4-(4'-methylphenyl)amino-6-nitroquinazoline | 1120331-47-6

• 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: 4-(4'-methylphenyl)amino-6-nitroquinazoline
• 英文别名: N-(4-methylphenyl)-6-nitro-quinazolin-4-amine；N-(4-methylphenyl)-6-nitroquinazolin-4-amine
• CAS: 1120331-47-6
• 化学式: C₁₅H₁₂N₄O₂
• 分子量: 280.286
• InChiKey: ILFAVOGAJFOUAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4'-methylphenyl)amino-6-nitroquinazoline 在 10% palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 1.0h， 生成 N-(3,4-dichlorophenyl)-N'-[4-(4-toluidino)quinazolin-6-yl]urea
  参考文献：
  名称：

  寻找新的药效抗疟疾活性。第二部分：新型6-脲基-4-苯胺基喹唑啉的合成及抗疟活性

  摘要：

  已经完成了新的6-脲基-4-苯胺基喹唑啉的合成，并且已经研究了它们对氯喹敏感的恶性疟原虫的体外抗疟活性。在评估的64种化合物中，还记录了MIC值为0.25μg/ mL的16种化合物的IC 50值。其中一种化合物（24g）的IC 50值为2.27 ng / mL，与生物测定中使用的标准药物氯喹等效。导致一个模拟的发现该系列中的几种化合物的体内评价（30克）显示40％的治疗活性（28天）对MDR P. yoeilli nigeriensis在100毫克/公斤×4天的口服剂量。

  DOI：

  10.1016/j.bmc.2008.11.005
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 溶剂黄146 、 三氯氧磷 作用下， 反应 3.0h， 生成 4-(4'-methylphenyl)amino-6-nitroquinazoline
  参考文献：
  名称：

  10.1016/j.ejps.2024.106789

  摘要：

  DOI：

  10.1016/j.ejps.2024.106789

文献信息

• Discovery of Potent EGFR Inhibitors With 6-Arylureido-4-anilinoquinazoline Derivatives
  作者：Meng Li、Na Xue、Xingang Liu、Qiaoyun Wang、Hongyi Yan、Yifan Liu、Lei Wang、Xiaowei Shi、Deying Cao、Kai Zhang、Yang Zhang

  DOI：10.3389/fphar.2021.647591

  日期：——

  According to the classical pharmacophore fusion strategy, a series of 6-arylureido-4-anilinoquinazoline derivatives (Compounds 7a–t) were designed, synthesized, and biologically evaluated by the standard CCK-8 method and enzyme inhibition assay. Among the title compounds, Compounds 7a, 7c, 7d, 7f, 7i, 7o, 7p, and 7q exhibited promising anti-proliferative bioactivities, especially Compound 7i, which had excellent antitumor activity against the A549, HT-29, and MCF-7 cell lines (IC₅₀ = 2.25, 1.72, and 2.81 μM, respectively) compared with gefitinib, erlotinib, and sorafenib. In addition, the enzyme activity inhibition assay indicated that the synthesized compounds had sub-micromolar inhibitory levels (IC₅₀, 11.66–867.1 nM), which was consistent with the results of the tumor cell line growth inhibition tests. By comparing the binding mechanisms of Compound 7i (17.32 nM), gefitinib (25.42 nM), and erlotinib (33.25 nM) to the EGFR, it was found that Compound 7i could extend into the effective region with a similar action conformation to that of gefitinib and interact with residues L85, D86, and R127, increasing the binding affinity of Compound 7i to the EGFR. Based on the molecular hybridization strategy, 14 compounds with EGFR inhibitory activity were designed and synthesized, and the action mechanism was explored through computational approaches, providing valuable clues for the research of antitumor agents based on EGFR inhibitors.

  根据经典药效团融合策略，设计、合成并通过标准CCK-8方法和酶抑制活性评估了一系列6-芳基脲基-4-苯胺基喹唑啉衍生物（化合物7a–t）。在这些化合物中，化合物7a、7c、7d、7f、7i、7o、7p和7q展现出有希望的抗增殖生物活性，特别是化合物7i，对A549、HT-29和MCF-7细胞系表现出优秀的抗肿瘤活性（IC₅₀分别为2.25、1.72和2.81 μM），与吉非替尼、厄洛替尼和索拉非尼相比。此外，酶活性抑制实验显示，合成的化合物具有亚微摩尔水平的抑制活性（IC₅₀为11.66–867.1 nM），与肿瘤细胞系生长抑制实验结果一致。通过比较化合物7i（17.32 nM）、吉非替尼（25.42 nM）和厄洛替尼（33.25 nM）对EGFR的结合机制，发现化合物7i能够延伸到有效区域，与吉非替尼相似的作用构象相互作用于残基L85、D86和R127，增加化合物7i与EGFR的结合亲和力。基于分子杂交策略，设计并合成了14个具有EGFR抑制活性的化合物，并通过计算方法探索了作用机制，为基于EGFR抑制剂的抗肿瘤药物研究提供了宝贵线索。
• Design, Synthesis, and biological evaluation of HDAC6 inhibitors based on Cap modification strategy
  作者：Xuedong Li、Xingang Liu、Songsong Wang、Xiaoxing Shi、Ming Lu、Xinyue Hao、Yan Fu、Yang Zhang、Qingzhong Jia、Dian He

  DOI：10.1016/j.bioorg.2022.105874

  日期：2022.8

  The abnormal biological functions of HDAC6 were closely related to the occurrence and development of various tumors, making HDAC6 gradually become promising therapeutic target for cancer treatment and inspiring researchers to explore and develop selective HDAC inhibitors. In this study, based on the classical pharmacophore model of HDAC inhibitors, 20 compounds were designed and synthesized by modifying

  HDAC6的异常生物学功能与多种肿瘤的发生、发展密切相关，使得HDAC6逐渐成为癌症治疗的有希望的治疗靶点，并激励着研究人员探索和开发选择性HDAC抑制剂。本研究基于HDAC抑制剂的经典药效团模型，通过修饰Cap组设计合成了20个化合物，并通过抗增殖和酶抑制实验评估了目标化合物的生物学活性。标题化合物对选定的肿瘤细胞系表现出不同程度的抑制活性，尤其是化合物9m、9q和12c，在酶水平上进一步评估。酶抑制试验表明化合物12c具有广谱酶抑制活性，化合物9m和9q更倾向于抑制HDAC6，在代表性亚型中表现出一定的选择性抑制活性。此外，通过计算方法进一步探索了化合物9q和12c在HDAC1和6中的结合模式，以阐明选择性抑制活性的分子机制，为发现新型HDAC6抑制剂提供有价值的提示。
• Microwave-accelerated Dimroth rearrangement for the synthesis of 4-anilino-6-nitroquinazolines. Application to an efficient synthesis of a microtubule destabilizing agent
  作者：Alicia Foucourt、Carole Dubouilh-Benard、Elizabeth Chosson、Cécile Corbière、Catherine Buquet、Mauro Iannelli、Bertrand Leblond、Francis Marsais、Thierry Besson

  DOI：10.1016/j.tet.2010.04.066

  日期：2010.6

  A useful and rapid access to 4-anilino-6-nitroquinazolines was investigated in a multi-gram scale via microwave-accelerated condensation and Dimroth rearrangement of the starting anilines with imines obtained by reaction of anthranilonitriles with formamide dimethylacetal. A novel short and efficient route to AZiXa (TM) (EPi28495, MPC-6827), a microtubule destabilizing agent and apoptosis inducer, was performed with success demonstrating that well controlled parameters offer comfortable using of microwave technology with safe and environmental benefits. (C) 2010 Elsevier Ltd. All rights reserved.
• 4-Arylamino-6-nitroquinazolines: Synthesis and their activities against neglected disease leishmaniasis
  作者：Syed Muhammad Saad、Nida Ghouri、Shahnaz Perveen、Khalid Mohammed Khan、M. Iqbal Choudhary

  DOI：10.1016/j.ejmech.2015.11.016

  日期：2016.1

  4-Arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC50 values = 1.87-61.48 mu M. Among the twenty four synthetic derivatives, 4-[4'-(methylsulfanyl)phenyljamino-6-nitroquinazoline (21), and 4-(2'-methoxyphenyl)amino-6-nitroquinazoline (8) showed excellent antileishmanial activities with IC50 values 1.87 +/- 0.31 and 437 +/- 0.02 mu M, respectively, more active than the standard drug, pentamidine (IC50 = 5.09 +/- 0.09 mu M). Compound 16 (IC50 = 6.53 +/- 0.21 mu M) displayed an activity comparable to the standard. Compounds 15 (IC50 = 9.04 +/- 0.03 mu M), 18 (IC50 = 12.28 +/- 0.18 mu M),14 (IC50 = 19.87 +/- 0.22 mu M), and 5 (IC50 = 24.03 +/- 2.71 mu M) also showed good activities. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Search for new pharmacophores for antimalarial activity. Part II: Synthesis and antimalarial activity of new 6-ureido-4-anilinoquinazolines
  作者：S. Madapa、Z. Tusi、A. Mishra、K. Srivastava、S.K. Pandey、R. Tripathi、S.K. Puri、S. Batra

  DOI：10.1016/j.bmc.2008.11.005

  日期：2009.1

  Synthesis of new 6-ureido-4-anilinoquinazolines have been accomplished and their in vitro antimalarial activity against chloroquine-sensitive P. falciparum have been examined. Out of 64 compounds evaluated, the IC50 of 16 compounds which have displayed MIC of 0.25 μg/mL were also recorded. One of the compounds (24g) had IC50 value of 2.27 ng/mL which was equipotent to the standard drug chloroquine

  已经完成了新的6-脲基-4-苯胺基喹唑啉的合成，并且已经研究了它们对氯喹敏感的恶性疟原虫的体外抗疟活性。在评估的64种化合物中，还记录了MIC值为0.25μg/ mL的16种化合物的IC 50值。其中一种化合物（24g）的IC 50值为2.27 ng / mL，与生物测定中使用的标准药物氯喹等效。导致一个模拟的发现该系列中的几种化合物的体内评价（30克）显示40％的治疗活性（28天）对MDR P. yoeilli nigeriensis在100毫克/公斤×4天的口服剂量。