Design, synthesis and anti-tumoractivity of novel amidine derivatives of doxifluridine

A series of novel amidine derivatives of doxifluridine were synthesized using acid amide as the starting material, and their anti-tumor activity was evaluated in A549 cells. Compounds 10 and 11 demonstrated were more potent than 5-Fu, which was used as a positive control. Compound 10, which were found to be the most potent one with IC50 of 3.2 μmol/L, was 16 times more potent than 5-Fu with IC50 of 52 μM to the A549 cells. A new route was designed to synthesize 5′-deoxy-5-fluorocytidine. All compounds were characterized by 1H NMR, MS and X-ray spectras in detail.