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

RSC Medicinal Chemistry Pub Date: 2021-03-01 DOI: 10.1039/D0MD00423E

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-1H-indol-3-yl)-6-methylpyridazin-3(2H)-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.

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