Sterol O-acyltransferase (SOAT) is a membrane-bound enzyme that aids the esterification of cholesterol and fatty acids to cholesterol esters. SOAT has been studied extensively as a potential drug target, since its inhibition can serve as an alternative to statin therapy. Two SOAT isozymes that have discrete functions in the human body, namely, SOAT1 and SOAT2, have been characterized. Over three decades of research has focused on candidate SOAT1 inhibitors with unsatisfactory results in clinical trials. Recent research has focused on targeting SOAT2 selectively. In this perspective, we summarize the literature covering various SOAT inhibitory agents and discuss the design, structural requirements, and mode of action of SOAT inhibitors.

We report the development of a one-pot Bunte’s reaction-enabled expeditious platform under aqueous conditions for the scalable conversion of sulfonylureas to synthetically versatile thio-sulfonylureas. The reaction was further propagated in the same pot to yield diverse chiral and achiral isothiosulfonyl analogs. The protocol enabled the synthesis of various drug-like molecules and was applied to an enantiomeric synthesis of a cannabinoid receptor antagonist SLV326.