(+)-6,7-dimethoxy-2-(oct-7-ynyl)-1S-phenyl-1,2,3,4-tetrahydroisoquinoline | 853650-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (+)-6,7-dimethoxy-2-(oct-7-ynyl)-1S-phenyl-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1S)-6,7-dimethoxy-2-oct-7-ynyl-1-phenyl-3,4-dihydro-1H-isoquinoline
• CAS: 853650-69-8
• 化学式: C₂₅H₃₁NO₂
• 分子量: 377.527
• InChiKey: QWCXDILKTCAYSR-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-6,7-dimethoxy-2-(oct-7-ynyl)-1S-phenyl-1,2,3,4-tetrahydroisoquinoline 、 N-(2-azidoethyl)-1,2,3,4-tetrahydroacridine-9-amine 在 copper(l) iodide 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 N-[2-[4-[6-[(1S)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine
  参考文献：
  名称：

  In Situ Selection of Lead Compounds by Click Chemistry:  Target-Guided Optimization of Acetylcholinesterase Inhibitors

  摘要：

  The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with a variety of acetylene reagents that were not previously known to interact with the enzyme's peripheral binding site. The triazole products, formed by the enzyme, were identified by HPLC-mass spectrometry analysis of the crude reaction mixtures. The target-guided lead discovery search was also successful when performed with reagent mixtures containing up to 10 components. From 23 acetylene reagents, the enzyme selected two phenyltetrahydroisoquinoline (1310) building blocks that combined with the tacrine azide within the active center gorge to form multivalent inhibitors that simultaneously associate with the active and peripheral binding sites. These new inhibitors are up to 3 times as potent as our previous phenylphenanthridinium-derived compounds, and with dissociation constants as low as 33 femtomolar, they are the most potent noncovalent AChE inhibitors known. In addition, the new compounds lack a permanent positive charge and aniline groups and possess fewer fused aromatic rings. Remarkably, despite the high binding affinity, the enzyme displayed a surprisingly low preference for one IQ enantionner over the other.

  DOI：

  10.1021/ja043031t
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 调呋酸 、 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 24.0h， 生成 (+)-6,7-dimethoxy-2-(oct-7-ynyl)-1S-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  In Situ Selection of Lead Compounds by Click Chemistry:  Target-Guided Optimization of Acetylcholinesterase Inhibitors

  摘要：

  The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with a variety of acetylene reagents that were not previously known to interact with the enzyme's peripheral binding site. The triazole products, formed by the enzyme, were identified by HPLC-mass spectrometry analysis of the crude reaction mixtures. The target-guided lead discovery search was also successful when performed with reagent mixtures containing up to 10 components. From 23 acetylene reagents, the enzyme selected two phenyltetrahydroisoquinoline (1310) building blocks that combined with the tacrine azide within the active center gorge to form multivalent inhibitors that simultaneously associate with the active and peripheral binding sites. These new inhibitors are up to 3 times as potent as our previous phenylphenanthridinium-derived compounds, and with dissociation constants as low as 33 femtomolar, they are the most potent noncovalent AChE inhibitors known. In addition, the new compounds lack a permanent positive charge and aniline groups and possess fewer fused aromatic rings. Remarkably, despite the high binding affinity, the enzyme displayed a surprisingly low preference for one IQ enantionner over the other.

  DOI：

  10.1021/ja043031t