Synthesis and Antiviral Evaluation of Cyclic and Acyclic 2-Methyl-3-hydroxy-4-pyridinone Nucleoside Derivatives

Karine Barral (1) , Jan Balzarini (2) , Johan Neyts (2) , Erik de Clercq (2) , Robert Hider (3) , Michel Camplo (1)

1 GCOMM - Groupe de chimie organique et matériaux moléculaires
2 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
3 King‘s College London

A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbrüggen 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(III) 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.

Domains: Chemical Sciences; Chemical Sciences; Medicinal Chemistry

Karine Barral, Jan Balzarini, Johan Neyts, Erik de Clercq, Robert Hider, et al.. Synthesis and Antiviral Evaluation of Cyclic and Acyclic 2-Methyl-3-hydroxy-4-pyridinone Nucleoside Derivatives. Journal of Medicinal Chemistry, 2006, 49 (1), pp.43-50. ⟨10.1021/jm0504306⟩. ⟨hal-02061660⟩