Biphenyl versus phenylpyridazine derivatives: the role of the heterocycle in a series of Acyl-CoA:cholesterol acyl transferase inhibitors = 바이페닐계와 페닐피라진계간의 활성 비교 분석

Abstract

A series of alkylamido- (1) and alkylaminobiphenyl (2) derivatives were synthesized as possible bioisosters of the reported ACAT inhibitors phenylpyridazine analogues (I). Both 1 and 2 were tested on the human ACAT-1 and ACAT-2 isoforms. The amino derivatives 2 were found to be inactive, contrary to the related pyridazine derivatives. By contrast, the ortho-substituted amides la and Id showed an interesting activity. These results support the essential role of the pyridazine nucleus. Modeling studies were also performed.