5-氯-8-硝基喹唑啉-4-醇 | 400784-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 5-氯-8-硝基喹唑啉-4-醇
• 英文名称: 5-chloro-8-nitroquinazolin-4-ol
• 英文别名: 4-hydroxy-5-chloro-8-nitro-quinazoline；5-Chloro-8-nitroquinazolin-4-OL；5-chloro-8-nitro-3H-quinazolin-4-one
• CAS: 400784-50-1
• 化学式: C₈H₄ClN₃O₃
• 分子量: 225.591
• InChiKey: IUHHPBONKCSYOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氯-8-硝基喹唑啉-4-醇 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 13.0h， 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 水 为溶剂， 反应 8.67h， 生成 5-氯-8-硝基喹唑啉-4-醇
  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

• Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking
  作者：Yongqiang Zhao、Feifei Liu、Guojing He、Ke Li、Changcheng Zhu、Wei Yu、Conghai Zhang、Mingjin Xie、Jun Lin、Jihong Zhang、Yi Jin

  DOI：10.1016/j.bmcl.2019.126711

  日期：2019.12

  against HepG2 cell. All synthesized compounds were evaluated for anti-angiogenesis capability. Compound 7o showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC and HepG2 cell lines with IC50 values of 0.58 and 0.23 µM, respectively). The molecular docking analysis revealed 7o is a Type-II inhibitor of VEGFR-2 kinase. In general, these results indicated

  本文中，我们以先前报道的XL-6f为先导化合物，着手进行结构优化运动，旨在发现新型抗癌药。基于VEGFR-2高度保守的活性位点，已合成了23种化合物的文库。几种标题化合物显示出对VEGFR-2的选择性抑制活性，还显示出对HepG2细胞的选择性抗增殖能力。评价所有合成的化合物的抗血管生成能力。化合物7o显示出最有效的抗血管生成能力和有效的细胞毒活性（体外针对HUVEC和HepG2细胞系，IC 50值分别为0.58和0.23 µM）。分子对接分析显示7o是VEGFR-2激酶的II型抑制剂。通常，这些结果表明这些芳基酰胺-5-苯胺基喹唑啉-8-硝基衍生物是用于潜在治疗抗血管生成的VEGFR-2抑制剂。
• Novel 5-anilinoquinazoline-8-nitro derivatives as inhibitors of VEGFR-2 tyrosine kinase: synthesis, biological evaluation and molecular docking
  作者：Liang Xi、Jian-Qiang Zhang、Zhi-Cheng Liu、Ji-Hong Zhang、Ju-Fang Yan、Yi Jin、Jun Lin

  DOI：10.1039/c3ob40368h

  日期：——

  Vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibition is a well-established strategy to promptly tackle tumor growth by suppression of angiogenesis. We report herein a series of 5-anilinoquinazoline derivatives substituted by 1,3-disubstituted urea. All the newly synthesized compounds described were evaluated for VEGFR-2 kinase inhibition and antiproliferative activity against various cancer cells. The novel 1-aryl, 3-aryl-disubstituted urea quinazolines were effective VEGFR-2 kinase inhibitors with in vitro IC50 values in the submicromolar range (compound 6f, IC50 12.0 nM), but showed a weak to moderate inhibitory activity on cancer cells. Molecular interactions of the compounds were studied using molecular docking studies.

  血管内皮生长因子受体-2（VEGFR-2）激酶抑制是一种公认的策略，旨在通过抑制血管生成来迅速应对肿瘤生长。本文报告了一系列以1,3-双取代脲为取代基的5-氨基喹唑啉衍生物。所有新合成的化合物均经过评估，以测试其对VEGFR-2激酶的抑制作用和对多种癌细胞的抗增殖活性。新型的1-芳基、3-芳基-双取代脲喹唑啉是有效的VEGFR-2激酶抑制剂，其体外IC50值在亚微摩尔范围内（化合物6f，IC50为12.0 nM），但在癌细胞上表现出较弱到中等的抑制活性。采用分子对接研究了这些化合物的分子相互作用。
• 一种喹唑啉类芳基脲及其制备方法和用途
  申请人：云南大学

  公开号：CN103102315B

  公开（公告）日：2016-01-20

  本发明公开了一类喹唑啉类芳基脲类化合物及其制备方法和用途，如下具体有通式I的化合物。这类具有喹唑啉基及芳基取代脲的新化合物展示有非常高的抑制肿瘤细胞生长的活性，尤其对于VEGFR高表达的HUVEC细胞的生长具有显著的抑制效果，半数抑制IC50值能达到1.8μg/mL。本发明也提供了这类化合物的制备方法。。
• 4′-Alkoxyl substitution enhancing the anti-mitotic effect of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents
  作者：Yi Jin、Zu-Yu Zhou、Wei Tian、Qiang Yu、Ya-Qiu Long

  DOI：10.1016/j.bmcl.2006.08.058

  日期：2006.11

  Mitosis inhibitors are powerful anticancer drugs. Based on a novel anti-microtubule agent of 5-(4'-methoxy)anilino-4-hydroxy-8-nitroquinazoline, a series of 5-(3',4',5'-substituted)anilino-4-hydroxy-8- nitroquinazolines were designed and synthesized to investigate the effect of the substitution on the inhibitory activity against mitotic progression of tumor cells. The large alkoxyl substitution on the 4'-position of 5-anilino ring is beneficial for the potency. The 5-(3',4,5'-trimethoxy)anilino-8-nitroquinazoline (1h) displays an overwhelming activity in arresting the cells at the G2/M phase, providing a promising new template for further development of potent microtubule-targeted anti-mitotic drugs. (c) 2006 Elsevier Ltd. All rights reserved.
• 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