DE3407507A1 - Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them - Google Patents

Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them

Info

Publication number
DE3407507A1
DE3407507A1 DE19843407507 DE3407507A DE3407507A1 DE 3407507 A1 DE3407507 A1 DE 3407507A1 DE 19843407507 DE19843407507 DE 19843407507 DE 3407507 A DE3407507 A DE 3407507A DE 3407507 A1 DE3407507 A1 DE 3407507A1
Authority
DE
Germany
Prior art keywords
dichloroanilino
phenylacetic acid
ester
compounds
formula
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Withdrawn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
DE19843407507
Other languages
German (de)
Inventor
Hans Dipl.-Chem. Dr. 5014 Kerpen Betzing
Sigurd Dipl.-Biol. Dr. 5024 Pulheim Leyck
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.)
A Natterman und Cie GmbH
Original Assignee
A Natterman und Cie GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by A Natterman und Cie GmbH filed Critical A Natterman und Cie GmbH
Priority to DE19843407507 priority Critical patent/DE3407507A1/en
Publication of DE3407507A1 publication Critical patent/DE3407507A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids

Landscapes

  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to novel dichloroanilinophenylacetic acid derivatives of the general formula I <IMAGE> a process for their preparation, and pharmaceutical preparations containing them.

Description

Titel: Neue o-(2,6-Dichloranilino)-phenylessigsäure-Title: New o- (2,6-dichloroanilino) phenylacetic acid

ester, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate. esters, processes for their preparation and pharmaceutical products containing them Preparations.

Beschreibung Die Erfindung betrifft neue Dichloranilinophenylessigsäureester, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zubereitungen und ihre Verwendung bei der Prophylaxe und Therapie rheumatischer Erkrankungen wie z.B. Arthrosen oder chronischer Polyarthritis.Description The invention relates to new dichloroanilinophenylacetic acid esters, Process for their preparation and pharmaceutical compositions containing these compounds Preparations and their use in the prophylaxis and therapy of rheumatic Diseases such as osteoarthritis or rheumatoid arthritis.

Die entzündungshemmende Wirkung von o-(2,6-Dichloranilino)-phenylessigsäure (INN Diclofenac) ist bekannt (DE-PS 15 43 639).The anti-inflammatory effects of o- (2,6-dichloroanilino) phenylacetic acid (INN Diclofenac) is known (DE-PS 15 43 639).

Obwohl diese Verbindung gute therapeutische Eigenschaften besitzt, zeigt sie die Nachteile der bekannten nichtsteroidalen entzündungshemmenden Therapeutika wie Magenunverträglichkeit mit Ulcusbildung oder gastrointestinale Irritationen.Although this compound has good therapeutic properties, it shows the disadvantages of the known nonsteroidal anti-inflammatory therapeutics such as gastric intolerance with ulcer formation or gastrointestinal irritation.

Es wurde nun gefunden, daß o-(2,6-Dichloranilino)-phenylessigsäure-Derivate der allgemeinen Formel I in der n eine ganze Zahl von 1-4, R1 Wasserstoff, C1,3-Alkyl r R2=R3 Wasserstoff, Halogen, C1,3-Alkylgruppen, Cl2-Tri fluoralkylgruppen, Hydroxylgruppen oder Ac etoxygruppen bedeuten, wertvolle pharmakologische Eigenschaften aufweisen.It has now been found that o- (2,6-dichloroanilino) phenylacetic acid derivatives of the general formula I. in the n is an integer from 1-4, R1 is hydrogen, C1,3-alkyl r R2 = R3 is hydrogen, halogen, C1,3-alkyl groups, Cl2-tri fluoroalkyl groups, hydroxyl groups or acetoxy groups, have valuable pharmacological properties.

Besonders bevorzugt sind dabei Verbindungen, in denen n eine ganze Zahl von 1-3, R1 C1-3-Alkyl und.R2 bzw. R3 Halogen, Trifluormethyl oder Hydroxyl bedeuten.Particularly preferred are compounds in which n is a whole Number from 1-3, R1 C1-3-alkyl and R2 or R3 halogen, trifluoromethyl or hydroxyl mean.

Erfindungsgemäße Verbindungen sind beispielsweise o-(2,6-Dichloranilino)-phenylessigsäure-2-methoxyethylester o-(2,6-Dichloranilino)-phenylessigsäure-3-methoxypropylester o-(2,6-Dichloranilino)-phenylessigsäure-o-chlor-phenacylester o-(2,6-Dichloranilino)-phenylessigsäure-p-fluor-phenacylester o-(2,6-Dichloranilino)-phenylessigsäure-m-trifluormethylphena cylester o-(2,6-Dichloranilino)-phenylessigsäure-m-methOxy-phenacylester o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxyphena cylester o-(2,6-Dichloranilino)-phenylessigsäure-3,4-diacetoxyphena cylester o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxybenzylester o-(2,6-Dichloranilino)-phenylessigsäure-3,4-diacetoxybenzylester o-(2,6-Dichloranilino)-phenylessigsäure-p-fluor-benzylester o-(2,6-Dichloranilino)-phenylessigsäure-m-trifluormethylbenzylester o-(2,6-Dichloranilino)-phenylessigsäure-p-chlor-benzylester o-(2,6-Dichloranilino)-phenylessigsäure-m-methOxy-benzylester Die erfindungsgemäßen Verbindungen zeigen antithrombotische, antiarteriosklerotische, analgetische sowie ausgeprägte antiphlogistische Wirksamkeit. Sie eignen sich besonders zur Therapie von rheumatischen Krankheiten, wie z.B. Arthrosen oder chronischer Polyarthritis, wobei die neuen Verbindungen sich durch eine sehr gute Verträglichkeit auszeichnen, da sie geringe Toxizität zeigen und im Gegensatz zu bekannten entzündungshemmenden Therapeutika keine Magenunverträglichkeit, wie z.B. Ulcusbildung oder gastrointestinale Irritation, zeigen.Compounds according to the invention are, for example, o- (2,6-dichloroanilino) phenylacetic acid 2-methoxyethyl ester 3-methoxypropyl o- (2,6-dichloroanilino) phenylacetate, o- (2,6-dichloroanilino) phenylacetic acid, o-chlorophenacyl ester o- (2,6-Dichloroanilino) -phenylacetic acid-p-fluoro-phenacyl ester o- (2,6-dichloroanilino) -phenylacetic acid-m-trifluoromethylphenacyl ester o- (2,6-dichloroanilino) -phenylacetic acid-m-methoxy-phenacyl ester o- (2,6-Dichloroanilino) phenylacetic acid 3,4-dihydroxyphenacyl ester o- (2,6-Dichloroanilino) phenylacetic acid 3,4-diacetoxyphena Cyl ester 3,4-dihydroxybenzyl o- (2,6-dichloroanilino) phenylacetic acid 3,4-diacetoxybenzyl o- (2,6-dichloroanilino) phenylacetate o- (2,6-dichloroanilino) -phenylacetic acid-p-fluoro-benzyl ester o- (2,6-dichloroanilino) -phenylacetic acid-m-trifluoromethylbenzyl ester o- (2,6-Dichloroanilino) -phenylacetic acid-p-chlorobenzyl ester o- (2,6-Dichloranilino) -phenylacetic acid-m-methoxy-benzyl ester The compounds according to the invention show antithrombotic, antiarteriosclerotic, analgesic as well as pronounced anti-inflammatory effectiveness. You are suitable particularly for the treatment of rheumatic diseases such as arthrosis or chronic ones Polyarthritis, the new compounds being very well tolerated excel as they show low toxicity and unlike known anti-inflammatory Therapeutics no gastric intolerance, such as ulcer formation or gastrointestinal Irritation, show.

Die Darstellung der erfindungsgemäßen Verbindungen der Formel I erfolgt nach an sich bekannten Verfahren, indem man entweder ein Alkalisalz der o-(2,6-Dichloranilino)-phenylessigsäure mit Halogenverbindungen der Formeln II, III oder IV in denen R1, R2 und R3 die gleiche Bedeutung wie in Formel I haben und X ein Halogenatom wie Chlor oder Brom darstellt, in einem geeigneten organischen Lösungsmittel wie z.B. Dimethylformamid bei Temperaturen von 20-60"C umsetzt, oder o-(2,6-Dichloranilino)-phenylessigsäurechlorid in einem indifferenten organischen Lösungsmittel wie z.B.The compounds of the formula I according to the invention are prepared by processes known per se by either adding an alkali metal salt of o- (2,6-dichloroanilino) phenylacetic acid with halogen compounds of the formulas II, III or IV in which R1, R2 and R3 have the same meaning as in formula I and X is a halogen atom such as chlorine or bromine, in a suitable organic solvent such as dimethylformamide at temperatures of 20-60 "C, or o- (2.6 -Dichloranilino) -phenylacetic acid chloride in an inert organic solvent such as

Chloroform sowie Lösungsmittelgemischen, gegebenenfalls unter Zusatz von üblichen Basen, wie z.B. tertiären Aminen, Metalloxiden, Metallcarbonaten mit einem Alkohol oder Alkoholat von Verbindungen der Formel II-IV, wobei X eine hydroxyl- bzw. Alkalialkoholatgruppe bedeutet, zur Umsetzung bringt.Chloroform and solvent mixtures, optionally with additives of common bases such as tertiary amines, metal oxides, metal carbonates with an alcohol or alcoholate of compounds of the formula II-IV, where X is a hydroxyl or alkali alcoholate group means, brings to implementation.

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 Zubereitung 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, which the active pharmaceutical ingredients alone or together with a customary, pharmaceutically acceptable carrier material contain. The pharmaceutical preparation of the active ingredient is advantageously located in the form of single doses that are tailored to the desired administration, such as.

Tabletten, Dragees, Kapseln, Suppositorien, Granulate, Lösungen, Emulsionen oder Suspensionen.Tablets, coated tablets, capsules, suppositories, granulates, solutions, emulsions or suspensions.

Die Dosierung der Verbindungen liegt üblicherweise zwischen 5 - 250 mg pro Dosis, vorzugsweise zwischen 20 und 100 mg je Dosis und kann ein- oder mehrmals, bevorzugt zwei- bis dreimal täglich, verabreicht werden.The dosage of the compounds is usually between 5-250 mg per dose, preferably between 20 and 100 mg per dose and can be used one or more times, are preferably administered two to three times a day.

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 o-(2,6-Dichloranilino)-phenylessigsäure-2-methOxy-ethylester 31,7 g (0,1 Mol) o-(2,6-Dichloranilino)-phenylessigsäure-Natriumsalz werden in 200 ml trockenem Dimethylformamid gelöst und mit 9,5 g (0,1 Mol) 2-Methoxyethylchlorid 24 Stunden bei Raumtemperatur gerührt. Das Reaktionsprodukt wird mit Wasser versetzt, der entstandene Rückstand abfiltriert, getrocknet und aus Chloroform-Hexan umkristallisiert.Example 1 o- (2,6-dichloroanilino) -phenylacetic acid-2-methoxy-ethyl ester 31.7 g (0.1 mol) of o- (2,6-dichloroanilino) phenylacetic acid sodium salt are added in 200 ml of dry dimethylformamide and dissolved with 9.5 g (0.1 mol) of 2-methoxyethyl chloride Stirred for 24 hours at room temperature. The reaction product is mixed with water, the residue formed is filtered off, dried and recrystallized from chloroform-hexane.

Ausbeute: 25 g (80 % d.Th.) Fp. 103"C In analoger Weise werden hergestellt o-(2,6-Dichloranilino)-phenylessigsäure-4-chlorbenzylester Ausbeute: 40 g (95 % d.Th.) Fp. 79-800C o-(2,6-Dichloranilino)-phenylessigsäure-4-fluorbenzylester Ausbeute: 28 g (70 % d.Th.) Fp. 50-53"C o-(2,6-Dichloranilino)-phenylessigsäure-trifluormethylbenzylester Ausbeute: 33 g (73 % d.Th.) Fp. 88-89"C Beispiel 2 o-(2,6-Dichloranilino)-phenylessigsäure-3,4-díacetoxyphenacylester 15,8 g (0,05 Mol) o-(2,6-Dichloranilino)-phenylessigsäure-Natriumsalz werden mit 13,5 g (0,05 Mol) 3,4-Diacetoxyphenacylchlorid, katalytischen Mengen Kaliumjodid und 150 ml Ethylmethylketon 20 Stunden bei 400C gerührt. Nach dem Abdestillieren des Lösungsmittels im Vakuum wird der entstandene Rückstand in wenig Chloroform gelöst und die Lösung mit Wasser gewaschen. Nach dem Trocknen der Chloroformlösung mit Natriumsulfat destilliert man das Lösungsmittel im Vakuum ab und kristallisiert den Rückstand aus Methanol um.Yield: 25 g (80% of theory) melting point 103 "C. Preparations are carried out in an analogous manner 4-chlorobenzyl o- (2,6-dichloroanilino) phenylacetate Yield: 40 g (95% d.Th.) Mp. 79-800C o- (2,6-dichloroanilino) -phenylacetic acid-4-fluorobenzyl ester Yield: 28 g (70% of theory) mp 50-53 "of C o- (2,6-dichloroanilino) phenylacetic acid trifluoromethylbenzyl ester Yield: 33 g (73% of theory) mp 88-89 "C Example 2 3,4-diacetoxyphenacyl ester of o- (2,6-dichloroanilino) phenylacetic acid 15.8 g (0.05 mol) of o- (2,6-dichloroanilino) -phenylacetic acid sodium salt are with 13.5 g (0.05 mol) of 3,4-diacetoxyphenacyl chloride, catalytic amounts of potassium iodide and 150 ml of ethyl methyl ketone were stirred at 40 ° C. for 20 hours. After distilling off of the solvent in vacuo, the residue formed is dissolved in a little chloroform dissolved and the solution washed with water. After drying the chloroform solution the solvent is distilled off in vacuo with sodium sulfate and crystallized the residue from methanol.

Ausbeute: 25,5 g (96 % d.Th.) Fp. 1530C Beispiel 3 o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxyphenacylester 25,5 g o-(2,6-Dichloranilino)-phenylessigsäure-3,4-diacetoxy-phenacylester werden in 150 ml trockenem Chloroform gelöst und mit 8,35 ml Morpholin 15 Stunden bei Raumtemperatur gerührt. Danach wird die Reaktionslösung wiederholt mit Wasser gewaschen. Die Chloroformlösung wird mit Natriumsulfat getrocknet und durch teilweises Abdestillieren des Lösungsmittels im Vakuum stark aufkonzentriert. Der gebildete Niederschlag wird abgesaugt, mit wenig kaltem Ether nachgewaschen und getrocknet.Yield: 25.5 g (96% of theory) mp 1530C Example 3 3,4-dihydroxyphenacyl o- (2,6-dichloroanilino) phenylacetate 25.5 g of o- (2,6-dichloroanilino) -phenylacetic acid-3,4-diacetoxy-phenacyl ester become dissolved in 150 ml of dry chloroform and mixed with 8.35 ml of morpholine for 15 hours at room temperature touched. Thereafter, the reaction solution is repeatedly washed with water. The chloroform solution is dried with sodium sulfate and partially distilled off the solvent strongly concentrated in vacuo. The precipitate formed is filtered off with suction Washed a little cold ether and dried.

Ausbeute: 20 g (90 % d.Th.) Fp. 200-203"C In analoger Weise wird hergestellt o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxybenzylester Ausbeute: 18,6 g (81 % d.Th.) Fp. 132"CYield: 20 g (90% of theory) melting point 200-203 "C The preparation is carried out in an analogous manner 3,4-dihydroxybenzyl o- (2,6-Dichloroanilino) phenylacetic acid Yield: 18.6 g (81% of theory) m.p. 132 "C

Claims (1)

Titel: Neue o-(2,6-Dichloranilino)-phenylessigsäureester, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate. Title: New o- (2,6-dichloroanilino) phenylacetic acid esters, method for their manufacture and pharmaceutical preparations containing them. Patentansprüche Neue Dichloranilinophenylessigsäure-Derivate der allgemeinen Formel I worin n eine ganze Zahl von 1 - 4 R1 Wasserstoff, C1,3-Alkyl R2=R3 Wasserstoff, Halogen, C1,3-Alkylgruppen, C1,2-Trifluoralkylgruppen, Hydroxylgruppen oder Acetoxygruppen bedeuten.Claims New dichloroanilinophenylacetic acid derivatives of the general formula I. wherein n is an integer from 1 to 4 R1 hydrogen, C1,3-alkyl R2 = R3 hydrogen, halogen, C1,3-alkyl groups, C1,2-trifluoroalkyl groups, hydroxyl groups or acetoxy groups. 2. Verbindungen der Formel I gemäß Anspruch 1, in denen n eine ganze Zahl von 1-3 und R1 einen C1,3-Alkylrest bedeuten.2. Compounds of formula I according to claim 1, in which n is a whole Number from 1-3 and R1 is a C1,3-alkyl radical. 3. Verbindungen der Formel I gemäß Anspruch 1, in denen n eine ganze Zahl von 1-3, R2 Wasserstoff und R3 Halogen oder die Trifluormethylgruppe bedeuten.3. Compounds of formula I according to claim 1, in which n is a whole Number from 1-3, R2 signifies hydrogen and R3 signifies halogen or the trifluoromethyl group. 4. Verbindungen der Formel I gemäß Anspruch 1, in denen n eine ganze Zahl von 1-3, R2 und R3 Hydroxyl- bzw.4. Compounds of formula I according to claim 1, in which n is a whole Number from 1-3, R2 and R3 hydroxyl resp. Acetoxygruppen bedeuten. Mean acetoxy groups. 5. o-(2,6-Dichloranilino)-phenylessigsäure-2-methOxyethylester 6. o-(2,6-Dichloranilino)-phenylessigsäure-3-methOxypropylester 7. o-(2,6-Dichloranilino)-phenylessigsäure p-chlor-phenacylester 8. o-(2,6-Dichloranilino)-phenylessigsäure p-fluor-phenacylester 9. o-(2,6-Dichloranilino)-phenylessigsäure m-trifluormethyl-phenacylester 10. o-(2,6-Dichloranilino)-phenylessigsäure-m-methOxyphenacylester 11. o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxyphenacylester 12. o-(2,6-Dichloranilino)-phenylessigsäure-3,4-diacetoxyphenacylester 13. o-(2,6-Dichloranilino)-phenylessigsäure-3,4-dihydroxybenzylester 14. o-(2,6-Dichloranilino)-phenylessigsäure-3,4-diacetoxybenzylester 15. o-(2,6-Dichloranilino)-phenylessigsäure-p-fluor-benzylester 16. o-(2,6-Dichloranilino)-phenylessigsäure-m-trifluormethyl-benzylester 17. o-(2,6-Dichloranilino)-phenylessigsäure-p-chlor-benzylester 18. o-(2,6-Dichloranilino)-phenylessigsäure m-methoxybenzylester 19. Verfahren zur Herstellung von Verbindungen gemäß den Ansprüchen 1-18, dadurch gekennzeichnet, daß man a) Halogenverbindungen der allgemeinen Formel II, III oder IV in denen R1, R2 und R3 die gleiche Bedeutung wie in Formel 1 haben und X ein Halogenatom darstellt, in einem geeigneten organischen Lösungsmittel mit einem Alkalisalz der o-(2, 6-Dichloranilino)-phenylessigsäure umsetzt.5. o- (2,6-dichloroanilino) -phenylacetic acid-2-methoxyethyl ester 6. o- (2,6-dichloroanilino) -phenylacetic acid-3-methoxypropyl ester 7. o- (2,6-dichloroanilino) -phenylacetic acid p-chloro phenacyl ester 8. o- (2,6-dichloroanilino) phenylacetic acid p-fluorophenacyl ester 9. o- (2,6-dichloroanilino) phenylacetic acid m-trifluoromethyl phenacyl ester 10. o- (2,6-dichloroanilino) - phenylacetic acid m-methoxyphenacyl ester 11. o- (2,6-dichloroanilino) phenylacetic acid 3,4-dihydroxyphenacyl ester 12. o- (2,6-dichloroanilino) phenylacetic acid 3,4-diacetoxyphenacyl ester 13. o- (2, 6-dichloroanilino) phenylacetic acid 3,4-dihydroxybenzyl ester 14. o- (2,6-dichloroanilino) phenylacetic acid 3,4-diacetoxybenzyl ester 15. o- (2,6-dichloroanilino) phenylacetic acid p-fluoro-benzyl ester 16. o- (2,6-dichloroanilino) -phenylacetic acid-m-trifluoromethyl-benzyl ester 17.o- (2,6-dichloroanilino) -phenylacetic acid-p-chlorobenzyl ester 18.o- (2,6-dichloroanilino) - phenylacetic acid m-methoxybenzyl ester 19. A process for the preparation of compounds according to Claims 1-18, characterized in that a) halogen compounds of the general formula II, III or IV in which R1, R2 and R3 have the same meaning as in formula 1 and X represents a halogen atom, is reacted in a suitable organic solvent with an alkali salt of o- (2,6-dichloroanilino) phenylacetic acid. b) o-(2,6-Dichloranilino)-phenylessigsäurechlorid in einem indifferenten organischen Lösungsmittel mit einem Alkohol oder Alkoholat von Verbindungen der allgemeinen Formeln II-IV, wobei X eine Hydroxyl-bzw. Alkalialkoholatgruppe darstellt, gegebenenfalls unter Zusatz eines Säureakzeptors, umsetzt. b) o- (2,6-dichloroanilino) phenylacetic acid chloride in an indifferent organic solvent with an alcohol or alcoholate of compounds of the general formulas II-IV, where X is a hydroxyl or. Represents alkali alcoholate group, optionally with the addition of an acid acceptor. 20. Arzneimittelzubereitungen, dadurch gekennzeichnet, daß sie rnindestens eine Verbindung gemäß den Ansprüchen 1-18 zusammen rnit einem geeigneten Verdünnungsmittel oder Trägermaterial enthalten.20. Medicinal preparations, characterized in that they contain at least a compound according to claims 1-18 together with a suitable diluent or contain carrier material.
DE19843407507 1984-03-01 1984-03-01 Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them Withdrawn DE3407507A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19843407507 DE3407507A1 (en) 1984-03-01 1984-03-01 Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19843407507 DE3407507A1 (en) 1984-03-01 1984-03-01 Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them

Publications (1)

Publication Number Publication Date
DE3407507A1 true DE3407507A1 (en) 1985-09-05

Family

ID=6229259

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19843407507 Withdrawn DE3407507A1 (en) 1984-03-01 1984-03-01 Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them

Country Status (1)

Country Link
DE (1) DE3407507A1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0211102A1 (en) * 1985-08-08 1987-02-25 T P O "Pharmachim" Esters of the o-(2,6-dichlorophenylamino)phenylacetic acid and process for their preparation
DE3636125A1 (en) * 1985-10-25 1987-04-30 Espanola Prod Quimicos METHOD FOR PRODUCING DIETHYLENE GLYCOLESTERS
WO1994004484A1 (en) * 1992-08-20 1994-03-03 Corlay S.L. Nitric esters of derivatives of the 2-(2,6-di-halophenylamino)phenylacetic acid and process for their preparation
US5607966A (en) * 1994-12-23 1997-03-04 Alcon Laboratories, Inc. Esters and amides of non-steroidal anti-inflammatory carboxylic acids which may be used as anti-oxidants, 5-lipoxygenase inhibitors and non-steroidal anti-inflammatory prodrugs
US5643943A (en) * 1994-12-23 1997-07-01 Alcon Laboratories, Inc. Systemic administration of esters and amides of antioxidants which may be used as antioxidant prodrug therapy for oxidative and inflammatory pathogenesis
US5811453A (en) * 1994-12-23 1998-09-22 Alcon Laboratories, Inc. Viscoelastic compositions and methods of use
US5908849A (en) * 1995-09-12 1999-06-01 Alcon Laboratories, Inc. Anti-oxidant esters of non-steroidal anti-inflammatory agents

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0211102A1 (en) * 1985-08-08 1987-02-25 T P O "Pharmachim" Esters of the o-(2,6-dichlorophenylamino)phenylacetic acid and process for their preparation
DE3636125A1 (en) * 1985-10-25 1987-04-30 Espanola Prod Quimicos METHOD FOR PRODUCING DIETHYLENE GLYCOLESTERS
WO1994004484A1 (en) * 1992-08-20 1994-03-03 Corlay S.L. Nitric esters of derivatives of the 2-(2,6-di-halophenylamino)phenylacetic acid and process for their preparation
US5597847A (en) * 1992-08-20 1997-01-28 Corlay S.L. Nitric esters of derivatives of the 2-(2,6-di-halo-phenylamino) phenylacetic acid and process for their preparation
US5607966A (en) * 1994-12-23 1997-03-04 Alcon Laboratories, Inc. Esters and amides of non-steroidal anti-inflammatory carboxylic acids which may be used as anti-oxidants, 5-lipoxygenase inhibitors and non-steroidal anti-inflammatory prodrugs
US5643943A (en) * 1994-12-23 1997-07-01 Alcon Laboratories, Inc. Systemic administration of esters and amides of antioxidants which may be used as antioxidant prodrug therapy for oxidative and inflammatory pathogenesis
US5811438A (en) * 1994-12-23 1998-09-22 Alcon Laboratories, Inc. Esters and amides of non-steroidal anti-inflammatory carboxylic acids which may be used as anti-oxidants, 5-lipoxygenase inhibitors and non-steroidal anti-inflammatory products
US5811453A (en) * 1994-12-23 1998-09-22 Alcon Laboratories, Inc. Viscoelastic compositions and methods of use
US6242480B1 (en) 1994-12-23 2001-06-05 Alcon Laboratories, Inc. Ophthalmic viscoelastic compositions
US5908849A (en) * 1995-09-12 1999-06-01 Alcon Laboratories, Inc. Anti-oxidant esters of non-steroidal anti-inflammatory agents
US5998465A (en) * 1995-09-12 1999-12-07 Alcon Laboratories, Inc. Esters of non-steroidal anti-flammatory carboxylic acids

Similar Documents

Publication Publication Date Title
DE2636582C2 (en) 2-Amino-3- (5- and 6-) benzoylphenylacetic acids, their esters and metal salts, processes for the preparation of these compounds and medicaments containing them
EP0026317B1 (en) Optically active 1,4-dihydropyridines, processes for their preparation and their use as medicaments
DE3702755A1 (en) 3,5-DI-TERT.-BUTYL-4-HYDROXYBENZOESAEUREAMID, MISCELLANEOUS OF THE DERIVATIVES THEREOF, METHOD FOR PRODUCING THESE COMPOUNDS, THE MEDICINAL PRODUCTS CONTAINING THEM AND THEIR USE
DE3407507A1 (en) Novel o-(2,6-dichloroanilino)phenylacetic acid esters, process for their preparation, and pharmaceutical preparations containing them
EP0061056A1 (en) 5,6-Dimethylpyrrolo (2,3-b) pyridines, process for their preparation and their use as medicaments
DE3204854C2 (en) 2-Amino-3- (halobenzoyl) -methylphenylacetic acids, their esters and salts, pharmaceutical compositions containing these compounds
DE2434929C2 (en) p-Acetylaminophenol esters of phenylsalicylic acids, processes for their preparation and pharmaceuticals containing these compounds
DE69023045T2 (en) Carboxamide derivatives.
DE2462460C3 (en) 2- (4-Quinolylamino) -benzoic acid 2- (4-phenylpiperazino) -ethyl ester substituted in the 8-position of the quinoline ring, process for their preparation and pharmaceuticals containing them
DE2600325A1 (en) BUTAZONE DERIVATIVES, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THEM
DE3034005C2 (en) Indole acetic acid derivatives, process for their preparation and pharmaceutical preparations containing them
EP0313935A2 (en) Enolethers of 6-chloro-4-hydroxy-2-methyl-N-(2-pyridyl)-2H-thieno(2,3-e)-1,2-thiazin-3-carboxylic acid amide-1,1-dioxide, a process for their preparation and their use
DE2755122C2 (en) New acyl derivatives of Hellebrigenin, processes for their production and medicinal products containing them
DE3215648A1 (en) MEDICINE WITH NEW INFLAMMATORY AND IMMUNEGULATORY PYRIDINES
DE3105111A1 (en) &#34;2-DESOXY-3 &#39;, 5-DI-O-ALKYLCARBONYL-5-FLUORURIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THEIR USE FOR TREATING TUMORS AND ANTITUARY MEDICINES&#34;
DE2065420C2 (en) d-2- (Methoxy-2-naphthyl) -propanal, process for its production and medicinal products containing it
AT293361B (en) Process for the preparation of new β-aminoacrylophenones and their salts
AT294049B (en) Process for the preparation of new β-aminoacrylophenones and their salts
CH533619A (en) Phenyl-substd pyrrole derivs with anti- - inflammatory activity
DE2609574A1 (en) MONOSUBSTITUTED PIPERAZINE DERIVATIVE, PROCESS FOR ITS MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING IT
DE2012667A1 (en) Substd benzo-imidazolones-oxazolinones - and thiazolinones, anti-inflammatory
DE3242922A1 (en) PHENYLPROPANOLAMINE, THEIR PRODUCTION AND USE
DD145754A5 (en) PROCESS FOR THE PRODUCTION OF ESTERS FROM METHYL-1 PIPERIDINOL-4
AT365179B (en) METHOD FOR PRODUCING NEW UREA AND AMIDO COMPOUNDS
AT281780B (en) METHOD FOR PRODUCING NEW HALOGENATED ALCANDIOLS

Legal Events

Date Code Title Description
8139 Disposal/non-payment of the annual fee