7-(4-(2,2-bis-(diethoxy-phosphoryl)-ethyl)-piperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 186899-47-8

• 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: 7-(4-(2,2-bis-(diethoxy-phosphoryl)-ethyl)-piperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-{4-[2,2-bis(diethoxyphosphoryl)ethyl]piperacin-1-yl}-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid；7-[4-[2,2-bis(diethoxyphosphoryl)ethyl]piperazin-1-yl]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 186899-47-8
• 化学式: C₂₆H₄₀FN₃O₉P₂
• 分子量: 619.564
• InChiKey: USFNKTLYJLNEEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.84
• 重原子数：
  41.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  136.84
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  7-(4-(2,2-bis-(diethoxy-phosphoryl)-ethyl)-piperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 三甲基溴硅烷 作用下， 以 氯仿 为溶剂， 反应 4.0h， 以92%的产率得到7-{4-[2,2-bis(phosphono)ethyl]piperacin-1-yl}-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  QUINOLONE ANTIBACTERIAL AGENTS LINKED TO OSTEOTROPIC BISPHOSPHONATE MOIETIES

  摘要：

  Bisphosphonates are widely used in diagnosis and therapy of different bone diseases. Due to their potential to accumulate in the inorganic bone matrix hydroxylapatite they are useful agents in osteotic vectorization of different types of drugs. We linked bisphosphonate moieties to antibacterial quinolones like norfloxacin to enable a selective targeting of these agents to bone tissue. The quinolones (1,4-dihydro-4-oxo-quinoline-3-carboxylic acids) were modified at position 1 and 7 using alkylbisphosphonates with ethene-, amino- and carboxylic-groups. After coupling with the quinolones, the alkylbisphosphonic esters could smoothly be hydrolyzed via the corresponding silyl esters to obtain the free bisphosphonic acids.

  DOI：

  10.1080/10426500108040581
• 作为产物：
  描述：

  1,1-双(二乙氧基磷酰基)乙烯 、 诺氟沙星 以 氯仿 为溶剂， 反应 1.0h， 以73%的产率得到7-(4-(2,2-bis-(diethoxy-phosphoryl)-ethyl)-piperazin-1-yl)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  QUINOLONE ANTIBACTERIAL AGENTS LINKED TO OSTEOTROPIC BISPHOSPHONATE MOIETIES

  摘要：

  Bisphosphonates are widely used in diagnosis and therapy of different bone diseases. Due to their potential to accumulate in the inorganic bone matrix hydroxylapatite they are useful agents in osteotic vectorization of different types of drugs. We linked bisphosphonate moieties to antibacterial quinolones like norfloxacin to enable a selective targeting of these agents to bone tissue. The quinolones (1,4-dihydro-4-oxo-quinoline-3-carboxylic acids) were modified at position 1 and 7 using alkylbisphosphonates with ethene-, amino- and carboxylic-groups. After coupling with the quinolones, the alkylbisphosphonic esters could smoothly be hydrolyzed via the corresponding silyl esters to obtain the free bisphosphonic acids.

  DOI：

  10.1080/10426500108040581

文献信息

• Osteoadsorptive Bisphosphonate Derivatives of Fluoroquinolone Antibacterials
  作者：Pál Herczegh、Thomas B. Buxton、James C. McPherson、Árpád Kovács-Kulyassa、Phyllis D. Brewer、Ferenc Sztaricskai、Gary G. Stroebel、Kent M. Plowman、Dan Farcasiu、John F. Hartmann

  DOI：10.1021/jm0105326

  日期：2002.5.1

  Bisphosphonates conjugated to fluoroquinolone antibacterials through an intermediate carbon had better activity than conjugates lacking the carbon. Virtually all molar-based activity of these esterified bisphosphonate derivatives was identical to that of its parent. De-esterified free-acid forms retained good activity against most Gram-negative bacteria, but not against Gram-positives. A free-acid derivative remained bound to washed bone and completely inhibited Staphylococcus aureus growth. The more potent parent, ciprofloxacin, failed to bind significantly, and bacterial growth occurred.