title: 3-Acrylamide-4-aryloxyindoles: synthesis, biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists.
abstract: A series of potent and selective EP(3) receptor antagonists are described. Utilizing a pharmacophore model developed for the EP(3) receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays.
authors.affiliation: Medicinal Chemistry Department, deCODE Chemistry, 2501 Davey Road, Woodridge, IL 60517, USA.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhou
authors.forename: Wayne
authors.initials: W
authors.lastname: Zeller
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Onua
authors.forename: Alex S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Jose
authors.initials: J
authors.lastname: Ramirez
authors.forename: Gudrún
authors.initials: G
authors.lastname: Palsdottir
authors.forename: Gudrún
authors.initials: G
authors.lastname: Halldorsdottir
authors.forename: Thornorkell
authors.initials: T
authors.lastname: Andrésson
authors.forename: Mark E
authors.initials: ME
authors.lastname: Gurney
authors.forename: Jasbir
authors.initials: J
authors.lastname: Singh
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D000882:Haplorhini; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype
chemical_list: D000178:Acrylamides; D007211:Indoles; C545647:PTGER3 protein, human; C545648:Ptger3 protein, mouse; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype