Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors.
Fiche publication
Date publication
avril 2021
Journal
RSC medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SAPI Janos, Dr VELARD Frédéric, Dr AUDONNET Sandra , Dr GERARD Stéphane, Dr COCHARD Marie
Tous les auteurs :
Allart-Simon I, Moniot A, Bisi N, Ponce-Vargas M, Audonnet S, Laronze-Cochard M, Sapi J, Hénon E, Velard F, Gérard S
Lien Pubmed
Résumé
Cyclic nucleotide phosphodiesterase type 4 (PDE4), which controls the intracellular level of cyclic adenosine monophosphate (cAMP), has aroused scientific attention as a suitable target for anti-inflammatory therapy of respiratory diseases. This work describes the development and characterization of pyridazinone derivatives bearing an indole moiety as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4-(5-methoxy-1-indol-3-yl)-6-methylpyridazin-3(2)-one possesses promising activity, and selectivity towards PDE4B isoenzymes and is able to regulate potent pro-inflammatory cytokine and chemokine production by human primary macrophages.
Référence
RSC Med Chem. 2021 Apr 28;12(4):584-592