Effects of molecular modification on hypocholesteremic activity of 1,3-bis(substituted phenoxy)-2-propanones and related derivatives

Abstract

A series of 1,3-bis(substituted phenoxy)-2-propanones, long-chain ketones and related derivatives were synthesized. Certain analogues produce significant lowering of serum cholesterol levels in Sprague-Dawley rats. These compounds possess no estrogenic properties and are nontoxic at 10 mg/kg per day. Physical studies on these compounds include an attempt to correlate hypocholesteremic activity with the lipophilic, electronic and steric properties of the compounds. The 1-octanol-H2O partition coefficient was measured for certain derivatives and the .pi. constant for the substituents was calculated. Hammett''s .sigma. constants for aromatic substituents were obtained for the literature. The only correlation found to exist is between hypocholesteremic activity and steric size and position of the aromatic substituents in the propanones.