公开(公告)号：EP0665226A1

公开(公告)日：1995-08-02

申请号：EP93923647.7

申请日：1993-10-27

申请人： TOYAMA CHEMICAL CO., LTD.

发明人： TAKEDA, Kenji ,  TERASHIMA, Nobuo ,  NAKANO, Joji ,  MINAMI, Hisashi ,  KOBAYASHI, Toyokazu ,  FURUHATA, Kunikazu ,  TAKAKURA, Tadakazu ,  TAKATA, Makoto ,  KAWAFUCHI, Hiroyo ,  HIRAIWA, Toru

IPC分类号： C07D261/20 ,  C07D413/12 ,  C07D417/12 ,  A61K31/42 ,  A61K31/425 ,  A61K31/495 ,  A61K31/535 ,  A61K31/44 ,  A61K31/445

CPC分类号： C07D413/04 ,  C07D261/20 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

摘要： A 1,2-benzisoxazole derivative represented by general formula (I) and a salt thereof, said compound (I) being excellent in the protection against cerebral hypoxia, having the macrobiotic effect on the animals suffering from cerebral ischemia and an antispasmodic effect, having reduced effect on the central nervous system, and having a high safety, thus being useful for treating not only the acute stage of cerebral circulation disorder but also the chronic stage thereof, sequelae of the trauma of the head and epilepsy. In formula (I), R represents hydrogen, halogen, nitro, cyano, hydroxy, optionally substituted lower alkyl, lower alkenyl, lower alkynyl, aralkyl, aryl, lower alkyloxy, cycloalkyl, aralkyloxy, aryloxy, amino, lower acyl, arylcarbonyl, lower alkanesulfonyl, arenesulfonyl, lower alkylthio, carbamoyl, heterocycle, lower alkylene or lower alkenylene; R₁ and R₂, which may be the same or different from each other, represent each hydrogen or optionally substituted lower alkyl; R₃ represents hydrogen, optionally substituted lower alkyl, aryl, aralkyl or heterocycle; R₄ represents optionally substituted lower alkyl, aryl or heterocycle, or alternatively R₃ and R₄ may be combined together to represent lower alkylene; and R₅ and R₆, which may be the same or different from each other, represent each hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkynyl, lower acyl, lower alkyloxycarbonyl or aralkyl.

摘要翻译： 由通式（I）表示的1,2-苯并异恶唑衍生物及其盐，所述化合物（I）具有优异的脑缺氧保护作用，对患有脑缺血和解痉作用的动物具有长效作用， 减少对中枢神经系统的影响，并具有高度的安全性，因此不仅可用于治疗脑循环障碍的急性阶段，而且可治疗其慢性阶段，头部创伤和癫痫的后遗症。 在式（I）中，R代表氢，卤素，硝基，氰基，羟基，任选取代的低级烷基，低级烯基，低级炔基，芳烷基，芳基，低级烷氧基，环烷基，芳烷氧基，芳氧基，氨基，低级酰基， 烷磺酰基，芳磺酰基，低级烷硫基，氨基甲酰基，杂环，低级亚烷基或低级亚烯基; R 1和R 2可以彼此相同或不同，表示每个氢或任选取代的低级烷基; R 3代表氢，任选取代的低级烷基，芳基，芳烷基或杂环; R 4代表任选取代的低级烷基，芳基或杂环，或者R 3和R 4可以结合在一起表示低级亚烷基; R 5和R 6可以相同或不同，表示氢，任选取代的低级烷基，低级链烯基，低级炔基，低级酰基，低级烷氧基羰基或芳烷基。