Method for preparing r-methyl-derivatives of 3,5-diamino-1,2,4-triazole

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for synthesis of novel R-methyl-derivatives of 3,5-diamino-1,2,4-triazole of the general formula (I):

wherein R means benzene ring possibly substituted with one or some substitutes, such as branched or linear (C1-C4)-alkyl, -O-(C1-C4)-alkyl, -N-[(C1-C4)-alkyl]2, halogen atom, nitro-group; or R means naphthalene or heterocycle of the order: thiophene, furan substituted possibly with methyl group. Method is carried out by successive interaction of 1-acetyl-3,5-diamino-1,2,4-triazole (II) with sodium hydroxide, acetic acid and aldehyde of the formula: R-C(=O)H (III) and sodium boron hydride in the mole ratio of reagents (II) : sodium hydroxide : (III) : sodium boron hydride = 1:(1.0-1.2):(0.9-1.0):(1.2-2.0), respectively. Method provides decreasing the cost of compounds of the formula (I) and enhancing safety of process in their synthesis. Synthesized compounds can be used in manufacture of medicaments and biologically active substances.

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

2 cl, 13 ex

 

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

A method of obtaining alkyl derivatives of 3,5-diamino-1,2,4-triazole by heating 3,5-dichloro-1,2,4-triazole with an excess of aliphatic amine in a closed vessel at a temperature of 100-270° (H. Becker, Eisenschmidt V., K. Wehner Patent GDR 59288. MCI 07 D). The disadvantage of this method is the use of expensive and hard-to-reach 3,5-dichloro-1,2,4-triazole, the need for synthesis at high pressure and associated risk process.

A method of obtaining alkyl derivatives of 3,5-diamino-1,2,4-triazole interaction hydrobromide N-alkyl-S-utilizationfocused with allylisothiocyanate, formed by alkylation of alkyl derivatives of isothiourea ethyl iodide with the formation of alkyl derivatives of diazolidinylurea and subsequent boiling of these compounds with hydrazinehydrate (Dukes M. Application No. 1946315 patent Germany. Chem. Abstr. 1970. Vol.73. 25482d). The disadvantage of this method is the use of expensive N-alkyl-S-utilizationfocused and toxic allylisothiocyanate.

A method of obtaining 3-amino-5-alkylamino-1,2,4-triazoles alkaline cyclization of 3-isopropylideneuridine-1-alkylthiomethyl (Blank Century, D.M. Nichols, P.D. Vaidya Synthesis of 1,2,4-triazoles as potentil hypoglycemic agents // J. Med. Chem. 1972. Vol.15. No. 6. P.694-696). The disadvantage of this method is the use of difficult and expensive 3-isopropylideneuridine-1-alkylthiomethyl obtained by condensation isopropylideneuridine with toxic and expensive allylisothiocyanate.

A method of obtaining 5-amino-3-(2-mercaptoethylamine)-1,2,4-triazole by the interaction of 2-renominalisation with hydrazine (U.S. Patent 5028716, MKI 07 D 249/08). The disadvantage of this method is the possibility of obtaining only mercaptoethylamine 3,5-diamino-1,2,4-triazole, namely compounds of formula (I), in which the substituent R may be the only group CH2SH.

The closest technical result is a method for alkyl derivatives of 3,5-diamino-1,2,4-triazole by reacting dimethyl ether of cyanocarbonimidate (dimethylcarbamodithioato) alliteratively, the obtained reaction of the methyl esters of N-cyano-1-methyl-2-airlinereservations.com with aliphatic amines and subsequent cyclization of the resulting intermediates in the presence of hydrochloric acid or by the reaction of dimethyl ether cyanocarbonimidate (dimethylcarbamodithioato) with aliphatic amines with subsequent interaction of the formed N-cyano-N'-alkyl-S-methylisothiazoline with hydrazine U.S. Patent 4764612, MCI 07 D 295/012). The disadvantage of this method is the use of expensive dimethyl ether cyanocarbonimidate (dimethylcarbamodithioato), the complexity of the isolation and purification of intermediate products, the selection process for the synthesis of toxic mercaptan.

The objective of the invention is a cheaper way of getting alkyl derivatives of 3,5-diamino-1,2,4-triazole of the General formula (I) and increase security through the use of cheaper raw materials and exclusion from the process operations that require the use of high pressure or associated with the release of toxic gaseous products.

This object is achieved in that a suspension of 1-acetyl-3,5-diamino-1,2,4-triazole (II) in a lower aliphatic alcohol poured an aqueous solution of sodium hydroxide, the reaction mixture is heated under stirring at a temperature of 50-100°until complete homogenization, then neutralized with acetic acid to a pH of 7-9 and added the aldehyde (III), where R has the above significance, is stirred at a temperature of 50-100°then added in portions of borohydride sodium and continue mixing at a temperature of 50-100°s, and the process is conducted the next time a molar ratio of reagents: (II):sodium hydroxide:(III):sodium borohydride 1:(1,0-1,2):(0,9-1,0):(1,2-2,0).

In the present method ot the men expensive dimethyl ether cyanocarbonimidate uses cheap raw materials - 1-acetyl-3,5-diamino-1,2,4-triazole (II), which can be obtained by a known method (Patent of Russia 2148579. MCI 07 In 249/14). This allows to reduce the cost of target products. All manufacturing operations are carried out at atmospheric pressure during synthesis is not toxic gaseous products, which increases process safety. Specified in the invention the temperature interval from 50 to 100°C is optimal. At lower temperatures the process is too slow, and occurs at higher yield due to the occurrence of adverse reactions. The molar ratio of (II):NaOH:(III):NaBH4=1:(1.0-1.2):(0.9-1.0):(1.2-2.0) is optimal, the change results in the reduction of the yield of the target product, or to incomplete consumption of one of the reagents and economically feasible.

The method is as follows:

1-Acetyl-3,5-diamino-1,2,4-triazole (II) are suspended in an aliphatic alcohol (methanol, ethanol, isopropanol or other) and the suspension poured an aqueous solution of sodium hydroxide based 1-1 .2 mol NaOH 1 mol of compound (II), the reaction mixture is stirred at a temperature of 50-100°With (depending on the boiling point of ethanol) until complete dissolution (II). This is accompanied by hydrolysis of compound (II) with the formation of water-alcohol solution of 3,5-diamino-1,2,4-triazole and ACET is the sodium. The mixture is then neutralized with acetic acid, was added the aldehyde (III) of 0.9-1.0 mol of aldehyde to 1 mol of starting compound (II) and stirred at a temperature of 50-100°With (depending on the boiling point of ethanol) for 10-20 minutes. At this stage, is the condensation of 3,5-diamino-1,2,4-triazole with aldehyde and formation of a solution or suspension of the corresponding Schiff bases. Next, to the reaction mixture under stirring at a temperature of 50-100°gradually add to borohydride sodium within 10-20 minutes from the calculation of 1.2-2.0 mol NaBH41 mol (II), then stirred at this temperature for another 20 minutes. When this occurs, the hydrogenation of the Schiff bases and the formation of R-methylpropanol 3,5-diamino-1,2,4-triazole. The reaction mixture was evaporated, diluted with water, the precipitation is filtered off and recrystallized. Get the compound of General formula (I).

Example 1

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 50 ml of ethanol is poured with stirring, a solution of 4.8 g (0.12 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 65-75°until complete homogenization (10-15 min), then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring 10.1 g (0.09 mol) of thiophene-2-carboxaldehyde. The reaction mixture is stirred at a temperature of 65-75°10 minutes for the eat portions add 4.56 g (0.12 mol) of sodium borohydride in 10 minutes, stirred at a temperature of 75°20 minutes and then evaporated to small volume. To the residue add 30 ml of water and the resulting solution evaporated twice, cooled, precipitated precipitate is filtered off. Obtain 9.8 g (50%) of 5-amino-3-thiophene-2-ylmethylamino-1,2,4-triazole. TPL=138-139° (of water).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.35 (2H, CH2, J=5.8), 5.63 of user. (2H, NH2), 5.81 of user. s (1H, NH), 6.91 m (2H, CH), 7.30 m (1H, CH), 10.7 (1H, NH).

Found (%): 43.13; N, 4.62; N 36.00.

C7H9N5S.

Calculated (%): 43.06; H 4.65; N 35.87.

Example 2

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 50 ml of ethanol is poured with stirring, a solution of 4.8 g (0.12 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 65-75°until complete homogenization (10-15 min), then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 13.6 g (0.1 mol) of 4-methoxybenzaldehyde in 10 ml of ethanol. The reaction mixture is stirred at a temperature of 65-75°With 15 minutes, then added in several portions 7.60 g (0.2 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 75°20 minutes and then add 30 ml of water and the reaction mixture was evaporated to small volume. To the residue add an additional 30 ml of water and the resulting precipitate is filtered off. Obtain 16.7 g (76%) of 5-amino-3-pair-label is benzylamino-1,2,4-triazole. TPL=194-196°C (from ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 3.69 (3H, och3), 4.11 (2H, CH2, J=6.5), 5.37 of user. (2H, NH2), 5.85 of user. s (1H, NH), 6.82 (2H, arene., J=8.6), 7.21 (2H, arene., J=8.6), is 10.68 (1H, NH).

Found (%): 54.70; N, 5.99; N 32.00.

With10H13N5O.

Calculated (%): 54.78; N, 5.98; N 31.94.

Example 3

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of methanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 65°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 13.6 g (0.09 mol) of 3-nitrobenzaldehyde in 30 ml of methanol. The reaction mixture is stirred at a temperature of 65°With 15 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 65°20 minutes, evaporated twice and add 60 ml of water. The precipitation is filtered off and get 14.5 g (62%) of 5-amino-3-meta-nitrobenzylamine-1,2,4-triazole. TPL=178-180°C (from ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.31 (2H, CH2, J=5.9), 5.65 of user. (2H, NH2), 6.16 of user. s (1H, NH), 7.57 m (1H, arene.), 7.76 m (1H, arene), 8.04 m (1H, arene), 8.17 (1H, arene), 10.71 (1H, NH).

Found (%): 46.18; N, 4.32; N 36.00.

C9H10N6About2.

Calculated (%): 4615; H 4.30; N 35.88.

Example 4

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 16.6 g (0.09 mol) of meta-bromobenzaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°With 15 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and get 16.73 g (78%) of 5-amino-3-meta-bromobenzylamine-1,2,4-triazole. TPL=207-208°With (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.19 (2H, CH2, J=6.4), 5.42 of user. (2H, NH2), 6.15 of user. s (1H, NH), 7.25 m (2N, arene.), 7.37 m (1H, arene), 7.47 (1H, arene), 10.73 of user. s (1H, NH).

Found (%): 40.3; N, 3.9; N 26.00.

C9H10BrN5.

Calculated (%): 40.32; N, 3.76; N 26.12.

Example 5

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 50 ml of ethanol is poured with stirring, a solution of 4.8 g (0.12 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 65-75°until complete homogenization (10-15 min), then neutralize the UKS the red acid to a pH of 7-9, and added dropwise with stirring a solution of 16.6 g (0.1 mol) of 3,4-dimethoxybenzaldehyde in 10 ml of ethanol. The reaction mixture is stirred at a temperature of 65-75°With 15 minutes, then added in several portions 7.60 g (0.2 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 75°20 minutes, then add 30 ml of water and the reaction mixture was evaporated to small volume. To the residue add an additional 30 ml of water and the resulting precipitate is filtered off. Obtain 17.5 g (70%) of 5-amino-3-(3,4-dimethoxyphenethylamine)-1,2,4-triazole. TPL=238-240°C (from ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 3.69 (3H, CH3), 3.70 (3H, CH3), 4.11 (2H, CH2, J=6.4), 5.50 of user. (3H, NH+NH2), 6.82 m (2N, arene.), 6.92 (1H, arene), 10.70 of user. s (1H, NH).

Found (%): 53.14; H 6.20; N 27.99.

C11H15N5O2.

Calculated (%): 53.00; H 6.07; N 28.09.

Example 6

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 50 ml of ethanol is poured with stirring, a solution of 4.8 g (0.12 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 65-75°until complete homogenization (10-15 min), then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring 9.9 g (0.09 mol) of 5-methylfuran-2-carboxaldehyde. The reaction mixture is stirred at a temperature of 65-75°10 minutes, then added in several portions 4.56 g (0.12 mol) of sodium borohydride for 10 minutes, stirred at a temperature of 75°20 minutes and then UPrev the Ute to a small volume. To the residue add 30 ml of water and the resulting solution evaporated twice, cooled, precipitated precipitate is filtered off. Obtain 10.4 g (60%) of 5-amino-3-(5-methylfuran-2-yl)methylamino-1,2,4-triazole. TPL=15-117° (of water).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.28 (3H, CH3), 4.35 (2H, CH2, J=5.6), 5.60 of user. (2H, NH2), 5.82 of user. s (1H, NH), 5.90 m (1H, arene.), 6.21 (1H, arene.), 10.5 c (1H, NH).

Found (%): 48.01; N, 5.80; N 36.00.

C8H11N5O.

Calculated (%): 49.73; N, 5.74; N 36.25.

Example 7

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 14.0 g (0.09 mol) of 1-naphthaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°30 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and obtain 15.5 g (72%) of 5-amino-3-(1-naphthyl)methylamino-1,2,4-triazole. TPL=118-120°With (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.28 (2H, CH2, J=6.0), 5.38 of user. C (N, NH2), 6.05 of user. s (1H, NH), 7.40-8.18 m (7H, arene.), 10.70 user. s (1H, NH).

Found (%): 65.50; N, 5.50; N 29.00.

C13H13N5.

Calculated (%): 65.26; N, 5.48; N 29.27.

Example 8

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 10.8 g (0.09 mol) of meta-methylbenzaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°20 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and obtain 15.0 g (82%) of 5-amino-3-meta-methylbenzylamino-1,2,4-triazole. TPL=175-176°C (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.31 (3H, CH3), 4.17 (2H, CH2, J=6.4), 5.42 of user. (2H, NH2), 6.15 of user. s (1H, NH), 7.02-7.18 m (4H, arene.), 10.71 user. s (1H, NH).

Found (%): 59.10; H 6.50; 34.41.

C10H13N5.

Calculated (%): 59.10; N, 6.45; N 34.46.

Example 9

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 m is l) of NaOH in 10 ml of N 2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution 13.32 g (0.09 mol) of para-isopropylbenzaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°30 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and get 16.22 g (78%) of 5-amino-3-para-isopropylbenzylamine-1,2,4-triazole. TPL=125-127°With (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 1.20 (6N, 2CH3), 2.81 m (1H, CH), 4.20 (2H, CH2, J=6.2), 5.42 of user. (2H, NH2), 6.15 of user. s (1H, NH), 7.13 (2H, arene., J=8.0), 7.31 (2H, arene., J=8.0), 10.80 of user. s (1H, NH).

Found (%): 62.41; N, 7.28; N 30.31.

C12H17N5.

Calculated (%): 62.31; N, 7.41; N 30.28.

Example 10

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution 13.41 g (0.09 mol) of para-dimethylaminobenzaldehyde in 30 ml of ethanol is. The reaction mixture is stirred at a temperature of 75-80°30 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and get 14.82 g (71%) of 5-amino-3-(para-dimethylaminophenyl)amino-1,2,4-triazole. TPL=174-176°With (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 2.89 (6N, 2CH3), 4.20 (2H, CH2, J=6.4), 5.40 of user. (2H, NH2), 6.10 user. s (1H, NH), 6.63 (2H, arene., J=8.0), 7.20 (2H, arene., J=8.0), 10.72 of user. s (1H, NH).

Found (%): 56.90; N, 6.88; N 36.22.

With11H16N6.

Calculated (%): 56.88; N, 6.94; N 36.18.

Example 11

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 9.54 g (0.09 mol) of benzaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°20 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation of Otti throwaway and obtain 9.4 g (55%) of 5-amino-3-benzylamino-1,2,4-triazole. TPL=147-148°C (from ethanol).

An NMR spectrum1N,δ 5, ppm (DMSO-d6): 4.20 (2H, CH2, J=6.2), 5.32 of user. (2H, NH2), 6.09 of user. s (1H, NH), 7.17-7.28 m (5H, Ph), 10.72 (1H, NH).

Found (%): 57.21; H 5.90; N 36.89.

C9H11N5.

Calculated (%): 57.13; H 5.86; N 37.01.

Example 12

To a suspension of 14.1 g (0.1 mol) of 1-acetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 12.65 g (0.09 mol) of para-chlorobenzaldehyde in 30 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°30 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and obtain 13.1 g (65%) of 5-amino-3-para-chlorobenzylamino-1,2,4-triazole. TPL=193-194°With (from a mixture of DMF/ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.18 (2H, CH2, J=6.3), 5.50 of user. (2H, NH2), 6.0 of user. s (1H, NH), 7.26-7.35 m (4H, arene.), 10.7 user. s (1H, NH).

Found (%): 48.41; N, 4.58; N 31.37.

C9H10N5Cl.

Calculated (%): 48.33; H 4.51; N 31.31.

Example 13

To a suspension of 14.1 g (0.1 mol) 1-is cetyl-3,5-diamino-1,2,4-triazole in 60 ml of ethanol is poured with stirring, a solution of 4.4 g (0.11 mol) of NaOH in 10 ml of N 2O. the Reaction mixture is stirred at a temperature of 75-80°until complete homogenization, then neutralized with acetic acid to a pH of 7-9, and added dropwise with stirring a solution of 11.2 g (0.09 mol) of para-forventelige in 20 ml of ethanol. The reaction mixture is stirred at a temperature of 75-80°20 minutes, then added in several portions 5.7 g (0.15 mol) of sodium borohydride for 20 minutes, stirred at a temperature of 50-65°20 minutes, evaporated to small volume and add 60 ml of water. The precipitation is filtered off and obtain 11.2 g (60%) of 5-amino-3-para-forbindelsen-1,2,4-triazole. TPL=164-166°C (from ethanol).

An NMR spectrum1N, δ, ppm (DMSO-d6): 4.22 (2H, CH2, J=6.0), 5.62 of user. (2H, NH2), 6.0 of user. s (1H, NH), 6.98 m (2N, arene.), 7.33 m (2N, arene.), 10.6 user. c (1H, NH).

Found (%): 52.09; N, 4.88; N 33.60.

C9H10N5F.

Calculated (%): 52.17; H 4.86; N 33.80.

The method of obtaining R-methylpropionic 3,5-diamino-1,2,4-triazole of the General formula (I),

where R is a benzene ring, possibly substituted by one or more substituents, such as branched or non-branched (C1-C4)-alkyl, O-(C1-C4)-alkyl, N((C1-C4)-alkyl)2, halogen, nitro, or R is naphthalene or a heterocycle from the series of thiophene, furan, possibly replacing the military methyl group,

wherein the suspension of 1-acetyl-3,5-diamino-1,2,4-triazole (II)

in a lower aliphatic alcohol poured an aqueous solution of sodium hydroxide, the reaction mixture is heated under stirring at a temperature of 50-100°until complete homogenization, then neutralized with acetic acid to a pH of 7-9 and added the aldehyde (III)

where R has the above values

stirred at a temperature of 50-100°then added in portions of borohydride sodium and continue mixing at a temperature of 50-100°s, and the process is conducted at the following molar ratio of reagents:

(II) : sodium hydroxide : (III) : sodium borohydride 1 : (1,0-1,2) : (0,9-1,0) : (1,2-2,0).



 

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SUBSTANCE: compound is represented by structural formula

or its pharmaceutically permissible salts, where R1 is the hydrogen atom (1), C1-8acyl(2), hydroxyl (3), halogen atom (5), C2-8acyl (3), C1-8-alcocsy (4), substituted with phenyl or C2-8acyl, substituted with NR2R3; R2R3 independently represent hydrogen atom (1) or C1-8acyl(2), X and Y each independently representing C (1), CH (2) or N (3). is (1) single or (2) double bond. is 5-7-member carbocyclic group or 5-7-member partially or fully saturated heterocyclic group defined in claim 1 of invention. A is one of A1 to A5 groups defined by claim 1 of the invention. The compounds show inhibiting properties relative to poly(ADP-ribose)polymerase are usable as prophylactic and/or curative drugs for treating ischemic diseases (in brain, spinal cord, heart, digestive tract, skeletal muscle, eye retina, e.t.c.), inflammatory diseases (intestinal inflammation, disseminated sclerosis, arthritis, e.t.c.), neurodegenerative disorders (extrapyramidal disorder, Alzheimer disease, muscle dystrophy, cerebrospinal canal stenosis in lumbar segment of the vertebral column, e.t.c.), diabetes, stroke, cerebral injury, hepatic insufficiency, hyperalgesia, e.t.c. The compounds are also of use in struggling against retroviruses (HIV and others), as sensitizing agents for treating cancer cases and immunodepressant agents.

EFFECT: enhanced effectiveness of treatment.

19 cl, 90 tbl

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel C-2'-methylated derivatives of paclitaxel of the formula (I): wherein R represents trifluoromethyl group, phenyl, 2-furyl, 2-thienyl; R1 represents tert.-butoxycarbonyl or benzoyl group; R2 represents hydroxy-group; R3 means hydrogen atom or in common with R2 forms residue of cyclic carbonate of the formula: under condition that when R3 means hydrogen atom then R is not phenyl. Also, invention relates to a pharmaceutical composition based on thereof and using for preparing medicinal agents possessing an antitumor activity. Invention provides preparing novel derivatives of paclitaxel that possess antitumor activity.

EFFECT: valuable medicinal property of derivatives and pharmaceutical composition.

4 cl, 1 tbl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compound of the formula (IA) wherein X means -NH; R5a represents optionally substituted 5-membered heteroaromatic ring chosen from the group of the following formulae: (a) (b) (c) (d) (e) (f) (g) (h) (i) or (j) wherein * means the addition position to the group X in the formula (IA); R60 and R61 from group of the formula (k) wherein p and q mean independently 0 or 1; R1' and R1'' represent independently hydrogen atom, hydroxy-group wherein T represents C=O, sulfur atom (S), -C(=NOR)CO, -C(O)C(O) wherein R represents hydrogen atom, (C1-C6)-alkyl and phenyl; V represents independently hydrogen atom, hydroxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy-, (C2-C6)-alkenyloxy-group, trifluoromethyl, phenyl optionally substituted with (C1-C6)-alkoxy- or (C1-C6)-alkanoyloxy-group or (C3-C7)-cycloalkyl; or V represents -N(R63)R64 wherein one of R63 and R64 is chosen independently from hydrogen atom, (C1-C10)-alkyl optionally substituted with hydroxy-group, (C1-C6)-alkoxycarbonyl and (C1-C6)-alkoxyl; and (C2-C6)-alkenyl and another represents (C1-C6)-alkyl optionally substituted 1 or 2 with (C1-C4)-alkoxyl, cyano-group, (C1-C4)-alkoxycarbonyl, (C2-C4)-alkanoyloxy- or hydroxy-group; heteroaryl-(C1-C6)-alkyl wherein heteroaryl represents 5-6-membered ring comprising 1-2 heteroatoms chosen from oxygen (O), sulfur (S) and nitrogen (N) atoms and optionally substituted with (C1-C6)-alkyl; phenyl or phenyl-(C1-C6)-alkyl optionally substituted with 1, 2 or 3 groups chosen from halogen atom, N,N-di-(C1-C6)-alkyl)-amino-, N-(C1-C6)-alkyl)-amino-, (C1-C6)-alkoxy-group, (C2-C6)-alkanoyl, trifluoromethyl, cyano-group, (C1-C6)-alkyl optionally substituted with hydroxy- or cyano-group, carbamoyl, hydroxy-, trifluoromethoxy-, nitro-, (C1-C6)-alkylthio-, amino-group, -O-(C1-C3)-alkyl-O- and (C1-C6)-alkylcarbonyl; heteroaryl chosen from pyridyl, furanyl and indolyl optionally substituted with 1 or 2 hydroxy-groups, halogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; (C3-C7)-cycloalkyl or (C3-C7)-cycloalkyl-(C1-C6)-alkyl optionally substituted with hydroxy-group; or R63 and R64 in common with nitrogen atom to which they are bound form 5-6-membered ring that can comprise additionally heteroatom N or O and can be optionally substituted with (C1-C6)-alkyl, hydroxy-group, hydroxy-(C1-C6)-alkyl or carbamoyl; R62 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl or carbamoyl; R1' represents hydrogen atom; R2' represents (C1-C5)-alkoxy-group; R3' represents -X1R9 wherein X1 represents -O- and R9 is chosen from the following groups: (1) (C1-C5)-alkyl; (2) (C1-C5)-alkyl-X3R20 wherein X3 represents -NR25- wherein R25 represents hydrogen atom or (C1-C3)-alkyl; R20 represents (C1-C3)-alkyl, cyclopentyl and (C1-C3)-alkyl group can comprise 1 or 2 substitutes chosen from oxo-, hydroxy-group, halogen atom and (C1-C4)-alkoxy-group; (3) represents (C1-C5)-X4-(C1-C5)-alkyl-X5R26 wherein each among X4 and X5 represents -NR31- wherein R31 represents hydrogen atom or (C1-C3)-alkyl; R26 represents hydrogen atom or (C1-C3)-alkyl; (4) (C1-C5)-alkyl-R32 wherein R32 represents 5-6-membered saturated heterocyclic group bound through carbon or nitrogen atom with 1-2 heteroatoms chosen independently from O and N and wherein heterocyclic group can comprise 1 or 2 substitutes chosen from hydroxy-group, (C1-C4)-alkyl and (C1-C4)-hydroxyalkyl; (5) (C1-C3)-alkyl-X9-(C1-C3)-alkyl-R32 wherein X9 represents -NR57- wherein R57 represents hydrogen atom or (C1-C3)-alkyl and R32 is given above; R4' represents hydrogen atom; or to its pharmaceutically acceptable salts. Compounds are inhibitors of kinase aurora 2 and can be used for preparing a medicinal agent used in treatment of proliferative diseases, in particular, in cancer treatment. Except for, invention relates to a pharmaceutical composition possessing the abovementioned activity and a method for preparing compounds of the formula (IA).

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

14 cl, 30 tbl, 477 ex

FIELD: organic chemical, pharmaceuticals.

SUBSTANCE: invention relates to new compounds having JAK3 kinase inhibitor activity, methods for production thereof, intermediates, and pharmaceutical composition containing the same. In particular disclosed are aromatic 6,7-disubstituted 3-quinolinecarboxamide derivatives of formula I and pharmaceutically acceptable salts thereof useful in production of drugs for treatment of diseases mediated with JAK3. In formula n = 0 or 1; X represents NR3 or O; Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrasolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indasolyl, wherein each residue may be substituted with one or more groups selected from halogen, hydroxy, cyano, C1-C8-alkoxy, CO2R8, CONR9R10 C1-C8-alkyl-O-C1-C8-alkyl, etc., wherein R-groups are independently hydrogen atom or C1-C8-alkyl; meanings of other substitutes are as define in description.

EFFECT: new compounds having value biological properties.

17 cl, 222 ex

FIELD: organic chemistry, medicine, virology, pharmacy.

SUBSTANCE: invention relates to new non-nucleoside inhibitors of reverse transcriptase activity of the formula (1): wherein R1 represents oxygen atom (O), sulfur atom (S); R2 represents optionally substituted nitrogen-containing heterocycle wherein nitrogen atom is at position 2 relatively to the bond with (thio)urea; R3 represents hydrogen atom (H), (C1-C3)-alkyl; R4-R7 are chosen independently from hydrogen atom (H), (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, halogen-(C1-C6)-alkyl, (C1-C6)-alcanoyl, halogen-(C1-C6)-alcanoyl, (C1-C6)-alkoxy-, halogen-(C1-C6)-alkoxy-group, hydroxy-(C1-C)-alkyl, cyano-group, halogen atom, hydroxy-group; X represents group of the formula: -(CHR8)-D-(CHR8)m- wherein D represents -O or -S-; R8 represents hydrogen atom (H); n and m represent independently 0, 1 or 2, and to its pharmaceutically acceptable salts. Also, invention relates to a pharmaceutical composition based on these compounds possessing inhibitory effect with respect to activity of HIV-1 reverse transcriptase, and to using these compounds in preparing medicinal agents used in treatment of HIV-1 and to intermediates compounds.

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

45 cl, 1 tbl, 57 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of aminoquinoline and aminopyridine. Invention describes compounds of the general formula (I): wherein R1 means hydrogen atom or direct or branched (C1-C4)-alkyl group; R2 means hydrogen atom or direct or branched (C1-C4)-alkyl group; R3 means hydrogen atom or direct or branched (C1-C4)-alkyl group or phenyl group, thienyl group or furyl group optionally substituted with one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group or halogen atom; R4 and R5 form in common 1,3-butadienyl group optionally substituted with methylenedioxy-group or one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group, hydroxy-group or halogen atom; R6 means hydrogen atom or cyano-group; R7 means hydrogen atom or direct or branched (C1-C4)-alkyl group, phenyl group, benzyl group, thienyl group, or furyl group optionally substituted with methylenedioxy-group or one or more direct or branched (C1-C4)-alkyl group, direct or branched (C1-C4)-alkoxy-group, hydroxy-group, trifluoromethyl group, cyano-group or halogen atom; X means -NH-group, -NR8-group or sulfur atom, or oxygen atom, or sulfo-group, or sulfoxy-group wherein R8 means direct or branched (C1-C4)-alkyl group or (C3-C6)-cycloalkyl group; n = 0, 1 or 2, and their salts. Also, invention describes a method for preparing compounds of the formula (I). a pharmaceutical composition based on thereof, using compounds of the formula (I) as antagonists of A3 receptors for preparing a pharmaceutical composition used in treatment of different diseases (variants), compounds of the formula (IA), (II), (III) and (IV) given in the invention description. Invention provides preparing new compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

15 cl, 6 tbl, 6 dwg, 172 ex

FIELD: organic chemistry, chemical technology, medicine, veterinary science.

SUBSTANCE: invention describes the compound R-(-)-1-[2-(7-chlorobenzo[b]thiophene-3-ylmethoxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole of the formula (I) and its salts, in particular, its mononitrate. Also, invention relates to a method for preparing compound of the formula (I) possessing antifungal effect based on compound of the formula (I), and using compound of the formula (I) as an active component of the antifungal composition. Compound of the formula (I) can be used in compositions for treatment of fungal infections in humans or animals and against diseases of agricultural crops.

EFFECT: improved preparing method, valuable properties of compound and composition.

15 cl, 1 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of diphenylazathedinone of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another (0-C30)-alkylene-L wherein one or some C-atoms of alkylene residue can be substituted with -O-, -(C=O)- or -NH- and, except for, R1-R6 can represent hydrogen atom (H), fluorine atom (F), and L represents compound of the formula: , and their pharmaceutically tolerated salts also. Compounds of the formula (I) elicit hypolipidemic effect and can be used in therapeutic aims. Also, invention describes a medicinal agent and its using.

EFFECT: valuable medicinal properties of compounds.

7 cl, 31 ex

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

SUBSTANCE: invention relates to new biologically active heterocyclic retinoid compounds. Invention describes retinoid compounds corresponding to the formula (I): or their pharmaceutically acceptable salts, solvates or hydrates wherein n means a whole number from 0 to 2; A represents optionally substituted phenyl; B represents oxygen (O), sulfur (S) atom or -NR6 wherein R6 represents hydrogen atom or alkyl; Y represents -OR7 wherein R7 represents hydrogen atom, alkyl, optionally substituted phenyl, aralkyl wherein aryl fragment means optionally substituted phenyl, cycloalkyl or cycloalkylalkyl; Z represents -C(R101)2-, -R102C=CR102-, -C≡C-, -C(R103)2S-, -C(O)O- or -C(O)NR10- wherein each among R10, R101, R102 and R103 represents independently hydrogen atom or alkyl; R1 and R2 represent independently hydrogen atom or alkyl; R3 represents hydrogen atom or alkyl; R4 and R5 represent independently hydrogen atom, (C1-C8)-alkyl or arylalkyl wherein aryl fragment means optionally substituted phenyl. Also, invention describes methods for preparing retinoid compounds, a pharmaceutical composition based on thereof and a method for treatment and/or prophylaxis of respiratory ways obstructive disease, cancer or dermatological disturbance or disorder. Invention provides preparing new compounds possessing useful biological properties.

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

28 cl, 10 tbl, 16 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to (2S)-N-{5-[amino(imino)methyl]-2-thienyl}methyl-1-{(2R)-2-[(carboxymethyl)amino}-3,3-diphenylpropanoyl}-2-pyrrolidine carboxamide maleate of the formula (1): . Also, invention relates to a method for preparing this compound by interaction of free compound of the formula (1) with maleic acid in the presence of organic solvent. This salt can be used as thrombin inhibitor.

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

4 cl, 2 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: compound is represented by structural formula

or its pharmaceutically permissible salts, where R1 is the hydrogen atom (1), C1-8acyl(2), hydroxyl (3), halogen atom (5), C2-8acyl (3), C1-8-alcocsy (4), substituted with phenyl or C2-8acyl, substituted with NR2R3; R2R3 independently represent hydrogen atom (1) or C1-8acyl(2), X and Y each independently representing C (1), CH (2) or N (3). is (1) single or (2) double bond. is 5-7-member carbocyclic group or 5-7-member partially or fully saturated heterocyclic group defined in claim 1 of invention. A is one of A1 to A5 groups defined by claim 1 of the invention. The compounds show inhibiting properties relative to poly(ADP-ribose)polymerase are usable as prophylactic and/or curative drugs for treating ischemic diseases (in brain, spinal cord, heart, digestive tract, skeletal muscle, eye retina, e.t.c.), inflammatory diseases (intestinal inflammation, disseminated sclerosis, arthritis, e.t.c.), neurodegenerative disorders (extrapyramidal disorder, Alzheimer disease, muscle dystrophy, cerebrospinal canal stenosis in lumbar segment of the vertebral column, e.t.c.), diabetes, stroke, cerebral injury, hepatic insufficiency, hyperalgesia, e.t.c. The compounds are also of use in struggling against retroviruses (HIV and others), as sensitizing agents for treating cancer cases and immunodepressant agents.

EFFECT: enhanced effectiveness of treatment.

19 cl, 90 tbl

FIELD: chemistry of polymers, chemical technology.

SUBSTANCE: invention relates to sulfoxides or sulfones grafted on polymers, polymeric compositions, a method for grafting and method for stabilization of polymers. Invention describes polymers comprising a grafted compound of the formula (I): [R1-SOm]n-R-SOp-R2 (I) wherein total symbols have values given in cl. 1 of the invention claim and represents a composition comprising thereof, a method for grafting compound of the formula (I) on polymers and a method for stabilization of polymers. Polymers comprising grafted sulfoxides or sulfones possess high stability against oxidative, thermal, dynamic destruction caused by the light effect and/or destruction caused by ozone effect.

EFFECT: improved preparing method, improved and valuable properties of polymers.

14 cl, 14 tbl, 24 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chromane of the formula (I): and its salts. Method involves direct reaction of 5-(4-fluorophenyl)pyridine-3-carbaldehyde of the formula (II): with 2-aminomethylchromane or its salts under reductive conditions resulting to formation of compound of the formula (I). Synthesized compound of the formula (I) is converted to one of its salts by treatment with acid. Method provides simplifying process based on decreasing amount of by-side products formed.

EFFECT: improved method of synthesis.

8 cl, 2 dwg, 4 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 2-cyano-4-fluoropyrrolidine of the formula (I): or its pharmaceutically acceptable salt wherein A represents group of the general formula (II): wherein B represents carbonyl or sulfonyl group; R1 represents (C1-C6)-alkyl that can be optionally substituted with group chosen from the group comprising -OH or atoms of fluorine, chlorine, bromine or iodine, phenyl optionally substituted with -CN or morpholinyl group, or if B represents carbonyl then R1 can mean hydrogen atom; R2 represents (C1-C6)-alkyl optionally substituted with hydroxyl group or hydrogen atom. Compounds of the formula (I) are inhibitors of enzyme dipeptidyl peptidase IV that allows its using in pharmaceutical composition that is designated for treatment of insulin-dependent diabetes mellitus (diabetes of type 1), non-insulin-dependent diabetes mellitus (diabetes of type 2), diseases associated with resistance to insulin or obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 8 tbl, 11 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new benzofuran derivatives of formula 1 , wherein X represents group of formula -N= or -CH=; Y represents optionally substituted amino group, optionally substituted cycloalkyl group, or optionally substituted saturated heterocycle; A represents direct bond, carbon chain optionally containing double bond in molecular or in the end(s) thereof, or oxygen atom; R1 represents hydrogen, halogen, lower alkoxy, cyano, or amino optionally substituted with lower alkyl B represents optionally substituted benzene ring of formula ; and R2 represents hydrogen or lower alkyl; or pharmaceutically acceptable salt thereof. Invention also relates to pharmaceutical composition containing abovementioned compounds, uses thereof and method for thrombosis treatment.

EFFECT: new compounds for thrombosis treatment.

27 cl, 2 tbl, 429 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to benzamide derivatives possessing with inhibitory activity with respect to tyrosine kinase Flt-1-receptors VEGF that can be used in treatment of neoplastic disease. Invention describes a pharmaceutical substance comprising compounds of the group 2-[(4-pyridyl)methyl]-amino-N-[R1]-benzamide wherein R1 means 4-chlorophenyl, 4-methylphenyl, 4-chloro-3-(trifluoromethyl)phenyl or 3-(trifluoromethyl)phenyl possessing with the inhibitory activity with respect to tyrosine kinase Flt5-2-receptors VEGF associated with neoplastic disease and angiogenesis. Also, invention describes novel compounds of the group 2-[(nitrogen-containing heterocycle)methyl]-amino-N-[R1]-benzamide wherein nitrogen-containing heterocycle is represented by 4-pyrodyl, 4- or 5-quinolinyl, 2-imidazolyl, and a method for their synthesis. Also, invention describes a pharmaceutical composition comprising abovementioned compounds possessing the inhibitory activity with respect to tyrosine kinase VEGF receptors used in treatment of neoplastic disease.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 74 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 2-phenylaminoimidazoline phenylketone that can be used as IP antagonists. Invention describes 2-phenylaminoimidazoline phenylketone of the general formula (I): wherein R1 mean optionally substituted aryl wherein R1 is optionally substituted with 1, 2 or 3 substitutes chosen independently from series including alkoxy-group, aryl aryloxy-, aralkyloxy-group, halogen atom, ethylenedioxy-group or optionally substituted heterocyclyl that means a monovalent saturated carbocyclic radical comprising from 3 to 7 atoms in cycle and comprising one or two heteroatoms chosen independently from nitrogen and oxygen atoms, and can be optionally substituted with one or more substitutes chosen independently from alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl sulfonyl, furanyloxy-group; R2 means hydrogen atom; A means -C(O)-(CH2)n- or -C(O)-CH2-O-; index n means a whole number from 2 to 6, or its pharmaceutically acceptable salt or solvate. Invention provides preparing novel compounds showing useful biological properties.

EFFECT: valuable properties of compounds.

16 cl, 1 tbl, 23 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel amino- and hydroxy-derivatives of phenyl-3-aminomethylquinolone-2 of the general formula (1):

wherein R1, R2, R3 and R4 are independently similar or different and R1 is chosen from hydrogen atom (H), Alk, OAlk; R2 is chosen from H, Alk, OAlk, -OCF3; R3 is chosen from H, Alk, OAlk, -SCH3; R4 is chosen from H. Alk, OAlk, or R2 and R3 are chosen from -(CH2)3, -OCH2O-, -OCH2CH2O-; R5 means H or Alk; R6, R7 and R9 mean H; R8 is chosen independently from the following substitutes:

wherein n = 1, 2, 3; Het represents furan; R represents hydrogen atom or alkyl. In case of hydroxy-derivatives at least one among R6, R7, R8 or R9 is -OH and other represent H. Also, invention relates to methods for synthesis of these compounds and to a pharmaceutical composition based on these compounds inhibiting activity of NO-synthase. Invention provides preparing novel compounds and pharmaceutical compositions based on thereof in aims for treatment of diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

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

32 cl, 1 tbl, 132 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzopyrane substituted with secondary amines comprising tetrazole, their stereoisomers or their pharmaceutical acceptable salts of the formula (I): wherein R1 represents hydrogen (H), fluorine (F), chlorine (Cl), bromine (Br) atom, -CF3, -NO2, -CN, -ORa, -NH2, or -OS(O)lRa under condition that Ra represents hydrogen atom (H) or unbranched or branched (C1-C4)-alkyl; l means a whole number 0-2; R2 represents -CH2ORa, under condition that Ra has values given above; Rb and Rc represent independently unbranched or branched (C1-C4)-alkyl; R3 represents -OH or under condition that Ra has values given above; R4 and R5 represent independently H, F, Cl, Br, unbranched or branched (C1-C3)-alkyl, -ORa, -CF3, -OCF3, -NO2, or -SO3Ra under condition that Ra has values given above; R6 represents H, unbranched or branched (C1-C3)-alkyl; n and m mean independently a whole number 0-2; * represents chiral carbon atom. Also, invention relates to a method of synthesis of these compounds and a pharmaceutical composition based on thereof. Invention provides preparing novel derivatives of benzopyrane possessing antioxidant activity.

EFFECT: improved preparing method, valuable properties of compounds and pharmaceutical compositions.

15 cl, 14 tbl, 118 ex

FIELD: organic chemistry, medicine, virology, pharmacy.

SUBSTANCE: invention relates to new non-nucleoside inhibitors of reverse transcriptase activity of the formula (1): wherein R1 represents oxygen atom (O), sulfur atom (S); R2 represents optionally substituted nitrogen-containing heterocycle wherein nitrogen atom is at position 2 relatively to the bond with (thio)urea; R3 represents hydrogen atom (H), (C1-C3)-alkyl; R4-R7 are chosen independently from hydrogen atom (H), (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, halogen-(C1-C6)-alkyl, (C1-C6)-alcanoyl, halogen-(C1-C6)-alcanoyl, (C1-C6)-alkoxy-, halogen-(C1-C6)-alkoxy-group, hydroxy-(C1-C)-alkyl, cyano-group, halogen atom, hydroxy-group; X represents group of the formula: -(CHR8)-D-(CHR8)m- wherein D represents -O or -S-; R8 represents hydrogen atom (H); n and m represent independently 0, 1 or 2, and to its pharmaceutically acceptable salts. Also, invention relates to a pharmaceutical composition based on these compounds possessing inhibitory effect with respect to activity of HIV-1 reverse transcriptase, and to using these compounds in preparing medicinal agents used in treatment of HIV-1 and to intermediates compounds.

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

45 cl, 1 tbl, 57 ex

FIELD: medicine.

SUBSTANCE: compound is represented by structural formula

or its pharmaceutically permissible salts, where R1 is the hydrogen atom (1), C1-8acyl(2), hydroxyl (3), halogen atom (5), C2-8acyl (3), C1-8-alcocsy (4), substituted with phenyl or C2-8acyl, substituted with NR2R3; R2R3 independently represent hydrogen atom (1) or C1-8acyl(2), X and Y each independently representing C (1), CH (2) or N (3). is (1) single or (2) double bond. is 5-7-member carbocyclic group or 5-7-member partially or fully saturated heterocyclic group defined in claim 1 of invention. A is one of A1 to A5 groups defined by claim 1 of the invention. The compounds show inhibiting properties relative to poly(ADP-ribose)polymerase are usable as prophylactic and/or curative drugs for treating ischemic diseases (in brain, spinal cord, heart, digestive tract, skeletal muscle, eye retina, e.t.c.), inflammatory diseases (intestinal inflammation, disseminated sclerosis, arthritis, e.t.c.), neurodegenerative disorders (extrapyramidal disorder, Alzheimer disease, muscle dystrophy, cerebrospinal canal stenosis in lumbar segment of the vertebral column, e.t.c.), diabetes, stroke, cerebral injury, hepatic insufficiency, hyperalgesia, e.t.c. The compounds are also of use in struggling against retroviruses (HIV and others), as sensitizing agents for treating cancer cases and immunodepressant agents.

EFFECT: enhanced effectiveness of treatment.

19 cl, 90 tbl

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