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

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• 作者：Matthew O’ ; Connell ; Wayne Zeller ; James Burgeson ; Rama K. Mishra ; Jose Ramirez ; Alex S. Kiselyov ; Þ ; orkell André ; sson ; Mark E. Gurney ; Jasbir Singh
• 关键词：Prostanoid receptor antagonists ; EP₃ receptor antagonists ; Peri-substituted indoles ; Acylsulfonamide ; Hexahydro-indolones
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 February 2009
• 年：2009
• 卷：19
• 期：3
• 页码：778-782
• 全文大小：211 K

文摘

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.