EP0906306A1 - Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa - Google Patents

Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa

Info

Publication number
EP0906306A1
EP0906306A1 EP97925046A EP97925046A EP0906306A1 EP 0906306 A1 EP0906306 A1 EP 0906306A1 EP 97925046 A EP97925046 A EP 97925046A EP 97925046 A EP97925046 A EP 97925046A EP 0906306 A1 EP0906306 A1 EP 0906306A1
Authority
EP
European Patent Office
Prior art keywords
pyrrolylquinoxalinediones
formula
hydrogen
alkyl
cooh
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Withdrawn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
EP97925046A
Other languages
German (de)
English (en)
Inventor
Wilfried Lubisch
Berthold Behl
Hans-Peter Hofmann
Laszlo Szabo
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.)
BASF SE
Original Assignee
BASF SE
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 BASF SE filed Critical BASF SE
Publication of EP0906306A1 publication Critical patent/EP0906306A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to pyrrolylquinoxalinediones of the formula I.
  • R 2 is hydrogen, Ci-Ce-alkyl, C 2 -C6-alkenyl, C2-C 6 -alkynyl, a chlorine, fluorine or bromine atom, a trihalomethyl, cyano- or nitro group or S ⁇ 2 -C ⁇ -C 4 -Alkyl,
  • R 3 COOH or a radical hydrolyzable to the carboxyl group
  • the invention further relates to processes for their preparation and their use for combating diseases.
  • Quinoxalinedione derivatives of the formula A which carry a heterocycle as substituent R 3 are also known.
  • EP-A-556 393 describes imidazoles, triazoles, pyrazoles.
  • Quinoxalindione derivatives which carry a pyrrolyl radical as R 3 are known from EP-A-572 852 and from WO 95/35 289.
  • DE-A-43 400 45 mentions pyrrole derivatives which carry a urea residue as glutamate antagonists.
  • the known pyrrolylquinoxalinedione compounds are not always completely satisfactory in terms of their pharmacological action.
  • the invention was therefore based on the object of providing pyrrolylquinoxalinedione derivatives with improved effectiveness and, at the same time, good physiological tolerance.
  • R 1 represents hydrogen or branched or unbranched C 1 -C 6 alkyl, substituted by hydroxyl or carboxyl, for example hydroxyethyl or carboxymethyl.
  • Ci-C ⁇ -alkyl means, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl.
  • alkyl is preferably C 2 -C. 6 alkyl.
  • R 2 stands for hydrogen, Ci-Ce-alkyl, for example as mentioned above, C 2 -C 6 alkenyl or alkynyl - for example vinyl, ethynyl, propenyl, isopropenyl, fluorine, chlorine, bromine, trihalomethyl - for example trichloro- methyl or trifluoromethyl, cyano or nitro and also S 2 -C 4 -alkyl, where the alkyl radical includes the abovementioned meanings.
  • Particularly preferred radicals R 2 are hydrogen, chlorine, trifluoromethyl or nitro.
  • R 3 stands for a carboxyl group COOH or for a radical which can be hydrolyzed to the carboxyl group, for example for an amide group, a carboxylic anhydride group or in particular an ester group COOR 4 , in which R 4 is C 1 -C 4 -alkyl, for example COOCH 3 or COOC 2 H 5 means.
  • R 4 is C 1 -C 4 -alkyl, for example COOCH 3 or COOC 2 H 5 means.
  • both can form a cyclic anhydride.
  • the free COOH group or its salts is particularly preferred for the pharmacological effect.
  • n 1 or 2, in particular 1.
  • the substituent (s) R 3 can be arranged in the meta, para or ortho position to the urea residue.
  • the para and / or meta position is preferred.
  • R 1 is hydrogen
  • R 2 is hydrogen, chlorine, a trifluoromethyl or nitro group
  • n 1 or 2.
  • R 2 is hydrogen, chlorine, a trifluoromethyl or nitro group
  • R 3 means COOH
  • n 1 or 2.
  • the compounds I according to the invention can be prepared according to reaction scheme 1.
  • amino-substituted quinoxalinediones of the formula II are reacted with a 1,4-dicarbonyl compound or cyclic acetals (III and VI) derived therefrom to form the pyrroles I and IV with elimination of water.
  • the usual procedures are used, for example in A.R. Katritzky and C.W. Rees, "Comprehensive Heterocyclic Chemistry", Vol. 4, Part 306, p. 313ff, in C. Ferri, "Reactions of Organic Synthesis", Thieme Verlag 1978, p. 708ff or in the published patent applications EP-A-572 852 and DE -A-43 400 45 are described.
  • Pyrrole synthesis is usually acid-catalyzed in the presence of acetic acid or toluenesulfonic acid.
  • the acid can also serve as a solvent when used in large quantities.
  • it is customary to carry out the reaction in a solvent such as toluene or in a solvent mixture such as toluene / dimethylformamide at a reaction temperature of 50 to 150 ° C., preferably 100 to 150 ° C., or in concentrated acetic acid at temperatures of 50 ° C. to at the boiling point.
  • the dicarbonyl compound used such as compound III in Scheme 1 bears an amino group, this is protected beforehand.
  • Known protective groups such as amides, urethanes or benzyl radicals can be used, trifluoroacetyl preferably being used.
  • Other possible protecting groups and metho- for introduction are in Th.W. Green and PGM Wuts, "Protective Groups in Organic Synthesis", Wiley & Sons 1991, Chap. 7.
  • the protective groups are removed in the usual manner after synthesis of the pyrrole ring, the amine V being obtained.
  • acids or bases such as lithium hydroxide in solvents or solvent mixtures such as tetrahydrofuran / water at reaction temperatures between 10 and 60 ° C., preferably at 20 to 30 ° C.
  • the amines of the formula V can then be reacted in a known manner with isocyanates to give the compounds of the formula I according to the invention, it being possible to use the corresponding anilines instead of the isocyanate, which in a known manner with phosgene or analogous compounds, such as Carbonyldimidazole, are reacted in situ to the isocyanates.
  • isocyanates instead of the isocyanate, which in a known manner with phosgene or analogous compounds, such as Carbonyldimidazole, are reacted in situ to the isocyanates.
  • the corresponding aldehyde can also be used, which is then converted into the amines V in a reductive amination reaction.
  • the pyrrolylquinoxalinediones according to the invention can be obtained directly by using the acetals VI.
  • the ester in the urea derivative I can be converted into the corresponding acid using acids or bases. This is preferably done with bases such as lithium hydroxide in solvent mixtures such as tetrahydrofuran / water at 20 to 30 ° C.
  • AMPA AMPA receptor
  • CNS central nervous system
  • Glutamate antagonists including in particular NMDA antagonists or their modulators (such as glycine antagonists) and the AMPA antagonists, are suitable for therapeutic use as agents against neurodegenerative diseases (Huntington's and Parkinson's diseases), neurotoxic disorders after hypoxia, anoxia or ischemia, as they occur after "stroke", or also as antiepileptics, antidepressants and anxiolytics (cf. Medicinal Research 1990, 40, 511-514; TIPS, 1990, 11, 334-338 and drugs of the Future 1989, 14 (11), 1059-1071).
  • the pharmacological activity of the compounds I was investigated on isolated membrane material from rat cerebrum.
  • the membrane material in the presence of the compounds according to the invention with the radioactively labeled substances 3 H-2-amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid ( 3 H-AMPA), [ 3 H] -glycine or [ 3 H] -Cainates treated these bind to specific receptors (AMPA, NMDA or kainate receptors).
  • AMPA specific receptors
  • NMDA NMDA
  • kainate receptors specific receptors
  • the resulting dissociation constant Ki (I inhibitor), which is a measure of the displacement effect of the active substance according to the invention, was determined by iterative non-linear regression analysis with the Statical Analysis System (SAS) on an IBM computer, similar to the program "Ligand” by PJ Munson and D. Rodbard (Analytical Biochem. 107, 220 (1980), Ligand: Versatile Computerized Approach for Characterization of Ligand Binding Systems) determined.
  • SAS Statical Analysis System
  • a buffer solution A consisting of 30 mM tris (hydroxymethyl) methylamine hydrochloride (TRIS-HCL) and 0.5 mM ethylenediaminetetraacetic acid (EDTA) - pH 7.4 - Homogenized using an Ultra-Turrax stirrer.
  • the suspension was 20 min. centrifuged at 48000 g. After the supernatant liquid had been separated off, the proteinaceous membrane material contained in the sediment was washed three times by suspending it in buffer solution A and then centrifuging at 48,000 g for 20 minutes each. The membrane material was then suspended in a 15-fold volume of buffer solution A and 30 min. incubated at 37 ° C. The protein material was then washed twice by centrifugation and suspension and frozen at -70 ° C until used.
  • TriS-HCL tris (hydroxymethyl) methylamine hydrochloride
  • EDTA ethylenediaminetetraacetic acid
  • the protein material thawed at 37 ° C. was centrifuged twice at 48,000 g (20 min.) And then suspended in a buffer solution B consisting of 50 mM TRIS-HCL, 0.1 M potassium thiocyanate and 2.5 mM calcium chloride. pH 7.1 - washed. Then 0.25 mg of membrane material, 0.1 ⁇ Ci 3H-AMPA (60 Ci / mmol) and compound I were dissolved in 1 ml of buffer solution B and 60 min. incubated on ice. The incubated solution was filtered through a CF / B filter (Whatman), which had previously been treated with a 0.5% aqueous solution of polyethyleneimine for at least 2 hours.
  • a buffer solution B consisting of 50 mM TRIS-HCL, 0.1 M potassium thiocyanate and 2.5 mM calcium chloride. pH 7.1 - washed.
  • the membrane residue was then washed with 5 ml of cold buffer solution B in order to separate bound and free 3H-AMPA from one another. After measuring the radioactivity of the bound 3 H-AMPA in the membrane material by scintillation counting, the KI value was determined by evaluating the displacement curves by means of regression analysis.
  • the membrane suspension 15 min. incubated at 37 ° C in a shaking water bath. After 4 further washing steps (each time 20 min. Centrifugation at 48000 g and resuspending in preparation buffer), the membranes were frozen at -70 ° C. until further use.
  • the frozen membranes were thawed at 37 ° C. and washed twice by centrifugation at 48,000 g (20 min.) And then resuspending in binding buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl 2 ).
  • binding buffer 50 mM Tris-HCl pH 7.4, 10 mM MgCl 2 .
  • One incubation batch contained 0.25 mg protein
  • the membranes contained in the pellet washed a total of 3 times by resuspending in the preparation buffer and centrifuging at 48000 g (each 20 min.). After the third wash step, the membranes were washed twice by centrifugation and resuspension and frozen at -70 ° C. until further use.
  • the frozen membranes were thawed at 37 ° C., suspended in binding buffer (50 mM Tris-HCl, pH 7.4) and 20 mm. centrifuged at 48000 g. The membranes in the pellet were resuspended in binding buffer.
  • An incubation batch contained 0.25 mg protein (membranes), 0.058 Ci (58 Ci / mmol) and the substances to be tested in total 1 ml binding buffer. Non-specific binding was determined in the presence of 0.1 mM glutamate. After 60 mm. Incubation on ice was bound and free ligand separated by filtration through CF / B filters and subsequent washing with 5 ml of ice-cold binding buffer. The CF / B filters had previously been treated with 0.5% polyethylene imine for at least 2 hours. The displacement curves were evaluated and the dissociation constants were calculated using a non-linear adaptation program or in accordance with the equation by Cheng and Prusoff.
  • EAA Excitatory Amino Acids
  • MCA middle cerebral artery
  • An experimental cerebral infarction is produced in the rat by permanent occlusion of the middle cerebral artery, the extent of which is determined after 24 hours on the basis of the dead tissue.
  • the volume of the cortical infarction can be reduced by the test substances, even if the treatment only takes 90 min. after vascular occlusion is started.
  • the therapeutic use of the substances in human stroke can be derived from this.
  • the substances according to the invention are suitable for the treatment of all diseases in which a positive influence by glutamate antagonists can be expected.
  • Possible indications are neurotoxic disorders, especially acute and chronic oxygen / nutrient deficiency states of the central nervous system. These are to be understood as acute hypoxic or ischemic conditions, e.g. B. due to cerebral infarction, subarachnoid hemorrhage or vascular spasms of other gees, even after cardiovascular failure - e.g. B. cardiac arrest, cardiac arrhythmias or circulatory shock - occur; CNS damage after hypoglycemia, as a result of perinatal asphyxia or after traumatic brain injury, spinal cord trauma, transient ischemic attacks (TIAs), prolonged reversible ischemic neurological deficits (PRINDs), multi-infarct dementia and atherosclerotic dementia and migraines .
  • Further possible indications are neurodegenerative diseases, e.g. B. Parkinson's disease, Huntington's chorea, Alzheimer's disease, amyotropic lateral sclerosis (ALS).
  • glutamate antagonists are suitable for use as anti-epileptics, as anxiolytics and as antidepressants, and for pain therapy, as well as for the treatment of schizophrenia, withdrawal symptoms in addicts and as muscle relaxants for spasticity of the skeletal muscles, e.g. B. in multiple sclerosis (MS).
  • MS multiple sclerosis
  • the pharmaceutical preparations according to the invention contain a therapeutically effective amount of the compounds I.
  • the active ingredients can be contained in the usual concentrations.
  • the active ingredients are present in an amount of 0.0001 to 1% by weight, preferably 0.001 to 0.1% by weight.
  • the preparations are administered in single doses. 0.1 to 100 mg per kg body weight are given in a single dose.
  • the preparations can be administered daily in one or more doses depending on the type and severity of the diseases.
  • the pharmaceutical preparations according to the invention contain, in addition to the active ingredient, the customary carriers and diluents.
  • pharmaceutical-technical auxiliaries such as ethanol, isopropanol, ethoxylated castor oil, ethoxylated hydrogenated castor oil, polyacrylic acid, polyethylene glycol, polyethylene glycol stearate, ethoxylated fatty alcohols, paraffin oil, vase line and wool fat can be used.
  • z As milk sugar, propylene glycol, ethanol, starch, talc and polyvinyl pyrrolidone.
  • Antioxidants such as tocopherol and butylated hydroxyanisole and butylated hyderoxytoluene, taste-improving additives, stabilizers, emulsifiers and lubricants can also be present.
  • the substances contained in the preparation in addition to the active substance and the substances used in the production of the pharmaceutical preparation are toxicologically harmless and compatible with the respective active substance.
  • the pharmaceutical preparations are prepared in a conventional manner, eg. B. by mixing of the active ingredient with the other conventional carriers and diluents.
  • the pharmaceutical preparations can be administered in various ways, such as orally, parenterally, subcutaneously, intraperitoneally and topically.
  • Forms of preparation such as tablets, emulsions, infusion and injection solutions, pastes, ointments, gels, creams, lotions, powders and sprays are possible.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des pyrrolylquinoxalindiones de formule (I), dans laquelle les variables ont la signification suivante: R1 représente hydrogène, alkyle C¿1?-C6, substitué par hydroxyle ou carboxyle; R?2¿ représente hydrogène, alkyle C¿1?-C6, alcényle C2-C6, alcynyle C2-C6, un atome de chlore, de fluor ou de brome, un groupe trihalogéno-méthyle, cyano ou nitro, ou SO2-C1-C4-alkyle; R?3¿ représente COOH ou un résidu pouvant être hydrolysé en un groupe carboxyle; n vaut 1 ou 2. L'invention concerne également les formes tautomères ou isomères, ainsi que les sels physiologiquement acceptables, desdites pyrrolylquinoxalindiones.
EP97925046A 1996-06-21 1997-06-05 Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa Withdrawn EP0906306A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19624808 1996-06-21
DE19624808A DE19624808A1 (de) 1996-06-21 1996-06-21 Pyrrolylchinoxalindione, ihre Herstellung und Verwendung
PCT/EP1997/002913 WO1997049701A1 (fr) 1996-06-21 1997-06-05 Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa

Publications (1)

Publication Number Publication Date
EP0906306A1 true EP0906306A1 (fr) 1999-04-07

Family

ID=7797594

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97925046A Withdrawn EP0906306A1 (fr) 1996-06-21 1997-06-05 Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa

Country Status (7)

Country Link
US (1) US6277850B1 (fr)
EP (1) EP0906306A1 (fr)
JP (1) JP2000513345A (fr)
CN (1) CN1081636C (fr)
AU (1) AU3032397A (fr)
DE (1) DE19624808A1 (fr)
WO (1) WO1997049701A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6348461B1 (en) * 1997-09-01 2002-02-19 Kyorin Pharmaceutical Co., Ltd. 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid derivatives, addition salts thereof, and processes for the preparation of both
JP2002519373A (ja) * 1998-07-02 2002-07-02 エーザイ株式会社 製薬組成物及びそれらの使用
JP2000309586A (ja) * 1999-02-26 2000-11-07 Kyorin Pharmaceut Co Ltd ６−置換−７−ヘテロキノキサリンカルボン酸誘導体とその付加塩及びそれらの製造方法
JP2000309585A (ja) * 1999-02-26 2000-11-07 Kyorin Pharmaceut Co Ltd ６−置換ヘテロキノリンカルボン酸誘導体とその付加塩及びそれらの製造方法
US7470718B2 (en) * 2000-10-03 2008-12-30 Albert Einstein College Of Medicine Of Yeshiva University Method for treating a demyelinating condition
DE10306202A1 (de) * 2003-02-13 2004-08-26 Grünenthal GmbH Arzneimittel enthaltend substituierte 2-Aryl-Aminoessigsäure-Verbindungen und/oder substituierte 2-Heteroaryl-Aminoessigsäure-Verbindungen
WO2010053757A1 (fr) * 2008-10-29 2010-05-14 Gilead Palo Alto, Inc. Inhibiteurs, à base de 2-oxoquinoxaline, des canaux sodiques tardifs
US20100113514A1 (en) 2008-10-30 2010-05-06 Gilead Palo Alto, Inc. Fused heterocyclic compounds as ion channel modulators
US11376294B2 (en) 2016-07-19 2022-07-05 Nektium Pharma S.L. Mangiferin-containing compositions for improving sports performance
US20220392645A1 (en) * 2021-06-08 2022-12-08 Exocad Gmbh Automated treatment proposal

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IE66149B1 (en) 1986-09-16 1995-12-13 Novo Nordisk As Quinoxaline compounds and their preparation and use
NO179551C (no) 1987-11-10 1996-10-30 Novo Nordisk As Analogifremgangsmåte for fremstilling av terapeutisk virksomme kinoxalinforbindelser
DK715888D0 (da) 1988-12-22 1988-12-22 Ferrosan As Quinoxalinforbindelser, deres fremstilling og anvendelse
DK716188D0 (da) 1988-12-22 1988-12-22 Ferrosan As Quinoxalinforbindelser, deres fremstilling og anvendelse
DK69790D0 (da) 1990-03-16 1990-03-16 Novo Nordisk As Heterocykliske forbindelser, deres fremstilling af anvendelse
JP2550456B2 (ja) 1990-11-06 1996-11-06 山之内製薬株式会社 縮合ピラジン誘導体
PT101004B (pt) 1991-10-26 1999-10-29 Schering Ag Derivados da quinoxalina, processo para a sua preparacao e composicoes farmaceuticas que os contem
DE4135871A1 (de) 1991-10-26 1993-04-29 Schering Ag Chinoxalinderivate, deren herstellung und verwendung in arzneimitteln
DE4217952A1 (de) 1992-05-30 1993-12-02 Basf Ag Chinoxalin-2,3(1H,4H)-dione
DE4340045A1 (de) * 1993-11-24 1995-06-01 Basf Ag Neue Chinoxaline und Arzneimittel daraus
DE4428152A1 (de) * 1994-06-22 1996-01-04 Basf Ag Neue Amido-chinoxalindione, ihrer Herstellung und Verwendung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9749701A1 *

Also Published As

Publication number Publication date
JP2000513345A (ja) 2000-10-10
AU3032397A (en) 1998-01-14
WO1997049701A1 (fr) 1997-12-31
CN1081636C (zh) 2002-03-27
US6277850B1 (en) 2001-08-21
CN1211980A (zh) 1999-03-24
DE19624808A1 (de) 1998-01-02

Similar Documents

Publication Publication Date Title
EP0572852B1 (fr) Quinoxalines-2,3(1H,4H)-diones utiles comme médicament
DE19920936A1 (de) Heterozyklisch substituierte Benzimidazole, deren Herstellung und Anwendung
DE4242675A1 (de) Neue Hydroxyiminoalkylindolcarbonsäure-Derivate, ihre Herstellung und Verwendung
WO2000029384A1 (fr) 2-phenylbenzimidazoles et 2-phenylindoles, leur production et leur utilisation
WO2000064878A1 (fr) Benzimidazoles a substitution cycloalkyle, et leur utilisation comme inhibiteurs de la parp
DE60102473T2 (de) Indolochinazolinone
EP0906306A1 (fr) Pyrrolylquinoxalindiones, leur fabrication et leur utilisation comme antagonistes du recepteur ampa
EP0691970B1 (fr) Derives d'imidazolo-quinoxalinone utilises comme antagonistes d'aminoacides a effet excitatif
EP0799224B1 (fr) Quinoxalines et medicaments prepares a partir desdites quinoxalines
EP0785932B1 (fr) Pyrrolyltetrahydrobenzoquinoxalindiones, leur preparation et leur utilisation comme antagonistes des recepteurs de glutamate
EP0783506A1 (fr) Nouvelles imidazoloquinoxalinones heterocycliques substituees, leur preparation et leur utilisation
JPH06228112A (ja) （１ｈ，４ｈ）キノキサリン誘導体
DE4428152A1 (de) Neue Amido-chinoxalindione, ihrer Herstellung und Verwendung
EP0673377B1 (fr) Nouvelles triazoloquinazolines, leur production et leur utilisation
EP0160173A1 (fr) Dérivés de benzothiazole, leurs procédés de préparation et médicament les contenant
US6407109B1 (en) Pyrrolyl tetrahydroquinoxalin diones, their production and use in the treatment of diseases
DE4329970A1 (de) Neue Imidazolo-chinoxalinone, ihre Hestellung und Verwendung
DE19611476A1 (de) Neue heterocyclische substituierte Imidazolo-chinoxalinone, ihre Herstellung und Verwendung
AT375347B (de) Verfahren zur herstellung von neuen substituierten 1-benzoyl-2-phenylimino-imidazolidinen und von deren salzen
DE19503825A1 (de) Neue heterocyclische substituierte Imidazolo-chinoxalinone, ihre Herstellung und Verwendung
DE4201554A1 (de) Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
WO1994013673A1 (fr) Nouvelles triazolopyrimidones, leur fabrication et leur utilisation

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19980610

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): CH DE FR GB IT LI NL

17Q First examination report despatched

Effective date: 20020221

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040103