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

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 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.

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Título según WOS: ID WOS:000079636000003 Not found in local WOS DB
Título de la Revista: JOURNAL OF MEDICINAL CHEMISTRY
Volumen: 42
Número: 7
Editorial: AMER CHEMICAL SOC
Fecha de publicación: 1999
Página de inicio: 1145
Página final: 1150
DOI:

10.1021/jm980327z

Notas: ISI