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Uracil derivatives and production thereof

Assignee: Takeda Pharmaceutical Co Ltd
•
Filing: 1979-06-13
•
Granted: 1982-05-11
•
Expires: 1999-06-13
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Abstract

Abstract New derivatives of the formula: <IMAGE> (wherein X is O or NH; R1 is -OH which may optionally be etherified or esterified, etherified mercapto or -NH2 which may optionally be substituted; R2 and R3, respectively, mean H, lower alkyl or <IMAGE> and Y is an esterified or amidated carboxyl group, or CN). These derivatives are produced, by fluorination of corresponding 1,2,3,4-tetrahydro-2,4-dioxopyrimidine compounds and can be converted into 5-fluorouracil derivatives under hydrolytic conditions. The new derivatives are able to prolong the lives of animals having carcinomas or have antiviral activity.

Inventors

  • 👤 Osamu Miyashita
  • 👤 Koichi Matsumura
  • 👤 Hiroshi Shimadzu
  • 👤 Naoto Hashimoto

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-29 15:11
CPC Classifications
C; C07; C07D; C07D239/00; C07D239/02; C07D239/24; C07D239/28; C07D239/46; C07D239/52; C07D239/54; C07D239/545; C07D239/557; A; A61; A61P; A61P35/00; C07C; C07C273/00; C07C273/18; C07C273/1854; C07D239/20; C07D239/22; C07D239/553; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804

Claims Analysis

Total Claims: 64
Claim 1
Independent Claim 180 words
A compound having the formula: ##STR36## wherein X is O; Y is a group of the formula --COOY' wherein Y' is cycloalkyl or alkyl of 1 to 18 carbon atoms, allyl, phenalkyl of 7 to 8 carbon atoms or phenyl, alkylphenyl, alkoxyphenyl, halophenyl, haloalkylphenyl or aminophenyl of 6 to 8 carbon atoms, said alkyl group of 1 to 18 carbon atoms being unsubstituted or substituted by halogen or ethoxy or CN; R 1 is a member of the group consisting of (1) hydroxy, (2) etherified hydroxyl selected from the group consisting of alkoxy and cycloalkoxy groups of 1 to 18 carbon atoms, hydroxyethoxy, chloroethoxy, methoxyethoxy, ethoxyethoxy, trifluoroethoxy, allyloxy, cyclohexenyloxy, propargyloxy, 3-butynyloxy, 2-butynyloxy, benzyloxy, p-chlorobenzyloxy, p-fluorobenzyloxy, phenethyloxy and phenoxy, alkylphenoxy, haloalkylphenoxy of 6 to 8 carbon atoms, (3) etherified mercapto corresponding to the etherified hydroxyl as defined above, (4) β-naphthylmercapto and (5) esterified hydroxyl selected from the group consisting of alkanoyloxy or haloalkanoyloxy having 1 to 4 carbon atoms, benzoyloxy, p-methoxybenzoyloxy, p-chlorobenzoyloxy, p-methoxybenzoyloxy, phenylacetyloxy, p-toluenesulfonyloxy and methanesulfonyloxy; and R 2 and R 3 , respectively, are H, lower alkyl or ##STR37##
Claim 2
Dependent Claim 180 words
A compound having the formula: ##STR36## wherein X is O; Y is a group of the formula --COOY' wherein Y' is cycloalkyl or alkyl of 1 to 18 carbon atoms, allyl, phenalkyl of 7 to 8 carbon atoms or phenyl, alkylphenyl, alkoxyphenyl, halophenyl, haloalkylphenyl or aminophenyl of 6 to 8 carbon atoms, said alkyl group of 1 to 18 carbon atoms being unsubstituted or substituted by halogen or ethoxy or CN; R 1 is a member of the group consisting of (1) hydroxy, (2) etherified hydroxyl selected from the group consisting of alkoxy and cycloalkoxy groups of 1 to 18 carbon atoms, hydroxyethoxy, chloroethoxy, methoxyethoxy, ethoxyethoxy, trifluoroethoxy, allyloxy, cyclohexenyloxy, propargyloxy, 3-butynyloxy, 2-butynyloxy, benzyloxy, p-chlorobenzyloxy, p-fluorobenzyloxy, phenethyloxy and phenoxy, alkylphenoxy, haloalkylphenoxy of 6 to 8 carbon atoms, (3) etherified mercapto corresponding to the etherified hydroxyl as defined above, (4) β-naphthylmercapto and (5) esterified hydroxyl selected from the group consisting of alkanoyloxy or haloalkanoyloxy having 1 to 4 carbon atoms, benzoyloxy, p-methoxybenzoyloxy, p-chlorobenzoyloxy, p-methoxybenzoyloxy, phenylacetyloxy, p-toluenesulfonyloxy and methanesulfonyloxy; and R 2 and R 3 , respectively, are H, lower alkyl or ##STR37##
Claim 3
Dependent Claim 42 words
A compound according to claim 1, wherein Y is a group of the formula --COOY' as defined in claim 1; R 1 is the etherified hydroxyl as defined in claim 1; R 2 is H or ##STR38## and R 3 is H.
Claim 4
Dependent Claim 34 words
A compound according to claim 2, wherein Y is a group of the formula --COOY' having 2 to 9 carbon atoms; and R 1 is an etherified hydroxyl having 1 to 12 carbon atoms.
Claim 5
Dependent Claim 50 words
A compound according to claim 2, wherein Y is a group of the formula --COOY' having 2 to 5 carbon atoms wherein Y' is alkyl having 1 to 4 carbon atoms; R 1 is alkoxy having 1 to 8 carbon atoms; and both R 2 and R 3 are H.
Claim 6
Dependent Claim 6 words
Methyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 7
Dependent Claim 6 words
Methyl 5-fluoro-6-methoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 8
Dependent Claim 6 words
Ethyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 9
Dependent Claim 6 words
Isopropyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 10
Dependent Claim 6 words
n-Butyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 11
Dependent Claim 6 words
sec-Butyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 12
Dependent Claim 6 words
2-Chloroethyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 13
Dependent Claim 6 words
Methyl 5-fluoro-6-hydroxy-3-methyl-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 14
Dependent Claim 6 words
Methyl 5-fluoro-1-(2-tetrahydrofuryl)-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 15
Dependent Claim 6 words
Methyl 6-acetoxy-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 16
Dependent Claim 6 words
n-Octyl 5-fluoro-6-acetoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 17
Dependent Claim 6 words
Stearyl 5-fluoro-6-ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 18
Dependent Claim 5 words
5-Fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carbonitrile, according to claim 1.
Claim 19
Dependent Claim 1 words
3,5-difluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carbonitrile.
Claim 20
Dependent Claim 1 words
3,5-difluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carbonitrile.
Claim 21
Dependent Claim 5 words
5-Fluoro-6-acetoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carbonitrile, according to claim 1.
Claim 22
Dependent Claim 6 words
Methyl 5-fluoro-6-cyclohexyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 23
Dependent Claim 6 words
Methyl 5-fluoro-6-n-octyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 24
Dependent Claim 6 words
n-Butyl 5-fluoro-6-n-butoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 25
Dependent Claim 6 words
Ethyl 5-fluoro-6-ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 26
Dependent Claim 6 words
Ethyl 5-fluoro-6-allyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 27
Dependent Claim 6 words
Ethyl 5-fluoro-6-propargyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 28
Dependent Claim 6 words
Ethyl 5-fluoro-6-tert-butyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 29
Dependent Claim 6 words
Ethyl 5-fluoro-6-n-octadecyloxy-1,2,3,4,5,6-heaxhydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 30
Dependent Claim 6 words
Ethyl 5-fluoro-6-neopentyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 31
Dependent Claim 6 words
Isopropyl 5-fluoro-6-isopropyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 32
Dependent Claim 6 words
sec-Butyl 5-fluoro-6-sec-butyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate according to claim 1.
Claim 33
Dependent Claim 6 words
n-Octyl 5-fluoro-6-n-octyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 34
Dependent Claim 6 words
Ethyl 5-fluoro-6-ethylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 35
Dependent Claim 6 words
Ethyl 5-fluoro-6-tert-butylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 36
Dependent Claim 6 words
Ethyl 5-fluoro-6-cyclohexylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 37
Dependent Claim 6 words
Ethyl 5-fluoro-6-n-decylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 38
Dependent Claim 6 words
Ethyl 5-fluoro-6-n-octadecylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 39
Dependent Claim 6 words
Methyl 5-fluoro-6-phenylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 40
Dependent Claim 6 words
n-Octyl 5-fluoro-6-ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 41
Dependent Claim 6 words
n-Octyl 5-fluoro-6-hydroxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 42
Dependent Claim 6 words
Methyl 6-benzoyloxy-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 43
Dependent Claim 6 words
Methyl 6-benzyloxy-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 44
Dependent Claim 6 words
Ethyl 6-benzylthio-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 45
Dependent Claim 6 words
Ethyl 6-allylthio-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 46
Dependent Claim 6 words
Ethyl 5-fluoro-6-β-naphthylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 47
Dependent Claim 6 words
Ethyl 5-fluoro-6-(2,2,2-trifluoro)ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 48
Dependent Claim 6 words
Methyl 5-fluoro-6-ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 49
Dependent Claim 6 words
Ethyl 5-fluoro-6-methoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 50
Dependent Claim 6 words
Ethyl 5-fluoro-6-isopropoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 51
Dependent Claim 6 words
Methyl 5-fluoro-6-butoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 52
Dependent Claim 6 words
Ethyl 5-fluoro-6-butoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 53
Dependent Claim 6 words
Ethyl 5-fluoro-6-isobutoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 54
Dependent Claim 6 words
Ethyl 5-fluoro-6-sec-butoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 55
Dependent Claim 6 words
Ethyl 5-fluoro-6-benzyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 56
Dependent Claim 6 words
Ethyl 5-fluoro-6-phenoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 57
Dependent Claim 6 words
Methyl 5-fluoro-6-butylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 58
Dependent Claim 6 words
Ethyl 5-fluoro-6-phenylthio-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 59
Dependent Claim 5 words
5-Fluoro-6-ethoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carbonitrile, according to claim 1.
Claim 60
Dependent Claim 6 words
Ethyl 5-fluoro-6-octyloxy-2,4-dioxo-1,2,3,4,5,6-hexahydropyrimidine-5-carboxylate, according to claim 1.
Claim 61
Dependent Claim 6 words
Ethyl 5-fluoro-t-6-octyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-r-5-carboxylate, according to claim 1.
Claim 62
Dependent Claim 6 words
Ethyl 5-fluoro-c-6-octyloxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-r-5-carboxylate, according to claim 1.
Claim 63
Dependent Claim 6 words
Ethyl 6-acetoxy-5-fluoro-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.
Claim 64
Dependent Claim 6 words
Methyl 6-acetoxy-5-fluoro-1-(2-tetrahydrofuryl)-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate, according to claim 1.

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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1985-05-10 1985-11-09 1986-05-11 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1989-05-10 1989-11-09 1990-05-11 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1993-05-10 1993-11-09 1994-05-11 $7700.00 Window Closed / Lapsed

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