Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase

J Med Chem. 1993 Apr 16;36(8):1024-31. doi: 10.1021/jm00060a010.


In an effort to develop potent human purine nucleoside phosphorylase (PNP) inhibitors as immunosuppressive and chemotherapeutic agents, several 8-aminoguanine derivatives were synthesized and evaluated as potential PNP inhibitors. These studies were designed to investigate the hydrophobic effect of a substituent on the N-9 of the purine heterocycle and/or the C-5' positions. Compounds such as 8-aminoguanosine, guanosine, formycin B, and 8-aminoacyclovir containing a p-(fluorosulfonyl)benzoyl moiety were synthesized. The affinity of these compounds to erythrocytic PNP was determined and none of these compounds showed a better affinity than those of the parent compounds. However, we found that the effect of hydrophobicity at the N-9 and the C-5' positions might play an important role in binding to the active site of PNP. Thus, 8-amino-5'-deoxy-5'-(phenylthio)guanosine (19) was found to be the best inhibitor in this series of compounds with a Ki = 0.45 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Formycins / chemical synthesis*
  • Formycins / chemistry
  • Formycins / pharmacology
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanine / pharmacology
  • Humans
  • Kinetics
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
  • Purine-Nucleoside Phosphorylase / metabolism
  • Structure-Activity Relationship


  • Formycins
  • 8-aminoguanine
  • Guanine
  • Purine-Nucleoside Phosphorylase