JPS63301880A - 5-fluorouracil derivative - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [R<1> is pyridyl having 1-4 substituent group, which is OH, halogen, NH2, carboxyl, carbamoyl, alkyl, (substituted)phenylcarbamoyl, alkenyl, tetrahydrofuranyl, etc.; A is arylene; R<2> is 5-fluorouracil derivative residue capable of converting to 5-fluorouracil in vivo and bond with the adjacent carbonyl group is ester bond or amide bond]. EXAMPLE:5-Fluoro-3-[3-(4-pentanoyloxy-2-pyridyloxycarbonyl)benzoyl]-1- (2-tetra hydrofuranyl)uracil. USE:An antitumor agent. PREPARATION:A compound expressed by the formula R<2>H is reacted with a compound expressed by formula II (X is halogen) to afford a compound expressed by formula III, which is then reacted with a compound expressed by the formula R<1>-O-R<9> (R<9> is H or trialkylsilyl) to provide the compound expressed by formula I.

Description

[Detailed description of the invention] 1 Chestnut, Godanri Momme 1 The present invention relates to novel 5-fluorouracil derivatives.

i-Kome 151 Eiichiken The derivative of the present invention is a novel compound that has not been described in any literature.

Problems to be Solved by the Invention The purpose of the present invention is to provide a compound useful as a medicine, as described later.

Means for Solving the Problems The above objects are achieved by a 5-fluorouracil derivative represented by the following general formula (1).

General formula [In the formula, R1 is a hydroxyl group, a halogen atom, an amino group, a carboxyl group, a cyano group, a nitro group, an oxo group, a carbamoyl group, a lower alkyl group, a lower alkylcarbamoyl group, and a halogen as a substituent on the phenyl ring. phenylcarbamoyl group, lower alkenyl group, lower alkoxycarbonyl group, tetrahydrofuranyl group, phthalidyl group, lower alkoxy lower alkyl group, phenyl, which may have 1 to 3 groups selected from atoms, lower alkoxy groups and lower alkyl groups. represents a pyridyl group having 1 to 4 groups selected from the group consisting of a lower alkoxy lower alkyl group, a lower alkoxycarbonyl lower alkylcarbamoyl group, and an acyloxy group, and A represents an arylene group. R2 is a 5-fluorouracil derivative residue that can be converted into 5-fluorouracil in vivo, and the bond between this group and the adjacent carbonyl group is an ester bond or an amide bond. - As a result of intensive studies aimed at improving the antitumor effect and/or reducing the toxicity of fluorouracil derivatives, we found that the compound has the above general formula and exhibits an excellent anticancer effect that meets the above objectives. It has been found that it is extremely useful as a tumor agent.

Each group defined in this specification is as follows.

Lower alkyl groups include methyl, ethyl, propyl,
C1-C6 alkyl groups such as isopropyl, butyl, t-butyl, pentyl, hexyl groups, lower alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, pentyloxy,
An alkoxy group having 1 to 6 carbon atoms such as hexyloxy group,
Examples of the lower alkenyl group include alkenyl groups having 2 to 6 carbon atoms such as vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, and 2-hexenyl, and examples of the halogen atom include fluorine. , chlorine, bromine,
Examples include iodine atoms. Furthermore, each group defined in this specification is as follows.

Examples of the lower alkylcarbamoyl group include N-methylcarbamoyl, N-ethylcarbamoyl, N-bropylcarbamoyl, N-impropylcarbamoylthylcarbamoyl, N-hexylcarbamoylrubamoyl, N,N-diethylcarbamoyl, and N.

N-dipropylcarbamoyl, N-isopropyl-N-
Methylcarbamoyl, N-ethyl-N-methylcarbamoylrubamoyl, N-propyl-N-pentylcarbamoyl, N. Alkyl having 1 to 2 alkyl groups having 1 to 6 carbon atoms such as N-diethylcarbamoyl, N-ethyl-N-hexylcarbamoyl, N-hexyl-N-pentylcarbamoyl, N,N-diethylcarbamoyl group, etc. An example is a carbamoyl group.

As a phenylcarbamoyl group that may have 1 to 3@ of a group selected from a halogen atom, a lower alkoxy group, and a lower alkyl group as a substituent on the phenyl ring, N
-(2-chlorophenyl)carbamoylcarbamoyl, N-(3-methoxyphenyl)carbamoyl, N-(4-propoxyphenyl)carbamoyl, N-(2-methylphenyl)carbamoyl, N-(
4-ethyl)phenylcarbamoyl, N- (3-isopropylphenyl)carbamoyl, N- (4-hexylphenylyl, N-phenylcarbamoyl, N,N-
A phenyl group, such as a diphenylcarbamoyl group, which may have 1 to 3 substituents on the phenyl ring selected from a halogen atom, an alkoxy group having 1 to 6 carbon atoms, and an alkyl group having 1 to 6 carbon atoms. An example is a carbamoyl group substituted with one or two.

Examples of lower alkoxycarbonyl groups include carbonyl groups having an alkoxy group having 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, t-butoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl groups. can be exemplified.

Examples of the lower alkoxy lower alkyl group include methoxymethyl, 3-methoxypropyl, 4-ethoxybutyl, 6-
Propoxyhexyl, 5-isopropoxypentyl, 1
, 1-dimethyl-2-butoxyethyl, 2-methyl-3
-t-butoxypropyl, 2-pentyloxyethyl,
Examples include alkoxyalkyl groups in which the alkoxy moiety and the alkyl moiety each have 1 to 6 carbon atoms, such as a 2-hexyloxyethyl group.

Examples of the lower alkoxy lower alkyl group having a phenyl group include benzyloxymethyl, 2-benzyloxyethyl, 5-(2-phenylpentyloxy)pentyl,
6-benzyloxyhexyl, 6-(4-phenylhexyloxy)hexyl, 2-phenylethoxymethyl,
2-(phenylmethoxy)ethyl, 2-(phenylmethoxy)propyl, 4-(phenylmethoxy)butyl, 5
-(phenylmethoxy)pentyl, 6-(phenylmethoxy)hexyl, 2-(2-phenylethoxy)ethyl, 2-(4-phenylbutoxy)ethyl, 4-(4-phenylbutoxy)butyl, 6-phenylmed Examples include alkoxyalkyl groups having a phenyl group as a substituent, such as a xyhexyl group, and in which the alkoxy moiety and the alkyl moiety each have 1 to 6 carbon atoms.

Examples of the lower alkoxycarbonyl lower alkylcarbamoyl group include methoxycarbonylmethylcarbamoyl, 3
-methoxycarbonylpropylcarbamoyl, 4-ethoxycarbonylbutylcarbamoylrubamoyl, 5-isopropoxycarbonylpentylcarbamoylxycarbonylethylcarbamoyl, 2-methyl-3-
Examples include t-butoxycarbonylpropylcarbamoyl, 2-pentyloxycarbonylethylcarbamoyl, hexyloxycarbonylethylcarbamoyl, and carbamoyl groups substituted with one alkoxycarbonylalkyl group having 1 to 6 carbon atoms in the alkyl moiety.

The phenyl lower alkyl group of the phenyl lower alkyloxy group which may have 1 to 3 groups selected from halogen atoms, lower alkoxy groups and lower alkyl groups as substituents on the phenyl ring includes benzyl, 2-methyl, Benzyl, 3-methylbenzyl, 4-methylbenzyl, 2
-Ethylbenzyl, 3-ethylbenzyl, 4-ethylbenzyl, 2-propylbenzyl, 3-propylbenzyl, 4-propylbenzyl, 2-butylbenzyl, 3-butylbenzyl, 4-butylbenzyl, 2-t-butylbenzyl , 3-t-butylbenzyl, 4-1-butylpenzyl, 2-pentylbenzyl, 3-pentylbenzyl,
4-pentylbenzyl, 2-hexylbenzyl, 3-hexylbenzyl, 4-hexylbenzyl, 2,3-dimethylbenzyl, 2,4-dimethylbenzyl, 2,5-dimethy, rubenzyl, 2,6-dimethyl benzyl, 3,4
-dimethylbenzyl, 3.5-dimethylbenzyl, 2.
3,4-trimethylbenzyl, 2,4.5-trimethylbenzyl, 2.3.5-trimethylbenzyl, 2,4.
6-trimethylbenzyl, 3°benzyl, 2,4-diethylbenzyl, 2,5-diethylbenzyl, 2,6-diethylbenzyl, 2.4.6-triethylbenzyl, 2
, 4-dipropylbenzyl, 3,4.5-triethylbenzyl, 3-methyl-4-ethylbenzyl, 1-phenylethyl, 2-phenylethyl, 2-phenyl-1-methylethyl, 1- (2-methyl phenyl)ethyl, 2
- (2-methylphenyl)ethyl, 2-(3-methylphenyl)ethyl, 2-(4-methylphenyl)ethyl, 1- (2,4-dimethylphenyl)ethyl, 2-
(2,4-dimethylphenyl)ethyl, 1-(2,4,
6-drimethylphenyl)ethyl, 2-(2,4,6
-trimethylphenyl)ethyl, 3-phenylpropyl, 3-(4-methylphenyl)propyl, 4-phenylbutyl, 4-(2-methylphenyl)butyl, 5-phenylpentyl, 5-(3-methylphenyl) Pentyl, 6-phenylhexyl, 6-(4-methylphenyl)hexyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 2.3-dimethoxybenzyl, 2,4-dimethoxybenzyl, 2.5- dimethoxybenzyl, 3-methoxy-4-ethoxybenzyl,
2,6-dimethoxybenzyl, 3,4-dimethoxybenzyl, 3.5-dimethoxybenzyl, 2,3.4-trimethoxybenzyl, 2,4.5-trimethoxybenzyl, 2,3.5-trimethoxybenzyl , 2゜4.6-trimethoxybenzyl, 3,4.5-trimethoxybenzyl, 2-ethoxybenzyl, 4-proboxybenzyl,
3-butoxybenzyl, 2-1-butoxybenzyl, 3
-Pentyloxybenzyl, 4-hexyloxybenzyl, 2,3-jethoxybenzyl, 1-(4-methoxyphenyl)ethyl, 2-(3,4-dimethoxyphenyl)ethyl, 3-(4-methoxyphenyl) Propyl, 4-(2-methoxyphenyl)butyl, 5-(4-
methoxyphenyl)pentyl, 6-(4-methoxyphenyl)hexyl, 6-(3,4゜5-tripentyloxyphenyl)hexyl, 2-fluorobenzyl, 3-
Fluorobenzyl, 4-fluorobenzyl, 2,3-difluorobenzyl, 2,4-difluorobenzyl, 2.
5-difluorobenzyl, 2-fluoro-3-chlorobenzyl, 2-fluoro-3-bromobenzyl, 2゜6-
Difluorobenzyl, 2,3.4-trifluorobenzyl, 2,4.5-trifluorobenzyl, 2,3.5-
Trifluorobenzyl, 2,4゜rotrifluorobenzyl, 3,4.5-trifluorobenzyl, 1-(2-
fluorophenyl)ethyl, 2-(2-fluorophenyl)ethyl, 3-(3-fluorophenyl)propyl, 4-(2-fluorophenyl)butyl, 5-(2-
fluorophenyl)pentyl, 6-(3-fluorophenyl)hexyl, 2-bromobenzyl, 3-promobenzyl, 4-bromobenzyl, 2,3-dibromobenzyl, 2-bromo-3-fluorobenzyl, 2-fluoro- 4-bromobenzyl, 2゜4-dibromobenzyl, 2
, 5-dibromobenzyl, 2,6-dibromobenzyl,
2,3.4-tribromobenzyl, 2,4.5-i-libromobenzyl, 2,3.5-tribromobenzyl, 2
, 4゜6-tribromobenzyl, 3,4.5-tribromobenzyl, 1-(2-bromophenyl)ethyl, 2-
(2-bromophenyl)ethyl, 3-(2-bromophenyl)propyl, 4-(3-bromophenyl)butyl, 5-(2-bromophenyl)pentyl, 6-(4-
bromophenyl)hexyl, 2-chlorobenzyl, 3-
Chlorobenzyl, 4-chlorobenzyl, 2,3-dichlorobenzyl, 2゜4-dichlorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 2-bromo-4-chlorobenzyl, 2-fluoro-4 -chlorobenzyl, 2,3.4-trichlorobenzyl, 2゜4.5-
Trichlorobenzyl, 2,3.5-trichlorobenzyl, 2,4.6-trichlorobenzyl, 3,4.5-trichlorobenzyl, 1-(4-chlorophenyl)ethyl,
2-(4-chlorophenyl)ethyl, 3-(2-chlorophenyl)propyl, 4-(4-chlorophenyl)
Butyl, 5-(3-chlorophenyl)pentyl, 6-(
4-chlorophenyl)hexyl, 2-(3,4-dichlorophenyl)ethyl, 2-iodobenzyl, 3-iodobenzyl, 4-iodobenzyl, 3,4-shortbenzyl, 3,4.5-triiodobenzyl, 2 -(3-
iodophenyl)ethyl, 6-(2-iodophenyl)
1 or more carbon atoms as a substituent on the phenyl ring such as hexyl group
Examples include phenylalkyl groups in which the alkyl moiety has 1 to 3 carbon atoms, an alkoxy group having 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, and 1 to 3 groups separated from a halogen atom, and in which the alkyl moiety has 1 to 6 carbon atoms. .

Furthermore, the acyl group of the acyloxy group includes those belonging to the following groups.

(1) A furukayl group having 1 to 20 carbon atoms, which may or may not have as a substituent a group selected from the group consisting of a halogen atom, a hydroxyl group, a lower alkoxy group, an aryloxy group, and a substituted or unsubstituted aryl group.

Examples include formyl, acetyl, propionyl,
Butyryl, imbutyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl,
Unsubstituted alkanoyl groups having 1 to 20 carbon atoms such as tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, eicosanoyl groups, and monochloroacetyl, monobromoacetyl, dichloroacetyl, trichloroacetyl, 3 −
Alkanoyl groups having 2 to 6 carbon atoms substituted with 1 to 3 halogen atoms such as chloropropionyl, 4-chlorobutyryl, 5-chloropentanoyl, 6-chloropentanoyl groups; hydroxyacetyl, 3-hydroxypropionyl,
5-hydroxypentanoyl, 4-hydroxybutanoyl, 6-hydroxyhexanoyl and other hydroxyl group-substituted alkanoyl ethoxyacetyl having 2 to 6 carbon atoms, 3-propoxypropionyl, 6-
C2-6 alkoxy substituted with C1-6 such as hexyloxyhexanoyl, 3-methoxypropionyl, etc.
Alkanoyl group; phenoxyacetyl, 2-phenoxypropionyl, 3-phenoxypropionyl, 4-phenoxybutyryl, 5-phenoxypentanoyl, 6-
Phenoxy- or naphthyloxy-substituted carbon atoms such as hunynoxyhexanoyl and α-naphthyloxyacetyl groups with 2 or more carbon atoms
Alkanoyl group of 6: α-phenylacetyl, 2-phenylpropionyl, 3-phenylpropionyl, 4-phenylbutyryl, 5-phenylpentanoyl, 6-phenylhexanoyl, α-(2-chlorophenyl)acetyl, α-( 4-methylphenyl)acetyl, α-(3,
4,5-trimethoxyphenyl)acetyl, α-(3,
4-dimethoxyphenyl)acetyl, 6-(4-carboxyphenyl)hexanoyl, 4-(4-ethoxycarbonylphenyl)pentanoyl, α-(4-ditrophenyl)acetyl, α-(4-cyanophenyl)acetyl, α -A halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a carboxyl group as a substituent on the aryl ring (phenyl ring, naphthyl ring, etc.) such as naphthylacetyl, β-naphthylacetyl group, etc. 1 to 3 groups selected from the group consisting of an alkoxycarbonyl group, a nitro group, and a cyano group whose alkoxy moiety has 1 to 6 carbon atoms.
Aryl substitution with or without 2 to 6 carbon atoms
Examples include alkanoyl groups.

(2) One substituent selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a lower alkylamino group, a nitro group, and a cyano group as a substituent on the aryl ring. ~
Arylcarbonyl group which may have 3 members.

Examples include benzoyl, α-naphthylcarbonyl, β-naphthylcarbonyl, 2-methylbenzoyl, 3
-Methylbenzoyl, 4-methylbenzoyl, 2,4-
Dimethylbenzoyl, 3,4.5-trimethylbenzoyl, 4-ethylbenzoyl, 2-methoxybenzoyl,
3-methoxybenzoyl, 4-methoxybenzoyl, 2
, 4-dimethoxybenzoyl, 3,4゜5-trimethoxybenzoyl, 4-ethoxybenzoyl, 2-methoxy-4-ethoxybenzoyl, 2-propoxybenzoyl, 3-propoxybenzoyl, 4-propoxybenzoyl, 2.4-dimethoxybenzoyl Propoxybenzoyl, 3,4.5-triproboxybenzoyl, 2-carboxybenzoyl,
3-carboxybenzoyl, 4-゛ carboxybenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl,
4-chlorobenzoyl, 2,3-dichlorobenzoyl,
2,4-dichlorobenzoyl, 2,4.6-trichlorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 4-fluorobenzoyl, 2-methoxycarbonylbenzoyl, 3-methoxycarbonylbenzoyl, 4
Dimethoxycarbonylbenzoyl, 2-ethoxycarbonylbenzoyl 3-ethoxycarbonylbenzoyl, 4
-Ethoxycarbonylbenzoyl, 2-propoxycarbonylbenzoyl, 3-propoxycarbonylbenzoyl, 4-propoxycarbonylbenzoyllulu, 4-impropoxycarbonylbenzoyl, 2-butoxycarbonylbenzoyl, 3-butoxycarbonylbenzoylbenzoyl, 2-t-butoxy Carbonylbenzoylinzoyl, 4-t-butoxycarbonylbenzoyl, 2
-Pentyloxycarbonylbenzoyl, 3-pentyloxycarbonylbenzoyl, 4-pentyloxycarbonylbenzoyl-hexyloxycarbonylbenzoyl, 3-hexyloxycarbonylbenzoyl, 4-hexyloxycarbonylbenzoyl, 3,5-dimethoxycarbonylbenzoyl, 3,4.5-Trimethoxycarbonylbenzoyl, β-methyl-α-naphthylcarbonyl-β-naphthylcarbonyl, β-chloro-α-.

naphthylcarbonyl, 4-dimethylaminobenzoyl,
Alkyl groups having 1 to 6 carbon atoms as substituents, such as 3-diethylaminobenzoyl, 4-propylaminobenzoyl, 2-cyanobenzoyl, 4-cyanobenzoyl, 2-nitrobendiyl, 4-nitrobenzoyl groups, and 1 carbon number
~6 alkoxy groups, halogen atoms, carboxyl groups,
Aryl having or not having 1 to 3 groups selected from the group consisting of an alkylamino group having 1 to 6 carbon atoms, a nitro group, a cyano group, and an alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety; An example is a carbonyl group.

(3) A 5- or 6-membered unsaturated heterocyclic carbonyl group having a nitrogen atom, sulfur atom, or oxygen atom as a heteroatom.

Examples include 2-furanylcarbonyl, 3-furanylcarbonyl, 2-chenylcarbonyl, 3-chenylcarbonyl, 4-thiazolylcarbonyl, 2-quinolylcarbonyl, 2-pyrazinylcarbonyl, Examples include furanylcarbonyl such as 3-pyridylcarbonylcarbonyl, chenylcarbonyl, thiazolylcarbonyl, quinolylcarbonyl, pyrazinylcarbonyl, and pyridylcarbonyl.

(4) Carbonate residues such as aryloxycarbonyl groups, chain or cyclic saturated or unsaturated alkoxycarbonyl groups.

Examples include phenoxycarbonyl, α-naphthyloxycarbonyl, β-naphthyloxycarbonyl,
-methylphenoxycarbonyl, 3-methylphenoxycarbonyl, 4-methylphenoxycarbonyl, 2,4
-dimethylphenoxycarbonyltylphenoxycarbonyl, 4-ethylphenoxycarbonyl, 3-methoxyphenoxycarbonyl, 4-methoxyphenoxycarbonyl, 2,4-dimethoxyphenoxycarbonyl, 3,4.5-trimethoxyphenoxycarbonyl, 4-ethylphenoxycarbonyl carbonyl, 2-
Propoxyphenoxycarbonyl, 3-propoxyphenoxycarbonyl, 4-propoxyphenoxycarbonylcarbonyl, 3,4.5-tripropoxyphenoxycarbonyl, 2-chlorophenoxycarbonyl, 3-chlorophenoxycarbonyl, 4-chlorophenoxycarbonyl, 2. 3-dichlorophenoxycarbonyl, 2.4.
A halogen atom, number of carbon atoms as a substituent on an aryl ring (phenyl ring, naphthyl ring, etc.) such as 6-trichlorophenoxycarbonyloxycarbonyl, 4-fluorophenoxycarbonylnylbonyl, and β-chloro-α-naphthyloxycarbonyl group. Aryloxycarbonyl group having or not having 1 to 3 alkoxy groups having 1 to 6 carbon atoms and 1 to 3 alkyl groups having 1 to 6 carbon atoms; methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
Isopropoxycarbonyl, t-butoxycarbonyl,
Alkoxycarbonyl groups whose alkoxy moiety has 1 to 6 carbon atoms such as butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl groups; cyclopropyloxycarbonyl, cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, cyclo Cycloalkoxycarbonyl groups in which the cycloalkyl moiety has 3 to 8 carbon atoms, such as butyloxycarbonyl and cyclooctyloxycarbonyl groups;
vinyloxycarbonyl, allyloxycarbonyl, 2
-butenyloxycarbonyl, 3-butenyloxycarbonyl, 2-hexenyloxycarbonyl, 1-methylallyloxycarbonyl, 2-pentenyloxycarbonyl, 3-hexenyloxycarbonyl, etc., where the alkenyl moiety has 2 to 6 carbon atoms; Certain alkenyloxycarbonyl groups; the alkynyl moiety has 2 to 6 carbon atoms, such as ethynyloxycarbonyl, propionyloxycarbonyl, 2-butynyloxycarbonyl, 1-methyl-3-pentynyloxycarbonyl, 4-hexynyloxycarbonyl, etc.
Examples include alkynyloxycarbonyl groups.

(5) Substituted or unsubstituted cycloalkylcarbonyl group.

Examples include cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, Schiff O hebutylcarbonyl, cyclooctylcarbonyl, 2-chlorocyclohexylcarbonyl, 3-hydroxycyclopentylcarbonyl, 3-
A cycloalkyl ring such as methylcyclohexylcarbonyl or 4-methoxycyclohexylcarbonyl group may have a halogen atom, hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, or an alkyl group having 1 to 6 carbon atoms as a substituent. , and a cycloalkylcarbonyl group in which the cycloalkyl ring has 3 to 8 carbon atoms.

(6) Lower alkenyl (or lower alkynyl) carbonyl group.

Examples include vinylcarbonyl, allylcarbonyl, 2-butenylcarbonyl, 3-butenylcarbonyl,
1-methylallylcarbonyl, 2-pentenylcarbonyl, 3-hexenylcarbonyl, ethynylcarbonyl,
Propynylcarbonyl, 2-butynylcarbonyl, 1-
Examples include alkenyl or alkynyl carbonyl groups having an alkenyl group or an alkynyl group having 2 to 6 carbon atoms, such as -methyl-3-pentynylcarbonyl group and 4-hexynylcarbonyl group.

Furthermore, as the lower alkanoyloxy group, straight-chain or branched alkanoyl having 1 to 6 carbon atoms such as formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, hexanoyloxy group, etc. An example is an oxy group.

Examples of the lower alkanoyloxy lower alkoxycarbonyl group include acetyloxymethoxycarbonyl, 4-(formyloxy)butoxycarbonyl, 6-(propionyloxy)hexyloxycarbonyl, 5-(imbutyryloxy)pentyloxycarbonyl, 6-( Examples include alkanoyloxydialkoxycarbonyl groups in which the alkanoyl moiety and the alkoxy moiety each have 1 to 6 carbon atoms, such as hexanoyloxy)hexyloxycarbonyloxy)ethoxycarbonylxy)ethoxycarbonyl and acetyloxymethoxycarbonyl groups.

In addition, the arylene group represented by A in general formula (1) is an aromatic hydrocarbon or a 5- or 6-membered aromatic heterocyclic ring having 1 to 2 nitrogen atoms and oxygen atoms as petro atoms. Indicates a divalent group in which one hydrogen atom bonded to an atom is removed, and the arylene group (A)
Specific examples include 1,2-phenylene, 1.

Phenylene W such as 3-phenylene and 1,4-phenylene
:1,2 naphthylene, 1,3-naphthylene, 1,4-
Naphthylene groups such as naphthylene, 1,5-naphthylene, 1,6-naphthylene, 1,7-naphthylene, 1,8-naphthylene; 2.

3-pyridinediyl, 2,4-pyridinediyl, 2,5
-pyridinediyl, 2,6-pyridinediyl, 3,4-
Pyridinediyl groups such as pyridinediyl, 3,5-pyridinediyl; 2,3-pyridinediyl, 2,6-pyridinediyl, 2.

Pyrazindiyl group such as 5-pyrazindiyl; 2.

Furandiyl groups such as 3-furandiyl, 3,4-furandiyl, 2゜5-furandiyl; 4-pyridone-1-methyl-2,3-diyl, 4-pyridone-1-methyl-2
, 5-diyl, and 4-pyridone-1-lower alkyl-diyl groups such as 4-pyridone-1-methyl-2,6-diyl.

In the general formula (1) representing the compound of the present invention, R' (
Among the substituents of (substituted pyridyl group), hydroxyl group, halogen atom, amino group, carboxyl group, cyano group, nitro group,
The oxo group, lower alkyl group, lower alkenyl group, lower alkoxycarbonyl group, carbamoyl group, and acyloxy group are preferably 2-position, 3-position, 4-position, 5-position of the pyridine ring.
1 to 4 substitutions are made at either position or position 6. Also, among the substituents on the pyridine ring, a carbamoyl group, a lower alkylcarbamoyl group, a phenylcarbamoyltalidyl group that may have 1 to 3 halogen atoms, lower alkyl groups, and lower alkoxy groups as substituents on the phenyl ring, The lower alkoxy lower alkyl group, the lower alkoxy lower alkyl group having a phenyl group, and the lower alkoxy carbonyl lower alkylcarbamoyl group are preferably bonded to the 1-position of the pyridine ring.

Particularly preferred examples of the pyridyloxycarbonylarylenecarbonyl group containing the substituted pyridyl group (R1 group) are represented by the following general formulas (a) to (d).

[In the formula, A is the same as above. Rla is a hydrogen atom, a halogen atom, an amino group, a carboxyl group, a cyano group, a nitro group,
Indicates a lower alkyl group, lower alkenyl group, or lower alkoxycarbonyl group.

Is Rlb a hydroxyl group or phenyl lower alkyloxy? group or acyloxy group. Q represents 1 or 2 and is either the 2nd, 4th or 6th position of the lysine ring, and the R1b group is substituted at at least one of the remaining 2nd, 4th and 6th positions. ]R↓l.

[In the formula, A and Rla are the same as above. R10 is a carbamoyl group, a lower alkylcarbamoyl group, a phenylcarbamoyl group which may have 1 to 3 groups selected from halogen atoms, lower alkoxy groups and lower alkyl groups as substituents on the phenyl ring, a tetrahydrofuranyl group, The phthalidyl group, lower alkoxy lower alkyl group, lower alkoxy lower alkyl group having a phenyl group, or lower alkoxycarbonyl lower alkyl group shall be bonded to the 4- or 6-position of the pyridone ring. ] [In the formula, A, R1a and RIC are the same as above. However, it shall be bonded to the 6th position. ] [In the formula, A, R and Rlc are the same as above. However, it shall be bonded to the 6th position. ] The R1a group defined by the above general formulas (a) to (d) is particularly preferably a cyano group or a halogen atom.

Furthermore, the group represented by R2 is a 5-fluorouracil derivative residue that can be converted into 5-fluorouracil in vivo, and the group is bonded to its adjacent carbonyl group through an ester bond or an amide bond. do. The R
As the 5-fluorouracil derivative forming two groups,
Any of various known 5-fluorouracil derivatives can be exemplified. Typical examples include those represented by the following general formulas (e) to (C+).

[In the formula, R3 represents a hydrogen atom, a tetrahydrofuranyl group, a lower alkylcarbamoyl group, a phthalidyl group, a lower alkoxy lower alkyl group, or a lower alkanoyloxy lower alkoxycarbonyl group. [In the formula, R4 represents a hydrogen atom, a hydroxyl group, or an acyloxy group, and R5 represents a hydroxyl group, an acyloxy group, or 1 to 3 groups selected from a lower alkyl group, a lower alkoxy group, and a halogen atom as substituents on the phenyl ring. R6 represents a phenyl lower alkyloxy group which may have a hydrogen atom, a hydroxyl group, an acyloxy group, or one to three groups selected from a lower alkyl group, a lower alkoxy group and a halogen atom as substituents on the phenyl ring. Indicates a phenyl lower alkyloxy group that may have a phenyl lower alkyloxy group. However, when R4 is a hydrogen atom, one of R5 and R6 is phenyl lower alkyloxy, which may have 1 to 3 groups selected from lower alkyl groups, lower alkoxy groups, and halogen atoms as substituents on the phenyl ring. group, and the other cannot be a hydroxyl group or an acyloxy group. ] [In the formula, R7 represents a lower alkoxycarbonyl group, and R8
When the lower alkoxy group or the group R2 is a group shown in the above general formula (e), the group R2 can be bonded to the 3-position of the 5-fluorouracil ring or to form an amide bond.

When R2 is a group represented by the above general formula (f), the group group R2 can form a bond or an ester bond with the nitrogen atom at the 3-position of the 5-fluorouracil ring or the hydroxyl group of the sugar moiety.

When R2 is a group represented by the above general formula (0), the group group R2 is
It can be bonded to the 1-position of the 5-fluorouracil ring or to form an amide bond.

Keto-enol type tautomers may exist in the compounds of the present invention having the pyridyloxycarbonylarylenecarbonyl group, and the present invention naturally includes these isomers.

Among the pyridyloxycarbonylarylenecarbonyl groups represented by the general formula <a>, those in which R is a cyano group and Rlb is a benzoyl group which may have a halogen atom are particularly preferred. Among the 5-fluorouracil derivatives represented by the general formula (e), those in which R3 is a lower alkoxy lower alkyl group are particularly preferred.

Behind the compound of the present invention represented by the above general formula (1),
A particularly preferred one is represented by the following general formula (1A).

[In the formula, R and Rb are the same or different and represent a hydrogen atom or a halogen atom. Ro represents a lower alkyl group. ]

Representative examples of the compound of the present invention represented by the above general formula (1) are as follows.

05-fluoro-3-(3-(4-pentanoyloxy-2-pyridyloxycarbonylzoyl)-1-(2-
tetrahydrofuranyl) uracil o3- (3- (4-ethoxycarbonyloxy-2
-pyridyloxycarbonyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil Q5-fluoro-3- (3- (2- (2-methylbenzoyloxy)-4-pyridyloxycarbonylovuranyl)uracil o3- (3-(2-Benzoyloxy-4-pyridyloxycarbonylfluoro-1-(2-tetrahydrofuranyl)uracil05-fluoro-3-(3-(4-(2-naphthoyloxy)-2-pyridyloxy carbonylbenzoyl)-1-(2-tetrahydrofuranyl)uracil 05-fluoro-3-(3-(4-phenylacetyloxy-2-pyridyloxycarbonylbenzoyl)-1
-(2-tetrahydrofuranyl)uracil o3- (3- (1,2-dihydro-2-oxo-4
-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil03-(3-(1-ethoxymethyl-1,2-dihydro-2-oxo-4-pyridyloxycarbonyl)benzoyl) -5-fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3- (1-N-ethylcarbamoyl-1).

2-dihydro-2-oxo-4-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil 05-fluoro-3-(4-
(4-(3-pyridylcarbonyloxy)-2-pyridyloxycarbonyl]benzoyl)-1-(2-tetrahydrofuranyl)uracil05-fluoro-3-(3-(4-(2-thenoyloxy)-2-pyridyl) oxycarbonyl)benzoyl)-
1-(2-tetrahydrofuranyl)uracil O3-(3-(4-(2-furoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-
1-(2-tetrahydrofuranyl)uracil O3-(3-(4-benzoyloxy-5-bromo-2
-pyridyloxycarbonyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil O3-(3-(4-benzoyloxy-5-cyano-
2-Pyridyloxycarbonyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil O3- (3- (4-benzoyloxy-5-nitro-2-pyridyloxycarbonyl)benzoyl-5-
Fluoro-1-(2-tetrahydrofuranyl)uracil O3- (3- (4-acetoxy-5-chloro-2-
Pyridyloxycarbonyl 5-fluoro-1-(2-tetrahydrofuranyl)uracil O3- (3- (2-acetoxy-5-chloro-4-
pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil03-(3-(4-benzoyloxy-5-chloro-
2-Pyridyloxycarbonyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil O3- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoyl-5-
Fluoro-1-(2-tetrahydrofuranyl)uracil O3- (3- (4-(2-chloro-3-methylbenzoyloxy)-2-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(2-tetrahydrofuranyl ) uracil 05-fluoro-3- (3- (4- (4-methoxybenzoyloxy)-5-chloro-2-pyridyloxycarbonyl (2-tetrahydrofuranyl) uracil 05-fluoro-3- (3- (4- Phenol carbonyloxy
5-chloro-2-pyridyloxycarbonyl)benzoyl)-1-(2-tetrahydrofuranyl)uracil O5-fluoro-3- (3- (4- (3,4.5
-trimethoxybenzoyloxy)-5-chloro-2-
pyridyloxycarbonyl)benzoyl)-1-(2-
Tetrahydrofuranyl)uracil O3- (3- (5-chloro-4-(4-dimethylaminobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil 03- ( 3-(5-chloro-4-octadecanoyloxy-2-pyridyloxycarbonylnzoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil03-(3-(1-benzyloxymethyl-5-chloro) -1,2-dihydro-2-oxo-4-pyridyloxycarbonyl-fluoro-1-(2-tetrahydrofuranyl)uracil o3-(3-(5-chloro-1,2-dihydro-2-oxo-1- (2-Tetrahydrofuranyl)-4-pyridyloxycarbonyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil 03- (3- (1-ethoxymethyl-1,2-dihydro-2-oxo-4-pyridyl) Oxycarbonyl(2-tetrahydrofuranyl)uracil 03- (3-
(5-chloro-4-hydroxy-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-
Tetrahydrofuranyl) uracil 03- (3- (1,2-dihydro-2-oxo-6
-pyridyloxycarbonyl)benzoyl]-5-fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3- (3-chloro-6-(4-fluorobenzoyloxy)-2-pyridyloxycarbonyl]benzoyl)- 5-Fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3-(3-carbamoyl-
6-toxybenzoyloxy)-2-pyridyloxycarbonyl 1-(2-tetrahydrofuranyl)uracil o3- (
3- (4-Amino-3-cyano-6-penzoyloxy-2-pyridyloxycarbonyltetrahydrofuranyl)uracil o3- (3- (6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoylcy5-
Fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3- (3-cyano-6- (3,4.5-
trimethoxybenzoyloxy)-2-pyridyloxycarbonylo-1-(2-tetrahydrofuranyl)uracil 03- (3-(3-cyano-6-nicotinoyloxy-2-pyridyloxycarbonyl)benzoylcy 5
-Fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3- (3-cyano-6-(2-furoyloxy)-2-pyridyloxycarbonylnzoyl)-5
-Fluoro-1-(2-tetrahydrofuranyl)uracil 03- (3-(3-cyano-6-(2-tenoyloxy)-2-pyridyloxycarbonyl)benzoyl)-
5-Fluoro-1-(2-tetrahydrofuranyl)uracil 03- (3- (3-cyano-6- (2,4-dichlorobenzoyloxy)-2-pyridyloxycarbonyl-(2-tetrahydrofuranyl) uracil 03- (3
-(3-cyano-6-acetoxy-2-pyridyloxycarbonyl)benzoylcy5-fluoro-1-(2-
Tetrahydrofuranyl)uracil 03- (3-(3-cyano-6-octazocanoyloxy)-2-pyridyloxycarbonylbenzoyl)
-5-Fluoro-1-(2-tetrahydrofuranyl)uracil o3- (3-(6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl)-5-
Fluoro-1-(N-hexylcarbamoyl)uracil o3- (3-(3-cyano-6-(2-]Oylylcy)-2-pyridyloxycarbonyl)benzoyl)
-5-fluoro-1-(N-hexylcarbamoyl)uracil o3- (3- (4-acetoxy-5-chloro-2=
Pyridyloxycarbonyl 5-fluoro-1-(N-hexylcarbamoyl)uracil o3- (3-(4-benzoyloxy-5-chloro-
2-pyridyloxycarbonyl)benzoyl]-5-fluoro-1-(N-hexylcarbamoyl)uracil o3-(3-(2-benzoyloxy-5-chloro-4
-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(N-hexylcarbamoyl)uracil o3-(3-(5-chloro-4-hydroxy-2-pyridyloxycarbonyl)benzoyl2-5-fluoro-
1-(N-hexylcarbamoyl)uracil o3-(3-(3-chloro-6-(4-fluorobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(3-phthalidyl)uracil o3- (3-(4-amino-6-penzoyloxy-3-cyano-2-pyridyloxycarbonylphthalidyl)uracil o3- (3- (6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl25 −
Fluoro-1-(3-phthalidyl)uracil o3-(3-(3-cyano-6-(3,4.5-trimethoxybenzoyloxy)-2-pyridyloxycarbonyl]benzoyl)-5-fluoro-1- (3-phthalidyl)uracil o3- (3- (3-cyano-6
- (2,4-dichlorobenzoyloxy)-2-pyridyloxycarbonyl-(3-phthalidyl)uracil 03- (3- (4-acetoxy-5-chloro-2-
Pyridyloxycarbonyl 5-fluoro-1-(3-phthalidyl)uracil o3- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)-5-fluoro-1-(3-7thalidyl) Uracil 03- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl-5-fluoro-1-(3-phthalidyl) uracil o3- (3- (5-chloro-1,2-dihydro- 2
-oxo-1-(2-tetrahydrofuranyl)-4-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(3-7talidyl)uracilol-acetoxymethoxycarbonyl-3-(3-[3
-carbamoyl-6-benzoyloxy)-2-pyridyloxycarbonyl]benzoyl)-5-fluorouracil o1-acetoxymethoxycarbonyl-3-[3-(6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl-fluorouracil ol) -acetoxymethoxycarbonyl-3-(3-(3
-cyano-6-nicotinoyloxy-2-pyridyloxycarbonyl)benzoyl)-5-fluorouracil 01-acetoxymethoxycarbonyl-3-(3-[3
-cyano-6-(2-thenoyloxy)-2-pyridyloxycarbonyl-5-fluorouracil ol-acetoxymethoxycarbonyl-3-[3-(4
-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl2-5-fluorouracilol-acetoxymethoxycarbonyl-3-[3-(2
-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoyl2-5-fluorouracil 01-acetoxymethoxycarbonyl-3-(3-[5
-chloro-4-(3,4,5-trimethoxybenzoyloxy)-2-pyridyloxycarbonyl]benzoyl)-5-fluorouracil o3- (3-(3-chloro-6-(4-fluorobenzoyloxy)- 2-Pyridyloxycarbonyl]benzoyl)-5,6-cyhydro-5-ethoxycarbonyl-5-fluoro-6-furfurylideneaminooxyuracil 03- (3-(6-penzoyloxy-3-cyano-
2-pyridyloxycarbonyl)benzoyl)-5,6
-Sihydro-5-ethoxycarbonyl-5-fluoro-
6-furfurylideneaminooxyuracil o3- (3-(3-cyano-6-(3,4,5-trimethoxybenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5,6-cyhydro-5-ethoxycarbonyl -5-fluoro-6-furfurylideneaminooxyuracil o3- (3-(6-acetoxy-3-cyano-2-pyridyloxycarbonyl5,6-dihydro-5-ethoxycarbonyl-5-fluoro-6-furfurylidene) Aminooxyuracil o3- (3- (3-cyano-6-octazocanoyloxy-2-pyridyloxycarbonyl)benzoyl)
-5,6-sihydro-5-ethoxycarbonyl-aminooxyuracil o3- (3-(4-acetoxy-5-chloro-2-pyridyloxycarbonyl)benzoyl)-5,6-sihydro-5-ethoxycarbonyl-5- Fluoro-6-furfurylideneaminooxyuracil o3- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl)-5.
6-Sihydro-5-ethoxycarbonyl-5-fluoro-6-furfurylideneaminooxyuracil 03- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoyl)-5.
6-Sihydro-5-ethoxycarbonyl-5-fluoro-6-furfurylideneaminooxyuracil o3- (3- (4-acetoxy-5-chloro-2-
Pyridyloxycarbonyl 1-ethoxymethyl-5-fluorouracil o3-(3
- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl-1-ethoxymethyl-5-fluorouracil 03- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)- 1-Ethoxymethyl-5-fluorouracil o3- (3- (4- (2-chloro-3-methylbenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl-5-fluorouracil 03- (3- (5-chloro-4- (3,4.5-
trimethoxybenzoyloxy)-2-pyridyloxycarbonyloxymethyl-5-fluorouracil o3- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl2-5-
Fluorouracil o3- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)-5-fluorouracil o3- (3- (1,2-dihydro-2-oxo-6
-pyridyloxycarbonyl)benzoyl)-5-fluorouracil Q3- (3- (3-carbamoyl-6-(4-methoxybenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5'-deoxy-2', 3' −
Ziroacetyl-5-fluorouridine o3- (3- (6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl25'
-deoxy-2',3'-ziloacetyl-5-fluorouridine o3- (3-(3-cyano-6-(2-furoyloxy)-2-pyridyloxycarbonyl]benzoyl)
-5'-deoxy-2', 3'-di-acetyl-5-fluorouridine O3- (3- (4-acetoxy-5-chloro-2-pyridyloxycarbonyl)benzoyl-5'-deoxy-2', 3 ' -di-0-acetyl-5-fluorouridine 03- (3- (2-acetoxy-5-chloro-4-
pyridyloxycarbonyl)benzoyl]-5'-deoxy-2', 3'-di-0-acetyl-5-fluorouridine o3- (3-(4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl) -5′
-deoxy-2', 3'-di-0-acetyl-5-
Fluorouridine 03”- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoyl2 5
'-deoxy-2', 3'-di-acetyl-5
-Fluorouridine o3- (3- (5-chloro-4-(4-methoxybenzoyloxy)-2-pyridyloxycarbonyl3'-di0-acetyl-5-fluorouridine 03- (3- (4-benzoyloxy) -5-chloro-2-pyridyloxycarbonyl 2'-deoxy-3', 5'-zilobenzyl-5-fluorouridine o3- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl) Lucy2'-deoxy-3',5'-G〇-(4
-chlorobenzyl)-5-fluorouridine o3- (3- (2-benzoyloxy-5-'chloro-4-pyridyloxycarbonyl-2'-deoxy-3', 5'-zilowbenzyl-5-fluorouridine o3 - (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoylcy2'
-deoxy-3',5'-di〇-(4-chlorobenzyl)-5-fluorouridine o3- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl2-5-
Fluoro-2',3',5'-tri-acetyluridine03-(3-(2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)5-fluoro-2',3',5'-tri rhoacetyluridine o3- (3- (5-chloro-1,2-dihydro-2
-oxo-1-(2-tetrahydrofuranyl)-4-pyridyloxycarbonyl-5-fluoro-2',3',5'-triloacetyluridine o3- (3- (4-acetoxy-5-chloro-2 −
Pyridyloxycarbonyl2'-deoxy-3',5'-di-O-acetyl-5-fluorouridine o3- (3-(4-benzoyloxy-5-chloro-
2-pyridyloxycarbonyl]-2'-deoxy-3', 5'-di-acetyl-5-fluorouridine o3- (3- <2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)benzoyl]- 2'
-deoxy-3', 5'-di-O-acetyl-5
-fluorouridine o3- (3- (5-chloro-4-(4-methoxybenzoyloxy)-2-pyridyloxycarbonyl5'-diO-acetyl-5-fluorouridine o3- (3-(5-chloro-4- Hydroxy-2-pyridyloxycarbonyl)benzoyl2'-deoxy-3',5'-diO-acetyl-5-fluorouridine03- (3-(4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)benzoyl Two 5-
Fluorouracil o3- (3- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl) benzoyl2-5-
Fluorouracil o3- (3- (1,2-dihydro-2-oxo-6
-pyridyloxycarbonyl-5-fluorouracil ol- (3- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl-5-fluorouracil ol- (3- (6-penzoyloxy-3-cyano-2-pyridyloxy) carbonyl)-5-fluorouracil o3-(4- (1,2-dihydro-2-oxo-4-
(4-(6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil ) Uracil 03- (4-(2-benzoyloxy-5-chloro-
4-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(3-phthalidiyl)uracil o3- (4- (4-acetoxy-5-chloro-2-
(pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(3-phthalidiyl)uracil o3- (4- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)-5-fluoro-2', 3 ' , 5' -tri〇-acetyluridine 03- (4- (6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)-3-furoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil o3- ( 4-(6-penzoyloxy-3-cyano-2-pyridyloxycarbonylloyl)-21-deoxy-3',5'-diO
-acetyl-5-fluorouridine o3- (4- (4-benzoyloxy-5-chloro-2-pyridyloxycarbonyl)-3-furoyl-5-fluoro-2',3',5'-tri〇-acetyluridine 03- (4- (2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)-3-furoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil03- (4- (4-acetoxy-5-chloro- 2-
Pyridyloxycarbonyl-5-fluoro-2',3',5'-tri-
Acetyluridine 03- (5-(6-penzoyloxy-3-cyano-
2-pyridyloxycarbonyl)-3-nicotinoyl]
-5-fluoro-1-(2-tetrahydrofuranyl)uracil 03-(5-(6-penzoyloxy-3-cyano-2)
-pyridyloxycarbonyl)-3-nicotinoyl]-
5'-deoxy-2', 3'-di-O-acetyl-5-fluorouridine 01- (5-(6-penzoyloxy-3-cyano-2-pyridyloxycarbonyl)-3-nicotinoyl]-5-fluorouracil o3 - (5-(4-benzoyloxy-5-chloro-
2-pyridyloxycarbonyl)-3-nicotinoyl]
-5'-deoxy-2',3'-di-O-acetyl-5-fluorouridine o3- (5-(2-benzoyloxy-5-chloro-4-pyridyloxycarbonyl)-3-nicotinoyl]-5- Fluoro-1-(2-tetrahydrofuranyl)uracil o3- (4-(6-penzoyloxy-3-cyano-
2-pyridyloxycarbonylphthoyl]-5-fluoro-1-(2-tetrahydrofuranyl)uracil 03-(4-(2-benzoyloxy-5-chloro-
4-pyridyloxycarbonyl)-2-naphthoyl-1-ethoxymethyl-5-fluorouracil ol- (3- (4-acetoxy-5-chloro-2-
pyridyloxycarbonyl]-5-fluorouracil o3- (6- (6-penzoyloxy-3-cyano-2-pyridyloxycarbonylthyl-4-pyridon-2-ylcarbonyl 5-fluorouracil) Oxymethyl-5-chloro-1,2-dihydro-2-oxo-4-pyridyloxycarbonyl)-1-methyl-4-pyridon-2-ylcarbonylo-1-(2-tetrahydrofuranyl)uracil o3- ( 6-(2-benzoyloxy-4-pyridyloxycarbonyllbonyl)-2'-deoxy-3', 5'-di0
-Acetyl-5-fluorouridine The compound of the present invention represented by the above general formula (1) can be prepared by the following reaction scheme -1 or -
It can be manufactured by the method shown in 2.

Reaction Scheme-1>(2> (3) R' -0-R9 (In the formula, R1, R2 and A are the same as above. X represents a halogen atom. R9 represents a hydrogen atom or a tri-lower alkylsilyl group. According to the method shown in Reaction Scheme-1, first, a known compound (
Intermediate (4) is obtained by reacting 2) with known compound (3).

This reaction is carried out in a suitable solvent in the presence of a suitable deoxidizing agent. As the deoxidizing agent, commonly used ones can be used, such as inorganic basic compounds such as sodium bicarbonate, sodium carbonate, and potassium carbonate, and organic basic compounds such as triethylamine, N,N-dimethylaminopyridine, and pyridine. As a solvent, various solvents that do not adversely affect the reaction, such as ethers such as dioxane and tetrahydrofuran, nitriles such as acetonitrile, aromatic hydrocarbons such as benzene and toluene, methylene chloride, chloroform, carbon tetrachloride, etc. Halogenated hydrocarbons, pyridine, N,N-dimethylformamide, etc. can be used.

The amount of compound (3) to be used relative to compound (2) is not particularly limited, but is usually selected from a range of at least equimolar, preferably from equimolar to 3 times the molar amount. . The reaction temperature is generally -30~100℃,
The temperature is preferably room temperature to about 100''C, and the reaction is completed in about 10 minutes to 20 hours.

Next, the target compound (1) of the present invention can be obtained by reacting the resulting intermediate (4) with a known or common compound (5). Depending on the type of compound (5), when using a compound (5) in which R9 is a hydrogen atom, this reaction is carried out under the same conditions as the reaction between compound (2) and compound (3) above. . Further, when using a compound (5) in which R9 is a tri-lower alkylsilyl group, the reaction is carried out in a suitable solvent, such as ethers such as diethyl ether, dioxane, and tetrahydrofuran, nitriles such as acetonitrile, and aromatic solvents such as benzene and toluene. group hydrocarbons,
It is carried out using aprotic solvents such as halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, etc., preferably in anhydrous state. In either case, the reaction temperature is usually -30 to 100°C, preferably about room temperature to 60°C, and the reaction is completed in about 1 to 20 hours.

In the reaction between the above intermediate (4) and compound (5),
Catalytic amounts of Lewis acids such as aluminum chloride, stannic chloride, zinc chloride, etc. can also be used.

The amount of compound (5) to be used is determined as appropriate, but it is usually appropriate to use at least an equimolar amount, preferably about equimolar to three times the molar amount, relative to intermediate (4).

<Reaction Scheme-2> 2l-1 [In the formula, R1, R2, A and X are the same as above. ] The reaction between compound (6) and compound (3) shown in reaction scheme-2 is as follows:
Compound (2) and compound (3) shown in the reaction scheme-1 above
) is carried out in the same manner as the reaction with

The reaction between intermediate (7) thus obtained and compound (2) can also be carried out in the same manner as the reaction between compound (2) and compound (3) described above.

Compound (5) and compound (6) used in the above reaction scheme -1 or -2 include some new compounds. These compounds can be produced, for example, by any of the methods shown below or by an appropriate combination of these methods.

The reaction for introducing an acyloxy group onto the pyridine ring, for example, the reaction for obtaining compounds (5) and compounds (6) in which the R1 group is a pyridyl group having an acyloxy group as a substituent, is as follows:
This is carried out by using a pyridine compound having a corresponding hydroxyl group or tri-lower alkylsilyloxy group as a raw material and reacting it with a suitable acylating agent. This acylation reaction can be carried out in the same manner as the reaction of compound (2> and compound (3) shown in Reaction Scheme-1 above).

A reaction in which a substituent selected from a carbamoyl group, a lower alkylcarbamoyl group, and a phenylcarbamoyl group that may have the above substituent on the phenyl ring is introduced into the 1-position of the pyridine ring, for example, a pyridyl group in which the R1 group has the above substituent. The reaction to obtain compounds (5) and (6), which are groups, is carried out by using a (1 day)-pyridone derivative as a raw material, and adding about 1 to 2 times the molar amount of isocyanate or an isocyanate having the above substituent, The reaction is preferably carried out in the presence of a basic compound in a suitable solvent. The conditions for this reaction (basic compound used, type of solvent, reaction temperature, reaction time, etc.) are also the same as those for the reaction between compound (2) and compound (3) shown in reaction scheme-1 above. can do.

A reaction in which a substituent selected from a tetrahydrofuranyl group, a phthalidyl group, a lower alkoxy lower alkyl group that may have a phenyl group, and a lower alkyl group is introduced into the 1-position of the pyridine ring, for example, the R1 group has the above substituent. The reaction to obtain compounds (5) and (6), which are pyridyl groups, is carried out using the corresponding (tri-lower alkylsilyloxy)pyridine derivatives having a hydroxyl group protected by a tri-lower alkylsilyl group as raw materials, and adding the general formula % Formula % (8) [In the formula, R1d represents a lower alkoxy lower alkyl group or a lower alkyl group that may have a phenyl group. X is the same as above. ] A compound represented by the general formula % formula % (9) (In the formula, R10 represents a lower alkyl group. R18 is a lower alkoxy lower alkyl group that may have a tetrahydrofuranyl group, a phthalidyl group, a phenyl group, and a lower alkyl group) represents a group selected from ].This reaction is carried out in an appropriate solvent in the presence or absence of a Lewis acid.As a solvent, diethyl ether , ethers such as tetrahydrofuran and dioxane, aromatic hydrocarbons such as benzene and toluene, acetonitrile, acetone, ethyl acetate, etc., and as Lewis acids, boron trifluoride, tin tetrachloride, zinc chloride, etc. are preferably used. can.

Compound (8) or compound (9) is preferably used in an amount of about 1 to 2 times the molar amount of the starting compound, and the reaction is generally completed in about 1 to 4 hours at a temperature of room temperature to 60°C. .

In addition, the reaction of introducing a tri-lower alkylsilyloxy group onto the pyridine ring, for example the reaction to obtain the compound (5) in which R9 is a tri-lower alkylsilyl group, can be carried out by reacting a silylating agent with the corresponding pyridine derivative having a hydroxyl group. It can be implemented by Here, as the silylating agent, common ones such as tri-lower alkyldisilazanes such as 1,1゜1.3,3,3-hexamethyldisilazane, halogenated tri-lower alkylsilanes such as trimethylchlorosilane, N
, O-bistrimethylacetamide, and other silylated acetamides can be used. The silylating agent is generally used in an amount of about 1 to 3 times the molar amount of the starting compound. In addition, when the above-mentioned halogenated trialkylsilanes are used as a silylating agent, amines such as triethylamine, dimethylaniline, diethylaminopyridine, pyridine, etc. are further added to the reaction system in an amount of about 1 to 10% per silylating agent. It is desirable to add 3 times the molar amount. Alternatively, in this case or when silylated acetamide is utilized as the silylating agent, the reaction is carried out in a suitable solvent, such as diethyl ether,
It is preferably carried out in a solvent such as an ether such as dioxane or tetrahydrofuran, a nitrile such as acetonitrile, or a halogenated hydrocarbon such as methylene chloride or chloroform.

When tri-lower alkyldisilazane is used as the silylating agent, the silylating agent itself also functions as a solvent, so there is no need to use any other solvent. The above-mentioned silylation reaction is usually carried out at a temperature from room temperature to around the boiling point of the reaction solvent, and takes about 1 to 15 hours.

Furthermore, in the compounds of the present invention, a compound in which the R1 group is a pyridyl group having a phenyl lower alkyloxy group can be converted into a compound in which the R1 group is a pyridyl group having a water M group by subjecting this to a normal catalytic reduction operation. can be induced.

The target compound and the compound of the present invention obtained in each of the above reaction steps are separated from the reaction system by conventional separation means and further purified. As this separation and purification means, for example, reprecipitation method, recrystallization method, silica pull column chromatography, ion exchange column chromatography, gel chromatography, affinity chromatography, etc. can be employed.

The compounds of the present invention thus obtained have excellent anticancer effects, are low in toxicity, have few side effects such as weight loss, and are very useful as antitumor agents for cancer treatment in humans and animals. . In particular, the compound of the present invention has (1) good absorption, (2) good persistence, (3) good stability, and (4)
) Gastrointestinal toxicity such as diarrhea, urination, and gastrointestinal bleeding is extremely low; (5) there is a large difference between the dose that exerts its original anticancer effect and the dose that causes side effects such as toxicity, and the therapeutic coefficient is excellent. It has excellent features such as high safety and safety.

The compound of the present invention is usually used in the form of a common pharmaceutical preparation. The formulation contains commonly used fillers, extenders, binders,
It is adjusted using diluents or excipients such as wetting agents, disintegrants, surfactants, and lubricants. Various forms of this pharmaceutical preparation can be selected depending on the therapeutic purpose, and representative examples include tablets, emulsions, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquid , suspensions, etc.), ointments, etc. When forming into a tablet, carriers such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, water, ethanol, propatool, simple syrup, etc. , glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac,
Binders such as methylcellulose, potassium phosphate, polyvinylpyrrolidone, dry starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, Disintegrants such as lactose, disintegration inhibitors such as sucrose, stearin, cocoa butter, hydrogenated oil, etc.
Absorption enhancers such as grade ammonium bases and sodium lauryl sulfate, moisturizing agents such as glycerin and starch, starch,
Adsorbents such as lactose, kaolin, bentonite, and colloidal silicic acid, and lubricants such as purified talc, stearate, boric acid powder, and polyethylene glycol can be used. If necessary, the tablets can be provided with a conventional coating, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, or multilayer tablets. When forming into an emulsion, carriers such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin,
Excipients such as talc, binders such as gum arabic powder, tragacanth powder, gelatin, ethanol, and disintegrants such as laminaran and agar can be used. When forming into a suppository, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthetic glycerides, etc. can be used as carriers. Capsules are prepared by mixing the compound of the present invention with the various carriers exemplified above and filling them into hard gelatin capsules, soft capsules, etc. according to conventional methods. When prepared as injections, solutions, emulsions and suspensions are preferably sterilized and isotonic with blood, and when molded into these forms, diluents such as water, ethyl alcohol, macrogol, etc. , propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like can be used. In this case, a sufficient amount of salt, glucose, or glycerin may be included in the pharmaceutical preparation to adjust the isotonic solution, and usual solubilizing agents, buffers, soothing agents, etc. may be added. It's okay. Furthermore, coloring agents, preservatives, perfumes, flavoring agents, sweeteners, etc., and other pharmaceuticals may be included in the pharmaceutical preparation, if necessary. When forming pastes, creams and gels, diluents such as white petrolatum, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone,
Bentonite etc. can be used.

The amount of the compound of the present invention to be contained in the pharmaceutical formulation of the present invention is not particularly limited and may be appropriately selected within a wide range, but it is usually preferably 1 to 70% by weight in the pharmaceutical formulation.

The administration method of the above pharmaceutical preparation is not particularly limited, and is determined depending on various preparation forms, age, sex and other conditions of the patient, and the severity of the patient. For example, tablets, emulsions, solutions, suspensions, emulsions, granules and capsules are administered orally. Injections are administered intravenously alone or mixed with conventional replacement fluids such as glucose and amino acids, and further intramuscularly, intradermally, subcutaneously, or intraperitoneally, if necessary. Suppositories are administered rectally.

The dosage of the above pharmaceutical preparation is appropriately selected depending on the usage, age, sex and other conditions of the patient, degree of disease, etc., but the amount of the compound of the present invention, which is an active ingredient, is usually about 0.5 to 1 kO body weight per day. The dosage is preferably about 20 mg, and the preparation contains 1
It can be administered in 1 to 4 divided doses per day.

! --Small Window--V Hereinafter, production examples of raw material compounds used in the production of the compounds of the present invention will be listed as reference examples, followed by production examples of the compounds of the present invention as examples, and further pharmacological tests conducted on the compounds of the present invention. Give an example.

Reference Example 1 Production of 4-acetoxy-5-chloro-2-pyridone 5-chloro-4-hydroxy-2-pyridone 5, OOg
and 3.66 ml of acetyl chloride were stirred in 250 ml of pyridine at air temperature for 3 hours. The reaction solution was concentrated, and the residue was washed successively with ethyl acetate and water to obtain the target compound 3.
．． 39 g (yield 52%) was obtained.

'HNMR (DMSOds) δ: 11, 91 (1H, bs, N-H) 7.81 (1
H,s, Cs-H of pyridine ring)6,35 (1)
f, S, pyridine ring 03-H)2.32 (3H
, S , CH3) Reference Examples 2 to 4 The following compounds were produced in the same manner as in Reference Example 1.

Reference example 2 4-benzoyloxy-5-chloro-2-pyridone Melting point 196-197°C Reference example 3 5-chloro-4-octadecanoyloxy-2-pyridone'HNMR (DMSOds) δ: 11,87 ( 1H, bs, N-H) 7.80 (I
H,s, Cs H of pyridine ring)6.32 (1H
, S, 03 H>2.60 (2H,
t, J=7)-12, CdanLCO)1.24 (30
H, bs, CH2Xl 5) 0.85 (3H,t,
J=7Hz, CH3) Reference Example 4 4-(2-naphthoyloxy)-2-pyridone'HNMR (DMSO-d6) δ: 11.72
(IH, bs, N-H) 8.81-7.64 (7H, m, H of naphthalene ring
) 7.51 (1H, d, J=8Hz, Cs H of the pyridine ring) 6.33-6.25 (2H, m, 03 of the pyridine ring
．． 5H) Reference Example 5 Production of 2-benzoyloxy-4-hydroxypyridine In 50 g of methylene chloride, 2.65 g of benzoyl chloride was added to 4.0 g of 2,4-di(trimethylsilyloxy)pyridine.
0 and 0.2 mg of stannic chloride were added, and the mixture was stirred at room temperature for about 1 hour. After distilling off the solvent, the residue was subjected to silica gel column chromatography and ethyl acetate-benzene (2:
3) to obtain 1.00 g of the target compound (yield 29.6
%) was obtained.

Melting point 124-127°C Reference example 6 4-hydroxy-2-(2-methylbenzoyloxy)
Production of pyridine The target compound was obtained in the same manner as in Reference Example 5.

Melting point 116-119°C Reference Example 7 Production of 5-chloro-4-hydroxy-1-(2-tetrahydrofuranyl)-2-pyridone 5-chloro-4-hydroxy-2(1H>-pyridone 1.OOa, hexane 10 mf2 of methyldisilazane was added and refluxed for 6 hours. Excess hexamethyldisilazane was then distilled off, and the oily residue was dissolved in 50 m12 of dichloromethane. 1.OOQ of 2-acetoxytetrahydrofuran and 0 stannic chloride were added thereto.
．． 11tli2 was added and stirred overnight at room temperature. After neutralization with triethylamine, the solvent was distilled off, methanol was added to the residue, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off again,
The residue was eluted with 2% methanol-chloroform using a silica gel column to obtain 1.07 g of the target compound (yield 73
．． 5%).

Melting point 170-173℃ 'HNMR (DMSO-66) δ: 11.6 (1H, bs, 0H) 7.59 (IH,S, Cs H>5.76 (1
H, S, 03 H) 4, 39-3.73 (2H,
m, f) The following compounds were produced in the same manner as in Reference Example 7.

Reference Example 8 1-Benzyloxymethyl-5-chloro-4-hydroxy-2-pyridone Melting point 165-167°C'HNMR (DMSOds) δ: 11.65 (1H, bs, 0H) 7.92 (IH, s, Cs H) 7.31 (5
H,S, phenyl-H)5.77 (1H,S,C
3H> 5.27 (2H,s, -NC DanLO->4,55
(2H,s, -〇C Ruba D) Reference Example 9 2-benzoyloxymethyl-5-chloro-4-hydroxypyridine Melting point Softened at 184°C'HNMR (DMSOd6) δ: 8.27 (IH,S,Cs H) 6.91 (1
H, S, C3H> Reference Example 10 Production of 6-penzoyloxy-3-cyano-2-hydroxypyridine 3-cyano-2,6-cyhydroxypyridine 1.00C
0.51ml of triethylamine and 0.4ml of benzoyl chloride were added to 40ml of N,N-dimethylacetamide solution.
3 ml was added and stirred at air temperature for 15 minutes. Further, 0.51+ni2 of triethylamine and 0.4311112 of benzoyl chloride were added to the reaction solution, and the mixture was stirred at room temperature for 15 minutes. The reaction solution was filtered, the solution was concentrated under reduced pressure, and the residue was washed with chloroform and water to obtain the target compound (1.060%).
(yield: 60%).

'H-NMR (DMSO-66) δ: 12, 76 (1H, bs, OH or NH>8.33
(1H, d, J=8H2, Ct H of pyridine ring
) 6.95 (1H, d, J=8Hz, CsH in pyridine ring) Reference Examples 11 to 15 The following compounds were produced in the same manner as in Reference Example 10.

Reference Example 11 3-cyano-6-(2,4-dichlorobenzoyloxy)-2-hydroxypyridine'HNMR ((CD3)
2 Go) δ: 8.29 (IH, d, J=8Hz
, pyridine ring CaH) 7.61 (1H, dd, J=8Hz, J=2Hz
.

7,01 (1H, d, J=8H2, 'r:') Syn MU) Cs H) Reference Example 12 3-cyano-6-(2-furoyloxy)-2-hydroxypyridine'H-NMR (DMSO, d s ) δ: 8.32 (
IH, d, J = 8 Hz, Ct H of pyridine ring) 7.63 (1H, dd, J = 1 Hz, J = 4 Hz
.

6.95 (IH, d, J=8Hz, CsH of pyridine ring) Reference example 13 3-cyano-6-(3,4,5-trimethoxybenzoyloxy)-2-hydroxypyridine'HNMR (DMSOds) δ: 8.32 (1H, d, J = 8 Hz, Ca H of pyridine ring > 6.93 (1H, d, J = 8 Hz, Cs H of pyridine ring) Reference example 14 3-cyano-6-(2- thenoyloxy)-2-hydroxypyridine'H-NMR (DMSO-66) δ: 8.32 (1H, d, J = 8 Hz, CtH of pyridine ring) 6.96 (1H, d, J = 8 Hz, pyridine ring Cs H) Reference Example 15 3-chloro-6-(4-fluorobenzoyloxy)-
2-Hydroxypyridine 1H NMR (DMSO-ds) δ near, 96 (I
H, d, J = 8 Hz, Ca H of pyridine ring) 6.79 (1 H, d, J = 8 Hz, Cs H of pyridine ring) Example 1 3- (3-(1,2-dihydro-2-oxo -4-Pyridyloxycarbonyl)benzoyl-Preparation of 5-fluoro-1-(2-tetrahydrofuranyl)uracil A solution of 1.000 parts of 5-fluoro-1-(2-tetrahydrofuranyl) uracil in 30 mf2 of dry dioxane contains 1.00 parts of isophthaloyl chloride. 000 and triethylamine 0.70
1+1f2 were added and refluxed for 2 hours.

Furthermore, triethylamine 1. Add OOmG and after 2 hours of fast flow, 4-hydroxy-2(IH)-pyridone 0.609
was added and refluxed for 3 hours. After evaporating the solvent, 30 mQ of ethyl acetate and 30 mG of water were added to the residue, and after removing insoluble matter, the ethyl acetate layer was separated, dried over anhydrous sodium sulfate, and concentrated. The residue was eluted with chloroform to 2% methanol-chloroform using a silica gel column, and the fractions corresponding to the target product were collected and concentrated to give a powdery substance with 0.
40(](118%).

'HNMR (DMSO-ds) δ: 11.7
4 (IH, bs, NH, 7 with D20 addition, 51 (
1)-1,d, J=8)-12, Cs of pyridine ring
H) 6.34-6.26 (2H,m, 03 of the pyridine ring
．． 5H) 5.93 (1H,t,'J=4H2,Ca'
-H>4.41-4.20, 3.92-3.72 (1 each
8. m, Ca'H) 2.27 1.92
(4H,m,C2',3'-H) Example 2 3-(4-(1,2-dihydro-2-oxo-4-pyridyloxycarbonyl)-5-fluoro-1-(2-tetrahydrofura Production of uracil) The target compound was obtained in the same manner as in Example 1.

' H-NMR (DMSO d s ) δ:'l
1.73 (1H, bs, -NH-, disappeared upon addition of D20) 8,28 (4H, s, phenyl-H).

8, 14 (1H, d, J = 7Hz, Cs H) 7, 5
2 (1H, d, J=8Hz, Cs of pyridine ring
H) 6,33-6.25 (2H.m, 03 of pyridine ring
, s -H) 5,92 (1H, bt, J=4Hz, C1' -H
>4, 49-4.26 and 4.03-3.77 (1H each,
m, C4' H) 2, 30 1.92 (4H, m, C2'.3' -
H) Example 3 3-(3-(4-benzoyloxy-5-chloro-2
-pyridyloxycarbonyl)benzoyl)-2'-deoxy-3',5'-di-O-acetyl-5-fluorouridine Production of the target compound was obtained in the same manner as in Example 1.

Cs H) 7,39 (1H,s, 03H of pyridine ring)6
, 27 (1H.t, J-8Hz, Ca'-
H) 5, 29 5.17 (IH, m, C3'
H) 4,51-4.28 (3H,m,Ca',s
' -H) 2,70-2.08 (8H,m, C2'H and COCH3x2> Example 4 3- (3- (2-benzoyloxy-5-chloro-
Production of 4-pyridyloxycarbonyl)benzoyl]-5-fluoro-1-(2-tetrahydrofuranyl)uracil The target compound was obtained in the same manner as in Example 1.

Ce H) 7,41 (1H,s, 03H of pyridine ring)6
, 00-5. 90 (I H, m
, Ca'-H)4,42 3.87(2
H, m, Ct' H) 2, 55 1.89 (4H
, IIl. C2', C3'-H) Example 5 3-(3- (4-benzoyloxy-5-chloro-2
-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil In the same manner as in Example 1, the target compound was obtained.

Cs H) 7.38 (1H,s, 03H of pyridine ring)6
．． 02 5.90 (1H,m, C1'-H)4
．． 45 3.87 (2H, m, Ca' H)2.
55 1.89 (4H, m, C2', C3'-H) Example 6 3- (3-(2-acetoxy-5-chloro-4-pyridyloxycarbonyl)benzoyl)-5-fluoro-
Preparation of 1-(2-tetrahydrofuranyl)uracil 1-(2-tetrahydrofuranyl)-5-fluorouracil 1. 5.53 mg of triethylamine and 1.5 mg of isophthaloyl chloride in a solution of OOg in 50 mL of dry dioxane.
20 was added, and the mixture was subjected to distant flow for 1 hour.

Next, the reaction solution was filtered, the filtrate was concentrated, and the residue was dissolved in 50 mQ of acetonitrile, and 3.46 ml of triethylamine and 2-acetoxy-5-chloro-4-
1.40 g of hydroxypyridine was added and stirred for 2 hours under air temperature. After the reaction solution was filtered and concentrated, the residue was purified by silica gel column chromatography using chloroform as an eluent to obtain 530 mp (20%) of the target compound.

7.54 (1H, d, J-6Hz, CsH)
7.27 (1H,S, 03H of pyridine ring)5
．． 98-5.90 (IH, m, C+'-H)4
．． 29 4.04 (2H,m,C4'H)2.3
5 (3H,s, COCH3)2.43-1.89
(4H,m,C2',3'-H) Example 7 3-(3-(2-acetoxy-5-chloro-4-pyridyloxycarbonyl)benzoyl)-5'-deoxy-2',3'- Production of G-O-7 cetyl-5-fluorouridine The target compound was obtained in the same manner as in Example 6.

7.48 (IH, d, J-6Hz, CsH)
7.26(1)-1,S, pyridine ring CaH)5
．． 93 (1H, d, J=5Hz, C+'H
)5.31 (1H, t, J=6H2,C2'H)
5.03 (IH, T, J=6Hz, C3'
H) 4.38 4.12 (IH, m, Ca' H
)2.35 (3H,s, C0CH5 on pyridine ring)
2.10 and 2.01 (3H, S, COCH3 respectively) 1
．． 46 (3H, d, J-6H2, Cs' H
) Example 8 3-(3-(4-benzoyloxy-5-chloro-2
-pyridyloxycarbonylzoyl-5-fluoro-2', 3', 5'-
Production of tri-acetyluridine The target compound was obtained in the same manner as in Example 6.

7.39 (IH,S, 03H of pyridine ring)6
．． 12-6.05 (1H, m, C+'H>5.3
4-5.29 (2H,m,C2',3'
-H) 4.38 (3H, bs, Ca', s' H)
2.18, 2.11 and 2.03 (3H, S respectively.

C0CH5) Example 9 3-(3-(4-acetoxy-5-chloro-2-pyridyloxycarbonyl)benzoyl-5-fluoro-
Production of 1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Example 6.

' H-NMR (CDCQ3) δ: 8.65-8.19 (4H, m.

Cs H) 7.53 (1H, d, J=6Hz, Cs H
)7.18 (IH,s, 03H of pyridine ring)6
．． 02-5.90 (1H,m, C1'-H)
4.45-3.87 (2H,m, CA'-1
-1>2, 44-1.90 (7H,m, COCH
3 and C2', 3' H) Example 1d 5-Fluoro-3-(3-(2-(2-methylbenzoyloxy)-4-pyridyloxycarbonyl]benzoyl)-1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Production Example 6.

' HNMR (CDCQ3) δ: 8.67-7.21 (12H, m, phenyl H.

H on the pyridine ring and Cs H) 6.00-5.90 (IH,m, C1' H)4
．． 40 3.90 (2H,m, C4'-H)2.
69 (3H, s, CH3) 2.60 1.95 (4H, m, C2', C3'-
H) Example 11 3-(3-(2-benzoyloxy-4-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(2
-Tetrahydrofuranyl)uracil Production The target compound is obtained in the same manner as in Example 6.

' H-NMR (CDC93) δ: Pyridine ring Cs H) 7.79-7.40 (5H, m.

7.34-L 23 (2H,m, C3 of pyridine ring
,5H) 6.00-5.90 (1H,m,C+'H
)4.45-3.87 (2H,m, CA'-
H) 2.55 1.89 (4H, m, C2', C3'-
H) Example 12 3-(3-(1-benzyloxymethyl-5-chloro-1,2-dihydro-2-oxo-4-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-
Preparation of (tetrahydrofuranyl) uracil The target compound is obtained in the same manner as in Example 6.

O Cs H and pyridine ring 5.98 5.91 (1H, m, C+' H) 5.4
2 (2H,S, NCH20) 4.27-3.89
(2H,m,Ct'-H)2.57 1.90(
4H, m, C2', C3'-H) Example 13 3- (3-(5-chloro-1,2-dihydro-2-oxo-1-(2-tetrahydrofuranyl)-4-pyridyloxycarbonyl) benzoyl)-5-fluoro-1
-Production of (2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Example 6.

Cs H and Cs H of pyridine ring) 6.58 (1
H, S, C3H of pyridine ring) 6.18-5.91
(2H,m, C+ HX2 of furanyl group > 4,33-3.87 (4t-1,m, Ct HX2 of furanyl group > 2.67-1.78 (8H,m, 02 of furanyl group
, C3-HX2> Example 14 3-(3-(4-benzoyloxy-5-chloro-2
-pyridyloxycarbonyl)benzoyl)-21-deoxy-3',5'-di0-benzyl-5-fluorouridine Production The target compound is obtained in the same manner as in Example 6.

' H-NMR (CDCQ3) δ: and 03 H of the pyridine ring) 6.31 (IH, bt, J=7Hz, C1' H
)4.50 (2H,d, J=2Hz.

4.28 4.22 (2H, m, C3' H.

Ct' H) 3.91 3.52 (2H, m, Cs' - H>2
．． 66-2.04 (2H,m,C2'H) Example 15 3-(3-(4-benzoyloxy-5-chloro-2
-pyridyloxycarbonylzoyl)-2'-deoxy-3', 5'-diO-
Production of (4-chlorobenzyl)-5-fluorouridine The target compound is obtained in the same manner as in Example 6.

6.29 (1H, bt, J=7H2, C+'
H) 4.45 (2H,d, J=2Hz.

4.24 4.18 (2H, m, C3' H.

C4'H) 3.90-3.51 (2H,m, Cs'H
)2.67-2.03 (2H,m, C2'-H)
Example 16 Preparation of 5-fluoro-3-[3-(4-(2-naphthoyloxy)-2-pyridyloxycarbonyllofuranyl)uracil] The target compound is obtained in the same manner as in Example 6.

'H NMR (CDC93) δ: 8, 75-
7.20 (15H,m, naphthyl-H.

Phenyl-H, H of pyridine ring and Cs H) 5,97-5.90 (1H,m,C+'-H)
4,52 3.85 (2H,m,Ca'H)2
, 52 1.78 (4H, m, C2', C3'-H
> Example Core 3- Production Example of (3-(3-chloro-6-(4-fluorobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in 6.

Cs H) of pyridine ring 5,97-5.89 (IH,m, C+'-H)
4,34 3.84 (2H,m, Ca'-H
)2,47-1.86 (4H,m,C2'-H
.

C3' H) Example 18 3- (3- (6-penzoyloxy-3-cyano-
Preparation of 2-pyridyloxycarbonyl)benzoyl-5-fluoro-1-(2-tetrahydrofuranyl)uracil The desired compound was prepared in the same manner as in Example 6.

Jin ring Cs H) 5,96 5.87 (1H,m,C+ 'H>
4,30 3.80(2H,m,Ca'H)2,
50 1.85 (4H, m, C2'-H.

C3' H) Example 19 3-(3-(3-cyano-6-(3.4.5-trimethoxybenzoyloxy>-2-pyridyloxycarbonyl)benzoyl)-5-fluoro-1-(2- Preparation of (tetrahydrofuranyl) uracil The target compound is obtained in the same manner as in Example 6.

7.54 (IH, d, J=6Hz, C, ε-H)
7.42 (1H, d, J=8Hz, Ca H of pyridine ring) 5.97 5.90 (1H, m, C1' H) 4.3
4 3.81 (11H, m, C4' H and 2.50
1.87 (4H, m, C2'H.

C3' -H) Example 20 3- (3-(3-cyano-6-(2-furoyloxy)-2-pyridyloxycarbonylbenzoyl)-5-
Preparation of fluoro-1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Example 6.

Cs H, 6, 61 of pyridine ring (1H, dd, J-2Hz, J=4Hz
.

5,98 5.88 (1H,m, C1'-H
)4,27 3.84 (2H,m,C4'H
)2,36-1.86(4H,m,C2'H.

C3' H) Example 21 3- (4- (6-penzoyloxy-3-cyano-
2-pyridyloxycarbonyl)-3-furoyl2 5
-Production of fluoro-1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Example 6.

'H NMR (CDCQ3) δ: Ca H and Cs H of pyridine ring) 5,92-5.82 (1H,m, Ca'-H>
4,22 3.71 (2H,m,Ca'H)2
, 33 1.68 (4H,m,C2'H.

Ca' H) Example 22 3-(3-(6-penzoyloxy-3-cyano-2
-pyridyloxycarbonylzoyl)-5'-deoxy-2',3'-di-acetyl-5-fluorouridine Production of the target compound is obtained in the same manner as in Example 6.

Cs H) 5.96 (IH, dd, J=1Hz and J=5H2°C
+'H) 5, 32 (1tI, t, J=6H2,
C2'H)5.03(1H,T,J=6H2
, C3' H) 4.30 4.18 (IH, m,
Ca'H)2.09 (3H,S,C2'
0COC once or C3' 0COC DanL) 2.00 (3H,s, C2' -0COC once or C3' 0COC DanL) 1.46 (3H,d, J=6Hz, Cs'
H>Example 23 3- (3-(3-cyano-6-(2-thenoyloxy)-2-pyridyloxycarbonylbenzoyl)-5-
Preparation of fluoro-1-(2-tetrahydrofuranyl)uracil The target compound is obtained in the same manner as in Example 6.

C4 H of pyridine ring > 8,03 (1 H, dd, J=1 Hz, J=4H
z.

7, 53 (1 H, d, J = 6 Hz, Cs - H
)7,44 (1H,d, J=8Hz, Cs H of pyridine ring) 6,00 5.90 (1H,m, C1'-H
)4,28 3.87 (2H,m.C4'H
)2'. 50 1.89 (4H.m.C2'
H.

C3'H) Example 24 3- (3- (3-cyano-6-(2.4-dichlorobenzoyloxy)-2-pyridyloxycarbonyl)
Preparation of (benzoyl)-5-fluoro-1-(2-tetrahydrofuranyl)uracil The desired compound is obtained in the same manner as in Example 6.

Pyridine ring Ca H) 7, 57 7.33 (4H, m, Cs H.

Cs H of pyridine ring and 4,35 3.82 (2H,m,C4'H)2
, 50 1.80 (4H,m, C2'-H.

C3'-H) Example 25 3- (5- (6-penzoyloxy-3-cyano-
Production of 2-pyridyloxycarbonyl-nicotinoyl]-5-fluoro-1-(2-tetrahydrofuranyl)uracil In the same manner as in Example 6,
Obtain the target compound.

' H NMR (CDCQ3) δ: 5.94-5
．． 88 (1H,m, (,+'H>4.34
3.71 (2H, m, Ct'H>2.50
1.88 (4H,m,C2'H.

C3' H) Example 26 Preparation of 3-(3-(1,2-dihydro-2-oxo-6-pyridyloxycarbonyl)benzoyl) 5-fluoro-1-(2-tetrahydrofuranyl)uracil 5-fluoro- To a solution of 1.OOg of 1-(2-tetrahydrofuranyl)uracil in 50 mQ of dioxane were added 1.5 (]] of isophthaloyl chloride and 6.0 mQ of trinitriamine, and the mixture was refluxed for 1.5 hours. The precipitate was removed, and the furnace liquid was concentrated. 50-methylene chloride was added to the residue, and 2.
6-bis(trimethylsilyloxy)pyridine 1.50
0 methylene chloride solution was added thereto, and the mixture was left to stand at room temperature for 3 hours. After evaporating the solvent, the residue was eluted with 2% methanol-chloroform using a silica gel column to obtain 0.30 g (14%) of the target compound.

UU and pyridine ring Ca H) 7.52 (1H, d, J=6H2, Cs H)6
．． 77 and 6.68 (1H, d respectively, J=8H2.

03.5 H) of pyridine ring 5.99-5.92 (1H, m, Ct' H) 4.3
0 3.88 (2H, m, Ct'H>2.44
1.89 (4H,m,C2',3'-H) Example 27 3-(3-(5-chloro-4-hydroxy-2-pyridyloxycarbonyl)benzoyl)-2'-deoxy-3', Production of 5'-di-O-acetyl-5-fluorouridine The target compound was obtained in the same manner as in Example 26.

06 H) of the pyridine ring and Cs H) 6.76 (1H,S, 03 H of the pyridine ring) 6
．． 19 (IH, bt, J-7H2, C+'H)5
．． 23-5.16 (1H,m,C3'-H)4
．． 32 4.24 (3H, m, Ca' H.

Cs’　　H) 2.60-1.85 (8H, m, C2'-H.

COCH3X2> Example 28 3-(3-(3-cyano-6-penzoyloxy-2
-Pyridyloxycarbonylzoyl)-1-ethoxymethyl-5-fluorouracil Production The target compound was obtained in the same manner as in Example 6.

Melting point 162-164℃ 'H-NMR (CDCQ3) δ: C4-H of the ring) and Cs of the pyridine ring H) 5.15 (2H,s,N CH2) 3.62 (2
H, Q, J = 7H2, -CH2CH3) 1.22 (3
H, t, J = 7Hz, -CH3>Example 29 3- (3-(3-cyano-6-(4-chlorobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl-5- Production of fluorouracil The target compound was obtained in the same manner as in Example 6.

Melting point 156-158℃ and Cs H and Cs H of pyridine ring) 5,16 (2H,s, N-CH2>3.63 (
2H, q, J = 7Hz, -CH2CH3) 1.23 (
3H,t,J=7H2,-CH3) Example 30 3-(3-(3-cyano-6-(2,4-dichlorobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl- Production of 5-fluorouracil The target compound was obtained in the same manner as in Example 6.

, melting point 140-142℃ C4H of pyridine ring) and Cs H and Cs H of pyridine ring) 5,16 (2H,s, N-CH2) 3.63 (
2H, q, J = 7Hz, -CH2CH3) 1.22 (
3H, t, J-7H2, -CH3) Example 31 3- (3-(3-cyano-6-(2-chlorobenzoyloxy)-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl-5- Production of fluorouracil The target compound was obtained in the same manner as in Example 6.

Properties Powder-H) 7.34-7.25 (2H, m, 03.
5 H) 5.14 (2H,s, N CH2>3.61 (
2H, Q, J=7Hz, -CH2CH3) 1.20 (
3H,t,J=7H2,CH3) Example 32 3-(3-(5-cyano-6-benzyloxy-2
-Pyridyloxycarbonyl)benzoyl-1-ethoxymethyl-5-fluorouracil The desired compound was obtained in the same manner as in Example 6.

Properties Powder 8.00 (1H, d, J=8Hz, pyridine ring 6.88 (1H,d, J=8Hz, pyridine ring 03H) 5.15 (2H,s, N CH2>3.63 ( 2
H, Q, J=7Hz, -CH20H3) 1.22 (3
H, t, J-7H2, CH3) Example 33 3- (4-(3-cyano-6-penzoyloxy-2
-Pyridyloxycarbonyl)benzoyl-1-ethoxymethyl-5-fluorouracil The desired compound was obtained in the same manner as in Example 6.

Properties Powder C6H and pyridine ring Cs H) 5.14 (2H,S,N CH2) 3.61 (
2H, q, J = 7Hz, -CH2CH3) 1.22 (
3H,t,J=7H2,CH3) Example 34 3- (4-(3-cyano-6-furoyloxy-2-
pyridyloxycarbonyl)-3-furoyl)-1-(
Production of 2-tetrahydrofuranyl)-5-fluorouracil The target compound was obtained in the same manner as in Example 6.

Properties Powder 'H-NMR (CDCQ3) δ: 8.41 and 8.38 (1H, d each, J = 2H2.

8.20 (1H, d, J-8Hz, Ca H of pyridine ring) 7.49 7.20 (3H, m, Cs H and Cs H of pyridine ring and 6.64 (1H, dd, J=4Hz, 2Hz.

5.92-5.83 (1H, m, C+'-H)
4.28 3.57 (2H, m, Ca'H>2.
38-1.67 (4H, m, C2', 3' -H) Example 35 3-(4-(4-acetoxy-5-chloro-2-pyridyloxycarbonyl)-1-(2-tetrahydrofuranyl )-5-Fluorouracil Production The target compound was obtained in the same manner as in Example 6.

Properties Powder'H-NMR (CDCQ3) δ: 8.39-8.38 (2H, m, C67 of pyridine ring
, 38 (1H, d, J=6Hz, Cs H)7.
02 (1H,S, 03H of pyridine ring)5.92
5.81 (1H, m, C+'H) 4.24
-3.80 (2H,m,Ct'-H)2,3
8 1.68 (4H,m, COCH3 and 02',
3' H) Example 36 3-(4-(3-cyano-6-thenoyloxy-2-pyridyloxycarbonylfuroyl)-1-(2-tetrahydrofuranyl)-5-
Production of fluorouracil The target compound was obtained in the same manner as in Example 6.

Properties Powder 1H NMR (CDCQ3) δ: 8, 41 and 8
．． 37 (1H, d each, J=2Hz.

8, 19 (IH, d, J=8Hz, C.-H of pyridine ring) 8, 03 (1 H, dd, J=4Hz, 1
Hz, Cs H of thiophene ring) 7,76 (1H, dd, J=5Hz, 1Hz,
C of thiophene ring: a H> 7, 40 (1H, d., J = 8 Hz, Cs H of pyridine ring) 7, 37 (1H, d., J = 6 Hz, Cs H) 7,
21 (IH, d, J=4Hz, 1Hz, CaH of thiophene ring) 5,94-5.83 (1H,m, C1'-H)4
,26 3.75(2H,m,C4'H)2,4
4 1.72 (4H, m.c2',3' -H) Example 37 3- (3- (5-cyano-6-hydroxy-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl-5- Production of fluorouracil 3- (3-(6-benzyloxy-5-cyano-2-
Pyridyloxycarbonyl-1-ethoxymethyl-5-fluorouracil 780m
g was dissolved in 30 mf2 of acetone and 80 mG of isopropyl alcohol. 100 mg of 10% palladium-carbon was added to this, and a catalytic reduction reaction was carried out at room temperature for 2 hours. The catalyst was removed and the solution was concentrated under reduced pressure to obtain the target compound 5201+10 (80%).

8, 14 (IH, d, J = 8 Hz, 0 of the pyridine ring
4H) 6,89 (1H.d, J=8Hz, 03H of pyridine ring) 5,09 (2H,S, N CH2)3,53
(2H, q.J=7Hz, -CH2 CH3) 1, 0
5 (3H, t, J-7Hz, CH3 > Pharmacological test example ■ Sarco-? (
3arcoma)-180 was diluted with physiological saline and an amount of 2×10 7 per mouse was subcutaneously implanted into the back of syngeneic mice and used for experiments. A drug suspended in 5% gum arabic was orally administered once a day for 7 days starting 2 hours after tumor implantation.

On the 10th day after tumor transplantation, a solid tumor under the skin of the back was excised, and the tumor weight was measured.The tumor weight (T) of the drug-administered group and the tumor type of the control group that was not administered the drug! Find the ratio (T/C) with (C),
From the dose-response curve of the drug dose and the ratio (T/C), T/
(FF1 for 50% tumor suppression with J<0.5 (ED50
value) was calculated.

The results are shown in Table 1 below. Table 1 also shows the results of using an anticancer drug containing 5-fluoro-1-(2-tetrahydrofuranyl)uracil and uracil in a 1:4 (weight ratio) combination as a control drug.

Table 1 Test compound EDso (mg/kg) Compound of Example 1 10 Compound of Example 3 7 Compound of Example 4 25 Compound of Example 5 18 Compound of Example 7 12 Compound of Example 8 22 Implementation Compound of Example 13 28 Compound of Example 14 5 Compound of Example 20 18 Compound of Example 28 5 Control drug 30 Examples of formulations using the compounds of the present invention are listed below.

Formulation Example 1 Compound of Example 1 0.025mg Starch 132mg Magnesium Stearate 18mc+Milk M
50mc + total approximately 200mg in 1 tablet by conventional method,
Tablets of the above composition were manufactured.

Formulation Example 2 Compound of Example 2 0.25mg Starch 130mg Magnesium Stearate 20m(] Lactose 50mg Total
Tablets containing about 200 mg of the above composition were prepared in a conventional manner.

Formulation Example 3 Compound of Example 3 12.5 mg polyethylene glycol (molecule 1:4000) 0.3 (J sodium chloride 0.9 g polyoxyethylene sorbitan monooleate 0.4 g sodium metabisulfite 0.1 (It methyl -Paraben 0.18g Propyl-paraben
0.02g distilled water for injection
100m (2) Dissolve the above parabens, sodium metabisulfite and sodium chloride in distilled water at 80"C with stirring. Cool the resulting solution to 40°C and add the compound of the present invention, polyethylene glycol and polyoxy Ethylene sorbitan monooleate was sequentially dissolved, and then the solution was adjusted to the final volume by adding distilled water for injection,
The solution is sterilized by sterile filtration using an appropriate filter paper, and then dispensed into ampoules to prepare an injection.

(that's all)

Claims (1)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R^1 is a substituent such as a hydroxyl group, a halogen atom, an amino group, a carboxyl group, a cyano group, a nitro group, an oxo group, a carbamoyl group, or a lower alkyl group. group, lower alkylcarbamoyl group, phenylcarbamoyl group, lower alkenyl group, lower alkoxycarbonyl group that may have 1 to 3 groups selected from halogen atoms, lower alkoxy groups, and lower alkyl groups as substituents on the phenyl ring. ,
1 to 4 groups selected from the group consisting of a tetrahydrofuranyl group, a phthalidyl group, a lower alkoxy lower alkyl group, a lower alkoxy lower alkyl group having a phenyl group, a lower alkoxycarbonyl lower alkylcarbamoyl group, a phenyl lower alkyloxy group, and an acyloxy group , and A represents an arylene group. R^2 can be converted to 5-fluorouracil in vivo5
- A fluorouracil derivative residue, in which the bond between the group and the adjacent carbonyl group is an ester bond or an amide bond. ] A 5-fluorouracil derivative represented by: