Synthesis and testing of novel phenyl substituted side-Chain analogues of classical cannabinoids

A series of novel phenyl substituted side-chain analogues of classical cannabinoids were synthesized and their CB1 and CB2 binding affinities were evaluated relative to Δ8-THC and compound 2. CB1 and CB2 binding assays indicate that the dimethyl and ketone analogues (3) and (6) display selectivity for the CB2 receptor in comparison to Δ8-THC and compound 2. This study provides newer insights into the geometrical and functional group requirements of the ligand binding pockets of the CB1 and the CB2 receptors.