1-Bromo-3-(1′,1′-dimethylalkyl)-1-deoxy-Δ8-tetrahydrocannabinols: New selective ligands for the cannabinoid CB2 receptor

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 22; pp. 7809 - 7815
• Main Authors: Huffman, John W., Hepburn, Seon A., Lyutenko, Nataliya, Thompson, Alicia L.S., Wiley, Jenny L., Selley, Dana E., Martin, Billy R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 15.11.2010
• Subjects: Biological and medical sciences; Medical sciences; Miscellaneous; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Ligand; CB2 cannabinoid receptor; Selectivity; Tricyclic compound; Oxygen heterocycle; In vitro; 1-Deoxy cannabinoids; Biological fixation; receptor; Structure activity relation; Affinity; Bromine Organic compounds; Aromatic compound; Chemical synthesis; Nontraditional cannabinoids; CB
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.09.061

Δ 8 -Tetrahydrocannabinol ( 26 ), 3-(1′,1′-dimethylbutyl)-( 12 ), 3-(1′,1′-dimethylpentyl)-( 13 ), 3-(1′,1′-dimethylhexyl)-( 14 ) and 3-(1′,1′-dimethylheptyl)-Δ 8 -tetrahydrocannabinol ( 15 ) have been converted into the corresponding 1-bromo-1-deoxy-Δ 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 CB 1 and CB 2 receptors were determined. All of these compounds showed selectivity for the CB 2 receptor and one of them, 1-bromo-1-deoxy-3-(1′,1′-dimethylhexyl)-Δ 8 -tetrahydrocannabinol ( 10 ), exhibits 52-fold selectivity for this receptor with good (28 nM) affinity.