1,1,1,3,3,3-hexafluoropropan-2-yl 4-(1-phenyl-1H-pyrazol-3-yl)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(1-phenyl-1H-pyrazol-3-yl)piperidine-1-carboxylate
• 英文别名: 1,1,1,3,3,3-Hexafluoropropan-2-yl 4-(1-phenylpyrazol-3-yl)piperidine-1-carboxylate；1,1,1,3,3,3-hexafluoropropan-2-yl 4-(1-phenylpyrazol-3-yl)piperidine-1-carboxylate
• 化学式: C₁₈H₁₇F₆N₃O₂
• 分子量: 421.342
• InChiKey: JEZZQVWVDVULKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-乙酰基哌啶-1-甲酸叔丁酯 在 氧气 、 copper diacetate 、 一水合肼 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 158.05h， 生成 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(1-phenyl-1H-pyrazol-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase

  摘要：

  Monoacylglycerol lipase (MAGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the CNS. MAGL catalyzes the conversion of 2-AG to arachidonic acid (AA), a precursor to the proinflammatory eicosannoids such as prostaglandins. Herein we describe highly efficient MAGL inhibitors, identified through a parallel medicinal chemistry approach that highlighted the improved efficiency of azetidine and piperidine-derived carbamates. The discovery and optimization of 3-substituted azetidine carbamate irreversible inhibitors of MAGL were aided by the generation of inhibitor-bound MAGL crystal structures. Compound 6, a highly efficient and selective MAGL inhibitor against recombinant enzyme and in a cellular context, was tested in vivo and shown to elevate central 2-AG levels at a 10 mg/kg dose.

  DOI：

  10.1021/acs.jmedchem.7b01531