Collect. Czech. Chem. Commun. 2006, 71, 1099-1106

New N4-Hydroxycytidine Derivatives: Synthesis and Antiviral Activity

Maksim A. Ivanova, Elena V. Antonovaa, Aleksey V. Maksimova, Lyudmila K. Pigusovaa, Evgenii F. Belanovb and Lyudmila A. Aleksandrovaa,*

a Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov Str., Moscow 119991, Russian Federation
b State Research Center of Virology and Biotechnology "Vektor", Koltsovo, Novosibirsk Region 633159, Russian Federation


Two series of N4-hydroxycytidine derivatives were synthesized and evaluated as potential antipox virus agents. Acylation of N4-hydroxycytidine (1) with an excess of acyl chloride or imidazolide yielded the corresponding N4-(acyloxy) derivatives. 5'-Phosphonates of 1 were prepared by the reaction of cytidine 5'-phosphonates with aqueous hydroxylamine hydrochloride (pH 6.0). Nucleoside 1 and its N4-(acyloxy) derivatives inhibited replication of pox viruses in cell cultures, N4-(pivaloyloxy)- and N4-(benzoyloxy)cytidines being the most potent. The synthesized 5'-phosphonates were more cytotoxic than the parent nucleoside.

Keywords: Nucleosides; Nucleoside analogs; N4-Hydroxycytidine; Nucleoside phosphonates; Hydroxylamine; Pyrimidines; Antiviral agents; Pox viruses.

References: 25 live references.