[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-ylacetonitrile | 916140-55-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: [3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-ylacetonitrile
• CAS: 916140-55-1
• 化学式: C₂₃H₂₈N₄
• 分子量: 360.502
• InChiKey: JPBVJAXYLDNYOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  33.51
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-ylacetonitrile 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 苯酚 为溶剂， 反应 18.5h， 生成 N-[2-[4-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperazin-1-yl]ethyl]acridin-9-amine
  参考文献：
  名称：

  A Chimeric Ligand Approach Leading to Potent Antiprion Active Acridine Derivatives:  Design, Synthesis, and Biological Investigations

  摘要：

  Human transmissible neurodegenerations including Creutzfeldt-Jakob disease are unique, since they are caused by prions, an infectious agent that replicates without nucleic acids but instead by inducing conversion of a host-resident normal prion protein to a misfolded conformational isoform. For pharmacotherapy of these unusual diseases, tricyclic heterocyclic compounds such as quinacrine have been considered, but with ambiguous success in vivo, so far. On the basis of the synergistic antiprion effects of quinacrine and iminodibenzyl derivatives, we introduce a novel class of potential pharmaceuticals representing structural chimeras of quinacrine and imipramine analogues. We describe the chemical synthesis and bioassays of a focused library of these compounds. The most potent target compound 2a revealed an EC50 value of 20 nM determined with a cell model of prion disease, thus substantially improving the antiprion efficacy of quinacrine.

  DOI：

  10.1021/jm060773j
• 作为产物：
  描述：

  5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓 在 sodium carbonate 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 32.0h， 生成 [3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-ylacetonitrile
  参考文献：
  名称：

  A Chimeric Ligand Approach Leading to Potent Antiprion Active Acridine Derivatives:  Design, Synthesis, and Biological Investigations

  摘要：

  Human transmissible neurodegenerations including Creutzfeldt-Jakob disease are unique, since they are caused by prions, an infectious agent that replicates without nucleic acids but instead by inducing conversion of a host-resident normal prion protein to a misfolded conformational isoform. For pharmacotherapy of these unusual diseases, tricyclic heterocyclic compounds such as quinacrine have been considered, but with ambiguous success in vivo, so far. On the basis of the synergistic antiprion effects of quinacrine and iminodibenzyl derivatives, we introduce a novel class of potential pharmaceuticals representing structural chimeras of quinacrine and imipramine analogues. We describe the chemical synthesis and bioassays of a focused library of these compounds. The most potent target compound 2a revealed an EC50 value of 20 nM determined with a cell model of prion disease, thus substantially improving the antiprion efficacy of quinacrine.

  DOI：

  10.1021/jm060773j