6-nitro-N-(3,4,5-trimethoxyphenyl)quinazolin-4-amine | 1233868-72-8

• 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: 6-nitro-N-(3,4,5-trimethoxyphenyl)quinazolin-4-amine
• 英文别名: N-(3,4,5-trimethoxyphenyl)-6-nitroquinazolin-4-amine；6-Nitro-N-(3,4,5-trimethoxyphenyl)quinazolin-4-amine
• CAS: 1233868-72-8
• 化学式: C₁₇H₁₆N₄O₅
• 分子量: 356.338
• InChiKey: RFCHMWSNFCYKCW-UHFFFAOYSA-N

物化性质

• 熔点：
  258 °C
• 沸点：
  514.2±50.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-nitro-N-(3,4,5-trimethoxyphenyl)quinazolin-4-amine 在 铁粉 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 1-(4-(bis(2-chloroethyl)amino)phenyl)-3-(4-(3,4,5-trimethoxyphenylamino)quinazolin-6-yl)urea
  参考文献：
  名称：

  Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.01.055
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 6-nitro-N-(3,4,5-trimethoxyphenyl)quinazolin-4-amine
  参考文献：
  名称：

  新型喹唑啉衍生物作为抗脂多糖诱导的大鼠急性肺损伤的抗炎剂的设计，合成和生物学评估

  摘要：

  据报道，喹唑啉具有多种生物活性。这项研究的目的是发现新的喹唑啉衍生物通过抗炎作用对脂多糖诱导的急性肺损伤具有预防作用。合成了33种4-氨基喹唑啉衍生物，并筛选了脂多糖诱导的巨噬细胞的抗炎活性。最有效的四种化合物6h，6m，6p和6q对脂多糖诱导的TNF-α和IL-6释放具有剂量依赖性抑制作用。然后，进行了初步的结构-活性关系和定量的结构-活性关系分析。为了进一步确定喹唑啉类药物对急性肺损伤的治疗作用，采用了脂多糖诱导的急性肺损伤模型。在滴注脂多糖之前，先对雄性Sprague Dawley大鼠进行6m或6q预处理。结果表明，6m和6q，尤其是6q明显减轻了脂多糖引发的肺组织病理学变化，炎性细胞浸润和细胞因子mRNA表达。两者合计，这项工作表明，6m和6q通过抑制体内和体外的炎症反应来抑制脂多糖诱导的急性肺损伤，表明喹唑啉可能作为治疗急性肺损伤的潜在药物，值得继续进行药物开发和研究。

  DOI：

  10.1111/cbdd.12454

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Quinazoline Derivatives as Anti-inflammatory Agents against Lipopolysaccharide-induced Acute Lung Injury in Rats
  作者：Jie Hu、Yali Zhang、Lili Dong、Zhe Wang、Lingfeng Chen、Dandan Liang、Dengjian Shi、Xiaoou Shan、Guang Liang

  DOI：10.1111/cbdd.12454

  日期：2015.6

  inhibition against lipopolysaccharide‐induced TNF‐α and IL‐6 release. Then, the preliminary structure–activity relationship and quantitative structure–activity relationship analyses were conducted. To further determine the effects of quinazolines on acute lung injury treatment, lipopolysaccharide‐induced acute lung injury model was employed. Male Sprague Dawley rats were pretreated with 6m or 6q before instillation

  据报道，喹唑啉具有多种生物活性。这项研究的目的是发现新的喹唑啉衍生物通过抗炎作用对脂多糖诱导的急性肺损伤具有预防作用。合成了33种4-氨基喹唑啉衍生物，并筛选了脂多糖诱导的巨噬细胞的抗炎活性。最有效的四种化合物6h，6m，6p和6q对脂多糖诱导的TNF-α和IL-6释放具有剂量依赖性抑制作用。然后，进行了初步的结构-活性关系和定量的结构-活性关系分析。为了进一步确定喹唑啉类药物对急性肺损伤的治疗作用，采用了脂多糖诱导的急性肺损伤模型。在滴注脂多糖之前，先对雄性Sprague Dawley大鼠进行6m或6q预处理。结果表明，6m和6q，尤其是6q明显减轻了脂多糖引发的肺组织病理学变化，炎性细胞浸润和细胞因子mRNA表达。两者合计，这项工作表明，6m和6q通过抑制体内和体外的炎症反应来抑制脂多糖诱导的急性肺损伤，表明喹唑啉可能作为治疗急性肺损伤的潜在药物，值得继续进行药物开发和研究。
• 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.
• 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.
• Exploring MDR‐TB Inhibitory Potential of 4‐Aminoquinazolines as <i>Mycobacterium tuberculosis N</i> ‐Acetylglucosamine‐1‐Phosphate Uridyltransferase (GlmU ^MTB ) Inhibitors
  作者：Harun M. Patel、Mahesh Palkar、Rajshekhar Karpoormath

  DOI：10.1002/cbdv.202000237

  日期：2020.8

  Drug resistance tuberculosis is one of the challenging tasks that dictates the desperate need for the development of new anti-tubercular agents which operate via novel modes of action. Here, we are reporting the 4-amino quinazolines as M. tuberculosis N -acetylglucosamine-1-phosphate uridyltransferase (GlmU MTB) inhibitors to overcome the problem of the MDR-TB. Amongst the synthesized compounds HMP-05

  耐药结核病是一项具有挑战性的任务，迫切需要开发通过新型作用方式起作用的新型抗结核药物。在这里，我们报告了 4-氨基喹唑啉作为结核分枝杆菌 N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶 (GlmU MTB) 抑制剂，以克服 MDR-TB 的问题。在合成的化合物中，观察到 HMP-05 和 HMP-15 是该系列的有效化合物 [IC 50 = 6.4 µM (H37Rv)，MIC = 25 µM (MDR-TB) 和 IC 50 = 2.9 µM (H37Rv)， MIC = 6.25 µM (MDR-TB) 分别]。