{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonic acid, benzyl methyl ester | 345953-51-7

• 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-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonic acid, benzyl methyl ester
• 英文别名: 1-benzyl 3-methyl 2-{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonate；1-Benzyl 3-methyl 2-{4-[(di-tert-butoxyphosphoryl) (difluoro)methyl]benzyl}malonate；3-O-benzyl 1-O-methyl 2-[[4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl-difluoromethyl]phenyl]methyl]propanedioate
• CAS: 345953-51-7
• 化学式: C₂₇H₃₅F₂O₇P
• 分子量: 540.541
• InChiKey: MNIOKWRQVDICPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  {4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonic acid, benzyl methyl ester 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
• 作为产物：
  描述：

  苄基丙二酸二甲酯 、 (4-bromomethylphenyl) difluoromethylphosphonic acid di-tert-butyl ester 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 {4-[(di-tert-butoxyphosphoryl)(difluoro)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 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。
• PHOSPHONIC ACID DERIVATIVES AS INHIBITORS OF PTP-1B
  申请人：Merck Frosst Canada & Co.

  公开号：EP1115729A1

  公开（公告）日：2001-07-18
• US6174874B1
  申请人：——

  公开号：US6174874B1

  公开（公告）日：2001-01-16
• [EN] PHOSPHONIC ACIDS DERIVATIVES AS INHIBITORS OF PTP-1B<br/>[FR] DERIVES DE L'ACIDE PHOSPHONIQUE UTILES COMME INHIBITEURS DE LA PTP-1B
  申请人：MERCK FROSST CANADA INC

  公开号：WO2000017211A1

  公开（公告）日：2000-03-30

  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.