Hypolipidemic Activity of New Phenoxyacetic Derivatives Related to α‐Asarone with Minimal Pharmacophore Features

Five new series of potential hypolipidemic agents 3–7 were synthesized, in order to establish the minimal pharmacophore features associated to the potent hypocholesterolemic activity of natural α‐asarone ( 1 ) and synthetic clofibrate mimetic derivatives 2 . The compounds were examined in hyperlipidemic male mice after oral administration of 25, 50, and 100 mg/Kg for 6 days. The isomeric series of acids and esters 3a–3c and 4a–4c were unexpectedly less active than the most simple structural isomeric compounds 5–7 . This reveals that the phenoxyacetic acid scaffold carrying a hydrocarbon side chain, also found in derivatives 2 , seems to be the most favorable lead for further development of potent hypolipidemic drugs. Drug Dev. Res. 60:186–195, 2003. © 2003 Wiley‐Liss, Inc.