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    • 4. 发明公开
    • SUBSTITUTED CYCLOALKENE DERIVATIVE
    • 取代的环烯烃衍生物
    • EP1935879A1
    • 2008-06-25
    • EP06810068.4
    • 2006-09-13
    • Daiichi Sankyo Company, Limited
    • KIMURA, TomioOHKAWA, NobuyukiNAGASAKI, TakayoshiSUGIDACHI, AtsuhiroANDO, Osamu
    • C07C311/14A61K31/215A61K31/336A61K31/343A61K31/357A61K31/385A61K31/39A61K31/40A61K31/4025A61K31/443A61K31/5375A61P43/00C07D207/50C07D303/36C07D307/94C07D311/96C07D317/72C07D319/08C07D327/04C07D339/06C07D405/12
    • C07C311/14C07C2601/16C07C2602/50C07D303/38C07D307/94C07D317/72C07D319/08C07D321/10C07D327/04C07D339/06C07D339/08C07D493/04C07D493/10
    • [Object]
      To provide a substituted cycloalkene derivative having an action to supress intracellular signal transduction or cell activation induced by endotoxin and to suppress cell responses due to the intracellular signal transduction and cell activation such as an excess generation of inflammatory mediators such as TNF-α, pharmacologically acceptable salts therefor, a medicament containing them as an active ingredient, a preparation method therefor, and a medicament containing the aforementioned substituted cycloalkene derivative as an active ingredient which is superior in prophylaxis and/or treatment of diseases such as sepsis (septic shock, disseminated intravascular coagulation, multiple organ failure and the like), that are associated with intracellular signal transduction or cell activation induced by endotoxin and to cell responses to the intracellular signal transduction and cell activation.
      [Solution]
      A compound represented by the general formula (I):

      {wherein
      X and Y represent a group in which X and Y together with a carbon atom to which they are bound form ring A (the ring is 3- to 7-membered heterocyclyl ring or 3- to 7-membered cycloalkyl ring), each represents a hydrogen atom, or X and Y together represent a substituent of ring B.
      1 and m, independently from each other, represent an integer of 0 to 3, and 1 + m is 1 to 3.
      R 1 is an aliphatic hydrocarbon group and the like which may be substituted with a group selected from Substituent group β and
      Substituent group γ. n represents an integer of 0 to 3.
      R 2 is a C 1 -C 6 alkyl group and the like which may be substituted with a group selected from a hydrogen atom and Substituent
      group β.
      R 3 is a phenyl group, 5- to 6-membered heteroaryl group and the like which may be substituted with a group selected from Substituent group ε.
      R 5 is a C 1 -C 6 alkyl group and the like which may be substituted with a group selected from a hydrogen atom and Substituent group β.
      Provided that in the case where R 3 is a phenyl group which may be substituted with a group selected from Substituent group ε, X and Y represent a group in which X and Y together with a carbon atom to which they are bound form ring A, or X and Y together represent a substituent of ring B.
    • 本发明提供一种取代的环烯烃衍生物,其具有抑制由内毒素诱导的细胞内信号传导或细胞活化的作用,并且抑制由细胞内信号转导和细胞活化引起的细胞应答,例如过量代炎症介质如TNF-α ,其药理学上可接受的盐,含有它们作为活性成分的药物,其制备方法和含有上述取代的环烯烃衍生物作为活性成分的药物,其在预防和/或治疗诸如败血症(败血性休克) ,弥散性血管内凝血,多器官功能衰竭等),其与内毒素诱导的细胞内信号转导或细胞激活以及细胞对细胞内信号转导和细胞活化的应答有关。 由通式(I)表示的化合物:其中X和Y表示其中X和Y与它们所键合的碳原子一起形成环A的基团(该环是3-至7-元 杂环基环或3至7元环烷基环)各自表示氢原子,或者X和Y一起表示环B的取代基。1和m彼此独立地表示0至3的整数,并且1 + m是1至3.R 1是可以被选自取代基组β和取代基组γ的基团取代的脂族烃基等。 n表示0至3的整数.R 2为可以被选自氢原子和取代基组β的基团取代的C 1 -C 6烷基等。 R3是可以被选自取代基组ε的基团取代的苯基,5至6元杂芳基等。 R5是可以被选自氢原子和取代基组β的基团取代的C1-C6烷基等。 只要在R3是可以被选自取代基组ε的基团取代的苯基的情况下,X和Y表示其中X和Y与它们所键合的碳原子一起形成环A的基团,或 X和Y一起表示环B的取代基。