DE3421386A1 - Novel N-pyrazoyl-1,2-benzothiazine-3-carboxamides and pharmaceutical preparations containing them - Google Patents
Novel N-pyrazoyl-1,2-benzothiazine-3-carboxamides and pharmaceutical preparations containing themInfo
- Publication number
- DE3421386A1 DE3421386A1 DE19843421386 DE3421386A DE3421386A1 DE 3421386 A1 DE3421386 A1 DE 3421386A1 DE 19843421386 DE19843421386 DE 19843421386 DE 3421386 A DE3421386 A DE 3421386A DE 3421386 A1 DE3421386 A1 DE 3421386A1
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- benzothiazine
- methyl
- hydroxy
- dioxide
- carboxamide
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- 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
- C07D417/12—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 chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Titel: Neue N-Pyrazolyl-1,2-benzothiazin-3-Title: New N-Pyrazolyl-1,2-Benzothiazin-3-
carboxamide und diese enthaltende pharmazeutische Präparate. carboxamides and pharmaceutical preparations containing them.
Beschreibung Die Erfindung betrifft neue N-Pyrazolyl-benzothiazincarbonsäureamide und deren physiologisch verträgliche Additionssalze und diese Verbindungen enthaltende pharmazeutische Zubereitungen und ihre Verwendung bei der Prophylaxe und Therapie rheumatischer Erkrankungen, besonders bei Arthros e.Description The invention relates to new N-pyrazolyl-benzothiazine carboxamides and their physiologically acceptable addition salts and containing these compounds pharmaceutical preparations and their use in prophylaxis and therapy rheumatic diseases, especially osteoarthritis e.
3-Carbamoyl-1, 2-benzothiazin-1, 1-dioxide mit einem heterocyclischen Substituenten aus Amid-Stickstoff wurden zum erstenmal im US-Patent 3,591,584 beschrieben. Da die Substanzen gute antiinflammatorische und analgetische Eigenschaften zeigen, werden einige in der Therapie von Erkrankungen des rheumatischen Formenkreises verwendet, obwohl sie die Nachteile aller bekannten nichtsteroidalen Therapeutika wie Magenunverträglichkeit mit Ulcusbildung oder gastrointestinalen Irritationen aufweisen.3-carbamoyl-1, 2-benzothiazine-1, 1-dioxide with a heterocyclic Amide nitrogen substituents were first described in U.S. Patent 3,591,584. Since the substances show good anti-inflammatory and analgesic properties, some are used in the therapy of rheumatic diseases, although they have the disadvantages of all known nonsteroidal therapeutics how Have gastric intolerance with ulcer formation or gastrointestinal irritation.
Es wurde nun gefunden, daß Benzothiazincarbonsäureamide der Formel I bedeutet und R1, R2, R3 für Wasserstoff, C1-C3-Alkyl, C1-C3-Alkoxy, Halogen, C1-C3-Trifluoralkyl, Phenyl oder gegebenenfalls durch C1-C3-Alkyl, C1-C2-Trifluoralkyl, Hydroxyl, C1-C3-Alkoxy, C1-C3-Alkoxycarbonyl substituiertes Phenyl stehen und deren pharmazeutisch verträgliche Salze wertvolle pharmakologische Eigenschaften aufweisen.It has now been found that benzothiazine carboxamides of the formula I and R1, R2, R3 for hydrogen, C1-C3-alkyl, C1-C3-alkoxy, halogen, C1-C3-trifluoroalkyl, phenyl or optionally by C1-C3-alkyl, C1-C2-trifluoroalkyl, hydroxyl, C1- C3-alkoxy, C1-C3-alkoxycarbonyl-substituted phenyl and their pharmaceutically acceptable salts have valuable pharmacological properties.
In der Erfindung enthalten sind auch pharmazeutisch verwendbare Additionssalze von Verbindungen der Formel I, die als Enole saure Eigenschaften zeigen und mit geeigneten anorganischen oder organischen Basen entsprechende Salze bilden können. Verwendet werden z.B. Natrium-, Kalium-, Lithium- und Calciumhydroxid bzw. Diethylamin, Triethylamin und Triethanolamin.Also included in the invention are pharmaceutically acceptable addition salts of compounds of the formula I which, as enols, show acidic properties and with suitable inorganic or organic bases can form corresponding salts. For example, sodium, potassium, lithium and calcium hydroxide or diethylamine are used, Triethylamine and triethanolamine.
Erfindungsgemäße Verbindungen sind beispielsweise: 4-Hydroxy-2-methyl-tI-3-pyrazolyl-2H-1,2-benzothiazin-3-carboxamid-l,l-dioxid 4-Hydroxy-2-methyl-N-3-(1-methylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid 4-Hydroxy-2-metllyl-N-3-( 1-phenylpyrazolyl) -211-1, 2-benzothiazin-3-carboxamid-1, 1-dioxid 4-Hydroxy-2-methyl-N-3-(5-methylpyrazolyl)-2H-1,2-benzothiazol-3-carboxamid-l,l-dioxid 4-Hydroxy-2-methyl-N-3-(1,5-dimethylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid 4-Hydroxy-2-methyl-N-3-(1,4-dimethylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1 , 1-dioxid 4-Hydroxy-2-methyl-N-3- ( 4-ethoxycarbonylpyrazolyl) -2H-1 , 2-benzothiazin-3-carboxamid-1 , 1-dioxid 4-EIydroxy-2-methyl-N-4-(1,3-dimethyl-5-carboxypyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid 4-Hydroxy-2-methyl-N-3-(1-methyl-4-chlorpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1 , 1-dioxid 4-Hydroxy-2-methyl-N-3-(4-carboxypyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-l, 1-dioxid 4-Hydroxy-2-methyl-N-3-g1-(3-trifluormethylphenyl)-pyrazolyll-2H-1,2-benzothiazin-3-carboxamid-l,l-dioxid 4-Hydroxy-2-methyl-N-3-g1-(3-trifluormethylphenyl)-pyrazolinyl-2-7-2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid Die Verbindungen der Formel I weisen wertvolle pharmakologische Eigenschaften auf. Insbesondere besitzen sie eine ausgeprägte antiinflammatorische Wirkung, die sich durch Reduktion des durch Carragenin erzeugten Pfotenödems und im Adjuvans-Arthritis-Modell nachweisen läßt. Sie eignen sich daher besonders zur Therapie von rheumatischen Krankheiten, wie z.B. Arthrosen.Examples of compounds according to the invention are: 4-Hydroxy-2-methyl-tI-3-pyrazolyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyl-N-3- (1-methylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyllyl-N-3- (1-phenylpyrazolyl) -211-1, 2-benzothiazine-3-carboxamid-1, 1-Dioxide 4-Hydroxy-2-methyl-N-3- (5-methylpyrazolyl) -2H-1,2-benzothiazole-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyl-N-3- (1,5-dimethylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyl-N-3- (1,4-dimethylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1 , 1-dioxide 4-hydroxy-2-methyl-N-3- (4-ethoxycarbonylpyrazolyl) -2H-1, 2-benzothiazine-3-carboxamide-1 , 1-Dioxide 4-hydroxy-2-methyl-N-4- (1,3-dimethyl-5-carboxypyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyl-N-3- (1-methyl-4-chloropyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1 , 1-dioxide 4-hydroxy-2-methyl-N-3- (4-carboxypyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1, 1-Dioxide 4-Hydroxy-2-methyl-N-3-g1- (3-trifluoromethylphenyl) -pyrazolyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide 4-Hydroxy-2-methyl-N-3-g1- (3-trifluoromethylphenyl) -pyrazolinyl-2-7-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide The compounds of the formula I have valuable pharmacological properties. In particular, they have a pronounced anti-inflammatory effect by Reduction of the paw edema produced by carrageenin and im Adjuvant arthritis model can be demonstrated. They are therefore particularly suitable for therapy of rheumatic diseases such as osteoarthritis.
Die Darstellung der erfindungsgemäßen Verbindungen der Formel I erfolgt nach an sich bekannten Verfahren, indem man z.B. einen Benzothiazincarbonsäureester der Formel II, worin R4 eine Alkyl- bzw. Alkoxyalkylgruppe bedeutet, mit einem Amin der Formel R-SH2 umsetzt.The compounds of the formula I according to the invention are prepared by processes known per se, for example by adding a benzothiazine carboxylic acid ester of the formula II in which R4 is an alkyl or alkoxyalkyl group, with an amine of the formula R-SH2.
Die Aminolyse des Esters wird vorteilhafterweise bei der Siedetemperatur des verwendeten Lösungsmittels durchgeführt, wobei der freiwerdende Alkohol entweder durch azeotrope Destillation oder mit Hilfe eines Molekularsiebes entfernt wird. Die für die Reaktion bevorzugten Lösungsmittel sind Xylol und Toluol.The aminolysis of the ester is advantageously carried out at the boiling point of the solvent used, with the liberated alcohol either is removed by azeotropic distillation or with the aid of a molecular sieve. The preferred solvents for the reaction are xylene and toluene.
Nach einem weiteren Verfahren werden Sulfonamidester der allgemeinen Formel III mit Hilfe von basischen Katalysatoren zu 4-Hydroxy-2-methyl-2H-1, 2-benzothiazin-3-carboxamid-1, 1-dioxiden cyclisiert. Die Umsetzung wird bei Temperaturen von 600-1200C in einem geeigneten protischen oder aprotischen Lösungs- mittel wie z.B. Methanol, Dioxan, Dimethylformamid und Tetrahydrofuran durchgeführt. Als Basen kommen Alkalihydride, -amide oder -alkoholate in Betracht.According to a further process, sulfonamide esters of the general formula III cyclized with the aid of basic catalysts to give 4-hydroxy-2-methyl-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxides. The reaction is carried out at temperatures of 600-1200C in a suitable protic or aprotic solvent such as, for example, methanol, dioxane, dimethylformamide and tetrahydrofuran. Alkali hydrides, amides or alcoholates are suitable as bases.
Die vorliegende Erfindung betrifft ebenfalls pharmazeutische Präparate, welche Verbindungen der Formel I enthalten. Bei den erfindungsgemäßen pharmazeutischen Präparaten handelt es sich um solche zur enteralen wie oralen oder rektalen sowie parenteralen Verabreichung, welche die pharmazeutischen Wirkstoffe allein oder zusammen mit einem üblichen, pharmazeutisch anwendbaren Trägermaterial enthalten. Vorteilhafterweise liegt die pharmazeutische Zubereituny des Wirkstoffes in Form von Einzeldosen vor, die auf die gewünschte Verabreichung abgestimmt sind, wie z.B.The present invention also relates to pharmaceutical preparations, which compounds of formula I contain. In the pharmaceutical according to the invention Preparations are those for enteral such as oral or rectal as well parenteral administration containing the active pharmaceutical ingredients alone or together with a conventional, pharmaceutically applicable carrier material. Advantageously if the pharmaceutical preparation of the active ingredient is available in the form of single doses, tailored to the desired administration, e.g.
Tabletten, Dragees, Kapseln, Suppositorien, Granulate, Lösungen, Emulsionen oder Suspensionen. Die Dosierung der Substanzen liegt bei oraler Applikation üblicherweise zwischen 10 und 1000 mg pro Tag, vorzugsweise zwischen 30 und 300 mg und kann ein- oder mehrmals, bevorzugt zwei- bis dreimal täglich, verabreicht werden.Tablets, coated tablets, capsules, suppositories, granulates, solutions, emulsions or suspensions. The dosage of the substances is usually in the case of oral administration between 10 and 1000 mg per day, preferably between 30 and 300 mg and can be a or several times, preferably two to three times daily, are administered.
Die Herstellung der erfindungsgemäßen Verbindungen wird durch die folgenden Beispiele näher erläutert. Die angegebenen Schmelzpunkte wurden mit einem Büchi 510-Schmelzpunktbestimmungsapparat gemessen und sind mit OC angegeben und nicht korrigiert.The preparation of the compounds according to the invention is carried out by the following examples are explained in more detail. The specified melting points were with a Büchi 510 melting point apparatus and are indicated with OC and not corrected.
Beispiel 1 4-Hydroxy-2-methyl-N-3-pyrazolyl-2H-1,2-benzothiazin-3-carboxamid-l,l-dioxid.Example 1 4-Hydroxy-2-methyl-N-3-pyrazolyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Ein Gemisch von 16 g (0,056 Mol) 2-Ethyl-4-hydroxy-2-methyl-2H-1,2-benzothiazin-3-carboxylat, 5,2 g (0,062 Mol) 3-Aminopyrazol und 200 ml Xylol wird in einem 1 Liter-Dreihalskolben, der mit Tropftrichter und Destillationsaufsatz ausgerüstet ist, unter Rühren zum Sieden erhitzt, wobei ungefähr ein Volumen von 100 ml Xylol pro Stunde abdestillieren soll. Die Zugabe von frischem Xylol wird so eingestellt, daß das Volumen im Destillationskolben ungefähr konstant bleibt. Nach 20-40 Stunden wird das Reaktionsgemisch im Eisbad abgekühlt, der entstandene Niederschlag abfiltriert, mit n-Hexan gewaschen und aus Acetonn-Hexan umkristallisiert.A mixture of 16 g (0.056 mol) of 2-ethyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate, 5.2 g (0.062 mol) of 3-aminopyrazole and 200 ml of xylene are placed in a 1 liter three-necked flask, which is equipped with a dropping funnel and distillation attachment, with stirring for Heated to boiling, with about a volume of 100 ml of xylene distilling off per hour target. The addition of fresh xylene is adjusted so that the volume in the distillation flask remains roughly constant. After 20-40 hours, the reaction mixture is placed in an ice bath cooled, the resulting precipitate filtered off, washed with n-hexane and removed Recrystallized acetone-hexane.
Ausbeute: 7,1 g (36 % der Theorie) Fp. 221-227"C Beispiel 2 4-Hydroxy-2-methyl-N-3-(1-methylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-l,l-dioxid.Yield: 7.1 g (36% of theory). Mp. 221-227 "C example 2 4-Hydroxy-2-methyl-N-3- (1-methylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Eine Mischung von 31,5 g (0,1 Mol) 2-Methoxyethyl-4-hydroxy-2-methyl-2H-(1,2)-benzothiazin-3-carboxylat, 1,2 g (0,14 Mol) l-Methyl-3-aminopyrazol und 300 ml Xylol wird wie unter Beispiel 1 beschrieben behandelt. Nach 24 Stunden wird das Reaktionsgemisch analog Beispiel 1 aufgearbeitet.A mixture of 31.5 g (0.1 mol) of 2-methoxyethyl-4-hydroxy-2-methyl-2H- (1,2) -benzothiazine-3-carboxylate, 1.2 g (0.14 mol) of 1-methyl-3-aminopyrazole and 300 ml of xylene is as in Example 1 described. After 24 hours, the reaction mixture is analogous to the example 1 worked up.
Ausbeute: 32 g (85,5 % der Theorie) Fp. 265-2700C In analoger Weise werden hergestellt: 4-Hydroxy-2-methyl-N-3- ( 5-methylpyrazolyl ) -211-1, 2-benzothiazin-3-carboxamid-1,1-dioxid Ausbeute: 47,7 % der Theorie Fp. 270-2730C 4-Hydroxy-2-methyl-N-3-(1,5-dimethylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1 ,1-dioxid Ausbeute: 38,4 % der Theorie Fp. 220-2250C 4-Hydroxy-2-methyl-N-3-(1,4-dimethyl-5-carboxypyrazolyl)-2H-1,2- benzothiazin-3-carboxamid-1, l-dioxid Ausbeute: 20,5 % der Theorie Fp. 192-1940C 4-Hydroxy-2-methyl-N-4-(1,3-dimethylpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid Ausbeute: 48 % der Theorie Fp. 227°C 4-Hydroxy-2-methyl-N-3- ( 4-carboxypyrazolyl ) -211-1, 2-benzothiazin-3-carboxamid-1,1-dioxid Ausbeute: 29,5 % der Theorie Fp. 2650C Beispiel 3 4-Hydroxy-2-methyl-N-3- ( 1-phenylpyrazolyl ) -211-1, 2-benzothiazin-3-carboxamid-l, 1-dioxid Zu 21,4 g (0,05 Mol) 2-Methyl-carbonyl-phenylsulfonyl-N-3-(l-phenylpyrazolyl)-sarkosinamid in 500 ml Tetrahydrofuran werden 2,4 g Natriumhydrid gegeben und 54 Stunden unter Rückfluß erhitzt. Das Lösungsmittel wird im Vakuum eingedampft und der Rückstand zwischen Wasser und Chloroform verteilt. Die Wasserphase wird abgetrennt, mit 2-normaler Salzsäure angesäuert und dreimal mit je 100 ml Chloroform extrahiert. Die organische Phase wird gewaschen, über Natriumsulfat getrocknet, eingeengt und der Rückstand aus Aceton/Hexan auskristallisiert.Yield: 32 g (85.5% of theory) mp 265-2700C in an analogous manner are prepared: 4-Hydroxy-2-methyl-N-3- (5-methylpyrazolyl) -211-1, 2-benzothiazine-3-carboxamide-1,1-dioxide Yield: 47.7% of theory. Mp. 270-2730C 4-Hydroxy-2-methyl-N-3- (1,5-dimethylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1 , 1-dioxide Yield: 38.4% of theory mp 220-2250C 4-Hydroxy-2-methyl-N-3- (1,4-dimethyl-5-carboxypyrazolyl) -2H-1,2- benzothiazine-3-carboxamide-1,1-dioxide Yield: 20.5% of theory, melting point 192-1940C 4-Hydroxy-2-methyl-N-4- (1,3-dimethylpyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide Yield: 48% of theory. Mp. 227 ° C. 4-Hydroxy-2-methyl-N-3- (4-carboxypyrazolyl ) -211-1, 2-benzothiazine-3-carboxamide-1,1-dioxide Yield: 29.5% of theory. 2650C Example 3 4-Hydroxy-2-methyl-N-3- (1-phenylpyrazolyl) -211-1, 2-benzothiazine-3-carboxamide-l, 1-dioxide To 21.4 g (0.05 mol) of 2-methyl-carbonyl-phenylsulfonyl-N-3- (1-phenylpyrazolyl) -sarcosinamide in 500 ml of tetrahydrofuran 2.4 g of sodium hydride are added and 54 hours under Heated to reflux. The solvent is evaporated in vacuo and the residue distributed between water and chloroform. The water phase is separated off with 2 normal Hydrochloric acid acidified and extracted three times with 100 ml of chloroform each time. The organic Phase is washed, dried over sodium sulfate and concentrated, and the residue crystallized from acetone / hexane.
Ausbeute: 1,2 g (6,1 96 der Theorie) Fp. 234-2370C In analoger Weise werden hergestellt: 4-Hydroxy-2-methyl-N-3-£1- ( 3-trifluormethylphenyl ) -pyrazolylJ -2H-1,2-benzothiazin-3-carboxamid-1,1-dioxid Ausbeute: 5 % der Theorie Fp. 243-245"C 4-Hydroxy-2-methyl-N-3-(1-methyl-4-chlorpyrazolyl)-2H-1,2-benzothiazin-3-carboxamid-l , l-dioxid Ausbeute: 6 96 der Theorie Fp. 185-1920CYield: 1.2 g (6.196 of theory) mp 234-2370C in an analogous manner are prepared: 4-Hydroxy-2-methyl-N-3- £ 1- (3-trifluoromethylphenyl) -pyrazolylJ -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide Yield: 5% of theory. Mp. 243-245 "C 4-Hydroxy-2-methyl-N-3- (1-methyl-4-chloropyrazolyl) -2H-1,2-benzothiazine-3-carboxamide-1 , l-dioxide Yield: 6,96 of theory, mp 185-1920C
Claims (17)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843421386 DE3421386A1 (en) | 1984-06-08 | 1984-06-08 | Novel N-pyrazoyl-1,2-benzothiazine-3-carboxamides and pharmaceutical preparations containing them |
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| Application Number | Priority Date | Filing Date | Title |
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| DE19843421386 DE3421386A1 (en) | 1984-06-08 | 1984-06-08 | Novel N-pyrazoyl-1,2-benzothiazine-3-carboxamides and pharmaceutical preparations containing them |
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| DE3421386A1 true DE3421386A1 (en) | 1985-12-12 |
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| DE19843421386 Withdrawn DE3421386A1 (en) | 1984-06-08 | 1984-06-08 | Novel N-pyrazoyl-1,2-benzothiazine-3-carboxamides and pharmaceutical preparations containing them |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4237634A1 (en) * | 1992-11-07 | 1994-05-11 | Nokia Deutschland Gmbh | Video receiving device with a switching power supply |
| WO2004098590A1 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4-bromo-5- (2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (1-(aminocarbonyl) eth-1-yl) amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
| WO2004099155A2 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4-bromo-5-(2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (phenyl) amide derivates and related compounds as bradykinin b1 receptor antagonists for the treatment of inflamatory diseases |
| WO2004098589A1 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4- bromo - 5 - (2- chloro - benzoylamino) - 1h - pyrazole - 3 - carboxylic acid amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
-
1984
- 1984-06-08 DE DE19843421386 patent/DE3421386A1/en not_active Withdrawn
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4237634A1 (en) * | 1992-11-07 | 1994-05-11 | Nokia Deutschland Gmbh | Video receiving device with a switching power supply |
| WO2004098590A1 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4-bromo-5- (2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (1-(aminocarbonyl) eth-1-yl) amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
| WO2004099155A2 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4-bromo-5-(2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (phenyl) amide derivates and related compounds as bradykinin b1 receptor antagonists for the treatment of inflamatory diseases |
| WO2004098589A1 (en) * | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4- bromo - 5 - (2- chloro - benzoylamino) - 1h - pyrazole - 3 - carboxylic acid amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
| WO2004099155A3 (en) * | 2003-05-02 | 2005-11-10 | Elan Pharm Inc | 4-bromo-5-(2-chloro-benzoylamino)-1h-pyrazole-3-carboxylic acid (phenyl) amide derivates and related compounds as bradykinin b1 receptor antagonists for the treatment of inflamatory diseases |
| JP2006526015A (en) * | 2003-05-02 | 2006-11-16 | エラン ファーマシューティカルズ，インコーポレイテッド | 4-Bromo-5- (2-chloro-benzoylamino) -1H-pyrazole-3-carboxylic acid amide derivatives and related compounds as bradykinin B1 receptor antagonists for the treatment of inflammatory diseases |
| US7417152B2 (en) | 2003-05-02 | 2008-08-26 | Elan Pharmaceuticals, Inc. | 4-bromo-5-(2-chloro-benzoylamino)-1H-pyrazole-3-carboxylic acid amide derivatives and related compounds as bradykinin B1 receptor antagonists for the treatment of inflammatory diseases |
| US7432379B2 (en) | 2003-05-02 | 2008-10-07 | Elan Pharmaceuticals, Inc. | Substituted pyrazole derivatives and related compounds as bradykinin B1 receptor antagonists |
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