N-(4-(2-ethyl-6-methyl-1H-benzo[d]imidazol-1-yl)butyl)-2,4-dimethylaniline

• 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-(4-(2-ethyl-6-methyl-1H-benzo[d]imidazol-1-yl)butyl)-2,4-dimethylaniline
• 英文别名: N-[4-(2-ethyl-6-methyl-benzimidazol-1-yl)butyl]-2,4-dimethyl-aniline；N-[4-(2-ethyl-6-methylbenzimidazol-1-yl)butyl]-2,4-dimethylaniline
• 化学式: C₂₂H₂₉N₃
• 分子量: 335.492
• InChiKey: KNRKNQLZMOBCTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (9ci)-2-乙基-5-甲基-1H-苯并咪唑 在 potassium carbonate 、 sodium iodide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 N-(4-(2-ethyl-6-methyl-1H-benzo[d]imidazol-1-yl)butyl)-2,4-dimethylaniline
  参考文献：
  名称：

  Identification of Phenoxyalkylbenzimidazoles with Antitubercular Activity

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00546

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.