NO310355B1 - Tetrahydrokinoliner som NMDA-antagonister, anvendelse derav, fremgangsmåte for fremstilling derav og farmasöytisk preparat - Google Patents

Tetrahydrokinoliner som NMDA-antagonister, anvendelse derav, fremgangsmåte for fremstilling derav og farmasöytisk preparat Download PDF

Info

Publication number: NO310355B1
Authority: NO; Norway
Prior art keywords: carboxylic acid; dichloro; quinoline; tetrahydro; solution
Prior art date: 1995-09-29

Application number

NO19981396A

Other languages

English (en)

Norwegian (no)

Other versions

NO981396D0 (no

NO981396L (no

Inventor

Romano Di Fabio

Simone Giacobbe

Barbara Bertani

Fabrizio Micheli

Original Assignee

Glaxo Wellcome Spa

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.)

1995-09-29

Filing date

1998-03-27

Publication date

2001-06-25

1995-09-29 Priority claimed from GBGB9519893.3A external-priority patent/GB9519893D0/en

1996-08-17 Priority claimed from GBGB9617306.7A external-priority patent/GB9617306D0/en

1998-03-27 Application filed by Glaxo Wellcome Spa filed Critical Glaxo Wellcome Spa

1998-03-27 Publication of NO981396D0 publication Critical patent/NO981396D0/no

1998-05-27 Publication of NO981396L publication Critical patent/NO981396L/no

2001-06-25 Publication of NO310355B1 publication Critical patent/NO310355B1/no

Links

238000000034 method Methods 0.000 title claims description 17
239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
238000002360 preparation method Methods 0.000 title description 19
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 title description 6
239000005557 antagonist Substances 0.000 title description 4
150000003530 tetrahydroquinolines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 158
-1 carbamoylmethyl Chemical group 0.000 claims description 64
238000006243 chemical reaction Methods 0.000 claims description 43
239000001257 hydrogen Substances 0.000 claims description 33
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150000003839 salts Chemical class 0.000 claims description 24
125000006239 protecting group Chemical group 0.000 claims description 23
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 13
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
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125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
OSJVTYVKQNOXPP-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CCC2=C1 OSJVTYVKQNOXPP-UHFFFAOYSA-N 0.000 claims description 5
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238000007363 ring formation reaction Methods 0.000 claims description 5
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LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims description 4
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125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
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238000005160 1H NMR spectroscopy Methods 0.000 description 40
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239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
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239000012047 saturated solution Substances 0.000 description 19
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239000012044 organic layer Substances 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/24—Antidepressants
- 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
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Virology (AREA)
Molecular Biology (AREA)
Oncology (AREA)
Addiction (AREA)
Cardiology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Communicable Diseases (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Otolaryngology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

NO19981396A 1995-09-29 1998-03-27 Tetrahydrokinoliner som NMDA-antagonister, anvendelse derav, fremgangsmåte for fremstilling derav og farmasöytisk preparat NO310355B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9519893.3A GB9519893D0 (en)	1995-09-29	1995-09-29	Heterocyclic compounds
GBGB9617306.7A GB9617306D0 (en)	1996-08-17	1996-08-17	Heterocyclic compounds
PCT/EP1996/004206 WO1997012870A1 (en)	1995-09-29	1996-09-26	Tetrahydroquinolines as nmda antagonists

Publications (3)

Publication Number	Publication Date
NO981396D0 NO981396D0 (no)	1998-03-27
NO981396L NO981396L (no)	1998-05-27
NO310355B1 true NO310355B1 (no)	2001-06-25

Family

ID=26307841

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981396A NO310355B1 (no)	1995-09-29	1998-03-27	Tetrahydrokinoliner som NMDA-antagonister, anvendelse derav, fremgangsmåte for fremstilling derav og farmasöytisk preparat

Country Status (28)

Country	Link
US (1)	US5977136A (de)
EP (1)	EP0854867B1 (de)
JP (1)	JP4108123B2 (de)
KR (1)	KR100464895B1 (de)
CN (1)	CN1130346C (de)
AP (1)	AP876A (de)
AR (1)	AR005233A1 (de)
AT (1)	ATE221520T1 (de)
AU (1)	AU708148B2 (de)
BR (1)	BR9610733A (de)
CA (1)	CA2232509A1 (de)
CZ (1)	CZ292379B6 (de)
DE (1)	DE69622731T2 (de)
DK (1)	DK0854867T3 (de)
EA (1)	EA000875B1 (de)
ES (1)	ES2180799T3 (de)
HU (1)	HUP9900040A3 (de)
IL (1)	IL123322A0 (de)
IS (1)	IS4677A (de)
MX (1)	MX9801967A (de)
NO (1)	NO310355B1 (de)
NZ (1)	NZ319596A (de)
PL (1)	PL186781B1 (de)
PT (1)	PT854867E (de)
SI (1)	SI0854867T1 (de)
TR (1)	TR199800531T1 (de)
TW (1)	TW460465B (de)
WO (1)	WO1997012870A1 (de)

Families Citing this family (17)

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Publication number	Priority date	Publication date	Assignee	Title
GB9617305D0 (en)	1996-08-17	1996-09-25	Glaxo Wellcome Spa	Heterocyclic compounds
GB9706294D0 (en) *	1997-03-26	1997-05-14	Glaxo Wellcome Spa	Heterocyclic compound
MY125037A (en)	1998-06-10	2006-07-31	Glaxo Wellcome Spa	1,2,3,4 tetrahydroquinoline derivatives
TW555757B (en) *	1998-07-31	2003-10-01	Akzo Nobel Nv	Aminomethylcarboxylic acid derivatives
EP1103552A4 (de) *	1998-08-07	2003-01-15	Takeda Chemical Industries Ltd	Benzothiepin-derivate, verfahren zu ihrer herstellung und ihre verwendungen
GB9929037D0 (en)	1999-12-08	2000-02-02	Glaxo Wellcome Spa	Heterocyclic derivatives
AU2002359875B2 (en) *	2001-12-28	2009-01-08	Acadia Pharmaceuticals Inc.	Tetrahydroquinoline analogues as muscarinic agonists
DE10236910A1 (de) *	2002-08-12	2004-03-11	Grünenthal GmbH	Substituierte 1,2,3,4-Tetrahydrochinolinderivate
JP4754566B2 (ja)	2005-07-22	2011-08-24	持田製薬株式会社	新規なヘテロシクリデンアセトアミド誘導体
RU2451014C2 (ru) *	2005-07-22	2012-05-20	Мотида Фармасьютикал Ко., Лтд.	Новое производное гетероциклиден ацетамида
AU2009221179A1 (en) *	2008-03-05	2009-09-11	Boehringer Ingelheim International Gmbh	Tricyclic pyridine derivatives, medicaments containing such compounds, their use and process for their preparation
EP2286808A1 (de) *	2009-08-18	2011-02-23	Rheinische Friedrich-Wilhelms Universität	Cytohesininhibitoren
KR20120123089A (ko)	2010-02-16	2012-11-07	화이자 인코포레이티드	5-ＨＴ₄ 수용체의 부분 효능제인 (Ｒ)-4-((4-((4-(테트라히드로푸란-3-일옥시)벤조［ｄ］이속사졸-3-일옥시)메틸)피페리딘-1-일)메틸)테트라히드로-2Ｈ-피란-4-올
AU2011217206A1 (en)	2010-02-19	2012-08-02	Boehringer Ingelheim International Gmbh	Tricyclic pyridine derivatives, medicaments containing such compounds, their use and process for their preparation
EP2760868B1 (de)	2011-08-17	2018-04-25	Boehringer Ingelheim International GmbH	Furo[3,4-c]chinolinderivate, medikamente mit solchen verbindungen, ihre verwendung und herstellungsverfahren dafür
WO2016114655A1 (en) *	2015-01-12	2016-07-21	Ry Pharma B.V.	Treating neuromuscular or neurologic disease through reducing gabaergic and/or glycinergic inhibitory neurotransmitter overstimulation
WO2017065602A1 (en) *	2015-10-13	2017-04-20	Ry Pharma B.V.	Treating neuromuscular or neurologic disease through reducing gabaergic and/or glycinergic inhibitory neurotransmitter overstimulation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL93610A0 (en) *	1989-03-08	1990-12-23	Merck Sharp & Dohme	Tetrahydroquinoline derivatives,their preparation and pharmaceutical compositions containing them

1996
- 1996-09-26 CZ CZ1998940A patent/CZ292379B6/cs not_active IP Right Cessation
- 1996-09-26 BR BR9610733A patent/BR9610733A/pt not_active IP Right Cessation
- 1996-09-26 PL PL96325966A patent/PL186781B1/pl not_active IP Right Cessation
- 1996-09-26 IL IL12332296A patent/IL123322A0/xx not_active IP Right Cessation
- 1996-09-26 AU AU72148/96A patent/AU708148B2/en not_active Ceased
- 1996-09-26 CA CA002232509A patent/CA2232509A1/en not_active Abandoned
- 1996-09-26 DK DK96933399T patent/DK0854867T3/da active
- 1996-09-26 US US09/029,860 patent/US5977136A/en not_active Expired - Fee Related
- 1996-09-26 NZ NZ319596A patent/NZ319596A/en not_active IP Right Cessation
- 1996-09-26 AT AT96933399T patent/ATE221520T1/de not_active IP Right Cessation
- 1996-09-26 PT PT96933399T patent/PT854867E/pt unknown
- 1996-09-26 ES ES96933399T patent/ES2180799T3/es not_active Expired - Lifetime
- 1996-09-26 SI SI9630523T patent/SI0854867T1/xx unknown
- 1996-09-26 DE DE69622731T patent/DE69622731T2/de not_active Expired - Lifetime
- 1996-09-26 EP EP96933399A patent/EP0854867B1/de not_active Expired - Lifetime
- 1996-09-26 HU HU9900040A patent/HUP9900040A3/hu unknown
- 1996-09-26 WO PCT/EP1996/004206 patent/WO1997012870A1/en not_active Ceased
- 1996-09-26 KR KR10-1998-0702321A patent/KR100464895B1/ko not_active Expired - Fee Related
- 1996-09-26 EA EA199800230A patent/EA000875B1/ru not_active IP Right Cessation
- 1996-09-26 TR TR1998/00531T patent/TR199800531T1/xx unknown
- 1996-09-26 AP APAP/P/1998/001212A patent/AP876A/en active
- 1996-09-26 JP JP51394797A patent/JP4108123B2/ja not_active Expired - Fee Related
- 1996-09-26 CN CN96198560A patent/CN1130346C/zh not_active Expired - Fee Related
- 1996-09-30 AR ARP960104543A patent/AR005233A1/es active IP Right Grant
- 1996-10-04 TW TW085112168A patent/TW460465B/zh not_active IP Right Cessation
1998
- 1998-02-27 IS IS4677A patent/IS4677A/is unknown
- 1998-03-12 MX MX9801967A patent/MX9801967A/es not_active IP Right Cessation
- 1998-03-27 NO NO19981396A patent/NO310355B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
MX9801967A (es)	1998-08-30
JPH11512728A (ja)	1999-11-02
BR9610733A (pt)	1999-07-13
JP4108123B2 (ja)	2008-06-25
KR100464895B1 (ko)	2005-05-16
NZ319596A (en)	1999-09-29
ATE221520T1 (de)	2002-08-15
DK0854867T3 (da)	2002-12-02
NO981396D0 (no)	1998-03-27
AP876A (en)	2000-09-27
CA2232509A1 (en)	1997-04-10
PT854867E (pt)	2002-12-31
IL123322A0 (en)	1998-09-24
HUP9900040A3 (en)	2001-01-29
SI0854867T1 (en)	2003-02-28
EP0854867A1 (de)	1998-07-29
AU708148B2 (en)	1999-07-29
CZ94098A3 (cs)	1998-07-15
TW460465B (en)	2001-10-21
KR19990063850A (ko)	1999-07-26
IS4677A (is)	1998-02-27
AP9801212A0 (en)	1998-03-31
ES2180799T3 (es)	2003-02-16
WO1997012870A1 (en)	1997-04-10
CZ292379B6 (cs)	2003-09-17
US5977136A (en)	1999-11-02
PL325966A1 (en)	1998-08-17
EP0854867B1 (de)	2002-07-31
EA199800230A1 (ru)	1998-10-29
HUP9900040A2 (hu)	1999-04-28
PL186781B1 (pl)	2004-02-27
AU7214896A (en)	1997-04-28
TR199800531T1 (xx)	1998-06-22
CN1202887A (zh)	1998-12-23
NO981396L (no)	1998-05-27
EA000875B1 (ru)	2000-06-26
DE69622731T2 (de)	2003-02-20
AR005233A1 (es)	1999-04-28
HK1009133A1 (en)	1999-05-28
CN1130346C (zh)	2003-12-10
DE69622731D1 (de)	2002-09-05

Legal Events

Date	Code	Title	Description
2011-05-09	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
DK169890B1 (da)	1995-03-27	3-Substitueret 2-carboxy-indolderivater, farmaceutisk præparat indeholdende forbindelserne, fremgangsmåde til fremstilling af forbindelserne samt anvendelse af forbindelserne til fremstilling af et lægemiddel
US6232313B1 (en)	2001-05-15	Pyridazino quinoline compounds
AP877A (en)	2000-09-27	Tetrahydroquinoline derivatives as EAA antagonists.
JP4108123B2 (ja)	2008-06-25	Ｎｍｄａアンタゴニストとしてのテトラヒドロキノリン
SK44996A3 (en)	1997-01-08	Indole derivatives, manufacturing process thereof and pharmaceutical composition containing them
NO309323B1 (no)	2001-01-15	Indolderivater, anvendelse derav og farmasöytisk preparat
MXPA97006605A (en)	1998-02-01	Indol derivatives as antagonists of amino acids exited
KR100586762B1 (ko)	2006-06-08	글리신 길항제로서의 테트라히드로퀴놀린 유도체
MXPA00012155A (en)	2002-03-05	Tetrahydroquinoline derivatives as glycine antagonists
HK1009133B (en)	2003-02-28	Tetrahydroquinolines as nmda antagonists
MXPA99008720A (en)	2000-01-01	Quinoline-2-carboxylic acid derivative and its use as excitatory amino acids antagonist
MXPA99001557A (en)	1999-09-01	Tetrahydroquinoline derivatives as eaa antagonists