DD296923A5 - Piperidinylbenzimidazoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeperate - Google Patents

Piperidinylbenzimidazoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeperate Download PDF

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Publication number: DD296923A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; choh; compounds; reaction; meaning
Prior art date: 1989-08-03

Application number

DD90343200A

Other languages

German (de)

English (en)

Inventor

Albert A Carr

John M Kane

Francis P Miller

Original Assignee

��@��@��@��Kk��

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.)

1989-08-03

Filing date

1990-08-02

Publication date

1991-12-19

1990-08-02 Application filed by ��@��@��@��Kk�� filed Critical ��@��@��@��Kk��

1991-12-19 Publication of DD296923A5 publication Critical patent/DD296923A5/de

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239000003814 drug Substances 0.000 title claims abstract description 4
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238000000034 method Methods 0.000 title claims description 49
229940079593 drug Drugs 0.000 title description 2
238000004519 manufacturing process Methods 0.000 title description 2
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
239000001257 hydrogen Substances 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 14
239000002253 acid Substances 0.000 claims abstract description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
JUYQSMXGDBGGSX-UHFFFAOYSA-N 2-piperidin-1-yl-1h-benzimidazole Chemical class C1CCCCN1C1=NC2=CC=CC=C2N1 JUYQSMXGDBGGSX-UHFFFAOYSA-N 0.000 claims description 41
238000002360 preparation method Methods 0.000 claims description 20
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VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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230000007062 hydrolysis Effects 0.000 description 3
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Classifications

- 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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

DD90343200A 1989-08-03 1990-08-02 Piperidinylbenzimidazoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeperate DD296923A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US38903689A	1989-08-03	1989-08-03

Publications (1)

Publication Number	Publication Date
DD296923A5 true DD296923A5 (de)	1991-12-19

Family

ID=23536563

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD90343200A DD296923A5 (de)	1989-08-03	1990-08-02	Piperidinylbenzimidazoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeperate

Country Status (9)

Country	Link
EP (1)	EP0411631B1 (fr)
JP (1)	JP2954992B2 (fr)
AT (1)	ATE104294T1 (fr)
AU (1)	AU625238B2 (fr)
CA (1)	CA2022451C (fr)
DD (1)	DD296923A5 (fr)
DE (1)	DE69008069T2 (fr)
DK (1)	DK0411631T3 (fr)
ES (1)	ES2055241T3 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4908372A (en) *	1988-10-13	1990-03-13	Merrell Dow Pharmaceuticals Inc.	Antihistaminic piperidinyl benzimidazoles
FI932687L (fi) *	1990-12-14	1993-06-11	Merrell Dow Pharma	Antiallergiska foereningar
JPH08508030A (ja) *	1993-03-18	1996-08-27	メルクシヤープエンドドームリミテツド	ベンゾイミダゾール誘導体
GB9305644D0 (en) *	1993-03-18	1993-05-05	Merck Sharp & Dohme	Therapeutic agents
GB9306578D0 (en) *	1993-03-30	1993-05-26	Merck Sharp & Dohme	Therapeutic agents
WO1994024105A1 (fr) *	1993-04-15	1994-10-27	Merck Sharp & Dohme Limited	Derives d'indole utiles comme antagonistes de la dopamine d4
WO2011026241A1 (fr) *	2009-09-04	2011-03-10	Zalicus Pharmaceuticals Ltd.	Dérivés hétérocycliques substitués pour le traitement de la douleur et de l'épilepsie
WO2014134306A1 (fr)	2013-03-01	2014-09-04	Zalicus Pharmaceuticals, Ltd.	Inhibiteurs hétérocycliques du canal sodique

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PH23995A (en) *	1984-01-09	1990-02-09	Janssen Pharmaceutica Nv	4((bicycle heterocyclyl)-methyl and hetero)piperidines
US4908372A (en) *	1988-10-13	1990-03-13	Merrell Dow Pharmaceuticals Inc.	Antihistaminic piperidinyl benzimidazoles

1990
- 1990-08-01 CA CA002022451A patent/CA2022451C/fr not_active Expired - Fee Related
- 1990-08-02 DK DK90114860.1T patent/DK0411631T3/da active
- 1990-08-02 AU AU60123/90A patent/AU625238B2/en not_active Ceased
- 1990-08-02 DD DD90343200A patent/DD296923A5/de unknown
- 1990-08-02 ES ES90114860T patent/ES2055241T3/es not_active Expired - Lifetime
- 1990-08-02 JP JP2204059A patent/JP2954992B2/ja not_active Expired - Fee Related
- 1990-08-02 EP EP90114860A patent/EP0411631B1/fr not_active Expired - Lifetime
- 1990-08-02 AT AT90114860T patent/ATE104294T1/de not_active IP Right Cessation
- 1990-08-02 DE DE69008069T patent/DE69008069T2/de not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0411631B1 (fr)	1994-04-13
JP2954992B2 (ja)	1999-09-27
DE69008069D1 (de)	1994-05-19
JPH0366683A (ja)	1991-03-22
DE69008069T2 (de)	1994-07-28
CA2022451A1 (fr)	1991-02-04
AU625238B2 (en)	1992-07-02
ATE104294T1 (de)	1994-04-15
CA2022451C (fr)	2001-01-23
EP0411631A1 (fr)	1991-02-06
AU6012390A (en)	1991-02-07
ES2055241T3 (es)	1994-08-16
DK0411631T3 (da)	1994-05-16

Legal Events

Date	Code	Title	Description
2004-04-28	IF04	In force in the year 2004	Expiry date: 20100803

Publication	Publication Date	Title
DE68922366T2 (de)	1995-09-28	Piperidinyl-Benzimidazole als Antihistaminica.
DE69031649T2 (de)	1998-02-26	Oxoindolderivate
DE69129090T2 (de)	1998-08-06	Derivate von cyclischen Amiden
US5877187A (en)	1999-03-02	Benzimidazole derivatives with antihistaminic activity
DE69027794T2 (de)	1997-01-02	N-Phenyl-N-(4-piperidinyl)-amide, verwendbar als Analgetika
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DE69326650T2 (de)	2000-06-08	Piperidinderivate von Benzimidazole als antihistaminische und antiallergische Mittel
DE69407176T2 (de)	1998-07-02	Antipsychotische benzimidazolderivate
DE68906801T2 (de)	1993-09-23	1,4-disubstituierte piperidin-verbindungen.
DE69722858T2 (de)	2004-05-13	Intimale verdickungsinhibitoren
US4680296A (en)	1987-07-14	Piperidine derivatives and pharmaceutical compositions containing them
DE3200304A1 (de)	1982-08-26	3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel
DE60313895T2 (de)	2008-01-17	2,7-disubstituierteindole und ihre verwendung als 5-ht6 modulatoren
DE69408668T2 (de)	1998-07-09	Benz(b)azepin-2,5-dione verwendbar in der behandlung neurodegenerativer störungen
DE68905845T2 (de)	1993-08-05	Tetrazolverbindungen als antagonisten der excitatorischen aminosaeurerezeptoren.
JP3057763B2 (ja)	2000-07-04	抗精神病薬としてのベンゾイソオキサゾール及びインダゾール誘導体
DE3002292A1 (de)	1980-08-21	4-(naphthylmethyl)piperidin-derivate, verfahren zu deren herstellung und deren verwendung
DE69008069T2 (de)	1994-07-28	Antipsychotische Verbindungen.
DE2905876A1 (de)	1980-08-28	Neue piperidinopropylderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE69919575T2 (de)	2005-09-29	Benzoxazolderivate und medikamente die diese als aktiven wirkstoff enthalten
US5182399A (en)	1993-01-26	Process for preparing piperidinyl benzimidazoles
DE2847624A1 (de)	1979-05-10	Arylaether von n-alkyl-piperidinen und deren saeureadditionssalze, verfahren zu ihrer herstellung und ihre verwendung
DE68912252T2 (de)	1994-07-07	Imidazolantiarrythmische Mittel.
DE3850222T2 (de)	1994-09-22	1,4-Disubstituierte-piperidinyl-Verbindungen.
EP0389425B1 (fr)	1995-04-26	Benzothiopyranylamines