N-hexyl-2-(chloromethyl)benzimidazole

• 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: N-hexyl-2-(chloromethyl)benzimidazole
• 英文别名: 2-(chloromethyl)-1-hexyl-1H-benzimidazole；2-(chloromethyl)-1-hexyl-1H-benzo[d]imidazole；2-(Chloromethyl)-1-hexylbenzimidazole
• 化学式: C₁₄H₁₉ClN₂
• 分子量: 250.771
• InChiKey: OCRYTHJUJCXRGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-hexyl-2-(chloromethyl)benzimidazole 、 环丙沙星 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以45.7%的产率得到1-cyclopropyl-6-fluoro-7-(4-((1-hexyl-1H-benzimidazol-2-yl)methyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

  摘要：

  A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 mu M concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.01.052
• 作为产物：
  描述：

  溴己烷 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 N-hexyl-2-(chloromethyl)benzimidazole
  参考文献：
  名称：

  Design, Synthesis and Antimicrobial Evaluation of Novel Benzimidazoleincorporated Naphthalimide Derivatives as Salmonella typhimurium DNA Intercalators, and Combination Researches

  摘要：

  目标：设计并制备一系列新颖的苯并咪唑基那酰亚胺衍生物，以应对不断增加的抗生素耐药性。 方法：通过氨解反应、N烷基化等方法，从商业4-溴-1，8-萘酐和邻苯二胺合成目标的新型苯并咪唑基那酰亚胺衍生物。通过双倍稀释技术在体外评估合成化合物的抗菌活性。利用UV-Vis光谱方法研究化合物10g与伤寒沙门氏菌DNA的相互作用。 结果：在这一系列中，携带2,4-二氯苯甲基基团的化合物10g相对于其他化合物表现出最佳的抗菌活性；尤其是，在与参考药物诺氟沙星（MIC = 4 μg/mL）相比较时，它对伤寒沙门氏菌表现出可比较的活性。进一步研究表明，化合物10g能有效地插入到伤寒沙门氏菌DNA中形成10g-DNA复合物，这可能与其抑制活性相关。分子对接结果表明，那酰亚胺化合物10g能通过π-π堆积与DNA六聚体双链的碱基对相互作用。此外，强活性化合物与临床药物的组合展现出比单独使用它们更好的抗菌效果，剂量更小，抗菌谱更广。值得注意的是，这些组合系统对氟康唑不敏感的红色链霉菌更为敏感。 结论：这项工作为优化苯并咪唑基那酰亚胺衍生物的结构，使其成为有效的抗菌剂提供了一个有前途的起点。

  DOI：

  10.2174/1573406417666210712105922

文献信息

• Discovery of Benzimidazole-Quinolone Hybrids as New Cleaving Agents toward Drug-Resistant <i>Pseudomonas aeruginosa</i> DNA
  作者：Ya-Nan Wang、Rammohan R. Yadav Bheemanaboina、Wei-Wei Gao、Jie Kang、Gui-Xin Cai、Cheng-He Zhou

  DOI：10.1002/cmdc.201700739

  日期：2018.5.23

  new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2‐fluorobenzyl derivative 5 b (ethyl 7‐chloro‐6‐fluoro‐1‐[[1‐[(2‐fluorophenyl)methyl]benzimidazol‐2‐yl]methyl]‐4‐oxo‐quinoline‐3‐carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas

  设计并合成了一系列作为新型潜在抗菌剂的苯并咪唑-喹诺酮杂化物。生物活性测定表明，一些制备的化合物表现出有效的抗菌和抗真菌活性。值得注意的是，2-氟苄基衍生物5 b（乙基7-氯-6-氟-1-基[[1-[（（2-氟苯基）甲基]苯并咪唑-2-基]甲基] -4-氧-喹啉-3-羧酸酯）对分离自感染患者的铜绿假单胞菌和热带假丝酵母具有显着的抗菌活性。活性分子5b不仅可以迅速杀死测试的菌株，而且对Hep-2细胞的毒性低。触发铜绿假单胞菌细菌耐药性的发展更加困难与针对诺氟沙星的5b相比。分子对接表明5b可以与拓扑异构酶IV-DNA复合物有效结合，并且量子化学研究从理论上阐明了化合物5b的良好抗菌活性。初步的实验反应机理探索表明，衍生物5b不能插入从耐药铜绿假单胞菌分离的DNA中，但能够有效切割DNA，这可能进一步阻止DNA复制，从而发挥强大的生物活性。另外，化合物5b是具有膜破坏能力的有前途的抗菌剂。
• Design, Synthesis and Antimicrobial Evaluation of Novel Benzimidazoleincorporated Naphthalimide Derivatives as Salmonella typhimurium DNA Intercalators, and Combination Researches
  作者：Hui-Zhen Zhang、Zhi-Wei Ning、Cheng-He Zhou

  DOI：10.2174/1573406417666210712105922

  日期：2022.5

  A series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared in an effort to overcome the increasing antibiotic resistance.

  The target novel benzimidazole-incorporated naphthalimide derivatives were synthesized from commercial 4-bromo-1,8-naphthalic anhydride and o-phenylene diamine by aminolysis, Nalkylation and so on. The antimicrobial activity of the synthesized compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of compound 10g with Salmonella typhimurium DNA was studied using UV-vis spectroscopic methods.

  Compound 10g bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively; especially, it exhibited comparable activity against Salmonella typhimurium in comparison with the reference drug Norfloxacin (MIC = 4 μg/mL). Further research showed that compound 10g could effectively intercalate into the Salmonella typhimurium DNA to form the 10g–DNA complex, which might correlate with the inhibitory activity. Molecular docking results demonstrated that naphthalimide compound 10g could interact with base-pairs of DNA hexamer duplex by π–π stacking. Additionally, the combination of the strong active compound with clinical drugs exhibited better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separate use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive M. ruber.

  This work provides a promising starting point to optimize the structures of benzimidazole- incorporated naphthalimide derivatives as potent antimicrobial agents.

  目标：设计并制备一系列新颖的苯并咪唑基那酰亚胺衍生物，以应对不断增加的抗生素耐药性。 方法：通过氨解反应、N烷基化等方法，从商业4-溴-1，8-萘酐和邻苯二胺合成目标的新型苯并咪唑基那酰亚胺衍生物。通过双倍稀释技术在体外评估合成化合物的抗菌活性。利用UV-Vis光谱方法研究化合物10g与伤寒沙门氏菌DNA的相互作用。 结果：在这一系列中，携带2,4-二氯苯甲基基团的化合物10g相对于其他化合物表现出最佳的抗菌活性；尤其是，在与参考药物诺氟沙星（MIC = 4 μg/mL）相比较时，它对伤寒沙门氏菌表现出可比较的活性。进一步研究表明，化合物10g能有效地插入到伤寒沙门氏菌DNA中形成10g-DNA复合物，这可能与其抑制活性相关。分子对接结果表明，那酰亚胺化合物10g能通过π-π堆积与DNA六聚体双链的碱基对相互作用。此外，强活性化合物与临床药物的组合展现出比单独使用它们更好的抗菌效果，剂量更小，抗菌谱更广。值得注意的是，这些组合系统对氟康唑不敏感的红色链霉菌更为敏感。 结论：这项工作为优化苯并咪唑基那酰亚胺衍生物的结构，使其成为有效的抗菌剂提供了一个有前途的起点。
• 一种萘酰亚胺苯并咪唑类化合物及其制备方法与应用
  申请人：临沂大学

  公开号：CN110862374B

  公开（公告）日：2022-11-08

  本发明属于药物化学技术领域，公开了如式I所示的萘酰亚胺苯并咪唑类化合物及其制备方法与应用，该化合物具有较强的体外抗微生物活性，尤其是对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、枯草杆菌、藤黄微球菌等革兰阳性菌、大肠杆菌、变形杆菌、铜绿假单胞菌、伤寒沙门菌等革兰阴性菌、以及产朊假丝酵母菌、黄曲霉菌、啤酒酵母菌、白色念珠菌、假丝酵母菌等真菌都表现出很高的抑制活性，能够用于制备抗细菌和/或抗真菌药物，有助于解决日趋严重的耐药性、顽固的致病性微生物以及新出现的有害微生物等临床治疗问题。
• 喹诺酮苯并咪唑类化合物及其制备方法和应 用
  申请人：西南大学

  公开号：CN104974138B

  公开（公告）日：2018-01-05

  本发明公开了喹诺酮苯并咪唑类化合物及其制备方法和应用，结构如通式(I)所示，该化合物具有抗微生物活性，对革兰氏阳性菌、革兰氏阴性菌和真菌都有一定的抑制活性，用于制备抗细菌和/或抗真菌药物，还可以与药学上的辅料组合制成单方或复方制剂。并且本发明公开的化合物所涉及的制备原料商业化程度高、便宜易得，制备路线短、方法简便，生产成本低，为临床抗微生物治疗提供更多高效、安全的候选药物。通用分子式中R1、R2、R3、R4、R5、R6、R7和X如权利要求书所定义。
• Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove
  作者：Ya-Nan Wang、Rammohan R. Yadav Bheemanaboina、Gui-Xin Cai、Cheng-He Zhou

  DOI：10.1016/j.bmcl.2018.03.046

  日期：2018.5

  A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus ( MIC = 4 mu g/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c-DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity. (C) 2018 Elsevier Ltd. All rights reserved.