title: Discovery of 4-[1-[([1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl]carbonyl)amino]cyclopropyl]benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory pain.
abstract: The discovery of a highly potent and selective EP(4) antagonist MF-766 is discussed. This N-benzyl indole derivative exhibits good pharmacokinetic profile and unprecedented in vivo potency in the rat AIA model.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Canada Ltd, Kirkland, Quebec, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.forename: Carl
authors.initials: C
authors.lastname: Berthelette
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Chiasson
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
authors.forename: Yves
authors.initials: Y
authors.lastname: Ducharme
authors.forename: Rick
authors.initials: R
authors.lastname: Friesen
authors.forename: Mark
authors.initials: M
authors.lastname: Wrona
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Levesque
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Rino
authors.initials: R
authors.lastname: Stocco
authors.forename: Alex G
authors.initials: AG
authors.lastname: Therien
authors.forename: Patsy
authors.initials: P
authors.lastname: Clarke
authors.forename: Steve
authors.initials: S
authors.lastname: Rowland
authors.forename: Daigen
authors.initials: D
authors.lastname: Xu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D001168:Arthritis / Q000188:drug therapy; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004285:Dogs; D055808:Drug Discovery; D004355:Drug Stability; D022781:Hepatocytes; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy*; D010599:Pharmacokinetics; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013329:Structure-Activity Relationship
chemical_list: D001565:Benzoates; D007211:Indoles; C545650:PTGER4 protein, human; C545652:Ptger4 protein, rat; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype