New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis

Virginie Andrzejak (1) , Giulio G. Muccioli (2) , Mathilde Body-Malapel (3) , Jamal El Bakali (1) , Madjid Djouina (3) , Nicolas Renault (1) , Philippe Chavatte (1) , Pierre Desreumaux (3) , Didier Lambert (2) , Régis Millet (1)

1 ICPAL - Institut de Chimie Pharmaceutique Albert Lespagnol
2 UCL - Université Catholique de Louvain = Catholic University of Louvain
3 LIRIC - Lille Inflammation Research International Center - U 995

Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we report the first series of carboxamides derivatives possessing FAAH inhibitory activities. Among them, compound 39 displayed significant inhibitory FAAH activity (IC(50)=0.088 μM) and reduced colitis induced by intrarectal administration of TNBS.

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

Virginie Andrzejak, Giulio G. Muccioli, Mathilde Body-Malapel, Jamal El Bakali, Madjid Djouina, et al.. New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis. Bioorganic and Medicinal Chemistry, 2011, 19 (12), pp.3777 - 3786. ⟨10.1016/j.bmc.2011.04.057⟩. ⟨hal-01936354⟩