3-{3-[(4-ethyl-1-piperazinyl)carbonyl]phenyl}-8-isopropoxybenzo[b][1,6]naphthyridine | 1437302-50-5

• 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: 3-{3-[(4-ethyl-1-piperazinyl)carbonyl]phenyl}-8-isopropoxybenzo[b][1,6]naphthyridine
• CAS: 1437302-50-5
• 化学式: C₂₈H₃₀N₄O₂
• 分子量: 454.572
• InChiKey: PMOPCAXXUJLDQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  58.56
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  methyl 3-((trimethylsilyl)ethynyl)benzoate 在 ammonium hydroxide 、 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 三甲基铝 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 34.25h， 生成 3-{3-[(4-ethyl-1-piperazinyl)carbonyl]phenyl}-8-isopropoxybenzo[b][1,6]naphthyridine
  参考文献：
  名称：

  Overcoming Compound Fluorescence in the FLiK Screening Assay with Red-Shifted Fluorophores

  摘要：

  In the attempt to discover novel chemical scaffolds that can modulate the activity of disease-associated enzymes, such as kinases, biochemical assays are usually deployed in high-throughput screenings. First-line assays, such as activity-based assays, often rely on fluorescent molecules by measuring a change in the total emission intensity, polarization state, or energy transfer to another fluorescent molecule. However, under certain conditions, intrinsic compound fluorescence can lead to difficult data analysis and to false-positive, as well as false-negative, hits. We have reported previously on a powerful direct binding assay called fluorescent labels in kinases ('FLiK'), which enables a sensitive measurement of conformational changes in kinases upon ligand binding. In this assay system, changes in the emission spectrum of the fluorophore acrylodan, induced by the binding of a ligand, are translated into a robust assay readout. However, under the excitation conditions of acrylodan, intrinsic compound fluorescence derived from highly conjugated compounds complicates data analysis. We therefore optimized this method by identifying novel fluorophores that excite in the far red, thereby avoiding compound fluorescence. With this advancement, even rigid compounds with multiple pi-conjugated ring systems can now be measured reliably. This study was performed on three different kinase constructs with three different labeling sites, each undergoing distinct conformational changes upon ligand binding. It may therefore serve as a guideline for the establishment of novel fluorescence-based detection assays.

  DOI：

  10.1021/ja403074j