N-((1H-benzo[d]imidazol-2-yl)methyl)-4-fluoroaniline | 73259-31-1

• 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-((1H-benzo[d]imidazol-2-yl)methyl)-4-fluoroaniline
• 英文别名: N-(1H-benzoimidazol-2-ylmethyl)-4-fluoro-aniline；N-(1H-benzimidazol-2-ylmethyl)-4-fluoroaniline
• CAS: 73259-31-1
• 化学式: C₁₄H₁₂FN₃
• 分子量: 241.268
• InChiKey: WRVUICYHHFPLKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 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：
  40.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-(6-bromohexyloxy)-4-methyl-2H-chromen-2-one 、 N-((1H-benzo[d]imidazol-2-yl)methyl)-4-fluoroaniline 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以39.6%的产率得到7-(6-(((1H-benzo[d]imidazol-2-yl)methyl)(4-fluorophenyl)amino)hexyloxy)-4-methyl-2H-chromen-2-one
  参考文献：
  名称：

  Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole

  摘要：

  A novel series of benzimidazole type of Fluconazole analogues were synthesized and characterized by H-1 NMR, C-13 NMR, IR, MS and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by two-fold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles gave comparable or even stronger antibacterial and antifungal efficiency in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5m and its hydrochloride 7 respectively with antibacterial Chloromycin, Norfloxacin or antifungal Fluconazole showed better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separated use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive Aspergillus flavus and methicillin-resistant MRSA. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.049
• 作为产物：
  描述：

  邻苯二胺 在 盐酸 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 N-((1H-benzo[d]imidazol-2-yl)methyl)-4-fluoroaniline
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

  摘要：

  一系列新的苯并咪唑衍生物被合成并通过红外（IR）、氢核磁共振（1H NMR）、碳核磁共振（13C NMR）、质谱（MS）和高效液相色谱（HRMS）谱图进行了表征。所有新化合物通过两倍系列稀释技术在体外进行了抗微生物活性筛选。生物活性评估显示，3,5-双(三氟甲基)苯基苯并咪唑的抗菌和抗真菌活性与参考药物氯霉素、诺氟沙星和氟康唑相当或更强。2,4-二氟苄基苯并咪唑衍生物5l及其盐酸盐7分别与抗菌药物氯霉素、诺氟沙星和抗真菌药物氟康唑的联合使用，对耐甲氧西林的金黄色葡萄球菌（MRSA）和氟康唑不敏感的黄曲霉菌（A. flavus）更为敏感。此外，化合物5l与小牛胸腺DNA的相互作用表明，该化合物能有效嵌入DNA中形成化合物5l-DNA复合物，可能阻断DNA复制，从而发挥良好的抗微生物活性。

  DOI：

  10.1007/s11426-014-5087-x

文献信息

• Novel tertiary sulfonamide derivatives containing benzimidazole moiety as potent anti-gastric cancer agents: Design, synthesis and SAR studies
  作者：Jian-Song、Qiu-Lei Gao、Bo-Wen Wu、Dong Li、Lei Shi、Ting Zhu、Jian-Feng Lou、Cheng-Yun Jin、Yan-Bing Zhang、Sai-Yang Zhang、Hong-Min Liu

  DOI：10.1016/j.ejmech.2019.111731

  日期：2019.12

  With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more

  期望找到具有高效率和选择性的新型抗胃癌药物，合成了一系列新型的叔磺酰胺衍生物，并在三种选定的癌细胞系（MGC-803，PC-3， MCF-7）体外。一些合成的化合物可以显着抑制这些经过测试的癌细胞的增殖，并且比阳性对照（5-Fu）更有效。本报告探讨了叔磺酰胺衍生物的构效关系。在测试的化合物中，含苯并咪唑部分的化合物13g对MGC-803细胞（IC50 = 1.02μM），HGC-27细胞（IC50 = 1.61μM），SGC-7901（IC50 = 2.30μM）细胞表现出最佳的抗增殖活性以及癌细胞与正常细胞之间的良好选择性。细胞机制研究阐明了化合物13g抑制胃癌细胞株的集落形成。同时，化合物13g将细胞周期阻滞在G2 / M期并诱导细胞凋亡。从机理上讲，化合物13g显着降低p-Akt和pc-Raf表达，这表明化合物13g通过干扰AKT / mTOR和RAS / Raf / MEK / E
• 10.1021/acs.joc.4c00902
  作者：He, Shiyun、Liu, Xingyu、Lv, Guanghui、Fan, Hongying、Zhang, Xue、Ren, Yun、Luo, Wei、Hai, Li、Wu, Yong

  DOI：10.1021/acs.joc.4c00902

  日期：——

  A visible-light-induced radical–radical cross-coupling reaction between 1,3,4-oxadiazoles and hydroxamic acid derivatives has been realized under base- and metal-free conditions. The protocol was characterized by broad substrate scope, excellent functional group tolerance, and simple operation procedures. By using this protocol, a variety of biologically important 5-aryl-1,3,4-oxadiazole-2-methylamines

  在无碱和无金属条件下，实现了 1,3,4-恶二唑和异羟肟酸衍生物之间的可见光诱导的自由基-自由基交叉偶联反应。该方案具有底物范围广、官能团耐受性好、操作步骤简单等特点。通过使用该方案，以良好的收率和优异的化学选择性获得了多种具有生物学重要意义的5-芳基-1,3,4-恶二唑-2-甲胺。
• A unique one-pot reaction via CC cleavage from aminomethylene benzimidazoles to access benzimidazolones with wide potentiality
  作者：Hui-Zhen Zhang、Sheng-Feng Cui、Sangaraiah Nagarajan、Syed Rasheed、Gui-Xin Cai、Cheng-He Zhou

  DOI：10.1016/j.tetlet.2014.05.113

  日期：2014.7

  A unique one-pot reaction via C-C cleavage from aminomethylene benzimidazoles with commercial halides to access novel benzimidazolones is reported for the first time. The previously unexploited transformation is able to perform smoothly in the presence of commercial potassium carbonate, while the stronger inorganic bases or organic amines as catalysts are not favorable to the transformation. Significant influential factors including base, temperature, solvent, water content, and molar ratio of substrates to this reaction are investigated, and possibly mechanistic consideration is also discussed. Some synthesized benzimidazolones were evaluated and exhibited better bioactivities against tested strains than clinical drugs chloromycin, norfloxacin, and fluconazole. (C) 2014 Elsevier Ltd. All rights reserved.
• Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole
  作者：Hui-Zhen Zhang、Guri L.V. Damu、Gui-Xin Cai、Cheng-He Zhou

  DOI：10.1016/j.ejmech.2013.03.049

  日期：2013.6

  A novel series of benzimidazole type of Fluconazole analogues were synthesized and characterized by H-1 NMR, C-13 NMR, IR, MS and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by two-fold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles gave comparable or even stronger antibacterial and antifungal efficiency in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5m and its hydrochloride 7 respectively with antibacterial Chloromycin, Norfloxacin or antifungal Fluconazole showed better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separated use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive Aspergillus flavus and methicillin-resistant MRSA. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs
  作者：HuiZhen Zhang、JianMei Lin、Syed Rasheed、ChengHe Zhou

  DOI：10.1007/s11426-014-5087-x

  日期：2014.6

  A series of new benzimidazole derivatives was synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.

  一系列新的苯并咪唑衍生物被合成并通过红外（IR）、氢核磁共振（1H NMR）、碳核磁共振（13C NMR）、质谱（MS）和高效液相色谱（HRMS）谱图进行了表征。所有新化合物通过两倍系列稀释技术在体外进行了抗微生物活性筛选。生物活性评估显示，3,5-双(三氟甲基)苯基苯并咪唑的抗菌和抗真菌活性与参考药物氯霉素、诺氟沙星和氟康唑相当或更强。2,4-二氟苄基苯并咪唑衍生物5l及其盐酸盐7分别与抗菌药物氯霉素、诺氟沙星和抗真菌药物氟康唑的联合使用，对耐甲氧西林的金黄色葡萄球菌（MRSA）和氟康唑不敏感的黄曲霉菌（A. flavus）更为敏感。此外，化合物5l与小牛胸腺DNA的相互作用表明，该化合物能有效嵌入DNA中形成化合物5l-DNA复合物，可能阻断DNA复制，从而发挥良好的抗微生物活性。