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- W61003746 abstract "The inhibitory effects of about 30 compounds, mainly pyrimidine and pyridine derivatives, on 5-fluorouracil degradation catalyzed by dihydrouracil dehydrogenase (DHU dehydrogenase) were investigated. The inhibitory activities of 5-substituted uracil derivatives decreased time-dependently during preincubation with liver extracts, indicating that these compounds are substrates of DHU dehydrogenase. During preincubation, 4,6-dihydroxypyrimidine derivatives were found to be converted to barbituric acid derivatives, which have stronger activities. The inhibitory activity of 2,4-dihydroxypyridine (3-deazauracil), which was stronger than that of uracil, did not change during preincubation, indicating that this compound is not a substrate but is an inhibitor of DHU dehydrogenase, and suggesting that 2,6-dihydroxypyridine (1-deazauracil) could be a potent inhibitor. In the light of these findings, we examined various derivatives of barbituric acid, 2,4-dihydroxypyridine and 2,6-dihydroxypyridine. Among these compounds, 3-cyano-2,6-dihydroxypyridine and 5-chloro-2,4-dihydroxypyridine were the strongest inhibitors with Ki values for DHU dehydrogenase of 2.3 X 10(-7) M and 3.6 X 10(-7) M, respectively." @default.
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- W61003746 date "1987-07-01" @default.
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- W61003746 title "Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts." @default.
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