AM755

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: AM755
• 化学式: C₂₇H₃₄O₂
• 分子量: 390.566
• InChiKey: URGQRYZWPGGROA-QGTPSMLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.84
• 重原子数：
  29.0
• 可旋转键数：
  1.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  29.46
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  5-(2-hydroxy-2-adamantyl)methyl-1,3-dimethoxybenzene 在 三溴化硼 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 6.0h， 生成 AM755
  参考文献：
  名称：

  Adamantyl Cannabinoids:  A Novel Class of Cannabinergic Ligands

  摘要：

  Structure-activity relationship studies have established that the aliphatic side chain plays a pivotal role in determining the cannabinergic potency of tricyclic classical cannabinoids. We have now synthesized a series of analogues in which a variety of adamantyl substituents were introduced at the C3 position of Delta(8)-THC. Our lead compound, (-)-3-(1-adamantyl)-Delta(8) tetrahydrocannabinol (1a, AM411), was found to have robust affinity and selectivity for the CB I receptor as well as high in vivo potency. The X-ray crystal structure of 1 a was determined. Exploration of the side chain conformational space using molecular modeling approaches has allowed us to develop cannabinoid side chain pharmacophore models for the CB1 and CB2 receptors. Our results suggest that although a bulky group at the C3 position of classical cannabinoids could be tolerated by both CB1 and CB2 binding sites, the relative orientation of that group with respect to the tricyclic component can lead to receptor subtype selectivity.

  DOI：

  10.1021/jm058175c

文献信息

• Adamantyl Cannabinoids:  A Novel Class of Cannabinergic Ligands
  作者：Dai Lu、Zhaoxing Meng、Ganesh A. Thakur、Pusheng Fan、John Steed、Cindy L. Tartal、Dow P. Hurst、Patricia H. Reggio、Jeffrey R. Deschamps、Damon A. Parrish、Clifford George、Torbjörn U. C. Järbe、Richard J. Lamb、Alexandros Makriyannis

  DOI：10.1021/jm058175c

  日期：2005.7.1

  Structure-activity relationship studies have established that the aliphatic side chain plays a pivotal role in determining the cannabinergic potency of tricyclic classical cannabinoids. We have now synthesized a series of analogues in which a variety of adamantyl substituents were introduced at the C3 position of Delta(8)-THC. Our lead compound, (-)-3-(1-adamantyl)-Delta(8) tetrahydrocannabinol (1a, AM411), was found to have robust affinity and selectivity for the CB I receptor as well as high in vivo potency. The X-ray crystal structure of 1 a was determined. Exploration of the side chain conformational space using molecular modeling approaches has allowed us to develop cannabinoid side chain pharmacophore models for the CB1 and CB2 receptors. Our results suggest that although a bulky group at the C3 position of classical cannabinoids could be tolerated by both CB1 and CB2 binding sites, the relative orientation of that group with respect to the tricyclic component can lead to receptor subtype selectivity.