Synthesis and pharmacology of 11-nor-1-methoxy-9-hydroxyhexahydrocannabinols and 11-nor-1-deoxy-9-hydroxyhexahydrocannabinols: New selective ligands for the cannabinoid CB₂ receptor

详细信息	查看全文 | 推荐本文 |

• 作者：Karla-Sue C. Marriott ; John W. Huffman ; Jenny L. Wiley and Billy R. Martin
• 关键词：Cannabinoids ; Structure– ; activity relationships ; CB₂ cannabinoid receptors ; Deoxycannabinoids
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2006
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 April 2006
• 卷：14
• 期：7
• 页码：2386-2397
• 文件大小：220 K

摘要

Fourteen novel CB₂ receptor selective cannabinoids were synthesized via initial Lewis acid catalyzed rearrangement of resorcinol precursors to obtain the cannabinoid moiety. These are the 1-methoxy-9-hydroxyhexahydrocannabinols and the 1-deoxy-9-hydroxyhexahydrocannabinols, with 1′,1′-dimethylalkyl side chains of four to seven carbon atoms at C-3 of the cannabinoid nucleus. The cannabinols synthesized and described in this paper all exhibit greater affinity for the CB₂ receptor than for the CB₁ receptor. Exceptionally high CB₂ affinity was observed for 1-deoxy-9β-hydroxy-dimethylhexylhexahydrocannabinol (JWH-361, 9, n = 3) K_i = 2.7 nM and 1-deoxy-9β-hydroxydimethylpentylhexahydrocannabinol (JWH-300, 9, n = 2) K_i = 5.3 nM. In general, the stereochemistry of the 9-hydroxy group is important and the β-orientation enhances both CB₂ receptor affinity and selectivity.