New Pyrimidine Nucleosides with Potent Antiviral Activity

  • B. Leyland-Jones
Part of the Developments in Oncology book series (DION, volume 23)

Abstract

Several years ago, the Organic Chemistry Laboratory of the Memorial Sloan-Kettering Cancer Center embarked upon a program for the synthesis of 2’-substituted arabinosyl-pyrimidine nucleosides as potential anticancer and/or antiviral agents. Cytosine arabinoside, a potent antitumor drug, also inhibits the multiplication of several DNA viruses in cell culture. Therapeutic trials of cytosine arabinoside in herpes infections in animal models were not encouraging because its therapeutic to toxic ratio approached unity. Although arabinofuranosyluracil and some of its 5-alkylated derivatives had been shown to exhibit anti-herpes virus activities, the more attractive of these was arabinosylthymine which was active against HSV types I and II, as well as against equinine herpes virus. It was therefore obvious that the nature of the substituent at C-5 of the pyrimidine nucleoside was an important factor in the determination of biological activity. Since activity was noted for both the arabino- as well as for 2’-deoxyribo-pyrimidine nucleosides, the C-2’ substituent must also play a role. Fox and Watanabe therefore undertook the synthesis of a series of 5-substituted-1-(2’deoxy-2’-f luoro-β-D-ara- binofuranosyl) pyrimidines as potential antiviral agents.

Keywords

Pyrimidine Nucleoside Cytosine Uracil Acyclovir 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fox JJ, Lopez C, Watanabe KA: 2-Fluoro-arabinosyl pyrimidine nucleosides: chemistry, antiviral, and potential anticancer activities. In: Vega S (ed) Medicinal chemistry advances, 1981, pp 27–40.Google Scholar
  2. 2.
    Lopez C, Watanabe KA, Fox JJ: 2-Fluoro-5-iodo-araacytosine, a potent and selective anti-herpes virus agent. Antimicrob Agents Chemotherap. (17): 803–806, 1980.Google Scholar
  3. 3.
    Chou TC, Feinberg A, Grant AJ, Vidal P, Reichman W, Watanabe KA, Fox JJ, and Philips FS: Pharmacologic disposition and metabolic fate of 2’-fluoro-5-iodo-1-β-D-arabinofuranosylcytosine in mice and rats. Cancer Res (41): 3336–3342, 1981.PubMedGoogle Scholar
  4. 4.
    Young CW, Schneider R, Leyland-Jones B, Armstrong D, Tan CTC, Lopez C, Watanabe KA, Fox JJ, Philips FS: Phase I evalution of 2’fluoro-5-iodo- 1-β-D-arabinofuranosylcytosine in immunosuppressed patients with herpes virus infection. Cancer Res (43): 5006–5009, 1983.PubMedGoogle Scholar
  5. 5.
    Leyland-Jones B, Feinberg A, Vidal P, Fanucchi M, Williams L, Young C, Fox J, Philips F: Human metabolism of 2’fluoro-5-iodo-1-β -D-arabino-sylcytosine (FIAC). Proceedings of the Amer. Assoc. for Cancer Res. (24): 136, 1983.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • B. Leyland-Jones

There are no affiliations available

Personalised recommendations