CH647511A5 - Process for the preparation of hydantoin derivatives - Google Patents

Abstract

The hydantoin derivatives of the formula I are prepared by alkylating a compound of the formula X using an active ester derivative of an alcohol of the formula J<3>-OH. The substituents in formulae I and X have the definitions given in Patent Claim 1. The compounds of the formula I have pharmacological properties which are related to those of the natural prostaglandins. <IMAGE>

Description

The invention relates to the production of hydantoin derivatives.

The hydantoin derivatives, which are defined in more detail below as compounds of the formula I, have pharmacological properties which are related to those of the natural prostaglandins. This is reflected in their ability to mimic or counteract the physiological effects of natural prostaglandins in various biological preparations. In particular, it has been found that certain compounds of the formula I inhibit platelet aggregation as effectively as the prostaglandin egg.

In the compounds of formula I

0

Z-N

N.

0

mean

Z alkyl; one of the groups

Z 'and Z2 are the group -CH2-X-X'-X2, wherein

X is phenylene, -C = C-, ice or trans-CH = CH- or -CH2-CQ2-, where each Q is independently hydrogen and alkyl, such as ethyl, or the two Q together are an alkylene group with 4, 5 or 6 Represent carbon atoms;

XI is a covalent bond or a straight-chain or branched-chain alkylene chain having 1 to 6 carbon atoms, in which one of its methylene groups may be replaced by a

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0xa (-0-) group is replaced, provided that at least one carbon atom separates the oxa group from a -C = C-, -CH = CH- or -CO group; and X: 5-tetrazolyl, carboxyl, carboxamide, hydroxymethylene or alkoxycarbonyl, and the other of the groups Z1 and Z2 the group -Y-Y'-Y2-Y3, wherein

Y -CR.2-CH: -, where each R is independently hydrogen and methyl;

Y1 carbonyl, methylene, a methylene group substituted by hydroxy or by hydroxy and alkyl;

Y: a covalent bond or a straight-chain or branched-chain alkylene group having 1 to 7 carbon atoms, which may optionally be substituted on the carbon atom adjacent to Y1 by one or two independent alkyl, bicycloalkyl or cycloalkyl groups; Y3 is hydrogen, hydroxy, alkoxy having 1 to 7, preferably 1 to 4, carbon atoms, cycloalkyl, bicycloalkyl, phenyl, benzyl, phenoxy or benzyloxy, wherein each of the groups phenyl, benzyl, phenoxy and benzyloxy in the benzene ring through one or more of the groups hydroxy , Halogen, nitro, amino, acylamino, alkenyl, alkoxy, phenyl and alkyl, which in turn can be substituted by one or more halogens; or

Y is a bond, -CH: - or -CH2-CH2-; and

Y1, Y2 and Y3 together form a cycloalkyl group substituted by a hydroxyl group, which preferably has 3 carbon atoms which separate them from the hydantoin ring.

Unless otherwise stated, in the present description, in the compounds of the formula I and in compounds of the other formulas, the alkyl groups preferably denote methyl, ethyl, propyl, butyl, pentyl and hexyl, including all of their isomers. For example, in the definitions of Y1 and Y2, the alkyl groups in particular methyl and the alkyl portion of the alkoxycarbonyl group in particular methyl or ethyl. So alkenyl groups with 2 to 4 carbon atoms, for example vinyl, are likewise preferred.

In the compound of formula I, the cycloalkyl groups preferably have 3 to 10 carbon atoms and the bicycloalkyl groups preferably 4 to 10 carbon atoms, for example adamantyl.

In a compound of formula I the bond of the divalent phenylene group can be ortho, meta or para and the oxa group is preferably adjacent to phenylene or, if X is other than phenylene, X1 is preferably -CH2-O-CH2-.

The compounds of formula I also include the salts of the corresponding carboxylic acids and tetrazoles when X2 is carboxyl or tetrazolyl. Particularly valuable salts for medical purposes are salts which have a pharmaceutically acceptable cation, such as ammonium, or a cation of an alkali metal, such as sodium or potassium, an alkaline earth metal, such as calcium and magnesium, or an organic base, in particular an amine. such as ethanolamine. Salts without a pharmaceutically acceptable cation also fall within the scope of the present invention since they are useful as intermediates for pharmaceutically acceptable salts or acids or esters of the compound of formula I.

Unless expressly stated otherwise, all stereoisomers are included in the compounds of the formula I and all other compound formulas mentioned in the description. In particular, these formulas include the enantiomeric forms, these mixtures are called racemates, and the diastereoisomers.

It has been found that the compounds of the formula I

wherein

Z alkyl having 1 to 4 carbon atoms, for example methyl or butyl; one of the groups Z1 and Z2 -CH2-X-X1 -X2-, in which 5 X and X1 together are an alkylene having 3 to 7, preferably 5, carbon atoms; and

X2 represents alkoxycarbonyl, carboxyl or a salt thereof, and the other of the groups Z1 and Z2-Y-Y'-Y2-Y3-, wherein 10 Y, Y1 and Y2 have the meaning as above; and Y3 represents hydrogen, cycloalkyl having 4 to 7 carbon atoms, phenyl or benzyl, are compounds which have particularly interesting properties related to prostaglandin.

15 The compounds of formula I can be prepared in the manner known for compounds of analogous structure.

According to the invention, the hydantoins of the formula I are obtained by alkylating a compound of the formula X

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0

25th

Y-N

(X)

30th

wherein

J is hydrogen or alkyl;

35 and J2 is hydrogen or Z2

mean with an active ester derivative of an alcohol of the formula J3 • OH, where J3 is alkyl or Z2

40 means provided one of the groups J and J2 is hydrogen and J3 does not have the same meaning as J or J2. Suitable active ester derivatives include chlorides, bromides and iodides and sulfonates such as p-toluenesulfonate, methanesulfonate and benzene sulfonate. The alkylation can be carried out under known suitable reaction conditions, e.g. in the presence of a base, e.g. an alkali metal hydride, an alkali metal amide or an alkali metal alkoxide, often sodium hydride or a 50% sodium alkoxide, e.g. Sodium methoxide or sodium ethoxide.

The reaction is usually carried out in an inert solvent which simply acts as a diluent for the reactants, e.g. Toluene, 55 dioxane, ether, dimethylformamide, tetrahydrofuran,

Dimethyl sulfoxide or acetonitrile. If the base is an alkali metal alkoxide, the corresponding alkanol can be used.

It should also be pointed out that the intermediate products of the formula X, in which J is hydrogen, are also pharmacologically active compounds. The compounds of formula X can be prepared by adapting already known methods (see e.g. Chemical Reviews 46 (1950), pages 403-425).

When preparing the hydantoins of the formula I with a hydroxyl group in a side chain, it may be desirable to protect them during the course of the reaction. This can easily be done in a known manner by a protecting group

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take place, e.g. by acyl, aroyl, tetrahydropyran-2-yl, 1-ethoxyethyI or aralkyl, e.g. Benzyl.

The protective groups can be removed by suitable known methods, for example an acyl group can be removed by acid or base hydrolysis and a benzyl group by reducing cleavage.

In addition, a ketone of formula I, wherein Y1 is carbonyl, can be incorporated into the corresponding secondary alcohol by reduction with a suitable reducing agent, e.g. Sodium borohydride. An alcohol of formula I, wherein Y1 is -CH2OH-, can also be oxidized to the corresponding ketone using Jones reagent, acid dichromate or another suitable reagent.

In the same way, the compounds of the formula I which have a —C = C or —CH = CH bond can be converted into the corresponding ethylene or saturated compounds by means of conventional hydrogenation processes, for example according to Lindlar or with an Adams catalyst .

The hydantoin derivatives of the formula I have an asymmetric 5-carbon atom and in the compounds of the formula I in which Y1 contains a hydroxyl group there is another asymmetric center. These alcohols therefore exist as four isomers, which can be separated into two diastereomers by means of thin layer chromatography or high performance liquid chromatography (HPLC), each of which is a racemic mixture of two isomers. When the diastereomers are separated, a di-stereomer can be converted into a mixture of the four isomers by adding a base, for example an alkali metal hydroxide, and then “reseparated” to form two diastereomers. Repeated use of this technique enables the actual conversion of one diasteromer into the other. This may be desirable if one diastereomer has a preferred biological activity over the other.

With all the preceding chemical processes, it is of course clear that the choice of the reactant is determined in part by the functional groups present in the material and that if necessary, reactants must be used which have a suitable selective mode of action.

The hydantoin derivatives of the formula I have valuable pharmacological properties which are related to those of the natural prostaglandins. This means that the hydantoin derivatives mimic or counteract the biological effects of prostaglandins (PG) "A", "B", "C", "D", "E" and "F" series. It has been found that the hydantoin derivatives of the formula I have the same inhibitory effect on the aggregation of platelets as the PGE and that they inhibit the contraction induced by PGE2 or PGF2 on the smooth muscles of rat stomach, rat intestine, the rectum of chickens and the trachea of Counteract guinea pigs. In general, the antagonistic properties, as opposed to the mimicking ones, were observed when larger doses of the hydantoin derivatives were used. The pharmacological "profile", by which one understands the relative modes of action, namely the mimicking or the antagonistic, compared to the natural prostaglandins, naturally varies depending on the specific hydantoin derivative under consideration.

Due to their prostaglandin-related properties, the hydantoin derivatives of the formula I are useful in the pharmacological characterization and differentiation of the biological effects of the natural prostaglandins and their receptors. Understanding the physiological effects of prostaglandins is of great value when looking for new and improved therapeutic substances.

The hydantoin derivatives of the formula I are also of great use as therapeutic active ingredients. In particular, the hydantoin derivatives described above with an inhibitory effect on the aggregation of platelets are useful when platelet aggregation is to be inhibited or to reduce the ability of the platelets to stick. They can be used to treat or prevent thrombosis in mammals, including humans. For example, the present compounds are useful in the treatment and prevention of myocardial infarction, for the treatment and prevention of thrombosis, and for improving the patency of vascular grafts after surgery. They are also suitable for the treatment of arteriosclerosis and conditions such as atherosclerosis, disorders of blood clotting as a result of lipaemia and other clinical conditions in which the cause of the disease is related to an impaired lipid balance or with hyperlipidemia.

Furthermore, these compounds can be used as additives to blood and other fluids, which are used for the artificial maintenance of a circulation outside the body or for flushing through isolated parts of the body.

A group of compounds of the formula X which have also been found to be valuable as inhibitors of platelet aggregation are the compounds of the formula X, in which J is hydrogen and Z1 is carboxylalkylene, in which the alkylene part has 3 to 9 carbon atoms, and J2 Z2, where Z2 is a group - (CH :): • CH • OH • Y2 • Y2, wherein Y2 has a branched chain alkylene with a tertiary carbon atom adjacent to the hydroxy-substituted carbon, and Y3 has the meaning as in formula I. The compounds in which Z1 is carboxyhexyl and Y3 is a cycloalkyl having 4 to 7 carbon atoms have proven particularly effective in this group.

It has furthermore been found that the hydantoin derivatives of the formula I bring about a relaxation of the vascular smooth muscles in a similar way to the prostaglandins of the groups "A" and "E". This property is also shown by some compounds of formula X, e.g. the 5- (6-carboxy-hexyl) -l- (3-hydroxy-4,4-dimethyloctyl) hydantoin and the 5- (6-carboxyhexyl) -1 - (3-hydroxy-4,4-dimethyl-5 -phenyl-pentyl) -hydantoin. The compounds that relax the vascular smooth muscles therefore have a vasodilatory effect and thus antihypertensive properties and can therefore be used to lower blood pressure in mammals and humans. They can be administered either alone or with an agent blocking the adrenaline-ß receptors or another antihypertensive agent for the treatment of all types and strengths of elevated blood pressure including essential, malignant and secondary hypertension.

A compound of formula X, namely the compound 5- (6-carboxyhexyl) -1 - (3-hydroxy-4,4-dimethyloctyI) -hydan-toin also has the same effect as PGE, namely to counteract the bronchoconstriction caused by histamine. The hydantoin derivatives of the formula I, which also have this property, can be used for the treatment or prophylaxis of bronchial asthma and bronchitis by eliminating the bronchial constriction which is associated with these clinical pictures.

The hydantoin derivatives of formula I, e.g. 5- (6-carboxy-xyhexyl) -3-methyl-1- (3-oxooctyl) -hydantoin and also some of the compounds of formula X, such as 5- (6-

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Carboxyhexyl) -l- (3-hydroxyoctyl) -hydantoin, the 5- (6-car-boxyhexyl) -l- (3-oxo-octyl) -hydantoin and the 5- (6-carboxy-xyhexyl) -l- ( 4-phenoxybutyl) hydantoin, which inhibit gastric acid secretion caused by pentagastrin and reduce the formation of aspirin-related gastric ulcers in rats, can serve to reduce excess gastric secretion, furthermore to reduce or prevent the formation of gastrointestinal ulcers or else Accelerate healing of such ulcers and damage that is already present in the gastrointestinal tract. This can occur either with spontaneous ulcers or with ulcers that are associated with polyglandular adenoma syndrome.

It has also been found that intravenous infusions of certain hydantoin derivatives of the formula I or certain compounds of the formula X, for example 5- (6-carboxy-xyhexyl) -l- (3-hydroxyoctyl) hydantoin, increase the urine volume in dogs, which indicates a possible use of these derivatives as diuretics. This application enables the treatment of edema, such as those that occur in heart defects, liver or kidney damage in humans or mammals.

A further use of the hydantoin derivatives of the formula I, the effect of which is similar to the effect on the smooth muscles of the uterus of PGE2 and PGF2a, is the effect as an antifertility agent, in particular as an abortion.

The amount of a compound of formula I required to achieve the desired biological effect depends, of course, on a number of factors, for example the type of compound chosen, the particular use, the dosage form and the recipient. In general, daily doses can range from 1 to 20 mg / kg body weight. For example, an intravenous dose may range from 5 µg to 1 mg / kg body weight, which can generally be administered as an infusion of 0.01 to 50 µg / kg and per minute generally contain 0.001 to 100, for example 0.01 to 10 (i / ml. Single doses generally contain 10 to 100 mg of a compound of the formula I. Ampoules for injection can be, for example, 0.01 to 1 mg and orally administrable single-dose preparations, such as for example tablets or capsules, can generally contain 0.1 to 50 mg, for example 2 to 20 mg, of the active ingredient.

If a compound of formula I is to be used to inhibit platelet aggregation, it is generally appropriate to, for example, have a concentration in the appropriate fluid, either in the patient's blood or in a perfusion fluid, of about 1 µg to 10 mg 10 (ig to 1 mg, per liter).

The above doses relate to the acids, amides, esters, alcohols and tetrazoles of the formula I. If a salt is used, the dose should be chosen based on the corresponding anion.

For the treatment or prophylaxis of the conditions described above, the hydantoin derivatives can be administered as a crude product, but their administration in the form of pharmaceutical preparations with a suitable carrier is preferred. The carrier must of course be "acceptable" in the sense that it is compatible with the other components of the preparation and is not harmful to the recipient. The carrier can be either solid or liquid and is produced with a hydantoin derivative, preferably as a single dose preparation, for example as a tablet, which can generally contain 0.05 to 95% by weight of the hydantoin derivative. Other pharmacologically active substances can also be present in the preparations. The hydantoin derivatives can be processed in the preparations either in their acid form or as a salt or ester. The preparations can be prepared in all ways known in pharmacy, essentially mixing the components of the preparations together.

Suitable preparations are, for example, those for oral, rectal, local (for example buccal, such as sub-lingual), parenteral (that is to say subcutaneous, intramuscular and intravenous) administration, the suitable administration form in each case depending on the type and severity of the disease to be treated and depends on the type of hydantoin derivative.

Preparations for oral administration can be in divided single doses, such as capsules, cachets, lozenges or tablets, each unit containing a predetermined amount of the hydantoin derivative. Furthermore, the preparations can be in the form of powders or granules, as a solution or suspension in an aqueous or non-aqueous liquid, furthermore as an oil-in-water emulsion or as a water-in-oil emulsion. These formulations can be prepared in any manner known in pharmacy, the hydantoin derivative being mixed with the carrier which consists of one or more ingredients. In general, they are prepared by uniformly and intimately mixing the hydantoin derivative with the liquid or finely divided solid carrier or with both, and then brought into the desired dosage form as required. For example, tablets can be produced by pressing or molding a powder or granulate of the hydantoin derivative, optionally with one or more auxiliaries. Pressed tablets can be obtained by pressing the active component in a free-flowing form, e.g. as a powder or in the form of granules, optionally mixed and pressed with a binder, lubricant, inert diluent, surface-active agent or dispersant using a suitable machine. Shaped tablets can be shaped by molding the powdered hydantoin derivative moistened with an inert liquid diluent using a suitable machine.

Preparations for buccal (sub-lingual) administration are mostly lozenges which contain a hydantoin derivative in a flavor base, usually sucrose, gum arabic or tragacanth. Furthermore, for this administration, lozenges can also be present which contain the hydantoin derivative in an inert basis, such as, for example, gelatin and glycerol, or sucrose and gum arabic.

The preparations intended for the parenteral dosage form contain sterile aqueous preparations of a hydantoin compound, which are preferably isotonic with the blood of the recipient. These preparations are preferably administered intravenously, although the administration can also take place as a subcutaneous or intramuscular injection. These preparations can usually be prepared by mixing the hydantoin derivative with water and sterilizing and by producing the isotonicity with the blood.

Preparations for rectal administration are preferably in single dose suppositories. These can be prepared by mixing the hydantoin derivative with one or more of the conventional solid carriers, such as cocoa butter, and shaping the resulting mixture.

In summary, the main effects of the new compounds of the

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Formula I listed: lowering blood pressure in mammals including humans, treatment or prophylaxis of thrombosis in humans and mammals or mammalian tissues, vasodilation in humans and mammals, treatment and prophylaxis of gastrointestinal lesions in humans and mammals, bronchial dilation in humans and mammals , Treatment and prophylaxis of allergic conditions in humans and mammals, abortion of a fetus in humans and mammals, infertility in humans and mammals, upon administration of a non-toxic, effective amount of a compound of formula I.

The following examples serve to illustrate the invention without restricting it.

example 1

Preparation of 3-butyl-5- (6-carboxyhexyl) -l-octylhydan-toin

To a solution of 308 mg sodium in 40 ml ethanol was added 5- (6-ethoxycarbonylhexyl) -l-octylhydantoin followed by 1.8 g butyl bromide and the solution was heated under reflux for 24 hours. The solvent was evaporated, water was added and the insoluble oil was extracted with ether. The washed-out and dried extract was evaporated and 3-butyl-5- (6-ethoxycarbonylhexyl) -1-octylhydantoin resulted.

3.2 g of this ester was dissolved in 15 ml of ethanol and 15 ml of 2N sodium hydroxide solution and left to stand at room temperature for 1 hour. The acidic product was isolated by extraction with ether and purified by chromatography on silica gel, whereupon the 3-butyl-5- (6-carboxyhexyl) -l-octylhydantoin resulted as a colorless oil.

The 5- (6-ethoxycarbonylhexyl) -1 -octylhydantoin, melting point 46 to 48 ° C, was analogous to the following procedure for the preparation of 5- (6-carboxyhexyl) -l- (5-phenylpentyl) hydantoin using the corresponding Alkyl halides prepared: A mixture of 25.9 g of diethyl 2-aminononanedioate and 22.7 g of 5-phenylpentyl bromide was heated in a water bath at 100 ° C. for 3 hours. After cooling, 100 ml of ether was added to the mixture, which was then left to stand at 0 ° C for 2 hours. 21.95 g of the colorless solid that crystallized out was collected and dried. This diethyl- [2- (5-phenylpentvl) amino] nonanedioate hydrobromide melted at 70 to 72 ° C.

A solution of 4.86 g of this hydrobromide in 20 ml of ethanol and 5 ml of 2N hydrochloric acid was cooled in ice and stirred while gradually adding a solution of 1.62 g of potassium cyanate in 5 ml of water. The solution was then left to stand at room temperature for 18 hours. The alcohol was evaporated, water was added and the insoluble oil extracted with ether, the ether extract dried and evaporated. A slightly yellow oil resulted. This was heated on a steam bath for 6 hours and the 5- (6-ethoxycarbonylhexyl) -1- (5-phenylpentyl) hydantoin resulted.

Example 2

A) Preparation of l- (6-ethoxycarbonylhexyl) -5-octylhy-dantoin

16.0 g of 2-aminocapric acid (J. Am. Chem. Soc., 68 (1946), 450) was added in portions to a cooled (-10 ° C.) mixture of 70 ml of absolute ethanol and 6 ml of thionyl chloride with stirring added. The resulting solution was set aside for 2 hours at room temperature, then heated under reflux for 1 hour, cooled, poured into ice water, and the pH of the solution was adjusted to 9 with aqueous sodium hydroxide solution. The mixture was extracted with ether, the extract was dried, concentrated and distilled. The ethyl 2-aminodecanoate (75%) resulted as a colorless oil, boiling point 82 to 84 ° C / 0.2 mm Hg.

A solution of 18 g of the above amino ester and 20 g of ethyl 7-bromheptanoate in 50 ml of absolute ethanol was heated under reflux for 24 hours and then the ethanol was evaporated. The addition of ether precipitated a hydrobromide salt, melting point 98 ° C., which was dissolved in a little dichloromethane, one equivalent of triethylamine was added, and the mixture was washed thoroughly with water and dried. After removing the solvent, the ethyl 2- (6-ethoxycarbonylhexylamino) decanoate (52%) resulted as a colorless viscous oil, boiling point 142 to 144 ° C / 0.001 mm Hg.

7.4 g of ethyl 2- (6-ethoxycarbonylhexylamino) decanoate was reacted with potassium cyanate and hydrochloric acid and the result was l- (6-ethoxycarbonylhexyl) -5-octylhydantoin, which consists of light petroleum (boiling point 60 to 80 ° C) colorless crystals with a melting point of 68 to 70 ° C.

B) Preparation of 3-butyl-l- (6-carboxyhexyl) -5-octylhy-dantoin

In the manner described in Example 1, 1- (6-ethoxycarbonylhexyl) -5-octylhydantoin was converted to 3-butyl-1- (6-ethoxycarbonylhexyl) -5-octylhydantoin, which was hydrolysed to 3-butyl -l- (6-carboxyhexyl) -5-octyl-hydantoin was converted as a colorless oil.

5- (6-Carboxyhexyl) -3-methyl-l- (3-hydroxyoctyl) hydantoin and l- (6-carboxyhexyl) -3-methyl-5-octylhydantoin can also be prepared by the processes given in Examples 1 and 2 will.

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Claims (7)

647 511 1 PATENT CLAIMS 1. Process for the preparation of hydantoin derivatives of the formula I 0 Z-N 0 wherein Z alkyl; one of the groups 7) and Z2 the group -CHi-X-X'-X2, wherein X is phenylene, -C = C-, ice or trans-CH = CH- or -CH2-CQ2-, wherein each Q independently represents hydrogen and alkyl or the two Q together represent an alkylene group with 4.5 or 6 carbon atoms; XI is a covalent bond or a straight-chain or branched-chain alkylene chain having 1 to 6 carbon atoms, in which one of its methylene groups may be replaced by a 0xa (-0-) group, provided that at least one carbon atom represents the oxa group of an -OC-, -CH = separates CH or -CO group; and X2 is 5-tetrazolyl, carboxyl, carboxamide, hydroxymethylene or alkoxycarbonyl, and the other of the groups Z1 and Z2 is the group -Y-Y'-Y2-Y3, in which Y is -CR2CH2-, each run dependent hydrogen and methyl; Y1 carbonyl, methylene, a methylene group substituted by hydroxy or by hydroxy and alkyl; Y2 is a covalent bond or a straight-chain or branched-chain alkylene group having 1 to 7 carbon atoms, which may optionally be substituted on the carbon atom adjacent to Y1 by one or two independent alkyl, bicycloalkyl or cycloalkyl groups; Y3 is hydrogen, hydroxy, alkoxy having 1 to 7 carbon atoms, cycloalkyl, bicycloalkyl, phenyl, benzyl, phenoxy or benzyloxy, in which each of the groups phenyl, benzyl, phenoxy and benzyloxy in the benzene ring by one or more of the groups hydroxyl, halogen, nitro , Amino, acylamino, alkenyl, alkoxy, phenyl and alkyl can be substituted, which in turn can be substituted by one or more halogens; or Y is a bond, -CH2- or -CH2 • CH2-; and Y1, Y2 and Y3 together form a cycloalkyl group substituted by a hydroxyl group, which separates them from the hydantoin ring, and their salts, characterized in that a compound of the formula X 0 0 wherein J is hydrogen or alkyl and J2 is hydrogen or Z2, with an active ester derivative of an alcohol of the formula J3-OH, wherein J3 means alkyl or Z2, provided that one of the groups J and J2 represents hydrogen and J3 does not have the same meaning as J or J2, alkylates and, if appropriate, converts the compound of the formula I obtained into another desired salt of the formula I. 2. The method according to claim 1, characterized in that one carries out the reaction in the presence of a base. 3. The method according to claim 1 or 2, characterized in that one carries out the reaction in the presence of an alkali metal hydride, amide or alkoxide. 4. The method according to any one of claims 1 to 3, characterized in that one carries out the reaction in the presence of sodium ethoxide. 5. The method according to any one of claims 1 to 4, characterized in that a chloride, bromide, iodide or a sulfonate is used as the alkylating agent. 6. The method according to any one of claims 1 to 5, characterized in that an alkyl bromide is used as the alkylating agent. 7. The method according to any one of claims 1 to 6, characterized in that 5- (6-carboxyhexyl) -3-methyl-l (3-hydantoinoxooctyl), their salts or esters are prepared.