Two novel series of acyclonucleosides active as nonnucleoside reverse transcriptase inhibitors (NNRTI) against the human immunodeficiency virus (HIV) have been synthesized. Structural modifications, inverting the selectivity of classical NNRTI, considerably more active against HIV-1 than HIV-2, are reported. In these series, an increase in anti-HIV-2 activity is correlated with an increase of the cytotoxicity of these new molecules.