di(tert-butyl)difluoro[4-(3-oxo-2,3-diphenylpropyl)phenyl]methylphosphonate | 345953-50-6

• 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: di(tert-butyl)difluoro[4-(3-oxo-2,3-diphenylpropyl)phenyl]methylphosphonate
• 英文别名: 3-[4-[Bis[(2-methylpropan-2-yl)oxy]phosphoryl-difluoromethyl]phenyl]-1,2-diphenylpropan-1-one；3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl-difluoromethyl]phenyl]-1,2-diphenylpropan-1-one
• CAS: 345953-50-6
• 化学式: C₃₀H₃₅F₂O₄P
• 分子量: 528.576
• InChiKey: JOYWQOOJSIGIRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di(tert-butyl)difluoro[4-(3-oxo-2,3-diphenylpropyl)phenyl]methylphosphonate 在 potassium tert-butylate 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 [4-(2-{4-[difluoro(phosphono)methyl]benzyl}-3-oxo-2,3-diphenylpropyl)phenyl](difluoro)methylphosphonic acid
  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：

  二苯基乙酮 、 (4-bromomethylphenyl) difluoromethylphosphonic acid di-tert-butyl ester 在 NaH 、 ammonium chloride 作用下， 以 正己烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 di(tert-butyl)difluoro[4-(3-oxo-2,3-diphenylpropyl)phenyl]methylphosphonate
  参考文献：
  名称：

  Phosphonic acid derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B)

  摘要：

  该发明涵盖了由公式I代表的新型化合物类别，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了药物组合物和治疗或预防PTP-1B介导的疾病的方法，包括糖尿病、肥胖以及与糖尿病相关的疾病。

  公开号：

  US20020058644A1

文献信息

• Phosphonic acid derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B)
  申请人：——

  公开号：US20020058644A1

  公开（公告）日：2002-05-16

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

  该发明涵盖了由公式I代表的新型化合物类别，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了药物组合物和治疗或预防PTP-1B介导的疾病的方法，包括糖尿病、肥胖以及与糖尿病相关的疾病。
• US6486142B2
  申请人：——

  公开号：US6486142B2

  公开（公告）日：2002-11-26
• 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.