1-(5-(tert-butyl)isoxazol-3-yl)-3-(3-methyl-4-((6-morpholinopyrimidin-4-yl)oxy)phenyl)urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-(tert-butyl)isoxazol-3-yl)-3-(3-methyl-4-((6-morpholinopyrimidin-4-yl)oxy)phenyl)urea
• 英文别名: 1-(5-Tert-butyl-1,2-oxazol-3-yl)-3-[3-methyl-4-(6-morpholin-4-ylpyrimidin-4-yl)oxyphenyl]urea；1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-methyl-4-(6-morpholin-4-ylpyrimidin-4-yl)oxyphenyl]urea
• 化学式: C₂₃H₂₈N₆O₄
• 分子量: 452.513
• InChiKey: JNMOJLRVOMREFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-甲基-4-硝基苯酚 在 铁粉 、 potassium carbonate 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.17h， 生成 1-(5-(tert-butyl)isoxazol-3-yl)-3-(3-methyl-4-((6-morpholinopyrimidin-4-yl)oxy)phenyl)urea
  参考文献：
  名称：

  Integrated bioinformatics, computational and experimental methods to discover novel Raf/extracellular-signal regulated kinase (ERK) dual inhibitors against breast cancer cells

  摘要：

  Beginning with our previously reported ERK inhibitor BL-EI001, we found Raf1 to be an important regulator in the ERK interactive network, and then we designed and synthesized a novel series of Raf1/ERIC dual inhibitors against human breast cancers through integrative computational, synthetic and biological screening methods. Moreover, we found that compound 9d suppressed the proliferation of breast cancer cell lines and induced cellular apoptosis via a mitochondrial pathway with only partial dependence on Raf1 and ERK. Our results suggest that an integrative method including in silico design, chemical synthesis, biological screening and bioinformatics analysis could be an attractive strategy for the discovery of multi-target inhibitors against breast cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.009

文献信息

• Integrated bioinformatics, computational and experimental methods to discover novel Raf/extracellular-signal regulated kinase (ERK) dual inhibitors against breast cancer cells
  作者：Yin Chen、Yaxin Zheng、Qinglin Jiang、Feifei Qin、Yonghui Zhang、Leilei Fu、Gu He

  DOI：10.1016/j.ejmech.2016.11.009

  日期：2017.2

  Beginning with our previously reported ERK inhibitor BL-EI001, we found Raf1 to be an important regulator in the ERK interactive network, and then we designed and synthesized a novel series of Raf1/ERIC dual inhibitors against human breast cancers through integrative computational, synthetic and biological screening methods. Moreover, we found that compound 9d suppressed the proliferation of breast cancer cell lines and induced cellular apoptosis via a mitochondrial pathway with only partial dependence on Raf1 and ERK. Our results suggest that an integrative method including in silico design, chemical synthesis, biological screening and bioinformatics analysis could be an attractive strategy for the discovery of multi-target inhibitors against breast cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.