ethyl 2-(3-((4,5-dimethylthiazol-2-yl)methyl)phenyl)-6-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate | 1373767-74-8

• 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 2-(3-((4,5-dimethylthiazol-2-yl)methyl)phenyl)-6-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 2-[3-[(4,5-dimethylthiazol-2-yl)methyl]phenyl]-6-fluoro-7-methoxy-4-oxo-1H-quinoline-3-carboxylate；ethyl 2-[3-[(4,5-dimethyl-1,3-thiazol-2-yl)methyl]phenyl]-6-fluoro-7-methoxy-4-oxo-1H-quinoline-3-carboxylate
• CAS: 1373767-74-8
• 化学式: C₂₅H₂₃FN₂O₄S
• 分子量: 466.533
• InChiKey: AWRARLHFZUAXOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氟-3-甲氧基苯胺 在 四(三苯基膦)钯 、 caesium carbonate 、 溶剂黄146 、 间氯过氧苯甲酸 、 三氯氧磷 、 三溴氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 、 乙醇 、 氯仿 、 水 为溶剂， 反应 14.0h， 生成 ethyl 2-(3-((4,5-dimethylthiazol-2-yl)methyl)phenyl)-6-fluoro-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

  摘要：

  Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

  DOI：

  10.1021/jm201642z