A thymidine phosphorylase-stable analogue of BVDU with significant antiviral activity.
(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogue lacking OH groups at both the 2'- and 3'-position that shows pronounced activity against HSV-1 replication.
Guenther
Sven
S
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, USA.
Balzarini
Jan
J
De Clercq
Erik
E
Nair
Vasu
V
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D003587:Cytomegalovirus / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000737:chemistry*; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D013939:Thymidine Phosphorylase; D001973:Bromodeoxyuridine