3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ8-THC and related compounds: synthesis of selective ligands for the CB2 receptor Original Research Article

The synthesis and pharmacology of 15 1-deoxy-Δ8-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-Δ8-THC (), 1-deoxy-Δ8-THC (), 1-deoxy-3-butyl-Δ8-THC (), 1-deoxy-3-hexyl-Δ8-THC () and a series of 3-(1′,1′-dimethylalkyl)-1-deoxy-Δ8-THC analogues (, n=0–4, 6, 7, where n=the number of carbon atoms in the side chain−2). Three derivatives () of deoxynabilone () were also prepared. The affinities of each compound for the CB1 and CB2 receptors were determined employing previously described procedures. Five of the 3-(1′,1′-dimethylalkyl)-1-deoxy-Δ8-THC analogues (, n=1–5) have high affinity (Ki=<20 nM) for the CB2 receptor. Four of them (, n=1–4) also have little affinity for the CB1 receptor (Ki=>295 nM). 3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ8-THC (, n=2) has very high affinity for the CB2 receptor (Ki=3.4±1.0 nM) and little affinity for the CB1 receptor (Ki=677±132 nM).