2-(3-nitro-1H-1,2,4-triazol-1-yl)-N-(4-phenylpyrimidin-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(3-nitro-1H-1,2,4-triazol-1-yl)-N-(4-phenylpyrimidin-2-yl)acetamide
• 英文别名: 2-(3-nitro-1,2,4-triazol-1-yl)-N-(4-phenylpyrimidin-2-yl)acetamide
• 化学式: C₁₄H₁₁N₇O₃
• 分子量: 325.286
• InChiKey: AAONOLDNLGQRIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-苯基嘧啶-2-胺 在 三乙胺 、 potassium hydroxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 9.5h， 生成 2-(3-nitro-1H-1,2,4-triazol-1-yl)-N-(4-phenylpyrimidin-2-yl)acetamide
  参考文献：
  名称：

  Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation

  摘要：

  3-Nitro-1H-1,2,4-triazole-and 2-nitro-1H-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. All 3-nitrotriazole-based derivatives were extremely potent anti-Trypanosoma cruzi agents at sub nM concentrations and exhibited a high degree of selectivity for the parasite. The 2-nitroimidazole analogs were only moderately active against T. cruzi amastigotes and exhibited low selectivity. Both types of compound were active against Leishmania donovani axenic amastigotes with excellent selectivity for the parasite, whereas three 2-nitroimidazole-based analogs were also moderately active against infected macrophages. However, no compound demonstrated selective activity against Trypanosoma brucei rhodesiense. The most potent in vitro anti-T. cruzi compounds were tested in an acute murine model and reduced the parasites to an undetectable level after five days of treatment at 13 mg/kg/day. Such compounds are potential inhibitors of T. cruzi CYP51 and, being excellent substrates for the type I nitroreductase (NTR) which is specific to trypanosomatids, work as prodrugs and constitute a new generation of effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.014

文献信息

• Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Ivan P. O’Shea、Shane R. Wilkinson、Marcel Kaiser、Eric Chatelain、Jean-Robert Ioset

  DOI：10.1016/j.bmc.2015.08.014

  日期：2015.10

  3-Nitro-1H-1,2,4-triazole-and 2-nitro-1H-imidazole-based amides with an aryloxy-phenyl core were synthesized and evaluated as antitrypanosomal agents. All 3-nitrotriazole-based derivatives were extremely potent anti-Trypanosoma cruzi agents at sub nM concentrations and exhibited a high degree of selectivity for the parasite. The 2-nitroimidazole analogs were only moderately active against T. cruzi amastigotes and exhibited low selectivity. Both types of compound were active against Leishmania donovani axenic amastigotes with excellent selectivity for the parasite, whereas three 2-nitroimidazole-based analogs were also moderately active against infected macrophages. However, no compound demonstrated selective activity against Trypanosoma brucei rhodesiense. The most potent in vitro anti-T. cruzi compounds were tested in an acute murine model and reduced the parasites to an undetectable level after five days of treatment at 13 mg/kg/day. Such compounds are potential inhibitors of T. cruzi CYP51 and, being excellent substrates for the type I nitroreductase (NTR) which is specific to trypanosomatids, work as prodrugs and constitute a new generation of effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Ltd. All rights reserved.