2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl trifluoromethanesulfonate | 1623153-48-9

• 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: 2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl trifluoromethanesulfonate
• CAS: 1623153-48-9
• 化学式: C₁₁H₈F₄N₂O₄S
• 分子量: 340.255
• InChiKey: NJKQXILUWKDAJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78.26
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl trifluoromethanesulfonate 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: Pharmacophore mapping from known antibacterial leads

  摘要：

  Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl) urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 mu M, and not cytotoxic at 50 mu M in eukaryotic cell line. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.018
• 作为产物：
  描述：

  2-氯-5-氟-3-氨基吡啶 在 N-甲基二环己基胺 、 palladium diacetate 、 caesium carbonate 、 Tetra(tert-butyl)phosphonium-tetrafluoroborat 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl trifluoromethanesulfonate
  参考文献：
  名称：

  Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: Pharmacophore mapping from known antibacterial leads

  摘要：

  Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. Compound 1-(4-fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl) urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 mu M, and not cytotoxic at 50 mu M in eukaryotic cell line. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.018

文献信息

• Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors
  作者：Karyakulam Andrews Bobesh、Janupally Renuka、Rudraraju Reshma Srilakshmi、Swapna Yellanki、Pushkar Kulkarni、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmc.2015.11.039

  日期：2016.1

  Recently numerous non-fluoroquinolone-based bacterial type II topoisomerase inhibitors from both the GyrA and GyrB classes have been reported as antibacterial agents. Inhibitors of the GyrA class include aminopiperidine-based novel bacterial type II topoisomerase inhibitors (NBTIs). However, inhibition of the cardiac ion channel remains a serious liability for the aminopiperidine based NBTIs. In this paper we replaced central aminopiperidine linker with piperazine moiety and tested for its biological activity. We developed a series of twenty four compounds with a piperazine linker 1-(2-(piperazin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one, by following a multistep protocol. Among them compound 4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)-N-(4-nitrophenyl)piperazine-1-carboxamide (11) was the most promising inhibitor with Mycobacterium tuberculosis (MTB) DNA gyrase enzyme supercoiling IC50 of 0.29 +/- 0.22 mu M, with a good MTB MIC of 3.45 mu M. These kind of compounds retains good potency and showed reduced cardiotoxicity compared to aminopiperidines. (C) 2015 Elsevier Ltd. All rights reserved.