| Abstract
| - New [2‘,5‘-bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]-3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) (TSAO) derivatives substituted at the 4‘ ‘-amino group of the spiro moietywith different carbonyl functionalities have been designed and synthesized. Various syntheticprocedures, on the scarcely studied reactivity of the 3‘-spiroaminooxathioledioxide moiety, havebeen explored. The compounds were evaluated for their inhibitory effect on both wild-type andTSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amidegroups (12) at the 4‘ ‘-position conferred the highest anti-HIV-1 activity, while the free oxalylacid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presenceat this position of (un)substituted ureido or acyl groups markedly diminished or annihilatedthe anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition ofhuman cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never beenobserved previously for TSAO derivatives. In particular, compound 26 represents the first TSAOderivative with dual anti-HIV-1 and -HCMV activity.
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