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).
Huffman
John W
JW
Howard L. Hunter Laboratory, Clemson University, Clemson, SC 29634-1905, USA. huffman@clemson.edu
Bushell
Simon M
SM
Miller
John R A
JR
Wiley
Jenny L
JL
Martin
Billy R
BR
D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D013759:Dronabinol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D011869:Radioligand Assay; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008024:Ligands; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol