Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3149-52. doi: 10.1016/s0960-894x(02)00646-7.

Abstract

We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC(50)=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC(50)=3.5 nM, PDE6/PDE5=7).

Publication types

  • Comparative Study

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Alkylation
  • Animals
  • Area Under Curve
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Drug Design
  • Electric Stimulation
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Penis / drug effects
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / metabolism*
  • Piperazines / pharmacology
  • Purines
  • Rabbits
  • Sildenafil Citrate
  • Structure-Activity Relationship
  • Sulfones
  • Xanthines / chemical synthesis*
  • Xanthines / pharmacology*

Substances

  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Xanthines
  • Sildenafil Citrate
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5