1-Methoxy-, 1-deoxy-11-hydroxy- and 11-hydroxy-1-methoxy-Delta(8)-tetrahydrocannabinols: new selective ligands for the CB2 receptor.

Three series of new cannabinoids were prepared and their affinities for the CB(1) and CB(2) 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)-Delta(8)-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 CB(2) receptor than for the CB(1) receptor, however only 1-methoxy-3-(1',1'-dimethylhexyl)-Delta(8)-THC (JWH-229, 6e) has effectively no affinity for the CB(1) receptor (K(i)=3134+/-110nM) and high affinity for CB(2) (K(i)=18+/-2nM).