6-(2-fluoro-4-nitrophenoxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine | 1428154-95-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(2-fluoro-4-nitrophenoxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine
• 英文别名: 6-(2-Fluoro-4-nitrophenoxy)-9-(oxan-2-yl)purine；6-(2-fluoro-4-nitrophenoxy)-9-(oxan-2-yl)purine
• CAS: 1428154-95-3
• 化学式: C₁₆H₁₄FN₅O₄
• 分子量: 359.317
• InChiKey: KOOCJCHFFZENQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(2-fluoro-4-nitrophenoxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以69%的产率得到3-fluoro-4-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yloxy)aniline
  参考文献：
  名称：

  Inhibitors of the TAM subfamily of tyrosine kinases: Synthesis and biological evaluation

  摘要：

  The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design a type II inhibitor specific for this family, i.e. able to interact with the allosteric pocket and with the hinge region of the kinase. We report the synthesis of several series of purine analogues of BMS-777607. The structural diversity of the designed inhibitors was expected to modify the interactions formed in the binding site and consequently to modulate their selectivity profiles. The most potent inhibitor 6g exhibits K(d)s of 39, 42, 65 and 200 nM against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for active and inactive forms of Abl1, an RTK protein that does not belong to the TAM subfamily, together with the binding modes of 6g predicted by docking studies, indicates that 6g displays some selectivity for the TAM family and may act as a type II inhibitor. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.005
• 作为产物：
  描述：

  2-氟-4-硝基苯酚 、 6-氯-9-(四氢-2-吡喃基)嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以58%的产率得到6-(2-fluoro-4-nitrophenoxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine
  参考文献：
  名称：

  Inhibitors of the TAM subfamily of tyrosine kinases: Synthesis and biological evaluation

  摘要：

  The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design a type II inhibitor specific for this family, i.e. able to interact with the allosteric pocket and with the hinge region of the kinase. We report the synthesis of several series of purine analogues of BMS-777607. The structural diversity of the designed inhibitors was expected to modify the interactions formed in the binding site and consequently to modulate their selectivity profiles. The most potent inhibitor 6g exhibits K(d)s of 39, 42, 65 and 200 nM against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for active and inactive forms of Abl1, an RTK protein that does not belong to the TAM subfamily, together with the binding modes of 6g predicted by docking studies, indicates that 6g displays some selectivity for the TAM family and may act as a type II inhibitor. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.005