N-(4-nitrophenyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine | 1428155-01-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N-(4-nitrophenyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
• 英文别名: 9H-Purin-6-amine, N-(4-nitrophenyl)-9-(tetrahydro-2H-pyran-2-yl)-；N-(4-nitrophenyl)-9-(oxan-2-yl)purin-6-amine
• CAS: 1428155-01-4
• 化学式: C₁₆H₁₆N₆O₃
• 分子量: 340.341
• InChiKey: LFXYEKCJUYRMEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 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：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(4-nitrophenyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 9.0h， 生成 1-(3-fluorophenyl)-2-oxo-N-[4-(7H-purin-6-ylamino)phenyl]pyridine-3-carboxamide
  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：

  4-硝基苯胺 、 6-氯-9-(四氢-2-吡喃基)嘌呤 在 palladium diacetate 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 水 、 叔丁醇 为溶剂， 反应 15.0h， 以91%的产率得到N-(4-nitrophenyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
  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