5-(3-hydroxy-5-nitro-1H-indazol-1-yl)-3-oxapentyl bromide | 1152708-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-(3-hydroxy-5-nitro-1H-indazol-1-yl)-3-oxapentyl bromide
• 英文别名: 1-[2-(2-bromoethoxy)ethyl]-5-nitro-2H-indazol-3-one
• CAS: 1152708-69-4
• 化学式: C₁₁H₁₂BrN₃O₄
• 分子量: 330.138
• InChiKey: YPOCVYLWTBSACB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  87.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(3-hydroxy-5-nitro-1H-indazol-1-yl)-3-oxapentyl bromide 在 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 50.0h， 生成 N-methyl-5-(3-methoxy-5-nitro-1H-indazol-1-yl)-3-oxapentylamine
  参考文献：
  名称：

  New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5-nitroindazoles

  摘要：

  The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1,4) and 3-alkoxy-1-(omega-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different morphological forms of Trypanosoma cruzi are reported. These compounds were prepared using simple alkylation reactions and, usually, taking advantage of the reactivity of some indazole-derived betaines previously studied by us. Most indazole derivatives showed in vitro activities similar or higher than those of the reference drug benznidazole; this fact, along with low unspecific cytotoxicities against Vero cells shown by some of them, led to very good selectivity indexes (SI). The high efficiency of 5-nitroindazoles 1 and 2 against T cruzi was confirmed by further in vitro studies on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. Complementary analyses of the changes in the metabolites excreted by the parasite and on the ultrastructural alterations induced after treatment with indazole derivatives 1 and 2 were also conducted. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.025
• 作为产物：
  描述：

  2-氯-5-硝基苯甲酰氯 在 氢溴酸 、 碳酸氢钠 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 29.0h， 生成 5-(3-hydroxy-5-nitro-1H-indazol-1-yl)-3-oxapentyl bromide
  参考文献：
  名称：

  New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5-nitroindazoles

  摘要：

  The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1,4) and 3-alkoxy-1-(omega-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different morphological forms of Trypanosoma cruzi are reported. These compounds were prepared using simple alkylation reactions and, usually, taking advantage of the reactivity of some indazole-derived betaines previously studied by us. Most indazole derivatives showed in vitro activities similar or higher than those of the reference drug benznidazole; this fact, along with low unspecific cytotoxicities against Vero cells shown by some of them, led to very good selectivity indexes (SI). The high efficiency of 5-nitroindazoles 1 and 2 against T cruzi was confirmed by further in vitro studies on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. Complementary analyses of the changes in the metabolites excreted by the parasite and on the ultrastructural alterations induced after treatment with indazole derivatives 1 and 2 were also conducted. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.025

文献信息

• Study of 5-nitroindazoles' anti-Trypanosoma cruzi mode of action: Electrochemical behaviour and ESR spectroscopic studies
  作者：Jorge Rodríguez、Alejandra Gerpe、Gabriela Aguirre、Ulrike Kemmerling、Oscar E. Piro、Vicente J. Arán、Juan Diego Maya、Claudio Olea-Azar、Mercedes González、Hugo Cerecetto

  DOI：10.1016/j.ejmech.2008.07.018

  日期：2009.4

  New indazole derivatives have been developed to know about structural requirements for adequate anti-Trypanosoma cruzi activity. In relation to position 1 of indazole ring, we have observed that a butylaminopentyl substituent (14) affords good activity, but N-oxidation of omega-tertiary amino moiety yields completely inactive compounds (17,18); the substituent at position 3 of indazole ring affects drastically the in vitro activity, 3-OH derivative 13 being completely inactive. On the other hand, since compound 22, denitro-analogue of active compound 4, does not show activity, the 5-nitro substituent of indazole ring seems to be essential. Intramolecular cyclization of side chain at position 1 also affords inactive compounds (19, 20). The electrochemical studies showed that the trypanocidal 5-nitroindazole derivatives yielded nitro-anion radical via one-electron process at physiological pH. This electrochemical behaviour occurs in the parasite according to ESR experiment with the T cruzi microsomal fraction showing that 5-nitroindazole derivatives suffer bio-reduction without reactive oxygen species generation. (C) 2008 Elsevier Masson SAS. All rights reserved.
• New perspectives on the synthesis and antichagasic activity of 3-alkoxy-1-alkyl-5-nitroindazoles
  作者：Beatriz Muro、Felipe Reviriego、Pilar Navarro、Clotilde Marín、Inmaculada Ramírez-Macías、María José Rosales、Manuel Sánchez-Moreno、Vicente J. Arán

  DOI：10.1016/j.ejmech.2013.12.025

  日期：2014.3

  The synthesis and antiprotozoal activity of some 3-alkoxy-1-alkyl- (1,4) and 3-alkoxy-1-(omega-aminoalkyl)-5-nitroindazoles (2, 3, 5-8) against different morphological forms of Trypanosoma cruzi are reported. These compounds were prepared using simple alkylation reactions and, usually, taking advantage of the reactivity of some indazole-derived betaines previously studied by us. Most indazole derivatives showed in vitro activities similar or higher than those of the reference drug benznidazole; this fact, along with low unspecific cytotoxicities against Vero cells shown by some of them, led to very good selectivity indexes (SI). The high efficiency of 5-nitroindazoles 1 and 2 against T cruzi was confirmed by further in vitro studies on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. Complementary analyses of the changes in the metabolites excreted by the parasite and on the ultrastructural alterations induced after treatment with indazole derivatives 1 and 2 were also conducted. (C) 2014 Elsevier Masson SAS. All rights reserved.