title: 3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis.
abstract: 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.
authors.affiliation: Université Lille Nord de France, EA4481, Institut de Chimie Pharmaceutique Albert Lespagnol, IFR114, 3 Rue du Pr. Laguesse, BP83, F-59006 Lille, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Tourteau
authors.forename: Virginie
authors.initials: V
authors.lastname: Andrzejak
authors.forename: Mathilde
authors.initials: M
authors.lastname: Body-Malapel
authors.forename: Lucas
authors.initials: L
authors.lastname: Lemaire
authors.forename: Amélie
authors.initials: A
authors.lastname: Lemoine
authors.forename: Roxane
authors.initials: R
authors.lastname: Mansouri
authors.forename: Madjid
authors.initials: M
authors.lastname: Djouina
authors.forename: Nicolas
authors.initials: N
authors.lastname: Renault
authors.forename: Jamal
authors.initials: J
authors.lastname: El Bakali
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.forename: Natascha
authors.initials: N
authors.lastname: Leleu-Chavain
authors.forename: Régis
authors.initials: R
authors.lastname: Millet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D019073:HT29 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007555:Isoxazoles / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D007555:Isoxazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate
keywords: CB(2); Cannabinoid; IBD; Isoxazoles