Azaheterocycles, combinatorial library, focused library, pharmaceutical composition, method of obtaining

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to novel azaheterocycles of general formula 1.1-13 and 2, as well as their pharmaceutically acceptable salts, which possess anti-carcinogenic activity, pharmaceutical composition with their application and combinatorial and focused libraries including novel azaheterocycles. In general formulae 1.1-1.3 and 2.

.

For compounds 1.1-1.3 each of R1a R2a independently on each other represent possibly substituted C1-C6alkyl; each of R1d, R2d, R3d, R4d, R5d, R6d and R7d independently on each other represent substitutes of cyclic system, preferably hydrogen atom, or for compounds 1.1 and 1.3 independently R1d and R2d, R3d and R4d, R5d and R6d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R5d and R6d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; or for compounds 1.2 independently R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; for compound 2 R1a represents amino group substitute, excluding hydrogen atom, such as possibly substituted C1-C6alkyl, possibly substituted phenyl; R2a represents possibly substituted C1-C6alkyl; R3a represents amino group substitute, such as hydrogen atom, possibly substituted C1-C6alkyl; Rnd represents one or two substitutes of cyclic system, preferably hydrogen atom, solid line with accompanying it dotted line represent single or double bond.

EFFECT: obtaining novel azaheterocycles and their pharmaceutically acceptable salts, which possess anti-carcinogenic activity.

9 cl, 4 dwg, 3 tbl, 7 ex

 

The text descriptions are given in facsimile form.

1. Substituted azaheterocycle General formula 1.1-1.3 or their pharmaceutically acceptable salts

where each of R1a, R2aindependently from each other represent a possibly substituted C1-C6alkyl;

each of R1d, R2d, R3d, R4d, R5d, R6dand R7dindependently from each other represent a Deputy cyclic system, preferably a hydrogen atom,

or for compounds 1.1 and 1.3 independent R1dand R2d, R3dand R4d, R5dand R6dtogether with the atoms to which they are linked, may form a through R1dand R2d, R3dand R4d, R5dand R6d

accordingly, it is possible substituted aromatic cycle, such as benzene, 5-6-membered heterocycle comprising at least one heteroatom selected from S;

or for connections Tim R 1dand R2d, R3dand R4d, R4dand R5d, R6dand R7dtogether with the atoms to which they are linked, may form a through R1dand R2d, R3dand R4d, R4dand R5d, R6dand R7daccordingly, it is possible substituted aromatic cycle, such as benzene, 5-6-membered heterocycle comprising at least one heteroatom selected from S;

the solid line with its accompanying dashed linerepresents a single or double bond.

2. Azaheterocycle General formula 2, or their pharmaceutically acceptable salts

where R1ais a Deputy amino group excluding a hydrogen atom, such as possibly substituted C1-C6alkyl, possibly substituted phenyl;

R2arepresents a possibly substituted C1-C6alkyl;

R3ais a Deputy amino group, such as a hydrogen atom, possibly substituted C1-C6alkyl;

Rndis aboutin or two Vice-cyclic system, preferably a hydrogen atom.

2. The method of producing azaheterocycles General formula 1.1-1.3 according to claim 1 interaction isonitrile General formula2the primary amine of General formula3substituted acid selected from the General formula 3.1(1)-3.1(3), and halogen carbonyl compounds selected from the General formula 3.2(1)-3.2(2), in the environment of an organic solvent with subsequent cyclization of the resulting adducts:

where R1a, R2a, R1d, R2d, R3d, R4d, R5d, R6dand R7dhave the meanings specified above for azaheterocycles General formula 1.1-1.3.

4. The method of producing azaheterocycles General formula 1.1-1.3 according to claim 1 interaction isonitrile General formula2the primary amine of General formula3corresponding halogen-substituted acid selected from the General formula 3.3(1)-3.3(3), and corresponding substituted carbonyl compounds selected from the General formula 3.4(1)-3.4(2), in the environment of an organic solvent with subsequent cyclization of the resulting

where R1a, R2a, R1d, R2d, R3d, R4d, R5d, R6dand R7dhave the meanings specified above for azaheterocycles General formula 1.1-1.3.

5. The method of producing azaheterocycles General formula 1.1-1.3 according to claim 1 interaction isonitrile General formula2the primary amine of General formula3and the corresponding bifunctional reagent selected from the General formula 3.5(1)-3.5(3), in the environment of organic solvent:

where R1a, R2a, R1d, R2d, R3d, R4d, R5d, R6dand R7dhave the meanings specified above for azaheterocycles General formula 1.1-1.3.

6. The method of producing azaheterocycles General formula 2 according to claim 2 interaction of isonitrile General formula2the primary amine of General formula3and bifunctional reagent of General formula 4 in the medium of organic solvent

where R1a, R2a, R3aand Rndhave the meanings specified above for azaheterocycles General formula 2.

7. A combinatorial library of compounds with anti-cancer activity, to identify compounds leaders, consisting of azaheterocyclic compounds of the General formula 1.1-1.3 according to claim 1 and/or azaheterocyclic compounds of the General formula 2 according to claim 2.

8. Focused library of compounds with anti-cancer activity, to identify compounds leaders, containing at least one of azaheterocyclic compound of General formula 1.1-1.3 according to claim 1 and/or azaheterocyclic compound of General formula 2 according to claim 2.

9. Pharmaceutical composition having anti-cancer activity and is intended to obtain drugs for treating and preventing various diseases mediated by the activity of protein kinases, in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as the active ingredient pharmaceutically effective amount of at least one of azaheterocyclic compounds of General formula 1.1-1.3 according to claim 1 and/or azaheterocyclic compounds about the formula 2 according to claim 2 or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to method of obtaining 4-amino-3-quinolinecarbonitryl, which includes: a) combining aminocompound with cyanoacetic acid and acid catalyst obtaining cyanoacetomide; b) condensing cyanoacetomide from stage a with aniline, alcohol solvent and trialkylorthoformiate obtaining 3-amino-2-cyanoakrylamide; and c) combining 3-amino-2-cyanoakrylamide with phosphorus oxychloride in acetonitryl, butyronitrile, toluol or xylol, optionally in presence of catalyst, obtaining 4-amino-3-quinolinecarbonitryl. Also described is method (version) of obtaining 4-amino-3-quinolinecarbonitryl, method of obtaining 7-aminothieno[3,2-b]pyridine-6-carbonitrile and method of obtaining cyanoacetamide.

EFFECT: creation of efficient method of obtaining 4-amino-3-quinolinecarbonitryl.

24 cl, 50 ex

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

EFFECT: effective application for preparation of medical products for oncologic therapy.

14 cl, 3 dwg, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

FIELD: agriculture.

SUBSTANCE: new chemically biologically active compound 3-amino-4,5,6-trimethyl-2-(benzimidazolyl-2)tieno[2,3-b]pyridine of formula 1 revealing growth regulating properties is described.

EFFECT: increasing sugar beet crop yield and sugar content.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted indoles of general formula , where: X stands for -S(O)n-, -C(O)-; A stands for C1-C6alkyl, -(CH2)p-NRaRb; R1, R2, R3 and R4 each is independently selected from group including H, halogen, halogen(C1-C6)alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, NO2, -NRaRb, phenyl, benzyl and benzyloxy, said phenyl cycles are optionally substituted with substituent, selected from group including C1-C6alkyl, halogen, NO2, halogen(C1-C6)alkyl, C1-C6alkoxy; R5 stands for H, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy C1-C6alkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, hydroxyl-(C1-C6)alkyl, hydroxy(C1-C6)alkylamino, halogen, halogen(C1-C6)alkyl-NRaRb, -NRc-( C1-C6)alkylene-NRaRb, or R5 and A together form radical C2-C3alkylene; R6 stands for H, C1-C6alkyl; R' and R" each independently stand for H, C1-C6alkyl; Ra, Rb and Rc each is independently chosen from group including H, C1-C6alkyl, hydroxy(C1-C6)alkyl, C2-C6alkenyl, C3-C6cycloalkyl-(C1-C6)alkyl, or Ra and Rb together with nitrogen atom, to which they are attached, form 5-7 member non-aromatic heterocyclic cycle, optionally containing in cycle O as additional heteroatom; m is equal 1 or 2; n is equal 0, 1 or 2 under condition that, if n is equal 0, R5 does not stand for NRaRb, and p is equal 0, 1 or 2; or their pharmaceutically acceptable salts.

EFFECT: obtaining compounds possessing agonistic activity which allows using them in pharmaceutical composition.

24 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to substituted 3-cyanotiophenacetamides of general formula I , in which R1 and R2 are independently designate (lower) alkyl, or R1 and R2 together with carbon atoms, to which they are bound, including bond between said carbon atoms, form 5-6 member, unsubstituted carbocyclic or 6-member heterocyclic cycle, probably having substitutes, independently selected from group, including (lower) alkyl, alkylsulfonyl and alkoxycarbonyl, R3 is selected from group, which includes (lower) alkyl, unsubstituted aryl, unsubstituted aralkyl and unsubstituted cycloalkyl, R4 - hydrogen, n is zero, or their pharmaceutically acceptable salts. Compounds can be applied for treatment and/or prevention of diseases, associated with antagonistic action on glucagon receptor, such as diabetes. Pharmaceutical composition based on compounds I and their application are also described.

EFFECT: obtaining substituted 3-cyanotiophenacetamides, which can be applied for treatment and/or prevention of diseases, associated with antagonistic action on glucagon receptor, such as diabetes.

22 cl, 23 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of formula I their pharmaceutically acceptable salts and solvate I where X represents O or S; Y and Z mutually independently denote hydrogen or halogen; R1 is hydroxy-C1-C7-alkyl, carboxy, C1-C7-alkyloxycarbonyl, or substitute of formula II R2 is hydrogen, carboxy or alkyloxycarbonyl. Compounds can be used as inhibitors of cytokine or inflammation mediator producing. Intermediate compounds of compounds I and application of compounds 1 are also described.

EFFECT: production of compounds used as inhibitors of cytokine or inflammation mediator producing.

12 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: (I) , in which R1 and R2 independently represent C1-6alkyl, C3-5cycloalkyl C1-3alkyl or C3-6dikloalkyl; Q represents CR4R5, where R4 represents hydrogen; or C1-6alkyl, and R5 represents carbon; Ar represents 5-6-membered aromatic ring system, where heteroatoms can represent up to 2 ring atoms, independently selected from nitrogen and sulphur, notably that this ring system can be substituted by one or more then one substitute, independently selected from C1-4alkyl; Ar2 represents 5-6-membered aromatic ring system containing up to 2 ring atoms, independently selected from nitrogen and sulphur, notably the ring contains at least one heteroatom and can be substituted by one or more then one group, independently selected from C1-4alkyl. The compositions can be used in autoimmune disease modulation. The methods of compounds production, pharmaceutical composition and use of the compounds in the treatment of respiratory disease are described.

EFFECT: production of thienopyrimidindion compounds for autoimmune disease modulation and respiratory disease treatment.

14 cl, 3 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to derivatives of thienopyrimidine with general formula I , where R1 represents C1-4alkyl; R2 represents C1-6alkyl, possibly substituted (1') by a hydroxyl group, (2') C1-4alkoxy, (3') C1-4alkoxycarbonyl, (4') di-C1-4alkylcarbamoil, (5') 5-6-member nitrogen containing heterocyclic group, (6') C1-C4alkylcarbonyl and (7') halogen, 5-6-member nitrogen containing heterocyclic group, phenyl, which can contain a substitute, R3 - C1-4alkyl, R4 - C1-4alkoxy. The compounds have antagonist activity to gonadotropin releasing hormones (GnRH). Description is given of a medicinal preparation based on formula I compounds, used of the compounds in making pharmaceutical compositions and the antagonist effect of the compounds on gonadotropin releasing hormone.

EFFECT: obtaining derivatives of thienopyrimidine with antagonist effect on gonadotropin releasing hormones.

17 cl, 143 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to thienopyrimidine diones with general formula (I), , where R1 and R2 each independently represents C1-6alkyl, C3-5cycloalkylC1-3alkyl or C3-6cycloalkyl; R3 represents a CO-G group, where G is a 5- or 6-member ring, containing a nitrogen atom and a second oxygen heteroatom, adjacent to the nitrogen atom. This ring can be substituted by at least one group, chosen from C1-4alkyl and hydroxyl; Q represents CR4R5, where R4 represents hydrogen or C1-6alkyl, and R5 represents hydrogen; and Ar represents a 5-10-member aromatic ring system, where up to 3 ring atoms can represent heteroatoms, independently chosen from nitrogen and sulphur. This ring system can be substituted with one or more groups. The invention also relates to pharmaceutical salts and solvates of thienopyrimidine diones. Description is also given of the method of obtaining these compounds, pharmaceutical compositions containing them, and their use in therapy, particularly in immunosuppressive therapy.

EFFECT: obtaining thienopyrimidine diones for use in immunosuppressive therapy.

17 cl, 29 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of pyridine [2,3-d] pyrimidine of general formula (I) and their pharmaceutically acceptable salts, which possess properties of KDR and FGFR inhibitors. Compounds can be applied to produce medications for treatment of cancer, for instance, of mammary gland, large intestine, lungs and prostate gland. In general formula (I) , Ar and Ar' independently on each other are selected from group that includes phenyl; phenyl substituted with 1-3 substituents selected from group C1-C4alkyl, hydroxy, halogen, halogen-substituted C1-C4alkyl, C1-C4alkoxy; 6-member nitrogen-containing heteroaryl and 6-member nitrogen-containing heteroaryl substituted with C1-C4alkoxygroup, on condition that Ar standing for heteroaryl does not represent 2-pyridyl, and standing for substituted heteroaryl does not represent substituted 2-pyridyl, R1 is selected from group including phenyl, C1-C10alkyl, C1-C10alkyl independently containing substituents selected from group that includes phenyl, C3-C6cycloalkyl. Invention also relates to intermediate compounds for compounds of general formula (I) and to pharmaceutical compositions.

EFFECT: obtaining derivatives and their pharmaceutically acceptable salts which possess properties of selective KDR and FGFR inhibitors.

21 cl, 2 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: described is obtaining and pharmaceutical application of substituted derivatives of arylalkane acid of formula I , where ring A, ring B, R1, R2, R3, R4, R5, X, Alk1, Alk2, Ar1 and Ar2 are such as determined in said description. Said compounds, as selective agonists activating (RAPPs) receptors, activated by peroximal proliferator, in particular, RXRs/RAPPs-alfa, RXRs/RAPPs-gamma and RXRs/RAPPs-delta heterodimers, are applied in treatment and/or prevention of type 2 diabetes and connected with it metabolic syndrome, such as hypertension, obesity, insulin-resistence, hyperlipidemia, hyperglycemia, hyperolesterinemia, artheriaslerosis, coronary artery disease, and other cardio-vascular disorders, and possess improved profile of side effects, connected with common RAPPs-gamma agonists.

EFFECT: obtaining compunds, which possess improved profile of side effects, connected with common RAPPs-gamma agonists.

22 cl, 38 ex, 2 tbl, 10 dwg

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: in substituted with carbamate groups pyrazolpyridines of general formula (I): R1 stands for group -NR3C(=O)OR4, R2 stands for hydrogen atom or NH2, R3 stands for hydrogen atom or alkyl group with number of carbon atoms from one to four, R4 stands for alkyl group with number of carbon atoms from one to six, as well as to their salt, isomers and hydrates; to methods of their obtaining, medication based on them, as well as to application of said compounds for manufacturing medications for cardio-vascular diseases.

EFFECT: useful biological properties of compounds.

13 cl, 9 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new histamine receptor blockers in the form of 2,3,4,5-tetrahydro-1H-pyrido-[3,4-b]indoles of the general formula 1 , where: R1 is an aminogroup substitute selected out of optionally substituted C1-C5alkyl; R2i is one or several same or different substitutes selected out of hydrogen, halogen, C1-C3 alkyl, CF3; Ar is phenyl or 5-6-member heterocycle containing 1-2 nitrogen or sulphur atoms in the cycle, unsubstituted or substituted by halogen, C1-C5alkyl, C1-C5alkoxy, substituted aminogroup or trifluormethyl; W is CH2 group optionally substituted CH2CH2 group or optionally substituted CH=CH group.

EFFECT: enhanced antiallergic and autoimmune effect.

4 tbl

FIELD: chemistry.

SUBSTANCE: in novel compounds of formula (I) R1 is selected from , R2 stands for hydrogen or (lower) alkoxy; R3, R4, R5 and R6 are selected each independently from hydrogen, (lower) alkyl, halogenated (lower) alkyl, haloid or cycloalkyl; on condition that R2, R3, R4, R5 and R6 do not all stand for hydrogen; R7, R8 and R9 stand each independently for hydrogen, (lower) alkyl, (lower) alkoxy, (lower) hydroxyalkyl or halogenated (lower) alkyl; on condition that R7, R8 and R9 do not all stand for hydrogen; R10 stands for (lower) alkyl or halogenated (lower) alkyl.

EFFECT: obtaining novel biologically active compounds with improved properties.

16 cl, 38 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to new substituted 2,3,4,5-tetrahydro-1N-pyrido[4,3-b]indoles with general formula 1.1, 1.2 or 1.3, their pharmaceutical salts and/or hydrates with antihistamine activity. In general formulae 1.1, 1.2 or 1.3 radicals assume values given below . In 1.1 compounds, R1 represents a substitute, chosen from hydrogen or unsubstituted C1-C5 alkyl; R2 represents a hydrogen atom or C1-C4 alkyl; R3i represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3; n=0 or 1-3; in 1.2 compounds R1 represents a substitute of an amino group, chosen from hydrogen or optionally substituted C1-C5 alkyl; R3 represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3, and Ar1 represents an aryl or heterocyclyl, containing at least one carboxyl and/or alkoxycarboxyl substitute or R3i represents a carboxyl and/or alkyloxycarboxyl substitute, and Ar1 represents optionally substituted aryl or heterocyclyl; in 1.3 compounds, R2 represents a hydrogen atom or C1-C4 alkyl; R3i represents one or more single or different substitutes, chosen from hydrogen, halogen, C1-C3 alkyl or CF3, and Ar2 represents optionally substituted aryl or heterocyclyl; k=0 or 1-4; m=1 or 2.

EFFECT: compounds can be used for making drug formulation for treating allergies, autoimmune diseases such as pollen allergy, urticaria, bronchial asthma etc.

17 cl, 10 dwg, 2 tbl,13 ex

FIELD: chemistry.

SUBSTANCE: invention refers to of serotonin receptor 5-NT6 antagonists, simultaneously regulating calcium ions homeostasis in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of general formula I, its pharmaceutically acceptable salt and/or hydrate. In general formula I where: R1 is amides substitute selected from optionally substituted C1-C5 alkyl; R2i represents one or number of identical or various substitutes selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar represents halogen unsubstituted or substituted C1-C6 alkyl, C1-C6 alkoxy, phenyl substituted with amides or trifluoromethyl or optionally substituted aromatic hexamerous heterocycle containing 1-2 nitrogen atoms per one cycle, W represents ethyl group-CH2CH2 - vinyl group or ethynyl group. Invention also concerns new compounds selected from group of compounds of formula 1, methods of production thereof, pharmaceutical compositions and methods of their use.

EFFECT: production of composition that simultaneously regulates calcium ions homeostasis in cells.

34 cl, 7 dwg, 4 tbl, 9 ex

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

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