Bicyclic nucleoside inhibitors of Varicella-Zoster virus: the effect of branching in the p-alkylphenyl side chain.
Further to the discovery of bicyclic furanopyrimidine nucleoside analogues (BCNAs) as potent anti-VZV agents, a branched series of this family of compounds was synthesised. The aim was to study the impact of the geometry and steric hindrance in the side chain as well as lipophilic role of this moiety on biological activity. The results showed a detrimental effect of branching on antiviral activity, with a different magnitude depending on the position of branching in the side chain. This study again showed the importance of this moiety for biological activity, as well as the limited efficacy of the ClogP value as a tool for predicting the potency of BCNAs, while suggesting an alternative rationale behind the design of future series.
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Giovanna
G
Luoni
Christopher
C
McGuigan
Graciela
G
Andrei
Robert
R
Snoeck
Erik
E
De Clercq
Jan
J
Balzarini
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009705:Nucleosides