7-甲基-2,3-二氢-1H-吡咯并[1,2-a]苯并咪唑-3-胺 | 244151-81-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 7-甲基-2,3-二氢-1H-吡咯并[1,2-a]苯并咪唑-3-胺
• 英文名称: 3-amino-2,3-dihydro-7-methyl-1H-pyrrolo[1,2-a]benzimidazole
• 英文别名: 7-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-3-amine
• CAS: 244151-81-3
• 化学式: C₁₁H₁₃N₃
• 分子量: 187.244
• InChiKey: CHPLLCHAQOELOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-甲基-2,3-二氢-1H-吡咯并[1,2-a]苯并咪唑-3-胺 在 盐酸 、 ALTUS 20 CLEC acyltransferase 作用下， 反应 9.5h， 生成 (3R)-7-甲基-2,3-二氢-1H-吡咯并[1,2-a]苯并咪唑-3-胺
  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：

  3-hydroxylimino-2,3-dihydro-7-methyl-1H-pyrrolo[1,2-a]benzimidazole 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以75%的产率得到7-甲基-2,3-二氢-1H-吡咯并[1,2-a]苯并咪唑-3-胺
  参考文献：
  名称：

  Pyrrolobenzimidazoles Linked to Heterocycles and Peptides. Design of DNA Base Pair Specific Phosphate Hydrolyzing Agents and Novel Cytotoxic Agents

  摘要：

  Work in this laboratory has been involved with the design of aziridinyl quinone-based cancer drugs (PBIs) capable of both recognizing the DNA major groove and cleaving the phosphate backbone upon reduction to the hydroquinone. The hydroquinone species recognizes the major groove of DNA at single base pairs by Hoogsteen-type hydrogen bonding. The present study extends recognition beyond a single base pair by adding amino acid residues to the 3-amino center of the PBI system. Thus, extension with proline or proline-glycine results in phosphate cleavage at 5'-AA-3' with insignificant N(7) guanine alkylation. Molecular models were used to validate the observed sequence specificity. This report also describes the design of PBIs not capable of DNA alkylation. Removal of major groove interactions by methylation or the presence of steric bulk prevented DNA alkylation reactions upon reductive activation. From these studies it was concluded that DNA alkyation was not necessary for PBI cytostatic and cytotoxic activity. For example, linkage of two phenylalanines to the PBI results in highly selective cytostatic and cytotoxic activity against melanoma, although this compound is a weak DNA alkylator.

  DOI：

  10.1021/jm0302750

文献信息

• Treatment of neoplasms with yujungamycins
  申请人：Arizona Board of Regents acting for and on behalf of Arizona State University

  公开号：US06998413B1

  公开（公告）日：2006-02-14

  Yungamycin A has been demonstrated to have unexpected in vivo anticancer activity. New compounds Yungamycin B and C are also disclosed, and have been demonstrated to be specific for DT-diaphorase, as well as to have in vivo anticancer activity.

  Yungamycin A已被证明具有意外的体内抗癌活性。新化合物Yungamycin B和C也已被披露，并已被证明对DT-二氧化还原酶具有特异性，并具有体内抗癌活性。
• Pyrrolobenzimidazoles Linked to Heterocycles and Peptides. Design of DNA Base Pair Specific Phosphate Hydrolyzing Agents and Novel Cytotoxic Agents
  作者：Arman Ghodousi、Xiaofen Huang、Zheng Cheng、Edward B. Skibo

  DOI：10.1021/jm0302750

  日期：2004.1.1

  Work in this laboratory has been involved with the design of aziridinyl quinone-based cancer drugs (PBIs) capable of both recognizing the DNA major groove and cleaving the phosphate backbone upon reduction to the hydroquinone. The hydroquinone species recognizes the major groove of DNA at single base pairs by Hoogsteen-type hydrogen bonding. The present study extends recognition beyond a single base pair by adding amino acid residues to the 3-amino center of the PBI system. Thus, extension with proline or proline-glycine results in phosphate cleavage at 5'-AA-3' with insignificant N(7) guanine alkylation. Molecular models were used to validate the observed sequence specificity. This report also describes the design of PBIs not capable of DNA alkylation. Removal of major groove interactions by methylation or the presence of steric bulk prevented DNA alkylation reactions upon reductive activation. From these studies it was concluded that DNA alkyation was not necessary for PBI cytostatic and cytotoxic activity. For example, linkage of two phenylalanines to the PBI results in highly selective cytostatic and cytotoxic activity against melanoma, although this compound is a weak DNA alkylator.
• Design of Highly Active Analogues of the Pyrrolo[1,2-<i>a</i>]benzimidazole Antitumor Agents
  作者：William A. Craigo、Benjamin W. LeSueur、Edward B. Skibo

  DOI：10.1021/jm990029h

  日期：1999.8.1

  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.