N-(4-nitrophenyl)-N'-(3-(((quinazolin-4-yl)amino)methyl)phenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(4-nitrophenyl)-N'-(3-(((quinazolin-4-yl)amino)methyl)phenyl)urea
• 英文别名: N-(4-nitrophenyl)-N'-{3-[(quinazolin-4-amino)methyl]phenyl}urea；1-(4-Nitrophenyl)-3-[3-[(quinazolin-4-ylamino)methyl]phenyl]urea；1-(4-nitrophenyl)-3-[3-[(quinazolin-4-ylamino)methyl]phenyl]urea
• 化学式: C₂₂H₁₈N₆O₃
• 分子量: 414.423
• InChiKey: DJETYTDGCPLLHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯喹唑啉 在 三乙胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 8.0h， 生成 N-(4-nitrophenyl)-N'-(3-(((quinazolin-4-yl)amino)methyl)phenyl)urea
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents

  摘要：

  Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.045

文献信息

• Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents
  作者：Jia-Nian Chen、Xian-Fu Wang、Ting Li、De-Wen Wu、Xiao-Bo Fu、Guang-Ji Zhang、Xing-Can Shen、Heng-Shan Wang

  DOI：10.1016/j.ejmech.2015.10.045

  日期：2016.1

  Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds (7g, 7m, 7o, 8e, 8g, and 8m) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.