Water-soluble PDE4 inhibitors for the treatment of dry eye

Bioorg Med Chem Lett. 2010 May 1;20(9):2928-32. doi: 10.1016/j.bmcl.2010.03.023. Epub 2010 Mar 7.

Abstract

PDE4 inhibitors have the potential to alleviate the symptoms and underlying inflammation associated with dry eye. Disclosed herein is the development of a novel series of water-soluble PDE4 inhibitors. Our studies led to the discovery of coumarin 18, which is effective in a rabbit model of dry eye and a tear secretion test in rats.

MeSH terms

  • 4-Aminopyridine / analogs & derivatives*
  • 4-Aminopyridine / chemical synthesis
  • 4-Aminopyridine / chemistry
  • 4-Aminopyridine / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / therapeutic use
  • Binding Sites
  • Computer Simulation
  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / therapeutic use
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy
  • Phosphodiesterase 4 Inhibitors*
  • Rabbits
  • Rats
  • Water / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Coumarins
  • Phosphodiesterase 4 Inhibitors
  • Water
  • 4-Aminopyridine
  • Cyclic Nucleotide Phosphodiesterases, Type 4

Associated data

  • PDB/3LY2