Epiminocyclohepta[b]indole analogs as 5-HT₆ antagonists

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• 作者：Alan J. Hendersonp>ap>p> ; p>p>alan.henderson@amriglobal.comp> ; Peter R. Guzzop>ap> ; Animesh Ghoshp>bp> ; Jagjit Kaurp>bp> ; Jia-Man Koop>bp> ; Kassoum Nacrop>bp> ; Shailaja Pandugap>bp> ; Rashmi Pathakp>bp> ; Bharat Shimpukadep>bp> ; Valentina Tanp>bp> ; Kai Xiangp>bp> ; Jonathan D. Wierschkep>cp> ; Matthew L. Isherwoodp>bp>
• 关键词：Serotonin ; 5-HT6 ; SAR ; Cognition ; Weight loss
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：15 February, 2012
• 年：2012
• 卷：22
• 期：4
• 页码：1494-1498
• 全文大小：517 K

文摘

A new series of epiminocyclohepta[m>bm>]indoles with potent 5-HT₆ antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT₆ receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT₆ receptor as shown by ex vivo autoradiography.