title: 4-Oxo-1,4-dihydropyridines as selective CB₂ cannabinoid receptor ligands. Part 2: discovery of new agonists endowed with protective effect against experimental colitis.
abstract: Further on to our earlier work on the 4-oxo-1,4-dihydropyridine, we describe herein our strategy to get access to potent selective CB₂ receptor agonists. Thus, we designed and synthesized 29 compounds, evaluated on both hCB₁ and hCB₂ cannabinoid receptors, and assessed 11 of them in the TNBS-induced colitis model in mice. Compound 48 was found to be the most efficient of our series, exhibiting an exquisite protection against experimental colitis, superior to the one observed after treatment with Pentasa.
authors.affiliation: ICPAL, Université Lille Nord de France , EA4481, IFR114, 3 Rue du Pr. Laguesse, BP 83, F-59006 Lille Cedex, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: El Bakali
authors.forename: Pauline
authors.initials: P
authors.lastname: Gilleron
authors.forename: Mathilde
authors.initials: M
authors.lastname: Body-Malapel
authors.forename: Roxane
authors.initials: R
authors.lastname: Mansouri
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Madjid
authors.initials: M
authors.lastname: Djouina
authors.forename: Amélie
authors.initials: A
authors.lastname: Barczyk
authors.forename: Frédérique
authors.initials: F
authors.lastname: Klupsch
authors.forename: Virginie
authors.initials: V
authors.lastname: Andrzejak
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lipka
authors.forename: Christophe
authors.initials: C
authors.lastname: Furman
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.forename: Régis
authors.initials: R
authors.lastname: Millet
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism; D016466:CHO Cells; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007408:Intestinal Absorption; D008024:Ligands; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D008024:Ligands; D011725:Pyridines; D043885:Receptor, Cannabinoid, CB2; D014302:Trinitrobenzenesulfonic Acid; D000218:Adamantane