Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir) and related compounds.

Treatment of 5-azacytosine sodium salt with diisopropyl [(2-chloroethoxy)methyl]phosphonate followed by removal of ester groups with BrSi(CH3)3 afforded 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (3). Reaction of 5-azacytosine with [(trityloxy)methyl]-(2S)-oxirane followed by etherification with diisopropyl (bromomethyl)phosphonate and removal of ester groups gave 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1). The synthesis of 6-azacytosine congener 2 was analogous using N4-benzoylated intermediates.

Efficacy of DNA hypomethylating capacities of 5-aza-2'-deoxycytidine and its alpha anomer.

In this paper, we have compared hypomethylating ability of classical beta-d-anomer of 5-aza-2'-deoxycytidine (5-aza-CdRf) and its alpha anomer in cell cultures. Alpha anomers of nucleosides generally exhibit low biological activity compared to their beta counterparts. It is reported that alpha anomer of 5-aza-CdRf efficiently hypomethylated genomic DNA in human T-lymphoblastoid CCRF-CEM cells.