ARYL-ISOXAZOLO-4-YL-OXADIAZOLE DERIVATIVES

摘要

The present invention is concerned with isoxazol-4-yl-oxadiazole derivatives of formula (I) wherein R<SUP>1</SUP> is hydrogen, halogen, aryl, heterocyclyl, heteroaryl, cyano, lower alkyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-cycloalkyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-N(R)<SUB>2</SUB>, -(CH<SUB>2</SUB>)<SUB>n</SUB>-O-lower alkyl or -(CH<SUB>2</SUB>)<SUB>n</SUB>-OH; n is 0,1 or 2 R is hydrogen or lower alkyl; R<SUP>2</SUP> is cycloalkyl, aryl, heteroaryl or heterocyclyl, which are optionally substituted by one or more substituents, selected from the group consisting of halogen, cyano, nitro, lower alkyl, lower alkoxy, lower alkoxy substituted by halogen, lower alkyl substituted by halogen, C(O)O-lower alkyl, lower alkylsulfonyl, -NR<SUP>a</SUP>R<SUP>b</SUP>, -C(O)-NR<SUP>a</SUP>R<SUP>b</SUP>, -C(O)-heterocyclyl, benzyloxy, heterocyclyl optionally substituted by hydroxy, halogen or lower alkyl, or is heteroaryl optionally substituted by lower alkyl; R<SUP>a</SUP> and R<SUP>b</SUP> are independently hydrogen, lower alkylsulfonyl, -C(O)H, -(CH<SUB>2</SUB>)<SUB>n</SUB>-N(R)<SUB>2</SUB>, -(CH<SUB>2</SUB>)<SUB>n</SUB>-O-lower alkyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-S-lower alkyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-S(O)<SUB>2</SUB>-lower alkyl, heteroarylsulfonyl, lower alkyl, -(CH2)n-heterocyclyl, optionally substituted by lower alkyl, or is -(CH<SUB>2</SUB>)<SUB>n</SUB>-cycloalkyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-heteroaryl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-OH, -(CO)-R', wherein R' is lower alkyl, cycloalkyl or heteroaryl; R<SUP>3</SUP> is aryl or heteroaryl, which are optionally substituted by halogen or lower alkyl substituted by halogen; as well as pharmaceutically acceptable acid addition salts thereof. It has been found that this class of compounds show high affinity and selectivity for GABA a5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders like Alzheimer's disease.