Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors. Issue 4 (1st March 2021) - Allart-Simon, Ingrid
Abstract : This work describes the development of pyridazinone derivatives bearing an indole moiety as PDE4B inhibitors and their evaluation as anti-inflammatory agents. Abstract : 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 H -indol-3-yl)-6-methylpyridazin-3(2 H )-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.