1-(2-(4-(4-fluorobenzyl)piperazin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

• 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: 1-(2-(4-(4-fluorobenzyl)piperazin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one
• 英文别名: 1-[2-[4-[(4-Fluorophenyl)methyl]piperazin-1-yl]ethyl]-7-methoxy-1,5-naphthyridin-2-one；1-[2-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]ethyl]-7-methoxy-1,5-naphthyridin-2-one
• 化学式: C₂₂H₂₅FN₄O₂
• 分子量: 396.465
• InChiKey: ARDDDECUUZZLNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperazine-1-carboxylate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.17h， 生成 1-(2-(4-(4-fluorobenzyl)piperazin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2015.11.039

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.