Abstract

The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3.5-3.7 mu g/mL, cytotoxicity (CC50) greater than or equal to 40 mu g/mL, MCC 20 mu g/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HTV-1) and HTV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.