Synthesis and SAR of novel imidazoles as potent and selective cannabinoid CB2 receptor antagonists with high binding efficiencies.

Abstract The synthesis and structure–activity relationship studies of imidazoles are described. The target compounds 6 – 20 represent a novel chemotype of potent and CB 2 /CB 1 selective cannabinoid CB 2 receptor antagonists/inverse agonists with very high binding efficiencies in combination with favourable log  P and calculated polar surface area values. Compound 12 exhibited the highest CB 2 receptor affinity ( K i  = 1.03 nM) in this series, as well as the highest CB 2 /CB 1 subtype selectivity (>9708-fold).