7-azido-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid | 1367348-75-1

• 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: 7-azido-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
• 英文别名: 1-cyclopropyl-6-fluoro-7-azido[1,8]naphthyridin-4(1H)-one-3-carboxylic acid；7-Azido-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 1367348-75-1
• 化学式: C₁₂H₈FN₅O₃
• 分子量: 289.226
• InChiKey: QCFMIAFPKAFKQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-azido-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid 、 3-溴丙炔 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 正丁醇 为溶剂， 以76%的产率得到1-cyclopropyl-6-fluoro-7-(4-bromomethyl-[1,2,3] triazol-1-yl)-[1,8]naphthyridin-4(1H)-one-3-carboxylic acid
  参考文献：
  名称：

  一种1-环丙基-7-氨甲基三唑-氟萘啶酮羧酸类 衍生物及其制备方法和应用

  摘要：

  本发明公开了一种1?环丙基?7?氨甲基三唑?氟萘啶酮羧酸类衍生物及其制备方法和应用，采用如下式I化学结构通式：式I中，R为二甲氨基、二乙氨基、哌啶基、吗啉基、吡咯烷基、哌嗪基或取代哌嗪基。本发明的一种1?环丙基?7?氨甲基三唑?氟萘啶酮羧酸类衍生物，实现了在优势药效团骨架—环丙氟萘啶酮羧酸与有效取代基7?氨基间插入功能三唑杂环，从而提高了新化合物的抗耐药活性，可以作为新的抗菌活性物质开发全新结构的抗感染类药物。

  公开号：

  CN104817558B
• 作为产物：
  描述：

  ethyl 7-azido-1-cyclopropyl-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 3.0h， 生成 7-azido-1-cyclopropyl-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

文献信息

• Structure aided design of chimeric antibiotics
  作者：Tomislav Karoli、Sreeman K. Mamidyala、Johannes Zuegg、Scott R. Fry、Ernest H.L. Tee、Tanya A. Bradford、Praveen K. Madala、Johnny X. Huang、Soumya Ramu、Mark S. Butler、Matthew A. Cooper

  DOI：10.1016/j.bmcl.2012.02.019

  日期：2012.4

  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.
• 一种1-环丙基-7-氨甲基三唑-氟萘啶酮羧酸类 衍生物及其制备方法和应用
  申请人：河南大学

  公开号：CN104817558B

  公开（公告）日：2016-07-20

  本发明公开了一种1?环丙基?7?氨甲基三唑?氟萘啶酮羧酸类衍生物及其制备方法和应用，采用如下式I化学结构通式：式I中，R为二甲氨基、二乙氨基、哌啶基、吗啉基、吡咯烷基、哌嗪基或取代哌嗪基。本发明的一种1?环丙基?7?氨甲基三唑?氟萘啶酮羧酸类衍生物，实现了在优势药效团骨架—环丙氟萘啶酮羧酸与有效取代基7?氨基间插入功能三唑杂环，从而提高了新化合物的抗耐药活性，可以作为新的抗菌活性物质开发全新结构的抗感染类药物。