Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. The synthesis and biological activity of a series of malonester amides

The synthesis and structure-activity relationships of a series of malonester amide ACAT inhibitors are described. One of these compounds, 4s, was shown to be a potent inhibitor of both the intestinal and arterial enzymes, bioactive upon oral dosing (ex vivo bioassay) and efficacious in a clinically relevant rodent model of preestablished hypercholesterolemia.