申请人:Mitsubishi Pharma Corporation
公开号:US06455528B1
公开(公告)日:2002-09-24
The present invention relates to a piperazine compound of the formula
wherein R1 and R2 are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4 and R5 are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6 and R7 are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8 and R9 are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-&agr; production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-&agr; production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-&agr; production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-&agr; mediated diseases.
本发明涉及一种哌嗪化合物,其化学式为
其中R1和R2分别为氢、卤素、低烷基、低烷氧基、氨基、取代氨基、硝基、羟基或氰基,R3、R4和R5分别为氢、卤素、低烷基、低烷氧基、硝基、氨基、取代氨基或羟基,R6和R7分别为氢、低烷基、受卤素取代的低烷基、芳基烷基、酰基或受卤素取代的低酰基,R8和R9分别为氢或低烷基,Y为低烷基烯基等,环A为苯基、嘧啶基、噻唑基、吡啶基、吡啉基或咪唑基,其药学上可接受的盐及含有这些化合物的药物制剂。本发明的化合物具有优越的TNF-α产生抑制作用和/或IL-10产生促进作用,由于它不含或仅显示对中枢神经系统有显著减少的作用,该化合物可用作高度安全和优越的TNF-α产生抑制剂和/或IL-10产生促进剂,并可用作预防或治疗由异常TNF-α产生引起的各种疾病的药剂,例如可用于治疗可通过IL-10治愈的慢性炎症性疾病、急性炎症性疾病、感染引起的炎症性疾病、自身免疫疾病、过敏性疾病和TNF-α介导的疾病。