Patent Evaluation: Dideoxynucleoide Esters and Related Structures as Potential Anti-HIV Agents

Summary

Novelty: Novel dideoxynucleoside/phosphonoformic acid complexes having retroviral (e.g. HIV) inhibitory activity are disclosed. The complexes are claimed to be more effective than either component used individually and to show lower toxicity to host cells.

Biology: A range of in vitro assays using a stock solution of the preferred compound dispersed in RMPI 1640 cell growth media are described. The preferred compound inhibits reverse transcriptase 50%, in HIV-1 infected Jurkat cells, at 0.5 μM. A Jurkat cell prophylaxis model shows that the preferred compound is five-fold more potent than AZT and PFA; in infected human peripheral blood leukocytes it is equipotent with AZT. Host cell cytotoxicity is lower than that produced by AZT.

Chemistry: 3′-Azido-3′-deoxy-5′-[P-(ethoxycarbonyl)-P-hydroxyphosphinyl]thymidine, ammonium salt, is one of six exemplified compounds of which three are specifically claimed. Full preparative details using standard techniques are presented.

Structure: