5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline

• 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: 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline
• 英文别名: LJK-11；5-(4-methoxyanilino)-8-nitro-3H-quinazolin-4-one
• 化学式: C₁₅H₁₂N₄O₄
• 分子量: 312.285
• InChiKey: LRQQNILSLYXOIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 8-amino-5-((4-methoxyphenyl)amino)quinazoline-4(3H)-one
  参考文献：
  名称：

  3,4-Dihydroquinazolin-8-yl-3-phenylurea Derivatives: Synthesis, VEGFR-2 Kinase Inhibiting Activity, and Molecular Docking

  摘要：

  DOI：

  10.1134/s107036322109022x
• 作为产物：
  描述：

  3-氯-2-甲基乙酰苯胺 在 盐酸 、 potassium permanganate 、 硫酸 、 硝酸 、 magnesium sulfate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 8.67h， 生成 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline
  参考文献：
  名称：

  Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as EGFR signaling-targeted inhibitors

  摘要：

  The synthesis and biological activity of a series of novel 5-substituted-4-hydroxy-8-nitroquinazolines that may function as inhibitors of EGFR- and/or ErbB-2-related oncogenic signaling are described. These compounds were prepared by SNAr reaction of 5-chloro-4-hydroxy-8-nitroquinazo line with alkyl or aryl amines, or alkyl alcohol as nucleophiles. Although the enzyme assay showed a weak inhibition effect against both EGFR and ErbB-2 tyrosine kinases, the cell-based antitumor activity turned out promising. Compounds having 5-anilino substituent exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h) being the best dual EGFR/ErbB-2 inhibitors, which effectively inhibited the growth of both EGFR (MDA-MB-468, IC50 < 0-01 mu M) and ErbB-2 (SK-BR-3, IC50 = 13 mu M) overexpressing human tumor cell lines in vitro. More interestingly, the variation of the substituent(s) at the 3- and/or 4-position of the 5-anilino portion was found to modulate the selectivity and potency dramatically. However, compounds having an alkylamino or alkyloxy group at the 5-position of 4-hydroxy-8-nitroquinazolines are essentially inactive. These results are consistent with molecular modeling observations. This study was the first attempt to identify new structural types of dual EGFR/ErbB-2-related signaling inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8-nitroquinazolines' core structure, providing promising new templates for further development of potent inhibitors targeting both EGFR and ErbB-2 tyrosine kinases. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.045

文献信息

• 3,4-Dihydroquinazolin-8-yl-3-phenylurea Derivatives: Synthesis, VEGFR-2 Kinase Inhibiting Activity, and Molecular Docking
  作者：Kunming Jiang、Nali Song、Chen Yang、Shiyun Tang、Zhibang Wu、Zhihua Liu、Zhenjie Li

  DOI：10.1134/s107036322109022x

  日期：2021.9
• Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as EGFR signaling-targeted inhibitors
  作者：Yi Jin、Hui-Yuan Li、Li-Ping Lin、Jinzhi Tan、Jian Ding、Xiaomin Luo、Ya-Qiu Long

  DOI：10.1016/j.bmc.2005.05.045

  日期：2005.10

  The synthesis and biological activity of a series of novel 5-substituted-4-hydroxy-8-nitroquinazolines that may function as inhibitors of EGFR- and/or ErbB-2-related oncogenic signaling are described. These compounds were prepared by SNAr reaction of 5-chloro-4-hydroxy-8-nitroquinazo line with alkyl or aryl amines, or alkyl alcohol as nucleophiles. Although the enzyme assay showed a weak inhibition effect against both EGFR and ErbB-2 tyrosine kinases, the cell-based antitumor activity turned out promising. Compounds having 5-anilino substituent exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h) being the best dual EGFR/ErbB-2 inhibitors, which effectively inhibited the growth of both EGFR (MDA-MB-468, IC50 < 0-01 mu M) and ErbB-2 (SK-BR-3, IC50 = 13 mu M) overexpressing human tumor cell lines in vitro. More interestingly, the variation of the substituent(s) at the 3- and/or 4-position of the 5-anilino portion was found to modulate the selectivity and potency dramatically. However, compounds having an alkylamino or alkyloxy group at the 5-position of 4-hydroxy-8-nitroquinazolines are essentially inactive. These results are consistent with molecular modeling observations. This study was the first attempt to identify new structural types of dual EGFR/ErbB-2-related signaling inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8-nitroquinazolines' core structure, providing promising new templates for further development of potent inhibitors targeting both EGFR and ErbB-2 tyrosine kinases. (c) 2005 Elsevier Ltd. All rights reserved.