1-(4-bromobutyl)-2-ethyl-1H-benzo[d]imidazole

• 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-bromobutyl)-2-ethyl-1H-benzo[d]imidazole
• 英文别名: 1-(4-Bromobutyl)-2-ethylbenzimidazole
• 化学式: C₁₃H₁₇BrN₂
• 分子量: 281.195
• InChiKey: WAKGFBZAOJQWCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  1-(4-bromobutyl)-2-ethyl-1H-benzo[d]imidazole 、 2-萘硫醇 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到2-ethyl-1-(4-(naphthalen-2-ylthio)butyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Improved Phenoxyalkylbenzimidazoles with Activity against Mycobacterium tuberculosis Appear to Target QcrB

  摘要：

  The phenoxy alkyl benzimidazoles (PABs) have good antitubercular activity. We expanded our structure activity relationship studies to determine the core components of PABs required for activity. The most potent compounds had minimum inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar range with very little cytotoxicity against eukaryotic cells as well as activity against intracellular bacteria. We isolated resistant mutants against PAB compounds, which had mutations in either Rvl 339, of unknown function, or ticrB, a component of the cytochrome b(c1) oxidase of the electron transport chain. QcrB mutant strains were resistant to all PAB compounds, whereas Rv1339 mutant strains were only resistant to a subset, suggesting that QcrB is the target. The discovery of the target for PAB compounds will allow for the improved design of novel compounds to target intracellular M. tuberculosis.

  DOI：

  10.1021/acsinfecdis.7b00112
• 作为产物：
  描述：

  邻苯二胺 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 生成 1-(4-bromobutyl)-2-ethyl-1H-benzo[d]imidazole
  参考文献：
  名称：

  Improved Phenoxyalkylbenzimidazoles with Activity against Mycobacterium tuberculosis Appear to Target QcrB

  摘要：

  The phenoxy alkyl benzimidazoles (PABs) have good antitubercular activity. We expanded our structure activity relationship studies to determine the core components of PABs required for activity. The most potent compounds had minimum inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar range with very little cytotoxicity against eukaryotic cells as well as activity against intracellular bacteria. We isolated resistant mutants against PAB compounds, which had mutations in either Rvl 339, of unknown function, or ticrB, a component of the cytochrome b(c1) oxidase of the electron transport chain. QcrB mutant strains were resistant to all PAB compounds, whereas Rv1339 mutant strains were only resistant to a subset, suggesting that QcrB is the target. The discovery of the target for PAB compounds will allow for the improved design of novel compounds to target intracellular M. tuberculosis.

  DOI：

  10.1021/acsinfecdis.7b00112

文献信息

• Identification of Phenoxyalkylbenzimidazoles with Antitubercular Activity
  作者：N. Susantha Chandrasekera、Torey Alling、Mai A. Bailey、Megan Files、Julie V. Early、Juliane Ollinger、Yulia Ovechkina、Thierry Masquelin、Prashant V. Desai、Jeffrey W. Cramer、Philip A. Hipskind、Joshua O. Odingo、Tanya Parish

  DOI：10.1021/acs.jmedchem.5b00546

  日期：2015.9.24

  We conducted an evaluation of the phenoxyalkylbenzimidazole series based on the exemplar 2-ethyl-1-(3-phenoxypropyl)-1H-benzo[d]imidazole for its antitubercular activity. Four segments of the molecule were examined systematically to define a structure activity relationship with respect to biological activity. Compounds had submicromolar activity against Mycobacterium tuberculosis; the most potent compound had a minimum inhibitory concentration (MIC) of 52 nM and was not cytotoxic against eukaryotic cells (selectivity index = 523). Compounds were selective for M. tuberculosis over other bacterial species, including the closely related Mycobacterium smegmatis. Compounds had a bacteriostatic effect against aerobically grown, replicating M. tuberculosis, but were bactericidal against nonreplicating bacteria. Representative compounds had moderate to high permeability in MDCK cells, but were rapidly metabolized in rodents and human liver microsomes, suggesting the possibility of rapid in vivo hepatic clearance mediated by oxidative metabolism. These results indicate that the readily synthesized phenoxyalkylbenzimidazoles are a promising class of potent and selective antitubercular agents, if the metabolic liability can be solved.
• Improved Phenoxyalkylbenzimidazoles with Activity against <i>Mycobacterium tuberculosis</i> Appear to Target QcrB
  作者：N. Susantha Chandrasekera、Bryan J. Berube、Gauri Shetye、Somsundaram Chettiar、Theresa O’Malley、Alyssa Manning、Lindsay Flint、Divya Awasthi、Thomas R. Ioerger、James Sacchettini、Thierry Masquelin、Philip A. Hipskind、Joshua Odingo、Tanya Parish

  DOI：10.1021/acsinfecdis.7b00112

  日期：2017.12.8

  The phenoxy alkyl benzimidazoles (PABs) have good antitubercular activity. We expanded our structure activity relationship studies to determine the core components of PABs required for activity. The most potent compounds had minimum inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar range with very little cytotoxicity against eukaryotic cells as well as activity against intracellular bacteria. We isolated resistant mutants against PAB compounds, which had mutations in either Rvl 339, of unknown function, or ticrB, a component of the cytochrome b(c1) oxidase of the electron transport chain. QcrB mutant strains were resistant to all PAB compounds, whereas Rv1339 mutant strains were only resistant to a subset, suggesting that QcrB is the target. The discovery of the target for PAB compounds will allow for the improved design of novel compounds to target intracellular M. tuberculosis.