Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold
Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold
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DOI：
10.1016/j.bmc.2012.09.011
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Lambert, Didier M.
中科院分区：
文献类型：
--
作者：
Morera, Ludovica;Labar, Geoffray;Lambert, Didier M.
合成了一系列（1H-苯并[d][1，2，3]三唑-1-基）（4-苄基哌嗪-1-基）甲酮和（1H-苯并[d] [1，2，3]三唑-1-基）（4-苯基哌嗪-1-基）甲酮，并对人脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）进行了活性测定。在苄基哌嗪基系列中，化合物29（ML 30）对MAGL表现出0.54 nM的IC 50值，结合相对于FAAH的1000倍选择性，而化合物11和16作为有效的双重FAAH-MAGL抑制剂（IC 50
A series of (1H-benzo[d][1,2,3]triazol-1-yl)(4-benzylpiperazin-1-yl)methanones and of (1H-benzo[d] [1,2,3]triazol-1-yl)(4-phenylpiperazin-1-yl)methanones has been prepared and tested on human fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). In the benzylpiperazinyl series, compound 29 (ML30) exhibited an IC50 value of 0.54 nM on MAGL, combined with a 1000-fold selectivity versus FAAH, while compounds 11 and 16 acted as potent dual FAAH-MAGL inhibitors (IC50