7-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid | 1027237-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
• 英文别名: 7-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-6-fluoro-1-(4-methoxyphenyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 1027237-49-5
• 化学式: C₂₂H₂₃FN₄O₄
• 分子量: 426.447
• InChiKey: DSOQVNMHFIQIQV-BETUJISGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  95
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 7-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-6-fluoro-1-(4-hydroxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  A Prodrug Approach toward the Development of Water Soluble Fluoroquinolones and Structure−Activity Relationships of Quinoline-3-carboxylic Acids

  摘要：

  A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine g) at C-7 resulted in some of the most active analogues.

  DOI：

  10.1021/jm0497895
• 作为产物：
  描述：

  ethyl 2-(2,6-dichloro-5-fluoro-pyridine-3-carbonyl)-3-ethoxyacrylate 在 氢氧化钾 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 7-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-6-fluoro-1-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  A Prodrug Approach toward the Development of Water Soluble Fluoroquinolones and Structure−Activity Relationships of Quinoline-3-carboxylic Acids

  摘要：

  A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine g) at C-7 resulted in some of the most active analogues.

  DOI：

  10.1021/jm0497895

文献信息

• A Prodrug Approach toward the Development of Water Soluble Fluoroquinolones and Structure−Activity Relationships of Quinoline-3-carboxylic Acids
  作者：William R. Baker、Shaopei Cai、Martin Dimitroff、Liming Fang、Kay K. Huh、David R. Ryckman、Xiao Shang、Ribhi M. Shawar、Joseph H. Therrien

  DOI：10.1021/jm0497895

  日期：2004.9.1

  A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine g) at C-7 resulted in some of the most active analogues.