ethyl 1-cyclopropyl-7-(4-(((2,4-diaminopyrimidin-5-yl)methoxy)methyl)-1H-1,2,3-triazol-1-yl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate | 1367348-76-2

• 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: ethyl 1-cyclopropyl-7-(4-(((2,4-diaminopyrimidin-5-yl)methoxy)methyl)-1H-1,2,3-triazol-1-yl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate
• CAS: 1367348-76-2
• 化学式: C₂₂H₂₂FN₉O₄
• 分子量: 495.473
• InChiKey: PNYSEKZLCMFCDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  178.95
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  ethyl 1-cyclopropyl-7-(4-(((2,4-diaminopyrimidin-5-yl)methoxy)methyl)-1H-1,2,3-triazol-1-yl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以54%的产率得到1-cyclopropyl-7-(4-(((2,4-diaminopyrimidin-5-yl)methoxy)methyl)-1H-1,2,3-triazol-1-yl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Structure aided design of chimeric antibiotics

  摘要：

  The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.019
• 作为产物：
  描述：

  2,4-二氨基-5-羟甲基嘧啶 在 氢溴酸 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 甲醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 ethyl 1-cyclopropyl-7-(4-(((2,4-diaminopyrimidin-5-yl)methoxy)methyl)-1H-1,2,3-triazol-1-yl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Structure aided design of chimeric antibiotics

  摘要：

  The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.019