NO300173B1 - Substituerte benzensulfonylurinstoffer og -tiourinstoffer og deres anvendelse til fremstilling av farmasöytika, samt legemidler inneholdende disse - Google Patents
Substituerte benzensulfonylurinstoffer og -tiourinstoffer og deres anvendelse til fremstilling av farmasöytika, samt legemidler inneholdende disse Download PDFInfo
- Publication number
- NO300173B1 NO300173B1 NO940600A NO940600A NO300173B1 NO 300173 B1 NO300173 B1 NO 300173B1 NO 940600 A NO940600 A NO 940600A NO 940600 A NO940600 A NO 940600A NO 300173 B1 NO300173 B1 NO 300173B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- stands
- hydrogen
- formula
- methoxy
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 229940079593 drug Drugs 0.000 title claims description 6
- 150000003585 thioureas Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- -1 (fluoro)methyl Chemical group 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 17
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- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
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- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 230000033764 rhythmic process Effects 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 206010049418 Sudden Cardiac Death Diseases 0.000 claims description 4
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- 229910052736 halogen Inorganic materials 0.000 description 6
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
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- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
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- 229950011590 rilmakalim Drugs 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical group [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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- 125000000542 sulfonic acid group Chemical group 0.000 description 1
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- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UVVUGWBBCDFNSD-UHFFFAOYSA-N tetraisocyanatosilane Chemical compound O=C=N[Si](N=C=O)(N=C=O)N=C=O UVVUGWBBCDFNSD-UHFFFAOYSA-N 0.000 description 1
- NOGBKWXHNPDHFA-UHFFFAOYSA-N tetraisothiocyanatosilane Chemical compound S=C=N[Si](N=C=S)(N=C=S)N=C=S NOGBKWXHNPDHFA-UHFFFAOYSA-N 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- NONOKGVFTBWRLD-UHFFFAOYSA-N thioisocyanate group Chemical class S(N=C=O)N=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
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- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/52—Y being a hetero atom
- C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
- C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
- C07C311/58—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/40—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of thiourea or isothiourea groups further bound to other hetero atoms
- C07C335/42—Sulfonylthioureas; Sulfonylisothioureas
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4305450 | 1993-02-23 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO940600D0 NO940600D0 (no) | 1994-02-22 |
NO940600L NO940600L (no) | 1994-08-24 |
NO300173B1 true NO300173B1 (no) | 1997-04-21 |
Family
ID=6481073
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO940600A NO300173B1 (no) | 1993-02-23 | 1994-02-22 | Substituerte benzensulfonylurinstoffer og -tiourinstoffer og deres anvendelse til fremstilling av farmasöytika, samt legemidler inneholdende disse |
Country Status (18)
Country | Link |
---|---|
US (6) | US5574069A (pl) |
EP (1) | EP0612724B1 (pl) |
JP (1) | JP2778450B2 (pl) |
AT (1) | ATE146775T1 (pl) |
AU (1) | AU664940B2 (pl) |
CA (1) | CA2116165C (pl) |
CY (1) | CY2034A (pl) |
DE (1) | DE59401361D1 (pl) |
DK (1) | DK0612724T3 (pl) |
ES (1) | ES2098069T3 (pl) |
FI (1) | FI114152B (pl) |
GR (1) | GR3022550T3 (pl) |
HK (1) | HK1006166A1 (pl) |
HU (1) | HU219639B (pl) |
NO (1) | NO300173B1 (pl) |
NZ (1) | NZ250925A (pl) |
PL (2) | PL179268B1 (pl) |
TW (1) | TW429245B (pl) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2098069T3 (es) | 1993-02-23 | 1997-04-16 | Hoechst Ag | Bencenosulfonil-ureas y -tioureas sustituidas, procedimiento para su preparacion y su utilizacion como agentes farmaceuticos. |
DE19503136A1 (de) * | 1995-02-01 | 1996-08-08 | Hoechst Ag | Substituierte Thiophenylsulfonylharnstoffe und -thioharnstoffe, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
DE19504379A1 (de) * | 1995-02-10 | 1996-08-14 | Hoechst Ag | Substituierte Benzolsulfonylharnstoffe und -thioharnstoffe, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung pharmazeutischer Präparate sowie sie enthaltende pharmazeutische Präparate |
HU226462B1 (en) * | 1995-02-17 | 2008-12-29 | Hoechst Ag | Substituted benzol-sulfonyl-ureas and -thioureas, process for producing them, pharmaceutical compositions containing them, and their use |
DE19505397A1 (de) * | 1995-02-17 | 1996-08-22 | Hoechst Ag | Substituierte Benzolsulfonylharnstoffe und -thioharnstoffe, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
ZA961314B (en) * | 1995-02-21 | 1996-08-27 | Hoechst Ag | Substituted benzenesulfonylureas and -thioreas processes for their preparation their use for the production of pharmaceutical preparations and medicaments containing them |
DE19540995A1 (de) * | 1995-11-03 | 1997-05-07 | Hoechst Ag | Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
DE19542306A1 (de) * | 1995-11-14 | 1997-05-15 | Hoechst Ag | Sulfonylamino-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
PL316439A1 (en) * | 1995-11-20 | 1997-05-26 | Hoechst Ag | Novel substituted derivatives of benzoyloguanidine, method of obtaining them, their application in production of pharmaceutic and diagnostic agents and pharmaceutic agent as such |
DE19546736A1 (de) * | 1995-12-14 | 1997-06-19 | Hoechst Ag | Substituierte Chromanylsulfonyl(thio)harnstoffe, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung pharmazeutischer Präparate |
DE19647000A1 (de) * | 1996-11-14 | 1998-05-20 | Hoechst Ag | 3-Amido-chromanylsulfonyl(thio)harnstoffe, Verfahren zu ihrer Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
DE19832009A1 (de) * | 1998-07-16 | 2000-01-20 | Hoechst Marion Roussel De Gmbh | 2,5-Substituierte Benzolsulfonylharnstoffe und -thioharnstoffe, Verfahren zu ihrer Herstellung, ihre Verwendung und sie enthaltende pharamazeutische Präparate |
CN1195524C (zh) * | 1998-09-10 | 2005-04-06 | 阿文蒂斯药物德国有限公司 | 苯磺酰(硫)脲与β-受体阻滞剂联合在制备用于心脏迷走神经机能障碍治疗和预防的药物中的用途 |
DE19917233A1 (de) * | 1999-04-16 | 2000-10-19 | Aventis Pharma Gmbh | Kristalline Formen des Natriumsalzes des 5-Chlor-2-methoxy-N-(2-(4-methoxy-3-methylaminothiocarbonylaminosulfonyl-phenyl)-ethyl)- benzamids |
DE19923086A1 (de) * | 1999-05-20 | 2000-11-23 | Aventis Pharma Gmbh | Cinnamoylaminoalkyl-substituierte Benzolsulfonamidderivate, Verfahren zu ihrer Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
US6888028B2 (en) | 2000-10-17 | 2005-05-03 | Asahi Kasei Kabushiki Kaisha | Process for preparation polyisocyanate composition |
DE10054482A1 (de) | 2000-11-03 | 2002-05-08 | Aventis Pharma Gmbh | Heteroarylacryloylaminoalkyl-substituierte Benzolsulfonamidderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
DE10054481A1 (de) | 2000-11-03 | 2002-05-08 | Aventis Pharma Gmbh | Acylaminoalkyl-substituierte Benzolsulfonamidderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
US8472428B2 (en) | 2001-02-27 | 2013-06-25 | Verizon Data Services Llc | Methods and systems for line management |
DE10129704A1 (de) * | 2001-06-22 | 2003-01-02 | Aventis Pharma Gmbh | Verwendung von Benzolsulfonyl(thio)harnstoffen in der Behandlung des septischen Schocks |
US6835853B2 (en) * | 2001-10-31 | 2004-12-28 | Synthon Bv | Process for resolution of tamsulosin and compounds, compositions, and processes associated therewith |
DE102004061017A1 (de) * | 2004-12-18 | 2006-06-22 | Sanofi-Aventis Deutschland Gmbh | Piperidinsulfonylharnstoffe und -thioharnstoffe, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
EP2026766A1 (en) | 2006-05-17 | 2009-02-25 | Synthon B.V. | Tablet composition with a prolonged release of tamsulosin |
EP2865381A1 (en) | 2006-05-18 | 2015-04-29 | Pharmacyclics, Inc. | ITK inhibitors for treating blood cell malignancies |
WO2008148468A1 (en) * | 2007-06-05 | 2008-12-11 | Sanofi-Aventis | Di(hetero)arylcyclohexane derivatives, their preparation, their use and pharmaceutical compositions comprising them |
US8465770B2 (en) * | 2008-12-24 | 2013-06-18 | Synthon Bv | Low dose controlled release tablet |
WO2010148177A2 (en) * | 2009-06-17 | 2010-12-23 | The Board Of Trustees Of The Leland Stanford Junior University | Compounds, compositions, methods of synthesis, and methods of treatment |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE243821C (pl) * | ||||
DE1185180B (de) * | 1963-10-19 | 1965-01-14 | Hoechst Ag | Verfahren zur Herstellung von Benzolsulfonylharnstoffen |
DE1518874C3 (de) * | 1964-10-07 | 1975-03-13 | Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt | Benzolsulfonylharnstoffe und Verfahren zu ihrer Herstellung |
DE1443919C3 (de) * | 1964-12-28 | 1973-11-29 | Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt | Benzolsulfonylharnstoffe, Ver fahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitun gen |
NL128362C (pl) * | 1965-03-16 | |||
US3297696A (en) * | 1965-05-28 | 1967-01-10 | Sandoz Ag | 6-amino-8, 9-dihydro-13bh-isoquinolo-[2, 1-c] quinazolines and intermediates therefor |
GB1122830A (en) * | 1965-10-09 | 1968-08-07 | Ferranti Ltd | Improvements relating to character transmission and reproduction systems |
US3917690A (en) * | 1966-11-29 | 1975-11-04 | Hoechst Ag | Benzenesulfonyl ureas and process for their manufacture |
DE1568648C3 (de) * | 1966-12-19 | 1975-03-27 | Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt | Benzolsulfonylharnstoffe, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
US3517015A (en) * | 1969-03-10 | 1970-06-23 | Sandoz Ag | Tetrahydro-isoquino(2,1-d)(1,4)benzodiazepines |
US3965173A (en) * | 1971-05-21 | 1976-06-22 | Chubb Francis L | Process for preparing p-(5-chloro-2-methoxy-benzamidoethyl)-benzene sulfonamide |
DE2413514C3 (de) * | 1974-03-21 | 1982-03-04 | Hoechst Ag, 6000 Frankfurt | N-Acylaminoathylbenzolsulfonyl-N'-methylharnstoffe, Verfahren zu ihrer Herstellung und deren Verwendung |
US3988968A (en) * | 1974-12-23 | 1976-11-02 | Miller Fluid Power Corporation | Stop tube for cylinder assemblies |
DE2600513A1 (de) * | 1976-01-08 | 1977-07-28 | Hoechst Ag | Acylamino(alkyl)benzolderivate und verfahren zu ihrer herstellung |
DE3011153A1 (de) * | 1980-03-22 | 1981-10-15 | Hoechst Ag, 6000 Frankfurt | Verwendung von n-(4- spitze klammer auf 2-(5-chlor-2-methoxy-benzamido)-aethylspitze klammer zu -benzolsulfonyl)-n'-methyl-harnstoff |
US5215985A (en) * | 1990-07-20 | 1993-06-01 | E. R. Squibb & Sons, Inc. | Method for treating ischemic insult to neurons employing an ATP-sensitive potassium channel blocker |
ES2098069T3 (es) * | 1993-02-23 | 1997-04-16 | Hoechst Ag | Bencenosulfonil-ureas y -tioureas sustituidas, procedimiento para su preparacion y su utilizacion como agentes farmaceuticos. |
-
1994
- 1994-02-16 ES ES94102321T patent/ES2098069T3/es not_active Expired - Lifetime
- 1994-02-16 EP EP94102321A patent/EP0612724B1/de not_active Expired - Lifetime
- 1994-02-16 DE DE59401361T patent/DE59401361D1/de not_active Expired - Lifetime
- 1994-02-16 AT AT94102321T patent/ATE146775T1/de active
- 1994-02-16 DK DK94102321.0T patent/DK0612724T3/da active
- 1994-02-21 NZ NZ250925A patent/NZ250925A/en not_active IP Right Cessation
- 1994-02-21 FI FI940810A patent/FI114152B/fi not_active IP Right Cessation
- 1994-02-21 AU AU55279/94A patent/AU664940B2/en not_active Expired
- 1994-02-22 PL PL94326170A patent/PL179268B1/pl unknown
- 1994-02-22 PL PL94302325A patent/PL175795B1/pl unknown
- 1994-02-22 CA CA002116165A patent/CA2116165C/en not_active Expired - Lifetime
- 1994-02-22 JP JP6024119A patent/JP2778450B2/ja not_active Expired - Lifetime
- 1994-02-22 NO NO940600A patent/NO300173B1/no not_active IP Right Cessation
- 1994-02-23 HU HU9400525A patent/HU219639B/hu unknown
- 1994-03-25 TW TW083102607A patent/TW429245B/zh not_active IP Right Cessation
-
1995
- 1995-02-23 US US08/393,027 patent/US5574069A/en not_active Expired - Lifetime
-
1996
- 1996-09-03 US US08/707,103 patent/US5698596A/en not_active Expired - Lifetime
- 1996-11-07 US US08/744,314 patent/US5776980A/en not_active Expired - Lifetime
-
1997
- 1997-02-12 GR GR970400240T patent/GR3022550T3/el unknown
-
1998
- 1998-02-20 CY CY203498A patent/CY2034A/xx unknown
- 1998-05-19 US US09/081,143 patent/US6090981A/en not_active Expired - Lifetime
- 1998-06-12 HK HK98105247A patent/HK1006166A1/xx not_active IP Right Cessation
-
2000
- 2000-01-24 US US09/490,078 patent/US6335467B1/en not_active Expired - Lifetime
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2001
- 2001-11-29 US US09/995,782 patent/US6506937B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US20020058838A1 (en) | 2002-05-16 |
FI940810A (fi) | 1994-08-24 |
JP2778450B2 (ja) | 1998-07-23 |
DE59401361D1 (de) | 1997-02-06 |
FI940810A0 (fi) | 1994-02-21 |
AU5527994A (en) | 1994-09-01 |
PL175795B1 (pl) | 1999-02-26 |
US6506937B2 (en) | 2003-01-14 |
US6090981A (en) | 2000-07-18 |
CA2116165A1 (en) | 1994-08-24 |
HUT71104A (en) | 1995-11-28 |
EP0612724A1 (de) | 1994-08-31 |
US6335467B1 (en) | 2002-01-01 |
NO940600D0 (no) | 1994-02-22 |
ES2098069T3 (es) | 1997-04-16 |
ATE146775T1 (de) | 1997-01-15 |
EP0612724B1 (de) | 1996-12-27 |
US5574069A (en) | 1996-11-12 |
JPH07304728A (ja) | 1995-11-21 |
NZ250925A (en) | 1995-09-26 |
DK0612724T3 (da) | 1997-06-16 |
PL302325A1 (en) | 1994-09-05 |
AU664940B2 (en) | 1995-12-07 |
HK1006166A1 (en) | 1999-02-12 |
CY2034A (en) | 1998-02-20 |
US5698596A (en) | 1997-12-16 |
FI114152B (fi) | 2004-08-31 |
NO940600L (no) | 1994-08-24 |
PL179268B1 (pl) | 2000-08-31 |
HU9400525D0 (en) | 1994-05-30 |
HU219639B (hu) | 2001-06-28 |
US5776980A (en) | 1998-07-07 |
TW429245B (en) | 2001-04-11 |
CA2116165C (en) | 2006-02-21 |
GR3022550T3 (en) | 1997-05-31 |
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