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    • 45. 发明公开
    • Leukotriene antagonists
    • Leukotrienantagonisten。
    • EP0123541A1
    • 1984-10-31
    • EP84302718.6
    • 1984-04-19
    • MERCK FROSST CANADA INC.
    • Belanger, PatriceGuindon, YvanFortin, RejeanYaokim, ChristianeRokach, Joshua
    • C07C59/90C07C51/347C07C149/40C07C147/107C07D317/14C07D233/78C07D207/44C07D303/02A61K31/19
    • C07D285/10C07C45/71C07C49/84C07C49/86C07C59/90C07C255/00C07D257/04
    • Compounds of the formula:
      and their pharmaceutically acceptable salts, which are novel, are antagonists of leukotrienes of C4, D4 and E., the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic and anti-inflammatory agents and are made into pharmaceutical compositions.
      In the formula, R, is a radical of formula COOR 3 , where R 3 is hydrogen or an alkyl or cycloalkyl group containing not more than six carbon atoms; CH 2 OH; CHO; CH 2 NHSO 2 R 4 , where R 4 is OH; C 1-6 alkyl, C 1-6 alkoxy phenyl, phenyl substituted by Ci-3 alkyl or Ci- 3 alkoxy, halogen, hydroxy, haloalkyl, COOH, CN, formyl, C 1-6 acyl or C 1-4 perfluoroalkyl; CN; or CON(R 5 ) 2 , where each R 5 , independently of the other, is H, OH or C 1-4 alkyl; a tetrazolyl radical, a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group; or a radical of formula
      where each s, independently of the other, is 0,1, 2 or 3; R 7 is

      (A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms, one being N, and the other (if any) being N or S, each ring in the heterocyclic radical having 5 or 6 atoms, or
      (B) a radical X-R 8 where X is O, S or NH and R 8 contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical derived from an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom that is N, 0 or S in the ring; and each R 10 , independently of the other is H or Ci-4 alkyl;
      R 6 is H or Ci-4 alkyl;
      R 2 is a halogen atom; and
      R 9 is a hydrogen atom or hydroxyl group.
    • 下式的化合物及其药物上可接受的盐是C4,D4和E4的白三烯拮抗剂,即过敏反应缓慢的物质。 这些化合物可用作抗哮喘,抗过敏和抗炎剂并制成药物组合物。 在该式中,R 1是式COOR 3的基团,其中R 3是氢或含有不超过6个碳原子的烷基或环烷基; CH2OH; CHO; CH2NHSO2R4,其中R4是OH; C 1-6烷基,C 1-6烷氧基苯基,被C 1-3烷基或C 1-3烷氧基取代的苯基,卤素,羟基,卤代烷基,COOH,CN,甲酰基,C 1-6酰基或C 1-4四氟烷基; CN; 或CON(R5)2,其中每个R5独立于H,OH或C1-4烷基; 四唑基,含有酸性@羟基的单环或双环杂环; 或式的基团,其中每个s独立于0,2,2或3; R2是(A)含有3至12个核碳原子和1或2个核杂原子的单环或双环杂环基,一个为N,另一个为N或S,杂环基中的每个环均为5 或6个原子,或(B)基团X-R8,其中X是O,S或NH和R8含有至多21个碳原子,并且是(1)烃基或(2)衍生自有机非环或 在环中含有不多于1个N,O或S的杂原子的单环羧酸; 每个R 10独立地为H或C 1-4烷基; R6是H或C1-4烷基; R2是卤原子; R9为氢原子或羟基。