NO300923B1 - Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater - Google Patents
Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater Download PDFInfo
- Publication number
- NO300923B1 NO300923B1 NO911586A NO911586A NO300923B1 NO 300923 B1 NO300923 B1 NO 300923B1 NO 911586 A NO911586 A NO 911586A NO 911586 A NO911586 A NO 911586A NO 300923 B1 NO300923 B1 NO 300923B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- compound
- formula
- carboxylate
- mixture
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 7
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 9
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 128
- 239000000203 mixture Substances 0.000 claims description 86
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- 229910001868 water Inorganic materials 0.000 claims description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 77
- -1 5-methyl-2-oxo-1,3-dioxolen-4-yl Chemical group 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 44
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- 239000007858 starting material Substances 0.000 claims description 4
- 150000003536 tetrazoles Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
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- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 238000007344 nucleophilic reaction Methods 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- HTQMVQVXFRQIKW-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 HTQMVQVXFRQIKW-UHFFFAOYSA-N 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
- BCPWNYREAURMOP-UHFFFAOYSA-N ethyl 2-ethoxy-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate Chemical compound C1=2C(C(=O)OCC)=CC=CC=2N=C(OCC)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 BCPWNYREAURMOP-UHFFFAOYSA-N 0.000 abstract description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 abstract 1
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- FFWDHZHBAMSJBU-UHFFFAOYSA-N cyclohexyl 1-[2-ethoxy-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazol-4-yl]ethyl carbonate Chemical compound CCOC1=NC2=C(C(C)OC(=O)OC3CCCCC3)C=CC=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 FFWDHZHBAMSJBU-UHFFFAOYSA-N 0.000 abstract 1
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- 229930195733 hydrocarbon Natural products 0.000 abstract 1
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- 125000006850 spacer group Chemical group 0.000 abstract 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
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- 238000000921 elemental analysis Methods 0.000 description 52
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 43
- 238000002844 melting Methods 0.000 description 38
- 230000008018 melting Effects 0.000 description 38
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
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- 238000005481 NMR spectroscopy Methods 0.000 description 30
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 28
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- 229910002027 silica gel Inorganic materials 0.000 description 25
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- 239000012044 organic layer Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000006188 syrup Substances 0.000 description 18
- 235000020357 syrup Nutrition 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
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- 101150041968 CDC13 gene Proteins 0.000 description 11
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- 239000002585 base Substances 0.000 description 11
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- 238000000354 decomposition reaction Methods 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
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- 150000001556 benzimidazoles Chemical class 0.000 description 9
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 9
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- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 8
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
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- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
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- LERUETMARSWZRK-UHFFFAOYSA-N methyl 3-amino-2-[[4-(2-cyanophenyl)phenyl]methylamino]benzoate Chemical compound COC(=O)C1=CC=CC(N)=C1NCC1=CC=C(C=2C(=CC=CC=2)C#N)C=C1 LERUETMARSWZRK-UHFFFAOYSA-N 0.000 description 4
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- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/28—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Polyesters Or Polycarbonates (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11314890 | 1990-04-27 | ||
| JP14194290 | 1990-05-30 | ||
| JP20866290 | 1990-08-06 | ||
| JP26457990 | 1990-10-01 | ||
| JP41367990 | 1990-12-24 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO911586D0 NO911586D0 (no) | 1991-04-22 |
| NO911586L NO911586L (no) | 1991-10-28 |
| NO300923B1 true NO300923B1 (no) | 1997-08-18 |
Family
ID=27526589
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO911586A NO300923B1 (no) | 1990-04-27 | 1991-04-22 | Analogifremgangsmåte for fremstilling av terapeutisk aktive benzimidazolderivater |
| NO970195A NO302752B1 (no) | 1990-04-27 | 1997-01-16 | Fremgangsmåte for fremstilling av en C-type-krystall av 1-(cykloheksyloksykarbonyloksy)etyl-2-etoksy-1-££2'-(1H-tetrazol-5-yl)bifenyl-4-yl|metyl|benzimidazol-7-karboksylat |
| NO1998018C NO1998018I1 (no) | 1990-04-27 | 1998-06-17 | Candesartan |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO970195A NO302752B1 (no) | 1990-04-27 | 1997-01-16 | Fremgangsmåte for fremstilling av en C-type-krystall av 1-(cykloheksyloksykarbonyloksy)etyl-2-etoksy-1-££2'-(1H-tetrazol-5-yl)bifenyl-4-yl|metyl|benzimidazol-7-karboksylat |
| NO1998018C NO1998018I1 (no) | 1990-04-27 | 1998-06-17 | Candesartan |
Country Status (22)
| Country | Link |
|---|---|
| US (4) | US5196444A (fi) |
| EP (2) | EP0720982B1 (fi) |
| JP (2) | JP2514282B2 (fi) |
| KR (1) | KR100200541B1 (fi) |
| CN (2) | CN1048486C (fi) |
| AT (2) | ATE146779T1 (fi) |
| CA (2) | CA2040955C (fi) |
| CY (1) | CY2150B1 (fi) |
| DE (3) | DE19875004I2 (fi) |
| DK (2) | DK0459136T3 (fi) |
| ES (2) | ES2181742T3 (fi) |
| FI (2) | FI108434B (fi) |
| GR (1) | GR3022172T3 (fi) |
| HK (1) | HK1000803A1 (fi) |
| HU (2) | HU213266B (fi) |
| IE (1) | IE911317A1 (fi) |
| LU (1) | LU90224I2 (fi) |
| LV (1) | LV10258B (fi) |
| NL (1) | NL970044I2 (fi) |
| NO (3) | NO300923B1 (fi) |
| NZ (1) | NZ237949A (fi) |
| PT (1) | PT97451B (fi) |
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| DE4036706A1 (de) * | 1990-11-17 | 1992-05-21 | Hoechst Ag | Verfahren zur behandlung der cardialen sowie der vasculaeren hypertrophie und hyperplasie |
| GB9027208D0 (en) * | 1990-12-14 | 1991-02-06 | Smithkline Beecham Plc | Medicaments |
| GB9027198D0 (en) * | 1990-12-14 | 1991-02-06 | Smithkline Beecham Plc | Medicaments |
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1991
- 1991-04-18 US US07/687,238 patent/US5196444A/en not_active Expired - Lifetime
- 1991-04-19 DE DE1998175004 patent/DE19875004I2/de active Active
- 1991-04-19 DK DK91106330.3T patent/DK0459136T3/da active
- 1991-04-19 AT AT91106330T patent/ATE146779T1/de active
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- 1991-04-19 EP EP91106330A patent/EP0459136B1/en not_active Expired - Lifetime
- 1991-04-19 DE DE69123784T patent/DE69123784T2/de not_active Expired - Lifetime
- 1991-04-19 DE DE69133149T patent/DE69133149T2/de not_active Expired - Lifetime
- 1991-04-19 DK DK95118796T patent/DK0720982T3/da active
- 1991-04-19 ES ES91106330T patent/ES2095266T3/es not_active Expired - Lifetime
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- 1991-04-22 NO NO911586A patent/NO300923B1/no not_active IP Right Cessation
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- 1991-04-22 FI FI911936A patent/FI108434B/fi active Protection Beyond IP Right Term
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- 1991-04-23 HU HU911347A patent/HU213266B/hu unknown
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- 1991-04-23 CN CN91102569A patent/CN1048486C/zh not_active Expired - Lifetime
- 1991-04-23 KR KR1019910006525A patent/KR100200541B1/ko not_active IP Right Cessation
- 1991-04-26 NZ NZ237949A patent/NZ237949A/en unknown
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1992
- 1992-12-30 LV LVP-92-567A patent/LV10258B/xx unknown
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1993
- 1993-01-05 US US07/997,703 patent/US5328919A/en not_active Expired - Lifetime
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- 1993-10-05 US US08/131,667 patent/US5705517A/en not_active Expired - Lifetime
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1995
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1996
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1997
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1998
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