2'-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743.
We report the preparation of 2'-alpha-F, 2'-beta-F and 2',2'-difluoro analogues of the leading anti-varicella zoster virus (VZV) pentylphenyl BCNA Cf 1743. VZV thymidine kinase showed the highest phosphorylating capacity for the beta-fluoro derivative, that retained equal antiviral potency as the parent compound. In contrast, the alpha-fluoro- and 2',2'-difluoro BCNA derivatives were markedly less (approximately 100-fold) antivirally active.
McGuigan
Christopher
C
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF103XF, UK. mcguigan@cf.ac.uk
Derudas
Marco
M
Quintiliani
Maurizio
M
Andrei
Graciela
G
Snoeck
Robert
R
Henson
Geoffrey
G
Balzarini
Jan
J
D000998:Antiviral Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004347:Drug Interactions; D005459:Fluorides / Q000737:chemistry; D006367:HeLa Cells; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; C500967:Cf 1743; D009705:Nucleosides; D011741:Pyrimidine Nucleosides; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D005459:Fluorides