Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome.

Abstract Herein we report the identification of a highly potent and selective CB2 agonist, RQ-00202730 ( 40 ), obtained by lead optimization of the benzimidazole scaffold. Compound 40 showed strong agonistic activity with an EC 50 of 19 nM and excellent selectivity (>1300-fold) over the CB1 receptor. Compound 40 displayed a dose dependent analgesic effect on TNBS-induced visceral hypersensitivity in rats by oral administration (ED 50 0.66 mg/kg at 2.5 h after oral administration). In addition, 40 did not show a significant effect on body temperature in rats after oral administration at 300 mg/kg. These findings suggest that highly selective CB2 agonists will be effective agents for IBS therapy.