NO871375L - BIS-TERTIAER BUTYLAMINO-SUBSTITUTED 1,3,5-TRIAZINE DERIVATIVES, PROCEDURES FOR THEIR PREPARATION, PHARMACEUTICALS CONTAINING THESE COMPOUNDS AND THEIR USE. - Google Patents

Description

The invention relates to new bis-tertiary butylamino-substituted 1,3,5-triazine derivatives, methods for the preparation of the compounds, pharmaceutical agents containing the active compounds according to the invention and their use as pharmaceuticals, especially for the prophylaxis and treatment of epilepsy and of anxiety states.

2,4,6-tris-tertiarybutylamino-1,3,5-triazine has already been discussed (compare, for example, US Patent 2,691,021). Corresponding to the information in the literature, these 1,3,5-triazine derivatives are used in the production of synthetic resins and surfactants (US patent 2 691 021). The use against mycobacteria (US patent 3,591,693) and against the progression of arthritis (US patent 4,269,832) was also mentioned.

Surprisingly, it was now found that 2,4-bis-(tertiarybutylamino)-1,3,5-triazines of the general formula I

has antiepileptic and anxiolytic effects.

The invention therefore relates to 2,4-bis-(tertiarybutylamino)-1,3,5-triazines of the general formula I, wherein

R<1>means C^-C^-alkyl, Cg-C^-monohydroxyalkyl, C3-C5-dihydroxyalkyl, Cj-C^-trihydroxyalkyl, alkoxyalkyl with a total of 3 to 7 carbon atoms, C3-Cy-alkenyl, C3-Cy -cycloalkyl, cycloalkylalkyl with a total of 4 to 7 carbon atoms, C^-C^-alkylamino, dialkylamino with a total of 2 to 10 carbon atoms or an amino residue

with formula

in which

R<3>and R<*>together means an alkylene chain with 3 to 6 methylene groups, one of which is optionally substituted with 0 or S or one of which is optionally substituted;with C^-C3-alkyl, and;R<2>means hydrogen, C₁-C₁-alkyl, C2-C₅-hydroxyalkyl, ; alkoxyalkyl with a total of 3 to 7 carbon atoms or ; C3-C₂-alkenyl or; R-1- and R<2> form together with the nitrogen atom 4 to 7 ; member 1, 2 or 3 nitrogen atom-containing, unsaturated, partially hydrogenated or saturated heterocyclic ring system, which is optionally substituted with C^-C3~alkyl, or r! and R<2> forms together with the nitrogen atom morphol in or the thiomorpholine residue, however, R<1> does not mean tertiary butyl and R<2> means hydrogen at the same time. ;In the above and the following, alkyl, alkoxy and alkenyl are understood to mean straight-line as well as branched residues. Alkoxyalkyl radicals have 1 or 2 alkoxy groups. ;r! preferably means C1-C4-alkyl, C1-C4-mono-, di- or tri-hydroxyalkyl, C5-C6-cycloalkyl, dialkylamino with a total of 2 to 4 carbon atoms or an amino residue; ; wherein R<3>, R^ and the nitrogen atom together mean a pyrrolidino, piperidino, morpholino or thiomorpholino residue. R<2> preferably means hydrogen, C₁-C₁-alkyl or C₄-C₅-monohydroxyalkyl. ;If R-*- and R<2> together with the nitrogen atom form a heterocyclic ring, then this is preferably 5-6-membered, has 1 to 2 nitrogen atoms and is saturated or unsaturated.

The invention further relates to methods for the preparation of the compounds of the general formula I, which are characterized in that in a manner known per se

a) a compound of the general formula II

and an amine of the general formula III in which R<1> and R<2> have the same meanings as given for formula I, are reacted with each other or b) a compound of the general formula IV

wherein R-1- and R<2> likewise have the same meanings as indicated for

formula I, is reacted with tertiary butylamine.

The preparation of the compounds according to formula I according to method variant a) from a compound of the general formula II and an amine of the general formula III is conveniently carried out at a temperature between 20° and 200°C, preferably in the presence of an organic solvent, optionally in a pressure vessel. Suitable inert solvents for this purpose are aliphatic, alicyclic and aromatic hydrocarbons, especially petroleum ether, cyclohexane, chlorobenzene, toluene, xylene or mesitylene, ethers such as t rahydrofuran, dioxane or dimethoxyethane as well as sulfolane or α-pyridone. Preferred solvents are cyclohexane, tetrahydrofuran, toluene and xylene.

The production of the compounds according to the invention with formula I according to process variant b) from a compound of the general formula IV with tertiary butylamine preferably takes place at a temperature between 80° and 200°C, especially at a temperature between 100° and 170°C in a pressure vessel presence of one of the solvents listed above.

In process variant a) and b), the solvent can also be replaced with an excess of the amine. After completion of the reaction, the desired reaction product is separated from the amino hydrochloride formed and the solvent. The purification advantageously takes place by means of recrystallization or column chromatography.

As amines of formula III, in addition to those mentioned in the examples, the following amines can preferably be used: Primary amines: methylamine, ethylamine, 1-propylamine, 1-butylamine, isobuty1amine, 2-penty1amine, isopentylamine, neopentylamine, 1-hexylamine, 2 -hexylamine, 3-hexylamine, 1-methylpentylamine, 2-ethylbutylamine, 2-hydroxyethylamine, 2-hydroxypropylamine, 3-hydroxypropylamine, 2-amino-l-butanol, 4-amino-l-butanol, 2-methoxyethylamine, 2-( diethoxy)-ethylamine, allylamine, cyclopropylamine, cyclobutylamine and cyclohexylmethylamine.

Secondary amines: dimethylamine, dipropylamine, dibutylamine, methylbutylamine, methyl isopropylamine, methyl-tert-butylamine, diallylamine, methylallylamine, cyclohexylmethylamine, cyclohexylallylamine.

Hydrazines: Methylhydrazine, ethylhydrazine, propylhydrazine, isopropylhydrazine, butylhydrazine, 2-butylhydrazine, isobutyl-hydrazine, tert-butylhydrazine, N,N-diethylhydrazine, N,N'-diethylhydrazine, N,N-methyl propylhydrazine, N-methy 1-N'-butylhydrazine, N-aminopyrrolidine, N-aminomorpholine.

Cyclic amines: 3-pyrroline, 4-methylpiperidine, 2-ethylpiperidine, 3,5-dimethylpiperidine, 1,2,5,6-tetrahydropyridine, hexamethyleneimine, morpholine, thiomorpholine, imidazole, 2-methylimidazole, 4-ethylimidazole , pyrazole and 1,2,4-triazole.

The compounds of the general formula I have pharmacological properties, which characterize them as possible anticonvulsant and anxiolytic drugs.

The anticonvulsant (anticonvulsant) effect of the compounds according to the invention was investigated on mice against pentetrazole- and against electroshock-induced convulsions in the device of

SWINYARD.

1. Antagonism against pentetrazole-induced convulsions (mice) Method (E.A. SWINYARD, J. Pharmacol. Exp. Ther. 106,

(1952), 319-330): Groups of 10 male mice (strain: NMRI, SPF-71, KF) weighing 18-22 g are used in this experiment. The substances to be examined are suspended in a l# suspension of "Tylose"

(methyl-hydroxy-ethyl-cellulose) in water and is administered orally via a swallowing tube in a volume of 10 ml/kg body weight. The control groups receive a similar volume of tylose suspension without test substance.

Pentetrazole ("Cardiazole") is injected subcutaneously in aqueous solution at a dose of 125 mg/kg body weight 1 hour after administration of the test substances. This dose produces tonic extensor spasms of the hind limbs in 90-100$ of the control animals during the observation period of 60 minutes after injection. The protective effect of the test substances is assessed when the number of animals with convulsions is reduced compared to the control group.

If there is a protective effect of the test substance, a mean effective dose (ED-50) is determined graphically (Licht-field and Wilcoxon) or arithmetically (probit analysis). 2. Antagonism against electricity. 1 occ-induced seizure (mouse) Method (E.A. SWINYARD, in "Experimental Models of Epilepsy", Raven Press, New York, 1972, pp. 433-458): Groups of 6 male mice (strain: NMRI, SPF-71 , KF) with a weight of 18-22 g are used in this experiment. The substances to be examined are suspended in a 1% slurry of tylose (methyl-hydroxy-ethyl-cellulose) in water and administered orally via a swallowing tube in a volume of 10 mg/kg body weight. The control group receives an equivalent volume of tylose suspension without test substance.

One hour after the addition of the test substance, the animals are administered an electroshock via Cornea electrodes (current strength 12-22 mA, duration 0.2 sec., 50 Hz), after a current strength that had been determined in advance on another control group produced a tonic extensor spasm of the hind limbs. The number of animals protected against an extensor spasm by the test substance serves as a measure of the anticonvulsant effect in this test.

If there is a protective effect of the test substance, a mean effective dose (ED-50) is determined graphically (Licht-field and Wilcoxon) or arithmetically (probit analysis).

The established $50 inhibitory doses by oral administration are between 2.0 and 30 mg/kg for pentetrazole convulsions and 14 and 46 mg/kg for electroshock-induced convulsions (see table). The anxiolytic effect of the compounds according to the invention was investigated in the "Lick-shock-conflict-Test" according to VOGEL and in the "Geller-Seifter-Conflict-Test" according to GELLER and SEIFTER on WISTAR rats.

3. Lick- shock- conflict- test

Method (Vogel, J.R. Psychopharmacologia 21, (1971), 1-7).

Male Wistar rats from own breeding (SPF Hattersheim) weighing between 90 and 120 g are used. The animals will be deprived of drinking water 48 hours before the start of the test. For the test, the animals are placed in a plastic box (14x12x28 cm, wxdxh), which is equipped with a water bottle with a metal drinking tube and which also makes it possible, via an electronic link, to measure the number of contacts of the animals' tongue with the drinking tube. The bottom of the box consists of metal rods that can be energized by the control electronics.

After being placed in the box, the animals have 5 minutes to find the drinking tube and to lick it 50 times. Animals that have not found the drinking tube during this time are not used for the experiment. After these 50 licking processes (lickings), the drinking tube and bottom rods are respectively placed under current for 5 seconds (direct current 300 pA) and released again for a further 5 seconds. This sequence is continued alternately for a period of 5 minutes, the number of drinking tube contacts by the animal during the irritation current and the irritation current-free phase being registered on different electronic counters.

Groups of respectively 8 animals per dose is treated with the test substances that are suspended in a l$-ig tylose gel, orally per swallowing tube. The injection volume is 5 mg/kg body weight. The examination in the above-mentioned test apparatus takes place 1 and 2 hours after application of the test substance. The number of drinking pipe contacts in the irritation current phase serves as a test item in ab 1e. The average number of contacts in this phase in the control group is set to 100$ and the increase and decrease in the number of contacts in the animals treated with the test substance is expressed as a percentage with reference to the control group.

In this test, anxiolytics usually cause a clear increase in water intake (licking) in the irritation current phase compared to untreated controls. If a linear or logarithmic relationship between dose and effect has been given, an ED + 100 (ie the dose that causes an increase in water intake by 100$ above the control group) is calculated using regression analysis. If there is no linear dose dependence, then a minimum effective dose (MED) is determined, i.e. the lowest dose of the test substance which still causes a statistically significant increase in water absorption compared to the control group (p = 0.05, Dunnet test).

4. Geller- Seifter- Conflict test

Method (Geiler, I. and Seifter, J. Psychopharmacologia 1

(1962), 482): Male Wistar rats of own breeding (SPF Hattersheim) weighing between 240 and 370 g are used and assigned to experimental groups of 8 animals each. Each time, 4 animals are put together in plastic cages (56x38x20 cm) and kept using a weighed amount of lining of approx. 80$ of their normal body weight.

The animals are trained in a Skinne box to press a button to get a reward in the form of sweetened condensed milk. The box contains two keys with microswitches, a speaker, a house light, two signal lights above the keys and a floor made of metal rods. The training schedule was derived from the work of Geiler and Seitfter (1962) as modified by Davidson & Cook (Psychopharmacologia 15 (1969), 159-168): Each session consists of four 15-minute sections all composed of a 12-minute "" Variable interval" (VI) phase and a 3-minute "Fixed ration" (FR) phase. During the VI phase, the animals receive a milk reward at the push of a button in an interval of 10-110 seconds controlled by a chance generator with a mean value of 60 15 seconds During the FR phase, the animals receive a reward for each key press, in addition, however, every 3 key presses a painful electrical irritation is administered over the floor bars to produce a conflict situation.

The current strength of the electrical irritation is set for each animal individually (0.3-0.6 mA) so that the degree of key pressure in the overall FR phase is between 5 and 15.

The training takes place 5 days a week, tests with test substances are carried out once a week. As the animals serve as their own controls, for each experiment with test substances at least two preliminary values without test substance are carried out. The compounds to be examined are suspended in a 1% tylose gel and administered 30 minutes before the start of the test orally via a swallowing tube in a volume of 2 ml/kg. Changes in the degree of keystrokes in the VI phase are considered to affect the motor activity and increases in the degree of keystrokes in the FR phase are considered to indicate an "anti-conflict" resp. "anxiolytic" effect. The minimum effective dose (MED) of the test substance is mostly determined, i.e. the lowest investigated dose which still causes a statistically significant change in the degree of keypressing (p = 0.05, Wilcoxon matched pairs signed rank test).

The MEDs determined in these two experimental models after oral administration are between 2.5 and 30 mg/kg experimental animals (see table). The table also shows the percentage increases of the assumed rewards (water or milk).

The following table shows the results of the animal experiments mentioned above. It shows the antiepileptic and anxiolytic effect of bis-tertiarybutyl-substituted 1,3,5-triazine derivatives according to the invention.

As epileptic seizures are frequently triggered by stress and anxiety situations, the combination of antiepileptic and anxiolytic action of the compounds according to the invention is particularly valuable for the therapy of epileptic diseases.

The invention further relates to the use of 2,4-bis-(tertiarybutylamino)-1,3,5-triazine derivatives of formula I in the treatment and prophylaxis of epileptic diseases and anxiety states, further the use of said compounds in the preparation of pharmaceuticals used for treatment and prophylaxis of the above-mentioned diseases.

A further object of the invention is pharmaceuticals containing these compounds.

The medicines are manufactured according to methods known in and of themselves, common to the person skilled in the art. As a medicine, a pharmacologically effective amount of a compound according to the invention is used as active substance either as such or preferably in combination with suitable excipients in the form of tablets, dragees, capsules, suppositories, emulsions, suspensions or solutions, the active substance content being up to about. 95$, preferably between 10 and 75$.

Which excipients are suitable for the desired drug formula are known to the person skilled in the art due to his professional knowledge. Alongside tablet excipients, solvents, gel formers, suppository bases and other active substance carriers, for example, antioxidants, dispersing agents, emulsifiers, foam breakers, taste correctors, preservatives, solubilizers or dyes can be used.

The active substance can be applied orally, parenterally, intravenously or rectally, the oral application being preferred.

For an oral application form, the active compound is mixed with the appropriate additives such as carriers, stabilizers or inert diluents and brought by the usual methods into suitable administration forms, such as tablets, dragees, suppositories, aqueous, alcoholic or oily suspensions or aqueous, alcoholic or oily solutions. For example, gum arabic, magnesia, magnesium carbonate, milk sugar, glucose or starch, especially corn starch, can be used as inert carriers. Thereby, the preparation can take place as well as dry as well as moist granules. For example, vegetable or animal oils, such as sunflower oil or cod liver oil, come into consideration as oily carriers.

For subcutaneous or intravenous application, the active substance, if desired, is brought into solution, suspension or emulsion with the usual substances such as dissolution agents, emulsifiers or additional excipients. Solvents include, for example, water, physiological sodium chloride solution or alcohols, for example ethanol, propanol, glycerol, and also sugar solutions such as glucose or mannitol solutions or a mixture of the various solvents mentioned.

The daily administrable dose is to choose one that is adapted to the effect of the triazine derivative used and the desired effect. Per patient, approx. 5 to 200 mg, preferably orally. When used as an antiepileptic, the dosage is preferably 10 to 100 mg daily, with the dosage depending on the unit suitably being 2.5 to 25 mg. As an anxiolytic, approx. 5 to 50 mg in single doses between approx. 1.0 and 20 mg. It is of course also possible to use higher or lower-lying dosing units, which may need to be divided before application or to diversify.

Example 1

2. 4- bis-( tert.-butylamino)- 6- piperidino- 1. 3. 5- triazine

25.8 g of 2,4-bis-(tert-butylamino)-6-chloro-1,3,5-triazine is dissolved in a mixture of 18 g of piperidine and 300 ml of tetrahydrofuran while stirring. The reaction mixture is then heated under reflux to boiling until complete reaction, which can be monitored by thin-layer chromatography using Merckk DC-ready plates silica gel 60F-254, detection under UV lamp 254 nm, eluent chloroform/methanol, 9:1 (v/ v), Rf 0.81.

In a rotary evaporator, the solvent is removed under vacuum and the residue absorbed in a two-phase system (250 ml methylene chloride/250 ml water). The methylene chloride solution is obtained after separation of the aqueous phase for purification over an aluminum oxide/neutral column. From the colorless solution, 2,4-bis-(tert.-butylamino)-6-piperidino-1,3,5-triazine is obtained in crystalline form with a melting point of 208°C.

Yield: 28.8 g ($94 of the theoretical).

According to example 1, using the solvents listed above, further substances according to the invention are obtained (examples 2 to 11): Example 2 2,4-bis-(tert.-butylamino)-6-pyrroidino-1,3,5-triazine, melting point 246°C. Example 3 2,4-bis-(tert.-butyl)-6-(piperidino-amino)-1,3,5-triazine, melting point 206°C. Example 4 2,4-bis-(tert-butylamino)-6-(morpholino-amino)-1,3,5-triazine, melting point 185°C. Example 5 2,4-bis-(tert-butylamino)-6-imidazolyl-1,3,5-triazine, melting point 187°C.

Example 6

2,4-bis-(tert-butylamino)-6-(N'-dimethylhydrazino)-1,3,5-triaziine, melting point 193°C.

Example 7

2,4-bis-(tert-butylamino)-6-diethylamino-1,3,5-triazine, melting point 121°C.

Example 8 2,4-bis-(tert.-butylamino)-6-isopropylamino-1,3,5-triazine, melting point 146°C.

Example 9

2,4-bis-(tert-butylamino)-6-cyclopentylamino-1,3,5-triazine, melting point 150°C.

Example 10

2,4-bis-(tert-butylamino)-6-(1,2-dimethylpropylamino)-1,3,5-triazine, melting point 143°C.

Example 11

2,4-bis-(tert. -buty 1 am i no ) - 6 - ( 4-hy dr oxybutylamino )-1,3,5-triazine, melting point 175°C.

Example 12

2,4-bis-(tert-butylamino)-6-(1,1-dimethyl-3-hydroxypropyl-amino)-1,3,5-triazine.

12.9 g of 2,4-bis-(tert-butylamino)-6-chloro-1,3,5-triazine and

13.5 g of 3-methyl-3-amino-butanol (1) is kept with 300 ml of p-xylene in a pressure vessel for 24 hours at 150°C. After cooling, the reaction mixture is stirred with 300 ml of water. The residue of the organic is now stirred with 200 ml of petroleum ether. The desired reaction product shows after isolation and drying in a thin layer chromatogram (conditions as stated in example 1) Rf = 0.43. Melting point 147°C / yield 15.3 g (94.2$ of the theoretical).

According to example 12, the following substances according to the invention were formed: Example 13

2,4-bis-(tert-butylamino)-6-N-methyl-n-butylamino-1,3,5-triazine, melting point 139°C.

Example 14 2,4-bis-(tert.-butylamino)-6-(2-butylamino)-1,3,5-triazine, melting point 133°C.

Example 15 2,4-bis-(tert-butylamino)-6-pentylamino-1,3,5-triazine, melting point 108°C.

Example 16

2,4-bis-(tert.-butylamino)-6-(3-pentylamino)-1,3,5-triazine, melting point 125°C.

Example 17

2,4-bis-(tert-butylamino)-6-diisobutylamino-1,3,5-triazine, melting point 81°C.

Example 18

2,4-bis-(tert-butylamino)-6-(N-isopropyl-N-methylamino-1,3,5-triazine, melting point 199°C.

Example 19

a) 2,4-dichloro-6-diisopropylamino-1,3,5-triazine.

To a solution of 18.4 g of 2,4,6-trichloro-1,3,5-triazine in 100

ml of tetrahydrofuran are added dropwise while stirring at 0°C to 22 g di in sopropylamine. It is then left to stir at 0°C for a further 30 minutes. precipitated diisopropylamine hydrochloride is separated and the filter residue is washed with tetrahydrofuran. The residue recovered from the combined filtrates shows in a thin-layer chromatogram (see example 1, eluent, however, acetic acid ethyl ester/hexane 1:3) Rf = 0.77. The melting point is at 102°C. Yield 24.3 g (97.5 of the theoretical). b) 2,4-bis-(tert-butylamino)-6-diisopropylamino-1,3,5-triazine.

12.5 g of 2,4-dichloro-6-diisopropylamino-1,3,5-triazine are reacted with 200 ml of tert-butylamine at 50°C for 24 hours in a pressure vessel. The excess tert-butylamine is recovered by means of a rotary evaporator in vacuum. The residue is now dissolved in a two-phase system of 250 ml chloroform and 250 ml water. The desired 2,4-bis-(tert-butylamino)-6-diisopropylamino-1,3,5-triazine is obtained from the separated organic phase and recrystallized from ethanol.

Colorless crystals. Yield 14.7 g (91$ of the theoretical) Melting point 145°C. Thin layer chromatography (see also example 1), eluent acetic acid ethyl ester Rf 0.56, detection UV lamp 254 nm.

Example 20

2,4-bis-(tert-butylamino)-6-dimethylamino-1,3,5-triazine, melting point 192°C.

This triazine derivative is prepared analogously to example 19b using 2,4-dichloro-6-dimethylamino-1,3,5-triazine (melting point 108°C).

Example 21

2,4-bis-(tert-butylamino)-6-(1,1-dimethyl-2-hydroxy-ethyl-amino)-1,3,5-triazine. 45 g of 2-amino-2-methylpropanol (1) and 12.9 g of 2,4-bis-(tert-butylamino)-6-chloro-1,3,5-triazine are stirred for 3 hours at 150°C.

The reaction mixture is then thoroughly stirred with 1000 ml of distilled water at approx. 35-40°C. The insoluble part is isolated and washed with water. After drying in vacuum, it is recrystallized from toluene. Yield 14.2 g ($91.0 of the theoretical). Melting point 163°C. DC see example 1, eluent acetic acid ethyl ester, Rf = 0.38.

Example 22

2,4-bis-(tert-butylamino)-6-(1,1-bis-hydroxymethylethyl-amino-)-1,3,5-triazine, melting point 198°C.

Example 23

2,4-bls-(tert-butylamino)-6-(tris-hydroxymethyl-methylamino)-1,3,5-triazine, m.p. 236°C.

Examples 22 and 23 were carried out analogously to example 21. In example 23, the reaction temperature was increased to 175-180°C.

Claims (1)

1. Process for the preparation of 2,4-bis-(tertiarybutylamino)-1,3,5-triazines of the general formula I in which R 1 means C 1 -C 2 -alkyl, C 2 -C 6 -monohydroxyalkyl, C 2 -C-b- dihydroxyalkyl, C^C^tTTh^hydroxyalkyl, alkoxyalkyl with a total of 3 to 7 carbon atoms, C3-Cy-alkenyl, C3-C7-cycloalkyl, cycloalkylalkyl with a total of 4 to 7 carbon atoms, C^-C^-alkylamino, dialkylamino with a total of 2 to 10 carbon atoms or an amino residue of formula in which R <3> ___and R <4> together means an alkylene chain with 3 to 6 methylene groups, one of which is optionally substituted with 0 or S or one of which is optionally substituted with C^ -C3~ alkyl, and R <2> means hydrogen, C₁ -C₂ -alkyl, C₃ -C₂ -hydroxyalkyl, Alkoxyalkyl with a total of 3 to 7 carbon atoms or C3 -Cy-alkenyl or R-1- and R<2> together with the nitrogen atom form a 4 to 7-membered 1,2 or 3 nitrogen atom-containing, unsaturated, partially hydrogenated or saturated heterocyclic ring system, which is optionally substituted with C^ -C^ -alkyl, or R- 1- and R <2> together with the nitrogen atom form the morpholine or thiomorpholine residue, however, not at the same time R <1> is tertiary butyl and R <2> hydrogen, characterized by ata) a compound of the general formula II and an amine of the general formula III in which Ri and R<2> have the same meanings as stated above for formula I, are reacted with each other to a compound of formula I, in which R^ and R<2> have the stated meanings, orb) a compound of the general formula IV in which R<1> and R<2> likewise have the same meanings as for formula I, is reacted with tertiary butylamine. Method according to claim 1, characterized in that a compound of formula I is produced, wherein R 1 means C 1 -C 4 -alkyl, C 1 -C 4 -mono-, di- or tri- hydroxyalkyl, C 1 -C 5 -cycloalkyl, dialkylamino with a total of 2 to 4 carbon atoms, or an amino residue wherein R<3> and R^ and the nitrogen atom together form a pyrrolidino, piperidino, morpholino or thiomor-folino residue, R <2> means hydrogen, C^-C^ -alkyl or C^Ck-monohydroxy- alkyl or R <1> and R <2> together with the nitrogen atom form a hetero- cyclic 5-6 membered ring, which has 1 to 2 nitrogen atoms and is saturated or unsaturated. 3. 2,4-bis-(tertiarybutylamino)-1,3,5-triazines of the formula I specified in claim 1 obtained by the method according to claim 1. 4. Process for the preparation of a medicinal product, characterized in that an effective amount of a compound of formula I according to claim 1 is transferred in a suitable administration form.