Hypolipidemic Activity of New Phenoxyacetic Derivatives Related to X-Asarone with Minimal Pharmacophore Features

Abstract

Five new series of potential hypolipidemic agents 3-7 were synthesized, in order to establish the minimal pharmacophore features assoc iated to the potent h ypocholesterolemic acti vity of natural :x-asarone (1) and synthetic clofibrate mimetic derivatives 2. The compounds were exam ined in hyperlipidemic male mice after oral administration of 25, 50, and 1 00 mg/Kg for 6 days. The isomeric series of acids and esters 3a-3c and 4a-4c were unexpectedly less active than the most simpl e structural isomeric compounds S-7. This reveals that the phenoxyacetic acid scaffold car rying a h ydrocarbon side chain, also found in deri vatives 2, seems to be the most favorable lea d for further development of potent hypolipidemic drugs.