N-(3-((5-fluoro-2-(4-((tetrahydro-2-furanyl)methoxy)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-((5-fluoro-2-(4-((tetrahydro-2-furanyl)methoxy)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide
• 英文别名: N-[3-[[5-fluoro-2-[4-(oxolan-2-ylmethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide
• 化学式: C₂₄H₂₄FN₅O₃
• 分子量: 449.485
• InChiKey: VJYBVJIHUKIUBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.4
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  四氢糠醇 在 铁粉 、 potassium carbonate 、 氯化铵 、 三氟乙酸 作用下， 以 甲醇 、 水 、 乙腈 、 仲丁醇 为溶剂， 反应 26.0h， 生成 N-(3-((5-fluoro-2-(4-((tetrahydro-2-furanyl)methoxy)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide
  参考文献：
  名称：

  Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines

  摘要：

  A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor 7j, with IC50 values of 10.5 AM against Ramos cells and 19.1 AM against Raji cells, also displayed slightly higher inhibitory ability than the novel agent ibrutinib. Moreover, compound 7j is not sensitive to normal cells PBMC, indicating low cell cytotoxicity. In addition, flow cytometry analysis indicated that 7j significantly induced the apoptosis of Ramos cells, and arrested the cell cycle at the GO/G1 phase. These explorations provided new clues to discover pyrimidine scaffold as more effective BTK inhibitors. 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.047

文献信息

• Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines
  作者：Dan Zhao、Shanshan Huang、Menghua Qu、Changyuan Wang、Zhihao Liu、Zhen Li、Jinyong Peng、Kexin Liu、Yanxia Li、Xiaodong Ma、Xiaohong Shu

  DOI：10.1016/j.ejmech.2016.11.047

  日期：2017.1

  A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor 7j, with IC50 values of 10.5 AM against Ramos cells and 19.1 AM against Raji cells, also displayed slightly higher inhibitory ability than the novel agent ibrutinib. Moreover, compound 7j is not sensitive to normal cells PBMC, indicating low cell cytotoxicity. In addition, flow cytometry analysis indicated that 7j significantly induced the apoptosis of Ramos cells, and arrested the cell cycle at the GO/G1 phase. These explorations provided new clues to discover pyrimidine scaffold as more effective BTK inhibitors. 2017 Elsevier Masson SAS. All rights reserved.