title: Discovery of a novel class of PPARdelta partial agonists.
abstract: Anthranilic acid GW9371 was identified as a novel class of PPARdelta partial agonist through high-throughput screening. The design and synthesis of SAR analogues is described. GSK1115 and GSK7227 show potent partial agonism of the PPARdelta target genes CPT1a and PDK4 in skeletal muscle cells.
authors: Department of Metabolic Chemistry, Metabolic Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. barry.g.shearer@gsk.com
authors: Barry G
authors: BG
authors: Shearer
authors: Hari S
authors: HS
authors: Patel
authors: Andrew N
authors: AN
authors: Billin
authors: James M
authors: JM
authors: Way
authors: Deborah A
authors: DA
authors: Winegar
authors: Millard H
authors: MH
authors: Lambert
authors: Robert X
authors: RX
authors: Xu
authors: Lisa M
authors: LM
authors: Leesnitzer
authors: Raymond V
authors: RV
authors: Merrihew
authors: Stephane
authors: S
authors: Huet
authors: Timothy M
authors: TM
authors: Willson
mesh_terms: D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D006801:Humans; D015394:Molecular Structure; D047494:PPAR delta / Q000819:agonists*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C531989:GSK1115; C531990:GSK7227; C531988:GW9371; D047494:PPAR delta; D044005:Tetrahydroisoquinolines; D062367:ortho-Aminobenzoates; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4