Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1380-5. doi: 10.1016/j.bmcl.2009.01.045. Epub 2009 Jan 19.

Abstract

Crystallography-driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of a series of quinoline derivatives that were highly potent and selective inhibitors of PDE4 with a good pharmacokinetic profile in the rat. Quinolines 43 and 48 have potential as oral medicines for the treatment of COPD.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Cattle
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Humans
  • Male
  • Phosphodiesterase 4 Inhibitors*
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Phosphodiesterase Inhibitors / chemistry*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Quinolines / administration & dosage*
  • Quinolines / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

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