Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists

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• 作者：Rong Jiang ; Xinyi Song ; Purva Bali ; Anthony Smith ; Claudia Ruiz Bayona ; Li Lin ; Michael D. Cameron ; Patricia H. McDonald ; Paul J. Kenny ; Theodore M. Kamenecka ; ^{kameneck@scripps.edu}
• 关键词：Orexin ; GPCR ; Addiction
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 June, 2012
• 卷：22
• 期：12
• 页码：3890-3894
• 文件大小：5012 K

摘要

A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.