ethyl 1,4-dihydro-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline-1-[4-O-(phosphoric acid monobenzyl ester)phenyl]-3-carboxylate | 402923-54-0

• 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 1,4-dihydro-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline-1-[4-O-(phosphoric acid monobenzyl ester)phenyl]-3-carboxylate
• 英文别名: Ethyl 6-fluoro-1-[4-[hydroxy(phenylmethoxy)phosphoryl]oxyphenyl]-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylate
• CAS: 402923-54-0
• 化学式: C₃₀H₃₁FN₃O₇P
• 分子量: 595.564
• InChiKey: VOIKUEBVOFIWFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  ethyl 1,4-dihydro-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline-1-[4-O-(phosphoric acid monobenzyl ester)phenyl]-3-carboxylate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以81%的产率得到1,4-dihydro-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline-1-[4-O-(phosphoric acid monobenzyl ester)phenyl]-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 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 80.01h， 生成 ethyl 1,4-dihydro-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline-1-[4-O-(phosphoric acid monobenzyl ester)phenyl]-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

• 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.