Synthesis and Biological Evaluation of Novel 1,2,3-Triazolonucleotides

A general procedure for the preparation of 1,2,3‐triazole analogs of nucleosides from diethyl 2‐azidoethoxymethyl‐ and 2‐azidoethoxyethylphosphonates was elaborated. The application of microwave irradiation shortened the reaction time to 10 min in comparison to ca. 48 h when 1,3‐dipolar cycloadditions were performed under standard conditions. All compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses. None of the compounds were antivirally active at subtoxic concentrations. Compound 17k exhibited moderate inhibitory effects on the proliferation of human T‐lymphocyte cells (IC50 = 64 µM for CEM). The inhibitory activity of cell proliferation for HEL cells as well as L1210, CEM, and HeLa cells of several 1,2,3‐triazole analogs of nucleotides was evaluated. The 1,2,3‐triazole derivatives appeared to be cytostatic (with IC50 values reaching the middle to higher micromolar range: 60–250 µM).