Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH)

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• 作者：Douglas S. Johnson ; Kay Ahn ; Suzanne Kesten ; Scott E. Lazerwith ; Yuntao Song ; Mark Morris ; Lorraine Fay ; Tracy Gregory ; Cory Stiff ; James B. Dunbar Jr. ; Marya Liimatta ; David Beidler ; Sarah Smith ; Tyz
• 关键词：FAAH inhibitor ; Fatty acid amide hydrolase ; Urea ; Activity-based protein profiling ; Covalent inhibitor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 May 2009
• 年：2009
• 卷：19
• 期：10
• 页码：2865-2869
• 全文大小：1344 K

文摘

The synthesis and structure–activity relationships (SAR) of a series of benzothiophene piperazine and piperidine urea FAAH inhibitors is described. These compounds inhibit FAAH by covalently modifying the enzyme’s active site serine nucleophile. Activity-based protein profiling (ABPP) revealed that these urea inhibitors were completely selective for FAAH relative to other mammalian serine hydrolases. Several compounds showed in vivo activity in a rat complete Freund’s adjuvant (CFA) model of inflammatory pain.