C3-heteroaroyl cannabinoids as photolabeling ligands for the CB2 cannabinoid receptor.
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.
Department of Chemistry, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI 96822, USA.
Darryl D
DD
Dixon
Marcus A
MA
Tius
Ganesh A
GA
Thakur
Han
H
Zhou
Anna L
AL
Bowman
Vidyanand G
VG
Shukla
Yan
Y
Peng
Alexandros
A
Makriyannis
D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D002186:Cannabinoids / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry*; D014466:Ultraviolet Rays
D001578:Benzopyrans; D002186:Cannabinoids; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013876:Thiophenes