N-(3-chlorophenyl)-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine

• 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-(3-chlorophenyl)-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine
• 化学式: C₂₂H₁₅ClF₃N₃S
• 分子量: 445.9
• InChiKey: FGVPKZAUTBFRSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-[[4-(trifluoromethyl)phenyl]methylsulfanyl]-3H-quinazolin-4-one 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(3-chlorophenyl)-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine
  参考文献：
  名称：

  2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K

  摘要：

  A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MIT assay. Among them, compound 9n showed the most potent cytotoxicity against breast cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Meanwhile, compound 9n induced cell cycle arrest at G1 phase and cell apoptosis, as well as increased accumulation of intracellular ROS. Furthermore, compound 9n exerted anti-tumor effects in vitro via decreasing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 9n markedly decreased p-EGFR and p-PI3K expression, which revealed that compound 9n targeted breast cancer cells via interfering with EGFR-PI3K signaling pathway. Molecular docking suggested that compound 9n could indeed bind into the active pocket of EGFR. All the findings suggest that compound 9n might be a valuable lead compound for anti-tumor agents targeting breast cancer cells. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.030

文献信息

• 2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K
  作者：Er-dong Li、Qiao Lin、Ya-qi Meng、Lu-ye Zhang、Pan-pan Song、Na Li、Jing-chao Xin、Peng Yang、Chong-nan Bao、Dan-qing Zhang、Yang Zhang、Ji-kuan Wang、Qiu-rong Zhang、Hong-min Liu

  DOI：10.1016/j.ejmech.2019.03.030

  日期：2019.6

  A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MIT assay. Among them, compound 9n showed the most potent cytotoxicity against breast cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Meanwhile, compound 9n induced cell cycle arrest at G1 phase and cell apoptosis, as well as increased accumulation of intracellular ROS. Furthermore, compound 9n exerted anti-tumor effects in vitro via decreasing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 9n markedly decreased p-EGFR and p-PI3K expression, which revealed that compound 9n targeted breast cancer cells via interfering with EGFR-PI3K signaling pathway. Molecular docking suggested that compound 9n could indeed bind into the active pocket of EGFR. All the findings suggest that compound 9n might be a valuable lead compound for anti-tumor agents targeting breast cancer cells. (C) 2019 Elsevier Masson SAS. All rights reserved.