Peri-substituted hexahydro-indolones as novel, potent and selective human EP3 receptor antagonists

Matthew O'Connell, Wayne Zeller, James Burgeson, Rama K. Mishra, Jose Ramirez, Alex S. Kiselyov, Thorkell Andrésson, Mark E. Gurney, Jasbir Singh*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

A series of peri-substituted [4.3.0] bicyclic non-aromatic heterocycles have been identified as potent and selective hEP3 receptor antagonists. These molecules adopt a hair-pin conformation that overlaps with the endogenous ligand PGE2 and fits into an internally generated EP3 pharmacophore model. Optimized compounds show good metabolic stability and improved solubility over their corresponding bicyclic aromatic analogs.

Original languageEnglish (US)
Pages (from-to)778-782
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number3
DOIs
StatePublished - Feb 1 2009

Keywords

  • Acylsulfonamide
  • EP receptor antagonists
  • Hexahydro-indolones
  • 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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    O'Connell, M., Zeller, W., Burgeson, J., Mishra, R. K., Ramirez, J., Kiselyov, A. S., Andrésson, T., Gurney, M. E., & Singh, J. (2009). Peri-substituted hexahydro-indolones as novel, potent and selective human EP3 receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 19(3), 778-782. https://doi.org/10.1016/j.bmcl.2008.12.027