• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A process for the preparation of azabicyclo-octanecarboxylic acids of general formula (I): Soon x-Vv. N-CO-CH- (CH2) ci-X-R, R where A is vinylene or ethene; q is O or 1; R is lower alkyl; J X - S or NH; RJ is hydrogen or CH-E3 CO-Rj group where the lower alkoxy group; R is straight or branched alkyl, phenylalkyl containing not more than 8 carbon atoms, or the group CHj-S-CH-Rg I J R4 where RJ is lower alkyl or cyclopro. . drank; R - is cyclopropyl or alkoxy (lower) carbonyl, in the form of racemates or optical i CO isomer, or their salts with mineral or organic base, or additive compounds I, where X is NH, with mineral or organic acid, o T, and by the fact that the azabicyclo-octane carboxylic acid or its ester of the general formula (II) is xtv-COE ACHINE where A has the indicated meanings; ; R is a hydroxyl or a lower alkoxy group, is acted upon by functional derivatives, such as a chloride or a complex of a hydroxybenzotriazole of a substituted car: fighting acid is of general formula (III) X (CH2) ct-CH-COOH R where q have the indicated values; X is S or NH, protected with an acetyl residue or 1ret-butoxycarbonyl.
    公开号:SU1138022A3
    申请号:SU813346599
    申请日:1981-10-20
    公开日:1985-01-30
    发明作者:Винсен Мишель；Ремон Жорж；Лоби Мишель
    申请人:Адир (Фирма)；
    IPC主号:
    专利说明:

    with the subsequent removal of the protecting groups of the compound of the general formula (IV) formed thereby
    ... COR,
     - CH- (CH2) 1 R
    and the selection of the target product or, if necessary, the compound (I) where RJ is hydrogen}
    X - NH,
    subjected to reductive alkylation with a compound of the general formula (V).
    RJ-CO-CO-RS
    RJ and Rl have the indicated meanings for the preparation of compound (I),
    X - NH;
    R) (group
    CH Ra
    I
    CO-R2
    and the target products are isolated in the form of racemates or an optical isomer, or their salts with a mineral or organic base, or additive compounds (I), where X is NH, with a mineral or organic acid.
    This invention relates to the field of the preparation of new azabicyclooctane carboxylic acids, which can be used as antihypertensive agents. The production of amides by the reaction of loranhydrides or carboxylic acid esters with amines L is known. Also known is the reductive alkylation of amines by reacting amines with ketones in the presence of an appropriate reducing agent | 2 .., The purpose of the invention is to develop, using a known method, a method of obtaining new compounds with valuable pharmacological properties. The goal is achieved by the method of obtaining azabicyclooctanecarboxylic acids of the general formula soon / TV. k-co-CH- (CH 2) q-X-HI where A is vinylene or eten; q- O or 1; R is lower alkyl; X- S or NH hydrogen or group where. where or, the nix is a lower alkoxy group; 3 straight or branched alkyl, phenylalkyl containing not more than 8 carbon atoms, CH —S — CH — RS R — lower alkyl or cyclopropyl; cyclopropyl or alkoxy (lower) ka bonil, in the form of racemates or optical, isomer, their salts with a mineral or organic base, or additive inions (I), where X is NH, with a minena or organic acid, in which azabicyc tancarboxylic acid or its ester of the general formula. has the specified zlacheni; hydroxyl or lower alkoxy. affect functional derivatives such as oxybenzotriazole chloride or ester of a substituted carboxylic acid of the general formula xHsn2 c1-cn-soon where R and q have the indicated X-S or NH values protected by an acetic residue or Tert-butyl xycarbonyl, followed by removal of the protective groups of the compound of the general formula vi, N - co - CH- (CH2) R formed by this and the isolation of the target product or, if necessary, the compound (where R, is hydrogen; X - NH, is subjected to reductive alkylation with a compound of the general formula 1 2 -CO-CO-Hz V where R- and R. has the indicated meanings for the preparation of compound (I). where X is NH; the CH-Rj group CO-Bg and the target products are isolated in the form of racemates or optical isomer or their salts with a mineral or organic base, as well as additive compounds I, where X is NH with a mineral or organic acid. Compounds of formula (I) contain at least two as-carbon atoms, Depending on n substituents and the degree of hydrogenation in the compound of formula (I) from 2 to 8 asymmetry centers. Racemic compounds can be ECTION known manner on a mixture of epimers or diastereomers or enantiomers. Remark m Mercapto-3- (118) methyl-2-propionyl Jaza-2- (RS) -carbox-e- -J - 3-dicyclo (2.2.2) octane, Stage A. Aza-2 (RS) carboxy-3-dicyclo (2.2, 2) octane, 3.8 g (0.0148 mol) of dihydro-8.8 thioxo-1, 3-ethane-5.8-phenyl-2 (2H, 5H) imidazo ( 1,5a) pyridine is suspended in a solution of 30 ml of 4N sodium hydroxide and 10 ml of methanol. The mixture is heated with reflux for 24 hours, cooled, filtered, the filtrate is acidified with 30 ml of 4N hydrochloric acid, then passed through 200 ml of Dowex 50 ion exchange resin. After washing the resin with distilled water until no chloride ion is present in the eluate, the desired compound is eluted with 500 ml of 1N ammonia solution. Ammonia eluates were dry dried, the residue was the desired product, Weight 1.8 g (78%) T, mp. (In Joe Kofler) 253-255c, Stage B. N Acetya-3 (RS) Methyl-2-propionIy aza-2- (RS) Carboxy-3-Dicyclo (2.2.2) octane. 0.850 g (0.0055 mol) aza-2- (K8) carboxy-3-dicyclo (2.2.2) octane, obtained in the previous step, are suspended in a solution of 1.33 g (0.011 mole of N-dimethylaniline in 40 ml methylene chloride, 1 g (0.0055 mol) of acid chloride. acetylthio-3 (RS) methyl 2-propionic acid is added dropwise 5 minutes to the previous solution, stirred at ambient temperature. Stirring is continued for 15 hours. a mixture consisting of 150 g of sawn ice and 30 ml of 1N hydrochloric acid; the organic phase is extracted, washed with 1N hydrochloric acid, then distilled water to neutrality, drying, t over calcium sulfate, filter, evaporate to dryness and evaporate the residue after chromatography on silica gel Merck F 254, eluting with methylene chloride / methanol (95.5), 0.550 g (34%) of the desired product is obtained in the form of oil; IR 5 and NMR spectra confirm the expected structure of the reactor. . Stage C. N Mercapto-3 (E8) -methyl-2-propionyl aza-2 (RS) carboxy-3-dicyclo (2.2,2) octane, 0.500 g (0.017 mol) H acetylthio-3 (K5) methyl-2- Propionic 1-aza-2 (RS) carboxy-3-dicyclo (2.2.2) octane, obtained in the preceding stage, is diluted under nitrogen in a mixture, 1.7 ml of 1 and an aqueous solution of caustic soda and 25 ml ethanol. After contacting for 15 hours, ethanol is distilled off under vacuum and an aqueous solution extracted with ether and neutralized with exactly 1.7 ml of 1N. The aqueous solution of hydrochloric acid is evaporated to dryness. The residue is the desired product (0.3 g) mixed with 0.0995 g of sodium chloride. Example 2. K- {y- (K8) Ethoxycarbonyl-1-pentyl- (3) alansh1 aza-2 (RS) carboxy-3-dicyclo (2.2.2) -4 (RS) 7 (RS) oKTeH- five. Stage ft. Aza-2 (RS) carboxy-3-dicyclo (2.2, 2) -4- (RS), 7 (RS) oKTeH-5. 34.5 g (0.119 mol) of dioxo-1 3 ethane-5, 8 (chloro-4-phenyl) -2- (2H, 5H) -im dazo (1.5a) pyridine is heated with reflux under nitrogen atmosphere- 5 hours 355 ml (1.42 mol) 4n. aqueous solution of caustic soda. After cooling to 5 ° C, 14 g of chloro-4-aniline are squeezed and the filtrate is acidified to pH 1 with concentrated hydrochloric acid. The solution is filtered Pass through 800 ml of resin Dowex / / N / 50 WX-8. After washing with distilled water to the complete absence of chloride ion, the desired product is eluted with 2,250 ml of 1N. ammonia. Ammonia eluates are evaporated to dryness in a vacuum created by a water-jet pump at 40 C. Weight 17.5 g, yield 96.2%. Composition CgH ,, N02,%: Estimated C 62.72 H 7.22 N 9.14 Found C 62.30 H 6.87 N 9.10 Stage; 8. Aza-2 (RS) hydrochloride metoxycarbyl nyl-3-dicyclo (2,2,2) -4 (RS), 7 (RS) octene-5. 1 g (0.00655 mol) of the amino acid obtained in the preceding stage is dissolved in 15 ml of anhydrous methanol and added dropwise, without allowing 226 temperatures to rise above + 5 ° C, 1.5 mol of thionyl chloride. The mixture is heated with reflux for 2 hours, then evaporated to dryness under vacuum, created by a water-jet pump, at 40 ° C. Obtain 1.2 g (yield 90%) of the desired product. T. pl. 207 ° C (decomposed). The crude product is used in the next step without further purification. Stage C. N (} j (treg -Butoxycarbonyl) alanyl aza-2 (RS) methoxycarbonyl-3-dicyclo (2.2.2) -4 (RS), 7 (RS) oKTeH-5. 8.9 g (0.044 mol) The ester prepared according to the procedure described in the previous step is dissolved in 70 ml of dimethylformamide (DMF) in the presence of 6.15 ml (0.044 mol) of triethylamine. To the resulting solution at ambient temperature is added 8.3 g / S / Trg-butoxycarbonylalanine dissolved in 45 ml of DMF, 6.45 g (0.044 mol) of bxibenzotriazole1 (MBT) dissolved in 55 ml of DMF, 9.05 g (0.044 mol) of dicyclohexylcarbodiimide (DCCI) dissolved in 80 ml of chloroform. After After stirring for 24 hours, the resulting dicyclohexyl urea (DCM) is filtered and the filtrate is evaporated to dryness in a vacuum created by a water-jet pump at 50 C. The residue is dissolved in 250 ml of ethyl acetate and the solution is filtered and washed successively: 2 x 50 ml of a saturated aqueous solution of sodium chloride ; 3 x 50 ml of a 10% aqueous solution of citric acid 2 X 50 ml of an aqueous solution of sodium chloride; 3 x 50 ml saturated aqueous sodium bicarbonate solution; 2 X 50 ml saturated aqueous sodium chloride solution; then dried over calcium sulfate, filtered and evaporated to dryness. 12.8 g (86.5%) of the desired product is obtained in the form of a very viscous oil. Composition C ,,,%: Calculated C 60.34 H 7.74 N 8.28 Found C 60.10 N 7.79 N 8.21 Step 3). (tert-Butoxycarbonyl) - (8) alanyl aza-2- (RS) -carboxy-3-dicyclo (2.2.2) -4- (K8), 7 (RS) oKTeH75.
    12.8 g (0.038 mol) of the compound obtained in the previous step are dissolved in 140 ml of methanol in the presence of 40 ml of 1N sodium hydroxide solution. After stirring for 8 hours at ambient temperature, the solution is evaporated to dryness in a vacuum created by a water jet pump. at 30 ° C, and the residue, dissolved in 1.50 ml of water, is extracted with a small amount of ethyl acetate to separate the remaining substances, then acidified with 2x100 ml of sulfuric ether, the ether solution is dried over calcium sulfate, filtered and evaporated to dryness.
    11.1 g are obtained (yield 90% of the desired product i).
    Stage E.
    N (G) Alanyl aza-2- (K8) carboxy-3-dicyclo (2.2.2) -4- (K8), 7 (RS) -oKten-5.
    11.1 g (0.034 mol) of the compound obtained in the previous step are dissolved in 95 ml of methylene chloride and to this solution, cooled to 0 - (+ 5) C, is added dropwise, with stirring, 75 ml of trifluoroacetic acid dissolved in 80 ml of methylene chloride. After contacting with stirring for 1 h at 0 - (+ 5) s, then another 1 h at which the solution is evaporated to dryness i in a vacuum created by a water-jet pump, then by a centrifugal vane pump (0.1 mm Hg).
    The resulting crude residue (13.6 g) is passed as an aqueous solution over a resin (Dowex 50 N), the resin is washed with distilled water, and the desired product is eluted with 1 l of 1N. ammonia. After evaporation of the ammonia eluates to dryness, the desired product is obtained.
    Weight 6.3 g (yield 83%).
    Composition C., H gNjO-}. %:
    Estimated С 58.91 Н 7.19 N 12.50
    Found C 57.80 N 7.09 N 12.83
    Stage F.
    (RS) -Etoxycarbonyl-1-penty (S) alanyl - aza-2- (RS) -carboxy-3-dicyclo (2,2,2) -4 (K8), 7 (H8) -octene-5.
    h
    1 g (0.045 mol) of the compound obtained at the previous stage is dissolved with stirring in 55 mp of anhydrous ethanol in the presence of a TL-molar sieve A A and 2.85 g (0.018 mol) of ethyloxo-2-hexanoate
    (E | 5 89-91 C). After stirring for 1 hour at ambient temperature, a solution of 0.28 g (0.0045 mol) of sodium cyanoborohydride 5 in 2.25 ml of anhydrous ethanol is added over 6 hours. Stirring is continued for 15 hours, then the solution is filtered and evaporated to dryness. then dissolved in 50 ml of an aqueous solution of sodium chloride. After extraction with ether, the aqueous phase is adjusted to pH 3 by addition of a small amount of 1N to remove the excess ketoester. hydrochloric acid, then extracted with ethyl acetate. The organic phase is dried over calcium sulfate, then filtered and evaporated to dryness. The residue after evaporation is the desired product as the sodium salt.
    Composition CjgHj, Oy,%: Estimated C 58.75 N 7.53 N 7.21 Found C 58.74 H 7.71 N 7.48
    In tab. 1 shows compounds
    according to the examples given, as well as other compounds of formula (I) obtained in the same manner.
    The compounds of formula (I), as well as their salts, have interesting pharmacological properties. They significantly inhibit the conversion of decapeptidangiotensin I to octapeptidangiotensin II by suppressing the conversion enzyme,
    5 In addition, the formulas of compound (I) have an inhibitory effect on enzymes such as carboxy polypeptidases or enkephalinases. Consequently, their use in therapeutic
    0 aims to reduce or even completely eliminate the effect of these enzymes by acting on one of the mechanisms directly responsible for hypertension or cardiac
    5 failure.
    The proposed compounds were tested by intravenous or oral administration of a live dog.
    Dog blood pressure was measured using a pressure transducer.
    Statham.P 23 Db after aortic catheterization with the femoral artery. Recorded by Brush recorder
    5 Angiotensins I and II were administered intravenously to animals at a dose of 0.3 µg / kg. A dose / activity curve was plotted for each of these hormones. Then, the proposed compounds are administered orally or intravenously. dose, 1-10 mg / kg. A second dose / activity curve for antiotensin G and II is constructed after administration of the test product,
    The condition of suppressing hypertonic activity by 50-100% after 30-90 minutes and maintaining this suppression by 40-80% to 6 hours or more after the administration, which is not observed - with one of the known compounds of this
    type In addition, the proposed compounds do not exhibit acute toxicity (DL (j 500 m / kg intraperitoneally in mice),
    Table 2 shows the comparative data of the antihypertonic activity of the proposed compounds and captoprilas.
    The results show
    that the proposed compounds have a longer activity than captopril.
    m
    w
    W
    h "
    h.- /
    4
    g
    "Y-
    :
    to
    W u
    CJ
    l
    ate
    sch
    N
    her and
    to and
    C4
    CNf
    five
    with S
    Yu

    with
    4 cr.
    ate “n
    to and
    with
    with
    m
    and and

    Ry
    U
    cho
    15
    sixteen
    1138022
    table 2
    权利要求:
    Claims (1)
    [1]
    The method of producing azabicyclooctanecarboxylic acids of General formula (I)
    A soon where A is vinyl or ethene;
    q is 0 or 1;
    R is lower alkyl;
    t X is S or NH;
    R | - hydrogen or group ’
    CH-R, 1 , co-r 2 'lower alkoxy; straight or branched alkyl, phenylalkyl containing not more than 8 carbon atoms: OR-Group
    CH 2 -S-CH-R s I, R 4 where R ^ is lower alkyl or cyclopropyl;
    Rj is cyclopropyl or alkoxy (lower) carbonyl, in the form of racemates or an optical isomer, or their salts with a mineral or organic base, or additive compounds I, where X is NH, with a mineral or organic acid, which is known as on azabicyclooctanecarboxylic acid or its ester of General formula (II)
    C0R 'where A has the indicated meanings;
    .; R 1 - hydroxyl or lower alkoxy group, is exposed to a functional derivative, such as chloride or a complex $ oxybenzotriazole substituted carboxylic acid of general formula (III)
    X- (CH 2 ) q - CH - COOH
    R 1 where R * h q have the indicated meanings;
    X 7 - S or NH, protected by acetyl SU with a 1138022 residue or tert-butoxycarbonyl,>
    1138022.
    followed by removal of the protective groups of the resulting compound of the general formula (IV) where 'R t -CO-CO-Bs-t
    Rj and R have the indicated meanings for the preparation of compound (I), wherein
    X is MN;
    a group and the incorporation of the target product or, if necessary, compound (I) where R ( is hydrogen;
    X - NH, is subjected to reductive alkylation with a compound of General formula (V)
    CH-R 3
    I 4 co-r 2
    I and the target products are isolated in the form of racemates or an optical isomer, or their salts with a mineral or organic base, or additive compounds (I), where X is NH, with a mineral or organic acid.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1138022A3|1985-01-30|Method of obtaining azabycyclooctanecarbonic acids in form of racemates or optical isomer or their salts
    FI81087C|1990-09-10|Process for the Preparation of New Therapeutically Useful 1-Acyl-2-a zabicyclo [3.3.3] -3-Carboxylic Acids
    US4714708A|1987-12-22|Derivatives of cis, endo-2-azabicyclo[5.3.0]decane-3-carboxylic acid, and their use for treating hypertension
    SU1153827A3|1985-04-30|Method of obtaining substituted aminodiacids,their racemates or optical isomers,or their pharmaceutically acceptable salts
    US4508729A|1985-04-02|Substituted iminodiacids, their preparation and pharmaceutical compositions containing them
    EP0089637B1|1986-10-15|Bicyclic amino acid derivatives, process for their preparation, agents containing them and their application, bicyclic amino acids as intermediates, and process for their preparation
    EP0119161B1|1989-06-28|Benzazocinoneand benzazoninone derivatives, process for their preparation, pharmaceutical preparations containing these compounds, and their therapeutical use
    EP0031741A1|1981-07-08|Substituted imino-acids, process for their preparation and their use as enzyme inhibitors
    DE3000628C2|1988-09-08|
    US4789681A|1988-12-06|Cytoprotective guanidine derivatives useful in ischemic diseases
    US4035370A|1977-07-12|Alkaloid esters
    US4077998A|1978-03-07|Phthaloyl amino acid hydroxamic acids
    EP0206090A2|1986-12-30|Peptide renin inhibitors
    DE3925496C2|1992-04-30|
    EP0115345B1|1988-01-07|Process for the resolution of racemic optically active bicyclic imino-alpha-carboxylic acid esters and use of the compounds obtainable in this way for the synthesis of carboxyalkyl dipeptides
    US4565819A|1986-01-21|Substituted imino diacids, their preparation and pharmaceutical compositions which contain them
    US4490386A|1984-12-25|Phosphate salts of 1-[2-[|-amino]-1-oxoalkyl]octahydro-1H-indole-2-carboxylic acids, preparation of, and medical compositions thereof
    SU1428200A3|1988-09-30|Method of producing racemic or optically active derivatives of 9-or 11-aminoeburnancarboxylic acid or acid-additive salts thereof
    US4537967A|1985-08-27|1-Oxo-1,2,3,4-tetrahydro-3-isoquinoline carboxylic acid derivatives
    EP0203450B1|1992-04-01|Derivatives of bicyclic amino acids process for their preparation, agents containing them and their use
    US4616030A|1986-10-07|Perhydroindole-2-carboxylic acids as antihypertensives
    US4616029A|1986-10-07|Perhydromdole-2-carboxylic acids as antihypertensives
    EP0066254B1|1987-02-04|Mercapto amino acids, process for their preparation and pharmaceutical compositions containing them
    EP0101633B1|1986-12-03|Pyridinecarboxylic esters of dopamine and of its n-alkyl derivatives
    US4866173A|1989-09-12|Therapeutic substituted semicarbazides
    同族专利:
    公开号 | 公开日
    JPS61126025A|1986-06-13|
    OA06930A|1983-05-31|
    AU540609B2|1984-11-29|
    FI73678C|1987-11-09|
    ES506222A0|1983-01-01|
    FI73678B|1987-07-31|
    MA19307A1|1982-07-01|
    ES8301927A1|1983-01-01|
    US4397857A|1983-08-09|
    ZA817251B|1982-09-29|
    NO155098C|1987-02-11|
    KR830007570A|1983-10-21|
    JPS5798281A|1982-06-18|
    NO813541L|1982-04-22|
    JPS6146453B2|1986-10-14|
    FR2492381B1|1983-08-12|
    FR2525604A2|1983-10-28|
    DD201891A5|1983-08-17|
    MX155032A|1988-01-21|
    DE3165428D1|1984-09-13|
    EG15419A|1986-03-31|
    PT73857B|1983-01-25|
    EP0051020A1|1982-05-05|
    FR2492381A1|1982-04-23|
    PT73857A|1981-11-01|
    FR2525604B2|1985-06-07|
    YU245481A|1984-04-30|
    EP0051020B1|1984-08-08|
    IE812460L|1982-04-21|
    KR860001877B1|1986-10-24|
    PH17338A|1984-08-01|
    IL64075D0|1982-01-31|
    DK460181A|1982-04-22|
    GR75389B|1984-07-13|
    DK162444C|1992-03-23|
    AT8892T|1984-08-15|
    CA1183140A|1985-02-26|
    NO155098B|1986-11-03|
    AR228621A1|1983-03-30|
    YU42587B|1988-10-31|
    NZ198701A|1984-07-06|
    JPS6112911B2|1986-04-10|
    HU185058B|1984-11-28|
    AU7662481A|1982-04-29|
    FI813279L|1982-04-22|
    IE51823B1|1987-04-01|
    DK162444B|1991-10-28|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE94175C|
    GB1095105A|1965-04-12|1967-12-13|Scherico Ltd|Novel n--isoquinuclidine-carboxamides|
    US3740408A|1967-09-11|1973-06-19|Upjohn Co|Oxygenated 3-aza bicyclononanes|
    IE52663B1|1980-04-02|1988-01-20|Warner Lambert Co|Substituted acyl derivatives of octahydro-1h-indole-2-carboxylic acids|DE3174844D1|1980-10-23|1986-07-24|Schering Corp|Carboxyalkyl dipeptides, processes for their production and pharmaceutical compositions containing them|
    IE54551B1|1982-01-22|1989-11-22|Ici Plc|Amide derivatives|
    DE3227055A1|1982-07-20|1984-01-26|Hoechst Ag, 6230 Frankfurt|NEW DERIVATIVES OF 2-AZA-BICYCLOOCTAN-3-CARBONIC ACID, METHOD FOR THE PRODUCTION THEREOF, THEIR SUBSTANCES AND THE USE THEREOF, AND 2-AZA-BICYCLOOCTAN-3-CARBONIC ACID AS ANSWER FOR THEIR PRODUCTION|
    DE3246757A1|1982-12-17|1984-06-20|Hoechst Ag, 6230 Frankfurt|NEW 2-AZABICYCLOHEPTAN DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR SUBSTANCES AND THE USE THEREOF, AND 2-AZABICYCLOHEPTAN DERIVATIVES AS INTERMEDIATE PRODUCTS AND METHOD FOR THE PRODUCTION THEREOF|
    DE3303344A1|1983-02-02|1984-08-02|Hoechst Ag, 6230 Frankfurt|METHOD FOR PRODUCING N-ALKYLATED AMINO ACIDS AND THEIR ESTERS|
    US4693996A|1985-12-23|1987-09-15|Warner-Lambert Company|Method of treating heart failure and medicaments therefor|
    DE3707911C1|1987-03-12|1988-03-31|Texaco Ag|Bicyclic amine catalysts|
    FR2619813B1|1987-08-28|1991-05-03|Adir|NOVEL DERIVATIVES OF AZA-2 ACID BICYCLOOCTANE CARBOXYLIC-3, THEIR PREPARATION METHODS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
    FR2635684A1|1988-08-24|1990-03-02|Adir|USE OF DERIVATIVES OF AZA ACID - 2 BICYCLOOCTANECARBOXYLIC - 3 FOR THE PRODUCTION OF MEDICINES FOR THE TREATMENT OF DISEASES CONSECUTIVE TO ALTERATION OF THE VASCULAR WALL AS WELL AS MICROCIRCULATION DISORDERS|
    JPH0426348U|1990-06-25|1992-03-02|
    TW197945B|1990-11-27|1993-01-11|Hoechst Ag|
    LT3872B|1993-12-06|1996-04-25|Hoechst Ag|Novel peptides and pharmaceutical compositionscontaining them|
    FR2746394B1|1996-03-20|1998-05-29|Roussel Uclaf|NOVEL TRICYCLIC COMPOUNDS, THEIR PREPARATION PROCESS, AND INTERMEDIATES THEREOF, THEIR APPLICATION AS MEDICAMENTS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
    AT212990T|1996-03-20|2002-02-15|Hoechst Ag|INHIBITORS OF BONE RESORPTION AND VITRONECTIN RECEPTOR ANTAGONISTS|
    DE19653647A1|1996-12-20|1998-06-25|Hoechst Ag|Vitronectin receptor antagonists, their preparation and their use|
    DE19821483A1|1998-05-14|1999-11-18|Hoechst Marion Roussel De Gmbh|New imidazolidine derivatives useful as leukocyte adhesion and migration inhibitors and/or VLA-4 receptor antagonists for treating E.G. inflammatory and allergic disorders|
    US7001911B2|2000-06-28|2006-02-21|Bristol-Myers Squibb Company|Fused cyclic modulators of nuclear hormone receptor function|
    EP1854798A3|2000-09-19|2007-11-28|Bristol-Myers Squibb Company|Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function|
    WO2002000617A2|2000-06-28|2002-01-03|Bristol-Myers Squibb Company|Selective androgen receptor modulators and methods for their identification, design and use|
    US20040077605A1|2001-06-20|2004-04-22|Salvati Mark E.|Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function|
    US6953679B2|2000-09-19|2005-10-11|Bristol-Myers Squibb Company|Method for the preparation of fused heterocyclic succinimide compounds and analogs thereof|
    US20040087548A1|2001-02-27|2004-05-06|Salvati Mark E.|Fused cyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function|
    US7087636B2|2001-12-19|2006-08-08|Bristol-Myers Squibb Company|Fused heterocyclic compounds and analogs thereof, modulators of nuclear hormone receptor function|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8022438A|FR2492381B1|1980-10-21|1980-10-21|
    [返回顶部]