4-[4-(benzotriazole-1-carbonyl)piperazin-1-yl]-3-nitro-N-propan-2-ylbenzamide | 1403353-56-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[4-(benzotriazole-1-carbonyl)piperazin-1-yl]-3-nitro-N-propan-2-ylbenzamide
• CAS: 1403353-56-9
• 化学式: C₂₁H₂₃N₇O₄
• 分子量: 437.458
• InChiKey: CNDXLYXHWHHBSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-3-硝基苯甲酸 在 氯化亚砜 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 4-[4-(benzotriazole-1-carbonyl)piperazin-1-yl]-3-nitro-N-propan-2-ylbenzamide
  参考文献：
  名称：

  Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold

  摘要：

  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 <10 nM). In the phenylpiperazinyl series, compounds 37, 38, 42, and 43 displayed IC50 values against MAGL in the nanomolar range, whilst being between one and two orders of magnitude less potent on the FAAH, while compounds 31 and 32 were potent FAAH inhibitors (IC50 <20 nM) and over 12-fold selective versus MAGL. The key structural determinants driving the structure-activity relationships were explored by the minimization of the inhibitors inside the active site of both enzymes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.011

文献信息

• Development and characterization of endocannabinoid hydrolases FAAH and MAGL inhibitors bearing a benzotriazol-1-yl carboxamide scaffold
  作者：Ludovica Morera、Geoffray Labar、Giorgio Ortar、Didier M. Lambert

  DOI：10.1016/j.bmc.2012.09.011

  日期：2012.11

  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 <10 nM). In the phenylpiperazinyl series, compounds 37, 38, 42, and 43 displayed IC50 values against MAGL in the nanomolar range, whilst being between one and two orders of magnitude less potent on the FAAH, while compounds 31 and 32 were potent FAAH inhibitors (IC50 <20 nM) and over 12-fold selective versus MAGL. The key structural determinants driving the structure-activity relationships were explored by the minimization of the inhibitors inside the active site of both enzymes. (C) 2012 Elsevier Ltd. All rights reserved.