DK161327B - SUBSTITUTED 2-PIPERAZINOPTERIDINES, PROCEDURES FOR PREPARING THEREOF, AND MEDICINALS CONTAINING THE COMPOUNDS - Google Patents

Description

DK 161327 B

This invention relates to substituted 2-piperazinopteridines, processes for their preparation, and to drugs containing such compounds.

U.S. Patent No. 2,940,972 discloses substituted 5 pteridines which exhibit valuable pharmacological properties, namely coronary expanding, sedative, antipyretic and analgesic effects.

It has been found that certain novel substituted 2-piperazinopteridines as well as their physiologically acceptable acid addition salts with inorganic or organic acids exhibit valuable pharmacological properties, e.g. antithrombotic, metastatic and tumor weight inhibiting properties.

Accordingly, the compounds are

According to the invention, they are described by the general formula I

R NN / N

A (i) 6 wherein is a dialkylamino, phenylalkylamino, N-alkyl-phenylalkylamino, pyrrolidino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, thiazolidino, 30 or 1-oxidothiazolidino group;

R 9 is H, alkyl or phenyl; and R-y is an alkylamino, dialkylamino, phenylalkylamino, N-alkylphenylalkylamino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, or piperazine group; wherein in R 2, R 9 and Ry each alkyl moiety may contain 1-3 carbon atoms and in R 2 and R

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both alkyl groups in the case of C 2 -C 3 alkyl be substituted at the 2- or 3-position with OH; or are acid addition salts thereof, preferably physiologically acceptable acid addition salts with inorganic or organic acids.

Examples of R 1, R 9 and Ry are mentioned for R 2 dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, N-methylethylamino, N-ethyl-n-propylamino, benzylamino, , N-methyl-benzylamino-, N-ethyl-10-benzylamino-, Nn-propyl-benzylamino-, 1-phenylethylamino-, 2-phenylethylamino-, 3-phenylpropylamino-, N-methyl-1-phenylethylamino -, N-ethyl-2-phenylethylamino-, N-ethyl-3-phenylpropylamino-, bis (2-hydroxyethyl) -amino-, bis (2-hydroxy-n-propyl) -amino-, bis (3-hydroxy- n-propyl) -amino-, N- (2-hydroxyethyl) -2-hydroxy-n-propylamino-, N-methyl-2-hydroxy-ethylamino-, N-ethyl-2-hydroxyethyl-amino-, N- methyl 2-hydroxy-n-propylamino, N-isopropyl-2-hydroxyethylamino, N- (2-hydroxyethyl) benzylamino, pyrrolidino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino , the thiazolidino or 1-oxidothiazolidino group; for the Rg H, methyl, ethyl, n-propyl, isopropyl or phenyl group and for

Ry methylamino, ethylamino, n-propylamino, isopropylamino, dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, N-methyl-ethylamino, N-ethyl-n-propylamino, , benzylamino-, N-methyl-benzylamino-, N-ethyl-benzylamino-, Nn-propyl-benzylamino-, 1-phenylethylamino-, 2-phenylethylamino-, 3-phenylpropylamino-, N-methyl-1 -phenylethylamino-, N-ethyl-2-phenylethylamino-, N-ethyl-3-phenylpropylamino-, 2-hydroxyethylamino-, 2-hydroxy-n-propylamino-, 3-hydroxy-n-propylamino-, 2-hydroxyisopropylamino -, bis (2-hydroxyethyl) amino, bis (2-hydroxy-n-propyl) amino, bis (3-hydroxy-n-propyl) amino, N- (2-hydroxyethyl) -2 -hydroxy-n-propylamino, N-methyl-2-hydroxyethylamino, N-ethyl-2-hydroxyethylamino, N-methyl-2-hydroxy-n-propylamino, N-isopropyl-2-hydroxy-3

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the ethylamino, N- (2-hydroxyethyl) benzylamino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, thiazolidino, 1-oxidothiazolidino or piperazino group.

Preferred compounds of the above Formula I are those wherein R 4 is dimethylamino, N-methyl-2-hydroxyethylamino, bis (2-hydroxyethyl) amino, benzylamino, N-methyl-benzylamino, pyrrolidino -, piperidino, morpholino, thio-morpholino, 1-oxidothiomorpholino, thiazolidino or 1-oxidothiazolidino group,

R 9 is H, methyl or phenyl and

Ry is the dimethylamino, N-methyl-2-hydroxyethylamino, benzylamino, N-methyl-benzylamino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino or piperazine group, as well as their acid addition salts, especially their physiological acceptable acid addition salts.

Particularly preferred compounds of the above general formula I are those wherein R 9 is as defined above, R 4 is a pyrrolidino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino or N-methyl-2-hydroxyethylamino group and

Ry is a dimethylamino, benzylamino, N-methyl-benzyl-amino, morpholino, thiomorpholino or 1-oxidothio-morpholino group.

A medicament according to the invention is characterized in that it contains a compound according to the invention or a physiologically acceptable acid addition salt thereof together with one or more inert carriers and / or diluents. Such a medicament according to the invention is produced by the non-chemical cooperation of the above-mentioned ingredients in the drug.

The present compounds are prepared according to the invention by a process which is characterized in that 4

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(a) translates a compound of general formula II

'ΎΪΥ 5 r6 ^ nXT'n * 4 wherein R ^ and Rg are as defined above; 10 is one of or is a group exchangeable by a nucleophilic substitution reaction, preferably a halogen atom, and the other of or Z 1 is a piperazine group or a group as indicated for R above, or if a compound of formula I is desired wherein R 1 is a piperazine group, also a group exchangeable by a nucleophilic substitution reaction, preferably a halogen atom; with an amine of the general formula III;

Η - X III

Wherein X is a piperazine group or a group designated for R 7 above or is a piperazine group protected by a group removable by hydrolysis; and removes any protecting group used; or b) for the preparation of compounds of the general formula I wherein R 1 is a 1-oxidothiomorpholino or 1-oxydothiazolidino group and / or R 1 is a 1-oxidothiomorpholino group oxidizing a compound of the general formula IV: 30> 1H '(IV)

r6 I

R 4 is wherein R 9 is as defined above and R 2 and R 2 have the same meaning as R 2 and R 2 respectively, wherein 5

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however, at least one of 'or' must be a thio-morpholino group or R 'must be a thiazolidino group; and, if desired, transferring a compound of formula I thus obtained in its acid addition salt, preferably physiologically acceptable acid addition salt, with an inorganic or organic acid.

With respect to these processes, it is noted that the reactions under (a) are advantageously carried out in a solvent such as tetrahydrofuran, dioxane, benzene, toluene, dimethylsulfoxide or dimethylglycol ether at temperatures between 0-150 ° C, preferably at temperatures between room temperature and the solvent boiling point, or at a melt, whereby it may be advantageous to use an acid-binding agent such as sodium carbonate, triethylamine or pyridine; the decomposition of any protecting group optionally used is either hydrolytic in the presence of an acid such as hydrochloric or sulfuric acid or a base such as sodium hydroxide or potassium hydroxide, preferably 20 in an aqueous solvent such as methanol / water, ethanol / water or dioxane / water at temperatures. up to the boiling point of the solvent used, the cleavage of an applied protecting group may also occur during the reaction if excess amine of the general formula III is used; and that

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The oxidations under b) are preferably carried out in a solvent or mixture of solvents, e.g. in water, water / pyridine, acetone, glacial acetic acid, methylene chloride, dioxane, dilute sulfuric acid or trifluoroacetic acid, depending on the oxidizing agent at temperatures between 0-150 ° C.

Advantageously, oxidation is carried out with one equivalent of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at 0-20 ° C, or in acetone at 0-60 ° C, with a peracidic acid as acetic acid in glacial acetic acid or trifluoroacetic acid at 0-50 ° C, or with m chlorperbenzoic acid in methylene chloride or chloroform at 0-60 ° C, with sodium metaperiodate in dioxane or ethanol at 80-100 ° C, with bromine in glacial acetic acid or aqueous acetic acid, with N-bromosuccinimide in ethanol, with iodobenzodichloride in aqueous pyridine at 0 -50 ° C, with nitric acid in glacial acetic acid at 0-20 ° C and with chromic acid in glacial acetic acid or in acetone at 0-20 ° C.

The compounds of the invention can be transferred into their acid addition salts, especially in their physiologically acceptable salts by inorganic or organic acids. As acids, for example, mention hydrochloric, hydrobromic, sulfuric, phosphoric, lactic, citric, tartaric, succinic, maleic or fumaric acids.

The compounds of general formula II-IV used as starting substances are largely known or can be prepared according to US-A-2,940,972. (See 30 Examples A-D).

As already mentioned, the novel compounds of general formula I, as well as their physiologically acceptable acid addition salts with inorganic or organic acids, exhibit valuable pharmacological properties, in particular antithrombotic and metastasis inhibitory and inhibitory effects on phosphodiesterase and on growth of phosphodiesterase. tumors.

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By way of example, the following compounds have been investigated: A = 4,7-dimorpholino-6-phenyl-2-piperazino-pteridine, B = 4-morpholino-7- (1-oxidothiomorpholino) -2-piperazino-5-6-phenyl -pteridine, C = 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-no-pteridine, D = 7-dimethylamino-6-phenyl-2-piperazino-4-pyrrolidino-pteridine, and E = 7- benzylamino-4- (N-methyl-2'-hydroxyethylamino) -2-piperazino-pteridine for their inhibitory effect on phosphodiesterase (PDE) from tumor cells and from human platelets in vitro by a method based on von Poch et al. s method (see Naunyn-Schmiedebergs Arch. Pharmak. 268, 272-291 (1971)): a) Extraction of enzyme:

Phosphodiesterase from Bl6 melanoma tissue is recovered from mice by centrifugation of the tissue homogenate at 20,000 g (15 min. 4 ° C). The tissue was homogenized by repeated freezing / thawing and homogenization according to Potter-Elvehern, by ultrasound, respectively. The centrifugate from the homogenate containing PDE was divided into portions and frozen at -25 ° C.

The recovery of phosphorus diesterase from human thrombocytes proceeded in the same manner.

b) Determination of PDE inhibition (PDE assay):

In determining the PDE inhibition of the compounds to be tested, 1 µmol per ml was used.

3 30 1 H-cAMP as substrate. PDE inhibition was measured by measuring 3 3

elongation of the degradation of H-cAMP in the substrate for H-AMP

and compared with a control sample without added substance.

3

The resulting H-AMP was precipitated with zinc sulfate-3-barium hydroxide and thereby separated from unreacted H-cAMP.

The calculation of IC IC q as the concentration that reduced PDE activity to 50% was done by linear regression analysis.

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PDE inhibition (IC IC q in µmol / l)

Substance thrombocytes B1 6 tumor cells A 0.54 4.3 5 B 2.2 3.1 C 0.5 0.096 D 3.6 0.78 E 3.7 8.3 10 Acute toxicity:

An orientation value for the acute toxicity of the compounds to be tested was determined on groups each consisting of 10 mice, following oral administration of a single dose (control time: 14 days): 15

Substance Orientation acute toxicity A> 250 mg (0 out of 5 animals dead) C> 250 mg (0 out of 5 animals dead) 20 D> 250 mg (0 out of 5 animals dead) E> 250 mg (0 out of 5 animals died)

The novel compounds of the invention are of the general prior art

25 and their physiologically acceptable acid addition salts are suitable because of the above pharmacological properties for the prevention of thromboembolic diseases such as coronary infarction, cerebral infarction, so-called transient ischemic seizures, amaurosis fugax, and for the prevention of metastasis for the prevention and prevention of arteriosclerosis. limiting growth of tumors.

The dose required to achieve the above effect is at 2-4 times daily administration of 0.1-4 mg / kg body weight, preferably 0.2-3 mg / kg body weight.

Here, the compounds of the invention of general formula I can be used

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as well as their physiologically acceptable acid addition salts with inorganic or organic acids, optionally combined with other active substances, and together with one or more inert carriers and / or diluents, e.g. with corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerol, water / sorbitol, nonionic surfactants such as polyoxyethylene fatty acid esters, water polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethyl cellulose, or fatty substances such as hardened fat or suitable mixtures thereof, in normal pharmaceutical preparations such as tablets, dragees, capsules, powders, suspensions, drops, drops, or small 15 suppositories.

The following examples will illustrate the invention in more detail:

Example A

2.7-Dichloro-4-morpholino-pteridine 20 7.03 g (0.03 mol) 2,4,7-trichloropteridine is dissolved in 100 ml of chloroform and reacted at 5 ° C with a solution of 3.0 g (0.03 mole) of potassium hydrogen carbonate in 50 ml of water. Thereafter, 2.62 g (0.03 mole) of morpholine in 50 ml of chloroform is added dropwise and stirred for 45 minutes at room temperature. The organic phase is separated, dried over sodium sulfate and evaporated in vacuo. The residue is recrystallized from ethanol.

Yield: 7.4 g (86% of theory), mp: 187-188 ° C.

Analogously to Example A, the following compounds are provided: 2.7-dichloro-4-piperidino-pteridine

Yield: 67% theoretical, mp: 152-154 ° C (ethanol) 2,7-dichloro-4-benzylamino-pteridine

Yield: 75% theoretical, mp: 150-152 ° C (methanol) 10

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2.7-Dichloro-4- (1-oxidothiomorpholino) -pteridine Yield: 65% theoretical, mp: 230-235 ° C

2.7-Dichloro-4- (N-methyl-2'-hydroxyethylamino) -pteridine Yield: 74% theoretical, mp: 178-180 ° C

2,7-dichloro-4-diethanolamino-pteridine

Yield: 71% theoretical, mp: 173-174 ° C (ethanol) 2,7-dichloro-6-methyl-7-morpholino-pteridine

Yield: 73% theoretical, mp: 230-232 ° C (ethanol)

Example B

2,7-Dichloro-6-phenyl-4-thiomorpholino-pteridine 35.5 g (0.114 mol) of 2,4,7-trichloro-6-phenyl-pteridine are dissolved in 500 ml of acetone and reacted with 11.5 g ( 0.13 mol) sodium bicarbonate in 120 ml of water. Then a solution of 11.8 g (0.114 mole) of thio-morpholine is added and the mixture is stirred for 45 minutes at room temperature. This solution is poured into 2 liters of water, the precipitate formed is separated and recrystallized from ethylene chloride.

Yield: 36 g (84% theory), mp: 225-227 ° C.

Analogously to Example B, the following compounds are prepared:

2.7-Dichloro-4- (1-oxidothiomorpholino) -6-phenylpteridine Yield: 88% theoretical, mp: 222-224 ° C

2,7-dichloro-4-morpholino-6-phenylpteridine

Yield: 78% theoretical, mp: 198-201 ° C

2,7-dichloro-6-phenyl-4-piperidino-pteridine

Yield: 69% theoretical, mp: 168-170 ° C (acetic acid ester) 11

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2.7-Dichloro-4-dimethylamino-6-phenylpteridine Yield: 77% theory, mp: 236-238 ° C (ethylene chloride) 2.7-dichloro-4- (N-methyl-2'-hydroxyethylamino) -6-phenyl -5 pteridine

Yield: 76% theoretical, mp: 162-164 ° C (ethanol) 2.7-dichloro-4- (N-benzyl-methylamino) -6-phenylpteridine Yield: 59% theoretical, mp: 141-143 ° C (ethanol / dioxane) 2,7-dichloro-6-phenyl-4-pyrrolidino-pteridine

Yield: 81% theoretical, m.p .: 199-200 ° C (acetic acid ester) 2.7-dichloro-6-phenyl-4-thiazolidino-pteridine Yield: 82% theoretical, mp: 169-171 ° C (acetic acid ester)

Example C

7-Chloro-2- (N-formylpiperazino) -6-phenyl-4-thiomorpholino-pteridine To a solution of 7.6 g (0.02 mol) of 2,7-dichloro-6-phenyl-4-thiomorpholino pteridine in 100 ml of dioxane is added 5.5 g (0.048 mol) of N-formylpiperazine in 10 ml of dioxane and stirred at 40 ° C for 1 hour. The reaction mixture is poured into 600 ml of water, the precipitate is sucked off and boiled with acetic acid ester.

Yield: 88% theoretical, mp: 223-226 ° C

Analogously to Example C, the following compounds are prepared: 7- chloro-4- (N-formylpiperazino) -4- (1-oxidothiomorpholino) -30 6-phenylpteridine

Yield: 90% theoretical, mp: 230 ° C (decomposition) 7-chloro-2- (N-formylpiperazino) -4-morpholino-6-phenylpteridine Yield: 90% theoretical, mp: 247 ° C ( decomposition) 12

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7-chloro-2- (N-formylpiperazino) -6-phenyl-4-piperidino-pteridine

Yield: 66% theoretical, m.p .: 210-213 ° C (acetic acid ester) 5 7-Chloro-4-dimethylamino-2- (N-formylpiperazino) -6-phenylpteridine

Yield: 89% theoretical, mp: 232-234 ° C (acetic acid ester) 7-chloro-2- (N-formylpiperazino) -4- (N-methyl-2 * -hydroxy-ethylamino) -6-phenyl-pteridine

Yield: 86% theoretical, m.p .: sintering above 170 ° C

7-Chloro-2- (N-formylpiperazino) -4- (N-methylbenzylamino) -6-phenylpteridine Yield: 63% theoretical, mp: 143-145 ° C (acetic acid ester) 7- chloro-2- ( N-formylpiperazino) -6-phenyl-4-pyrrolidino-pteridine

Yield: 60% theoretical, m.p .: 210 ° C (dec.) 20 7-Chloro-2- (N-formylpiperazino) -6-phenyl-4-thiazolidino-pteridine

Yield: 82% theoretical, mp: 180-190 ° C (acetic acid ester)

Example D

2-Chloro-4,7-dimorpholino-pteridine 7.4 g (0.025 mol) 2,7-dichloro-4-morpholino-pteridine is dissolved in 150 ml of methylene chloride and stirred with 4.4 g (0.05 mol) morpholine for 15 minutes at 40 ° C. 30 are cooled, 200 ml of water is added, the organic phase is separated, dried over sodium sulfate and evaporated in vacuo. The residue is recrystallized from ethanol.

Yield 57% theoretical, mp: 253-255 ° C.

Analogously to Example D, the following compounds are prepared: 13

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7-Benzylamino-2-chloro-4-piperidino-pteridine Yield: 94% theoretical, snip .: 220-222 ° C (dioxane) 4-benzylamino-2-chloro-7- (1-oxidothiomorpholino) -pteridine Yield: 45% theoretical, m.p .: 264-265 ° C (ethanol) 7-benzylamino-2-chloro-4- (1-oxidothiomorpholino) pteridine Yield: 65% theoretical, mp: 239-240 ° C (dioxane / ethanol) 2-Chloro-4- (N-methyl-2'-hydroxyethylamino) -7-morpholino-pteridine

Yield: 74% theoretical, mp: 190-192 ° C

7-Benzylamino-2-chloro-4- (N-methyl-2'-hydroxyethylamino) -pteridine

Yield: 66% theoretical, mp: 169-170 ° C

2-chloro-4- (N-methyl-2'-hydroxyethylamino) -7-thiomorpholin-lino-pteridine

Yield: 80% theoretical, mp: 214-215 ° C

7-Benzylamino-2-chloro-4-diethanolamino-pteridine Yield: 79% theoretical, mp: 188-189 ° C (dioxane) 2-chloro-4-diethanolamino-7-morpholino-pteridine Yield: 74% theoretical, mp: 197-199 ° C (ethanol)

2-Chloro-6-methyl-4,7-dimorpholino-pteridine Yield: 29% theoretical, m.p .: 195-200 ° C

2-Chloro-6-methyl-4-morpholino-7-thiomorpholino-pteridine Yield: 27% theoretical, mp: 150-155 ° C.

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Example 1 4,7-Dimorpholino-2-piperazino-pteridine 4.2 g (0.0125 mol) of 2-chloro-4,7-dimorpholino-pteridine are dissolved in 200 ml of dimethyl sulfoxide and stirred with a solution of 10.8 g (0.125 mol) anhydrous piperazine at room temperature for 1 hour. Next, 1 liter of water is added and extracted with 2 x 100 ml of methylene chloride. The organic phases are dried over sodium sulfate and evaporated by rotary evaporation. The residue is washed with ether.

Yield: 85% theoretical, mp: 257-259 ° C (dec.)

Analysis:

Calculated: C 55.94 H 6.78 N 24.00

Found: 56.26 6.90 23.60 λ max (ethanol): 380, 279, 248 nm

Example 2 7-Benzylamino-2-piperazino-4-piperidino-pteridine 5.3 g (0.015 mol) of 7-benzylamino-2-chloro-4-piperidino-pteridine are dissolved in 250 ml of chloroform and boiled with a solution of 10.3 g (0.12 mol) of piperazine under reflux. After 2 hours, the mixture is shaken with 200 ml of water, the organic phase is dried over sodium sulfate and evaporated in vacuo. The residue is recrystallized from dioxane.

Yield: 79% theoretical, mp: 185-188 ° C Analysis:

Calculated: C 65.32 H 6.98 N 27.70

Found 65.21 7.35 27.46 λ max (ethanol): 370, 280, 242 nm

Example 3 4-Benzylamino-7- (1-oxidothiomorpholino) -2-piperazino-pteridine

Prepared analogously to Example 2 from 4-benzyl-35-amino-2-chloro-7- (1-oxidothiomorpholino) pteridine and piperazine.

Yield: 85% theoretical, mp: 190-192 ° C (methanol) 15

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Analysis:

Calculated: C 57.51 H 5.98 N 25.55 S 7.31

Found: 57.35 6.12 25.29 7.24 λ max (ethanol): 375, 275, 247 nm 5

Example 4 7-Benzylamino-4- (1-oxidothiomorpholino) -2-piperazino-pteridine

Prepared analogously to Example 2 from 7-benzyl-10-amino-2-chloro-4- (1-oxidothiomorpholino) pteridine and piperazine.

Yield: 90% theoretical, mp: 259-261 ° C (methanol)

Analysis:

Calculated: C 57.52 H 5.48 N 25.55 S 7.31 Found: 57.46 5.84 25.60 7.66 λ max (ethanol): 375, 286, 247 nm

Example 5 4- (N-Methyl-2'-hydroxyethylamino) -7-morpholino-2-piperazino-pteridine

Prepared analogously to Example 2 from 2-chloro-4- (N-methyl-2'-hydroxyethylamino) -7-morpholino-pteridine and piperazine.

Yield: 78% theoretical, mp: 172-174 ° C Analysis:

Calculated: C 54.53 H 7.00 N 29.93

Found: 54.68 7.40 29.64 λ max (ethanol): 384, 278, 247 nm Example 6 7-Benzylamino-4- (N-methyl-2'-hydroxyethylamino) -2-pipe-ra zino -pteride in

Prepared analogously to Example 2 from 7-benzylamino-2-chloro-4- (N-methyl-2'-hydroxyethylamino) pteridine and piperazine.

Yield: 70% theoretical, mp: 220-222 ° C

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Analysis:·

Calculated: C 60.84 H 6.64 N 28.41

Found: 61.03 6.45 28.12 λ max (ethanol): 372, 277, 243 nm 5

Example 7 4- (N-methyl-2'-hydroxyethylamino) -2-piperazino-7-thio-morpholino-pteridine

Prepared analogously to Example 2 from 2-chloro-4-10 (N-methyl-2'-hydroxyethylamino) -7-thiomorpholino-pteridine and piperazine.

Yield: 65% theoretical, mp: 175-177 ° C Analysis:

Calculated: C 52.28 H 6.71 N 28.70 S 8.21 Found: 52.06 6.44 28.42 8.35 λ max (ethanol): 384, 278, 247 nm

Example 8 7-Benzylamino-4-diethanolamino-2-piperazino-pteridine 20 Prepared analogously to Example 2 from 7-benzylamino-2-chloro-4-diethanolamino-pteridine and piperazine.

Yield: 76% theoretical, mp: 203-208 ° C Analysis:

Calculated: C 59.42 H 6.65 N 26.40 Found: 59.24 6.76 26.24 λ max (ethanol): 372, 278, 243 nm

Example 9 4-Diethanolamino-7-morpholino-2-piperazino-pteridine 30 Prepared analogously to Example 2 from 2-chloro-4-diethanolamino-7-morpholino-pteridine and piperazine.

Yield: 62% theoretical, mp: 187-195 ° C Analysis:

Calculated: C 53.46 H 6.98 N 27.70 Found: 53.11 6.94 27.53 λ max (ethanol): 382, 278, 247 nm DK 161327 3 η

Example 10 6-methyl-4,7-dimorpholino-2-piperazino-pteridine

Prepared analogously to Example 2 from 2-chloro-6-methyl-4,7-dimorpholino-pteridine and piperazine.

Yield: 66% theoretical, mp: 180-185 ° C Analysis:

Calculated: C 56.98 H 7.05 N 27.98

Found: 56.78 6.78 27.70 λ max (ethanol): 382, 279, 248 nm 10

Example 11 6-Methyl-4-morpholino-2-piperazino-7-thiomorpholino pteridine

Prepared analogously to Example 2 from 2-chloro-6-methyl-4-morpholino-7-thiomorpholino-pteridine and piperazine.

Yield: 58% theoretical, mp: 185-188 ° C Analysis:

Calculated: C 54.77 H 6.78 N 26.90 S 7.70 Found: 54.99 7.05 26.69 7.93 λ max (ethanol): 382, 280, 247 nm

Example 12 4- (N-methyl-2'-hydroxyethylamino) -7- (1-oxidothiomorpholino) -2-piperazino-pteridine 2.92 g of 4- (N-methyl-21-hydroxyethylamino) -7-thio -Morpholino-2-piperazino-pteridine is dissolved in 50 ml of methylene chloride and stirred with a solution of 1.72 g of m-chloroperbenzoic acid for 2 hours at room temperature.

Then, by rotary evaporation, evaporate and wash the residue with ether. The residue is dissolved in a little water, made alkaline with 2N sodium hydroxide solution and then extracted with methylene chloride. The organic phases are dried and evaporated by rotary evaporation.

Yield: 1.1 g (36% theory), mp: 223-226 ° C.

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Analysis:

Calculated: C 50.23 H 6.45 S 7.88

Found: 49.93 6.42 8.03 λ max (ethanol): 386, 278, 245 nm 5

Example E

7-Benzylamino-2- (N-formylpiperazino) -6-phenyl-4-thio-morpholino-pteridine 3.2 g (7 mmol) 7-chloro-2- (N-formylpiperazino) -6-10 phenyl 4-Thiomorpholino-pteridine is heated with reflux with 2.2 g (21 mmol) of benzylamine in 15 ml of dioxane.

After 3 hours, the solvent is removed in vacuo and the oily residue is poured into 100 ml of water. The precipitated product is collected, dried and chromatographed through a short silica gel column with acetic acid ethyl ester / methanol 15: 1 as eluent. Then it is recrystallized from acetic acid ester.

Yield: 80% theoretical, mp: 218-221 ° C

Analogously to Example E, the following compounds are prepared: 2- (N-formylpiperazino) -7- (N-methyl-2'-hydroxyethylamino) -6-phenyl-4-thiomorpholino-pteridine Yield: 55% theoretical, m.p. above 130 ° C (acetic acid ester) 2- (N-formylpiperazino) -4-morpholino-7- (1-oxidothiomorpholino) -6-phenylpteridine Yield: 50% theoretical, mp: 250-252 ° C ( water) 2- (N-formylpiperazino) -4- (N-methyl-2'-hydroxyethylamino) -7-morpholino-6-phenylpteridine

Yield: 80% theoretical, mp: 165-175 ° C

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2- (N-Formylpiperazino) -7- (N-methyl-benzylamino) -4- (N-methyl-2'-hydroxy-ethylamino) -6-phenyl-pteridine Yield: 80% theory, m.p .: 135 -155 ° C

2- (N-Formylpiperazino) -4- (N-methyl-21-hydroxyethylamino) -7-thiomorpholino-6-phenylpteridine

Yield: 80% theoretical, m.p .: sintering above 155 ° C

4,7-di- (N-methyl-benzylamino) -2- (N-formylpiperazino) -6-phenyl-pteridine

Yield: 50% theoretical, mp: 50-70 ° C

7-Dimethylamino-2- (N-formylpiperazino) -4- (N-methyl-benzylamino) -6-phenyl-pteridine

Yield: 90% theoretical, m.p .: sintering above 90 ° C

2- (N-formylpiperazino) -4- (N-methyl-benzylamino) -7-mother-morpholino-6-phenyl-pteridine

Yield: 80% theoretical, m.p .: sintering above 40 ° C

20

Example 13 7-Benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine 1.58 g (3 mmol) of 7-benzylamino-2- (N-formylpiperazino) -6-phenyl-4-thiomorpholino pteridine is heated for 30 minutes under reflux with 15 ml of 10% hydrochloric acid.

After cooling, the solution is added aqueous potassium carbonate solution and extracted with chloroform. The organic phase is evaporated in vacuo and the product is chromatographed over a silica gel column with 80: 1 methanol / concentrated ammonia as eluent.

Yield: 0.8 g (54% theory), mp: 115-130 ° C Analysis:

Calculated: C 65.03 H 6.06 N 22.47 Found: 65.20 6.22 22.07 λ max (ethanol): 386, 292, 248 nm

DK 161327 B

Example in 4- 7- (N-methyl-2'-hydroxyethylamino) -6-phenyl-2-piperazino-4-thiomorpholino-pteridine

Prepared from 2- (N-formylpiperazino) -7- (N-methyl-2'-hydroxyethylamino) -6-phenyl-4-thiomorpholino-pteridine analogous to Example 13.

Yield: 52% theoretical, m.p .: sintering above 70 ° C. Analysis:

Calculated: C 59.20 H 6.48 N 24.02 Found: 59.44 6.22 23.85 λ max (ethanol): 400, 297, 258 nm

Example 15 4-morpholino-7- (1-oxidothiomorpholino) -6-phenyl-2-pipe-15-azino-pteridine

Prepared from 2- (N-formylpiperazino) -4-morpholin-7- (1-oxidothiomorpholino) -6-phenylpteridine analogous to Example 13.

Yield: 43% theoretical, mp: 196-199 ° C Analysis:

Calculated: C 58.28 H 6.11 N 22.66 S 6.48

Found: 57.93 6.31 22.72 6.44 λ max (ethanol): 400, 295, 258 nm Example 16 4- (N-methyl-2'-hydroxyethylamino) -7-morpholino-6-phenyl 2-piperazino-pteridine

Prepared from 2- (N-formylpiperazino) -4- (N-methyl-2'-hydroxyethylamino) -7-morpholino-6-phenylpteridine analogous to Example 13.

Yield: 31% theoretical, m.p .: sintering above 90 ° C. Analysis:

Calculated: C 61.30 H 6.71 N 24.87

Found: 61.52 6.73 24.75 λ max (ethanol): 398, 296, 258 nm 21

DK 161327 B

Example 17 7- (N-methyl-benzylamino) -4- (N-methyl-2'-hydroxyethyl-amino) -6-phenyl-2-piperazino-pteridine

Prepared from 2- (N-formylpiperazino) -7- (N-methyl-benzylamino) -4- (N-methyl-2'-hydroxyethylamino) -6-phenyl-pteridine analogous to Example 13.

Yield: 19% theoretical, mp: 80-110 ° C Analysis:

Calculated: C 66.91 H 6.66 N 23.13 Found: 66.80 6.58 22.70 λ max (ethanol): 395, 294, 258 nm

Example 18 4- (N-methyl-2'-hydroxyethylamino) -6-phenyl-2-piperazino-7-thiomorpholino-pteridine

Prepared from 2- (N-formylpiperazino) -4- (N-methyl-2 '-hydroxyethylamino) -6-phenyl-7-thiomorpholino-pteridine analogous to Example 13.

Yield: 13% theoretical, mp: 100-140 ° C Analysis:

Calculated: C, 59.20; H, 6.48; N, 24.02

Found: 59.66 6.45 23.74 λ max (ethanol): 398, 296, 258 nm Example 19 4,7-Bis- (N-methyl-benzylamino) -6-phenyl-2-piperazino-pteridine

Prepared from 2- (N-formylpiperazino) -4,7-bis- (N-methyl-benzylamino) -6-phenylpteridine analogous to Example 13.

Yield: 56% theoretical, m.p .: resinous product Analysis:

Calculated: C, 72.47; H, 6.46; N, 21.12

Found: 72.60 6.62 20.90 λ max (ethanol): 398, 294, 258 nm 22

DK 161327 B

Example 20 7-Dimethylamino-4- (N-methyl-benzylamino) -6-phenyl-2-piperazino-pteridine

Prepared from 2- (N-formylpiperazino) -7-dimethyl-5-amino-4- (N-methyl-benzylamino) -6-phenyl-pteridine analogous to Example 13.

Yield: 69% theoretical, mp: 129-132 ° C (acetic acid ester) Analysis:

Calculated: C 68.69 H 6.65 N 24.65 Found: 68.84 6.81 24.37 λ max (ethanol): 396, 294, 258 nm

Example 21 4- (N-Methyl-benzylamino) -7-morpholino-6-phenyl-2-piperazino-pteridine

Prepared from 2- (N-formylpiperazino) -4- (N-methyl-benzylamino) -7-morpholino-6-phenylpteridine analogous to Example 13.

Yield: 60% theoretical, mp: 70-100 ° C Analysis:

Calculated: C 67.71 H 6.50 N 22.57

Found: 67.96 6.49 22.55 λ max (ethanol): 396, 294, 258 nm Example 22 7-Dimethylamino-6-phenyl-2-piperazino-4-pyrrolidino-pteridine

Prepared from 2- (N-formylpiperazino) -7-dimethylamino-6-phenyl-4-pyrrolidino-pteridine analogous to Example 13.

Yield: 30% theoretical, mp: 125-130 ° C Analysis:

Calculated: C, 59.20; H, 6.48; N, 24.02

Found: 59.44 6.71 23.65 λ max (ethanol): 394, 294, 257 nm 2 3

DK 161327 B

Example 23 7-morpholino-6-phenyl-2-piperazino-4-thiazolidino-pteridine

Prepared from 2- (N-formylpiperazino) -7-morpholin-6-phenyl-4-thiazolidino-pteridine analogous to Example 13.

Yield: 56% theoretical, mp: 120-150 ° C Analysis:

Calculated: C 59.46 H 6.07 N 24.12 S 6.90 Found: 59.13 6.13 24.36 6.68 λ max (ethanol): 396, 294, 258 nm

Example 24 7-morpholino-4- (1-oxidothiazolidino) -6-phenyl-2-piperazino-pteridine 0.93 g (2 mmol) 7-morpholino-6-phenyl-2-piperazino-4 Thiazolidino-pteridine is dissolved in 15 ml of dioxane and heated together with 0.86 g of sodium metaperiodate in 5 ml of water 1.5 hours at reflux. Then 20 is evaporated by rotary evaporation, the residue is dissolved in chloroform and chromatographed over a silica gel column with ethanol / ammonia 25: 1 as eluent.

Yield: 31% theoretical, mp: 190-250 ° C Analysis: Calculated: C 57.49 H 5.87 S 6.67

Found: 57.24 6.10 7.15 λ max (ethanol): 394, 290, 258 nm

Example 2 4- (N-methyl-21-hydroxyethylamino) -7- (1-oxidothiomorpholino) -6-phenyl-2-piperazino-pteridine

Prepared analogously to Example 24 from 4- (N-methyl-2 L-hydroxyethylamino) -7-thiomorpholino-6-phenyl-2-piperazino-pteridine.

Yield: 58% theoretical, m.p .: sintering above 110 ° C

0.24

DK 161327 B

Analysis:

Calculated: C 57.25 H 6.27 S 6.64

Found: 57.45 6.59 6.96 λ max (ethanol): 396, 296, 255 nm

Example 26 4.7-Bis-dimethylamino-6-phenyl-2-piperazino-pteridine

Prepared from 4,7-bis-dimethylamino-2- (N-formyl-piperazino) -6-phenyl-pteridine by example. 13th

Yield: 85% theoretical, m.p .: sintering above 50 ° C. Analysis:

Calculated: C 63.46 H 6.93 N 29.61

Found: 63.22 7.07 29.82 λ max (ethanol): 394, 293, 257 nm

Example 27 6-Phenyl-2-piperazino-4,7-dipiperidino-pteridine

Prepared from 2- (N-formylpiperazino) -6-phenyl-4.7-dipiperidino-pteridine analogous to Example 13.

Yield: 43% theoretical, m.p .: sintering above 90 ° C. Analysis:

Calculated: C 68.10 H 7.47 N 24.43

Found: 68.00 7.47 24.29 λ max (ethanol): 400, 299, 260 nm 25

Example 28 2.7-Dipiperazino-4-morpholino-6-phenyl-pteridine 25.2 g (0.07 mol) of 2,7-dichloro-4-morpholino-6-phenyl-pteridine are stirred with 36 g of piperazine in 70 ml. ml of ethanol for 1 hour at room temperature. The mixture is then stirred with 700 ml of water, the resulting precipitate is sucked off, dissolved in 4 N acetic acid and precipitated again with 8 N sodium hydroxide solution.

Yield: 24 g (74% theoretical), m.p .: sintering above 130 ° C

25

DK 161327 B

Analysis:

Calculated: C, 62.44; H, 6.77; N, 27.31

Found: 62.78 6.70 27.31 λ max (ethanol): 400, 298, 260 nm 5

Example 29 2,7-Dipiperazino-4-thiomorpholino-6-phenylpteridine

Prepared from 2,7-dichloro-4-thiomorpholino-6-phenylpteridine analogous to Example 28 · 10 Yield: 79% theoretical, m.p .: sintering above 80 ° C Analysis:

Calculated: C, 60.35; H, 6.54; N, 6.71

Found: 60.20 6.67 6.92 λ max (ethanol): 400, 299, 259 nm

Example 30 7-Morpholino-4- (1-oxidothiomorpholino) -6-phenyl-2-piperazino-pteridine 4.6 g (0.01 mole) of 7-chloro-2- (N-formylpiperazino) -20 (1-oxidothiomorpholino) -6-phenyl-pteridine is heated for 1 hour at 100 ° C in 8.7 g (0.1 mole) of morpholine. The solution is evaporated in vacuo and the residue is chromatographed on a silica gel column with 50: 1 methanol / ammonia as eluent.

Yield: 1.5 g (30% theoretical), mp: 151-154 ° C (methanol)

Analysis:

Calculated: C 58.28 H 6.11 N 22.66 S 6.48

Found: 57.99 6.13 22.22 6.65 λ max (ethanol): 398, 294, 258 nm

Example 31 7-Benzylamino-4- (1-oxidothiomorpholino) -6-phenyl-2-piperazino-pteridine 35 Prepared from 7-chloro-2- (N-formyl-piperazino) - 4- (1-oxidothiomorpholino) - 6-phenylpteridine and benzylamine analogous to Example 30.

26

DK 161327 B

Yield: 50% theoretical, mp: 200 ° C (dec.)

Analysis:

Calculated: C 63.01 H 5.88 N 21.77 S 6.23

Pound: 62.89 6.07 21.45 6.20 5

Example 32 7-Benzylamino-4-morpholino-6-phenyl-2-piperazino-pteridine

Prepared from 7-chloro-2- (N-formyl-piperazino) -4-10 morpholino-6-phenyl-pteridine and benzylamine analogous to Example 30.

Yield: 35% theoretical, mp: 135-138 ° C (acetic acid ester) Analysis:

Calculated: C 67.20 H 6.27 N 23.22 Found: 67.25 6.34 23.42 λ max (ethanol): 385, 290, 248 nm

Example 3 3 4,7-Dimorpholino-6-phenyl-2-piperazino-pteridine 20 Prepared from 7-chloro-2- (N-formyl-piperazino) -4-morpholino-6-phenyl-pteridine and morpholine analogous to Example 30 .

Yield: 13% theoretical, mp: 220-223 ° C Analysis: Calculated: C 62.32 H 6.54 N 24.23

Found: 62.21 6.64 24.05 λ max (ethanol): 400, 296, 259 nm

Example 3 4,7-Bis- (1-oxidothiomorpholino) -6-phenyl-2-piperazinopteridine and

Prepared from 7-chloro-2- (N-formyl-piperazino) - 4- (1-oxidothiomorpholino) -6-phenylpteridine and 1-oxido-thiomorpholine analogous to Example 30.

Yield: 25% theoretical, mp: 250 ° C (dec.)

Analysis:

Calculated: C, 54.73; H, 5.74; N, 24.28

Found: 54.60 5.71 24.04 x max (ethanol): 400, 296, 259 nm 27

DK 161327 B

Example I

Dragées with 4 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine

Composition: 5 1 dragon cores contain:

Active substance. (1) 4.0 mg Milk sugar (2) 27.0 mg

Corn starch (3) 14.5 mg

Polyvinylpyrrolidone (4) 4.0 mg Magnesium stearate (5) 0.5 mg 50.0 mg

Preparation:

The starting materials 1-3 are wetted with an aqueous solution of 4 regularly, sifted through 1 mm 15 size masks, dried and sieved again through 1 mm masks.

Starting substance 5 is mixed and the mixture is pressed into dragon cores.

Dragon core: 5 mm 0, biconvex, round

Coating: 20 Usual sugar coating, final weight: 70 mg

Example II

Tablets with 8 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine 1 tablet contain:

Active agent 8.0 mg Milk sugar 23.0 mg

Corn starch 14.5 mg

Polyvinylpyrrolidone 4.0 mg Magnesium stearate 0.5 mg 50.0 mg

Preparation:

Analogous to the dragon cores.

Description of tablets: 35 Weight: 50 mg

Average: 5 mm, biplane, facets on both sides.

28

DK 161327 B

Example III

Suppositories containing 25 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine 1 suppository contain: 5 Active agent 0.025 g Cured fat (eg Witepsol H 19 1.695 g and Witepsol H 45) 1.700 g

Preparation:

The cured fat is melted. The active substance 10 is ground and dispersed homogeneously in the melt at 38 ° C. It is cooled to 35 ° C and poured into slightly precooled suppository molds.

Weight of suppositories: 1.7 g

Example IV

Suspension with 8 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine per 5 ml of 100 ml suspension contains:

Active agent 0.16 g Carboxymethyl cellulose 0.1 g p-hydroxybenzoic acid methyl ester 0.05 g p-hydroxybenzoic acid propyl ester 0.01 g Tube sugar 10.0 g

Glycerin 5.0 g Sorbitol Solution 70% 20.0 g

Flavor 0.3 g

Distilled water at 100.0 ml

Preparation:

Distilled water is heated to 70 ° C. Herein, p-hydroxybenzoic acid methyl ester and propyl ester are dissolved, with stirring, in addition to glycerine and carboxymethyl cellulose. Cool to room temperature, add the active agent and disperse homogeneously. The sugar is added and dissolved, then the sorbitol solution and the aroma, and the suspension is kept under stirring under vacuum to deaerate.

29

DK 161327 B

Example V

Tablets containing 100 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine

Composition: 5 1 tablet contains:

Active agent 100.0 mg Milk sugar 80.0 mg

Maize starch 34.0 mg

Polyvinylpyrrolidone 4.0 mg Magnesium stearate 2.0 mg 220.0 mg

Preparation:

Active agent, milk sugar and starch are regularly mixed and wetted with an aqueous solution of polyvinylpyrrolidone. The moist mass is sifted through 2.0 mm masks and dried in a drying cabinet at 50 ° C, after which the mass is again sieved, this time with 1.5 mm mesh size and the lubricant added. The now ready-to-use mixture is processed into tablets.

Tablet weight: 220 mg

Average size: 10 mm, biplane with facets on both sides and split notches on one side.

25

Example VI

Hard gelatin capsules with 150 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine 1 capsule contain: 30 Active agent 150.0 mg Dried corn starch approx. 180.0 mg

Powdered milk sugar approx. 87.0 mg

Magnesium stearate 3.0 mg approx. 320.0 mg Preparation:

The active agent is mixed with the excipients, 30

DK 161327 B

are screened through 0.75 mm masks and mixed homogeneously in a suitable container.

Then fill in size 1 hard gelatin capsules.

5 Contents of capsules: approx. 320 mg

Capsule casings: Hard gelatin capsule size 1.

Example VII

10 suppositories containing 150 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine 1 suppository contain:

Active agent 150.0 mg

Polyethylene glycol 1500 550.0 mg Polyethylene glycol 6000 460.0 mg

Polyoxyethylene sorbitan monostearate 840.0 mg 2,000.0 mg

Preparation:

The excipients are melted and the active agent is distributed homogeneously therein, after which the melt is poured into pre-cooled molds.

Example VIII

Suspension with 50 mg of 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine per 5 ml of 100 ml suspension contains:

Active agent 1.0 g

Carboxymethyl cellulose sodium salt 0.1 g p-hydroxybenzoic acid methyl ester 0.05 g p-hydroxybenzoic acid propyl ester 0.01 g cane sugar 10.0 g

Glycerin 5.0 g 70% sorbit solution 20.0 g

Flavor 0.3 g 35 Distilled water in 100.0 ml

Preparation:

Distilled water is heated to 70 ° C. Herein dissolve 31

DK 161327 B

p-hydroxybenzoic acid methyl ester and propyl ester in addition to glycerine and carboxymethyl cellulose sodium salt are stirred. It is cooled to room temperature, the active agent is added and homogeneously dispersed therein. Then the sugar, sorbit solution and aroma are added and dissolved, and the suspension is stirred under vacuum to vent it.

5 ml suspension contains 50 mg of active agent.

Example IX

Tablets containing 150 mg of 7-benzylamine-6-phenyl-2-piperazino-4-thiomorpholin-pteridine Composition: 1 tablet contains: 15 Active agent 150.0 mg

Powdered milk sugar 89.0 mg

Corn starch 40.0 mg

Colloidal silica 10.0 mg

Polyvinylpyrrolidone 10.0 mg Magnesium stearate 1.0 mg 300.0 mg

Preparation:

The active agent is mixed with milk sugar, corn starch and silicic acid and wetted with a 20% aqueous solution of polyvinylpyrrolidone, then pressed through a 1.5 mm mesh screen.

The granulate is dried at 45 ° C, pressed again through the same sieve and mixed with the specified amount of magnesium stearate. The tablets are pressed from this mixture.

Tablet weight: 300 mg

Piston: 10 mm, flat

Example X

Dragees containing 75 mg of 7-benzylamino-6-phenyl-2-piperazino-4-35 thiomorpholino-pteridine 1 dragees contain:

Active agent 75.0 mg of calcium phosphate 93.0 mg

Claims (8)

20 Then they get a shiny surface using beeswax. Dragon weight: 245 mg In the preceding pharmaceutical preparations, all other compounds of general formula I can also be used as active agents. Substituted 2-piperazinopteridines, known by describing them with the general formula I R * 7 R N / \, U Y T Ύ / JL Λ (I) Wherein R4 is a dialkylamino, phenylalkylamino, N-alkyl-phe- ; R 9 is H, alkyl or phenyl; and R7 is an alkylamino, dialkylamino, phenylalkylamino, N-alkylphenylalkylamino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, or piperazine group; wherein in R 2, R 9 and R 2 each alkyl moiety may contain 1-3 carbon atoms, and in R 4 and R at the same time, in the case of alkyl, one or both alkyl groups may be substituted at the 2- or 3-position with OH; or are acid addition salts thereof, preferably physiologically acceptable acid addition salts with inorganic or organic acids. Pteridines of the general formula I according to claim 1, characterized in that R 4 is a dimethylamino, N-methyl-2-hydroxyethylamino, 20 bis (2-hydroxyethyl) amino, benzylamino, N-methyl-benzene, zylamino, pyrrolidino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, thiazolidino, or 1-oxidothiazolidino group; R 9 is H, methyl or phenyl; and R7 is a dimethylamino, N-methyl-2-hydroxyethylamino, benzylamino, N-methylbenzylamino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, or piperazine group; as well as their acid addition salts. Pteridines of the general formula I according to claim 1, characterized in that R 1 is a pyrrolidino, piperidino, morpholino, thiomorpholino, 1-oxidothiomorpholino, or N-methyl-2-hydroxyethylamino group; Rg is as defined in claim 2; and 35 is a dimethylamino, benzylamino, N-methyl-benzylamino, morpholino, thiomorpholino, or 1-oxido-thiomorpholino group; as well as their acid addition salts. DK 161327 B The compound 7-benzylamino-6-phenyl-2-piperazino-4-thiomorpholino-pteridine according to claim 1 as well as its acid addition salts. 5-. Medicament, characterized in that it contains a compound according to claims 1 to 4 or a physiologically acceptable acid addition salt thereof together with one or more inert carriers and / or diluents. Process for the preparation of a medicament part, characterized in that a compound according to claims 1 to 4 or a physiologically acceptable acid addition salt thereof is cooperated non-chemically with one or more inert carriers and / or diluents. 15 7. A process for the preparation of compounds according to claims 1 to 4, characterized in that a) a compound of the general formula II is reacted Wherein Rj and Rg are as defined in claims 1 to 4, one of Z 1 or Zy is a group exchangeable by a nucleophilic substitution reaction, preferably a halogen atom, and the other of Z 1 or Zy is a piperazo group or a a group as defined for Ry in claims 1 to 4, or, if a compound of formula I is desired wherein Ry is a piperazine group, also a group exchangeable by a nucleophilic substitution reaction, preferably a halogen atom; with an amine of the general formula III: Η - X III DK 161327 B wherein X is a piperazine group or a group thereof. for Ry in claims 1 to 4 or is a piperazine group protected by a group removable by hydrolysis; and then removes any protecting group used; or b) for the preparation of compounds of general formula I wherein a 1-oxidothiomorpholino or 1-oxy-dothiazolidino group and / or Ry is a 1-oxidothiomorpholino group oxidizes a compound of general formula IV: 10-S . R * N N tf NH I.jC w ”* 6 * 15 R. wherein R 9 is as defined in claims 1 to 4 and R 1 and Ry 1 have the same meaning as R 1 and Ry respectively in claims 1 to 4, however, at least one of R 4 'or Ry' must be a thiomorpholino group. , or R 2 'must be a thiazolidino group; and, if desired, transferring a compound of formula I thus obtained in its acid addition salt, preferably physiologically acceptable acid addition salt, with an inorganic or organic acid.