(E)-2-((4-fluorophenyl)sulfonyl)-3-(1H-pyrrol-2-yl)acrylonitrile | 1313612-96-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-2-((4-fluorophenyl)sulfonyl)-3-(1H-pyrrol-2-yl)acrylonitrile
• 英文别名: (2E)-2-[(4-fluorophenyl)sulfonyl]-3-(1h-pyrrol-2-yl)acrylonitrile；(E)-2-(4-fluorophenyl)sulfonyl-3-(1H-pyrrol-2-yl)prop-2-enenitrile
• CAS: 1313612-96-2
• 化学式: C₁₃H₉FN₂O₂S
• 分子量: 276.291
• InChiKey: MOGTUPCCTRCJGJ-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2-((4-fluorophenyl)sulfonyl)-3-(1H-pyrrol-2-yl)acrylonitrile 、 3-硝基苯磺酰氯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84%的产率得到(E)-2-(4-fluorophenylsulfonyl)-3-(1-(3-nitrophenylsulfonyl)-1H-pyrrol-2-yl)acrylonitrile
  参考文献：
  名称：

  Discovery and Optimization of Sulfonyl Acrylonitriles as Selective, Covalent Inhibitors of Protein Phosphatase Methylesterase-1

  摘要：

  The serine hydrolase protein phosphatase methylesterase-1 (PME-1) regulates the methylesterification state of protein phosphatase 2A (PP2A) and has been implicated in cancer and Alzheimer's disease. We recently reported a fluorescence polarization-activity-based protein profiling (fluopol-ABPP) high-throughput screen for PME-1 that uncovered a remarkably potent and selective class of aza-beta-lactam (ABL) PME-1 inhibitors. Here, we describe a distinct set of sulfonyl acrylonitrile inhibitors that also emerged from this screen. The optimized compound, 28 (AMZ30), selectively inactivates PME-1 and reduces the demethylated form of PP2A in living cells. Considering that 28 is structurally unrelated to ABL inhibitors of PME-1, these agents, together, provide a valuable set of pharmacological probes to study the role of methylation in regulating PP2A function. We furthermore observed that several serine hydrolases were sensitive to analogues of 28, suggesting that more extensive structural exploration of the sulfonyl acrylonitrile chemotype may result in useful inhibitors for other members of this large enzyme class.

  DOI：

  10.1021/jm200502u
• 作为产物：
  描述：

  2-吡咯甲醛 、 4-氟苯磺酰基乙腈 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以86%的产率得到(E)-2-((4-fluorophenyl)sulfonyl)-3-(1H-pyrrol-2-yl)acrylonitrile
  参考文献：
  名称：

  Discovery and Optimization of Sulfonyl Acrylonitriles as Selective, Covalent Inhibitors of Protein Phosphatase Methylesterase-1

  摘要：

  The serine hydrolase protein phosphatase methylesterase-1 (PME-1) regulates the methylesterification state of protein phosphatase 2A (PP2A) and has been implicated in cancer and Alzheimer's disease. We recently reported a fluorescence polarization-activity-based protein profiling (fluopol-ABPP) high-throughput screen for PME-1 that uncovered a remarkably potent and selective class of aza-beta-lactam (ABL) PME-1 inhibitors. Here, we describe a distinct set of sulfonyl acrylonitrile inhibitors that also emerged from this screen. The optimized compound, 28 (AMZ30), selectively inactivates PME-1 and reduces the demethylated form of PP2A in living cells. Considering that 28 is structurally unrelated to ABL inhibitors of PME-1, these agents, together, provide a valuable set of pharmacological probes to study the role of methylation in regulating PP2A function. We furthermore observed that several serine hydrolases were sensitive to analogues of 28, suggesting that more extensive structural exploration of the sulfonyl acrylonitrile chemotype may result in useful inhibitors for other members of this large enzyme class.

  DOI：

  10.1021/jm200502u