6-(benzyloxy)quinoline 1-oxide | 476661-72-0

• 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: 6-(benzyloxy)quinoline 1-oxide
• 英文别名: 1-Oxido-6-phenylmethoxyquinolin-1-ium
• CAS: 476661-72-0
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: PNLOEJIISLMINU-UHFFFAOYSA-N

物化性质

• 沸点：
  446.5±37.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  34.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(benzyloxy)quinoline 1-oxide 在 4-甲苯磺酸酐 、 叔丁胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以20 mg的产率得到6-(benzyloxy)quinolin-2-amine
  参考文献：
  名称：

  Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery

  摘要：

  Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phox(SH3A-B)) with K-D values of 400-600 mu M. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phox(SH3A-B) and these competed with p22phox for binding to p47phox(SH3A-B). Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phox(SH3A-B)-p22phox interaction (K-i of 20 mu M). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.

  DOI：

  10.1021/acs.jmedchem.9b01492
• 作为产物：
  描述：

  溴甲苯 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6-(benzyloxy)quinoline 1-oxide
  参考文献：
  名称：

  Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery

  摘要：

  Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phox(SH3A-B)) with K-D values of 400-600 mu M. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phox(SH3A-B) and these competed with p22phox for binding to p47phox(SH3A-B). Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phox(SH3A-B)-p22phox interaction (K-i of 20 mu M). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.

  DOI：

  10.1021/acs.jmedchem.9b01492

文献信息

• Facile Installation of β-Hydroxyarylethylamino Motifs at the C2-Position of Quinoline Moiety via Copper-Catalyzed [3+3]-Cycloaddition Reaction of N-Oxide with N-Ts Aziridine
  作者：Animesh Das、Monuranjan Konwar、Tapashi Das、Arpan Naskar、Ranjit Murmu

  DOI：10.1055/a-2184-4940

  日期：——

  synthesis of quinoline-C2-substituted β-hydroxyarylethylamino derivatives was achieved by copper-catalyzed [3+3]-cycloaddition reaction of N-oxide with N-Ts aziridines. Notably, temperature has a huge impact on this transformation as evidenced by the fact that, at 80 °C, exclusively the [3+3] cycloadduct was isolated whereas, at elevated temperature (140 °C), it has been converted into the aminated product

  通过N-氧化物与N - Ts氮丙啶的铜催化[3+3]-环加成反应，实现了喹啉-C2-取代的β-羟基芳基乙基氨基衍生物的通用且原子有效的合成。值得注意的是，温度对这种转变有巨大影响，事实证明，在 80 °C 时，仅分离出 [3+3] 环加合物，而在高温 (140 °C) 下，它已转化为胺化物。产品收率良好。值得注意的是，整个过程中没有副产品。使用无碱条件、优异的位点选择性和良好的官能团耐受性是该过程的重要特征。
• [EN] QUINOLINE-BASED DERIVATIVES AS VAP-1 INHIBITORS<br/>[FR] DÉRIVÉS À BASE DE QUINOLÉINE UTILISÉS COMME INHIBITEURS DE VAP-1<br/>[ZH] 作为VAP-1抑制剂的喹啉类衍生物
  申请人：MEDSHINE DISCOVERY INC

  公开号：WO2020063854A1

  公开（公告）日：2020-04-02

  公开了一类喹啉类衍生物及其在制备治疗与VAP-1有关疾病的药物中的应用，具体公开了式（II）所示化合物及其药学上可接受的盐。
• ORGANIC COMPOUNDS
  申请人：Novartis AG

  公开号：EP2029572B1

  公开（公告）日：2010-11-03