This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC(50)<20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC(50)>10 microM for CB2; CB2/CB1>1000).

Triazole derivatives R 0280 1,2,3-Triazole Derivatives as New Cannabinoid CB1 Receptor Antagonists. -With a view to their potential biological activity, compounds such as (IV) and (VIII) are prepared. Among them some derivatives, e.g. (VIIIb) and (VIIIc), inhibit CB1 with an IC50 value less than 20nM having a high CB2 selectivity (some yields not given).-(HOU*, D.-R.; ALAM, S.; KUAN, T.-C.; RAMANATHAN, M.; LIN, T.-P.; HUNG, M.-S.; Bioorg. Med.