1,7-Disubstituted oxyindoles are potent and selective EP(3) receptor antagonists

Nian Zhou; Alexandre M Polozov; Matthew O'Connell; James Burgeson; Peng Yu; Wayne Zeller; Jun Zhang; Emmanuel Onua; Jose Ramirez; Gudrun A Palsdottir; Gudrun V Halldorsdottir; Thorkell Andresson; Alex S Kiselyov; Mark Gurney; Jasbir Singh

doi:10.1016/j.bmcl.2010.02.028

1,7-Disubstituted oxyindoles are potent and selective EP(3) receptor antagonists

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2658-64. doi: 10.1016/j.bmcl.2010.02.028. Epub 2010 Feb 25.

Authors

Nian Zhou¹, Alexandre M Polozov, Matthew O'Connell, James Burgeson, Peng Yu, Wayne Zeller, Jun Zhang, Emmanuel Onua, Jose Ramirez, Gudrun A Palsdottir, Gudrun V Halldorsdottir, Thorkell Andresson, Alex S Kiselyov, Mark Gurney, Jasbir Singh

Affiliation

¹ deCODE Chemistry, Woodridge, IL 60517, USA.

PMID: 20303752
DOI: 10.1016/j.bmcl.2010.02.028

Abstract

A series of novel 1,7-disubstituted oxyindoles were shown to be potent and selective EP(3) receptor antagonists. Variation of substitution pattern at the C-3 position of indole enhanced in vitro metabolic stability of the resulting derivatives. Series 27a-c showed >1000-fold selectivity over a panel of prostanoid receptors including IP, FP, EP(1), EP(2) and EP(4). These agents also featured low CYP inhibition and good activity in the functional rat platelet aggregation assay.

MeSH terms

Animals
Indoles / chemistry
Indoles / pharmacology*
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / chemistry
Platelet Aggregation Inhibitors / pharmacology*
Rats
Receptors, Prostaglandin E / antagonists & inhibitors*
Receptors, Prostaglandin E, EP3 Subtype

Substances

Indoles
Platelet Aggregation Inhibitors
Ptger3 protein, rat
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP3 Subtype