3-((6-(quinolin-8-yloxy)pyrimidin-4-yl)oxy)aniline

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-((6-(quinolin-8-yloxy)pyrimidin-4-yl)oxy)aniline
• 英文别名: 3-(6-Quinolin-8-yloxypyrimidin-4-yl)oxyaniline；3-(6-quinolin-8-yloxypyrimidin-4-yl)oxyaniline
• 化学式: C₁₉H₁₄N₄O₂
• 分子量: 330.346
• InChiKey: LPXURQVLEHYANP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  8-羟基喹啉 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-((6-(quinolin-8-yloxy)pyrimidin-4-yl)oxy)aniline
  参考文献：
  名称：

  Structure guided design of potential inhibitors of human calcium–calmodulin dependent protein kinase IV containing pyrimidine scaffold

  摘要：

  Calmodulin dependent protein kinase IV (CAMKIV) belongs to the serine/threonine protein kinase family and considered as an encouraging target for the development of novel anticancer agents. The interaction and binding behavior of three designed inhibitors of human CAMKIV, containing pyrimidine scaffold, was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. In silico docking studies were performed to screen several compounds containing pyrimidine scaffold against CAMKIV. Molecular docking calculation predicted the binding of these ligands in active-site cavity of the CAMKIV structure correlating such interactions with a probable inhibition mechanism. Finally, three active pyrimidine substituted compounds (molecules 1-3) have been successfully synthesized and characterized by H-1 and C-13 NMR. Molecule 3 is showing very high binding-affinity for the CAMKIV, with a binding constant of 2.2 X 10(8), M-1 (+/- 0.20). All three compounds are nontoxic to HEK293 cells up to 50 mu M. The cell proliferation inhibition study showed that the molecule 3 has lowest IC50 value (46 +/- 1.08 mu M). The theoretical and experimental observations are significantly correlated. This study reveals some important observations to generate an improved pyrimidine based compound that holds promise as a therapeutic agent for the treatment of cancer and neurodegenerative diseases. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.098

文献信息

• Structure guided design of potential inhibitors of human calcium–calmodulin dependent protein kinase IV containing pyrimidine scaffold
  作者：Huma Naz、Ehtesham Jameel、Nasimul Hoda、Ashutosh Shandilya、Parvez Khan、Asimul Islam、Faizan Ahmad、B. Jayaram、Md. Imtaiyaz Hassan

  DOI：10.1016/j.bmcl.2015.12.098

  日期：2016.2

  Calmodulin dependent protein kinase IV (CAMKIV) belongs to the serine/threonine protein kinase family and considered as an encouraging target for the development of novel anticancer agents. The interaction and binding behavior of three designed inhibitors of human CAMKIV, containing pyrimidine scaffold, was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. In silico docking studies were performed to screen several compounds containing pyrimidine scaffold against CAMKIV. Molecular docking calculation predicted the binding of these ligands in active-site cavity of the CAMKIV structure correlating such interactions with a probable inhibition mechanism. Finally, three active pyrimidine substituted compounds (molecules 1-3) have been successfully synthesized and characterized by H-1 and C-13 NMR. Molecule 3 is showing very high binding-affinity for the CAMKIV, with a binding constant of 2.2 X 10(8), M-1 (+/- 0.20). All three compounds are nontoxic to HEK293 cells up to 50 mu M. The cell proliferation inhibition study showed that the molecule 3 has lowest IC50 value (46 +/- 1.08 mu M). The theoretical and experimental observations are significantly correlated. This study reveals some important observations to generate an improved pyrimidine based compound that holds promise as a therapeutic agent for the treatment of cancer and neurodegenerative diseases. (C) 2015 Elsevier Ltd. All rights reserved.