Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides.

Ugo Pradère, Vincent Roy, Aurélien Montagu, Ozkan Sari, Manabu Hamada, Jan Balzarini, Robert Snoeck, Graciela Andrei, Luigi A Agrofoglio

Institut de Chimie Organique et Analytique, UMR 7311 CNRS, Université d'Orléans, 45067 Orléans, France.

European journal of medicinal chemistry 2012 Nov

filter terms:

Seventeen hitherto unknown bis(POM) prodrugs of novel (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides were prepared in a straight approach and at good yields. Those compounds were synthesized by the reaction of purine nucleobases directly with the phosphonate synthon 3 bearing POM biolabile groups under Mitsunobu conditions. All obtained compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex viruses 1 and 2, varicella zoster virus, Feline herpes virus, human cytomegalovirus, HIV-1 and HIV-2. Among these molecules, some of them exhibit anti-VZV and anti-HIV activity at submicromolar concentrations. This class of compound will be of further interest for lead optimization as anti-infectious agents. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Citation

Ugo Pradère, Vincent Roy, Aurélien Montagu, Ozkan Sari, Manabu Hamada, Jan Balzarini, Robert Snoeck, Graciela Andrei, Luigi A Agrofoglio. Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides. European journal of medicinal chemistry. 2012 Nov;57:126-33