Patent Evaluation: Novel Nucleosides as Antiretroviral Agents

Summary

Novelty: The preparation of novel nucleoside derivatives, especially those with the 2′,3′-dideoxy-3′-C-hydroxymethyl structure feature, is disclosed. These nucleosides offer potential therapy for viral infections which are caused by reverse transcriptase producing viruses, such as HIV and hepatitis B.

Biology: Data are presented which show the inhibition of human immunodeficiency virus multiplication in cell culture. The preferred compound, 1-(2,3-dideoxy-3-C-hydroxymethyl-β-D-erythro-pentofuranosyl)cystosine, had IC₅₀ of 0.01 μM, whereas in cellular toxicity tests the concentration required to inhibit 50% of H9 cells was 1 mM.

Chemistry: The syntheses, using standard methodology, of twenty-four examples are presented. 1-[2′,3′-(Dideoxy-3-C-hydroxymethyl-β-D-erythropentofuranosyl)cytosine is the preferred derivative.

Structure: