Substituted 2-alkylmino-3-sulfonyl-pyrazolo[1,5-a]pyrimidines, serotonin 5-ht6 receptor antagonists, methods of producing and using said compounds

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-alkylamino-3-sulfonyl-pyrazolo[1,5-a]pyrimidines, their pharmaceutically acceptable salts and/or hydrates which have serotonin 5-HT6 receptor antagonist properties and can be used in treating or preventing development of various central nervous system diseases, whose pathogenesis is related to 5-HT6 receptors, particularly Alzheimer's disease, Parkinson's disease, Huntington disease, schizophrenia, other neurodegenerative diseases, cognitive and anxiety disorders and obesity. In general formula (I):

R1 and R3 independently denote optionally identical C1-C3alkyl, R2 is a -(CH2)nX group or R1 and R3 independently denote different substitutes selected from C1-C3 alkyl or a -(CH2)nX group, and R2 is a hydrogen atom or C1-C3alkyl; R4 is C1-C3alkyl; Ri5 is a hydrogen atom, one or two identical or different halogen atoms, C1-C3alkyl; i is equal to 0, 1 or 2; n is equal to 0, 1, 2 or 3; X is a carboxyl CO2H, C1-C3alkyloxycarbonyl, aminocarbonyl CONR6R7 or a NR6R7 amino group; R6 and R7 denote optionally identical hydrogen atom, optionally substituted C1-C3 alkyl, C3-C7cycloalkyl or an optionally substituted 5-7-member azaheterocyclyl containing 1-2 nitrogen atoms in the ring, where the substitutes are selected from C1-C3alkyl; or R6 and R7 together with the nitrogen atom to which they are bonded form an optionally substituted 5-6-member azaheterocyclyl containing 1-2 nitrogen atoms in the ring, where the substitutes are selected from C1-C3alkyl.

EFFECT: obtaining new biologically active compounds.

26 cl, 12 dwg, 4 tbl, 14 ex

 

The text descriptions are given in facsimile form.

1. Substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of General formula 1 and their pharmaceutically acceptable salts and/or hydrates,

where R1and R3independently from each other are not necessarily the same C1-C3alkyl, and R2represents a group -(CH2)nX or
R1and R3independently from each other represent different substituents selected from C1-C3the alkyl or the group -(CH2)nX, and R2represents a hydrogen atom or a C1-C3alkyl;
R4represents a C1-C3alkyl;
Ri5represents a hydrogen atom, one or two identical or different halogen atom, a C1-C3alkyl;
i represents the number 0, 1 or 2;
n represents the number 0, 1, 2 or 3;
X represents carboxyl CO2H, C1-C3allyloxycarbonyl, aminocarbonyl CONR6R7or aminogroup is at NR 6R7; excluding the compounds in which R3represents a group -(CH2)nX, where X is an amino group NR6R7and n=0; and compounds in which R2represents a group -(CH2)nX, where X is an amino group NR6R7and n=0;
R6and R7are not necessarily the same hydrogen atom, optionally substituted C1-C3alkyl, C3-C7cycloalkyl or optionally substituted 5-7-membered azaheterocyclic containing 1-2 nitrogen atom in the cycle, where the substituents are selected from C1-C3of alkyl; or R6and R7together with the nitrogen atom to which they are bound, form an optionally substituted 5-6-membered azaheterocyclic containing 1-2 nitrogen atom in the cycle, where the substituents are selected from C1-C3the alkyl.

2. Compounds according to claim 1, which represents the esters of General formula 1.1, 1.2 or 1.3 and their pharmaceutically acceptable salts and/or hydrates

where n and Ri5have the above value.

3. Compounds according to claim 1, which represents an acid of General formula 1.4, 1.5 or 1.6, and their pharmaceutically acceptable salts and/or hydrates

where n and Ri5they who have the above value.

4. Compounds according to claim 1, which represents the amides of General formula 1.7, 1.8 or 1.9 and their pharmaceutically acceptable salts and/or hydrates

where n, Ri5, R6and R7have the above value.

5. Compounds according to claim 1, which represents the diamines of General formula 1.10, 1.11 or 1.12 and their pharmaceutically acceptable salts and/or hydrates

where Ri5, R6and R7have the above value of n is 1, 2, 3.

6. Compounds according to claim 5, which represents a 6-aminomethyl-5,7-dimethyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.10(2), 6-(2-amino-ethyl)-5,7-dimethyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.10(3), 6-(3-aminopropyl)-5,7-dimethyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.10(4), 6-aminomethyl-5,7-dimethyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(5), 6-aminomethyl-5,7-dimethyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.10(6), 6-aminomethyl-5,7-dimethyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(7), 6-(2-amino-ethyl)-5,7-dimethyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(8), 6-(2-amino-ethyl)-5,7-dimethyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,-a]pyrimidine 1.10(9), 5,7-dimethyl-6-dimethylaminomethyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.10(10), 5,7-dimethyl-6-dimethylaminomethyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(11), 5,7-dimethyl-6-dimethylaminomethyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.10(12), 5,7-dimethyl-6-dimethylaminomethyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(13), 5,7-dimethyl-6-(2-dimethylamino-ethyl)-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.10(14), 5,7-dimethyl-6-(2-dimethylamino-ethyl)-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(15), 5,7-dimethyl-6-(2-dimethylamino-ethyl)-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.10(16), 5,7-dimethyl-6-(2-dimethylamino-ethyl)-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.10(17), 5-aminomethyl-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.11(1), 5-aminomethyl-7-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.11(2), 5-(2-amino-ethyl)-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.11(3), 5-(3-aminopropyl)-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.11(4), 5-aminomethyl-7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(5), 5-aminomethyl-7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.11(6), 5-aminomethyl-7-methyl-2-methylamino-3-(4-fluoro-3-chlorophenyl sulfonyl)-pyrazolo[1,5-a]the pyrimidine 1.11(7), 5-(2-amino-ethyl)-7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(8), 5-(2-amino-ethyl)-7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.11(9), 5-dimethylaminomethyl-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.11(10), 5-dimethylaminomethyl-7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(11), 5-dimethylaminomethyl-7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.11(12), 5-dimethylaminomethyl-7-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(13), 5-(2-dimethylamino-ethyl)-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.11(14), 5-(2-dimethylamino-ethyl)-7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(15), 5-(2-dimethylamino-ethyl)-7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.11(16), 5-(2-dimethylamino-ethyl)-7-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.11(17), 7-aminomethyl-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.12(1), 7-aminomethyl-5-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.12(2), 7-(2-amino-ethyl)-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.12(3), 7-(3-aminopropyl)-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.12(4), 7-aminomethyl-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimi the Jn 1.12(5), 7-aminomethyl-5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.12(6), 7-aminomethyl-5-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(7), 7-(2-amino-ethyl)-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(8), 7-(2-amino-ethyl)-5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.12(9), 7-dimethylaminomethyl-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.12(10), 7-dimethylaminomethyl-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(11), 7-dimethylaminomethyl-5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.12(12), 7-dimethylaminomethyl-5-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(13), 7-(2-dimethylamino-ethyl)-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.12(14), 7-(2-dimethylamino-ethyl)-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(15), 7-(2-dimethylamino-ethyl)-5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.12(16), 7-(2-dimethylamino-ethyl)-5-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.12(17) and their pharmaceutically acceptable salts and/or hydrates

< / br>











7. The method of producing esters of the General formula 1.1 according to claim 2 interaction-amino-4-sulfonyl-2H-pyrazoles of General formula 2 with the corresponding β-dicarbonyl compounds of General formula 3,

where n, R1, R3, R4and Ri5have the above value.

8. The method of producing esters of the General formula 1.2, 1.3 according to claim 2 interaction 3-amino-4-sulfonyl-2H-pyrazoles of General formula 2 with the corresponding β-dicarbonyl compounds of General formula 4, followed by separation and purification or separation of the reaction products,

where n, R1, R3, R4and Ri5have the above value.

9. The method of obtaining the acids of General formula 1.4, 1.5, 1.6 according to claim 3 by hydrolysis of the corresponding esters of the General formula 1.1, 1.2, 1.3.

10. The method of obtaining the amides of General formula 1.7, 1.8, 1.9 according to claim 4 interaction of the corresponding acids of General formula 1.4, 1.5, 1.6, or derivatives thereof, with amines of General formula 5,

where R6and R7have the above value.

11. The method of obtaining the amides of General formula 1.7 according to claim 4 interaction of 3-amino-4-sulfonyl-2H-pyrazoles of General formula 2 with the corresponding β-dicarbonyl compounds of General formula 6,

where n, R1, R3, R4, Ri5, R6and R7have the above value.

12. The method of obtaining the amides of General formula 1.8, 1.9 on the .4 the interaction of 3-amino-4-sulfonyl-2H-pyrazoles of General formula 2 with the corresponding β-dicarbonyl compounds of General formula 7 with subsequent isolation and purification or separation of the reaction products,

where n, R1, R3, R4, Ri5, R6and R7have the above value.

13. The method of obtaining amines of General formula 1.10, 1.11, 1.12 on any of pp.5 and 6 serial conversion of the acids of General formula 1.4, 1.5, 1.6 in appropriate arylazide General formula 1.13, 1.14, 1.15 under the action of sodium azide, obtained by thermal decomposition of azides in the isocyanates of General formula 1.16, 1.17, 1.18 and hydrolysis of the latter in the amines of General formula 1.10, 1.11, 1.12, respectively,


where n, R1, R3, R4and Ri5have the above value.

14. The method of obtaining amines of General formula 1.10, 1.11, 1.12 on any of pp.5 and 6 reductive alkylation of the corresponding amines of General formula 1.10, 1.11, 1.12, in which R6and R7represent a hydrogen atom, carbonyl compounds of General formula 8,

where R8and R9are not necessarily the same hydrogen atom, optionally substituted C1-C3alkyl, or R8and R9together with the carbon atom to which they are bound, form an optionally C is displaced C 5-C7cycloalkyl or azaheterocyclic, including one heteroatom of nitrogen and 4-6 carbon atoms.

15. Substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines according to any one of claims 1 to 6, having the properties of antagonists of serotonin 5-HT6receptors.

16. Substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines according to any one of claims 1 to 6 for studying the molecular mechanism of action of compounds on the inhibition of the serotonin 5-HT6receptors.

17. Substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines according to any one of claims 1 to 6 as the drug began to pharmaceutical compositions and medicines.

18. Pharmaceutical composition having the properties of antagonists of serotonin 5-HT6receptors that are suitable for treating and preventing conditions and disorders of the Central nervous system containing a pharmaceutically effective amount of a medicinal beginning on 17.

19. A method of obtaining a pharmaceutical composition according p mixture with an inert filler and/or solvent medicinal beginning on 17.

20. The drug is in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, for the prevention and treatment of diseases of the Central nervous system, the pathogenesis of which is associated with 5-HT 6receptors, comprising pharmaceutically effective amount of a medicinal beginning on 17 or pharmaceutical composition according p.

21. Drug in claim 20, for the prevention and treatment of cognitive disorders and neurodegenerative diseases.

22. Drug in claim 20, for the prevention and treatment of mental disorders.

23. Drug having anxiolytic activity, according to claim 20, for the prevention and treatment of anxiety disorders.

24. Drug with neuroprotective activity, item 21 to improve mental abilities.

25. Drug in claim 20, for the prevention and treatment of obesity.

26. Method for the prevention and treatment of diseases of the Central nervous system, the pathogenesis of which is associated with 5-HT6receptors, which consists in introducing an effective amount of the drug beginning at 17, or the pharmaceutical composition according p, or drugs on any of p-25.



 

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60 cl, 7 tbl, 101 ex

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2 cl, 2 tbl

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16 cl, 2 tbl, 21 ex

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25 cl, 2 tbl, 12 ex

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24 cl, 9 dwg, 4 tbl, 19 ex

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27 cl, 32 tbl, 22 ex, 16 dwg

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31 cl, 11 dwg, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R8R9), NR10, O, S; R1 is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R2 is hydrogenor lower alkyl; R3 and R4 are hydrogen; R5 and R6 are hydrogen; R7 is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R11; R8 and R9 denote hydrogen; R10 denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R11 denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)2, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O2)R13, C(O)R14, NO2, NR15R16, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R12 denotes hydrogen or lower alkyl; R13 denotes lower alkyl, NR17R18 or fluoro-lower alkyl; R14 denotes NR19 R20, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R15 and R16 independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR15R16 denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R17 and R18 independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR17 R18 denotes morpholinyl; R19 and R20 independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR19 R20 denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and medicine, namely to a new hypolipidemic preparation representing a molecular complex of atorvastatin and β-glycyrrhizic acid at the mole ration of atorvastatin: β-glycyrrhizic acid 1: (1-4).

EFFECT: invention exhibits high efficiency with much smaller dosage than initial atorvastatin.

5 ex, 2 dwg, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to use of existing and novel N-sulfamoyl- N'-arylpiperazines and their physiologically compatible acid-addition salts of formula I , where Ar denotes a monocyclic or bicyclic C6-C10aryl in which ring carbon atoms are optionally substituted with 1-3 nitrogen or oxygen atoms, and/or where the C6-C10aryl ring system optionally contains 3-5 double bonds, and/or where the C6-C10aryl ring system is optionally substituted with 1 or 2 substitutes which can be identical or different and which can be selected from a group containing halogen, trifluoromethyl, cyano group, nitro group, C1-C4alkyl, C1-C4alkoxy group, C1-C4alkylsulfonyl; and two oxygen atoms which are bonded to two neighbouring carbon atoms of the C6-C10aryl ring system and are bonded by a C1-C2alkylene bridge; or where the C6-C10aryl ring system is substituted with phenyl which can optionally be substituted in the phenyl ring by one substitute which can be selected from a group containing halogen; for preventing or treating obesity and related diseases.

EFFECT: design of a method of obtaining the said compounds and a pharmaceutical composition based on the said compounds.

25 cl, 9 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: there are claimed pharmaceutical compositions of atorvastatin, which contain effective quantity of atorvastatin for reduction of low-density lipoprotein level and pharmaceutically acceptable carrier, and method of preparing such compositions. Composition contains atorvastatin with average particle size maximum 50 micron or micronised atorvastatin.

EFFECT: compositions by invention insure reduction of food impact on biological availability of atorvastatin.

48 cl, 1 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention relates to pharmacology. Application of preparation which contains combination: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds, which contain unoxidisable structural unit of a fatty acid, for obtaining pharmaceutical or food composition, as well as composition for prevention and/or treatment of resistance to insulin, obesity, diabetes, fatty infiltration of the liver, hypercholesterolemia, dyslipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, secondary stenosis, myocardium infarction, stroke, hypertension, endothelial dysfunction, state of hypercoagulability, polycystic ovary syndrome, metabolic syndrome, malignant tumour, inflammatory disorder and proliferative skin disturbance. Application of animal food containing common food components and combination of: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds which contain structural elements of fatty acids which cannot be β-oxidised for improvement of general lipid composition in animal organism. Method of obtaining product of animal origin with improved composition of fatty acids, which includes feeding of the animal intended for product obtaining, with animal food which contains common food components and combination of: 1) fermented and/or hydrolysed protein material, and 2) one or several compounds which contain structural elements of fatty acids which cannot be β-oxidised. Invention also relates to application of preparation which contains combination of: 1) protein material and 2) oil or fish oil for prevention of said diseases, and to composition for prevention and/or treatment of hypercholesterolemia and states which are negatively influenced by said diseases, which contains said combination.

EFFECT: invention ensures increase of efficiency of prevention and treatment of said diseases.

82 cl, 12 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of general formula 1, their pharmaceutically acceptable salts and/or hydrates having serotonin 5-HT6 receptor antagonist properties. The compounds can be used in treating and preventing various diseases of the central nervous system, pathogenesis of which is associated with 5-HT6 receptors, particularly cognitive disorders, neurodegenerative diseases and psychiatric disorders. The compounds have anxiolytic and nootropic effect and can also be used for preventing and treating anxiety disorder and for enhancing metal capacity. In formula 1 , R1 is a hydrogen atom, C1-C3 alkyl, (C1-C3)alkyloxy(C1-C3)alkyl, hydroxy(C1-C3)alkyl, pyridyl; R2 is a hydrogen atom, halogen atom, C1-C3 alkyl, phenyloxy or pyridyloxy; R3 is a hydrogen atom, C1-C3 alkyl, C1-C3 alkyloxy, (C1-C3)alkyloxy(C1-C3)alkyl, hydroxy(C1-C3)alkyl, pyridyl; R4 is C1-C3 alkyl; R5 is a hydrogen atom, one or two halogen atoms, C1-C3 alkyl, C1-C3 alkyloxy or hydroxyl; X is a sulphur atom or thionyl group (SO).

EFFECT: obtaining compounds which can be used in treating and preventing various diseases of the central nervous system.

24 cl, 9 dwg, 4 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of general formula 1, their pharmaceutically acceptable salts and/or hydrates having serotonin 5-HT6 receptor antagonist properties. The compounds can be used to treat and prevent development of various diseases of the central nervous system, pathogenesis of which is associated with 5-HT6 receptors, particularly Alzheimer's disease, Parkinson's disease, Huntington disease, schizophrenia, other neurodegenerative diseases and cognitive disorders. In general formula 1 , R1 is a hydrogen atom, C1-C3alkyl, C1-C3alkyloxyC1-C3alkyl, hydroxyC1-C3alkyl, adamantyl, optionally substituted phenyl, 5-6-member heterocyclyl containing a nitrogen or oxygen heteroatom, possibly condensed with a benzene ring; R2 is a hydrogen atom, halogen atom, C1-C3alkyl, pyridyloxy; R3 is a hydrogen atom; C1-C3alkyl; optionally substituted amino group selected from amino, mono- or di(C1-C3alkyl)amino, di(C1-C3alkyl)aminoC2-C3alkylamino, N-[di(C1-C3alkyl)aminoC2-C3alkyl]-N-(C1-C3alkyl)-amino; C1-C3alkyloxy, C1-C3alkyloxyC1-C3alkyl, hydroxyC1-C3alkyl; 6-member azaheterocyclyl, possibly containing an extra nitrogen or oxygen atom, a -N(C1-C3alkyl) group; R4 is C1-C3alkyl; R5 is a hydrogen atom, one or two halogen atoms or C1-C3alkyl.

EFFECT: design of a method of obtaining compounds, a pharmaceutical composition and a medicinal agent for treating and preventing various diseases of the central nervous system.

25 cl, 12 dwg, 3 tbl, 20 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely for teacheability and memory improvement in mammals. An infant takes a milk formula containing casein glycomacropeptide in amount sufficient to ensure introducing at least 100 mg/kg of sialic acid a day.

EFFECT: method extends the range of products for teacheability and memory improvement in an infant.

11 cl, 14 tbl, 13 dwg, 7 ex

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