Abstract
Previously we identified a series of amidoalkylindoles as potent and selective CB(2) partial agonists. In the present study, we report our continuous effort to improve the aqueous solubility by introducing N atoms to the amidoalkylindole framework. Synthesis, characterization, and pharmacology evaluations were described. Bioisosteric replacements of the indole nucleus with an indazole, azaindole and benzimidazole were explored. Benzimidazole 43 (EC(50,CB(1)) = NA, EC(50,CB(2)) = 0.067 μM) and azaindole 24 (EC(50,CB(1)) = NA, EC(50,CB(2)) = 0.048 μM) were found to be potent and selective CB(2) receptor partial agonists, both with improved aqueous solubility.