title: Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.
abstract: We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.
authors.affiliation: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hall
authors.forename: Andy
authors.initials: A
authors.lastname: Billinton
authors.forename: Susan H
authors.initials: SH
authors.lastname: Brown
authors.forename: Anita
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Clayton
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Mairi
authors.initials: M
authors.lastname: Gibson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goldsmith
authors.forename: David N
authors.initials: DN
authors.lastname: Hurst
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Peet
authors.forename: Tiziana
authors.initials: T
authors.lastname: Scoccitti
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wilson
authors.forename: Wendy
authors.initials: W
authors.lastname: Winchester