Patent Evaluation: Acyclic Phosphonate Nucleotide Analogues as Highly Potent Antivirals

Summary

Novelty: Acyclic purine phosphonate nucleotide analogues (and pharmaceutically acceptable salts thereof) which are effective against both herpes-type virus and against retroviruses such as HIV are disclosed.

Biology: In vitro data are presented which show that 9-(3′-phosphono-1′-propoxymethyl) guanine and its monoethylester (compounds 1 and 2, respectively) have activity comparable to vidarabine against HSV-1TK⁺ (virus Ratiny 1.4 and ED₅₀ = 10 μg/ml); in addition, compound 2 and 9-(3′-phosphono-1-hydroxymethylpropoxymethyl)guanine monoethyl ester (compound 5) have good activities against human CMV (ED₅₀ = 10 μg/ml and 0.1–3.2 μg/ml, respectively). In vivo data reveal that compound 2 has comparable activity to acyclovir against HSVTK⁺ virus. In vitro data against HIV reveal that compound 1 inhibits reverse transcriptase by 75% at 8 μM and compound 2 shows 100% inhibition at 1 μM. The ED₅₀ values are 40–50 μg/ml and 30 μg/ml, respectively.

Chemistry: Twenty-five compounds are synthesized, of which five are specifically claimed.