title: Hypocholesterolemic agents V: Inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by substituted 4-biphenylylalkyl carboxylic acids and methyl esters.
abstract: Eleven substituted 4-biphenylylalkyl carboxylic acids and three methyl esters were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Five of the acids were analogs, resulting from various isosteric replacements of the carbonyl and ether oxygens of the previously described reversible inhibitor 1-(4-biphenylyl)pentyl hydrogen succinate. No significant change in activity was noted, except upon introduction of an amide linkage where a decrease in inhibition was found. Six carboxylic acids and three methyl esters, all containing the 4-biphenylyl radical but lacking the n-butyl side chain found in 1-(4-biphenylyl)pentyl hydrogen succinate, also were inhibitors of the reductase.
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000924:Anticholesteremic Agents; D002264:Carboxylic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000429:Alcohol Oxidoreductases