2-(1-adamantyl)-propan-2-amine | 3433-03-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(1-adamantyl)-propan-2-amine
• 英文别名: 2-(1-Adamantyl)propan-2-amine
• CAS: 3433-03-2
• 化学式: C₁₃H₂₃N
• mdl: MFCD02632308
• 分子量: 193.332
• InChiKey: NDDFDYJBIHXQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-羟基-4-甲氧基苯甲醛 、 2-(1-adamantyl)-propan-2-amine 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以67%的产率得到
  参考文献：
  名称：

  Chemical Probes for Blocking of Influenza A M2 Wild-type and S31N Channels

  摘要：

  We report on using the synthetic aminoadamantane-CH2-aryl derivatives 1-6 as sensitive probes for blocking M2 S31N and influenza A virus (IAV) M2 wild-type (WT) channels as well as virus replication in cell culture. The binding kinetics measured using electrophysiology (EP) for M2 S31N channel are very dependent on the length between the adamantane moiety and the first ring of the aryl headgroup realized in 2 and 3 and the girth and length of the adamantane adduct realized in 4 and 5. Study of 1-6 shows that, according to molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, all bind in the M2 S31N channel with the adamantyl group positioned between V27 and G34 and the aryl group projecting out of the channel with the phenyl (or isoxazole in 6) embedded in the V27 cluster. In this outward binding configuration, an elongation of the ligand by only one methylene in rimantadine 2 or using diamantane or triamantane instead of adamantane in 4 and 5, respectively, causes incomplete entry and facilitates exit, abolishing effective block compared to the amantadine derivatives 1 and 6. In the active M2 S31N blockers 1 and 6, the phenyl and isoxazolyl head groups achieve a deeper binding position and high kon/low koff and high kon/high koff rate constants, compared to inactive 2-5, which have much lower kon and higher koff. Compounds 1-5 block the M2 WT channel by binding in the longer area from V27-H37, in the inward orientation, with high kon and low koff rate constants. Infection of cell cultures by influenza virus containing M2 WT or M2 S31N is inhibited by 1-5 or 1-4 and 6, respectively. While 1 and 6 block infection through the M2 block mechanism in the S31N variant, 2-4 may block M2 S31N virus replication in cell culture through the lysosomotropic effect, just as chloroquine is thought to inhibit SARS-CoV-2 infection.

  DOI：

  10.1021/acschembio.0c00553
• 作为产物：
  描述：

  2-(1-金刚烷基)-2-丙醇 在 lithium aluminium tetrahydride 、 sodium azide 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 2-(1-adamantyl)-propan-2-amine
  参考文献：
  名称：

  以伯叔烷基胺为基石的方法

  摘要：

  初级叔烷基胺包括金刚烷胺的类似物，通常连接到药效基团的片段，以提高生物活性。伯叔烷基胺的制备被认为是一个难题。四个合成步骤，其中一些已经用于与胺的合成已有报道初级（RCH 2 NH 2）或仲（RR'CHNH 2）烷基和/或芳基，伯合成进行了测试叔烷基胺（RR'R''CNH 2）包括金刚烷加合物在内的脂族系列。这些程序包括在形成和还原的叔烷基叠氮化物，在标准和改良条件Ritter反应，在加入有机金属试剂以ñ -叔丁基亚磺酰基酮亚胺和一锅在路易斯酸的存在下，Τi（IPRO）腈和有机金属试剂之间的反应4或CeCl 3.对于伯叔烷基胺，尚未开发这些合成途径。当前缺乏对伯叔烷基胺的合成路线的研究。研究了每种方法的反应条件和底物限制，第一种方法是最通用的方法，也适用于带有大分子加合物的化合物。

  DOI：

  10.1016/j.tet.2019.06.016

文献信息

• NOVEL INDOLE DERIVATIVES AND THEIR USE IN NEURODEGENERATIVE DISEASES
  申请人：Merck Patent GmbH

  公开号：US20160168090A1

  公开（公告）日：2016-06-16

  The present invention relates to indole compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of P2X7, and for the treatment of P2X7-related disorders.

  本发明涉及吲哚化合物及其药用可接受的组合物，用作P2X7拮抗剂，用于治疗与P2X7相关的疾病。
• 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。
• METHODS AND COMBINATION THERAPIES FOR TREATING ALZHEIMER'S DISEASE
  申请人：Hung David T.

  公开号：US20100152108A1

  公开（公告）日：2010-06-17

  The invention provides methods and combination therapies for treating and/or preventing and/or slowing the onset and/or development of Alzheimer's disease using a hydrogenated pyrido (4,3-b) indole (e.g., dimebon) in conjunction with another compound, pharmaceutically acceptable salt thereof or therapy for Alzheimer's disease.

  该发明提供了一种治疗和/或预防和/或减缓阿尔茨海默病的发作和/或发展的方法和联合疗法，使用氢化吡啶并哌啶(例如二甲苯胺)与另一化合物、其药用盐或治疗阿尔茨海默病的疗法结合。
• Novel treatment for alzheimer's disease
  申请人：EPFL Ecole Polytechnique Fédérale de Lausanne

  公开号：EP2111858A1

  公开（公告）日：2009-10-28

  The present invention concerns a new pharmaceutical composition comprising an antagonist and a co-agonist of the N-methyl-D-aspartate-type glutamate receptor (NMDAR). The inventors found that the co-administration of these two compounds effectively inhibits production of amyloide-β peptide. In patient's suffering from Alzheimer's disease, these peptides are deposited in the extracellular matrix forming neuritic "plaques". Therefore, the present inventors identified a new possibility for prophylaxis and/or treatment of Alzheimer's disease by stopping the continued formation of neuropathological extracellular deposits.

  本发明涉及一种新的药物组合物，包括N-甲基-D-天门冬氨酸型谷氨酸受体（NMDAR）的拮抗剂和共激动剂。发明人发现这两种化合物的联合使用有效地抑制了淀粉样β肽的产生。在患有阿尔茨海默病的患者中，这些肽沉积在细胞外基质中形成神经突起“斑块”。因此，本发明人发现了一种新的预防和/或治疗阿尔茨海默病的可能性，即通过阻止神经病理性细胞外沉积物的持续形成。