Diethoxyphosphono-chloressigsaeure-methylester | 34255-81-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: Diethoxyphosphono-chloressigsaeure-methylester
• 英文别名: methyl 2-chloro-2-(diethoxyphosphoryl)acetate；Methyl-chlor(diethoxyphosphinyl)acetat
• CAS: 34255-81-7
• 化学式: C₇H₁₄ClO₅P
• 分子量: 244.612
• InChiKey: WXPLBIUNDHLEPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  14.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Diethoxyphosphono-chloressigsaeure-methylester 、 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 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， 生成 methyl (S)-2-chloro-4-((S)-3-(4-fluorophenyl)-2-(5-methylisoxazole-3-carboxamido)propanamido)-5-((S)-2-oxopiperidin-3-yl)pent-2-enoate 、 methyl (S)-2-chloro-4-((S)-3-(4-fluorophenyl)-2-(5-methylisoxazole-3-carboxamido)propanamido)-5-((S)-2-oxopiperidin-3-yl)pent-2-enoate
  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：

  二乙基膦酰基乙酸叔丁酯 在 磺酰氯 、 五氯化磷 作用下， 以 乙醚 为溶剂， 生成 Diethoxyphosphono-chloressigsaeure-methylester
  参考文献：
  名称：

  Bodnarchuk,N.D. et al., Journal of general chemistry of the USSR, 1971, vol. 41, p. 1470 - 1473

  摘要：

  DOI：