title: Discovery of GSK1997132B a novel centrally penetrant benzimidazole PPARγ partial agonist.
abstract: The peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor, thought to play a role in energy metabolism, glucose homeostasis and microglia-mediated neuroinflammation. A novel benzimidazole series of centrally penetrant PPARγ partial agonists has been identified. The optimization of PPARγ activity and in vivo pharmacokinetics leading to the identification of GSK1997132B a potent, metabolically stable and centrally penetrant PPARγ partial agonist, is described.
authors.affiliation: Neurosciences Centre for Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, CM19 5AW, United Kingdom. m.sime@beatson.gla.ac.uk
authors.forename: Mairi
authors.initials: M
authors.lastname: Sime
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Allan
authors.forename: Paul
authors.initials: P
authors.lastname: Chapman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Fieldhouse
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Mark P
authors.initials: MP
authors.lastname: Healy
authors.forename: Millard H
authors.initials: MH
authors.lastname: Lambert
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Leesnitzer
authors.forename: Ann
authors.initials: A
authors.lastname: Lewis
authors.forename: Raymond V
authors.initials: RV
authors.lastname: Merrihew
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rutter
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sasse
authors.forename: Barry G
authors.initials: BG
authors.lastname: Shearer
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Willson
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Wilson
authors.forename: Robert X
authors.initials: RX
authors.lastname: Xu
authors.forename: David J
authors.initials: DJ
authors.lastname: Virley
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D015394:Molecular Structure; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; C568622:GSK 1997132B; D047495:PPAR gamma; C031000:benzimidazole