Synthesis and biological evaluation of pyridazinone derivatives as potential anti-inflammatory agents

Eur J Med Chem. 2018 Feb 25:146:139-146. doi: 10.1016/j.ejmech.2018.01.035. Epub 2018 Jan 17.

Abstract

Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells.

Keywords: Anti-inflammatory; PDE4; Phosphodiesterase inhibitors; Pyridazinone.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Neutrophils / drug effects
  • Phosphodiesterase 4 Inhibitors / chemical synthesis
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Pyridazines / chemical synthesis
  • Pyridazines / chemistry
  • Pyridazines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Phosphodiesterase 4 Inhibitors
  • Pyridazines
  • Cyclic Nucleotide Phosphodiesterases, Type 4