title: Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides.
abstract: 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.
authors.affiliation: Institut de Chimie Organique et Analytique, UMR 7311 CNRS, Université d'Orléans, 45067 Orléans, France.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pradère
authors.forename: Vincent
authors.initials: V
authors.lastname: Roy
authors.forename: Aurélien
authors.initials: A
authors.lastname: Montagu
authors.forename: Ozkan
authors.initials: O
authors.lastname: Sari
authors.forename: Manabu
authors.initials: M
authors.lastname: Hamada
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Luigi A
authors.initials: LA
authors.lastname: Agrofoglio
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004267:DNA Viruses / Q000187:drug effects* / Q000254:growth & development; D004285:Dogs; D015195:Drug Design; D055808:Drug Discovery; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D011355:Prodrugs; D011684:Purine Nucleosides