Heterocyclic 1,7-disubstituted indole sulfonamides are potent and selective human EP3 receptor antagonists

Georgeta Hategan, Alexandre M. Polozov, Wayne Zeller, Hua Cao, Rama K. Mishra, Alex S. Kiselyov, Jose Ramirez, Gudrún Halldorsdottir, Thorkell Andrésson, Mark E. Gurney, Jasbir Singh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We have developed a pharmacophore model for the EP3 receptor antagonists based on its endogenous ligand PGE2. This ligand-based design yielded a series of novel peri-substituted [4.3.0] bicyclic aromatics featuring 1-alklyaryl 7-heterocyclic sulfonamide substituents. The synthesized molecules are potent antagonists of human EP3 receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels.

Original languageEnglish (US)
Pages (from-to)6797-6800
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number23
DOIs
StatePublished - Dec 1 2009

Keywords

  • 3-Amino-isoxazoles
  • Acylsulphonamide
  • Animoazoles
  • EP receptor antagonists
  • Peri-substituted indoles
  • Prostanoid receptor antagonists

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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