1,7-Disubstituted oxyindoles are potent and selective EP(3) receptor antagonists.
Authors:
Zhou, N Polozov, AM O'Connell, M Burgeson, J Yu, P Zeller, W Zhang, J Onua, E Ramirez, J Palsdottir, GA Halldorsdottir, GV Andresson, T Kiselyov, AS Gurney, M Singh, J
Citation:
Zhou N, etal., Bioorg Med Chem Lett. 2010 Apr 15;20(8):2658-64. doi: 10.1016/j.bmcl.2010.02.028. Epub 2010 Feb 25.
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.