The synthesis of three isotopomers of 2-methyl-2-(4-[3-[1-(4-methylbenzyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]propyl]phenoxy)propionic acid, a potent and selective peroxisome proliferator-activated receptor alpha agonist

✍ Scribed by Fengjiun Kuo; Dean K. Clodfelter; Nagy A. Farid; William J. Wheeler; Lennon H. McKendry

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 184 KB
• Volume: 50
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1395

✦ Synopsis

Abstract

Although fenofibrate (1a) is commercially available and clinically effective in lowering serum triglycerides, its activity and sub‐type selectivity at the PPARα receptors are only moderate; therefore, there exists a need for more potent and sub‐type selective PPARα agonists. To that end, discovery efforts have identified 2‐methyl‐2‐(4‐[3‐[1‐(4‐methylbenzyl)‐5‐oxo‐4,5‐dihydro‐1__H__‐[1,2,4]triazol‐3‐yl]propyl]phenoxy)propionic acid (2), a potent and selective human PPARα receptor agonist. In support of pre‐clinical ADME studies and bioanalysis, three isotopomers of 2 have been synthesized. The results of these efforts are described below. Copyright © 2007 John Wiley & Sons, Ltd.