2-(2-nitro-1H-imidazol-1-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(2-nitro-1H-imidazol-1-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone
• 英文别名: 2-(2-Nitroimidazol-1-yl)-1-(4-pyrimidin-2-ylpiperazin-1-yl)ethanone；2-(2-nitroimidazol-1-yl)-1-(4-pyrimidin-2-ylpiperazin-1-yl)ethanone
• 化学式: C₁₃H₁₅N₇O₃
• 分子量: 317.307
• InChiKey: SVRRSHIMBSPADA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 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-(2-nitro-1H-imidazol-1-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  3-Nitrotriazole-based piperazides as potent antitrypanosomal agents

  摘要：

  Novel linear 3-nitro-1H-1,2,4-triazole-based piperazides were synthesized and evaluated as anti-trypanosomal agents. In addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. Most 3-nitrotriazole-based derivatives were potent and selective against Trypanosoma cruzi parasites, but only one displayed these desired properties against Trypanosoma brucei rhodesiense. Moreover, two 3-nitrotriazole-based chlorophenylpiperazides were moderately and selectively active against Leishmania donovani. Although the bisarylpiperazineethanones were active or moderately active against I cruzi, none of them demonstrated an acceptable selectivity. In general, 3-nitrotriazole-based piperazides were less toxic to host L6 cells than the previously evaluated 3-nitrotriazole-based piperazines and seven of 13 were 1.54- to 31.2-fold more potent antichagasic agents than the reference drug benznidazole. Selected compounds showed good ADMET characteristics. One potent in vitro antichagasic compound (3) was tested in an acute murine model and demonstrated antichagasic activity after a 10-day treatment of 15 mg/kg/day. However, neither compound 3 nor benznidazole showed a statistically significant P value compared to control due to high variability in parasite burden among the untreated animals. Working as prodrugs, 3-nitrotriazole-based piperazides were excellent substrates of trypanosomal type I nitroreductases and constitute a novel class of potentially effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.042

文献信息

• 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Ivan P. O'Shea、Shane R. Wilkinson、Marcel Kaiser

  DOI：10.1016/j.ejmech.2015.08.042

  日期：2015.10

  Novel linear 3-nitro-1H-1,2,4-triazole-based piperazides were synthesized and evaluated as anti-trypanosomal agents. In addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. Most 3-nitrotriazole-based derivatives were potent and selective against Trypanosoma cruzi parasites, but only one displayed these desired properties against Trypanosoma brucei rhodesiense. Moreover, two 3-nitrotriazole-based chlorophenylpiperazides were moderately and selectively active against Leishmania donovani. Although the bisarylpiperazineethanones were active or moderately active against I cruzi, none of them demonstrated an acceptable selectivity. In general, 3-nitrotriazole-based piperazides were less toxic to host L6 cells than the previously evaluated 3-nitrotriazole-based piperazines and seven of 13 were 1.54- to 31.2-fold more potent antichagasic agents than the reference drug benznidazole. Selected compounds showed good ADMET characteristics. One potent in vitro antichagasic compound (3) was tested in an acute murine model and demonstrated antichagasic activity after a 10-day treatment of 15 mg/kg/day. However, neither compound 3 nor benznidazole showed a statistically significant P value compared to control due to high variability in parasite burden among the untreated animals. Working as prodrugs, 3-nitrotriazole-based piperazides were excellent substrates of trypanosomal type I nitroreductases and constitute a novel class of potentially effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Masson SAS. All rights reserved.