Synthesis of a new series of phosphonylated 1,2,3-triazoles as acyclic analogs of ribavirin.
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).
Faculty of Pharmacy, Bioorganic Chemistry Laboratory, Medical University of Łódź, Łódź, Poland. iwona.glowacka@umed.lodz.pl
Iwona E
IE
Głowacka
Jan
J
Balzarini
Andrzej E
AE
Wróblewski
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004267:DNA Viruses / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010766:Phosphorylation; D012328:RNA Viruses / Q000187:drug effects; D012254:Ribavirin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
D000998:Antiviral Agents; D014230:Triazoles; D012254:Ribavirin
1,2,3-Triazoles; Antiviral; Azidophosphonates; Cycloaddition; Cytostatic