4-(2-Nitroimidazol-1-yl)butan-1-amine | 325490-82-2

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 4-(2-Nitroimidazol-1-yl)butan-1-amine
• CAS: 325490-82-2
• 化学式: C₇H₁₂N₄O₂
• 分子量: 184.198
• InChiKey: JGOLPQTVRZLMAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  89.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-2-苯基喹唑啉 、 4-(2-Nitroimidazol-1-yl)butan-1-amine 以 丙醇 为溶剂， 以51%的产率得到N-[4-(2-nitro-1H-imidazol-1-yl)butyl]-2-phenylquinazolin-4-amine hydrochloride
  参考文献：
  名称：

  Novel 3-Nitro-1H-1,2,4-triazole-Based Aliphatic and Aromatic Amines as Anti-Chagasic Agents

  摘要：

  A series of novel 2-nitro-1H-imidazole- and 3-nitro-1H-1,2,4-triazole-based aromatic and aliphatic amines were screened for antitrypanosomal activity and mammalian cytotoxicity by the Drugs for Neglected Diseases initiative (DNDi). Out of 42 compounds tested, 18 3-nitro-1,2,4-triazoles and one 2-nitroimidazole displayed significant growth inhibitory properties against T. cruzi amastigotes (IC50 ranging from 40 nM to 1.97 mu M), without concomitant toxicity toward the host cells (L6 cells), having selectivity indices (SI) 44-1320. Most (16) of these active compounds were up to 33.8-fold more potent than the reference drug benznidazole, tested in parallel. Five novel 3-nitro-1,2,4-triazoles were active against bloodstream-form (BSF) T. b. rhodesiense trypomastigotes (IC50 at nM levels and SI 220-993). An NADH-dependent nitroreductase (TbNTR) plays a role in the antiparasitic activity because BSF T. b. brucei trypomastigotes with elevated TbNTR levels were hypersensitive to tested compounds. Therefore, a novel class of affordable 3-nitro-1,2,4-triazole-based compounds with antitrypanosomal activity has been identified.

  DOI：

  10.1021/jm201215n

文献信息

• Novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Shane R. Wilkinson、Marcel Kaiser

  DOI：10.1016/j.ejmech.2014.09.045

  日期：2014.11

  and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides (including 3-nitrotriazole-, 2- and 4-nitroimidazole-based compounds) as potential antitrypanosomal agents. All nitrotriazoles displayed significant growth inhibitory properties against T. cruzi with the most potent generating IC50 values of <1 μM and up to >1400-fold selectivity toward the

  先前我们已经表明，基于3-nitro-1 H -1,2,4-三唑的芳基酰胺和芳基磺酰胺类药物在体外对锥虫锥虫（查加斯病的致病性寄生虫）表现出显着的活性。更重要的是，几种这样的类似物在体内显示出显着的抗chagasic活性，优于当前的临床标准苯并硝唑。我们现在报告合成和体外评估一小系列的新型基于硝基（三唑/咪唑）的杂芳基酰胺/磺酰胺（包括基于3-硝基三唑，2-和4-硝基咪唑的化合物）作为潜在的抗锥虫剂。所有硝基三唑均显示出对克氏锥虫的显着生长抑制特性具有最强的生成IC 50值，<1μM，对寄生虫的选择性最高> 1400倍。基于2-硝基咪唑的衍生物对克鲁维酵母具有中等活性，并显示出<50的选择性，而4-硝基咪唑则大多没有活性。几种基于3-硝基三唑的类似物显示出对罗氏锥虫的活性，但是没有一种测试化合物显示出对利什曼原虫的活性。从此处提供的详细SAR信息中，我们确定了基于3-硝基三唑的氯化噻吩/苯
• The antitrypanosomal and antitubercular activity of some nitro(triazole/imidazole)-based aromatic amines
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Marcel Kaiser

  DOI：10.1016/j.ejmech.2017.07.060

  日期：2017.9

  were active against hypoxic Mtb with MIC values 2.89–9.18 μM. The present data support our previous observations that 2-nitroimidazole-based aromatic amines are selectively active against nonreplicating Mtb, while 3-nitrotriazole-based aromatic amines are potent antichagasic agents.

  合成了数量有限的新颖的3-硝基三唑和2-硝基咪唑连接的喹啉和喹唑啉，并筛选了其在体外抗胰锥虫和抗结核的活性以及在正常细胞中的细胞毒性。所有化合物均对克鲁斯氏锥虫具有活性，而除一种化合物外，其余所有化合物均对克氏杆菌具有活性或中度活性。罗得岛。但是，只有两种氯喹啉对克氏锥虫表现出令人满意的选择性指数（SI），并且只有其中一个对T.b表现出令人满意的SI 。罗得岛。所有测试的化合物对有氧Mtb的最低抑菌浓度（MIC）≥200μM。但是，基于2-硝基咪唑的类似物对缺氧的Mtb具有活性，MIC值为2.89–9.18μM。本数据支持我们以前的观察结果，即基于2-硝基咪唑的芳香胺对非复制型Mtb具有选择性活性，而基于3-硝基三唑的芳香胺则是有效的抗chachagasic剂。
• Method of Treating Latent Tuberculosis
  申请人：Papadopoulou V. Maria

  公开号：US20080076797A1

  公开（公告）日：2008-03-27

  2-Nitroimidazolyl-alkylaminoquinolines, and compositions containing the same, useful in the treatment of tuberculosis are disclosed. Methods of treating tuberculosis using the 2-nitroimidazolyl-alkylaminoquinolines, and compositions containing the same, also are disclosed.

  本发明揭示了2-硝基咪唑基-烷基氨基喹啉及其含量，对于治疗结核病有用。本发明还揭示了使用2-硝基咪唑基-烷基氨基喹啉及其含量治疗结核病的方法。
• Design, synthesis and biological evaluation of novel tumor hypoxia-activated EGFR tyrosine kinase inhibitors
  作者：Tingting Jia、Ruoyang Miao、Jiaohua Lin、Chong Zhang、Linghui Zeng、Jiankang Zhang、Jiaan Shao、Zongfu Pan、Haiping Wang、Huajian Zhu、Weiyan Cheng

  DOI：10.1016/j.bioorg.2022.106138

  日期：2022.12

  Hypoxia is widespread in solid tumors, such as NSCLC, and has become a very attractive target. On the basis of AZD9291 scaffold, novel hypoxia-targeted EGFR inhibitors without the acrylamide warhead but containing hypoxic reductive activation groups were described. Among them, compound JT21 exhibited impressive inhibitory activity (IC50 = 23 nM) against EGFRL858R/T790M and displayed about 21-fold inhibitory

  缺氧在非小细胞肺癌等实体瘤中普遍存在，并已成为一个非常有吸引力的靶点。在AZD9291支架的基础上，描述了无丙烯酰胺弹头但含有缺氧还原活化基团的新型缺氧靶向EGFR抑制剂。其中，化合物JT21对 EGFR L858R/T790M表现出令人印象深刻的抑制活性（IC 50  = 23 nM），对 EGFR wt的抑制活性降低约 21 倍。在缺氧条件下，JT21对 H1975 细胞 (IC 50  = 7.39 ± 2.20 nM) 和 HCC827 细胞 (IC 50 = 5.88 ± 0.85 nM) 比 AZD9291，比常氧活性高约 5 倍。同时，JT21对A549和BEAS-2B细胞的抑制作用较弱，提示JT21可能是一种选择性低毒EGFR突变抑制剂。此外，JT21可在缺氧条件下诱导 H1975 细胞凋亡，并显示出良好的生物还原特性。
• Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Marcel Kaiser、Eric Chatelain、Jean-Robert Ioset

  DOI：10.1016/j.bmc.2013.08.022

  日期：2013.11

  We have previously shown that 3-nitro-1H-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against Trypanosoma cruzi, the causative parasite of Chagas disease. In the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional SARs. All nitrotriazole-based derivatives were active or moderately active against T. cruzi; however two of them did not fulfill the selectivity criteria. Five derivatives were active or moderately active against Trypanosoma brucei rhodesiense while one derivative was moderately active against Leishmania donovani. Active compounds against T. cruzi demonstrated selectivity indexes (toxicity to host cells/toxicity to T. cruzi amastigotes) from 117 to 1725 and 12 of 13 compounds were up to 39-fold more potent than the reference compound benznidazole. Detailed SARs are discussed. (C) 2013 Elsevier Ltd. All rights reserved.