Synthesis and antitumor activity of 1- or 3-(alpha-hetero substituted)alkyl-5-fluorouracil derivatives

Two classes of 5-fluorouracil (5-FU) derivatives were prepared from 1,3-bis(hydroxymethyl)-5-fluorouracil (1). The first group was obtained by the direct esterification of 1 with various acids. The second one was derived by the nucleophilic substitution of N-(chloromethyl)-5-FUs, which were easily prepared by halogenation of 1, with hetero nucleophiles. The antitumor activities of the prepared compounds were examined against Leukemia L1210 and the results were compared with that of 1-hexylcarbamoyl-5-fluorouracil (HCFU, Carmofur).