DESIGN, SYNTHESIS, AND STRUCTURE-ACTIVITY RELATIONSHIP STUDIES FOR A NEW IMIDAZOLE SERIES OF J774 MACROPHAGE SPECIFIC ACYL-COA-CHOLESTEROL ACYLTRANSFERASE (ACAT) INHIBITORS

Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme invo lved in intracellular cholesterol esterification. Arterial wall infilt ration by macrophages and subsequent uncontrolled esterification of ch olesterol leading to foam cell formation is believed to be an importan t process which leads to the development of fatty streaks. Inhibitors of the ACAT enzyme may retard this atherogenic process. We have recent ly discovered a series of imidazoles which are potent in vitro ACAT in hibitors in the J774 macrophage cell culture assay. This paper will de scribe the design, synthesis, and structure-activity relationship for this very potent series of compounds