• 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:
    The invention relates to substituted dihydropyridines, in particular 1.4 dihydropyridines of the general formula CHR-CX CY-NH-C (CH) CZ (l), where X is -C
    公开号:SU1279528A3
    申请号:SU3618704
    申请日:1983-07-19
    公开日:1986-12-23
    发明作者:Фрейзер Кэмпбелл Симон；Эдвард Кросс Петер；Кендрик Стаббс Джон
    申请人:Пфайзер Корпорейшн (Фирма)；
    IPC主号:
    专利说明:

    N3
    WITH
    ate
    权利要求:
    Claims (2)
    [1]
     o 112 The invention relates to methods for the preparation of new 1,4-dihydropyridine derivatives of the general formula H R R LOOCs: .cOOR2 HzC CH2-0- (CH2) 2-X H where R is mono- and dichlorophenyl; R and R - (C, -C4.) - alkyl; X is trimethylimidazole-; 2hydride, 1,2,4-triazol-4-yl, or their hydrochlorides with calcium antagonist properties. The purpose of the invention is the development, on the basis of a known method, of a method for the preparation of new derivatives of 1,4-dihydropyridines with valuable pharmacological properties. Example 1. 4- (2-Chlorophenyl) -3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2- 2- (2,4,5-trimethyl-1-imidazolyl) ethoxymethyl -1, 4-dihydropyridine, hydrochloride salt. Ethyl 4- 2- (2,4,5-7 trnmethyl-1-imide zolyl) ethoxy acetoacetate (6.4 g1, 2-chlorbeneepdegil (3.2 g), methyl 3-aminocrotonate (2.6 g) and acetic acid (31 ml) in ethanol (15 ml) is mixed and refluxed for 4.4 h. Then the cooled reaction mixture is evaporated to dryness and the residue is distributed between 2N hydrochloric acid (100 ml) and toluene (50 ml) The acid layer is separated, extracted with methylene chloride (3 x 20 ml) and the extracts are washed with a saturated aqueous solution of sodium carbonate (30 ml), dissolved over sodium carbonate, filtered and evaporated. the current is chromatographed on a small amount of toluene on silica gel, eluting with methylene chloride with 30% by volume of petroleum ether. The appropriate fractions are combined, evaporated to dryness and redissolved in ethyl acetate. The addition of the ethereal solution of hydrogen chloride results in precipitation of the hydrochloride salt, which is recrystallized from ethyl acetate to obtain the target compound (ls2 g), melt 167-168 ° C. Found: C, 57.30; H 6.07; N 7.7G, C HjjClN O J HC1. Calculated,%: C 57.99; H 6.18; N 7.80. 8 Example
    [2]
    2. ((D- (3-Dichlorophenyl) -4-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyrid, -2-nni) methoxy), 2,4-triazole, Ethyl ester solution (1 , 2,4-triazol-4-yl) ethoxy acetoacetic acid (4.8 g), 2,3-dichlorobenzaldehyde (3.4 g), 3-aminocrotonic acid methyl ester (2.3 g) and acetic acid ( 1.0 ml) in 30 ml of ethyl alcohol is heated under reflux for 16 hours and evaporated. The residue was partitioned between ethyl acetate and water, and the organic layer was washed with water, dried over sodium sulfate, and evaporated. The residue is purified by chromatography on silica gel (60 g) using toluene with 0-100% ethyl acetate as an eluant. The appropriate fractions are combined and boiled, the residue is subjected to crystallization from ether, the target compound of the example is obtained: (1.3 g), t .ll 86-88 C. Found,% g C 53.17; H 5.20; N 10.91. С ,, Н ,, С1гН, 05 Calculated,%: C 53.34; H 4.85, N 11.31. To assess the effects of calcium antagonists (compounds of examples 1 and 2), their effects on the coronary circulation of anesthetized dogs are investigated. ) and record the time required to reduce by 50% the maximum effect of coronary vascular resistance. The following data was obtained: Compound Half-period 5-3 h In Example 1 6.5 h In Example 2 5-10 min. Nifedipine The IC value is the molar concentration of the compound, which is necessary to reduce the sensitivity of an isolated rat aorta to calcium ions by 50%. . For the compound of example ICjo is 5.01 x x, for example 2, 2.63 "10m. For the compound of examples 1 and 2, the symptom of acute toxicity was not found when conducting experiments on an animal at a dose of up to 20 mg / kg (for dogs) or 60 mg / kg (for rats). The invention The method of obtaining 1,4-dihydropyridines of the general formula I H R R LOO C x. COOR 2 (CH 2) 2-X H where R is mono- and dichlorophenyl; RI and EZ - (C, -C4) -alkyl, X - trimethylimidazol-2-sh1, 1,2,4-triazol-4-yl, or their hydrochloro-. RIDOV, characterized in that the compounds of the general formulas II, III, IV are reacted by the Ganch / COORo CH2 C 0 H2- method (HCH2VX where R, R ,, R, X have the indicated meanings, in ethanol with the subsequent separation of the target product in free form or in the form of hydrochloride.
    类似技术:
    公开号 | 公开日 | 专利标题
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    同族专利:
    公开号 | 公开日
    AU1716583A|1984-01-26|
    SU1279528A1|1986-12-23|
    DK333683A|1984-01-23|
    FI832648A0|1983-07-20|
    EP0100189A2|1984-02-08|
    ES8504126A1|1985-04-16|
    IE55797B1|1991-01-16|
    DD211340A5|1984-07-11|
    DK333683D0|1983-07-20|
    JPS6348271B2|1988-09-28|
    GR78880B|1984-10-02|
    EP0100189A3|1984-05-23|
    CS235334B2|1985-05-15|
    IE831713L|1984-01-22|
    PL139905B1|1987-03-31|
    AU542962B2|1985-03-28|
    ES524236A0|1985-04-16|
    IL69284A|1986-08-31|
    CA1248961A|1989-01-17|
    DE3363743D1|1986-07-03|
    NZ204964A|1986-02-21|
    FI79103B|1989-07-31|
    US4616024A|1986-10-07|
    YU156783A|1986-06-30|
    FI79103C|1989-11-10|
    JPS5942380A|1984-03-08|
    AT20064T|1986-06-15|
    FI832648A|1984-01-23|
    IL69284D0|1983-11-30|
    PH30061A|1996-11-08|
    PT77072A|1983-08-01|
    EP0100189B1|1986-05-28|
    PT77072B|1986-04-09|
    ZA835310B|1984-04-25|
    KR840005425A|1984-11-12|
    NO832632L|1984-01-23|
    HU190725B|1986-10-28|
    PL243130A1|1984-10-22|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE2248150A1|1972-09-30|1974-04-04|Bayer Ag|DIHYDROPYRIDINE POLYESTER, METHOD FOR MANUFACTURING AND USING THEM AS A MEDICINAL PRODUCT|
    US3946028A|1972-09-30|1976-03-23|Bayer Aktiengesellschaft|2,3,5,6-Tetracarboxy-4-pyridyl-1,4-dihydropyridine derivatives|
    US3946027A|1972-09-30|1976-03-23|Bayer Aktiengesellschaft|3,5,6-Tricarboxy-4-pyridyl-1,4-dihydropyridine derivatives|
    US3943140A|1972-09-30|1976-03-09|Bayer Aktiengesellschaft|2,3,5,6-Tetracarboxy-1,4-dihydropyridine derivatives|
    GB1552911A|1975-07-02|1979-09-19|Fujisawa Pharmaceutical Co|1,4 dihydropyridine derivatives and the preparation thereof|
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    US4307103A|1978-09-08|1981-12-22|Fujisawa Pharmaceutical Co., Ltd.|Dihydropyridine derivative, processes for preparation thereof and pharmaceutical composition comprising the same|
    JPS5547656A|1978-09-29|1980-04-04|Dainippon Pharmaceut Co Ltd|2--1,4-dihydropyridine derivative and its derivative|
    SE7910521L|1979-12-20|1981-06-21|Haessle Ab|NEW 2-METHYL-6-SUBSTITUTED-4- -1,4-DIHYDROPYRIDINE-3,5-DIESTERS WITH HYPOTHESIVE PROPERTIES, AND PROCEDURES FOR THEIR PREPARATION AND PHARMACEUTICAL PREPARATION|
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    CS228917B2|1981-03-14|1984-05-14|Pfizer|Method of preparing substituted derivatives of 1,4-dihydropyridine|
    JPH0128746B2|1981-04-23|1989-06-05|Banyu Pharma Co Ltd|
    NZ201395A|1981-07-30|1987-02-20|Bayer Ag|Pharmaceutical compositions containing 1,4-dihydropyridines and certain of these dihydropyridines|
    EP0100189B1|1982-07-22|1986-05-28|Pfizer Limited|Dihydropyridine anti-ischaemic and antihypertensive agents|
    JP5547656B2|2008-01-15|2014-07-16|ザボードオブトラスティーズオブザレランドスタンフォードジュニアユニバーシティー|Methods for manipulating phagocytosis mediated by CD47|EP0100189B1|1982-07-22|1986-05-28|Pfizer Limited|Dihydropyridine anti-ischaemic and antihypertensive agents|
    PT77842B|1982-12-21|1986-05-05|Pfizer|Process for preparing dihydropyridines|
    US4568677A|1983-07-23|1986-02-04|Pfizer Inc.|2- dihydropyridine anti-ischaemic and antihypertensive agents|
    GB8401288D0|1984-01-18|1984-02-22|Pfizer Ltd|Therapeutic agents|
    GB8412208D0|1984-05-12|1984-06-20|Pfizer Ltd|Quinolone inotropic agents|
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    GB8415386D0|1984-06-15|1984-07-18|Pfizer Ltd|Therapeutic agents|
    GR851819B|1984-08-17|1985-11-26|Wyeth John & Brother Ltd|
    GB8421039D0|1984-08-17|1984-09-19|Wyeth John & Brother Ltd|Heterocyclic compounds|
    EP0225175A3|1985-11-28|1988-12-28|FISONS plc|Dihydropyridine derivatives, processes for their preparation and pharmaceutical compositions thereof|
    DE3601196A1|1986-01-17|1987-07-23|Merck Patent Gmbh|1,4-DIHYDROPYRIDINE|
    GB8601382D0|1986-01-21|1986-02-26|Pfizer Ltd|Dihydropyridine antiischaemic & antihypertensive agents|
    GB8602518D0|1986-02-01|1986-03-05|Wyeth John & Brother Ltd|1 4-dihydropyridines|
    GB8620880D0|1986-08-29|1986-10-08|Pfizer Ltd|Therapeutic agents|
    NO874194L|1986-11-07|1988-05-09|Pfizer Ltd|PROCEDURE FOR THE PREPARATION OF DIHYDRO-PYRIDINE DERIVATIVES|
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    US5739333A|1995-05-16|1998-04-14|Tanabe Seiyaku Co., Ltd.|Sulfonamide derivative and process for preparing the same|
    US5977369A|1995-12-28|1999-11-02|Napp Technologies, Inc.|Process to prepare dihydropyridine and derivatives thereof|
    IT1283793B1|1996-08-23|1998-04-30|Lusochimica Spa|DIHYDROPYRIDINE PREPARATION PROCESS|
    IT1310933B1|1999-11-16|2002-02-27|Luigi Benatti|MULTIFUNCTIONAL MACHINE FOR LOCOREGIONAL MONITORING AND DITERAPY CONTROL IN ONCOLOGY.|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB8221214|1982-07-22|
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