3-Acrylamide-4-aryloxyindoles: synthesis, biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1528-31. doi: 10.1016/j.bmcl.2008.12.112. Epub 2009 Jan 8.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / metabolism*
  • Acrylamides / pharmacology
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Drug Stability
  • Haplorhini
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / metabolism*
  • Indoles / pharmacology
  • Mice
  • Rats
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP3 Subtype

Substances

  • Acrylamides
  • Indoles
  • PTGER3 protein, human
  • Ptger3 protein, mouse
  • Ptger3 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype