2-(pyrrolidin-1-yl)ethyl 6-fluoro-7-methoxy-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate | 1373766-81-4

• 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: 2-(pyrrolidin-1-yl)ethyl 6-fluoro-7-methoxy-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate
• 英文别名: 2-pyrrolidin-1-ylethyl 6-fluoro-7-methoxy-4-oxo-2-(3-phenoxyphenyl)-1H-quinoline-3-carboxylate
• CAS: 1373766-81-4
• 化学式: C₂₉H₂₇FN₂O₅
• 分子量: 502.542
• InChiKey: GFAJHPAVCVHVEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  ethyl 4-chloro-6-fluoro-7-methoxyquinoline-3-carboxylate 在 四(三苯基膦)钯 、 水 、 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 potassium hydroxide 、 三溴氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.5h， 生成 2-(pyrrolidin-1-yl)ethyl 6-fluoro-7-methoxy-4-oxo-2-(3-phenoxyphenyl)-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

文献信息

• Lead Optimization of 3-Carboxyl-4(1<i>H</i>)-Quinolones to Deliver Orally Bioavailable Antimalarials
  作者：Yiqun Zhang、Julie A. Clark、Michele C. Connelly、Fangyi Zhu、Jaeki Min、W. Armand Guiguemde、Anupam Pradhan、Lalitha Iyer、Anna Furimsky、Jason Gow、Toufan Parman、Farah El Mazouni、Margaret A. Phillips、Dennis E. Kyle、Jon Mirsalis、R. Kiplin Guy

  DOI：10.1021/jm201642z

  日期：2012.5.10

  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.