Carbocyclic analogues of 5-substituted uracil nucleosides: synthesis and antiviral activity.

Abstract

Carbocyclic analogues of 3'-deoxyuridines, 3'-deoxyuridines, and uridines with substituents at position 5 of the uracil moiety were prepared by direct halogenation (5-bromo and 5-iodo groups) and by displacement of the 5-bromo group by amino and substituted-amino groups. The analogue of 5-(hydroxymethyl)uridine was prepared via reaction of the isopropylidene derivative of the uridine analogue with paraformaldehyde. The carbocyclic analogues of thymidine and of 5-bromo-, 5-iodo-, and 5-(methylamino)-2'-deoxyuridine were highly active in vitro against herpes simplex virus, types 1 and 2. The corresponding analogues of 5-substituted 3'-deoxyuridines and of 5-substituted uridines were not active in this assay.