Guanine, pyrazolo[3,4-d]pyrimidine, and triazolo[4,5-d]pyrimidine (8-azaguanine) phosphonate acyclic derivatives as inhibitors of purine nucleoside phosphorylase

J Med Chem. 1996 Feb 16;39(4):949-56. doi: 10.1021/jm950736k.

Abstract

Phosphonate acyclic derivates of guanines, pyrazolo[3,4-d]pyrimidines, and triazolo[4,5-d]-pyrimidines (8-azaguanines) are inhibitors of the enzyme purine nucleoside phosphorylase (PNPase) with Ki' values ranging from 0.05 to 1.6 microM. These compounds are enzymatically stable congeners of the potent PNPase inhibitor acyclovir diphosphate (53).

Publication types

  • Comparative Study

MeSH terms

  • Azaguanine / analogs & derivatives*
  • Azaguanine / chemical synthesis*
  • Azaguanine / chemistry
  • Azaguanine / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Erythrocytes / enzymology
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis*
  • Guanine / pharmacology
  • Humans
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology
  • Pteridines / chemical synthesis*
  • Pteridines / chemistry
  • Pteridines / pharmacology
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
  • Purine-Nucleoside Phosphorylase / blood
  • Purine-Nucleoside Phosphorylase / isolation & purification
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Organophosphonates
  • Pteridines
  • Guanine
  • Purine-Nucleoside Phosphorylase
  • Azaguanine