title: Structure-activity relationships and pharmacokinetic parameters of quinoline acylsulfonamides as potent and selective antagonists of the EP(4) receptor.
abstract: A new series of EP(4) antagonists based on a quinoline acylsulfonamide scaffold have been identified as part of our on-going efforts to develop treatments for chronic inflammation. These compounds show subnanomolar intrinsic binding potency towards the EP(4) receptor, and excellent selectivity towards other prostanoid receptors. Acceptable pharmacokinetic profiles have also been demonstrated across a series of preclinical species.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, 16711 Trans-Canada Highway, Kirkland, Que., Canada H9H 3L1. jason_burch@merck.com
authors.forename: Jason D
authors.initials: JD
authors.lastname: Burch
authors.forename: Michel
authors.initials: M
authors.lastname: Belley
authors.forename: Réjean
authors.initials: R
authors.lastname: Fortin
authors.forename: Denis
authors.initials: D
authors.lastname: Deschênes
authors.forename: Mario
authors.initials: M
authors.lastname: Girard
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Julie
authors.initials: J
authors.lastname: Farand
authors.forename: Alex G
authors.initials: AG
authors.lastname: Therien
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Erika
authors.initials: E
authors.lastname: Vigneault
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lévesque
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gagné
authors.forename: Mark
authors.initials: M
authors.lastname: Wrona
authors.forename: Daigen
authors.initials: D
authors.lastname: Xu
authors.forename: Patsy
authors.initials: P
authors.lastname: Clark
authors.forename: Steve
authors.initials: S
authors.lastname: Rowland
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D004285:Dogs; D006168:Guinea Pigs; D006801:Humans; D008253:Macaca mulatta; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C545650:PTGER4 protein, human; D011804:Quinolines; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides