Benzofuran and pyrrole derivatives as cannabinoid receptor modulators with in vivo efficacy against ulcerative colitis.

Aim: Highlighting the need for effective therapies for the treatment of ulcerative colitis, novel series of potential CB₂ modulators (benzofuran and pyrrole carboxamides) were developed and tested for their functional activities on CB₁/CB₂ receptors. Results: In the benzofuran series, the cannabinoid (CB) receptor selectivity and the functional profile were dependent on the nature of the amide substituent and the position of the methoxy group, meanwhile the pyrrole derivatives, displayed an exclusive selectivity to the CB₂ receptor and a functionality that is controlled by the nature of the pyrrole nitrogen substituent. Conclusion: Remarkably, we succeeded to develop potent and selective pyrrole-based CB₂ receptor agonists, represented by compound 25a, which also demonstrated an exquisite anti-inflammatory effect in a dextran sodium sulfate-induced colitis model in mice.