NO325617B1 - Anvendelse av 7-(2-oksa-5,8-diazabicyklo[4.3.0]non-8-yl)-kinolonkarboksylsyre og naftyridonkarboksylsyrederivater for fremstilling av legemidler for behandling av helicobacter pylori infeksjoner og dermed forbundede gastroduodenale sykdommer, diastereomerrene og enantiomerrene forbindelser, anvendelse derav samt legemiddel inneholdende disse. - Google Patents

Anvendelse av 7-(2-oksa-5,8-diazabicyklo[4.3.0]non-8-yl)-kinolonkarboksylsyre og naftyridonkarboksylsyrederivater for fremstilling av legemidler for behandling av helicobacter pylori infeksjoner og dermed forbundede gastroduodenale sykdommer, diastereomerrene og enantiomerrene forbindelser, anvendelse derav samt legemiddel inneholdende disse. Download PDF

Info

Publication number: NO325617B1
Authority: NO; Norway
Prior art keywords: stands; oxa; diazabicyclo; oxo; methyl
Prior art date: 1996-12-16

Application number

NO19992903A

Other languages

English (en)

Norwegian (no)

Other versions

NO992903L (no

NO992903D0 (no

Inventor

Klaus Schaller

Michael Matzke

Stephan Bartel

Thomas Himmler

Thomas Schenke

Uwe Petersen

Thomas Jaetsch

Harald Labischinski

Hans-Otto Werling

Bernd Baasner

Original Assignee

Bayer Ag

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.)

1996-12-16

Filing date

1999-06-14

Publication date

2008-06-30

1999-06-14 Application filed by Bayer Ag filed Critical Bayer Ag

1999-06-14 Publication of NO992903L publication Critical patent/NO992903L/no

1999-06-14 Publication of NO992903D0 publication Critical patent/NO992903D0/no

2008-06-30 Publication of NO325617B1 publication Critical patent/NO325617B1/no

Links

-1 naphthyridone carboxylic acid derivatives Chemical class 0.000 title claims abstract description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 16
206010019375 Helicobacter infections Diseases 0.000 title claims abstract description 13
238000011282 treatment Methods 0.000 title claims description 27
239000003814 drug Substances 0.000 title claims description 16
201000010099 disease Diseases 0.000 title claims description 14
238000004519 manufacturing process Methods 0.000 title claims description 12
229940079593 drug Drugs 0.000 title claims description 5
239000003795 chemical substances by application Substances 0.000 title description 4
HBOHUPRFLRTLDQ-UHFFFAOYSA-N 7-(3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b][1,4]oxazin-6-yl)-2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1C2NCCOC2CN1C1=CC=C2C=C(C(=O)O)C(=O)NC2=C1 HBOHUPRFLRTLDQ-UHFFFAOYSA-N 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 18
150000004677 hydrates Chemical class 0.000 claims abstract description 14
150000001875 compounds Chemical class 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 14
FYMHQCNFKNMJAV-HOTGVXAUSA-N finafloxacin Chemical compound C12=C(C#N)C(N3C[C@@H]4OCCN[C@H]4C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 FYMHQCNFKNMJAV-HOTGVXAUSA-N 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
CGANRUYCDLGZCY-UHFFFAOYSA-N 7-(3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b][1,4]oxazin-6-yl)-1-cyclopropyl-8-(difluoromethoxy)-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(OC(F)F)C(N3CC4OCCNC4C3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 CGANRUYCDLGZCY-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 abstract description 15
239000002253 acid Substances 0.000 abstract description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
238000002844 melting Methods 0.000 description 23
230000008018 melting Effects 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 20
238000000354 decomposition reaction Methods 0.000 description 19
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
238000000034 method Methods 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
238000001816 cooling Methods 0.000 description 15
239000000725 suspension Substances 0.000 description 15
238000010992 reflux Methods 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 13
230000008029 eradication Effects 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
239000002244 precipitate Substances 0.000 description 11
MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
241000590017 Helicobacter felis Species 0.000 description 9
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
229910052801 chlorine Inorganic materials 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
238000003756 stirring Methods 0.000 description 9
210000002784 stomach Anatomy 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
PXTYIFUOEXJZEN-UHFFFAOYSA-N 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=C(C#N)C(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 PXTYIFUOEXJZEN-UHFFFAOYSA-N 0.000 description 7
241000589989 Helicobacter Species 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
241000894006 Bacteria Species 0.000 description 6
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 6
229960003022 amoxicillin Drugs 0.000 description 6
239000003242 anti bacterial agent Substances 0.000 description 6
229940088710 antibiotic agent Drugs 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000007789 gas Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 6
BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 6
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 6
150000002978 peroxides Chemical class 0.000 description 6
UMIZTIYZNFUATK-WDSKDSINSA-N (4as,7as)-2,3,4,4a,5,6,7,7a-octahydropyrrolo[3,4-b][1,4]oxazine Chemical compound O1CCN[C@H]2CNC[C@@H]21 UMIZTIYZNFUATK-WDSKDSINSA-N 0.000 description 5
XZOPHCHUGFSLOX-UHFFFAOYSA-N 2,4-dichloro-1-fluoro-3,5-dimethylbenzene Chemical compound CC1=CC(F)=C(Cl)C(C)=C1Cl XZOPHCHUGFSLOX-UHFFFAOYSA-N 0.000 description 5
OQVWKNMVCSCNOK-UHFFFAOYSA-N 3-cyano-2,4,5-trifluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(F)C(C#N)=C1F OQVWKNMVCSCNOK-UHFFFAOYSA-N 0.000 description 5
ZMHXHDXZVQIKEG-UHFFFAOYSA-N 3-cyano-2,4,5-trifluorobenzoyl fluoride Chemical compound FC(=O)C1=CC(F)=C(F)C(C#N)=C1F ZMHXHDXZVQIKEG-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
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208000025865 Ulcer Diseases 0.000 description 5
238000009835 boiling Methods 0.000 description 5
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238000010172 mouse model Methods 0.000 description 5
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SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 5
239000012071 phase Substances 0.000 description 5
235000011121 sodium hydroxide Nutrition 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
DMKUCTUBRVDHLN-BNTLRKBRSA-N (4ar,7ar)-2,3,4,4a,5,6,7,7a-octahydropyrrolo[3,4-b][1,4]oxazine;dihydrobromide Chemical compound Br.Br.O1CCN[C@@H]2CNC[C@H]21 DMKUCTUBRVDHLN-BNTLRKBRSA-N 0.000 description 4
RCWIWNUVHNAUQC-UHFFFAOYSA-N 1-fluoro-3,5-dimethylbenzene Chemical group CC1=CC(C)=CC(F)=C1 RCWIWNUVHNAUQC-UHFFFAOYSA-N 0.000 description 4
GVEOELVSEIKARK-UHFFFAOYSA-N 2,4-dichloro-3-(dichloromethyl)-1-fluoro-5-(trichloromethyl)benzene Chemical compound FC1=CC(C(Cl)(Cl)Cl)=C(Cl)C(C(Cl)Cl)=C1Cl GVEOELVSEIKARK-UHFFFAOYSA-N 0.000 description 4
BEQRAINSLWDPAZ-UHFFFAOYSA-N 2,4-dichloro-3-cyano-5-fluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=C(Cl)C(C#N)=C1Cl BEQRAINSLWDPAZ-UHFFFAOYSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
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AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 4
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229920001817 Agar Polymers 0.000 description 3
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IKCORZMITOGHBM-UHFFFAOYSA-N ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(C#N)C(F)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 IKCORZMITOGHBM-UHFFFAOYSA-N 0.000 description 3
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201000006549 dyspepsia Diseases 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000011841 epidemiological investigation Methods 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
MVUMJYQUKKUOHO-AATRIKPKSA-N ethyl (e)-3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)\C=C\N(C)C MVUMJYQUKKUOHO-AATRIKPKSA-N 0.000 description 1
DGJOXROOIUSLHR-UHFFFAOYSA-N ethyl 2-(3-cyano-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)prop-2-enoate Chemical compound C=1C(F)=C(F)C(C#N)=C(F)C=1C(=O)C(C(=O)OCC)=CNC1CC1 DGJOXROOIUSLHR-UHFFFAOYSA-N 0.000 description 1
HXOBDDHTICDHSU-UHFFFAOYSA-N ethyl 2-(3-cyano-2,4,5-trifluorobenzoyl)-3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)C(=CN(C)C)C(=O)C1=CC(F)=C(F)C(C#N)=C1F HXOBDDHTICDHSU-UHFFFAOYSA-N 0.000 description 1
QHCOZOGCDMVPMB-UHFFFAOYSA-N ethyl 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=C(C#N)C(Cl)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 QHCOZOGCDMVPMB-UHFFFAOYSA-N 0.000 description 1
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
229960001596 famotidine Drugs 0.000 description 1
XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
208000010749 gastric carcinoma Diseases 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
230000002070 germicidal effect Effects 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000002357 guanidines Chemical class 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229940037467 helicobacter pylori Drugs 0.000 description 1
239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
229940077716 histamine h2 receptor antagonists for peptic ulcer and gord Drugs 0.000 description 1
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 1
230000028993 immune response Effects 0.000 description 1
239000000411 inducer Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000009630 liquid culture Methods 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
229960002422 lomefloxacin Drugs 0.000 description 1
230000007774 longterm Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
210000003563 lymphoid tissue Anatomy 0.000 description 1
239000003120 macrolide antibiotic agent Substances 0.000 description 1
229940041033 macrolides Drugs 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
238000003328 mesylation reaction Methods 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
229960004872 nizatidine Drugs 0.000 description 1
SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
229960001699 ofloxacin Drugs 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229960005019 pantoprazole Drugs 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000001991 pathophysiological effect Effects 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000004540 pour-on Substances 0.000 description 1
238000012545 processing Methods 0.000 description 1
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
229960000620 ranitidine Drugs 0.000 description 1
VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
239000012488 sample solution Substances 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000005049 silicon tetrachloride Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
201000000498 stomach carcinoma Diseases 0.000 description 1
239000000126 substance Substances 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940040944 tetracyclines Drugs 0.000 description 1
229960005053 tinidazole Drugs 0.000 description 1
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
WVPSKSLAZQPAKQ-CDMJZVDBSA-N trovafloxacin Chemical compound C([C@H]1[C@@H]([C@H]1C1)N)N1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F WVPSKSLAZQPAKQ-CDMJZVDBSA-N 0.000 description 1
229960000497 trovafloxacin Drugs 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines having two or more nitrogen atoms in the same ring, e.g. oxadiazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO19992903A 1996-12-16 1999-06-14 Anvendelse av 7-(2-oksa-5,8-diazabicyklo[4.3.0]non-8-yl)-kinolonkarboksylsyre og naftyridonkarboksylsyrederivater for fremstilling av legemidler for behandling av helicobacter pylori infeksjoner og dermed forbundede gastroduodenale sykdommer, diastereomerrene og enantiomerrene forbindelser, anvendelse derav samt legemiddel inneholdende disse. NO325617B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19652239A DE19652239A1 (de)	1996-12-16	1996-12-16	Verwendung von 7-(2-Oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-chinolon- und -naphthyridoncarbonsäure-Derivaten zur Therapie von Helicobacter-pylori-Infektionen und den damit assoziierten gastroduodenalen Erkrankungen
PCT/EP1997/006781 WO1998026779A1 (de)	1996-12-16	1997-12-04	Verwendung von 7-(2-oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-chinoloncarbonsäure- und -naphthyridoncarbonsäure-derivaten zur therapie von helicobacter-pylori-infektionen und den damit assoziierten gastroduodenalen erkrankungen

Publications (3)

Publication Number	Publication Date
NO992903L NO992903L (no)	1999-06-14
NO992903D0 NO992903D0 (no)	1999-06-14
NO325617B1 true NO325617B1 (no)	2008-06-30

Family

ID=7814837

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19992903A NO325617B1 (no)	1996-12-16	1999-06-14	Anvendelse av 7-(2-oksa-5,8-diazabicyklo[4.3.0]non-8-yl)-kinolonkarboksylsyre og naftyridonkarboksylsyrederivater for fremstilling av legemidler for behandling av helicobacter pylori infeksjoner og dermed forbundede gastroduodenale sykdommer, diastereomerrene og enantiomerrene forbindelser, anvendelse derav samt legemiddel inneholdende disse.

Country Status (27)

Country	Link
US (2)	US6133260A (da)
EP (1)	EP0946176B1 (da)
JP (3)	JP3463939B2 (da)
KR (1)	KR100536153B1 (da)
CN (1)	CN100335054C (da)
AT (1)	ATE214929T1 (da)
AU (1)	AU717751B2 (da)
BG (1)	BG64615B1 (da)
BR (1)	BR9714032A (da)
CA (1)	CA2274894C (da)
CZ (2)	CZ297363B6 (da)
DE (2)	DE19652239A1 (da)
DK (1)	DK0946176T3 (da)
EA (1)	EA002477B1 (da)
EE (1)	EE04090B1 (da)
ES (1)	ES2175519T3 (da)
HU (1)	HU226523B1 (da)
IL (1)	IL130311A (da)
NO (1)	NO325617B1 (da)
NZ (2)	NZ336228A (da)
PL (1)	PL191193B1 (da)
PT (1)	PT946176E (da)
RS (1)	RS49684B (da)
SK (2)	SK283224B6 (da)
TR (1)	TR199901754T2 (da)
UA (1)	UA57055C2 (da)
WO (1)	WO1998026779A1 (da)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19633805A1 (de) *	1996-02-23	1997-08-28	Bayer Ag	Gegenenenfalls substituierte 8-Cyan-l-cyclopropyl-7-(2,8-diazabicyclo-[4.3.0]-nonan-8-yl)-6-fluor-1,4-dihydro-4-oxo-3-chinolincarbonsäuren und ihre Derivate
ATE245140T1 (de) *	1998-11-18	2003-08-15	Asahi Glass Co Ltd	Derivate der aminoacryl-säure und ein verfahren zur herstellung derselben
DE19917617A1 (de) *	1999-04-19	2000-10-26	Bayer Ag	-(-)Enantiomeres des 2-[2-(1-Chlor-cyclopropyl)-3-(2-chlorphenyl) 2-hydroxy-propyl]-2,4-dihydro-[1,2,4]-triazol-3-thions
IL147043A0 (en) *	1999-07-01	2002-08-14	Wakunaga Pharma Co Ltd	Quinolinecarboxylic acid derivative or salts thereof
ATE285821T1 (de) *	1999-10-08	2005-01-15	Affinium Pharm Inc	Fab i inhibitoren
CA2444597A1 (en) *	2001-04-06	2002-10-06	Affinium Pharmaceuticals, Inc.	Fab i inhibitors
EP1575951B1 (en)	2002-12-06	2014-06-25	Debiopharm International SA	Heterocyclic compounds, methods of making them and their use in therapy
DE602004016831D1 (de)	2003-03-17	2008-11-13	Affinium Pharm Inc	Pharmazeutische zusammensetzungen inhibitoren von fab i und weitere antibiotika enthaltend
EP1669354B1 (en)	2003-09-29	2013-03-20	Daiichi Sankyo Company, Limited	8-cyanoquinolonecarboxylic acid derivative
CN1244582C (zh) *	2004-04-21	2006-03-08	中国医学科学院医药生物技术研究所	喹诺酮羧酸类化合物及其制备方法和医药用途
US7759362B2 (en)	2004-04-21	2010-07-20	Institut Of Medicinal Biotechnology Chinese Academy Of Medical Sciences	Quinolonecarboxylic acid compounds, preparation methods and pharmaceutical uses thereof
EP2848614A3 (en)	2004-06-04	2015-07-29	Debiopharm International SA	Acrylamide derivatives as antibiotic agents
EP1973902A2 (en) *	2005-12-05	2008-10-01	Affinium Pharmaceuticals, Inc.	3-heterocyclylacrylamide compounds as fabi inhibitors and antibacterial agents
EP2687533B1 (en)	2006-07-20	2017-07-19	Debiopharm International SA	Acrylamide derivatives as FAB I inhibitors
WO2008098374A1 (en)	2007-02-16	2008-08-21	Affinium Pharmaceuticals, Inc.	Salts, prodrugs and polymorphs of fab i inhibitors
WO2011003091A1 (en)	2009-07-02	2011-01-06	Alcon Research, Ltd.	Compositions comprising finafloxacin and methods for treating ophthalmic, otic, or nasal infections
RU2449805C1 (ru)	2011-01-27	2012-05-10	Общество С Ограниченной Ответственностью "Гармония"	Пептидная фармацевтическая композиция, средство на ее основе для лечения гастродуоденальных заболеваний, вызываемых helicobacter pylori, и способ его использования
SI2861608T1 (sl)	2012-06-19	2019-08-30	Debiopharm International Sa	Derivati predzdravila (E)-N-metil-N-((3-metilbenzofuran-2-IL)metil)- 3-(7-okso-5,6,7,8-tetrahidro-1 ,8-nafthiridin-3-il)akrilamid
US9504691B2 (en) *	2012-12-06	2016-11-29	Alcon Research, Ltd.	Finafloxacin suspension compositions
CA2916535A1 (en)	2013-08-12	2015-02-19	Novartis Ag	Method for treating otic infections after tympanostomy tube placement
DE102014115951A1 (de) *	2014-11-03	2016-05-04	Merlion Pharmaceuticals Pte Ltd.	Zusammensetzungen, die Finafloxacin und Tris enthalten
DE102015100068A1 (de)	2015-01-06	2016-07-07	Merlion Pharmaceuticals Pte Ltd.	Finafloxacin zur verwendung bei der behandlung von harnwegsinfektionen
BR122023021456A2 (pt)	2016-02-26	2024-02-20	Debiopharm International S.A.	Uso de di-hidrogeno fosfato de {6- [(e)-3-{metil[(3-metil-1-benfofuran-2- iol)metil]amino)-3- oxopro-1-en-1-il]-2-oxo-3,4-di-hidro-1,8-naftiridin-1(2h)- il}metila para tratamento de osteomielite do pé diabético e composição farmacêutica
CN107987074B (zh) *	2017-10-27	2020-12-29	浙江美诺华药物化学有限公司	一种普拉沙星的合成方法
CA3098060A1 (en) *	2018-04-25	2019-10-31	Bayer Animal Health Gmbh	Process for the hydrolysis of quinolone carboxylic esters
LT3923914T (lt)	2019-02-14	2023-07-25	Debiopharm International S.A.	Afabicino kompozicija, jos gamybos būdas
CN113939306B (zh)	2019-06-14	2024-07-19	德彪药业国际股份公司	用于治疗涉及生物膜的细菌感染的药物及其用途

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4822801A (en) *	1984-07-20	1989-04-18	Warner-Lambert Company	4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivative as antibacterial agents
JPS62205060A (ja) *	1986-03-04	1987-09-09	Kyorin Pharmaceut Co Ltd	８位置換キノロンカルボン酸誘導体
DE3702393A1 (de) *	1987-01-28	1988-08-11	Bayer Ag	8-cyano-1-cyclopropyl-1,4-dihydro-4-oxo- 3-chinolincarbonsaeuren, verfahren zu ihrer herstellung und diese enthaltende antibakterielle mittel
US5563138A (en) *	1987-04-16	1996-10-08	Otsuka Pharmaceutical Company, Limited	Benzoheterocyclic compounds
US4889857A (en) *	1987-10-12	1989-12-26	Yoshitomi Pharmaceutical Industries, Ltd.	Quinolonecarboxylic acid compounds and pharmaceutical use thereof
WO1989005643A1 (en) *	1987-12-18	1989-06-29	Pfizer Inc.	Heterocyclic-substituted quinoline-carboxylic acids
JP2844079B2 (ja) *	1988-05-23	1999-01-06	塩野義製薬株式会社	ピリドンカルボン酸系抗菌剤
DE3906365A1 (de) *	1988-07-15	1990-01-18	Bayer Ag	7-(1-pyrrolidinyl)-3-chinolon- und -naphthyridoncarbonsaeure-derivate, verfahren sowie substituierte (oxa)diazabicyclooctane und -nonane als zwischenprodukte zu ihrer herstellung, und sie enthaltende antibakterielle mittel und futterzusatzstoffe
US5147873A (en) *	1988-08-23	1992-09-15	Pfizer Inc.	Amino-substituted bridged azabicyclic quinolone carboxylic acids and esters
CA2001203C (en) *	1988-10-24	2001-02-13	Thomas P. Demuth, Jr.	Novel antimicrobial dithiocarbamoyl quinolones
US5262417A (en) *	1988-12-06	1993-11-16	The Upjohn Company	Antibacterial quinolone compounds
US5407932A (en) *	1989-03-31	1995-04-18	Wakunaga Seiyaku Kabushiki Kaisha	Quinolone derivatives and antibacterial agents containing the same
US5140033A (en) *	1989-04-03	1992-08-18	Bayer Aktiengesellschaft	Antibacterial 5-alkylquinolonecarboxylic acids
DE3910663A1 (de) *	1989-04-03	1990-10-04	Bayer Ag	5-alkylchinoloncarbonsaeuren
US5252734A (en) *	1989-04-03	1993-10-12	Bayer Aktiengesellschaft	Antibacterial 5-alkylquinolonecarboxylic acids
US5164402A (en) *	1989-08-16	1992-11-17	Pfizer Inc	Azabicyclo quinolone and naphthyridinone carboxylic acids
KR910009330B1 (ko) *	1989-10-23	1991-11-11	재단법인 한국화학연구소	항균작용을 갖는 퀴놀린계 화합물과 그의 제조방법
TW209865B (da) *	1992-01-10	1993-07-21	Bayer Ag
DE4200415A1 (de)	1992-01-10	1993-07-15	Bayer Ag	Enantiomerenreine 2-oxa-5,8-diazabicyclo(4.3.0)nonane sowie verfahren zu ihrer herstellung
NO301165B1 (no) *	1992-12-25	1997-09-22	Daiichi Seiyaku Co	Bicykliske aminderivater og antibakterielle midler inneholdende disse
DE4309964A1 (de)	1993-03-26	1994-09-29	Bayer Ag	Verfahren zur Herstellung enantiomerenreiner trans-2-Oxa-5,8-diazabicyclo[4.3.0]nonane
WO1994025464A1 (en) *	1993-04-24	1994-11-10	Korea Research Institute Of Chemical Technology	Novel quinolone carboxylic acid derivatives and process for preparing the same
US5532239A (en) *	1993-08-02	1996-07-02	Assistance Publique - Hopitaux De Paris	Therapeutic application of fluoroquinolone derivatives
DE4329600A1 (de) *	1993-09-02	1995-03-09	Bayer Ag	Pyrido [1,2,3-d,e] [1,3,4] benzoxadiazinderivate
DE69504392T2 (de) *	1994-04-07	1999-02-11	Pfizer Inc., New York, N.Y.	Verwendung von Trovafloxacin oder dessen Derivaten zur Herstellung eines Arzneimittels zur Behandlung von H.Pylori Infektionen
GB2289674A (en) *	1994-05-23	1995-11-29	Pfizer	Antibacterial naphthyridine
JPH0848629A (ja) *	1994-08-08	1996-02-20	Dainippon Pharmaceut Co Ltd	ピリドンカルボン酸誘導体およびそれを有効成分とする抗ピロリ菌剤

1996
- 1996-12-16 DE DE19652239A patent/DE19652239A1/de not_active Withdrawn
1997
- 1997-04-12 UA UA99074093A patent/UA57055C2/uk unknown
- 1997-12-04 SK SK1496-2000A patent/SK283224B6/sk not_active IP Right Cessation
- 1997-12-04 HU HU0000450A patent/HU226523B1/hu unknown
- 1997-12-04 WO PCT/EP1997/006781 patent/WO1998026779A1/de not_active Ceased
- 1997-12-04 IL IL13031197A patent/IL130311A/en not_active IP Right Cessation
- 1997-12-04 KR KR10-1999-7005330A patent/KR100536153B1/ko not_active Expired - Lifetime
- 1997-12-04 DK DK97954354T patent/DK0946176T3/da active
- 1997-12-04 CA CA002274894A patent/CA2274894C/en not_active Expired - Lifetime
- 1997-12-04 AT AT97954354T patent/ATE214929T1/de active
- 1997-12-04 CZ CZ0216899A patent/CZ297363B6/cs not_active IP Right Cessation
- 1997-12-04 JP JP52725098A patent/JP3463939B2/ja not_active Expired - Lifetime
- 1997-12-04 EA EA199900526A patent/EA002477B1/ru not_active IP Right Cessation
- 1997-12-04 DE DE59706808T patent/DE59706808D1/de not_active Expired - Lifetime
- 1997-12-04 PL PL333928A patent/PL191193B1/pl unknown
- 1997-12-04 CN CNB971817200A patent/CN100335054C/zh not_active Expired - Lifetime
- 1997-12-04 BR BR9714032-5A patent/BR9714032A/pt not_active IP Right Cessation
- 1997-12-04 SK SK795-99A patent/SK283223B6/sk not_active IP Right Cessation
- 1997-12-04 CZ CZ20003148A patent/CZ297364B6/cs not_active IP Right Cessation
- 1997-12-04 PT PT97954354T patent/PT946176E/pt unknown
- 1997-12-04 RS YUP-274/99A patent/RS49684B/sr unknown
- 1997-12-04 TR TR1999/01754T patent/TR199901754T2/xx unknown
- 1997-12-04 ES ES97954354T patent/ES2175519T3/es not_active Expired - Lifetime
- 1997-12-04 US US09/319,888 patent/US6133260A/en not_active Expired - Lifetime
- 1997-12-04 AU AU58541/98A patent/AU717751B2/en not_active Expired
- 1997-12-04 NZ NZ336228A patent/NZ336228A/xx not_active IP Right Cessation
- 1997-12-04 EE EEP199900248A patent/EE04090B1/xx unknown
- 1997-12-04 EP EP97954354A patent/EP0946176B1/de not_active Expired - Lifetime
1999
- 1999-06-08 BG BG103474A patent/BG64615B1/bg unknown
- 1999-06-14 NO NO19992903A patent/NO325617B1/no not_active IP Right Cessation
- 1999-11-08 US US09/436,316 patent/US6432948B1/en not_active Expired - Lifetime
2000
- 2000-05-25 JP JP2000154543A patent/JP4463380B2/ja not_active Expired - Lifetime
- 2000-08-04 NZ NZ506162A patent/NZ506162A/en not_active IP Right Cessation
2009
- 2009-07-22 JP JP2009171127A patent/JP5112395B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
AU717751B2 (en)	2000-03-30
IL130311A (en)	2004-01-04
JP4463380B2 (ja)	2010-05-19
CZ297363B6 (cs)	2006-11-15
WO1998026779A1 (de)	1998-06-25
EE04090B1 (et)	2003-08-15
HUP0000450A2 (hu)	2000-10-28
PL333928A1 (en)	2000-01-31
KR100536153B1 (ko)	2005-12-14
JP5112395B2 (ja)	2013-01-09
DE19652239A1 (de)	1998-06-18
CA2274894C (en)	2009-04-07
PT946176E (pt)	2002-08-30
CA2274894A1 (en)	1998-06-25
HU226523B1 (en)	2009-03-30
US6133260A (en)	2000-10-17
CZ216899A3 (cs)	2000-02-16
CN100335054C (zh)	2007-09-05
ATE214929T1 (de)	2002-04-15
SK79599A3 (en)	2001-01-18
TR199901754T2 (xx)	1999-09-21
CZ297364B6 (cs)	2006-11-15
DK0946176T3 (da)	2002-06-10
US6432948B1 (en)	2002-08-13
EA002477B1 (ru)	2002-06-27
AU5854198A (en)	1998-07-15
SK283224B6 (sk)	2003-03-04
EP0946176A1 (de)	1999-10-06
NO992903L (no)	1999-06-14
JP2009235106A (ja)	2009-10-15
NZ506162A (en)	2001-06-29
BR9714032A (pt)	2000-05-09
JP2000351781A (ja)	2000-12-19
JP2000514825A (ja)	2000-11-07
IL130311A0 (en)	2000-06-01
KR20000069483A (ko)	2000-11-25
BG103474A (en)	2000-01-31
SK283223B6 (sk)	2003-03-04
RS49684B (sr)	2007-11-15
NO992903D0 (no)	1999-06-14
JP3463939B2 (ja)	2003-11-05
YU27499A (sh)	2002-10-18
EP0946176B1 (de)	2002-03-27
DE59706808D1 (de)	2002-05-02
CN1245428A (zh)	2000-02-23
UA57055C2 (uk)	2003-06-16
BG64615B1 (bg)	2005-09-30
HUP0000450A3 (en)	2001-02-28
PL191193B1 (pl)	2006-03-31
HK1025517A1 (zh)	2000-11-17
EE9900248A (et)	1999-12-15
SK14962000A3 (sk)	2003-01-09
NZ336228A (en)	2000-12-22
ES2175519T3 (es)	2002-11-16
EA199900526A1 (ru)	2000-08-28

Legal Events

Date	Code	Title	Description
2013-06-17	CHAD	Change of the owner's name or address (par. 44 patent law, par. patentforskriften)	Owner name: BAYER INTELLECTUAL PROPERTY GMBH, DE
2017-12-11	MK1K	Patent expired

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