RESUMEN

The Simmons-Smith-Furukawa reaction was used to generate 4'/5'-spirocyclopropanated uridine analogs from electron-rich exocyclic enol esters. During synthesis, the native hydroxylation pattern of the nucleoside is preserved and offers the possibility for a late stage 5'-phosphorylation at the spirocyclopropanol moiety. All synthesized spirocyclopropanated uridine derivatives, including the corresponding 5'-monophosphate (cpUMP), were evaluated with respect to their antiviral activity in an HRSV assay showing moderate, but promising activity.

Asunto(s)

Antivirales/farmacología , Ciclopropanos/farmacología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Compuestos de Espiro/farmacología , Uridina/farmacología , Antivirales/síntesis química , Antivirales/química , Cristalografía por Rayos X , Ciclopropanos/síntesis química , Ciclopropanos/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Conformación Molecular , Compuestos de Espiro/síntesis química , Compuestos de Espiro/química , Uridina/análogos & derivados , Uridina/síntesis química