N-(3,5-dimethoxyphenyl)-2-[4-(2-dimethylaminoethyl)-1-piperazinyl]-4-(4-isopropylphenyl)-4-oxobutanamide | 1615217-69-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3,5-dimethoxyphenyl)-2-[4-(2-dimethylaminoethyl)-1-piperazinyl]-4-(4-isopropylphenyl)-4-oxobutanamide
• 英文别名: N-(3,5-dimethoxyphenyl)-2-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-4-oxo-4-(4-propan-2-ylphenyl)butanamide
• CAS: 1615217-69-0
• 化学式: C₂₉H₄₂N₄O₄
• 分子量: 510.677
• InChiKey: QRDKGYDBWCBKAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  74.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (E)-4-(4-isopropylphenyl)-4-oxo-2-butenoic acid 在 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 N-(3,5-dimethoxyphenyl)-2-[4-(2-dimethylaminoethyl)-1-piperazinyl]-4-(4-isopropylphenyl)-4-oxobutanamide
  参考文献：
  名称：

  Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations

  摘要：

  Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.008

文献信息

• Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations
  作者：Maja D. Vitorović-Todorović、Catherine Koukoulitsa、Ivan O. Juranić、Ljuba M. Mandić、Branko J. Drakulić

  DOI：10.1016/j.ejmech.2014.05.008

  日期：2014.6

  Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.