NO309190B1 - Neurobeskyttende kromanforbindelser og farmasöytisk blanding - Google Patents
Neurobeskyttende kromanforbindelser og farmasöytisk blanding Download PDFInfo
- Publication number
- NO309190B1 NO309190B1 NO963186A NO963186A NO309190B1 NO 309190 B1 NO309190 B1 NO 309190B1 NO 963186 A NO963186 A NO 963186A NO 963186 A NO963186 A NO 963186A NO 309190 B1 NO309190 B1 NO 309190B1
- Authority
- NO
- Norway
- Prior art keywords
- hydroxy
- fluorophenyl
- piperidin
- chroman
- acid
- Prior art date
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Classifications
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- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
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- Obesity (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cosmetics (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18947994A | 1994-01-31 | 1994-01-31 | |
| PCT/IB1994/000365 WO1995020587A1 (en) | 1994-01-31 | 1994-11-21 | Neuroprotective chroman compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO963186L NO963186L (no) | 1996-07-30 |
| NO963186D0 NO963186D0 (no) | 1996-07-30 |
| NO309190B1 true NO309190B1 (no) | 2000-12-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO963186A NO309190B1 (no) | 1994-01-31 | 1996-07-30 | Neurobeskyttende kromanforbindelser og farmasöytisk blanding |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US5744483A (ja) |
| EP (1) | EP0741724B1 (ja) |
| JP (1) | JP2866743B2 (ja) |
| CN (1) | CN1048247C (ja) |
| AT (1) | ATE183184T1 (ja) |
| AU (1) | AU684568B2 (ja) |
| BR (2) | BR9408506A (ja) |
| CA (1) | CA2182101C (ja) |
| CO (1) | CO4230161A1 (ja) |
| CZ (1) | CZ286757B6 (ja) |
| DE (1) | DE69420053T2 (ja) |
| DK (1) | DK0741724T3 (ja) |
| EG (1) | EG20672A (ja) |
| ES (1) | ES2134361T3 (ja) |
| FI (1) | FI113769B (ja) |
| GR (1) | GR3031356T3 (ja) |
| HU (1) | HU221633B1 (ja) |
| IL (1) | IL112415A (ja) |
| MY (1) | MY111623A (ja) |
| NO (1) | NO309190B1 (ja) |
| NZ (1) | NZ275151A (ja) |
| PE (1) | PE43795A1 (ja) |
| PL (1) | PL179448B1 (ja) |
| RU (1) | RU2126404C1 (ja) |
| TW (1) | TW449591B (ja) |
| WO (1) | WO1995020587A1 (ja) |
| ZA (1) | ZA95692B (ja) |
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| CA2232059A1 (en) * | 1995-09-15 | 1997-03-20 | Bertrand Leo Chenard | Phenol derivatives with pharmaceutical activity |
| TW498067B (en) * | 1996-07-19 | 2002-08-11 | Hoffmann La Roche | 4-hydroxy-piperidine derivatives |
| EP1674087A1 (en) | 2000-10-02 | 2006-06-28 | Pfizer Products Inc. | Prophylactic use of n-methyl-d-aspartate (NMDA) antagonists |
| ZA200108038B (en) * | 2000-10-02 | 2003-04-01 | Pfizer Prod Inc | Prophylactic use of n-methyl-d-asparrate (NMDA) antagonists. |
| SE0100902D0 (sv) | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
| JP4864719B2 (ja) * | 2003-11-26 | 2012-02-01 | ファイザー・プロダクツ・インク | Ｇｓｋ−３インヒビターとしてのアミノピラゾール誘導体 |
| CA2628173A1 (en) | 2005-11-03 | 2007-05-10 | F. Hoffmann-La Roche Ag | Arylsulfonylchromans as 5-ht6 inhibitors indolylmaleimide derivatives as protein kinase inhibitors |
| JP5047992B2 (ja) * | 2006-01-20 | 2012-10-10 | シェーリング コーポレイション | ガンマセクレターゼ阻害剤としての、炭素環および複素環アリールスルホン |
| EP2522647B1 (en) * | 2011-05-10 | 2014-04-30 | DSM IP Assets B.V. | Process of separating chiral isomers of chroman compounds and their derivatives and precursors |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3294804A (en) * | 1961-01-27 | 1966-12-27 | Sterling Drug Inc | 1-(3-hydroxy-3-phenylpropyl)-4-phenyl-4-propionoxy-piperidine |
| FR5733M (ja) * | 1966-09-27 | 1968-01-22 | ||
| GB1495526A (en) * | 1974-05-31 | 1977-12-21 | Beecham Group Ltd | Chroman derivatives |
| US4016281A (en) * | 1975-02-22 | 1977-04-05 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Tetralone and indanone compounds |
| US4082755A (en) * | 1977-02-14 | 1978-04-04 | Janssen Pharmaceutica N.V. | 1-[(Diarylmethyl)aminoalkyl]piperidimes |
| WO1980000152A1 (en) * | 1978-07-03 | 1980-02-07 | Sandoz Ag | 3-aminopropoxy-aryl derivates,preparation and use thereof |
| US4358456A (en) * | 1980-05-03 | 1982-11-09 | John Wyeth & Brother Limited | Antipsychotic piperidinomethyl-indole derivatives |
| DE3045688A1 (de) * | 1980-12-04 | 1982-07-08 | C.H. Boehringer Sohn, 6507 Ingelheim | Neue 8-arylalkyl-3-phenyl-3-nortropanole, deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zu ihrer herstellung |
| ATE23718T1 (de) * | 1981-09-25 | 1986-12-15 | Beecham Group Plc | Benzopyran-verbindungen mit pharmazeutischer wirkung. |
| EP0093534A1 (en) * | 1982-04-28 | 1983-11-09 | Beecham Group Plc | Novel chromanols |
| GB8308064D0 (en) * | 1983-03-24 | 1983-05-05 | Beecham Group Plc | Active compounds |
| FR2581993B1 (fr) * | 1985-05-14 | 1988-03-18 | Synthelabo | Derives de (benzoyl-4 piperidino)-2 phenyl-1 alcanols, leur preparation et leur application en therapeutique |
| US4957928A (en) * | 1986-06-26 | 1990-09-18 | Ciba-Geigy Corporation | Hydrogenated 1-benzooxacycloalkylpyridinecarboxylic acid compounds |
| US4968678A (en) * | 1988-02-19 | 1990-11-06 | Eli Lilly And Company | Tetrazole excitatory amino acid receptor antagonists |
| FR2640266B2 (fr) * | 1988-07-12 | 1992-07-10 | Synthelabo | Derives de (hydroxy-1 piperidinyl-2 alkyl) indolones-2, quinoleinones-2, benzo(b)azepinones-2 et benzimidazolones-2, leur preparation et leur application en therapeutique |
| US4968878A (en) * | 1989-02-07 | 1990-11-06 | Transitions Research Corporation | Dual bumper-light curtain obstacle detection sensor |
| US4902695A (en) * | 1989-02-13 | 1990-02-20 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
| SK279476B6 (sk) * | 1989-05-17 | 1998-11-04 | Pfizer | Deriváty 2-piperidino a 2-pyrolidino-1-alkanolov a |
| WO1991012005A1 (en) * | 1990-02-06 | 1991-08-22 | Pfizer Inc. | Neuroprotective 3-piperidino-4-hydroxychroman derivatives and analogs |
| US5192751A (en) * | 1992-07-24 | 1993-03-09 | Eli Lilly And Company | Use of competitive NMDA receptor antagonists in the treatment of urinary incontinence |
-
1994
- 1994-11-21 CN CN94194940A patent/CN1048247C/zh not_active Expired - Fee Related
- 1994-11-21 AU AU80663/94A patent/AU684568B2/en not_active Ceased
- 1994-11-21 CA CA002182101A patent/CA2182101C/en not_active Expired - Fee Related
- 1994-11-21 HU HU9602100A patent/HU221633B1/hu not_active IP Right Cessation
- 1994-11-21 WO PCT/IB1994/000365 patent/WO1995020587A1/en active IP Right Grant
- 1994-11-21 CZ CZ19962256A patent/CZ286757B6/cs not_active IP Right Cessation
- 1994-11-21 RU RU96117381A patent/RU2126404C1/ru not_active IP Right Cessation
- 1994-11-21 PL PL94315681A patent/PL179448B1/pl unknown
- 1994-11-21 DE DE69420053T patent/DE69420053T2/de not_active Expired - Fee Related
- 1994-11-21 NZ NZ275151A patent/NZ275151A/en unknown
- 1994-11-21 JP JP7519959A patent/JP2866743B2/ja not_active Expired - Lifetime
- 1994-11-21 US US08/687,542 patent/US5744483A/en not_active Expired - Fee Related
- 1994-11-21 ES ES94931668T patent/ES2134361T3/es not_active Expired - Lifetime
- 1994-11-21 DK DK94931668T patent/DK0741724T3/da active
- 1994-11-21 EP EP94931668A patent/EP0741724B1/en not_active Expired - Lifetime
- 1994-11-21 BR BR9408506A patent/BR9408506A/pt not_active Application Discontinuation
- 1994-11-21 AT AT94931668T patent/ATE183184T1/de not_active IP Right Cessation
- 1994-11-22 TW TW083110873A patent/TW449591B/zh active
-
1995
- 1995-01-18 PE PE1995259688A patent/PE43795A1/es not_active Application Discontinuation
- 1995-01-23 IL IL11241595A patent/IL112415A/xx not_active IP Right Cessation
- 1995-01-27 CO CO95003001A patent/CO4230161A1/es unknown
- 1995-01-27 MY MYPI95000224A patent/MY111623A/en unknown
- 1995-01-28 EG EG6795A patent/EG20672A/xx active
- 1995-01-30 BR BR9500380A patent/BR9500380A/pt not_active IP Right Cessation
- 1995-01-30 ZA ZA95692A patent/ZA95692B/xx unknown
- 1995-01-30 FI FI950403A patent/FI113769B/fi not_active IP Right Cessation
-
1996
- 1996-07-30 NO NO963186A patent/NO309190B1/no unknown
-
1999
- 1999-09-29 GR GR990402449T patent/GR3031356T3/el unknown
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