Patent Evaluation: Anti-HIV Nucleoside Analogues

Summary

Novelty: Novel substituted 1,3-oxathiolanes and substituted 1,3-ditholanes having antiviral activity are disclosed. Processes for preparing these compounds and intermediates useful in their preparation are described. Pharmaceutical compositions containing these compounds and their use as antiviral agents are also described.

Biology: Anti-HIV-1 activity was determined in MT-4 cells. CD₅₀ and ID ₅₀ values obtained for cis -2-hydroxymethyl-4-(adenosine-9′-yl)-1,3-oxathiolane and 2′,3′-dideoxyinosine were 100μg/ml (both compounds), 2.1 μg/ml and 2.3 μg/ml respectively.

Chemistry: The syntheses of the compounds are outlined in three reaction schemes. Twenty-seven examples are given. Fourteen compounds are specifically claimed including cis-2-hydroxymethyl-4-(6′-chloropurin-9-yl)-1,3-oxathiolane.

Structure: