CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.

Abstract

The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.

• Authors: R P Alexander, G J Warrellow, M A W Eaton, E C Boyd, J C Head, J R Porter, J A Brown, J T Reuberson, B Hutchinson, P Turner, B Boyce, D Barnes, B Mason, A Cannell, R J Taylor, A Zomaya, A Millican, J Leonard, R Morphy, M Wales, M Perry, R A Allen, N Gozzard, B Hughes, G Higgs
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 12 Issue 11 Pg. 1451-6 (Jun 03 2002) ISSN: 0960-894X [Print] England
• PMID: 12031318 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Phosphodiesterase Inhibitors
• Pyridines
• Tumor Necrosis Factor-alpha
• CDP 840
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Rolipram

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors)
• Administration, Oral
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (blood, chemical synthesis, pharmacology)
• Asthma (drug therapy)
• Bronchoconstriction (drug effects)
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Dose-Response Relationship, Drug
• Ferrets
• Guinea Pigs
• Humans
• Inhibitory Concentration 50
• Phosphodiesterase Inhibitors (blood, chemical synthesis, pharmacology)
• Pyridines (blood, chemical synthesis, pharmacology)
• Rats
• Rolipram (analogs & derivatives)
• Saccharomyces cerevisiae (enzymology)
• Structure-Activity Relationship
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)