7-fluoro-2-hydroxy-8-methylphenazine 5,10-dioxide | 1254359-60-8

• 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: 7-fluoro-2-hydroxy-8-methylphenazine 5,10-dioxide
• 英文别名: 7-Fluoro-8-methyl-5,10-dioxidophenazine-5,10-diium-2-ol；7-fluoro-8-methyl-5,10-dioxidophenazine-5,10-diium-2-ol
• CAS: 1254359-60-8
• 化学式: C₁₃H₉FN₂O₃
• 分子量: 260.224
• InChiKey: VQSPSEXAYZLBNK-UHFFFAOYSA-N

物化性质

• 沸点：
  530.9±60.0 °C(predicted)
• 密度：
  1.51±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-fluoro-6-methylbenzo[c][1,2,5]oxadiazole 1-oxide 、 对苯二酚 在 甲醇 、 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 7-fluoro-2-hydroxy-8-methylphenazine 5,10-dioxide 、 8-fluoro-2-hydroxy-7-methylphenazine 5,10-dioxide
  参考文献：
  名称：

  Structural modifications on the phenazine N,N′-dioxide-scaffold looking for new selective hypoxic cytotoxins

  摘要：

  We have identified phenazine 5,10-dioxides as prodrugs for antitumour therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here, we investigated some structural modifications in order to find new selective hypoxic cytotoxins and to establish the structural requirements for adequate activity. Three different chemical-series were prepared and the clonogenic survival of V79 cells on aerobic and anaerobic conditions was determined. Electrochemical- and DNA-interaction studies were done for the most relevant derivatives. The new fluoro-derivative 7-fluoro-2-aminophenazine 5,10-dioxide displayed selective toxicity towards hypoxic V79 cells having adequate hypoxic cytotoxicity ratio (HCR = 6.8) and being the most potent hypoxic cytotoxins (P = 2.5 mu M) described for this family of bioreductive agents. The reduction potential of the N-oxide moiety in this new fluoro-derivative was in the range for adequate bioreduction property. According to the fluorescence studies, the DNA-interaction mechanism was especially operative in the phenazine drugs more than in the corresponding prodrugs, phenazine dioxides. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.08.061

文献信息

• Structural modifications on the phenazine N,N′-dioxide-scaffold looking for new selective hypoxic cytotoxins
  作者：María Laura Lavaggi、Marcos Nieves、Mauricio Cabrera、Claudio Olea-Azar、Adela López de Ceráin、Antonio Monge、Hugo Cerecetto、Mercedes González

  DOI：10.1016/j.ejmech.2010.08.061

  日期：2010.11

  We have identified phenazine 5,10-dioxides as prodrugs for antitumour therapy that undergo hypoxic-selective bioreduction to form cytotoxic species. Here, we investigated some structural modifications in order to find new selective hypoxic cytotoxins and to establish the structural requirements for adequate activity. Three different chemical-series were prepared and the clonogenic survival of V79 cells on aerobic and anaerobic conditions was determined. Electrochemical- and DNA-interaction studies were done for the most relevant derivatives. The new fluoro-derivative 7-fluoro-2-aminophenazine 5,10-dioxide displayed selective toxicity towards hypoxic V79 cells having adequate hypoxic cytotoxicity ratio (HCR = 6.8) and being the most potent hypoxic cytotoxins (P = 2.5 mu M) described for this family of bioreductive agents. The reduction potential of the N-oxide moiety in this new fluoro-derivative was in the range for adequate bioreduction property. According to the fluorescence studies, the DNA-interaction mechanism was especially operative in the phenazine drugs more than in the corresponding prodrugs, phenazine dioxides. (C) 2010 Elsevier Masson SAS. All rights reserved.