DE2410611A1 - N-(2-cyano-3-forylamino-3-hydroxyallylidene)hydrazides - derived from heterocyclic acids, with xanthinoxidase inhibiting activity - Google Patents

Abstract

N-(2-cyano-3-formylamino-3-hydroxyallylidene) hydrazides of formula (I), and their tautomers and salts, are new: (where alk is 1-5 C alkylene, pref. CH2 or CH2CH2; n = 0 or 1; R3 is an opt. hydrogenated heteroaromatic residue, opt. substd.). Cpds. (I) are xanthinoxidase inhibitors and are esp. useful for treating gout; their toxicity is lower than that of allopurinol and they can be used in lower doses, e.g. 50-500 mg compared with 100-800 mg. They also have antiarrhythmic activity and can be used to treat coronary insufficiency, and can also be used as intermediates for 4(1H)-pyrimidiones with similar activity (DT-2410650).

Description

New heterocyclically substituted 2-hydrazonomethyl-3-hydroxy-4-aze-2, 4-peritadiene nitriles, process for their preparation and pharmaceuticals containing them The invention relates to therapeutically valuable substituted 2-hydrazonomethyl-3-hydroxy-4-aza-2,4-pentad-enenitrile with in particular the xanthine oxidase inhibiting properties.

Derivatives of pyrazolo [3,4-d] pyrimidine have been known for a long time, which have enzyme-inhibiting properties. For example, 4-hydroxy-1H-pyrazolo [3,4-d] -pyrimidine inhibits known as "allopurinol", the enzyme xanthine oxidase. This Enzyme catalyzes the oxidation of purine derivatives to uric acid in vivo. In the same Allopurinol suppresses the oxidation of 6-mercapto-purine to 6-thiouric acid (German Offenlegungsschrift 1 904 894). Because allopurinol is involved in the purine metabolism levels of uric acid formed greatly diminished, it becomes therapeutic used to treat gout0 A disadvantage of allopurinol, however, is that it has a relatively high acute toxicity and compared to its toxicity used in relatively high doses ranging from 100 to 800 mg per person per day will. It was therefore desirable to develop products that did a lot of work lower toxicity also inhibit xanthine oxidase and for treatment the gout used horses can.

The present invention relates to substituted 2-hydrazonomethyl-3-hydroxy-4-aza-2,4-pentadiene nitriles of the general formula I and their tautomers and salts, in which alk is a straight-chain or branched alkyl group having 1 to 5 carbon atoms, and preferably a methylene or ethylene group, n is 0 or 1 and R3 is a heterocyclic radical of aromatic character or a partially or perhydrogenated derivative of such a radical .

Heterocyclic radicals of aromatic character are mono-, bi- or polycyclic one or more nitrogen, oxygen and / or sulfur atoms as Radicals of aromatic character containing hetero ring members, which optionally by one or more, preferably one to three, identical or different substituents can be substituted, and in particular mono- or bicyclic monoaza-, monothia-, monooxa-, thiaza, oxaza- or diazacyclic radicals such as pyridyl radicals, e.g. pyridyl (2), (3) or (4), pyrazinyl residues, e.g. pyrazinyl- (2), pyridazinyl residues, e.g. pyridazinyl- (3) or (4), O-pyrrolyl radicals, e.g. pyrrolyl- (2) or d (3), thienyl radicals, see B. Thienyl (2) or (3), furyl residues, e.g. furyl- (2) or (3), oxazolyl residues, e.g. oxazolyl- (2), (3) or (5), isoxazolyl radicals, e.g. isoxazolyl (3), (4) or (5), thiazolyl radicals, e.g. thiazolyl- (2), (3) or (5), isothiazolyl residues, e.g. isothiazolyl- (3) 1 (4) or (5), pyrazolyl radicals, e.g. pyrazolyl- (3), (4) or (5), imidazolyl radicals, e.g. Imidazolyl (2) or (4), pyrimidinyl residues, e.g. pyrimidinyl (2), (4) or (5), indolyl residues, e.g. indolyl- (2), (3), (4) or (5), indazolyl radicals, e.g. indazolyl- (3), (4) or (5), Benzo [b] furyl residues, e.g. Benzo [b] furyl- (2), (3) or (4), Benzo [b] thienyl residues, e.g. benzo [b] thienyl- (2), (3) or (4) 1 quinolyl residues, e.g. cliinolyl- (2), (4), (5), (6) or (8), isoquinolyl radicals, e.g. isoquinolyl- (1), (3), (4) or (5), Cinnolinyl, Phthalazinyl, quinazolinyl or quinoxalinyl radicals 1 which are replaced by one or more, preferably one to three of the substituents mentioned below: be substituted Partially or perhydrogenated derivatives of a heterocyclic radical are preferred those which are derived from the heterocyclic radicals preferably mentioned above, such as piperidyl, di- or tetrahydropyridyl, piperazinyl, pyrrolidinyl, Pyrrolinyl residues, e.g. (2 or 3) -pyrrolinyl residues, tetrahydrothienyl residues, dihydrothienyl residues, e.g.

(1,2 or 2,3) -dihydrothienyl residues, tetrahydrofuryl residues, dihydrofuryl residues, e.g. (1,2 or 2,3) -dihydrofuryl residues 1 oxazolidinyl residues, oxazolinyl residues, isooxazolidinyl residues, Thiazolidinyl residues, thiazolinyl residues, pyrazolidinyl residues, pyrazolinyl residues, e.g. 3-pyrazolinyl residues, imidazolidinyl residues, imidazolinyl residues, e.g.

2-imidazolinyl residues, di-, tetra- or hexahydropyrimidinyl residues 1 Indolinyl residues, hexahydroindolinyl residues or tetrahydroquinol yl residues, e.g. 1,2,3,4-tetrahydroquinolyl residues; which like the heterocyclic radicals of aromatic character by one or more, preferably one or two of the substituents mentioned below may be substituted can.

Substituents of the heterocyclic radicals can be: alkyl, alkoxy or alkyl mereapto groups each having 1 to 7 carbon atoms, cycloalkyl groups With 5 to 6 carbon atoms each, phenyl, phenylalkyl groups, wherein the alkyl radical can have 1 to 6 carbon atoms, carboxy groups or carboxyalkyl groups with up to 7 carbon atoms or functional derivatives thereof, llydroxy- or mercapto groups, amino, alkylaniino or dialkylamino groups, in which alkyl Can contain up to 4 carbon atoms, halogen, such as fluorine or iodine, in particular Chlorine or bromine, trifluoromethyl, nitro, nitroso, formyl, alkanoyl groups with 2 to 7 carbon atoms, benzoyl, phenylalkanoyl groups, in which the alkanoyl radical is 2 to May contain 7 carbon atoms, sulfo groups or sulfamoyl groups.

An alkyl group having 1 to 7 carbon atoms can be straight-chain or be branched and is for example a methyl, ethyl, propyl, isopropyl, Butyl, isobutyl, sec-butyl or tert-butyl, pentyl, isopentyl, 1- or 2-methyl-butyl, tert-pentyl, hexyl, isohexyl, 1-, 2- or 3-methylpentyl, 1-, 2- or 3-ethyl-butyl, 1,2-, 1,3- or 2,3-dimethylbutyl group, heptyl or isoheptyl group, it can but also be unsaturated and is then e.g. a vinyl, allyl, 2-methyl-allyl, Propen-1-yl, buten-1 or 2-yl, penten-1, 2- or 3-yl, hexenyl or 2-methyl-propen-1-yl group.

An alkoxy or alkyl mercapto group of up to 7 carbon atoms is, for example, one of the above-mentioned alkyl groups of up to 7 carbon atoms derived alkoxy group, such as a methoxy, ethoxy, propoxy, isopropoxy, Butoxy, isobutoxy, sec-butoxy or tert-butoxy group, or one derived therefrom Alkyl mercapto group, such as a methyl mercapto, ethyl mercapto, propyl mercapto, isopropyl mercapto or butyl mercapto group.

A cycloalkyl group having 5 to 6 carbon atoms is, for example a cyclopentyl, 2- or 3-methylcyclopentyl or cyclohexyl group.

A straight-chain or branched alkylene group alk having 1 to 5 carbon atoms is for example a methylene, 1,1-ethylene, 1,2-ethylene, trimethylene, propylidene, 1- or 2-methylethylene, tetramethylene, i-, 2- or 3-methyl-trimethylene-, flutylidene-., 1- or 2-ethyl-ethylene, pentylidene, pentamethylene or hexamethylene group, furthermore also a 1-, 2-, 3- or 4-methyl-tetramethylene-, 1- or 2-propyl-ethylene-, 1- or 2-isopropylethylene, 1-, 2- or 3-ethyl-trimethylene, 1-methyl-2-ethyl-ethylene, 2-methyl-1-ethyl-ethylene or 1,3-dimethyl-trimethylene group.

In a phenylalkyl group, the alkyl group can be any of the above for have a straight-chain or branched alkyl group. One For example, phenylalkyl group is one. Benzyl or an oc- or phenyl-ethyl group.

For example, an alkylamino group of up to 4 carbon atoms is one Methylamino, ethylamino, propylamino, isopropylamino, butylamino, sec-butylamino or tert-butylamino group. A dialkylamino group in which the alkyl groups are up to can contain up to 4 carbon atoms is one of the above-mentioned alkylamino groups by Replacement of the hydrogen atom by an alkyl radical derived Dialkylamino and is, for example, a dimethylamino, diethylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, dipropylamino or diisopropylamino group.

A carboxyalkyl group with up to 7 carbon atoms is derived of one of the aforementioned alkyl radicals with up to 7 carbon atoms by replacement of a hydrogen atom through the carboxy group and is, for example, a carboxymethyl or a 1- or 2-carboxyethyl group In a functional derivative of a carboxy or carboxyalkyl group is the carboxy group by a functionally modified one Replaced carboxy group. A functionally modified carboxy group is included for the Example with an alkoxycarbonyl group. up to 5 carbon atoms, a cyano or a carbamoyl group.

An alkoxycarbonyl group of up to 5 carbon atoms is one derived from one of the above-mentioned alkoxy groups with up to 4 carbon atoms Alkoxycarbonyl group, such as a methoxycarbonyl, ethoxycarbonyl, propoycarbonyl, -Isopropoxycarbonyl, butoxycarbonyl or isobutoxycarbonyl group.

A carbamoyl group or a sulfamoyl group is preferably unsubstituted, but can also be replaced by one or two identical or different of the aforementioned alkyl groups, which can contain up to 4 carbon atoms, mono- or disubstituted on the nitrogen atom be.

Alkanoyl radicals with 2 to 7 carbon atoms are acyl radicals of straight-chain ones or branched alkane carboxylic acids with 2 to 7 carbon atoms2 in which the alkyl radical with 1 to 6 carbon atoms one of the meanings given above for an alkyl group has, preferably the remainder of the acetic or propionic acid.

In a phenylalkanoyl group, the alkanoyl radical has 2 to 7 Carbon atoms one of the meanings given above. A p-lenylalkanoyl group is for example a phenylacetyl, i- or 2-phenyl-propionyl or ene cinnamoyl group.

The inventive compounds of general formula I and - their tautomers and pharmacologically acceptable salts have valuable 'pharmacological Properties and accordingly can be used as a medicine. she in particular have an inhibitory effect that is novel for such a group of substances compared to the ferment xanthine oxidase and have an extremely low level Toxicity. The new compounds are effective in doses of 10 to 100 mg / kg in rats when administered orally, a marked decrease in the uric acid blood level.

The new compounds and their pharmacologically acceptable salts can therefore be used as valuable therapeutic agents, preferably for the treatment of gout, also as an agent for the treatment of coronary insufficiency and with antiarrhythmic Effect, can be used.

Those according to the invention have particularly valuable properties Compounds of the formula I and their salts in which R³ is one of the following heterocyclic Radicals which are replaced by one to three identical or different substituents from the group Alkyl with 1 to 7 carbon atoms, preferably methyl, alkoxy with 1 to 7 carbon atoms, preferably methoxy, hydroxyl, halogen or phenyl, means: Pyridyl radicals, e.g. pyridyl- (2), pyridyl- (3), pyridyl- (4), 3-hydroxypyridyl- (2), 6-hydroxypyridyl- (3), 2-chloropyridyl- (3) or 2,6-didhydroxypyridyl- (4), pyrazinyl radicals, E.g. pyrazinyl- (2), pyrimidinyl residues, e.g. pyrimidinyl- (4), 2,4-dihydroxypyrimidinyl- (5) or .. 2,4-dihydroxy-pyrimidinyl- (6), pyrazolyl residues, e.g. 1,3,5-triphenyl-pyrazolyl- (4), Piperidyl, e.g. piperidyl- (1) or piperidyl- (4), tetrahydropyridyl, e.g. 4-hydroxy-1,2,5,6-tetrdahydropyridyl- (3) or 2-hydroxy-3,4,5,6 tetrahydropyridyl- (3), Piperazinyl residues, E.g. piperazinyl- (1), pyrrole radical, e.g. 1-methyl-pyrrolyl- (2), pyrrolidinyl radical, E.g. pyrrolidinyl- (2), 4-hydroxypyrrolidinyl- (2) or 1-methylpyrrolidinyl- (2), Pyrrolinyl residues, e.g. 5-hydroxy-4-pyrrolinyl- (2) or 5-hydroxy-4-pyrrolinyl- (3), Thienyl residues, e.g. thienyl- (2) or thienyl- (3) 1 furyl residues, e.g. furyl- (2) or Furyl (3), imidazolyl radicals, e.g. imidazolyl (2) or Ijiiidazolyl (4), thiazolidinyl radicals, e.g. thiazolidinyl- (4) X indolyl residues, e.g. indolyl- (2), indolyl- (3), indolyl- (5), @ 5-chloro-indolyl- (2) or 5-methoxyindolyl- (2), indazolyl radicals, e.g. indazolyl- (3) 1 quinolyl residues, e.g. quinolyl- (2), quinolyl- (4), quinolyl- (5), quiniolyl- (6), quinolyl- (8), 3-hydroxyquinolyl- (4) or 2-hydroxy-quinolyl- (4).

The compounds can still be used as valuable intermediates, e.g. for the production of other, especially pharmacologically active compounds, Find use.

For example, 4 (1H) -pyrimidinones can be prepared from the compounds according to the invention, as described in the German patent application filed at the same time by the same applicant "New heterocyclically substituted 4 (1H) -pyrimidinone compounds, processes for their preparation and pharmaceuticals containing them" are: 4 (1H) -pyrimidinone compounds of the general formula wherein R3, alk and n have the meanings given for formula 1, are prepared by otine a substituted 2-hydrazonomethyl-3-hydroxy-4-aza-3,4-penta dienonitrile of the general formula I or its tautomer or salt heated in opposition to an oxygen- or nitrogen-free organic solvent and / or treated with organic or inorganic acids. The compounds I are heated in or without the presence of an oxygen- or nitrogen-free solvent or solvent mixture, preferably to temperatures of 100 to 1800 C, or with organic or inorganic acids in or without the presence of organic solvents or solvent mixtures with cooling or at elevated temperatures Temperatures, preferably from 0 ° to 100 ° C., in particular from 70 to 100 ° C., and expediently under anhydrous conditions. Suitable organic solvents are, for example, benzene, toluene, xylene and o-dichlorobenzene.

As organic or inorganic acids, e.g.

can be used: hydrogen halide, preferably hydrogen chloride, p-Toluenesulfonic acid, formic acid, acetic acid, sulfuric acid - or perchloric acid 1 where the acids used should be present in at least catalytic amounts. The 4 (1H) -pyrimidinones and their salts have with the compounds of the formula I. comparable pharmacological effects, in particular an inhibitory effect the ferment xanthine oxidase, and can therefore be preferred as valuable therapeutic agents1 used to treat gout.

The invention also relates to a process for the preparation of compounds of the general formula I and their tautomers and salts, characterized in that a compound of the general formula II or III or their tautomers, in which R10 is an -OR11-, -SR11- or -NE5R6 group, R11 is an alkyl, phenyl or phenylalkyl radical and R5 and R6 have the meanings below, with a connection of the general formula IV, H2N -NH-CO- (alk) II -R3 IV in which R3, alk and n have the aforementioned meanings, converts and, if desired, converts a free compound into the salts, in particular pharmacologically acceptable salts, in a compound obtained with a salt-forming group , or a obtained salt in the free compound or in another, in particular pharmacologically acceptable salt, converted-The reactions are preferably in chloroform, benzene, organic solvents, for example, in chloroform, benzene, toluene, xylene, dioxane, dimethylformamide or ethyl acetate under Cooling or carried out at elevated temperatures, for example the boiling point of the solvent, or preferably at room temperature.

The reaction conditions of the reactions described above are taking into account all the substituents in the reactants chosen.

The invention also relates to those embodiments of the method, one of which at some stage in the process as an intermediate available connection goes out, and carries out the additional procedural steps, or stop the process at any stage, or use one as a starting material Compound under the reaction conditions or in the form of a reactive Derivatives, a tautomeric form or a salt used.

R5 and R6 are identical or different and represent a hydrogen atom, a straight-chain or branched alkyl radical with 1 to 7, preferably 1 to 4, Carbon atoms in which a methylene group is optionally replaced by an oxygen atom can be replaced, or a cycloalkyl radical having 5 to 6 carbon atoms or hilden together an alkylene group with 2 to 5 carbon atoms, in which optionally one or more methylene groups through a hetero atom such as -0- or -S-, or through an e -NR7 group, e.g.

a 3-aza or 3-thia, preferably a 3-oxapentamethylene group and in particular a pentamethylene group, R7 means a hydrogen atom or an alkyl radical has 1 to 7, in particular 1 to 5, carbon atoms.

6 Eiiie alkylene group formed from the radicals R5 and R- with 2 to 5 carbon atoms is straight-chain or branched and is e.g. an ethylene, trimethylene, 1- or 2-methylethylene, tetramethylene, 1-, 2- or 3-methyltrimethylene, 1- or 2-ethyl-ethylene or pentamethylene group.

The new compounds with salt-forming groups can vary depending on the Reaction conditions in free form or in the form of their salts with inorganic or organic acids or bases are obtained, which forms in per se known Way are convertible into one another.

The salts of the compounds according to the invention can easily be dissolved in water or sparingly soluble, the sparingly soluble salts especially for the production of sustained release forms of the compounds according to the invention can be used.

As starting materials for the process of the present invention are preferably those used in addition to those described above as being particularly valuable Connections lead.

The starting materials of the formulas II, III and IV are known or will be produced by known methods.

Compounds of formula IV can be in a known manner from the prepare corresponding carboxylic acid alkyl esters with hydrazine hydrate.

The compounds according to the invention can optionally be used as isomer mixtures, lçie racemates, or in the form of the pure isomers, such as optically active components, are present. If mixtures of isomers are obtained, the separation into the optical active isomers happen according to known methods. Racemates can e.g.

due to physicochemical differences in the optically active ones Separate antipodes, e.g. due to the different solubility properties of drastereomeric salts, or by fractional crystallization from one optically active solvents, or by chromatography, especially thin layer chromatography on an optically active carrier material, in particular derpharmacologically more effective and / or less toxic pure antipode is isolated.

Drugs may have been made that contain one or more of the compounds according to the invention in free form or in pharmacological form compatible salt as active ingredient, if necessary also in a mixture with other pharmacologically effective Substances included. These medicines can be prepared by as usual the active ingredient is combined with a pharmaceutical carrier, such as a filler, a diluent, a corrector and / or other common medicinal products Components. The means can, for example. in the solid state as tablets or capsules or in liquid form as solutions or suspensions.

The pharmaceutical carrier can also use the usual diluents or Contain tablet additives, such as cellulose powder, corn starch, lactose and talc, as is customary for such purposes.

The production of the pharmaceutical preparations takes place in itself in a known manner, e.g. by means of conventional mixing, granulating or coating processes. The pharmaceutical preparations contain about 0.1% to about 75 eD, preferably -about 1 d% to about 50%, of the active ingredient. Administration can be enteral, e.g. orally or parenterally, the individual doses being between 10 and 1000 mg, preferably at 50 to 500mg, active ingredient.

The specified doses can be taken 1 to 4 times a day, e.g. with meals and / or in the evening. The single dose, the frequency of administration and the duration of the treatment depend on the nature and severity of the Illness.

Counterstaiid of the invention are therefore also medicaments, in particular used to treat gout caused by the content of one or more compounds of general formula I in free form or in pharmacologically acceptable form Salts are labeled, as well as their manufacture.

Example of an approach for the production of 75,000 tablets of 100 each m @ Active ingredient components: 7.500 kg N '- (2-cyano-3-formylamino-3-bydroxyallylidene) nicotinic acid hydrazide 4.875 corn starch 0.225 kg amorphous silica 0.300 kg sodium lauryl sulfate 0.375 kg polyvinylpyrrolidone 1.200 kg pectin 0.375 kg talc 0.150 kg nagnesium stearate 15.000 kg The active ingredient, the Nais starch, the amorphous silica and the sodium lauryl sulfate 'are mixed and sifted. This mixing with a solution of polyvinylpyrrolidone moistened in 214 l of ethanol and passed through a sieve with a mesh size of 1.25 mm Granulated. The granulate is dried at 40 ° C and mixed with the pectin, talc and lund Magnesium stearate mixed. This mixture is turned into tablets on a rotary machine pressed at 200 mg and 8 mm in diameter.

Example of an approach - for the production of 200,000 capsules of 100mg each Active ingredient components: 20,000 kg N '- (2-cyano-3-formylamino-3-hydroxy allylidene) nicotinic acid hydrazide 0050 kg of amorphous silica 20.050 kg of ethyl 3- (2-cyano-3-formylamino-3-hydroxy-allylidene) carbazate in finely powdered form - - and the unpressed amorphous silica are mixed well and filled in size 4 hard gelatine capsules.

The following examples explain the invention in more detail, without it to restrict.

Example 1.68 g of 3-ethoxy-2-cyano-N-formyl-acrylamide and 1.37 g of nicotinic acid hydrazide apply for 4 hours at room temperature in 50 ml of ethyl acetate. The yellow precipitate is filtered off with suction, washed with acetonitrile and dried.

1.8 g (69.5% of theory) of N '- (2-cyano-3-formylamino-3-hydroxy-allylidene) nicotinic acid hydrazide are obtained with a decomposition point of 135 ° C.

The following compounds of the formula I (n = 0) can be obtained analogously from 3-ethoxy-2-cyano-N-formyl-acrylamide and an acid hydrazide of the formula R³-CO-NH-NH2 iR3- tX .tt: '* -I --- -' ÄusbeteC 1 - ~~~~~~~~~~~~~~~ - r * ri itt, - - 96 ~; sr,; ~} - t'ers H; C6 3 c112- ç S4Tn! 1 L ,: '. ,, - H \ CLH,.> T f>,. -. >. 6 5 CII -6 5

Claims (2)

P atent answer @@@@@@@@@@@@@@@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@ @@@@@@@@@@@@@@@@@@@@@@@@@@ 1. Substituted 2-hydrazonomethyl-1-hynnoxy-4-hza 2,4-pentadiene nitriles of the general formula I @@@@ @@@@@ @@@@ @@@@ @@@@@@@ @@ @@@ @@@ @@@@@@@@: @@@@@@ @@ @@ @@@@@ @@@@@@ and their tautomers and salts, in which alk is a straight-chain or branched alkyl group with 1 to 5 carbon atoms, and preferably a methylene or ethylene group, n @ is 0 or 1 and @@@ @ @@ @@@@@@ on @@@@ @ @@@@@@@ R³ denotes a heterocyclic radical of aromatic character or a partially or perhydrogenated derivative of such a radical. 2. Process for the preparation of substituted 2-hydrazonomethyl-3-hydroxy-4-aza-2,4-pentadiennitrile @ of the general formula I. and their tautomers and salts, in which alk is a straight-chain or branched alkylene group having 1 to 5 carbon atoms, and preferably a methylene or ethylene group, n is 0 or 1 and R3 is a beterocyclic radical of aromatic character or a. means partially or perhydrogenated derivative of such a radical, characterized in that a compound of the more general formula II. or III or their tautomer in which R10 is an -OR11-, -SR11- or -NR5R6 group, R11 is an alkyl, phenyl or phenylalkyl radical, R5 and R6 are identical or different and are a hydrogen atom, a straight-chain or branched alkyl radical with 1 to 7, preferably 1 to 4, carbon atoms, in which a methylene group can optionally be replaced by an oxygen atom, or a cycloalkyl radical with 3 to 6 carbon atoms or together an alkylene group with 2 to 5 carbon atoms, optionally one or more methylene groups. a heteroatom, such as -0- or -S-, or can be replaced by an -NR7 group, for example a 3-aza or 3-thia, preferably a 3-oxapentamethylene group and in particular a pentamethylene group, and wherein R7 is a hydrogen atom or an alkyl radical having 1 to 7, in particular 1 to 5 carbon atoms, is with a compound of the general formula IV, H2N - NH - CO - (alk) - R3 IV n in which R3, alk and n have the meanings given above, converts and, if desired, in a compound obtained with a salt-forming group a free compound into the salts1, in particular pharmacologically acceptable salts, converted or a obtained salt in the free compound or in eSn other, in particular pharmacologically compatible salt, transferred. 3 * marked medicinal products, especially for the treatment of gout by the content of one or more of the substituted ones mentioned in claim 1 2-hydrazonomethyl-3-hydroxy-4-aza-2,4-pentadiene nitrile, of their tautomers or of their pharmacologically acceptable salts.