Synthesis of novel derivatives of 5-carboxyuracil

Abstract

The synthesis and characterization of 13 new 5-carboxyuracil derivatives bearing ester and amide groups is described. Five previously synthesised 5-carboxyuracil esters were prepared by a new procedure using carbodiimide as a coupling reagent. The prepared compounds were tested as inhibitors of DNA polymerases, particularly M. MuLV and HIV-1 reverse transcriptases. In addition, it is shown that the methyl, ethyl, propyl, isopropyl, butyl, cyclohexyl, cyclooctyl, and prop-2-ynyl esters of 5-carboxyuracil are substrates of thymidine phosphorylase, thus allowing enzymatic synthesis of novel modified nucleosides.