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.
Van Aerschot
Arthur
A
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. Arthur.VanAerschot@REGA.KULeuven.ac.be
Schepers
Guy
G
Busson
Roger
R
Rozenski
Jef
J
Neyts
Johan
J
De Clercq
Erik
E
Herdewijn
Piet
P
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects / Q000254:growth & development; D006564:Herpesviridae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013402:Sugar Alcohols / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry; D015005:Yellow fever virus / Q000187:drug effects / Q000254:growth & development
D000998:Antiviral Agents; D013402:Sugar Alcohols; D014230:Triazoles; D012254:Ribavirin