3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor.
The synthesis and pharmacology of 15 1-deoxy-delta8-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-delta8-THC (5), 1-deoxy-delta8-THC (6), 1-deoxy-3-butyl-delta8-THC (7), 1-deoxy-3-hexyl-delta8-THC (8) and a series of 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-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-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, 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).
Huffman
J W
JW
Howard L. Hunter Laboratory, Clemson University, SC 29634-1905, USA. huffman@clemson.edu
Liddle
J
J
Yu
S
S
Aung
M M
MM
Abood
M E
ME
Wiley
J L
JL
Martin
B R
BR
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism*; D002460:Cell Line; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
C405341:3-(1',1'-dimethylbutyl)-1-deoxy-delta(8)-tetrahydrocannabinol; D002186:Cannabinoids; D008024:Ligands; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol