Substituted 8-sulphonyl-2,3,4,5-tetrahydro-1h-gamma-carbolines, ligands, pharmaceutical composition, synthesis method and use thereof

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 8-sulphonyl-2,3,4,5-tetrahydro-1H-γ-carbolines of general formula 1 or pharmaceutically acceptable salts thereof, which are ligands with a wider range of simultaneous activity towards alpha adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors, sigma receptors, norepiniphrine receptors and serotonin receptors. In compounds of general formula 1 R1 is an amino group substitute selected from hydrogen; C1-C3alkyl optionally substituted with phenyl; C1-C4alkyloxycarbonyl; R2 is a cyclic system substitute selected from hydrogen, C1-C3alkyl optionally substituted with phenyl, pyridin-(3- or 4-yl), (6-methylpyridin-3-yl); C1-C3alkenyl substituted with phenyl; or optionally substituted phenylsulphonyl; R3 is an optionally halogen-substituted phenyl, six member aromatic azaheterocycle, mono- or di-C1-C3alkylamino group, phenylamino group which is optionally substituted with halogen atoms on the phenyl ring, or a substituted six member azaheterocycle containing an additional nitrogen atom, substituted with C1-C3alkyl.

EFFECT: compounds can be used in treating and preventing diseases and pathological conditions of the central nervous system, such as anxiety disorders, cognitive disorders, neurodegenerative diseases and depression.

18 cl, 2 dwg, 6 tbl, 23 ex

 

The text descriptions are given in facsimile form.

1. Substituted 8-sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline General formula 1 or pharmaceutically acceptable salt,

where R1 represents a Deputy amino group selected from hydrogen, C1-C3the alkyl, optionally substituted by phenyl; C1-C4allyloxycarbonyl;
R2 represents a Deputy cyclic system selected from hydrogen, C1-C3the alkyl, optionally substituted phenyl, pyridine-(3 - or 4-yl)ω, (6-methylpyridin-3-yl)ω; C1-C3alkenyl, substituted phenyl; or optionally substituted phenylsulfonyl;
R3 represents optionally substituted by halogen atoms phenyl, a six-membered aromatic azaheterocyclic, mono - or di-C1-C3alkyl, amino group, phenylaminopropyl, optionally substituted on the phenyl ring by halogen atoms, or a saturated six-membered azaheterocyclic containing an additional nitrogen atom, substituted C1-C3the alkyl.

2. Compounds according to claim 1, which represents an 8-arylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline General formula is 1.1 and amides 2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids of General formula 1.2 or their pharmaceutically acceptable salts,

where Rl and R2 have the above meanings;
Ar represents optionally substituted by halogen phenyl or azaheterocyclic;
R4 and R5 are not necessarily the same substituents representing hydrogen, optionally substituted C1-C3alkyl, optionally substituted phenyl, provided that R4 and R5 cannot simultaneously denote hydrogen or R4 and R5 together with the nitrogen atom to which they are linked, form a saturated six-membered azaheterocyclic containing an additional nitrogen atom, substituted C1-C3the alkyl.

3. Compounds according to claim 2, represents a substituted 8-phenylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline General formula 1.1.1 and substituted phenylamide 2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids of General formula 1.2.1 or their pharmaceutically acceptable salts,

where R6 and R7 are not necessarily the same hydrogen or methyl;
R8 represents hydrogen, chlorine or fluorine.

4. Compounds according to claim 3, including: 2-methyl-8-phenylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(1), 2-methyl-8-(3-chlorophenyl)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(2), 2-methyl-8-(3-forfinal)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(3), 2,5-dimethyl-8-phenylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(4), 2,5-dimethyl-8-(3-harfe the Il)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(5), 2,5-dimethyl-8-(3-forfinal)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(6), 5-methyl-8-phenylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(7), 5-methyl-8-(3-chlorophenyl)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(8), 5-methyl-8-(3-forfinal)sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline 1.1.1(9), 2-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids of phenylamide 1.2.1(1), 2-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-chlorpheniramine 1.2.1(2), 2-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-tortenelme 1.2.1(3), 2,5-dimethyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids of phenylamide 1.2.1(4), 2,5-dimethyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-chlorpheniramine 1.2.1(5), 2,5-dimethyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-tortenelme 1.2.1(6), 5-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids of phenylamide 1.2.1(7), 5-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-chlorpheniramine 1.2.1(8), 5-methyl-2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfonic acids 3-tortenelme 1.2.1(9) or their pharmaceutically acceptable salts,








5. The way to obtain 8-arylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carbolines, which General formula 1.1 according to claim 2 interaction of 8-bromo-2,3,4,5-tetrahydro-1H-γ-carbolines, which General formula 2 with sulfinamide acids of General formula 3 in the presence of adnoidectomy copper, N,N'-dimethylethylenediamine and grounds in the environment aprotic solvent:

where R1, R2 and Ar have the above values.

6. The way to obtain 8-arylsulfonyl-2,3,4,5-tetrahydro-1H-γ-carbolines, which General formula 1.1 according to claim 2 interaction 2,3,4,5-tetrahydro-1H-γ-carboline-8-sulinowo acid of General formula 4 with arylidene General formula 5 in the presence of adnoidectomy copper, N,N'-dimethylethylenediamine and grounds in the environment aprotic solvent:

where R1, R2 and Ar have the above values.

7. The method of producing amides 2,3,4,5-tetrahydro-1H-γ-carboline-8-sulphonic acids of General formula 1.2 according to claim 2 interaction 2,3,4,5-tetrahydro-1H-γ-carboline-8-sulfochloride General formula 6 with amines of formula 7 in the presence of a base,

where R1, R2, R4 and R5 have the above values.

8. Ligands with simultaneous activity against alpha-adrenoceptors, dopamine p the receptors, histamine receptors, imidazoline receptors, Sigma receptors, norepinephrine receptors, serotonin receptors, represents a substituted 8-sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline General formula 1 according to claim 1 in the form of free bases or pharmaceutically acceptable salts.

9. The ligands, which has antagonistic activity against serotonin 5-HT6receptors and represents a substituted 8-sulfonyl-2,3,4,5-tetrahydro-1H-γ-carboline General formula 1 according to claim 1 in the form of free bases or pharmaceutically acceptable salts.

10. The ligand of General formula 1 according PP and 9 in the form of free bases or pharmaceutically acceptable salts as an active ingredient for pharmaceutical compositions and medicines intended for the treatment and prevention of pathological conditions and diseases of the Central nervous system.

11. Pharmaceutical composition having simultaneous activity against alpha-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors, Sigma receptors, norepinephrine receptors and serotonin receptors containing as an active ingredient pharmaceutically effective amount of a ligand of General formula 1 of claim 10 or its pharmaceutically acceptable salt.

12. The way to get pharmaceuticalcompanies according to claim 11, which consists in mixing at least one ligand of claim 10 with an inert filler and/or diluent.

13. Drug, with simultaneous activity against alpha-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors, Sigma receptors, norepinephrine receptors, serotonin receptors intended for treatment and prevention of pathological conditions and diseases of the Central nervous system, in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, incorporating the ligand of claim 10 or the pharmaceutical composition according to item 11.

14. The method of treatment and/or prevention of diseases and pathological conditions of the Central nervous system by introducing a pharmaceutically effective amount of the active component of claim 10, or a pharmaceutical composition according to claim 11, or a medicinal product by item 13.

15. The method according to 14 for the treatment and/or prevention of anxiety disorders.

16. The method according to 14 for the treatment and/or prevention of cognitive disorders and neurodegenerative diseases.

17. The method according to 14 for the treatment and/or prevention of psychotic disorders.

18. The method according to 14 for the treatment and/or prevention of depression.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula IB , where radicals R1-R5 have values, given in invention formula. In range of claimed invention also described are pharmaceutical compositions, which include compounds of IB formula, and methods of application of such compounds and compositions for treatment of different malfunctions, mainly selected from immune response reactions.

EFFECT: compounds by claimed invention have inhibiting action with respect to proteinkinases and, in particular with respect to JAK-3, ROCK or Aurora kinases.

55 cl, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula: I, where R1 is selected from hydrogen or methoxy; R2 is selected from a group consisting of hydroxy, lower alkoxy, provided that R2 does not denoe methoxy when R1 denotes methoxy, lower alkoxy, mono- or di-substituted with a hydroxy group, benzyloxy, amino, alkylamino, dialkylamino, cyano group, unsubstituted phenyl or tetrazolyl, -O-(CH2)m-C(O)-NR8R9, where m equals 1 or 2, and where R8 and R9 are independently selected from hydrogen, lower alkyl or tetrazolyl, or R8 and R9 together with the nitrogen atom with which they are bonded form morpholinyl or piperazinyl, -O-(CH2)n-COOR10, where n equals 1 or 2 and R10 denotes hydrogen or lower alkyl, -O-(CH2)p-NH-C(O)-OR11, where p equals 1 or 2,and where R11 denotes lower alkyl, -O-SO2-R12, where R12 denotes lower alkyl, -NR13R14, where R13 denotes hydrogen or lower alkyl, and R14 denotes lower alkyl or benzyl, and -NH-CO-(CH2)q-R15, where q equals 1 or 2, and where R5 denotes tetrazolyl; R3 is selected from a group consisting of hydrogen, hydroxy, lower alkoxy, lower alkoxy which is mono- or di-substituted with a hydroxy group, alkoxy or unsubstituted phenyl, and -O-(CH2)m-C(O)-NR8R9, where m equals 1 or 2, and where R8 and R9 are independently selected from hydrogen or lower alkyl, or R8 and R9 together with the nitrogen atom with which they are bonded form morpholinyl or piperazinyl, which can be substituted with lower alkyl; R4 is or , where R5 is selected from lower alkyl; or R5 can also denote hydrogen when selected from a group consisting of -(CH2)m-C(O)-NR8R9, -O-(CH2)p-NH-C(O)-OR11, -O-SO2-R12, -NR13R14, -NH-CO-(CH2)q-R15 and lower alkoxy which is mono- or di-substituted with a group selected from hydroxy, benzyloxy, amino or cyano; R6 is selected from a group consisting of hydrogen and lower alkyl; R7 is selected from a group consisting of lower alkyl and lower halogenalkyl; and to pharmaceutically acceptable salts of said compounds. The invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having DPP-IV enzyme inhibiting activity.

22 cl, 50 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives of general formula , where R is an optional ortho- or meta-substitute selected from halogen and (C1-4)alkyloxy; R1 is halogen or CF3; R2 is H, (C1-4)alkyloxy or halogen; R3 is H or (CH2)n-NR5R6; R4 is H or (C1-6)alkyl, optionally substituted COOR7 or NR8R9; R5 and R6 independently denote H, (C3-8)cycloalkyl, quinuclidin-3-yl, (C2-6)alkenyl or (C1-6)alkyl, optionally substituted mono-substituted with CF3, (C3-8)cycloalkyl, (C6)aryl, a 5- or 6-member heteroaryl group, OH, (C1-6)alkyloxy, (C6-10)aryloxy, CONR11R12, NR13R14 or NR13SO2(C1-4)alkyl; or R5 and R6 together with a nitrogen atom to which they are bonded form a 4-8-member saturated heterocyclic ring which also contains 1 heteroatom selected from O, SO2 and NR15, where the ring is optionally mono-substituted or di-substituted with oxo, (C1-4)alkyl, (C3-8)cycloalkyl, NR16R17 or CONR18R19; R7 is H or (C1-4)alkyl; R8 and R9 independently denote H, (C1-4)alkyl (optionally substituted di(C1-4)alkylamino) or (C3-8)cycloalkyl; or R8 and R9 together with a nitrogen atom with which they are bonded form a 4-8-member saturated heterocyclic ring which also contains one heteroatom which is O; R11 and R12 independently denote H or (C1-4)alkyl; R13 and R14 independently denote H or (C1-4)alkyl; R15 is H, (C1-4)alkyl (optionally mono-substituted OH, (C1-4)alkyloxy or di(C1-4)alkylamino), phenyl, pyridyl or COR20; R16 and R17 denote (C1-4)alkyl; or R16 and R17 together with a nitrogen atom with which they are bonded from a 4-8-member saturated heterocyclic ring; R18 and R19 denote H; R20 is (C1-4)alkyl, (C3-8)cycloalkyl or furyl; and n equals 0 or 1; or its pharmaceutically acceptable salt. The invention also relates to use of formula I compounds to prepare a medicinal agent and to a pharmaceutical composition based on formula I compound.

EFFECT: novel derivatives have catepsin S and K inhibitory activity.

9 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound which exhibits inhibitory effect on the FAAH enzyme having formula I , where n denotes an integer from 1 to 6; A denotes a group X; where when n equals an integer from 2 to 6, groups A are identical or different; X denotes C1-2-alkylene; R1 denotes a hydrogen atom; R2 denotes a hydrogen atom or a group selected from the following groups: phenyl, phenyloxy; R3 denotes either 2,2,2-trifluoroethyl or phenyl, if necessary substituted with one or more halogen atoms or C1-3-alkyl, C1-3-alkoxy, trifluoromethyl; provided that: the formula 1 compound is not 2,2,2-trifluoroethyl benzylcarbamate, when R3 denotes 2,2,2-trifluoroethyl and group -[A]n- denotes a -CH2- group, when R3 denotes phenyl, if necessary substituted, and group -[A]n-denotes a -CH2-, -CH2CH2-,-CH2CH2CH2- group, then R2 is not a hydrogen atom and is in form of a base, an addition salt with a pharmaceutically acceptable acid, as well as to a method for synthesis of the formula I compound and a pharmaceutical composition having inhibitory effect on FAAH, containing at least one formula I compound.

EFFECT: improved method.

5 cl, 6 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to novel pyrrolo[3,2-b]pyridine derivatives of formula I , where values of radicals R1-R5 are given in the description. The invention also covers pharmaceutically acceptable salts of these compounds, methods of producing these compounds and pharmaceutical compositions containing these compounds. Pyrrolo[3,2-b]pyridine derivatives and their pharmaceutically acceptable salts can provide proton pump reversible inhibitory effect.

EFFECT: obtaining novel pharmaceutically acceptable salts which can provide proton pump reversible inhibitory effect.

5 cl, 2 tbl, 289 ex

FIELD: medicine.

SUBSTANCE: invention refers to compounds having anxiolytic and antidepressant activity, which are derivatives of the formula 1 (a-b), or formula 2 (a-b) at that compounds of formula 2 (a-b) are intermediate products in synthesis of compounds of the formula , where R-Cl is a compound 1a or R'=COOC2H5 - compound 1b, , where R=COOC2H5 and R'=C1 - compound 2a; R=R-COOC2H5 - compound 2b.

EFFECT: obtaining new biologically active compounds that differ from analogues as intended in low toxicity and lack of side effects.

5 cl, 3 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. The disclosed compounds have CDK1 and/or CDK2 kinase inhibiting activity. In formula R1 is selected from hydrogen, hydroxy-lower alkyl, C3-C6 cycloalkyl and R2-(X)n; X is selected from lower alkylene, hydroxy-lower alkylene, lower cycloalkylene or lower alkanoyloxy-lower alkylene; R2 is and is selected from phenyl and a 5- or 6-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of sulphur and nitrogen; R5 and R6 are independently selected from a group consisting of hydrogen, lower alkyl, halogen and lower alkoxy; and n equals 0 or 1.

EFFECT: design of a pharmaceutical composition for treating and preventing diseases whose condition can be improved by inhibiting CDK1 and/or CDK2 kinase, containing an effective amount of formula I compounds.

47 cl, 19 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: invention relates to new compounds of formula where L1 and L2 independently denote a bond, -S-, -NH- or unsubstituted C1-C5alkylene; A1 denotes a 6-member substituted aryl or unsubstituted heteroaryl; A2 denotes aryl or heteroaryl; R1 denotes halogen, -OR5, -NR6R7, -C(Z)R8, -S(O)wR9, -CN, -NO2, -S(O)2NH2, alkyl, aryl or heteroaryl; X1 denotes -C(R2)=, -C(R2)(R3)-, -N(R4)- or -O-; R2 and R3 independently denote hydrogen, -OR5 or alkyl; R4 denotes hydrogen or alkyl; Z denotes O or NH; w is integer from 0 to 2; R5 independently denotes hydrogen or alkyl; R6 and R7 independently denote hydrogen, -S(O)2R11 alkyl or heteroalkyl; R11 denotes hydrogen or alkyl; R8 independently denotes hydrogen, -NR14R15, -OR16, heteroalkyl or cycloalkyl; R14, R15 and R16 independently denote hydrogen, alkyl, cycloalkyl, heteroalkyl or heterocycloalkyl; R9 independently denotes hydrogen or alkyl; and where R6 and R7, R14 and R15 independently and optionally together with the nitrogen atom to which they are bonded form a substituted or unsubstituted heterocycloalkyl. The invention also relates to a method of modulating protein kinase activity, as well as to use of compounds in paragraph 1 and a pharmaceutical composition based on the said compounds.

EFFECT: new compounds which can be useful in treating diseases mediated by kinase activity are obtained and described.

47 cl, 2 ex, 40 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to benzazepin derivatives of formula (I), where R1 is unsubstituted cyclobutyl, R2 is 3-pyrazinyl, substituted CON(H)(Me) or 2-pyridinyl-M-pyrrolidinyl, where the said pyrrolidinyl group is substituted with a =O group; which is: methylamide 5-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy) pyrazine-2-carboxylic acid

or 1-{6-[(3-cyclbutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone

EFFECT: obtaining compounds which have affinity to histamine H3 receptor and pharmaceutical compositons containing said compounds.

11 cl, 288 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to neurology and concerns the EGF/GHRP-6 combination for central nervous system neuroregeneration after an autoimmune damage. Substance of the invention involves a pharmaceutical combination which represents therapeutically effective concentrations of epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP - 6) and which is introduced in an individual who suffers the symptoms of multiple sclerosis and neuromyelitis optica, and corrects demyelinisation in the central nervous system caused by autoreactive cells.

EFFECT: improved clinical effectiveness.

8 cl, 4 ex, 8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of general formula (I) and its pharmaceutically acceptable salts. In general formula (I) , Y represents group -CONH(Q)- or -NHCONH(Q)-; Q represents 6-member aromatic ring or 5-10-member heteroaromatic ring, containing one or two N heteroatoms or two O heteroatoms; R represents hydrogen, halogen, linear or branched (C1-C6)alkyl; (C1-C6)alkoxy; di-(C1-C6)alkylamino, 5-member heteroaromatic ring, containing one O or S heteroatom; 6- or 9-member heteroaromatic ring, containing one or two N heteroatoms; phenyl, mono- or disubstituted with halogen, (C1-C6)alkyl, halogeno(C1-C6)alkyl, (C1-C6)alkoxy, acyl; hydroxy; piano; di-(C1-C6)alkylamino, acylamino' carbamoyl; X represents group : where Z represents CH2, N or O; m represents integer number from 1 to 3; p is equal 0, 1; R" is selected from group, consisting of di-( C1-C6)alkylaminocarbonyl, (C1-C6)alkyl, acyl. Invention also relates to pharmaceutical composition, containing as active ingredient, invention compound, to application of invention compound for manufacturing pharmaceutical composition, to method of inhibition of nicotinic acetylcholine receptor α7.

EFFECT: obtaining compound, which possesses agonistic activity with respect to nicotinic acetylcholine receptor (nAChR) α7.

7 cl, 2 tbl, 4 dwg, 270 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, and concerns application of Madopar as a medicinal agent for correction motivation, cognitive and emotional disturbances in autistic spectrum disorders in children.

EFFECT: enhanced correction of motivation, cognitive and emotional disturbances in children with autistic spectrum disorders due to the administration of Madopar.

1 cl, 12 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a peptide copolymer containing lysine, alanine, tyrosine and glutaminic acid residues in ratio of 0.4-0.45:0.3-0.36:0.09-0.11:0.14-0.18, including its acid addition salt - acetate, and having average molecular weight in the interval 8.7-14.5 kDa, which can be used in a pharmaceutical composition for preparing a medicinal agent against multiple sclerosis, particularly medicinal agent Glatiramer acetate. The peptide copolymer is obtained through copolymerisation of N-carboxyanhydride of Nε-trifluoroacetyl-L-lysine and/or N-carboxyanhydride of Nε-benzyloxycarbonyl-L-lysine with N-carboxyanhydrides of L-alanine, gamma-O-benzyl-L-glutaminic acid and L-tyrosine with an initiator diethylamine in a medium of aprotic solvents dioxane or tetrahydrofuran or mixtures thereof. Benzyl type protective groups are removed from lysine and glutaminic acid residues using a solution of hydrogen bromide in acetic acid with a catalytic amount of water, and volatile amines diethylamine or methylamine in form of their aqueous solution are used to remove protective trifluoroacetyl groups from lysine residues.

EFFECT: method enables control of such properties of the product as average molecular weight and amino acid composition.

3 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrazole-pyrimidine derivatives having metabotropic glutamate receptor (mGluR2) antagonist properties and having formula (1): , where A is selected from a group consisting of: Ra is H, halogen or C1-6-alkyl; R1 is II, halogen, C1-6-alkoxy, C1-6-alkyl, C1-6-haloalkyl, C1-6-haloalkoxy; R2 is a halogen, C1-6-haloalkyl; R3 is NRbRc, where Rb and Rc are independently selected from a group consisting of H and C1-6-alkyl which is possibly substituted with one or more substitutes selected from a group consisting of hydroxy and -NRb'Rc', where Rb' and Rc' are independently selected from a group consisting of H and C1-6-alkyl; or Rb and Rc together with the nitrogen atom to which they are bonded form a possibly substituted heterocyclic group containing 5-6 ring atoms, possibly containing an additional N heteroatom, where the substitutes are selected from a group consisting of hydroxy and C1-6-alkyl, R4 is C1-6-haloalkyl or C3-4-cycloalkyl; as well as to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition and use of the compounds in preparing a medicinal agent for treating or preventing diseases and conditions in which mGluR2 activation plays a role.

EFFECT: improved properties of compounds.

10 cl, 2 dwg, 1 tbl, 129 ex

FIELD: chemistry.

SUBSTANCE: invention describes an amide of formula:

where A and B are independently selected from CH or N; D is H; Z is selected from hydrogen, unsubstituted C1-8alkyl, each L is independently selected from -CraRb-, -CRa=, -CO-, -O- or -NRa-; k, m, n, q, x and w are integers independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, provided that k+m+n+q+x+w equals at least 4; R1-R6 are independently selected from hydrogen, CN or halogen; Ra and Rb are independently selected from hydrogen, unsubstituted C1-8alkyl, or its pharmaceutically acceptable salt. The invention describes a pharmaceutical composition, use of the compounds to treat AChE-mediated diseases, a treatment method, as well as an amide synthesis method and use of the formula (I) amide as a chemical agent for inhibiting acetylcholinesterase in biological research.

EFFECT: compounds have high acetylcholinesterase or butyrylcholinesterase inhibiting activity.

24 cl, 27 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel malonamide derivatives of general formula , to their pharmaceutically acceptable salts of acid bonding and to all forms of their optically pure enantiomers, racemates or diastereomers and diastereomer mixtures, possessing inhibiting activity with respect to γ-secretase, as well as to pharmaceutical preparation, containing one or more than one of claimed compounds, and to application of claimed compounds for manufacturing of drugs. Values of substituents R, R1, R2, R3, as well as X, n are given in invention formula.

EFFECT: obtaining compounds that can be applied in treatment of Alzheimer's disease.

19 cl, 6 dwg, 111 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, ophthalmology, and can be used for treatment of optic atrophy in children of age from 1 to 6 months. For this purpose regions of large and small fontanelles of head and upper sympathetic ganglia at the level of cervical spine at C1-C2 level are exposed to polarised light of apparatus "Bioptron". Exposures to light are carried out daily during 10 days in therapeutic dose 12 J/cm2 from the distance 5 cm from skin surface with light spot diametre 5 cm, irradiation intensity 40 mW/cm2 exposure duration 30 seconds on region of fontanelles and 1 minute on regions of ganglia. On finishing light impact nootropic medications cortexin and/or actovegin or cerebrolisin are introduced in age dose. Courses of treatment are carried out from 1 month to 6 month age until desired therapeutic effect is obtained.

EFFECT: method allows to improve cerebral and intraocular blood supply and metabolic processes of brain and optic nerve, improve delivery of nootropic medications to optic analyser, obtain therapeutic concentrations of medications without side effects.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention is aimed at dipyrazole compounds of formula I and their pharmaceutically acceptable salts, where radicals and groups are defined in claim 1 of the formula of invention. Disclosed compounds modulate AMPA and NMDA receptor functioning. A pharmaceutical composition based on formula I compounds and separate dipyrazole compounds are also part of the subject of invention.

EFFECT: possibility of using compounds as pharmaceutical agents, mainly for treating psychoneurological diseases.

16 cl, 2 tbl, 39 ex

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

FIELD: medicine.

SUBSTANCE: there are described compound of formula, its pharmaceutically acceptable salt or their mixture, enentiomerically pure 4-{(R)-(3-aminophenyl)[4-(4-fluorobenzyl)pyperazin-1-yl]-N,N-diethylbenzamide or its pharmaceutically acceptable salt. Also described are method of anxiety therapy, method of pain therapy and method of depression therapy in animal.

EFFECT: compounds are of use in therapy, in particular for elimination of pain, depression and anxiety.

5 cl, 1 tbl, 9 ex

Up!