6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine | 1318250-01-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine
• 英文别名: 6-[[5-[3-(4-Cyclohexylpiperazin-1-yl)propyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]hexan-1-amine
• CAS: 1318250-01-9
• 化学式: C₂₉H₄₉N₃O
• 分子量: 455.728
• InChiKey: SEJKSCCKOYRZGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 15.0h， 生成 6-amino-2-(6-{1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy}hexyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione
  参考文献：
  名称：

  Novel Derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) with Improved Fluorescent and σ Receptors Binding Properties

  摘要：

  Despite the promising potentials of sigma(2) receptors in cancer therapy and diagnosis, there are still ambiguities related to the nature and physiological role of the a, protein. With the aim of providing potent and reliable tools to be used in sigma(2) receptor research, we developed a novel series of fluorescent sigma(2) ligands on the basis of our previous work, where high-affinity sigma(2) ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine (1, PB28) was used as the pharmacophore. Compared to the previous compounds, these novel ligands displayed improved fluorescence and a, binding properties, were sigma(2)-specifically taken up by breast tumor cells, and were successfully employed in confocal microscopy. Compound 14, which was the best compromise between pharmacological and fluorescent properties, was successfully employed in flow cytometry, demonstrating its potential to be used as a tool in nonradioactive binding assays for studying the affinity of putative sigma(2) receptor ligands.

  DOI：

  10.1021/jm401874n
• 作为产物：
  描述：

  N-(6-溴己基)邻苯二甲酰亚胺 在 potassium carbonate 、 一水合肼 、 sodium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine
  参考文献：
  名称：

  Fluorescent Derivatives of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a Tool for Uptake and Cellular Localization Studies in Pancreatic Tumor Cells

  摘要：

  Fluorescent derivatives of sigma(2) high affinity ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) were synthesized. NBD or dansyl fluorescent tags were connected through a 5- or 6-atom linker in two diverse positions of 1 structure. Good sigma(2) affinities were obtained when the fluorescent tag was linked to 5-methoxytetralin nucleus replacing the methyl function. NBD-bearing compound 16 displayed high sigma(2) affinity (K(i) = 10.8 nM) and a optimal fluorescent properties. Its uptake in pancreatic tumor cells was evaluated by flow cytometry, showing that it partially occurs through endocytosis. In proliferating cells, the uptake was higher supporting that sigma(2) receptors are markers of cell proliferation and that the higher the proliferation is, the stronger the antiproliferative effect of sigma(2) agonists is. Colocalization of 16 with subcellular organelles was studied by confocal microscopy: the greatest was in endoplasmic reticulum and lysosomes. Fluorescent sigma(2) ligands show their potential in clarifying the mechanisms of action of sigma(2) receptors.

  DOI：

  10.1021/jm200591t

文献信息

• Novel Derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) with Improved Fluorescent and σ Receptors Binding Properties
  作者：Carmen Abate、Mauro Niso、Roberta Marottoli、Chiara Riganti、Dario Ghigo、Savina Ferorelli、Giulia Ossato、Roberto Perrone、Enza Lacivita、Don C. Lamb、Francesco Berardi

  DOI：10.1021/jm401874n

  日期：2014.4.24

  Despite the promising potentials of sigma(2) receptors in cancer therapy and diagnosis, there are still ambiguities related to the nature and physiological role of the a, protein. With the aim of providing potent and reliable tools to be used in sigma(2) receptor research, we developed a novel series of fluorescent sigma(2) ligands on the basis of our previous work, where high-affinity sigma(2) ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine (1, PB28) was used as the pharmacophore. Compared to the previous compounds, these novel ligands displayed improved fluorescence and a, binding properties, were sigma(2)-specifically taken up by breast tumor cells, and were successfully employed in confocal microscopy. Compound 14, which was the best compromise between pharmacological and fluorescent properties, was successfully employed in flow cytometry, demonstrating its potential to be used as a tool in nonradioactive binding assays for studying the affinity of putative sigma(2) receptor ligands.
• Fluorescent Derivatives of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a Tool for Uptake and Cellular Localization Studies in Pancreatic Tumor Cells
  作者：Carmen Abate、John R. Hornick、Dirk Spitzer、William G. Hawkins、Mauro Niso、Roberto Perrone、Francesco Berardi

  DOI：10.1021/jm200591t

  日期：2011.8.25

  Fluorescent derivatives of sigma(2) high affinity ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) were synthesized. NBD or dansyl fluorescent tags were connected through a 5- or 6-atom linker in two diverse positions of 1 structure. Good sigma(2) affinities were obtained when the fluorescent tag was linked to 5-methoxytetralin nucleus replacing the methyl function. NBD-bearing compound 16 displayed high sigma(2) affinity (K(i) = 10.8 nM) and a optimal fluorescent properties. Its uptake in pancreatic tumor cells was evaluated by flow cytometry, showing that it partially occurs through endocytosis. In proliferating cells, the uptake was higher supporting that sigma(2) receptors are markers of cell proliferation and that the higher the proliferation is, the stronger the antiproliferative effect of sigma(2) agonists is. Colocalization of 16 with subcellular organelles was studied by confocal microscopy: the greatest was in endoplasmic reticulum and lysosomes. Fluorescent sigma(2) ligands show their potential in clarifying the mechanisms of action of sigma(2) receptors.