diethyl 1-(4-aminophenyl)-2-chloroethylphosphonate | 449777-35-9

• 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: diethyl 1-(4-aminophenyl)-2-chloroethylphosphonate
• CAS: 449777-35-9
• 化学式: C₁₂H₁₉ClNO₃P
• 分子量: 291.715
• InChiKey: QGDLHHXZNYJGGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.55
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 diethyl 1-(4-aminophenyl)-2-chloroethylphosphonate 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 2.5h， 以94%的产率得到diethyl 2-chloro-1-(4-dimethylaminophenyl)ethylphosphonate
  参考文献：
  名称：

  Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids

  摘要：

  2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure-activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino. and 3- and 4-trimethyl-ammonium. Phosphonic acids 1 were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K-i = 180 muM) and potency (IC50 = 19 muM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion-monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by 1 bound at the active site. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00391-1
• 作为产物：
  描述：

  diethyl 2-chloro-1-(4-nitrophenyl)ethylphosphonate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以100%的产率得到diethyl 1-(4-aminophenyl)-2-chloroethylphosphonate
  参考文献：
  名称：

  Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids

  摘要：

  2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure-activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino. and 3- and 4-trimethyl-ammonium. Phosphonic acids 1 were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K-i = 180 muM) and potency (IC50 = 19 muM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion-monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by 1 bound at the active site. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00391-1