EP0636124A1 - Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant - Google Patents

Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant

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Publication number
EP0636124A1
EP0636124A1 EP93909013A EP93909013A EP0636124A1 EP 0636124 A1 EP0636124 A1 EP 0636124A1 EP 93909013 A EP93909013 A EP 93909013A EP 93909013 A EP93909013 A EP 93909013A EP 0636124 A1 EP0636124 A1 EP 0636124A1
Authority
EP
European Patent Office
Prior art keywords
radical
alk
dichloro
dioxide
dihydro
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.)
Ceased
Application number
EP93909013A
Other languages
German (de)
English (en)
French (fr)
Inventor
Jean-Claude Aloup
François Audiau
Dominique Damour
Patrick Jimonet
Serge Mignani
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.)
Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
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
Priority claimed from FR929204612A external-priority patent/FR2690159B1/fr
Priority claimed from FR9211675A external-priority patent/FR2696457B1/fr
Application filed by Rhone Poulenc Rorer SA filed Critical Rhone Poulenc Rorer SA
Publication of EP0636124A1 publication Critical patent/EP0636124A1/fr
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • A61P25/04—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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/15—Six-membered rings
    • C07D285/16—Thiadiazines; Hydrogenated thiadiazines
    • C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
    • C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
    • C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/06—Peri-condensed systems

Definitions

  • R8 represents an alkyl or phenylalkyl radical
  • - alk represents an alkyl or alkylene radical.
  • Convertible groups in vivo are those that cut easily in the human body to lead to acid.
  • groups convertible into a carboxy radical in vivo mention may be made of the radicals -CO-R11 in which Rj -j represents a radical -O-alk-R-
  • This reaction is carried out at a temperature close to 100 ° C.
  • This reaction is preferably carried out in an inert solvent such as dimethylformamide, dimethoxyethane, dioxane, at a temperature between 20 ° C and the reflux temperature of the reaction medium.
  • an inert solvent such as dimethylformamide, dimethoxyethane, dioxane
  • an ester When an ester is used, the operation is carried out either in an organic medium, optionally in the presence of an acid acceptor such as butyllithium, the lithian of diisopropylamine or an organic nitrogenous base (trialkylamine, pyridine, diaza-1, 8 bicyclo [5.4.0] undecene-7 or diaza-1, 5
  • an acid acceptor such as butyllithium, the lithian of diisopropylamine or an organic nitrogenous base
  • R has the same meanings as in formula (I) except hydrogen and X represents a halogen atom and preferably a chlorine or bromine atom.
  • salts with alkali metals sodium, potassium, lithium
  • alkaline earth metals calcium, magnesium
  • the ammonium salt the tetraalkylammonium salts (tetrabutylammonium for example)
  • salts of nitrogenous bases ethanolamine, trimethylamine, methylamine, benzylamine, N-benzyl- ⁇ -phenethylamine, choline, arginine, leucine, lysine, N-methyl glucamine.
  • Example 18 The procedure is as in Example 18, starting with 2.1 g of 6,8-dichloro-3,4-dihydro-2- (1-naphthylmethyl) -2H-1, 2,4-benzothiadiazine-1, 1 -dioxide-3-carbo xylate, 9 cm3 of 0.5N sodium hydroxide and 25 cm3 of tetrahydrofuran. After stirring overnight at a temperature in the region of 20 ° C., the reaction medium is concentrated to dryness under reduced pressure and the residue taken up in distilled water. The organic phase is extracted with dichloromethane and discarded. The aqueous phase is acidified using 1N hydrochloric acid and the precipitate formed filtered, washed with water and then with dichloromethane.
  • the 2-amino-4,6-dichloro-N- (2-methoxybenzyl) -benzenesulfonamide can be obtained in the following manner: under nitrogen and at a temperature in the region of 20 ° C, 3.6 cm3. of 2-methoxybenzylamine dissolved in 30 cm3 of tetrahydrofuran are added dropwise to a solution of 6.0 g of 2-amino-4,6-dichlorobenzenesulfonyl chloride and 3.23 cm3 of triethylamine in 30 cm3 of tetrahydrofuran. After a night of commotion in at the same temperature, the reaction medium is concentrated to dryness under reduced pressure.
  • a white product crystallizes; it is filtered and dried to yield 1 g of 6,8-dichloro-3,4-dihydro-2- (3,4-dichlorobenzyl) -2H-1, 2,4-benzothîadîazine-1, 1-dioxide acid -3- carboxy melting at 218 ° C.
  • 6,8-dichloro-3,4-dihydro-2- [3- (4-phenyl-1-piperazinyl) propyl] -2H-1, 2,4-benzothiadiazine-1, 1-dioxide-3-carboxylate d ethyl can be prepared as follows: under nitrogen, 15 cm3 of a solution of 3 g of 6,8-dichloro-3,4-dihydro-2H-1, 2,4-benzothiadiazine- are added dropwise 1, 1- ethyl dioxide-3-carboxylate in anhydrous tetrahydrofuran, with 0.44 g of 50% sodium hydride suspended in 15 cm3 of the same solvent.
  • 2-amino-4,6-dichloro-N- [4- (2-methylphenyl) butyl] -benzenesulfonamide can be obtained in the following manner: under nitrogen and at a temperature in the region of 20 ° C, 3 g of 4- (2-methylphenyl) butylamine dissolved in 30 cm3 of tetrahydrofuran are added dropwise to a solution of 4.8 g of 2-amino-4,6-dichlorobenzenesulfonyl chloride and 2.6 cm3 of triethylamine in 30 cm3 of tetrahydrofuran.
  • 1-iodo-4- (3-methylphenyl) -butane can be prepared as follows: 9.85 g of 1-chloro-4- (3-methylphenyl) -butane and 20.3 g of sodium iodide dissolved in 200 cm3 of 2-butanone are stirred at reflux for 24 hours. The precipitate formed is removed and the filtrate concentrated to dryness under reduced pressure. The residue is taken up in distilled water and the organic phase extracted with ethyl ether, dried and concentrated to dryness 13.5 g of 1-iodo-4- (3-methylphenyl) -butane are thus obtained in the form of orange oil used as is in subsequent syntheses.
  • Ethyl 6,8-dichloro-3,4-dihydro-2- (3,5-dimethylbenzyl) -2H-1,2,4-benzothia diazine-1, 1-dioxide-3-carboxylate can be prepared from as follows: to 3.5 g of 2-amino-4,6-dichloro-N- (3,5-dimethylbenzyl) -benzene sulfonamide in 50 cm3 of absolute ethanol brought to reflux, 1 is added dropwise, 64 g of giyoxylic acid in solution in 50 cm3 of absolute ethanol in the presence of 4.5 cm3 of concentrated sulfuric acid.
  • 3- (3,5-dichlorophenoxy) benzylamine can be prepared in the following way: under nitrogen, 10.65 g of 3- (3,5-dichlorophenoxy) benzafdehyde oxime dissolved in 60 cm3 are added dropwise anhydrous tetrahydrofuran containing 1.86 g of lithium aluminum hydride in 30 cm3 of the same solvent maintained at 0 ° C. After 6 hours of reaction at reflux, the reaction medium is cooled to a temperature in the region of 20 ° C. then treated dropwise with 50 cm3 of distilled water. After adding 100 cm3 of dichloromethane, the organic phase is decanted, washed with water, dried over magnesium sulfate and concentrated to dryness under reduced pressure.
  • 3- (4-chlorophenoxy) benzylamine can be prepared in the following manner: 5.3 g of 3- (4-chlorophenoxy) benzaldehyde oxime dissolved in 30 cm3 of anhydrous tetrahydrofuran are added dropwise under nitrogen. 1.10 g of lithium aluminum hydride in 20 cm 3 of the same solvent maintained at 0 ° C. After 10 hours of reaction at reflux, the reaction medium is cooled to a temperature in the region of 20 ° C. then treated dropwise with 50 cm3 of distilled water. After addition of dichloromethane, the organic phase is decanted, washed with water, dried over magnesium sulfate and concentrated to dryness under reduced pressure.
  • the 2-amino-4,6-dichloro-N- [3- (4-methoxyphenoxy) benzyl] -benzenesulfona mide can be obtained in the following manner: under nitrogen and at a temperature in the region of 20 ° C., 1.6 g of 3- (4-methoxyphenoxy) benzylamine dissolved in 50 cm3 of tetrahydrofuran are added dropwise to a solution of 1.56 g of 2-amino-4,6-dichlorobenzenesulfonyl chloride and 1.69 cm3 of triethylamine in 50 cm3 of the same solvent.
  • 3- (4-methoxyphenoxy) benzaldehyde-oxime can be prepared according to the following method: at a temperature in the region of 20 ° C, 3.3 g of hydroxylamine hydrochloride dissolved in 20 cm3 of water are added dropwise distilled in the presence of 4.8 cm3 of concentrated sodium hydroxide, to 10 g of 3- (4-chlorophenoxy) benzaldehyde in solution in 10 cm3 of absolute ethanol. After 3 hours of reaction at the same temperature, the precipitate formed is filtered, washed with water and dried. 8.4 g of 3- (4-methoxyphenoxy) benzaldehyde-oxime are obtained in the form of a white powder melting at 119 ° C.
  • Ethyl 6,8-dichloro-3,4-dihydro-2- (3,5-difluorobenzyl) -2H-1,2,4-benzothiadiazine-1,1-doxide-3-carboxylate can be prepared from as follows: under nitrogen, 40 cm3 of a solution of 3 g of 6,8-dichloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-1, 1-dioxide-3 are added dropwise ethyl carboxylate in anhydrous tetrahydrofuran, at 0.44 g of sodium hydride at 50% in suspension in 10 cm 3 of the same solvent After 30 minutes of stirring at a temperature close to 20 ° C., it is poured dropwise drop a solution of 3.8 g of (3,5-difluoro) benzyl bromide in 20 cm3 of dimethylformamide.
  • Ethyl 2- (3,5-dinitrobenzyl) -6,8-dichloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide-3-carboxylate can be prepared from as follows: under nitrogen, 20 cm3 of a solution of 4 g of 6,8-dichloro-3,4-dihydro-2H-1, 2,4-benzothiadiazine-1, 1-dioxide-3 are added dropwise -carboxy late of ethyl in anhydrous tetrahydrofuran, with 0.59 g of sodium hydride at 50% in suspension in 20 cm3 of the same solvent.
  • the 2-amino-5-chlorobenzenesulfonamide can be prepared according to US Patent 2,986,573.
  • 2-amino-4-methylbenzenesulfonamide can be prepared according to the method described by V. DE SMEDT and A. BRUYLANTS, Bull. Soc. Chim. Belg., 74, 344 (1965).
  • 2-amino-6-methylbenzenesulfonamide can be prepared according to the method described by G. J. THOMAS, J. Agric Food Chem., 32, 747 (1984).
  • Example 95 The procedure is as in Example 95, but using 1.86 g of 2-amino-4,6-difluorobenzenesulfonamide and 1.23 g of giyoxylic acid. 1.44 g of 6,8-difluoro-2H-3,4-dihydro-1,2,4-benzothia diazine-1, 1-dioxide-3-carboxylic acid, melting at 234 ° C., are obtained (dec.)
  • the 2-amino-4,6-difluorobenzenesulfonamide can be prepared as described in Example 96 for the preparation of 2-amino-4-iodobenzenesulfonamide but starting from 10 g of 3,5-difluoroaniIine.
  • 3,5-dibromoaniline can be prepared according to the method described by RG SHEPHERD, J. Org. Chem., 12, 275 (1947).
  • compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
  • the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
  • inert diluents such as starch, cellulose, sucrose, lactose or silica
  • These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.

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  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
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EP93909013A 1992-04-15 1993-04-09 Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant Ceased EP0636124A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
FR929204612A FR2690159B1 (fr) 1992-04-15 1992-04-15 Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant.
FR9204612 1992-04-15
FR9211675 1992-10-02
FR9211675A FR2696457B1 (fr) 1992-10-02 1992-10-02 Dérivés de 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxyde, leur préparation et les médicaments les contenant.
PCT/FR1993/000360 WO1993021170A1 (fr) 1992-04-15 1993-04-09 Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant

Publications (1)

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EP0636124A1 true EP0636124A1 (fr) 1995-02-01

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EP93909013A Ceased EP0636124A1 (fr) 1992-04-15 1993-04-09 Derives d'acide 3,4-dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur preparation et les medicaments les contenant

Country Status (9)

Country Link
EP (1) EP0636124A1 (fi)
JP (1) JPH07505411A (fi)
AU (1) AU3957093A (fi)
CA (1) CA2130096A1 (fi)
FI (1) FI944854A0 (fi)
HU (1) HUT70955A (fi)
IL (1) IL105390A0 (fi)
NO (1) NO943898L (fi)
WO (1) WO1993021170A1 (fi)

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Publication number Priority date Publication date Assignee Title
FR2702150B1 (fr) * 1993-03-03 1995-04-07 Rhone Poulenc Rorer Sa Application de dérivés de 2H-1,2-4-benzothiadiazine-3(4H)-one-1,1-dioxyde comme antagonistes non compétitifs du récepteur NMDA.
FR2710062B1 (fr) * 1993-09-17 1995-12-01 Rhone Poulenc Rorer Sa Dérivés d'acide 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxyde-3-carboxylique, leur préparation et les médicaments les contenant.
AU4345297A (en) * 1996-09-17 1998-04-14 Regents Of The University Of California, The Benzothiadiazide derivatives and their use as allosteric up-modulators of the ampa receptor
WO1999041246A1 (en) * 1998-02-11 1999-08-19 Du Pont Pharmaceuticals Company Novel cyclic sulfonamide derivatives as metalloproteinase inhibitors
IL137720A0 (en) * 1998-02-18 2001-10-31 Neurosearch As Compounds and their use as positive ampa receptor modulators
US6943159B1 (en) 1998-02-18 2005-09-13 Neurosearch A/S Compounds and their use as positive AMPA receptor modulators
FR2801587B1 (fr) * 1999-11-30 2002-01-11 Adir Nouveaux derives de benzothiadiazines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
DE10004572A1 (de) * 2000-02-02 2001-08-09 Boehringer Ingelheim Pharma Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
FR2833950B1 (fr) * 2001-12-21 2005-12-16 Servier Lab Nouveaux derives de benzothiazine et de benzothiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR2943342B1 (fr) 2009-03-20 2011-03-04 Servier Lab Nouveaux derives de benzothiadiazepines,leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
US9670162B2 (en) * 2013-03-14 2017-06-06 The Board Of Trustees Of The Leland Stanford Junio Mitochondrial aldehyde dehyrogenase-2 modulators and methods of use thereof

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GB1009013A (en) * 1961-05-23 1965-11-03 Richard Hurmer Benzothiadiazine compounds
DE69007196T2 (de) * 1989-07-13 1994-06-30 Rhone Poulenc Sante 2-Imino-3 heterocyclylamino-benzothiazoline, ihre Herstellung und sie enthaltende Arzneimittel.

Non-Patent Citations (1)

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Title
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IL105390A0 (en) 1993-08-18
WO1993021170A1 (fr) 1993-10-28
NO943898D0 (no) 1994-10-14
NO943898L (no) 1994-10-14
HUT70955A (en) 1995-11-28
JPH07505411A (ja) 1995-06-15
HU9402980D0 (en) 1995-02-28
FI944854A (fi) 1994-10-14
AU3957093A (en) 1993-11-18
FI944854A0 (fi) 1994-10-14
CA2130096A1 (fr) 1993-10-28

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