Discovery of Orally Active 3-Pyridinyl-tropane As a Potent Nociceptin Receptor Agonist for the Management of Cough

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• 作者：Shu-Wei Yang ; Ginny Ho ; Deen Tulshian ; William J. Greenlee ; John Anthes ; Xiomara Fernandez ; Robbie L. McLeod ; John A. Hey ; Xiaoying Xu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 10, 2009
• 年：2009
• 卷：52
• 期：17
• 页码：5323-5329
• 全文大小：837K
• 年卷期：v.52,no.17(September 10, 2009)
• ISSN：1520-4804

文摘

A series of 3-pyridinyl-tropane analogues based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. From the SAR study and our lead optimization efforts, compound 10 was found to possess potent oral antitussive activity in the capsaicin-induced guinea pig model. The rationale for compound selection and the biological profile of the optimized lead (10) are disclosed.