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

doi:10.1016/j.bmcl.2008.12.027

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

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	778-782
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2008.12.027
State	Published - 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

Access to Document

10.1016/j.bmcl.2008.12.027

Cite this

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

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.",

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AU - O'Connell, Matthew

AU - Zeller, Wayne

AU - Burgeson, James

AU - Mishra, Rama K.

AU - Ramirez, Jose

AU - Kiselyov, Alex S.

AU - Andrésson, Thorkell

AU - Gurney, Mark E.

AU - Singh, Jasbir

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AB - 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.

KW - Acylsulfonamide

KW - EP receptor antagonists

KW - Hexahydro-indolones

KW - Peri-substituted indoles

KW - Prostanoid receptor antagonists

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