DESIGN AND SYNTHESIS OF 4 '-CYANO DIDEOXY ISONUCLEOSIDES AND THEIR ACTIVITY AGAINST HIV-1 AND HBV

摘要

Nucleoside reverse-transcriptase inhibitors are major antiviral agents against HIV-1 and HBV. Here, we describe the synthesis of a novel 4'-cyano dideoxy isonucleoside 6 and its phosphoramidate prodrug 7. Intermediate 16 is a promising precursor for the preparation of isonucleosides bearing substituents at the 4' position with various nucleobases. In addition, 6 and 7 were evaluated for their antiviral properties against HIV-1 and HBV. Compound 7 displayed weak anti-HIV activity (EC50 = 61.4 mu M) and had no observed cytotoxicity in two different cell systems.