Hypocholesterolemic agents III: inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by half acid esters of 1-(4-biphenylyl)pentanol.
A series of half acid esters of 1-(4-biphenylyl)pentanol was synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and ester groups was varied from zero to six. A minimum of one methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isomeric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutarate analog by incorporating a 3-hydroxyl group increased activity sixfold.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D007536:Isomerism; D008862:Microsomes, Liver / Q000201:enzymology; D000439:Pentanols / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D015003:Yeasts / Q000201:enzymology
D000924:Anticholesteremic Agents; D001713:Biphenyl Compounds; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000439:Pentanols; D000429:Alcohol Oxidoreductases