title: Switching cannabinoid response from CB(2) agonists to FAAH inhibitors.
abstract: A series of 3-carboxamido-5-aryl-isoxazoles designed as CB2 agonists were evaluated as FAAH inhibitors. The pharmacological results led to identify structure-activity relationships enabling to switch cannabinoid response from CB2 agonists to FAAH inhibitors. Two compounds were selected for their FAAH and/or CB2 activity, and evaluated in a colitis model for their anti-inflammatory activity. Results showed that compounds 10 and 11 inhibit the development of DSS-induced acute colitis in mice and then, are interesting leads to explore new drug candidates for IBD.
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors: Aurélien
authors: A
authors: Tourteau
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors: Natascha
authors: N
authors: Leleu-Chavain
authors: Université Lille Nord de France, U995 INSERM, Digestive Inflammatory Diseases: Pathophysiology and Development of Therapeutic Targets, IFR114, Amphis J&K, Boulevard du Pr. Leclercq, F-59045 Lille, France.
authors: Mathilde
authors: M
authors: Body-Malapel
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors: Virginie
authors: V
authors: Andrzejak
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors: Amélie
authors: A
authors: Barczyk
authors: Université Lille Nord de France, U995 INSERM, Digestive Inflammatory Diseases: Pathophysiology and Development of Therapeutic Targets, IFR114, Amphis J&K, Boulevard du Pr. Leclercq, F-59045 Lille, France.
authors: Madjid
authors: M
authors: Djouina
authors: Université Catholique de Lille, HEI, EA4481, Laboratoire de Pharmacochimie, 13 Rue de Toul, F-59046 Lille, France.
authors: Benoit
authors: B
authors: Rigo
authors: Université Lille Nord de France, U995 INSERM, Digestive Inflammatory Diseases: Pathophysiology and Development of Therapeutic Targets, IFR114, Amphis J&K, Boulevard du Pr. Leclercq, F-59045 Lille, France.
authors: Pierre
authors: P
authors: Desreumaux
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors: Philippe
authors: P
authors: Chavatte
authors: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 rue du Pr. Laguesse, BP83, F-59006 Lille, France. Electronic address: regis.millet@univ-lille2.fr.
authors: Régis
authors: R
authors: Millet
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002186:Cannabinoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000218:Adamantane; D000581:Amidohydrolases; D000893:Anti-Inflammatory Agents; D002186:Cannabinoids; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases
keywords: CB(2); Cannabinoid; FAAH; IBD; Isoxazoles