Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents.
Fiche publication
Date publication
février 2018
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SAPI Janos, Dr VELARD Frédéric, Dr GERARD Stéphane, Dr COCHARD Marie
Tous les auteurs :
Barberot C, Moniot A, Allart-Simon I, Malleret L, Yegorova T, Laronze-Cochard M, Bentaher A, Médebielle M, Bouillon JP, Hénon E, Sapi J, Velard F, Gérard S
Lien Pubmed
Résumé
Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells.
Mots clés
Anti-Inflammatory Agents, Non-Steroidal, chemical synthesis, Cyclic Nucleotide Phosphodiesterases, Type 4, metabolism, Dose-Response Relationship, Drug, Humans, Models, Molecular, Molecular Structure, Neutrophils, drug effects, Phosphodiesterase 4 Inhibitors, chemical synthesis, Pyridazines, chemical synthesis, Structure-Activity Relationship
Référence
Eur J Med Chem. 2018 Feb 25;146:139-146