Substituted pyrrolo[4,3-b]indoles, combinatory and focused library, pharmaceutical composition, methods for their preparing and using

FIELD: organic chemistry, medicine, neurology, pharmacy.

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

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

20 cl, 2 tbl, 12 ex

 

The text descriptions are given in facsimile form.

1. Hydrogenated pyrrolo[4,3-b]indoles of General formula 1, their racemates, their optical isomers, geometrical isomers, pharmaceutically acceptable salts and/or hydrates

where the dotted line with its accompanying solid line (represents a single or double bond; R1and R2independently from each other, represent substituents of the amino group selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, nitrogen heteroaryl; C1-C6alkoxycarbonyl, possibly substituted phenyl, possibly substituted, carbylamine or thiocarbanilide, substituted acyl, possibly substituted arylsulfonyl, while the Deputy is specified in R 1and R2independently selected from C1-C6of alkyl, halogen atoms, nitro, carboxy, alkoxy, aryl; Rinrepresents one or more identical or different substituents of the cyclic system selected from hydrogen, alkyl, aryl, cyano, halogen, 5-6-membered nitrogen-containing heteroaryl; ex:

1,2,3,4-tetrahydropyrrolo[4,3-b]indole(1), 2-methyl - And(2), 2-butyl And(3), 2-cyclohexyl - A(4), 2-fenetidin - A(5), 2-(1-methyl-2-phenylethyl)- A(6), 2-carbethoxy - A(7) and 2-benzyl-4-phenyl-1,2,3,4-tetrahydropyrrolo[4,3-b]indole And(8); 3-(2-butyl - A(9) and 3-(2-cyclohexyl-1,2,3,4-tetrahydropyrrolo[4,3-b]indol-4-yl)-propionitrile And(10); 2-butyl-4-(2-dimethylaminoethyl)And(11), 3-(2-cyclohexyl-4-(2-dimethylaminoethyl)And(12), 2-butyl-4-[3-(4-methylpiperazin-1-yl)propyl] (13) and 2-cyclohexyl-4-[3-(4-methylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydropyrrolo[4,3-b]indole And(14); 2-isopropyl - And(15), 2-tertbutyl And(16), 2-benzyl - (17) and 2-(4-methoxybenzyl)-4-phenylsulfonyl-1,2,3,4-tetrahydropyrrolo[4,3-b]indole And(18); 2 carbethoxy-7-fluoro - (19)7-fluoro-4-(4-forfinal)And(20), 2-carbethoxy-7-fluoro-4-(4-forfinal)And(21), 2-methyl-7-fluoro-4-(4-forfinal)And(22), 2-propyl-7-fluoro-4-(4-forfinal)And(23), 2-(3,3-dimethylbutyl)-7-fluoro-4-(4-forfinal)(24), 2-phenethyl-7-fluoro-4-(4-forfinal)And(25), 2-benzyl-7-fluoro-4-(4-forfinal)And(26), 2-propionyl 7-fluoro-4-(4-forfinal)And(27), 2-(3,3-dimethylbutanol)-7-fluoro-4-(4-forfinal)And(28), 2-[4-oxo-4-(4-forfinal)] (29) 2-(4-hydroxy-4-phenyl) - (30), 2-[4-hydroxy-4-(4-forfinal)]- A(31), 2-[5-oxo-5-(4-forfinal)]- A(32) and 2-[5-hydroxy-5-(4-forfinal)]-1,2,3,4-tetrahydropyrrolo[4,3-b]indole And(33); CIS-1,2,3,3A,4,8b-hexahydropyrazino[4,3-b]indole And(34); 7-methyl-2-benzyl-1,2,3,4-tetrahydropyrrolo[4,3-b]indole And(35).

A: R1=H (1, 20); CH3(2, 21); (C4H9(3, 9, 11, 13); With6H5-CH2CH2(4, 24); C6H5-CH2(5, 17, 25); cyclohexyl(6, 10, 12, 14); CO2With2H5(7, 28); ISO-C3H7(15); tert.-With4H9(16); 4-CH3O-C6H4(18); (C3H7(22); (CH3)3CH2CH2CH2(23); CH3CH2FROM (26); (CH3)3CH2CH2FROM (27); 4-F-C6H4-C(O)CH2CH2CH2(29);6H5-C(OH)CH2CH2CH2(30); 4-F-C6H4-C(OH)CH2CH2CH2(31); 4-F-C6H4-C(O)CH2CH2CH2CH2(32); 4-F-C6H4-C(OH)CH2CH2CH2CH2(33).

2. Compounds according to claim 1, represents the substance of a CIS-1,2,3,3A,4,8b-hexahydropyrazino[4,3-b]indoles of General formula 1.2.

where R1, R2Rinhave the above value.

3. Compounds according to any one of claims 1 and 2, which represents a 1,2,3,4-tetrahydro-pyrrolo[4,3-b]indoles of General formula 1.1.1, 1.1.2, 1.1.3 or CIS-1,2,3,3A,4,8b-hexahydro-pyrrolo[4,3-b]indoles of General formula 1.2.1, 1.2.2, 1.2.3.

where the dotted line with its accompanying solid line (), R1, R2and Rinhave the above value.

4. Compounds according to any one of claims 1 and 2, representing hydrogenated pyrrolo[4,3-b]indoles of General formula 1.1.4-1.1.9, 1.2.4-1.2.9.

where R1and Rnihave the above meanings; R4represents a possibly substituted alkyl, possibly substituted aryl, carboxylation, possibly substituted aryl; R5represents CN, possibly substituted aryl or heterocyclyl, carboxyethyl; R6is carboxyethyl, carbarnoyl, CN, possibly substituted aryl or possibly substituted gets recycler; R7represents a possibly substituted alkyl, possibly substituted aryl or possibly substituted heteroaryl.

5. Compounds according to any one of claims 1 and 2, representing hydrogenated pyrrolo[4,3-b]indoles of General formula 1.1.10-1.1.15, 1.2.10-1.2.15.

where R2, R4, R5, R6, R7and Rnihave the above values.

6. The method of obtaining compounds of General formula 1 according to claim 1 interaction phenylhydrazine General formula 2 (or their salts) with N-substituted pyrrolidin-3-one of General formula 3

where R1, R2and Rnihave the above value.

7. The method of obtaining compounds of General formula 1.2 according to claim 2 by hydrogenation of the corresponding compounds of General formula 1 with hydrogen in the presence of PtO2in the environment of an organic solvent.

8. Method of preparing compounds according to claim 4, excluding the compounds in which R1=N, the interaction of the corresponding compounds 1.1.1 or 1.2.1 in the environment of an organic solvent with an electrophilic reagent selected from: alkyl-, aryl - or heterotic the Il halides of General formula 5 in the presence of a base; electrophilic alkenes of General formula 6 in the presence of a base as catalyst; aldehydes of General formula 7 and NaBH(AcO)3, anhydrides or halides of carboxylic acids of General formula 8 in the presence of a base; ISO(thio)tiantou General formula 9 or sulfochloride General formula 10 in the presence of base

where R4, R5, R6and R7have the above value, X represents a halogen atom; Y represents a halogen atom, a hydroxide 3H-imidazol-1-Yuma, R7-C(O)O.

9. Method of preparing compounds according to claim 4, in which R1=N, by removing the hydrolysis of the protective group in the respective compounds according to claim 4, in which R1represents a protective group such as 2-ethoxycarbonylphenyl group (R1=CO2With2H5) or 2-tert.-butyloxycarbonyl group (R1=CO2C(CH3)3).

10. Method of preparing compounds according to claim 4, in which R1=CH3by restoring lydialydia protective group in the respective compounds according to claim 4, in which R1represents a protective group such as 2-ethoxycarbonyl the group (R 1=CO2C2H5).

11. Method of preparing compounds according to claim 5 interaction corresponding compounds 1.1.2, 1.1.3 or 1.2.2, 1.2.3 in the environment of an organic solvent with an electrophilic reagent selected from alkyl-, aryl - or heterocyclic halides of General formula 5 in the presence of a base; electrophilic alkenes of General formula 6 in the presence of a base as catalyst; aldehydes of General formula 7 and NaBH(ASO)3, anhydrides or halides of carboxylic acids of General formula 8 in the presence of a base; ISO(thio)tiantou General formula 9 or sulfochloride General formula 10 in the presence of base

where R4, R5, R6, R7X and Y have the above meaning.

12. A combinatorial library of compounds with neuroprotective, cognitive stimulating and antihistaminic activity, to identify compounds hits and leaders consisting of compounds of General formula 1 according to claim 1.

13. Focused library of compounds with neuroprotective, cognitive stimulating and antihistaminic activity, for determining and/or optimizing connections-leaders, the content is Asa, at least one compound of General formula 1 according to claim 1.

14. Pharmaceutical composition having neuroprotective, cognitive stimulating and antihistaminic activity, in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of at least one hydrogenated pyrrolo[4,3-b]indole of General formula 1 according to claim 1 or its racemate, or optical isomer, or a geometric isomer, or pharmaceutically acceptable salt and/or hydrate.

15. A method of obtaining a pharmaceutical composition according to 14, which consists in mixing the active substance with an inert filler and/or a solvent, characterized in that the active substance used pharmacologically effective amount of at least one hydrogenated pyrrolo[4,3-b]indole of General formula 1 according to claim 1, or its racemate, or optical isomer, or its geometric isomer, or its pharmaceutically acceptable salt and/or hydrate.

16. The use of the pharmaceutical composition according to 14 for the preparation of drugs for treating and preventing various diseases, pathogenesis of which is associated with excessive intracellular content of ions of Ca+2and/or diseases associated with naru is the group of histaminergic neurotransmitter systems.

17. Use item 16 to obtain drugs for the treatment of neurological disorders, and neurodegenerative diseases.

18. Use item 16 to obtain drugs for the treatment of allergic and autoimmune diseases.



 

Same patents:

FIELD: organic chemistry, chemical technology, medicine.

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

EFFECT: valuable medicinal properties of compound.

3 tbl, 1 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

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

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

19 cl, 17 tbl, 4 ex

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

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

13 cl, 147 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

26 cl, 10 tbl, 17 ex

FIELD: organic chemistry, medicine, pharmacy.

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

9 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

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

35 cl, 16 sch, 13 tbl, 43 ex

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

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

15 cl, 9 ex

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

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EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition, improved method of synthesis.

25 cl, 2 tbl, 12 ex

FIELD: medicine, pharmaceuticals.

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EFFECT: composition of improved neuroprotective characteristics.

50 cl, 3 tbl

FIELD: organic chemistry, medicine, pharmacy, biochemistry.

SUBSTANCE: invention relates to a method for treatment of states caused by activity of p38 kinase. Method involves administration to a patient needed in this treatment of at least one compound of the formula (I): or its pharmaceutically acceptable salt or solvate wherein R3 means hydrogen atom, methyl, perfluoromethyl, methoxy-group, halogen atom, cyano-group or NH2-group; X is chosen from -O-, -OC(=O)-, -S-, -S-, -S(=O)-, -SO2-, -C(=O)-, -CO2-, -NR10-, -NR10C(=O)-, -NR10C(=O)NR11-, -NR10CO2-, -NR10SO2-, -NR10SO2NR11-, -SO2NR10-, -C(=O)NR10, halogen atom, nitro- and cyano-group, or X is absent; Z is chosen from oxygen (O), sulfur (S), nitrogen (N) atoms, and -CR20 being wherein Z means -CR20 optionally substituted bicyclic aryl or heteroaryl with R4 or R5; R1 means hydrogen atom, -CH3, -OH, -OCH3, -SH, -SCH3, -OC()=O)R21, -S(=O)R22, -SO2NR23R25, -CO2R21, -C(=O)NR24R25, -NH2, -NR24R25, -NR21SO2NR24R25, -NR21SO2R22, -NR24C(=O)R25, -NR24CO2R25, -NR21C(=O)NR24R25, halogen atom, nitro- or cyano-group; R2 is chosen from the following group: (a) hydrogen atom under condition that R2 doesn't mean hydrogen atom if X means -S(=O)-, -SO2-, -NR10CO2- or -NR10SO2-; (b) alkyl, alkenyl and alkynyl comprising up to four R26 groups or pentafluoroalkyl as substitutes; (c) aryl and heteroaryl comprising up to three groups R27 as substitutes, and (d) heterocyclo-group or heteroalkyl optionally comprising keto-group (=O), up to three groups R27 as substitutes, and/or comprising carbon-carbon bridge comprising 3-4 carbon atoms, or (e) R2 is absent if X means halogen atom, nitro- or cyano-group; R4 means substituted aryl, aryl comprising NOSE-alkyl, substituted heteroaryl or optionally substituted bicyclic 7-11-membered saturated or unsaturated carbocyclic or heterocyclic fragment as a substitute, and R5 means hydrogen atom, alkyl or substituted alkyl with exception of cases when Z means O or S and then R5 is absent, or R4 and R5 in common with Z form optionally substituted bicyclic 7-11-membered aryl or heteroaryl; R6 means hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group, substituted heterocyclo-group, -NR7R8, -OR7 or halogen atom; R10 and R11 are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heterocyclo-group and substituted heterocyclo-group; R7, R8, R21, R24 and R25 are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group and substituted heterocyclo-group; R20 means hydrogen, lower alkyl or substituted alkyl, or R20 can absent if carbon atom to which is bound and in common with R4 and R5 represents part of bicyclic aryl or heteroaryl; R22 means alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group or substituted heterocyclo-group; R26 is chosen from the following group: halogen atom, trifluoromethyl, halogenalkoxy-group, keto (=O)-, nitro-, cyano-group, -SR28, -OR28, -NR28R29, -NR28SO2, -NR28SO2R29, -SO2R28, -SO2NR28R29, -CO2R28, -C(=O)R28, -C(=O)NR28R29, -OC(=O)R28, -C(=O)NR28R29, -NR28C(=O)R29, -NR28CO2R29,=N-OH, =N-O-alkyl; aryl optionally comprising as a substitute from one to three R27 groups; cycloalkyl optionally comprising a substituted keto-group (=O), from one to three R27 groups, or carbon-carbon-containing bridge comprising of 3-4 carbon atoms; and heterocyclo-group comprising optionally as a substitute keto-group (=O), from one to three R27 groups or comprising carbon-carbon bridge comprising 3-4 carbon atoms, and wherein each R28 and R29 is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C3-C7)-cycloalkyl and (C3-C7)-heterocycle, or they can form in common (C3-C7)-heterocycle; and each R28 and R29, in turn, can comprise optionally up to two substitutes representing alkyl, alkenyl groups, halogen atoms, halogenalkyl groups, halogenalkoxy-, cyano-, nitro-, amino-, hydroxy-, alkoxy-, alkylthio-groups, phenyl, benzyl, phenyloxy- and benzyloxy-groups; and R27 is chosen from the following group: alkyl, R32 and (C1-C4)-alkyl comprising as substitutes from one to three R32groups and wherein each R32 group is chosen independently from the following group: halogen atom, halogenalkyl, halogenalkoxy-, nitro-, cyano-groups, -SR30, -OR30, -NR30R31, -NR30SO2, -NR30SO2R31, -SO2R30, -SO2NR30R31, -CO2R30, -C(=O)R30, -C(=O)NR30R31, --OC(=O)R30, -OC(=O)NR30R31, -NR30C(=O)R31, -NR30CO2R31 and from 3-7-membered carbocyclic or heterocyclic ring comprising optionally as a substitute alkyl, halogen atom, hydroxy-, alkoxy-group, halogenalkyl, halogenalkoxy-, nitro-, amino- or cyano-group, and wherein each R30 and R31 is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C3-C7)-cycloalkyl, and heterocycle, or they in common can form (C3-C7)-heterocycle. Also, invention describes pyrrolotriazine compounds, a pharmaceutical composition based on thereof and a method for treatment of inflammatory diseases using above proposed compounds and pharmaceutical compositions.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

30 cl, 14 tbl, 152 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to compound of the formula (I): or (II): wherein R1 and R2 are chosen independently from hydrogen, optionally substituted alkyl or the group: -D-E wherein R represents a covalent bond or alkylene; E represents optionally substituted alkoxy-group, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkenyl or optionally substituted alkynyl under condition that if D represents a covalent bond then E can't represents alkoxy-group; R3 represents hydrogen atom, optionally substituted alkyl or optionally substituted cycloalkyl; X represents optionally substituted arylene or heteroarylene; Y represents a covalent bond or alkylene wherein one carbon atom can be substituted optionally for -O-, -S- or -NH-, and optionally substituted hydroxy-, alkoxy-, optionally substituted amino-group or -COR wherein R represents hydroxy-, alkoxy- or amino-group under condition that if an optional substitute represents hydroxy- or amino-group then it can't be adjacent with a heteroatom; Z represents hydrogen atom, optionally substituted monocyclic aryl or optionally substituted monocyclic heteroaryl under condition that Z represents hydrogen atom only under condition that Y represents a covalent bond, and X represents optionally substituted 1,4-pyrazolene, and under condition that if X represents optionally substituted arylene then Z represents optionally substituted monocyclic heteroaryl. Also, invention describes a method for treatment of the morbid state by inhibition of adenosine receptors describes as A2B based on compounds of the formula (I) or the formula (II). Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

32 cl, 35 ex

FIELD: medicine, experimental cardiology.

SUBSTANCE: one should intragastrically introduce claritromycin at the dosage of 30 mg/kg 15 min before coronary occlusion in the course of experimental coronary occlusion myocardial infarction. The innovation provides significant decrease of the necrosis area due to cardioprotector action of claritromycin.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: medicine, experimental cardiology.

SUBSTANCE: the present innovation deals with restricting the necrosis area in the course of experimental coronary occlusion myocardial infarction due to intragastric introduction of roxytromycin at the dosage of 30 mg/kg 15 min before coronary occlusion. The innovation provides significant decrease of the necrosis area due to cardioprotector action of roxytromycin.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions containing inhibitor of cholesterol esters-transporting protein (CETP) and a water-insoluble additive increasing its concentration. As CETP inhibitor invention uses S-{2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl}-2-methylpropanethioate or a prodrug that forms in vivo S-{2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl}-thiol. A water-insoluble additive increasing the concentration of CETP inhibitor represents crospovidon. Indicated compositions show improved bioavailability in medium wherein they are used that allows using in methods for treatment of cardiovascular disorders.

EFFECT: improved and valuable pharmaceutical properties of compositions.

13 cl, 11 tbl, 5 dwg, 9 ex

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

SUBSTANCE: invention describes novel derivatives of triazolo[4,5-d]pyrimidine of the general formula (I): wherein R1 means (C3-C5)-alkyl that can be substituted with halogen atom; R2 means phenyl that can be substituted with fluorine atom; R3 and R4 are similar and mean hydroxy-group; R means XOH wherein X means -CH2, -OCH2CH2 or a bond, or their pharmaceutically acceptable salt or solvate of solvate of such salt under condition that when X means -CH2 or a bond then R1 doesn't mean propyl group; when X means -CH2 and R1 means -CH2CHCF3, butyl or pentyl groups then phenyl group at R2 must be substituted with fluorine atom; when X means -OCH2CH2 and R1 means propyl then phenyl group at R2 must be substituted with fluorine atom. Also, invention describes a pharmaceutical composition based on these compounds, method for their synthesis and novel intermediate compounds of the formula (II) , (V) and R-(R*,R*)-2,3-dihydroxybutanedioate (1:1) of compound of the formula (III): . Also, invention relates to a method for treatment of diseases mediated by P2T-receptors, such as myocardium infarction, prophylaxis or propagation of tumors and others.

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

15 cl, 9 ex

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

SUBSTANCE: invention relates to novel hydrogenated azepino[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers and their pharmaceutically acceptable salts and/or hydrates. In the general formula (1) a dotted line with accompanying unbroken line represents a simple or double bond; R1 and R2 represent independently of one another substitutes of amino-group chosen from hydrogen atom, possibly substituted (C1-C8)-alkyl possibly substituted with aryl, 5-6-membered azaheterocyclyl, (C1-C8)-alkoxycarbonyl, possibly substituted phenyl, possibly substituted carbonylamino- or thiocarbonylamino-group, substituted acyl, (C1-C8)-alkylsulfonyl, possibly substituted arylsulfonyl and wherein substitutes in indicated R1 and R2 are chosen independently from (C1-C8)-alkyl, halogen atoms, nitro-, carboxy-, alkoxy-group, aryl; Rin represents one or some similar or different substitutes of cyclic system chosen from hydrogen atom, (C1-C8)-alkyl, (C6-C10)-aryl, halogen atom, 5-6-membered azaheterocyclyl. Also, invention relates to methods for synthesis of these compounds, their using and pharmaceutical composition and libraries of compounds. Synthesized compounds possess neuroprotective, cognitive-stimulating and anti-histaminic properties and can be used in treatment of different neurological disorders, allergic and autoimmune diseases, for example, for memory improvement.

EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition, improved method of synthesis.

25 cl, 2 tbl, 12 ex

FIELD: biologically active substances.

SUBSTANCE: invention relates to improved method of obtaining total amount of phenol acid including following steps: (a) multi-rooted sage is extracted with water and filtered; (b) filtrate is placed in polyamide column and washed with water to neutral reaction, wash water is removed, and polyamide column is eluted with weak aqueous alkali solution, and obtained fractions are connected; (c) alkali fractions obtained in step (b) are acidified and placed in absorption column with macroporous resin, column is washed to neutral state, wash water is removed, column is eluted with aqueous or anhydrous lower alcohol, eluent is collected, evaporated at reduced pressure to remove alcohol, and dried. Yield of final product exceeds 4% based on amount of crude drug and content of total amount of phenol acid exceeds 80%. Thus obtained total amount of phenol acid can be used as drug for prevention and treatment of brain vessel diseases.

EFFECT: enlarged resource of vegetable material for preparation of vascular drugs.

15 cl, 7 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to using inhibitor of absorption of sterol of the formula (VIII): or its pharmaceutically acceptable salts or solvates. This compound is used for preparing a medicinal agent that is used for decreasing the concentration of at least one sterol in plasma or tissues or their mixture of mammals wherein this sterol is not cholesterol or 5α-stanol. Also, invention relates to a method for decreasing the concentration of at least one sterol in plasma or tissue and involves administration to mammal a compound of the formula (VIII) in the dose 0.3-10 mg/1 kg of body mass per 24 h. Decreasing the content of content of indicated sterols in plasma or tissues provides prophylaxis or attenuation of such states as arteriosclerosis, risk of cardiovascular attack.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 6 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using compounds of (R,S)-2-arylpropionic acids of the formula (Ia) , and their (R)- and (S)-isomers as inhibitors of neutrophile (PMN leukocytes) chemotaxis induced by IL-8. These compounds elicit unexpected ability to inhibit effectively IL-8-induced chemotaxis and degranulation of neutrophiles being without significant effect on activity of cyclooxygenases. These compounds can be used in treatment of such diseases as psoriasis, ulcerated colitis, melanoma, chronic obstructive pulmonary disease, bulla pemphigus, rheumatic arthritis, idiopathic fibrosis, glomerulonephritis, and for prophylaxis and treatment of damages induced by ischemia and reperfusion.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

9 cl, 3 tbl, 43 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel indolyl-derivatives of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkyl substituted with from one to three halogen atoms; R2 means hydrogen atom, (C1-C8)-alkyl; R3 means (C1-C8)-alkoxy-group; R4 means hydrogen atom; A means oxygen atom or sulfur atom; n = 1,2 or 3. Synthesized compounds possess agonistic activity with respect to PPARα- and/or PPARγ-receptors. Also, invention relates to methods for their synthesis, a pharmaceutical composition based on thereof and their using for preparing medicinal agents, and to a method for treatment and/or prophylaxis of diseases.

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

29 cl, 1 tbl, 7 sch, 17 ex

FIELD: medicine, oral surgery.

SUBSTANCE: before surgical interference one should intravenously once inject by drops 0.03%-sodium hypochlorite solution at 1:40 against the volume of a patient's circulating blood. In 2 h one should intravenously once by drops inject rexod preparation at 16 mg. Then comes surgical interference in the course of which one should additionally carry out sanitation with 0.06%-sodium hypochlorite solution. In post-surgical period for 2 d after interference it is necessary to inject the same quantity of 0.03%-sodium hypochlorite solution. Rexod should be injected during the 1st d after operation at the same dosage, and during the next 3 d - per 8 mg. Additionally, locally during the 1st phase of wound process one should treat purulent wound with 0.06%-sodium hypochlorite solution, During the 2nd phase of wound process till applying early secondary sutures one should apply "Soderm" ointment onto the wound, and in the 3d phase - "Contractubex" gel onto cicatricial tissue. The innovation enables to avoid the progress of inflammatory process and shorten terms of therapy due to combined general and local impact of preparations being of detoxication and antioxidant action.

EFFECT: higher efficiency of therapy.

1 ex

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