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(S)-1-(3-Hydroxy-2-(phosphonylmethoxy)propyl)cytosine (HPMPC): A Potent Antiherpesvirus Agent

  • Joanne J. Bronson
  • Louis M. Ferrara
  • Michael J. M. Hitchcock
  • Hsu-Tso Ho
  • Kathleen L. Woods
  • Ismail Ghazzouli
  • Earl R. Kern
  • Kenneth F. Soike
  • John C. Martin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 278)

Abstract

(S)-1-(3-Hydroxy-2-(phosphonylmethoxy)propyl)cytosine (HPMPC; 1, fig. 1, left) has been identified from a series of phosphonate nucleotide analogues as having the greatest therapeutic index against lethal herpes simplex virus (HSV) infections in mice (1, 2). The prototype compound of the series is the adenine analogue 2 (HPMPA; 2, fig. 1, right), which was first described by De Clercq et al. in 1986 as a broad-spectrum antiviral agent (3). HPMPA was shown to have a mechanism of action that involves, at least in part, two intracellular phosphorylations to give a diphosphate, which then selectively inhibits the viral polymerase. Since the discovery of HPMPA, additional studies have shown that many related phosphonylmethoxy nucleotide analogues have broad-spectrum in vitro activity (4, 5). Of this class of nucleotide analogues, HPMPC has been described as having the best in vitro therapeutic index against cytomegalovirus (CMV) (2, 6).

Keywords

Nucleotide Analogue 29th Interscience Simian Varicella Virus Cesium Carbonate Adenine Analogue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bronson, J. J., Ghazzouli, I., Hitchcock, M. J. M., Webb, R. R. & Martin, J. C. (1989) J. Med Chem. 32, 1457–1463.PubMedCrossRefGoogle Scholar
  2. 2.
    Bronson, J. J., Ghazzouli, I., Hitchcock, M. J. M., Webb, R. R., Kern, E. R. & Martin, J. C. (1989) in Nucléotide Analogues as Antiviral Agents, ed. Martin, J. C. ( American Chemical Society, Washington, D.C. ), pp. 88–102.CrossRefGoogle Scholar
  3. 3.
    De Clercq, E., Holy, A., Rosenberg, I., Sakuma, T., Balzarini, J. & Maudgal, P. C. (1986) Nature (London) 323, 464–467.CrossRefGoogle Scholar
  4. 4.
    Votruba, I., Bernaerts, R., Sakuma, T., De Clercq, E., Merta, A., Rosenberg, I. & Holy, A. (1987) Mol. Phannacol. 32, 524–529.Google Scholar
  5. 5.
    De Clercq, E., Sakuma T., Baba, M., Pauwels, R., Balzarini, J., Rosenberg, I. & Holy, A. (1987) Antiviral Res. 8, 261–272.PubMedCrossRefGoogle Scholar
  6. 6.
    Snoeck, R., Sakuma, T., De Clercq, E., Rosenberg, I. & Holy, A. (1988) Antimicrob. Agents Chemother. 32, 1839–1844.PubMedGoogle Scholar
  7. 7.
    Kern, E. R. & Vogt, P. E. 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Tex., September 19, 1989, Abstr. 751 (abstracts published by ASM, Washington, D.C.).Google Scholar
  8. 8.
    Webb, R. R., Wos, J. A., Bronson, J. J. & Martin, J. C. (1988) Tetrahedron Lett. 29, 5475–5478.CrossRefGoogle Scholar
  9. 9.
    Holy, A. (1978) Collect. Czech. Chem. Commun. 43, 2054–2061.CrossRefGoogle Scholar
  10. 10.
    Zemlicka, J., Chladek, S., Holy, A. & Smrt, J. (1966) Collect. Czech. Chem. Commun. 31, 3198–3211.Google Scholar
  11. 11.
    Holy, A. & Rosenberg, I. (1982) Collect. Czech. Chem. Commun. 47, 3447–3463.CrossRefGoogle Scholar
  12. 12.
    Hitchcock, M. J. M., Woods, K., Bronson, J. J. & Martin, J. C. 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Tex., September 19, 1989, Abstr. 739 (abstracts published by ASM, Washington, D.C.).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Joanne J. Bronson
    • 1
  • Louis M. Ferrara
    • 1
  • Michael J. M. Hitchcock
    • 1
  • Hsu-Tso Ho
    • 1
  • Kathleen L. Woods
    • 1
  • Ismail Ghazzouli
    • 1
  • Earl R. Kern
    • 2
  • Kenneth F. Soike
    • 3
  • John C. Martin
    • 1
  1. 1.Bristol-Myers SquibbWallingfordUSA
  2. 2.University of AlabamaBirminghamUSA
  3. 3.Delta Regional Primate CenterTulane UniversityCovingtonUSA

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