Potential antiatherosclerotic agents. 4. [(Functionalized-alkyl)amino]benzoic acid analogs of cetaben

• Published in: Journal of medicinal chemistry Vol. 26; no. 10; pp. 1411 - 1421
• Main Authors: DeVries, Vern G, Largis, Elwood E, Miner, Thomas G, Shepherd, Robert G, Upeslacis, Janis
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-10-1983
• Subjects: 4-Aminobenzoic Acid - chemical synthesis; 4-Aminobenzoic Acid - pharmacology; 4-Aminobenzoic Acid - therapeutic use; Aminobenzoates - chemical synthesis; Aminobenzoates - pharmacology; Aminobenzoates - therapeutic use; Animals; Arteriosclerosis - drug therapy; Drug Evaluation, Preclinical; Male; Methods; para-Aminobenzoates; Rats; Rats, Inbred Strains; Sterol O-Acyltransferase - antagonists & inhibitors; Sterols - blood; Structure-Activity Relationship; Triglycerides - blood
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00364a011

The synthesis of a series of analogues in which the alkyl group of cetaben is substituted with various functional groups or replaced entirely by a functionalized alkanoyl moiety is described. Also reported are the syntheses of branched-chain (alkylamino)benzoic acids in which branching is specifically localized at the terminus of the alkyl chain. Structure-activity relationships of these compounds, both as hypolipidemic agents and as inhibitors of the enzyme fatty acyl-CoA:cholesterol acyltransferase (ACAT), are discussed. Certain compounds were specifically synthesized to test the hypothesis that groups located near the terminus of the alkyl chain of cetaben might retard metabolic degradation of the molecule and, thus, enhance biological activity. Some of these (48-50) were found to be the most active analogues synthesized.