Novel 6-Azapyrimidine-2′-Deoxy-4′-Thionucleosides: Synthesis, Biological Evaluation and Conformational Analysis

Abstract

We report the synthesis of novel 1-(2′-deoxy-4′-thio-β-D- erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides and the subsequent preparation of a series of N3-substituted analogues. All the novel compounds were evaluated against a range of viruses, however they lacked any measurable activity. The lack of anti-herpetic activity may be a result of the parent nucleoside having poor affinity for herpes simplex virus type 1 thymidine kinase. Conformational analysis of the parent nucleoside showed a twist (3T2) sugar conformation commonly displayed by 2′-deoxy-4′-thionucleosides and the anti-human immunodeficiency virus type 1 agents zidovudine and 3′-fluoro-ddT.