SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1291-4. doi: 10.1016/j.bmcl.2003.12.027.

Abstract

Development of structure-activity relationship of cyclic guanines I lead us to discovery of a potent and selective series of phosphodiesterase 5 inhibitors 52-59 (IC50=1.3-11.0 nM, PDE6/5=116-600).

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Drug Delivery Systems / methods*
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / enzymology*
  • Guanine / administration & dosage
  • Guanine / chemistry*
  • Humans
  • Male
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Polycyclic Compounds / administration & dosage
  • Polycyclic Compounds / chemistry
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase Inhibitors
  • Polycyclic Compounds
  • Guanine
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human