title: Identification of a series of PPAR gamma/delta dual agonists via solid-phase parallel synthesis.
abstract: We have developed a general solid-phase synthesis for identification of PPAR ligands. Synthesis of a 480-member library led to the identification of a potent PPAR gamma/delta dual agonist 23. Compound 23 showed good plasma exposure in rats and demonstrated antihyperglycemic and antihyperlipidemic efficacy in diabetic fatty Zucker rats.
authors.affiliation: Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. kevin_liu@stromix.com
authors.forename: K G
authors.initials: KG
authors.lastname: Liu
authors.forename: M H
authors.initials: MH
authors.lastname: Lambert
authors.forename: L M
authors.initials: LM
authors.lastname: Leesnitzer
authors.forename: W
authors.initials: W
authors.lastname: Oliver
authors.forename: R J
authors.initials: RJ
authors.lastname: Ott
authors.forename: K D
authors.initials: KD
authors.lastname: Plunket
authors.forename: L W
authors.initials: LW
authors.lastname: Stuart
authors.forename: P J
authors.initials: PJ
authors.lastname: Brown
authors.forename: T M
authors.initials: TM
authors.lastname: Willson
authors.forename: D D
authors.initials: DD
authors.lastname: Sternbach
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000819:agonists*; D003920:Diabetes Mellitus / Q000628:therapy; D020536:Enzyme Activators / Q000138:chemical synthesis* / Q000494:pharmacology; D006943:Hyperglycemia / Q000517:prevention & control; D006949:Hyperlipidemias / Q000517:prevention & control; D008024:Ligands; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
chemical_list: D004268:DNA-Binding Proteins; D020536:Enzyme Activators; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors