tert-butyl (3,5-dimethyladamantan-1-yl)(9-((4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepin-11(12H)-yl)nonyl)carbamate | 1402933-96-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: tert-butyl (3,5-dimethyladamantan-1-yl)(9-((4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepin-11(12H)-yl)nonyl)carbamate
• 英文别名: tert-butyl N-(3,5-dimethyl-1-adamantyl)-N-[9-[(1S,12S,14R)-14-hydroxy-9-methoxy-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-4-yl]nonyl]carbamate
• CAS: 1402933-96-3
• 化学式: C₄₂H₆₄N₂O₅
• 分子量: 676.981
• InChiKey: DRXIKXIBHUTQAV-BOJZPVQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (3,5-dimethyladamantan-1-yl)(9-((4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepin-11(12H)-yl)nonyl)carbamate 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以75%的产率得到(1S,12S,14R)-4-[9-[(3,5-dimethyl-1-adamantyl)amino]nonyl]-9-methoxy-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol
  参考文献：
  名称：

  Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease

  摘要：

  Herein we report on a novel series of multitargeted compounds obtained by linking together galantamine and memantine. The Compounds were designed by taking advantage of the crystal structures of acetylcholinesterase (AChE) in complex with galantamine derivatives Sixteen hovel derivatives. were :synthesized, Using spacers of different lengths and chemical composition. The molecules were then; tested as inhibitors Of AChE and as binders of the N-methyl-D-aspartate (NMDA) receptor (NMDAR). Some of the new compounds were nanomolar inhibitors of AChE and showed micromolar affinities for NMDAR. All compounds were also tested for selectivity toward NMDAR containing the 2B subunit (NR2B). Some of the new derivatives showed a micromolar affinity for NR2B. Finally, selected compounds were tested using a cell-based assay to measure.,,their,neuroprotective activity. Three of them showed a remarkable neuroprotective profile, inhibiting the NMDA-induced neurotoxicity at subnanomolar concentrations (e g, 5, named memagal, IC50 = 0.28 nM).

  DOI：

  10.1021/jm3009458
• 作为产物：
  描述：

  盐酸美金刚 在 4-二甲氨基吡啶 、 sodium carbonate 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 99.5h， 生成 tert-butyl (3,5-dimethyladamantan-1-yl)(9-((4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepin-11(12H)-yl)nonyl)carbamate
  参考文献：
  名称：

  Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease

  摘要：

  Herein we report on a novel series of multitargeted compounds obtained by linking together galantamine and memantine. The Compounds were designed by taking advantage of the crystal structures of acetylcholinesterase (AChE) in complex with galantamine derivatives Sixteen hovel derivatives. were :synthesized, Using spacers of different lengths and chemical composition. The molecules were then; tested as inhibitors Of AChE and as binders of the N-methyl-D-aspartate (NMDA) receptor (NMDAR). Some of the new compounds were nanomolar inhibitors of AChE and showed micromolar affinities for NMDAR. All compounds were also tested for selectivity toward NMDAR containing the 2B subunit (NR2B). Some of the new derivatives showed a micromolar affinity for NR2B. Finally, selected compounds were tested using a cell-based assay to measure.,,their,neuroprotective activity. Three of them showed a remarkable neuroprotective profile, inhibiting the NMDA-induced neurotoxicity at subnanomolar concentrations (e g, 5, named memagal, IC50 = 0.28 nM).

  DOI：

  10.1021/jm3009458