Synthesis and dual PPARα/δ agonist effects of 1,4-disubstituted 1,2,3-triazole analogues of GW 501516

Ten 1,4-disubstituted 1,2,3-triazoles 2a-2j were prepared and tested for their ability to increase oleic acid oxidation in human myotubes using a high-throughput multiwell assay. Compounds 2e (2-{4-[(1-(3-fluoro-4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methylphenoxy}acetic acid) and 2i (2-{4-[(1-(3-chloro-4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methylthio]-2-methyl-phenoxy)acetic acid) exhibited potent agonist activities. Compounds 2e and 2i also exhibited powerful agonist effects for both PPAR alpha and PPAR delta in a luciferase-based assay. Consequently, these triazoles can be categorized as dual PPAR agonists. (c) 2010 Elsevier Masson SAS. All rights reserved.