title: Synthesis and dual PPARalpha/delta agonist effects of 1,4-disubstituted 1,2,3-triazole analogues of GW 501516.
abstract: 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-methylphenoxy}acetic acid) exhibited potent agonist activities. Compounds 2e and 2i also exhibited powerful agonist effects for both PPARalpha and PPARdelta in a luciferase-based assay. Consequently, these triazoles can be categorized as dual PPAR agonists.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO BOX 1068, Blindern, N-0316 Oslo, Norway.
authors.forename: Calin C
authors.initials: CC
authors.lastname: Ciocoiu
authors.forename: Natasa
authors.initials: N
authors.lastname: Nikolić
authors.forename: Huyen Hoa
authors.initials: HH
authors.lastname: Nguyen
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
authors.forename: Arne J
authors.initials: AJ
authors.lastname: Aasen
authors.forename: Trond Vidar
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D013844:Thiazoles / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C425931:GW 501516; D047493:PPAR alpha; D047494:PPAR delta; D013844:Thiazoles; D014230:Triazoles