Synthesis of a New Series of Phosphonylated 1,2,3-Triazoles as Acyclic Analogs of Ribavirin


Correspondence: Dr. Iwona E. Głowacka, Faculty of Pharmacy, Bioorganic Chemistry Laboratory, Medical University of Łódź, Łódź, Poland.

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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 CH2NHBoc 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).