7-nitro-2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazole | 1378999-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 7-nitro-2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazole
• CAS: 1378999-99-5
• 化学式: C₁₈H₂₁N₅O₂
• 分子量: 339.397
• InChiKey: RXAHJXJAUIDDTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  25.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.78
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  7-nitro-2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazole 在 盐酸 、 potassium dihydrogenphosphate 、 potassium nitrososulfonate 、 5%-palladium/activated carbon 、 水 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、600.01 kPa 条件下， 反应 17.25h， 生成 2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazol-7,15-dione
  参考文献：
  名称：

  COMPARE analysis of the toxicity of an iminoquinone derivative of the imidazo[5,4-f]benzimidazoles with NAD(P)H:quinone oxidoreductase 1 (NQO1) activity and computational docking of quinones as NQO1 substrates

  摘要：

  Synthesis and cytotoxicity of imidazo[5,4-f]benzimidazolequinones and iminoquinone derivatives is described, enabling structure-activity relationships to be obtained. The most promising compound (an iminoquinone derivative) has undergone National Cancer Institute (NCI) 60 cell line (single and five dose) screening, and using the NCI COMPARE program, has shown correlation to NQO1 activity and to other NQO1 substrates. Common structural features suggest that the iminoquinone moiety is significant with regard to NQO1 specificity. Computational docking into the active site of NQO1 was performed, and the first comprehensive mitomycin C (MMC)-NQO1 docking study is presented. Small distances for hydride reduction and high binding affinities are characteristic of MMC and of iminoquinones showing correlations with NQO1 via COMPARE analysis. Docking also indicated that the presence of a substituent capable of hydrogen bonding to the His194 residue is important in influencing the orientation of the substrate in the NQO1 active site, leading to more efficient reduction. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.063
• 作为产物：
  描述：

  2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazole 在 硫酸 、 硝酸 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 3.0h， 以92%的产率得到7-nitro-2,3,4,5,10,11,12,13-octahydro-1H,9H-azepino[1,2-a]azepino[1',2':1,2]imidazo[5,4-f]benzimidazole
  参考文献：
  名称：

  COMPARE analysis of the toxicity of an iminoquinone derivative of the imidazo[5,4-f]benzimidazoles with NAD(P)H:quinone oxidoreductase 1 (NQO1) activity and computational docking of quinones as NQO1 substrates

  摘要：

  Synthesis and cytotoxicity of imidazo[5,4-f]benzimidazolequinones and iminoquinone derivatives is described, enabling structure-activity relationships to be obtained. The most promising compound (an iminoquinone derivative) has undergone National Cancer Institute (NCI) 60 cell line (single and five dose) screening, and using the NCI COMPARE program, has shown correlation to NQO1 activity and to other NQO1 substrates. Common structural features suggest that the iminoquinone moiety is significant with regard to NQO1 specificity. Computational docking into the active site of NQO1 was performed, and the first comprehensive mitomycin C (MMC)-NQO1 docking study is presented. Small distances for hydride reduction and high binding affinities are characteristic of MMC and of iminoquinones showing correlations with NQO1 via COMPARE analysis. Docking also indicated that the presence of a substituent capable of hydrogen bonding to the His194 residue is important in influencing the orientation of the substrate in the NQO1 active site, leading to more efficient reduction. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.063