6-Fluoro-1-[4-(methoxymethoxy)phenyl]-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid | 402923-40-4

• 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: 6-Fluoro-1-[4-(methoxymethoxy)phenyl]-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
• CAS: 402923-40-4
• 化学式: C₂₃H₂₄FN₃O₅
• 分子量: 441.459
• InChiKey: BNHSSMIHFVQIBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-Fluoro-1-[4-(methoxymethoxy)phenyl]-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydride 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 Benzyl 1-[4-bis(phenylmethoxy)phosphoryloxyphenyl]-6-fluoro-7-(4-methylpiperazin-1-yl)-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
• 作为产物：
  描述：

  4-(甲氧基甲氧基)苯胺 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 6.17h， 生成 6-Fluoro-1-[4-(methoxymethoxy)phenyl]-7-(4-methylpiperazin-1-yl)-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

文献信息

• QUINOLINE ANTIBACTERIAL COMPOUNDS AND METHODS OF USE THEREOF
  申请人：CHIRON CORPORATION

  公开号：EP1313708A1

  公开（公告）日：2003-05-28
• [EN] QUINOLINE ANTIBACTERIAL COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSES DE QUINOLINE ANTIBACTERIENS ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：CHIRON CORP

  公开号：WO2002018345A1

  公开（公告）日：2002-03-07

  Methods, compounds and compositions are provided for inhibiting the growth of pathogenic microbes in vitro and of treatment of pathogenic bacterial infections in vivo using novel antibacterial quinoline compounds.
• 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.