2,2-di{4-[difluoro(phosphono)methyl]benzyl}malonic acid, benzyl methyl ester | 261175-07-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2,2-di{4-[difluoro(phosphono)methyl]benzyl}malonic acid, benzyl methyl ester
• 英文别名: 2,2-Bis-[4-(difluoro-phosphono-methyl)-benzyl]-malonic acid benzyl ester methyl ester；[[4-[2-[[4-[difluoro(phosphono)methyl]phenyl]methyl]-2-methoxycarbonyl-3-oxo-3-phenylmethoxypropyl]phenyl]-difluoromethyl]phosphonic acid
• CAS: 261175-07-9
• 化学式: C₂₇H₂₆F₄O₁₀P₂
• 分子量: 648.439
• InChiKey: PVVRPRVMELWOLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  2,2-di{4-[difluoro(phosphono)methyl]benzyl}malonic acid, benzyl methyl ester 以 水 、 三氟乙酸 为溶剂， 生成 2,2-di{4-[difluoro(phosphono)methyl]benzyl}malonic acid
  参考文献：
  名称：

  Phosphonic acids derivatives as inhibitors of protein tyrosine phosphate 1B (PTP-1B)

  摘要：

  该发明涵盖了由公式I表示的新型化合物类，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了制药组合物和治疗或预防PTP-1B介导疾病的方法。

  公开号：

  US06174874B1
• 作为产物：
  描述：

  苄基丙二酸二甲酯 在 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2,2-di{4-[difluoro(phosphono)methyl]benzyl}malonic acid, benzyl methyl ester
  参考文献：
  名称：

  The development of potent non-peptidic PTP-1B inhibitors

  摘要：

  The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.048

文献信息

• PHOSPHONIC ACID DERIVATIVES AS INHIBITORS OF PTP-1B
  申请人：Merck Frosst Canada & Co.

  公开号：EP1115729B1

  公开（公告）日：2003-02-19
• Phosphonic acids derivatives as inhibitors of protein tyrosine phosphate 1B (PTP-1B)
  申请人：Merck Frosst Canada & Co.

  公开号：US06174874B1

  公开（公告）日：2001-01-16

  The invention encompasses the novel class of compounds represented by formula I which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases.

  该发明涵盖了由公式I表示的新型化合物类，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了制药组合物和治疗或预防PTP-1B介导疾病的方法。
• The development of potent non-peptidic PTP-1B inhibitors
  作者：Claude Dufresne、Patrick Roy、Zhaoyin Wang、Ernest Asante-Appiah、Wanda Cromlish、Yves Boie、Farnaz Forghani、Sylvie Desmarais、Qingping Wang、Kathryn Skorey、Deena Waddleton、Chidambaram Ramachandran、Brian P. Kennedy、Lijing Xu、Robert Gordon、Chi Chung Chan、Yves Leblanc

  DOI：10.1016/j.bmcl.2003.11.048

  日期：2004.2

  The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM). (C) 2004 Elsevier Ltd. All rights reserved.