EP0390842A1 - Nouveaux derives benzoglyoxaline - Google Patents

Nouveaux derives benzoglyoxaline

Info

Publication number
EP0390842A1
EP0390842A1 EP89900594A EP89900594A EP0390842A1 EP 0390842 A1 EP0390842 A1 EP 0390842A1 EP 89900594 A EP89900594 A EP 89900594A EP 89900594 A EP89900594 A EP 89900594A EP 0390842 A1 EP0390842 A1 EP 0390842A1
Authority
EP
European Patent Office
Prior art keywords
methoxy
hydrogen
benzyloxy
compounds
benzimidazole
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP89900594A
Other languages
German (de)
English (en)
Inventor
Bernhard Kohl
Ernst Sturm
Richard Riedel
Georg Rainer
Volker Figala
Gerhard Grundler
Hartmann Schaefer
Jörg Senn-Bilfinger
Uwe Krüger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takeda GmbH
Original Assignee
Byk Gulden Lomberg Chemische Fabrik GmbH
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.)
Filing date
Publication date
Application filed by Byk Gulden Lomberg Chemische Fabrik GmbH filed Critical Byk Gulden Lomberg Chemische Fabrik GmbH
Publication of EP0390842A1 publication Critical patent/EP0390842A1/fr
Withdrawn legal-status Critical Current

Links

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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems

Definitions

  • 1-4C-alkyl represents straight-chain or branched AI kylreste;
  • the butyl, i-butyl, sec-butyl, t-butyl, propyl, isopropyl, ethyl and especially the methyl radical may be mentioned.
  • 1-4C-Alkoxy-1-4C-alkyl represents 1-4C-alkyl which is substituted by 1-4C-alkoxy.
  • the ethoxymethyl, propoxybutyl, methoxymethyl and especially the methoxyethyl and ethoxyethyl radicals may be mentioned.
  • 2-5C-alkynyloxy represents alkynyloxy radicals such as the ethynyloxy and in particular the prop-2-ynyloxy radical.
  • R1 means hydrogen
  • R2 is hydrogen, methyl, ethyl, methoxy, ethoxy, 1,1,2,2-tetrafluoroethoxy
  • 1,1,2-trifluoroethylene dioxy or 1-chloro-1,2,2-trifluoroethylene dioxy means, R3 1,1,2,2-tetrafluoroethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, difluoromethoxy, 2-chloro-1, 1,2-trifluoroethoxy or together with R3 means difluoromethylene dioxy, 1,1,2-trifluoroethylene dioxy or 1-chloro-1,2,2-trifluoroethylene dioxy, R4 means hydrogen, R5 means hydrogen, R6 means hydrogen or methyl, R7 means methoxy or ethoxy means R8 means benzyloxy and n represents the number 0 or 1, and the salts of these compounds.
  • R4 means hydrogen
  • the invention further relates to a process for the preparation of the compounds of the formula I in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and the meanings given above and their salts.
  • the compounds II-XIV can be used as such or, if appropriate, in the form of their salts.
  • a metal atom M ' is, for example, an alkali metal (Li, Na or K), or an alkaline earth metal atom (eg Mg) which is substituted by a halogen atom (eg Br, Grignard reagent) or any other optionally substituted metal atom , which is known to react in substitution reactions of organometallic compounds such as the metals mentioned above.
  • a metal atom M is, for example, an alkali metal (Li, Na or K), or an alkaline earth metal atom (eg Mg) which is substituted by a halogen atom (eg Br, Grignard reagent) or any other optionally substituted metal atom , which is known to react in substitution reactions of organometallic compounds such as the metals mentioned above.
  • the reaction temperature is (depending on the reactivity of the oxidizing agent and
  • reaction according to process variant f) is carried out in a manner known to the person skilled in the art in suitable solvents such as tetrahydrofuran or acetonitrile, optionally with the addition of a base (if Y 'represents a leaving group) or without addition of base (if Y' represents a reactive group). If the substituents R1, R2 and R3 are asymmetrically distributed, this reaction gives mixtures of isomers which have to be separated by suitable separation processes (e.g. chromatography).
  • suitable solvents such as tetrahydrofuran or acetonitrile
  • the salts are obtained by dissolving the free compounds in one Suitable solvents, for example in a chlorinated hydrocarbon, such as methylene chloride or chloroform, a low molecular weight aliphatic alcohol (ethanol, isopropanol), an ether (diisopropyl ether), a ketone (acetone) or water, which contains the desired acid or base, or which the desired acid or base - optionally in the precisely calculated stoichiometric amount - is then added.
  • a chlorinated hydrocarbon such as methylene chloride or chloroform
  • a low molecular weight aliphatic alcohol ethanol, isopropanol
  • an ether diisopropyl ether
  • a ketone acetone
  • Example Aa According to the procedure given in Example Aa), 5.1 g (85 g) are obtained by reacting 4.86 g of 4-benzyloxy-2-hydroxymethyl-3-methoxypyridini umchl ori d with 3 g of thionyl chloride in 50 ml of methylene chloride at + 5 ° C % of theory) the title compound as a colorless solid of mp 117-118 ° C (dec.).
  • the pharmaceuticals are produced by methods known per se and familiar to the person skilled in the art.
  • the pharmaceutical preparations can also include one or more pharmacologically active constituents of other pharmaceutical groups, such as antacids, for example aluminum hydroxide, magnesium aluminate; Tranquillizers, such as benzodiazepines, for example diazepam; Antispasmodics, such as Bietami verin, camylofin; Anticholinergics such as oxyphencyclimine, phencarbamide; Local anesthetics, such as tetracaine, procaine; optionally also contain ferments, vitamins or amino acids.
  • antacids for example aluminum hydroxide, magnesium aluminate
  • Tranquillizers such as benzodiazepines, for example diazepam
  • Antispasmodics such as Bietami verin, camylofin
  • Anticholinergics such as oxyphencyclimine, phencarbamide
  • Local anesthetics such as tetracaine, procaine

Landscapes

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

Abstract

Des dérivés de benzoglyoxaline ayant la formule (I), dans laquelle les substituants ont la signification donnée dans la description, et leurs sels, constituent de nouveaux composés à effet gastroprotecteur marqué.
EP89900594A 1987-12-11 1988-12-08 Nouveaux derives benzoglyoxaline Withdrawn EP0390842A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH484487 1987-12-11
CH4844/87 1987-12-11

Publications (1)

Publication Number Publication Date
EP0390842A1 true EP0390842A1 (fr) 1990-10-10

Family

ID=4283543

Family Applications (1)

Application Number Title Priority Date Filing Date
EP89900594A Withdrawn EP0390842A1 (fr) 1987-12-11 1988-12-08 Nouveaux derives benzoglyoxaline

Country Status (5)

Country Link
EP (1) EP0390842A1 (fr)
JP (1) JPH03501609A (fr)
AU (1) AU2817989A (fr)
WO (1) WO1989005299A1 (fr)
ZA (1) ZA889194B (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4808591A (en) * 1988-02-16 1989-02-28 Pfizer Inc. Antiulcer 8-(2-pyrimidylsulfinyl)quinolines
US5049674A (en) * 1989-12-20 1991-09-17 Aktiebolaget Hassle Therapeutically active fluoro substituted benzimidazoles
US4965269A (en) * 1989-12-20 1990-10-23 Ab Hassle Therapeutically active chloro substituted benzimidazoles
ES2140391T3 (es) * 1990-06-20 2000-03-01 Astra Ab Derivados de dialcoxi-piridinil-bencimidazol, procedimiento para su preparacion y su uso farmaceutico.
SE9002206D0 (sv) * 1990-06-20 1990-06-20 Haessle Ab New compounds
NZ244301A (en) * 1991-09-20 1994-08-26 Merck & Co Inc Preparation of 2-pyridylmethylsulphinylbenzimidazole and pyridoimidazole derivatives from the corresponding sulphenyl compounds
ES2176251T3 (es) 1993-07-28 2002-12-01 Aventis Pharma Ltd Compuestos utilizados como inhibidores de pde iv y del factor de necrosis tumoral(tnf).
DE19745692A1 (de) * 1997-07-24 1999-01-28 Bayer Ag Verfahren zur Herstellung von 2-Chlor-benzimidazol-Derivaten
CA3036250C (fr) 2016-09-14 2023-09-26 Yufeng Jane Tseng Nouveaux derives de benzimidazole substitues utilises en tant qu'inhibiteurs de la d-amino-acide oxydase (daao)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL75400A (en) * 1984-06-16 1988-10-31 Byk Gulden Lomberg Chem Fab Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same
JPS62201885A (ja) * 1985-02-12 1987-09-05 Banyu Pharmaceut Co Ltd インド−ル誘導体、その製造法及び用途
US4738975A (en) * 1985-07-02 1988-04-19 Takeda Chemical Industries, Ltd. Pyridine derivatives, and use as anti-ulcer agents
DE3722810A1 (de) * 1987-07-10 1989-01-19 Hoechst Ag Substituierte benzimidazole, verfahren zu deren herstellung, diese enthaltende pharmazeutische zubereitungen und deren verwendung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8905299A1 *

Also Published As

Publication number Publication date
ZA889194B (en) 1989-08-30
AU2817989A (en) 1989-07-05
WO1989005299A1 (fr) 1989-06-15
JPH03501609A (ja) 1991-04-11

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