The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT_2C receptor agonist

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• 作者：Bayard R. Huck ; Luis Llamas ; Michael J. Robarge ; Thomas C. Dent ; Jianping Song ; William F. Hodnick ; Chris Crumrine ; Alain Stricker-Krongrad ; John Harrington ; Kurt R. Brunden and Youssef L. Bennani
• 关键词：Obesity ; 5-HT_2C ; GPCR
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2006
• 出版时间：1 August 2006
• 年：2006
• 卷：16
• 期：15
• 页码：4130-4134
• 全文大小：135 K

文摘

5-HT_2C agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT_2C agonists. SAR was developed around this chemotype and compounds were identified that were potent (K_i < 15 nM) and selective relative to other 5-HT₂ receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats.