NO301979B1 - Analogifremgangsmåte for fremstilling av neurobeskyttende indolon- og beslektede derivater - Google Patents

Analogifremgangsmåte for fremstilling av neurobeskyttende indolon- og beslektede derivater Download PDF

Info

Publication number: NO301979B1
Authority: NO; Norway
Prior art keywords: hydroxy; mmol; ethyl acetate; product; hydrogen
Prior art date: 1990-05-10

Application number

NO924310A

Other languages

English (en)

Norwegian (no)

Other versions

NO924310L (no

NO924310D0 (no

Inventor

Bertrand Leo Chenard

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-05-10

Filing date

1992-11-09

Publication date

1998-01-05

1992-11-09 Application filed by Pfizer filed Critical Pfizer

1992-11-09 Publication of NO924310L publication Critical patent/NO924310L/no

1992-11-09 Publication of NO924310D0 publication Critical patent/NO924310D0/no

1998-01-05 Publication of NO301979B1 publication Critical patent/NO301979B1/no

Links

238000000034 method Methods 0.000 title claims abstract description 31
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230000000324 neuroprotective effect Effects 0.000 title description 6
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FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 title 1
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150000003840 hydrochlorides Chemical class 0.000 description 1
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
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239000012312 sodium hydride Substances 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- 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
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms

Landscapes

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)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)

NO924310A 1990-05-10 1992-11-09 Analogifremgangsmåte for fremstilling av neurobeskyttende indolon- og beslektede derivater NO301979B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US52233290A	1990-05-10	1990-05-10
PCT/US1991/001470 WO1991017156A1 (en)	1990-05-10	1991-03-04	Neuroprotective indolone and related derivatives

Publications (3)

Publication Number	Publication Date
NO924310L NO924310L (no)	1992-11-09
NO924310D0 NO924310D0 (no)	1992-11-09
NO301979B1 true NO301979B1 (no)	1998-01-05

Family

ID=24080448

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO924310A NO301979B1 (no)	1990-05-10	1992-11-09	Analogifremgangsmåte for fremstilling av neurobeskyttende indolon- og beslektede derivater

Country Status (30)

Country	Link
US (1)	US5306723A (cs)
EP (1)	EP0554247B1 (cs)
JP (1)	JPH0699423B2 (cs)
KR (1)	KR0163355B1 (cs)
CN (1)	CN1037439C (cs)
AT (1)	ATE192149T1 (cs)
AU (1)	AU642994B2 (cs)
BR (1)	BR9106432A (cs)
CA (1)	CA2080475C (cs)
CZ (1)	CZ280560B6 (cs)
DE (1)	DE69132141T2 (cs)
DK (1)	DK0554247T3 (cs)
EG (1)	EG19647A (cs)
ES (1)	ES2146578T3 (cs)
FI (1)	FI109121B (cs)
GR (1)	GR3034005T3 (cs)
HU (1)	HU221193B1 (cs)
IE (1)	IE911569A1 (cs)
IL (1)	IL98056A (cs)
MY (1)	MY107799A (cs)
NO (1)	NO301979B1 (cs)
PH (1)	PH29902A (cs)
PL (1)	PL169267B1 (cs)
PT (1)	PT97602B (cs)
RU (1)	RU2068414C1 (cs)
SK (1)	SK280833B6 (cs)
TW (1)	TW198720B (cs)
WO (1)	WO1991017156A1 (cs)
YU (1)	YU48528B (cs)
ZA (1)	ZA913494B (cs)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HUT65836A (en) *	1991-04-18	1994-07-28	Pfizer	Process for producing phenol-esters of 1-(hydroxy-phenyl)-2-piperidino-1-alkanol derivatives and pharmaceutical compositions containing them
US5594007A (en) *	1991-04-18	1997-01-14	Pfizer Inc.	Method for treating spinal cord trauma with phenolic 2-piperidino-1-alkanols
PL169884B1 (pl) *	1991-07-17	1996-09-30	Pfizer	Sposób wytwarzania nowych pochodnych 2-(4-hydroksypiperydyno)-1-alkanolowych PL PL PL
FR2688504B1 (fr) *	1992-03-13	1995-05-05	Synthelabo	Derives de 2-(piperidin-1-yl)ethanol, leur preparation et leur application en therapeutique.
US5319096A (en) *	1992-04-03	1994-06-07	Hoechst-Roussel Pharmaceuticals Inc.	(1H-indol-1-yl)-2-(amino) acetamides and related (1H-indol-1-yl)-(aminoalkyl)amides, pharmaceutical composition and use
US6255322B1 (en)	1992-06-19	2001-07-03	Pfizer Inc.	2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents
US5436255A (en) *	1992-07-23	1995-07-25	Pfizer Inc.	Method of treating diseases susceptable to treatment by blocking NMDA-receptors
WO1994010166A1 (en) *	1992-10-30	1994-05-11	Pfizer Inc.	Neuroprotective 3,4-dihydro-2(1h)-quinolone compounds
US5498610A (en) *	1992-11-06	1996-03-12	Pfizer Inc.	Neuroprotective indolone and related derivatives
CA2197451C (en) *	1994-08-18	2001-01-23	Bertrand L. Chenard	Neuroprotective 3-(piperidinyl-1)-chroman-4,7-diol and 1-(4-hydrophenyl)-2-(piperidinyl-1)-alkanol derivatives
GB9510459D0 (en)	1995-05-24	1995-07-19	Zeneca Ltd	Bicyclic amines
ZA9610741B (en)	1995-12-22	1997-06-24	Warner Lambert Co	4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610738B (en)	1995-12-22	1997-06-24	Warner Lambert Co	Subtype selective nmda receptor ligands and the use thereof
ZA9610745B (en) *	1995-12-22	1997-06-24	Warner Lambert Co	4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610736B (en) *	1995-12-22	1997-06-27	Warner Lambert Co	2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists
TW427978B (en) *	1996-02-03	2001-04-01	Hoffmann La Roche	Tetrahydroisoquinoline derivatives
IL126882A0 (en) *	1996-05-13	1999-09-22	Zeneca Ltd	Bicyclic amines as insecticides
GB9623944D0 (en) *	1996-11-15	1997-01-08	Zeneca Ltd	Bicyclic amine derivatives
GB9624114D0 (en) *	1996-11-20	1997-01-08	Zeneca Ltd	Pesticidal bicyclic amine derivatives
GB9624611D0 (en)	1996-11-26	1997-01-15	Zeneca Ltd	Bicyclic amine compounds
DE69727694T2 (de)	1996-11-26	2004-07-29	Syngenta Ltd., Guildford	8-azabicyclo 3.2.1]octan-, 8-azabicyclo 3.2.1]oct-6-en-, 9-azabicyclo 3.3.1]nonan-, 9-aza-3-oxabicyclo 3.3.1]nonan- und 9-aza-3-thiabicyclo 3.3.1]nonan-derivate, ihre herstellung und ihre verwendung als insektizide
EP0846683B1 (en) *	1996-12-03	2001-09-19	F. Hoffmann-La Roche Ag	4-Hydroxy-piperidine derivatives
CA2220649C (en)	1996-12-03	2007-02-13	F. Hoffmann-La Roche Ag	4-hydroxy-piperidine derivatives
WO2000064422A2 (en) *	1999-04-27	2000-11-02	Smithkline Beecham P.L.C.	Novel treatment of neurotraumatic conditions with raf inhibitor
US6291499B1 (en)	1999-10-29	2001-09-18	Merck & Co., Inc.	2-cyclohexyl benzimidazole NMDA/NR2B antagonists
AU1153601A (en)	1999-10-29	2001-05-08	Merck Sharp & Dohme Limited	Method to treat pain utilizing benzimidazole NMDA NR2B antagonists
US6316474B1 (en)	1999-10-29	2001-11-13	Merck & Co., Inc.	2-benzyl and 2-heteroaryl benzimidazole NMDA/NR2B antagonists
US6380205B1 (en)	1999-10-29	2002-04-30	Merck & Co., Inc.	2-cyclohexyl quinazoline NMDA/NR2B antagonists
US6476041B1 (en)	1999-10-29	2002-11-05	Merck & Co., Inc.	1,4 substituted piperidinyl NMDA/NR2B antagonists
US6432976B1 (en)	1999-10-29	2002-08-13	Merck & Co., Inc.	8-aza-bicyclo[3.2.1]octane NMDA/NR2B antagonists
US6489477B1 (en)	1999-10-29	2002-12-03	Merck & Co., Inc.	2-aza-bicyclo[2.2.2]octane NMDA/NR2B antigonists
US6495561B2 (en)	1999-10-29	2002-12-17	Merck & Co., Inc.	2-cyclohexyl imidazopyridine NMDA/NR2B antagonists
US6369076B1 (en)	1999-10-29	2002-04-09	Merck & Co. Inc.	5-benzyl-octahydroindole and 6-benzyl-decahydroquinoline NMDA/NR2B antagonists
CZ20032258A3 (cs)	2001-02-23	2004-01-14	Merck & Co., Inc.	N-substituované nearylové heterocyklické sloučeniny
WO2002080928A1 (en)	2001-04-03	2002-10-17	Merck & Co., Inc.	N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists
US7148236B2 (en) *	2002-01-17	2006-12-12	Merck & Co., Inc.	Modulators of acetylcholine receptors
US6713490B2 (en)	2002-04-26	2004-03-30	Pfizer, Inc.	3,4-dihydroquinolin-2(1H)-one compounds as NR2B receptor antagonists
EP1673367A1 (en) *	2003-10-08	2006-06-28	Pfizer, Inc.	Fused lactam compounds
EP1838705A2 (en) *	2005-01-13	2007-10-03	Neurosearch A/S	3,8-substituted 8-aza-bicyclo [3.2.1] octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors

Family Cites Families (16)

* Cited by examiner, † Cited by third party
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 (cs) *	1966-09-27	1968-01-22
JPS51118772A (en) *	1975-04-09	1976-10-18	Otsuka Pharmaceut Co Ltd	Method for preparing carbostyryl derivatives
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
PH17194A (en) *	1980-03-06	1984-06-19	Otsuka Pharma Co Ltd	Novel carbostyril derivatives,and pharmaceutical composition containing the same
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
JPS57142972A (en) *	1981-02-27	1982-09-03	Otsuka Pharmaceut Co Ltd	Carbostyril derivative
FR2534580A1 (fr) *	1982-10-13	1984-04-20	Synthelabo	Derives de phenyl-1 piperidino-2 propanol, leur preparation, et medicaments qui les contiennent
FR2546166B1 (fr) *	1983-05-19	1985-10-25	Synthelabo	Enantiomeres du erythro (benzyl-4 piperidino)-2 (hydroxy-4 ou benzyloxy-4 phenyl)-1 propanol, leur preparation et leur application en therapeutique
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
KR910006138B1 (ko) *	1986-09-30	1991-08-16	에자이 가부시끼가이샤	환상아민 유도체
EP0322361A3 (de) *	1987-12-23	1990-01-24	Ciba-Geigy Ag	Weitere hydrierte 1-Benzooxacycloalkylpyridincarbonsäureverbindungen
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
EP0398578B1 (en) *	1989-05-17	1997-03-12	Pfizer Inc.	2-piperidino-1-alkanol derivatives as antiischemic agents

1991
- 1991-03-04 EP EP91905608A patent/EP0554247B1/en not_active Expired - Lifetime
- 1991-03-04 KR KR1019920702794A patent/KR0163355B1/ko not_active IP Right Cessation
- 1991-03-04 WO PCT/US1991/001470 patent/WO1991017156A1/en active IP Right Grant
- 1991-03-04 CA CA002080475A patent/CA2080475C/en not_active Expired - Fee Related
- 1991-03-04 BR BR919106432A patent/BR9106432A/pt not_active Application Discontinuation
- 1991-03-04 HU HU9203515A patent/HU221193B1/hu not_active IP Right Cessation
- 1991-03-04 JP JP3505475A patent/JPH0699423B2/ja not_active Expired - Fee Related
- 1991-03-04 DK DK91905608T patent/DK0554247T3/da active
- 1991-03-04 RU RU9192016415A patent/RU2068414C1/ru not_active IP Right Cessation
- 1991-03-04 AU AU74565/91A patent/AU642994B2/en not_active Ceased
- 1991-03-04 AT AT91905608T patent/ATE192149T1/de not_active IP Right Cessation
- 1991-03-04 PL PL91296711A patent/PL169267B1/pl not_active IP Right Cessation
- 1991-03-04 ES ES91905608T patent/ES2146578T3/es not_active Expired - Lifetime
- 1991-03-04 DE DE69132141T patent/DE69132141T2/de not_active Expired - Fee Related
- 1991-03-04 US US07/941,118 patent/US5306723A/en not_active Expired - Fee Related
- 1991-04-02 TW TW080102540A patent/TW198720B/zh active
- 1991-04-24 PH PH42344A patent/PH29902A/en unknown
- 1991-05-03 IL IL9805691A patent/IL98056A/en not_active IP Right Cessation
- 1991-05-08 PT PT97602A patent/PT97602B/pt active IP Right Grant
- 1991-05-08 CZ CS911354A patent/CZ280560B6/cs not_active IP Right Cessation
- 1991-05-08 EG EG27191A patent/EG19647A/xx active
- 1991-05-08 MY MYPI91000778A patent/MY107799A/en unknown
- 1991-05-08 SK SK1354-91A patent/SK280833B6/sk unknown
- 1991-05-08 ZA ZA913494A patent/ZA913494B/xx unknown
- 1991-05-09 YU YU81091A patent/YU48528B/sh unknown
- 1991-05-09 CN CN91103022A patent/CN1037439C/zh not_active Expired - Fee Related
- 1991-05-09 IE IE156991A patent/IE911569A1/en not_active IP Right Cessation
1992
- 1992-11-09 NO NO924310A patent/NO301979B1/no not_active IP Right Cessation
- 1992-11-09 FI FI925069A patent/FI109121B/fi not_active IP Right Cessation
2000
- 2000-07-24 GR GR20000401691T patent/GR3034005T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
IL98056A (en)	1995-11-27
JPH05506433A (ja)	1993-09-22
CZ280560B6 (cs)	1996-02-14
CN1037439C (zh)	1998-02-18
AU7456591A (en)	1991-11-27
BR9106432A (pt)	1993-05-04
SK280833B6 (sk)	2000-08-14
FI109121B (fi)	2002-05-31
PT97602B (pt)	1998-08-31
KR930700482A (ko)	1993-03-15
JPH0699423B2 (ja)	1994-12-07
DE69132141D1 (de)	2000-05-31
KR0163355B1 (ko)	1998-12-01
US5306723A (en)	1994-04-26
EP0554247A1 (en)	1993-08-11
HU221193B1 (en)	2002-08-28
CA2080475A1 (en)	1991-11-11
IE911569A1 (en)	1991-11-20
YU48528B (sh)	1998-11-05
MY107799A (en)	1996-06-29
NO924310L (no)	1992-11-09
RU2068414C1 (ru)	1996-10-27
HU9203515D0 (en)	1993-01-28
CA2080475C (en)	2001-04-17
PH29902A (en)	1996-09-16
PT97602A (pt)	1992-02-28
CS135491A3 (en)	1992-05-13
FI925069A (fi)	1992-11-09
GR3034005T3 (en)	2000-11-30
DE69132141T2 (de)	2000-09-21
FI925069A0 (fi)	1992-11-09
WO1991017156A1 (en)	1991-11-14
EP0554247B1 (en)	2000-04-26
DK0554247T3 (da)	2000-08-07
PL169267B1 (pl)	1996-06-28
TW198720B (cs)	1993-01-21
ES2146578T3 (es)	2000-08-16
EG19647A (en)	1995-08-30
NO924310D0 (no)	1992-11-09
CN1056497A (zh)	1991-11-27
YU81091A (sh)	1993-11-16
ZA913494B (en)	1992-12-30
AU642994B2 (en)	1993-11-04
IL98056A0 (en)	1992-06-21
HUT62879A (en)	1993-06-28
ATE192149T1 (de)	2000-05-15

Legal Events

Date	Code	Title	Description
2005-11-14	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO301979B1 (no)	1998-01-05	Analogifremgangsmåte for fremstilling av neurobeskyttende indolon- og beslektede derivater
US7737170B2 (en)	2010-06-15	Uses of 2-(1H-indolylsulfanyl)-benzyl amine derivatives as SSRIS
US6395742B1 (en)	2002-05-28	2,4-diaminopyrimidine derivatives
US20020103205A1 (en)	2002-08-01	Muscarinic antagonists
SK278321B6 (en)	1996-10-02	Isatin derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same
US6046213A (en)	2000-04-04	Neuroprotective 3-(piperidinyl-1)-chroman-4,7-diol and 1-(4-hydroxyphenyl)-2-(piperidinyl-1)-alkanol derivatives
US5498610A (en)	1996-03-12	Neuroprotective indolone and related derivatives
TW201038269A (en)	2010-11-01	Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
NO178399B (no)	1995-12-11	Analogifremgangsmåte for fremstilling av terapeutisk aktive 3-piperidino-4-hydroksykromanderivater og analoger derav
NO180445B (no)	1997-01-13	2-(4-hydroksypiperidino)-1-alkanol-derivater som anti-iskemiske midler
US6355642B1 (en)	2002-03-12	Tetrahydrobenzindole compounds
CA2903276A1 (en)	2014-09-25	Muscarinic agonists
ES2299033T3 (es)	2008-05-16	Derivados de indol-2-ona para el tratamiento de trastornos del sistema nervioso central, trastornos gastrointestinales y trastornos cardiovasculares.
EP1860100B1 (en)	2011-03-02	2-(1H-indolylsulfanyl)-benzyl amine derivatives as SSRI
JPS63233972A (ja)	1988-09-29	新規なインドールカルボキサミド誘導体及びその塩類、それらの製造法及び中間体、これら誘導体の医薬品への使用並びにそれらを含有する組成物