N-hydroxy-N-ethylcarbamate 4-chlorophenyl ester

• 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-hydroxy-N-ethylcarbamate 4-chlorophenyl ester
• 英文别名: (4-chlorophenyl) N-ethyl-N-hydroxycarbamate
• 化学式: C₉H₁₀ClNO₃
• 分子量: 215.636
• InChiKey: YIBONFFNBFPVLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 N-hydroxy-N-ethylcarbamate 4-chlorophenyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 115.0h， 以48%的产率得到S-(N-ethyl-N-hydroxycarbamoyl)glutathione
  参考文献：
  名称：

  Role of Hydrophobic Interactions in Binding S-(N-Aryl/Alkyl-N-hydroxy- carbamoyl)glutathiones to the Active Site of the Antitumor Target Enzyme Glyoxalase I

  摘要：

  Hydrophobic interactions play an important role in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active sites of human, yeast, and Pseudomonas putida glyoxalase I, as the log K-i values for these mechanism-based competitive inhibitors decrease linearly with increasing values of the hydrophobicity constants (pi) of the N-aryl/alkyl substituents. Hydrophobic interactions also help to optimize polar interactions between the enzyme and the glutathione derivatives, given that the K-i value for S-(N-hydroxycarbamoyl)glutathione (pi = 0) with the human enzyme is 35-fold larger than the interpolated value for this compound obtained from the log K-i versus pi plot. Computational studies, in combination with published X-ray crystallographic measurements, indicate that human glyoxalase I binds the syn-conformer of S-(N-aryl-N-hydroxycarbamoyl)glutathione in which the N-aryl substituents are in their lowest-energy conformations. These studies provide both an experimental and a conceptual framework for developing better inhibitors of this antitumor target enzyme.

  DOI：

  10.1021/jm000160l
• 作为产物：
  描述：

  乙醛肟 、 4-氯苯基氯甲酸酯 以 氯仿 为溶剂， 生成 N-hydroxy-N-ethylcarbamate 4-chlorophenyl ester
  参考文献：
  名称：

  Role of Hydrophobic Interactions in Binding S-(N-Aryl/Alkyl-N-hydroxy- carbamoyl)glutathiones to the Active Site of the Antitumor Target Enzyme Glyoxalase I

  摘要：

  Hydrophobic interactions play an important role in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active sites of human, yeast, and Pseudomonas putida glyoxalase I, as the log K-i values for these mechanism-based competitive inhibitors decrease linearly with increasing values of the hydrophobicity constants (pi) of the N-aryl/alkyl substituents. Hydrophobic interactions also help to optimize polar interactions between the enzyme and the glutathione derivatives, given that the K-i value for S-(N-hydroxycarbamoyl)glutathione (pi = 0) with the human enzyme is 35-fold larger than the interpolated value for this compound obtained from the log K-i versus pi plot. Computational studies, in combination with published X-ray crystallographic measurements, indicate that human glyoxalase I binds the syn-conformer of S-(N-aryl-N-hydroxycarbamoyl)glutathione in which the N-aryl substituents are in their lowest-energy conformations. These studies provide both an experimental and a conceptual framework for developing better inhibitors of this antitumor target enzyme.

  DOI：

  10.1021/jm000160l

文献信息

• Role of Hydrophobic Interactions in Binding <i>S</i>-(<i>N</i>-Aryl/Alkyl-<i>N</i>-hydroxy- carbamoyl)glutathiones to the Active Site of the Antitumor Target Enzyme Glyoxalase I
  作者：Avinash Kalsi、Malcolm J. Kavarana、Tianfen Lu、Dale L. Whalen、Diana S. Hamilton、Donald J. Creighton

  DOI：10.1021/jm000160l

  日期：2000.10.1

  Hydrophobic interactions play an important role in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active sites of human, yeast, and Pseudomonas putida glyoxalase I, as the log K-i values for these mechanism-based competitive inhibitors decrease linearly with increasing values of the hydrophobicity constants (pi) of the N-aryl/alkyl substituents. Hydrophobic interactions also help to optimize polar interactions between the enzyme and the glutathione derivatives, given that the K-i value for S-(N-hydroxycarbamoyl)glutathione (pi = 0) with the human enzyme is 35-fold larger than the interpolated value for this compound obtained from the log K-i versus pi plot. Computational studies, in combination with published X-ray crystallographic measurements, indicate that human glyoxalase I binds the syn-conformer of S-(N-aryl-N-hydroxycarbamoyl)glutathione in which the N-aryl substituents are in their lowest-energy conformations. These studies provide both an experimental and a conceptual framework for developing better inhibitors of this antitumor target enzyme.