Development of PAR2 antagonists for the treatment of IBS

Leader: Régis Millet

Workpackage: WP4

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor that has a pivotal role in inflammatory and nociceptive processes. Experiments in animal models suggest that PAR2 is important for visceral hypersensitivity. Moreover, endogenous PAR2 agonists seem to be released by the colonic tissue of patients with IBS. It may this have a role in visceral pain perception. Hence, PAR2 receptors are exciting targets for the treatment of visceral pain. In this context, we would like to develop PAR2 receptor antagonists. A structure-based virtual screening of our in-house chemical library has allowed us to identify new oxazole antagonists which are actually optimized by focusing on the synthesis of new constrained analogs and new bicyclic oxazoles.