New N4-hydroxycytidine derivatives:: Synthesis and antiviral activity

Two series of N-4-hydroxycytidine derivatives were synthesized and evaluated as potential antipox virus agents. Acylation of N-4-hydroxycytidine ( 1) with an excess of acyl chloride or imidazolide yielded the corresponding N-4-( 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 N-4-(acyloxy) derivatives inhibited replication of pox viruses in cell cultures, N-4-(pivaloyloxy)- and N-4-(benzoyloxy) cytidines being the most potent. The synthesized 5'-phosphonates were more cytotoxic than the parent nucleoside.