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

Although fenofibrate (1a) is commercially available and clinically effective in lowering serum triglycerides, its activity and sub-type selectivity at the PPAR alpha receptors are only moderate; therefore, there exists a need for more potent and sub-type selective PPAR alpha agonists. To that end, discovery efforts have identified 2-methyl-2-(4-[3-[1-(4methylbenzyl)-5-oxo-4,5-dihydro-1H-[1,2,4]tiiazol-3-yl]propyl]phenoxy)propionic acid (2), a potent and selective human PPAR alpha 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 (c) 2007 John Wiley & Sons, Ltd.