8-(2-ethoxyethoxy)quinolin-2-amine

• 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: 8-(2-ethoxyethoxy)quinolin-2-amine
• 英文别名: 8-(2-Ethoxy-ethoxy)-quinolin-2-ylamine
• 化学式: C₁₃H₁₆N₂O₂
• 分子量: 232.282
• InChiKey: PVKHCFVJUHKBPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  8-(2-ethoxyethoxy)quinoline 在 4-甲苯磺酸酐 、 叔丁胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 8-(2-ethoxyethoxy)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

文献信息

• Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 1
  作者：Andrew J. Souers、Dariusz Wodka、Ju Gao、Jared C. Lewis、Anil Vasudevan、Robert Gentles、Sevan Brodjian、Brian Dayton、Christopher A. Ogiela、Dennis Fry、Lisa E. Hernandez、Kennan C. Marsh、Christine A. Collins、Philip R. Kym

  DOI：10.1016/j.bmcl.2004.07.032

  日期：2004.10

  A high-throughput screen was performed in order to identify chemotypes that are bound by the melanin concentrating hormone receptor-1 (MCHr1). A novel 2-amino-8-alkoxyquinoline compound (1) was identified and subsequently optimized using a parallel and automated procedure for the rapid production of multiple analogs. The structure-activity relationships that emerged from this effort are described, along with selected pharmacokinetic parameters of compound (d)-61 when dosed orally in diet-induced obese mice. (C) 2004 Elsevier Ltd. All rights reserved.
• Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery
  作者：Sara Marie Øie Solbak、Jie Zang、Dilip Narayanan、Lars Jakobsen Høj、Saskia Bucciarelli、Charlotte Softley、Sebastian Meier、Annette Eva Langkilde、Charlotte Held Gotfredsen、Michael Sattler、Anders Bach

  DOI：10.1021/acs.jmedchem.9b01492

  日期：2020.2.13

  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.