New orally active PDE4 inhibitors with therapeutic potential

Bioorg Med Chem Lett. 2004 Jan 5;14(1):29-32. doi: 10.1016/j.bmcl.2003.10.025.

Abstract

Structural optimization of pyrazolopyridine derivative 2, which is one of the newly discovered chemical leads for PDE4 inhibitors from our in-house library, was carried out successfully. The process of discovery of new orally active PDE4 inhibitors, which are expected to possess therapeutic potential, is presented and their structure-activity relationships are discussed.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Administration, Oral
  • Animals
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology
  • Bronchoconstrictor Agents / administration & dosage
  • Bronchoconstrictor Agents / therapeutic use
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Ferrets
  • Gastric Emptying / drug effects
  • Guinea Pigs
  • Humans
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pyrazoles / administration & dosage
  • Pyrazoles / chemistry
  • Pyrazoles / therapeutic use
  • Pyridines / administration & dosage
  • Pyridines / chemistry
  • Pyridines / therapeutic use
  • Rats
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vomiting / chemically induced

Substances

  • Bronchoconstrictor Agents
  • Phosphodiesterase Inhibitors
  • Pyrazoles
  • Pyridines
  • Tumor Necrosis Factor-alpha
  • pyrazolopyridine
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4