[Development of fluorinated pyrimidines in Japan]

Four fluorinated pyrimidines that are in the stage of clinical trials at present in Japan were reviewed: BOF-A2, Ro09-1390, TT-62 and S-1. Both BOF-A 2 and S-1 are a compound of 5-FU derivative combined or mixed with an inhibitor of 5-FU degradation in order to prolong the blood 5-FU level as well as increase selective toxicity to tumor. Furthermore, an inhibitor of 5-FU phosphorylation in G1 tract contained in S-1 reduces G1 toxicity such as diarrhea etc due to prolongation of blood 5-FU level. Ro09-1390 is an improved compound of 5'-DFUR, which intends to reduce diarrhea caused by the latter. TT-62 is a FdUMP derivative and an active metabolite of 5-FU for oral formulation, which is superior to available 5-FU type anticancer agents in efficacy, and doesn't show cross tolerance to 5-FU.