Hypocholesterolemic Agents IV: Inhibition of β‐Hydroxy‐β‐Methylglutaryl Coenzyme A Reductase by Arylalkenyl and Arylepoxy Hydrogen Succinates and Glutarates

Two series of half acid esters of succinic and glutaric acids were synthesized and assayed for inhibition of rat liver β‐hydroxy‐β‐methylglutaryl coenzyme A reductase. Irreversible inhibition was studied by incorporation of a potential alkylating group (the epoxide function) into the side chain of the alcohol portion of the half acid esters. Incorporation of a terminal olefin function into the side chain of the alcohol portion of the half acid esters provided a group that could form a charge–transfer complex. Neither irreversible inhibition nor formation of a charge–transfer complex was indicated from these studies; however, the two series of half acid esters exhibited reversible inhibition.