5-anilino-4-hydroxy-8-nitro quinazoline

• 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-anilino-4-hydroxy-8-nitro quinazoline
• 英文别名: 4-hydroxy-5-anilino-8-nitroquinazoline；5-anilino-8-nitro-4-hydroxyquinazoline；5-anilino-8-nitro-3H-quinazolin-4-one
• 化学式: C₁₄H₁₀N₄O₃
• 分子量: 282.258
• InChiKey: XGARSWWIBXHPMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-anilino-4-hydroxy-8-nitro quinazoline 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-chloro-2,4-difluoro-6-(4-oxo-5-(phenylamino)-3,4-dihydroquinazolin-8-ylamino)isophthalonitrile
  参考文献：
  名称：

  聚卤苄腈喹唑啉-4（3H）-一衍生物的合成及抑菌活性

  摘要：

  合成了一系列新颖的多卤代苄腈喹唑啉-4（3 H）-一衍生物，并通过NMR，IR，MS和HRMS光谱进行了表征。筛选了所有新制备的化合物对四种细菌（革兰氏阳性细菌：金黄色葡萄球菌和蜡状芽孢杆菌;革兰氏阴性细菌：大肠杆菌和铜绿假单胞菌）和一株真菌（白色念珠菌）的抗菌活性。在合成的化合物中，5-（二甲基氨基）-8-（2,4,5-三氯-间苯二甲腈）喹唑啉-4（3 H）-一（7k）对革兰氏阳性细菌，革兰氏阴性细菌和真菌菌株表现出显着的活性。该化合物的MIC（0.8–3.3μg/ mL）和MBC（2.6–7.8μg/ mL）接近于诺氟沙星，百菌清和氟康唑，使其成为该系列中最有效的抗菌剂。

  DOI：

  10.1016/j.bmcl.2013.08.068
• 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 32.67h， 生成 5-anilino-4-hydroxy-8-nitro quinazoline
  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