C3-Heteroaroyl cannabinoids as photolabeling ligands for the CB2 cannabinoid receptor

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Dixon, Darryl D.¹  Tius, Marcus A.¹  Thakur, Ganesh A.²  Zhou, Han²  Bowman, Anna L.²  Shukla, Vidyanand G.²  Peng, Yan²  Makriyannis, Alexandros² 

[1] Univ Hawaii Manoa, Dept Chem, Honolulu, HI 96822 USA

[2] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA

关键词: CB2;    Cannabinoid;    Ligand-assisted protein structure;    Photolabeling;    Photoactivatable group;   

DOI  :  10.1016/j.bmcl.2012.06.013

来源: Elsevier

【 摘 要 】

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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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