Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides

Abstract
A series of base-modified pyrimidine 3''-azido-2'',3''-dideoxynucleosides and 3''-substituted purine and pyrimidine 2'',3''-dideoxynucleosides have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV) replication in MT-4 cells. The following pyrimidine derivatives emerged as the most potent and/or selective inhibitors of HIV-induced cytopathogenicity (in order of decreasing selectivity: 3''-azido-3''-deoxythymidine (AZT), 3''-azido-2'',3''-dideoxyuridine (AzddUrd), 3''-azido-2'',3''-dideoxy-5-methylcytidine (AzddMeCyd), 3''-fluoro-ddUrd (FddUrd), 3''-fluoro-ddThd (FddThd), the N4-hydroxylated derivative of AzddMeCyd and the N4-methylated derivative of AzddMeCyd. Among the purine 2'',3''-dideoxynucleosides, 3''-azido-2'',3''-dideoxyguanosine (AzddGuo), 3''-fluoro-ddGuo (FddGuo), and 3''-fluoro-2,6-diaminopurine 2'',3''-dideoxynucleoside (FddDAPR) were the most selective inhibitors of HIV replication.

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