2-benzyl-3-methyl-5-(2-(1-methylpiperidin-2-yl)ethyl)-1-oxo-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile

• 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: 2-benzyl-3-methyl-5-(2-(1-methylpiperidin-2-yl)ethyl)-1-oxo-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile
• 英文别名: 2-Benzyl-3-methyl-5-[2-(1-methylpiperidin-2-yl)ethyl]-1-oxopyrido[1,2-a]benzimidazole-4-carbonitrile；2-benzyl-3-methyl-5-[2-(1-methylpiperidin-2-yl)ethyl]-1-oxopyrido[1,2-a]benzimidazole-4-carbonitrile
• 化学式: C₂₈H₃₀N₄O
• 分子量: 438.572
• InChiKey: YIMOVOMAUJHSCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  50.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氰甲基苯并咪唑 、 2-苄基乙酰乙酸乙酯 在 ammonium acetate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 25.75h， 生成 2-benzyl-3-methyl-5-(2-(1-methylpiperidin-2-yl)ethyl)-1-oxo-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile
  参考文献：
  名称：

  Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy

  摘要：

  Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.

  DOI：

  10.1021/acs.jmedchem.5b00428

文献信息

• Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy
  作者：Marco Pieroni、Diana Machado、Elisa Azzali、Sofia Santos Costa、Isabel Couto、Gabriele Costantino、Miguel Viveiros

  DOI：10.1021/acs.jmedchem.5b00428

  日期：2015.8.13

  Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.