3-{4-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-yl}propylamine | 916140-62-0

• 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-{4-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-yl}propylamine
• 英文别名: 3-[4-[3-(5,6-Dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperazin-1-yl]propan-1-amine
• CAS: 916140-62-0
• 化学式: C₂₄H₃₄N₄
• 分子量: 378.561
• InChiKey: MRAGYPYKWNVKKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{4-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-yl}propylamine 、 9-氯吖啶 以 苯酚 为溶剂， 反应 18.0h， 以55%的产率得到N-[3-[4-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperazin-1-yl]propyl]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：

  亚氨基二苄 在 lithium aluminium tetrahydride 、 sodium carbonate 、 sodium amide 、 sodium iodide 作用下， 以 乙醚 、 甲苯 、 乙腈 为溶剂， 反应 54.0h， 生成 3-{4-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]piperazin-1-yl}propylamine
  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

文献信息

• 9-AMINO-ACRIDINE DERIVATIVES AND THEIR USE FOR ELIMINATING MISFOLDED PROTEINS
  申请人：Korth Carsten

  公开号：US20090124001A1

  公开（公告）日：2009-05-14

  The invention relates to compounds according to general formula (1) and/or their enantiomers, diastereomers as well as their pharmaceutically compatible salts, and to the use thereof for producing a medicament suited for treating diseases associated with misfolded proteins.

  本发明涉及通式（1）的化合物和/或其对映体，非对映异构体以及其药学上相容的盐，以及将其用于制备适用于治疗与错折蛋白相关的疾病的药物。
• 9-AMINO-ACRIDINE DERIVATIVES AND METHOD OF TREATING AUTOIMMUNE DISEASES USING THE SAME
  申请人：Korth Carsten

  公开号：US20090209516A1

  公开（公告）日：2009-08-20

  The invention relates to compounds according to general formula (1) and/or their enantiomers, diastereomers, and their pharmaceutically compatible salts, and their use to manufacture a medication as well as medications. The compounds are suited for treatment of diseases connected with misfolded proteins.

  本发明涉及通式(1)及/或其对映体、二对映异构体及其药学上相容的盐，以及它们的用途制造药物以及药物。该化合物适用于治疗与蛋白质错折相关的疾病。
• US7951796B2
  申请人：——

  公开号：US7951796B2

  公开（公告）日：2011-05-31
• A Chimeric Ligand Approach Leading to Potent Antiprion Active Acridine Derivatives:  Design, Synthesis, and Biological Investigations
  作者：Silke Dollinger、Stefan Löber、Ralf Klingenstein、Carsten Korth、Peter Gmeiner

  DOI：10.1021/jm060773j

  日期：2006.11.1

  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.