{4-[4-(4-Oxalyl-phenoxymethyl)-benzyloxy]-phenyl}-oxo-acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: {4-[4-(4-Oxalyl-phenoxymethyl)-benzyloxy]-phenyl}-oxo-acetic acid
• 英文别名: 2-[4-[[4-[(4-oxalophenoxy)methyl]phenyl]methoxy]phenyl]-2-oxoacetic acid
• 化学式: C₂₄H₁₈O₈
• 分子量: 434.402
• InChiKey: HNHFGJRWYYEILT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-(4-hydroxyphenyl)acetate 在 吡啶 、 sodium hydroxide 、 乙醇 、 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 26.0h， 生成 {4-[4-(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

文献信息

• PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR, PREPARATION METHODS AND USES THEREOF
  申请人：Shanghai Institute Of Materia Medica Chinese Academy of Sciences

  公开号：EP2133342A1

  公开（公告）日：2009-12-16

  PTP1B inhibitors with the following structure (formula I). Experiments indicate that these inhibitors can effectively inhibit the activity of protein tyrosine phosphatase 1B (PTP1B). They can be used as insulin sensitisers. They can be used to prevent, delay or treat diseases which are related to insulin antagonism mediated by PTP1B, especially diabetes type II and obesity. The invention also provides methods for preparing these inhibitors.

  具有以下结构（式 I）的 PTP1B 抑制剂。实验表明，这些抑制剂能有效抑制蛋白酪氨酸磷酸酶 1B（PTP1B）的活性。它们可用作胰岛素增敏剂。它们可用于预防、延缓或治疗与 PTP1B 介导的胰岛素拮抗作用有关的疾病，特别是 II 型糖尿病和肥胖症。本发明还提供了制备这些抑制剂的方法。
• Protein Tyrosine Phosphatase 1B Inhibitor, Preparation Methods and Uses Thereof
  申请人：Nan Fajun

  公开号：US20100197927A1

  公开（公告）日：2010-08-05

  PTP1B inhibitors with the following structure (formula I). Experiments indicate that these inhibitors can effectively inhibit the activity of protein tyrosine phosphatase 1B (PTP1B). They can be used as insulin sensitisers. They can be used to prevent, delay or treat diseases which are related to insulin antagonism mediated by PTP1B, especially diabetes type II and obesity. The invention also provides methods for preparing these inhibitors.
• US8183383B2
  申请人：——

  公开号：US8183383B2

  公开（公告）日：2012-05-22
• 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.