CY2123B1 - Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides drugs containing these compounds and use of such drugs - Google Patents
Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides drugs containing these compounds and use of such drugsInfo
- Publication number
- CY2123B1 CY2123B1 CY9800032A CY9800032A CY2123B1 CY 2123 B1 CY2123 B1 CY 2123B1 CY 9800032 A CY9800032 A CY 9800032A CY 9800032 A CY9800032 A CY 9800032A CY 2123 B1 CY2123 B1 CY 2123B1
- Authority
- CY
- Cyprus
- Prior art keywords
- drugs
- compounds
- isoxazole
- hydroxyalkylidene
- carboxamides
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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
- C07D277/82—Nitrogen atoms
-
- 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
- A61K31/275—Nitriles; Isonitriles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/23—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same unsaturated acyclic carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
- C07C317/40—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Air Conditioning Control Device (AREA)
- Photoreceptors In Electrophotography (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4016178 | 1990-05-18 | ||
DE4017043 | 1990-05-26 | ||
DE4017020 | 1990-05-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
CY2123B1 true CY2123B1 (en) | 2002-06-21 |
Family
ID=27201216
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CY9800032A CY2123B1 (en) | 1990-05-18 | 1998-09-29 | Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides drugs containing these compounds and use of such drugs |
Country Status (28)
Country | Link |
---|---|
US (2) | US5494911A (fi) |
EP (1) | EP0527736B1 (fi) |
JP (3) | JP2995086B2 (fi) |
KR (1) | KR100188801B1 (fi) |
CN (1) | CN1051074C (fi) |
AT (1) | ATE151633T1 (fi) |
AU (2) | AU649421B2 (fi) |
BR (1) | BR9008022A (fi) |
CA (1) | CA2083179C (fi) |
CY (1) | CY2123B1 (fi) |
CZ (4) | CZ290474B6 (fi) |
DE (1) | DE59010701D1 (fi) |
DK (1) | DK0527736T3 (fi) |
ES (1) | ES2102367T3 (fi) |
FI (1) | FI105683B (fi) |
GR (1) | GR3023638T3 (fi) |
HU (1) | HU222234B1 (fi) |
IE (1) | IE911694A1 (fi) |
IL (1) | IL98163A (fi) |
LV (1) | LV10575B (fi) |
NO (1) | NO180118C (fi) |
NZ (1) | NZ238165A (fi) |
PT (1) | PT97689B (fi) |
RU (2) | RU2084223C1 (fi) |
SK (3) | SK281317B6 (fi) |
TW (2) | TW205004B (fi) |
WO (1) | WO1991017748A1 (fi) |
YU (1) | YU48765B (fi) |
Families Citing this family (76)
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GB9200275D0 (en) * | 1992-01-08 | 1992-02-26 | Roussel Lab Ltd | Chemical compounds |
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DE59407413D1 (de) * | 1993-01-08 | 1999-01-21 | Hoechst Ag | Verwendung von Leflunomid zur Hemmung von Interleukin 1 beta |
ATE174220T1 (de) * | 1993-01-08 | 1998-12-15 | Hoechst Ag | Verwendung von leflunomid zur hemmung von interleukin 8 |
ATE174219T1 (de) * | 1993-01-08 | 1998-12-15 | Hoechst Ag | Verwendung von leflunomid zur hemmung von tumornekrosefaktor alpha |
DE59407412D1 (de) * | 1993-01-08 | 1999-01-21 | Hoechst Ag | Verwendung von Leflunomid zur Hemmung von Interleukin 1 alpha |
TW314467B (fi) * | 1993-03-31 | 1997-09-01 | Hoechst Ag | |
GB9313365D0 (en) * | 1993-06-29 | 1993-08-11 | Roussel Lab Ltd | Chemical compounds |
DE4323636A1 (de) * | 1993-07-15 | 1995-01-19 | Hoechst Ag | Arzneistoffzubereitungen aus umhüllten, schwerstwasserlöslichen Arzneistoffen für Inhalationsarzneiformen und Verfahren zu ihrer Herstellung |
GB9322781D0 (en) * | 1993-11-04 | 1993-12-22 | Roussel Lab Ltd | Aromatic amides |
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US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
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GB9520092D0 (en) * | 1995-10-02 | 1995-12-06 | Hoechst Roussel Ltd | Chemical compounds |
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DE19547648A1 (de) * | 1995-12-20 | 1997-06-26 | Hoechst Ag | Zubereitung, enthaltend High Density Lipoproteine und Crotonsäureamidderivate |
DE59712561D1 (de) * | 1996-03-12 | 2006-04-13 | Sanofi Aventis Deutschland | Neuartige Prodrugs für die Therapie von Tumoren und entzündlichen Erkrankungen |
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CN110325514B (zh) | 2017-02-24 | 2023-06-13 | 默克专利有限责任公司 | 作为二氢乳清酸加氧酶抑制剂的1,4,6-三取代的-2-烷基-1H-苯并[d]咪唑衍生物 |
AU2018242623B2 (en) | 2017-03-31 | 2024-05-02 | Aurigene Oncology Limited | Compounds and compositions for treating hematological disorders |
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KR20200080254A (ko) | 2017-10-31 | 2020-07-06 | 쿠리스 인코퍼레이션 | 혈액학적 장애를 치료하기 위한 화합물 및 조성물 |
EA201992528A1 (ru) | 2018-02-20 | 2020-02-28 | Ориджин Дискавери Текнолоджиз Лимитед | Способы применения тризамещенных производных бензотриазола в качестве ингибиторов дигидрооротатоксигеназы |
TR202022336A2 (tr) | 2020-12-30 | 2022-07-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A film coated tablet comprising teriflunomide |
EP4162933A1 (en) | 2021-10-08 | 2023-04-12 | Algiax Pharmaceuticals GmbH | Compound for treating non-alcoholic fatty liver disease and related diseases |
EP4382097A1 (en) | 2022-11-25 | 2024-06-12 | Sanovel Ilac Sanayi Ve Ticaret A.S. | A tablet comprising teriflunomide |
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ES448386A1 (es) * | 1975-06-05 | 1978-04-16 | Hoechst Ag | Procedimiento para la preparacion de anilidas de acido 5-me-til-isoxazol-4-carboxilico. |
NL186239B (nl) * | 1975-06-05 | Hoechst Ag | Werkwijze voor de bereiding van een geneesmiddel met antiflogistische en/of analgetische werking, alsmede werkwijze voor de bereiding van een 2-hydroxyethylideencyaanazijnzuuranilide geschikt voor toepassing bij deze werkwijze. | |
DE2524959C2 (de) * | 1975-06-05 | 1983-02-10 | Hoechst Ag, 6000 Frankfurt | 5-Methyl-isoxazol-4-carbonsäureanilide, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Mittel |
DE2555789A1 (de) * | 1975-12-11 | 1977-07-07 | Hoechst Ag | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
DE2557003A1 (de) * | 1975-12-18 | 1977-06-23 | Hoechst Ag | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
DE2655009A1 (de) * | 1976-12-04 | 1978-06-15 | Hoechst Ag | Isoxazolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
DE2854439A1 (de) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | Ein isoxazolderivat, verfahren zu seiner herstellung, diese verbindung enthaltende mittel und verwendung |
DE3405727A1 (de) * | 1984-02-17 | 1985-08-22 | Hoechst Ag, 6230 Frankfurt | Isoxazol-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
GB8619433D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
US4816467A (en) * | 1987-01-09 | 1989-03-28 | Farmitalia Carlo Erba S.R.L | Heteroaryl 3-oxo-propanenitrile derivatives, pharmaceutical compositions and use |
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1990
- 1990-10-24 DE DE59010701T patent/DE59010701D1/de not_active Expired - Lifetime
- 1990-10-24 RU RU9092016445A patent/RU2084223C1/ru active
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- 1990-10-24 CA CA002083179A patent/CA2083179C/en not_active Expired - Lifetime
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- 1990-10-24 DK DK90915462.7T patent/DK0527736T3/da active
- 1990-10-24 US US07/938,048 patent/US5494911A/en not_active Expired - Lifetime
- 1990-10-24 BR BR909008022A patent/BR9008022A/pt not_active Application Discontinuation
- 1990-10-24 RU RU94033835A patent/RU2142937C1/ru active
- 1990-10-24 KR KR1019920702895A patent/KR100188801B1/ko not_active IP Right Cessation
- 1990-10-24 WO PCT/EP1990/001800 patent/WO1991017748A1/de active IP Right Grant
- 1990-10-24 HU HU9203619A patent/HU222234B1/hu active IP Right Grant
- 1990-10-24 AT AT90915462T patent/ATE151633T1/de not_active IP Right Cessation
- 1990-10-27 TW TW079109110A patent/TW205004B/zh active
- 1990-10-27 TW TW081101406A patent/TW211558B/zh active
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1991
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- 1991-05-16 PT PT97689A patent/PT97689B/pt not_active IP Right Cessation
- 1991-05-16 SK SK1450-91A patent/SK281316B6/sk not_active IP Right Cessation
- 1991-05-16 CZ CS19911450A patent/CZ290474B6/cs not_active IP Right Cessation
- 1991-05-16 SK SK542-99A patent/SK281318B6/sk not_active IP Right Cessation
- 1991-05-16 CN CN91103182A patent/CN1051074C/zh not_active Expired - Lifetime
- 1991-05-17 IE IE169491A patent/IE911694A1/en not_active IP Right Cessation
- 1991-05-20 YU YU88491A patent/YU48765B/sr unknown
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1992
- 1992-11-17 FI FI925211A patent/FI105683B/fi active
- 1992-11-17 NO NO924433A patent/NO180118C/no not_active IP Right Cessation
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1993
- 1993-05-07 LV LVP-93-310A patent/LV10575B/en unknown
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1994
- 1994-03-23 AU AU57992/94A patent/AU662465B2/en not_active Expired
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1995
- 1995-06-07 US US08/476,278 patent/US5532259A/en not_active Expired - Lifetime
- 1995-08-24 CZ CZ19952176A patent/CZ290717B6/cs not_active IP Right Cessation
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1997
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1999
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