NO300066B1 - N-oksykarbonylsubstituerte 5'-deoksy-5-fluorcytidiner - Google Patents

N-oksykarbonylsubstituerte 5'-deoksy-5-fluorcytidiner Download PDF

Info

Publication number: NO300066B1
Authority: NO; Norway
Prior art keywords: deoxy; cytidine; fluoro; fluorocytidine; acetyl
Prior art date: 1992-12-18

Application number

NO934671A

Other languages

English (en)

Norwegian (no)

Other versions

NO934671D0 (no

NO934671L (no

Inventor

Motohiro Arasaki

Hideo Ishitsuka

Isami Kuruma

Masanori Miwa

Chikako Murasaki

Nobuo Shimma

Isao Umeda

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-12-18

Filing date

1993-12-17

Publication date

1997-04-01

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8210304&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO300066(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1993-12-17 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1993-12-17 Publication of NO934671D0 publication Critical patent/NO934671D0/no

1994-06-20 Publication of NO934671L publication Critical patent/NO934671L/no

1997-04-01 Publication of NO300066B1 publication Critical patent/NO300066B1/no

Links

-1 N-oxycarbonyl-substituted 5'-deoxy-5-fluorocytidines Chemical class 0.000 title claims abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 47
206010028980 Neoplasm Diseases 0.000 claims abstract description 16
239000012453 solvate Substances 0.000 claims abstract description 10
150000004677 hydrates Chemical class 0.000 claims abstract description 8
230000004962 physiological condition Effects 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 6
UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 6
230000000259 anti-tumor effect Effects 0.000 claims description 6
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 6
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
OJLIMLARCDSSCZ-PNHWDRBUSA-N propyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 OJLIMLARCDSSCZ-PNHWDRBUSA-N 0.000 claims description 4
PPVCPOIDSSQXMR-UORFTKCHSA-N 3-methylbutyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCCC(C)C)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 PPVCPOIDSSQXMR-UORFTKCHSA-N 0.000 claims description 3
GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical group C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 3
GIEDPOVIGXKYGR-AXTGTSHSSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-[5-fluoro-2-oxo-4-(propoxycarbonylamino)pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate Chemical compound C1=C(F)C(NC(=O)OCCC)=NC(=O)N1[C@H]1[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](C)O1 GIEDPOVIGXKYGR-AXTGTSHSSA-N 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000005975 2-phenylethyloxy group Chemical group 0.000 claims description 2
CZXJHPLUTVRXCN-QBBVKUELSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-[5-fluoro-2-oxo-4-(2-phenylethoxycarbonylamino)pyrimidin-1-yl]-2-methyloxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1N1C(=O)N=C(NC(=O)OCCC=2C=CC=CC=2)C(F)=C1 CZXJHPLUTVRXCN-QBBVKUELSA-N 0.000 claims description 2
KXINDFSMIQLNEG-GWBBYGMBSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-[5-fluoro-4-(3-methylbutoxycarbonylamino)-2-oxopyrimidin-1-yl]-2-methyloxolan-3-yl] acetate Chemical compound C1=C(F)C(NC(=O)OCCC(C)C)=NC(=O)N1[C@H]1[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](C)O1 KXINDFSMIQLNEG-GWBBYGMBSA-N 0.000 claims description 2
VMLNDJWBPQWPTH-UGKPPGOTSA-N butyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical group C1=C(F)C(NC(=O)OCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 VMLNDJWBPQWPTH-UGKPPGOTSA-N 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 1
YSNABXSEHNLERR-ZIYNGMLESA-N 5'-Deoxy-5-fluorocytidine Chemical class O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)N=C(N)C(F)=C1 YSNABXSEHNLERR-ZIYNGMLESA-N 0.000 abstract description 11
229920006395 saturated elastomer Polymers 0.000 abstract description 5
125000006239 protecting group Chemical group 0.000 abstract description 3
239000004215 Carbon black (E152) Substances 0.000 abstract 2
125000004432 carbon atom Chemical group C* 0.000 abstract 2
229930195733 hydrocarbon Natural products 0.000 abstract 2
150000003254 radicals Chemical class 0.000 abstract 2
YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 abstract 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
229910052799 carbon Inorganic materials 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
239000000243 solution Substances 0.000 description 14
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000000034 method Methods 0.000 description 9
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 8
ZARBPJCRKSPIRN-UHFFFAOYSA-N 6-fluoro-1h-pyrimidine-2,4-dione Chemical compound FC1=CC(=O)NC(=O)N1 ZARBPJCRKSPIRN-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
101710186969 Acylamidase Proteins 0.000 description 6
241000282693 Cercopithecidae Species 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
102000005922 amidase Human genes 0.000 description 6
ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 6
229960002949 fluorouracil Drugs 0.000 description 6
231100000419 toxicity Toxicity 0.000 description 6
230000001988 toxicity Effects 0.000 description 6
241000282412 Homo Species 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
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IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000003480 eluent Substances 0.000 description 4
XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 4
229960004413 flucytosine Drugs 0.000 description 4
239000010410 layer Substances 0.000 description 4
210000004185 liver Anatomy 0.000 description 4
239000002207 metabolite Substances 0.000 description 4
239000002243 precursor Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000010898 silica gel chromatography Methods 0.000 description 4
ZJZVFCZVDKFJAS-UGKPPGOTSA-N 2,2-dimethylpropyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)N=C(NC(=O)OCC(C)(C)C)C(F)=C1 ZJZVFCZVDKFJAS-UGKPPGOTSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
201000009030 Carcinoma Diseases 0.000 description 3
102100026846 Cytidine deaminase Human genes 0.000 description 3
108010031325 Cytidine deaminase Proteins 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
239000012267 brine Substances 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
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LDJHWIPDHFPDJK-UORFTKCHSA-N 3,3-dimethylbutyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)N=C(NC(=O)OCCC(C)(C)C)C(F)=C1 LDJHWIPDHFPDJK-UORFTKCHSA-N 0.000 description 2
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238000005481 NMR spectroscopy Methods 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
NWJBWNIUGNXJGO-RPULLILYSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1N1C(=O)N=C(N)C(F)=C1 NWJBWNIUGNXJGO-RPULLILYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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MKDKBFCGAQDVFJ-UORFTKCHSA-N 2,3-dimethylbutan-2-yl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OC(C)(C)C(C)C)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 MKDKBFCGAQDVFJ-UORFTKCHSA-N 0.000 description 1
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KRORKAPSTCUGTA-PNHWDRBUSA-N 2-methoxyethyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCCOC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 KRORKAPSTCUGTA-PNHWDRBUSA-N 0.000 description 1
BDPHEOFPHIHPJA-UGKPPGOTSA-N 2-methylpropyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCC(C)C)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 BDPHEOFPHIHPJA-UGKPPGOTSA-N 0.000 description 1
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IWVJLGPDBXCTDA-UHFFFAOYSA-N cyclohexyl carbonochloridate Chemical compound ClC(=O)OC1CCCCC1 IWVJLGPDBXCTDA-UHFFFAOYSA-N 0.000 description 1
PKNVPTBVNXPGRI-LHNIVKCTSA-N cyclohexyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)N=C(NC(=O)OC2CCCCC2)C(F)=C1 PKNVPTBVNXPGRI-LHNIVKCTSA-N 0.000 description 1
MRCCJZAFDGHCBP-QGMIFYJMSA-N cyclohexylmethyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)N=C(NC(=O)OCC2CCCCC2)C(F)=C1 MRCCJZAFDGHCBP-QGMIFYJMSA-N 0.000 description 1
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ILUBJJYTJLYREH-BPGGGUHBSA-N heptyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCCCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 ILUBJJYTJLYREH-BPGGGUHBSA-N 0.000 description 1
CYXWQMGIIQZTTI-XIDUGBJDSA-N hexyl n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate Chemical compound C1=C(F)C(NC(=O)OCCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 CYXWQMGIIQZTTI-XIDUGBJDSA-N 0.000 description 1
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125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
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150000003839 salts Chemical class 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
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URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
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125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicinal Preparation (AREA)

NO934671A 1992-12-18 1993-12-17 N-oksykarbonylsubstituerte 5'-deoksy-5-fluorcytidiner NO300066B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP92121538		1992-12-18

Publications (3)

Publication Number	Publication Date
NO934671D0 NO934671D0 (no)	1993-12-17
NO934671L NO934671L (no)	1994-06-20
NO300066B1 true NO300066B1 (no)	1997-04-01

Family

ID=8210304

Family Applications (1)

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NO934671A NO300066B1 (no)	1992-12-18	1993-12-17	N-oksykarbonylsubstituerte 5'-deoksy-5-fluorcytidiner

Country Status (41)

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US (1)	US5472949A (pl)
EP (1)	EP0602454B1 (pl)
JP (1)	JP2501297B2 (pl)
KR (1)	KR100347218B1 (pl)
CN (1)	CN1035617C (pl)
AT (1)	ATE137244T1 (pl)
AU (1)	AU671491B2 (pl)
BG (1)	BG61485B1 (pl)
BR (1)	BR9305089A (pl)
CA (1)	CA2103324C (pl)
CZ (1)	CZ284788B6 (pl)
DE (1)	DE69302360T2 (pl)
DK (1)	DK0602454T3 (pl)
EE (1)	EE03086B1 (pl)
ES (1)	ES2086856T3 (pl)
FI (1)	FI112365B (pl)
GE (1)	GEP20074251B (pl)
GR (1)	GR3020286T3 (pl)
HK (1)	HK1005875A1 (pl)
HR (1)	HRP931430B1 (pl)
HU (2)	HU218291B (pl)
IL (1)	IL108000A0 (pl)
IS (1)	IS4108A (pl)
LT (1)	LT3115B (pl)
LV (1)	LV10625B (pl)
MY (1)	MY109282A (pl)
NO (1)	NO300066B1 (pl)
NZ (1)	NZ250414A (pl)
PH (1)	PH30168A (pl)
PL (1)	PL174100B1 (pl)
RO (1)	RO112619B1 (pl)
RU (2)	RU2458932C2 (pl)
SA (1)	SA93140409B1 (pl)
SI (1)	SI9300648B (pl)
SK (1)	SK281403B6 (pl)
SV (1)	SV1993000080A (pl)
TW (1)	TW372239B (pl)
UA (1)	UA39158C2 (pl)
UY (1)	UY23697A1 (pl)
YU (1)	YU49411B (pl)
ZA (1)	ZA939293B (pl)

Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5476932A (en) *	1994-08-26	1995-12-19	Hoffmann-La Roche Inc.	Process for producing N4-acyl-5'-deoxy-5-fluorocytidine derivatives
NZ330360A (en) *	1997-06-02	1999-03-29	Hoffmann La Roche	5'-deoxy-cytidine derivatives, their manufacture and use as antitumoral agents
EP0882734B1 (en) *	1997-06-02	2009-08-26	F. Hoffmann-La Roche Ag	5'-Deoxy-cytidine derivatives
US6005098A (en) *	1998-02-06	1999-12-21	Hoffmann-La Roche Inc.	5'deoxycytidine derivatives
CA2342981A1 (en) *	1998-09-25	2000-04-06	Warner-Lambert Company	Chemotherapy of cancer with acetyldinaline in combination with gemcitabine, capecitabine or cisplatin
US20080113025A1 (en) *	1998-11-02	2008-05-15	Elan Pharma International Limited	Compositions comprising nanoparticulate naproxen and controlled release hydrocodone
US20070122481A1 (en) *	1998-11-02	2007-05-31	Elan Corporation Plc	Modified Release Compositions Comprising a Fluorocytidine Derivative for the Treatment of Cancer
BR0108728A (pt) *	2000-02-28	2003-12-30	Aventis Pharma Sa	Combinação farmacêutica terapêutica, e, método para tratar um c ncer.
WO2001076581A1 (en) *	2000-04-11	2001-10-18	Sayuri Yamada	Curcumin compositions
KR100730768B1 (ko) *	2000-08-09	2007-06-21	코오롱생명과학 주식회사	5'-데옥시-ｎ-알킬옥시카르보닐-5-플루오로사이토신-5'-카르복실산 및 그 유도체와 이들의 제조방법
KR100631754B1 (ko) *	2000-08-09	2006-10-09	주식회사 코오롱	Ｎ-알킬옥시카르보닐-5-플루오로사이토신 유도체 및 그의제조방법
GB0113374D0 (en) *	2001-06-04	2001-07-25	Jerram Clare	Washing line umbrella
AU2003235761A1 (en) *	2002-01-14	2003-07-24	Novartis Ag	Combinations comprising epothilones and anti-metabolites
EP2316468A1 (en)	2002-02-22	2011-05-04	Shire LLC	Delivery system and methods for protecting and administering dextroamphetamine
JP2006508974A (ja) *	2002-11-15	2006-03-16	ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー	癌を治療するためのｍｅｋ阻害剤およびカペシタビン（ｃａｐｅｃｉｔａｂｉｎｅ）を含む併用化学療法
EP1631278A4 (en) *	2003-05-20	2006-09-20	Aronex Pharmaceuticals Inc	COMBINATION SCHEMOTHERAPY WITH CAPECITABIN AND A LIPOSOMAL PLATINUM COMPLEX
DE602004016376D1 (de) *	2003-11-13	2008-10-16	Pharma Mar Sau	Kombination von et-743 mit 5-fluorouracil pro-drugs zur behandlung von krebs
CA2550299C (en) *	2003-12-22	2010-03-30	Christopher R. Roberts	Process for fluorocytidine derivatives
ES2364495T3 (es)	2005-02-03	2011-09-05	The General Hospital Corporation	Método para tratar cáncer resistente a gefitinib.
AU2006228581A1 (en) *	2005-04-01	2006-10-05	F. Hoffmann-La Roche Ag	Method for administration of capecitabine
CA2615374A1 (en)	2005-07-18	2007-01-25	Ernest Kun Kun	Treatment of cancer
US20080292729A1 (en)	2005-07-21	2008-11-27	Nuvo Research Inc.	Stabilized Chlorite Solutions in Combination with Fluoropyrimidines for Cancer Treatment
JP2009514870A (ja)	2005-11-04	2009-04-09	ワイス	ｍＴＯＲインヒビター、ハーセプチン、および／またはＨＫＩ−２７２の抗悪性腫瘍性組み合わせ
EP2455382B1 (en)	2005-12-13	2016-10-26	Incyte Holdings Corporation	Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
US20100160442A1 (en) *	2006-07-18	2010-06-24	Ossovskaya Valeria S	Formulations for cancer treatment
US20080085310A1 (en) *	2006-10-06	2008-04-10	Maria Oksana Bachynsky	Capecitabine rapidly disintegrating tablets
CN100425617C (zh) *	2006-10-31	2008-10-15	浙江海正药业股份有限公司	一种含氟嘧啶类化合物烷氧羰酰化的方法
ITMI20070435A1 (it)	2007-03-05	2008-09-06	Innovate Biotechnology Srl	2',3'-di-o-acil-5-fluoronucleosidi
BRPI0810067A2 (pt) *	2007-04-20	2014-10-21	Reddys Lab Ltd Dr	Processo para a preparação de capecitabina
WO2008145403A1 (en) *	2007-06-01	2008-12-04	Synthon B.V.	Processes related to making capecitabine
EP3070090B1 (en)	2007-06-13	2018-12-12	Incyte Holdings Corporation	Use of salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h- pyrazol-1-yl)-3- cyclopentylpropanenitrile
US7842675B2 (en) *	2007-09-15	2010-11-30	Protia, Llc	Deuterium-enriched capecitabine
WO2009042064A2 (en)	2007-09-21	2009-04-02	Nektar Therapeutics Al, Corporation	Oligomer-nucleoside phosphate conjugates
US8022216B2 (en)	2007-10-17	2011-09-20	Wyeth Llc	Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof
KR101013312B1 (ko) *	2007-11-19	2011-02-09	한미홀딩스 주식회사	카페시타빈의 제조방법 및 이에 사용되는 β-아노머가강화된 트리알킬카보네이트 화합물의 제조방법
AR064165A1 (es)	2007-12-06	2009-03-18	Richmond Sa Com Ind Y Financie	Un procedimiento para la preparacion de capecitabina e intermediarios utilizables en dicho procedimiento
WO2009088989A1 (en) *	2008-01-03	2009-07-16	Plus Chemicals, S.A.	Process for the preparation of capecitabine
US20090311335A1 (en) *	2008-06-12	2009-12-17	Scott Jenkins	Combination of a triptan and an nsaid
ES2692769T3 (es)	2008-06-17	2018-12-05	Wyeth Llc	Combinaciones antineoplásicas que contienen HKI-272 y vinorelbina
CN105147713A (zh)	2008-08-04	2015-12-16	惠氏有限责任公司	4-苯胺基-3-氰基喹啉和卡培他滨的抗肿瘤组合
WO2010065586A2 (en) *	2008-12-02	2010-06-10	Dr. Reddy's Laboratories Ltd.	Preparation of capecitabine
WO2010063080A1 (en) *	2008-12-05	2010-06-10	Commonwealth Scientific And Industrial Research Organisation	Amphiphile prodrugs
SG174382A1 (en)	2009-04-06	2011-11-28	Wyeth Llc	Treatment regimen utilizing neratinib for breast cancer
FR2945211A1 (fr)	2009-05-06	2010-11-12	Sanofi Aventis	Combinaison antitumorale comprenant la cabazitaxel et la capecitabine
SG176111A1 (en)	2009-05-22	2011-12-29	Incyte Corp	3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors
JP2012533618A (ja) *	2009-07-23	2012-12-27	サイノファームタイワンリミテッド	フルオロシチジン誘導体の製造プロセス
WO2011067588A1 (en)	2009-12-04	2011-06-09	Generics [Uk] Limited	Cyclic sulphinyl esters of cytidine
WO2011104540A1 (en) *	2010-02-24	2011-09-01	Generics [Uk] Limited	One step process for the preparation of capecitabine
PT3354652T (pt)	2010-03-10	2020-07-20	Incyte Holdings Corp	Derivados de piperidin-4-ilazetidina como inibidores de jak1
ME02464B (me)	2010-03-12	2017-02-20	Genzyme Corp	Kombinovana terapija za lečenje raka dojke
RS54824B1 (sr)	2010-05-21	2016-10-31	Incyte Holdings Corp	Topikalna formulacija za inhibiciju jak-a
CN102260309B (zh) *	2010-05-24	2014-10-22	重庆福安药业(集团)股份有限公司	一种高纯度卡培他滨的制备方法
CA2818542A1 (en)	2010-11-19	2012-05-24	Incyte Corporation	Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
CN102558262A (zh) *	2010-12-23	2012-07-11	天津泰普药品科技发展有限公司	一种高纯度卡培他滨的制备方法
MY165963A (en)	2011-06-20	2018-05-18	Incyte Holdings Corp	Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
CN102266303A (zh) *	2011-07-07	2011-12-07	程雪翔	一种卡培他滨药用组合物及其制备方法
UA111854C2 (uk)	2011-09-07	2016-06-24	Інсайт Холдінгс Корпорейшн	Способи і проміжні сполуки для отримання інгібіторів jak
CN102516338B (zh) *	2011-12-09	2014-04-02	海南锦瑞制药股份有限公司	一种卡培他滨化合物、其药物组合物及其制备方法
TWI560195B (en) *	2012-01-13	2016-12-01	Pharmaessentia Corp	Novel synthesis of 5-deoxy-5'-fluorocytidine compounds
CN113384546A (zh)	2012-11-15	2021-09-14	因赛特公司	鲁索利替尼的缓释剂型
WO2014138168A1 (en)	2013-03-06	2014-09-12	Incyte Corporation	Processes and intermediates for making a jak inhibitor
SG10201801069QA (en)	2013-08-07	2018-03-28	Incyte Corp	Sustained release dosage forms for a jak1 inhibitor
CN105555313A (zh) *	2013-08-20	2016-05-04	因赛特公司	在c-反应蛋白水平较高的实体肿瘤患者中的存活益处
EP2883959A1 (en)	2013-12-13	2015-06-17	Plasmia Biotech, S.L.	Enzymatic production of cytosinic nucleoside analogues
CN103897006A (zh) *	2013-12-18	2014-07-02	吉林修正药业新药开发有限公司	一种卡培他滨异构体的制备方法
WO2015191563A1 (en)	2014-06-09	2015-12-17	Lipomedix Pharmaceuticals Ltd.	Combination chemotherapy comprising a liposomal prodrug of mitomycin c
CN104530164A (zh) *	2014-12-31	2015-04-22	辰欣药业股份有限公司	一种卡培他滨的合成工艺
KR20160117060A (ko)	2015-03-31	2016-10-10	이승주	유아용 탁자
CN105646625B (zh) *	2015-12-29	2019-06-11	江苏吴中医药集团有限公司	一种卡培他滨的制备方法
US11584733B2 (en)	2017-01-09	2023-02-21	Shuttle Pharmaceuticals, Inc.	Selective histone deacetylase inhibitors for the treatment of human disease
WO2018129533A1 (en)	2017-01-09	2018-07-12	Shuttle Pharmaceuticals, Llc	Selective histone deacetylase inhibitors for the treatment of human disease
TR201702500A2 (tr) *	2017-02-20	2017-07-21	Anadolu Ueniversitesi	Serani̇b-2?ni̇n akci̇ğer kanseri̇ ve meme kanseri̇ni̇n tedavi̇si̇nde kullanimi
US10435429B2 (en)	2017-10-03	2019-10-08	Nucorion Pharmaceuticals, Inc.	5-fluorouridine monophosphate cyclic triester compounds
AR113922A1 (es)	2017-12-08	2020-07-01	Incyte Corp	Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas
US11407723B2 (en)	2018-01-09	2022-08-09	Shuttle Pharmaceuticals, Inc.	Selective histone deacetylase inhibitors for the treatment of human disease
EP3752511A4 (en)	2018-01-10	2021-12-29	Nucorion Pharmaceuticals, Inc.	Phosphor(n)amidatacetal and phosph(on)atalcetal compounds
US11427550B2 (en)	2018-01-19	2022-08-30	Nucorion Pharmaceuticals, Inc.	5-fluorouracil compounds
WO2019143860A1 (en) *	2018-01-19	2019-07-25	Nucorion Pharmaceuticals, Inc.	5-fluorouracil compounds
EA202091830A1 (ru)	2018-01-30	2020-12-29	Инсайт Корпорейшн	Способы и промежуточные соединения для получения ингибитора jak
MD3773593T2 (ro)	2018-03-30	2024-10-31	Incyte Corp	Tratament hidradenitei supurative utilizând inhibitori ai JAK
AU2020207026A1 (en)	2019-01-11	2021-07-29	Lipomedix Pharmaceuticals Ltd.	Liposome composition comprising liposomal prodrug of mitomycin C and method of manufacture
CN114206896B (zh)	2019-07-17	2024-12-17	纽科利制药公司	环状脱氧核糖核苷酸化合物
US12552820B2 (en)	2020-04-21	2026-02-17	Ligand Pharmaceuticals Incorporated	Benzyloxy phosph(on)ate compounds
CN115605492B (zh)	2020-04-21	2025-09-16	配体制药股份有限公司	核苷酸前药化合物
US11833155B2 (en)	2020-06-03	2023-12-05	Incyte Corporation	Combination therapy for treatment of myeloproliferative neoplasms
AU2021331658A1 (en)	2020-08-31	2023-03-30	Emory University	5'-substituted nucleoside monophosphates, prodrugs thereof, and uses related thereto
WO2023177894A1 (en)	2022-03-18	2023-09-21	Ideaya Biosciences, Inc.	Combination therapy comprising a mat2a inhibitor and an antimetabolite agent
EP4382093B1 (en)	2022-12-05	2025-08-27	a Fine House S.A.	Oral suspensions comprising capecitabine

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1135258A (en) *	1979-06-15	1982-11-09	Richard D'souza	Process for the preparation of 5'deoxy-5-fluorouridine
ATE92499T1 (de) *	1984-12-04	1993-08-15	Lilly Co Eli	Tumorbehandlung bei saeugetieren.
CA1327358C (en) *	1987-11-17	1994-03-01	Morio Fujiu	Fluoro cytidine derivatives

1993
- 1993-11-12 AU AU50690/93A patent/AU671491B2/en not_active Expired
- 1993-11-15 TW TW082109533A patent/TW372239B/zh not_active IP Right Cessation
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- 1993-11-23 HR HR92121538.0A patent/HRP931430B1/xx not_active IP Right Cessation
- 1993-12-01 ES ES93119349T patent/ES2086856T3/es not_active Expired - Lifetime
- 1993-12-01 AT AT93119349T patent/ATE137244T1/de active
- 1993-12-01 DK DK93119349.4T patent/DK0602454T3/da active
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- 1993-12-07 SA SA93140409A patent/SA93140409B1/ar unknown
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- 1993-12-10 HU HU9303525A patent/HU218291B/hu active Protection Beyond IP Right Term
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- 1993-12-13 CZ CZ932731A patent/CZ284788B6/cs not_active IP Right Cessation
- 1993-12-13 IL IL10800093A patent/IL108000A0/xx not_active IP Right Cessation
- 1993-12-14 FI FI935616A patent/FI112365B/fi not_active IP Right Cessation
- 1993-12-14 US US08/167,392 patent/US5472949A/en not_active Expired - Lifetime
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- 1993-12-16 KR KR1019930027962A patent/KR100347218B1/ko not_active Expired - Lifetime
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- 1993-12-16 RU RU93056196/04A patent/RU2458932C2/ru active Protection Beyond IP Right Term
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1994
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1995
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1996
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1998
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Publication number	Publication date
IS4108A (is)	1994-06-19
DE69302360D1 (de)	1996-05-30
NO934671D0 (no)	1993-12-17
HU218291B (en)	2000-07-28
JP2501297B2 (ja)	1996-05-29
SA93140409B1 (ar)	2004-07-24
SK281403B6 (sk)	2001-03-12
FI112365B (fi)	2003-11-28
BG61485B1 (bg)	1997-09-30
RU2493162C1 (ru)	2013-09-20
ZA939293B (en)	1994-06-18
PL301541A1 (en)	1994-06-27
LV10625A (lv)	1995-04-20
YU77993A (sh)	1996-10-18
SI9300648A (en)	1994-09-30
HK1005875A1 (en)	1999-01-29
JPH06211891A (ja)	1994-08-02
SI9300648B (sl)	2000-06-30
MY109282A (en)	1996-12-31
KR940014428A (ko)	1994-07-18
SV1993000080A (es)	1996-01-26
CZ284788B6 (cs)	1999-03-17
EE03086B1 (et)	1998-04-15
BR9305089A (pt)	1994-07-05
HRP931430A2 (en)	1998-06-30
YU49411B (sh)	2006-01-16
EP0602454B1 (en)	1996-04-24
ATE137244T1 (de)	1996-05-15
NZ250414A (en)	1995-12-21
RO112619B1 (ro)	1997-11-28
US5472949A (en)	1995-12-05
FI935616L (fi)	1994-06-19
DE69302360T2 (de)	1996-10-31
FI935616A0 (fi)	1993-12-14
PH30168A (en)	1997-01-21
RU2135511C1 (ru)	1999-08-27
GEP20074251B (en)	2007-12-10
ES2086856T3 (es)	1996-07-01
LV10625B (en)	1996-04-20
AU5069093A (en)	1994-06-30
EP0602454A1 (en)	1994-06-22
HU211965A9 (en)	1996-01-29
PL174100B1 (pl)	1998-06-30
CA2103324C (en)	1997-12-23
HU9303525D0 (en)	1994-04-28
UA39158C2 (uk)	2001-06-15
UY23697A1 (es)	1994-06-08
GR3020286T3 (en)	1996-09-30
DK0602454T3 (da)	1996-07-29
CN1035617C (zh)	1997-08-13
CN1094056A (zh)	1994-10-26
RU2458932C2 (ru)	2012-08-20
NO934671L (no)	1994-06-20
LTIP1627A (en)	1994-07-15
CZ273193A3 (en)	1994-07-13
IL108000A0 (en)	1994-04-12
SK144493A3 (en)	1994-10-05
BG98304A (bg)	1994-01-03
AU671491B2 (en)	1996-08-29
KR100347218B1 (ko)	2003-01-24
CA2103324A1 (en)	1994-06-19
LT3115B (en)	1994-12-27
HRP931430B1 (en)	1999-08-31
HUT65757A (en)	1994-07-28
TW372239B (en)	1999-10-21

Legal Events

Date	Code	Title	Description
2014-01-13	MK1K	Patent expired

Publication	Publication Date	Title
NO300066B1 (no)	1997-04-01	N-oksykarbonylsubstituerte 5'-deoksy-5-fluorcytidiner
HK1005875B (en)	1999-01-29	N-oxycarbonyl substituted 5'-deoxy-5-fluorocytidines
JP4737934B2 (ja)	2011-08-03	ヌクレオシドホスホリラーゼ及びヌクレオシダーゼのインヒビター
RU2503673C2 (ru)	2014-01-10	Новое производное 5-фторурацила
BRPI1100050A2 (pt)	2016-05-03	"sistema de controle de inclinação de lâmina,gerador de turbina eólica, e método de controle de inclinação de lâmina".
CA2182707C (en)	2000-05-30	3'-substituted nucleoside derivative
JPWO1996018636A1 (ja)	1997-03-25	３′−置換ヌクレオシド誘導体
CN118359588A (zh)	2024-07-19	作为ctps1抑制剂的化合物
US8058261B2 (en)	2011-11-15	3′-ethynylcytidine derivative
AU2004222163A1 (en)	2004-09-30	Nucleotide lipid ester derivatives
Cook	1977	Fluorinated pyrimidine nucleosides. 1. Synthesis of a nitrogen analog of the antitumor agent 2, 2'-anhydro-1-. beta.-D-arabinofuranosyl-5-fluorocytosine hydrochloride
KR100730768B1 (ko)	2007-06-21	5'-데옥시-ｎ-알킬옥시카르보닐-5-플루오로사이토신-5'-카르복실산 및 그 유도체와 이들의 제조방법
US20100056466A1 (en)	2010-03-04	2'-Cyanopyrimidine Nucleoside Compound
US5283331A (en)	1994-02-01	2-halogeno-oxetanocin A and phosphoric ester thereof
KR100631754B1 (ko)	2006-10-09	Ｎ-알킬옥시카르보닐-5-플루오로사이토신 유도체 및 그의제조방법
JPH09249689A (ja)	1997-09-22	３′−カルバモイルアルキルヌクレオシド誘導体
JPH10330394A (ja)	1998-12-15	ヒドロキシアミノ置換ヌクレオシド誘導体