ARYL-ISOXAZOL-4-YL-IMIDAZOLE DERIVATIVES

摘要

The present invention is concerned with aryl-isoxazol-4-yl-imidazole derivatives of formula (I), wherein R¹ to R³ are each independently hydrogen or halogen; R⁴ is hydrogen, lower alkyl, cycloalkyl, -(CH₂)_n-O-lower alkyl or lower alkyl substituted by hydroxy; R⁵ is -(CH₂)_m-aryl or -(CH₂)_m-heteroaryl which are optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, nitro, lower alkyl, lower alkoxy, lower alkylsulfanyl, lower alkyl substituted by halogen, -C(O)-lower alkyl, -C(O)-O-lower alkyl, -NH-C(O)-O-lower alkyl or -C(O)-NH-R', wherein R' is lower alkynyl or lower alkyl substituted by halogen, or is -(CH₂)_n-cycloalkyl, -(CH₂)_n-heterocyclyl, -(CH₂)_n-heteroaryl or -(CH₂)_n-aryl, optionally substituted by halogen; R⁶ is hydrogen, -C(O)H, -(CH₂)_n-O-lower alkyl, -C(O)O-lower alkyl, lower alkyl substituted by hydroxy or halogen, or is cycloalkyl, aryl, or is -(CH₂)_n-O-CH₂-aryl, optionally substituted by halogen or lower alkyl, or is -(CH₂)_n-O-CH₂-heteroaryl, optionally substituted by halogen, lower alkyl or lower alkyl substituted by halogen, or is -(CH₂)_n-NH-(CH₂)_o-heterocyclyl; n is 0, 1, 2 or 3 m is 0 or 1; o is 1, 2 or 3; as well as with pharmaceutically acceptable acid addition salts thereof. It has been found that this class of compounds show high affinity and selectivity for GABA A a5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders like Alzheimer's disease.