title: Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists.
abstract: The design, synthesis and structure-activity relationships of a novel series of N-phenyl-substituted pyrrole, 1,2-pyrazole and 1,2,3-triazole acid analogs as PPAR ligands are outlined. The triazole acid analogs 3f and 4f were identified as potent dual PPARalpha/gamma agonists both in binding and functional assays in vitro. The 3-oxybenzyl triazole acetic acid analog 3f showed excellent glucose and triglyceride lowering in diabetic db/db mice.
authors.affiliation: Metabolic Diseases Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Denis E
authors.initials: DE
authors.lastname: Ryono
authors.forename: Pratik
authors.initials: P
authors.lastname: Devasthale
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Malley
authors.forename: Dennis
authors.initials: D
authors.lastname: Farrelly
authors.forename: Liqun
authors.initials: L
authors.lastname: Gu
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrity
authors.forename: Michael
authors.initials: M
authors.lastname: Cap
authors.forename: Cuixia
authors.initials: C
authors.lastname: Chu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Locke
authors.forename: Litao
authors.initials: L
authors.lastname: Zhang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lippy
authors.forename: Lori
authors.initials: L
authors.lastname: Kunselman
authors.forename: Nathan
authors.initials: N
authors.lastname: Morgan
authors.forename: Neil
authors.initials: N
authors.lastname: Flynn
authors.forename: Lisa
authors.initials: L
authors.lastname: Moore
authors.forename: Vinayak
authors.initials: V
authors.lastname: Hosagrahara
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Pathanjali
authors.initials: P
authors.lastname: Kadiyala
authors.forename: Carrie
authors.initials: C
authors.lastname: Xu
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Aneka
authors.initials: A
authors.lastname: Bell
authors.forename: Chiehying
authors.initials: C
authors.lastname: Chang
authors.forename: Jodi
authors.initials: J
authors.lastname: Muckelbauer
authors.forename: Robert
authors.initials: R
authors.lastname: Zahler
authors.forename: Narayanan
authors.initials: N
authors.lastname: Hariharan
authors.forename: Peter T W
authors.initials: PT
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line / Q000201:enzymology; D018360:Crystallography, X-Ray; D015195:Drug Design; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008822:Mice, Transgenic; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001393:Azoles; D047493:PPAR alpha; D047495:PPAR gamma