3-Formylchromone (1), 3-methyl-7-hydroxychromone (2) and Schiff bases of 3-formylchromone 3–19 have been synthesized and their anti-thymidine phosphorylase inhibitory activity was evaluated. Compounds 1–19 showed a varying degree of thymidine phosphorylase inhibition with IC 50 values 19.77±3.25 to 480.21±2.34μM. Their activity was compared with the standard 7-deazaxanthine (IC 50 =39.28±0.76μM). Compound 12 showed an excellent thymidine phosphorylase inhibitory activity with an IC 50 value of 19.77±3.25μM, better than the standard. Compound 4 also showed an excellent inhibitory activity (IC 50 =40.29±4.56μM). The parent 3-formylchromone (1) and 3-methyl-7-hydroxychromone (2) were found to be inactive. The structures of the compounds were elucidated by using spectroscopic techniques, including 1 H NMR, EI MS, IR, UV and elemental analysis.