2-(3,4-diaminophenyl)-5-phenyl-benzimidazole | 237429-60-6

• 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-(3,4-diaminophenyl)-5-phenyl-benzimidazole
• 英文别名: 2-(3,4-diaminophenyl)-5-phenylbenzimidazole；5-phenyl-2-[3,4-diaminophenyl]benzimidazole；4-(6-phenyl-1H-benzimidazol-2-yl)benzene-1,2-diamine
• CAS: 237429-60-6
• 化学式: C₁₉H₁₆N₄
• 分子量: 300.363
• InChiKey: DFMUNQPMDLZRPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3,4-diaminophenyl)-5-phenyl-benzimidazole 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 、 硝基苯 为溶剂， 反应 1.5h， 生成 5-phenyl-2-[2'-(3,4-diaminophenyl)benzimidazol-5'yl]benzimidazole
  参考文献：
  名称：

  2“取代的5-苯基叔苯并咪唑作为拓扑异构酶I毒物。

  摘要：

  5-苯基苯并咪唑（1）具有拓扑异构酶I毒（拓扑I）的活性，对人肿瘤细胞具有细胞毒性。当针对喜树碱抗性细胞系CPT-K5进行评估时，没有观察到交叉抗性。但是，在2“位置被1取代的衍生物确实表现出对该细胞系的交叉耐药性。该细胞系对CPT抗性的基础是它具有topo I的突变形式。这些结果表明，取代基在2”-位的“α”可能靠近野生型酶。因此，我们假设具有2“取代基的苯并咪唑能够与酶相互作用，从而影响此类topo I毒物的活性。5-苯并苯并咪唑与羟基，羟甲基，巯基，氨基，N-苯甲酰氨基甲基，氯，合成了2′-位的三氟甲基和三氟甲基。另外，制备了几种在乙基-的2-位含有甲氧基，羟基，氨基或N-乙酰氨基的2”-乙基-5-苯基叔苯并咪唑。链。这些2“-取代的5-苯基叔苯并咪唑被评估为topo I毒物并具有细胞毒活性。在2”-位存在强吸电子基团，例如氯或三氟甲基，确实增强了topo I的中毒活性。和细胞毒性。

  DOI：

  10.1016/s0968-0896(00)00054-7
• 作为产物：
  描述：

  3,4-二硝基苯甲醛 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 、 硝基苯 为溶剂， 反应 1.5h， 生成 2-(3,4-diaminophenyl)-5-phenyl-benzimidazole
  参考文献：
  名称：

  Terbenzimidazoles:  Influence of 2‘‘-, 4-, and 5-Substituents on Cytotoxicity and Relative Potency as Topoisomerase I Poisons

  摘要：

  Terbenzimidazoles poison the nuclear enzyme topoisomerase I and possess significant cytotoxic activity against several human tumor cell lines. The relative pharmacological activity of 4,5- and 5,6-benzoterbenzimidazoles was compared to that of 5-phenylterbenzimidazole (3). 5,6-Benzoterbenzimidazole is inactive as a topoisomerase I poison and did not exhibit significant cytotoxic activity. In contrast, 4,5-benzoterbenzimidazole retained activity as a topoisomerase I poison but exhibited weak cytotoxic activity relative to 3. While 5-(1-naphthyl)terbenzimidazole is less potent than 3 as a topoisomerase I poison and cytotoxic agent, 5-(2-naphthyl)terbenzimidazole has comparable activity to 3. The presence of a p-methoxy or p-chloro substituent on the phenyl moiety did not dramatically alter the pharmacological activity of 3. Several analogs of 3 were synthesized wherein the 2''-substituent varied from methyl, ethyl, propyl, isopropyl, phenyl to p-methoxyphenyl, Evaluation of the intrinsic activity of these analogs as topoisomerase I poisons indicates that topoisomerase I poisoning was not diminished by the presence of a methyl, ethyl, propyl, and isopropyl substituent at the 2''-position. Among the various 2''-substituted analogs evaluated, only in the case of 2''-(p-methoxyphenyl)-5-phenylterbenzimidazole was a significant decrease in cytotoxicity observed.

  DOI：

  10.1021/jm960658g

文献信息

• Heterocyclic topoisomerase poisons
  申请人：Rutgers, The State University of New Jersey

  公开号：US20010009919A1

  公开（公告）日：2001-07-26

  The invention provides a topoisomerase poison of formula I: 1 wherein R 1 -R 8 have any of the meanings defined in the specification, or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising a compound of formula I or a salt thereof, intermediates useful for preparing a compound of formula I, and therapeutic methods comprising administering a compound of formula I or a salt thereof.

  本发明提供了一种式 I 的拓扑异构酶毒物： 1 其中 R 1 -R 8 或其药学上可接受的盐，以及包含式 I 化合物或其盐的药物组合物、用于制备式 I 化合物的中间体和包括施用式 I 化合物或其盐的治疗方法。
• Heterocyclic bibenzimidazole derivatives as topoisomerase I inhibitors
  作者：Song Jin、Jung Sun Kim、Sai-Peng Sim、Angela Liu、Daniel S. Pilch、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/s0960-894x(00)00087-1

  日期：2000.4

  A series of 2'-heterocyclic derivatives of 5-phenyl-2,5'-1H-bibenzimidazoles were evaluated for topoisomerase I poisoning activity and cytotoxicity. Topo I poisoning activity was associated with 2'-derivatives that possessed a hydrogen atom capable of hydrogen bond formation, suggesting that the interatomic distances between such hydrogen atoms and the heteroatoms on the adjacent benzimidazole influence activity. (C) 2000 Elsevier Science Ltd. All rights reserved.
• HETEROCYCLIC TOPOISOMERASE POISONS
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：EP1054870A1

  公开（公告）日：2000-11-29
• US6063801A
  申请人：——

  公开号：US6063801A

  公开（公告）日：2000-05-16
• US6221892B1
  申请人：——

  公开号：US6221892B1

  公开（公告）日：2001-04-24