3-Acrylamide-4-aryloxyindoles: Synthesis, biological evaluation and metabolic stability of potent and selective EP₃ receptor antagonists

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• 作者：Nian Zhou ; Wayne Zeller ; Jun Zhang ; Emmanuel Onua ; Alex S. Kiselyov ; Jose Ramirez ; Guð ; rú ; n Palsdottir ; Guð ; rú ; n Halldorsdottir ; Þ ; orkell André ; sson ; Mark E. Gurney ; Jasbir Sin
• 关键词：Prostanoid receptor antagonists ; EP₃ receptor antagonists ; Peri-substituted indoles ; Acylsulfonamide
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 March 2009
• 年：2009
• 卷：19
• 期：5
• 页码：1528-1531
• 全文大小：357 K

文摘

A series of potent and selective EP₃ receptor antagonists are described. Utilizing a pharmacophore model developed for the EP₃ receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays.