Cytosine deoxyribonucleoside anti-HIV analogues : a small chemical substitution allows relevant activities

The search for new nucleoside analogue compounds targeting the virally encoded reverse transcriptase was developed by modifying the nucleoside structure to create inhibitor compounds. In this review, the structure-activity relationship of antiviral compounds synthesised from the naturally existing cytosine deoxyribonucleoside (dC) was evaluated. The line of research starting from dC led to the synthesis of 2',3'-dideoxycytidine (ddC; zalcitabine), 2',3'-dideoxy-3'-thiacytidine (3TC; lamivudine) and 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC; emtricitabine) and looks very interesting because each product comes from a single small change in the chemical structure of the former compound, resulting in a progressive improvement in terms of activity, pharmacokinetics, tolerability and emergence of resistance.