著者

川瀬 雅子 鮫島 啓二郎 岡田 正志 越智 清成 松永 功

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.6, pp.2395-2402, 1985-06-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

2 5

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Derivatives of 5-fluorouracil (5-FU) substituted at the N-1 position were synthesized in order to investigate their enzymatic conversion to N1-(2-formylethyl)-5-FU, which is expected to give 5-FU with concomitant release of acrolein. Proton nuclear magnetic resonance spectroscopic studies of authentic N1-(2-formylethyl)-5-FU suggested that the compound exists in an equilibrium mixture of free aldehyde and cyclic hemiacetal forms. Spontaneous liberation of 5-FU from N1-(2-formylethyl)-5-FU at neutral pH was demonstrated by thin-layer chromatography using both the authentic compound and N1-(3-aminopropyl)-5-FU after treatment with amine oxidase, but the release of 5-FU seemed to be limited. Cytotoxicity was observed with N1-(2-formylethyl)-5-FU and N1-(3-aminopropyl)-5-FU, but none of the derivatives of 5-FU presently prepared showed a positive effect on P388 leukemia inoculated into mice.