Patent Evaluation: Purine Derivatives as Antiviral Agents

Summary

Novelty: Eighteen novel phosphono-alkene derivatives of purine are claimed and are proposed to be antiviral agents.

Biology: Plaque reduction data for HSV, VZV and CMV are presented for several compounds. Compound(I) has IC₅₀ values (μg/ml) of <3 against HSV-1, HSV-2 and VZV and 0.16 against CMV. No cytotoxicity was evident up to 100 μg/ml. Against Visna virus and HIV, compund (I) was active at <0.003 μg/ml and 0.01 μg/ml resepectively. Inhibition of HIV viral antigen and RNA was 93% complete at a concentration of 0.1 μM.

Chemistry: Compound (I), (E)-9-(4-phosphonobut-3-enyloxy)guanine, was prepared from 2-[di-(κ-butoxycarbonyl)]amino-9-hydroxy-6-methoxypurine and diisopropyl-(E)-4-hydroxybut-1-enylphosphonate using a Dead Cat reaction, followed by treatment with bromotrimethylsilane.

Structure: