Discovery of oral and inhaled PDE4 inhibitors

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5528-32. doi: 10.1016/j.bmcl.2013.08.056. Epub 2013 Aug 21.

Abstract

The optimization of oxazole-based PDE4 inhibitor 1 has led to the identification of both oral (compound 16) and inhaled (compound 34) PDE4 inhibitors. Selectivity against PDE10/PDE11, off target screening, and in vivo activity in the rat are discussed.

Keywords: Asthma; COPD; PDE4 inhibitor.

MeSH terms

  • Administration, Oral
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Drug Evaluation, Preclinical
  • Half-Life
  • Inhalation
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry*
  • Oxazoles / pharmacokinetics
  • Phosphodiesterase 4 Inhibitors / chemical synthesis
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / pharmacokinetics
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / chemistry
  • Proline / pharmacokinetics
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Oxazoles
  • Phosphodiesterase 4 Inhibitors
  • Quinolines
  • Proline
  • Cyclic Nucleotide Phosphodiesterases, Type 4