Synthesis of 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridine-6-yl)-benzoic acid: a potent and selective phosphodiesterase type 4D inhibitor

Bioorg Med Chem Lett. 2002 Jan 21;12(2):233-5. doi: 10.1016/s0960-894x(01)00720-x.

Abstract

The synthesis of a 6,8-disubstituted 1,7-naphthyridine 1 and its characterization as a potent and selective phosphodiesterase type 4D inhibitor (IC(50)=1.5nM) are described. The compound inhibited TNFalpha-release from human peripheral blood mononuclear cells and was orally active in a model of adjuvant-induced arthritis in rats.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Benzoates / chemical synthesis*
  • Benzoates / pharmacology
  • Cells, Cultured
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Humans
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Naphthyridines / chemical synthesis*
  • Naphthyridines / pharmacology
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 4-(8-benzo(1,2,5)oxadiazol-5-yl-(1,7)naphthyridine-6-yl)-benzoic acid
  • Benzoates
  • Naphthyridines
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4