ethyl (2R)-2-[4-[[3,5-bis[[4-[(1R)-2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]phenoxy]methyl]phenyl]methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate | 458550-64-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (2R)-2-[4-[[3,5-bis[[4-[(1R)-2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]phenoxy]methyl]phenyl]methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate
• CAS: 458550-64-6
• 化学式: C₅₄H₆₉N₃O₁₅
• 分子量: 1000.15
• InChiKey: LMCPRGMALBJSKC-HRGNWNEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  72
• 可旋转键数：
  30
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  222
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  ethyl (2R)-2-[4-[[3,5-bis[[4-[(1R)-2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]phenoxy]methyl]phenyl]methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate 在 吡啶 、 sodium hydroxide 、 copper(II) sulfate 、 乙醛酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 {4-[3,5-Bis-(4-oxalyl-phenoxymethyl)-benzyloxy]-phenyl}-oxo-acetic acid
  参考文献：
  名称：

  Divalent and Trivalent α-Ketocarboxylic Acids as Inhibitors of Protein Tyrosine Phosphatases

  摘要：

  Protein tyrosine phosphatases (PTPases) are important targets for the treatment of insulin resistance in patients with type II diabetes and as antibacterial agents. As a result, there is a growing interest in the development of potent and specific inhibitors for these enzymes. This paper describes a series of inhibitors that contain two or three alpha-ketocarboxylic acid groups that are designed to form multiple contacts with residues inside or near the active site of phosphatases. The inhibitors have been assayed against three PTPases: the Yersinia PTPase, PTP1B, and LAR. The best of the inhibitors has IC50 values against the Yersinia PTPase and PTP1B of 0.7 and 2.7 muM, respectively. These divalent and trivalent compounds are significantly more potent than their corresponding monovalent analogues. In addition, they show good selectivity for PTP1B and the Yersinia PTPase as compared to LAR.

  DOI：

  10.1021/jm020093q
• 作为产物：
  描述：

  1,3,5-三(溴甲基)苯 、 sodium ethanolate 、 (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-(4-hydroxyphenyl)acetate 在 乙醇 作用下， 反应 23.0h， 以21%的产率得到ethyl (2R)-2-[4-[[3,5-bis[[4-[(1R)-2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]phenoxy]methyl]phenyl]methoxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate
  参考文献：
  名称：

  Divalent and Trivalent α-Ketocarboxylic Acids as Inhibitors of Protein Tyrosine Phosphatases

  摘要：

  Protein tyrosine phosphatases (PTPases) are important targets for the treatment of insulin resistance in patients with type II diabetes and as antibacterial agents. As a result, there is a growing interest in the development of potent and specific inhibitors for these enzymes. This paper describes a series of inhibitors that contain two or three alpha-ketocarboxylic acid groups that are designed to form multiple contacts with residues inside or near the active site of phosphatases. The inhibitors have been assayed against three PTPases: the Yersinia PTPase, PTP1B, and LAR. The best of the inhibitors has IC50 values against the Yersinia PTPase and PTP1B of 0.7 and 2.7 muM, respectively. These divalent and trivalent compounds are significantly more potent than their corresponding monovalent analogues. In addition, they show good selectivity for PTP1B and the Yersinia PTPase as compared to LAR.

  DOI：

  10.1021/jm020093q

文献信息

• Divalent and Trivalent α-Ketocarboxylic Acids as Inhibitors of Protein Tyrosine Phosphatases
  作者：Yen Ting Chen、Christopher T. Seto

  DOI：10.1021/jm020093q

  日期：2002.8.1

  Protein tyrosine phosphatases (PTPases) are important targets for the treatment of insulin resistance in patients with type II diabetes and as antibacterial agents. As a result, there is a growing interest in the development of potent and specific inhibitors for these enzymes. This paper describes a series of inhibitors that contain two or three alpha-ketocarboxylic acid groups that are designed to form multiple contacts with residues inside or near the active site of phosphatases. The inhibitors have been assayed against three PTPases: the Yersinia PTPase, PTP1B, and LAR. The best of the inhibitors has IC50 values against the Yersinia PTPase and PTP1B of 0.7 and 2.7 muM, respectively. These divalent and trivalent compounds are significantly more potent than their corresponding monovalent analogues. In addition, they show good selectivity for PTP1B and the Yersinia PTPase as compared to LAR.