DE2655009C2 - - Google Patents

Info

Publication number
DE2655009C2
DE2655009C2 DE19762655009 DE2655009A DE2655009C2 DE 2655009 C2 DE2655009 C2 DE 2655009C2 DE 19762655009 DE19762655009 DE 19762655009 DE 2655009 A DE2655009 A DE 2655009A DE 2655009 C2 DE2655009 C2 DE 2655009C2
Authority
DE
Germany
Prior art keywords
formula
general formula
compounds
methyl
methylisoxazole
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.)
Expired - Lifetime
Application number
DE19762655009
Other languages
German (de)
Other versions
DE2655009A1 (en
Inventor
Friedrich-Johannes Dr. 6203 Hochheim De Kaemmerer
Rudolf Dr. 6238 Hofheim De Schleyerbach
Guenther Dr. 6233 Kelkheim De Heubach
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.)
Hoechst AG
Original Assignee
Hoechst AG
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 Hoechst AG filed Critical Hoechst AG
Priority to DE19762655009 priority Critical patent/DE2655009A1/en
Priority to CH1393477A priority patent/CH608498A5/en
Priority to NL7713151A priority patent/NL7713151A/en
Priority to LU78628A priority patent/LU78628A1/xx
Priority to DK538677A priority patent/DK538677A/en
Priority to AT866377A priority patent/AT362366B/en
Priority to IT3035277A priority patent/IT1126219B/en
Priority to CA292,302A priority patent/CA1102341A/en
Priority to IE245277A priority patent/IE46269B1/en
Priority to GB5034777A priority patent/GB1596383A/en
Priority to JP14562277A priority patent/JPS5371070A/en
Priority to FR7736547A priority patent/FR2372830A2/en
Priority to BE183170A priority patent/BE861503R/en
Publication of DE2655009A1 publication Critical patent/DE2655009A1/en
Application granted granted Critical
Publication of DE2655009C2 publication Critical patent/DE2655009C2/de
Granted legal-status Critical Current

Links

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
    • C07D417/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

Gegenstand des Hauptpatents 25 24 959 sind 5-Methyl-isoxazol-4-carbonsäureanilide der allgemeinen FormelThe main patent 25 24 959 are 5-methyl-isoxazole-4-carboxylic acid anilides of the general formula

worin R¹ ein Wasserstoff- oder Fluoratom, R² ein Wasserstoff- oder Halogenatom oder eine Trifluormethylgruppe, R³ ein Halogenatom, eine Trifluormethyl- oder Nitrogruppe, oder wenn R¹ Wasserstoff bedeutet, R² und R³ zusammen die 3′,4′-Methylendioxygruppe bedeuten.wherein R¹ is hydrogen or fluorine, R² is hydrogen or halogen atom or a trifluoromethyl group, R³ is a halogen atom, a trifluoromethyl or nitro group, or when R¹ is hydrogen, R² and R³ together which mean 3 ', 4'-methylenedioxy group.

In weiterer Ausbildung des Gegenstandes des Hauptpatentes wurden nun neue pharmakologisch wirksame 5-Methyl-isox­ azol-4-carbonsäureamide der Formel IIn further training of the subject of the main patent new pharmacologically effective 5-methyl-isox azole-4-carboxamides of the formula I.

gefunden, in der R einen durch ein Chlor- oder Bromatom substituierten Pyridylrest bedeutet, sowie die Salze dieser Verbindungen mit einer physiologisch verträglichen Säure. found in which R denotes a pyridyl radical substituted by a chlorine or bromine atom, as well as the salts of these compounds with a physiologically acceptable acid.  

Das Verfahren zur Herstellung der Verbindungen der Formel I ist dadurch gekennzeichnet, daß man ein 5-Methylisoxazol-4-carbon­ säure-Derivat der Formel IIThe process for the preparation of the compounds of formula I is characterized in that a 5-methylisoxazole-4-carbon acid derivative of formula II

in der X ein Halogenatom, vorzugsweise Chlor oder Brom, eine YO- oder ZO-CO-O-Gruppe bedeutet, wobei Y für gegebenenfalls durch Fluor, Chlor, Brom, Jod, Methyl, Äthyl, Methoxy, Äthoxy, Trifluormethyl, Nitro oder Cyan einfach, zweifach oder dreifach substituiertes Phenyl oder für den Acylrest entsprechend der Formel II und Z für (C₁-C₄)-Alkyl, Benzyl oder Phenyl stehen, mit einem Amin der allgemeinen Formel IIIin which X is a halogen atom, preferably chlorine or bromine, a YO or ZO-CO-O group, where Y is optionally by fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, Trifluoromethyl, nitro or cyan single, double or triple substituted phenyl or for the acyl radical corresponding to the Formula II and Z represent (C₁-C₄) alkyl, benzyl or phenyl, with an amine of the general formula III

H₂N-R (III)H₂N-R (III)

worin R die zu Formel I angegebene Bedeutung hat, umsetzt.wherein R has the meaning given for formula I.

Die Reaktion wird zweckmäßig in einem Verteilungs- oder Lösungsmittel durchgeführt, das sich gegenüber den Reaktionspartnern indifferent verhält. Hierfür kommen polare Lösungsmittel, beispielsweise Nitrile, wie Acetonitril, Äther, wie Diäthyläther, Tetrahydrofuran oder Dioxan und Alkohole, wie Methanol, Äthanol, Propanol oder Isopropanol in Frage, sowie unpolare Lösungsmittel wie Benzol, Toluol und Cyclohexan.The reaction is conveniently carried out in a distribution or solvent carried out, which is towards the reactants behaves indifferently. Polar solvents are used for this, for example Nitriles, such as acetonitrile, ethers, such as diethyl ether,  Tetrahydrofuran or dioxane and alcohols, such as methanol, ethanol, Propanol or isopropanol in question, as well as non-polar solvents such as benzene, toluene and cyclohexane.

Bevorzugtes Herstellungsverfahren ist die Umsetzung des Carbonsäurechlorids der allgemeinen Formel II mit einem Amin der allgemeinen Formel III. Dabei ist es vorteilhaft, die Umsetzung in Gegenwart von säurebindenden Mitteln wie Kalium- oder Natriumcarbonat, Alkali- oder Erdalkalihydroxiden oder -alkoholaten, organischen Basen, beispielsweise Triäthylamin, Pyridin, Picolin oder Chinolin oder dem jeweiligen im Überschuß eingesetzten Amin, bei Temperaturen zwischen 0 und 160°C, vorzugsweise zwischen 20 und 30°C durchzuführen. Die Reaktionszeiten können wenige Minuten bis zu zwei Stunden betragen.The preferred production process is the conversion of the carboxylic acid chloride of the general formula II with an amine of the general formula III. Here it is advantageous to implement in the presence of acid-binding Agents such as potassium or sodium carbonate, alkali or alkaline earth metal hydroxides or alcoholates, organic bases, for example Triethylamine, pyridine, picoline or quinoline or the respective Amine used in excess, at temperatures between 0 and 160 ° C, preferably between 20 and 30 ° C. The Response times can range from a few minutes to two hours.

Die als Ausgangsstoffe benötigten 5-Methylisoxazol-4-carbonsäure- Derivate der Formel II werden entsprechend DRP 6 34 286 durch Umsetzung von Äthoxymethylidenacetessigester mit Hydroxylamin zum 5-Methylisoxazol-4-carbonsäureester, saures Verseifen des so erhaltenen Esters, vorzugsweise mit einem Gemisch aus Eisessig und konzentrierter Salzsäure im Verhältnis 1 : 1, zur 5- Methylisoxazol-4-carbonsäure, Überführen dieser Carbonsäure nach üblichen Methoden in die Carbonsäurehalogenide, Ester oder gemischten Anhydride, erhalten. Als Carbonsäure-Derivate der Formel II kommen beispielsweise in Betracht 5-Methylisoxazol-4-carbonsäurephenylester, insbesondere 2,4-Dichlorphenylester und 2,4,6-Trichlorphenylester, weiterhin 5-Methylisoxazol-4-carbonsäureanhydride, insbesondere solche, in denen X den Methoxycarbonyloxyrest, Äthoxycarbonyloxyrest, Phenoxycarbonyloxyrest oder Benzyloxycarbonyloxyrest bedeuten.The 5-methylisoxazole-4-carboxylic acid Derivatives of formula II are in accordance with DRP 6 34 286 Reaction of ethoxymethylideneacetoacetic ester with hydroxylamine to 5-methylisoxazole-4-carboxylic acid ester, acid saponification of the thus obtained ester, preferably with a mixture of glacial acetic acid and concentrated hydrochloric acid in a ratio of 1: 1, for 5- Methylisoxazole-4-carboxylic acid, transfer of this carboxylic acid after usual methods in the carboxylic acid halides, esters or mixed Anhydrides. As carboxylic acid derivatives of the formula II are, for example, 5-methylisoxazole-4-carboxylic acid phenyl ester, in particular 2,4-dichlorophenyl ester and 2,4,6-trichlorophenyl ester, furthermore 5-methylisoxazole-4-carboxylic acid anhydrides, in particular those in which X represents the methoxycarbonyloxy radical, ethoxycarbonyloxy radical, Phenoxycarbonyloxy group or benzyloxycarbonyloxy group mean.

Die erfindungsgemäßen Verbindungen gemäß der allgemeinen Formel I sind in der Regel gut kristallisierbare Substanzen. Sie können mit physiologisch verträglichen Säuren in Salze übergeführt werden. Hierfür kommen insbesondere starke Säuren wie Halogenwasserstoffsäuren, insbesondere Salzsäure, Schwefel-, Phosphor-, p-Toluolsulfon-, Methansulfon- und Cyclohexylamidosulfonsäure in Frage. The compounds of general formula I according to the invention are in the Generally well crystallizable substances. You can with physiological compatible acids converted into salts will. Strong acids such as hydrohalic acids, especially hydrochloric acid, sulfuric, phosphoric, p-toluenesulfonic, methanesulfonic and cyclohexylamidosulfonic acid in question.  

Die 5-Methyl-isoxazol-4-carbonsäureamide der Formel I haben wertvolle pharmakologische Eigenschaften. Insbesondere zeigen sie antiphlogistische, antipyretische und analgetische Eigenschaften. Ihre Toxizität ist gering, die Magenverträglichkeit gut.The 5-methyl-isoxazole-4-carboxamides of the formula I have valuable pharmacological properties. In particular show anti-inflammatory, anti-pyretic and analgesic Properties. Their toxicity is low, the tolerance to the stomach Good.

Das geht aus der folgenden Tabelle hervor, die aus dem Hauptpatent (Spalten 5 und 6) entnommen wurde und in welche noch die entsprechenden Werte für Phenylbutazon (Vergleich) und die erfindungsgemäßen VerbindungenThis can be seen from the following table, which from the Main patent (columns 5 and 6) and in which the corresponding values for phenylbutazone (comparison) and the compounds of the invention

N-(5-Chlor-2-pyridyl)-5-methyl-isoxazol-4-carboxamid und
N-(5-Brom-2-pyridyl)-5-methyl-isoxazol-4-carboxamidN- (5-chloro-2-pyridyl) -5-methyl-isoxazole-4-carboxamide and
N- (5-bromo-2-pyridyl) -5-methyl-isoxazole-4-carboxamide

mit aufgenommen wurden. Die Werte wurden nach den im Hauptpatent angegebenen Methoden bestimmt. were included. The values were according to those in the main patent specified methods determined.  

Tabelle table

HerstellungsbeispieleManufacturing examples

1. N-(5-Brom-2-pyridyl)-5-methylisoxazol-4-carboxamid der Formel I1. N- (5-bromo-2-pyridyl) -5-methylisoxazole-4-carboxamide of the formula I.

  • a) 0,1 Mol 2-Amino-5-brompyridin der Formel III (17,3 g) gelöst in 200 ml Tetrahydrofuran, werden bei Raumtemperatur tropfenweise mit einer Lösung von 0,05 Mol 5-Methylisoxazol-4- carbonsäurechlorid der Formel II (7,3 g) in 20 ml Tetrahydrofuran unter Rühren versetzt. Nach weiteren 10 Minuten Rühren filtriert man den ausgefallenen Niederschlag ab und dampft das Filtrat unter vermindertem Druck zur Trockene ein. Man erhält 13,6 g (96% der Theorie) eines farblosen kristallinen Produktes; Schmelzpunkt aus Äthanol: 168-169°C.a) 0.1 mol of 2-amino-5-bromopyridine of the formula III (17.3 g) dissolved in 200 ml of tetrahydrofuran, are added dropwise at room temperature with a solution of 0.05 mol 5-methylisoxazole-4- carboxylic acid chloride of formula II (7.3 g) in 20 ml of tetrahydrofuran added with stirring. After another 10 minutes The precipitate which has precipitated is filtered off and stirred evaporate the filtrate to dryness under reduced pressure. 13.6 g (96% of theory) of a colorless product are obtained crystalline product; Melting point from ethanol: 168-169 ° C.
  • b) 0,1 Mol 2-Amino-5-brompyridin der Formel III (17,3 g) und 0,1 Mol (2,4-Dichlor)phenyl-5-methylisoxazol-4-carboxylat der Formel II (27,2 g), gelöst in 150 ml Tetrahydrofuran, werden 75 Minuten unter Rückfluß erhitzt. Man bringt anschließend die Lösung unter vermindertem Druck zur Trockene und digeriert die öligen Rückstände mit Cyclohexan.
    Nach Dekantieren wird der Rückstand in 300 ml Chloroform gelöst und mit 200 ml 2 n-Salzsäure geschüttelt.
    Die Chloroformphase wird mit Wasser neutral gewaschen, getrocknet und unter vermindertem Druck zur Trockene gebracht. Man erhält 21,4 g (76% der Theorie) eines kristallinen Produktes; Schmelzpunkt nach Umkristallisation aus Äthanol: 168 bis 169°C.    b) 0.1 mol of 2-amino-5-bromopyridine of the formula III (17.3 g) and 0.1 mol (2,4-dichloro) phenyl-5-methylisoxazole-4-carboxylate of the formula II (27.2 g), dissolved in 150 ml of tetrahydrofuran, are heated under reflux for 75 minutes. The solution is then brought to dryness under reduced pressure and the oily residues are digested with cyclohexane.
    After decanting, the residue is dissolved in 300 ml of chloroform and shaken with 200 ml of 2N hydrochloric acid.
    The chloroform phase is washed neutral with water, dried and brought to dryness under reduced pressure. 21.4 g (76% of theory) of a crystalline product are obtained; Melting point after recrystallization from ethanol: 168 to 169 ° C.
  • c) 0,1 Mol 2-Amino-5-brompyridin der Formel II (17,3 g) und 0,1 Mol Benzyloxycarbonyl-5-methylisoxazol-4-carboxylat der Formel II (26,1 g), gelöst in 200 ml Tetrahydrofuran, werden 90 Minuten unter Rückfluß erhitzt. Man bringt die Mischung unter vermindertem Druck zur Trockene und digeriert den Rückstand mit Cyclohexan. Nach Dekantieren wird der Rückstand in 300 ml Chloroform gelöst und mit 200 ml 2 n-Salzsäure geschüttelt. Die Chloroformphase wird mit Wasser neutral gewaschen, getrocknet und unter vermindertem Druck zur Trockene gebracht. Man erhält so 20,6 g (73% der Theorie) eines kristallinen Produktes; Schmelzpunkt nach Umkristallisieren aus Äthanol 168 bis 169°C.c) 0.1 mol of 2-amino-5-bromopyridine of the formula II (17.3 g) and 0.1 Moles of benzyloxycarbonyl-5-methylisoxazole-4-carboxylate Formula II (26.1 g), dissolved in 200 ml of tetrahydrofuran Heated under reflux for 90 minutes. You bring the mix under reduced pressure to dryness and digest the residue  with cyclohexane. After decanting, the residue becomes 300 ml of chloroform dissolved and shaken with 200 ml of 2N hydrochloric acid. The chloroform phase is washed neutral with water, dried and to dryness under reduced pressure brought. This gives 20.6 g (73% of theory) of one crystalline product; Melting point after recrystallization from ethanol 168 to 169 ° C.

2. Die gleiche Verbindung wie in Beispiel 1 erhält man z. B. auch durch Umsetzung von 5-Methylisoxazol-4-carbonsäurechlorid der Formel II mit dem 2-Amino-5-brompyridin der Formel III.2. The same compound as in Example 1 is obtained, for. B. also through implementation from 5-methylisoxazole-4-carboxylic acid chloride of the formula II with the 2-Amino-5-bromopyridine of the formula III.

3. In analoger Weise erhält man das N-(5-Chlor-2-pyridyl)-5-methyl­ isoxazol-4-carboxamid der Formel I durch Umsetzung von 5-Methylisoxazol-4-carbonsäurechlorid der Formel II mit 2-Amino- 5-chlorpyridin der Formel III. 3. The N- (5-chloro-2-pyridyl) -5-methyl is obtained in an analogous manner isoxazole-4-carboxamide of the formula I by reacting 5-methylisoxazole-4-carboxylic acid chloride of the formula II with 2-amino 5-chloropyridine of the formula III.  

Tabelle 1 Table 1

5-Methylisoxazol-4-carbonsäureamide der Formel I 5-methylisoxazole-4-carboxamides of the formula I.

Claims (3)

1. 5-Methyl-isoxazol-4-carbonsäureamide der allgemeinen Formel I in der R einen durch ein Chlor- oder Bromatom substituierten Pyridylrest bedeutet, sowie die Salze dieser Verbindungen mit einer physiologisch verträglichen Säure.1. 5-methyl-isoxazole-4-carboxamides of the general formula I in which R is a pyridyl radical substituted by a chlorine or bromine atom, and the salts of these compounds with a physiologically acceptable acid. 2. Verfahren zur Herstellung der Verbindungen der allgemeinen Formel I in Anspruch 1, dadurch gekennzeichnet, daß man in an sich bekannter Weise ein 5- Methylisoxazol-4-carbonsäure-Derivat der allgemeinen Formel II in der X ein Halogenatom, eine YO- oder ZO-CO-O-Gruppe bedeutet, wobei Y für Phenyl oder durch Fluor-, Chlor-, Brom- oder Jodatome, Methyl-, Äthyl-, Methoxy-, Äthoxy-, Trifluormethyl-, Nitro- oder Cyangruppen ein- bis dreifach substituiertes Phenyl oder für den Acylrest entsprechend der Formel II und Z für eine (C₁-C₄)-Alkyl-, Benzyl- oder Phenylgruppe stehen, mit einem Amin der allgemeinen FormelH₂N-R (III)worin R die zu Formel I angegebene Bedeutung hat, umsetzt anschließend die Verbindungen der allgemeinen Formel I isoliert und/oder mit einer physiologisch verträglichen Säure zu Salzen der Verbindungen der Formel I umsetzt.2. A process for the preparation of the compounds of the general formula I in claim 1, characterized in that a 5-methylisoxazole-4-carboxylic acid derivative of the general formula II is obtained in a manner known per se in which X represents a halogen atom, a YO or ZO-CO-O group, where Y represents phenyl or by fluorine, chlorine, bromine or iodine atoms, methyl, ethyl, methoxy, ethoxy or trifluoromethyl , Nitro or cyano groups mono- to trisubstituted phenyl or for the acyl radical corresponding to the formula II and Z are a (C₁-C₄) alkyl, benzyl or phenyl group, with an amine of the general formula H₂N-R (III) in which R has the meaning given for formula I, then reacting the compounds of the general formula I in isolation and / or reacting with a physiologically tolerable acid to give salts of the compounds of the formula I. 3. Arzneimittel, gekennzeichnet durch einen Gehalt an einer Verbindung der allgemeinen Formel I in Anspruch 1, in Mischung mit einem pharmazeutisch üblichen Trägerstoff und/oder Konstituens.3. Medicinal products characterized by a content of a compound of general formula I in claim 1, in a mixture with a pharmaceutically customary carrier and / or constituent.
DE19762655009 1976-12-04 1976-12-04 ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEANS CONTAINING THESE COMPOUNDS Granted DE2655009A1 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
DE19762655009 DE2655009A1 (en) 1976-12-04 1976-12-04 ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEANS CONTAINING THESE COMPOUNDS
CH1393477A CH608498A5 (en) 1976-12-04 1977-11-15 Process for the preparation of novel 5-methylisoxazole- 4-carboxamides
NL7713151A NL7713151A (en) 1976-12-04 1977-11-29 ISOXAZOLE DERIVATIVES, THEIR PREPARATION AND MEDICINAL PRODUCTS WITH THESE SUBSTANCES.
IT3035277A IT1126219B (en) 1976-12-04 1977-12-02 ISOSSAZOLIC DERIVATIVES, PROCESS FOR THEIR PREPARATION AND MEANS CONTAINING SUCH COMPOUNDS
DK538677A DK538677A (en) 1976-12-04 1977-12-02 ISOXAZOLE DERIVATIVES PROCEDURE FOR THEIR PREPARATION AND MEASURES CONTAINING THESE COMPOUNDS
AT866377A AT362366B (en) 1976-12-04 1977-12-02 METHOD FOR PRODUCING NEW 5-METHYL- -ISOXAZOLE-4-CARBONIC ACID AMIDES AND THEIR SALTS
LU78628A LU78628A1 (en) 1976-12-04 1977-12-02
CA292,302A CA1102341A (en) 1976-12-04 1977-12-02 Isoxazole derivatives, process for their manufacture and agents containing these compounds
IE245277A IE46269B1 (en) 1976-12-04 1977-12-02 Isoxazole derivatives,process for their manufacture and preparations containing these compounds
GB5034777A GB1596383A (en) 1976-12-04 1977-12-02 Isoxazole derivatives process for their manufacture and preparations containing these compounds
JP14562277A JPS5371070A (en) 1976-12-04 1977-12-03 Isooxazole derivative and process for preparing same
BE183170A BE861503R (en) 1976-12-04 1977-12-05 NEW ISOXAZOLES DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS
FR7736547A FR2372830A2 (en) 1976-12-04 1977-12-05 ISOXAZOLE DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR THERAPEUTIC APPLICATION

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19762655009 DE2655009A1 (en) 1976-12-04 1976-12-04 ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEANS CONTAINING THESE COMPOUNDS

Publications (2)

Publication Number Publication Date
DE2655009A1 DE2655009A1 (en) 1978-06-15
DE2655009C2 true DE2655009C2 (en) 1990-03-29

Family

ID=5994666

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19762655009 Granted DE2655009A1 (en) 1976-12-04 1976-12-04 ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEANS CONTAINING THESE COMPOUNDS

Country Status (13)

Country Link
JP (1) JPS5371070A (en)
AT (1) AT362366B (en)
BE (1) BE861503R (en)
CA (1) CA1102341A (en)
CH (1) CH608498A5 (en)
DE (1) DE2655009A1 (en)
DK (1) DK538677A (en)
FR (1) FR2372830A2 (en)
GB (1) GB1596383A (en)
IE (1) IE46269B1 (en)
IT (1) IT1126219B (en)
LU (1) LU78628A1 (en)
NL (1) NL7713151A (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1980000964A1 (en) * 1978-11-03 1980-05-15 American Cyanamid Co Anti-inflammatory agents including 2-carbonyl-3-hydroxy-2-alkenonitriles
EP0035285A3 (en) * 1979-08-17 1981-10-14 American Cyanamid Company Novel isoxazole carboxylic acid phenyl esters, pharmaceutical compositions containing certain of said esters, and process for preparing said esters
DE2854438A1 (en) * 1978-12-16 1980-07-03 Hoechst Ag ISOXAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING THESE COMPOUNDS AND THEIR USE
DE3247454A1 (en) * 1982-12-22 1984-06-28 Laboratorios Bago S.A., Buenos Aires Substituted 3-phenyl-5-methylisoxazole-4-carboxanilides, process for their preparation and pharmaceutical compositions containing these compounds
GB8619433D0 (en) * 1986-08-08 1986-09-17 Lilly Industries Ltd Pharmaceutical compounds
GB8619432D0 (en) * 1986-08-08 1986-09-17 Lilly Industries Ltd Pharmaceutical compounds
US4935434A (en) * 1988-01-26 1990-06-19 Bristol-Myers Company Antiarthritic isoxazole-4-carboxamides
IT1228288B (en) * 1989-01-09 1991-06-07 Zambon Spa COMPOUNDS WITH ANTI-SEROTONIN ACTIVITY
US5001124A (en) * 1990-02-02 1991-03-19 Syntex (U.S.A.) Inc. 4-isoxazolecarboxamide derivatives
ZA913762B (en) 1990-05-18 1992-01-29 Hoechst Ag Isoxazole-4-carboxamides and hydroxyalkylidenecyanoacetamides,pharmaceuticals containing these compounds and their use
WO1991017748A1 (en) * 1990-05-18 1991-11-28 Hoechst Aktiengesellschaft Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides, drugs containing these compounds and use of such drugs
US7338956B2 (en) * 2002-08-07 2008-03-04 Sanofi-Aventis Deutschland Gmbh Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals
CN103772376B (en) * 2012-10-24 2017-01-11 中国医学科学院医药生物技术研究所 Substituted benzo-1,3-miscellaneous azole compound and preparation method and application thereof
US20170088545A1 (en) * 2014-05-14 2017-03-30 Novartis Ag Carboxamide inhibitors
TWI714528B (en) * 2014-05-14 2021-01-01 瑞士商諾華公司 Carboxamide derivatives

Also Published As

Publication number Publication date
DK538677A (en) 1978-06-05
GB1596383A (en) 1981-08-26
FR2372830A2 (en) 1978-06-30
DE2655009A1 (en) 1978-06-15
ATA866377A (en) 1980-10-15
CH608498A5 (en) 1979-01-15
LU78628A1 (en) 1978-07-11
IE46269L (en) 1978-06-04
CA1102341A (en) 1981-06-02
IT1126219B (en) 1986-05-14
IE46269B1 (en) 1983-04-20
AT362366B (en) 1981-05-11
NL7713151A (en) 1978-06-06
JPS5371070A (en) 1978-06-24
FR2372830B2 (en) 1980-06-20
BE861503R (en) 1978-06-05

Similar Documents

Publication Publication Date Title
DE2655009C2 (en)
EP0007019A1 (en) 5-Phenyl-pyrazole derivatives and their salts, processes for their preparation and medicines containing them
DE69632919T2 (en) PROCESS FOR PREPARING 2-CHLORO-5-CHLOROMETHYL-THIAZOLE
DE2823938A1 (en) 5-Methyl-isoxazole-4-carbox:anilide derivs. - with antiphlogistic, analgesic and antipyretic activity
DE2732213A1 (en) DERIVATIVES OF THE CYCLOPROPANCARBONIC ACID DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND THEIR USE AS INTERMEDIATE PRODUCTS IN THE MANUFACTURING OF INSECTICIDES
DE1935404C3 (en) Process for the manufacture of quinazolines
EP1007507B1 (en) Process for preparing 2-cyanoindan-1-ones
DD239591A5 (en) PROCESS FOR THE PREPARATION OF 2,4-DICHLOR-5-FLUORO BENZOESAEURE
EP0245646B1 (en) Process for the preparation of 1-aryl-5-amino-pyrazoles
EP0302227B1 (en) 5-halo-6-amino-nicotinic acid halides, their preparation and their use
DE2655094A1 (en) ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND THE PRODUCTS CONTAINING THE SAME
CH630341A5 (en) Process for the preparation of novel cyanoacetic anilide derivatives.
EP0012435A2 (en) Isoxazole derivatives, process for their preparation, medicines containing them and intermediates required in this process
DE2106303C3 (en) NJM-Dimethyl-O- [1-alkyl-4-cyano-S-alkoxypyrazol (3) yl] -carbamic acid ester, process for their preparation and their use as insecticides and acaricides
DE936747C (en) Process for the production of new pyrimidine derivatives and their salts
DE2326308A1 (en) METHOD FOR MANUFACTURING TETRAMISOL
EP0004322A1 (en) Isoquinolines, process for their preparation and their use for the preparation of medicines
EP0746548B1 (en) Method of preparing 6-aryloxymethyl-1-hydroxy-4-methyl-2-pyridones
EP0115811B1 (en) 2,4-dichlor-5-thiazolecarboxaldehyd and a process for its preparation
DE3323510A1 (en) 2-KETOSULPHONAMIDES AND METHOD FOR THE PRODUCTION THEREOF
DE1768130C3 (en) Isocyanodiphenyl (thio) ethers and processes for their preparation and their use for combating acarids
CH655930A5 (en) METHOD FOR PRODUCING 3-HYDROXYBENZEDIAZEPINONES.
DE2640616B2 (en) Process for the preparation of N-acyl-2-arylglycines
EP0087657B1 (en) Process for the preparation of 1-(4-chlorbenzoyl)-5-methoxy-2-methyl-3-indolylacetoxy-acetic acid
AT242128B (en) Process for the preparation of new benzofuryl (3) ethylamines and their salts

Legal Events

Date Code Title Description
AF Is addition to no.

Ref country code: DE

Ref document number: 2524959

Format of ref document f/p: P

8110 Request for examination paragraph 44
AF Is addition to no.

Ref country code: DE

Ref document number: 2524959

Format of ref document f/p: P

D2 Grant after examination
8364 No opposition during term of opposition