CZ355892A3 - thiazolyl-substituted derivatives of quinolylmethoxyphenylacetic acid - Google Patents

Abstract

Thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives of these compounds are obtained by reacting haloacetoacetic acid esters with thioamides quinolylmethoxyphenylacetic acid; of the corresponding amides with Lawesson's reagent. Listed the substances can be used as enzymatic inhibitors in medicaments reactions in the metabolism of arachidonic acid.

Description

Thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives

The present invention relates to thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives, processes for their preparation and their use in pharmaceuticals.

BACKGROUND OF THE INVENTION

EP 200 101 A2 discloses aryl and heteroaryl ethers having lipoxygenase inhibitory and anti-inflammatory and antiallergic effects.

In addition, substituted 4- (quinolin-2-ylmethoxy) phenylacetic acid derivatives and α-substituted 4- (quinolin-2-ylmethoxy) phenyl acetic acid derivatives are known from EP 344 519 (US 4 970 215) and EP 339 416.

Further, EP 351 194 describes a process for the production of lipoxygenase-inhibiting aryl-substituted thiazoles.

The essence of the invention

The present invention provides thiazolyl-substituted quinolylmethoxyphenyl acetic acid derivatives of the general formula I

A G

(B)

O

S (I),

wherein k, B, D, E, G, LaM are the same or different and denote a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a carboxyl group, a nitro group, a trifluoromethyl group or a trifluoromethoxy group or a straight or branched alkyl or alkoxy group. Or (C 6 -C 10) aryl group optionally substituted by a halogen atom, a hydroxy group, a nitro group or a cyano group,

R @ ¹ denotes a straight or branched alkyl group having up to 8 carbon atoms which is optionally substituted by a phenyl or cycloalkyl group having 3 to 12 carbon atoms or a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a straight or branched alkyl group; a branched alkyl group having up to 8 carbon atoms;

T represents a straight or branched alkyl group having up to 6 carbon atoms, or a group of the formula

in which

R ⁵ represents a hydrogen atom or a straight or branched alkyl group having up to 8 carbon atoms or a benzyl or cycloalkyl group having 3 to 12 carbon atoms, and

R ³ represents a radical -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ , wherein

R ⁵ represents a hydrogen atom or a straight or branched alkyl group of up to 6 carbon atoms or a benzyl group,

R ⁶ represents an aryl group having 6 to 10 carbon atoms, which is optionally up to two times the same or differently substituted by halogen, cyano, hydroxy, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio or a straight or branched alkyl or alkoxy group each having up to 8 carbon atoms or a straight or branched alkyl group having up to 8 carbon atoms which is optionally substituted by a phenyl group which may be substituted by a halogen atom, a cyano group, a nitro group, a trifluoromethyl group, a trifluoromethoxy group, a trifluoromethylthio group or a straight or branched alkyl or alkoxy group. C 6-6 atoms, optionally in isomeric form, and salts thereof.

Physiologically acceptable salts are preferred within the scope of the present invention. Physiologically acceptable salts of thiazolyl-substituted quinolylmethoxyphenyl acetic acid derivatives include salts of the compounds of the present invention with mineral acids, carboxylic acids, or sulfonic acids, particularly preferred are salts with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid. , toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid.

Salts within the scope of the present invention are furthermore salts with monovalent metals such as alkali metals or ammonium salts. Sodium, potassium and ammonium salts are preferred.

The compounds of the present invention exist in stereoisomeric forms (*) which behave either as image and mirror image (enantiomers) or not as image and mirror image (diastereomers). The present invention relates to both antipodes and racemic forms as well as diastereomeric mixtures. Racemic forms, like diastereomers, can be resolved into stereoisomerically uniform components by known methods (see E. L. Eliel, Stereochemistry of Carbon Compounds, McGraw Hill, 1962).

Preferred are compounds of formula I wherein:

A, B, D, E, G, L, and M are the same or different and are hydrogen, hydroxy, fluoro, chloro, bromo, carboxyl, nitro, trifluoromethyl, trifluoromethoxy, or straight or branched alkyl or alkoxy in each case up to 6 carbon atoms or a phenyl group which is optionally substituted by a fluorine atom, a chlorine atom, a bromine atom, a hydroxy group, a nitro group or a cyano group,

R @ ¹ denotes a straight or branched alkyl group having up to 6 carbon atoms, which is optionally substituted by a phenyl group, a cyclopropyl group, a cyclopentyl group, a cyclopentyl group or a cycloheptyl group or a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group , a cycloheptyl group or a cyclooctyl group, which are optionally substituted by a straight or branched alkyl group having up to 6 carbon atoms, and

T represents a straight or branched alkyl group having up to 4 carbon atoms, or a group of the formula

in which

R ² represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, or benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl and

R ² represents the radical -OR ⁴ or -NR ⁵ -SO ₂ -R ^6, wherein

R ⁴ represents a hydrogen atom or a straight or branched alkyl group of up to 6 carbon atoms,

R ⁵ represents a hydrogen atom or a straight or branched alkyl group having up to 4 carbon atoms

R ⁶ denotes a phenyl group which is optionally substituted by a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a cyano group or a straight or branched alkyl or alkoxy group of up to 6 carbon atoms or a straight or branched alkyl group of up to 6 carbon atoms optionally substituted by a phenyl group, which may be substituted by a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group or a straight or branched alkyl or alkoxy group of up to 4 carbon atoms each, optionally in isomeric form, and salts thereof.

Particularly preferred are compounds of formula I wherein:

A, B, D, E, G, L, and M are the same or different and denote a hydrogen atom, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom or a straight or branched alkyl group of up to 4 carbon atoms,

R @ ¹ denotes a straight or branched alkyl group having up to 6 carbon atoms, which is optionally substituted by phenyl, cyclopropyl, cyclopentyl or cyclohexyl, or cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl groups which are optionally substituted by a straight or branched alkyl group having up to 4 carbon atoms; and

T represents a methyl group or a group of the formula wherein

R ² represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R ³ represents a radical of formula -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ wherein R ⁴ denotes hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,

R ⁵ denotes a hydrogen atom, a methyl group or an ethyl group and r ⁶ denotes a phenyl group which is optionally substituted by a fluorine atom, an atom, a chlorine atom, a bromine atom, an iodine atom, a methoxy or trifluoromethyl group or a straight or branched alkyl group having up to 4 carbon atoms which is optionally substituted by a phenyl group, which may be substituted by a fluorine atom, a chlorine atom, a bromine atom, a methyl group or a methoxy group, optionally in isomeric form, and salts thereof.

Particularly preferred are compounds of formula I wherein:

A, B, D, E, G, and LaM are hydrogen.

Also particularly preferred are compounds in which the remainder of the formula is CHR.

at position 4 to the quinolylmethoxyl residue.

The present invention further provides a process for the preparation of compounds of the formula I which comprises reacting thioamides of the formula II in which they have the meaning:

A, B, D, E, G, L, M and R ¹ above with the haloacetic acid ester derivatives or the halo ketones III

Cl - ch ₂ - CO - ch ₂ - W (III), in which

W represents a hydrogen atom, an alkyl group having 1 to 67 carbon atoms or a group -CO-R, wherein:

R ⁷ denotes an alkoxy group having 1 to 4 carbon atoms, in organic solvents, optionally in the presence of water, and in the case of acids (R ³ OH), the esters are saponified by customary methods, and when R ² does not denote a hydrogen atom, alkylation, and in the case of sultonamides (R ³ = -NH-SO ₂ R ⁶ ) amidation is carried out in inert solvents, optionally in the presence of

Base and / or adjuvant, wherein the substituents A, B, D, E, G, LaM may be altered at any of the above stages by methods known in the literature.

The process of the present invention can be illustrated by the following reaction scheme:

CJ-C--CO-CH ^COq-C ^ s

NaOH

Suitable solvents for the individual reaction steps are generally inert organic solvents which do not change under the reaction conditions. These preferably include ethers such as dioxane, tetrahydrofuran or diethyl ether, halogenated hydrocarbons such as dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane or trichlorethylene, hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane or the like. petroleum fractions and nitromethane, dimethylformamide, acetonitrile, acetone or hexamethylphosphoric triamide. It is also possible to use mixtures of the solvents mentioned. Toluene is preferred for reaction with compounds of Formula II.

Said process is generally carried out at a temperature in the range of 0 ° C to 150 ° C, preferably 25 ° C to 40 ° C.

The process is generally carried out under normal pressure, but it is also possible to operate under reduced or elevated pressure, for example in the range of 0.5 to 5 bar.

Suitable solvents for the alkylation are also customary organic solvents which do not change under the reaction conditions. These preferably include ethers such as diethyl ether, dioxane, tetrahydrofuran or glycol dimethyl ether, hydrocarbons such as benzene, toluene xylene, hexane, cyclohexane or petroleum fractions, halogenated hydrocarbons such as dichloromethane, trichloromethane carbon tetrachloride, dichlorethylene, trichlorethylene or chlorobenzene and ethyl acetate, triethylamine pyridine, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone or nitromethane. It is also possible to use mixtures of the solvents mentioned. Dichloromethane is preferred.

The alkylation is carried out in the abovementioned solvents at temperatures ranging from 0 ° C to 150 ° C, preferably at room temperature to 100 ° C and under normal pressure.

The amidation is generally carried out in inert solvents in the presence of a base and a dehydrating agent.

Suitable solvents here are inert organic solvents which do not change under the reaction conditions. These include halogenated hydrocarbons such as dichloromethane, trichloromethane, carbon tetrachloride,

1,2-dichloroethane, trichloroethane, trichlorethylene or tetrachloroethane, hydrocarbons such as benzene, xylene, toluene, hexane, cyclohexane or petroleum fractions and further nitromethane, dimethylformamide, acetonitrile or hexamethylphosphoric triamide. It is also possible to use mixtures of the solvents mentioned. Dichloromethane is particularly preferred

Suitable bases for amidation are conventional basic compounds. These preferably include alkali metal and alkaline earth metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide or barium hydroxide, alkali metal hydrides such as sodium hydride, alkali metal or alkaline earth metal carbonates such as sodium carbonate or potassium carbonate, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide or potassium tert-butylate, or organic amines such as benzyltrimethylammonium hydroxide, tetrabutylammonium hydroxide, pyridine, triethylamine, piperidine or N -methylpiperidine.

Potassium carbonate, sodium hydride, sodium bicarbonate and piperidine are preferred.

The amidation is generally carried out at a temperature in the range of 0 to 150 ° C, preferably 25 to 40 ° C.

The amidation is generally carried out at normal pressure, but it is also possible to work under reduced or elevated pressure, for example in the range from 0.5 to 5 bar.

In carrying out the amidation, the base is generally used in an amount of 1 to 3 mol, preferably 1 to 1.5 mol, based on 1 mol of carboxylic acid.

Suitable dehydrating agents are carbodiimides such as diisopropylcarbodiimide, dicyclohexylcarbodiimide or N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride, carbonyl compounds such as carbonyldiimidazole, 1,2-oxazolium compounds such as 2-ethyl -5-phenyl-1,2-oxazolium-3-sulfonate, propanephosphonic anhydride, isobutyl chloroformate, benzotriazolyloxy-tris- (dimethylamino) phosphonium hexafluoro14 phosphate, diphenyl ester phosphonic acid or methanesulfonic acid, optionally in the presence of bases, such as triethylamine, N-ethylmorpholine, N-methylpiperidine, dicyclohexylcarbodiimide or N-hydroxysuccinimide (see, for example, JC Sheehan, SL Ledis, J. Am. Chem. Soc., 95, 875 (1973); FE Freeman et al., J. Biol Chem.

225, 507 (1982); Benoton, B. Kluroda, Int. Prot. Res. 13: 403 (1979); 17: 187 (1979).

The saponification of carboxylic acid esters is carried out by methods known per se by treating the ester in inert solvents with bases.

Suitable bases for saponification are conventional inorganic bases. These include preferred alkali metal or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide or barium hydroxide, or alkali metal carbonates such as sodium carbonate, potassium carbonate or sodium bicarbonate. Sodium hydroxide or potassium hydroxide is particularly preferred.

Suitable solvents for saponification are water or the organic solvents customary for saponification. These preferably include alcohols such as methanol, ethanol, propanol, isopropanol or butyl alcohol, ethers such as tetrahydrofuran or dioxane, or dimethylformamide and dimethyl sulfoxide. Particularly preferred are alcohols, in particular methanol, ethanol, propanol or isopropanol. It is also possible to use mixtures of the solvents mentioned.

The saponification is generally carried out at a temperature in the range of 0 ° C to 100 ° C, in particular 20 ° C to 80 ° C.

In general, the saponification is carried out under normal pressure, but it is also possible to operate under reduced or elevated pressure, for example in the range of 0.5 to 5 bar.

In carrying out the saponification, the base is generally used in an amount of 1 to 3 mol, preferably 1 to 1.5 mol, per mole of ester. Molar amounts of reactants are particularly preferably used.

The compounds of the formula II are largely novel and can be prepared by reacting the amides of the formula

IV

A G

(IV), wherein A, B, D, E, G, L, M and R ^{1 are} as defined above, with a Laweson reagent of formula V with

in inert solvents, optionally under a protective atmosphere.

Compounds of formula (IV) are partially included as intermediates in the range of EP 399 291, but as specific agents of the compounds are novel and can be prepared by reacting compounds of formula (VI)

(VI), in which A, B, D, E, G, L, M and R ^{1 are} as defined above, with carbonylimidazole in inert solvents, optionally in the presence of the abovementioned bases to compounds of formula VII

(VD),

A, B, D, E, G, L, M and R ¹ as defined above and then amides are prepared in the presence of ammonium chloride and ammonia in inert solvents.

Suitable solvents are those mentioned above. It is preferred to carry out both steps in tetrahydrofuran as a solvent.

In general, the process is carried out under normal pressure, but it is also possible to operate under reduced or elevated pressure, for example in the range of 0.5 to 5 bar.

Said process is carried out at a temperature in the range of 0 ° C to 100 ° C, preferably 15 ° C to 70 ° C.

The compounds of formula VI are known (see US 4 970 715).

The compounds of formula (VII) are novel and can be prepared by the above methods.

E

Compounds of formula V are known (see MSD 2.2069 B).

The compounds of formula (II) are partially known or novel and in this case can be prepared by the above methods.

The chloroacetic acid derivatives of the formula III are known (see, for example, Beilstein 3, 663, vol. 1,

653).

For example, the pure enantiomers of the compounds of formula (I) may be prepared by resolving the corresponding enantiomerically pure acids by known methods and then reacting as described above.

The compounds of the present invention can be used as active ingredients in pharmaceuticals. These substances can act as inhibitors of enzymatic reactions in the metabolism of arachidonic acid, in particular 5-lipoxygenase.

The compounds of formula I exhibit surprisingly high activity in vitro as inhibitors of leukotriene synthesis and a potent effect in vivo after oral administration.

Thus, they are useful for the treatment and prevention of respiratory diseases such as allergies / asthma, bronchitis, emphysema, pulmonary shock, pulmonary hypertonia, inflammatory rheumatism and swelling, thrombosis and thromboembolism, ischemia (peripheral, cardiac, cerebral blood circulation disorders), cardiac and cerebral heart attack disorders, angina pectoris, arteriosclerosis, in tissue transplants, dermatoses such as psoriasis, inflammatory dermatoses such as eczema, dermatophyteninfections, bacterial skin infections, metastases, and for cytoprotection in the gastrointestinal tract.

The compounds of the present invention can be used in both human medicine and veterinary medicine.

The pharmacological data of the effect of the compounds according to the invention are determined by the following method:

As a measure of 5-lipoxygenase inhibition in vitro, the release of leukotriene B _s (LTB ₄ ) on polymorphically granular human leukocytes (PMN) upon addition of substances and Ca-inophor was determined by reverse phase HPLC according to Borgeat P. et al. Nat. Acad. Sci. 76, 2148-2152 (1979).

The present invention also relates to pharmaceutical preparations which, in addition to inert, non-toxic and pharmaceutically acceptable excipients and carriers, contain one or more compounds of the formula I or consist of one or more active compounds of the formula I, as well as a process for preparing said preparations.

The active compounds of the formula I should be present in these preparations in concentrations of 0.1 to 99.5% by weight, preferably 0.5 to 95% by weight, based on the total mixture.

In addition to the active compounds of the formula I, the pharmaceutical preparations can also contain other pharmaceutically active compounds.

The above pharmaceutical preparations can be prepared by conventional methods using known methods, for example with an excipient or carrier or with excipients or carriers.

In general, it has been found advantageous to administer the active compound (s) of the formula I in a total amount of about 0.01 to about 100 mg / kg, preferably in a total amount of about 1 mg / kg to 50 mg / kg body weight, to achieve the desired effect. hours, optionally in the form of a plurality of individual doses.

However, it may optionally be advantageous to dispense with the indicated amounts, depending on the type and body weight of the object to be treated, the individual drug tolerance, the type and severity of the disease, the type of preparation and administration, and the time or interval of administration.

DETAILED DESCRIPTION OF THE INVENTION

Starting compounds

Example I

4- (2-Quinolinylmethoxy) phenyl-cycloheptylacetic acid imidazolide

409 g (2.1 mol) of the acid and 186.5 g (2.3 mol) of carbonyldiimidazole are stirred with 51 tetrahydrofuran at room temperature. After the first evolution of carbon dioxide had ceased, the reaction mixture was stirred at 40 ° C until completion of the reaction (HPLC-control / DC), after which the solvent was distilled off. The residue was dissolved in hot isopropanol and treated with water. The precipitate formed is filtered off with suction, washed with 500 ml of a mixture of isopropyl alcohol and water (1: 1) and then with 1 l of water. It is dried in a hot-air circulation drier at 50 ° C.

Yield: 417 g (90% of theory);

Example II

4- (2-quinolylmethoxy) phenyl cycloheptyl acetamide

g (0.011 mol) of the compound of Example I and a small amount of ammonium chloride are dissolved in 100 ml of tetrahydrofuran and heated to about 55 ° C. At this temperature, a stream of ammonia is introduced into the solution for 4 hours. The reaction mixture was allowed to cool, concentrated to a small volume, and the residue was stirred with dichloromethane.

Yield: 4.1 g (92.8% of theory)

Example III

4- (2-quinolylmethoxy) phenyl-cycloheptyl-thioacetamide

2.0 g (0.0052 mol) of the compound of Example II and 1.3 g (0.0031 mol) of Lawesson's reagent were heated in 15 ml of toluene under argon for 3 hours to boiling. Subsequent gel chromatography (silica gel 60, toluene / tetrahydrofuran 100: 5) afforded (Rf = 0.45) a slightly yellowish product which was crystallized from diisopropyl ether.

Yield: 0.9 g (43.2% of theory)

Manufacturing examples

Example 1

2- [4- (2-quinolylmethoxy) phenylcycloheptylmethyl] -4-methylthiazole

1.5 g (0.0037 mol) of the compound of Example III and 5 ml of chloroacetone are heated in an oil bath with 10 ml of water for 30 minutes at 100 ° C. It is then neutralized with sodium bicarbonate solution and extracted with dichloromethane. After drying over anhydrous sodium sulfate, it is concentrated to dryness in vacuo and the residue is crystallized from diisopropyl ether.

Yield: 1.3 g (79% of theory) of colorless crystals.

Example 2 2- / 4- (2-quinolylmethoxy) phenylcycloheptylmethyl-4-acetic acid ethyl ester

CO ₂ C ₃ H ₅

1.5 g (0.0037 mol) of the compound of Example III and 1.5 ml = 1.83 g (0.011 mol) of ethyl chloroacetate were heated together with 30 ml of toluene and 10 ml of water for one hour at 100 °. C. The reaction mixture is then neutralized with 10% sodium bicarbonate solution, the organic phase is separated, dried over sodium sulphate, concentrated to a small volume in vacuo and separated by column chromatography. Obtained as a yellow oil.

Yield: 1.5 g (78% of theory).

Example 3

2- / 4- (2-quinolylmethoxy) phenylcycloheptylmethyl / thiazole-4-acetic acid

1.4 g (0.00272 mol) of the compound of Example 2 are dissolved in 20 ml of ethanol, treated with 5 ml of 1N sodium hydroxide and heated at reflux for 2 hours. After cooling, this mixture was treated with 5 ml of 1N hydrochloric acid. The resulting colorless precipitate is filtered off and dried to give the product in amorphous form.

Yield: 1.3 g (98.2% of theory).

Example 4

N-methylsulfonyl-2- [4- (2-quinolylmethoxy) phenylcycloheptylmethyl] thiazole-4-acetamide

HaC so,

1.5 g (0.0031 mol) of the compound of Example 3,

0.38 g (0.004 mol) of methanesulfonamide. 0.75 g (0.004 m @ -1)

N-dimethylaminopropyl-N-ethylcarbodiimide hydrochloride a

0.75 g (0.0061 mol) of dimethylaminopyridine (DMAP) was dissolved in 30 ml of dried dichloromethane and stirred at room temperature overnight. It is then extracted twice with 30 ml of water, the organic phase is dried over sodium sulphate, concentrated to a small volume in vacuo and the residue is separated by column chromatography.

Rf = 0.8 (after solvent evaporation: colorless foam)

Yield: 57.6%.

Claims (10)

PATENT CLAIMS tyty-1 z 'nad ΑΛ3Γ30 ¥ AS3V?. \, A 3hd dvgn Thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives of the general formula I (D) in which: A, B, D, E, G, LaM are the same or different and denote a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a carboxyl group, a nitro group, a trifluoromethyl group or a trifluoromethoxy group or straight or branched alkyl or alkoxy group. atoms, or a C 6 -C 10 asylum group optionally substituted by a halogen atom, a hydroxy group, a nitro group or a cyano group, R ³ represents a straight or branched alkyl group having up to 8 carbon atoms which is optionally substituted by a phenyl or cycloalkyl group having 3 to 12 carbon atoms or a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a straight or branched chain alkyl of up to 8 carbon atoms; and T represents a straight or branched alkyl group having up to 6 carbon atoms, or a group of the formula in which R ⁵ represents a hydrogen atom or a straight or branched alkyl group having up to 8 carbon atoms or a benzyl or cycloalkyl group having 3 to 12 carbon atoms, and R ³ represents a radical -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ , wherein R ⁵ represents a hydrogen atom or a straight or branched alkyl group of up to 6 carbon atoms or a benzyl group, R ⁶ denotes aryl having 6 to 10 carbon atoms, which is optionally monosubstituted or disubstituted by identical or different halogen, cyano, hydroxyl, nitro, trifluoromethyl, triíluormethoxyskupinou, trifluoromethoxy or straight-chain or branched alkyl or alkoxy each having up to 8 carbon atoms or a straight or branched alkyl group having up to 8 carbon atoms which is optionally substituted by a phenyl group which may be substituted by a halogen atom, a cyano group, a nitro group, a trifluoromethyl group, a trifluoromethoxy group, a trifluoromethylthio group or a straight or branched alkyl or alkoxy group. C 6-6 atoms, optionally in isomeric form, and salts thereof. 2. A compound according to claim 1, wherein the quinolylmethoxyphenylacetic acid is a compound of formula A, B, D, E, G, L, and M are the same or different and are hydrogen, hydroxy, fluoro, chloro, bromo, carboxyl, nitro, trifluoromethyl, trifluoromethoxy, or straight or branched alkyl or alkoxy in each case up to 6 carbon atoms or a phenyl group optionally substituted by a fluorine atom, a chlorine atom, a bromine atom, a hydroxy group, a nitro group or a cyano group, R @ ¹ denotes a straight or branched alkyl group with from 6 carbon atoms optionally substituted by phenyl, cyclopropyl, cyclopentyl, cyclohexyl or cycloheptyl, or cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, optionally substituted by a straight or branched alkyl group a group of up to 6 carbon atoms, and T represents a straight or branched alkyl group having up to 4 carbon atoms, or a group of the formula in which R ² represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, or benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl and R ³ represents a radical -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ , wherein R ⁴ represents a hydrogen atom or a straight or branched alkyl group of up to 6 carbon atoms, R ⁵ represents a hydrogen atom or a straight or branched alkyl group having up to 4 carbon atoms and R ⁶ denotes phenyl which is optionally substituted by fluorine, chlorine, bromine, iodine, cyano or by straight-chain or branched one alkyl or alkoxy each having up to 6 carbon atoms or linear or branched alkyl radical having up to 6 carbon atoms, which is optionally substituted by a phenyl group, which may be substituted by a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group or a straight or branched alkyl or alkoxy group of up to 4 carbon atoms each, optionally in isomeric form, and salts thereof. 3. A compound according to claim 1, wherein the quinolylmethoxyphenylacetic acid is a compound of the formula: A, B, D, E, G, L, and M are the same or different and denote a hydrogen atom, a hydroxy group, a fluorine atom, a chlorine atom, a bromine atom or a straight or branched alkyl group of up to 4 carbon atoms, R ¹ represents a straight or branched alkyl group having up to 6 carbon atoms optionally substituted by a phenyl, cyclopropyl, cyclopentyl or cyclohexyl group, or a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl group which are optionally substituted by a straight or branched alkyl group of up to 4 carbon atoms and T represents a methyl group or a group of the formula CO-R ³ wherein R ² represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and R ³ represents a radical of formula -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ , wherein R ⁴ denotes a hydrogen atom or a straight or branched alkyl group of up to 4 carbon atoms, r 5 denotes a hydrogen atom, a methyl group or an ethyl group, and R® denotes a phenyl group which is optionally substituted by a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methoxy or a trifluoromethyl group, or a straight or branched alkyl group having up to 4 carbon atoms optionally substituted by a phenyl group which may be substituted a fluorine atom, a chlorine atom, a bromine atom, a methyl group or a methoxy group, optionally in isomeric form, and salts thereof. 4. A compound according to claim 1, wherein the compound is a compound of the formula: 32 in which A, B, D, E, G, L, and M denote a hydrogen atom. 5. A compound according to claim 1, wherein the remainder of the formula ^s -n -CHR, - ^ν Λ Τ is in position 4 of the quinolylmethoxy radical. 6. A compound according to claim 1, for use in diseases. The thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives according to claim 1. A process for the preparation of thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives of the general formula I AND G II E IM _t ^R 1 (D, γ S ^ N in which A, B, D, E, G, L, and . M are the same or different and denotes hydrogen atom, hydroxy, atom halogen, cyano, carboxyl group, nitro, tri- a fluoromethyl or trifluoromethoxy group, or a straight or branched alkyl or alkoxy group of up to 8 carbon atoms each, or an aryl group of 6 to 10 carbon atoms which is optionally substituted by a halogen atom, a hydroxy group, a nitro group or a cyano group, R @ ¹ denotes a straight or branched alkyl group having up to 8 carbon atoms optionally substituted by a phenyl or cycloalkyl group having from 3 to 12 carbon atoms or a cycloalkyl group having 3 to 12 carbon atoms optionally substituted by a straight or branched chain alkyl of up to 8 carbon atoms; and T represents a straight or branched alkyl group having up to 6 carbon atoms, or a group of the formula wherein r5 denotes a hydrogen atom or a straight or branched alkyl group having up to 8 carbon atoms or a benzyl or cycloalkyl group having 3 to 12 carbon atoms; R ³ represents a radical -OR ⁴ or -NR ⁵ -SO ₂ -R ⁶ , wherein R ⁵ represents a hydrogen atom or a straight or branched alkyl group of up to 6 carbon atoms or a benzyl group, R ⁶ represents an aryl group having 6 to 10 carbon atoms, which is optionally up to two times the same or differently substituted by halogen, cyano, hydroxy, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio or a straight or branched alkyl or alkoxy group each having up to 8 carbon atoms or a straight or branched alkyl group having up to 8 carbon atoms optionally substituted by a phenyl group, which may be substituted by a halogen atom, a cyano group, a nitro group, a trifluoromethyl group, a trifluoromethoxy group, a trifluoromethylthio group or a straight or branched alkyl or alkoxy group. up to 6 carbon atoms, optionally in isomeric form, and salts thereof, characterized in that thioamides of the formula II are reacted in which A, B, D, E, G, L, M and R ^{1 are} as defined above, with a derivative haloacetic acid esters or halo ketones of formula III Cl - _CH2 - CO - CH ₂ - W (III) wherein W represents hydrogen, alkyl having 1 to 6 carbon atoms or a group -CO-R ^7, wherein R ⁷ is C 1 -C 4 alkoxy, in organic solvents, optionally in the presence of water, and in the case of acids (R ³ - OH), the esters are saponified by conventional methods, and when R ^{2 is} not a hydrogen atom, alkylation, and in the case of sulfonamides (R ³ = -NH-SO ₂ R ⁶ ), amidation is carried out in inert solvents, optionally in the presence of a base and / or an adjuvant, wherein the substituents A, B, D, E, G, LaM may be in any of the above steps, vary using methods known in the literature. A medicament comprising at least one thiazolyl-substituted quinolylmethoxyphenylacetic acid derivative according to claim 1. Medicament according to claim 8 for the treatment and prevention of respiratory diseases such as allergy / asthma, bronchitis, emphysema, pulmonary shock, pulmonary hypertonia, inflammatory rheumatism and swelling, thrombosis and thromboembolism, ischemia (peripheral, cardiac, cerebral blood circulation disorders), cardiac and cerebral infarction heart rhythm disorders, angina pectoris, arteriosclerosis, tissue transplants, dermatoses such as psoriasis, inflammatory dermatoses such as eczema, dermatophyteninfections, skin infections caused by bacteria, metastases, and for gastrointestinal cystic protection. Use of the thiazolyl-substituted quinolylmethoxyphenylacetic acid derivatives according to claim 1 for the manufacture of medicaments.