ethyl 6,7-difluoro-1,4-dihydro-1-(4-hydroxyphenyl)-4-oxoquinoline-3-carboxylate | 108138-19-8

• 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 6,7-difluoro-1,4-dihydro-1-(4-hydroxyphenyl)-4-oxoquinoline-3-carboxylate
• 英文别名: Ethyl 6,7-difluoro-1-(4-hydroxyphenyl)-4-oxoquinoline-3-carboxylate
• CAS: 108138-19-8
• 化学式: C₁₈H₁₃F₂NO₄
• 分子量: 345.302
• InChiKey: TWALDZNXNNOZRM-UHFFFAOYSA-N

物化性质

• 沸点：
  523.6±50.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 6,7-difluoro-1,4-dihydro-1-(4-hydroxyphenyl)-4-oxoquinoline-3-carboxylate 在 盐酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 108.0h， 生成 6-Fluoro-1-(4-hydroxyphenyl)-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-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：

  2,4,5-三氟苯甲酰氯 在 乙酸酐 、 potassium carbonate 、 三乙胺 、 magnesium chloride 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 43.67h， 生成 ethyl 6,7-difluoro-1,4-dihydro-1-(4-hydroxyphenyl)-4-oxoquinoline-3-carboxylate
  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

• Glycosylation of Fluoroquinolones through Direct and Oxygenated Polymethylene Linkages as a Sugar-Mediated Active Transport System for Antimicrobials
  作者：Michael E. Jung、Eric C. Yang、Binh T. Vu、Mehrak Kiankarimi、Emmanouil Spyrou、Jon Kaunitz

  DOI：10.1021/jm990015b

  日期：1999.9.1

  We report herein the synthesis and biological testing of several glycosylated derivatives of some fluoroquinolone antibiotics. In particular, we have prepared several glycosylated derivatives of ciprofloxacin (2) in which the carbohydrate units are linked to the free secondary amine of the piperazine unit by: (a) no linker (e.g., a glycosylamine), (b) a beta-oxyethyl linker, and (c) a gamma-oxypropyl

  我们在这里报告了一些氟喹诺酮类抗生素的几种糖基化衍生物的合成和生物学测试。特别是，我们制备了环丙沙星（2）的几种糖基化衍生物，其中的碳水化合物单元通过以下方式与哌嗪单元的游离仲胺连接：（a）无接头（例如糖胺），（b）β-氧乙基接头，和（c）γ-氧丙基接头。葡萄糖和半乳糖都被用作碳水化合物，因此制备了六种这种类型的化合物，例如没有接头4a，b，氧乙基接头5a，b和氧丙基接头6a，b。另外，由活性的1-（4-羟苯基）氟喹诺酮（3）制备了葡萄糖和半乳糖的芳基糖苷（7a，b）。糖基胺4a的合成，b涉及葡萄糖和半乳糖与环丙沙星盐酸盐的直接缩合（2）。对于氧烷基连接的化合物，我们首先制备了全乙酰化的ω-溴烷基糖吡喃糖苷14a，b和15a，b，然后将它们与环丙沙星的烯丙基酯（11）偶联，在皂化除去所有酯后得到所需的酯。氟喹诺酮类碳水化合物5a，b和6a，b。由2,4,5-三氟苯甲酰氯（22）制备最终的系