title: Halophenyl furanopyrimidines as potent and selective anti-VZV agents.
abstract: Bicyclic furano pyrimidines have been previously reported by us to be highly potent and selective inhibitors of varicella zoster virus (VZV). p-Alkyl phenyl analogues are particularly potent with EC50 values below 1 nM. In this article we report the synthesis and anti-VZV activity of a series of halophenyl analogues, with variation in the nature (F, Cl, Br) and location (o, m, p) of the halogen substituent. The compounds show a range of activities from ca. 10 nM to > 50 microM. In most cases, ortho substitution leads to greatest activity, meta substitution is in general poor, and the effect of p-substitution shows a marked dependence on the halogen atom. The p-fluorophenyl compound is unique amongst compounds of this class in being inactive as an antiviral. The possible origins of these marked SARs are discussed.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, UK. mcguigan@cardiff.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.forename: Alison
authors.initials: A
authors.lastname: Jukes
authors.forename: Sally
authors.initials: S
authors.lastname: Blewett
authors.forename: Hubert
authors.initials: H
authors.lastname: Barucki
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Erichsen
authors.forename: Graciella
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured / Q000187:drug effects; D005663:Furans / Q000737:chemistry*; D006219:Halogens / Q000737:chemistry*; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005663:Furans; D006219:Halogens; D011741:Pyrimidine Nucleosides