Ribavirin derivatives with a hexitol moiety: synthesis and antiviral evaluation

Current standard therapy for the treatment of chronic infections with hepatitis C virus consists of combination therapy with (pegylated) interferon-alpha and ribavirin. 1,5-Anhydrohexitol nucleoside analogues are constrained congeners known to mimic the ribonucleoside conformation. Within this series some analogues are endowed with strong antiviral properties, particularly against herpesviruses. The six-membered anhydrohexitol ring was, therefore, combined with the triazolyl carboxamide moiety of ribavirin, thus providing a new series of ribavirin analogues. None of the newly synthesized compounds elicited any substantial antiviral activity, neither against herpes simplex virus type 1 and 2, nor against bovine viral diarrhoea virus (a surrogate for hepatitis C virus) or the yellow fever virus.