Novel use of 5-phenyl-2-furan esters, amides and ketones as neuroprotective agents
申请人:Norwich Eaton Pharmaceuticals, Inc.
公开号:EP0404233A2
公开(公告)日:1990-12-27
The present invention encompasses methods of using 5-phenyl-2-furan esters, amides and ketones and compositions thereof to prevent or limit neuronal death or degeneration in a human or lower animal. These methods comprise systemically administering to such human or other animal a safe and effective amount of a compound of the formula:
wherein
(1) X is halo or nil; and Y is a substituent selected from the group consisting of unsubstituted or halogen-substituted methyl, halo, nitro, amino, and methoxy; and
(2) R is R¹C(O)OH, R¹C(O)N(R³)₂, N(R³)₂, OR¹N(R³)₂, R¹N(R³)₂, N(R²)R¹N(R³)₂, or N(R²)N(R³)₂; where
R¹ is C₁-C₃ alkyl which is unsubstituted or substituted with C₁-C₂ alkyl;
R² is hydrogen or lower alkyl; and
each R³ is, independently, hydrogen or lower alkyl; or both R³ groups are connected to form a saturated 5- or 6-membered heterocycle containing 1 or 2 heteroatoms selected from oxygen and nitrogen, and said heterocycle is unsubstituted or substituted with lower alkyl or hydroxy-substituted lower alkyl;
or a pharmaceutically acceptable salt thereof.
本发明包括使用 5-苯基-2-呋喃酯、酰胺和酮及其组合物防止或限制人或低等动物神经元死亡或变性的方法。这些方法包括向人或其他动物全身施用安全有效量的式化合物:
式中
(1) X 是卤代或零;Y 是选自由未取代或卤代甲基、卤代、硝基、氨基和甲氧基组成的组的取代基;和
(2) R 是 R¹C(O)OH、R¹C(O)N(R³)₂、N(R³)₂、OR¹N(R³)₂、R¹N(R³)₂、N(R²)R¹N(R³)₂ 或 N(R²)N(R³)₂;其中
R¹ 是未取代或被 C₁-C₂ 烷基取代的 C₁-C₃ 烷基;
R² 是氢或低级烷基;以及
每个 R³ 独立地为氢或低级烷基;或两个 R³ 基团连接形成饱和的 5 或 6 元杂环,该杂环含有 1 或 2 个选自氧和氮的杂原子,且所述杂环未被取代或被低级烷基或羟基取代的低级烷基取代;
或其药学上可接受的盐。