2-(4-methoxy-phenyl)-1H-benzimidazole-6-carbaldehyde | 126824-22-4

• 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-(4-methoxy-phenyl)-1H-benzimidazole-6-carbaldehyde
• 英文别名: 2-(4-methoxyphenyl)-3H-benzimidazole-5-carbaldehyde
• CAS: 126824-22-4
• 化学式: C₁₅H₁₂N₂O₂
• 分子量: 252.272
• InChiKey: HZVSJGYAQYONTN-UHFFFAOYSA-N

物化性质

• 沸点：
  491.7±51.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methoxy-phenyl)-1H-benzimidazole-6-carbaldehyde 在 N-甲基邻苯二甲酰亚胺 、 氢溴酸 、 1-羟基苯并三唑 、 硝基苯 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.08h， 生成 2-((carboxymethyl){2-[(carboxymethyl)({N-[3-({3-[(2-{2-[2-(4-methyoxyphenyl)-1H-benzimidazol-6-yl]-1H-benzimidazol-6-yl}-1H-benzimidazol-6-yl)carbonylamino]propyl}methylamino)propyl]carbamoyl}methyl)-amino]ethyl}amino)acetic acid
  参考文献：
  名称：

  Molecular Recognition of DNA by Hoechst Benzimidazoles: Exploring Beyond the Pyrrole-Imidazole-Hydroxypyrrole Polyamide-Pairing Code

  摘要：

  A series of three-ring analogs of the minor-groove-binding molecule Hoechst 33258 (1), consisting of benzimidazole (B), imidazopyridine (P), and hydroxybenzimidazole (H) monomers, have been synthesized in order to investigate both their sequence specificity and binding modes. MPE.Fe-II Footprinting has revealed the preference of both PBB and BBB ligands for 5'-WGWWW-3' and 5'-WCWWW-3' tracts, as well as A T-rich sequences. Affinity-cleavage titrations show no evidence for a 2:1 binding mode of these Hoechst analogs. Importantly, all derivatives are oriented in one direction at each of their binding sites. The implications of these results for the design of minor-groove-binding small molecules is discussed.

  DOI：

  10.1002/1522-2675(20000906)83:9<2197::aid-hlca2197>3.0.co;2-n
• 作为产物：
  描述：

  (3,4-二氨基苯基)甲醇 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.0h， 生成 2-(4-methoxy-phenyl)-1H-benzimidazole-6-carbaldehyde
  参考文献：
  名称：

  催化 Fe(III)/Fe(II) 氧化还原循环向稠杂环的合成效用：取代苯并咪唑、双苯并咪唑和咪唑并吡啶衍生物的简便方法

  摘要：

  已经研究了催化 Fe(III)/Fe(II) 氧化还原循环方法，并将其应用于通过芳香邻二胺与芳香醛和杂环醛的氧化偶联来合成各种苯并咪唑、双苯并咪唑和咪唑并吡啶衍生物不同类型的取代基。进一步证明，这种通用且方便的方法特别适用于迅速提供许多新型双苯并咪唑类 Hoechst 33 258 类似物，以作为荧光核酸结合探针的潜在开发。这里介绍了三十种不同化合物的成功制备和表征。

  DOI：

  10.1055/s-2000-7111

文献信息

• Synthesis and investigation of novel benzimidazole derivatives as antifungal agents
  作者：Nishad Thamban Chandrika、Sanjib K. Shrestha、Huy X. Ngo、Sylvie Garneau-Tsodikova

  DOI：10.1016/j.bmc.2016.06.010

  日期：2016.8

  pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce

  多种病原性真菌菌株对抗真菌药物的抵抗性的上升和出现导致对新抗真菌药物的需求增加。过去已经研究了具有不同作用机理的多种杂环支架。本文中，我们报道了18种烷基化的单，双和三苯并咪唑衍生物的合成和抗真菌活性，它们对哺乳动物细胞的毒性以及在酵母细胞中诱导活性氧（ROS）的能力。我们的许多双苯并咪唑化合物对所有测试的真菌菌株均表现出中等至出色的抗真菌活性，MIC值为15.6至0.975μg/ mL。发现我们的双苯并咪唑类的真菌活性谱取决于烷基链长。
• Synthesis and biological evaluation of benzimidazole–oxindole conjugates as microtubule-targeting agents
  作者：Ahmed Kamal、B. Nagaseshadri、V. Lakshma Nayak、Vunnam Srinivasulu、Manda Sathish、Jeevak Sopanrao Kapure、C. Suresh Reddy

  DOI：10.1016/j.bioorg.2015.09.003

  日期：2015.12

  A series of benzimidazole–oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results

  合成了一系列苯并咪唑-羟吲哚缀合物，并评估了它们的细胞毒性活性。细胞毒性测定结果表明，缀合物5c和5p对人乳腺癌细胞系（MCF-7）显示出有希望的细胞毒性。细胞周期分析表明，这些缀合物诱导了MCF-7细胞在G2 / M期的细胞周期停滞。微管蛋白聚合测定结果表明，这些结合物抑制微管蛋白聚合，IC 50值分别为1.12和1.59μM。免疫荧光分析还表明，这些结合物可有效抑制MCF-7细胞中的微管组装。此外，分子对接研究表明这些缀合物5c和5p与微管蛋白相互作用并有效结合。总体而言，结果表明这些苯并咪唑-羟吲哚共轭物通过抑制微管蛋白聚合而具有细胞毒性。
• A Convenient Synthesis of Substituted Oxazolo-[5,4-b]Pyridines Using Lead Tetraacetate as Oxidative Cyclizing Agent
  作者：Yadagiri Bathini、J. William Lown

  DOI：10.1080/00397919108020814

  日期：1991.1

  Abstract Various substituted oxazolo[5,4-b]pyridines 5a-d have been synthesized by condensation of appropriate hydroxyaminopyridines and aldehydes followed by oxidative cyclization of the resulting Schiff's bases with lead tetraacetate. This method has been extended to the synthesis of the DNA minor groove binding ligands 5e and 5f related to Hoechst 33258 1.

  摘要 各种取代的恶唑并[5,4-b] 吡啶 5a-d 已通过适当的羟基氨基吡啶和醛的缩合，然后将所得席夫碱与四乙酸铅氧化环化而合成。该方法已扩展到与 Hoechst 33258 1 相关的 DNA 小沟结合配体 5e 和 5f 的合成。
• Structure-activity relationships of benzimidazoles and related heterocycles as topoisomerase I poisons
  作者：Jung Sun Kim、Qun Sun、Barbara Gatto、Chiang Yu、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/0968-0896(96)00047-8

  日期：1996.4

  the highest activity and was significantly more active than the 4-nitro positional isomer. The 5- and 6-nitro derivatives of 2-(4-methoxyphenyl) benzoxazole, 2-(4-methoxyphenyl)benzothiazole, and 2-(4-methoxyphenyl)indole were synthesized and their relative activity as topoisomerase I inhibitors determined. None of these heterocyclic analogues were effective in significantly inhibiting cleavable-complex

  合成了一系列取代的2-（4-甲氧基苯基）-1H-苯并咪唑类，并作为拓扑异构酶I的抑制剂进行了评估。存在5-甲酰基-，5-（氨基羰基）-或5-硝基（即取代基）能够充当氢键受体的分子）与选择的衍生物抑制拓扑异构酶I的潜力相关。与联苯并咪唑和叔苯并咪唑相反，作为拓扑异构酶I毒物具有活性的取代苯并咪唑显示出最低的DNA亲和力或没有DNA亲和力。5-硝基-2-（4-甲氧基苯基）-1H-苯并咪唑显示出最高的活性，并且比4-硝基位置异构体具有更高的活性。2-（4-甲氧基苯基）苯并恶唑，2-（4-甲氧基苯基）苯并噻唑的5-和6-硝基衍生物 合成了2-（4-甲氧基苯基）吲哚和2-（4-甲氧基苯基）吲哚，它们作为拓扑异构酶I抑制剂的相对活性。这些杂环类似物在DNA和拓扑异构酶I的存在下均不能有效地抑制可裂解复合物的形成，这表明与这些取代的苯并咪唑与酶或酶-DNA复合物的相互作用相关的高度结构特异性。在评估它们
• Synthesis and Evaluation of Terbenzimidazoles as Topoisomerase I Inhibitors
  作者：Qun Sun、Barbara Gatto、Chiang Yu、Angela Liu、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1021/jm00018a024

  日期：1995.9

  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.