Document Report Card

ID: ALA1132117

Journal: J Med Chem

Title: Novel potential agents for human cytomegalovirus infection: synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides.

Authors: Martinez A, Esteban AI, Castro A, Gil C, Conde S, Andrei G, Snoeck R, Balzarini J, De Clercq E.

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 micrograms/mL, cytotoxicity (CC50) >/= 40 micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.

CiteXplore: 10197958

DOI: 10.1021/jm980327z