{Cyano-[1H-pyridin-(2E)-ylidene]-methyl}-phosphonic acid diethyl ester | 130138-56-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: {Cyano-[1H-pyridin-(2E)-ylidene]-methyl}-phosphonic acid diethyl ester
• 英文别名: diethyl (cyano(pyridin-2(1H)-ylidene)methyl)phosphonate
• CAS: 130138-56-6
• 化学式: C₁₁H₁₅N₂O₃P
• 分子量: 254.225
• InChiKey: INNQKBPMHYVURM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  71.35
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-((S)-3-(4-fluorophenyl)-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopiperidin-3-yl)propan-2-yl)amino)propan-2-yl)-5-methyl-4H-1λ³-isoxazole-3-carboxamide 、 {Cyano-[1H-pyridin-(2E)-ylidene]-methyl}-phosphonic acid diethyl ester 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 作用下， 以 乙腈 为溶剂， 以20%的产率得到N-((S)-1-(((S,E)-4-cyano-1-((S)-2-oxopiperidin-3-yl)-4-(pyridin-2-yl)but-3-en-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-5-methylisoxazole-3-carboxamide
  参考文献：
  名称：

  Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease

  摘要：

  Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they have potential advantages in terms of efficacy, selectivity, and safety. TCIs have recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish the risk of haptenization and help optimize the drug-target residence time as needed. The enteroviral 3C protease (3C(pro)) is a valuable therapeutic target, but the development of 3C(pro) inhibitors is far from satisfactory. Therefore, we aimed to apply a reversible TCI approach to the design of novel 3C(pro) inhibitors. The introduction of various substituents onto the alpha-carbon of classical Michael acceptors yielded inhibitors bearing several classes of warheads. Using steady-state kinetics and biomolecular mass spectrometry, we confirmed the mode of reversible covalent inhibition and elucidated the mechanism by which the potency and reversibility were affected by electronic and steric factors. This research produced several potent inhibitors with good selectivity and suitable reversibility; moreover, it validated the reversible TCI approach in the field of viral infection, suggesting broader applications in the design of reversible covalent inhibitors for other proteases.

  DOI：

  10.1021/acs.jmedchem.9b00387
• 作为产物：
  描述：

  2-溴吡啶 、 氰甲基磷酸二乙酯 在 四(三苯基膦)钯 sodium hydride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 以72%的产率得到{Cyano-[1H-pyridin-(2E)-ylidene]-methyl}-phosphonic acid diethyl ester
  参考文献：
  名称：

  Palladium-catalyzed condensation of aryl halides with phenylsulfonylacetonitrile and diethyl cyanomethylphosphonate.

  摘要：

  用钯(0)催化的芳香卤化物与苯基磺酰乙腈和二乙基氰基甲基膦酸钠在二甲氧基乙烷中缩合，得到相应的α-苯基磺酰芳烃乙腈和二乙基芳氰基甲基膦酸酯，产率良好。α-苯基磺酰芳烃乙腈可以用锌轻松去磺化生成芳烃乙腈，而芳氰基甲基膦酸酯通过霍纳-艾蒙斯反应转化为烷基亚烯芳烃乙腈。

  DOI：

  10.1248/cpb.38.1513