3-<β-Dimethylamino-ethyl>-2-methyl-chinazolon-(4) | 4207-04-9

• 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: 3-<β-Dimethylamino-ethyl>-2-methyl-chinazolon-(4)
• 英文别名: 3-(2-dimethylamino-ethyl)-2-methyl-3H-quinazolin-4-one；3-(2-Dimethylamino-aethyl)-2-methyl-3H-chinazolin-4-on；3-[2-(Dimethylamino)ethyl]-2-methylquinazolin-4-one
• CAS: 4207-04-9
• 化学式: C₁₃H₁₇N₃O
• 分子量: 231.297
• InChiKey: MLNDKDGPXDXTOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-<β-Dimethylamino-ethyl>-2-methyl-chinazolon-(4) 、 间硝基苯甲醛 在 溶剂黄146 作用下， 反应 12.0h， 以69%的产率得到
  参考文献：
  名称：

  Distinct novel quinazolinone exhibits selective inhibition in MGC-803 cancer cells by dictating mutant p53 function

  摘要：

  The mutant p53 proteins and their corresponding cellular response can be manipulated by novel quinazolinone derivatives 4-8 (a-i) in p53 mutant cancer cells. Of the two most potent compounds, 4a exhibited promising broad-spectrum anti-cancer effects, whereas 6c showed selective and exclusive inhibition activity in p53 mutant cancer cell lines but low toxicity to wild-type p53 cancer cell A375 and normal lung fibroblast WI-38 cells. Furthermore, 6c exhibited a more sophisticated mechanism for celldestructive response by causing S/G2 phase arrest effect and cell size reduction. Compared with the cellular response of 6b and genetic background of cell lines studied, p53 mutation was found to be the key factor and main target for 6c evoked cell-destructive response. Molecular mechanism studies indicated that p53 phosphorylation and acetylation dual-targeting inhibitor 6c exerted anti-cancer activities with a special mechanism in evoking cell apoptosis by arresting mutant p53 function to trigger the deregulation of Cdk2 caused Bim-mediated apoptosis. To the best of our knowledge, 6c is the first quinazolinone derivative to dictate mutant p53 function for apoptotic cell death. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.053
• 作为产物：
  描述：

  邻氨基苯甲酸 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 10.0h， 生成 3-<β-Dimethylamino-ethyl>-2-methyl-chinazolon-(4)
  参考文献：
  名称：

  Distinct novel quinazolinone exhibits selective inhibition in MGC-803 cancer cells by dictating mutant p53 function

  摘要：

  The mutant p53 proteins and their corresponding cellular response can be manipulated by novel quinazolinone derivatives 4-8 (a-i) in p53 mutant cancer cells. Of the two most potent compounds, 4a exhibited promising broad-spectrum anti-cancer effects, whereas 6c showed selective and exclusive inhibition activity in p53 mutant cancer cell lines but low toxicity to wild-type p53 cancer cell A375 and normal lung fibroblast WI-38 cells. Furthermore, 6c exhibited a more sophisticated mechanism for celldestructive response by causing S/G2 phase arrest effect and cell size reduction. Compared with the cellular response of 6b and genetic background of cell lines studied, p53 mutation was found to be the key factor and main target for 6c evoked cell-destructive response. Molecular mechanism studies indicated that p53 phosphorylation and acetylation dual-targeting inhibitor 6c exerted anti-cancer activities with a special mechanism in evoking cell apoptosis by arresting mutant p53 function to trigger the deregulation of Cdk2 caused Bim-mediated apoptosis. To the best of our knowledge, 6c is the first quinazolinone derivative to dictate mutant p53 function for apoptotic cell death. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.053

文献信息

• Buzas; Hoffmann, Bulletin de la Societe Chimique de France, 1959, p. 1889
  作者：Buzas、Hoffmann

  DOI：——

  日期：——
• Distinct novel quinazolinone exhibits selective inhibition in MGC-803 cancer cells by dictating mutant p53 function
  作者：Guo-Hai Zhang、Wen-Bin Xue、Yun-Feng An、Jing-Mei Yuan、Jiang-Ke Qin、Cheng-Xue Pan、Gui-Fa Su

  DOI：10.1016/j.ejmech.2015.03.053

  日期：2015.5

  The mutant p53 proteins and their corresponding cellular response can be manipulated by novel quinazolinone derivatives 4-8 (a-i) in p53 mutant cancer cells. Of the two most potent compounds, 4a exhibited promising broad-spectrum anti-cancer effects, whereas 6c showed selective and exclusive inhibition activity in p53 mutant cancer cell lines but low toxicity to wild-type p53 cancer cell A375 and normal lung fibroblast WI-38 cells. Furthermore, 6c exhibited a more sophisticated mechanism for celldestructive response by causing S/G2 phase arrest effect and cell size reduction. Compared with the cellular response of 6b and genetic background of cell lines studied, p53 mutation was found to be the key factor and main target for 6c evoked cell-destructive response. Molecular mechanism studies indicated that p53 phosphorylation and acetylation dual-targeting inhibitor 6c exerted anti-cancer activities with a special mechanism in evoking cell apoptosis by arresting mutant p53 function to trigger the deregulation of Cdk2 caused Bim-mediated apoptosis. To the best of our knowledge, 6c is the first quinazolinone derivative to dictate mutant p53 function for apoptotic cell death. (C) 2015 Elsevier Masson SAS. All rights reserved.