title: Identification of novel glycine sulfonamide antagonists for the EP1 receptor.
abstract: A high-throughput screen targeting the EP(1) receptor identified non-acidic glycine sulfonamide derivative 2a with a pK(i) of 6.2. Analogue synthesis allowed a thorough investigation of the structure-activity relationship (SAR) and led to a 100-fold increase in recombinant potency.
authors.affiliation: Molecular Discovery Research, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Steve.C.McKeown@gsk.com
authors.forename: Stephen C
authors.initials: SC
authors.lastname: McKeown
authors.forename: Adrian
authors.initials: A
authors.lastname: Hall
authors.forename: Richard
authors.initials: R
authors.lastname: Blunt
authors.forename: Susan H
authors.initials: SH
authors.lastname: Brown
authors.forename: Iain P
authors.initials: IP
authors.lastname: Chessell
authors.forename: Anita
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Gerard M P
authors.initials: GM
authors.lastname: Giblin
authors.forename: Mark P
authors.initials: MP
authors.lastname: Healy
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Olivier
authors.initials: O
authors.lastname: Lorthioir
authors.forename: Anton D
authors.initials: AD
authors.lastname: Michel
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: Xiao
authors.initials: X
authors.lastname: Lewell
authors.forename: Shilina
authors.initials: S
authors.lastname: Roman
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Watson
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Winchester
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wilson
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D018684:Glycine Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D018684:Glycine Agents; D007202:Indicators and Reagents; C545635:PTGER1 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides; D003577:Cytochrome P-450 Enzyme System; D015232:Dinoprostone