2-(3H-苯并咪唑-5-基)-3H-苯并咪唑-5-甲醛 | 167959-20-8

• 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: 2-(3H-苯并咪唑-5-基)-3H-苯并咪唑-5-甲醛
• 英文名称: 5-formyl-2-(benzimidazol-5'-yl)benzimidazole
• 英文别名: [2,5'-Bi-1H-benzimidazole]-5-carboxaldehyde；2-(3H-benzimidazol-5-yl)-3H-benzimidazole-5-carbaldehyde
• CAS: 167959-20-8
• 化学式: C₁₅H₁₀N₄O
• 分子量: 262.271
• InChiKey: QXKGHONOKVYYEN-UHFFFAOYSA-N

物化性质

• 沸点：
  681.2±53.0 °C(Predicted)
• 密度：
  1.475±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 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：
  74.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3H-苯并咪唑-5-基)-3H-苯并咪唑-5-甲醛 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 、 硝基苯 为溶剂， 145.0 ℃ 、310.27 kPa 条件下， 反应 24.0h， 生成 5-amino-2-[2'-(benzimidazol-5''-yl)benzimidazole-5'-yl]benzimidazole
  参考文献：
  名称：

  Quantitative structure–activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents

  摘要：

  Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch pi value or the sigma(meta) and sigma(para) values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative pi values for the various subtituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or pi values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the it values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10021-9
• 作为产物：
  描述：

  1H-苯并咪唑-5-甲醛 在 aluminum nickel 甲酸 作用下， 以 硝基苯 为溶剂， 反应 4.0h， 生成 2-(3H-苯并咪唑-5-基)-3H-苯并咪唑-5-甲醛
  参考文献：
  名称：

  Synthesis and Evaluation of Terbenzimidazoles as Topoisomerase I Inhibitors

  摘要：

  The synthesis and pharmacological activity of a series of terbenzimidazoles are described. The ability of these derivatives to induce DNA cleavage in the presence of topoisomerase I was evaluated in vitro. These analogs were also assayed for their cytotoxicity in RPMI 8402 cells and the camptothecin-resistant CPT-K5 cells. In addition the potential for these compounds to serve as substrates for MDR1 was also determined. Several terbenzimidazoles exhibited similar cytotoxicity against variants of human tumor cells that either overexpress MDR1 or are camptothecin-resistant.

  DOI：

  10.1021/jm00018a024

文献信息

• Topoisomerase I inhibition and cytotoxicity of 5-Bromo- and 5-Phenylterbenzimidazoles
  作者：Meera Rangarajan、Jung Sun Kim、Sai-Peng Sim、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/s0968-0896(00)00188-7

  日期：2000.11

  Significant enhancement in the topoisomerase I poisoning activity and cytotoxicity of 5-phenylterbenzimidazole is observed when the 2"-position is substituted with either a chloro or trifluoromethyl substituent. The influence of such substituents on the biological activity of 5.6-dibromoterbenzimidazole (6a) was also explored. In the case of either 2"-chloro-5,6-dibromoterbenzimidazole (6b) or 2"-trifluoromethyl-5

  拓扑异构酶I是在转录，翻译和有丝分裂过程中维持DNA三维结构必不可少的酶。随着有效地中毒拓扑异构酶I的新临床药物的引入，该酶已被证明是开发抗癌药物中有吸引力的分子靶标。几种苯并咪唑已被确定为有效的拓扑异构酶I毒物。关于各种苯并咪唑的结构活性数据表明，在各种苯并咪唑的5位上存在亲脂性取代基与增强的细胞毒性有关。虽然尚未评估在5位和6位上都具有取代基的效果，但先前的研究确实表明在5位上存在稠合的苯并环 6位导致拓扑异构酶I中毒活性和细胞毒性显着降低。在本研究中，我们调查了不同的苯并咪唑的5位和6位上的取代基是否会保留topo I中毒活性。合成了5-溴和5-苯基叔苯并咪唑的6-溴，6-甲氧基或6-苯基衍生物，并评估了topo I的中毒活性以及它们对人淋巴母细胞瘤细胞的细胞毒性。数据表明，此类衍生物确实保留了类似的topo I中毒活性，并具有与5-溴-或5-苯基叔苯并咪唑相当的细胞毒性。当2“被观
• Terbenzimidazoles:  Influence of 2‘‘-, 4-, and 5-Substituents on Cytotoxicity and Relative Potency as Topoisomerase I Poisons
  作者：Jung Sun Kim、Chiang Yu、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1021/jm960658g

  日期：1997.8.1

  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.
• TRIBENZIMIDAZOLES USEFUL AS TOPOISOMERASE I INHIBITORS
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：EP0839140A1

  公开（公告）日：1998-05-06
• [EN] TRIBENZIMIDAZOLES USEFUL AS TOPOISOMERASE I INHIBITORS<br/>[FR] UTILISATION DE TRISBENZIMIDAZOLS EN TANT QU'INHIBITEURS DE LA TOPOISOMERASE I
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：WO1996036612A1

  公开（公告）日：1996-11-21

  (EN) The present invention provides anti-neoplastic topoisomerase I inhibitors of formula (I) wherein Ar is (C6-C12)aryl or (5- to 12-membered) heteroaryl comprising 1-3 N, S or non peroxyde O, wherein N is unsubstituted or is substituted with (C1-C4)alkyl; X is H, CN, CHO, OH, acetyl, CF3, O(C1-C4)alkyl, NO2, NH2, halogen or halo-(C1-C4)alkyl; each Y is individually H, (C1-C4)alkyl or aralkyl; Y' is H or (C1-C4)alkyl; n is 0 or 1; and each Z is individually H, (C1-C4)alkyl, halogen or halo(C1-C4)alkyl; or a pharmaceutically acceptable salt thereof.(FR) Cette invention concerne des inhibiteurs anti-néoplasiques de la topoisomérase I, de la formule (I), ou un sel de ceux-ci acceptable du point de vue pharmaceutique. Dans cette formule, Ar représente un aryle en C6-C12 ou un hétéroaryle (comportant de 5 à 12 éléments) comprenant 1-3 N, S ou O non peroxydé, N n'étant pas substitué ou substitué par alkyle en C1-C4, X représente H, CN, CHO, OH, acétyle, CF3, O(C1-C4)alkyle, NO2, NH2, halogène ou haloalkyle (C1-C4); chaque Y est individuellement H, alkyle (C1-C4) ou aralkyle, Y' représente H ou alkyle (C1-C4), n vaut 0 ou 1 et chaque Z est individuellement H, alkyle (C1-C4), halogène ou haloalkyle (C1-C4).
• Quantitative structure–activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents
  作者：Jung Sun Kim、Qun Sun、Chiang Yu、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/s0968-0896(97)10021-9

  日期：1998.2

  Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch pi value or the sigma(meta) and sigma(para) values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative pi values for the various subtituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or pi values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the it values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity. (C) 1998 Elsevier Science Ltd. All rights reserved.