1,7-Disubstituted oxyindoles are potent and selective EP₃ receptor antagonists

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• 作者：Nian Zhou ; Alex ; re M. Polozov ; Matthew O’ ; Connell ; James Burgeson ; Peng Yu ; Wayne Zeller ; Jun Zhang ; Emmanuel Onua ; Jose Ramirez ; Gudrun A. Palsdottir ; Gudrun V. Halldorsdottir ; Thorkell Andress
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 April 2010
• 年：2010
• 卷：20
• 期：8
• 页码：2658-2664
• 全文大小：615 K

文摘

A series of novel 1,7-disubstituted oxyindoles were shown to be potent and selective EP₃ 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, EP₁, EP₂ and EP₄. These agents also featured low CYP inhibition and good activity in the functional rat platelet aggregation assay.