Halophenyl Furanopyrimidines as Potent and Selective Anti-VZV Agents

Christopher McGuigan, Alison Jukes, Sally Blewett, Hubert Barucki, Jonathan T Erichsen, Graciella Andrei, Robert Snoeck, Erik De Clercq, Jan Balzarini
2003 Antiviral Chemistry & Chemotherapy  
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 EC 50 values below 1nM. 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 µM. In most cases, ortho
more » ... most cases, ortho substitution leads to greatest activity, meta substitution is in general poor, and the effect of psubstitution 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.
doi:10.1177/095632020301400306 pmid:14521333 fatcat:ds3lidzavfd7ngyetqwzcrfzza