New Pyrimidine Nucleosides with Potent Antiviral Activity
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.
KeywordsPyrimidine Nucleoside Cytosine Uracil Acyclovir
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