N¹-(3,5-dimethyladamantan-1-yl)propane-1,3-diamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹-(3,5-dimethyladamantan-1-yl)propane-1,3-diamine
• 英文别名: N'-(3,5-dimethyl-1-adamantyl)propane-1,3-diamine
• 化学式: C₁₅H₂₈N₂
• 分子量: 236.401
• InChiKey: FZFPYHMSWUAGEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  阿魏酸 、 N¹-(3,5-dimethyladamantan-1-yl)propane-1,3-diamine 在 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以39%的产率得到(E)-N-(3-((3,5-dimethyladamantan-1-yl)amino)propyl)-3-(4-hydroxy-3-methoxyphenyl)acrylamide
  参考文献：
  名称：

  Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease

  摘要：

  N-methyl-D-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid beta peptide (A beta) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from A beta neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 mu M). In addition, at 10 mu M concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate A beta production, as revealed by the observed increase of the non-amyloidogenic sAPP alpha in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving A beta burden and oxidative damage. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.011
• 作为产物：
  描述：

  盐酸美金刚 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N¹-(3,5-dimethyladamantan-1-yl)propane-1,3-diamine
  参考文献：
  名称：

  Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease

  摘要：

  N-methyl-D-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid beta peptide (A beta) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from A beta neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 mu M). In addition, at 10 mu M concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate A beta production, as revealed by the observed increase of the non-amyloidogenic sAPP alpha in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving A beta burden and oxidative damage. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.011

文献信息

• Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease
  作者：Michela Rosini、Elena Simoni、Roberta Caporaso、Filippo Basagni、Michele Catanzaro、Izuddin F. Abu、Francesca Fagiani、Federica Fusco、Sara Masuzzo、Diego Albani、Cristina Lanni、Ian R. Mellor、Anna Minarini

  DOI：10.1016/j.ejmech.2019.07.011

  日期：2019.10

  N-methyl-D-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid beta peptide (A beta) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from A beta neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 mu M). In addition, at 10 mu M concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate A beta production, as revealed by the observed increase of the non-amyloidogenic sAPP alpha in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving A beta burden and oxidative damage. (C) 2019 Elsevier Masson SAS. All rights reserved.