N-(4-nitrophenyl)-2-phenylquinazolin-4-amine | 1401688-30-9

• 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: N-(4-nitrophenyl)-2-phenylquinazolin-4-amine
• CAS: 1401688-30-9
• 化学式: C₂₀H₁₄N₄O₂
• 分子量: 342.357
• InChiKey: YIGNYKLWOLKRGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  N-(4-nitrophenyl)-2-phenylquinazolin-4-amine 在 铁粉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 calcium chloride 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.66h， 生成 5-chloro-N-(4-((2-phenylquinazolin-4-yl)amino)phenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modelling insights of 2-arylquinazoline benzamide derivatives as anti-tubercular agents

  摘要：

  DOI：

  10.1016/j.molstruc.2020.128493
• 作为产物：
  描述：

  2-苯基-4-[3H]喹唑啉酮 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 N-(4-nitrophenyl)-2-phenylquinazolin-4-amine
  参考文献：
  名称：

  发现新型喹唑啉衍生物作为强效抗肿瘤剂

  摘要：

  在这项工作中，我们设计并合成了一系列新型喹唑啉衍生物 6-19，然后分别评估了它们对 MGC-803、MCF-7、PC-9、A549 和 H1975 的广谱抗肿瘤活性。它们中的大多数对五种测试的细胞系表现出低微摩尔细胞毒性。特别是，化合物18对 MGC-803 细胞表现出纳摩尔水平的抑制活性，IC 50值为 0.85 μM，表明对 GES-1 的选择性约为 32 倍（IC 50 = 26.75 μM）。进一步的临床前评估表明，化合物18显着抑制 MGC-803 细胞的迁移，诱导 G2/M 细胞周期停滞，诱导 MGC-803 凋亡，导致 Bcl-2 和 Mcl-1 的表达降低，上调 Bax 的表达和裂解的 PARP。急性毒性试验未观察到小鼠死亡或明显的病理损伤。体内抗肿瘤评估表明，化合物18显着降低了平均肿瘤体积和肿瘤重量，对体重没有任何影响，优于5-Fu。因此，化合物18可作为未来进一步开发抗肿瘤药物的先导化合物。

  DOI：

  10.3390/molecules27123906

文献信息

• Synthesis and biological evaluation of quinazoline derivatives – A SAR study of novel inhibitors of ABCG2
  作者：Michael K. Krapf、Jennifer Gallus、Anna Spindler、Michael Wiese

  DOI：10.1016/j.ejmech.2018.10.026

  日期：2019.1

  One way to overcome MDR is to apply potent inhibitors of ABC transporters to restore the sensitivity of the cells toward cytostatic agents. This study focusses on the synthesis and evaluation of novel 2,4-disubstituted quinazoline derivatives regarding the structure-activity-relationship (SAR), their ability to reverse MDR and their mode of interaction with ABCG2. Hence, the inhibitory potency and

  多药耐药性（MDR）是有效进行癌症化学疗法治疗的主要障碍，常常导致治疗失败。MDR通常与ABC转运蛋白（如ABCB1或ABCG2）的过表达有关，这些蛋白以ATP水解为代价将有害物质排出细胞。克服MDR的一种方法是使用有效的ABC转运蛋白抑制剂来恢复细胞对细胞生长抑制剂的敏感性。这项研究的重点是合成和评估新型2，4-二取代喹唑啉衍生物的结构-活性-关系（SAR），其逆转MDR的能力以及与ABCG2相互作用的方式。因此，确定了对ABCG2的抑制效力和选择性。此外，研究了内在的细胞毒性和MDR的逆转。进行了与底物Hoechst 33342的相互作用类型研究以及ABCG2与5D3单克隆抗体的构象分析，以更好地了解其潜在机制。在我们的研究中，我们可以进一步增强对ABCG2的抑制作用（化合物31，IC 50：55纳米），并确定的结构特征是对于抑制效力至关重要的，在转运活性的影响，并结合蛋白。
• 4-Substituted-2-phenylquinazolines as inhibitors of BCRP
  作者：Kapil Juvale、Michael Wiese

  DOI：10.1016/j.bmcl.2012.08.024

  日期：2012.11

  We investigated several 2-phenylquinazolines with different substitutions at position 4 for their BCRP inhibition. Compounds with phenyl ring attached via an amine-containing linker at position 4 were found to be potent inhibitors of BCRP. In general compounds with meta substitution of phenyl ring at position 4 were found to have higher inhibitory effect, compound 12 being the most potent and selective towards BCRP. (C) 2012 Elsevier Ltd. All rights reserved.
• Investigation of quinazolines as inhibitors of breast cancer resistance protein (ABCG2)
  作者：Kapil Juvale、Jennifer Gallus、Michael Wiese

  DOI：10.1016/j.bmc.2013.10.007

  日期：2013.12

  Chemotherapy is one of the major forms of cancer treatment. Unfortunately, tumors are prone to multidrug resistance leading to failure of treatment. Breast cancer resistance protein (BCRP), the second member of ABC transporter subfamily G, has been found to play a major role in drug efflux and hence multidrug resistance. Until now, very few potent and selective BCRP inhibitors like Ko143 have been identified. In the search for more potent and selective BCRP inhibitors, we synthesized and investigated a series of differently substituted quinazoline compounds. Several variations at positions 2, 4, 6 and 7 of the quinazoline scaffold were carried out to develop a structure-activity-relationship analysis for these compounds. It was found that compounds bearing a phenyl substituent at position 2 of the 4-anilinoquinazoline scaffold were most potent. On the aniline ring at position 4 of the quinazoline moiety substituents like NO2, CN, CF3 led to very high BCRP inhibition potencies. The most potent compounds were further investigated for their intrinsic cytotoxicity and their ability to reverse the multidrug resistance. Compound 20, an anilinoquinazoline bearing a phenyl ring at position 2 and meta-nitro substitution on the 4-anilino ring, was found to have the highest therapeutic ratio. The most active compounds from each variation were also investigated for their effect on BCRP expression. It was found that compound 20 has no significant effect on BCRP expression, while compound 31 decreased the surface BCRP expression. The only difference in the two compounds was the presence of a 3,4-dimethoxyphenyl ring in compound 31 instead of phenyl substitution at position 2 of the quinazoline moiety. From the study of all target compounds, compound 20 was the most prominent compound having inhibitory potency even higher than Ko143, the most potent BCRP inhibitor known. Compound 20 was also found to be selective towards BCRP with a very high therapeutic ratio. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis, biological evaluation and molecular modelling insights of 2-arylquinazoline benzamide derivatives as anti-tubercular agents
  作者：Satyaveni Malasala、Md Naiyaz Ahmad、Jitendra Gour、Manjulika Shukla、Grace Kaul、Abdul Akhir、Srikanth Gatadi、Y.V. Madhavi、Sidharth Chopra、Srinivas Nanduri

  DOI：10.1016/j.molstruc.2020.128493

  日期：2020.10
• Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents
  作者：Zhenxi Niu、Shuli Ma、Lei Zhang、Qibing Liu、Shengnan Zhang

  DOI：10.3390/molecules27123906

  日期：——

  In this work, we designed and synthesized a novel series of quinazoline derivatives 6-19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC50

  在这项工作中，我们设计并合成了一系列新型喹唑啉衍生物 6-19，然后分别评估了它们对 MGC-803、MCF-7、PC-9、A549 和 H1975 的广谱抗肿瘤活性。它们中的大多数对五种测试的细胞系表现出低微摩尔细胞毒性。特别是，化合物18对 MGC-803 细胞表现出纳摩尔水平的抑制活性，IC 50值为 0.85 μM，表明对 GES-1 的选择性约为 32 倍（IC 50 = 26.75 μM）。进一步的临床前评估表明，化合物18显着抑制 MGC-803 细胞的迁移，诱导 G2/M 细胞周期停滞，诱导 MGC-803 凋亡，导致 Bcl-2 和 Mcl-1 的表达降低，上调 Bax 的表达和裂解的 PARP。急性毒性试验未观察到小鼠死亡或明显的病理损伤。体内抗肿瘤评估表明，化合物18显着降低了平均肿瘤体积和肿瘤重量，对体重没有任何影响，优于5-Fu。因此，化合物18可作为未来进一步开发抗肿瘤药物的先导化合物。