Certain 8-amino-9-(benzyl)guanines as potential purine nucleoside phosphorylase inhibitors

Abstract

Several 8-amino-9-(benzyl)guanines were selected for synthesis as potential purine nucleoside phosphorylase (PNP) inhibitors on the basis of the Topliss decision tree. These compounds were prepared by the treatment of oxazolo[5,4-d]pyrimidine intermediates with potassium carbonate in a 1-pot reaction. All compounds were evaluated for PNP inhibitory activity using an in vitro enzyme inhibition assay. The extent of binding to PNP appeared to be influenced by the presence of electron donating 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.