2-(4-nitrophenyl)-1H-benzo[d]imidazole-4-carboxamide

• 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-nitrophenyl)-1H-benzo[d]imidazole-4-carboxamide
• 英文别名: NU1091；2-(4'-nitrophenyl)benzimidazole-4-carboxamide；2-(4-nitrophenyl)-1H-benzimidazole-4-carboxamide
• 化学式: C₁₄H₁₀N₄O₃
• 分子量: 282.258
• InChiKey: AXPSEYPVFKMYID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-nitrophenyl)-1H-benzo[d]imidazole-4-carboxamide 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 反应 10.0h， 以83.8%的产率得到2-(4-aminophenyl)benzimidazole-7-carboxamide
  参考文献：
  名称：

  发现有效治疗胰腺癌的有效和新型双 PARP/BRD4 抑制剂

  摘要：

  靶向聚（ADP-核糖）聚合酶1 / 2（PARP1 / 2）是治疗乳腺癌易感基因（BRCA）突变的胰腺癌的有前景的策略。诱导同源重组（HR）修复缺陷是为更多胰腺癌患者拓宽PARP1/2抑制剂适应症的有效途径。据报道，含溴结构域的蛋白 4 (BRD4) 抑制会增加 HR 缺陷。因此，我们设计、合成和优化了一种PARP/BRD4双重抑制剂III - 16，具有全新的结构，对PARP1/2和BRD4具有高选择性。三- 16通过阻止细胞周期进程、抑制 DNA 损伤修复和促进自噬相关细胞死亡，在胰腺癌细胞和异种移植物中显示出良好的协同抗肿瘤功效。此外，III - 16逆转了奥拉帕尼诱导的细胞周期进程加速和 DNA 修复的恢复。III - 16优于奥拉帕尼的优势表明，双重 PARP/BRD4 抑制剂是治疗晚期胰腺癌的新型且有前景的药物。

  DOI：

  10.1021/acs.jmedchem.1c01535
• 作为产物：
  描述：

  2-氨基-3-硝基苯甲酰胺 在 ammonium acetate 、 氧气 、 铁粉 、 氯化铵 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-(4-nitrophenyl)-1H-benzo[d]imidazole-4-carboxamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy

  摘要：

  PARP-1 could repair the DNA damages induced by Topo inhibitors, therefore inhibiting Topo and PARP-1 simultaneously might be able to overcome resistance and improve outcomes. In this study a series of 4-amidobenzimidazole acridines were designed and synthesized as dual Topo and PARP-1 inhibitors. Compound 111 displayed good inhibitory activities against Topo and PARP-1, as well as significantly inhibited cancer cells proliferation. Further mechanistic evaluations indicated that 111 treatment in MCF-7 cells induced accumulated DNA double-strand breaks, prompted remarkable apoptosis, and caused prominent GO/G1 cell cycle arrest. Moreover, 111 greatly suppressed tumor growth in mice, and displayed favorable metabolic properties in liver microsomes. Our study suggested that single agents inhibiting Topo and PARP concurrently might be an alternative for cancer therapy and 111 represented a potential lead compound for development of antitumor agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.050

文献信息

• Resistance-Modifying Agents. 9. Synthesis and Biological Properties of Benzimidazole Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase
  作者：Alex W. White、Robert Almassy、A. Hilary Calvert、Nicola J. Curtin、Roger J. Griffin、Zdenek Hostomsky、Karen Maegley、David R. Newell、Sheila Srinivasan、Bernard T. Golding

  DOI：10.1021/jm000950v

  日期：2000.11.1

  PARP inhibitors. Derivatives of 2-phenyl-1H-benzimidazole-4-carboxamide (23, K(i) = 15 nM), in which the phenyl ring contains substituents, have been synthesized. Many of these derivatives exhibit K(i) values for PARP inhibition < 10 nM, with 2-(4-hydroxymethylphenyl)-1H-benzimidazole-4-carboxamide (78, K(i) = 1.6 nM) being one of the most potent. Insight into structure-activity relationships (SAR)

  核酶聚（ADP-核糖）聚合酶（PARP）促进DNA链断裂的修复，并与癌细胞对某些DNA破坏剂的抗性有关。PARP抑制剂作为抗药性改良剂具有临床潜力，能够增强放疗和某些形式的癌症化学疗法的细胞毒性。描述了2-芳基-1H-苯并咪唑-4-羧酰胺在癌症化疗中作为耐药修饰剂的临床前开发。1 H-苯并咪唑-4-羧酰胺，特别是2-芳基衍生物被认为是一类有效的PARP抑制剂。已经合成了其中苯环含有取代基的2-苯基-1H-苯并咪唑-4-羧酰胺的衍生物（23，K（i）= 15 nM）。这些衍生物中的许多衍生物对于PARP抑制作用的K（i）值<10 nM，其中2-（4-羟甲基苯基）-1H-苯并咪唑-4-羧酰胺（78，K（i）= 1.6 nM）是最有效的药物之一。通过研究2-（3-甲氧基苯基）-1H-苯并咪唑-4-羧酰胺之间形成的配合物，增强了对2-芳基-1H-苯并咪唑-4-羧酰胺的结构活性关系（SAR）的认识（44，K（
• A simple and metal-free one-pot synthesis of 2-substituted-1H-4-carboxamide benzimidazole using 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine(PYTZ) as catalyst
  作者：Li-Jie Zhang、Kang Yang、Chun-Yu Li、Ya-Quan Sun

  DOI：10.1007/s11696-019-00821-x

  日期：2019.11

  In this work, a simple and green method for the convenient synthetic protocol of 2-substituted-1H-4-carboxamide benzimidazole was reported from 2,3-diaminobenzamide and a variety of aldehydes by condensation. The results showed that 2,3-diaminobenzamide and aldehydes could react under visible light irradiation at ambient temperature in the presence of PYTZ and pumping air (or other oxidant) to obtain the desired compound with simple workup. The structures of 20 synthesized compounds were determined by NMR, IR and HRMS (new compound) techniques. The method was efficient, metal free, green, and selective.

  本研究以 2,3-二氨基苯甲酰胺和多种醛为原料，通过缩合反应，报道了一种简便的 2-取代-1H-4-甲酰胺苯并咪唑的绿色合成方法。结果表明，2,3-二氨基苯甲酰胺和醛在可见光照射下，在PYTZ和抽气（或其他氧化剂）存在的环境温度下发生反应，只需简单的操作即可得到所需的化合物。通过核磁共振、红外和 HRMS（新化合物）技术确定了 20 种合成化合物的结构。该方法具有高效、无金属、绿色和选择性强等特点。
• Benzimidazole compounds
  申请人：Newcastle University Ventures Limited

  公开号：US06100283A1

  公开（公告）日：2000-08-08

  Benzimidazole-4-carboxamide compounds (I) which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. In formula (I), R and R' may each be selected independently from hydrogen, alkyl, hydroxyalkyl (e.g. CH.sub.2 CH.sub.2 OH), acyl (e.g. acetyl or benzoyl) or an optionally substituted aryl (e.g. phenyl) or aralkyl (e.g. benzyl or carboxybenzyl) group. R is generally a substituted phenyl group in the most preferred compounds. The compounds may also be used in the form of pharmaceutically acceptable salts or pro-drugs. ##STR1##

  Benzimidazole-4-carboxamide化合物（I）可以作为DNA修复酶聚（ADP-核糖）聚合酶或PARP酶（EC 2.4.2.30）的有效抑制剂，因此可以与DNA损伤的细胞毒性药物或放疗一起使用，以增强后者的效果，从而提供有用的治疗化合物。在公式（I）中，R和R'可以各自独立地选择氢，烷基，羟基烷基（例如CH.sub.2 CH.sub.2 OH），酰基（例如乙酰或苯甲酰）或可选取代芳基（例如苯基）或芳基烷基（例如苄基或羧基苯甲基）基团。在最优化合物中，R通常是取代的苯基基团。这些化合物也可以以药学上可接受的盐或前药的形式使用。##STR1##
• BENZIMIDAZOLE COMPOUNDS
  申请人：NEWCASTLE UNIVERSITY VENTURES LIMITED

  公开号：EP0841924B1

  公开（公告）日：2002-10-02
• US6100283A
  申请人：——

  公开号：US6100283A

  公开（公告）日：2000-08-08