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

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

 

The text descriptions are given in facsimile form.

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

where R1represents a hydrogen atom, a C1-C3alkyl, C1-C3alkalosis1-C3alkyl, hydroxys1-C3alkyl, substituted, optionally substituted phenyl, 5-6-membered heterocyclyl; containing as the heteroatom nitrogen or oxygen, possibly condensed with a benzene ring;
R2represents a hydrogen atom, a halogen atom, a C1-C3alkyl, pyridyloxy;
R3represents a hydrogen atom; C1-C3alkyl; optionally substituted by an amino group selected from amino, mono - or di(C1-C3alkyl)amino, di(C1-C3alkyl)amino2-C3alkylamino, N-[di(C1-C3alkyl)amino2-C3alkyl]-N-(C1-C3alkyl)-amino; C1-C3alkyloxy,1-C3alkalosis1 -C3alkyl, hydroxys1-C3alkyl; 6-membered azaheterocyclic may contain an additional nitrogen atom or an oxygen atom, a group-N(C1-C3alkyl);
R4represents a C1-C3alkyl;
R5represents a hydrogen atom, one or two halogen atom or C1-C3alkyl;
excluding compounds of General formula 1 in which R1and R3simultaneously represent methyl, R2represents a hydrogen atom, and R4represents methyl, ethyl, 2-dimethylaminoethyl, 3-dimethylaminopropyl or para-tolyl.

2. Compounds according to claim 1, which represents a 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of General formula 1.1, and their pharmaceutically acceptable salts and/or hydrates

where R1, R3, R4and R5have the above value.

3. Compounds according to claim 2, representing a 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of General formula 1.1.1, 1.1.2, 1.1.3, 1.1.4, 1.1.5, 1.1.6, 1.1.7, 1.1.8, 1.1.9, 1.1.10, 1.1.11, 1.1.12 and their pharmaceutically acceptable salts and/or hydrates



where R1, R3, R4and R5have the above meaning; R6, R7, R9and R10independently from each other represent hydrogen or C1-C3alkyl, or R9and R10together with the nitrogen atom to which they are attached, form a 6-membered azaheterocyclic may contain an additional nitrogen atom, an oxygen atom or a group-N(C1-C3alkyl); R8is a Deputy hydroxy-group, selected from hydrogen or C1-C3of alkyl; PY represents a pyridyl; n=1-3.

4. Compounds according to claim 3, which represents a 2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.1(1), 2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.1(2), 2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.1(3), 2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.1(4), 2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.1(5), 5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.2(1), 5-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.2(2), 5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]the pyrimidine 1.1.2(3), 5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.2(4), 5-methyl-2-methylamino-3-(4-fluoro-3-chlorp ylsulphonyl)-pyrazolo[1,5-a]pyrimidine 1.1.2(5), 7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.3(1), 7-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.3(2), 7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.3(3), 7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.3(4), 7-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.3(5), 5-methyl-2-methylamino-7-methoxymethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.4(1), 5-methyl-2-methylamino-7-methoxymethyl-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.4(2), 5-methyl-2-methylamino-7-methoxymethyl-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.4(3), 5-methyl-2-methylamino-7-methoxymethyl-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.4(4), 5-methyl-2-methylamino-7-methoxymethyl-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.4(5), 7-methyl-2-methylamino-5-methoxymethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.5(1), 7-methyl-2-methylamino-5-methoxymethyl-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.5(2), 7-methyl-2-methylamino-5-methoxymethyl-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.5(3), 7-methyl-2-methylamino-5-methoxymethyl-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.5(4), 7-methyl-2-methylamino-5-methoxymethyl-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.5(5), 7-hydroxymethyl-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.6(1), 7-g is proximity-5-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.6(2), 7-hydroxymethyl-5-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.6(3), 7-hydroxymethyl-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.6(4), 7-hydroxymethyl-5-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.6(5), 5-hydroxymethyl-7-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.7(1), 5-hydroxymethyl-7-methyl-2-methylamino-3-(4-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.7(2), 5-hydroxymethyl-7-methyl-2-methylamino-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.7(3), 5-hydroxymethyl-7-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.7(4), 5-hydroxymethyl-7-methyl-2-methylamino-3-(4-fluoro-3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.7(5). 2-methylamino-5-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.8(1), 2-methylamino-5-(pyridin-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.8(2), 2-methylamino-5-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.8(3), 2-methylamino-5-(pyridine-3-yl)-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.8(4), 2-methylamino-5-(pyridin-3-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a] pyrimidine 1.1.8(5), 7-methyl-2-methylamino-5-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.8(6), 7-methyl-2-methylamino-5-(pyridine-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.8(7), 7-methyl-2-methylamino-5-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]p is rimidine 1.1.8(8), 7-methyl-2-methylamino-5-(pyridin-3-yl)-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.8(9), 7-methyl-2-methylamino-5-(pyridin-3-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.8(10), 2-methylamino-7-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]the pyrimidine 1.1.9(1), 2-methylamino-7-(pyridin-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.9(2), 2-methylamino-7-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.9(3), 2-methylamino-7-(pyridin-3-yl)-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.9(4), 2-methylamino-7-(pyridin-3-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.9(5), 5-methyl-2-methylamino-7-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.9(6), 5-methyl-2-methylamino-7-(pyridin-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.9(7), 5-methyl-2-methylamino-7-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.9(8), 5-methyl-2-methylamino-7-(pyridin-3-yl)-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.9(9), 5-methyl-2-methylamino-7-(pyridin-3-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.9(10), 5-methyl-2-methylamino-7-methoxy-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.10(1), 2-methylamino-7-methoxy-5-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.10(2), 2-methylamino-7-methoxy-5-(pyridin-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.10(3), 2-methylamino-7-methoxy-5-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.10(4), 5-methyl-2-methylamino-7-labels and-3-(3-fluoro-phenylsulfanyl)-pyrazolo[1,5-a]pyrimidine 1.1.10(5), 7-amino-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.11(1), 7-amino-5-methyl-2-methylamino-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.11(2), 5-(adamantane-1-yl)-7-amino-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.11(3), 7-amino-2-methylamino-5-phenyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.11(4), 7-amino-2-methylamino-3-phenylsulfonyl-5-(3-chlorophenyl)-pyrazolo[1,5-a]pyrimidine 1.1.11(5), 7-amino-2-methylamino-3-phenylsulfonyl-5-(furan-2-yl)-pyrazolo[1,5-a]pyrimidine 1.1.11(6), 7-amino-2-methylamino-5-(furan-2-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.11(7), 7-amino-2-methylamino-5-(1-methylindol-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.11(8), 7-amino-2-methylamino-5-(1-methylindol-3-yl)-3-(3-chlorophenylsulfonyl)-pyrazolo[1,5-a]pyrimidine 1.1.11(9), 7-amino-2-methylamino-5-(1-methylindol-3-yl)-3-(3-perpenicular)-pyrazolo[1,5-a]pyrimidine 1.1.11(10), 2,7-di(methylamino)-5-methyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(1), 7-dimethylamino-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(2), 7-[2-(dimethylamino)ethyl]amino-5-methyl-2-methylamino-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(3), 5-methyl-2-methylamino-7-(4-methylpiperidin-1-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(4), 5-methyl-2-methylamino-7-(morpholine-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(5), 7-[2-(dimethylamino)ethyl]methylamino-2-methylamino-5-phenyl-3-phenylsulfonyl-piraso what about[1,5-a]pyrimidine 1.1.12(6), 7-[2-(dimethylamino)ethyl]amino-2-methylamino-3-phenylsulfonyl-5-(furan-2-yl)-pyrazolo[1,5-a]pyrimidine 1.1.12(7), 7-dimethylamino-2-methylamino-5-(pyridin-2-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(8), 7-dimethylamino-2-methylamino-5-(pyridin-3-yl)-3-phenylsulfonyl-pyrazolo[1,5-a] pyrimidine 1.1.12(9), 7-dimethylamino-2-methylamino-5-(pyridin-4-yl)-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidine 1.1.12(10) and their pharmaceutically acceptable salts and/or hydrates



















5. The method of obtaining compounds of General formula 1.1.1, 1.1.2, 1.1.3, 1.1.4, 1.1.5, 1.1.8, 1.1.9 according to any one of claims 1 to 4 by the interaction of 3-amino-4-arylsulfonyl-2H-pyrazoles of General formula 2 with the corresponding β-dicarbonyl compounds of General formula 3 or the corresponding acetals with subsequent isolation or separation of the reaction products, if R1≠R3,

where R1, R2, R3, R4and R5have the above value.

6. The method according to claim 5 obtain the compounds of General formula 1.1.1 according to any one of p and 4 the interaction of 3-amino-4-arylsulfonyl-2H-pyrazoles of General formula 2 with tetraacetate malonic aldehyde 3.1

where R4and R5have the above value.

7. The method according to claim 5 obtain the compounds of General formula 1.1.2, 1.1.3 on any of PP and 4 the interaction of 3-amino-4-arylsulfonyl-2H-pyrazoles of General formula 2 with 1-substituted 3,3-dealkylase-propanone 3.2, followed by separation or separation of the reaction products

where R1, R4and R5have the above value.

8. The method according to claim 5 obtain the General formula 1.1.4, 1.1.5 on any of PP and 4 the interaction of 3-amino-4-arylsulfonyl-2H-piraso what s the General formula 2 with 1-methoxyphenyl-2,4-dione, 3.3, followed by separation or separation of the reaction products

where R4, R5, R6, R7and n have the above meaning.

9. The method according to claim 5 obtain the compounds of General formula 1.1.8, 1.1.9 on any of PP and 4 the interaction of 3-amino-4-arylsulfonyl-2H-pyrazoles of General formula 2 with a diketone of General formula 3.4, followed by separation or separation of the reaction products

where R4, R5, R6and PY have the abovementioned meaning.

10. The method of obtaining substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of General formula 1.1.2 according to any one of p and 4 recovery of chlorine substituted General formula 4

where R1, R4R5have the above value.

11. The method of obtaining compounds of General formula 1.1.6, 1.1.7 on any of PP and 4 action trichromate boron on the appropriate alkyloxyalkyl compounds of General formula 1.1.4 or 1.1.5.

12. The method of obtaining compounds of General formula 1.1.10 on any of PP and 4 by the interaction of chlorine substituted General formula 4 with an alkali metal alcoholate of the General formula 6

where R1, R4, R5and R8have the above significance; M represents a cation of an alkali metal.

So obtain the compounds of General formula 1.1.11 on any of PP and 4 the interaction of 3-amino-4-arylsulfonyl-2H-pyrazoles of General formula 2 with 3-aminocrotononitrile General formula 7

where R1, R4and R5have the above value.

14. The method of obtaining compounds of General formula 1.1.12 on any of PP and 4 by the interaction of chlorine substituted General formula 4 with primary or secondary amines of General formula 8

where R1, R4and R5have the above meaning; R9and R10independently from each other represent hydrogen or C1-C3alkyl, or R9and R10together with the nitrogen atom to which they are bound, form azaheterocyclic.

15. Antagonists Stratonovich 5-HT6receptors represents a substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of General formula 1 according to any one of claims 1 to 4.

16. Antagonists Stratonovich 5-HT6receptor according to any one of claims 1 to 4 as "molecular tools"designed to study the selective inhibition of serotonin 5-HT6receptors.

17. Substituted 2-alkylamino-3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines according to any one of claims 1 to 4, having the properties of antagonists Stratonovich 5-HT6receptors as drug began to pharmaceutical compositions and medicines.

18. Pharmaceutical composition having St is isthmi antagonists of serotonin 5-HT 6receptors 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-HT6receptors, 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 in claim 20, having anxiolytic action for the prevention and treatment of anxiety disorders.

24. Drug in claim 20, having a nootropic action to improve mental abilities.

25. Method of prevention and treatment of various Central nervous system diseases, pathogenesis of which is associated with 5-HT6receptors, the conclusion is decomposing in the introduction in the effective number of drug-beginning 17, or pharmaceutical composition according p, or drugs on any of PP-24.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to 1-(3-morpholinopropyl)-2-phenylimidazo[1,2-a]benzimidazole dihydrochloride of formula I:

having purine P2Y1-receptor antagonist properties, antiaggregant and antithrombotic activity.

EFFECT: obtaining a new compound which can be used in medicine for making a medicinal drug for therapy of diseases accompanied by increase in thrombogenic potential of the blood: atherosclerosis, ischemic heart disease, diabetic angiopathy.

1 cl, 5 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 7H-pyrrol[2,3-d]pyrimidine derivatives of formula I. In compounds of formula R1 is phenyl which is optionally substituted with a halogen, phenylalkyl, where the alkyl contains 1-4 carbon atoms, morpholinoalkyl, where the alkyl contains 1-4 carbon atoms, dialkylaminoalkyl, where the alkyl contains 1-4 carbon atoms, or pyridyl which is optionally substituted with alkyl which contains 1-4 carbon atoms, R2, R3 optionally represent methyl, or R2 and R3 together form a tetramethylene group, R4 is or or where R5 is phenyl which is optionally substituted with 1-3 groups selected from nitro, trifluoromethyl, benzyloxy, hydroxy, alkoxy, alkyl, where the alkyl contains 1-4 carbon atoms, cyano, dialkylamino, where the alkyl contains 1-4 carbon atoms, either a thiophene or naphthyl ring; R6, R7, R8 and R9 independently represent hydrogen, halogen, trifluoromethoxy, sulphonyl or alkyl containing 1-4 carbon atoms, R10 is hydrogen, a nitrile group, or an alkyl containing 1-4 carbon atoms, R11 is tert-butyl or phenyl, or together with X form a tetramethylene ring, or; R12 is phenyl which is possibly substituted with nitro, halogen, alkoxy, or phenyl-alkyl, where the alkyl contains 1-4 carbon atoms, X is carbon, or R11 together with X form a tetramethylene ring, otherwise X denotes nitrogen, methine, methylmethine, ethylmethine, propylmethine, isopropylmethine, tert-butylmethine or phenylmethine. The invention also relates to a pharmaceutical composition and a method of preparation.

EFFECT: obtaining compounds and pharmaceutically acceptable salts which have anti-inflammatory and anaesthetic effect.

10 cl, 3 tbl, 96 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a new pyrazole[1.5-a]pyrimidine derivative of formula [1]: , where ring A is a substituted pyrazole ring condensed with a neighbouring pyrimidine ring having formula , and group E is one of the following groups (ii)-(v): , and the rest of the radicals are defined in the description. The invention also relates to pharmaceutical compositions containing such compounds.

EFFECT: disclosed compositions and compositions have antagonistic effect on CB1 cannabinoid receptor.

19 cl, 82 tbl, 500 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I. In general formula I A is C or N; B, D and E independently represent CR4, NR5, N, O or S; and a ring containing groups A, B, D, E, selected from thienyl, furan, imidazole, oxazole, isothiazole, thiazole, pyrrol, pyrazole; provided that: b) when A is N, not any of B, D, E can be O or S; and c) when A is C, B is CR4 and one of D or E is N or NR5, when any of D or E cannot be NR5 or N; G is N or C; R1 represents one or more substitutes selected from H, Ra halogen, -OH and -ORa; R2 represents one or more substitutes selected from H, halogen and C1-6-alkyl, and also one of substitutes R2 can be -ORb' , -NRb' Rb', -SRb', -SORb', -SO2Rb', -SO2NRb' Rb'; R3 is H, or Cy, selected from phenyl optionally substituted with one or more substitutes selected from Rc , where Rc independently represents halogen, -ORg', where Rg' independently represents a Rg group, where Rg is C1-6-alkyl; each R4 independently represents H, Re, halogen, -CORe', -CO2Re', -CONRe'Re', -NRe'Re'; R5 independently represents H, Re, -CORe, -CONReRe, -SORe or -SO2Re; each Ra independently represents C1-6-alkyl or halogen- C1-6-alkyl; each R independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rb' independently represents H or Rb; each Rc independently represents halogen, -ORg', -CONRg'Rg', -NRg'Rg'; Rd is Cy optionally substituted with one or more Rf substitutes; each Rc independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rc and Cy*, or Re is Cy, where any of the groups Cy or Cy* can optionally be substituted with one or more substitutes selected from Rc and Rg ; each Re' independently represents H or Re; each Rf independently represents a halogen, -ORh', -CO2Rh; each Rg independently represents Rd or C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rg' independently represents H or Rg; each Rh independently represents C1-6-alkyl, halogen-C1-6-alkyl or hydroxy- C1-6-alkyl; each Rh' independently represents H or Rh; and Cy or Cy* given in definitions above is a partially saturated, saturated or aromatic 3-7-member monocyclic carbocyclic ring which optionally contains 1-2 heteroatoms selected from N and O, and where the ring or rings can be bonded to the remaining part of the molecule through a carbon or nitrogen atom.

EFFECT: obtaining formula I compounds with p38-kinase inhibitory properties which can be used in making drugs for treating such diseases as tumour immune and autoimmune diseases etc.

21 cl, 10 dwg, 8 tbl, 57 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new condensed compounds (versions) or their pharmaceutically acceptable salts having inhibitory effect on HER2 and/or EGFR kinase, having the following formula, for example: or , where R1a is a hydrogen atom; R2a is a C1-8alkyl group, C2-8alkenyl group or C2-8alkynyl group, each of which is substituted with substitute(s), R3a is a hydrogen atom or C1-6alkyl group; or R1a and R2a are optionally bonded with formation or R2a and R3a are optionally bonded with formation of C2-4alkylene; Ba is a benzene ring optionally substituted with 1-4 substitutes selected from halogen and optionally halogenated C1-4alkyl; Ca is a phenyl group substituted with 1-5 substitutes selected from (i) halogen, (ii) optionally halogenated C1-4alkyl, (iii) hydroxy- C1-4alkyl, (iv) a 5-8-member heterocycle- C1-4alkyl, where the said 5-8-member heterocycle contains 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and optionally oxidised sulphur atom, (v) optionally halogenated C1-4alkyloxy, (vi) cyano and (vii) carbamoyl, optionally substituted with C1-8alkyl, and, respectively, R2e is a C1-4alkyl group optionally substituted with -O-(CH2)n-OH, where n is an integer from 1 to 4; R3e is a hydrogen atom; Be is a benzene ring optionally substituted with a halogen; and Ce is a phenyl group optionally substituted with halogenated C1-4alkyl.

EFFECT: obtained new compounds can be used for treating cancer.

22 cl, 2 tbl, 280 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts of formula (I) where n equals 0, 1 or 2, A is a five- or six-member aromatic ring which optionally contains one or two heteroatoms independently selected from nitrogen, oxygen or sulphur, B is a 5-9-member ring containing 0 or 1 double bonds and optionally contains an additional heteroatom selected from nitrogen and oxygen; where the ring optionally contains one or two substitutes independently selected from a group comprising C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkyl, carboxy, cyano, hydroxy, hydroxy-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, (NR4R5)-carbonyl or oxo; R1 is selected from -C(O)NR4R5 - CO2R4, 5-tetrazolyl, cyano; each R2 is independently selected from a group comprising C1-C6-alkyl, amino, benzyloxy, halogen, hydroxyl; R3 is a 5-7-member cycloalkyl ring; values of the rest of the radicals are given in the formula of invention. The invention also relates to a method for synthesis of the said compounds, a method of inhibiting HCV replicon function and a method of inhibiting functioning of the HCV NS5B protein.

EFFECT: wider field of use of the compounds.

16 cl, 4 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel condensed heterocylic protein kinase modulators of formula I where L1 and L2 independently denote a bond, and R1 and R2 denote a substituted or unsubstituted heteroaryl or a substituted or unsubstituted aryl, as well as to pharmaceutical compositions containing such compounds, and methods of using the compounds to prepare medicine for diseases mediated by protein kinase activity.

EFFECT: increased effectiveness of using the compounds.

24 cl, 20 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to use of dihydrochloride 9-diethylaminoethyl-2,3-dihydroimidzo[1,2-a]benzimidazole as a compound which inhibits erythrocyte aggregation and reduces blood viscosity, and also reduces insulin resistance and restores tolerance of the body to glucose. The invention also relates to a pharmaceutical composition based on the said dihydrochloride.

EFFECT: new potential of the of the said compound has been studied.

3 cl, 4 dwg, 9 tbl, 7 ex

Hypolipidemic agent // 2392933

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is offered application of Benzohexonium as a hypolipidemic agent. Previously, Benzohexonium was used as a ganglionic blocking agent in bronchiospasms, peripheral vasospasm, for reduction of hypertensic crisis, for controlled hypotension, in gastric ulcer and duodenal ulcer. It is shown that Benzohexonium reduces concentration of cholesterol and triglycerides in blood, liver, aorta, and considerably decreases the atherogenic index. The intensity of hypolipidemic effect of Benzohexonium enables to consider this agent as close to a common lipid lowering preparation Gemfibrozil and exceeds the fibrate effect of Clofibrate and Probucol.

EFFECT: preclinical trials of Benzohexonium ensure to recommend it as a hypolipidemic agent for prevention and treatment of atherogenic dislipoproteinemia.

4 tbl

FIELD: chemistry.

SUBSTANCE: claimed compounds show effect on receptor activated by peroxysome proliferate δ (PPARδ). In formula I: [Formula I] , [Formula VII] , [Formula VI] , A is R1 is C1-4alkyl group; R3 groups are different and denote halogen atom or C1-4alkyl group substituted or unsubstituted by halogen; R4 is R5 is hydrogen atom or hydroxyl group; the other radicals are as defined in the invention claim. Also invention refers to methods of compound I obtainment, to intermediary compounds VI, VII and methods of their obtainment, to medicines of diabetes, obesity, atherosclerosis, hyperlipidemia treatment and prevention, containing thiazole derivative of the formula I as active component.

EFFECT: enhanced activity of derivatives.

21 cl, 10 tbl, 102 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biologically active analogues of steroid oestrogens. 17,17-dimethyl-D-homo-B-nor-8α-oestrone is synthesised, which has noticeably pronounced hypolipidemic and cardioprotector activity in the absence of uterotropic action. 17,17-dimethyl-D-homo-B-nor-8α-oestrone.

EFFECT: obtaining compounds which can be used in medicine as a basis for designing effective medicinal preparations for treating cardiovascular diseases.

1 cl, 1 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to serotonin 5-HT6 receptor antagonists - new substituted 3-sulphonyl-6,7,8,9-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-e]pyrimidines of formula and substituted 3-sulphonyl-5,6,7,8-tetrahydro-pyrazolo[1,5-a]pyrido[4,3-c1]pyrimidines of general formula 2, a medicinal base and pharmaceutical compositions containing the medicinal base in form of the said compounds, as well as to a method of treating and preventing development of different conditions and diseases of the central nervous system of humans and warm-blooded animals. In formulae and Ar is phenyl which is optionally substituted with halogen atoms, or a 6-member heteroaryl which contains a nitrogen atom in the ring; R1 is a hydrogen atom, C1-C3alkyl, hydroxy C1-C3alkyloxy group, C1-C3alkylsulphanyl group; R2 is a hydrogen atom or C1-C3alkyl, R3 is a hydrogen atom optionally substituted C1-C3alkyl or tert-butyloxycarbonyl.

EFFECT: obtaining compounds for preventing development of different conditions and diseases of the central nervous system of humans and warm-blooded animals.

16 cl, 3 tbl, 1 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I) and their pharmaceutically acceptable salts and esters. The disclosed compounds have LXR-alpha and/or LXR-beta agonist properties. In formula (I) R1 is hydrogen, halogen; R2 is lower alkyl, flouro-lower alkyl; R3 is hydrogen, phenyl; R4 is hydrogen, hydroxy; R5 is hydrogen; phenyl; R6 is phenyl, a 5-6-member heteroaryl with one or two heteroatoms selected from nitrogen and sulphur, a 9-member bicyclic heteroaryl with a sulphur atom as a heteroatom, which can be optionally substituted with a halogen, or R6 is , R7 is a lower alkyl; R8 is phenyl which is optionally substituted with one substitute selected from a group consisting of halogen, fluoro-lower alkyl, R9-O-C(O)-, R10R11NC(O)-, phenyl-lower alkoxy; R9, R10, R11 independently represent hydrogen or lower alkyl; L is a single bond, lower alkylene or lower alkenylene; m assumes values from 0 to 3; n is equal to 0 or 1.

EFFECT: obtaining a new compound and a pharmaceutical composition which contains the disclosed compound as an active ingredient for therapeutic and/or preventive treatment of diseases.

23 cl, 47 ex

FIELD: medicine.

SUBSTANCE: invention concerns a composition obtained from a combination of vegetable oil or cod-liver oil with a compound which contains fatty acids analogues resistant to β-oxidation. The invention also concerns animals' fodder produced form a combination of vegetable oil and cod-liver oil containing fatty acids analogues resistant to β-oxidation, to application of the fodder with the purpose of improving the animal's body composition and to the product obtained from the above animals.

EFFECT: production of pharmaceutical or edible composition for prevention and/or treatment of insulin resistance, obesity, diabetes, fatty liver, hypercholesterinemia, dislipidemia, atherosclerosis, coronary heart disease, thrombosis, stenosis, myocardial infarction, apoplexy, hypertension, endothelial dysfunction, hypercoagulability, polycystic ovary syndrome, metabolic syndrome, malignant tumour, inflammatory disorder and poliferous skin lesions.

47 cl, 12 tbl, 2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention belongs to medicine, particularly to hypercholesterinemia correction methods. To that end, probiotic - liquid sporobacterin - is orally administered by 1 ml twice per day for 30 days.

EFFECT: method ensures effective hypercholesterinemia treatment comparable with statins effect, by with no adverse reactions.

4 ex

FIELD: food industry.

SUBSTANCE: invention suggest using edible sorbitan derivative found in the product used for preventing fat absorption. Sorbitan derivative is used for cosmetic control of the body weight.

EFFECT: invention enables to help people suffering from obesity as well as to reduce risks of getting overweight.

9 cl, 4 dwg, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compounds of formula (I) and their pharmaceutically acceptable salts or esters having agonistic effect on PPARδ and/or PPARα, where X1 is selected from a group which includes O and CH2, R1 denotes hydrogen or C1-C7alkyl, R2 denotes C1-C7alkyl, or if X1 denotes CH2, then R2 denotes hydrogen, R3 denotes hydrogen or C1-C7alkyl, R4 and R8 are independently selected from a group which includes hydrogen, C1-C7alkyl, C1-C7alkoxy, halogen, R5, R6 and R7 are independently selected from a group which includes hydrogen, C1-C7alkoxy, halogen, where one of R5, R6 and R7 denotes , where X2 denotes O, R10 denotes hydrogen, R11 denotes hydrogen, one of R12 or R13 is selected from a group which includes hydrogen, C1-C7alkyl and fluoro(C1-C7)alkyl, and the other denotes an unshared electron pair, R14 denotes hydrogen, R15 denotes 4-trifluoromethoxyphenyl, and n equals 1, 2 or 3. The invention also relates to pharmaceutical compositions containing such compounds.

EFFECT: increased effectiveness of the compounds.

23 cl, 20 ex

FIELD: medicine.

SUBSTANCE: treating of lipidosis and body-weight reduction in the patients with cardiovascular diseases is ensured by diet therapy based on the lacto-vegetarian diet. It involves introduction of proteins in daily amount of 67-79 g, including animal 48-57%, fats in daily amount of 32-49 g, including animal 40-52%, carbohydrates in daily amount of 240-257 g, cholesterol in daily amount of 40-268 mg, cellulose in daily amount of 18-20 g, dietary fibers in daily amount of 150 mg, potassium (K) in daily amount of 4567-6433 mg, magnesium (Mg) in daily amount of 535-693 mg, vitamin E in daily amount of 44-53 mg, arginine in daily amount of 3.9-5.2 g, dehydrated powdered maral meat in daily amount of 1200 mg, microcrystalline cellulose in daily amount of 900 mg. Duration of the diet therapy course is 33 days.

EFFECT: method provides suppression of cholesterol biosynthesis and intensification of excretion thereof that reduces the atherogenic index, reduces manifestations of oxidative stress, with reduced risk of realisation of the modified factors of a cardiovascular pathology.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and aims at treating the conditions associated with amnesia and impaired cognition. A medically indigent patient is prescribed with the effective amount of a composition containing a mixed extract prepared of Scutellaria plants with high concentration of free V-ring flavonoids, including Baicalin, and an extract of Acacia plants with high concentration of flavanes, including catechine and epicatechin.

EFFECT: methods ensure restoration and preservation of cognition and memory.

44 cl, 15 ex, 2 tbl, 17 dwg

Up!