9, 1 15.8, 120.7, 127.1, 128, 6, 129.2, 130.1, 133.8, 134.0, 146.3, 148.7, 151.9, 161.3 (hidden 1 carbon); LCMS (electrospray) m / z 433 (M + H) +. 6-Chloro-2-ethyl-N- (4- (4-formylpiperidin-1-yl) benzyl) imidazo | 1,2-a] pyridine-3-carboxamide (351) - o
The x NH. "ER
SW TN 'Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.36 (t, J = 7.6 Hz, 3H), 1.74 - 1.84 (m, 2H), 2.01 - 2.05 (m, 2H), 2.37 - 2.44 (m, 1H), 2.84 - 2.91 (m, 2H), 2.92 (q, J = 7.6 Hz, 2H), 3.60 - 3.65 (m, 2H), 4, 59 (d, J = 5.6 Hz 2H), 5.99 (brt, J = 5.6 Hz, 1H), 6.92 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.27 (dd, J = 2.4, 9.6 Hz, 1H), 7.52 (d, Jy = 9.6 Hz, 1H), 9.52 ( d, J = 2.4 Hz, 1H), 9.70 (s, 1H); LCMS (electrospray) m / z 425 (M + H) +. 7-Chloro-2-ethyl-N- (4- (4-formylpiperidin-1-yl) benzyl) imidazo [1,2-alpyridine-3-carboxamide (352) | O AD
NX NH eRÁASN Pale yellow solid; 1H NMR (400 MHz, CDCl3); 5 1.35 (t, J = 7.6 Hz, 3H), 1.74 - 1.84 (m, 2H), 2.01 - 2.05 (m, 2H), 2.38 - 2.44 (m, 1H), 2.84 - 2.90 (m, 2H), 2.91 (q, J = 7.6 Hz, 2H), 3.59 - 3.64 (m, 2H), 4, 58 (d, J = 5.2 Hz, 2H), 5.98 (brt, J = 5.2 Hz, 1H), 6.88 (dd, J = 2.0.7.6 Hz, 1H), 6.91 (d, J = 84Hz 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 2.0 Hz, 1H), 9.34 (d, J = 7.68 Hz, 1H), 9.70 (s, 1H); LCMS (electrospray) m / z 425 (M + H) +. Example 3: Additional studies on imidazopyridine compounds Kinetics of inhibition and bactericidal activity Mycobacterium tuberculosis H37Rv was incubated in an initial inoculum of 2x106 bacteria / ml in Middlebrook 7H9 medium containing an increasing concentration of representative compound 47 or 54. Samples of. culture were collected over a period of 14 days. Serial dilutions of the bacterial suspension were performed and seeded in 7H10 medium. Colonies were counted for different dilutions after 3 weeks of incubation at 15 ° C under 5% CO; and compared to that obtained for the controls. negative for DMSO and positive for PA-824. PA-824 (Stover et al., 2000) is a small chemical compound TB Alliance currently in clinical phase experiments | for the treatment of tuberculosis. PA-824 possibly acts by generating radicals having non-specific toxic effects. However, the drug has been shown to inhibit the biosynthesis of mycolic acid and protein. In addition, PA-824 demonstrates aerobic activity.
Bactericidal activity was demonstrated by a decrease in the number of colony-forming units (CFU) after incubation with various concentrations of compound 47 or 54. The DMSO control showed no —in any decrease in numbers of CFU (figure 2) . The activity of both compounds was quite potent and reached 100% growth inhibition at approximately the same time as the reference compound PA- |
824. These data demonstrate the therapeutic utility of this scaffold for the treatment of tuberculosis.
Activity against MDR MIC strains of representative compounds 47 and 54, together with the Reference compounds isioniazide (INH) and moxifloxacin (MFX), were determined by the blue Alamar method for 10 clinical isolates resistant to multiple drugs (MDR) that exhibit different profiles antibiotics and 1 M of strain sensitive to the tuberculosis drug (strain lab H37Rv). In summary, Bacterial suspensions were incubated for 14 days in 7H9 medium containing increasing concentrations of compound.
Resazurin was added to a final concentration of 0.01% and fluorescence was measured to estimate bacterial viability after a 24 hour incubation period.
MIC was determined to be the first concentration providing 80% inhibition of bacterial growth compared to the DMSO control. All MDR strains tested showed a MIC less than or equal to 1.25 µM for compound 47 and 0.625 for compound 54,. while resistance to INH has been confirmed for all these strains (table 2). These values are similar to that obtained for the strain sensitive to the drug M. tuberculosis (1.25 µM and 0.625 µM, respectively). Both '20 compound 47 and compound 54 showed activity levels comparable to or better than MFX.
These data clearly show that this scaffold has therapeutic applicability for the treatment of tuberculosis and in particular, strains resistant to multiple drugs of the disease.
In Vivo Activity in a Murine Model The effect of compounds 177 and 185 on the bacterial load of TB-infected mice was compared to that of the reference compound Isoniazid (TNH). Eight-week-old female BalbC mice were infected with 6x10s M. tuberculosis H37Rv by intranasal instillation. The mice were sacrificed on day 1 to control the number of CFU in the lungs.
In the acute model of infection, the mice were treated for 4 weeks, starting on day 1. The compounds were recently dissolved in a 0.5% methylcellulose solution | and are administered by oral gavage 5 times / week. The bacterial load was estimated in the lungs and spleen after homogenization of the organs in IX PBS. Serial dilutions of organ homogenates were sprayed onto Middlebrook 7H1 1 plates and CFU was determined after incubation for 3 weeks at 37ºC over 5% CO.
In the acute model of infection (after 4 weeks of treatment; figure 3), a reduction of -2 log CFU compared to untreated mice was observed in the lungs of mice treated with 50 mg / kg of compound 177 or compound 185 administered orally ( figure 3 A). No CFU was detected in the spleen of those same mice, whereas the infection control mice showed an average of 2.5x104 CFU / spleen (figure 3B). No CFU was recovered from the lungs or spleen of mice treated with 25 mg / kg INH. In general, both compound 177 and compound 185 demonstrated a significant effect on the acute mouse infection model. 'One of the current challenges for TB drug discovery is iden-. tification of compounds that are active against persistent bacteria. Although the location and status of latent bacteria remains a matter of debate, a commonly shared hypothesis for mycobacterial persistence is that M, tuberculosis bacilli are able to survive in macrophages for prolonged periods of time and, unlike other bacteria are able to actively replicate. The intra-phagosome profile of M. tuberculosis is complex; a wide variety of genes are overexpressed and timely regulated and are also dependent on environmental factors. Together, this makes the identification of a specific tuber factor that can be selected as the difficult ideal target. Consequently, non-target cell-based assays are a critical tool in the search for intracellular M. tuberculosis inhibitors. The investigation of bacillus growth inhibitors within macrophages has long been limited due to embarrassing CFU sowing, slow bacillus growth, safety requirements and difficulties in establishing the appropriate infection conditions. As a consequence, this method it has always been used as a secondary assay after the initial selection of compounds that are active on extracellular growth in vitro. With the advent of automated confocal microscopy, the aforementioned limitations can be redirected and the methodology employed here demonstrates the feasibility of evaluating large-scale compounds.
Obviously the compounds found to be active against the growth of M. tuberculosis, both intracellular and in vitro, are the most promising. The best inhibitors isolated from this library have an inhibitory activity within the same range as INH and / or PA-824. Further linkage studies of structural activity will help to determine whether its activity can be further improved. Employed together, the results above show that monitoring of the growth of M. tuberculosis with automated fluorescence microscopy is highly robust and practicable and that this method enables rapid selection of potent anti-TB compounds.
q
Table 1 Compound QUM (HM) QIM (UM) Compound QUM (aN) QIM (uM) and + + x + + 1 2 3 4 o QRO + + FE * + 8 FLO-O + + O + ”n 7 8 Lo "Ex + + ua oe ++ +. 9 10 - RO n + + Ha," “” “1" “AR" RO + + RO * + 3 1a Í 8 H "O eg o us“ es. Ex + "++ sw i 16 o
N RP .. so 17 18 Activity range: +++ indicates <1 uM; ++ indicates between 1-20 µM; + indicates> 20 µM |
Compound GUM (pM) GIM (uM) Compound QUM (UM) QIM (JM) o ra, ... Era, oo 1 2 o So + + S & AI "+ + 22 3 Ro Qro. +. AP, Ex) | 24 Qdo + + and + + 28 26 -. + Z RO + “a7 2 29 'E" oo AE: * + E "+" +
N N - 31 3:% - nm: GO + ring +> »NO 4 su: E no oo NE. as Activity range: +++ indicates <1 µM; ++ Indicates between 1-20 ul; + indicates> 20 uM q
Compound - QuM (Am cmg - Compound - QuE (uy GIM (3H)% K DO '+ + + +: E, OE to QEMO à. AMO. Ne at 4o
N a 2 TO + + oO ".t + no N as, us Lo O LO" e ... + "+" ass 486 ROO La Ao o 47 Cc 4e | R OP a O o "mt" "ext” ” - 4s are LO R in ”es + + o” + 51 52 ex + + FO + bia
We are not
The Activity range: +++ indicates <1 µM; ++ indicates between 1-20 µM; + indicates> 20 µM |
Compound QUM (uM) GIM (JM) Compound QUM (uM) QIM (4H); THE
RO RD ss if FO and LO IS L): .. n the N ”rr Ex if the Lo e" + "+ MO rt rr ss 62 Eros meo am Er Or neo am E a“ Eee 6 EAR aa es es EAD The so is the s7 ss
ALI Qroo - ”" e eo + “+ ss To AX" +. "+ OSS + Ddss“ o “o 7 n Activity range: +++ indicates <1 µM; ++ indicates between 1-20 µM; + indicates> 20 µM |
Compound to a tuM) GIM (a) Compound QUM [UN QIM (pM) O. OO and o: "7" + “. et 7 “+".
PD e and PE 75 b 76 “A n +. The ".. +. N 7. 7 Te DO" and + QNoo ++ + ". 7th are the OOo neo mm Aros, "e mm s1 82 CG, AND THE ODO." + N. +. QUO "+ + 83 to 84 OO + aa Qi" + + Qt and 3 “a. + + A E, “+ o” s7 88 BOL es TA se so Activity range: +++ indicates <1 uM; ++ indicates between 1-20 µM; + indicates> 20 uM q
Compound QUMIKM) IM (no - Compound GQUM GuM) OM (éM)
C NH & NH o and TR e n if NA Cl Nº o ”.—. +“. N Os. ". +. Ss sa f) Qóe meo CRÔN aa Oo, bi O ss o ss o [2 RR and RUIDO OR Oo," o a 2 * "+". NA ON 5 RO mo a E 100 fe 2 = e er N 101 102 a, LI RT + AO o ne 104
Z to O AD ”+ + 3.". - ”li $ 05 LO 106 Activity range: +++ indicates <1 µM; ++ indicates between 1-20 µM; + indicates> 20 µM
Ia Cn ——— Ú ———————————— AA Compound QUM (uM) QI (; M) Compound QUM (ui) QIM (ui) mma Caput ana A a Gato td ita Lú OO "a LO Ya e. +. To E. ” "LE 107 x 108 to A o
HOT ”” A ”" + LES LE nm es 00 2000 do +. +++ n ". na Li READ 11 "02 £ Yr CA
DT LS and n .. .. + LE ..r na "13 114
PÔ F DOT a H Fr EE moro =. 16 Ee us
OO FOOT a e 147 + “. 1 "and Ls PP” "+ .. DO LO E Es. Ki. ++. 1. 119. ” F ”120 es Y Oo" OT 3 in s PD LO "”. + T .- "” OT mm and wing 12 to act o CUC CA ss rt Activity range; +++ indicates <1 uM; ++ indicates between 1-20 µM: + indicates> 20 µM na: not determined
SHOT II E + o a os O O Ee 1 “120 oO;
R dis nt. “0) .. Ed a Kx and 125 e" 126 es) y
LO "+" the PS + +. : mm o 128 FC, F 2 o FLIGHT,. 129 Fa and 'O 0) a. + "." rt>. "+ TE" sm LE are. ec e "+.. + e” +++ LO 133 and 134 oÉ 135 + ”" + LE 136 ++ + ”to O 20." "+ '» ne +. LE os Activity range: +++ indicates <1 µM; ++ indicates between 1-20 CU; + Indica> 20 uM union into areas —— C om QUM (4M) GIM (aM) Compound GUM (UM) QIM (AM) to A RA AND QUI GAM) QI (AM) AND En A as ”TQ ,. , + 138. "T ... o 140" +. ++ E ç Pr "t + ++ tm + + red" id 141 a: LO 142 O SODO7r, er EA AA ad
LI BE and 445 “” "144. A DE Ed Ss mem. 145 * + Activity range: +++ indicates <1 ul; 1º indicates between 1-26 ulM; + indicates> 20 uM
Compound QUM (7) OM Gm Compound QUM (UM) QU (UM) O ”” + * ”a" + Riad o 146 nO. U7
O o dd. "Nn" fear '+ * LIA 148 SN 149 E + + Da ”+ in the 150“ O 151
H and FO "Po +" RE O e + CT if bs 153 AX 'Es FO. “.." "HE. + + At 155 o CA $ da + + E + + and 156 SM 57 Ads RF!“ Es s ".." tn “+++ ad ob" Ps DS + + o. DO "o" + sm o. 160 er 161
E "... TOP + .. E E 6 Activity range: +++ indicates <1 ui; ++ indicates between 1-20 ul; + indicates> 20 uM ao," + +. LEIO, om 164 165 o O PX Ro q + + sX r 4a mr 166 º 167
LO OO s, “+ + Fe" na e 18 LR 16 or ao O Tn 171 '2200 ee eo a Dye LO 1m72 ão 173 DATA LOTA "LE o, So' DOS o E" rs "aa ex e ++ + "and LE 176 and 7 to” TT + to +++. + not 178 c o 17. oo 2 = oo + "." o. RS so e 10 Activity range: +++ indicates <1 µM: "indicates between 1-20 µM; + indicates> 29 uM
Compound QUM (UM) OIM (JM) Compound QUM (uM) QIM (pM); oo ”FIO" o ++ ”LO" + nd TR ee ss: o 9 O o. AO Aa "" à. "At Qd," + + NR qa 185
LX 34 Q. ns + 1. ed It hurts "+" .. LF 1es6 6 o RB +. "nm and O a +". ++ LE 188 “188 EO. 4 +++ + x and q +. + .. OE 1 »LE qm OR. ão ”at" o E + "t + o 182 er x 19 - + | Lx | now À ”A,” + "te Que, DP“ "” tou Lo 195 O Da + ”as tel“ u “+ PES 186 187 x 4 o + ... ++ &,” "” hollow ear. 158 189 Activity range: +++ indicates <1 µM; ++ indicates between 1-20 µM; + indicates> 20 µM 'not determined
Compound GUM (JM) Giga - Compound GUM (UM) QIM (ut) a LOOP + ". +" FLUID "+ +“. -. 200 Li 201 Ff F Qro "“ ".— O” "” 202 O zo Seo O + ao and OR + 204 205 OA ORM A 206 207
DÊ and CEO, and SS A. and PO * rr. "208 OT 209 A í e eo =" “.“ Ee> "rt” EE 210 OT 211 - o e o o ”Ú se" .. ”LE 212 EO TA O” = - .. LO “.. ne ao O 214 = ns OS mo am FOR mem mm “rs rs 216 217 Activity range; +++ indicates <1 µM; ++ Indicates between 1-20 UM: + indicates> 20 uM na: not determined
E rr RO to EO om oo =. RIO mom ROD ROO mm RODO Demos CERCO FT 4 +. Oo! "OOPS EA mo
RE TT RE E “oO RE o
Compound QuM IM) amy - Compound QUM (UM) QIM (JM) sas Pp "..“ E O. oo a Li 236 37 a Ro + RESTO 238 239 E + + & O * 2 ooa A + AEE o 242 aa TO. And the “aà eq 244 245 E to" a * ná a. + Box ss TS 26
E & nt na + nd ff
LE LE E: seo OX ”. AR 250 Be 251
F Ao ma NOR Has Activity range: +++ indicates <1 uM; ++ indicates between 1-20 CU; + indicates> 20 UM na: not determined
282 a “e> +". Nd Des do. + Nd 24 2565 ex P .. .. na KX = ". na 256 257 Q-OS AAA E memo It is mo 258 259 LORD a AOALDOP and “+ na XE + + 260 261 FO A o us LE 262. 263 = ES ms ADS 264 x 265 50 + nd A E +. “= 266 o 267 PO if Fes 265 rs 269 OD AO mo Activity range: srs indicates <Tu i + indicates between 120 UM; t indicates> 20UMO | na; not determined for eee— uu - Compound QuMtkM) emu - Compound QUM (ut) QIM (4M) oO OO + "e. í .. e m LE 273 = 2207 20" r nd «a" ”" na
LE TE o ”De SA + nd DO" nd rs “E and 276 am Os De Ko O LT. 278 279 os Dre à oO nn nm il il + + es 280 OT 281 OO oO : Fo" and n ++ mn E rs 282: 283: OO .s nm o ... zoo x 285 O Oo "C Çrr ÃO Pr + o 4 + e." + [$ E 286 287 LOTTO OOTm mm e E o Activity range: +++ indicates <1 UM: ++ indicates between 1-26 uM ; + indicates> 20 uM na: not determined
Compound QUM (UM) QIM (ut) Compound QuM UM) GIN GM) OT oO + Cs +. "+ E 290 Tm zs1 X ALIIA. OO:" +. "+" + m PP VA ma Do ao Lo Fo a meo 294 O 295 A FO AI, e 7 4. mm eq> + "mm 296 and 297 o” O o "+ nm OO ns 5 and 298 LO 299 O Da + na LOS "... na" o 30 = 2o1. ES Dt +. nd O DO .. + s 302 o 203 Ca r fm AL ARO ROD mm a o Eh AT am am OO mm mm o
SE E Activity range: +++ indicates <1 µM; ++ indicates between 1-20 CU; + indicates> 20 UM na: not determined
Compound QUM (MM) QIM (ut) Compound GQUM (HM) GIM (MM) O AAA Aa Ana a
OA DAI a, E p SA ”A mm nd +". +. En fros Fros: oo 200 "to as ++ ++" three o "SE 310 E to Px £ o. OO to O are "+. Nd mos O .. nd +. & 312 313 f" nm ne +. + OE Air 3u 315 Deo AL 2 ”” SI il o. and. er 316 E nn o 407 + nd, O a) nd nm ç as a o, FOO "+ nm ADO aa nd S 320 and 321 a fm 95º al" na FI Dm na na 222 'to 325. OT o DO to
Y E sm: SE 325
The Activity Range: +++ indicates <1 µM; ++ indicates between 1-20 µM; + indicator> 20 uM na: not determined
Compound QUM GN) ami - Compound QUM (UM) GIM (AM) oO TOO + + + x + na MM ax 327 O so ss E + + ”with E + + A) 328 o 232 Fes ese Ro oo '330 s sa :, oa O TOO + nd QL dr + ne o om 232 7 233. e 'o er, mo os o ”: 334 E eo, more DO am AA et ss7: Ut oo + nd Ei' * O + na A 328 339 LE O o na E SD e nd sso 3 xo, PA a and NO 342 24 Activity range: +++ indicates <1 µM; ++ indicates between 1-20 CU; + indicates> 20 uM na: not determined
Compound QUM (LM) Gu (ay - Compound QUM GM) QIM (AM) pretenÚ— C— o »oO EK moro e meo Ls 3744 345 Povoa Y aaa nd a. "+ no ER 3 be 347 Fr o AFA es SD TM 3 Te e ae." + nd e LO O ++ nd + E 50 CM 5 oa CT OD "and nd LE 352 Activity range: +++ indicates <1 UM; ++ indicates between 1-26 ul: + indica> 20 UM nd: not determined Table 2 [RE LL The tape O sensitive [ams [the RE RE Ro Ro o A and the family in Jow Tess To Tosa Tea Tizs [1 [99 T fas [53 ses [ones [91505 [o1505 headphones Te Tras [937 jest [637 Toas | ms Te oao To o Ts as [15 roe Tess Tosa Tess Joss Tom fas [13 Toas Tom

权利要求:
Claims (10)
[1]
1. Compound having the general formula la: see (Rn) <Ts. NOS gt la in which half, 1,2,3 or 4; no, 1,2,0u3; X, Y and Z are CH, N or N-oxide; R 'is, in each occurrence, independently selected from the group consisting of hydrogen, halogen, C; -Cio5 alkyl, C-C; 3 haloalkyl, C3C; cycloalkyl, hydroxyl, oxo, -ORº, -C (O) JORÍ, -C (O) RÍ, - CIOINIR) 2, -CN, -NOz -NH> z -N (R), -ORHeta, -ORN (R ), - CIOIN (RRHetA, -C (OIN (RHetA, -C (O) HetA, -C (OIN (RIRS (O) .RA4; -: S (O) AN (R) 2, -S (O0) 2RÍ, -N (RC (O) RSRº, -N (RRIS (O) 2Rº, -N (RS (O0) 2R *, - C (S) RÍ, aryl, for example, phenyl, benzyl, and heterocyclic, any of which '15 is optionally substituted; R' is, at each occurrence, independently selected from the group consisting of hydrogen, halogen, C1-C19 alkyl, C3-C19 cycloalkyl, C2> -Ci19 alkenyl, C3-C1,9 cycloalkenyl, C> -C19 alkynyl, C1-C19 haloalkyl, -OH, -ORô, Cy-C10 alkoxy, C3-C1 cycloalkoxy, C3-C15 cycloalkylaloxy, C3-Cis cycloalkylaiquita, -CN, -NO2, -NH2 -N (Rº) 2, -C (O) Rº, -C (O) ORS, - C (OIN (IRó) 2, -SRº, -S (OJRô, -S (O) LLR *, -S (O ) N (R ”) 2, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; Rô is, in each occurrence, independently selected from the group consisting of hydrogen, halogen o, C1-C1, o alkyl, C3-C19 cycloalkyl, hydroxyl, -ORº, -CN, -NO2, -NHa, -N (RÍC (O) Rô, -C (O) Rô, -C (O ) OR, - C (OINIRô) 2, -S (OJRº, -S (O) 2R, -S (O) 2N (Rº) 2, aryl, for example, phenyl, benzyl, heteroaryl, heterocyclyl, any of which are optionally substituted, or two groups of R * are connected to each other to form cyclic rings | —Cycliced five or six membered heterocyclics, any of which is optional
| 2/5 internationally replaced; Rº is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C10o alkyd, C3-C19 cycloalkyl, Ca-C19 alkenyl, C3-C19 cycloalkenyl, Ca-C19 alkynyl, C1-C19 haloalquita, -C (O ) R ”, -R '(RNC (IO) R !, -C (O) OR", -RN (RYCIO) JOR ”, -C (OINIR) 2, -R (RIC (OIN (R) a, - S (O) R ”, -S (O) 2R”, -S (O) 2aN (R ”) 2, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; and Ró, Rº and R are, in each occurrence, independently selected from the group consisting of hydrogen, C1-C19 alkyl, Ca-C406 cycloalkyl, C3-Cio alkenyl, C3-C19 cycloalkylene, C> -C15 alguinila , C1-C15 haloalkyl, aryl, for example, phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted, and pharmaceutically acceptable salts thereof.
[2]
2. Compound according to claim 1, having the formula gerallb: x “o (go - Rº [1 where 0 is 0 1,2,0uU3; né0, 1,20uU3; hand 1,2, 3ou4; A is NR ' !, C = O, C = S, OP (O), P = O, CH, or a heteroaryl selected from the group consisting of H NE NEON 8 in the el So HD HT HDD O Wé C = O, O , S, CH; or NR ", R '* is a selected portion of the group consisting of NR |
Ro ENA q: Sn E og 4 e, o. te. ER EQ AND THE "FERE Roo
R. Y> RD + Ce Gee Gr CC SEC = ”FS | no = ”R There is> Id CD O HO R $ FS FO FAR, a a O AR sounds, RIA o ECA N '- = fe a Ga, EO MEO "Oo Se OX + + n No NRP CX N-RE Mn - Os É NR
N R '* is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C19 alkyl, C3-C15 cycloalkyl, C2-C1o alkenyl, C3-C + 19 cycloalkenyl, Ca-C1o alkynyl, Cy-C1o haloalkyl , -OH, - OR " , C1-C1o alkoxy, C1-C1o cycloalkoxy, C3-C15 cycloalkitaloxy, Ca-C15 cyclo- —alkylalkyl, -NH>, -N (R '%, -C (OJR"%, -C (O0) OR " , -C (OINIR ) 2, -S (O) R”, - S (O) 2R " , -S (O) N (R )>, Aryl, for example , phenyl, benzyl, heteroaryl, and heterocyclyl, any of which is optionally substituted; R * is, at each occurrence, independently selected from the group consisting of hydrogen, C1-C109 alkyl, C3-C19 cycloalkyl, C2-C19 alkenyl, C3-C6 cycloalkenyl, C2-C105 alquinite, C7-C19 haloalkyl, hydroxyl, -OR *, -C (OIR, -RARICIOIRA, -C (O) JOR, -RARICIO) JOR '* 4, -ON, - NO2, “NH -N (R) s -CIOINIR) 2 -RM (RMCIONIR *) :, -S (O) R", - | S (O0) 2R "*, -S (O) N (R *) >, aryl, for example, phenyl, benzyl, heteroaryl, and he tertocyclyl, any of which is optionally substituted ; R ** is, in each occurrence, independently selected from the group consisting of hydrogen, C1-C1, alkyl, C3-C1.5 cycloalkyl, C2-C1o | alkenyl, C3-C19 cycloalkenite, C2-C15 alkynyl, C1-C19 haloalkyl, arite, by i 415 | : "| | for example, phenyl, benzyl, heteroaryl, and heterocyclic, any of which is optionally substituted; and 'R' * is, at each occurrence, independently selected from the | group consisting of optionally substituted hydrogen, C, -Cg alkyl with at least one hydroxyl or halogen; C3-C; cycloalkyl, C2-C19 alkenyl, C3-C105 cycloalkenyl, C2-C19 alkynyl, C1-C19 haloalkyl, aryl, for example, phenyl, benzyl, heteroaryl and heterocycly, any of which it is optionally replaced.
[3]
A compound according to claim 1 or 2, having one of formulas 1-352 as shown in table 1, preferably one of formulas 15, 16, 31, 32, 44, 45, 47, 49, 54-57, 60 -87, 89-103, 106, 107, 110, 111, 113, 116-135, 137-141, 143, 144, 147, 148, 152, 154, 157-159, 161- 167, 171-182, 184 -193, 196, 198, 199-202, 209-218, 221-227, 231, 248-260, 262-264, 267-269, 271-274, 280-293, 295-315, 317-318, 320 -321, 324, and 330 as shown in table 1, and pharmaceutically acceptable salts thereof.
[4]
A compound according to any one of claims 1 to 3, having one of formulas 47, 54, 177 and 185 as shown in table 1, | and pharmaceutically acceptable salts thereof.
[5]
A compound according to any one of claims 1 to 4, for use in the treatment of a bacterial infection. !
[6]
A compound according to claim 5, wherein said 'bacterial infection is tuberculosis.
[7]
A pharmaceutical composition comprising a compound co-defined in any one of claims 1 to 6, and a pharmaceutically acceptable carrier.
[8]
A method of treating a bacterial infection, in particular tuberculosis, comprising applying a suitable amount of a compound as defined in any of claims 1 to 6 or a pharmaceutical composition as defined in claim 7, to a person in need of it.
[9]
A compound that competitively inhibits specific binding of a compound according to any one of claims 1 to 6.
[10]
10. Method of treatment of a bacterial infection, in particular tuberculosis, comprising the application of an appropriate amount of a compound, the compound of which is characterized by the ability to competitively inhibit the specific binding of a compound as defined in any of the claims 1 to 6 or a pharmaceutical composition as defined in claim 7, for its target protein, to a person in need thereof. | r
D
LL Z = DD - Oo 2 o J & FT E + E Ee 8 * 7 -: + = *. It is 2+. 3 +. Z 8 +18 +, FANS gone AND AZ & + x 8 dh. as 1st 28 888 38 E RR 8 * "ê F & S" + E R + ”+: 3 *. in E EF. e e] E 2> + E HH o a z 2 SS 2 E E 7 É + = 2) ê TM = 18 8SR Se gRees 3 * '2 << mo O | | The
D = = + = be = healthy 2.12 2 2 = di, ao À Ses Ses so z z e = the e : tg "EE z— aa EE EN FNE 8 & e E + e E [sd o 5 Pt Fr Pr = - o º 8 E 8 SR 8 E 8 8 Rg o $ 8 88º O) uauWI98a19 after OFÓIQIUI SP% OS I59J9 ap OEÓIqIU | SP% Was Sp OESIAIU SP% ma 8 HF
JESE 2 o * o o o
E | 5 j F 8 8 | * i N | at d
NT AR H TEN | 5 - N. | N if. LOL
SN N N N 'IP "& N N N N: o
A R HH H 8 3 à ê: ê (inrl) oisodwos ap oedenuanuos <q O
2 2, 8 DDR
BEE
IBGSS ESTA o. «... 2 = D & ic:, o, i * i i &: 4 i; eg '%: & 1 “ei: fe” io: Y ”1 o * ie, i> £ q Z + 2% sss Ss = + 2 2 2 2: o nm 0589 / N4O" o = 2 o - BBE $ S & 2 2 SS 2 82,995 À 3 sissê 2 ESTSZS IS ESSTTÉZ eu res E ã 'ii * &' f & * Ht + 1 ay | i |% &% r: <a, | Fr i & eiie «He. I & , %%, << iei%; “&. Fr oeoe“ 7 Px & é o é à S $ sa%, 2 2 ê é é es MA 4 soguInd / No -

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法律状态:
2020-09-15| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2020-10-20| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |

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2021-04-13| B07E| Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|

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2021-06-15| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

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2021-09-14| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

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2021-11-23| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

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申请号 | 申请日 | 专利标题

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US31511310P| true| 2010-03-18|2010-03-18|

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US61/315,113|2010-03-18|

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US201161440937P| true| 2011-02-09|2011-02-09|

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US61/440,937|2011-02-09|

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PCT/EP2011/001345|WO2011113606A1|2010-03-18|2011-03-18|Anti-infective compounds|

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