Title: Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base
Authors: McGuigan, C ×
Yarnold, C J
Jones, G
Velázquez, S
Barucki, H
Brancale, A
Andrei, Graciela
Snoeck, Robert
De Clercq, Erik
Balzarini, Jan #
Issue Date: Nov-1999
Series Title: Journal of Medicinal Chemistry vol:42 issue:22 pages:4479-84
Abstract: We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C(8)-C(10), for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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