DE3115447A1 - Novel pyrimidinones, their preparation and their use as medicaments - Google Patents

Abstract

Novel pyrimidinones of the general formula <IMAGE> in which A and B, together with the two carbon atoms lying in between, form a pyridine or methoxyphenyl ring, D denotes an alkylene or hydroxyalkylene group, R3 and R6 each denote a hydrogen atom or an alkyl group, R4 denotes a hydrogen atom or an alkoxy group and R7 denotes an alkyl group, or an alkylene or hydroxyalkylene group which is terminally substituted by an optionally substituted phenyl group, and their salts, which have useful pharmacological properties, in particular a hypotensive, antiarrhythmic and beta -receptor-blocking action. The compounds of the formula I can be prepared by processes customary for analogous compounds.

Description

New pyrimidinones, their manufacture and their uses

Use as a drug / additive to the DBP (patent application P 30 46 871 in the German federal patent (file number: P 30 46 871.4) new quinazolinones of the general formula their acid addition salts and processes for their preparation as well as medicaments containing the above compounds are described.

The above-mentioned compounds have valuable pharmacological properties Properties, especially antihypertensive, anti-arrhythmic and B-receptor-blocking Effect.

In the general formula above, A and B represent together with the two intervening carbon atoms form a phenyl ring through the radicals R1 and / or R2 can be substituted, where R1 is a halogen atom, an amino or Nitro group, an alkyl or alkoxy group each having 1 to 3 carbon atoms and R2 represent an alkoxy group having 1 to 3 carbon atoms, R3 and R6 which can be the same or different, each a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, R4 with a hydrogen atom or an alkoxy group with 1 to 3 carbon atoms, R5 is a hydrogen atom or a hydroxyl group and R7 a straight or branched chain alkyl group having 1 to 6 carbon atoms or a straight-chain saturated one optionally substituted by a hydroxyl group Alkylene group with 2 to 4 carbon atoms, which is terminated by a phenyl or phenoxy group, the phenyl nucleus in each case by alkyl and / or Alkoxy groups with 1 to 3 carbon atoms can be mono- or disubstituted.

Surprisingly, it has now been found that the new compounds of the general formula in which R3, R4, R6 and R7 are as defined at the outset, A and B together with the two intervening carbon atoms form a pyridine ring or a methoxyphenyl ring, if D is a butylene group optionally substituted by a hydroxyl group or the propylene group and the group represents the 2-hydroxy-3- (4-methoxyphenoxy) propylamino group, and D represents an alkylene group with 3 to 4 carbon atoms optionally substituted by a hydroxyl group, and their acid addition salts, in particular their physiologically acceptable acid addition salts with inorganic or organic acids, the same valuable ones have pharmacological properties.

The present application thus relates to the new quinazolinones, Pyrido / 2,3-eJpyrimidinone and PyridoL3,4-e / pyrimi dinone of the above general Formula I.

For those in the definition of the radicals D, R3, R4, R6 and R7 at the beginning mentioned meanings come for example for D those of the propylene, Butylene, 2-hydroxy-propylene, 2-hydroxybutylene or 3-hydroxy-butylene group, for R3 and R6 each represent a hydrogen atom, the methyl, ethyl, propyl or Isopropyl group, for R4 that of a hydrogen atom, the methoxy, ethoxy, propoxy or Isopropoxy group, and for R7 that of the methyl, ethyl, propyl, isopropyl, butyl, Isobutyl, tert-butyl, pentyl, neopentyl, tert-pentyl, hexyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 2-hydroxy-3-phenylpropyl, 2-hydroxy-4-phenylbutyl, 3-hydroxy-4-phenyl-butyl-, 2- (methoxyphenyl) -ethyl-, 3- (methoxyphenyl) -propyl-, 4- 4- (methoxyphenyl) -butyl-, 2-hydroxy-3- (methoxyphenyl) -propyl-, 2- (ethoxyphenyl) -ethyl- 3- (isopropoxyphenyl) propyl, 2- (dimethoxyphenyl) ethyl, 3- (dimethoxyphenyl) propyl, 2-hydroxy-3- (dimethoxyphenyl) -propyl-, 2- (methylphenyl) -thyl-, 2- (isopropylphenyl) -ethyl-, 3- (methylphenyl) propyl, 2-hydroxy-3- (methylphenyl) propyl, 4- (methylphenyl) butyl, 2- (dimethylphenyl) -ethyl-, 3- (dimethylphenyl) -propyl-, 2-hydroxy- 3- (dimethylphenyl) -propyl-, 2-phenoxyethyl-, 3-phenoxypropyl-, 4-phenoxybutyl-, 2-hydroxy-3-phenoxypropyl-, 2-hydroxy-4-phenoxybutyl-, 3-hydroxy-4-phenoxybutyl-, 2- (methoxyphenoxy) -ethyl-, 3- (methoxyphenoxy) -propyl-i 4- (methoxyphenoxy) -butyl-, 2- (ethoxyphenoxy) -ethyl-, 3- (1 sopropoxyphenoxy) propyl, 2- (dimethoxyphenoxy) ethyl, 3- (dimethoxyphenoxy) propyl, 2-hydroxy-3- (dimethoxyphenoxy) propyl, 2-hydroxy-3- (dimethoxyphenoxy) propyl, 2- (methylphenoxy) -ethyl-, 2- (isopropylphenoxy) -ethyl-, 3- (methylphenoxy) -propyl-, 2-hydroxy-3- (methylphenoxy) propyl, 4- (methylhenoxy) butyl, 2- (dimethylphenoxy) -äthyl-, 3- (dimethylphenoxy) -propyl-, 2-hydroxy-3- (dimethylphenoxy) -propyl-, 2- (methylmethoxyphenyl) ethyl, 3- (methyl methoxyphenyl) propyl, 2-hydroxy 3- (methyl-methoxyphenyl) -propyl-, 4- (methyl-methoxyphenyl) -butyl-, 2- (methyl-ethoxyphenyl) -ethyl-, 3- (ethyl-xthoxyphenyl) -propyl-, 2-hydroxy- 3- (methyl-propoxyphenyl) -propyl -, 2- (methyl-methoxyphenoxy) -ethyl-, 3- (methyl-methoxyphenoxy) -propyl-, 2-hydroxy-3- (methyl-methoxyphenoxy) -propyl-, 4- (methyl-methoxyphenoxy) -butyl-, 2- (isopropyl-methoxyphenoxy) -ethyl-, 2-hydroxy-3- (methyl isopropoxyphenoxy) propyl or 2-hydroxy-3- (isopropyl isopropoxyphenoxy) propyl group into consideration.

Preferred compounds of the above general formula I, however, are those in which A and B are as defined at the outset, D is n-propylene, n-butylene, 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-n-butylene group, R3 is the Methyl group, R4 a hydrogen atom, R6 a hydrogen atom or an alkyl group with 1 to 3 carbon atoms and R7 is an alkyl group with 1 to 4 carbon atoms, one in the 2-position by a methoxyphenyl, dimethoxyphenyl or methoxyphenoxy group substituted ethyl group or one in the 3-position by a methoxyphenoxy or Methylphenoxy group-substituted 2-hydroxypropyl group, and their physiological compatible acid addition salts.

According to the invention, the new compounds are obtained by the following processes: a) By reacting a propoxyphenyl derivative of the general formula in which R3, R4, A, B and D are as defined at the outset, X represents a nucleophilically exchangeable group such as a halogen atom or X together with a β-hydrogen atom of the radical D represents an oxygen atom, with an amine of the general formula in which R6 and R7 are as defined at the beginning.

The reaction is optionally carried out in a solvent, e.g. in methanol, isopropanol, tetrahydrofuran, toluene, dimethylformamide or dimethyl sulfoxide, optionally in the presence of an acid-binding agent such as an alcoholate or alkali carbonate such as potassium tert-butoxide or potassium carbonate, and optionally in a pressure vessel at temperatures between 50 and 2000C, but preferably The reaction is particularly advantageous at temperatures between 70 and 150.degree but using an excess of the amine used, the general Formula III carried out as a solvent.

b) alkylation of a compound of the general formula in which R4, A, B and D are as defined at the outset, at least one of the radicals R3 ', R6' or R7 'represents a hydrogen atom and the rest of the radicals R3', R6 'or R71 are those mentioned at the beginning for R3, R6 or R7 Have meanings with a compound of the general formula z - y, (V) in which Z is a nucleophilically exchangeable group such as a halogen atom or a sulfonyloxy group, for example a chlorine, bromine or iodine atom, a methylsulfonyloxy, p-toluenesulfonyloxy or methoxysulfonyloxy group , or Z together with a ß-hydrogen atom of the radical R7 represents an oxygen and Y, with the exception of a hydrogen atom, has the meanings mentioned for R3, R6 and R7 at the beginning, or with formaldehyde / formic acid.

The alkylation is preferably carried out in a solvent such as acetone, Tetrahydrofuran, dioxane, dimethylformamide or dimethyl sulfoxide with a corresponding one Alkyl halide, e.g.

with methyl iodide, ethyl bromide, tert-butyl chloride, 2- (2-methoxyphenyl) ethyl bromide, 2- (2-methylphenoxy) ethyl bromide or 1-chloro-2-hydroxy-3- (4-methoxyphenoxy) propane, with a corresponding sulfonyloxy compound, e.g. with dimethyl sulfate, diethyl sulfate or tert-butyl-p-toluenesulfonate or a corresponding epoxide, e.g. with 3- (4-methoxyphenoxy) propylene oxide, optionally in the presence of an inorganic or tertiary organic base, e.g. in the presence of potassium carbonate, potassium tert-butoxide, triethylamine or pyridine, the latter can also serve as solvents, at temperatures between 0 and 1800C, but preferably at the boiling point of the reaction mixture, carried out.

However, the methylation can also be carried out with formaldehyde / formic acid elevated temperatures, but preferably at the boiling point of the reaction mixture, be performed.

The new compounds obtained according to the invention can then be if desired in their acid addition salts, especially in their physiological compatible salts with inorganic and organic acids. As acids for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, Lactic acid, citric acid, tartaric acid, oxalic acid or maleic acid can be considered.

The compounds of the general formulas II and III used as starting materials are obtained by processes known from the literature or are known from the literature. For example, a compound of the general formula II is obtained by reaction (see, for example, J. chem. Soc. 1972, 709; DE-OS 2 114 884 and Syn. Comm. 10, 241-243 (1980)) of a corresponding oxazine of the general formula with a corresponding amine of the general formula R3 - NH2, (VII) subsequent cleavage of the acetyl radical and subsequent alkylation with a corresponding halide of the general formula Br - D - X, (VIII) in which A, B, D, R3, R4 and X are as defined at the outset.

A compound of the general formula used as a starting material IV is obtained, for example, by reacting a corresponding pyrimidin-4-one with a corresponding amine.

As already mentioned at the beginning, the new compounds have the general Formula I and their physiologically acceptable acid addition salts with inorganic and organic acids have valuable pharmacological properties, in particular an antihypertensive, anti-arrhythmic and B-receptor blocking effect.

Because of their pharmacological properties, they are suitable according to the invention produced new compounds and their physiologically acceptable acid addition salts thus especially for the treatment of coronary diseases and high pressure. To the These can be used for pharmaceutical purposes, optionally in combination with other active substances, in the usual galenic preparation forms such as tablets, Work in coated tablets, capsules, powders, suspensions, ampoules, drops or suppositories. The single dose for adults with intravenous administration is 20 - 50 mg and for oral administration 50 - 250 mg 2 to 3 times a day.

The following examples serve to explain the invention in more detail. The chemical structure of the new compounds was determined by means of IR, W, NMR spectra and elemental analysis ensured.

Example A 2- (4-Hydroxyphenyl) -3-methyl-3,4-d-hydropyrido 9, 3-e / pyrimidine 4-one a) 2- (4-Acetoxv-phenYl2-psridot5,6-k) -3,1-oxazin-4-one 27.6 g (0.2 mol) 2-amino-nicotinic acid are suspended in 250 ml of pyridine and, while cooling and stirring, with 50.0 g (0.25 Mol) 4-acetoxybenzoyl chloride added. The reaction has ended after 2 hours and the mixture is poured onto about 1.5 l of ice water, the desired product fails. The precipitate is filtered off with suction, washed well with water and heated to 60.degree dried in a vacuum drying cabinet.

Melting point: 193-1960C, i Yield: 43.5 g (77% of theory) C15 10 2 ° 4 (282.25) Calc .: C 63.82 H 3.57 N 9.92 Found: 63.71 3.51 9.87 b) 2- (4-Hydroxy-benzamido) -nicotinic acid- methylamide 30 g (0.106 mol) of the product obtained according to Example a) are dissolved in 300 ml of 30% strength Methylamine solution heated in water on the steam bath. After 10 minutes the solution will evaporated in vacuo and the crystalline residue boiled up with about 300 ml of ethanol and sucked off. The precipitate obtained is at 60 ° C. in a vacuum drying cabinet dried.

Melting point: 218-220 ° C., yield: 19.8 g (73% of theory) 14 13 3 ° 3 (271.26) Calc .: C 61.98 H 4.83 N 15.49 Found: 61.87 4.69 15.52 c) 2- (4-Hydroxyphenyl) -3-methyl-3, 4-dihydro-pyrido £ 2,3-ejpyrimidin-4-one 18.5 g (0.068 mol) of the product obtained according to Example b) are dissolved in 200 ml of ethylene glycol and 4 ml of dimethylaminoethanolamine heated to 1800C for one hour. Afterward the reaction solution is cooled and poured onto 1.5 l of ice water. That crystallized out The end product is filtered off with suction, washed with plenty of water and at 60 ° C. in a vacuum drying cabinet dried.

0 Melting point: 256-258 c, yield: 9.4 g (54.6% of theory) 14 11 3 2 (253.25) Calc .: C 66.39 H 4.38 N 16.59 Found: 66.43 4.46 16.62 Example B 2-W4- (4-aminobutoxy) -phenylI-3-methyl-6-methoxy-3, 4-dihydroquinazolin-4-one a) 2- (4-acetoxophenyl) -6-methoxy-3,1-benzoxazin-4-one 16.7 g (0.1 mol) of 3-methoxyanthranilic acid are dissolved in 100 ml of pyridine and taken under 23.8 g (0.1 mol + 20%) of 4-acetoxybenzoyl chloride were added to cooling and stirring. After 2 hours the reaction has ended and the reaction mixture is poured onto ice water poured. The resulting precipitate is filtered off with suction, dried and removed Methanol crystallizes.

Melting point: 164-1660C, yield: 20.2 g (65% of theory) C17H13N05 (311.28) er .: C 65.59 H 4.21 N 4.50 Found: 65.51 4.27 4.58 b) 2- (4-Hydroxyphenyl) -3-methyl-6-methoxy-3,4-dihydro-quinazolinH 4-one 6.2 g (0.02 mol) of the product obtained according to Example a) are mixed with 60 ml of 40% strength methylamine solution heated in water in a steel bomb to 1200C. Implementation takes place after 3 hours ended, the reaction solution is evaporated in vacuo and the crude product obtained crystallized from methanol.

Melting point: 146-147 ° C, yield: 4.8 g (85% of theory) C16H14N2 ° 3 (282.30) Calc .: C 68.08 H 5.00 N 9.92 Found: 67.95 5.05 9.86 c) 2-t4- (4-chlorobutoxy) -pheny / -3-methyl -6-methoxy-3,4-dthydroquinazolin-4-one 4 g (0.014 mol) of the product obtained according to Example b) are dissolved in 30 ml of dimethyl sulfoxide dissolved and treated with 1.75 g (0.014 mol + 10%) potassium tert-butoxide while stirring. Then 4 ml of 1-bromo-4-chlorobutane are added and at room temperature until stirred for quantitative conversion. Then it is poured onto ice water, which is crystalline the precipitated end product is suctioned off, washed thoroughly with water and dried.

Melting point: 127-1300C, yield: 4.9 g (94% of theory) of C20H21ClN203 (372.85) Calc .: C 64.43 H 5.68 N 7.51 cl 9.51 Found: 64.28 5.61 7.53 9.59 d) 2- / 4-t4-aminobutoxy) -phenyl2-3-methyl-6-methoxy-3,4-d-hydroquinazolin-4-one 4.5 g (0.012 mol) of the product obtained in Example c) with 2.2 g (0.012 mol + 10%) 2,4-dimethoxybenzylamine added and left to react at 1200C. To The reaction has ended in 2 hours, and the product obtained is treated with 2N hydrochloric acid stirred at room temperature, then made alkaline with 2N sodium hydroxide solution and extracted with methylene chloride. The combined organic extracts are over Dried sodium sulfate and evaporated. The crude product obtained is a Silica gel column (grain size: 0.2-0.5 mm; eluent: methylene chloride: methanol = 19: 1), a colorless bl resulting after evaporation.

Yield: 2.6 g (61 8 of theory) C 20 23 3 ° 3 (353.42) Calc .: C 67.97 H 6.56 N 11.89 Found: 67.49 6.49 11.73 Example 1 2- / 4- (2-Hydroxy-3-isopropylamino-propoxy) -phenylS-3-methyl-3,4-dihydro -pyrido / 2,3-e; 7pyrimidin-4-one dihydrochloride a) 2-L4- (1t2-epoxy-propoxy) -phenylJ-3-methyl-3o4-dihydro-pyridot2, 3-e7pyrimidin-4-one 9.4 g (0.037 mol) of 2- (4-hydroxyphenyl) -3-methyl-3, 4-dihydropyridoE2,3-eipyrimidin-4-one are dissolved in 100 ml of dimethyl sulfoxide and mixed with 4.5 g (0.04 mol) of potassium tert-butoxide while stirring offset. After a clear solution has occurred, 9.4 ml of epibromohydrin are added added and stirred for one hour at room temperature. Then it is poured onto 600 ml of ice water poured and the crystalline product which has precipitated out is suctioned off and placed in a vacuum drying cabinet dried at 400C.

Melting point: 92-95 ° C., yield: 9.3 g (81% of theory) C17 15 3 3 (309.31) Calc .: C 66.00 H 4.89 N 13.58 Found: 66.13 4.96 13.42 b) 2- C4- (2-hydroxy- 3-isopropylamino-propoxy) phenyl] -3-methy 1-3, 4-dihydro-pyrido [2,3-e] pyrimidin-4-one dihydrochloride 2.9 g (0.009 mol) of the product obtained according to Example la are mixed with 30 ml of isopropylamine implemented in the steel bomb at 1200 C. After the reaction has ended, the excess becomes Amine is distilled off in vacuo and the remaining residue is passed through a silica gel column (Grain size: 0.2-0.5 mm; eluent: methylene chloride / methanol = 19: 1). The colorless oil obtained after evaporation is dissolved in 50 ml of acetone and mixed with ethereal hydrochloric acid precipitates the dihydrochloride.

Melting point of the dihydrochloride: 142-145 ° C, yield: 2.0 g (50 % of theory) C20H26cl2N4o3 (441.37) Calc .: C 54.42 H 5.94 N 12.69 Cl 16.07 Found: 54.20 6.11 12.87 16.00 Example 2 2- [4- (2-Hydroxy-3-tert-butylamino-propoxy) -phenyl] -3-methyl-3,4-dihydro-pyrido [2, 3-e] pyrimidin-4-one dihydrochloride prepared analogously to Example 1 from 2-t4- (1,2-epoxy-propoxy) -phenyl / -3-methyl-3,4-dihydro-pyrido g, 3-eç pyrimidin-4-one and and tert-butylamine.

Melting point of the dihydrochloride: 168-171 ° C., yield: 34% of theory C21H28C12N403 (455.37) Calcd .: C 55.38 H 6.19 N 12.30 Cl 15.57 Found: 55.30 6.25 12.26 15.52 Example 3 2- / 4- / 2-Hydroxy-3- (2- (4-methoxyphenoxy) -äthylamino) -propoxy-] phenyl] -3-methyl-3,4-dihydro-pyrido [2,3-e] pyrimidin-4-one 3-pyrimidin-4-one Prepared analogously to Example 1 from 2- [4- (1,2-epoxy-propoxy) -phenyl] -3-methyl-3,4-dihydro-pyrido [2,3-e] pyrimidin-4-one and 4-methoxy-phenoxy-ethylamine.

Melting point: 132-1350C, yield: 17 * of the theory C26H28N405 (476.51) Calc .: C 65.53 H 5.92 N 11.75 Found: 65.42 6.06 11.87 Example 4 2- [4- (2-Hydroxy-3-isopropylamino-propoxy) -phenyl] -3 -methyl-3,4-dihydro-pyrido [3,4-e] pyrimidin-4-one dihydrochloride Prepared analogously to Example 1 from 2- [4- (1,2-epoxy-propoxy) -phenyL / -3-methyl-3,4-d-hydropyrido / 3,4-e-pyrimidin-4-one and isopropylamine.

Melting point of the dihydrochloride: 122-125 ° C., yield: 68% of theory C201126Cl2N403 (441.35) Calc .: C 54.42 H 5.94 N 12.69 Cl 16.06 Found: 54.39 5.88 12.74 16.02 Example 5 2- / 4- (2-Hydroxy-3-tert-butylamino-propoxy) -phenylS-3-methyl-3,4-dihydro-pyridoE3, 4-Q / pyrimidin-4-one dihydrochloride Prepared analogously to Example 1 from 2-L4- (1,2-epoxy-propoxy) -phenyl] 7-3-methyl-3,4-dlhydro-pyrido [3,4- e] 4 pyrimidin-4-one and tert-butylamine.

Melting point of the dihydrochloride: 171-173 ° C, yield: 66.6% of the Theory.

21H28Cl2N4 ° 3 (455.37) Calc .: C 55.38 H 6.19 H 12.30 Cl 15.57 Found: 55.24 6.24 12.43 15.70 Example 6 2- [4- [4- (2-Hydroxy-3- (4-methoxyphenoxy) propylamino) butoxy-] phenyl7-3-methyl-6-methoxy-3, 4-dihydro-quinazolin-4-one 2.5 g (0.007 mol) 2- [4- (4-aminobutoxy) -phenyl] -3-methyl-6-methoxy -3,4-dihydro-quinazolin-2-one are with 1.5 g (0.007 mol + 20%) 1,2-epoxy-3- (4-methoxy) -phenoxy-propane at 120 ° C implemented.

After 3 hours, the reaction has ended and the crude product thus obtained has ended is over a silica gel column (grain size: 0.2-0.5 mm; eluent: methylene chloride / methanol - 49: 1) cleaned.

The yellowish oil obtained after evaporation is dissolved in acetone and the hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point of the hydrochloride: 105-107 ° C, yield: 2.3 g (57% of the Theory) C30H36ClN306 (570.08) Calc .: C 63.20 H 6.36 N 7.37 Cl 6.22 Found: 63.12 6.18 7.28 6.14 Example 7 .2-S- / §- (2-Hydroxy-3- (4-methoxyphenoxy) -propylamino) -propoxy / -phenyl? -8-methoxy-3, 4-dihydro-quinazolin-4-one a) 2- / 4- (3-chloropropoxy) -pheny -8-methoxy-3,4-dihydro-quinazolin-4-one 2.7 g (10 mmol) of 2- (4-hydroxyphenyl) -8-methoxy-3,4-dihydroquinazolin-4-one become dissolved in 30 ml sulfolane and mixed with 1.5 g (10 mmol + 10%) potassium carbonate. 2.7 ml of 1-bromo-3-chloropropane are added to the clear solution and then is stirred at room temperature until quantitative conversion. Then on ice water poured, extracted with ethyl acetate, the combined organic extracts dried over sodium sulfate and evaporated. The result is a colorless oil, which crystallizes on cooling.

Melting point: 50-55 ° C., yield: 3.0 g (88% of theory) C18H17C1N203 (344.80) Calc .: C 62.70 H 4.97 N 8.12 Cl 10.28 Found: 62.45 4.84 8.07 10.09 b) 2-e4-L3- (2- Hydroxy-3- (4-methoxyphenoxy) -propylamino) -propOxy / phenyl? -8-methoxy-3, 4-dihydro-quinazolin-4-one 1.5 g (4.4 mmol) of the according to Example 7a obtained with 1.05 g (4.4 mmol + 10%) of 2-hydroxy-3- (4-methoxy) -phenoxy-propylamine implemented at 120 ° C. After quantitative conversion, the crude product obtained in this way becomes through a silica gel column (grain size: 0.2-0.5 mm; eluent: methylene chloride / methanol = 19: 1) cleaned. The yellow oil obtained after evaporation is dissolved in acetone and the hydrochloride is precipitated with ethereal hydrochloric acid.

Melting point of the dihydrochloride: 190-193 ° C., yield: 1.4 g (56 % of theory) C28H33Cl2N306 (578.60) Calc .: C 58.12 H 5.75 N 7.26 Cl 12.26 Found: 58.34 5.71 7.34 11.98 Example A Tablets of 100 mg 2-4- (2-Hydroxy-3-tert-butylamino-propoxy) -phenyl / -3-methyl-3,4-dihydro-pyridot2,3-eS pyrimidin-4-one dihydrochloride Composition: Active ingredient 100.0 mg milk sugar 50.0 mg polyvinylpyrrolidone 5.0 mg carboxymethyl cellulose 19.0 mg magnesium stearate 1.0 mq 175.0 mg Manufacturing process: The active ingredient and the lactose are evenly moistened with an aqueous solution of polyvinylpyrrolidone and granulated. After drying, the granules are mixed with the remaining active ingredients and the mixture is compressed into tablets in the usual way.

Example B Suppositories containing 150 mg of 2- / 4- (2-hydroxy-3-tert-butylaminopropoxy) -phenyl-7-3-methyl-3,4-dihydro-pyridote-2,3-e-pyrimidin-4-one dihydrochloride Composition: Active ingredient 150.0 mg Suppository mass 1,550.0 mg 1,700.0 mg Production method: The active ingredient is evenly stirred into the melted suppository mass and suspended and the liquid mixture poured into chilled suppository molds.

Example C Coated tablets containing 50 mg of 2- £ 4- (2-hydroxy-3-tert-butylamino-propoxy) -phenyl] -3-methyl-3,4-dihydro-pyrido-4-one dihydrochloride 1 tablet core contains: active substance 50.0 mg dried corn starch 20.0 mg soluble Starch 2.0 mg Carboxymethyl cellulose 7.0 mg Magnesium stearate 1.0 mg 80.0 mg Manufacturing process: The mixture is processed as described in Example A to form tablet cores i, the then coated with sugar and gum arabic.

Example D Suspension with 250 mg of 2-t4- (2-hydroxy-3-tert-butylamino-propoxy) -phenyjl-3-methyl-3, 4-dihydro-pyrido £ 2, 3-7pyrimidin-4-one dihydrochloride 100 ml Suspension contain: Active ingredient 5.0 g carboxymethyl cellulose 0.1 g methyl p-hydroxybenzoate 0.05 g propyl p-hydroxybenzoate 0.01 g sugar 10.0 g glycerin 5.0 g sorbitol solution 70% 20.0 g flavor 0.3 g distilled Water ad 100.0 ml Manufacturing process: In the distilled one heated to 700C Water is stirred and p-hydroxybenzeo acid methyl ester and propyl ester as well Glycerine and carboxymethyl cellulose dissolved. The solution is cooled to room temperature and the active ingredient is added with stirring and dispersed homogeneously. After adding and Dissolving the sugar, the sorbitol solution and the aroma will vent the suspension evacuated with stirring.

Claims (16)

Claims = = == a === 1. New pyrimidinones of the general formula in which A and B together with the two intervening carbon atoms form a pyridine ring or also a methoxyphenyl ring, if D is a butylene group optionally substituted by a hydroxyl group or the propylene group and the group represents the 2-hydroxy-3- (4-methoxyphenoxy) propylamino group, D is an alkylene group with 3 or 4 carbon atoms which is optionally substituted by a hydroxyl group, R3 and R6, which can be the same or different, each have a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, R4 a hydrogen atom or an alkoxy group with 1 to 3 carbon atoms and R7 a straight-chain or branched alkyl group with 1 to 6 carbon atoms or a straight-chain saturated alkylene group with 2 to 4 carbon atoms which is optionally substituted by a hydroxyl group and terminated by a phenyl or phenoxy group is substituted, where the phenyl nucleus can in each case be mono- or disubstituted by alkyl and / or alkoxy groups each having 1 to 3 carbon atoms, and their acid addition salts. 2. New pyrimidinones of the general formula I according to claim 1, in of A and B are as defined in claim 1, D is n-propylene, n-butylene, 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-n-butylene group, R3 the methyl group, R4 a Hydrogen atom, R6 a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and R7 is an alkyl group having 1 to 4 carbon atoms, one in the 2-position through a methoxyphenyl, dimethoxyphenyl or methoxyphenoxy group substituted ethyl group or one substituted in the 3-position by a methoxyphenoxy or methylphenoxy group 2-hydroxypropyl group, and their physiologically acceptable acid addition salts with inorganic or organic acids. 3. New pyrimidinones of the general formula I according to claim 1, in of A, B, R3, R4, R6 and R7 are as defined in claim 2 and D is the 2-hydroxy-n-propylene group represents, and their physiologically acceptable acid addition salts with inorganic or organic acids. 4. New pyrimidinones of the general formula in which A and B are as defined in claim 2 and R6 and R7 together with the intermediate nitrogen atom are isopropylamino, tert-butylamino, 2- (4-methoxyphenoxy> -ethylamino- or 2-hydroxy-3- (4-methoxyphenoxy) ) -propylamino group, and their physiologically acceptable acid addition salts with inorganic or organic acids. 5. 2- 04- (2-Hydroxy-3-tert-butylamino-propoxy) -phenyl-7-3-methyl-3,4-dihydro-pyridoL2,3-epyrimidin-4-one and its acid addition salts. 6. 2- / 4- r-Hydroxy-3- (2- (4-methoxyphenoxy) -ethylamino) -propoxT / -1 phenyl7-3-methyl-3,4-dthydro-pyridoL2,3-g / pyrimidin-4-one and its acid addition salts. 7. 2- / 4- (2-Hydroxy-3-isopropylamino-propoxy) -phenyl / -3-methyl-3,4-dihydro-pyridor2,3-e7-pyrimidin-4-one and its acid addition salts. 8. Medicament containing a compound according to claims 1 to 7 in addition to one or more inert carriers and / or diluents. 9. Use of a compound according to claims 1 to 7 for the preparation of a drug by non-chemical means to combat hypertension and from Coronary diseases. 10. Process for the preparation of new pyrimidinones of the general formula in which A and B together with the two intervening carbon atoms form a pyridine ring or also a methoxyphenyl ring, if D is a butylene group optionally substituted by a hydroxyl group or the propylene group and the group represents the 2-hydroxy-3- (4-methoxyphenoxy) propylamino group, D represents an alkylene group with 3 or 4 carbon atoms which is optionally substituted by a hydroxyl group, R3 and R6, which can be identical or different, each have a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, R4 a hydrogen atom or an alkoxy group with 1 to 3 carbon atoms and R7 a straight-chain or branched alkyl group with 1 to 6 carbon atoms or a straight-chain saturated alkylene group with 2 to 4 carbon atoms which is optionally substituted by a hydroxyl group and terminated by a phenyl or phenoxy group is substituted, where the phenyl nucleus can in each case be mono- or disubstituted by alkyl and / or alkoxy groups each having 1 to 3 carbon atoms, mean and acid addition salts thereof, characterized in that a) a propoxyphenyl derivative of the general formula in which A, B, D, R3 and R4 are as defined at the outset, X represents a nucleophilically exchangeable group or X together with a β-hydrogen atom of the radical D represents an oxygen atom, with an amine of the general formula in which R6 and R7 are as defined at the outset, is reacted or b) a compound of the general formula in which A, B, D and R4 are as defined at the outset, at least one of the radicals R3 ', R6' or R7 'represents a hydrogen atom and the rest of the radicals R3', R6 'or R7 are those mentioned at the beginning for R3, R6 or R7 Have meanings with a compound of the general formula z - y, (v) in which Z is a nucleophilically exchangeable group or Z together with a β-hydrogen atom of the radical R7 represents an oxygen atom and Y with the exception of a hydrogen atom represents those for R3, R6 and R7 has the meanings mentioned at the outset, or is alkylated with formaldehyde / formic acid and, if desired, a compound of the general formula I thus obtained is then converted into its acid addition salt, in particular into its physiologically acceptable acid addition salt, with inorganic or organic acids. 11. The method according to claim 10a, characterized in that the Reaction at temperatures between 50 and 200 ° C, but preferably at temperatures between 70 and 1500C. 12. The method according to claims 10a and 11, characterized in that that the reaction is carried out in the presence of an acid-binding agent. 13. The method according to claims 10a, 11 and 12, characterized in that that the reaction is carried out in a solvent. 14. The method according to claim 10b, characterized in that the Reaction is carried out in a solvent. 15. The method according to claims 1Ob and 14, characterized in that that the reaction at temperatures between 0 and 1800C, but preferably at the boiling temperature of the reaction mixture is carried out. 16. The method according to claims 1Ob, 14 and 15, characterized in that that the reaction in the presence of an inorganic or tertiary organic base is carried out.