1-Bromo-3-(1?,1?-dimethylalkyl)-1-deoxy-?8-tetrahydrocannabinols: New selective ligands for the cannabinoid CB2 receptor
Huffman, J. W., Hepburn, S. A., Lyutenko, N., Thompson, A. L. S., Wiley, J., Selley, D. E., & Martin, B. R. (2010). 1-Bromo-3-(1?,1?-dimethylalkyl)-1-deoxy-?8-tetrahydrocannabinols: New selective ligands for the cannabinoid CB2 receptor. Bioorganic and Medicinal Chemistry, 18(22), 7809-7815. DOI: 10.1016/j.bmc.2010.09.061
?8-Tetrahydrocannabinol (26), 3-(1?,1?-dimethylbutyl)- (12), 3-(1?,1?-dimethylpentyl)- (13), 3-(1?,1?-dimethylhexyl)- (14) and 3-(1?,1?-dimethylheptyl)-?8-tetrahydrocannabinol (15) have been converted into the corresponding 1-bromo-1-deoxy-?8-tetrahydrocannabinols (25, 8–11). This was accomplished using a protocol developed in our laboratory in which the trifluoromethanesulfonate of a phenol undergoes palladium mediated coupling with pinacolborane. Reaction of this dioxaborolane with aqueous-methanolic copper(II) bromide provides the aryl bromide. The affinities of these bromo cannabinoids for the cannabinoid CB1 and CB2 receptors were determined. All of these compounds showed selectivity for the CB2 receptor and one of them, 1-bromo-1-deoxy-3-(1?,1?-dimethylhexyl)-?8-tetrahydrocannabinol (10), exhibits 52-fold selectivity for this receptor with good (28 nM) affinity.