3-Acrylamide-4-aryloxyindoles: synthesis, biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists.
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.
Zhou
Nian
N
Medicinal Chemistry Department, deCODE Chemistry, 2501 Davey Road, Woodridge, IL 60517, USA.
Zeller
Wayne
W
Zhang
Jun
J
Onua
Emmanuel
E
Kiselyov
Alex S
AS
Ramirez
Jose
J
Palsdottir
Gudrún
G
Halldorsdottir
Gudrún
G
Andrésson
Thornorkell
T
Gurney
Mark E
ME
Singh
Jasbir
J
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
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