AT391134B - Process for the preparation of novel glycinamide derivatives, their addition salts and their optical isomers - Google Patents

Abstract

In a process for preparing novel glycinamide derivatives I, in which R, R1 and R2 have the meaning stated in Claim 1, a nitrile II or an amidine III in which R, R1 and R2 have the meaning stated in Claim 1, is hydrolysed. <IMAGE>

Description

No. 391 134

Certain glycinamides are already known in chemical reactions, such as the compounds with the formulas C2H5NHCH2CONH2, iC3H7NHCH2CONH2, C4H9NHCH2CONH2,

Cyclo-C6HnNHCH2CONH2, C7H15NHCH2CONH2, C6H5NHCH2CONH2, C6H5CH2NHCH2CONH2, pClC6H4CH2NHCH2CONH2.

Other glycinamides are known from DE-OS 2511311 as fungicides.

Still other glycinamides are known to have certain pharmaceutical properties, such as the compound C2H ^ O-CO- (CH2) 3NH-CH2-CONH2 and the compounds described in BE-PS 636 245.

The invention is essentially based on the object to produce a class of derivatives of 2-aminoacetamide, which are of particular interest in the manufacture of medicaments, since they have excellent spasmolytic activity without sedation and for the treatment of various forms of epilepsy, of dyskinesis, such as Parkinson's disease, mental disorders such as depression, and memory disorders.

The new compounds which can be prepared according to the invention correspond to the general formula

R

n-ch-conh2

, (D R1 R2 in which R is a linear or branched alkyl group having 5 to 11 carbon atoms, a linear or branched alkenyl group having 5 to 18 carbon atoms, a linear or branched alkynyl group having 4 to 10 carbon atoms, a linear alkanoyl group with 5 carbon atoms or a linear or branched alkyl group with 1 to 10 carbon atoms, through a phenoxy, hydroxyl, acetoxy or carboxyl group, through a linear or branched alkoxycarbonyl group with 1 to 4 carbon atoms, through a carbonyl -, aldehyde, acetal or ketal group, is substituted by at least one phenyl group or by at least one phenyl group substituted by a halogen, preferably fluorine, chlorine or bromine,

Rj is hydrogen, a linear or branched alkanoyl group with 1 to 6 C atoms, a benzoyl group, a linear or branched alkoxycarbonyl group with 1 to 8 C atoms or a carboxamidomethyl group, R2 is hydrogen, a linear or branched alkyl group with 1 to 3 C- Is an atom or a phenyl group, and if both R j and R2 are hydrogen, R cannot be hydroxyethyl, heptyl, 1,1,3,3-tetramethylbutyl, ethoxycarbonylpropyl, benzyl or p-halobenzyl. The compounds of the general formula (I) which can be prepared according to the invention also include their addition salts formed with non-toxic, pharmaceutically acceptable acids and their optical isomers. The process according to the invention is characterized in that a nitrile of the general formula

R

or an amidine of the general formula

wherein R, Rj and R2 have the meaning given above, is hydrolyzed, whereupon, if desired, a compound of the general formula (I) with the meaning of hydrogen for Rj is converted into a compound of the general formula (I) with one of the other meanings of Rj and / or if desired, a compound of the general formula (I) obtained is converted into a salt or a salt of the -2-

No. 391 134 general formula (I) is converted into another salt or into the base and / or a mixture of optical isomers obtained is split into the individual optical isomers.

A preferred embodiment of the invention relates to the preparation of compounds of the general formula (I), in which R is a linear or branched alkyl group having 5 to 11 carbon atoms, a linear or branched alkenyl group having 5 to 18 carbon atoms, a linear or branched alkynyl group with 4 to 6 carbon atoms, a linear alkanoyl group with 5 carbon atoms, or a linear or branched alkyl group with 1 to 8 carbon atoms, through at least one phenyl group or through at least one through a halogen, preferably fluorine, chlorine or bromine substituted phenyl group, is substituted by a phenoxy, hydroxyl, acetoxy or carboxyl group, by a linear or branched alkoxycarbonyl group having 1 to 4 carbon atoms or by a carbonyl or carboxaldehyde group,

Rj is hydrogen, a linear or branched alkanoyl group with 1 to 4 carbon atoms, a benzoyl group, a linear or branched alkoxycarbonyl group with 1 to 8 carbon atoms or a carboxamidomethyl group and R2 is hydrogen, a linear or branched alkyl group with 1 to 3 carbon atoms Is an atom or a phenyl group, where if both Rj and R2 are hydrogen, R is not a hydroxyethyl group,

Heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group, benzyl group or p-halobenzyl group.

A further preferred embodiment relates to the preparation of compounds of the general formula (I), in which R is a linear or branched alkyl group having 5 to 9 C atoms, a linear or branched alkenyl group having 5 to 10 C atoms, a linear or branched alkynyl group 4 to 6 carbon atoms, a linear alkanoyl group with 5 carbon atoms, a linear or branched alkyl group with 1 to 4 carbon atoms, by at least one phenyl group, at least one phenyl group substituted by a halogen such as fluorine, chlorine or bromine is an acetoxy or carboxyl group, substituted by a linear or branched alkoxycarbonyl group having 1 to 4 carbon atoms or by a carboxaldehyde group, Rj

Is hydrogen, a linear or branched alkanoyl group having 1 to 4 carbon atoms, a carboxamidomethyl group or an alkoxycarbonyl group having 1 to 8 carbon atoms and R2 is hydrogen, a methyl or phenyl group, where, if both Rj and R2 are hydrogen, R cannot be a heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group, benzyl group or p-halobenzyl group.

A special class of the compounds which can be prepared according to the invention are those of the general formula (I), in which R is a linear or branched alkyl group having 5 to 9 C atoms, a linear or branched alkenyl group having 5 to 8 C atoms, a linear alkanoyl group having 5 C -Atoms, or a linear or branched alkyl group having 1 to 4 carbon atoms, which is substituted by a phenyl, acetoxy or carboxyl group, by an alkoxycarbonyl group having 1 or 2 carbon atoms or a carboxaldehyde group, Rj is hydrogen, a is a linear or branched alkanoyl group with 1 to 4 carbon atoms, an alkoxycarbonyl group with 1 to 8 carbon atoms or a carboxamidomethyl group and R2 is hydrogen, an alkyl group with 1 or 2 carbon atoms or a phenyl group, where if both Rj and R2 means hydrogen, R cannot be a heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group or benzyl group.

Another preferred class of compounds of the general formula (I) which can be prepared according to the invention are those in which R is a linear or branched alkyl group having 5 to 8 C atoms, a linear or branched alkenyl group having 5 to 8 C atoms, a linear or branched Alkynyl group with 5 to 8 carbon atoms or a linear or branched alkyl group with 1 to 4 carbon atoms which is substituted by a phenyl group, a carboxyl group, an alkoxycarbonyl group with 1 or 2 carbon atoms or a carboxaldehyde group, Rj is hydrogen, represents a benzoyl group or a carboxamidomethyl group and R2 represents hydrogen, an alkyl group having 1 or 2 C atoms or a phenyl group, where, if both Rj and R2 represent hydrogen, R is no heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group or can be a benzyl group.

Of particular advantage are compounds of the general formula (I) which can be prepared according to the invention, in which R is a linear or branched alkyl group having 5 to 7 C atoms, which is substituted by a carboxyl group or a linear or branched alkoxycarbonyl group having 1 to 4 C atoms, means Rj

Represents hydrogen or a carboxamidomethyl group and R2 represents hydrogen, a methyl group or a phenyl group, wherein if both Rj and R2 represent hydrogen, R cannot be a heptyl group, 1,1,33-tetramethylbutyl group or ethoxycarbonylpropyl group.

Of particular interest are the compounds of the general formula (I) in which R is an alkyl group having 2 to 4 carbon atoms, which is substituted by a phenyl group which is optionally substituted by a halogen such as fluorine, chlorine or bromine, Rj Is hydrogen and R2 is hydrogen, a methyl or phenyl group. -3-

No. 391134

Of particular interest are the compounds of the formula (I) in which R is a linear or branched alkyl group having 5 to 9 carbon atoms, Rj is hydrogen, a carboxamidomethyl group or a

Alkoxycarbonyl group having 1 to 8 carbon atoms and R2 means hydrogen, a methyl or phenyl group, where, if both Rj and R2 are hydrogen, R cannot be a heptyl group or 1,1,3,3-tetramethylbutyl group.

A preferred subclass of compounds of the general formula (I) are those in which R is a linear or branched alkyl group having 5 to 9 carbon atoms and Rj and R2 are hydrogen, where, if both Rj and R2 are hydrogen, R cannot be a heptyl group or 1,1,3,3-tetramethylbutyl group.

If the compounds of the general formula (I) are in the form of their acid addition salts, they can be converted into their free bases or into salts of other acids by means of the customary processes.

The most frequently used salts are the acid addition salts, in particular the addition salts with non-toxic, pharmaceutically usable salts, with suitable inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid or with suitable organic acids such as the aliphatic, cycloaliphatic, aromatic, araliphatic or heterocyclic carboxylic or sulfonic acids , e.g. Formic acid, acetic acid, a Dialkylessigsäure as dipropylacetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, hydroxybenzoic acid, salicylic acid, Phenylacetic acid, mandelic acid, embonic acid, methanesulfonic acid, ethanesulfonic acid, pantothenic acid, toluenesulfonic acid, sulfanilic acid, cyclohexylaminosulfonic acid, stearic acid, alginic acid, ß-hydroxypropionic acid, ß-hydroxybutyric acid, oxalic acid, malonic acid, galactaric acid and galacturonic acid. Salts can also be derived from natural or artificial amino acids such as lysine, glycine, arginine, ornithine, asparagine, glutamine, alanine, valine, threonine, serine, leucine or cysteine.

Examples of compounds which can be prepared according to the invention are: 2- (n-pentylamino) acetamide, 2- (n-octylamino) acetamide,

Methyl ester of 6 - [(dicarboxamidomethyl &gt; amino] hexanoic acid, 2- (n-decylamino) acetamide,

Methyl ester of 8 - [(dicarboxamidomethyl) amino] octanoic acid, 2- (n-hexylamino) acetamide, 2 - [(2-phenylethyl) amino] acetamide, 2- (n-octadecen-9-yl-amino ) -acetamide, 2 - [(N-carboxamidomethyl-N, n-hexyl) -amino] -acetamide, 2 - [(l, l-dimethyl-propin-2-yl) -amino-] acetamide, ethyl ester of Nn- Hexyl-N-carboxamidomethyl-carbamic acid, 2- (n-pentylamino) -butyramide, 2 - [(3-phenylpropyl) -amino] -acetamide, 2- (octen-7-yl-amino) -acetamide, 8-carboxamidomethylamino- octanoic acid, 2 - [(4-phenylbutyl) amino-] acetamide,

Methyl ester of 5 - [(carboxamidomethyl) amino] hexanoic acid or 2 - [(N-benzoyl-N-n-hexyl) amino] acetamide.

The connections that can be produced according to the invention can have one or more centers of asymmetry. Compounds with asymmetry centers can be in the form of optical antipodes or in the form of mixtures, which can be racemic. They can be separated into enantiomers by the formation of diastereoisomeric salts. For compounds which can be prepared according to the invention and which have two centers of asymmetry, two racemates with erythro or threo configuration can be obtained. These two racemates can be separated by conventional methods, for example by the formation of diastereoisomeric salts using optically active acids such as tartaric acid, diacetyltartaric acid, tartranilic acid, dibenzoyltartaric acid, ditoluyltartaric acid, and separation of the diastereoisomeric mixture by crystallization, distillation or chromatography with subsequent release of the optically active base from the salts.

The compounds which can be prepared according to the invention can accordingly be used in the form of mixtures which contain several diastereoisomers in any ratio, in the form of mixtures which contain enantiomeric pairs in the same ratio (racemic mixture) or in any ratio, and also in the form of optically pure compounds.

The compounds which can be prepared according to the invention can be used for the treatment of various forms of epilepsy, for the treatment of dyskinesis, such as Parkinson's disease, and for memory disorders. Furthermore, the use of certain products according to the invention for the treatment of mental disorders such as depression can be considered. -4-

No. 391 134

At least one compound of general formula (I) and / or its salts in combination with pharmaceutical preparations containing a pharmaceutical carrier can be in a form which makes them suitable for oral, rectal or parenteral administration. For example, the preparations for oral administration can be liquid or solid and can be in the form of compresses, dragees, coated compresses, capsules, granules, powders, syrups or suspensions. The dry preparations for oral administration contain additives and carriers, as are common in pharmaceutical pharmaceuticals, neutral diluents, disintegrants, binders and lubricants, such as lactose, starch, talc, gelatin, stearic acid, cellulose and its derivatives, silica , Magnesium stearate, polyvinyl pyrrolidone, calcium phosphate, calcium carbonate etc.

Such preparations can be carried out in such a way that their decay is delayed and the duration of action of the active ingredient contained is thereby prolonged. Aqueous suspensions, emulsions and oily solutions are added with added sweeteners such as dextrose or glycerin, flavors such. B. vanilla, and may also contain thickeners, wetting agents and preservatives. Oily emulsions and solutions are made using a vegetable or animal oil and can contain emulsifiers, flavors, dispersants, sweeteners and antioxidants. For parenteral administration, sterile water, an aqueous solution of poly vinyl pyrrolidinone, peanut oil, ethyl oleate, etc. are used as the carrier. The injectable aqueous or oily solutions can contain thickeners, wetting agents, dispersants and gelling agents.

The nitriles of the general formula (II) and the amidines of the general formula (III) can be hydrolyzed to the amides (I) both in the acidic and in the basic medium.

If the hydrolysis takes place under acidic conditions, concentrated sulfuric acid, a concentrated aqueous solution of hydrochloric acid, formic acid without the addition of a solvent and acetic acid in the presence of boron trifluoride can be used. In most cases it is advantageous to heat the reaction mixture to temperatures up to 200 ° C. Another way of converting nitrile to amide in an acidic environment is to treat the nitrile using hydrochloric acid in an alcohol such as ethanol. An imino ether is formed as an intermediate product, which thermally converts into an amide.

If the hydrolysis is carried out under basic conditions, the aqueous solution of an alkali metal or alkaline earth metal hydroxide is used in this case. The presence of hydrogen superoxide can promote the hydrolysis reaction. A proprietary process for the hydrolysis of nitrile has been developed which consists in adding one equivalent of copper chloride to the nitrile and carrying out the reaction in an aqueous solution of an alkali metal hydroxide with a pH = 10, preferably at ambient temperature. Here, too, it can be advantageous to carry out the hydrolysis at a temperature which is between the ambient temperature and the reflux temperature of the reaction mixture.

Another very classic method of basic hydrolysis of nitriles and amidines takes place using an alkali metal hydroxide, preferably potassium hydroxide, in t-butanol.

The starting materials of the general formula (Π) can according to the reaction scheme

R

NH

R

Ri ^ VII) R2CHO + YCN (IV) (V) - &gt; HO-CH-CN IL R2. (VI) &gt;

N-CH-CN

Ro

ÖD wherein R, Rj and R2 have the meanings given above, while Y is a cation.

The cyanohydrin of the formula (VI) can either be separated beforehand or prepared in situ from an aldehyde of the formula ÖV) and an inorganic or organic cyanide (V) such as sodium, potassium or trimethylsilyl cyanide or else an alkylaluminium or alkylammonium cyanide.

The condensation of the amine (VII) with the cyanohydrin (VD) is carried out in a neutral organic solvent, for example a chlorinated hydrocarbon such as chloroform or dichloromethane, an aromatic or aliphatic hydrocarbon such as benzene, toluene or petroleum ether or in an ether such as diethyl ether or dioxane. To get a good yield, it is sometimes advantageous to use -5-

No. 391134

Temperature between 20 and 120 ° C to work. An acid acts as a catalyst in this reaction. For example, a hydrohalic acid such as hydrochloric acid or an oxygen acid such as sulfuric acid or an organic acid such as p-toluenesulfonic acid can be selected for this purpose.

In principle, an amidine of the general formula (ΙΠ) is converted into an amide of the general formula (I) by means of acidic hydrolysis in an aqueous or alcoholic medium. The acid can be an inorganic acid such as hydrochloric acid or sulfuric acid or an organic acid such as acetic acid. The reaction takes place at a temperature in the range between the ambient temperature and the reflux temperature of the reaction mixture.

An amidine of the general formula (HI) can be prepared by reacting a nitrile of the general formula (Π) with an amine. It is often advantageous to activate one of the reactants in order to obtain the amidine (ΠΙ) with a better yield. An activated form of nitrile (Π) can be an imino ether or an iminohalide. The amine can be activated by forming a salt with an alkali or alkaline earth metal. Under these conditions, the amidines are obtained with a good yield.

The reaction between a hnium salt and a cyanide according to the reaction scheme R © H R \ / \ N = C + CN &quot; &gt; N-CH \ / 1 R1 R2 R1 R2 (Π) where R, Rj and R2 in turn have the meanings given above, leads to compound (Π) in the stated manner and takes place in a neutral organic solvent, for example in a chlorinated hydrocarbon such as Chloroform or dichloromethane or in an aromatic or aliphatic hydrocarbon such as benzene, toluene or petroleum ether instead, it being advantageous to work at a temperature between 0 ° C and the reflux temperature of the solvent.

A compound of the general formula (II) with a meaning other than hydrogen for Rj can be obtained from a compound of the general formula (II) with the meaning of hydrogen for Rj according to the reaction scheme

RiX R \

R-NH-CH-CN- &gt; N-CH-CN 1/1 r2 R1 r2 in which R, Rj and R2 have the meanings given above, but in this case Rj cannot be hydrogen, and X is a group which can be easily removed by a nucleophilic reaction, for example a halogen such as chlorine, Represents bromine or iodine or a tosyl, mesyl or acyloxy group. The reaction can take place in an organic solvent such as chloroform or dichloromethane, in an alcohol such as methanol or ethanol or in a saturated or aromatic hydrocarbon such as petroleum ether, benzene or toluene. The reaction takes place either at ambient temperature or at a temperature between 0 ° C and the reflux temperature of the solvent. The reaction can advantageously be carried out in the presence of an organic base such as, for example, triethylamine, pyridine or N-dimethylaniline, or in the presence of inorganic bases such as the hydroxides, carbonates and bicarbonates of the alkali or alkaline earth metals and finely powdered lime. Compounds of the general formula (II) can also be carried out in an analogous manner according to the reaction scheme

R

R ^ N-H + X-CH-CN- / 1

Marg

^ N-CH-CN, / L wherein R, Rj, R2 and X have the meaning given above, are prepared.

If the desired compounds (I) Rj represents an alkyl group and the group was introduced by acylation of the amine, the amide formed must be reduced to the amine. There are numerous procedures -6-

No. 391134 for performing such a reduction. Examples include hydrogenation in the presence of Raney nickel or copper chromite in inert solvents, e.g. B. in lower alcohols such as methanol or ethanol or in acetic acid, and the reduction by means of lithium and aluminum hydride in ethers such as diethyl ether, tetrahydrofuran or dioxane. It is understood that when choosing the reduction conditions it should be noted that the group -CN remains unchanged.

Another method for producing a compound (Π) follows the reaction scheme

Base Q r2ch2cn- &gt; r2chcn R

R - &gt; - CH-CN, / - (vm) (ix)

R \ R1 R2 N-OAlk (II) (X) where R, Rj and R2 again have the meaning given above and &quot; Alk &quot; means a lower alkyl group with 1 to 4 carbon atoms. First, the compound of formula (VIII) is converted into an anion of formula (IX) using a strong base in a neutral organic solvent. The base used can be an alcoholate such as potassium t-butoxide, a metal amide such as sodium or lithium amide or a complex base which is generally known as &quot; Cautere &quot; Base is called and which is a mixture of metal amides and alcoholates. The organic solvent is an aromatic or aliphatic hydrocarbon such as benzene, toluene or petroleum ether. Depending on the reactivity of the compound (VIII), the reaction temperature can be between -20 ° C. and the reflux temperature of the solvent.

The anion of formula (IX) is then reacted with an O-alkylated derivative of the hydroxylamine of formula (X) to the compound of formula (II), in a neutral organic solvent at a temperature between -20 ° C and the reflux temperature of the solvent is worked.

The compound of formula (II) can also be obtained by reacting an enamine of formula (XI) with hydrocyanic acid according to the reaction scheme

R3 H R R,

\ / \ ^ C = C. R + HCN- &gt; N-CH-CN, / \ / "/ J

N (XI) \

Ri

Ri Ro (Π) where R, Rj and R2 have the meanings given above and hiebei R2 from

R 3

, CH- is formed.

The hydrocyanic acid can be added as such or formed in situ. The addition reaction takes place in a neutral, preferably slightly polar, organic solvent, for example in chlorinated hydrocarbons such as chloroform or dichloromethane or also in acetonitrile, at a temperature between the ambient temperature and the reflux temperature of the solvent.

The reduction of the C-C double bond in an α-cyanoenamine of the formula (XII) also leads according to the reaction scheme -7-

No. 391134

r3 CN R &gt; N.cf './ x R reduction \ - &gt; N-CH-CN ./1

R 1

Marg

Ri (ΧΠ) (D) 10 wherein R, Rj and R2 have the meaning given above and hiebei R2 is formed by the group R3, CH-15, to the compound (II).

The C-C double bond is reduced in a conventional manner by hydrogenation in the presence of a catalyst which belongs to the class of transition metals, their oxides or their sulfates on a neutral support. Raney nickel, platinum, platinum oxide or also palladium on carbon can be mentioned as catalysts. The presence of a solvent is desirable. The solvent can be a lower alcohol such as methanol or ethanol or can be formed from glacial acetic acid and simple acetic acid esters. The reduction can take place under normal pressure or also under positive pressure. The reduction can also take place using hydrides such as sodium borohydride, preferably in the presence of Lewis acid or diborane in a solvent such as methanol, ethanol, diglyme, tetrahydrofuran or dioxane. The reduction conditions must be chosen carefully in such a way that the nitrile group is retained. It should also be mentioned that the more recent literature describes ways which generally open access to a-cyanoenamines of the formula (ΧΠ). 30 compounds of formula (II) with the meaning of hydrogen for Rj can be prepared in the following manner.

When working according to the reaction scheme

R-NH-CH-CN rx + h2n-ch-cn -

35 I r2 (II) R2 or

I 40 rnh2 + x-ch-cn - &gt; R-NH-CH-CN,

II r2 R2 (Π) 45 wherein R and R2 have the meanings given above and X represents a group which can be easily removed by a nucleophilic reaction, for example a halogen such as chlorine, bromine or iodine or a tosyl, mesyl or acyloxy group, the compounds of the formula (Π) are prepared under the working conditions specified in connection with the second reaction scheme. When working according to the reaction scheme 50 55 CN CN / * / reduction RNHo + O = C - &gt; R - N = C - &gt; RNH-CH-CNV \.

Marg

Rn (ΧΠΙ) (XIV) R2 (Π) -8-

No. 391134 in which R and R2 have the meaning given above, the amine with the carbonyl derivative of the formula (ΧΙΠ) in a conventional manner in a neutral and preferably water-immiscible organic solvent such as benzene or toluene, preferably in the presence of an inorganic acid or an organic acid such as p-toluenesulfonic acid, condensed, whereupon the imine thus obtained is reduced to the amine (Π) in a conventional manner.

The reduction preferably takes place in the presence of hydrogen and a hydrogenation catalyst such as platinum, platinum oxide or palladium on carbon, in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid at normal pressure or more advantageously at elevated pressure. The reduction can also take place using an alkali metal hydride such as sodium borohydride in a solvent such as methanol or using aluminum or lithium hydride in a solvent such as tetrahydrofuran. The imine is reduced in such a way that the group -CN is retained. If other starting materials are selected, the compound of the formula (Π) can be prepared in an analogous manner in accordance with the reaction scheme

(XV) (XVI) ff *

C = N - CH - CN

where R2 has the meaning given above and R5

CH- gives the group R, are prepared.

The method according to the invention is explained in more detail below by means of exemplary embodiments

Example 1: a) Preparation of hexylamino-acetonitrile c6h13nh2 + ho-ch2-cn- &gt; c6h13nh-ch2-cn + H20

In a round bottom flask of 100 ml content, 5.7 g of hydroxyacetonitrile (0.1 mol) was mixed with 11 g of hexylamine (0.11 mol), which was dissolved in 10 ml of methanol. During the mixing, the temperature rose rapidly. The solution was left to stand for 24 hours. The methanol was then evaporated and the liquid obtained was distilled at 72 ° C. under 1.07 mbar. b) Preparation of 2-n-hexylamino-acetamide

11.2 g of hexylaminoacetonitrile (0.081 mol) was added dropwise to 31 ml of H2SO4, which was diluted with 30 ml of ethanol and cooled with ice. After the addition, the ethanol was evaporated. 40 ml of H2SO4 were added to the white solid thus obtained. This solution was heated at 100 ° C. for 1 hour, then cooled and then added dropwise to 200 ml of ethanol, whereupon the mixture obtained was filtered and the filter residue was washed with 50 ml of ethanol. Mp = 151 to 152 ° C. -9-

No. 391 134

Analysis:% C% H% N calculated: 37.49 7.87 10.93 found: 37.80 7.80 10.90 Example 2: a) Preparation of 2- (n-pentylamino) butyronitrile c2h5

I.

C5Hj γΝΗ2 + KCN + C ^ CHO- &gt; C5Hj jNH-CH-CN

35 g of Na2S205 were dissolved in 95 ml of water in a round-bottomed flask of 250 ml content, which was provided with a magnetic stirrer. 14.9 ml of propionaldehyde (0.2 mol) were added to this solution, which was cooled with ice, and the resulting solution was stirred at 0 ° C. for 2 hours. A very light precipitation forms. After this solution had reached room temperature, 23.9 ml of amylamine (0.2 mol) was added dropwise. The solution was allowed to react for 2 hours, after which 13 g of KCN (0.2 mol) were added. After a reaction time of 24 h at room temperature, the solution was saturated with NaCl and extracted with ether. The ether phase was dried over MgSO 4 and with a solution of HCl

put in ether. The precipitate that formed was filtered off and dried. Mp = 104 to 105 ° C b) Preparation of 2- (n-pentylamino) -butyramide

C9Hc O

I HCl II C5HnNH-CH-CN - &gt; C5Hn-NH-CH-C-NH2 c2h5

1.9 g of 2- (n-pentylamino) valeronitrile (0.01 mol) were added to 17 ml of concentrated HCl in a round-bottomed flask of 50 ml content, which was provided with a magnetic stirrer and was cooled with ice. After the solids were completely dissolved, the solution was stored in the refrigerator for 24 hours. The hydrochloric acid was then evaporated using a rotary evaporator and the solution was neutralized with 1N NaOH. At pH = 6 the solution was washed several times with benzene. At pH = 11 to 12, the solution was extracted using ether. The ethereal extracts were combined, dried over MgSO 4 and evaporated. The residue obtained was

sublimed at 70 ° C and 0.027 mbar. Mp = 58 to 59 ° C

Analysis:% C% H% N calculated 62.75 11.70 16.26 found: 62.7 11.65 16.05

Example 3:

Preparation of 2 - [(N-benzoyl-N-n-hexyl) amino] acetamide

\ Z6 * 5

NC O C6H1 3n_ch2'c * nh2

In a three-necked flask of 250 ml content, which was equipped with a magnetic stirrer, a thermometer, a bromine ampoule and a cooler with an attached tube with calcium chloride, 100 ml of chloroform, 6.23 g of 2- (n-hexylamino) acetamide ( 0.04 mol) and 8 ml of triethylamine (0.055 mol) are mixed. To this solution, cooled to 10 ° C., a solution of 5.1 ml of benzoyl chloride (0.044 mol) in -10-

No. 391134

10 ml of chloroform added. The reaction mixture was refluxed for 20 hours, then cooled and washed three times with 1N HCl, once with water, twice with 1N NaOH and again twice with water. The chloroform solution was dried over MgSO4 and evaporated. The residue was recrystallized from a mixture of ether and pentane and then from cyclohexane. Mp = 97 to 98 ° C

Analysis% C% H% N calculated; 68.67 8.45 10.67 found: 68.7 8.25 10.60

Example 4:

Preparation of 2- (n-hexylamino) acetamide

O

CuCl2 II c6h13nhch2cn + h2o- &gt; c6h13nh-ch2-c-nh2

In a 250 ml Erlenmeyer flask were placed 1 g of n-hexylaminoacetonitrile (0.072 mol), 1.22 g of anhydrous copper chloride (0.072 mol) and 100 ml of water. Then ethanol was added until a homogeneous phase was obtained. The pH of the solution was then adjusted to 10 using 1N NaOH and the reaction mixture was stirred at room temperature for 4 h. A mauve solid forms, which is filtered off, then suspended in ammonia and extracted with dichloromethane. The organic phase was washed 3 times with water, dried over K2C03 and then evaporated. The residue was recrystallized from cyclohexane. Mp = 62 to 63 ° C

The melting points and the recrystallization solvents for compounds prepared according to the invention are given in Table I below.

Table I

IIR - N - CH - CONH2 R R1 r2 Fp (° Q recrystallization solvent nc8h17 HH 79 acetone / cyclohexane nC6H13 HH 62-63 cyclohexane nC5Hll HH 46 cyclohexane hckch2) 6 HH 96-97 AcOEt hckch2) 6 -CH7C \ nh2 H 115 Isopropanol -11-

No. 391 134

Table I. Continued R - N - CH - CONH2

No.R R1% Fp (0C) recrystallization- 10 solvent 15 0 II 6 CH3OC- (CH2) 5 -ch2-c H 116-117 isopropanol \ nh2 20 7 HO- (CH2) 4- HH 81 EtOH (1) 0 II 8 CH3OC- (CH2) 5 HH 160 MeOH (l) 25 9 nC7Hi5 HH 69 ether pentane 11 HH 79 cyclohexane 12 nC6H13 HH 152-153 ethanol (2) 30 14 nCioH2i HH 87 cyclohexane 0 II 35 15 CH3OC- (CH2 ) 7 HH 70-72 AcOEt 1 0 II 16 C2H5-OC- (CH2) 7 HH 139-140 EtOH (2) 40 17 CH3 (CH2) 7-CH = CH- (CH2) 8 h H 85-87 acetone 18 c7h15-ch HH 58-59 pentane 1 ch3 45 19 C8H17 c6h5-c ^ H 99 cyclohexane 50 20 C5H11 HH 151 ethanol (2) 21 (CH3) 2CH (CH2) 2CH 1 HH 50-51 hexane 55 ch3 -12-

No. 391 134

Table I. Continued R1 R2

I I R - N - CH - CONH2

No.R R1 R2 Fp (ÖC) recrystallization- 10 solvents 22 C5Hn-CH HH 52-53 pentane 15 1 ch3 20 23 0 II CH3OC- (CH2) 7 y -CHrC \ nh2 H 125 EtOH 25 24 (CH3) 2CH ( CH2) 3-CH 1 ch3 HH 63 pentane 30 25 nC6Hi3 y C6% C ^ H 97-98 cyclohexane 26 nC5Hll HH 115-125 ether (3) 35 27 nC6H13 HH 207 MeOH ether (1) 28 c4h9-ch HH 127 -128 ethanol ether (1) 40 29 | C2H5 nC6H13 HH 142-147 MeOH / ether (4) 45 30 nC8H17 // (CH3) jC.CH 68-69 pentane 31 nC5Hll HH 205-207 MeOH (1) 32 nC5Hll HH 104-105 acetone (3) 50 33 nC5Hll HH 149-151 MeOH (4) 34 C6H5- (CH2) 2 HH 90-91 ether pentane -13- 55

No. 391 134

Table I. Continued

R1 R2 IIR - N - CH - CONH2 R R1 R2 Fp (0C) recrystallization · solvent nC6H13 / CHoC H 183 ethanol (1) ch2 = ch (ch2) 5 \ nh2 HH 51 ether nC5Hll H C3 71-72 sublimation ch3 1 HC = CC- HH 75 ether ch3 nC10H21 HH 195-210 ethanol (2) 'nC6H13 (CH3) 3C-CH 15 pentane nC5Hll \ H C6H5 100-101 cyclohexane nC6H13 / ° H 52-53 pentane nC5Hll \ H C2H5 58-59 cyclohexane &lt; Q &gt; <CH2) 3 HH 215-218 MeOH (1) CH2 = CH- (CH2) 6 HH 63 AcOEt / Pentane HOOC (CH2) 7 HH 144-145 acetone / H20 (1) Θ 1 HH 208-210 ethanol (1 ) -14-

No. 391 134

Table I. Continued

R1 R2 I I R - N - CH - CONH2

No. R Rj R2 Fp (° C) recrystallization solvent 48 ((0) -yaHCBjfc.HH 106 acetone-pentane 49 (Ö \ -0- (012) 2 HH 209-211 ethanol (1) 50 (C2H50) 2 CH- (CH2) 3 HH 152 (0.027 mbar) 51 &lt; ^ cT) - (0¾ CI- H &lt; ° &gt; - 290-292 (dec.) Methanol (1) 52 (ö) -ch2 HH 92, 5 methanol 53 (CH3) 2CH-CH 1 ch3 HH 138-139 methyl ethyl ketone-MeOH (1) 54 CH3- (CH2) 3-C = 0 HH 154 AcOEt 55 CI- fo} - (0¾ HH 228-230 ethanol (1 )

No. 391 134

Table I. Continued

R1 R2 I I R - N - CH - C0NH2

No.R R1 r2 Fp (0Q recrystallization solvent 56 CI- ΛΛ - <CH2) 4 HH 75 hexane-AcOEt 57 nC5Hll C02C2H5 H 46 pentane 58 nC5Hll C02nC8H17 H 60 hexane 59 (Ö \ - (002) 4 co2c2H5 H 53 Pentane-ethanol (1) = HCl (2) = H2S04 (3) = benzoate (4) = H3PO4

The pharmacological and biochemical effects of the compounds which can be prepared according to the invention are given in Table Π below. In this table, the numbers in column 1 correspond to the numbers in column 1 of table I. The results given in this table should be interpreted as follows:

The anticonvulsant effect on tonic convulsions caused by bicuculline was examined. The compounds which can be prepared according to the invention were administered orally in doses of 10 to 100 mg / kg, in each case to five mice and 3 hours before the intravenous injection of bicuculline in a dose of 0.6 mg / kg. The number of mice protected from tonic cramps and from death was noted. The results are presented in the form of a score reflecting the total number of animals protected by doses of 10 and 100 mg / kg of the compounds.

The DLjQ values were calculated according to the method of Litchfield and Wilcoxon (Pharmacol. Exp. Ther. 96.99, 1949) and expressed in mg / kg. The products were administered to the mice orally

The effect on behavior was examined using a method derived from the method of S. Irvin (Gordon Res. Conf. On Medicinal Chem., 133, 1959). The substances suspended in 1% tragacanth mucus were administered orally to groups of 5 male mice using a gastric tube (strain CD1, Charles River, fasting for 18 h). If the available amount of the substances allows, the doses are 3000, 1000 and 300 mg / kg. If the latter dose is active, the effect of the substance is examined at 100, 30, 10 and possibly also 3 mg / kg. Behavior is examined at 2.4, 6 and 24 h after treatment. The observation is prolonged if at this time symptoms are still present. Mortality is recorded over 14 days following treatment. None of the tested products caused abnormal behavior in the mice. It should be mentioned in particular that the products are free from a sedative effect. -16- 5

No. 391 134

Table Π - Biological results

No. Bicucullin DL50 mg / kg No. Bicucullin DL50 mg / kg 10 1 4 2220 28 4 1950 2 4 780 29 6 1650 3 7 1925 30 5 &gt; 3000 4 4 &gt; 3000 31 6 2880 5 2 &gt; 3000 32 5 &gt; 3000 15 6 6 &gt; 3000 33 3 &gt; 3000 7 2 34 7 8 1 &gt; 3000 35 9 5 1425 36 4 11 2 1950 37 4 20 12 5 2800 38 6 14 6 2600 40 3 15 41 5 16 5 &gt; 1000 42 8 17 2 &gt; 3000 43 6 25 18 2 &gt; 1000 44 7 19 2 3000 45 6 20 1 &gt; 1000 46 6 21 3 640 47 7 22 5 640 48 4 30 23 7 &gt; 1000 49 5 24 5 650 25 5 3660 26 3 1950 27 4 860 35

The compounds that can be produced according to the invention have the property of preventing cramps caused by bicucullin in mice. This effect indicates that these substances have an anti-epileptic effect, 40 probably by acting on the GABA system. In fact, bicucullin is a specific antagonist of GABA. Incidentally, the effect of the products on the activity of the enzyme which causes the synthesis of GABA, namely on the glutamate decarboxylase (GAD), was investigated. The activity of the GAD (glutamate decarboxylase) was determined in homogenized rat him according to the method described by L. Parker (Methods in Enzymology, Ed. S. Fleischer, 1974, Vol. ΧΧΧΠ, Part V, page 779). The 45 products tested were added at a final concentration of IO "* M. The products that can be produced according to the invention have generally been found to be effective in this test. Products 3, 8, 17 and 31 are particularly noteworthy in this regard. In general, the compounds which can be prepared according to the invention increase the activity of glutamate decarboxylase without influencing the activity of GABA transaminase (GABA-T), the catabolism enzyme of GABA, which results in an increase in the GABA content in the amount of the 50 GABAergic neurons .

Of the substances which can be produced according to the invention, 2-n-pentylaminoacetamide and its chlorohydrate in particular have been particularly investigated. These products prevent cramps caused by bicucullin mice.

The DE ^ Q values are 11.2 and 5.74 mg / kg when administered orally. The chlorohydrate was also administered intravenously in 55. In this case the DE ^ Q value is 2.19 mg / kg. This value is not significantly smaller than the DE ^ Q value when administered orally, which indicates that good absorption takes place in the intestine. Table ΠΙ also shows the therapeutic index (DL ^ q / DE ^ q). For the compounds which can be prepared according to the invention, this therapeutic index is higher than that of diphenylhydantoin and phenobarbital. -17- 60

No. 391 134

Table ΠΙ

Cramps caused by bicuculline (0.6 mg / kg IV) in mice

Treatment 3 hours before the administration of bicuculline

Treatment DL50 DE50 DL5o / DE5o 2-n-pentylaminoacetamide 1925 11.2 172 Chlorohydrate of 2-n-pentylaminoacetamide 2240 5.74 390 Na-2-propylpentanoate 1250 89.1 14 Na-diphenylhydantoin 320 2.63 122 Na phenobaibital 185 2.11 88

Like Na-2-propylpentanoate, 2-n-pentylaminoacetamide is also ineffective in strychnine cramps. Its anticonvulsant effect therefore does not appear to be medullary, but central.

On the other hand, 2-n-pentylaminoacetamide and its chlorohydrate seem to act specifically on the GABA receptors. This assumption is based on the following results: 1. Its effect as an antidote to bicucullin cramps can be overcome by increasing the dose of bicucullin, 2. the 2-n-pentylaminoacetamide only weakly inhibits leptazole cramps in the mouse, 3. the chlorohydrate of 2-n-pentylaminoacetamide has no effect on picrotoxin cramps.

In fact, the leptazole does not act on the GABA receptors and the picrotoxin acts on a site linked to the GABA receptors, but not directly on these receptors. Furthermore, the 2-n-pentylaminoacetamide competes with bicuculline, which is a specific antagonist to GABA. The action of the chlorohydrate of 2-n-pentylaminoacetamide on the GABA system is also confirmed by the fact that this product, when administered orally at a dose of 200 mg / kg to rats, the activity of GAD (gentamate decarboxylase) increases by 26% without modifying that of GABA-T. The proportion of GABA in the black substance, which is rich in GABAergic endings, is increased by 28, 33 and 38% 2, 3 and 4 hours after the treatment.

The 2-n-heptylaminoacetamide has the property of protecting mice against death by KCN. This property can probably be explained by an effect on the energy metabolism in the brain during anoxia. This effect on brain energy metabolism has been confirmed for the chlorohydrate of 2-n-pentylaminoacetamide in a series of experiments on cerebral anoxia caused by decapitation in rats. The product was thus shown to prevent lactate accumulation in the brain during the first few seconds of anoxia.

On the other hand, the 2-n-pentylaminoacetamide increases the action of 1-tryptophan in mice, which relieves the central serotoninergic system and therefore indicates the presence of psychotropic properties, in particular antidepies properties. Incidentally, the 2-n-octylaminoacetamide in mice (50 mg / kg i.p.) was examined in a passive evasion test, where it delayed the decay of the behavior. This product and probably also other connections that can be produced according to the invention accordingly improve memory.

Some of the compounds that can be produced according to the invention inhibit the aggregation of the platelets in human blood plasma. The inhibition of platelet aggregation was measured using the turbulence method of G.V. R. Born and M. J. Cross (J. Physiol 168, 178, 1973). A platelet-rich plasma was inoculated 3 minutes before the addition of the aggregation-inducing agent, Trombofax. The inhibition of the maximum aggregation was determined using an upchurch &quot; Upchurch &quot; measured. In this experiment, compounds 1, 11, 14 and 18 were found to be active.

As already explained, 2-n-pentylaminoacetamide and its chlorohydrate act on the GABAergic system by promoting the transmission of GABA, as shown by the counteraction to Bucucullin. This -18-

Claims (10)

No. 391134 Effect can be based on activation of GAD. These products are therefore particularly indicated for the treatment of epilepsy and dyskinesis, such as Parkinson's disease, a syndrome that is likely due to GABA system insufficiency. The activity on brain energy metabolism and anoxia also allows the use of the product in ischemic himia to be considered. Finally, the effect of 2-n-octylaminoacetamide in the memory test and the effect of 2-n-pentylaminoacetamide on the serotoninergic system make it possible to suggest the treatment of memory impairments and certain psychiatric disorders, such as depression, as additional indications for the compounds which can be prepared according to the invention. The compounds which can be prepared according to the invention can be administered in daily doses of 10 mg to 2 g, the single dose being between 10 and 300 mg. In view of the very low toxicity of the compounds which can be prepared according to the invention, the doses mentioned can be increased without risk. 15 PATENT CLAIMS 20 1. Process for the preparation of new glycinamide derivatives of the general formula 25 N - CH - CONH2, (I) R1 R2 30 in which R is a linear or branched alkyl group having 5 to 11 carbon atoms, a linear or branched alkenyl group having 5 to 18 carbon atoms, a linear or branched alkynyl group having 4 to 10 C atoms, a linear alkanoyl group with 5 C atoms or a linear or branched alkyl group with 1 to 10 C atoms, the 35 by a phenoxy, hydroxyl, acetoxy or carboxyl group, by a linear or branched alkoxycarbonyl group with 1 to 4 C atoms, by a carbonyl, aldehyde, acetal or ketal group, by at least one phenyl group or by at least one phenyl group substituted by a halogen, preferably fluorine, chlorine or bromine, means Rj is hydrogen, a linear or branched alkanoyl group with 1 to 6 carbon atoms, one benzoyl group, one; 40 means linear or branched alkoxycarbonyl group with 1 to 8 C atoms or a carboxamidomethyl group, R2 means hydrogen, a linear or branched alkyl group with 1 to 3 C atoms or a phenyl group, where, if both Rj and R2 mean hydrogen, R means none Hydroxyethyl group, heptyl group, 1,1,33-tetramethylbutyl group, ethoxycarbonylpropyl group, benzyl group or p-halobenzyl group can be 45, as well as their addition salts formed with non-toxic, pharmaceutically acceptable acids and the optical isomers, characterized in that a nitrile of the general formula 50 , (Π) or an amidine of the general formula 55 , (m) -19- No. 391134 in which R, Rj and R2 have the meaning given above, is hydrolyzed, whereupon, if desired, a compound of the general formula (I) obtained with the meaning of hydrogen for Rj is converted into a compound of the general formula ( I) with one of the other meanings of R j and / or, if desired, converting a compound of the general formula (I) obtained into a salt or converting a obtained salt of the general formula (I) into another salt or into the base and / or a mixture of optical isomers obtained is split into the individual optical isomers. 2. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 11 carbon atoms, a linear or branched alkenyl group having 5 to 18 carbon atoms, a linear or branched alkynyl group with 4 to 6 carbon atoms, a linear alkanoyl group with 5 carbon atoms, or a linear or branched alkyl group with 1 to 8 carbon atoms, which is substituted by at least one phenyl group or by at least a phenyl group substituted by a halogen, preferably fluorine, chlorine or bromine, by a phenoxy, hydroxyl, acetoxy or carboxyl group, by a linear or branched alkoxycarbonyl group having 1 to 4 carbon atoms or by a carbonyl or carboxaldehyde group, Rj means hydrogen, a linear or branched alkanoyl group with 1 to 4 carbon atoms, a benzoyl group, a linear or branched alkox ycarbonyl group having 1 to 8 C atoms or a carboxamidomethyl group and R2 is hydrogen, a linear or branched alkyl group having 1 to 3 C atoms or a phenyl group, where, if both Rj and R2 are hydrogen, R is not a hydroxyethyl group, heptyl group, Can be 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group, benzyl group or p-halobenzyl group. 3. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group with 5 to 9 carbon atoms, a linear or branched alkenyl group with 5 to 10 C-atoms, a linear or branched alkynyl group with 4 to 6 C-atoms, a linear alkanoyl group with 5 C-atoms, a linear or branched alkyl group with 1 to 4 C-atoms through at least one phenyl group, at least one through a halogen such as Huor, chlorine or bromine substituted phenyl group, by an acetoxy or carboxyl group, by a linear or branched alkoxycarbonyl group having 1 to 4 carbon atoms or by a carboxaldehyde group, Rj is hydrogen, a linear or branched alkanoyl group with 1 up to 4 carbon atoms, a carboxamidomethyl group or an alkoxycarbonyl group with 1 to 8 carbon atoms and R2 is hydrogen, a Me means thyl or phenyl group, where, if both Rj and Rj are hydrogen, R cannot be heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group, benzyl group or p-halobenzyl group. 4. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 9 carbon atoms, a linear or branched alkenyl group having 5 up to 8 carbon atoms, a linear alkanoyl group with 5 carbon atoms, or a linear or branched alkyl group with 1 to 4 carbon atoms, through a phenyl, acetoxy or carboxyl group, through an alkoxycarbonyl group with 1 or 2 carbon atoms or a carboxaldehyde group is substituted, Rj is hydrogen, a linear or branched alkanoyl group having 1 to 4 C atoms, an alkoxycarbonyl group having 1 to 8 C atoms or a carboxamidomethyl group and R2 is hydrogen, an alkyl group having 1 or 2 C atoms or a phenyl group, where, if both Rj and R2 are hydrogen, R is no heptyl group, 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group e or benzyl group. 5. The method according to claim 1, characterized in that a compound of general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 8 carbon atoms, a linear or branched alkenyl group having 5 up to 8 C atoms, a linear or branched alkynyl group with 5 to 8 C atoms or a linear or branched alkyl group with 1 to 4 C atoms, which are replaced by a phenyl group, a carboxyl group, an alkoxycarbonyl group with 1 or 2 C atoms or a carboxaldehyde group is substituted, R 1 is hydrogen, a benzoyl group or a carboxamidomethyl group and R 2 is hydrogen, an alkyl group having 1 or 2 carbon atoms or a phenyl group, where, if both R 1 and R 2 are hydrogen, R is not a heptyl group, Can be 1,1,3,3-tetramethylbutyl group, ethoxycarbonylpropyl group or benzyl group. -20- No. 391134 6. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 7 carbon atoms, which is replaced by a carboxyl group or a linear or branched alkoxycarbonyl group is substituted with 1 to 4 carbon atoms, Rj means hydrogen or a carboxamidomethyl group and R2 means hydrogen, a methyl group or a phenyl group, where, if both Rj and R2 mean hydrogen, R is no heptyl group, 1.1 , 3,3-tetramethylbutyl group or ethoxycarbonylpropyl group. 7. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is an alkyl group having 2 to 4 carbon atoms, which may be replaced by a halogen such as fluorine , Chlorine or bromine substituted phenyl group means, Rj means hydrogen and R2 means hydrogen, methyl or phenyl group 8. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 9 carbon atoms, Rj is hydrogen, a carboxamidomethyl group or is an alkoxycarbonyl group having 1 to 8 carbon atoms and R2 is hydrogen, a methyl or phenyl group, where, if both Rj and R2 are hydrogen, R cannot be a heptyl group or 1,1,3,3-tetramethylbutyl group. 9. The method according to claim 1, characterized in that a compound of the general formula (I) is prepared by choosing appropriate starting materials and process steps, wherein R is a linear or branched alkyl group having 5 to 9 carbon atoms and Rj and R2 are hydrogen where, if both Rj and R2 are hydrogen, R cannot be a heptyl group or 1,1,3,3-tetramethylbutyl group. 10. The method according to claim 1 for producing the new 2- (n-pentylamino) acetamide, 2- (n-octylamino) acetamide, methyl ester of 6 - [(dicarboxamidomethyl) amino] hexanoic acid, 2- (n-decylamino ) acetamids, methyl esters of 8 - [(dicarboxamidomethyl) amino] octanoic acid, 2- (n-hexylamino) acetamids, 2 - [(2-phenylethyl) amino] acetamids, 2- (n-octadecen-9 -yl-amino) -acetamids, 2 - [(N-caiboxamidomethyl-N, n-hexyl) -amino] -acetamids, 2 - [(l, l-dimethyl-propin-2-yl) -amino-] acetamids, Ethyl ester of Nn-hexyl-N-carboxamidomethyl-carbamic acid, 2- (n-pentylamino) -butyramids, 2 - [(3-phenylpropyl) -amino -] - acetamids, 2- (octen-7-yl-amino) -acetamids ,. 8-carboxamidomethylamino-octanoic acid, 2 - [(4-phenylbutyl) amino -] - acetamids, methyl ester of 5 - [(carboxamidomethyl) amino] hexanoic acid or 2 - [(N-benzoyl-Nn-hexyl) amino ] acetamides, characterized in that the corresponding nitrile (Π) or amidine (III) is hydrolyzed. -21-