4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]-benzamide | 1428662-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]-benzamide
• 英文别名: 4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]benzamide
• CAS: 1428662-25-2
• 化学式: C₂₉H₃₆FN₃O
• 分子量: 461.623
• InChiKey: NXJWHXASKRKJAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]-benzamide 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]benzamide;hydrochloride
  参考文献：
  名称：

  Synthesis, Biological Activity and Molecular Modeling of 4-Fluoro-N-[ω-(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide Derivatives as Cholinesterase Inhibitors

  摘要：

  The aim of this study was to synthesize and determine the biological activity of new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition of cholinesterases. Compounds were synthesized in condensation reaction between 9-aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties towards inhibition of acetyl- and butyrylcholinesterase were estimated according to Ellman's spectrophotometric method. Among synthesized compounds the most active were compounds 4a and 4d. These compounds, in comparison with tacrine, were characterized by the similar values of IC50. Among all obtained compounds, 4d presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling studies revealed that all derivatives presented similar extended conformation in the gorge of acetylcholinesterase, however, there were 2 main conformations in the active center of butyrylcholinesterase: bent and extended conformation.

  DOI：

  10.1055/s-0032-1329963
• 作为产物：
  描述：

  9-氯-1,2,3,4-四氢吖啶 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 sodium iodide 作用下， 以 四氢呋喃 、 苯酚 为溶剂， 反应 28.0h， 生成 4-fluoro-N-[9-(1,2,3,4-tetrahydroacridin-9-ylamino)nonyl]-benzamide
  参考文献：
  名称：

  Synthesis, Biological Activity and Molecular Modeling of 4-Fluoro-N-[ω-(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide Derivatives as Cholinesterase Inhibitors

  摘要：

  The aim of this study was to synthesize and determine the biological activity of new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition of cholinesterases. Compounds were synthesized in condensation reaction between 9-aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties towards inhibition of acetyl- and butyrylcholinesterase were estimated according to Ellman's spectrophotometric method. Among synthesized compounds the most active were compounds 4a and 4d. These compounds, in comparison with tacrine, were characterized by the similar values of IC50. Among all obtained compounds, 4d presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling studies revealed that all derivatives presented similar extended conformation in the gorge of acetylcholinesterase, however, there were 2 main conformations in the active center of butyrylcholinesterase: bent and extended conformation.

  DOI：

  10.1055/s-0032-1329963

文献信息

• Synthesis, Biological Activity and Molecular Modeling of 4-Fluoro-N-[ω-(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide Derivatives as Cholinesterase Inhibitors
  作者：P. Szymański、M. Markowicz、M. Bajda、B. Malawska、E. Mikiciuk-Olasik

  DOI：10.1055/s-0032-1329963

  日期：——

  The aim of this study was to synthesize and determine the biological activity of new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition of cholinesterases. Compounds were synthesized in condensation reaction between 9-aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties towards inhibition of acetyl- and butyrylcholinesterase were estimated according to Ellman's spectrophotometric method. Among synthesized compounds the most active were compounds 4a and 4d. These compounds, in comparison with tacrine, were characterized by the similar values of IC50. Among all obtained compounds, 4d presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling studies revealed that all derivatives presented similar extended conformation in the gorge of acetylcholinesterase, however, there were 2 main conformations in the active center of butyrylcholinesterase: bent and extended conformation.