1-(4-chlorobenzyl)-2-(chloromethyl)-1H-benzo[d]imidazole | 7189-18-6

• 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: 1-(4-chlorobenzyl)-2-(chloromethyl)-1H-benzo[d]imidazole
• 英文别名: 2-(chloromethyl)-1-(4-chlorobenzyl)-1H-benzo[d] imidazole；1-(4-Chlorbenzyl)-2-chlormethylbenzimidazol；1-(4-chloro-benzyl)-2-chloromethyl-1H-benzoimidazole；1-(4-chloro-benzyl)-2-chloromethyl-1H-benzimidazole；1-(4-Chlor-benzyl)-2-chlormethyl-1H-benzimidazol；2-chloromethyl-1-(4-chlorobenzyl)-1H-benzimidazole；1-(4-chloro-benzyl)-2-chloromethyl-1H-benzoimidazole；2-(chloromethyl)-1-[(4-chlorophenyl)methyl]benzimidazole
• CAS: 7189-18-6
• 化学式: C₁₅H₁₂Cl₂N₂
• mdl: MFCD12740377
• 分子量: 291.18
• InChiKey: ANBWYOCAUUGZBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 储存条件：
  存储条件：2-8℃，干燥且密封保存。

反应信息

• 作为反应物：
  描述：

  1-(4-chlorobenzyl)-2-(chloromethyl)-1H-benzo[d]imidazole 以49的产率得到吡咯咪唑
  参考文献：
  名称：

  [EN] BENZIMIDAZOLE MODULATORS OF H1 RECEPTOR AND/OR NS4B PROTEIN ACTIVITY
  [FR] MODULATEURS DE L'ACTIVITÉ DES RÉCEPTEURS H1 ET/OU DE LA PROTÉINE NS4B À BASE DE BENZIMIDAZOLE

  摘要：

  本发明涉及新的苯并咪唑H1受体活性调节剂和/或NS4B蛋白活性抑制剂，其制药组合物和使用方法，公式（I）。

  公开号：

  WO2010118286A2
• 作为产物：
  描述：

  N-(对氯苄基)-2-硝基苯胺 在 盐酸 、 乙醇 、 镍 作用下， 生成 1-(4-chlorobenzyl)-2-(chloromethyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Jerchel et al., Justus Liebigs Annalen der Chemie, 1952, vol. 575, p. 162,167

  摘要：

  DOI：

文献信息

• Evaluation of Cytotoxic Activity of New Benzimidazole-Piperazine Hybrids Against Human MCF-7 and A549 Cancer Cells
  作者：Aysun Özdemir、Sümeyye Turanli、Burcu Çalişkan、Mustafa Arka、Erden Banoglu

  DOI：10.1007/s11094-020-02119-9

  日期：2020.2

  A series of benzimidazole-piperazine hybrids (14 – 37) were designed, synthesized and evaluated for their cytotoxic activity against human lung (A549) and breast (MCF-7) cancer cell lines. Preliminary evaluation revealed that most of these hybrid molecules (i.e., 16 – 25) exhibited noteworthy and preferential antiproliferative effect against human lung cancer (A549) with IC50 values of 2.8 – 7.8 μM. Among the synthesized molecules, compound 17 showed the most balanced cytotoxic effect against lung (A549) and breast (MCF-7) cancer cells with IC50 values of 5.4 and 4.2 μM, respectively. To explore the mechanistic aspects fundamental to the observed activity, further biological studies of compounds 16, 17 and 22 were carried out. In addition, these compounds induced PARP-1 cleavage and caspase 7 activation, caused morphological changes such as bleb formation in the treated cells, and significantly increased the nuclear fragmentation. Taken all together, our findings indicate that cytotoxic activities of newly synthesized benzimidazole-piperazine hybrids are mediated through the apoptotic cell death induction. These benzimidazole derivatives have the potential for further development as anticancer agents.

  一系列苯并咪唑-哌嗪杂化物（14-37）被设计、合成并评估其对人肺（A549）和乳腺（MCF-7）癌细胞系的细胞毒性活性。初步评估显示，大多数这些杂化分子（即16-25）对人肺癌（A549）表现出显著且优先的抗增殖效果，IC50值为2.8-7.8 μM。在合成的分子中，化合物17对肺（A549）和乳腺（MCF-7）癌细胞的细胞毒性效果最为均衡，IC50值分别为5.4和4.2 μM。为了探讨与观察到的活性相关的机制方面，进一步对化合物16、17和22进行了生物学研究。此外，这些化合物诱导了PARP-1裂解和凋亡酶7激活，造成处理细胞的形态变化，如气泡形成，并显著增加了核碎裂。综合来看，我们的研究结果表明，新合成的苯并咪唑-哌嗪杂化物的细胞毒性活性是通过诱导凋亡细胞死亡介导的。这些苯并咪唑衍生物具有进一步开发作为抗癌药物的潜力。
• 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。
• [EN] DEUTERIUM MODIFIED BENZIMIDAZOLES<br/>[FR] BENZIMIDAZOLES
  申请人：CONCERT PHARMACEUTICALS INC

  公开号：WO2010132810A1

  公开（公告）日：2010-11-18

  This invention relates to derivatives of 1-(p-chIorobenzyI)-2-(1-pyrrolidinylmethyl)benzimidazole according to Formula I wherein at least one Y is deuterium described herein and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering an inhibitor of hepatitis C virus (HCV) RNA replication.

  本发明涉及根据式I的1-(对氯苯基)-2-(1-吡咯烷甲基)苯并咪唑的衍生物，其中至少一个Y是本文描述的氘及其药学上可接受的盐。本发明还提供包含本发明化合物的组合物，并将这些组合物用于治疗通过给予丙型肝炎病毒（HCV）RNA复制抑制剂有益治疗的疾病和症状的方法。
• Antiulcer fused imidazole compounds
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04563455A1

  公开（公告）日：1986-01-07

  New fused imidazole compounds of the formula: ##STR1## wherein A is lower alkylene, R.sup.1 is hydrogen, lower alkyl, lower alkoxy or halogen, R.sup.2 is hydrogen, lower alkyl, cyclo(lower)alkyl, pyridyl, ar(lower)alkyl which may be substituted with halogen, or aryl which may be substituted with lower alkyl, lower alkoxy, hydroxy or halogen, R.sup.3 is N-containing unsaturated heterocyclic group which may be substituted with lower alkyl or amino, and Y is .dbd.C-- or .dbd.N--, and pharmaceutically acceptable salts thereof, and processes for preparation thereof and pharmaceutical composition comprising the same. These derivatives and salts thereof are useful as antiulcer agents.

  新的融合咪唑化合物的化学式如下：##STR1## 其中A为较低的烷基，R.sup.1为氢、较低的烷基、较低的烷氧基或卤素，R.sup.2为氢、较低的烷基、环(较低)烷基、吡啶基、含氮的不饱和杂环基，可以用卤素取代的芳基或被较低的烷基、较低的烷氧基、羟基或卤素取代的芳基，R.sup.3为可能用较低的烷基或氨基取代的含氮不饱和杂环基，Y为.dbd.C--或.dbd.N--，以及其药学上可接受的盐，以及其制备方法和包含它们的药物组合物。这些衍生物及其盐可用作抗溃疡药物。
• 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。