1-Methoxy-, 1-deoxy-11-hydroxy- and 11-Hydroxy-1-methoxy-Δ8-tetrahydrocannabinols: new selective ligands for the CB2 receptor Original Research Article

Three series of new cannabinoids were prepared and their affinities for the CB1 and CB2 cannabinoid recptors were determined. These are the 1-methoxy-3-(1′,1′-dimethylalkyl)-, 1-deoxy-11-hydroxy-3-(1′,1′-dimethylalkyl)- and 11-hydroxy-1-methoxy-3-(1′,1′-dimethylalkyl)-Δ8-tetrahydrocannabinols, which contain alkyl chains from dimethylethyl to dimethylheptyl appended to C-3 of the cannabinoid. All of these compounds have greater affinity for the CB2 receptor than for the CB1 receptor, however only 1-methoxy-3-(1′,1′-dimethylhexyl)-Δ8-THC (JWH-229, 6e) has effectively no affinity for the CB1 receptor (Ki=3134±110 nM) and high affinity for CB2 (Ki=18±2 nM).