PMID: 11907180Mar 22, 2002Paper

Pharmacological profile of a novel phosphodiesterase 4 inhibitor, 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridin-6-yl)-benzoic acid (NVP-ABE171), a 1,7-naphthyridine derivative, with anti-inflammatory activities

The Journal of Pharmacology and Experimental Therapeutics
Alexandre TrifilieffRene Hersperger

Abstract

We investigated the pharmacology of a new class of phosphodiesterase 4 (PDE4) inhibitor, 6,8-disubstituted 1,7-naphthyridines, by using 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridin-6-yl)-benzoic acid (NVP-ABE171) as a representative compound and compared its potency with the most advanced PDE4 inhibitor, undergoing clinical trials, Ariflo [cis-4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl-r-1-cyclohexanecarboxylic acid)]. NVP-ABE171 inhibited the activity of phosphodiesterase 4A, 4B, 4C, and 4D with respective IC(50) values of 602, 34, 1230, and 1.5 nM. Ariflo was about 40 times less potent. In human cells, NVP-ABE171 inhibited the eosinophil and neutrophil oxidative burst, the release of cytokines by T cells, and the tumor necrosis factor-alpha release from monocytes, in the nanomolar range. Ariflo presented a similar inhibition profile but was 7 to 50 times less potent. In BALB/c mice challenged with lipopolysaccharide, NVP-ABE171 inhibited the airway neutrophil influx and activation with an ED(50) in the range of 3 mg/kg. Ariflo was inactive up to a dose of 10 mg/kg. In ovalbumin sensitized Brown Norway rats, NVP-ABE171 inhibited the lipopolysaccharide-induced airway neutrophil influx and activation (ED(50) of 0.2 mg/kg) ...Continue Reading

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Citations

Jun 1, 2005·Pharmacology & Therapeutics·María Jesús SanzEsteban J Morcillo
Oct 16, 2003·Trends in Pharmacological Sciences·Nicolau BeckmannJohn R Fozard
Aug 15, 2012·Journal of Medicinal Chemistry·Neil J PressAlexandre Trifilieff
Mar 9, 2005·Respiration; International Review of Thoracic Diseases·Néstor A Molfino
Jun 7, 2003·American Journal of Respiratory and Critical Care Medicine·Shashi P SinghMohan L Sopori
Nov 23, 2005·Expert Opinion on Therapeutic Targets·Kam Y J ZhangGideon Bollag
Jul 23, 2004·Expert Opinion on Therapeutic Targets·Maria G BelvisiMark A Birrell
Jan 9, 2003·Expert Opinion on Investigational Drugs·David J Hele, Maria G Belvisi
Jan 25, 2005·Journal of Enzyme Inhibition and Medicinal Chemistry·Nicolas GouaultMichele David
Nov 1, 2011·International Immunopharmacology·Miki KobayashiYasuaki Shimizu
Oct 13, 2007·European Journal of Radiology·Nicolau BeckmannAlexandre Trifilieff
Jun 27, 2006·Pulmonary Pharmacology & Therapeutics·Néstor A Molfino, Peter K Jeffery
Mar 25, 2006·Phytotherapy Research : PTR·G D SinghR K Johri
Aug 2, 2003·The Journal of Pharmacology and Experimental Therapeutics·István KuruczNicholas Bodor
Jul 25, 2006·The Journal of Pharmacology and Experimental Therapeutics·Kerryn McCluskieG Roger Thomas
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miyako ArigaMarco Conti
Aug 26, 2014·Molecular Cancer Research : MCR·Ginny L PowersPaul C Marker
Feb 12, 2021·Journal of Medicinal Chemistry·Ross S ManciniMark A Reed
Jul 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Abid BhatMeena Kishore Sakharkar

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