Carbocyclic analogs of 5-substituted uracil nucleosides. Synthesis and antiviral activity

Abstract

Carbocyclic analogs 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 analog of 5-(hydroxymethyl)uridine was prepared via reaction of the isopropylidene derivative of the uridine analog with paraformaldehyde. The carbocyclic analog 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 analog of 5-substituted 3''-deoxyuridines and of 5-substituted uridines were not active in this assay.