(6aR,10aR)-3-(1-adamantyl)-1-hydroxy-6,6-dimethyl-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one | 1434116-54-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: (6aR,10aR)-3-(1-adamantyl)-1-hydroxy-6,6-dimethyl-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one
• CAS: 1434116-54-7
• 化学式: C₂₅H₃₂O₃
• 分子量: 380.527
• InChiKey: CSBZGWGFNNIKFV-SQWXZCMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6aR,10aR)-3-(1-adamantyl)-1-hydroxy-6,6-dimethyl-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one 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 27.25h， 生成 (6aR,9R,10aR)-3-(1-adamantyl)-9-[(Z)-2-methoxyethenyl]-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 三氟甲磺酸三甲基硅酯 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 8.0h， 以61%的产率得到(6aR,10aR)-3-(1-adamantyl)-1-hydroxy-6,6-dimethyl-7,8,10,10a-tetrahydro-6aH-benzo[c]chromen-9-one
  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