6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate | 123567-26-0

• 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: 6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate
• 英文别名: 6-acetamido-3-hydroxy-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate；(6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-yl) acetate
• CAS: 123567-26-0
• 化学式: C₁₅H₁₆N₄O₅
• 分子量: 332.316
• InChiKey: QWSDMCYOYUSIHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 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-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.5h， 以77%的产率得到6-acetamido-5-amino-7-methyl-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate
  参考文献：
  名称：

  Synthesis and physical studies of azamitosene and iminoazamitosene reductive alkylating agents. Iminoquinone hydrolytic stability, syn/anti isomerization, and electrochemistry

  摘要：

  DOI：

  10.1021/jo00297a040
• 作为产物：
  描述：

  1-溴-5-甲基-2,4-二硝基苯 在 palladium on activated charcoal 硫酸 、 氢气 、 硝酸 、 zinc(II) chloride 作用下， 反应 10.75h， 生成 6-acetamido-7-methyl-5-nitro-2,3-dihydro-1H-pyrrolo<1,2-a>benzimidazole 3-acetate
  参考文献：
  名称：

  Synthesis and physical studies of azamitosene and iminoazamitosene reductive alkylating agents. Iminoquinone hydrolytic stability, syn/anti isomerization, and electrochemistry

  摘要：

  DOI：

  10.1021/jo00297a040

文献信息

• Structure-activity studies of antitumor agents based on pyrrolo[1,2-a]benzimidazoles: new reductive alkylating DNA cleaving agents
  作者：Imadul Islam、Edward B. Skibo、Robert T. Dorr、David S. Alberts

  DOI：10.1021/jm00114a003

  日期：1991.10

  Described herein are structure-activity studies of new antitumor agents based on the pyrrolo[1,2-a]benzimidazole (PBI) ring system. These compounds were designed as new DNA cross-linkers mimicking the mitomycin antitumor agents. Actually, the PBI derivatives were found to have anthracycline-like features: (i) shared cross resistance with doxorubicin in a human myeloma line, (ii) cardiotoxicity, and

  本文描述了基于吡咯并[1,2-a]苯并咪唑（PBI）环系统的新型抗肿瘤药的结构活性研究。这些化合物被设计为模仿丝裂霉素抗肿瘤剂的新的DNA交联剂。实际上，发现PBI衍生物具有类似蒽环类的特征：（i）在人骨髓瘤细胞系中与阿霉素共有交叉耐药性，（ii）心脏毒性，以及（iii）优异的DNA链切割能力。DNA链的断裂被认为是由于DNA的还原性烷基化，随后是活性氧自由基的产生。研究的最佳抗肿瘤药物是6-N-叠氮基-3-羟基-7-甲基-2,3-二氢-1H-吡咯并-[1,2-a]苯并咪唑-5,8-二酮3-乙酸盐（PBI- A），其具有针对各种人类卵巢癌和结肠癌细胞系的纳摩尔IC50值。
• 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.
• ISLAM, IMADUL;SKIBO, EDWARD B., J. ORG. CHEM., 55,(1990) N0, C. 3195-3295
  作者：ISLAM, IMADUL、SKIBO, EDWARD B.

  DOI：——

  日期：——