- Synthesis of 5-fluorouracil derivatives containing an inhibitor of 5- fluorouracil degradation
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The reactivities of 5-fluorouracil (5-FUra) degradation inhibitors, 2,4- (2) and 2,6-dihydroxypyridines (3), were investigated. Acylation of 2 and 2,4-bis(trimethylsilyloxy)pyridines with equimolar amounts of acid chlorides preferentially occurred at the 4-OH and 2-OH positions, respectively, and the structure of monobenzoylated 5-chloro-2,4-dihydroxypyridine (2b) was determined as 4-benzoyloxy-5-chloro-2-pyridone (5b) by X-ray crystallographic analysis. Compounds 2 and 3, as well as the N-2-tetrahydrofuryl (11), N- alkyl (12), and N-carbamoyl (14) derivatives of 2, exhibit dynamic keto-enol tautomerism. The acyl derivatives of these pyridines are labile and are thought to be active esters. Monoacyl ester derivatives of these pyridines were combined with 5-FUra analogs to develop novel antitumor agents containing an inhibitor of 5-FUra degradation. One of them, 3-[3-(6- benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5- fluorouracil (BOF-A2) (22b), was the most effective and is currently undergoing late phase-II clinical trials.
- Hirohashi,Kido,Yamamoto,Kojima,Jitsukawa,Fujii
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p. 1498 - 1506
(2007/10/02)
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- 5-fluorouracil derivatives
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An anticancer compound is disclosed which is represented by the formula STR1 wherein one of R1 and R2 is a phenyl-lower alkyl optionally having a substituent, phenyl-lower alkenyl or naphthyl-lower alkyl, the other of R1 and R2 is hydrogen or acyl, and R3 is hydrogen, acyl or tetrahydrofuranyl, or represented by the formula STR2 wherein Rx is an optionally substituted pyridyl, Y is arylene and α is a known 5-fluorouracil derivative residue which can be converted to 5-fluorouracil in vivo and which is linked to the carbonyl by an ester or amide linkage.
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- 5-fluorouracil derivatives
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An anticancer compound is disclosed which is represented by the formula STR1 wherein one of R1 and R2 is a phenyl-lower alkyl optionally having a substituent, phenyl-lower alkenyl or naphthyl-lower alkyl, the other of R1 and R2 is hydrogen or acyl, and R3 is hydrogen, acyl or tetrahydrofuranyl, or represented by the formula STR2 wherein Rx is an optionally substituted pyridyl, Y is arylene and α is a known 5-fluorouracil derivative residue which can be converted to 5-fluorouracil in vivo and which is linked to the carbonyl by an ester or amide linkage.
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