N-(diethoxyphosphorylmethyl)-3-phenylaniline | 1026603-64-4

• 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: N-(diethoxyphosphorylmethyl)-3-phenylaniline
• CAS: 1026603-64-4
• 化学式: C₁₇H₂₂NO₃P
• 分子量: 319.34
• InChiKey: TTZFYPNSUHJOBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(diethoxyphosphorylmethyl)-3-phenylaniline 在 三甲基溴硅烷 作用下， 生成 [1-Ethoxy-1-oxo-3-(3-phenylphenyl)propan-2-yl]phosphonic acid
  参考文献：
  名称：

  Inhibition of Trypanosoma cruzi Hexokinase by Bisphosphonates

  摘要：

  Hexokinase is the first enzyme involved in glycolysis in most organisms, including the etiological agents of Chagas disease (Trypanosoma cruzi) and African sleeping sickness (Thypanosoma brucei). The T. cruzi enzyme is unusual since, unlike the human enzyme, it is inhibited by inorganic diphosphate (PPi). Here, we show that non-hydrolyzable analogues of PPi, bisphosphonates, are potent inhibitors of T. cruzi hexokinase (TcHK). We determined the activity of 42 bisphosphonates against TcHK, and the IC50 values were used to construct pharmacophore and comparative molecular similarity indices analysis (CoMSIA) models for enzyme inhibition. Both models revealed the importance of electrostatic, hydrophobic, and steric interactions, and the IC50 values for 17 active compounds were predicted with an average error of 2.4x by using the CoMSIA models. The Compound most active against T cruzi hexokinase was found to have a 2.2 mu M IC50 versus the clinically relevant intracellular amastigote form of T cruzi, but only a similar to 1-2 mM IC50 versus Dictyostelium discoideum and a human cell line, indicating selective activity versus T. cruzi.

  DOI：

  10.1021/jm0582625
• 作为产物：
  描述：

  聚合甲醛 、 3-氨基联苯 、 亚磷酸二乙酯 以 水 为溶剂， 反应 8.0h， 生成 N-(diethoxyphosphorylmethyl)-3-phenylaniline
  参考文献：
  名称：

  Inhibition of Trypanosoma cruzi Hexokinase by Bisphosphonates

  摘要：

  Hexokinase is the first enzyme involved in glycolysis in most organisms, including the etiological agents of Chagas disease (Trypanosoma cruzi) and African sleeping sickness (Thypanosoma brucei). The T. cruzi enzyme is unusual since, unlike the human enzyme, it is inhibited by inorganic diphosphate (PPi). Here, we show that non-hydrolyzable analogues of PPi, bisphosphonates, are potent inhibitors of T. cruzi hexokinase (TcHK). We determined the activity of 42 bisphosphonates against TcHK, and the IC50 values were used to construct pharmacophore and comparative molecular similarity indices analysis (CoMSIA) models for enzyme inhibition. Both models revealed the importance of electrostatic, hydrophobic, and steric interactions, and the IC50 values for 17 active compounds were predicted with an average error of 2.4x by using the CoMSIA models. The Compound most active against T cruzi hexokinase was found to have a 2.2 mu M IC50 versus the clinically relevant intracellular amastigote form of T cruzi, but only a similar to 1-2 mM IC50 versus Dictyostelium discoideum and a human cell line, indicating selective activity versus T. cruzi.

  DOI：

  10.1021/jm0582625

文献信息

• Inhibition of <i>Trypanosoma </i><i>c</i><i>ruzi</i> Hexokinase by Bisphosphonates
  作者：Michael P. Hudock、C. E. Sanz-Rodríguez、Yongcheng Song、Julian M. W. Chan、Yonghui Zhang、Sarah Odeh、Thomas Kosztowski、Annette Leon-Rossell、J. L. Concepción、Vanessa Yardley、Simon L. Croft、Julio A. Urbina、Eric Oldfield

  DOI：10.1021/jm0582625

  日期：2006.1.1

  Hexokinase is the first enzyme involved in glycolysis in most organisms, including the etiological agents of Chagas disease (Trypanosoma cruzi) and African sleeping sickness (Thypanosoma brucei). The T. cruzi enzyme is unusual since, unlike the human enzyme, it is inhibited by inorganic diphosphate (PPi). Here, we show that non-hydrolyzable analogues of PPi, bisphosphonates, are potent inhibitors of T. cruzi hexokinase (TcHK). We determined the activity of 42 bisphosphonates against TcHK, and the IC50 values were used to construct pharmacophore and comparative molecular similarity indices analysis (CoMSIA) models for enzyme inhibition. Both models revealed the importance of electrostatic, hydrophobic, and steric interactions, and the IC50 values for 17 active compounds were predicted with an average error of 2.4x by using the CoMSIA models. The Compound most active against T cruzi hexokinase was found to have a 2.2 mu M IC50 versus the clinically relevant intracellular amastigote form of T cruzi, but only a similar to 1-2 mM IC50 versus Dictyostelium discoideum and a human cell line, indicating selective activity versus T. cruzi.