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

Abstract

2-(l,t- and c-4-Dialkylcyclohex-r-l-yl)-2-oxoethyl arenesulfonates, 2-(4,4-dialkylcyclohex-l-yl)-2-oxoethyl arenesulfonates and related compounds were synthesized and evaluated for esterase-and chymotrypsin-inhibitory activities in vitro and for hypolipidemic effect in vivo. The transisomers of 2-(l,4-dialkylcyclohex-l-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). © 1987, The Pharmaceutical Society of Japan. All rights reserved.