Potent and selective xanthine-based inhibitors of phosphodiesterase 5

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2376-9. doi: 10.1016/j.bmcl.2006.11.019. Epub 2006 Nov 10.

Abstract

Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Biological Availability
  • Cattle
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dogs
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Erectile Dysfunction / drug therapy
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Pharmacokinetics
  • Protein Isoforms / drug effects
  • Structure-Activity Relationship
  • Xanthines / chemistry
  • Xanthines / pharmacology*

Substances

  • Enzyme Inhibitors
  • Protein Isoforms
  • Xanthines
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human