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5-Substituted Arabinofuranosyluracil Nucleosides as Antiherpesvirus Agents: From araT to BV-araU

  • Chapter
Nucleosides and Nucleotides as Antitumor and Antiviral Agents

Abstract

After the discovery of acyclovir, much effort was expanded to find new antiherpes-viral agents. Before that time, however, application of thymidine analogues as antiherpes-viral agents had been tried. The origin of this study is 2′ -deoxy-5-iodouridine (IDU). Although classical thymidine analogues such as IDU, trifluorothymidine, and 2′ -deoxy-5-ethyluridine (EDU), are used only topically due to their narrow selectivity, approach to application of thymidine analogues for selective antiviral agents was strongly emphasized by the findings by Jamieson et al.l,2 that herpes virus encodes deoxypyrimidine nucleoside kinase (dPyK or viral thymidine kinase), and this enzyme differs far from cellular thymidine kinase (TK) in substrate specificity. Then, in a decade from 1975, a variety of thymidine analogues and acyclic guanosine derivatives were synthesized and tested for antiherpesviral activity to seek new antiviral agents for clinical use. The majority of compounds showing selective antiherpesviral activity are a variety of 5-substituted 2′ -deoxy-uridine (dUrd) and arabinofuranosyluracil (araU) derivatives, acyclic guanosine analogues, and 2′-fluoro-arabinosylpyrimidine nucleosides. The rationale for the selective antiherpesviral agents is based on the preferential phosphorylation by the viral dPyK having broad substrate specificity in the infected cells.

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  1. Biology Laboratories, R & D Division, Yamasa Corporation, 10-1 Araoicho 2-chome, Choshi, Japan 288

    Haruhiko Machida

  2. Chemistry Laboratories R & D Division, Yamasa Corporation, 10-1 Araoicho 2-chome, Choshi, Japan 288

    Shinji Sakata

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  1. Haruhiko Machida
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  1. The University of Georgia, Athens, Georgia

    Chung K. Chu

  2. The University of Tennessee, Knoxville, Tennessee, USA

    David C. Baker

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Machida, H., Sakata, S. (1993). 5-Substituted Arabinofuranosyluracil Nucleosides as Antiherpesvirus Agents: From araT to BV-araU. In: Chu, C.K., Baker, D.C. (eds) Nucleosides and Nucleotides as Antitumor and Antiviral Agents. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2824-1_13

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  • DOI: https://doi.org/10.1007/978-1-4615-2824-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6221-0

  • Online ISBN: 978-1-4615-2824-1

  • eBook Packages: Springer Book Archive

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