N,3,5-trimethyladamantan-1-amine | 41100-49-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,3,5-trimethyladamantan-1-amine
• 英文别名: 1-N-Methylamino-3.5-dimethyl-adamantan；MRZ-2169；1-N-methylamino-3,5-dimethyl adamantane
• CAS: 41100-49-6
• 化学式: C₁₃H₂₃N
• 分子量: 193.332
• InChiKey: FQPYRWAIWQNTFQ-UHFFFAOYSA-N

物化性质

• 沸点：
  240.4±8.0 °C(Predicted)
• 密度：
  0.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N,3,5-trimethyladamantan-1-amine 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 75.5h， 生成 tert-butyl (3,5-dimethyladamantan-1-yl)(3-((3-((4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepin-11(12H)-yl)propyl)amino)propyl)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
• 作为产物：
  描述：

  聚合甲醛 、 盐酸美金刚 在 溶剂黄146 、 锌 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以75%的产率得到N,3,5-trimethyladamantan-1-amine
  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。
• Selective Monomethylation of Amines with Methanol as the C ₁ Source
  作者：Geunho Choi、Soon Hyeok Hong

  DOI：10.1002/anie.201801524

  日期：2018.5.22

  methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio‐related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method

  N-单甲基官能团是多种合成和天然化合物中的常见基序。然而，由于由过度甲基化引起的选择性问题，容易获得此类化合物仍然是有机合成中的基本挑战。为了解决这个问题，我们开发了一种方法，可以使用甲醇作为甲基化剂，对各种结构和功能多样的胺（包括通常存在问题的伯脂肪族伯胺）进行选择性催化单甲基化，这是一种可持续的化学原料。通过使用容易获得的钌催化剂在适当的温度和氢气压力下实现脂肪族胺单甲基化的动力学控制。各种底物（包括与生物有关的分子和药物）被选择性地单甲基化，
• Combination therapy using 1-aminocyclohexane derivatives and acetylcholinesterase inhibitors
  申请人：——

  公开号：US20040087658A1

  公开（公告）日：2004-05-06

  The invention relates to a novel drug combination therapy useful in the treatment of dementia comprising administering an 1-aminocyclohexane derivative such as memantine or neramexane and an acetylcholinesterase inhibitor (AChEI) such as galantamine, tacrine, donepezil, or rivastigmine.

  该发明涉及一种新型药物组合疗法，可用于治疗痴呆，包括给予一种1-氨基环己烷衍生物，如美万特或奈拉美喜，以及一种乙酰胆碱酯酶抑制剂（AChEI），如加兰他明、他克林、多奈哌齐或利伐替明。
• NMDA receptor antagonists and their use in inhibiting abnormal hyperphosphorylation of microtubule associated protein tau
  申请人：——

  公开号：US20040019118A1

  公开（公告）日：2004-01-29

  Aminocyclohexane and aminoalkylcyclohexane compounds, which are systemic-ally-active as NMDA receptor antagonists, are effective in inhibiting abnormal hyperphosphorylation of microtubule associated protein tau, method of treating disorders resulting from or associated with abnormal hyperphosphorylation of microtubule associated protein tau, and pharmaceutical compositions comprising the same.

  氨基环己烷和氨基烷基环己烷化合物作为NMDA受体拮抗剂在系统上具有活性，对抑制微管相关蛋白tau异常过度磷酸化有效。涉及治疗由于或与微管相关蛋白tau异常过度磷酸化相关的疾病的方法，以及包含这些化合物的药物组合物。
• [EN] METHODS AND COMPOSITIONS FOR IMPROVING COGNITIVE FUNCTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR AMÉLIORER LA FONCTION COGNITIVE
  申请人：GALLAGHER MICHELA

  公开号：WO2014153180A1

  公开（公告）日：2014-09-25

  This invention relates to methods and compositions for treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a a5 -containing GABAA receptor agonist in combination with memantine or a derivative or an analog thereof, in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease(AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia or bipolar disorder, amyotrophic lateral sclerosis, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism, compulsive behavior, and substance addiction.

  本发明涉及用于治疗与中枢神经系统（CNS）疾病相关的认知障碍的方法和组合物。具体而言，它涉及在需要或有风险的受试者中使用含有a5的GABAA受体激动剂与美拉替特或其衍生物或类似物结合，用于治疗与中枢神经系统（CNS）疾病相关的认知障碍，包括但不限于患有或有风险患上与年龄相关的认知障碍、轻度认知障碍（MCI）、遗忘性MCI（aMCI）、年龄相关记忆障碍（AAMI）、年龄相关认知衰退（ARCD）、痴呆症、阿尔茨海默病（AD）、前驱期AD、创伤后应激障碍（PTSD）、精神分裂症或躁郁症、肌萎缩侧索硬化、癌症治疗相关认知障碍、智力障碍、帕金森病（PD）、自闭症、强迫行为和物质成瘾。