Synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives

A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbruggen reaction. Iron chelation studies. and antiviral evaluation against a broad panel of viruses, were performed. The pK(a) value of ligand 25 and the stability constant of the corresponding iron(111) complex were compared to those of deferiprone. The pFe(3+) values were found to be similar. Some compounds showed moderate activity against both wild-type HSV-1 and HSV-2 as well as against a thymidine kinase deficient strain of HSV-1. These results suggest a novel mode of action for this group of nucleoside analogues.