Kynurenic acid derivatives useful in the treatment of neurodegenerative disorders
申请人:MERCK SHARP & DOHME LTD.
公开号:EP0303387A1
公开(公告)日:1989-02-15
4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, and their pharmaceutically acceptable salts, are potent specific antagonists of N-methyl-D-aspartate (NMDA) receptors and are therefore useful in the treatment of neurodegenerative disorders. 4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, other than carboxy or C₁₋₆ alkoxycarbonyl, are novel compounds, as also are compounds of formula II
wherein R² represents carboxy or a group convertible thereto in vivo, R⁶ is hydrogen and R⁵ and R⁷ represent C₁₋₆ alkyl or halogen, provided that R⁵ and R⁷ are not simultaneously chlorine or simultaneously bromine; a process for preparing the novel compounds is described, as also are pharmaceutical compositions containing the novel compounds.
具有 2-酸性基团或体内可转化基团的 4-氧代-1,4-二氢喹啉化合物及其药学上可接受的盐类是 N-甲基-D-天冬氨酸(NMDA)受体的强效特异性拮抗剂,因此可用于治疗神经退行性疾病。除羧基或 C₁₋₆ 烷氧羰基外,具有 2-酸性基团或在体内可转化的基团的 4-氧代-1,4-二氢喹啉化合物是新型化合物,如式 II 所示的化合物
其中 R² 代表羧基或体内可转化为羧基的基团,R⁶ 是氢,R⁵ 和 R⁷ 代表 C₁₋₆ 烷基或卤素,但 R⁵ 和 R⁷ 不能同时为氯或同时为溴。