Method of 2-sulphonilamine-1,2,4,-triazolo[1,5-a] pyrimidines production

FIELD: chemistry.

SUBSTANCE: invention refers to organic substances production and can be applied for production of herbicides and other bioactive compounds. Production of 2-sulphanilamine-1,2,4-triazolo[1,5-a]pyrimidine of general formula , where R1 is metal, phenylic, 4-methyl phenylic, 4-chlorophenylic group, R is phenylic, 4-methyl phenylic, 4-chlorophenylic, methoxyphenylic group, R is metal, phenylic, 4-methyl phenylic, 4-chlorophenylic group is sulphurization of 2-amino-4,7-dihydro-1,2,4-triazolo [1,5-a]pyrimidines (II) by sulphochlorides (III) in pyrimidine and oxidation of produced 2-sulphanilamine-4,7-dihydro-1,2,4-triazolo[1,5-a] pyrimidines (IV) by bromine in acetic acid with sodium acetate occurrence.

EFFECT: method allows to produce compounds using low-price and reasonable raw materials without any complicated processing steps applied.

1 cl, 7 ex

 

The invention relates to the field of production of organic substances and can be used in the production of herbicides and other biologically active compounds.

A method of obtaining 2-arylsulfonyl-5,7-dimethoxy-1,2,4-triazolo[1,5-a]pyrimidine-sulfonylamine 2-amino-5,7-dimethoxy-1,2,4-triazolo[1,5-a] pyrimidine aromatic sulfochloride in acetonitrile in the presence of pyridine [US Patent 6559101 Int. C1. C07D 487/04. N-(5,7-dimethoxy[1,2,4]triazolo[1,5-a]pyrimidin-2-yl) arylsulfonamide compounds and their use as herbicides // Johnson T.C., VanHeertum J.C., Ouse D.G., et al. - 06.05.2003]. The disadvantage of this method is the impossibility of obtaining sulfanilamidnyh, in which the substituents at positions 5 and 7 triazolopyrimidines cycle differ from a group of co3and the substituent in position 2 is not arylsulfonamides.

A method of obtaining 2-arylsulfonyl-1,2,4-triazolo[1,5-a]pyrimidine-cyclocondensation 3 arylsulfonyl-5-amino-1,2,4-triazoles with 1,3-dicarbonyl compounds in acetic acid [US Patent 4822404 Int. C1. C07D 487/04. Sulfonamides derived from substituted 2-amino-1,2,4-triazolo[1,5-a]pyrimidines and compositions and methods of controlling undesired vegetation // Kleschick W.A. - 18.04.1989].

The main disadvantage of this method is low regioselectivity and cyclocondensation reactions and the formation of mixtures of isomeric products when using nesime the ranks of 1,3-dicarbonyl compounds (R 2≠R3), as well as the high cost of the original 3-resultonline-5-amino-1,2,4-triazole and 1,3-dicarbonyl compounds.

The closest in technical essence and the achieved result is a method of obtaining 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidine-sulfonylamine 2-amino-1,2,4-triazolo[1,5-a]pyrimidines containing various substituents in the pyrimidine cycle, aromatic sulfochloride in pyridine [US Patent 4822404 Int. C1. C07D 487/04. Sulfonamides derived from substituted 2-amino-1,2,4-triazolo[1,5-a]pyrimidines and compositions and methods of controlling undesired vegetation // Kleschick W.A. - 18.04.1989]. The disadvantage of this method is the low yield of the target products and long duration of synthesis, because of the low nucleophilicity of the amino group due to electron impact π-deficient pyrimidine cycle, paired with a triazole ring, as well as the high cost of the starting 2-amino-1,2,4-triazolo[1,5-a]pyrimidines.

The objective of the invention is to develop a method of obtaining 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidines of General formula (I) from a cheap and available source of nutrients that can improve the yield of target products and to reduce the synthesis time.

This object is achieved by sulfonylamine 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine (II) sulfochloride (III) in pyridine and oxidation receive the data 2 sulfonylamino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine (IV) bromine (Br 2) in acetic acid in the presence of sodium acetate (CH3COONa)

We found that in contrast to 2-amino-1,2,4-triazolo[1,5-a]pyrimidine 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines easily sulfonylureas when interacting with sulfochloride in pyridine to form compound (IV). This is probably due to less electron-withdrawing ability dihydropyrimidinase fragment compared to the pyrimidine. Compounds (IV) are oxidized by bromine in acetic acid, yielding the target compound (I). The original 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines can be synthesized from 3,5-diamino-1,2,4-triazole and aromatic ketones and aldehydes [Desenko S.M., spike N.N., Tueni M., Orlov V.D. // HGS. No. 7. S-941].

In the proposed method of obtaining 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidines of General formula (I) to 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine of the General formula (II) add sulfochloride (III) at a molar ratio (II):(III)=1:1.1-1.3 and boil in pyridine. To the solution was added water, the precipitation of 2-sulfonylamino-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine of the General formula (IV) is filtered, mixed with sodium acetate and acetic acid, to the mixture was added bromine in a molar ratio of (IV):(Br2):(CH3COONa)=1:1.00-1.05:2.1-2.2 at a temperature of 0-25°and With stirring. The ZAT is to the resulting solution was added water, the precipitated 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidine of the General formula (I) is filtered off and recrystallized.

Studies have shown that changing the molar ratio (II):(III)=1:1.1-1.3 under sulfonylamine leads either to incomplete reaction and poor purity of the compounds (IV) (example 6, 7), or waste reagents that are economically unjustified.

The molar ratio of (IV):(Br2):(CH3COONa)=1:1.00-1.05:2.1-2.2 at the stage of oxidation is optimal. The change in the ratio leads either to incomplete reaction or the formation of by-products which contaminate the target compound (example 6). Conducting the reaction at temperatures below 0°reduces the speed of the process and increases the duration of the synthesis, which is technically impractical. The temperature increases above 25°reduces the yield of the target products due to the occurrence of side reactions (example 7).

Example 1

To a mixture of 1.0 g (4.4 mmol) of 2-amino-5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 5 ml of pyridine sprinkled with stirring 1.0 g (5.3 mmol) of n-toluensulfonate. The reaction mixture is refluxed for 10-15 minutes, cooled to 20°and diluted with 10 ml of water. The precipitation is filtered off. Obtain 1.4 g (87%) of 2-[(4-were)sulfonylamino]-5-methyl-7-phenyl-4,7-d the hydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL226-228°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 1.79 (3H, CH3), 2.34 (3H, CH3), 4.50 (1H, CH, J=3.7), 5.79 (1H, CH, J=3.7), 7.07 m (2N, arene.), 7.24-7.30 m (5H, arene.), 7.63 m (2N, arene.), 9.56 (1H, NH), 10.71 (1H, NH).

Found (%): 59.74; N, 5.04; N 18.39.

C19H19N5O2S

Calculated (%): 59.83; N, 5.02; N, 18.36.

To a mixture of 1.0 g (2.6 mmol) of 2-[(4-were)sulfonylamino]-5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.44 g (5.2 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.14 ml (2.6 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 20-30 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.9 g (90%) of 2-[(4-were)sulfonylamino]-5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine. TPL284-285°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.36 (3H, CH3), 2.58 (3H, CH3), 7.39 m (3H, arene.), 7.63 m (3H, arene.), 7.86 m (2N, arene.), 8.00 m (2N, arene.), 11.90 ush. c (1H, NH).

Found (%): 60.19; N, 4.26; N 18.28.

C19H17N5O2S

Calculated (%): 60.14; N, 4.52; N 18.46.

Example 2

To a mixture of 1.0 g (3.5 mmol) of 2-amino-5,7-diphenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 5 ml of pyridine sprinkled with stirring, 0.8 g (3.8 mmol) of p-chlorobenzenesulfonamide. The reaction mixture was refluxed for 15-20 minutes, cooled to 20°With and dilute the 10 ml of water. The precipitation is filtered off. Obtain 1.6 g (69%) of 2-[(4-chlorophenyl)sulfonylamino]-5,7-diphenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL274-276°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 5.15 (1H, CH, J=3.7), 6.03 (1H, CH, J=3.7), 7.16 m (2N, arene.), 7.31-7.38 m (6N, arene.), 7.52 m (4H, arene.), 7.76 m (2N, arene.), 10.02 (1H, NH), 11.05 (1H, NH).

Found (%): 59.60; N, 4.01; N, 15.29.

C23H18N5ClO2S

Calculated (%): 59.54; N, 3.91; N, 15.10.

To a mixture of 1.0 g (2.2 mmol) of 2-[(4-chlorophenyl)sulfonylamino]-5,7-diphenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.38 g (4.6 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.12 ml (2.3 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 20-25 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.96 g (94%) of 2-[(4-chlorophenyl)sulfonylamino]-5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine. TPL276-277°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 7.55-7.72 m (8H, arene.), 7.99 m (3H, arene.), 8.10 m (2N, arene.), 8.30 m (2N, arene.), 12.23 ush. s (1H, NH).

Found (%): 60.02; N, 3.26; N, 15.38.

C23H16N5ClO2S

Calculated (%): 59.80; N, 3.49; N, 15.16.

Example 3

To a mixture of 1.0 g (3.3 mmol) of 2-amino-5-phenyl-7-(4-were)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 5 ml of pyridine is poured with stirring, 0.3 ml (4.3 mmol) of methanesulfonamide. The reaction mixture bales which belong under reflux for 15-20 minutes, cooled to 20°and diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.75 g (60%) 2-methylsulfonylamino-5-phenyl-7-(4-were)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL238-240°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 2.27 (3H, CH3), 3.19 (3H, CH3), 5.17 (1H, CH, J=3.7), 6.04 (1H, CH, J=3.7), 7.14 m (4H, arene.), 7.38 m (3H, arene.), 7.57 m (2N, arene.), 10.07 (1H, NH), 10.48 (1H, NH).

Found (%): 59.70; N, 5.05; N, 18.29.

C19H19N5O2S

Calculated (%): 59.83; N, 5.02; N, 18.36.

To a mixture of 1.0 g (2.6 mmol) of 2-methylsulfonylamino-5-phenyl-7-(4-were)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.45 g (5.5 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.14 ml (2.7 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 25-30 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.89 g (90%) 2-methylsulfonylamino-5-phenyl-7-(4-were)-1,2,4-triazolo[1,5-a]pyrimidine. TPL288-289°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.44 (3H, CH3), 3.41 (3H, CH3), 7.44-7.59 m (5H, arene.), 8.05 (1H, CH), 8.19 m (2N, arene.), 8.35 m (2N, arene.), 11.59 ush. c (1H, NH).

Found (%): 60.01; N, 4.16; N 18.58.

C19H17N5O2S

Calculated (%): 60.14; N, 4.52; N 18.46.

Example 4

To a mixture of 1.0 g (3.3 mmol) of 2-amino-5-(4-were)-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]feast is Medina and 5 ml of pyridine is poured with stirring, 0.5 ml (4.0 mmol) of benzosulfimide. The reaction mixture is refluxed for 10-15 minutes, cooled to 20°and diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.86 g (59%) 2-phenylcarbonylamino-5-(4-were)-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL250-252°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 2.28 (3H, CH3), 5.10 (1H, CH, J=3.7), 6.01 (1H, CH, J=3.7), 7.15 m (4H, arene.), 7.28-7.62 m (8H, arene.), 7.78 m (2N, arene.), 9.96 (1H, NH), 10.92 (1H, NH).

Found (%): 64.89; H 5.06; N, 15.28.

C24H21N5O2S

Calculated (%): 64.99; N, 4.77; N, 15.79.

To a mixture of 1.0 g (2.2 mmol) of 2-phenylcarbonylamino-5-(4-were)-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.39 g (4.6 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.12 ml (2.3 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 20-25 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.87 g (90%) 2-phenylcarbonylamino-5-(4-were)-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine. TPL>320°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.37 (3H, CH3), 7.34 m (2N, arene.), 7.62 m (6N, arene.), 7.97-8.23 m (7H, arene.), 12.11 ush. s (1H, NH).

Found (%): 65.01; N, 4.21; N, 15.58.

C24H19N5O2S

Calculated (%): 65.29; N, 4.34; N 15.86.

Example 5

To a mixture of 1.0 g (3.1 mmol) of 2-amino-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-t is Iesolo[1,5-a]pyrimidine and 5 ml of pyridine sprinkled with stirring, 0.7 g (3.4 mmol) of p-chlorobenzenesulfonamide. The reaction mixture is refluxed for 10-15 minutes, cooled to 20°and diluted with 10 ml of water. The precipitation is filtered off. Obtain 1.1 g (71%) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL256-257°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 3.73 (3H, CH3), 5.12 (1H, CH, J=3.7), 5.97 (1H, CH, J=3.7), 6.87 m (2N, arene.), 7.11 m (2N, arene.), 7.36-7.56 m (7H, arene.), 7.76 m (2N, arene.), 9.97 (1H, NH), 10.37 (1H, NH).

Found (%): 59.50; N, 3.98; N, 14.22.

With24H20N5ClO3S

Calculated (%): 59.36; H 4.08; N, 14.18.

To a mixture of 1.0 g (2.0 mmol) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.34 g (4.2 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.11 ml (2.0 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 25-30 min, diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.89 g (91%) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-1,2,4-triazolo[1,5-a]pyrimidine. TPL280-282°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 3.90 (3H, CH3), 6.87 m (2N, arene.), 7.17 m (2N, arene.), 7.54-7.71 m (5H, arene.), 7.99 m (3H, arene.), 8.19 m (4H, arene.), 12.27 ush. s (1H, NH).

Found (%): 58.73; N, 3.51; N, 14.57.

With24H18N5ClO3S

Calculated (%): 58.60; N, 3.69; N, 14.24.

Example 6

To a mixture of 1.0 g (3.1 mmol) of 2-amino-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 5 ml of pyridine sprinkled with stirring, 0.7 g (3.1 mmol) of p-chlorobenzenesulfonamide. The reaction mixture was refluxed for 15-20 minutes, cooled to 20°and diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.8 g (52%) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL254-255°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 3.73 (3H, CH3), 5.12 (1H, CH, J=3.7), 5.97 (1H, CH, J=3.7), 6.87 m (2N, arene.), 7.11 m (2N, arene.), 7.36-7.56 m (7H, arene.), 7.76 m (2N, arene.), 9.97 (1H, NH), 10.37 (1H, NH).

Found (%): 59.50; N, 3.98; N, 14.22.

With24H20N5ClO3S

Calculated (%): 59.36; H 4.08; N, 14.18.

To a mixture of 1.0 g (2.0 mmol) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine, 0.34 g (4.2 mmol) of sodium acetate and 2 ml of acetic acid is poured 0.14 ml (2.5 mmol) of bromine. The reaction mass is stirred at a temperature of 0-25°C for 25-30 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.68 g (70%) of 2-[(4-chlorophenyl)sulfonylamino]-5-phenyl-7-(4-methoxyphenyl)-1,2,4-triazolo[1,5-a]pyrimidine. TPL280-282°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 3.90 (3H, CH3), 6.87 m (2N, arene.), 7.17 m (2H, d'aro is.), 7.54-7.71 m (5H, arene.), 7.99 m (3H, arene.), 8.19 m (4H, arene.), 12.27 ush. s (1H, NH).

Found (%): 58.73; N, 3.51; N, 14.57.

C24H18N5ClO3S

Calculated (%): 58.60; N, 3.69; N, 14.24.

Example 7

To a mixture of 1.0 g (4.4 mmol) of 2-amino-5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 5 ml of pyridine sprinkled with stirring, 1.4 g (7.5 mmol) of n-toluensulfonate. The reaction mixture is refluxed for 10-15 minutes, cooled to 20°and diluted with 10 ml of water. Precipitated amorphous precipitate is washed 2 times with water (10 ml) and filtered. Obtain 1.2 g (75%) of 2-[(4-were)sulfonylamino]-5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. TPL224-228°C.

An NMR spectrum1N, δ, ppm (J, Hz) (DMSO-d6): 1.79 (3H, CH3), 2.34 (3H, CH3), 4.50 (1H, CH, J=3.7), 5.79 (1H, CH, J=3.7), 7.07 m (2N, arene.), 7.24-7.30 m (5H, arene.), 7.63 m (2N, arene.), 9.56 (1H, NH), 10.71 (1H, NH).

Found (%): 59.74; N, 5.04; N 18.39.

C19H19N5O2S

Calculated (%): 59.83; N, 5.02; N, 18.36.

To a mixture of 1.0 g (2.6 mmol) of 2-[(4-were)sulfonylamino]-5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine and 0.44 g (5.2 mmol) of sodium acetate in 2 ml of acetic acid is poured 0.14 ml (2.6 mmol) of bromine. The reaction mass is stirred at a temperature of 35-40°C for 25-30 min, then diluted with 10 ml of water. The precipitation is filtered off. Obtain 0.6 g (61%) of 2-[(4 - were)sulfonylamino]5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine. TPL284-285°With (from a mixture of DMF/ethanol 1:5).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.36 (3H, CH3), 2.58 (3H, CH3), 7.39 m (3H, arene.), 7.63 m (3H, arene.), 7.86 m (2N, arene.), 8.00 m (2N, arene.), 11.90 ush. s (1H, NH).

Found (%): 60.19; N, 4.26; N 18.28.

C19H17N5O2S

Calculated (%): 60.14; N, 4.52; N 18.46.

The method of obtaining 2-sulfonylamino-1,2,4-triazolo[1,5-a]pyrimidines of General formula (I)

where R1represents a methyl, phenyl, 4-methylphenyl, 4-chloraniline group,

R2represents phenyl, 4-methylphenyl, 4-chloraniline, 4-metoksifenilny group,

R3represents a methyl, phenyl, 4-methylphenyl, 4-chloraniline group,

including sulfonylurea sulfochloride in the presence of pyridine,

wherein the mixture of 2-amino-4,7-dihydro-1,2,4-triazolo[1,5-a] pyrimidine of formula (II)

where R2and R3have the specified values, and pyridine is added to sulfochloride General formula (III)

where R1has the above values

when the molar ratio (II):(III)=1:1.1-1.3, the reaction mixture is refluxed, diluted with water, 2-sulfonium the on-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine of the General formula (IV)

where R1, R2and R3has the value

filtered off, mixed with acetic acid and sodium acetate, then add bromine in a molar ratio of (IV):(Br2):(CH3COONa)=1:1,00-1,05:2,1-2,2 and stirred at a temperature of 0-25°C.



 

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FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of heterocyclic compounds, which contain pyrrolo[1,2-а][1,4]diazepine fragment, annelated to aromatic and heteroaromatic ring. Method for preparation of derivatives of pyrrolo[1,2-а][1,4]diazepine of general formula I, where А =

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FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein R1 represents (C1-C4)-alkyl with branched or linear chain; R2 represents hydrogen atom (H); R3 represents (C1-C4)-alkyl with branched or linear chain; R4 represents (C1-C4)-alkyl with branched or linear chain, (C2-C4)-alkenyl; R5 represents -SO2NR10R11; R8 represents (C1-C4)-alkyl with branched or linear chain; each R10 and R11 represents independently H or (C1-C12)-alkyl with branched or linear chain; or R10 and R11 in common with nitrogen atom to which they are bound form pyrrolinone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl that are substituted optionally with (C1-C4)-alkyl with branched or linear chain, -NR14R15, phenyl group substituted optionally with -OH or phenyl group bound in common with other substituted phenyl group by carbonyl group; R13 represents (C1-C4)-alkyl with branched or linear chain, (C2-C6)-alkyl with branched or linear chain and substituted with hydroxyl; (C2-C6)-alkyl with branched or linear chain substituted with phenyl; (C2-C6)-hydrocarbon with branched or linear chain substituted with -CO2R8; wherein each radical among R14 and R15 represents independently H; (C1-C4)-alkyl with branched or linear chain, or its pharmaceutically acceptable salt. The claimed compounds possess inhibitory effect on activity of phosphodiesterase-5 and can be used for production of drug for treatment or prophylaxis of diseases associated with phospholipase and its function. Also, invention relates to pharmaceutical composition, medicinal composition for veterinary science, and intermediate compounds IA-IG used for synthesis of compound of the formula (I).

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8 cl, 2 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the general formula (I): wherein R1 is chosen from group consisting of hydrogen atom (H), -(CH2)3-, -(CH2)4-, -CH2-S-CH2-, -S-CH2-CH2-; R2 is chosen from group consisting of nitrogen (N), sulfur (S) atom; n = 0 or 1; Z is chosen from group consisting of (C2-C10)-alkyl; R3 is chosen from group consisting of H; m = 0-2; R4 is chosen from group consisting of oxygen atom (O), -CH2-; R5 is chosen from group consisting of the following groups:

wherein R6 is chosen from group consisting of H, alkyl-(C1-C5)-alkoxyl; W is chosen from group consisting of -NH wherein each "alkyl" can be linear or branched and can be also cyclic or linear, or branched and comprises such cyclic residues, and each "aryl" comprises monocyclic aromatic group comprising 5-12 carbon atoms bound with one or some heteroatoms chosen from N, O or S atoms, and to their salts and solvates. Also, invention relates to a pharmaceutical composition, to a method for their synthesis and using compounds by claims 1-6. Invention provides synthesis of novel active compounds and pharmaceutical compositions based on thereof that possess affinity to serotonin receptors of subtype 5-HT1A.

EFFECT: valuable medicinal properties of compounds, improved method of synthesis.

10 cl, 4 tbl, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compound of the general formula (I): wherein R0 represents hydrogen atom; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 can be similar or different and each represents independently hydrogen atom, halogen atom, perhalogenalkyl, substituted or unsubstituted groups, such as linear or branched (C1-C12)-alkyl, (C3-C7)-cyclaoalkyl, (C1-C12)-alkoxy, cyclo-(C3-C7)-alkoxy group, hydroxyalkyl; R13 and R14 can be similar or different and each represents independently hydrogen atom, substituted or unsubstituted groups, such as linear or branched (C1-C4)-alkyl, (C3-C7)-cycloalkyl, optionally, R13 and R14 in common with nitrogen atom can form 5-6-membered heterocyclic ring wherein heterocycle can be substituted also, and it can comprise one, two or three double bonds or "additional heteroatoms" chosen from nitrogen atom (N); "n" means a whole number in the range 1-6, and pharmaceutical compositions based on its. Indicated compounds are ligands of 5-HT (serotonin) and can be used in treatment in cases if modulation of activity of 5-HT and melatonin is desirable.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

21 cl, 31 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to novel hydrogenated pyrrolo[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers, pharmaceutically acceptable salts and/or hydrates that can be used, for example, in treatment and prophylaxis of different neurodegenerative diseases, such as Alzheimer's syndrome. In the general formula (1): a dotted line with accompanying unbroken line represents ordinary or double bond; R1 and R2 represent independently of one another substitutes of amino group chosen from hydrogen atom, possibly substituted (C1-C6)-alkyl substituted possibly with aryl, possibly substituted phenyl, possibly substituted carbonylamino or thiocarbonylamino group, substituted acyl, possibly substituted aryl sulfonate wherein substituted in indicated R1 and R2 are chosen from (C1-C6)-alkyl, halogen atoms, nitro, carboxy, alkoxy group, aryl; R1n represents one or some similar or different substituted of cyclic system chosen from hydrogen atom, alkyl, aryl, cyano group, halogen atom, 5-6-membered nitrogen-containing heteroaryl. Also, invention relates to methods for synthesis of these compounds, pharmaceutical compositions and their using, and to using compounds in libraries with their using.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved methods of synthesis.

20 cl, 2 tbl, 12 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to 1,4,5,6-tetrahydro-6-oxo-5-(2-piperazinoethyl)-4-phenyl-3-(4-chlorophenyl)pyrrolo[3.4]pyrazole dihydrochloride of the formula (I): . This compound is synthesized by interaction of 1-(2-piperazinoethyl)-5-phenyl-4-(4-chlorobenzoyl)-3-hydroxy-3-pyrrolin-2-one dihydrochloride with hydrazine hydrate. Synthesized compound can be used in medicine as agent decreasing arterial blood pressure and blood coagulation. Invention provides synthesis of a novel compound not described early that possesses hypotensive and anti-coagulant effect simultaneously.

EFFECT: valuable medicinal properties of compound.

3 tbl, 1 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention describes novel derivatives of 1,2,4-triazole of the general formula (I): wherein A and b can be taken separately or in common being when they are taken separately then A means (C1-C6)-alkyl or phenyl, and B means (C1-C6)-alkyl; A and B taken in common mean (C2-C5)-alkanediyl, and they form with C-atoms 3-6-membered cycle optionally substituted with (C1-C4)-alkylene, oxo, ethylenedioxy group, (C1-C4)-alkyl, 1-2 halogen atoms, (C1-C3)-alkoxy-(C1-C3)-alkoxy or hydroxy group; each R1 means independently hydrogen atom, -OH, halogen atom, (C3-C6)-cycloalkyl, (C1-C6)-alkyl optionally substituted with 1-3 halogen atoms; or two R1 groups near adjacent carbon atoms form 6-membered aryl cycle; R2 and R3 can be taken in common or separately, and when they are taken in common then they represent (C3-C8)-alkanediyl that forms condensed 5-10-membered nonaromatic cycle; when R2 and R3 are taken separately then R2 means (C1-C6)-alkyl possibly substituted with 1-3 halogen atoms or cyclopropyl, and R3 means cyclopropyl possibly substituted with (C1-C4)-alkyl, naphthyl, phenyl possibly substituted with halogen atom, -OH, (C1-C6)-alkyl wherein indicated (C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, -O-(C1-C6)-alkyl wherein indicated -O-(C1-C6)-alkyl is optionally substituted with 1-3 halogen atoms, phenyl or benzyloxy group, dihydrobenzofuranyl, benzothiadiazolyl or benzoimidazolyl possibly substituted with (C1-C6)-alkyl, their pharmaceutically acceptable salts or solvates, and pharmaceutical composition based on thereof. Proposed compounds are inhibitor of 11β-hydroxysteroid dehydrogenase I, and can be used in medicine in treatment of diabetes mellitus, obesity and dyslipidemia.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

19 cl, 17 tbl, 4 ex

FIELD: organic chemistry, medicine, oncology, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): or their pharmaceutically acceptable salts possessing the inhibitory effect on activity of tyrosine kinase. Proposed compounds can be used in treatment of proliferative disease, such as tumor. In the formula (I) each R1 and R2 means independently of one another hydrogen atom, methyl, ethyl, isopropyl, hydroxyethyl, piperidine-1-ylmethylcarbonyl, pyrrolidine-1-ylmethylcarbonyl, morpholine-4-ylmethylcarbonyl, 4-methylpiperazine-1-ylmethylcarbonyl, N,N-dimethylaminomethylcarbonyl, 4-ethylpiperazine-1-ylmethylcarbonyl, piperidine-1-ylethylcarbonyl, N,N-diethylaminoethylcarbonyl, N,N-dimethylaminopropylcarbonyl, 2-pyridylcarbonyl, tetrahydropyrane-4-yl, morpholine-4-ylethyl, N,N-diethylaminoethyl, tert.-butyl; or R1 and R2 in common with nitrogen atom to which they are bound form 4-ethylpiperazine-1-yl, pyrrolidine-1-yl, 4-methylpiperazine-1-yl, piperidine-1-yl, morpholine-4-yl, 3,5-dimethylpiperazine-1-yl; R3 is chosen from 3-chloro-4-fluorophenyl, phenyl, 4-benzyloxyphenyl, 3-hydroxy-4-methylphenyl, 3-hydroxy-4-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 2,5-dichlorophenyl, 3-methoxyphenyl, benzo[1,3]dioxol-5-yl, 6-methoxypyridine-3-yl, 2-methoxypyridine-4-yl, pyridine-2(1H)-one-5-yl, pyridine-2(1H)-one-4-yl, 3-methoxyphenyl, 3-methylphenyl, pyridine-2(1H)_one-4-yl; G means -CH2-; Q means -NH-; X absents or means -CH(CH3)-, -CH2- under condition that if X absents then R3 is bound by ring carbon atom. Also, invention relates to variants of methods for synthesis of compounds of the formula (I), preparing a pharmaceutical composition and using compounds proposed.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition, improved method for synthesis and preparing.

13 cl, 147 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): that are antagonists of CRF receptors and wherein Ar means optionally substituted phenyl or monocyclic 6-membered heteroaryl comprising one heteroatom chosen from nitrogen, oxygen or sulfur atoms; R1-R4 have values given in the invention claim, or to their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of indicated compounds and to pharmaceutical compositions containing these compounds that are useful for administration to a patient suffering from diseases that are relived in therapy using antagonists of CRF receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

26 cl, 10 tbl, 17 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivative of 1-[(indole-3-yl)carbonyl]piperazine of the formula (I): wherein R means substitute chosen from hydrogen atom (H), (C1-C4)-alkyl, (C1-C4)-alkyloxy-group (optionally substituted with halogen atom), halogen atom, -OH, -NH2, -CN and -NO2; R1 means (C5-C8)-cycloalkyl or (C5-C8)-cycloalkenyl; R2 means H, methyl or ethyl; radicals R3, R'3, R4, R'4, R5, R'5 and R'6 means independently hydrogen atom or (C1-C4)-alkyl optionally substituted with halogen atom or -OH; R6 means hydrogen atom or (C1-C4)-alkyl optionally substituted with (C1-C4)-alkoxy-group or halogen atom; or R6 in common with R7 forms 5-6-membered saturated heterocyclic ring; R7 means H, (C1-C4)-alkyl optionally substituted with -OH, halogen atom or (C1-C4)-alkoxy- group, or (C3-C5)-cycloalkyl, or its pharmaceutically acceptable salt. Compounds of the formula (I) possess agonistic activity with respect to CB1 receptors. Also, invention describes pharmaceutical composition possessing agonistic activity with respect to CB1 receptors and using compound of the formula (I) for preparing a drug used in pain treatment.

EFFECT: valuable medicinal and pharmacological properties of compounds and pharmaceutical composition.

9 cl, 1 tbl, 21 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to improved synthesis method of pyrlindone hydrochloride having formula (I) 1. Method features intramolecular cyclization of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole hydrochloride of formula IV 2 at 80°-140°C with alkali agent in presence of phase transfer catalyst to provide 1,2,5,6-tetrahydro-8-methyl-pyrazine[3,2,1-j,k]-4H-carbazole of formula VI 3 followed by reduction at 80°-120°C. Method of present invention makes in possible to produce compound of formula I with yield nearly 70 % and purity more than 99 %.

EFFECT: method of high yield with reduced amount of alkali agent and phase transfer catalyst.

7 cl, 2 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to novel pyrasolbenzodiazepines of formula I 1 (in formula R1 is hydrogen, -NO2, -CN, halogen, -OR5, -COOR7, -CONR8R9, -NR10R11, NHCOR12, NHSO2R13; each R2 and R4 independently of one another are hydrogen, halogen, -NO2, -CF3; R3 is hydpegen, C3-C8-cycloalkyl, aryl, in particular C6-C10-aromatic group having 1 or 2 rings, 5-10-membered heteroaryl, having 1 or 2 rings and1-3 heteroatoms, selected from N, O, and S, -COOR7, CN, C2-C6-alkenyl, -CONR8R9 or C1-C6-alkyl optionally substituted with OR9-group, F or aryl as mentioned above; R5 is C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; each independently of one another are hydrogen or C1-C6-alkyl optionally substituted with hydroxyl or NH2, or alternatively R8 and R9 together form morpholino group; each R10,R11 and R12 independently of one another are hydrogen or C1-C6-alkyl; R13 is C1-C6-alkyl optionally substituted with halogen or -NR14R15; each R14 and R15 independently of one another are hydrogen or C1-C6-alkyl optionally substituted with halogen; or alternatively -NR14R15 is morpholino group) or pharmaceutically acceptable salts thereof, as well as to certain pyrasolbenzodiazepine derivatives, thiolactam intermediates for production of compound (I) and pharmaceutical compositions containing the same. Compound and pharmaceutical composition of present invention are cycline-dependent kinase (CDK2) inhibitors and antiproliferation agents used in treatment or controlling disorders associated with cell proliferation, in particular breast, colon, lung and/or prostate tumors.

EFFECT: new antiproliferation agents.

20 cl, 12 tbl, 8 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: compounds satisfying the formula I 1 are disclosed, wherein each R1 and R2 independently to one another are H, OH, OA or Hal; or R1 and R2 together are -O-CH2-O- or -O-CH2-CH2-O-; R3 and R4 are A-group; X - group monosubstituted with R8, R5 or R7; R5 is linear or branched C1-C10-alkylene, wherein one or two CH2-groups may be substituted with oxygen atom; R7 is phenyl or phenylmethyl; R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN; F is C1-C6-alkyl; and Hal is F, Cl, Br, or I, as well as physiologically acceptable salts or solvates thereof. Methods for production of claimed compounds (I) and pharmaceutical composition containing the same also are disclosed. Said compounds and pharmaceutical composition have activity as phosphodiesterase V inhibitors and are useful in treatment of cardiovascular diseases and potency disorders.

EFFECT: pharmaceutically applicable compounds and compositions.

7 cl, 16 ex

FIELD: organic chemistry, medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to a pyrrolopyridazine derivative of the following formula: wherein R1 represents (C3-C7)-cycloalkyl-(C1-C6)-alkyl group that can be substituted optionally with (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group; R3 represents hydroxymethyl group, (C2-C6)-aliphatic acyloxymethyl group, (C6-C10)-arylcarbonyloxymethyl group, (C1-C6)-alkoxycarbonyloxymethyl group, formyl group, carboxyl group, (C1-C6)-alkoxycarbonyl group or (C6-C10)-aryloxycarbonyl group; R4 represents (C6-C10)-aryl group that can be substituted optionally with substitutes taken among the group consisting of (C1-C6)-alkyl groups, halogen-(C1-C6)-alkyl groups, (C1-C6)-alkoxy-groups, halogen-(C1-C6)-alkoxy-groups and halogen atoms; A represents imino-group, oxygen or sulfur atom, or its pharmaceutically acceptable salt. Pyrrolopyridazine derivatives elicit inhibitory activity with respect to gastric juice secretion and protective activity with respect to stomach mucosa and can be useful as a curative agent for prophylaxis or treatment of ulcer disease. Except for, invention relates to a pharmaceutical composition based on compounds of the invention and to a method for prophylaxis and treatment of ulcer disease.

EFFECT: valuable medicinal properties of compound.

25 cl, 1 tbl, 11 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention describes bicyclical nitrogen-containing heterocycles of the general formula (I): , wherein R1 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, pyridyl, naphthyl, furyl-(C1-C4)-alkyl, phenyl optionally substituted with di-(C1-C7)-alkylamino-(C1-C7)-group, halogen atom, (C1-C7)-alkoxy-group or hydroxy-(C1-C7)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group, amino-(C1-C7)-alkyl, amino-group or di-(C1-C7)-alkylamino-(C1-C7)-alkoxy-group; R2 means (C1-C7)-alkyl, (C3-C7)-cycloalkyl, furyl-(C1-C4)-alkyl, pyridyl or its N-oxide; phenyl optionally substituted with halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, hydroxy-group or trifluoromethyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group; R3 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, (C3-C7)-cycloalkenyl, pyridyl-(C1-C4)-alkyl, naphthyl, phenyl optionally substituted with phthalimido-(C1-C4)-alkyl, amino-(C1-C7)-alkyl, hydroxy-(C1-C7)-alkyl, (C1-C7)-alkylamino-(C1-C7)-alkyl, di-(C1-C7)-alkylamino-(C1-C7)-alkyl, morpholino-(C1-C4)-alkyl or piperazinyl-(C1-C4)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxycarbonyl or carboxy-group. Also, invention relates to pharmaceutically acceptable salts of compounds of the formula (I) as a base with acids or pharmaceutically acceptable salts of compounds of the formula (I) as acid with bases, and pharmaceutical composition based on thereof. Compounds described above show inhibitory activity with respect to tyrosine kinase and can be used in treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular diseases, for treatment of asthma, disorders in the central nervous system or complications associated with diabetes mellitus, or for prophylaxis against transplant rejection after surgery transplantation.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 1 tbl, 92 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (1)

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

26 cl, 1 tbl, 119 ex

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