Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6279-82. doi: 10.1016/j.bmcl.2008.09.108. Epub 2008 Oct 11.

Abstract

In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure-activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Erectile Dysfunction / drug therapy*
  • Humans
  • Male
  • Molecular Structure
  • Penile Erection / drug effects*
  • Phosphodiesterase 5 Inhibitors*
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Quinazolines / chemical synthesis*
  • Quinazolines / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors
  • Quinazolines