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    • 7. 发明公开
    • Benzoylacetylene derivatives
    • 苯甲酰乙酰胺衍生物。
    • EP0645379A2
    • 1995-03-29
    • EP94111896.0
    • 1994-07-29
    • Mitsubishi Chemical Corporation
    • Takayanagi, HisaoKitano, YasunoriInokawa, HarukiSuzuki, Tsuyoshi
    • C07D295/104C07D211/14C07D213/50C07D209/12C07D317/54C07D317/64C07D295/135C07C225/16C07C49/255C07C311/29C07C235/78A61K31/445A61K31/36C07F7/08
    • C07D213/30C07C17/2635C07C43/23C07C45/00C07C45/298C07C45/673C07C49/794C07C49/796C07C49/807C07C49/813C07C49/835C07C49/84C07C69/007C07C69/017C07C69/738C07C205/45C07C225/16C07C225/20C07C235/16C07C271/18C07C275/28C07C311/40C07C2601/14C07D209/14C07D213/50C07D213/74C07D295/104C07D295/135C07D317/58C07D317/62C07D317/64C07F7/0818C07C22/04C07C47/546
    • A compound of the following formula (I)


      wherein R 1 ~ R 5 are independently hydrogen; -OR 7 wherein R 7 is hydrogen, C 1 ~ C 5 alkyl optionally substituted by halogen or phenyl, or -COR 8 wherein R 8 is phenyl or C 1 ~ C 5 alkyl optionally substituted by phenyl; halogen;
      C 1 ~ C 5 alkyl optionally substituted by halogen; -NR 9 R 10 wherein R 9 and R 10 are independently hydrogen, phenyl,
      C 1 ~ C 5 alkyl optionally substituted by phenyl, benzoyl, or acetyl;
      -SOpR 11 wherein p is 0, 1 or 2, R 11 is C 1 ~ C 5 alkyl or phenyl; cyano; or nitro; or when adjacent substituents are taken together, they may represent C 1 ~ C 3 oxyalkylene having one or two oxygen atoms,
      R 6 is hydrogen; C 1 ~ C 5 alkyl;

      wherein Y 1 , Y 2 and Y 3 are independently hydrogen, pyridyl, C 1 ~ C 5 alkyl, phenyl or halogen;

      wherein Z 1 , Z 2 and Z 3 are independently hydrogen, C 1 ~ C 5 alkyl or halogen;
      C 3 - C 12 trialkylsilyl; -COR 12 wherein R 12 is C 1 ~ C 5 alkyl, phenyl, C 1 ~ C 5 alkoxy optionally substituted by phenyl, or -NR 13 R 14 wherein R 13 and R 14 are independently hydrogen, C 1 ~ C 5 alkyl optionally substituted by phenyl, or phenyl optionally substituted by halogen; or -CR 15 R 16 X wherein R 15 and R 16 are independently hydrogen, phenyl, C 1 ~ C 5 alkyl optionally substituted by phenyl, or C 3 - C 8 cycloalkyl, or when taken together to be C 3 - C 7 alkylene optionally substituted by C 1 ~ C 5 alkyl, X is -OR 17 wherein R 17 is hydrogen, C 1 ~ C 5 alkyl optionally substituted by phenyl, or -COR 18 wherein R 18 is phenyl or C 1 ~ C 5 alkyl optionally substituted by phenyl, -COR 19 wherein R 19 is hydroxyl, phenyl optionally substituted by C 1 ~ C 5 alkyl, C 1 ~ C 5 alkyl optionally substituted by phenyl, C 1 ~ C 5 alkoxy optionally substituted by phenyl, or
      -NR 20 R 21 wherein R 20 and R 21 are independently hydrogen, C 1 ~ C 5 alkyl or phenyl optionally substituted by halogen, -SOpR 22 wherein p is 0, 1 or 2, R 22 is
      C 1 ~ C 5 alkyl or phenyl, or -NR 23 R 24 wherein R 23 and R 24 are independently hydrogen, phenyl optionally substituted by halogen or C 1 ~ C 5 alkyl, or C 1 ~ C 5 alkyl optionally substituted by hydroxyl, phenyl, C 1 ~ C 5 alkylamino, C 2 ~ C 6 dialkylamino or indolyl, C 3 - C 8 cycloalkyl, pyridyl, -SO 2 R 27 wherein R 27 is phenyl optionally substituted by C 1 ~ C 3 alkoxy, or -COR 25 wherein R 25 is C 1 ~ C 5 alkyl, phenyl, or C 1 ~ C 5 alkoxy optionally substituted by pyridyl, N-methylpyridyl, N-oxopyridyl or phenyl optionally substituted by carboxyl or sodium carboxylate, or when R 23 and R 24 are taken together, they are C 3 - C 6 alkylene optionally containing therein -O-,
      or -NR 26 -
      wherein R 26 is hydrogen, phenyl or C 1 ~ C 5 alkyl, or C 3 - C 6 alkylene optionally substituted by C 1 ~ C 5 alkyl with a proviso that when R 6 is hydrogen, R 2 and R 3 are not methoxy,
      or its salt, and a pharmaceutical composition containing at least one of these compounds, which is useful as a tyrosine kinase inhibitor and useful for suppressing the growth of cancer cells.
    • 下式(I)的化合物其中R 1和R 5独立地是氢; -OR 7其中R 7为氢,任选被卤素或苯基取代的C 1 -C 5烷基或-COR 8,其中R 8为苯基或任选被苯基取代的C 1 -C 5烷基; 卤素; 任选被卤素取代的C 1 -C 5烷基; -NR 9 R 1其中R 9和R 1独立地是氢,苯基,任选被苯基,苯甲酰基或乙酰基取代的C 1 -C 5烷基; -SOpR 1其中p为0,1或2,R 1为C 1 -C 5烷基或苯基; 氰基; 或硝基; 或者当相邻取代基一起使用时,它们可以表示具有一个或两个氧原子的C 1 -C 3氧化烯,R 6是氢; C1类C5烷基; 其中Y 1,Y 2和Y 3独立地是氢,吡啶基,C 1 -C 5烷基,苯基或卤素; 其中Z 1,Z 2和Z 3独立地是氢,C 1 -C 5烷基或卤素; C3类似的C12三烷基甲硅烷基; -COR 1其中R 1 2是C 1 -C 5烷基,苯基,任选被苯基取代的C 1 -C 5烷氧基,或-NR 1 R 3,其中 R 1,R 3和R 4独立地是氢,任选被苯基取代的C 1 -C 5烷基或任选被卤素取代的苯基; 或-CR 1 R 5 R 1 X 6其中R 1和R 2独立地是氢,苯基,任选被苯基取代的C 1 -C 5烷基或C 3 类似的C 8环烷基,或者当它们一起作为任选被C 1 -C 6烷基取代的C 3 -C 7亚烷基时,X是-OR 1,其中R 1是氢,任选地被 苯基或-COR 1 8其中R 1 8是苯基或任选被苯基取代的C 1 -C 5烷基,-COR 1 9其中R 1 9是羟基, 任选被C 1 -C 5烷基取代的苯基,任选被苯基取代的C 1 -C 5烷基,任选被苯基取代的C 1 -C 5烷氧基或-NR 2 R 2其中R 2 <0 >和R 2独立地是氢,C 1 -C 5烷基或任选被卤素取代的苯基,-SO 2 R 2,其中p是0,1或2,R 2是C 1 类似的C 5烷基或苯基或-NR 2 3 R 2 4其中R 2和R 2都独立地是氢,任选被卤素取代的苯基 或C 1 -C 5烷基,或任选被羟基取代的C 1 -C 5烷基,苯基,C 1 -C 6烷基氨基,C 2 C 6二烷基氨基或吲哚基,C 3 -C 10环烷基,吡啶基,-SO 2 R 2,其中R 2, 其中R 2是C 1 -C 6烷基,苯基或任选被吡啶基,N-取代的C 1-6烷氧基取代的C 1 -C 5烷氧基, 甲基吡啶基,N-氧代吡啶基或任选被羧基或羧酸钠取代的苯基,或当R 2'3和R 2 <4>一起时,它们是任选地含有其中的C 1-3亚烷基C6亚烷基, CHEM>或-NR 2 <6> - 其中R 2是氢,苯基或C 1-6烯基,或任选被C 1 -C 6烷基取代的C 3 -C 6亚烷基,条件是当R 6 >是氢,R 2和R 3不是甲氧基或其盐,以及含有这些化合物中的至少一种的药物组合物,其可用作酪氨酸激酶抑制剂并且可用于抑制 纳入癌细胞的生长。