methyl 2,6-bis(4-fluorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: methyl 2,6-bis(4-fluorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate
• 英文别名: methyl (2S,6R)-4-(4-fluoroanilino)-1,2,6-tris(4-fluorophenyl)-3,6-dihydro-2H-pyridine-5-carboxylate
• 化学式: C₃₁H₂₄F₄N₂O₂
• 分子量: 532.537
• InChiKey: OYYNUOXEKAUSGR-MFMCTBQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对氟苯甲醛 、 乙酰乙酸甲酯 、 4-氟苯胺 在 bismuth (III) nitrate pentahydrate 作用下， 以 乙醇 为溶剂， 反应 12.33h， 以68%的产率得到methyl 2,6-bis(4-fluorophenyl)-1-(4-fluorophenyl)-4-(4-fluorophenylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate
  参考文献：
  名称：

  In vitro evaluation and in silico screening of synthetic acetylcholinesterase inhibitors bearing functionalized piperidine pharmacophores

  摘要：

  A series of densely functionalized piperidine (FP) scaffolds was synthesized following a diastereoselective one-pot multicomponent protocol under eco-friendly conditions. The FPs were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activity, and in silico studies for all the target compounds were carried out using pharmacophore mapping, molecular docking and quantitative structure-activity relationship (QSAR) analysis in order to understand the structural features required for interaction with the AChE enzyme and the key active site residues involved in the intermolecular interactions. Halogenation, nitration or 3,4-methylenedixoxy-substitution at the phenyl ring attached to the 2- and 6-positions of 1,2,5,6-tetrahydropyridine nucleus in compounds 14-17, 19, 20, 24 and 26 greatly enhanced the AChE inhibitory activity. The docking analysis demonstrated that the inhibitors are well-fitted in the active sites. The in silico studies enlighten the future course of studies in modifying the scaffolds for better therapeutic efficacy against the deadly Alzheimer's disease. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.005