2-(2-(naphthalen-2-yl)ethyl)benzo[d]isothiazol-3(2H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(2-(naphthalen-2-yl)ethyl)benzo[d]isothiazol-3(2H)-one
• 英文别名: 2-(2-Naphthalen-2-ylethyl)-1,2-benzothiazol-3-one；2-(2-naphthalen-2-ylethyl)-1,2-benzothiazol-3-one
• 化学式: C₁₉H₁₅NOS
• 分子量: 305.4
• InChiKey: JAMJYXGKSDKFBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,2-二硫二苯甲酰氯 在 氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 2-(2-(naphthalen-2-yl)ethyl)benzo[d]isothiazol-3(2H)-one
  参考文献：
  名称：

  Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines

  摘要：

  We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b01679