Synthesis and Structure—Activity Relationship Studies on a Novel Series of Naphthylidinoylureas as Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase (ACAT).

Abstract The synthesis and structure–activity relationships of N -phenyl- N′ -[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1- N - n butyl substitution, SM-32504 ( 3m ), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 ( 3m ), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model.