9-amino-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-ol | 1607589-55-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 9-amino-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-ol
• 英文别名: 9-bromo-6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amine；12-Aminotetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trien-10-ol；12-aminotetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trien-10-ol
• CAS: 1607589-55-8
• 化学式: C₁₅H₁₉NO
• 分子量: 229.322
• InChiKey: BBCUJOBPUZINQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-amino-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-ol 在 二乙胺基三氟化硫 、 hydrochloric acid diethyl ether 作用下， 以 二氯甲烷 为溶剂， 生成 9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine hydrochloride
  参考文献：
  名称：

  Novel benzopolycyclic amines with NMDA receptor antagonist activity

  摘要：

  A new series of benzopolycyclic amines active as NMDA receptor antagonists were synthesized. Most of them exhibited increased activity compared with related analogues previously published. All the tested compounds were more potent than clinically approved amantadine and one of them displayed a lower IC50 value than memantine, an anti-Alzheimer's approved drug. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.025
• 作为产物：
  描述：

  2-chloro-N-(9-hydroxy-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-yl)acetamide 在 溶剂黄146 、 硫脲 作用下， 以 乙醇 为溶剂， 生成 9-amino-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-ol
  参考文献：
  名称：

  Novel benzopolycyclic amines with NMDA receptor antagonist activity

  摘要：

  A new series of benzopolycyclic amines active as NMDA receptor antagonists were synthesized. Most of them exhibited increased activity compared with related analogues previously published. All the tested compounds were more potent than clinically approved amantadine and one of them displayed a lower IC50 value than memantine, an anti-Alzheimer's approved drug. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.025

文献信息

• Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer's disease
  作者：Andreea L. Turcu、Júlia Companys-Alemany、Matthew B. Phillips、Dhilon S. Patel、Christian Griñán-Ferré、M. Isabel Loza、José M. Brea、Belén Pérez、David Soto、Francesc X. Sureda、Maria G. Kurnikova、Jon W. Johnson、Mercè Pallàs、Santiago Vázquez

  DOI：10.1016/j.ejmech.2022.114354

  日期：2022.6

  accessible symptomatic therapies for Alzheimer's disease (AD), memantine is the only N-methyl-d-aspartate receptor (NMDAR) blocker approved by the FDA. This work further explores a series of memantine analogs featuring a benzohomoadamantane scaffold. Most of the newly synthesized compounds block NMDARs in the micromolar range, but with lower potency than previously reported hit IIc, results that were supported

  目前，在阿尔茨海默病 (AD) 的少数可用对症疗法中，美金刚是 FDA 批准的唯一N-甲基-d-天冬氨酸受体 (NMDAR) 阻滞剂。这项工作进一步探索了一系列具有苯并高金刚烷支架的美金刚类似物。大多数新合成的化合物在微摩尔范围内阻断 NMDAR，但其效力低​​于之前报道的 hit IIc ，这一结果得到了分子动力学模拟的支持。随后，对更有效的化合物进行电生理学研究，将IIc （一种低微摩尔、无竞争性、电压依赖性 NMDAR 阻滞剂）分类为美金刚样化合物。 IIc优异的体外DMPK 特性使其成为秀丽隐杆线虫( C. elegans ) 和 AD 5XFAD 小鼠模型体内研究的有希望的候选者。 IIc或美金刚的施用改善了线虫的运动并挽救了线虫的趋化行为。此外，这两种化合物都能增强 5XFAD 小鼠的工作记忆，并修饰 NMDAR 和 CREB ​​信号传导，从而可能预防突触功能障碍并调节神经退行性进展。
• Searching for novel applications of the benzohomoadamantane scaffold in medicinal chemistry: Synthesis of novel 11β-HSD1 inhibitors
  作者：Elena Valverde、Constantí Seira、Andrew McBride、Margaret Binnie、F. Javier Luque、Scott P. Webster、Axel Bidon-Chanal、Santiago Vázquez

  DOI：10.1016/j.bmc.2015.11.004

  日期：2015.12

  The structural and physicochemical properties of the adamantane nucleus account for its use as a chemical scaffold in multiple drugs. In the last years, we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As adamantane is a common structural feature in several 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitors, we have explored the ability of the 6,7,8,9,10,11-hexahydro-5H-5,9: 7,11-dimethanobenzo[9]annulen-7-yl scaffold to act as a surrogate of the adamantane nucleus in a novel series of 11 beta-HSD1 inhibitors. Of note, within this family of compounds one derivative is endowed with submicromolar 11 beta-HSD1 inhibitory activity. Molecular modeling studies support the binding of the compounds to the active site of the enzyme. However, a fine tuning of the hydrophobicity of the size-expanded nucleus may be beneficial for the inhibitory potency. (c) 2015 Elsevier Ltd. All rights reserved.