((S)-6-Bromo-7-methyl-5-nitro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl)-carbamic acid phenyl ester | 244152-38-3

• 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: ((S)-6-Bromo-7-methyl-5-nitro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl)-carbamic acid phenyl ester
• CAS: 244152-38-3
• 化学式: C₁₈H₁₅BrN₄O₄
• 分子量: 431.245
• InChiKey: JFRDGSAXWFWCOA-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  99.29
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ((S)-6-Bromo-7-methyl-5-nitro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl)-carbamic acid phenyl ester 在 palladium on activated charcoal 氨 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， -70.0~20.0 ℃ 、344.74 kPa 条件下， 反应 18.5h， 生成 ((S)-5-Amino-7-methyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl)-urea
  参考文献：
  名称：

  Design of Highly Active Analogues of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents

  摘要：

  The pyrrolo[1,2-a]benzimidazole (PBI) reductive alkylating agents have been investigated in this laboratory since their discovery in the late 1980s. Of all the structural modifications of the PBIs investigated so far, the variation of the 3-substituent has the greatest influence on cytotoxicity, toxicity, and in vivo antitumor activity. In the present study, we prepared both the R and S enantiomers of nitrogen-containing 3-substituents possessing hydrogen-bonding capability as well as varying basicity. The rationale was to take advantage of stereoselective DT-diaphorase reductive activation as well as hydrogen bonding in the DNA major groove. As a result of these studies, analogues were discovered possessing among the highest hollow fiber tumor assay scores observed in hundreds of natural and synthetic antitumor agents. Our findings indicate that a relatively basic 3-substituent is required for outstanding PBI cytotoxicity but that the importance of using pure enantiomers is still open to study.

  DOI：

  10.1021/jm990029h
• 作为产物：
  描述：

  (S)-7-Methyl-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-ylamine 在 吡啶 、 氨 、 溴 、 硝酸 、 乙酸酐 、 溶剂黄146 、 三氟乙酸 作用下， 反应 53.5h， 生成 ((S)-6-Bromo-7-methyl-5-nitro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-3-yl)-carbamic acid phenyl ester
  参考文献：
  名称：

  Design of Highly Active Analogues of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents

  摘要：

  The pyrrolo[1,2-a]benzimidazole (PBI) reductive alkylating agents have been investigated in this laboratory since their discovery in the late 1980s. Of all the structural modifications of the PBIs investigated so far, the variation of the 3-substituent has the greatest influence on cytotoxicity, toxicity, and in vivo antitumor activity. In the present study, we prepared both the R and S enantiomers of nitrogen-containing 3-substituents possessing hydrogen-bonding capability as well as varying basicity. The rationale was to take advantage of stereoselective DT-diaphorase reductive activation as well as hydrogen bonding in the DNA major groove. As a result of these studies, analogues were discovered possessing among the highest hollow fiber tumor assay scores observed in hundreds of natural and synthetic antitumor agents. Our findings indicate that a relatively basic 3-substituent is required for outstanding PBI cytotoxicity but that the importance of using pure enantiomers is still open to study.

  DOI：

  10.1021/jm990029h