Hypocholesterolemic agents III: Inhibition of β hydroxy β methylglutaryl coenzyme A reductase by half acid esters of 1 (4 biphenylyl)pentanol

Article abstract of DOI:10.1002/jps.2600650417

A series of half acid esters of 1 (4 biphenylyl)pentanol was synthetized and assayed for inhibition of rat liver β hydroxy β methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and esters groups was varied from zero to 6. A maximum of 1 methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isometric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutamate analog by incorporating a 3 hydroxyl group increased activity 6 fold.