title: The discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic acid (MK-2894), a potent and selective prostaglandin E2 subtype 4 receptor antagonist.
abstract: The discovery of highly potent and selective second generation EP(4) antagonist MK-2894 (34d) is discussed. This compound exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of pain/inflammation. It also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd., 16771 Trans-Canada Highway, Kirkland, QC, Canada. marc_blouin@merck.com
authors.forename: Marc
authors.initials: M
authors.lastname: Blouin
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
authors.forename: Jason
authors.initials: J
authors.lastname: Burch
authors.forename: Julie
authors.initials: J
authors.lastname: Farand
authors.forename: Christophe
authors.initials: C
authors.lastname: Mellon
authors.forename: Mireille
authors.initials: M
authors.lastname: Gaudreault
authors.forename: Mark
authors.initials: M
authors.lastname: Wrona
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lévesque
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: Erika
authors.initials: E
authors.lastname: Vigneault
authors.forename: Alex
authors.initials: A
authors.lastname: Therien
authors.forename: Patsy
authors.initials: P
authors.lastname: Clark
authors.forename: Steve
authors.initials: S
authors.lastname: Rowland
authors.forename: Daigen
authors.initials: D
authors.lastname: Xu
authors.forename: Gary
authors.initials: G
authors.lastname: O'Neill
authors.forename: Yves
authors.initials: Y
authors.lastname: Ducharme
authors.forename: Rick
authors.initials: R
authors.lastname: Friesen
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010146:Pain / Q000188:drug therapy; D011448:Prostaglandin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D001565:Benzoates; D003521:Cyclopropanes; D011448:Prostaglandin Antagonists; D018078:Receptors, Prostaglandin E; D013876:Thiophenes