3,3'-bis<(dimethylphosphono)difluoromethyl>biphenyl | 215731-87-6

• 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: 3,3'-bis<(dimethylphosphono)difluoromethyl>biphenyl
• CAS: 215731-87-6
• 化学式: C₁₈H₂₀F₄O₆P₂
• 分子量: 470.294
• InChiKey: OHNNPTYJPRDALA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.42
• 重原子数：
  30.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3,3'-bis<(dimethylphosphono)difluoromethyl>biphenyl 在 三甲基溴硅烷 、 碳酸氢铵 作用下， 生成 3,3'-bis<(phosphono)difluoromethyl>biphenyl ammonium salt
  参考文献：
  名称：

  Potent non-peptidyl inhibitors of protein tyrosine phosphatase 1B

  摘要：

  The development of inhibitors of protein tyrosine phosphatases (PTPs) has recently been the subject of intensive investigation due to their potential as chemotherapeutics and as tools for studying signal transduction pathways. Here we report the evaluation of a variety of small molecule, non-peptidyl inhibitors of protein tyrosine phosphatase 1B (PTP1B), bearing the alpha,alpha-difluoromethylenephosphonic acid (DFMP) group, a non-hydrolyzable phosphate mimetic. A series of phenyl derivatives bearing a single DFMP group were initially surveyed. In general, these were not significantly more potent inhibitors than the parent compound, alpha,alpha-difluorobenzylphosphonic acid, with the exception being the meta-phenyl substituted species which decreased the IC50 by approximately 17-fold relative to alpha,alpha-difluorobenzylphosphonic acid. However, certain compounds bearing two DFMP moieties were very potent inhibitors. Some of these are among the most potent small molecule inhibitors of any PTP reported to date with the best one exhibiting a K-i of 1.5 mu M. The structural basis for these results are discussed. One of the bis-DFMP inhibitors was examined in detail and it was found that the fluorines were essential for potent inhibition. Inhibition was independent of pH between pH 5.5-7.2 suggesting that both the mono and dianionic forms of the individual DFMP groups bind equally well. The trends observed in the inhibitory potency of these compounds with PTP1B were very similar to the trends observed by other workers on the K-m's of the analogous phenylphosphate substrates with rat PTP1. This indicates that studies of non-peptidyl substrates with rat PTP1 can be used as a guide for the development of human PTP1B inhibitors. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00075-3
• 作为产物：
  描述：

  3,3'-bis(dimethylphosphonomethyl)biphenyl 在 sodium hexamethyldisilazane 、 N-氟代双苯磺酰胺 作用下， 生成 3,3'-bis<(dimethylphosphono)difluoromethyl>biphenyl
  参考文献：
  名称：

  Potent non-peptidyl inhibitors of protein tyrosine phosphatase 1B

  摘要：

  The development of inhibitors of protein tyrosine phosphatases (PTPs) has recently been the subject of intensive investigation due to their potential as chemotherapeutics and as tools for studying signal transduction pathways. Here we report the evaluation of a variety of small molecule, non-peptidyl inhibitors of protein tyrosine phosphatase 1B (PTP1B), bearing the alpha,alpha-difluoromethylenephosphonic acid (DFMP) group, a non-hydrolyzable phosphate mimetic. A series of phenyl derivatives bearing a single DFMP group were initially surveyed. In general, these were not significantly more potent inhibitors than the parent compound, alpha,alpha-difluorobenzylphosphonic acid, with the exception being the meta-phenyl substituted species which decreased the IC50 by approximately 17-fold relative to alpha,alpha-difluorobenzylphosphonic acid. However, certain compounds bearing two DFMP moieties were very potent inhibitors. Some of these are among the most potent small molecule inhibitors of any PTP reported to date with the best one exhibiting a K-i of 1.5 mu M. The structural basis for these results are discussed. One of the bis-DFMP inhibitors was examined in detail and it was found that the fluorines were essential for potent inhibition. Inhibition was independent of pH between pH 5.5-7.2 suggesting that both the mono and dianionic forms of the individual DFMP groups bind equally well. The trends observed in the inhibitory potency of these compounds with PTP1B were very similar to the trends observed by other workers on the K-m's of the analogous phenylphosphate substrates with rat PTP1. This indicates that studies of non-peptidyl substrates with rat PTP1 can be used as a guide for the development of human PTP1B inhibitors. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00075-3