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Design, synthesis, and antiviral activity of novel phosphoramidates

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Abstract

Novel phosphoramidates 8a-b possessing structural features similar to nucleoside phosphonates HPMPA, PMEA, PMEG, and oxathiolane nucleoside BCH189 were synthesized by chemical methods. The designed molecules exhibited significant antiviral activities. We hypothesized that, as a masked membranesoluble form of the potential bioactive compounds 7a-b, phosphoramidates 8a-b may act as a proteinase substrate. Then, the potential drug 7a-b will be liberated inside the infected cells. The triphosphate anabolites of each could act as competitive substrates for the HIV reverse transcriptase and terminate DNA synthesis after being incorporated into the growing DNA strand. Phosphoramidates 8a-b were synthesized as racemates to allow access to both enantiomers.

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Authors and Affiliations

  1. Institute of Chemistry, Academia Sinica, Taipei, 115, Taiwan

    F. Valiyev, H. -J. Liu & G. H. Hakimelahi

  2. Center of General Education, Chang Gung University, 259 Wen-Hwa, Kwei-Shan, Taoyuan 333, Taiwan ROC

    F. -Y. Tsai

  3. Department of Chemistry, National Tsing Hua University, Hsinchu, 300, Taiwan

    H. -J. Liu

  4. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    A. A. Saboury, A. A. Moosavi-Movahedi & G. H. Hakimelahi

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  1. F. Valiyev
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  2. F. -Y. Tsai
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  4. H. -J. Liu
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  5. A. A. Moosavi-Movahedi
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  6. G. H. Hakimelahi
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Correspondence to F. -Y. Tsai.

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Valiyev, F., Tsai, F.Y., Saboury, A.A. et al. Design, synthesis, and antiviral activity of novel phosphoramidates. JICS 5, 228–237 (2008). https://doi.org/10.1007/BF03246112

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  • DOI: https://doi.org/10.1007/BF03246112

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