Hypocholesteremic derivatives of styrylacetic acid. 1. gem-Dimethyl analogs of benzalbutyric acid

Abstract

The preparation of alpha, alpha-dimethyl analogs of the hypocholesteremic and hypolipemic agent 3-methyl-4-phenyl-3-butenoic acid (beta-benzalbutyric acid, BBA) is described. These compounds were prepared as part of a continuing program directed toward a study of the structure-activity interrelationships of styryl- and phenoxyacetic acid antilipemic agents and the preparation of metabolically resistant analogs of BBA. Preliminary results on the in vitro ability of the compounds to inhibit cholesterol biosynthesis indicate that alpha, alpha-dimethyl substitution reduces activity although the potency of the p-chloro analog 6b was comparable to that of BBA.

Potential Hypocholesteremic Derivatives of Styrylacetic Acid II: cis- and trans-3-Methyl-4-phenyl-3-butenoic Acid Analogs

“…Compounds IIa, IIb, IIIa, and IIIb were examined for their ability to inhibit the incorporation of 2-14C-acetate into nonsaponifiable sterols by rat liver homogenates using the method described previously (1) ( Table I).…”