Pyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors. Issue 4 (1st March 2021)

• Record Type: Journal Article
• Authors: Allart-Simon, Ingrid; Moniot, Aurélie; Bisi, Nicolo; Ponce-Vargas, Miguel; Audonnet, Sandra; Laronze-Cochard, Marie; Sapi, Janos; Hénon, Eric; Velard, Frédéric; Gérard, Stéphane
• Is Part Of: RSC medicinal chemistry. Volume 12:Issue 4(2021)
• Page Start: 584
• Page End: 592
• Publication Date: 2021-03-01
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d0md00423e
• Languages: English
• ISSNs: 2632-8682

Abstract

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.