Syntheses of N3-substituted thymine acyclic nucleoside phosphonates and a comparison of their inhibitory effect towards thymidine phosphorylase

A series of N3-substituted thymine acyclic nucleoside phosphonates bearing a number of (phosphonomethoxy)alkyl groups were synthesized and investigated for their ability to inhibit the human thymidine phosphorylase expressed in V79 Chinese hamster cells, as well as thymidine phosphorylase from SD-lymphoma, Escherichia coli and human placenta. In comparison to N1- substituted analogues which possess a considerable inhibitory activity towards thymidine phosphorylase from SD-lymphoma, the results showed a marginal inhibitory effect of these compounds. None of the presented N3-substituted derivatives possess a significant cytostatic activity.

Graphical abstractThe synthesis and a comparison of inhibitory activity toward thymidine phosphorylase for N3-substituted thymine acyclic nucleoside phosphonate analogues 6, 7, and 10 of multisubstrate inhibitors is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide