Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides

Manbu Hamada, Vincent Roy, Tamara R. McBrayer, Tony Whitaker, Cesar Urbina Blanco, Steven Patrick Nolan, Jan Balzarini, Robert Snoeck, Graciela Andrei, Raymond F. Schinazi, Luigi A. Agrofoglio

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step.

All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.
Original languageEnglish
Pages (from-to)398-408
Number of pages11
JournalEuropean Journal Of Medicinal Chemistry
Volume67
Early online date4 Jul 2013
DOIs
Publication statusPublished - Sept 2013

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