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.
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.
Hersperger
Rene
R
Novartis Pharma AG, Arthritis & Bone Metabolism, CH-4002 Basel, Switzerland. rene.hersperger@pharma.novartis.com
Dawson
Janet
J
Mueller
Thomas
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
C449669:4-(8-benzo(1,2,5)oxadiazol-5-yl-(1,7)naphthyridine-6-yl)-benzoic acid; D001565:Benzoates; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4