Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors

Ingrid Allart-Simon (1) , Aurélie Moniot (2) , Nicolo Bisi (1) , Miguel Ponce-Vargas (1) , Sandra Audonnet (3) , Marie Laronze-Cochard (1) , Janos Sapi (1) , Eric Hénon (1) , Frédéric Velard (2) , Stéphane Gérard (1)

1 ICMR - Institut de Chimie Moléculaire de Reims - UMR 7312
2 BIOS - Biomatériaux et inflammation en site osseux - EA 4691
3 URCACyt - Plateau Technique de Cytométrie en Flux

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 antiinflammatory 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 antiinflammatory agents. Among these derivatives, 4-(5-methoxy-1H-indol-3-yl)-6-methylpyridazin-3(2H)-one possesses promising activity, and selectivity towards PDE4B isoenzymes and is able to regulate potent proinflammatory cytokine and chemokine production by human primary macrophages.

Domaines: Chimie thérapeutique

Ingrid Allart-Simon, Aurélie Moniot, Nicolo Bisi, Miguel Ponce-Vargas, Sandra Audonnet, et al.. Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors. RSC Medicinal Chemistry, 2021, 12, pp.584 - 592. ⟨10.1039/d0md00423e⟩. ⟨hal-03352041⟩