1,4-dichloro-5-nitrophthalazine

• 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: 1,4-dichloro-5-nitrophthalazine
• 英文别名: 1,4-dichloro-5-nitrobenzo[g]phthalazine；1,4-Dichloro-5-nitrophthalazine
• 化学式: C₈H₃Cl₂N₃O₂
• 分子量: 244.037
• InChiKey: VENRRAUSOZDMED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  组胺 、 1,4-dichloro-5-nitrophthalazine 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以25%的产率得到1-[2-(1H-imidazol-4-yl)ethylamino]-4-chloro-5-nitrophthalazine
  参考文献：
  名称：

  Synthesis and evaluation of in vitro and in vivo trypanocidal properties of a new imidazole-containing nitrophthalazine derivative

  摘要：

  A series of new phthalazine derivatives (1-4) containing imidazole rings and functionalized with nitro groups in the benzene ring of the phthalazine moiety were prepared and identified on the basis of their MS, elemental analyses and bidimensional H-1 and C-13 NMR data, and their trypanocidal activity was tested. The 8-nitrosubstituted compound (3) was more active in vitro against Trypanosoma cruzi and less toxic against Vero cells than the reference drug benznidazole, and showed a SI value that was 47-fold better than the reference drug in amastigote forms. It also remarkably reduced the infectivity rate in Vero cells and decreased the reactivation of parasitemia in immunodeficient mice. Ultrastructural alterations found in epimastigotes treated with 3 confirmed extensive cytoplasm destruction in the parasites, whereas histopathological analysis of the hearts of mice infected and treated with 3 resulted in a decrease in cardiac damage. Biochemical markers showed that livers, hearts, and kidneys of treated mice were substantially unaffected by the administration of 3, despite the presence of the potentially toxic nitro group. It was also found that this compound selectively inhibited the antioxidant parasite enzyme Fe-superoxide dismutase (Fe-SOD) in comparison with human CuZn-SOD, and molecular modeling suggested interaction with the H-bonding system of the iron-based moiety as a feasible mechanism of action against the enzyme. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.034
• 作为产物：
  描述：

  3-硝基邻苯二甲酸酐 在 一水合肼 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 水 、 乙二醇 为溶剂， 反应 2.0h， 生成 1,4-dichloro-5-nitrophthalazine
  参考文献：
  名称：

  Synthesis and evaluation of in vitro and in vivo trypanocidal properties of a new imidazole-containing nitrophthalazine derivative

  摘要：

  A series of new phthalazine derivatives (1-4) containing imidazole rings and functionalized with nitro groups in the benzene ring of the phthalazine moiety were prepared and identified on the basis of their MS, elemental analyses and bidimensional H-1 and C-13 NMR data, and their trypanocidal activity was tested. The 8-nitrosubstituted compound (3) was more active in vitro against Trypanosoma cruzi and less toxic against Vero cells than the reference drug benznidazole, and showed a SI value that was 47-fold better than the reference drug in amastigote forms. It also remarkably reduced the infectivity rate in Vero cells and decreased the reactivation of parasitemia in immunodeficient mice. Ultrastructural alterations found in epimastigotes treated with 3 confirmed extensive cytoplasm destruction in the parasites, whereas histopathological analysis of the hearts of mice infected and treated with 3 resulted in a decrease in cardiac damage. Biochemical markers showed that livers, hearts, and kidneys of treated mice were substantially unaffected by the administration of 3, despite the presence of the potentially toxic nitro group. It was also found that this compound selectively inhibited the antioxidant parasite enzyme Fe-superoxide dismutase (Fe-SOD) in comparison with human CuZn-SOD, and molecular modeling suggested interaction with the H-bonding system of the iron-based moiety as a feasible mechanism of action against the enzyme. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.034

文献信息

• Synthesis and evaluation of in vitro and in vivo trypanocidal properties of a new imidazole-containing nitrophthalazine derivative
  作者：Francisco Olmo、Fernando Gómez-Contreras、Pilar Navarro、Clotilde Marín、María J.R. Yunta、Carmen Cano、Lucrecia Campayo、David Martín-Oliva、María José Rosales、Manuel Sánchez-Moreno

  DOI：10.1016/j.ejmech.2015.10.034

  日期：2015.12

  A series of new phthalazine derivatives (1-4) containing imidazole rings and functionalized with nitro groups in the benzene ring of the phthalazine moiety were prepared and identified on the basis of their MS, elemental analyses and bidimensional H-1 and C-13 NMR data, and their trypanocidal activity was tested. The 8-nitrosubstituted compound (3) was more active in vitro against Trypanosoma cruzi and less toxic against Vero cells than the reference drug benznidazole, and showed a SI value that was 47-fold better than the reference drug in amastigote forms. It also remarkably reduced the infectivity rate in Vero cells and decreased the reactivation of parasitemia in immunodeficient mice. Ultrastructural alterations found in epimastigotes treated with 3 confirmed extensive cytoplasm destruction in the parasites, whereas histopathological analysis of the hearts of mice infected and treated with 3 resulted in a decrease in cardiac damage. Biochemical markers showed that livers, hearts, and kidneys of treated mice were substantially unaffected by the administration of 3, despite the presence of the potentially toxic nitro group. It was also found that this compound selectively inhibited the antioxidant parasite enzyme Fe-superoxide dismutase (Fe-SOD) in comparison with human CuZn-SOD, and molecular modeling suggested interaction with the H-bonding system of the iron-based moiety as a feasible mechanism of action against the enzyme. (C) 2015 Elsevier Masson SAS. All rights reserved.