Derivatives introperative, methods for their preparation and connection

 

(57) Abstract:

The invention relates to the derivatives of introperative General formula

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in which R1and R2each independently H, lower alkyl, lower alkenyl, phenyl, phenylalkyl, pyridyl or imidazolyl, and each of the groups lower alkyl, lower alkenyl, phenyl, phenylalkyl is optional from 1 to 5 substituents selected from carboxy, carbamoyl, cyano and hydroxy-group; or the group-Y - R2where Y is a carbonyl, thiocarbonyl or sulfonyl, and R3- H, lower alkyl, trifluoromethyl, phenyl, lower alkoxy, hydrazino, amino, phenylamino, carbarnoyl or Peregrina group, the lower alkyl or phenyl group are optionally 1 to 4 substituents such as hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, carboxy or cyano, or R1and R2taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyloxy the group may hydroxylamino lower alkyl group, G - pentasa or hexana group, X1and X2independently H or halogen, OH, lower alkoxy - or benzyloxy. The compounds have excellent antitumor
25 mg of the compound obtained in example a dissolved in 1.5 ml N,N-dimethylformamide, add 30 mg of alpha-picolinamides, and the resulting mixture was stirred at 80oC for 2 hours It is mixed with 50 ml of ethyl acetate, and the resulting mixture was washed successively with water and then saturated saline, dehydration anhydrous sodium sulfate and concentrated to dryness. The residue is dissolved in 1 ml of methanol, treated on a chromatographic column of Sephadex LH-20 /1,8 x 15 cm/ and elute with methanol. The fractions containing the desired product are concentrated to dryness to obtain 30 mg specified in the title compound, represented by formula 37.

Rf value: 0,58 /Kieselgel 60F254a product of Merck Co., exhibiting solvent: chloroform:methanol:tetrahydrofuran = 2:1:1/.

FAB-Mass spectrum /m/z/:640 /M+H/+< / BR>
1H-NMR /300 Mghz, DMCO-d6/ MD: 11,43 /1H/, 11,02 /1H/, 10,45 /1H/, 10,07 /1H/, 8,82 /1H, d, J=4,2 Hz/, 8,75 /1H, d, J=7,3 Hz/, 7,3 Hz/, 8,48 /1H, d, J=7.9 Hz/, 8,12 /2N, m/ 7,75 /1H, m, 7,20 /2H, t, J=7,0 Hz/, 7,00-7,15 /3H, m/ 5,45 /1H, d, J=6.3 Hz/, 5,40 /1H, Shir. with/, 5,25 /1H, d, J=6.3 Hz/, 4,96 /1H, Shir. with/, 4,04 /2N, m/, 3,76 /1H, m, 3,55-3,72 /2N, m/, 3,42 /1H, m/.

Example 36

The compound represented by formula 38

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30 mg of the compound obtained in example a, the solution is C for 2 hours Its concentrated to dryness. The residue is dissolved in 1 ml of methanol, treated on a chromatographic column of Sephadex LH-20 /1,8 x 20 cm/ and elute with methanol. The fraction containing the target product are concentrated to dryness to obtain 32 mg specified in the title compound, represented by formula 38, Rf value : 0,32 /Kieselgel 60F254, a product of Merck Co manifesting solvent: chloroform:methanol = 2:1/.

1H NMR /300 Mghz, DMCO-d6/ MD: IP, 91 /1H/, 10,35 /1H/, 9,98 /1H, Shir. with/, 8,70 /1H, d, J=6,7 Hz/, 8,53 /1H, d, J=6,9 Hz/, 7,18 /2H, t, J= 7,6 Hz/, 6,99-7,06 /3H, m/ 5,76 /1H, t, J=5,2 Hz/, 5,41 /1H, d, J=5.6 Hz/, 5,32 /1H, Shir. with/, 5,20 /1H, d, J=5,2 Hz/, 4,98/4,98 /1H, Shir. with/, 4,51 /1H, t, J=4,9 Hz/, 3,96-4,06 /2N, m/, to 3.73 /1H, m, 3,55-3,70 /4H, m/, 3,39 /1H, m, 3,12 /2N, m/.

Example 37

The compound represented by formula 39

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40 mg of the compound obtained in example a dissolved in 2 ml N,N-dimethylformamide, add 10 mg of 1-aminopropyldimethylamine and 0.1 ml of an aqueous solution of sodium bicarbonate, and the mixture was stirred at 80oC for 2 h To this add 40 ml of water, and the resulting mixture extracted with ethyl acetate /40 ml x 2/. Received an ethyl acetate layer dehydration anhydrous sodium sulfate and concentrated to dryness. The residue is dissolved in 1 ml of methanol, treated will procentriole to dryness to obtain 10.0 mg specified in the title compound, represented by formula 39.

Rf value: 0,33 /Kieselgel 60F254, a product of Merck Co., exhibiting solvent: chloroform:methanol = 4:1/.

FAB-Mass spectrum /m/z/:589 /M+H/+< / BR>
1H NMR /300 Mghz, DMCO-d6/ MD: 10,91 /1H/, 10,35/1H,c/, 9,95 /1H/, 8,78 /1H, d, J= 8,3/, charged 8.52 /1H, d, J=8,3 Hz/, 7,16/2H, t, J=7,6 Hz/, 6,9-7,06 /3H, m/, 5,40 /1H, d, J=5.6 Hz/, 5,33 /1H, t, J=5.7 Hz/, 5,18 /1H, d, J=5,5 Hz/, 4,85 /1H, d, J=4,8 Hz/, was 4.02 /2N, m/, 3,74 /1H, m, 3,53-3,68 /2N, m/, 3,30-3,42 /5H, m/ 1,97 /4H, m/.

Example 38

The compound represented by the formula 40

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90 mg of 6-benzoyloxymethyl-1,11-benzyloxy-12,13-degidro-5H-indolo [2,3-a] pyrrolo[3,4-c] carbazole-4,7/6N/-dione, compound, disclosed in PCT/W 091/18003, 1.3 g of silver oxide and 550 mg of molecular sieves 4A suspended in 30 ml of anhydrous benzene. After boiling under reflux for 20 min was added dropwise a solution of 416,4 mg-bromo-3-deoxy-3-asado-2,4,6-triacetyl-D-glucose in 5 ml of anhydrous benzene for 10 minutes and Then boiling under reflux continued for 2 days, insoluble material is filtered on Celite. The resulting filtrate is concentrated to dryness, and the residue is dissolved in 150 ml ethyl acetate, washed sequentially with 0.2 G. hydrochloric acid, water and then saturated saline, dehydration anhydrous sulfate is political column of Sephadex LH-20 /3,0 x 80 cm/, and elute with chloroform. The fraction containing the target product are concentrated to dryness and the residue purified using preparative thin-layer chromatography /n-hexane:acetone:tetrahydrofuran = :1:0,1; Rf : 0,5/, then toluene:acetone = 10:1 /Rf : 0,5/ /to get to 9.2 mg 6/benzoyloxymethyl-1,11-dimensions-12,13-dihydro-13-/ -D-glyukopiranozil/-5H-indolo-[2,3-a]pyrrolo-[3,4-c]carbazole-5,7-/6N/-Dion.

of 9.2 mg of the obtained compound was dissolved in 1 ml of hydrazinoacetate, and the resulting solution was stirred at room temperature for 4 hours It is mixed with 30 ml of ethyl acetate, and the resulting mixture was washed successively with 0.2 G. hydrochloric acid, water and then saturated saline, dehydration anhydrous sulfonate sodium and concentrate to dryness. The resulting residue is dissolved in 0.5 ml of tetrahydrofuran, 1 ml of the methanol extract of palladium black and the mixture is stirred in a stream of hydrogen at room temperature for 3 hours, the Insoluble part is filtered off on Celite, to the obtained filtrate add 1.5 ml of 10% mixture of chloride stands/methanol, and the resulting mixture was concentrated to dryness. The residue is dissolved in 0.5 ml of methanol, treated with chromatography on a column of Sephadex LH-20 /1.0 x 15 cm/, and elute meladinine: represented by formula 40.

Rf value: 0.5 /Kieselgel 60F254manifesting solvent: n-butanol:acetic acid: water = 4:1:1/.

FAB-Mass spectrum /m/z/:534 /M+H/+< / BR>
1H NMR /400 Mghz, DMCO-d6/ MD: 10,80 /1H/, 10,48 /1H/, 10,20 /1H/, 8,79 //1H, d, J=7.9 Hz/, charged 8.52 /3H, Shir. with/, 8,50 /1H, d, J=9,2 Hz/, to 7.61 /1H, d, J=6,6 Hz/, 7,16 /1H, DD, J=9,2 9,2 Hz/, 7,10 /1H, DD, J=9,2 9,2 Hz/, 7,05 /1H, DD, J=9,2 Hz/, 7,00 /1H, DD, J= 9,2 9,2 Hz/, 6.42 per /1H, d, J= 5,2 Hz/, 6,16 /1H, d, J=3,9 Hz/, 5,18 /1H, TL/, 4,93 /1H, Shir/, 4,40 /1H, m, 4,16 /1H, m, 4,03 /1H, m/ 3,78 /1H, m/ 3,68 /1H, m, 3,42 /1H, m/.

Example 39

The compound represented by formula 41.

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30 mg of the compound obtained in example a dissolved in 1.5 ml N,N-dimethylformamide, add 60 mg cyanoacetaldehyde, and the resulting mixture was stirred at 80oC for 9 hours the mixture is mixed with 30 ml of ethyl acetate, the resulting mixture was washed successively with water, then with saturated salt solution, and then an ethyl acetate layer dehydration anhydrous sodium sulfate and concentrated to dryness. The resulting residue is dissolved in a small amount of methanol, treated on a chromatographic column of Sephadex LH-20 /1.5 x 15 cm/ and elute with methanol. The fraction containing the target product are concentrated to dryness to obtain 27.8 mg specified in the title compound, oritel: chloroform:methanol:tetrahydrofuran = 3:1:0,1.

FAB-Mass spectrum /m/z/:601 /M+H/+< / BR>
1H NMR /300 Mghz, DMCO-d6/, /MD/: 11,14 /1H/, br11.01 /1H/, 10,42 /1H/, 10,04 /1H/, 8,65 /1H, d, J=7,6 Hz/, of 8.47 /1H, d, J=7,6 Hz/, 7,21 /2H, t, J=7,6 Hz/, 7,05 /3H, t, J=7,6 Hz/, 5,41 /2H, d, J=4.5 Hz/, 5,19 /1H, d, J=6,8/, 4,90 /1H, d, J=6,8 Hz/, 4,13 /2N,/, 4,04 /2N, W/, 3,75 /1H, m, 3,64 /2N, m/, 3,43 /1H, m/.

Example 40

The compound represented by formula 42

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1 g 12,13-dihydro-1,11-dihydroxy-13-/ -D-glyukopiranozil/ -5H-indolo[2,3-a] pyrrolo[3,4-c] carbazole-5,7/6N/-dione is dissolved in 25 ml of tetrahydrofuran, and added dropwise an ethereal solution of excess diazomethane; the resulting mixture was stirred at 4oC overnight, and the resulting yellow precipitate is collected by filtration. It is dissolved in 3 ml of hydrazinoacetate, and the resulting solution was left to react at room temperature for 1.5 hours After completion of the reaction, add 200 ml of purified water, and the precipitate is collected by filtration, washed successively with purified water and then with methanol, and dried under reduced pressure, resulting in a gain 683,4 mg specified in the title compound, represented by formula 42.

1 g 12,13-dihydro-1,11-dihydroxy-13-/ -D-glyukopiranozil/ -5H-indolo[2,3-a] pyrrolo[3,4-c]carbazole-5,7-/6N/-dione is dissolved in 25 ml of tetrahydrofuran, throughout the night, and the resulting yellow precipitate is collected by filtration. It is dissolved in 3 ml of hydrazinoacetate, and the solution is allowed to react at room temperature for 1.5 hours After completion of the reaction, add 200 ml of purified water, and the precipitate is collected by filtration, washed successively with purified water and then with methanol, dried under reduced pressure to obtain 683,4 mg specified in the title of the product represented by the formula 42. High-performance liquid chromatography /HPLC/: retention Time of 10.5 minutes /column Chromatics ODS, internal diameter 4 mm, length 250 mm, detector UV at 305 nm, flow rate : 1 ml/min, mobile phase methanol:water = 6 : 4/.

FAB-Mass spectrum /m/z/:563 /M+H/+< / BR>
1H NMR /300 Mghz, DMCO-d6/ MD: 10,9 /1H/, 8,87 /1H, d, J=7,8 Hz/, 8,65 /1H, d, J=7,8 Hz/, 7,35 /1H, t, J=7,8 Hz/, of 7.23 /1H, t, J=7,8 Hz/, 7,25 /1H, d, J=7,8 Hz/, 7,18 /1H, d, J=7,8 Hz/, 6,90 /1H, d, J=9,3 Hz/, 5,40 /1H, Shir. with/, 5,18 /1H, Shir. with/, 5,00 /2N, Shir. with/, 4,90 /2N, Shir. with/, 4,06 /6N,, 4,0 /2N, m/, 3,78 /1H, m, 3,63 /2N, m/, 3,42 /1H, m/.

Example 41

The compound represented by formula 43

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708,8 mg specified in the title compound, represented by formula 43, obtained from 679 mg of the compound obtained in example 40, according to the method of example 2.

Vsokoeffectiven 250 mm, detector UV at 310 nm, flow rate 1 ml/min, mobile phase acetonitrile:water = 2,8 --> acetonitrile:water = 6:4, linear gradient, 30 min/.

FAB-Mass spectrum /m/z/:618 /M/+< / BR>
1H-NMR /GC/, DMCO-d6/ MD: 13,5 /1H, Shir. with/, 11,1 /1H/, 9,01 /1H/, 8,83 /1H, d, J= 7,8 Hz/, 8,63 /1H, d, J=7,8 Hz/, 7,39 /1H, t, J=7,8 Hz/, 7,37 /1H, t, J=7,8 Hz/, 7,29 /1H, d, J=7,8 Hz/, 7,22 /1H, d, J=7,8 Hz/, 6,94 /1H, d, J=9,3 Hz/, 5,43 /1H, d, J=5.4 Hz/, 5,22 /1H, d, J=5.4 Hz/, 5,01 /1H, Shir. with/, 4,93 /1H, d, J=5.4 Hz/, 4,07 /6N,/, 4,05 /1H, m, 3,96 /1H, m, 3,79 /1H, m, 3,60 /3H, m/, 3,44 /1H, m/.

Example 42

The compound represented by formula 44

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704 mg of the compound obtained in example 41, dissolved in 10 ml of N,N-dimethylformamide, add 60 mg of 10% palladium on coal /Pd-C/, and the resulting mixture hydronaut at room temperature for 6 h under stirring, the reaction mixture is filtered, using a sheet of filter paper, which is distributed Celite to remove Pd-C. To the obtained filtrate add 200 ml of ethyl acetate, and the resulting mixture is extracted with 50 ml of aqueous sodium bicarbonate solution /pH 8/. the pH of the aqueous layer was adjusted to 2, and extracted with ethyl acetate. An ethyl acetate layer is extracted with 2% aqueous sodium bicarbonate solution /70 ml/. This layer of 2% aqueous solution of sodium bicarbonate concentrate when pengeluaran 300 ml of methanol. The methanol eluate concentrated to dryness, the residue dissolved in a small amount of N,N-dimethylformamide, and the resulting solution is treated by preparative high-performance liquid chromatographic column /column: Chromatics ODS, internal diameter 20 ml, length 250 mm, detector UV 310 nm, flow rate 9 ml/min, mobile phase acetonitrile: water = 25:75/. The fraction containing the target product, concentrate to dryness, and the residue is dissolved in a small amount of water treated on a chromatographic column of Sephadex G-15 /inner diameter 3 cm, length 63 cm/, and elute with water: methanol = 9:1. The fraction containing the target product, concentrated, and then dried by freezing to obtain 84,2 mg sodium salts specified in the title compound, represented by formula 44.

HPLC retention Time of 8.9 min /column Chromatics ODS, internal diameter 4.6 mm, length 250 mm, detector UV 310 nm, flow rate 1 ml/min, mobile phase acetonitrile:water:triperoxonane acid = 300:700:1/.

FAB-Mass spectrum /m/z/:643 /M+Na/+< / BR>
1H NMR /400 Mghz, DMCO-d6/ MD: 10,9 /1H, Shir. with/, cent to 8.85 /1H, d, J=7,8 Hz/, 8,62 /1H, d, J=7,8 Hz/, 7,33 /1H, T. J=7,8 Hz/, 7,31 /1H, t, J=7,8 Hz/, 7,24 /1H, d, J=7,8 Hz/, 7,16 /1H, d, J=7,8 Hz/, 6,89 /1H, d, J=9,3 Hz/, 5,63 /1H, Shir. with/, 5,42 /1H,="ptx2">

Example 43

The compound represented by formula 45

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23,8 mg specified in the title compound, represented by formula 45, obtained from 70 mg of the compound obtained in example 4 by the method of example 2.

FAB-Mass spectrum /m/z/:641 /M+H/+< / BR>
1H NMR /400 Mghz, DMCO-d6/ MD: 10,8 /1H,, 9,26 /1H, d, J=7,8 Hz/, which is 9.09 /1H, d, J=7,8 Hz/, 8,94 /1H/, 7,78 /1H, d, J=7,8 Hz/, 7,74 /1H, d, J= 7,8 Hz/, 7,50 /2H, t, J=7,8 Hz/, 6,98 /1H, d, J=9,3 Hz/, 5,44 /1H, d, J= 5,9 Hz/, 5,33 /1H, Shir. with/, 5,09 /1H, d, J=5.4 Hz/, 3,96 /2N, m/, 3,85 /1H, m, 3,67 /2N, m/, 3,59 /3H/, 3,56 /1H, m/.

Example 44

The compound represented by formula 46

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210 mg specified in the title compound, represented by formula 46, is obtained from 1 g of the compound obtained in example 43, by way of example 42.

FAB-Mass spectrum /m/z/: 643/M+H/+< / BR>
1H NMR /500 Mghz, DMCO-d6/ MD: 10,7 /N,/, 9,26 /1H, d, J=7,8 Hz/, which is 9.09 /1H, d, J=7,8 Hz/, 7,74 /1H, d, J=7,8/, 7,71 /1H, d, J=7,8 Hz/, 7,46 /2H, t, J=7,8 Hz/, 6,93 /1H, d, J=9,2 Hz/, 6,00 /1H, Shir. with/, 5,42 /1H, Shir. with/, 5,3/1H, Shir. with/, 5,03 /1H, Shir. with/, 3,96 /2N, Shir. with/, 3,85 /2N,/, 3,83 /1H, m, 3,59 /3H/, 3,50-3,70 /3H, m/.

Example 45

The compound represented by formula 47:

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48,2 mg specified in the title compound, represented by formula 47, obtained from 51,4 mg of the compound obtained in example 4, pic/, 10,8 /1H, Shir. with/, 9,20 /1H, m, 9,03 /1H, m, 8,48 /1H/, 7,75 /1H, d, J=7,8 Hz/, 7,70 /1H, d, J= 7,8 Hz/, 7,45 /2H, t, J=7,8 Hz/, 6,9 /1H, Shir.T. J=9,3 Hz/, 5,41 /2N, m/ 5,04 /1H, d, J=5,9 Hz/, 3,99 /2N, Shir. with/, 3,86 /1H, m, 3,60 /3H,, 3,52-3,67 /3H, m/.

Example 46

The compound represented by the formula 48

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13 mg specified in the title compound, represented by formula 48, derived from a 14.1 mg of the compound obtained in example 4 by the method of example 6.

FAB-Mass spectrum /m/z/: 627 /M+H/+< / BR>
1H NMR /500 Mghz, DMCO-d6/: MD: 10,8 /2N,/, 9,20 /1H, m, 9,04 /1H, m, 7,74 /2N, m/, 7,47 /2N, m/ 6,93 /1H, m, 5,41 /1H, m, 5,32 /1H, Shir. with/, 5,04 /1H, m, 3,96 /2N, Shir. with/, 3,85 /1H, m/, to 3.58 /3H/, 3,50-3,70 /3H, m/, 2,12 /3H, s/.

Example 47

The compound represented by formula 49:

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1 ml of hydrazinoacetate add to 3.2 mg of 12,13-dihydro-2,10-dihydroxy-13-/ -D-glyukopiranozil/-5H-indolo [2,3-a]-pyrrolo[3,4-c]carbazole-5,7/6N/dione, and the mixture was stirred at room temperature for 2 hours It evenly between layers ethyl acetate to 0.2 N. hydrochloric acid, and an ethyl acetate layer is washed successively with water, then saturated brine, and concentrated to dryness. The resulting residue is dissolved in a small amount of methanol, treated on a chromatographic column of Sephadex LH-20 /1.0 x 5 cm/ is in the title compound, represented by formula 49.

Rf value: 0,22 /Kieselgel 60F254, a product of Merck Co., exhibiting solvent: chloroform:methanol:tetrahydrofuran = 3:1:1/.

FAB-Mass spectrum /m/z/: 534 /M/+< / BR>
1H NMR /300 Mghz, DMCO-d6/ MD: 11,16 /1H/, 9,76 /1H/, 9,73 /1H/, 8,90 /1H, d, J=7,3 Hz/, 8,82 /1H, d, J=7,3 Hz/, 7,18 /1H, d, J=2.0 Hz/, 6,98 /1H, d, J=2.0 Hz/, 6,83 /2H, dt, J=2,0 7,3 Hz/, 5,97 /1H, d, J=7,2 Hz/, of 5.84 /1H, t, J=3.3 Hz/, 5,32 /1H, d, J=5.3 Hz/, 5,10 /1H, d, J=5.3 Hz/, 4,93 /1H, d, J= 5,2 Hz/, 4,90 /2H, s with Android 4.04-3,86 /2N, m/, 3:78 /1H, m, 3,60-3,35-3N/m/.

Example 48

The compound represented by the formula 50:

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0.4 ml of hydrazine hydrate is added added to to 7.1 mg 2,10-Diptera-12,13 - dihydro-13-/ -D-glyukopiranozil/-5H-indolo[2,3-a] -pyrrolo[3,4-c] carbazole-5,7-/6N/-dione, and the mixture was stirred at room temperature for 40 minutes To this type of 1.34 ml of concentrated hydrochloric acid, and the mixture was extracted with ethyl acetate. An ethyl acetate layer is washed with water and concentrated. The residue is dissolved in 3.7 ml of N,N-dimethylformamide and 0.37 ml of concentrated hydrochloric acid, and the resulting solution was stirred at room temperature overnight. It is distributed between ethyl acetate and water, and an ethyl acetate layer is concentrated to dryness. The resulting residue is dissolved in Nebolchi, containing the target product are concentrated to dryness to obtain 4,6 mg specified in the title compound represented by the formula 50.

FAB-Mass spectrum /m/z/: 566 /M/+< / BR>
1H NMR /400 Mghz, DMCO-d6/ MD: 11,9 /1H/, 10,8 /1H, Shir. with/, 9,07 /1H, DD, J=5,8 8,8 Hz/, 9,01 /1H, DD, J=5,9 9,8 Hz/, 8,45 /1H/, 7,93 /1H, Shir. with/ J=8,8 Hz/, 7,44 /1H, Shir. d, J=8,8 Hz/, 7,27 /2N, m/, 6,28 /1H, d, J=8,8 Hz/,6,20 /1H, Shir. with/, 5,42 /1H, Shir. with/, 5,13 /1H, Shir. d, J=5.4 Hz/, 4,96 /1H, d, J=5.4 Hz/, 4.09 to /1H, Shir. d, J=7,3 Hz/, 3,94 /2N, m/ 3,83 /1H, Shir. d, J=7,3 Hz/, to 3.58 /1H, m, 3,45 /1H, m/.

Example 49

The compound represented by formula 51

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where Bn represents a benzyl group.

100 mg of 6-benzoyloxymethyl-11.11 is dibenzyline-12,13-dihydro-5H-indolo[2,3-a] pyrrolo[3,4-c]carbazole-5,7/6N/-Dion, 1.4 g of silver oxide and 0.7 g of molecular sieves 4A suspended in 40 ml of anhydrous benzene, the resulting suspension is refluxed for 20 min, and then was added dropwise a solution of 1-bromo-2,3,5-tri-O-acetyl-D-ribose in 10 ml of anhydrous benzene over a period of time of 10 minutes the mixture is boiled then under reflux for 3 h, and then the insoluble portion removed by filtration using Celite.

The resulting filtrate is concentrated to dryness, and the residue is dissolved in 100 ml of ethyl acetate, and the tub over anhydrous sodium sulfate and concentrated to dryness. The resulting residue is dissolved in chloroform, treated on a chromatographic column of Sephadex LH-20 /2.5 x 20 cm/ and elute with chloroform. The fraction containing the target product, concentrate to dryness, and the residue is treated on a chromatographic column with silica gel /2.5 x 25 cm/ and elute with a mixture of toluene-ethyl acetate /3:1/. The fractions containing the product are concentrated to dryness. The residue is cleaned by further preparative thin-layer chromatography /malwarerelated = 5:1 /Rf = 0,6// to get 20,8 mg 6-benzoyloxymethyl-1,11-dibenzoate-12,13-/ -D-ribofuranosyl/ -5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7/6N/Dion.

20,8 mg of this compound was dissolved in 2 ml of hydrazinoacetate, and the resulting solution was stirred at room temperature for 2 hours It is mixed with 30 ml of ethyl acetate, the resulting mixture was sequentially washed with 0.2 g of hydrochloric acid, water and then saturated saline, and concentrated to dryness. The resulting residue is dissolved in methanol, treated on a chromatographic column of Sephadex LH-20 /1.0 x 15 cm/ and elute with methanol. The fraction containing the target product are concentrated to dryness and the residue purified using preparative thin-layer chromatography /chloroform:methanol = 10: 1/ /Rf = 0,5 / /to poll 60F254, a product of Merck Co., exhibiting solvent: chloroform:methanol = 10:1/.

FAB-Mass spectrum /m/z/: 684 /M/+< / BR>
1H NMR /300 Mghc/, DMCO-d6/ MD: 10,45 /1H/, 8,90 /1H, d, J=0,75 8,68 /1H, d, J=0.75 Hz/, 7,18 /2H, d, J=0.75 Hz/, 7,11 /2H, d, J= 0.75 Hz/, 7,20-7,50 /11N, m/ 5,35-5,45 /5H, m/, 5,17 /1H, d, J=0,38 Hz/, 5,10 /1H, d, J=0,45 Hz/, to 4.98 /2N,/, 3,90-4,00 /2N, m/, 3,60-3,70 /2N, m/.

Example 50

The compound represented by formula 52.

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of 33.0 mg of the compound obtained in example a dissolved in 3 ml of N,N-dimethylformamide, add 8,4 mg hydroxyethylhydrazine, and the resulting mixture was stirred at 80oC for 2 days. Its concentrated to dryness, and the resulting residue is dissolved in a small amount of methanol, treated on a chromatographic column of Sephadex LH-20 /1.5 x 25 cm/ and elute with methanol. The fraction containing the target product, concentrate to dryness, and the residue is dissolved in 30 ml of ethyl acetate. The resulting residue is dissolved in 30 ml of ethyl acetate. This solution is washed with water, and an ethyl acetate layer is dried over anhydrous sodium sulfate and concentrated to dryness. The residue is dissolved in a small amount of methanol, treated on a chromatographic column of Sephadex LH-20 /1.5 to 15 cm/, and elute with methanol. The fraction containing the target product, conc>FAB-Mass spectrum /m/z/: 593 /M+H/+< / BR>
1H NMR /300 Mghz, DMCO-d6/ MD: 11,00 /1H/, 10,55 /1H/, 10,41 /1H/, 10,02 /1H/, 8,63 /1H, d, J=7,8 Hz/, of 8.47 /1H, d, J=7,8 Hz/, 7,20 /2H, t, J=7,8 Hz/,? 7.04 baby mortality /3H, m/ 5,88 /1H, t, J=7,0 Hz/, 5,41 /1H, d, J=6.2 Hz/, 5,35 /1H, Shir/, 5,20 /1H, d, J=6.2 Hz/, 4,90 /1H, d, J=6.2 Hz/, 4,16 /2H, d, J=5.7 Hz/, 4,03 /2N, m/, 3,74 /1H, m, 3,59-3,68 /2N, m/, 3,39 /1H, m/.

Example 51

The compound represented by formula 53:

< / BR>
35 mg of the compound obtained in example a dissolved in 1.0 ml of N,N-dimethylformamide. Add 0.5 ml of saturated aqueous sodium bicarbonate solution, and the mixture was stirred at 80oC during the day. Its concentrated, and the residue is dissolved in a small amount of methanol and treated on a chromatographic column of Sephadex LH-20 /1.5 x 15 cm/, and elute with methanol. The fraction containing the target product are concentrated to dryness to obtain 20,8 mg specified in the title compound, represented by formula 53. P value: 0,5 /Kieselgel 60F254manifesting solvent: chloroform: methanol:tetrahydrofuran = 2:1:1/

FAB-Mass spectrum /m/z/: 563 /M+H/+< / BR>
1H NMR /300 Mghz, DMCO-d6/ MD: 10,90 /1H/, 10,35 /1H/, 9,96 /1H/, 8,72 /1H, d, J=7.9 Hz/, 8,54 /1H, d, J=7.9 Hz/, 7,17 /2H, t, J=7.9 Hz/, 7,03 /3H, m/ 5,72 /1H, t, J=4,8 Hz/, 5,41 /1H, d, J= 6.3 Hz/, 5,35 /1H, t, J=4.0 Hz/, to 5.21 /1H, d, J=4.0 FOR THE BR>
50 g of compound of example 5 is dissolved in the solution, which is dissolved Japanese Pharmacopoeia in 400 g of distilled water for injection, and the resulting solution is filtered to remove bacteria, using a filter of 0.2 μm. Portions of 5 ml of the filtrate is placed in washed and sterilized ampoules in the usual way, and the ampoule is closed and sealed to obtain solutions for injection containing 250 mg of the compound of example 5 in each of the vials. The drug is administered with an agent for internal injection, which add 5 or 10 ml of this drug for injection /i.e., 250 to 500 mg of the compound of example 5 and diluted with 500 ml of this liquid for infusion, such as glucose /5%/.

1. Derivatives introperative General formula I

< / BR>
in which R1and R2each independently is hydrogen, lower alkyl, lower Alchemilla, phenyl, fenilalanina, perederina or imidazolidinone groups, each lower alkyl, lower alkenylphenol, phenyl and phenylalaninol groups has (optional) 1 to 5 substituents selected from carboxy, carbamoyl, cyano and hydroxy-group, or a group of the General formula

- Y - R3,

in which Y is a carbonyl, thiocarbonyl or sulfonylurea group;

Oh, carnemolla or Peregrina group, the lower alkyl and the phenyl group are (optional) 1 to 4 substituents, such as hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, carboxy - and ceanography,

or R1and R2taken together, the lower alkylidene group which may have a carboxyl group, or R1and R2taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyloxy group, with (optional) hydroxylamino lower alkyl group;

G - pentasa or hexana group;

X1and X2each independently is hydrogen or halogen, a hydroxy-group, a lower alkoxy - or benzyloxy,

or their pharmaceutically acceptable salts.

2. Connection on p. 1 of General formula Ia

< / BR>
in which R11and R21each independently is hydrogen, lower alkyl, lower Alchemilla, phenyl, fenilalanina, perederina or imidazolidinone groups, each lower alkyl, lower alkenylphenol, phenyl and phenylalaninol groups have (optional) 1 to 5 substituents selected from carboxy, carbamoyl, cyano and hydroxy-group; or a group of the General formula is - hydrogen, lower alkyl, triptoreline or phenyl groups and lower alkyl and phenyl groups are (optional) 1 to 4 substituents, such as hydroxy - or carboxypropyl,

or R11and R21taken together, represent the lowest alkylidene group which may have a carboxyl group; or R11and R21taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyl group;

G1group of the formula

< / BR>
X11and R21attached to intolorable ring in 1 - or 2 - and 10 - or 11 - position, respectively, and each independently is hydrogen or halogen, hydroxy, lower alkoxy or benzyloxy.

3. Connection on p. 1 of General formula I(b)

< / BR>
in which R12is hydrogen or a lower alkyl group;

R22is hydrogen, a lower alkyl group which may have 1 to 3 substituent selected from the group consisting of carboxy, carbamoyl, hydroxy and cyano groups; phenyl or fenilalanina group, optionally substituted hydroxy or carboxypropyl; imidazolinone group, or a group

-Y - R32,

in which Y is a carbonyl, thiocarbonyl or strong, triptoreline or phenyl groups and lower alkyl and phenyl groups are (optional) 1 to 4 substituent such as a hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, and when Y is sulfonylurea group, then R32is lower alkyl or phenyl group;

or R12and R22taken together, the lowest alkylidene group containing carboxypropyl, or R12and R22taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyl group;

G1X11and X21matter under item 2.

4. The compound of General formula I on p. 1 or its pharmaceutically acceptable salt having antitumor activity.

5. The method of producing introperative General formula I under item 1 or pharmaceutically acceptable salts, characterized in that the compound of General formula II

< / BR>
in which X1X2and G have values in p. 1,

subjected to interaction with the compound of General formula P

< / BR>
in which R13and R23matter under item 1, respectively, for R1and R2provided that R13and R23taken together, are not inferior alkylidene gruperas R13, R23X1X2and G have the values

followed, if necessary, formirovanie, alkylation, alkenylamine, carbamoylethyl, thiocarbamoylation, alkanolamines or sulfonylamine amino

< / BR>
in the compound of formula Ic, when R13and R23both hydrogen, or a condensation compound Ic with a compound of General formula IV

OHC - R6,

in which R6- carboxypropyl or a lower alkyl group, a substituted carboxyl group,

and, if necessary, the double bond in compound Ic restore, when R13and R23is a double bond, and, if necessary, the obtained compound I in turn pharmaceutically acceptable salt.

6. The method of producing introperative General formula I under item 1 or its pharmaceutically acceptable salts, characterized in that the compound of General formula III

< / BR>
in which X1X2and G have values in p. 1,

subjected to interaction with the compound of General formula P

< / BR>
in which R13and R23matter under item 1, respectively, for R1and R2provided that R13and R23taken together, are lower alkylidene the entity, if necessary, formirovanie, alkylation, alkenylamine, carbamoylethyl, thiocarbamoylation, alkanolamines or sulfonylamine amino

< / BR>
in the compound of formula Ic, when R13and R23both hydrogen, or by condensation of the compounds of formula Ic with a compound of General formula IV

R6- CHO,

in which R6is carboxyl or lower alkyl group, a substituted carboxyl group,

followed, if necessary, restoration of double bonds in the compound of General formula Ic and, if necessary, the obtained compound of General formula I is transformed into a pharmaceutically acceptable salt.

7. The method of obtaining compounds of General formula II under item 5, characterized in that the compound of General formula III

< / BR>
in which X1X2and G have values in p. 1,

handle base.

8. The compound of General formula III

< / BR>
in which X1X2and G have values in p. 1,

and its derivative, in which a functional group is protected.

Priority signs:

01.09.92 - all signs under item 1 of the formula, in addition to R1and R2independently represent a lower alkyl group, and each of the lower alfredstrasse triptorelin group, phenyl, lower alkoxy-, hydrazino, phenylenecarbonyl or pyridyloxy group, with the phenyl group has the (optional) 1 to 4 substituent such as halogen atom, hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, carboxy, cyano, or R1and R2taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyloxy group, with (optional) hydroxylamino lower alkyl group, X1and X2each independently - benzyloxy, G - pentasa group, all signs on p. 2 of the formula, except: R11and R21each independently lower Alchemilla group, each of the lower alkenylphenol group has the (optional) 1 to 5 substituents selected from carbamoyl, ceanography, R31- triptoreline or phenyl group, with (optional) 1 to 4 substituent such as a hydroxyl or carboxyl group, R11and R21taken together with the nitrogen atom to which they are attached form a piperazinilnom or pyrrolidinyloxy group, X11and X21each independently - benzyloxy, all signs on p. 3 formula, except: R22- lower alkyl group which may have 1 to 3 C is when R32- triptoreline or phenyl group, and the phenyl group has the (optional) 1 to 4 substituent such as a hydroxyl group adjacent to the hydroxy-group-protected alkalinous group, and when Y is sulfonylurea group, then R32is a phenyl group; or R12and R22taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyl group; all signs on p. 4; all signs under item 5, except under alkenylamine connection Ic; all signs on p. 6, except under alkenylamine connection Ic;

18.02.92 - all signs under item 1 of the formula, except: R1and R2each independently represent lower alkenylphenol, phenyl, phenylalkyl, pyridyloxy or imidazolylalkyl group, and each of the lower alkenylphenol, phenyl and phenylalaninol groups has (optional) 1 to 5 substituents selected from carbamoyl, cyano or hydroxy groups, Y - thiocarbonyl or sulfonylurea group, R3- triptoreline, phenyl, lower alkoxy, hydrazino-, amino-, phenylamino-, carnemolla or Peregrina group, the lower alkyl and phenyl groups are (optional) 1 to 4 substituent such as halogen atom, hydroxy-group, minuete with the nitrogen atom, to which they are attached, form a piperazinilnom or pyrrolidinyloxy group, with (optional) hydroxylamino lower alkyl group, G - pentasa group, X1and X2each independently - benzyloxy; all signs on p. 2, except: R11and R21each independently lower Alchemilla, phenyl, fenilalanina, perederina or imidazolidine group, and each of the lower alkenylphenol, phenyl and phenylalaninol groups have (optional) 1 to 5 substituents selected from carbamoyl, cyano and hydroxy-group; Y - thiocarbonyl or sulfonylurea group, R31- triptoreline or phenyl group and lower alkyl and phenyl groups are (optional) 1 to 4 substituent, such as hydroxy - or carboxypropyl; or R11and R21taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyl group; X11and X21- benzyloxy; all signs on p. 3 formula, except: R22- lower alkyl group which may have 1 to 3 substituent selected from carbamoyl, hydroxy-, cyano groups, phenyl or fenilalanina group, optionally substituted hydroxy or carboxypropyl, ilide R32- triptoreline or phenyl group and lower alkyl and phenyl groups are (optional) 1 to 4 substituent such as a hydroxy-group adjacent to the hydroxy-group, substituted alkalinous group, and when Y is sulfonylurea group, then R32is lower alkyl or phenyl group, or R12and R22taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyl group; all signs on p. 4 formulas, all signs on p. 5 formulas, all signs on p. 6 of the formula, except under alkylation, alkenylamine, carbamylcholine, thiocarbamoylation or sulfating amino group in the compound Ic, all the signs on p. 7 formulas;

29.11.91 - all signs under item 1 of the formula, except: R1and R2represent the lowest alkenylphenol, phenyl, phenylalkyl, pyridyloxy or imidazolylalkyl group, and each of the lower alkenylphenol, phenyl and phenylalaninol groups has (optional) 1 to 5 substituents selected from carbamoyl, cyano and hydroxy-group, or a group of General formula-Y-R3in which Y is a carbonyl, thiocarbonyl or sulfonylurea group, R3is hydrogen, lower alkyl, triptoreline, phenyl, lower alkoxy, Gee, we have (optional) 1 - 4 substituent such as a hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, carboxy and cyano, or R1and R2taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidino group, with (optional) hydroxylamino lower alkyl group, G - pentasa group, X1and X2each independently - benzyloxy; all signs on p. 2 of the formula, except: R11and R21each independently lower Alchemilla, phenyl, fenilalanina, perederina or imidazolidine group, and each of the lower alkenylphenol, phenyl and phenylalaninol groups has (optional) 1 to 5 substituents selected from carbamoyl, cyano and hydroxy-group, or the group-Y - R31in which Y is a carbonyl, thiocarbonyl or sulfonylurea group, and R31is hydrogen, lower alkyl, triptoreline or phenyl group, the lower alkyl and the phenyl group has the (optional) 1 to 4 substituent, such as hydroxy - or carboxypropyl; or R11and R21taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyloxy group, X11and X21each independently - benzacridine, selected from the group consisting of carbamoyl, hydroxy and cyano groups, phenyl or fenilalanina group, optionally substituted hydroxy or carboxypropyl, imidazolidine group, -Y - R32in which Y is a carbonyl, thiocarbonyl or sulfonylurea group, and when Y is carbonyl or thiocarbonyl group, then R32is hydrogen, lower alkyl, triptoreline or phenyl groups and lower alkyl and phenyl groups are (optional) 1 to 4 substituents, such as hydroxy-group adjacent to the hydroxy-group-protected alkalinous group, and when Y is sulfonylurea group, then R32is lower alkyl or phenyl group, or R12and R22taken together with the nitrogen atom to which they are attached, form a piperazinilnom or pyrrolidinyloxy group, and G, X11and X21matter under item 2; all signs on p. 4; all signs on p. 5; all signs on p. 6, except under formirovaniya, alkylation, alkenylamine, carbamylcholine, thiocarbamoylation, alkanolamine or sulfonylurea amino

< / BR>
in the compound of formula Ic, when R13and R23both hydrogen

and, if necessary, the obtained compound of General formula

 

Same patents:

The invention relates to new derivatives of pyrimidine nucleoside having excellent antitumor activity
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d-arabinofuranosyl)-n-purine, method for their preparation and use and pharmaceutical composition" target="_blank">

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< / BR>
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The invention relates to oligonucleotides and their derivatives to suppress the expression of isoprenylation, pharmaceutical compositions containing such compounds and to the use of such compositions of oligonucleotides for the treatment or therapy of the human or animal diseases caused by abnormal and/or unregulated proliferation

FIELD: medicine.

SUBSTANCE: method involves carrying out hernia removal in intralaminar way. Posterior longitudinal ligament defect is covered with Tacho-Comb plate after having done disk cavity curettage. Subcutaneous fat fragment on feeding pedicle is brought to dorsal surface of radix and dural sac.

EFFECT: enhanced effectiveness of treatment; reduced risk of traumatic complications.

1 dwg

FIELD: medicine, obstetrics, gynecology.

SUBSTANCE: at the background of therapy conducted one should introduce derinate immunomodulator into the body of pregnant woman additionally nasally per 1-2 drops of 0.25%-solution into each nasal canal 5-8 times daily for 3-5 d and - parenterally per 5.0 ml of 1.5%-solution once daily for 3-8 d along with preparation that improves microcirculation and along with antioxidant at a certain sequence, moreover, derinate should be introduced 30-40 min after application of microcirculation-improving preparation, and antioxidant - 20-30 min after derinate's introduction. The present innovation favors decreased edemas, decreased body weight, stabilization of Macluer-Aldrich test that in its turn enables to avoid perinatal losses, decrease the risk for the development of fetoplacental insufficiency and intrauterine fetal infection.

EFFECT: higher efficiency of therapy.

1 ex, 2 tbl

FIELD: medicine, otolaryngology.

SUBSTANCE: the present innovation deals with introducing neomycin sulfate antibiotic in granules prepared by the following technique. Tablet of neomycin sulfate 1.0g should be put into a vial with 100 ml distilled water till tablet's decomposition. Then vial's content should be shaken and kept till suspension sedimentation. In a day one should take 1 ml of supernatant liquid to be put into another vial and diluted with distilled water at 1:100 ratio. This procedure should be repeated 4 times more, moreover, during the last procedure one should apply alcohol for dilution. Then one should transfer the drop of alcoholic solution into a vial with granules out of milk sugar to then shaken and kept open for 1 d till granules" drying up. The suggested preparation should be applied per 1 granule under the tongue, moreover, multiplicity and duration of the above-suggested intake should be matched individually by patient's sensitivity and obtaining the clinic effect. The method enables to improve the value of tonic threshold audiometry by about 30-50 dB, decrease perception threshold of vocal range frequencies and widen the range towards high frequencies.

EFFECT: higher efficiency of therapy.

1 dwg

FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for treatment of chronic lympholeukosis. Method involves intravenous drop and jet administration of antitumor chemopreparations and carrying out the autochemotherapy. At the 1-st and 8-th day of treatment cyclophosphan in the dose 750 mg/m2, vincristine in the dose 1.4 mg/m2 and doxorubicin in the dose 30 mg/m2 incubated with 200 ml of autoblood are administrated to patients. From the 1-st to 14-th day of treatment prednisolone is used every day in the therapeutic dose. The treatment course is repeated in 30-35 days depending on blood indices and patient state. The total treatment of courses is 4-5. Method provides reducing cardiotoxicity of doxorubicin and cumulative toxicity of chemopreparations that allows carrying out administration of antitumor chemopreparations in the full volume to patients of elderly age groups.

EFFECT: improved method for treatment.

1 ex

FIELD: medicine, oncohematology.

SUBSTANCE: the present innovation deals with treating elderly patients with chronic lympholeukosis accompanied with cardiovascular failure. The method deals with applying chemopreparations and cytoprotector. Moreover, 1 wk before the onset of chemotherapeutic therapy one should prescribe preductal at the dosage of 105 mg daily. At this background one should sample blood out of elbow vein at the volume of 200 ml into a vial with glugicir to centrifuge it, isolate plasma, divide into two portions, add into the 1st vial - cyclophosphan 600-800 mg/sq. m, vincristin 1.4 mg/sq. m, into the 2nd vial - adriamycin 50 mg/sq. m to be incubated for 30 min at 37 C and intravenously injected by drops for patients. Simultaneously, the intake of prednisolone should be prescribed at the dosage of 60 mg/sq. m since the 1st d and during the next 5 d and preductal at the dosage of 105 mg daily during a week, and then 2 wk more at the dosage of 60 mg daily. All the procedures should be repeated in above-mentioned sequence 4-6 times. The method enables to decrease toxic manifestations of chemotherapy while applying adequate dosages of cytostatics, anthracycline antibiotics, among them, at no great manifestations of their toxicity due to preductal's cardioprotective action.

EFFECT: higher efficiency of therapy.

1 ex, 5 tbl

FIELD: medicine, immunology, nucleic acids.

SUBSTANCE: invention relates to a method for stimulation of the immune response using nucleic acids-containing immunostimulating compositions, oligonucleotide-containing composition and to a method for treatment or prophylaxis of allergy or asthma. For stimulation of the immune response thymidine-enriched nucleic acid comprising poly-T sequences and/or comprising above 60% of thymidine-containing nucleotide residues is administrated. Invention provides the development of new method for stimulation of the immune response due to administration of the proposed immunostimulating nucleic acid.

EFFECT: valuable medicinal properties of nucleic acid.

27 cl, 12 dwg, 12 ex

FIELD: veterinary science.

SUBSTANCE: the suggested method should be performed under conditions of experimental modeling dystrophic process due to intraosseous introduction of glucosamine hydrochloride at the dosage of 15-25 mg/kg 1-2 times weekly during a month. The method provides high local concentrations of medicinal preparation, at its steady entering the circulation by leaving aside hepatic barrier and, as a result, optimization of chondroprotector action of glucosamine hydrochloride and better treatment of articular alterations induced in the course of an experiment in animals.

EFFECT: higher efficiency of correction.

8 dwg, 1 ex

FIELD: veterinary science.

SUBSTANCE: the suggested method should be implemented under conditions of experimental modeling dystrophic process due to intramuscular injection of glucosamine hydrochloride at the dosage of 15-25 mg/kg once or twice weekly for 1 mo. The method provides good effect in treating a lesion induced in the course of an experiment due to matching adequate dosages and a certain mode of injecting chondroprotector in animals.

EFFECT: higher efficiency of correction.

6 dwg

FIELD: medicine, neurology.

SUBSTANCE: method involves intravenous administration of autolymphocytes treated with an immunomodulating agent by extracorporal method using cycloferon (250 mg) as an immunomodulating agent. Simultaneously, the following medicinal mixture comprising lidocaine, 100 mg; lidazum, 32 U; dexamethasone, 4 mg; leukinferon, 10 000 U; 40% glucose solution, 4 ml is administrated into interspinal ligaments of spinal column at levels corresponding to thoracal and lumbar enlargements of the spinal cord. The procedure is repeated three times with interval for 48-72 h. Method provides enhancing the effectiveness of lymphostimulation and immunomodulation in cerebrospinal sclerosis. Invention can be used for lymphostimulation and immunomodulation in cerebrospinal sclerosis.

EFFECT: improved method for treatment.

1 tbl, 1 ex

FIELD: medicine, pulmonology.

SUBSTANCE: one should apply lycopid to study initial level of mature T-cells (CD3+) in % and solve following discriminant equation: D = 0.840 · (CD3+), and at D value being above 29.24 one should predict positive curative effect as a result of lycopid application, and at D value being below 29.24 on should predict no positive curative effect.

EFFECT: higher efficiency of lycopid-including therapy.

2 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to new glycosides of indolo[2,3-a]-pyrrolo[3,4-c]carbazol-5,7-diones of the general formula (1)

wherein: -R1 means residue of mono- or disaccharide in pyranose form taken among the group: D-Rib, L-Ara, D-Xyl, D-Gal, D-Glc, D-Lac; -R2 means hydrogen atom, methyl group or residue of mono- or disaccharide; -R3 means hydrogen atom, hydroxyl group, amino-group or formamido-group; each -X1 and -X2 means independently of one another hydrogen atom or bromine atom under condition that they can't mean hydrogen atom simultaneously and under condition also that if R1 means disaccharide residue then R2 differs from hydrogen atom. Prepared derivatives show, in particular, cytotoxic and antitumor activity against melanoma B16 and Ehrlich tumor.

EFFECT: valuable medicinal properties of derivatives.

3 cl, 3 tbl, 2 dwg, 8 ex

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