Open AccessPyridazinone derivatives as potential anti-inflammatory agents: synthesis and biological evaluation as PDE4 inhibitors
Author(s) -
Ingrid AllartSimon,
Aurélie Moniot,
Nicolo Bisi,
Miguel PonceVargas,
Sandra Audonnet,
Marie Laronze-Cochard,
János Sápi,
Éric Hé,
Frédéric Velard,
Stéphane Gérard
Publication year - 2021
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d0md00423e
Subject(s) - moiety , indole test , anti inflammatory , chemistry , combinatorial chemistry , pharmacology , stereochemistry , biochemistry , medicine
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.