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
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Benzoates / chemical synthesis*
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Benzoates / pharmacology
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Cells, Cultured
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Humans
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Monocytes / drug effects
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Monocytes / metabolism
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Naphthyridines / chemical synthesis*
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Naphthyridines / pharmacology
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Phosphodiesterase Inhibitors / chemical synthesis*
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Phosphodiesterase Inhibitors / pharmacology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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4-(8-benzo(1,2,5)oxadiazol-5-yl-(1,7)naphthyridine-6-yl)-benzoic acid
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Benzoates
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Naphthyridines
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Phosphodiesterase Inhibitors
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Tumor Necrosis Factor-alpha
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4