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

Bioorg Med Chem Lett. 2002 Jun 3;12(11):1451-6. doi: 10.1016/s0960-894x(02)00202-0.

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.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / 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
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyridines / blood
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Rats
  • Rolipram / analogs & derivatives
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 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