2. Academic Validation
  3. Heterocyclic 1,7-disubstituted indole sulfonamides are potent and selective human EP3 receptor antagonists

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

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6797-800. doi: 10.1016/j.bmcl.2009.09.084.
Georgeta Hategan 1,  Alexandre M Polozov,  Wayne Zeller,  Hua Cao,  Rama K Mishra,  Alex S Kiselyov,  Jose Ramirez,  Gudrún Halldorsdottir,  Thornorkell Andrésson,  Mark E Gurney,  Jasbir Singh
Affiliations

Affiliation

  • 1 Medicinal Chemistry Department, deCODE Chemistry, Inc, Woodridge, IL 60517, United States.
PMID: 19836233 DOI: 10.1016/j.bmcl.2009.09.084
Abstract

We have developed a pharmacophore model for the EP(3) receptor antagonists based on its endogenous ligand PGE(2). 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 EP(3) receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels.

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