ethyl 4-((4-((3-(4-ethylpiperazin-1-yl)propyl)amino)phenyl)amino)-6-(trifluoromethyl)quinoline-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 4-((4-((3-(4-ethylpiperazin-1-yl)propyl)amino)phenyl)amino)-6-(trifluoromethyl)quinoline-3-carboxylate
• 英文别名: ethyl 4-[4-[3-(4-ethylpiperazin-1-yl)propylamino]anilino]-6-(trifluoromethyl)quinoline-3-carboxylate
• 化学式: C₂₈H₃₄F₃N₅O₂
• 分子量: 529.605
• InChiKey: JXMKJNIOAIGALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  69.7
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl 4-((4-((3-(4-ethylpiperazin-1-yl)propyl)amino)phenyl)amino)-6-(trifluoromethyl)quinoline-3-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 以54%的产率得到4-((4-((3-(4-ethylpiperazin-1-yl)propyl)amino)phenyl)amino)-6-(trifluoromethyl)quinoline-3-carbohydrazide
  参考文献：
  名称：

  4-Aminoquinoline derivatives as novel Mycobacterium tuberculosis GyrB inhibitors: Structural optimization, synthesis and biological evaluation

  摘要：

  Mycobacterial DNA gyrase B subunit has been identified to be one of the potentially underexploited drug targets in the field of antitubercular drug discovery. In the present study, we employed structural optimization of the reported GyrB inhibitor resulting in synthesis of a series of 46 novel quinoline derivatives. The compounds were evaluated for their in vitro Mycobacterium smegmatis GyrB inhibitory ability and Mycobacterium tuberculosis DNA supercoiling inhibitory activity. The antitubercular activity of these compounds was tested over Mtb H37Rv strain and their safety profile was checked against mouse macrophage RAW 264.7 cell line. Among all, three compounds (23, 28, and 53) emerged to be active displaying IC50 values below 1 mu M against Msm GyrB and were found to be non-cytotoxic at 50 mu M concentration. Compound 53 was identified to be potent GyrB inhibitor with 0.86 +/- 0.16 mu M and an MIC (minimum inhibitory concentration) of 3.3 mu M. The binding affinity of this compound towards GyrB protein was analysed by differential scanning fluorimetry which resulted in a positive shift of 3.3 degrees C in melting temperature (T-m) when compared to the native protein thereby reacertaining the stabilization effect of the compound over protein. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.032
• 作为产物：
  描述：

  特定基氨基甲酸脂酶 在 potassium carbonate 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 ethyl 4-((4-((3-(4-ethylpiperazin-1-yl)propyl)amino)phenyl)amino)-6-(trifluoromethyl)quinoline-3-carboxylate
  参考文献：
  名称：

  4-Aminoquinoline derivatives as novel Mycobacterium tuberculosis GyrB inhibitors: Structural optimization, synthesis and biological evaluation

  摘要：

  Mycobacterial DNA gyrase B subunit has been identified to be one of the potentially underexploited drug targets in the field of antitubercular drug discovery. In the present study, we employed structural optimization of the reported GyrB inhibitor resulting in synthesis of a series of 46 novel quinoline derivatives. The compounds were evaluated for their in vitro Mycobacterium smegmatis GyrB inhibitory ability and Mycobacterium tuberculosis DNA supercoiling inhibitory activity. The antitubercular activity of these compounds was tested over Mtb H37Rv strain and their safety profile was checked against mouse macrophage RAW 264.7 cell line. Among all, three compounds (23, 28, and 53) emerged to be active displaying IC50 values below 1 mu M against Msm GyrB and were found to be non-cytotoxic at 50 mu M concentration. Compound 53 was identified to be potent GyrB inhibitor with 0.86 +/- 0.16 mu M and an MIC (minimum inhibitory concentration) of 3.3 mu M. The binding affinity of this compound towards GyrB protein was analysed by differential scanning fluorimetry which resulted in a positive shift of 3.3 degrees C in melting temperature (T-m) when compared to the native protein thereby reacertaining the stabilization effect of the compound over protein. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.032