Inhibitors of acyl CoA:cholesterol acyltransferase

Conformational restriction of previously disclosed acyclic diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the mo st potent ACAT inhibitor identified (IC50 = 0.04 mu M in an in vitro rat hepatic microsomal ACAT assay, ED(50) = 0.72 mg/kg/day in cholesterol-fed hamsters).