N-3-chlorobenzyl o-phenylenediamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-3-chlorobenzyl o-phenylenediamine
• 英文别名: N1-(3-chlorobenzyl)benzene-1,2-diamine；2-N-[(3-chlorophenyl)methyl]benzene-1,2-diamine
• 化学式: C₁₃H₁₃ClN₂
• 分子量: 232.713
• InChiKey: OCMDCHUZSIOFJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-3-chlorobenzyl o-phenylenediamine 在 2,2,6,6-四甲基哌啶氧化物 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以94%的产率得到2-(3-chloro-phenyl)-1H-benzoimidazole
  参考文献：
  名称：

  Metal-Free TEMPO-Promoted C(sp³)–H Amination To Afford Multisubstituted Benzimidazoles

  摘要：

  An efficient TEMPO-air/cat. TEMPO-O-2 oxidative protocol was developed to synthesize multisubstituted or fused tetracyclic benzimidazoles via a metal-free oxidative C-N coupling between the sp(3) C-H and free N-H of readily available N-1-benzyl/alkyl-1,2-phenylenediamines.

  DOI：

  10.1021/jo5005179
• 作为产物：
  描述：

  3-氯苄胺 在 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-3-chlorobenzyl o-phenylenediamine
  参考文献：
  名称：

  吲哚喹喔啉衍生物作为有前景的多功能抗阿尔茨海默病药物

  摘要：

  摘要 为了对抗阿尔茨海默病等具有复杂发病机制的疾病，多靶点定向配体的开发已成为一种有前途的药物发现方法。在我们致力于开发针对阿尔茨海默病的多靶点定向配体的过程中，设计并合成了一系列吲哚喹喔啉衍生物。体外胆碱酯酶抑制研究表明，所有合成的化合物都表现出中等至良好的胆碱酯酶抑制活性。6-(6-(Piperidin-1-yl)hexyl)-6 H -indolo[2,3- b ]quinoxaline 9f被确定为最有效和选择性的 BuChE 抑制剂 (IC 50= 0.96 µM，选择性指数 = 0.17)，与商业批准的参考药物多奈哌齐 (IC 50 = 1.87 µM)相比，BuChE 抑制活性高出 2 倍。此外，化合物9f还具有自诱导 Aβ 1-42聚集抑制活性（在 50 μM 浓度下抑制 51.24%）。该系列的一些化合物也显示出适度的抗氧化活性。为了解化合物9f的推定结合模式，进行了分子

  DOI：

  10.1080/07391102.2020.1840441

文献信息

• 黄连素苯并咪唑类化合物或其可药用盐及其 制备方法和应用
  申请人：西南大学

  公开号：CN105218537B

  公开（公告）日：2017-01-11

  本发明公开了通式I所示的黄连素苯并咪唑类化合物或其可药用盐；还公开了该类化合物的制备方法，以黄连素为起始原料经去甲基化及还原反应得到9‑去甲基四氢黄连素，再在三氟乙酸溶液中与六次甲基四胺反应获得四氢黄连素醛，后者在DMF‑水溶液中与多种取代的邻苯二胺反应即可制得通式I所示化合物。本发明的黄连素苯并咪唑类化合物或其可药用盐对革兰阳性菌、革兰阴性菌、真菌都有一定抑制活性，可用于制备抗细菌和/或抗真菌类药物。通用分子式中R1、R2、R3和R4如权利要求书所定义。
• Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration
  作者：Ponmani Jeyakkumar、Han-Bo Liu、Lavanya Gopala、Yu Cheng、Xin-Mei Peng、Rong-Xia Geng、Cheng-He Zhou

  DOI：10.1016/j.bmcl.2017.02.071

  日期：2017.4

  were conveniently designed and efficiently synthesized from berberine via direct cyclization of tetrahydroprotoberberine aldehyde and o-phenylene diamines under metal-free aerobic oxidation. All the new compounds were characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The antimicrobial evaluation revealed that the 5-fluorobenzimidazolyl derivative 5b was the most active antibacterial and antifungal

  方便地设计了一系列新颖的苯并咪唑基四氢小ber碱，并通过在无金属的有氧氧化作用下四氢小ber碱醛和邻苯二胺的直接环化反应，从小efficiently碱中高效合成了这些新的苯并咪唑基四氢小ber碱。所有新化合物均通过IR，1H NMR，13C NMR和HRMS光谱进行了表征。抗菌评估显示，与小Ber碱，绿霉素，诺氟沙星和氟康唑相比，5-氟苯并咪唑基衍生物5b是最活跃的抗菌和抗真菌分子，其光谱范围广。即使经过15代，它也几乎没有引发针对MRSA的抗药性。进一步的研究表明，化合物5b不仅可以通过氢键与Topo IA有效相互作用，而且可以插入小牛胸腺DNA中并切割pBR322 DNA，
• 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。
• Discovery of novel, orally available benzimidazoles as melanin concentrating hormone receptor 1 (MCHR1) antagonists
  作者：Pradip K. Sasmal、Sanjita Sasmal、P. Tirumala Rao、B. Venkatesham、M. Roshaiah、Chandrasekhar Abbineni、Ish Khanna、Vikram P. Jadhav、J. Suresh、Rashmi Talwar、Syed Muzeeb、Jean-Marie Receveur、Thomas M. Frimurer、Øystein Rist、Lisbeth Elster、Thomas Högberg

  DOI：10.1016/j.bmcl.2010.07.086

  日期：2010.9

  Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays role in several disorders such as obesity, stress, depression and anxiety. The synthesis and biological evaluation of novel benzimidazole derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified. (c) 2010 Elsevier Ltd. All rights reserved.
• Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents
  作者：Ling Zhang、Dinesh Addla、Jeyakkumar Ponmani、Ao Wang、Dan Xie、Ya-Nan Wang、Shao-Lin Zhang、Rong-Xia Geng、Gui-Xin Cai、Shuo Li、Cheng-He Zhou

  DOI：10.1016/j.ejmech.2016.01.052

  日期：2016.3

  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.