Department of Chemistry, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI 96822, USA.
Bioorg Med Chem Lett. 2012 Aug 15;22(16):5322-5. doi: 10.1016/j.bmcl.2012.06.013. Epub 2012 Jun 15.
A series of tricyclic cannabinoids incorporating a heteroaroyl group at C3 were prepared as probes to explore the binding site(s) of the CB1 and CB2 receptors. This relatively unexplored structural motif is shown to be CB2 selective with K(i) values at low nanomolar concentrations when the heteroaromatic group is 3-benzothiophenyl (41) or 3-indolyl (50). When photoactivated, the lead compound 41 was shown to successfully label the CB2 receptor through covalent attachment at the active site while 50 failed to label. The benzothiophenone moiety may be a photoactivatable moiety suitable for selective labeling.
一系列在 C3 位上引入杂芳酰基的三环大麻素被制备为探针，以探索 CB1 和 CB2 受体的结合部位。当杂芳基为 3-苯并噻吩基（41）或 3-吲哚基（50）时，该相对未探索的结构基序显示出对 CB2 的选择性，其 K(i) 值在低纳摩尔浓度下。当被光激活时，先导化合物 41 被证明能够通过在活性部位的共价结合成功标记 CB2 受体，而 50 则未能标记。苯并噻吩酮部分可能是适合选择性标记的光活化部分。
