The pyrimidine nucleus is a versatile core in the development of antiretroviral agents. On this basis, a series of pyrimidine-2,4-diones linked to an isoxazolidine nucleus have been synthesized and tested as nucleoside analogs, endowed with potential anti-HIV (human immunodeficiency virus) activity. Compounds 6a–c, characterized by the presence of an ethereal group at C-3, show HIV reverse transcriptase (RT) inhibitor activity in the nanomolar range as well as HIV-infection inhibitor activity in the low micromolar with no toxicity. In the same context, compound 7b shows only a negligible inhibition of RT HIV.

Key Points• The therapeutic efficacy of the AZT and IFN combination in ATL presumably reflects the inhibition of RT-related functions.• HTLV-1-RT activity from short-term cultured PBMCs may represent a predictive correlate of clinical response to AZT/IFN in ATL patients.

a b s t r a c tTruncated phosphonated C-1 0 -branched N,O-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology, starting from N-methyl-C-(diethoxyphosphoryl)nitrone 7. Preliminary biological assays show that b-anomers are able to inhibit HIV in vitro infection at concentrations in the micromolar range. Higher SI values with respect to AZT indicated that the compounds were endowed with low cytotoxicity.

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