Studies on Hypolipidemic Agents. V. Synthesis and Esterase-Inhibitory Activity of 2- (1, 4- and 4, 4-Dialkylcyclohexyl) -2- oxoethyl Arenesuffonates

Abstract

2- (1, t- and c-4-Dialkylcyclohex-r-1-yl) -2-oxoethyl arenesulfonates, 2- (4, 4-dialkylcyclohex-1-yl) -2-oxoethyl arenesulfonates and related compounds were synthesized and evaluated for esteraseand chymotrypsin-inhibitory activities in vitro and for hypolipidemic effect in vivo. The transisomers of 2- (1, 4-dialkylcyclohex-1-yl) -2-oxoethyl arenesulfonates showed much more potent esterase-inhibitory action (about 13 to 6200 times) than the cis-isomers as well as more potent hypolipidemic action (about 1.5 to 10 times) but the chymotrypsin-inhibitory actions of the two isomers were similarly low. On the other hand, the 2-oxoethyl arenesulfonates having a 4, 4- disubstituted cyclohexane ring mostly exhibited potent esterase-inhibitory action (order of IC₅₀; 10^-8 to 10^-9M) and marked hypolipidemic effect (78% to 95% reductions of plasma triglyceride).