4-chloro-N-(3-imidazol-1-ylpropyl)phthalazin-1-amine | 1403830-79-4

• 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: 4-chloro-N-(3-imidazol-1-ylpropyl)phthalazin-1-amine
• CAS: 1403830-79-4
• 化学式: C₁₄H₁₄ClN₅
• 分子量: 287.752
• InChiKey: PEDMHJXYRFPUDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(3-氨基丙基)咪唑 、 1,4-二氯酞嗪 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 45.0h， 以48%的产率得到4-chloro-N-(3-imidazol-1-ylpropyl)phthalazin-1-amine
  参考文献：
  名称：

  Phthalazine Derivatives Containing Imidazole Rings Behave as Fe-SOD Inhibitors and Show Remarkable Anti-T. cruzi Activity in Immunodeficient-Mouse Mode of Infection

  摘要：

  A series of new phthalazine derivatives 1-4 containing imidazole rings were prepared. The monoalkylamino substituted. derivatives 2 and 4 were more active in vitro against T. cruzi and less toxic against Vero cells than both their disubstituted analogues and the reference drug benznidazole. Compounds 2 and 4 highly inhibited the antioxidant parasite enzyme Fe-SOD, and molecular modeling suggested that they interact with the H-bonding system of the iron atom moiety. In vivo tests on the acute phase of Chagas disease gave parasitemia inhibition values twice those of benznidazole, and a remarkable decrease in the reactivation of parasitemia was found in the chronic phase for immunodeficient mice. Glucose metabolism studies showed that compounds 1-4 did not affect the succinate pathway but originated important changes in the excretion of pyruvate metabolites. The morphological alterations found in epimastigotes treated with 1-4 confirmed extensive cytoplasm damage and a high mortality rate of parasites.

  DOI：

  10.1021/jm3011004

文献信息

• Phthalazine Derivatives Containing Imidazole Rings Behave as Fe-SOD Inhibitors and Show Remarkable Anti-<i>T. cruzi</i> Activity in Immunodeficient-Mouse Mode of Infection
  作者：Manuel Sánchez-Moreno、Fernando Gómez-Contreras、Pilar Navarro、Clotilde Marín、Francisco Olmo、María J. R. Yunta、Ana María Sanz、María José Rosales、Carmen Cano、Lucrecia Campayo

  DOI：10.1021/jm3011004

  日期：2012.11.26

  A series of new phthalazine derivatives 1-4 containing imidazole rings were prepared. The monoalkylamino substituted. derivatives 2 and 4 were more active in vitro against T. cruzi and less toxic against Vero cells than both their disubstituted analogues and the reference drug benznidazole. Compounds 2 and 4 highly inhibited the antioxidant parasite enzyme Fe-SOD, and molecular modeling suggested that they interact with the H-bonding system of the iron atom moiety. In vivo tests on the acute phase of Chagas disease gave parasitemia inhibition values twice those of benznidazole, and a remarkable decrease in the reactivation of parasitemia was found in the chronic phase for immunodeficient mice. Glucose metabolism studies showed that compounds 1-4 did not affect the succinate pathway but originated important changes in the excretion of pyruvate metabolites. The morphological alterations found in epimastigotes treated with 1-4 confirmed extensive cytoplasm damage and a high mortality rate of parasites.