2,4-dinitrophenyl 4-benzylpiperidine-1-carbodithioate | 1381994-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2,4-dinitrophenyl 4-benzylpiperidine-1-carbodithioate
• 英文别名: (2,4-Dinitrophenyl) 4-benzylpiperidine-1-carbodithioate
• CAS: 1381994-29-1
• 化学式: C₁₉H₁₉N₃O₄S₂
• 分子量: 417.51
• InChiKey: AZGMAARRTGKISV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  152
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苄基哌啶 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2,4-dinitrophenyl 4-benzylpiperidine-1-carbodithioate
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 2,4-Dinitroaryldithiocarbamate Derivatives as Novel Monoacylglycerol Lipase Inhibitors

  摘要：

  Monoacylglycerol lipase (MAGL) is responsible for signal termination of 2-arachidonoylglycerol (2-AG), an endocannabinoid neurotransmitter endowed with several physiological effects. Previously, we showed that the arylthioamide scaffold represents a privileged template for designing MAGL inhibitors. A series of 37 compounds resulting from pharmacomodulations around the arylthioamide template were synthesized and tested to evaluate their inhibitory potential on MAGL activity as well as their selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. We have identified 2,4-dinitroaryldithiocarbamate derivatives as a novel class of MAGL inhibitors. Among the synthesized compounds, we identified [2,4-dinitrophenyl-4-(4-tert-butylbenzyl)piperazine-1-carbodithioate] (CK37), as the most potent MAGL inhibitor within this series (IC50= 154 nM). We have also identified [2,4-dinitrophenyl-4-benzhydrylpiperazine-1-carbodithioate] (CK16) as a selective MAGL inhibitor. These compounds are irreversible MAGL inhibitors that probably act by interacting with Cys208 or Cys242 and Ser122 residues of the enzyme. Moreover, CK37 is able to raise 2-arachidonoylglycerol (2-AG) levels in intact cells.

  DOI：

  10.1021/jm3006004

文献信息

• Synthesis and Pharmacological Evaluation of 2,4-Dinitroaryldithiocarbamate Derivatives as Novel Monoacylglycerol Lipase Inhibitors
  作者：Coco N. Kapanda、Julien Masquelier、Geoffray Labar、Giulio G. Muccioli、Jacques H. Poupaert、Didier M. Lambert

  DOI：10.1021/jm3006004

  日期：2012.6.28

  Monoacylglycerol lipase (MAGL) is responsible for signal termination of 2-arachidonoylglycerol (2-AG), an endocannabinoid neurotransmitter endowed with several physiological effects. Previously, we showed that the arylthioamide scaffold represents a privileged template for designing MAGL inhibitors. A series of 37 compounds resulting from pharmacomodulations around the arylthioamide template were synthesized and tested to evaluate their inhibitory potential on MAGL activity as well as their selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. We have identified 2,4-dinitroaryldithiocarbamate derivatives as a novel class of MAGL inhibitors. Among the synthesized compounds, we identified [2,4-dinitrophenyl-4-(4-tert-butylbenzyl)piperazine-1-carbodithioate] (CK37), as the most potent MAGL inhibitor within this series (IC50= 154 nM). We have also identified [2,4-dinitrophenyl-4-benzhydrylpiperazine-1-carbodithioate] (CK16) as a selective MAGL inhibitor. These compounds are irreversible MAGL inhibitors that probably act by interacting with Cys208 or Cys242 and Ser122 residues of the enzyme. Moreover, CK37 is able to raise 2-arachidonoylglycerol (2-AG) levels in intact cells.