Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine

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Abstract
In order to evaluate the influence of the cyano group on the antiviral activity of pyrimidine deoxyribonucleosides, a moderate yield, unified approach to the synthesis of 5-cyanouridine and 5-cyano-2''-deoxyuridine was developed. Treatment of the appropriate acetylated 5-bromouracil nucleoside with NaCN or KCN in Me2SO at 90-110.degree. C gave, after deblocking, 35-45% yields of the corresponding 5-cyanouracil nucleosides. 5-Cyanouridine was devoid of significant activity against vaccinia virus, herpes simplex-1 and vesicular stomatitis virus, but 5-cyano-2''-deoxyuridine, while lacking activity against herpes simplex, showed significant inhibition of vaccinia virus; for instance, 5-cyano-2''-deoxyuridine inhibited vaccinia virus replication at concentrations 10-20 times that required for inhibition by the known antivirals, 5-iodo-2''-deoxyuridine and 1-(.beta.-D-arabinofuranosyl)adenine. Replacement of the 5-halogeno substituents of pyrimidine deoxyribonucleosides decreases, but does not abolish, antiviral activity.