新型强效四氢大麻酚/花生四烯酸乙醇胺（混合型）类似物。
Novel, potent THC/anandamide (hybrid) analogs.
作者信息
Bourne Caryl, Roy Sucharita, Wiley Jenny L, Martin Billy R, Thomas Brian F, Mahadevan Anu, Razdan Raj K
机构信息
Organix, Inc., Woburn, MA 01801, USA.
出版信息
Bioorg Med Chem. 2007 Dec 15;15(24):7850-64. doi: 10.1016/j.bmc.2007.08.039. Epub 2007 Aug 25.
The structure-activity relationship (SAR) of the end pentyl chain in anandamide (AEA) has been established to be very similar to that of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). In order to broaden our understanding of the structural similarities between AEA and THC, hybrid structures 1-3 were designed. In these hybrids the aromatic ring of THC-DMH was linked to the AEA moiety through an ether linkage with the oxygen of the phenol of THC. Hybrid 1 (O-2220) was found to have very high binding affinity to CB1 receptors (K(i)=8.5 nM), and it is interesting to note that the orientation of the side chain with respect to the oxygen in the phenol is the same as in THCs. To further explore the SAR in this series the terminal carbon of the side chain was modified by adding different substituents. Several such analogs were synthesized and tested for their CB1 and CB2 binding affinities and in vivo activity (tetrad tests). The details of the synthesis and the biological activity of these compounds are described.
已证实花生四烯乙醇胺（AEA）中末端戊基链的构效关系（SAR）与Δ⁹-四氢大麻酚（Δ⁹-THC）非常相似。为了拓宽我们对AEA和THC之间结构相似性的理解，设计了杂合结构1 - 3。在这些杂合物中，THC - DMH的芳环通过与THC酚羟基的氧形成醚键与AEA部分相连。发现杂合物1（O - 2220）对CB1受体具有非常高的结合亲和力（K(i)=8.5 nM），有趣的是，侧链相对于酚中氧的取向与THC中的相同。为了进一步探索该系列中的构效关系，通过添加不同取代基对侧链的末端碳进行了修饰。合成了几种此类类似物，并测试了它们对CB1和CB2的结合亲和力以及体内活性（四联试验）。描述了这些化合物的合成细节和生物活性。
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