2,3,8,9-tetrahydro-1H,7H-pyrrolo[1,2-a]pyrrolo[1',2':1,2]imidazo[5,4-f]benzimidazole | 1237787-08-4

• 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: 2,3,8,9-tetrahydro-1H,7H-pyrrolo[1,2-a]pyrrolo[1',2':1,2]imidazo[5,4-f]benzimidazole
• 英文别名: 4,9,13,18-Tetrazapentacyclo[10.6.0.03,10.04,8.013,17]octadeca-1,3(10),8,11,17-pentaene
• CAS: 1237787-08-4
• 化学式: C₁₄H₁₄N₄
• 分子量: 238.292
• InChiKey: FHKCMXHLSSPTQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,3,8,9-tetrahydro-1H,7H-pyrrolo[1,2-a]pyrrolo[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85%的产率得到5-nitro-2,3,8,9-tetrahydro-1H,7H-pyrrolo[1,2-a]pyrrolo[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
• 作为产物：
  描述：

  3,7-Bis(3-phenylselanylpropyl)imidazo[4,5-f]benzimidazole 在 三正丁基氢锡 、 乙酸酐 、 1,1'-偶氮(氰基环己烷) 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以47%的产率得到2,3,8,9-tetrahydro-1H,7H-pyrrolo[1,2-a]pyrrolo[1',2':1,2]imidazo[5,4-f]benzimidazole
  参考文献：
  名称：

  One-pot double intramolecular homolytic aromatic substitution routes to dialicyclic ring fused imidazobenzimidazolequinones and preliminary analysis of anticancer activity

  摘要：

  介绍了 Bu3SnH/1,1′-偶氮双（环己烷腈）（ACN）介导的咪唑并[5,4-f]苯并咪唑和咪唑并[4,5-f]苯并咪唑的五元、六元和七元双烷基环化反应。所评估的醌衍生物对人类宫颈癌（HeLa）和前列腺癌（DU145）细胞系具有选择性毒性（对正常人细胞系 GM00637 的毒性可忽略不计）。只有 6-氨基咪唑并[5,4-f]苯并咪唑的 Fremy 氧化反应产生了亚氨基醌，它对前列腺癌细胞株（DU145）具有高度特异性。

  DOI：

  10.1039/c003511d

文献信息

• 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
  作者：Vincent Fagan、Sarah Bonham、Michael P. Carty、Patricia Saenz-Méndez、Leif A. Eriksson、Fawaz Aldabbagh

  DOI：10.1016/j.bmc.2012.03.063

  日期：2012.5

  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.
• One-pot double intramolecular homolytic aromatic substitution routes to dialicyclic ring fused imidazobenzimidazolequinones and preliminary analysis of anticancer activity
  作者：Vincent Fagan、Sarah Bonham、Michael P. Carty、Fawaz Aldabbagh

  DOI：10.1039/c003511d

  日期：——

  Bu3SnH/1,1′-azobis(cyclohexanecarbonitrile) (ACN)-mediated five, six, and seven-membered double alkyl radical cyclizations onto imidazo[5,4-f]benzimidazole and imidazo[4,5-f]benzimidazole are described. The quinone derivatives evaluated show selective toxicity towards human cervical (HeLa) and prostate (DU145) cancer cell lines (with negligible toxicity towards a normal human cell line, GM00637). Only the Fremy oxidation of the 6-aminoimidazo[5,4-f]benzimidazole gave iminoquinone, which showed high specificity towards the prostate cancer cell line (DU145).

  介绍了 Bu3SnH/1,1′-偶氮双（环己烷腈）（ACN）介导的咪唑并[5,4-f]苯并咪唑和咪唑并[4,5-f]苯并咪唑的五元、六元和七元双烷基环化反应。所评估的醌衍生物对人类宫颈癌（HeLa）和前列腺癌（DU145）细胞系具有选择性毒性（对正常人细胞系 GM00637 的毒性可忽略不计）。只有 6-氨基咪唑并[5,4-f]苯并咪唑的 Fremy 氧化反应产生了亚氨基醌，它对前列腺癌细胞株（DU145）具有高度特异性。