2-[(E)-2-(2H-1.3-benzodioxol-5-yl)ethenyl]quinazolin-4(3H)-one

• 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: 2-[(E)-2-(2H-1.3-benzodioxol-5-yl)ethenyl]quinazolin-4(3H)-one
• 英文别名: 2-(2-benzo[1,3]dioxol-5-yl-vinyl)-3H-quinazolin-4-one；2-(2-Benzo[1,3]dioxol-5-yl-vinyl)-3H-chinazolin-4-on；2-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]quinazolin-4(3H)-one；2-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-3H-quinazolin-4-one
• 化学式: C₁₇H₁₂N₂O₃
• 分子量: 292.294
• InChiKey: GKMYRYKJYRENIU-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(E)-2-(2H-1.3-benzodioxol-5-yl)ethenyl]quinazolin-4(3H)-one 在 乙醇 、 五氯化磷 、 铂 、 三氯氧磷 作用下， 生成 2-(2-benzo[1,3]dioxol-5-yl-ethyl)-4-methoxy-quinazoline
  参考文献：
  名称：

  Researches on Quinazolines. XLIII. The Synthesis of a Quinazoline Derivative Structurally Analogous to Cusparine

  摘要：

  DOI：

  10.1021/ja01300a060
• 作为产物：
  描述：

  2-氨基苯甲酰胺 在 溶剂黄146 作用下， 反应 12.5h， 生成 2-[(E)-2-(2H-1.3-benzodioxol-5-yl)ethenyl]quinazolin-4(3H)-one
  参考文献：
  名称：

  2-Styryl-4-aminoquinazoline derivatives as potent DNA-cleavage, p53-activation and in vivo effective anticancer agents

  摘要：

  Forty-eight analogues of CP-31398, an antitumor agent modulated the mutant p53 gene were synthesized and their cytotoxicities against four cancer cell lines with different p-53 status including bladder cell 724 (w-p53), gastric cell MGC-803 (m-p53), prostate cell DU145 (m-p53), prostate cell PC-3 (null-p53), lung cell A549 (w-p53) and normal liver cell line HL-7702 (w-p53) were examined. (E)-2-(4-Nitrostyryl)-4-(3-dimethylaminopropyl)-aminoquinazoline (10ah) was identified as the most potent compound in anti-proliferation against MGC-803 cells, with IC50 lowed to 1.73 mu M, far potency than that of CP-31398.Molecular mechanism study revealed that 10ah and CP-31398 differ greatly in mechanism to exert their antitumor properties. 10ah could intercalate into DNA and resulted in significant DNA double-strand break 10ah-treatment in MGC-803 cells increased the expression of p53, phosphorylated p53 (p-p53), CDK4, p21 to cause cell cycle arrest at G2/M phase, significantly up-regulated the levels of pro-apoptosis proteins Bak, Bax, Bim while down-regulated the anti-apoptosis proteins Bcl-2, Bcl-xL and the levels of cyclin B1, fluctuated the intracellular reactive oxygen species (ROS), Ca2+ and mitochondria! membrane potential, activated Caspase-9 and Caspase-3 to induce apoptosis. 10ah also displayed potent anticancer efficiency against MGC-803 xenograft tumors models, with tumor growth inhibition (TGI) up to 61.8% at 20 mg/kg without obvious toxicity. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111851

文献信息

• Bogert; Beal, Journal of the American Chemical Society, 1912, vol. 34, p. 522
  作者：Bogert、Beal

  DOI：——

  日期：——
• The p53 stabilizing agent CP-31398 and multi-kinase inhibitors. Designing, synthesizing and screening of styrylquinazoline series
  作者：Jacek Mularski、Katarzyna Malarz、Marcin Pacholczyk、Robert Musiol

  DOI：10.1016/j.ejmech.2018.12.012

  日期：2019.2

  Quinazoline derivatives constitute a large family of small-molecule inhibitors of tyrosine kinases. In the current study, the p53 protein reactivator CP-31398 was tested against a panel of kinases on the assumption that it was structurally similar to other active inhibitors. Although it was found to be active in the enzyme-based assay, this compound did not block the proliferation of cancer cells at a feasible concentration level. The styrylquinazoline was used to design new structures that might be potential multitarget inhibitors. Subsequently, a series of compounds was obtained and characterized. Their inhibitory activity in a panel of tyrosine kinases had an antiproliferative effect against several cancer cell lines that have different expression levels of those proteins. The mode of protein interaction was tested for the most active compound in docking experiments. (C) 2018 Elsevier Masson SAS. All rights reserved.