Biphenyl versus phenylpyridazine derivatives : the role of the heterocycle in a series of acyl-CoA : cholesterol acyl transferase inhibitors

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