Synthesis of Mimics to Thymidine and 5-(2″-Thienyl)-2′-Deoxyuridine Triphosphates

Abstract
Dicarboxylic acid 5′-monoesters of thymidine and 5-(2-thienyl)-2′′-deoxyuridine have been synthesised and evaluated as triphosphate mimics. Glutaric (25, 29), adipic (26, 30), pimelic (27, 31) and trans-1,4-cyclohexane dicarboxylic acids (28, 32) were employed to vary the distance between two carboxylate functions and were structurally compared to the triphosphate moiety by molecular modelling. The glutarate and adipate derivatives can assume conformations fitting the triphosphate, and the thienyl compounds 29 and 30 were the ones having overall best inhibitory activities against DNA pol α and HIV-1 RT.

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