title: Identification and optimization of novel 1,3,4-oxadiazole EP1 receptor antagonists.
abstract: A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with highest affinity displayed a binding IC50 of 2.5 nM (pIC50 8.6).
authors.affiliation: Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. adrian.2.hall@gsk.com
authors.forename: Adrian
authors.initials: A
authors.lastname: Hall
authors.forename: Susan H
authors.initials: SH
authors.lastname: Brown
authors.forename: Anita
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Mairi
authors.initials: M
authors.lastname: Gibson
authors.forename: Mark P
authors.initials: MP
authors.lastname: Healy
authors.forename: David G
authors.initials: DG
authors.lastname: Livermore
authors.forename: Richard J McArthur
authors.initials: RJ
authors.lastname: Wilson
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: D Anthony
authors.initials: DA
authors.lastname: Rawlings
authors.forename: Shilina
authors.initials: S
authors.lastname: Roman
authors.forename: Emma
authors.initials: E
authors.lastname: Ward
authors.forename: Caroline
authors.initials: C
authors.lastname: Willay
mesh_terms: D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013329:Structure-Activity Relationship
chemical_list: D010069:Oxadiazoles; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype