Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Chemistry, Medicinal, Chemistry, Multidisciplinary, Pharmacology & Pharmacy, Chemistry, Antiviral, Azidophosphonates, Cycloaddition, Cytostatic, 1, 2, 3-Triazoles, BIOLOGICAL EVALUATION, ANTIVIRAL ACTIVITY, CLICK-CHEMISTRY, HUISGEN CYCLOADDITION, FACILE SYNTHESIS, INHIBITORS, DERIVATIVES, AZIDES, DESIGN, AGENTS, 1,2,3-Triazoles, Animals, Antiviral Agents, Cell Proliferation, Chlorocebus aethiops, DNA Viruses, HeLa Cells, Humans, Inhibitory Concentration 50, Phosphorylation, RNA Viruses, Ribavirin, Triazoles, Vero Cells, Hela Cells, 0304 Medicinal and Biomolecular Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry

Abstract:

A novel series of phosphonylated 1,2,3-triazoles as structural acyclic analogs of ribavirin, in which the 1,2,3-triazole ring was substituted at C4' with COOMe, CONH2 , CONHOH, and CH2 NHBoc groups, were synthesized from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl-, 2-azidoethoxymethyl- and 2-azidoethoxyethylphosphonate. The efficient synthesis of diethyl azidomethylphosphonate from diethyl 4-nitrobenzenesulfonylmethylphosphonate employing the in situ formed azides is described. All synthesized compounds were evaluated in vitro for their inhibitory activity against a broad variety of RNA and DNA viruses. No antiviral activity was observed at 100 µM. Only compound 13g exhibited inhibitory effects on the proliferation of HeLa cells (IC50  = 169 ± 45 µM).