Ethyl 1-cyclopropyl-6-fluoro-4-oxo-7-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]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 1-cyclopropyl-6-fluoro-4-oxo-7-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]quinoline-3-carboxylate
• 英文别名: ethyl 1-cyclopropyl-6-fluoro-4-oxo-7-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]quinoline-3-carboxylate
• 化学式: C₂₆H₂₅F₄N₃O₅S
• 分子量: 567.561
• InChiKey: UUXCFISUJNJLSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  39.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  88.92
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  3-Cyclopropylamino-2-(2,4,5-trifluorbenzoyl)acrylsaeure-ethylester 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 189.0h， 生成 Ethyl 1-cyclopropyl-6-fluoro-4-oxo-7-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]quinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity

  摘要：

  Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacinbased hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 +/- 1.2 nM and 25.52 +/- 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 mu M and 1 mu M, respectively.

  DOI：

  10.1021/acsmedchemlett.0c00196

文献信息

• Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity
  作者：Srikanta Dana、Praveesh Valissery、Sharvan Kumar、Sumiran Kumar Gurung、Neelima Mondal、Suman Kumar Dhar、Pritam Mukhopadhyay

  DOI：10.1021/acsmedchemlett.0c00196

  日期：2020.7.9

  Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacinbased hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 +/- 1.2 nM and 25.52 +/- 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 mu M and 1 mu M, respectively.