CERTAIN 8-AMINO-9-(BENZYL)GUANINES AS POTENTIAL PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS

Several 8-amino-9-(benzyl)guanines were selected for synthesis as pote ntial purine nucleoside phosphorylase (PNP) inhibitors on the basis of the Topliss decision tree. These compounds were prepared by the treat ment of oxazolo[5,4-d] pyrimidine intermediates with potassium carbona te in a 1-pot reaction. All compounds were evaluated for PNP inhibitor y activity using an in vitro enzyme inhibition assay. The extent of bi nding to PNP appeared to be influenced by the presence of-electron don ating substituents on the phenyl ring of the benzyl group. None of the tested compounds were more active than the parent compound, 8-amino-9 -benzylguanine. The inhibitory activity seems to be most likely-sigma- dependent.