9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol | 1434124-99-8

• 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: 9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol
• 英文别名: (6aR,9R,10aR)-6a,7,8,9,10,10a-Hexahydro-1-hydroxy-6,6-dimethyl-3-tricyclo(3.3.1.13,7)dec-1-yl-6H-dibenzo(b,d)pyran-9-methanol；(6aR,9R,10aR)-3-(1-adamantyl)-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol
• CAS: 1434124-99-8
• 化学式: C₂₆H₃₆O₃
• 分子量: 396.57
• InChiKey: GQYXNRWEEUCMOZ-MMSALSPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol 在 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 碘 、 三苯基膦 、 三氯乙酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 苯 为溶剂， 反应 26.75h， 生成 (6aR,9R,10aR)-3-(1-adamantyl)-9-(2-hydroxyethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol
  参考文献：
  名称：

  Novel Adamantyl Cannabinoids as CB1 Receptor Probes

  摘要：

  In previous studies, compound 1 (AM411), a 3-(1-adamantyl) analogue of the phytocannabinoid (-)-Delta(8)-tetrahydrocannabinol (Delta(8)-THC), was shown to have improved affinity and selectivity for the CB1 receptor. In this work, we further explored the role of the 1-adamantyl group at the C-3 position in a series of tricyclic cannabinoid analogues modified at the 9-northern aliphatic hydroxyl (NAH) position. Of these, 9-hydroxymethyl hexahydrocannabinol 11 (AM4054) exhibited high CB1 affinity and full agonist profile. In the cAMP assay, the 9-hydroxymethyl cannabinol analogue 24 (AM4089) had a partial agonist profile, with high affinity and moderate selectivity for rCB1 over hCB2. In vivo results in rat models of hypothermia and analgesia were congruent with in vitro data. Our in vivo data indicate that 3-(1-adamantyl) substitution, within NAH cannabinergics, imparts improved pharmacological profiles when compared to the corresponding, traditionally used 3-dimethylheptyl analogues and identifies 11 and 24 as potentially useful in vivo CB1 cannabinergic probes.

  DOI：

  10.1021/jm4000775
• 作为产物：
  描述：

  (4R)-4-[4-(1-adamantyl)-2,6-dihydroxyphenyl]-6,6-dimethyl-2-norpinanone 在 sodium tetrahydroborate 、 正丁基锂 、 三氟甲磺酸三甲基硅酯 、 三氯乙酸 作用下， 以 四氢呋喃 、 甲醇 、 硝基甲烷 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 9.75h， 生成 9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol
  参考文献：
  名称：

  Novel Adamantyl Cannabinoids as CB1 Receptor Probes

  摘要：

  In previous studies, compound 1 (AM411), a 3-(1-adamantyl) analogue of the phytocannabinoid (-)-Delta(8)-tetrahydrocannabinol (Delta(8)-THC), was shown to have improved affinity and selectivity for the CB1 receptor. In this work, we further explored the role of the 1-adamantyl group at the C-3 position in a series of tricyclic cannabinoid analogues modified at the 9-northern aliphatic hydroxyl (NAH) position. Of these, 9-hydroxymethyl hexahydrocannabinol 11 (AM4054) exhibited high CB1 affinity and full agonist profile. In the cAMP assay, the 9-hydroxymethyl cannabinol analogue 24 (AM4089) had a partial agonist profile, with high affinity and moderate selectivity for rCB1 over hCB2. In vivo results in rat models of hypothermia and analgesia were congruent with in vitro data. Our in vivo data indicate that 3-(1-adamantyl) substitution, within NAH cannabinergics, imparts improved pharmacological profiles when compared to the corresponding, traditionally used 3-dimethylheptyl analogues and identifies 11 and 24 as potentially useful in vivo CB1 cannabinergic probes.

  DOI：

  10.1021/jm4000775

文献信息

• Novel Adamantyl Cannabinoids as CB1 Receptor Probes
  作者：Ganesh A. Thakur、Shama Bajaj、Carol Paronis、Yan Peng、Anna L. Bowman、Lawrence S. Barak、Marc G. Caron、Demon Parrish、Jeffrey R. Deschamps、Alexandros Makriyannis

  DOI：10.1021/jm4000775

  日期：2013.5.23

  In previous studies, compound 1 (AM411), a 3-(1-adamantyl) analogue of the phytocannabinoid (-)-Delta(8)-tetrahydrocannabinol (Delta(8)-THC), was shown to have improved affinity and selectivity for the CB1 receptor. In this work, we further explored the role of the 1-adamantyl group at the C-3 position in a series of tricyclic cannabinoid analogues modified at the 9-northern aliphatic hydroxyl (NAH) position. Of these, 9-hydroxymethyl hexahydrocannabinol 11 (AM4054) exhibited high CB1 affinity and full agonist profile. In the cAMP assay, the 9-hydroxymethyl cannabinol analogue 24 (AM4089) had a partial agonist profile, with high affinity and moderate selectivity for rCB1 over hCB2. In vivo results in rat models of hypothermia and analgesia were congruent with in vitro data. Our in vivo data indicate that 3-(1-adamantyl) substitution, within NAH cannabinergics, imparts improved pharmacological profiles when compared to the corresponding, traditionally used 3-dimethylheptyl analogues and identifies 11 and 24 as potentially useful in vivo CB1 cannabinergic probes.