(E)-4-oxo-4-(5,6,7,8-tetrahydronaphthalenyl)-2-butenoic acid (3,5-dimethoxyphenyl)-amide

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (E)-4-oxo-4-(5,6,7,8-tetrahydronaphthalenyl)-2-butenoic acid (3,5-dimethoxyphenyl)-amide
• 英文别名: (E)-N-(3,5-dimethoxyphenyl)-4-oxo-4-(5,6,7,8-tetrahydronaphthalen-1-yl)but-2-enamide
• 化学式: C₂₂H₂₃NO₄
• 分子量: 365.429
• InChiKey: VRZZPRVFXATLTL-ZHACJKMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  吗啉 、 (E)-4-oxo-4-(5,6,7,8-tetrahydronaphthalenyl)-2-butenoic acid (3,5-dimethoxyphenyl)-amide 以 二氯甲烷 、 甲苯 为溶剂， 以52.69%的产率得到N-(3,5-dimethoxyphenyl)-4-oxo-2-(4-morpholinyl)-4-(5,6,7,8-tetrahydronaphthalenyl)butanamide
  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
• 作为产物：
  描述：

  1,2,3,4-四氢萘 在 aluminum (III) chloride 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (E)-4-oxo-4-(5,6,7,8-tetrahydronaphthalenyl)-2-butenoic acid (3,5-dimethoxyphenyl)-amide
  参考文献：
  名称：

  (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization

  摘要：

  Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 mu M. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 mu M. Compound 23 had an oral LD50 in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.006