6-acetamido-3-hydroxy-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-benzoate | 136579-13-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-acetamido-3-hydroxy-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-benzoate
• 英文别名: (6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl) benzoate
• CAS: 136579-13-0
• 化学式: C₂₀H₁₈N₄O₅
• 分子量: 394.387
• InChiKey: OJJFLMLDSSASQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-acetamido-3-hydroxy-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-benzoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以94%的产率得到Benzoic acid 6-acetylamino-5-amino-7-methyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl ester
  参考文献：
  名称：

  Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity

  摘要：

  The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-a]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-a]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC(50) mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the S-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC(50) VS log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.

  DOI：

  10.1021/jm00001a016
• 作为产物：
  描述：

  6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate 在 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 10.33h， 生成 6-acetamido-3-hydroxy-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-benzoate
  参考文献：
  名称：

  Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity

  摘要：

  The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-a]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-a]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC(50) mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the S-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC(50) VS log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.

  DOI：

  10.1021/jm00001a016

文献信息

• Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity
  作者：William G. Schulz、Imadul Islam、Edward B. Skibo

  DOI：10.1021/jm00001a016

  日期：1995.1

  The influence of the 3-substituent on the cytotoxicity of the 6-aziridinylpyrrolo[1,2-a]benzimidazole quinones (PBIs), the 6-acetamidopyrrolo[1,2-a]benzimidazole quinones (APBIs), and the 6-acetamidopyrrolo[1,2-a]benzimidazole iminoquinones (imino-APBIs) was investigated by comparing LC(50) mean graphs consisting of 60 cancer lines. Increasing lipophilicity of the 3-substituent of PBIs and APBIs increased the cytotoxicity specifically in melanoma cell lines. The 3-substituent does not influence DNA cleavage by reduced PBIs, except for the S-carbamate derivative which shows enhanced cleavage. This property of the 3-carbamate is rationalized in terms of the PBI major groove binding model. The imino-APBIs show enhanced cytotoxicity in melanoma and renal cancer cell lines; the correlation coefficient for log LC(50) VS log lipophilicity is 0.8 to 0.9. COMPARE correlations revealed that the PBIs are activated by DT-diaphorase but that the APBIs and imino-APBIs are inactivated by this enzyme. Thus the latter two agents are cytotoxic only as quinones. It was noted that APBIs possess a similar cytotoxic profile to three anthracycline analogues. This observation suggests mechanistic similarities between both types of cytotoxic agents. Major conclusions of this study pertain to the design of agents displaying cytotoxicity specifically against melanoma and renal cancers and to the use of 60-cell line mean graphs and COMPARE in cancer drug QSAR.