Structural modifications of the cannabinoid side chain towards C3-aryl and 1′,1′-cycloalkyl-1′-cyano cannabinoids

The compounds reported in this study are Delta(8)-THC analogues in which the C3 five-carbon linear side chain of Delta(8)-THC was replaced with aryl and 1',1'-cycloalkyl substituents. Of the compounds described here analogues 2d (CB1, K-i = 11.7 nM. CB2, K-i = 9.39 nM) and 2f (CB1, K-i = 8.26 nM. CB2, K-i = 3.86 nM) exhibited enhanced binding affinities for CB1 and CB2, exceeding that of Delta(8)-THC. Efficient procedures for the synthesis of these novel cannabinoid analogues are described. (C) 2006 Elsevier Ltd. All rights reserved.