FI92701B - Förfarande för framställning av terapeutiskt användbara 4- eller 6-substituerade trimetylpyrrolo/2,3-b/indolkarbamater - Google Patents
Förfarande för framställning av terapeutiskt användbara 4- eller 6-substituerade trimetylpyrrolo/2,3-b/indolkarbamater Download PDFInfo
- Publication number
- FI92701B FI92701B FI905418A FI905418A FI92701B FI 92701 B FI92701 B FI 92701B FI 905418 A FI905418 A FI 905418A FI 905418 A FI905418 A FI 905418A FI 92701 B FI92701 B FI 92701B
- Authority
- FI
- Finland
- Prior art keywords
- cis
- hexahydro
- trimethylpyrrolo
- indol
- added
- Prior art date
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cephalosporin Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Claims (5)
1. Förfarande för framställning av terapeutiskt användbara 4- eller 6-substituerade trimetylpyrrolo- 5 [2,3-b]indolkarbamater med formeln I R\ ° \ Il / f3
10 H (I) x7 I H l Λ ch3 ch3 väri Rx är C1.4-alkyl, cyklohexyl, fenyl eller bensyl(C1.4-alkyl) och X är väte eller halogen; eller deras optiska 15 isomerer (inkluderande 3aS-cis- och 3aR-cis-isomererna) eller racemiska blandningar eller farmaceutiskt godtagbara syraadditionssalter, kännetecknat därav, att man omsätter en förening med formeln III 20 ^ Ρ>3 --1 u, IL 1 <in) y ' H I L3 ; 25 väri X betecknar sanuna som ovan, med ett isocyanat med formeln R1-N=C=0, väri Rx betecknar sanuna som ovan, i ett inert lösningsmedel i närvaro av en bicyklisk amidinkata-lysator, och, ifall önskvärt överför den erhällna före-ningen med formeln I tili ett farmaceutiskt godtagbart 30 syraadditionssalt.
2. Förfarande enligt patentkrav 1, kännetecknat därav, att man framställer cis-(±)-1,2,3,3a, 8,8a-hexahydro-l, 3a, 8-trimetylpyrrolo[2,3-b] in-dol-6-ylmetylkarbamat, dess 3aS-cis- eller 3aR-cis-isomer 35 eller dess farmaceutiskt godtagbart syraadditionssalt. • 11 39 92701
3. Förfarande enligt patentkrav 1, känne- t e c k n a t därav, att man framställer cis-(±)-5-brom-1,2,3,3a,8,8a-hexahydro-1,3a, 8-trimetylpyrrolo[2,3-b] in-dol-6-ylmetylkarbamat, dess 3aS-cis- eller 3aR-cis-isomer 5 eller dess farmaceutiskt godtagbart syraadditionssalt.
4. Förfarande enligt patentkrav 1, känne-t e c k n a t därav, att man framställer cis-(±)- 1,2,3,3a, 8,8a-hexahydro-l, 3a, 8-trimetylpyrrolo[ 2,3-b] in-dol-4-ylmetylkarbamat, dess 3aS-cis- eller 3aR-cis-isomer 10 eller dess farmaceutiskt godtagbart syraadditionssalt.
5. Förfarande enligt patentkrav 1, känne-t e c k n a t därav, att man framställer cis-(±)- 1,2,3,3a, 8,8a-hexahydro-l, 3a, 8-trimetylpyrrolo[2,3-b] in-dol-4-ylcyklohexylkarbamat, dess 3aS-cis- eller 3aR-cis-15 isomer eller dess farmaceutiskt godtagbart syraadditionssalt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI933119A FI94761C (sv) | 1989-11-03 | 1993-07-07 | 4- och 6-substituerade 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimetylpyrrolo/2,3-b/indolderivat |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/413,901 US4914102A (en) | 1989-09-28 | 1989-09-28 | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US41390189 | 1989-09-28 | ||
| US43110389 | 1989-11-03 | ||
| US07/431,103 US5081117A (en) | 1989-09-28 | 1989-11-03 | 4- and 6-carbamates related to physostigmine and intermediates for the preparation thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI905418A0 FI905418A0 (sv) | 1990-11-01 |
| FI92701B true FI92701B (sv) | 1994-09-15 |
| FI92701C FI92701C (sv) | 1994-12-27 |
Family
ID=40149690
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI904730A FI93961C (sv) | 1989-09-28 | 1990-09-26 | Förfarande för framställning av terapeutiskt användbara 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimetylpyrrolo/2,3-b/indol-5-ylmorfolinyl- och piperidinylkarbamater |
| FI905418A FI92701C (sv) | 1989-09-28 | 1990-11-01 | Förfarande för framställning av terapeutiskt användbara 4- eller 6-substituerade trimetylpyrrolo/2,3-b/indolkarbamater |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI904730A FI93961C (sv) | 1989-09-28 | 1990-09-26 | Förfarande för framställning av terapeutiskt användbara 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimetylpyrrolo/2,3-b/indol-5-ylmorfolinyl- och piperidinylkarbamater |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US4914102A (sv) |
| EP (2) | EP0420140B1 (sv) |
| JP (2) | JPH0723377B2 (sv) |
| KR (1) | KR100189665B1 (sv) |
| AT (2) | ATE156825T1 (sv) |
| AU (3) | AU639943B2 (sv) |
| CA (2) | CA2026381A1 (sv) |
| CZ (1) | CZ279604B6 (sv) |
| DE (2) | DE69031259T2 (sv) |
| DK (2) | DK0420140T3 (sv) |
| ES (2) | ES2104572T3 (sv) |
| FI (2) | FI93961C (sv) |
| GR (2) | GR3019468T3 (sv) |
| HU (1) | HU206355B (sv) |
| IE (1) | IE72153B1 (sv) |
| IL (2) | IL95807A (sv) |
| NO (2) | NO174469B (sv) |
| NZ (2) | NZ235460A (sv) |
| PL (1) | PL287618A1 (sv) |
| PT (2) | PT95449B (sv) |
| ZA (2) | ZA907725B (sv) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4791107A (en) * | 1986-07-16 | 1988-12-13 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use |
| US4971992A (en) * | 1989-03-27 | 1990-11-20 | Hoechst-Roussel Pharmaceuticals Inc. | Carbonate derivatives of eseroline |
| DE69020989T2 (de) * | 1989-09-19 | 1996-02-08 | Hoechst Roussel Pharma | Verfahren zur Racematspaltung von 5-alkoxy-substituierten (+/-)-1,3-dimethyloxindolylethylaminen. |
| US4914102A (en) * | 1989-09-28 | 1990-04-03 | Hoechst Roussel Pharmaceuticals, Inc. | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US5077289A (en) * | 1989-11-30 | 1991-12-31 | Hoechst Roussel Pharmaceuticals Inc. | Memory enhancing and analgesic aminocarbonylcarbamates related to physostigmine |
| ES2120407T3 (es) * | 1990-01-22 | 1998-11-01 | Hoechst Marion Roussel Inc | Procedimiento para la sintesis enantioselectiva de oxindoles alquilados, utilizados como productos intermedios en la preparacion de fisostigmina. |
| DE69032046T2 (de) * | 1990-06-27 | 1998-08-27 | Hoechst Marion Roussel Inc | Tetrahydroisochinolinylcarbamate von 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo [2,3-b] indol |
| US5171750A (en) * | 1991-09-26 | 1992-12-15 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted phenserines as specific inhibitors of acetylcholinesterase |
| EP0606366B1 (en) * | 1991-09-26 | 2003-06-04 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY of the DEPARTMENT OF HEALTH AND HUMAN SERVICES | Substituted phenserines and phenylcarbamates of (-)-eseroline, (-)-n1-noreseroline, and (-)-n1-benzylnoreseroline; as specific inhibitors of acetylcholinesterase |
| US5153193A (en) * | 1991-10-01 | 1992-10-06 | Hoechst-Roussel Pharmaceuticals Incorporated | Carbamate derivatives of 4-amino-3-isoxazolidinones, 3-amino-1-hydroxypyrrolidin-2-ones and 1-amino-1-cyclopropanecarboxylic acid analogs |
| IT1253007B (it) * | 1991-12-31 | 1995-07-10 | Aesculapius Farma Srl | Derivati dell'eserolina ad attivita' anticolinesterasica,procedimento per la loro preparazione e composizioni farmaceutiche che li contengono |
| NZ248180A (en) * | 1992-07-21 | 1995-02-24 | Hoechst Roussel Pharma | Process for the preparation of physostigmine carbamate derivatives |
| US5302721A (en) * | 1992-07-21 | 1994-04-12 | Hoechst-Roussel Pharmaceuticals Incorporated | Method of preparation of physostigmine carbamate derivatives from eseretholes |
| US5409948A (en) * | 1992-11-23 | 1995-04-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method for treating cognitive disorders with phenserine |
| US5665880A (en) * | 1996-10-31 | 1997-09-09 | Hoechst Marion Roussel, Inc. | Method of preparation of physostigmine carbamate derivatives from eseretholes |
| US5677457A (en) * | 1996-12-19 | 1997-10-14 | Hoechst Marion Roussel, Inc. | Method of preparation of physostigmine carbamate derivatives from eseroline ethers |
| US6218383B1 (en) | 1998-08-07 | 2001-04-17 | Targacept, Inc. | Pharmaceutical compositions for the prevention and treatment of central nervous system disorders |
| CN100375619C (zh) * | 2002-06-14 | 2008-03-19 | 富山化学工业株式会社 | 改善脑功能的药物组合物及其用途 |
| AU2004285893B2 (en) * | 2003-10-21 | 2011-12-15 | Colucid Pharmaceuticals, Inc. | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
| WO2005072713A2 (en) | 2004-01-27 | 2005-08-11 | The Feinstein Institute For Medical Research | Cholinesterase inhibitors for treating inflammation |
| US20050182044A1 (en) * | 2004-02-17 | 2005-08-18 | Bruinsma Gosse B. | Combinatorial therapy with an acetylcholinesterase inhibitor and (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3,-b]indol-5-yl phenylcarbamate |
| CA2508585A1 (en) * | 2004-06-01 | 2005-12-01 | Axonyx, Inc. | Transdermal delivery system for treatment of cognitive disorders |
| CA2509265A1 (en) * | 2004-06-08 | 2005-12-08 | Axonyx, Inc. | Methods of delaying alzheimer's disease progression using a beta-amyloid precursor protein inhibitor and hmg coa reductase inhibitor |
| WO2006060082A1 (en) * | 2004-10-22 | 2006-06-08 | THE GOVERNMENT OF THE U.S.A. as represented by THE SEC., DEPT. OF HEALTH & HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH | Tricyclic compounds, preparation thereof and use thereof as cholinesterase activity inhibitors |
| US20110212928A1 (en) | 2010-02-09 | 2011-09-01 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| EP2919788A4 (en) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | METHODS AND COMPOSITIONS FOR THE TREATMENT OF SCHIZOPHRENIA |
| NZ708595A (en) | 2012-12-13 | 2019-06-28 | H Lundbeck As | Compositions comprising vortioxetine and donepezil |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| ES2881081T3 (es) | 2013-03-15 | 2021-11-26 | Agenebio Inc | Procedimientos y composiciones para mejorar la función cognitiva |
| JP6899043B2 (ja) | 2015-05-22 | 2021-07-07 | エージンバイオ， インコーポレイテッド | レベチラセタムの持続放出性医薬組成物 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3897451A (en) * | 1973-04-27 | 1975-07-29 | Univ Ohio State Res Found | Synthesis of oxindoles from anilines and intermediates therein |
| IT1109003B (it) * | 1977-09-20 | 1985-12-16 | Univ Firenze | Derivati dell 1 2 3 8 3 a 8 a esai dropirrolo 23 b indolo |
| IT1199076B (it) * | 1984-03-01 | 1988-12-30 | Consiglio Nazionale Ricerche | Derivati della fisostigmina con proprieta'di inibizione della aceticolinesterasi e relativo procedimento di produzione |
| US4760083A (en) * | 1986-04-10 | 1988-07-26 | E. I. Dupont De Nemours & Company | 3,3-disubstituted indolines |
| US4791107A (en) * | 1986-07-16 | 1988-12-13 | Hoechst-Roussel Pharmaceuticals, Inc. | Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use |
| IT1225462B (it) * | 1987-04-03 | 1990-11-14 | Mediolanum Farmaceutici Srl | Sali organici di derivati della fisostigmina |
| US4741107A (en) * | 1987-07-31 | 1988-05-03 | Circle Jeffrey L | Artwork aid adapted for facilitating placement of lettering along arc of a circle |
| US4971992A (en) * | 1989-03-27 | 1990-11-20 | Hoechst-Roussel Pharmaceuticals Inc. | Carbonate derivatives of eseroline |
| US5006537A (en) * | 1989-08-02 | 1991-04-09 | Hoechst-Roussel Pharmaceuticals, Inc. | 1,3-dihydro-1-(pyridinylamino)-2H-indol-2-ones |
| DE69020989T2 (de) * | 1989-09-19 | 1996-02-08 | Hoechst Roussel Pharma | Verfahren zur Racematspaltung von 5-alkoxy-substituierten (+/-)-1,3-dimethyloxindolylethylaminen. |
| US4914102A (en) * | 1989-09-28 | 1990-04-03 | Hoechst Roussel Pharmaceuticals, Inc. | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| US5077289A (en) * | 1989-11-30 | 1991-12-31 | Hoechst Roussel Pharmaceuticals Inc. | Memory enhancing and analgesic aminocarbonylcarbamates related to physostigmine |
| ES2120407T3 (es) * | 1990-01-22 | 1998-11-01 | Hoechst Marion Roussel Inc | Procedimiento para la sintesis enantioselectiva de oxindoles alquilados, utilizados como productos intermedios en la preparacion de fisostigmina. |
-
1989
- 1989-09-28 US US07/413,901 patent/US4914102A/en not_active Expired - Fee Related
- 1989-11-03 US US07/431,103 patent/US5081117A/en not_active Expired - Fee Related
-
1990
- 1990-09-25 DE DE69031259T patent/DE69031259T2/de not_active Expired - Fee Related
- 1990-09-25 EP EP90118376A patent/EP0420140B1/en not_active Expired - Lifetime
- 1990-09-25 ES ES90118376T patent/ES2104572T3/es not_active Expired - Lifetime
- 1990-09-25 DK DK90118376.4T patent/DK0420140T3/da active
- 1990-09-25 AT AT90118376T patent/ATE156825T1/de not_active IP Right Cessation
- 1990-09-26 NZ NZ235460A patent/NZ235460A/xx unknown
- 1990-09-26 IL IL9580790A patent/IL95807A/en not_active IP Right Cessation
- 1990-09-26 FI FI904730A patent/FI93961C/sv not_active IP Right Cessation
- 1990-09-27 AU AU63227/90A patent/AU639943B2/en not_active Ceased
- 1990-09-27 JP JP2255477A patent/JPH0723377B2/ja not_active Expired - Lifetime
- 1990-09-27 NO NO904209A patent/NO174469B/no not_active IP Right Cessation
- 1990-09-27 PT PT95449A patent/PT95449B/pt not_active IP Right Cessation
- 1990-09-27 CA CA002026381A patent/CA2026381A1/en not_active Abandoned
- 1990-09-27 ZA ZA907725A patent/ZA907725B/xx unknown
- 1990-11-01 FI FI905418A patent/FI92701C/sv not_active IP Right Cessation
- 1990-11-01 KR KR1019900017657A patent/KR100189665B1/ko not_active IP Right Cessation
- 1990-11-01 NZ NZ235921A patent/NZ235921A/en unknown
- 1990-11-01 IL IL9620990A patent/IL96209A/en not_active IP Right Cessation
- 1990-11-02 PL PL28761890A patent/PL287618A1/xx unknown
- 1990-11-02 NO NO904783A patent/NO175980C/no not_active IP Right Cessation
- 1990-11-02 JP JP2295595A patent/JPH0780885B2/ja not_active Expired - Fee Related
- 1990-11-02 CZ CS905407A patent/CZ279604B6/cs not_active IP Right Cessation
- 1990-11-02 PT PT95772A patent/PT95772B/pt not_active IP Right Cessation
- 1990-11-02 IE IE396590A patent/IE72153B1/en not_active IP Right Cessation
- 1990-11-02 AU AU65712/90A patent/AU635575B2/en not_active Ceased
- 1990-11-02 ZA ZA908800A patent/ZA908800B/xx unknown
- 1990-11-02 HU HU906999A patent/HU206355B/hu not_active IP Right Cessation
- 1990-11-02 CA CA002029265A patent/CA2029265C/en not_active Expired - Fee Related
- 1990-11-07 ES ES90121267T patent/ES2085309T3/es not_active Expired - Lifetime
- 1990-11-07 DE DE69025941T patent/DE69025941T2/de not_active Expired - Fee Related
- 1990-11-07 AT AT90121267T patent/ATE135355T1/de not_active IP Right Cessation
- 1990-11-07 DK DK90121267.0T patent/DK0484573T3/da active
- 1990-11-07 EP EP90121267A patent/EP0484573B1/en not_active Expired - Lifetime
-
1993
- 1993-01-27 AU AU32046/93A patent/AU646986B2/en not_active Ceased
-
1996
- 1996-03-29 GR GR960400847T patent/GR3019468T3/el unknown
-
1997
- 1997-10-14 GR GR970402666T patent/GR3025021T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Patent granted |
Owner name: HOECHST MARION ROUSSEL, INC. |
|
| BB | Publication of examined application | ||
| PC | Transfer of assignment of patent |
Owner name: HOECHST MARION ROUSSEL, INC. |
|
| MM | Patent lapsed |
Owner name: HOECHST MARION ROUSSEL INC., INC. |