title: Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.
abstract: Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP(1) receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.
authors.affiliation: Neurology 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: Andy
authors.initials: A
authors.lastname: Billinton
authors.forename: Susan H
authors.initials: SH
authors.lastname: Brown
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Clayton
authors.forename: Anita
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hayhow
authors.forename: David N
authors.initials: DN
authors.lastname: Hurst
authors.forename: Ian R
authors.initials: IR
authors.lastname: Kilford
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: Barry
authors.initials: B
authors.lastname: Passingham
authors.forename: Lisa
authors.initials: L
authors.lastname: Winyard
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D010147:Pain Measurement; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype