1-(3-fluoro-4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea | 1268490-31-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-fluoro-4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea
• 英文别名: N-(3-fluoro-4-{[6-(methylamino)-4-pyrimidinyl]oxy}phenyl)-N'-[3-(trifluoromethyl)phenyl]urea；1-[3-Fluoro-4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]-3-[3-(trifluoromethyl)phenyl]urea
• CAS: 1268490-31-8
• 化学式: C₁₉H₁₅F₄N₅O₂
• 分子量: 421.354
• InChiKey: DVLXULKETFKWBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  88.2
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氟-4-硝基苯酚 在 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 2.17h， 生成 1-(3-fluoro-4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)-3-(3-(trifluoromethyl)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

• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011025798A1

  公开（公告）日：2011-03-03

  Disclosed are compounds having the formula: wherein R1 and R2 are as defined herein, and methods of making and using the same.

  揭示了具有以下式的化合物：其中R1和R2如本文所定义，并且涉及制备和使用这些化合物的方法。
• COMPOUNDS AND METHODS
  申请人：Graves, III Alan Peterson

  公开号：US20120157482A1

  公开（公告）日：2012-06-21

  Disclosed are compounds having the formula: wherein R 1 and R 2 are as defined herein, and methods of making and using the same.

  公开了具有以下式子的化合物：其中R1和R2如此定义，在制备和使用中的方法。
• 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.