[4-({5-[2-(4-tert-Butoxyoxalyl-phenoxy)-acetylamino]-2-phenylamino-phenylcarbamoyl}-methoxy)-phenyl]-oxo-acetic acid tert-butyl ester | 851875-41-7

• 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: [4-({5-[2-(4-tert-Butoxyoxalyl-phenoxy)-acetylamino]-2-phenylamino-phenylcarbamoyl}-methoxy)-phenyl]-oxo-acetic acid tert-butyl ester
• CAS: 851875-41-7
• 化学式: C₄₀H₄₁N₃O₁₀
• 分子量: 723.78
• InChiKey: WNOHIONCUPLVCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.51
• 重原子数：
  53.0
• 可旋转键数：
  14.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  175.43
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  [4-({5-[2-(4-tert-Butoxyoxalyl-phenoxy)-acetylamino]-2-phenylamino-phenylcarbamoyl}-methoxy)-phenyl]-oxo-acetic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以91%的产率得到Oxo-{4-[(3,4,11-trioxo-2-phenyl-9-oxa-2,12-diaza-tricyclo[11.2.2.2^5,8]nonadeca-1(16),5(19),6,8(18),13(17),14-hexaen-15-ylcarbamoyl)-methoxy]-phenyl}-acetic acid
  参考文献：
  名称：

  Investigations of linker structure on the potency of a series of bidentate protein tyrosine phosphatase inhibitors

  摘要：

  Protein tyrosine phosphatases (PTPases) and protein tyrosine kinase (PTKases) regulate the phosphorylation and dephosphorylation of tyrosine residues in proteins, events that are essential for a variety of cellular functions. PTPases such as PTP1B and the Yersinia PTPase play an important role in diseases including type 11 diabetes and bubonic plague. A library of 67 bidentate PTPase inhibitors that are based on the alpha-ketocarboxylic acid motif has been synthesized using parallel solution-phase methods. Two aryl alpha-ketocarboxylic acids were tethered to a variety of different diamine linkers through amide bonds. The compounds were assayed in crude form against the Yersinia PTPase, PTP1B, and TCPTP. Six compounds were selected for further evaluation, in purified form, against the Yersinia PTPase, PTP1B, TCPTP, LAR, and CD45. These compounds had IC50 values in the low micromolar range against the Yersinia PTPase, PTP I B, and TCPTP, showed good selectivity for PTP1B over LAR, and modest selectivity over CD45. The correlation between linker structure and inhibitor activity shows that aromatic groups in the linker can play an important role in determining binding affinity in this class of inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.001
• 作为产物：
  描述：

  (4-Benzyloxycarbonylmethoxy-phenyl)-oxo-acetic acid tert-butyl ester 在 palladium dihydroxide 4-二甲氨基吡啶 、 氢气 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 反应 26.0h， 生成 [4-({5-[2-(4-tert-Butoxyoxalyl-phenoxy)-acetylamino]-2-phenylamino-phenylcarbamoyl}-methoxy)-phenyl]-oxo-acetic acid tert-butyl ester
  参考文献：
  名称：

  Investigations of linker structure on the potency of a series of bidentate protein tyrosine phosphatase inhibitors

  摘要：

  Protein tyrosine phosphatases (PTPases) and protein tyrosine kinase (PTKases) regulate the phosphorylation and dephosphorylation of tyrosine residues in proteins, events that are essential for a variety of cellular functions. PTPases such as PTP1B and the Yersinia PTPase play an important role in diseases including type 11 diabetes and bubonic plague. A library of 67 bidentate PTPase inhibitors that are based on the alpha-ketocarboxylic acid motif has been synthesized using parallel solution-phase methods. Two aryl alpha-ketocarboxylic acids were tethered to a variety of different diamine linkers through amide bonds. The compounds were assayed in crude form against the Yersinia PTPase, PTP1B, and TCPTP. Six compounds were selected for further evaluation, in purified form, against the Yersinia PTPase, PTP1B, TCPTP, LAR, and CD45. These compounds had IC50 values in the low micromolar range against the Yersinia PTPase, PTP I B, and TCPTP, showed good selectivity for PTP1B over LAR, and modest selectivity over CD45. The correlation between linker structure and inhibitor activity shows that aromatic groups in the linker can play an important role in determining binding affinity in this class of inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.001