Bornyl- and Isobornyl-Δ8-tetrahydrocannabinols: A Novel Class of Cannabinergic Ligands

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• 作者：Dai Lu ; Jianxin Guo ; Richard I. Duclos ; ; Anna L. Bowman ; Alexandros Makriyannis
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：October 23, 2008
• 年：2008
• 卷：51
• 期：20
• 页码：6393-6399
• 全文大小：231K
• 年卷期：v.51,no.20(October 23, 2008)
• ISSN：1520-4804

文摘

Structure−activity relationship studies of classical cannabinoid analogues have established that the C3 aliphatic side chain plays a pivotal role in determining cannabinergic potency. In earlier work, we provided evidence for the presence of subsites within the CB1 and CB2 cannabinoid receptor binding domains that can accommodate bulky conformationally defined substituents at the C3 alkyl side chain pharmacophore of classical cannabinoids. We have now extended this work with the synthesis of a series of Δ⁸-THC analogues in which bornyl substituents are introduced at the C3 position. Our results indicate that, for optimal interactions with both CB1 and CB2 receptors, the bornyl substituents need to be within close proximity of the tricyclic core of Δ⁸-THC and that the conformational space occupied by the C3 substituents influences CB1/CB2 receptor subtype selectivity.