3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis

Aurélien Tourteau (1) , Virginie Andrzejak (1) , Mathilde Body-Malapel (2, 3) , Lucas Lemaire (1) , Amélie Lemoine (1) , Roxane Mansouri (1) , Madjid Djouina (2, 3) , Nicolas Renault (1, 3) , Jamal El Bakali (1) , Pierre Desreumaux (2, 3) , Giulio G. Muccioli (4, 5) , Didier Lambert (6, 5) , Philippe Chavatte (1, 3) , Benoît Rigo (1) , Natascha Leleu-Chavain (1) , Régis Millet (1)

1 ICPAL - Institut de Chimie Pharmaceutique Albert Lespagnol
2 LIRIC - Lille Inflammation Research International Center - U 995
3 IMPRT - Institut de médecine predictive et de recherche thérapeutique
4 Bioanalysis and pharmacology of bioactive lipids laboratory
5 UCL - Université Catholique de Louvain = Catholic University of Louvain
6 Unité de Pharmacologie Cellulaire et Moléculaire [Brussels]

Recent investigations showed that anandamide, the main endogenous ligand of CB1 and CB2 cannabinoid receptors, possesses analgesic, antidepressant and anti-inflammatory effects. In the perspective to treat inflammatory bowel disease (IBD), our approach was to develop new selective CB2 receptor agonists without psychotropic side effects associated to CB1 receptors. In this purpose, a new series of 3-carboxamido-5-aryl-isoxazoles, never described previously as CB2 receptor agonists, was designed, synthesized and evaluated for their biological activity. The pharmacological results have identified great selective CB2 agonists with in vivo anti-inflammatory activity in a DSS-induced acute colitis mouse model.

Mots clés: Isoxazoles; Cannabinoid; IBD; CB(2)

Domaines: Chimie; Sciences du Vivant [q-bio]

Aurélien Tourteau, Virginie Andrzejak, Mathilde Body-Malapel, Lucas Lemaire, Amélie Lemoine, et al.. 3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis. Bioorganic and Medicinal Chemistry, 2013, 21 (17), pp.5383 - 5394. ⟨10.1016/j.bmc.2013.06.010⟩. ⟨hal-01935812⟩