3-(3-nitro-1H-1,2,4-triazol-1-yl)butan-1-amine | 325490-60-6

• 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: 3-(3-nitro-1H-1,2,4-triazol-1-yl)butan-1-amine
• 英文别名: 4-(3-Nitro-1,2,4-triazol-1-yl)butan-1-amine；4-(3-nitro-1,2,4-triazol-1-yl)butan-1-amine
• CAS: 325490-60-6
• 化学式: C₆H₁₁N₅O₂
• 分子量: 185.186
• InChiKey: ZBQJHLVMAVSCSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氯-2-苯基喹唑啉 、 3-(3-nitro-1H-1,2,4-triazol-1-yl)butan-1-amine 以 丙醇 为溶剂， 以69%的产率得到N-[4-(3-nitro-1H-1,2,4-triazol-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 3-Nitro-1<i>H</i>-1,2,4-triazole-Based Amides and Sulfonamides as Potential Antitrypanosomal Agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Eric Chatelain、Marcel Kaiser、Shane R. Wilkinson、Caroline McKenzie、Jean-Robert Ioset

  DOI：10.1021/jm300508n

  日期：2012.6.14

  A series of novel 3-nitro-1H-1,2,4-triazole-based (and in some cases 2-nitro-1H-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against Trypanosoma cruzi intracellular amastigotes (IC50 ranging

  一系列新型 3-硝基-1 H -1,2,4-三唑基（在某些情况下是 2-硝基-1 H-咪唑基）酰胺和磺胺类药物的体外抗锥虫和抗利什曼原虫活性被表征为以及哺乳动物毒性。在测试的 36 种化合物中，29 种（主要是 3-nitro-1 H -1,2,4-三唑）对克氏锥虫细胞内无鞭毛体（IC 50范围为 28 nM 至 3.72 μM）显示出显着的活性，而对 L6 宿主细胞没有伴随的毒性（选择性 66–2782）。在平行测试中，这些活性化合物中有 23 种比参考药物苯并硝唑更有效（高达 58 倍）。此外，九种具有中等活性的硝基三唑 (0.5 μM ≤ IC 50< 6.0 μM) 对抗布氏罗得西亚锥虫类鞭毛体的活性高 5-31 倍，对抗血流形式的布氏锥虫类鞭毛体，其被设计为过表达减少的烟酰胺腺嘌呤二核苷酸依赖性硝基还原酶。最后，三种硝基三唑对杜氏利什曼原虫的无菌形式显示出中等活性。因此，基于 3-nitro-1
• 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。
• 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.
• Novel 3-Nitro-1<i>H</i>-1,2,4-triazole-Based Aliphatic and Aromatic Amines as Anti-Chagasic Agents
  作者：Maria V. Papadopoulou、Bernadette Bourdin Trunz、William D. Bloomer、Caroline McKenzie、Shane R. Wilkinson、Chaiya Prasittichai、Reto Brun、Marcel Kaiser、Els Torreele

  DOI：10.1021/jm201215n

  日期：2011.12.8

  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.