The method of obtaining 17-hydroxy-11-[4-(dimethylamino)phenyl]- 17-(prop-1-inyl)-Östra-4,9-dien-3-one

 

(57) Abstract:

The invention relates to improvements in method of obtaining 17-hydroxy-11-[4-(dimethylamino)phenyl] -17 -(prop-1-inyl)-östra - 4,9-Dien-3-one of formula I

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The method is realized by the interaction of the derived steroid 4-dimethylaminopyridinium in the presence of a catalyst in an environment of tetrahydrofuran, followed by separation of arillas steroid using saturated solution of ammonium chloride, dehydration and hydrolysis in the presence of an acid agent in the environment of the solvent at room temperature, followed by separation of the target product, while the oxidation of the derived steroid of General formula III

< / BR>
where (a) R = H b) R = tert-BuMe2Si, carried out by a complex of hydrogen peroxide - hexaferrite in an organic solvent in the presence of chiral phase transfer catalyst (N-benzylbenzamide) in a molar ratio of 1 : 2 : (0,03 - 0,10), respectively, and in the presence of pyridine. After separation of the organic layer highlight with the outputs 91 to 96.5 %, depending on R, the compound of General formula lV:

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where R has the above meanings and containing 5,10 - and 5,10-isomers in the ratio (7,5 - 14,2): 1, respectively, depending on R, oilbased with active pyrophoric form of magnesium, in a molar ratio of 1 : 1,9, respectively, in the presence of copper chloride at 0 - 5oC. After separation of the organic layer emit formed kilkeel steroid of General formula II:

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where R has the above significance. Purified by crystallization II is subjected to dehydration 25% solution of sulfuric acid in acetone at a molar ratio of 1 : 1,67 : 8, respectively, with subsequent isolation of the target product by treating the reaction solution with an aqueous solution of the base and the filter fell into the residue of the target product. Achieved high yield I (73,6%), counting on III. 2 C.p. f-crystals.

The invention relates to improvements in method of obtaining 17-hydroxy-11--[4-(dimethylamino)phenyl] -17--(prop-1-inyl)-östra-4,9-Dien-3-one of formula I

-

The first connection I received a firm Roussel-Uclaf [1]. Compound I is used in medical practice as a means for termination of early pregnancy [2] and is known under the international name for mifepristone, RU-486 [3].

The way to obtain I [5] involves acid hydrolysis of compounds IIA or trimethylsilyl ether and dehydrating them under the action of diluted (15-25%) aqueous sulfuric acid in acetone or other lower Etiam compounds IVa, or, respectively, its trimethylsilyl ether (IVC) (containing 5,10/ and 5,10/epoxyester in the ratio of (3,4-3,9): 1) with 4-dimethylaminopyridinium at a molar ratio of 1: (2,5-3,5) in the presence of chloride of copper in the environment of tetrahydrofuran at 0 to 10oC. the Resulting kilkeel steroid of formula II (a, b) is recovered by processing the obtained reaction mixture with a saturated aqueous solution of ammonium chloride, separation of the organic layer, followed by concentrating it and filtering crystalline precipitate, which is washed with aqueous tetrahydrofuran, dried and receive II (a, b) with the outputs of 81.5% and 75% of theoretical. considering 5.1/epoxyester, respectively. Compound IV (a, b) is obtained by oxidation of the steroid of formula IIIa or its trimethylsilyl ether (V) complex hexachloroacetone-hydrogen peroxide in the presence of a phosphate buffer with a pH of 7 (oxidative system) or complex HEXAFLUOROACETONE-hydrogen peroxide in the presence of pyridine (oxidative system B) in methylene chloride and at room temperature. After the usual selection of technical product is recrystallized from ether and receive: IVa with yield 72% of theory. and the ratio of isomers of 3.4:1 (method A) and 3.76:1 (method B); IVC with the release of 95.8% of theory. and soothes I is the relatively low yield of the target product in the calculation of the original compound IIIA. So, when synthesis via an intermediate compound IVa (with the above ratio of isomers) output I is 44.1%, counting on IIIA, and the synthesis via IVC - 53%, respectively.

The aim of the invention is to increase the yield of the target product, its quality and profitability (efficiency) of the process.

This goal is achieved by the improved method of obtaining 17-hydroxy-11/-[4-(dimethylamino)phenyl] -17--(prop-1-inyl)-östra-4,9-Dien-3-one of formula I, namely, that derived steroid of General formula III:

< / BR>
where (a) R=H;

b) R is tert.-BuMe2Si,

oxidize the hydrogen peroxide-hexaferrite in the two-phase water-chloroform with the use of chiral phase transfer catalyst, N-benzylbenzamide, in the presence of a base (e.g. pyridine or triethylamine), at a molar ratio of steroid/cat 1:(0,03-0,1) and room temperature. The organic layer is separated and after normal processing of produce technical product IV(a, b), with the content --apoxyomenos of 7.5:1 for IVa, and 14.2:1 IV, respectively. After recrystallization of the product from ether get crystal IV with yield 91% of theory. for IVa and 96.5% of theoretical. for IV, the proper interaction of 4-dimethylaminopropylamine with active pyrophoric form of magnesium (obtained in a known manner [6] decomposition of the complex magnesium-anthracene - MgC14H10THF) in tetrahydrofuran, at a molar ratio of steroid/ArMgBr 1:1.9 in the presence of chloride of copper in the environment of tetrahydrofuran at 0-5oC. the Resulting kilkeel II(a, b) with the above-mentioned R, isolated in the usual way with the release of 97% of theoretical. for IIA and 79% of theory. for IIB, considering on-isomer IV(a, b). Hydrolysis of compounds II(a, b) in a known manner [5] 25% aqueous sulfuric acid in the environment of acetone to obtain the target product I in the form of a crystalline powder with a yield of 73.6 per cent (IIA, R = H) and 65.6% (IIB, R = BuMe2Si) from theory., counting on the original connection IIIA, I. pl. 191,5-192.5 kgoC, [-]D = +139o.

Scheme of the proposed method of obtaining the target product I at the end of this description.

Intermediate compound IIIB are not described in literature, the structure is set on the basis of mass and PMR spectra, physico-chemical characteristics are given in example 5.

The inventive method for the oxidation of compounds III(a, b), which allowed to obtain compound IV(a, b) with the content of 5,10 - 5,10-epoxy-isomers in the ratio of 7.5: 1 and 14.2:1, respectively, for the first time we applied. Accordingly, compounds IV(a, b) with such a high content /isomers for the first time received by us.

The method of obtaining the above with the chemistry of the reaction Jozica and subsequent reactions epoxidation 5,10-double bond of a steroid [4].

The compound of formula IIIa is the source for the synthesis of I - receive interaction 3,3-Ethylenedioxy-östra-5(10), 9(11)-Dien-17-it (V) propanimidamide by the standard method [5] with the allocation of 102 - 104% of theoretical. technical oily product and the content of the main substance of 95 - 97% and steroid impurities not more than 3 - 5%. To obtain IIIB compound IIIa are siciliani tert-butyldimethylchlorosilane in a mixture of dimethylformamide-ethyl acetate (3: 2) in the presence of kislorodsvyazyvayushchei means, for example, pyridine, at room temperature. Formed 17/--(prop-1-inyl)-17-tert - butyldimethylsilyloxy-3,3-Ethylenedioxy-östra-5(10), 9(11)-the diene (IIIB) was isolated by filtration after washing with water, getting with the release of 96% (considering the content of the IIIA technical product). Compound III(a, b) is subjected to the action of a complex of hydrogen peroxide-HEXAFLUOROACETONE in the presence of pyridine using chiral phase transfer catalyst in chloroform at room temperature, followed by separation according to the usual scheme of compounds of General formula IV.

Obtain compounds of General formula IV(a,b) with a ratio of not less than 7.5: 1 for IVa and 14.2:1 IV, in the form of a colorless crystalline substances. These ratios were determined with pomoite on IIIA) 91% of theory. (after recrystallization) and IV to 96.5% (IIIB) from theory.

It is preferable to the synthesis of I through the connection IVa despite the fact that the ratio of the isomers in it below, namely 7,5:1 than to connect IV, for which the ratio of 14.2:1. Increased output connection IIA when interacting with IVa 4-dimethylaminopyridinium, compared with the output IIB in a similar processing IV generally compensates for the relatively low content of isomer and provides a higher yield of the target compound I, based on the common source connection IIIa, 8%.

The following examples illustrate the inventive method.

Example 1.

Getting 17-(prop-1-inyl)-3,3-Ethylenedioxy-5/--10-epoxy-östra 9(11)-EN-17-ol (add 5% molar interfacial catalyst).

The solution 14,67 g technical IIIa (basic substance content of 98.5% according to TLC, 40 mmol) in 55 ml of chloroform is cooled to 0oC. With efficient stirring, keeping the temperature 01,5oC, add 0.75 ml of pyridine, to 0.92 ml HEXAFLUOROACETONE of three-hydrate and 8.1 ml (80,5 mmol) of 30% hydrogen peroxide and 0.98 g (2 mmol) of N-benzylbenzamide. The mixture is stirred at this temperature for 15 minutes and then 8 hours at kakuu phase is washed with 50 ml of 10% aqueous sodium thiosulfate solution, 50 ml of a saturated aqueous solution of sodium chloride and 2 x 35 ml of distilled water. The chloroform evaporated in vacuum and get 15,48 g (104,5% of theoretical. per IIIA) prapinabracni product IVa with the ratio of the isomers, as 7,73:1 (PMR spectrum). By recrystallization from ether get 13,47 g of crystalline oxide IVa (91% of theory. per IIIA) with the same ratio of isomers in the technical product.

PMR-spectrum (CDCl3, , M. D.) to 5,10 oxide: 0,78 (C., H noted in 18 positions); 1,80 (C., H methyl b-C C-CH3); 3,88 (m, etelankyla), 6,07 (m , H at C in 11 positions).

PMR-spectrum (CDCl3, , M. D.) to 5,10 oxide: 0,74 (C., H noted in 18 positions); 1,81 (C., H methyl b-C C-CH3); 3,91 (m, H etelankyla); USD 5.76 (m, H at C in 11 positions).

Example 2.

Getting 17-(prop-1-inyl)-3,3-Ethylenedioxy-5// -10-epoxy-östra 9(11)-EN-17-ol (add 3% molar interfacial catalyst).

In the conditions of example 1 from 4,89 g technology. IIIa [content of the basic substance 4,72 g (13.3 mmole)] in 18 ml of chloroform in the presence of 0.25 ml of pyridine at 0.31 ml HEXAFLUOROACETONE of three-hydrate, and 2.7 ml (26.8 mmol) of 30% hydrogen peroxide and 0.20 g of N-benzylbenzamide (0.4 mmole) get 10.5 hours of 5.17 g (105% of theoretical. per IIIA) technical IVa in the form of a thick oil with the IRS IVa (88,6% of theoretical. per IIIA) with the same ratio of isomers in the technical product.

Example 3.

Poluchenie-(prop-1-inyl)-3,3-Ethylenedioxy-5/-10-epoxy-östra 9(11)-EN-17-ol (with the addition of 7.5% molar interfacial catalyst).

In the conditions of example 1 from 20,0 g technology. IIIa [basic substance content of 19.3 g (54,5 mmole) in 75 ml of chloroform in the presence of 1.0 ml of pyridine 1.25 ml HEXAFLUOROACETONE of three-hydrate, and 11.0 ml (109 mmol) of 30% hydrogen peroxide and 1.34 g (2,73 mmol) of N-benzylbenzamide for 6.5 hours get 21,07 g (104,5% of theoretical. per IIIA) technical IVa in the form of prapinabracni substances with a ratio of isomers as of 7.75:1 (PMR spectrum). By recrystallization from ether get 18,44 g of crystalline oxide IVa (91,4% of theoretical. per IIIA) with the same ratio of isomers in the technical product.

Example 4.

Poluchenie-(prop-1-inyl)-3,3-Ethylenedioxy-5-10-epoxy-östra 9(11)-EN-17-ol (add 10% molar interfacial catalyst).

In the conditions of example 1 from 2.5 g technology. IIIa [content of the basic substance to 2.41 g (6.8 mmol)] in 9 ml of chloroform in the presence of 0.15 ml of pyridine, 0.16 ml of HEXAFLUOROACETONE of three-hydrate, to 1.38 ml (13.7 mmol) of 30% hydrogen peroxide, 1 ml of water and 0.33 g of N-benzylbenzamide (0,68 msdelay chromatographytandem (eluent hexane-ethyl acetate - 9:1) and get 2,19 g of crystalline IVa (87% of theory. per IIIA). Also provide 210 mg of 17-(prop-1-inyl)-3,3-Ethylenedioxy-5, 10/--9,11-diepoxy-östra-17-ol (8% of theory. per IIIA). (V) in the form of a pale yellow oil.

PMR-spectrum (CDCl3, , M. D.) 0,75 (1,5 H, s, H methyl) 0,80 (1,5 H, s, H methyl), 1,30 (1,5 H, s, H methyl) and 3,86 (4H, m, H etelankyla). The ratio of isomers in IVa 7,68:1 (according to the PMR spectrum).

Example 5.

Getting 17-(prop-1-inyl)-17-tert-butyldimethylsilyloxy-3,3-Ethylenedioxy-östra-5(10)-9(11)-the diene (IIIB).

To 10.5 g technology. IIIa [content of the basic substance 10,13 g (26.8 mmol)] in 30 ml of a mixture of dimethylformamide-ethyl acetate-pyridine (4:1:1) under stirring add 8,07 g (53.6 mmol) of tert-butyldimethylchlorosilane at a temperature of 102oC. the Reaction mixture is stirred at this temperature for 1 hour, then at room another 5 hours. Pour in 380 ml of cold water and the resulting suspension is stirred for 2.5 hours. The precipitate is filtered off, washed with water and dried. Get a 12.05 g (96.1 per cent theoretical., counting on IIIA) IIIB. So pl. 117-120oC, the amount of impurities is less than 2% (by TLC).

PMR-spectrum (CDCl3, , M. D.): 0,07 (9H, s, H tert-Bu-); of 0.11 (6H, s, H methyl (CH3)2-Si-); 0,75 (C., H noted in 18 positions); 1,80 (C., H methyl b-C C-CH3); 3,89 CLASS="ptx2">

Getting 17-(prop-1-inyl)-17/--tert-butyldimethylsilyloxy-3,3-Ethylenedioxy-5-10-epoxy-östra 9(11)-ene (IV).

In the conditions of example 1 from a 12.05 g (of 25.7 mmol) IIIB (obtained in example 5) in 37 ml of chloroform in the presence of 0.48 ml of pyridine, 0,59 ml HEXAFLUOROACETONE of three-hydrate, and 5.2 ml (of 51.7 mmol) of 30% hydrogen peroxide and from 0.76 g of N-benzylbenzamide (1.5 mmol, 6% molar to the steroid) for 3.5 hours to obtain a solid residue, which is washed on the filter with 10 ml of cold (0oC) diisopropyl ether and dried in vacuum. Get 12,08 g IV (97.3% of theory. per IIIB, or 93,5% of theoretical. per IIIA) in the form of a crystalline powder with a ratio of isomers as 14,2:1 (PMR spectrum).

PMR-spectrum (CDCl3, , M. D.) for 5, 10-oxide: of 0.07 (9H, s, H methyl to tert-Bu-); to 0.10 (6H, H methyl (CH3)2-Si'-); 0,752 (C., H noted in 18 positions); 1,80 (H-C C-CH3); the 3.89 (m, H etelankyla);. 6,10 (m, H at C in 11 positions).

PMR-spectrum (CDCl3, , M. D.) for 5, 10-oxide: of 0.07 (9H, s, H methyl to tert-Bu); 0,11 (6H, H methyl (CH3)2-Si'-); 0,750 (C., H noted in 18 positions); 1,81 (H-C-C-CH3); the 3.89 (m, H etelankyla); 5,77 (H at C in 11 positions). Mass spectrum, m/z: M-483, M-- (CH3)3C(CH3)2SiOH 352.

Example 7.

The 11-[4-(DIMET the Va /the Grignard reagent of 1:1,9).

To suspensie 4,24 g (174,6 mmol) of freshly prepared active forms of magnesium (obtained in [6]) in 30 ml of absolute tetrahydrofuran with stirring in a stream of dry argon was added a solution of 35.6 g (178 mmol) of 4-bromomethane in 85 ml of abs. THF at a temperature of 10-15oC. and Stirred at this temperature for 30 minutes, then gradually raise the temperature of the reaction mixture to 50oC and stirred until complete dissolution of the magnesium. The reaction mixture was cooled to 0oC, load of 0.42 g (4.2 mmol) of copper chloride, stirred for 15 minutes, add a solution of 34 g (91,9 mmol) of IVa in 190 ml of dry tetrahydrofuran, maintaining the temperature not above 5oC. Upon completion of addition, the reaction mixture is stirred for 30 minutes, after which process the reaction mass of a saturated solution of ammonium chloride, separating the organic layer, wash it with a saturated solution of sodium chloride and evaporated in vacuo to start crystallization. The residue is cooled to 15oC and kept at this temperature for one hour. Vegascasinoonline precipitate is filtered off, washed with a mixture of THF-water (1:1), dried in vacuum. Get 38,81 g (97.2% of theory. in the calculation of 5,10-epoxy-isomer IVa, or 78.6% of theoretical. in the calculation of the original IIIA) crystal IIA with stuet literature data [4, 5].

Example 8.

The 11-[4-(dimethylamino)phenyl] -17-(prop-1-inyl)-17 tert-butyldimethylsilyloxy-3,3-Ethylenedioxy-extras-9-EN-5-ol (IIB), (IV, the ratio /-isomers of 14.2:1; the ratio of IV /a Grignard reagent of 1:1,9).

In the conditions of example 7 to the Grignard reagent [of 1.1 g of the active form of magnesium (45,2 mmol) and which 9.22 g (46,1 mmol) 4-bradymetabolic] in 30 ml of dry tetrahydrofuran was added 0.11 g (1.1 mmol) of copper chloride and then a solution of 11.5 g (of 23.8 mmol) of epoxide IV in 30 ml of absolute tetrahydrofuran. After processing in the conditions of example 7 receive or 10.60 g IIB in the form of a crystalline powder (79% of theory. per-isomer IV, or 69,0; per IIIa. Melting point 229-231oC (ethylacetate), the steroid content of impurities 2% (TLC).

PMR-spectrum (CDCl3, , M. D.): 0,07 (9H, s, H tert-butyl); to 0.10 (6H, s, methyl to tert-BuMe2Si-); 0,47 (C., H noted in 18 positions); 1,86 (C.,- C-C-CH3); to 2.29 (C., H (CH3)2N); 3,98 (m, H etelankyla); 4,40 (C., OH); 6,10 and 7,05 (AA'BB' 4H phenyl). Mass spectrum, m/z: M-604.

Example 9.

Getting 17-hydroxy-11 -[4-dimethylamino)phenyl]-17-(prop-1-inyl)-östra-4,9-Dien-3-one (I), (IIA: H2SO4: acetone, 1:1,67:8).

To a suspension of 35 g (from 71.3 mmol) of 11-[4-dimethylamino)dryers the agreement acids. The resulting solution was stirred for 40 minutes at room temperature. The reaction mixture is cooled with ice water and added dropwise to about 210 ml of 25% aqueous ammonia solution to pH 8. To the resulting mixture is poured 200 ml of water, precipitated precipitate is filtered off and washed with water until neutral and dried. Get 29,73 g (97.2% of theory., or to 76.4% of theory. per IIIa) of the target product I so pl. 189,5-191,5oC []D= +139o. So pl. 191,5-192.5 kgoC (from ethyl acetate-pentane).

PMR-spectrum (CDCl3, , M. D.): 0,54 (C., H noted in 18 positions); 1,91 (C., H-C-C-CH3); 2,92 (C., H (CH3)2N); 4,50 (D., H at C in 11 positions); 5,70 (C., H at C in 4 positions); 6,65 and 7,03 (AA'BB', 4H phenyl).

Example 10.

Getting 17-hydroxy-11-[4-dimethylamino)phenyl] -17-(prop-1-inyl)-östra-4,9-Dien-3-one (I). (IIb: H2SO4: acetone, 1:1,67:8).

To a suspension of 8 g (13,2 mmol) IIB in 60 ml of acetone was added 7.3 ml (22 mmol) of 25% aqueous sulfuric acid. The resulting solution was stirred for 1 hour at room temperature. After processing in the conditions described in example 9, the gain of 5.45 g (96,3% of theoretical. or 66,4% in the calculation of the original IIIA) of the desired product I. the melting point 187-189oC.

LITERATURE

[1] the Magazine D is od Ed. M. Negwer, Akademic-Verlag, Berlin, 1994, p.2569.

[4] Patent USSR, 1447289, class C 07 J 1/00, publ. 1988.

[5] the Eurasian patent EP-A-0104387, C 01 J 1/00 A 61 K 31/565, publ. 1997, a prototype.

[6] Journal Of Chem.Ber.", 1990, V. 123, N 7, p. 1517-1528.

Sposobnosti-hydroxy-11-[4-(dimethylamino)phenyl]-17(prop-1-inyl)östra-4,9-Dien-3-one of formula I

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interaction derived steroid 4-dimethylaminopyridinium in the presence of a catalyst in an environment of tetrahydrofuran, followed by separation of arillas steroid using saturated solution of ammonium chloride, dehydration and hydrolysis in the presence of an acid agent in the environment of the solvent at room temperature, followed by separation of the target product, characterized in that the oxidation-derived steroid of General formula III

< / BR>
where (a) R = H;

b) R = tert-Bu Me2Si,

is a complex of hydrogen peroxide - hexaferrite in an organic solvent in the presence of chiral phase transfer catalyst (N-benzylbenzamide) in a molar ratio of 1 : 2 : (0,03 - 0,10), respectively, and in the presence of pyridine; after separation of the organic layer isolated a compound of General formula IV

< / BR>
where R has the above significance,

aerodactyl with dimethylaminopropylamine, obtained by the reaction of 4-dimethylaminopropylamine with active pyrophoric form of magnesium in a molar ratio of 1 : 1,9, respectively, in the presence of copper chloride at 0 - 5oAfter separation of the organic layer emit formed kilkeel steroid of General formula II

< / BR>
where R has the above significance,

purified by crystallization II is subjected to dehydration 25% solution of sulfuric acid in acetone at a molar ratio of 1 : 1 : 8, respectively, with subsequent isolation of the target product by treating the reaction solution with an aqueous solution of the base and the filter fell into the residue of the target product.

2. The method according to p. 1, characterized in that through the use of special active forms of magnesium condensation steroid with arellanobond is carried out at a lower molar ratio of 1 : 1,9 respectively.

3. The method according to p. 1, characterized in that as starting compound ispolzuut-(prop-1-inyl)-17-tertBUTYLPEROXY-3,3-Ethylenedioxy-östra-5(10)-9(11)-the diene(IIIB).

 

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16 cl, 8 dwg, 2 tbl, 30 ex

FIELD: organic chemistry, steroids, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I) , their pharmaceutically acceptable salts, solvates, stereoisomers wherein in each case R1 and R2 mean independently hydrogen atom, possibly substituted alkyl, aryl, heteroalkyl wherein heteroatom means nitrogen atom, heteroaryl wherein a heteroatom means nitrogen, oxygen or sulfur atom; or R1 and R2 in common with N-atom to which they are bound can form a heterocyclic structure as a moiety of organic group comprising 6-12 carbon atoms and comprising optionally 1-6 heteroatoms chosen from nitrogen and oxygen atoms; R3 and R4 mean hydrogen atom or a protective group under condition that R and/or R4 represents part of the hydroxyl protective group; № from 1 to 17 mean carbon atoms wherein C-atoms at № 1, 2, 4, 11, 12, 15 and 16 can be substituted with two from R5 groups; C17-atom can be substituted with one of the following groups: =C(R5)(R5), =C=C(R5)(R5) or two from groups - R5 and -OR6; C-atoms at № 5, 8, 9, 10, 13 and 14 can be substituted with group R5 wherein R means hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, (C1-C6)-halogenalkyl; R6 means H, protective group, such as -OR6-protected OH-group wherein the group -OR6 can form cyclic protective structure for vicinal -OH groups. Proposed compounds can be components of pharmaceutical composition and useful in treatment and/or prophylaxis of different states including inflammation, asthma, allergic disease, chronic obstructive pulmonary disease, allergic dermatitis, solid neoplasms, ischemia and cardiac arrhythmia.

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

53 cl, 10 tbl, 24 ex

FIELD: organic chemistry, steroids, medicine.

SUBSTANCE: invention describes compounds or their salts of the general formula (I): wherein values C are disclosed in the invention description. These compounds can be used in preparing medicinal agents used in treatment of acute disorders in portal and hepatic venous circulation.

EFFECT: valuable medicinal properties of compounds.

4 cl, 1 tbl, 2 ex

FIELD: steroids, pharmacy.

SUBSTANCE: invention describes a method for preparing crystals showing the mean coarseness index in the required limits from 3 to 25 mcm and maximal size 100 mcm, not above. Method involves the crystallization process of supersaturated solution of compound representing 11β-benzaldoximestra-4,9-diene wherein it is subjected for wetted grinding by using the correspondence device designated for such wetted grinding to obtain suspension of primary grains. Also, invention crystals prepared by the proposed method and a pharmaceutical agent containing these crystals.

EFFECT: improved preparing method.

14 cl, 8 tbl, 4 dwg, 4 ex

FIELD: medicine, oncology.

SUBSTANCE: invention describes four groups of dialkyltriazenyl-carrying estrogens and anti-estrogens that can be used for using as chemotherapeutic drugs in treatment of human and animal gonad carcinomas.

EFFECT: valuable medicinal properties of drugs.

8 cl, 11 dwg, 38 ex

FIELD: chemistry.

SUBSTANCE: polyaminosteroid branched derivatives of general formula I are described, where R1 is saturated or unsaturated C2-C10alkyl (conjugated or branched) or methyl, R2 is COOH or branched polyamine fragments, R3 is H, OR19, where R19 is H or C1-6acyl, R4 is H, R5 is H, CH3, R6 is H, CH3, R7=R8=R9=H, R10 is H, CH3, R11 is OH,-OSO3, - O-acyl, -(Z)n-(NR-Z)p-N(R)2, Z is linear hydrocarbon diradical, n=0, 1, p=1, R-H, C1-6alkyl, C1-6aminoalkyl, possibly substituted by C1-6alkyl, R12=R13=R15=H, R16 is H, OH, R17 is H, R18 is H, CH3, possible double bond. Compounds possess bactericidal activity and can be used for prevention of bacterial infections.

EFFECT: production of polyaminosteroid derivatives, possessing bactericidal activity which can be used for prevention of bacterial infections.

27 cl, 31 ex, 1 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: 17β-oxoestratrienes of the general formula III and 17β-oxyestratrienes of the general formula II are used as intermediary products in obtaining 17α-alkyl-17β-oxyestra-1,3,5(10)-trienes of the general formula I with antiestrogenic effect, where Hal, R3, SK, R17', R17" represent elements listed in the invention claims.

EFFECT: improved method of obtaining the product.

19 cl, 4 ex

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