4'-(2,4-dichlorophenyl)-N-(3-methoxypropyl)-2'-methyl-2-phenyl-[4,5'-bipyrimidin]-6-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4'-(2,4-dichlorophenyl)-N-(3-methoxypropyl)-2'-methyl-2-phenyl-[4,5'-bipyrimidin]-6-amine
• 英文别名: 6-[4-(2,4-dichlorophenyl)-2-methylpyrimidin-5-yl]-N-(3-methoxypropyl)-2-phenylpyrimidin-4-amine
• 化学式: C₂₅H₂₃Cl₂N₅O
• 分子量: 480.397
• InChiKey: NPUNJIBVHIPYQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 26.0h， 生成 4'-(2,4-dichlorophenyl)-N-(3-methoxypropyl)-2'-methyl-2-phenyl-[4,5'-bipyrimidin]-6-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of new pyrazol-4-ylpyrimidine derivatives as potential ROS1 kinase inhibitors

  摘要：

  With the aim of discovering potent and selective kinase inhibitors targeting ROS1 kinase, we designed, synthesized and screened a series of new pyrazol-4-ylpyrimidine derivatives based on our previously discovered lead compound KIST301072. Compounds 6a-e and 7a-e showed good to excellent activities against ROS1 kinase, and seven out of tested compounds were more potent than KIST301072. Compound 7c was the most potent with IC50 of 24 nM. Moreover, compound 7c showed ROS1 inhibitory selectivity of about 170-fold, relative to that of ALK sharing about 49% amino acid sequence homology with ROS1 kinase in the kinase domain. In silica modeling of 7c at ROS1 active site revealed some essential features for ROS1 inhibitory activity. Based on this study as well as the previous studies, we could build a hypothetical model predicting the required essential features for ROS1 inhibitory activity. The model validity has been tested through a second set of compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.023

文献信息

• Synthesis and biological evaluation of new pyrazol-4-ylpyrimidine derivatives as potential ROS1 kinase inhibitors
  作者：Ahmed Z. Abdelazem、Mohammad M. Al-Sanea、Byung Sun Park、Hye Mi Park、Kyung Ho Yoo、Taebo Sim、Jong Bae Park、Seung-Hoon Lee、So Ha Lee

  DOI：10.1016/j.ejmech.2014.11.023

  日期：2015.1

  With the aim of discovering potent and selective kinase inhibitors targeting ROS1 kinase, we designed, synthesized and screened a series of new pyrazol-4-ylpyrimidine derivatives based on our previously discovered lead compound KIST301072. Compounds 6a-e and 7a-e showed good to excellent activities against ROS1 kinase, and seven out of tested compounds were more potent than KIST301072. Compound 7c was the most potent with IC50 of 24 nM. Moreover, compound 7c showed ROS1 inhibitory selectivity of about 170-fold, relative to that of ALK sharing about 49% amino acid sequence homology with ROS1 kinase in the kinase domain. In silica modeling of 7c at ROS1 active site revealed some essential features for ROS1 inhibitory activity. Based on this study as well as the previous studies, we could build a hypothetical model predicting the required essential features for ROS1 inhibitory activity. The model validity has been tested through a second set of compounds. (C) 2014 Elsevier Masson SAS. All rights reserved.