N-(3-methoxyphenyl)-6-nitroquinazolin-4-amine | 691385-34-9

• 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-(3-methoxyphenyl)-6-nitroquinazolin-4-amine
• 英文别名: 4-(3'-methoxyphenyl)amino-6-nitroquinazoline
• CAS: 691385-34-9
• 化学式: C₁₅H₁₂N₄O₃
• 分子量: 296.285
• InChiKey: GPUJVVFHMLJEGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 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：
  92.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-methoxyphenyl)-6-nitroquinazolin-4-amine 在 三乙酰氧基硼氢化钠 、 铁粉 、 氯化铵 、 三氟乙酸 作用下， 以 醋酸异丙酯 、 水 、 异丙醇 为溶剂， 反应 2.0h， 生成 N⁶-(3-methoxybenzyl)-N⁴-(3-methoxyphenyl)quinazoline-4,6-diamine
  参考文献：
  名称：

  鉴定 4-苯胺基-6-氨基喹唑啉衍生物作为潜在的 MERS-CoV 抑制剂。

  摘要：

  迫切需要治疗冠状病毒的新疗法。合成并评估了一系列 4-苯胺基-6-氨基喹唑啉衍生物，显示出高抗 MERS-CoV 活性。N 4 -(3-氯-4-氟苯基)- N 6 -(3-甲氧基苄基)喹唑啉-4,6-二胺 ( 1 ) 已在随机筛选中被鉴定为抑制 MERS-CoV 感染的热门化合物。在整个优化过程中，发现化合物20表现出高抑制作用（IC 50 = 0.157 μM，SI = 25），无细胞毒性，体内PK 特性适中。

  DOI：

  10.1016/j.bmcl.2020.127472
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 溶剂黄146 作用下， 反应 2.0h， 生成 N-(3-methoxyphenyl)-6-nitroquinazolin-4-amine
  参考文献：
  名称：

  Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors

  摘要：

  一系列4,6-取代的(二苯胺基)喹唑啉作为c-Src抑制剂已被制备，并且它们的生物活性也得到了评估。所有化合物都显示出潜在的抗增殖活性，在五种人肿瘤细胞系中的IC50值范围从3.42 μM到118.81 μM。特别是化合物15对测试的五种肿瘤细胞系表现出比其他小分子更高的细胞毒性。通常，根据它们相应的IC50值，这些化合物中的大多数在A549细胞和其他四种细胞之间显示出选择性。从体外酶 assay 获得的结果表明，化合物15对c-Src激酶具有显著的抑制活性，IC50值为27.3 nM，可与对照化合物相媲美。此外，通过DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd)进行的分子对接和QSAR研究探索了这些衍生物的结合模式和结构与活性关系(SAR)。

  DOI：

  10.1039/c3ob41161c

文献信息

• Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors
  作者：Jing-Ran Li、Dong-Dong Li、Fei Fang、Qian-Ru Du、Lin Lin、Jian Sun、Yong Qian、Hai-Liang Zhu

  DOI：10.1039/c3ob41161c

  日期：——

  A series of 4,6-substituted-(diaphenylamino)quinazolines as c-Src inhibitors have been prepared and their biological activity has also been evaluated. All the compounds displayed potential antiproliferation activities, with IC50 values ranging from 3.42 μM to 118.81 μM in five human tumor cell lines. Particularly, compound 15 exhibited higher cytotoxicity against the tested five tumor cell lines compared to the other small molecules. Generally, most of these compounds showed selectivity between the A549 cells and the other four cells, according to their corresponding IC50 values. The results obtained from the in vitro enzyme assay indicated compound 15 has remarkable inhibitory activity against c-Src kinase with an IC50 value of 27.3 nM, which is comparable to the control compounds. Furthermore, molecular docking and QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.

  一系列4,6-取代的(二苯胺基)喹唑啉作为c-Src抑制剂已被制备，并且它们的生物活性也得到了评估。所有化合物都显示出潜在的抗增殖活性，在五种人肿瘤细胞系中的IC50值范围从3.42 μM到118.81 μM。特别是化合物15对测试的五种肿瘤细胞系表现出比其他小分子更高的细胞毒性。通常，根据它们相应的IC50值，这些化合物中的大多数在A549细胞和其他四种细胞之间显示出选择性。从体外酶 assay 获得的结果表明，化合物15对c-Src激酶具有显著的抑制活性，IC50值为27.3 nM，可与对照化合物相媲美。此外，通过DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd)进行的分子对接和QSAR研究探索了这些衍生物的结合模式和结构与活性关系(SAR)。
• 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。
• Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates
  作者：Bhavin Marvania、Pei-Chih Lee、Ravi Chaniyara、Huajin Dong、Sharda Suman、Rajesh Kakadiya、Ting-Chao Chou、Te-Chang Lee、Anamik Shah、Tsann-Long Su

  DOI：10.1016/j.bmc.2011.01.055

  日期：2011.3

  A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase. (C) 2011 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.
• Identification of 4-anilino-6-aminoquinazoline derivatives as potential MERS-CoV inhibitors
  作者：Jun Young Lee、Young Sup Shin、Jihye Lee、Sunoh Kwon、Young-hee Jin、Min Seong Jang、Seungtaek Kim、Jong Hwan Song、Hyoung Rae Kim、Chul Min Park

  DOI：10.1016/j.bmcl.2020.127472

  日期：2020.10

  New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N4-(3-Chloro-4-fluorophenyl)-N6-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. Throughout optimization process, compound 20 was

  迫切需要治疗冠状病毒的新疗法。合成并评估了一系列 4-苯胺基-6-氨基喹唑啉衍生物，显示出高抗 MERS-CoV 活性。N 4 -(3-氯-4-氟苯基)- N 6 -(3-甲氧基苄基)喹唑啉-4,6-二胺 ( 1 ) 已在随机筛选中被鉴定为抑制 MERS-CoV 感染的热门化合物。在整个优化过程中，发现化合物20表现出高抑制作用（IC 50 = 0.157 μM，SI = 25），无细胞毒性，体内PK 特性适中。