2-(2-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)ethoxy)ethyl 4-methylbenzenesulfonate | 1402934-08-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)ethoxy)ethyl 4-methylbenzenesulfonate
• 英文别名: 2-(2-(N-Boc-N-(3,5-dimethyladamantan-1-yl)amino)ethoxy)ethyl p-toluenesulfonate；2-[2-[(3,5-Dimethyl-1-adamantyl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethoxy]ethyl 4-methylbenzenesulfonate；2-[2-[(3,5-dimethyl-1-adamantyl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethoxy]ethyl 4-methylbenzenesulfonate
• CAS: 1402934-08-0
• 化学式: C₂₈H₄₃NO₆S
• 分子量: 521.719
• InChiKey: DHTIYBJOEWRGDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  90.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)ethoxy)ethyl 4-methylbenzenesulfonate 在 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 50.0h， 生成 (1S,12S,14R)-4-[2-[2-[(3,5-dimethyl-1-adamantyl)amino]ethoxy]ethyl]-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：

  2-(2-((3,5-dimethyladamantan-1-yl)amino)ethoxy)ethanol 在 4-二甲氨基吡啶 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 3.5h， 生成 2-(2-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)ethoxy)ethyl 4-methylbenzenesulfonate
  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

文献信息

• [EN] DUAL TARGETING COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] COMPOSÉS À DOUBLE CIBLAGE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：UNIV BOLOGNA ALMA MATER

  公开号：WO2013160728A1

  公开（公告）日：2013-10-31

  Compounds of formula (I) wherein the groups are as defined in the description, are used as medicaments, in particular for the treatment of a disease selected from the group consisting of: cognitive impairment, memory dysfunction, neurodegenerative disorders and related dementia, Alzheimer's disease, Parkinson's disease, neuropsychiatric behavior associated with Alzheimer's disease, pain, depression, attention deficit hyperactivity disorder and for pharmacological addictive substance or intoxicant therapy; and for the neuroprotection from NMDA toxicity.

  式（I）中的化合物，其中所述的基团如描述中定义的那样，被用作药物，特别用于治疗从以下组中选择的疾病：认知障碍，记忆功能障碍，神经退行性疾病及相关痴呆症，阿尔茨海默病，帕金森病，与阿尔茨海默病相关的神经精神行为，疼痛，抑郁症，注意力缺陷多动障碍，以及用于药理学成瘾物质或中毒物质治疗；以及用于对抗NMDA毒性的神经保护。
• Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease
  作者：Elena Simoni、Simona Daniele、Giovanni Bottegoni、Daniela Pizzirani、Maria L. Trincavelli、Luca Goldoni、Glauco Tarozzo、Angelo Reggiani、Claudia Martini、Daniele Piomelli、Carlo Melchiorre、Michela Rosini、Andrea Cavalli

  DOI：10.1021/jm3009458

  日期：2012.11.26

  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).