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

JW Huffman, J Liddle, S Yu, MM Aung… - Bioorganic & medicinal …, 1999 - Elsevier
JW Huffman, J Liddle, S Yu, MM Aung, ME Abood, JL Wiley, BR Martin
Bioorganic & medicinal chemistry, 1999Elsevier
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 (5), 1-deoxy-Δ8-THC (6), 1-deoxy-3-butyl-Δ8-THC (7), 1-deoxy-3-hexyl-
Δ8-THC (8) and a series of 3-(1′, 1′-dimethylalkyl)-1-deoxy-Δ8-THC analogues (2, n= 0–
4, 6, 7, where n= the number of carbon atoms in the side chain− 2). Three derivatives (17–
19) of deoxynabilone (16) were also prepared. The affinities of each compound for the CB1 …
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 (5), 1-deoxy-Δ8-THC (6), 1-deoxy-3-butyl-Δ8-THC (7), 1-deoxy-3-hexyl-Δ8-THC (8) and a series of 3-(1′,1′-dimethylalkyl)-1-deoxy-Δ8-THC analogues (2, n=0–4, 6, 7, where n=the number of carbon atoms in the side chain−2). Three derivatives (17–19) of deoxynabilone (16) 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 (2, n=1–5) have high affinity (Ki=<20nM) for the CB2 receptor. Four of them (2, n=1–4) also have little affinity for the CB1 receptor (Ki=>295nM). 3-(1′,1′-Dimethylbutyl)-1-deoxy-Δ8-THC (2, n=2) has very high affinity for the CB2 receptor (Ki=3.4±1.0nM) and little affinity for the CB1 receptor (Ki=677±132nM).
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