4-amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline | 370104-07-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline
• 英文别名: 3'-(2-Methyl-4-amino-5-fluoroquinoline-3-ylmethylthiomethyl)-alpha,alpha,alpha-trifluoroacetophenone；1-[3-[(4-amino-5-fluoro-2-methylquinolin-3-yl)methylsulfanylmethyl]phenyl]-2,2,2-trifluoroethanone
• CAS: 370104-07-7
• 化学式: C₂₀H₁₆F₄N₂OS
• 分子量: 408.419
• InChiKey: VPRFBYAXJXJEIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以82%的产率得到1-[3-(4-Amino-5-fluoro-2-methyl-quinolin-3-ylmethylsulfanylmethyl)-phenyl]-2,2,2-trifluoro-ethanol
  参考文献：
  名称：

  A Structure-Based Design Approach to the Development of Novel, Reversible AChE Inhibitors

  摘要：

  Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.

  DOI：

  10.1021/jm010826r
• 作为产物：
  描述：

  3-溴甲基苯 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 magnesium 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.67h， 生成 4-amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline
  参考文献：
  名称：

  A Structure-Based Design Approach to the Development of Novel, Reversible AChE Inhibitors

  摘要：

  Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.

  DOI：

  10.1021/jm010826r

文献信息

• A Structure-Based Design Approach to the Development of Novel, Reversible AChE Inhibitors
  作者：Caroline Doucet-Personeni、Philip D. Bentley、Rodney J. Fletcher、Adrian Kinkaid、Gitay Kryger、Bernard Pirard、Anne Taylor、Robin Taylor、John Taylor、Russell Viner、Israel Silman、Joel L. Sussman、Harry M. Greenblatt、Terence Lewis

  DOI：10.1021/jm010826r

  日期：2001.9.1

  Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.