Phosphonate derivatives of N9-benzylguanine: a new class of potent purine nucleoside phosphorylase inhibitors

Abstract New phosphonate derivatives of N 9 -benzylguanine ( 5a – 5d ) have been designed and prepared as purine nucleoside phosphorylase inhibitors. Enzyme inhibition studies with PNP from calf spleen or human erythrocytes demonstrate that the trifluorophosphonate 5b , the fluorovinylphosphonate 5c and the vinylphosphonate 5d , with K i values around 1 nM, are the most potent inhibitors of PNP ever reported.