(A61K31/5377)

Partly saturated nitrogen-containing heterocyclic compound // 2641291
FIELD: chemistry.SUBSTANCE: invention relates to a compound of the formula (I'), (wherein W represents the formula -CR11R12CR13R14-; R11 represents a hydrogen atom, a fluorine atom, C1-4 alkyl or phenyl; R12 represents a hydrogen atom, a fluorine atom or C1-4 alkyl; provided that R11 and R12, together with the adjacent carbon atom, optionally form C3-8 cycloalkane or tetrahydropyran; R13 represents a hydrogen atom, a carbamoyl, C1-4 alkyl (C1-4 alkyl is optionally substituted by one group selected from the group consisting of hydroxy, C1-3 alkoxy and di-C1-3 alkylamino), halo-C1-4 alkyl, phenyl, pyridyl, benzyl or phenethyl; R14 represents a hydrogen atom, C1-4 alkyl or halogen-C1-4 alkyl; Y represents a single bond or C1-6 alkanediyl (C1-6 alkanediyl is optionally substituted by one hydroxy group and one of the carbon atoms in C1-6 alkanediyl is optionally substituted by cycloalkpropane-1,1-diyl); R2 represents a hydrogen atom, C1-6 alkyl, C3-8 cycloalkyl {C3-8 cycloalkyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl (C1-6 alkyl is optionally substituted by one phenyl group), phenyl (phenyl is optionally substituted by one halogen atom), C1-6 alkoxy [C1-6 alkoxy is optionally substituted by one group selected from the group consisting of C3-8 cycloalkyl, phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom and C1-6 alkyl) and pyridyl (pyridyl is optionally substituted by one halogen atom)], C3-8 cycloalkoxy, phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl) and pyridyloxy (pyridyloxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl)}, phenyl (phenyl is optionally substituted by one to three groups that are the same or different and which are selected from the group of α3 substituents), naphthyl, indanyl, tetrahydronaphthyl, pyrazolyl [pyrazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl (phenyl optionally substituted by one C1-6 alkyl)], imidazolyl [imidazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl], isoxazolyl [isoxazolyl is optionally substituted by one phenyl group (phenyl is optionally substituted by one halogen atom)], oxazolyl [oxazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl and phenyl], thiazolyl [thiazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl, phenyl and morpholino], pyridyl (pyridyl is optionally substituted by one or two groups that are are the same or different and are selected from the group of α5 substituents), pyridazinyl [pyridazinyl is optionally substituted by one C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl group)], pyrimidinyl [pyrimidinyl is optionally substituted by one group selected from the group consisting of halogen-C1-6 alkyl, C3-8 cycloalkyl, phenyl and phenoxy (phenoxy is optionally substituted by one C1-6 alkyl)], pyrazinyl [pyrazinyl is optionally substituted by one group selected from the group consisting of C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl), and phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl and C3-8 cycloalkyl)], benzothiophenyl, quinolyl, methylenedioxyphenyl (methylenedioxyphenyl is optionally substituted by one or two fluorine atoms), azetidinyl (azetidinyl is optionally substituted with one pyrimidinyl group), piperidinyl (piperidinyl is optionally substituted by one group selected from the group consisting of pyrimidinyl, phenyl-C1-3 alkyl, C3-8 cycloalkyl-C1-3 alkylcarbonyl and phenyl-C1-3 alkoxycarbonyl) or the following formula (I") -CONR5CH2-R6 (I") [wherein in formula (I") R5 represents a hydrogen atom or C1-3 alkyl and R 6 is phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom, halogen-C1-6 alkyl and phenyl)], Y4 represents C1-4 alkanediyl; R3 represents a hydrogen atom or methyl; R4 represents -COOH or -CONHOH).EFFECT: compound has a superior PHD2 inhibitory effect.16 cl, 28 tbl, 11 ex

Azadecalins condensed with heteroarylketones - glucocorticoid receptor modulators // 2639867
FIELD: medicine.SUBSTANCE: invention provides azadecalin compounds of formula ondensed with heteroarylketones, which are modulators of glucocorticoid receptors. The radicals and symbols in formula I have the definitions given in the claims. In some embodiments of the present invention, pharmaceutical composition is provided comprising a pharmaceutically acceptable excipient and a compound of formula (I). In some embodiments of the present invention, a method is provided for modulation of glucocorticoid receptors that comprises glucocorticoid receptors contacting with a compound of formula I, thereby modulating the glucocorticoid receptors, as well as a method for treatment of diseases by glucocorticoid receptors modulation, which comprises administration of a therapeutically effective amount of a formula I compound to a subject in need thereof, as a result, disease treatment takes place.EFFECT: increased efficiency of treatment.24 cl, 2 dwg, 1 tbl, 22 ex
Anti-cancer benzopyrazines acting through fgfr-kinases inhibition // 2639863
FIELD: pharmacology.SUBSTANCE: invention relates to benzopyrazine derivatives of the general formula (I) , including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein W is -N(R3)-; R2 is C1-4alkoxy; Y is -CR18=N-OR19 or -E-D; E is bond, C2-4alkynediyl, -CO-(CR22R23)s-, -NR22-(CR22R23)s-, -(CR22R23)s-CO-NR22-(CR22R23)s- or -(CR22R23)s-NR22-CO-(CR22R23)s-; D is phenyl, 3-6 membered cycloalkyl or 5-9 membered mono- or bicyclic saturated, partially saturated or aromatic heterocyclyl containing 1-4 heteroatoms selected from N, O or S, wherein the said phenyl, cycloalkyl and heterocyclyl can each optionally being substituted with 1-2 R1-groups; with the exception of the compounds indicated in the formula; R1 is halogen, cyano, C1-6alkyl, C1-6alkoxy, -C(=O)-O-C1-6alkyl, hydroxyC1-6alkyl, -NR4R5 , C1-6alkyl substituted by -O-C(=O)-C1-6alkyl, C1-6alkyl substituted by -NR4R5, -C(=O)-NR4R5, R6, C1-6alkyl substituted by R6, -C(=O)-R6; R3 is halogenC1-6alkyl, optionally substituted by -O-C(=O)-C1-6alkyl, hydroxyC1-6alkyl, hydroxyhalogenC1-6alkyl, C1-6alkoxyC1-6alkyl, where each C1-6alkyl may optionally be substituted by one hydroxyl group or -O-C(=O)-C1-6alkyl, C1-6alkyl substituted by R9, C2-6alkynyl substituted with R9, C1-6alkyl substituted by -NR10R11, C1-6alkyl substituted by -O-C(=O)-NR10R11; R4 and R5 are hydrogen, C1-6alkyl, C1-6alkyl substituted by -NR14R15, hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, where each C1-6alkyl may optionally be substituted by one hydroxyl group, -C(=O)-NR14R15, -C(=O)-O-C1-6alkyl, -C(=O)-R13; R6 is a 6-membered saturated or aromatic monocyclic heterocyclyl having 1 to 2 heteroatoms selected from N or O; the said heterocyclyl is optionally substituted by 1 substituent selected from C1-6alkyl, halogen, C1-6alkyl-O-C(=O)-; R9 is C3cycloalkyl or 3-6 membered monocyclic saturated, partially saturated or aromatic heterocyclyl containing 1-2 heteroatoms selected from N or O, the said heterocyclyl is optionally substituted by 1 substituent selected from =O, hydroxyC1-4alkyl, C1-4alkyl-C(=O)-, C1-4alkyl substituted by -NR14R15, C1-4alkoxy; R10 and R11 are hydrogen, C1-6alkyl, halogen C1-6alkyl, hydroxyC1-6alkyl or C1-6alkyl substituted by carboxyl; R13 is a saturated 6-membered monocyclic heterocyclyl containing 1-2 heteroatoms selected from N and O; R14 and R15 are hydrogen or C1-4alkyl; R18 and R19 are C1-6alkyl; R22 and R23 are hydrogen; n=2; s=0, 1, 2, or 3. Invention also relates to a pharmaceutical composition and a product based thereon, the use of a compound of formula (I) and a method of prevention or treatment of conditions mediated by FGFR kinase.EFFECT: new derivatives of benzopyrazine, useful for cancer treatment.28 cl, 4 tbl, 54 ex
Indasole inhibitors of wnt signal path and their therapeutic applications // 2638932
FIELD: medicine.SUBSTANCE: invention relates to a indasole derivative that has the following formula , or its pharmaceutically acceptable salt, as well as a pharmaceutical composition containing it. The invention relates to methods for treatment of disorders characterized by the activation of Wnt-signalling pathways (e.g., cancer, abnormal cell proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), including introduction of a therapeutically effective amount of this compound or pharmaceutically acceptable salt thereof. This compound can also be used in modulation of cellular events, mediated by Wnt-signalling, as well as for treatment of genetic diseases and neurological conditions/disorders/diseases due to mutations or disregulation of the Wnt pathway and/or one or more components of Wnt-signalling.EFFECT: inhibits the Wnt signalling pathway and can be used to treat various diseases and pathologies.28 cl, 8 tbl, 8 ex

Derivative cyclic amine and its pharmaceutical application // 2638549
FIELD: pharmacology.SUBSTANCE: invention refers to derivatives if cyclic amine of formula (I), where A is a group, represented by the general formula (IIa), (IIb) or (IIc), where A is a group, provided by the general formula (IIa) or (IIb), R1 represents an alkyl group containing 1 or 2 carbon atoms and optionally substituted by a hydroxyl group, amine group or carboxyl group, R2 represents a hydrogen atom, R3 is a hydrigen atom or alkyl group containing 1 or 2 carbon atoms, R4 is a hydrogen atom or an alkylcarbonyl group, containing 2 carbon atoms, or an alkyl group, containing 1 or 2 carbon atoms and optionally substituted by alkylcarbonylamine group, containing 2 carbon atoms, and n is 1 or 2, in which, when R3 and R4, each independently represent an alkyl group, containing 1 or 2 carbon atoms, R1 represents an alkyl group containing 1 or 2 carbon atoms and substituted by a hydroxyl group, amine group or carboxyl group; and when A is a group, represented by the general formula (IIc), R1 represents an alkyl group, containing 1 carbon atom and substituted by a carboxyl group, R2 represents a hydrogen atom and X represents CH2, O or -NR5 and R5 is an alkyl group, containing 1 carbon atom. Also, the invention relates to a prodrug of the compound of formula (I), pharmaceutical, analgetic agent and therapeutic agent based on compounds of formula (I), or its prodrug.EFFECT: new derivatives of imidazol, useful in the treatment of pain, have been obtained.11 cl, 24 dwg, 5 tbl, 73 ex
Dna-pk inhibitors // 2638540
FIELD: biotechnology.SUBSTANCE: invention relates to a novel compound of formula (I) or a pharmaceutically acceptable salt thereof, inhibiting DNA-dependent protein kinase (DNA-PK). The compounds can be used in the treatment of cancer. The compounds have a radiosensitizing effect on the line of cancer cells sensitive to radiation and can be used to enhance the effect of the therapeutic regimen for the treatment of cancer. In general formula (I), X is N or CRA5; RA1is F, C1-4-alkyl, C3-5cycloalkyl, OC1-4-alkyl, OC1-4-alkyl-C3-5cycloalkyl, NH2, NHC1-4-alkyl, NHC1-4-alkyl-C3-5cycloalkyl or C0-4-alkylheterocyclyl, the said heterocyclic ring system being selected from oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or morpholinyl, and each of the said alkyl, cycloalkyl or heterocyclyl is optionally substituted with a maximum of three F atoms, a maximum of three 2H atoms, a maximum of two non-hemin OH groups, or a maximum of two OC1-2-alkyl; each RA4 is independently H or 2H; RA5 is hydrogen, F, C1-4-alkyl or OC1-4-alkyl, each of the said alkyls being optionally substituted with a maximum of three F atoms or a maximum of three 2H atoms; RB3 is C (O) NHC1-4-alkyl. The said alkyl is optionally substituted with a maximum of three F atoms, a maximum of three 2H atoms, a maximum of two non-hemin OH groups, or a maximum of two OC1-2-alkyl; and each RB4 is independently hydrogen, deuterium, F, or C1-4-alkyl.EFFECT: improved compound properties.18 cl, 3 tbl, 14 ex
Triazolcarboxamide derivatives // 2637938
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula I. In formula IR1 is phenyl or pyridinyl optionally substituted by halogen, lower alkyl, lower alkoxy, lower alkyl, substituted halogen, and lower alkoxy substituted by halogen; X1 is -N = or CH; X2 is a CR2 or =N-; X3 is -N= or CH; provided that only two of X1, X2 or X3 are nitrogen; where is a triazole group selected from , or ; R2 is hydrogen or lower alkyl; Z is a bond, -O- or -CH2-. The compounds of the invention possess affinity for the receptors associated with trace amines (TAAR). The invention also relates to pharmaceutical compositions and to application of a compound for drug manufacture.EFFECT: new compounds of formula I are obtained that have a high affinity for the receptors associated with trace amines, especially TAAR1.12 cl, 1 tbl, 36 ex
Inhibitors of lrrk2 kinases activity // 2637936
FIELD: pharmacology.SUBSTANCE: R1, R2, R3 and R4 values are defined in the claims of this invention. Compounds of the formula (I) inhibit the LRRK2 activity. In addition, the invention relates to particular compounds as defined in claim 14. The invention also relates to a pharmaceutical composition comprising the compounds of the invention and to a method for neurodegenerative diseases treatment, for example those in which the disease is represented by α-synucleinopathy and in particular to a method for treatment of various diseases of the Parkinson's disease type, as well as a method for treatment of autoimmune diseases, such as Crohn's disease or ulcerative colitis.EFFECT: new method for neurodegenerative diseases treatment.22 cl, 10 tbl, 15 ex
Arylcycloalkylamines derivatives neuroprotector (versions), substances with combined neuroprotector, analgetic and antidepressive action, pharmaceutical compositions based thereon // 2637928
FIELD: pharmacology.SUBSTANCE: invention relates to new arylcycloalkylamines of the general formula . In the general formula (I), R1, R2 are H, linear or branched alkyl (C1-C4), linear or branched alkoxy (C1-C4), halogen; Y is -CH2-O-CH2-, - (CH2)n-, where n: 1-3; X is -CO-NH-(CH2)6-, -CO-(CH2)k-, -CH2-NH-(CH2)6-, -CH(CH3)-NH-(CH2)6-, -(CO)p-(CHR5)m, where p, m-: 0, 1, k: 2, 4-7, R5: H, linear alkyl C1-C5; R3, R4 are H, linear alkyl C1-C4, -CH2-C≡CH, -(CH2)2-O-(CH2)2-NH2, cyclopropyl, cyclopropylmethyl; 4-pyridinyl, an amino acid residue of a proteinogenic acyclic or aromatic α-amino acids, γ-aminobutyric acid, ε-aminocaproic acid, β-alanine; -CHR6-CH2-OR7, where R6: H or a linear or branched alkyl C1-C4, benzyl, R7: H, linear alkyl C1-C4, or R3, R4 together with the nitrogen to which they are attached, form a pyrrolidine, 2-(hydroxymethyl) pyrolidine, 4-aminopyridinium ring; G is (C1-C4) carboxylic acid, methanesulfonic acid or a mineral acid or water. As an acyclic or aromatic α-amino acid residue, they contain a proteinogenic α-amino acid residue. As (C1-C4) carboxylic acid, they contain at least one compound from the group consisting of acetic, fumaric, succinic, tartaric, malic and maleic acids. As a mineral acid, they contain at least one compound from the group consisting of hydrochloric, phosphoric, sulfuric acids. The preferred compounds are arylcycloalkylamine derivatives of the general formula , wherein Y: -CH2-O-CH2-, -(CH2)2-. The invention also relates to a pharmaceutical composition which can be a combination of arylcycloalkylamine derivatives and at least one substance from the group comprising levodopa, palmitoyle ethanolamide, N-(2-aminoethyl) palmitamide hydrochloride, rasagiline, risperidone, toloxaton, quetiapine, gamma-aminobutyric acid, sodium valproate, amitriptyline, clomepramine, fluoxetine, paroxetine, sertraline, phenylephrine, dexamethasone, prednisolone. The composition may be in the form of a tablet, capsule, pellet, powder for preparation of a solution for enteral administration, a solution for parenteral administration, a powder for preparation of a solution for parenteral administration.EFFECT: neuroprotective, analgesic and antidepressant action.11 cl, 13 tbl, 96 ex
Substituted pyrrolidines as xia factor inhibitors for thromboembolic diseases treatment // 2636050
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the general formula , their pharmaceutically acceptable salts, pharmaceutical compositions containing the said compounds.EFFECT: compounds of general formula I are XIa factor inhibitors and are suitable for thromboembolic diseases prevention or treatment.22 cl, 1 tbl, 115 ex
Aminopyridine derivatives as modulators of leucine-rich repeated kinase 2 (lrrk2) // 2634716
FIELD: pharmacology.SUBSTANCE: compounds are designed to treat a disease such as Parkinson's disease, in particular hereditary Parkinson's disease. In formula I, m is from 0 to 1; -NRa-; -O-; or -S(O)r- where r is from 0 to 2 and RA is hydrogen; R1 is C1-6-alkyl; R2 is halogen; cyano; or halo-C1-6-alkyl; R3 and R4 are independently halogen; C1-6-alkyl; C1-6-alkoxy; halo-C1-6-alkyl; or halo-C1-6-alkoxy; or R3 and R4 together with the atoms to which they are attached, can form a five- or six-membered ring which optionally includes one or two heteroatoms independently selected from O; and R5 is C1-6-alkylsulfonyl; or cyano.EFFECT: increased efficiency of treatment.17 cl, 3 tbl, 32 ex

New compounds for selective histone deacetylase inhibitors and pharmaceutical composition including such compounds // 2634694
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of formula I, their optical isomers or pharmaceutically acceptable salts that can be used for treatment of diseases mediated by histone deacetylase. In formula I, A is , Xa and Xb are CH, L1 and L2 independently hydrogen, -F, -Cl, -Br or -I, Q is C(=O), Y is selected from the group consisting of , and , M is C, O or N, l and m are independently 0 or 1, each of Ra1 and Ra2 is independently hydrogen; hydroxy; linear or branched -C1-4-alkyl, etc., n is 0, 1 or 2, Rb is hydrogen; hydroxy; linear or branched -C1-6-alkyl, etc., Z is selected from the group consisting of , etc., where each of Pa and Pb is independently ; hydrogen; hydroxy; linear or branched -C1-4-alkyl, etc., where is selected from phenyl, pyridine, pyrimidine, thiazole, indole, indazole, etc., each of x, y and z is independently 0 or 1, and each of Rg1, Rg2 and Rg3 is selected independently from hydrogen; hydroxy; -C1-3-alkyl, etc. The invention also relates to a pharmaceutical composition comprising compounds of formula I, a method for treatment of diseases mediated by histone deacetylase and application of said compounds for drugs preparation.EFFECT: increased effeciency of compound application.9 cl, 7 dwg, 16 tbl, 173 ex
Dyetherned phenylaminopyrimidine and pharmaceutical composition containing such connection // 2633694
FIELD: pharmacology.SUBSTANCE: invention relates to the deuterated phenylamino-pyrimidine of formula (I) or its pharmaceutically acceptable salts: . In the formula (I) R1, R2, R13, R14, R15, R16, R17, R18, R19, R20, R21 and R22 are each independently hydrogen or deuterium; R3, R4, R5, R6, R7, R8, R9, R10 and R11 are each independently hydrogen; R12 is hydrogen; Provided that at least one of R1, R2, R13, R14, R15, R16, R17, R18, R19, R20, R21 or R22 are deuterated or deuterium. The invention also relates to a pharmaceutical composition for inhibiting JAK kinase and to the use of compounds for the preparation of a pharmaceutical composition.EFFECT: new compounds of formula (I) having the properties of a JAK kinase inhibitor have been obtained.9 cl, 1 dwg, 4 tbl, 13 ex
Pyridinone and pyridazinone derivatives // 2632915
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I) or its pharmaceutically acceptable salts: , wherein J is a group of formula IIa, R1a is C1-C3alkyl; Y1a is N or CRxa, where Rxa is H, X2a is selected from the group consisting of: H, C1-C4alkyl; X1a is selected from the group consisting of: hydrogen, halogen, C1-C6alkyl, C1-C4haloalkyl,-O-C1-C4alkyl, -O-C1-C3alkylene-C3-C7cycloalkyl, -O-C1-C4haloalkyl, -O-C1-C3alkylene(5-membered heterocycloalkyl having 1 heteroatom selected from O), -O-C1-C6alkylene-N(R10)2, -O-C1-C3alkylene-C(O)OC1-C4alkyl, -C2-C4alkenylene-C(O)-O-C1-C4alkyl, -C(O)-C1-C4alkyl, C(O)O-C1-C4alkyl, C(O)NR10R12, -NR10-C1-C3alkylene-C(O)-C1-C4alkyl, -SO2NR10R12 and any of the groups: ii) 6-membered heterocycloalkenyl, which may be substituted with 1 R2; iii) 5-6 membered heterocycloalkyl with 1 to 2 heteroatoms selected from N, which may be substituted with 1-2 R3; iv) 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O, 9-10 membered bicyclic heteroaryl with 1 to 3 heteroatoms independently selected from N, S, which may be substituted with 1-2 R4; v) phenyl which may be substituted with 1-2 R6; X3 is LG where L is absent or is selected from the group consisting of: -O-, -O-C1-C3alkylene; and G is selected from the group consisting of: phenyl, 6-membered heteroaryl with 1 heteroatom selected from N, 9-membered bicyclic heteroaryl with 2 heteroatoms, selected from N, C3-C7cycloalkyl, 6-membered heterocycloalkyl with 1 heteroatom selected from N, O, where G may be substituted with 1-2 groups, A2 is CR18, and A1, A3 and A4 are CR19, values of the remaining substituents are indicated in the claims. The invention also relates to individual compounds, to a pharmaceutical composition and to a method for cancer treatment.EFFECT: new compounds with proliferative activity are obtained.20 cl, 6 tbl, 293 ex
Heterocyclic derivative and pharmaceutical means // 2632908
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic derivative or a pharmaceutically acceptable salt thereof, of the general formula , wherein ring A is a group represented by the general formulas , or , where X1 is NH, NC1-6alkyl or O; A1 is hydrogen; A2 is i) hydrogen; ii) halogen; iii) C1-6alkyl optionally substituted by one to three groups selected from a group consisting of halogen, amino, mono(C1-6alkyl)amino, di(C1-6alkyl)amino, carbamoyl, mono(C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, saturated cyclic aminocarbonyl, wherein the "saturated cyclic amino group" of the "saturated cyclic aminocarbonyl" part is 1-pyrrolidinyl, C1-6alkoxy and C1-6alkoxy-C1-6alkoxy; iv) C3-6cycloalkyl, optionally substituted by C1-6alkyl optionally substituted by one to three halogens; vi) a 4 to 5-membered saturated heterocyclic group containing one nitrogen or oxygen atom in the ring, optionally substituted by C1-6alkyl, (C1-6alkyloxy)carbonyl, (C1-6alkyl)carbonyl or hydroxy; (vii) C1-6alkylthio; (viii) C1-6alkylsulfonyl; ix) C1-6alkylsulfinyl; x) -NR3R4, where R3 and R4 are the same or different groups selected from a) hydrogen, b) optionally substituted C1-6alkyl, or c) C3-6cycloalkyl; or xi) saturated cyclic amino, wherein the "saturated cyclic amino" is piperidino, 1-piperazinyl or 4-morpholino, optionally substituted by C1-6alkyl, amino, mono(C1-6alkyl)amino, di(C1-6alkyl)amino, C1-6alkoxy or hydroxyl; R1 is phenyl, benzyl, naphthyl, C3-6cycloalkyl, C3-6cycloalkylmethyl, heteroaryl wherein heteroaryl is benzothiadiazolyl, benzothiazolyl, indolyl, 1,1-dioxobenzothiophenyl, quinolyl or 1,3-benzoxazol-2-yl, 1,2,3,4-tetrahydronaphthalen-5-yl, 1,2, 3,4-tetrahydronaphthalen-6-yl, 2,3-dihydro-1H-inden-4-yl, 2,3-dihydro-1H-inden-5-yl or C1-6alkyl, wherein the said phenyl, benzyl, cycloalkyl, cycloalkylmethyl and heteroaryl are optionally substituted; R2 is phenyl or pyridyl, wherein the said phenyl and pyridyl are optionally substituted. The invention also relates to a pharmaceutical composition and to an agent having the ability to inhibit mPGES-1 comprising a compound selected from the group consisting of a heterocyclic derivative of formula 1 and a pharmaceutically acceptable salt thereof as an active ingredient.EFFECT: heterocyclic derivatives possessing the inhibitory activity of mPGES-1.10 cl, 18 tbl, 257 ex
Heterocyclic amines and their application // 2632900
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein W is S; Y is N; X is N; R1 is selected from (a) C1-C6 alkyl optionally substituted with amino, methylamino, dimethylamino, C1-C6 alkoxy or isoindolyl; (B) -NR8R7, -CH2NR7R8, where R7 and R8 are joined to form optionally substituted C3-C7 non-aromatic ring which is pyrrolidine, morpholine, piperazine, piperidine, 1,4-diazepane, azepane, azetidine, 2-azabicyclo[2.2.1]heptane or 2,5-diazabicyclo[2.2.1]heptane and optionally substituted by one or more C1-C6alkyl, C1-C6alkoxy, methoxyethyl, 1-methoxypropane, isopropyloxymethyl, isopropyloxyethyl, -C(O(CH2)-methyl, -C(O)(CH2)-O-isopropyl, C1-C6haloalkyl, -S(O)2-methyl, -S(O)2-isopropyl, oxo, -C(O)(C1-C2)alkyl-N(methyl)2, -C(O)(C2)alkyl-(pyrrolidine), t-butyl-C(O)- or phenyl; or (c) -O-(tetrahydro-2H-pyran); each of R2, R3 and R5 are hydrogen; R4 is selected from C3-C6cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and optionally substituted heteroaryl selected from pyridine, pyrazole, pyridazine, pyrimidine. The said heteroaryl is optionally substituted with 1 to 2 substituents selected from C1-C6 alkyl and CN. The invention also relates to specific compounds as defined in the claims. The compounds of the invention are intended for the manufacture of a pharmaceutical composition having an inhibitory activity against an interleukin 1 receptor associated kinase 1 (IRAK-1) and an interleukin 1 receptor associated kinase 4 (IRAK-4). The compounds of the invention are also useful in a method for treatment of a disorder sensitive to inhibition of IRAK-1-mediated signalling.EFFECT: heterocyclic amines having inhibitory activity against an interleukin 1 receptor associated kinase 1 and interleukin 1 receptor associated kinase 4.24 cl, 4 tbl, 431 ex
Pyrazole derivative // 2632884
FIELD: pharmacology.SUBSTANCE: in the above formula , A represents a phenyl group which may be unsubstituted or substituted by 1 to 3 Q groups which are identical or different and are selected from the group consisting of a halogen atom, C1-6alkyl, C3-7cycloalkyl, C1-6haloalkyl, phenyl, -O-R2 and -O-C1-6haloalkyl; X and Z are CH and Y is a nitrogen atom; R is a hydrogen atom; R1 is a hydrogen atom and R2 is a hydrogen atom or C1-6alkyl group.EFFECT: compound has an inhibitory effect on xanthine oxidase, is well suited for treatment or prevention of diseases associated with xanthine oxidase such as gout, hyperuricemia, tumor lysis syndrome, stones in the urinary tract, hypertension, dyslipidemia, diabetes, cardiovascular disease, kidney disease, respiratory tract disease, autoimmune diseases, inflammatory bowel disease.10 cl, 7 tbl, 112 ex
Nitrogen-containing heterocyclic compound or its salt // 2632253
FIELD: chemistry.SUBSTANCE: invention relates to compound of the general formula [1]-(1): , where R2ais a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from a halogen atom; an amino-group; a C1-6alkylamino-group, which may be substituted by one or more halogen atoms, di(C1-6alkyl) amino-group, which may be substituted by one or more hydroxy-group, a C1-6alkylaminocarbonyl and di(C1-6alkyl) amino-group, or morpholinyl or piperazinyl group, which may be substituted by one or more substituents selected from hydroxy-group, a C1-6alkyl group and a hydroxy-C1-6alkyl group, R4a is a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more phenyl groups, R17a is a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from a halogen atom, the hydroxyl group, and a C1-6alkoxygroup, provided that R17a together with R4a, the nitrogen atom, to which R4a is attached, and the carbon atom, to which R17a is attached, may form a nitrogen-containing divalent azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom, a hydroxyl group, a C1-3alkyl group or a C1-6alkoxy group; R17b and R18b are the same or different and are a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom, a hydroxyl group and a C1-6alkoxy group, provided that R17b and R18b together with the carbon atom, to which they are attached, can form C(=O), or R17b and R18b together with the carbon atom, to which they are attached, may form a tetrahydropyrandyl group; R9a is a C1-6alkoxy group, pyrrolidinyl, piperidinyl, piperazinyl, pyrazolidine, triazoline, or morpholinyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom and a C1-3alkyl group, or N(R15)(R16), where R15 is a hydrogen atom or a C1-6alkyl group, and R16 is a C1-6alkyl group, which may be substituted by one or more groups selected from a halogen atom, a cyano group, a C3-6cycloalkyl group, a phenyl group, which may be substituted by one or more halogen atoms, a C1-6alkoxy group, di(C1-6alkyl) amino-group, and a morpholinyl, a tetrahydropyranyl, or a thiophenol group, a C3-8cycloalkyl group, a phenyl group, which may be substituted by one or more groups selected from a halogen atom, a cyano group, a C1-6alkyl group, a C1-6alkoxy group, or a pyridinyl or chinolyl group, which may be substituted by one or more C1-6alkoxy group, or R15 and R16 may form a cyclic amino-group, which may be substituted by one or more groups selected from halogen and a C1-3alkyl group, and R12a is a C1-6alkyl group, which may be substituted by one or more groups selected from the hydroxy groups, di(C1-6alkyl) amino-group or a pyridinyl, a morpholinyl, or a pyrrolidinyl group, a phenyl group, which may be substituted by one or more groups selected from the halogen atom; a cyano group; an amino-group, which may be protected by the acyl group; a carbamoyl group, which may be substituted by one or more groups selected from the C1-6alkyl groups and the C3-8cycloalkyl group; a C1-6alkyl group, which may be substituted by one or more groups selected from halogen and the triazoline group; a C1-6alkoxy group, which may be substituted with halogen; or pyrazolidine, triazoline, or thiazolidine group which may be substituted by one or more groups selected from C1-6alkyl group and ceanography, or pyridyloxy, izohinolinove, talinolol, isoxazolidine, isothiazolinone, thiadiazolidine, indazolinone, benzothiazolyl, chinolyl, benzoxazolyl, or pyrazolopyrimidinyl group, which may be substituted by one or more groups selected from halogen, a C1-6alkyl group, which may be substituted by one or more C1-6alkoxy group, a C1-6alkoxy group, a C1-6alkyl amino-group, a C1-6alkoxy carbonyl group, or a morpholinyl group; X2a is a C1-6alkylene group, which may be substituted by one or more substituents selected from exography and the C1-6alkyl group, a divalent C2-6alicyclic hydrocarbon group, or a divalent aromatic hydrocarbon group, which may be substituted by one or more groups selected from halogen, a C1-6alkyl group, which may be substituted by halogen and the C1-6alkoxy group, and X3a is a C2-6alkynyl amino-group, or N(R22)-C(=O), where R22 is a hydrogen atom.EFFECT: compounds are an inhibitor of Fms-like tyrosine kinase 3, which can be used as a therapeutic agent for acute myelogenous leukemia.21 cl, 261 tbl, 70 ex

New compounds - neurokinin 1 receptor antagonizer // 2631319
FIELD: pharmacology.SUBSTANCE: in formula n=1 or 2; R1 and R2, independently of each other, are hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy or halogen; R3 is hydrogen or C1-4 alkyl optionally substituted with hydroxy; R4 is hydrogen or oxo; R5 and R6, independently of one another, are hydrogen, C(=O)OR7, C(=O)NR8R9, C1-4 alkyl, wherein the said C1-4 alkyl is optionally substituted with hydroxy, NR8R9 or a 5- or 6-member heterocyclic ring with 1-4 heteroatoms selected from O and N, wherein the said 5- or 6-member heterocyclic ring is optionally substituted with C1-4 alkyl or C(=O)R7; or R5 and R6 together with the carbon atom to which they are attached form =CH2 or 5- or 6-member heterocycloalkyl with 1-4 heteroatoms selected from O and N, wherein the said heterocycloalkyl is optionally substituted with C1-4 alkyl; R7 is hydrogen or C1-4 alkyl; R8 and R9 are, independently of each other, hydrogen or C1-4 alkyl, or R8 and R9 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring with 1-4 heteroatoms selected from O and N. The invention also relates to a pharmaceutical composition, a method for prevention, treatment or alleviation of the severity of conditions accompanied by skin pruritus, application of the said compounds in the manufacture of a medicament for prevention, treatment or alleviation of the said diseases, and to intermediates of general formula wherein R10 is selected from the group consisting of hydrogen and C(O)OR14; R11 is selected from the group consisting of hydrogen and oxo; R12 and R13 are independently selected from the group consisting of hydrogen, C1-C4 alkyl, allyl and C(O)O(C1-C4alkyl); R14 is selected from the group consisting of C1-C4-alkyl; n is 1 or 2.EFFECT: possibility to use the compounds for prevention, treatment or alleviation of conditions accompanied by skin pruritus.27 cl, 3 dwg, 1 tbl, 122 ex
Pi-3 kinase dosage regime // 2630975
FIELD: medicine.SUBSTANCE: group of inventions relates to medicine and refers to the dosage regimen of a phosphatidylinositol-3-kinase inhibitor (PI3K) in cancer treatment. 5-(2,6-dimorpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethylpyridin-2-ylamine or a pharmaceutically acceptable salt thereof in a therapeutically effective amount of approx. 60 to approx. 120 mg per day, for five consecutive days in any seven-day period is used as the phosphatidylinositol-3-kinase inhibitor.EFFECT: reduced side effects of the therapy.9 cl, 2 tbl, 2 ex
Compound as wnt signal inhibitor, its compositions and application // 2627712
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of the general formula (I) or an N-oxide thereof, wherein X1, X2, X3 and X4 independently represent CR4 or N, where 0 or 1 of X1-X4 can be N; Y1, Y2 and Y3 are hydrogen; R1 is selected from hydrogen, , C6 aryl, 6-member heterocycloalkyl containing 2 heteroatoms selected from N and O, and 5- or 6-member heteroaryl containing 1-4 heteroatoms selected from N, O and S, wherein each of C6 aryl, 6-member heterocycloalkyl and 5- or 6-member heteroaryl may be optionally substituted with one R4; R2 is selected from hydrogen, halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl and 6-member heteroaryl may be optionally substituted with one R4. If X5 is N, R2 is selected from halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl, and 6-member heteroaryl may be optionally substituted with one R4; each R4 Is independently selected from hydrogen, halogen, cyano, oxo, C1-6 alkoxy, -C(O)OR5, -C(O)R5, C1-6 alkyl. Moreover , C1-6 alkyl may be optionally substituted with 1 to 3 substituents selected from halogen and cyano; R5 is C1-6 alkyl; and where the central structure of Formula I, limited by X5, X6, X7 and X8, is: or The invention also relates to particular compounds, a method for inhibiting the secretion of WNT signalling in a cell, use of a compound of formula (I), a method for treatment of a disorder mediated by WNT. .EFFECT: new heterocyclic compounds have been obtained that are useful for treatment of cancer, fibrosis and osteoarthritis.22 cl
Aza-aryl-1-h-pyrazol-1-yl-sulphonamides // 2627268
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) ,in which radicals and characters have values specified in the claims and their versions. The proposed compounds act as potent antagonists of CCR (9) receptor. Animal testing has shown that these compounds are useful for treatment of inflammation, disease with a hallmark for CCR (9). The compounds as a whole are arylsulfamide derivatives and are used in pharmaceutical compositions, methods for treatment of CCR (9) mediated diseases and as a control in assays for identification of CCR (9) antagonists.EFFECT: increased efficiency of compounds application.26 cl, 2 tbl, 33 ex

New pyrazole derivative // 2625790
FIELD: pharmacology.SUBSTANCE: in particular, invention relates to a compound represented by the following general formula (I): [wherein Ar1 is 2-methoxy-4-(2-pyridylmethoxy)phenyl, etc. and Ar2 is 1H-indole-6-yl group, etc.] or to salt thereof.EFFECT: increased efficiency of treatment.19 cl, 4 dwg, 1 tbl, 112 ex
Combined drug of anxiolithic, stress-protector, nootropic and antioxidant action // 2625754
FIELD: pharmacology.SUBSTANCE: invention is a combined drug of anxiolytic, stress-protective, nootropic and antioxidant action containing tryptophan, characterised by additional content of tiotriazoline at a quantitative ratio: tryptophan ranging from 1 to 7 wt parts per 1 wt part of thiotriazoline.EFFECT: agent has a higher anxiolytic and antioxidant activity compared to the known agents and has additional nootropic and stress-protective action.3 cl, 5 tbl, 2 ex
Bimatoprost and thymolol solutions not containing conservants // 2624534
FIELD: pharmacology.SUBSTANCE: invention relates to a composition of bimatoprost and timolol containing no preservatives to reduce intraocular pressure in a human, containing the following composition: 0.03% w/o bimatoprosta; 0.5% w/o timolol; 0.268% w/o sodium phosphate dibasic heptahydrate; 0.014% w/o citric acid monohydrate; 0.68% w/o sodium chloride and water, and having a pH of 7.3. The invention provides a formulation that does not contain any antimicrobial preservative that is stable in solution for a long time at ambient temperature and is also stable in the plastic packaging in which it is usually stored.EFFECT: compositions of the invention are more effective in treating increased IOP than compositions with preservatives, and have a lower risk of side effects.8 cl, 1 tbl

2-carboxamide cycloamino urea derivatives in combination with hsp90 inhibitors for treating proliferative diseases // 2624493
FIELD: pharmacology.SUBSTANCE: proposed: a pharmaceutical combination for treating melanoma comprising: (a) 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl) pyridin-4-yl] thiazol-2-yl}amide) (S)-pyrrolidine-1,2-dicarboxylic acid (compound A) or its pharmaceutically acceptable salt; and (b), at least, one Hsp90 inhibitor, representing ethylamide 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethyl-phenyl) isoxazole-3-carboxylic acid (AUY922) or its pharmaceutically acceptable salt; the use of the said combination for manufacturing drugs to treat melanoma and corresponding method for treating melanoma.EFFECT: synergistic effect of the compound combinations in reducing the tumour volume.4 cl, 9 dwg, 2 tbl, 6 ex
Azole derivatives // 2622639
FIELD: pharmacology.SUBSTANCE: invention relates to azole derivative of formula (I) or its pharmaceutically acceptable salt, wherein R1 is hydrogen atom or C1-5alkyl; R2 is hydrogen atom or C1-5alkyl; R3 is phenyl or pyridyl (where phenyl or pyridyl is optionally substituted with one or two fragments selected from the group consisting of C1-5alkoxy, halogen and trifluoromethyl atoms); each of R4 and R5, which can be the same or different, represent hydrogen atom or C1-5alkyl (where C1-5alkyl is optionally substituted with one fragment selected from the group consisting of hydroxy and C1-5alkoxy), or R4 and R5 together with nitrogen atom joining them form 4-7-membered saturated or unsaturated heterocycle, optionally compirsing one cyclic nitrogen, oxygen or sulfur atom, aside from the mentioned above joining nitrogen atom (where 4-7-membered saturated and unsaturated heterocycle is optionally substituted with one or two fragments, selected from the group consisting of hydroxy C1-5alkyl (where C1-5 alkyl is optionally substitued with one or two hydroxyl group), C1-5alkoxy, halogen atoms, cyano, C2-5alkanoyl, aminocarbonyl, mono-C1-5alkylaminocarbonyl, di-C1-5 alkylaminocarbonyl, trifluoromethyl, amino, mono-C1-5alkylamino, di-C1-5alkylamino and C2-5alkylamino, wherein the mentioned 4-7-membered saturated or unsaturated heterocycle optionally has C1-5alkylene fragment, joining two different cyclic carbon atoms), or form 2-oxa-6-azaspiro[3.3]hept-6-yl or 7-oxa-2-azaspiro[3.5]non-2-yl; azole cycle represented by formula (α) has any structure of group (II) formula, contained in invention formula, and wherein Ry is hydrogen atom or C1-5alkyl; X1 and X2 are such that: (i) if X1 means an ordinary link or fragment -CO-, X2 means -C1-5alkylene- or -O-C1-5alkylene-; and (ii) if X1 means a fragment -CONRx1-, X2means an ordinary link; Rx1 is hydrogen atom or C1-5alkyl; and cycle A is benzol cycle, pyridine cycle (where benzol cycle is optionally substituted with one or two fragments, selected from the group consisting of halogen atoms and C1-5alkoxy), 5-6-membered saturated or partly unsaturated heterocycle, containing one or two nitrogen atoms (where 5-6-membered saturated or unsaturated heterocycle is optionally substituted with one oxo group) or C3-7cycloalkane. The invention also relates to a pharmaceutical composition having antagonistic effect against V1b arginine-vasopressin receptor, and to agent for treating or preventing mood disorders, anxiety disorders or drug addiction, comprising azole derivative of formula (I) or its pharmaceutically acceptable salt as an active agent.EFFECT: azole derivative having antagonistic effect against V1b arginine-vasopressin receptor.12 cl, 22 tbl, 361 ex

Compound 8-fluorophthalazine-1(2h)-one as inhibitors of bruton tyrosine kinase // 2622391
FIELD: pharmacology.SUBSTANCE: compounds of 8-fluorophthalazine-1(2H)-ones of formula II are proposed, wherein one of X1, X2 and X3 represent N, and the other symbols have meanings defined in claim 1 of the invention formula, or stereoisomers, gautomers and pharmaceutically acceptable salts thereof. The compounds proposed inhibit the kinase Btk (Bruton tyrosine kinase) and can be used to treat immune disorders, such as inflammation, mediated by kinase Btk.EFFECT: increased efficiency while using the compounds of formula II for the diagnosis and treatment in vitro, in situ and in vivo such disorders in mammalian cells, or associated pathological conditions.25 cl, 8 dwg, 2 tbl, 69 ex
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

Apoptosis inducing agents selective for bcl-2 for cancer and immune diseases treatment // 2621052
FIELD: pharmacy.SUBSTANCE: invention relates to specific heterocyclic compounds containing the sulphonyl amino carbonyl group. The invention also relates to a pharmaceutical composition based on this compound.EFFECT: new heterocyclic compounds with inhibitory activity in terms of anti-apoptotic Bcl-2 proteins are obtained.2 cl, 3 tbl, 481 ex
Heterocyclic derivatives as receptors associated with tracer amines (taars) // 2621050
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula and to pharmaceutical compositions based thereof.EFFECT: new compounds are obtained with an affinity for the receptors to TAAR1 and can be used to treat depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder, disorders caused by stress, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, malnutrition, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, temperature homeostasis disorders, sleep disturbance, circadian dysregulation and cardiovascular disorders.23 cl, 16 dwg, 1 tbl, 55 ex
Pyrazole quinolinone derivatives, their preparation and therapeutic application // 2621037
FIELD: pharmacy.SUBSTANCE: invention relates to compounds according to formula (I) , wherein R1, R2 and R3 are as defined in claim cl. 1. The compounds of this invention are reversible and selective inhibitors of type 2 methionine aminopeptidase (MetAP2). The invention also relates to intermediates for preparing the compounds of formula (I), drug and pharmaceutical compositions based on the compounds of formula (I) and their therapeutic application.EFFECT: increased efficiency of compounds application.24 cl, 2 tbl, 25 ex

Phenyl derivatives // 2619105
FIELD: chemistry.SUBSTANCE: invention relates to new compounds of general formula containing two cyclic groups, especially where M1 - Ring 1 and M2 - Ring 2, each independently represents a phenoxy group. The compounds have high antagonistic activity against human S1P2.EFFECT: invention due to its properties can be used as a therapeutic agent for the treatment of S1P2-mediated diseases such as diseases, resulting from vasoconstriction, fibrosis and respiratory diseases.8 cl, 6 dwg, 5 tbl, 45 ex
Bruton's tyrosine kinase inhibitors // 2618529
FIELD: pharmacy.SUBSTANCE: invention relates to a compound of general formula I, below, or a pharmaceutically acceptable salt thereof. In the formula I compound, X is halogen; Y is H or lower alkyl; R is -R1-R2-R3; R1; R1 is pyridyl; R2 is -C (= O) or is absent; R3 is morpholinyl or pyrrolidinyl, optionally substituted by a lower alkyl. The above compounds are used to modulate OMB activity and treat diseases associated with excessive OMB activity. Furthermore, these compounds are used for treatment of inflammatory and autoimmune diseases associated with aberrant B-cell proliferation, such as rheumatoid arthritis. The invention also relates to the pharmaceutical composition comprising a compound of formula I and at least one carrier, diluent or excipient.EFFECT: increased efficiency of compounds application.20 cl, 2 tbl, 7 ex
Phenylpyrrole derivative // 2618228
FIELD: pharmacy.SUBSTANCE: invention relates to new derivatives of formula (I) Q: (A) or (B) phenylpyrrole, or pharmaceutically acceptable salts thereof, which are useful for prevention or treatment of diseases such as dementia, Alzheimer's disease, attention deficit, hyperactivity disorder, schizophrenia, epilepsy, "central" cramp, obesity, diabetes, hyperlipidemia, narcolepsy, idiopathic hypersomnia, behavior-induced insufficient sleep syndrome, sleep apnea syndrome, circadian rhythm, parasomnia, sleep-related traffic violation, insomnia and depression, or allergic rhinitis.EFFECT: increased compound application effeciency.13 cl, 3 tbl, 10 ex

Pyrazole compound and its pharmaceutical use // 2617678
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to a compound of general formula or pharmaceutically acceptable salt thereof. In formula (I) Cy represents phenyl, C3-8 cycloalkyl or C3-8 cycloalkenyl , Cya is a heterocyclic group with the structure given in the invention formula, R1a and R2b are groups defined in the formula. The objects of invention are also the pharmaceutical composition and the agent based on formula (I) compound, the method of diabetes treatment and prevention and compound application.EFFECT: invention is SGLT1 inhibitor and can be used to treat or prevent diabetes.24 cl, 4 tbl, 605 ex
Chloride 4-[(1e)-1-(6-chloro-4-oxo-4n-chromen-3-yl)-4-methylpent-1-en-3-yl]morpholine-4-yl, method of producing thereof and its antituberculosis effect // 2613633
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to chloride 4-[(1E)-1-(6-chloro-4-oxo-4H-chromen-3-yl)-4-methylpent-1-en-3-yl]morpholine-4-yl of formula I and method of producing thereof.EFFECT: new heterocyclic compound, may be used as a potential antituberculosis drug.3 cl, 5 dwg, 2 tbl, 2 ex
Dispiropyrrolidine derivatives // 2612534
FIELD: chemistry.SUBSTANCE: invention relates to a dispiropyrrolidine derivative of general formula (1), where ring A is a spiro compound 4-6-member saturated hydrocarbon ring, which can contain one or more substitutes, ring B is a benzene ring which can contain one or more substitutes, or a pyridine ring, which can contain one or more substitutes, R1 is an aryl group which can contain one or more substitutes, or heteroaryl group, which can contain one or more substitutes, R2 is a hydrogen atom; and R3 is a group presented by general formulae (2), (3) or (4), which inhibits protein interaction between Mdm2 and p53 protein and has antitumour activity.EFFECT: dispiropyrrolidine derivatives are disclosed.29 cl, 199 ex R3 :
Substituted dihydropyrazolones for treating cardiovascular and hematologic diseases, use thereof, drug and method of treating and/or preventing // 2611012
FIELD: chemistry; pharmaceutics.SUBSTANCE: present invention relates to use of dihydropyrazolone derivatives of formula (I), in which radicals and symbols are defined in p. 1 of patent claim.EFFECT: making drug for treating and/or preventing cardiac diseases of blood circulation, cardiac failure, anemia, chronic diseases of kidneys and renal failure, as well as medicinal agent containing said dihydropyrazolone derivatives, and method of treating and/or preventing said diseases in human and animals.4 cl, 10 tbl, 180 ex
orpholino-substituted derivatives of bicyclic pyrimidine urea or carbamate as mtor inhibitors // 2609208
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts . In formula (I) m is equal to 1; o equals 1 or 2; each R1 is independently selected from group consisting of H and unsubstituted C1-6alkyl; two R1 are possibly combined to form, together with ring, to which they are bonded, 8-oxa-3-azabicyclo[3.2.1]octane-3-yl or 3-oxa-8-azabicyclo[3.2.1]octane-8-yl ring; T1 is phenyl, where T1 is substituted by group N(R5a)C(O)N(R5bR5) and T1 is optionally additionally substituted with one or more R6, which are identical or different; R6 is halogen; each of R5a, R5b represents H; R5 represents H; T2; and C1-6alkyl, where C1-6alkyl is optionally substituted with one or more R8, which are identical or different; R8 represents halogen or OR9; R9 represents H; T2 is unsubstituted and selected from group consisting of phenyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl or tetrahydrofuranyl; Ra and Rb are selected to obtain one of formulae (Ik)–(Ip) or Ra, Rb, T1 are selected to obtain formula (Iq) R14, R14a, R14b, R14c are independently selected from group consisting of H; halogen or unsubstituted C1-6alkyl. Compounds of formula (I) possess mTOR inhibiting activity. Invention also relates to pharmaceutical composition containing compounds of formula (I), use of compounds for making drug and to method of treating.EFFECT: novel compounds of formula (I) are obtained, which have mTOR inhibitor activity, which can be used for treating or preventing mTOR related diseases and disorders.16 cl, 15 tbl, 82 ex

Use of sigma ligands in diabetes type-2 associated pain // 2608943
FIELD: chemistry.SUBSTANCE: invention relates to use of a sigma ligand, which is a 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine or a pharmaceutically acceptable salt thereof.EFFECT: prevention and/or treatment of pain associated with type 2 diabetes and related symptoms.6 cl, 9 dwg, 4 ex
Novel pyrrole compounds, synthesis method thereof and pharmaceutical compositions containing same // 2607788
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) possessing inhibitory activity on Bcl-2 family proteins. In formula (I) (I) A1 is hydrogen, (C1-C6)polyhaloalkyl group or (C1-C6)alkyl group, A2 is hydrogen, (C1-C6)polyhaloalkyl group, (C1-C6)alkyl group or cycloalkyl group, T denotes a hydrogen atom, (C1-C6)alkyl group, optionally substituted with one-three halogen atoms, group (C1-C4)alkyl-NR1R2 or group (C1-C4)alkyl-OR6, R1 and R2 each independently from each other is a hydrogen atom or (C1-C6)alkyl group, or R1 and R2 form with a nitrogen atom bearing them, heterocycloalkyl, R3 is (C1-C6)alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R4 is an aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R5 is hydrogen or halogen atom, R6 is a hydrogen atom or a linear or branched (C1-C6)alkyl group, Ra, Rb, Rc and Rd each independently from other represents hydrogen, linear or branched (C1-C6)alkyl, halogen atom, a linear or branched (C1-C6)alkoxy group, hydroxy group, R7-CO-NH-(C0-C6)alkyl-, R7-SO2-NH-(C0-C6)alkyl-, R7-NH-CO-NH-(C0-C6)alkyl-, R7-O-CO-NH-(C0-C6)alkyl-, or substitutes of pair (Rb, Rc) form together with carbon atoms carrying them, a ring consisting of 5–6 ring members, which may contain 1–2 oxygen atoms, R7 is hydrogen, linear or branched (C1-C6)alkyl, aryl or heteroaryl. Invention also relates to methods of producing compounds of formula (I), to a pharmaceutical composition, use of a pharmaceutical composition for preparing a drug, use of compound of formula (I) for preparing a drug.EFFECT: obtaining novel compounds of formula (I) possessing inhibitory activity on Bcl-2 family proteins.37 cl, 2 tbl, 473 ex

Aromatic derivatives of sulfanilamides carbonic anhydrase ii (ca ii) inhibitors, methods for production and use thereof // 2607630
FIELD: chemistry.SUBSTANCE: present invention relates to novel aromatic sulphonamide derivatives, general formula 1 and pharmaceutically acceptable salts thereof, which are selective inhibitors of carbonic anhydrase II (CA II). Substituted sulphonamides correspond to general formula 1 ,where A is phenyl or thiophene; R1 is C1-C5alkyl, C-3C6cycloalkyl, -C(O)R3; provided that R1 is not methyl, when A is phenyl, R2 represents hydrogen; R3 is a 5-6 member heterocyclyl with one or two heteroatoms, selected from nitrogen or oxygen atoms; R2 is C1-C3alkyl, C1-C3alkoxy. Invention also relates to a method of producing compounds of general formula 1. Method involves two stages: a) sulphochlorination of corresponding oxazole derivative of general formula 5 (a-o) or 6 (a-j) with a mixture chlorosulphonic acid and thionyl chloride to produce intermediate sulphochlorides of formula 7 (a-o) or 8 (a-j), respectively, and b) with subsequent conversion of obtained sulphochlorides into primary sulphamides of formula 9 (b-o) or 10 (a-j) by reacting with ammonia according to following scheme ,where ,where R1 is C1-C5alkyl, C3-C6cycloalkyl; NR'Rʺ is a morpholine or pyrrolidine.EFFECT: compounds can be used for treating glaucoma, in particular, open-angle glaucoma, and other diseases caused by high intraocular pressure, age-related macular degeneration, diabetic macular edema, diabetic retinopathy, hypertensive retinopathy and retinal vasculopathy mediated by activity of carbonic anhydrase II.11 cl, 2 dwg, 2 tbl, 57 ex
Pyrrolidinyl urea and pyrrolidinyl thiourea compounds as trka kinase inhibitors // 2606131
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula I given below, or to their stereoisomers, tautomers or pharmaceutically acceptable salts thereof. R1, R2, Ra, Rb, Rc, Rd, X, Y, B, and ring C are as defined by the invention formula. Wherein the Y-B moiety and the NH-C(=X)-NH moiety are in the trans configuration.EFFECT: compounds of formula I are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.56 cl, 31 tbl, 649 ex
Novel immune system modulators related applications // 2606114
FIELD: chemistry.SUBSTANCE: invention relates to novel compounds of formula I or a pharmaceutically acceptable salt thereof, which possess properties of TOLL-like receptor (TLR9) inhibitor and can be used for treating autoimmune diseases, mediated by TLR9 activity. Diseases can be selected from cutaneous and systemic lupus erythematosus, insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, atherosclerosis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, autoimmune hemolytic anemia, Behget's syndrome, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia, myasthenia gravis, pernicious anemia, polyarteritis nodosa, polymyositis/dermatomyositis, primary biliary sclerosis, sarcoidosis, sclerosing cholangitis, Sjogren's syndrome, systemic sclerosis (scleroderma and CREST syndrome), Takayasu's arteritis, temporal arteritis, and Wegener's granulomatosis. In Formula I X is absent or denotes aryl; Q is H, (CH2)qNR1R2, SR1 or CR1R2R2', where q is equal to 0 or 1; R1, R2 and R2', each independently, represent hydrogen, C1-C12 alkyl, or R1 and R2 together with a nitrogen atom, with which they are bonded form a 6-member heterocycle, containing two nitrogen atoms or a nitrogen atom and an oxygen atom, which can be optionally substituted with (C1-C4)alkyl or (CH2)pORa, where p is equal to 2-4; R7 is NR3R4; R3 and R4, each independently represent (C1-C12)alkyl, or R3 and R4, together with a nitrogen atom with which they are bonded, form or 6-member heterocycle containing 1-2 heteroatoms selected from a group consisting of O and N, and which can be optionally substituted with (C1-C4)alkyl; Y is NR11, where R11 is hydrogen or (C1-C12)alkyl; L is an alkyl or alkenyl, each containing from 2 to 10 carbon atoms; R5 is hydrogen, halogen, CF3, ORa, SRa, NRbRc or NH(CH2)pNRbRc; R6 is a halogen, (C1-C12)alkyl, CF3, phenyl, phenyl substituted with halogen, CN or CF3, or NH(CH2)pNRbRc; in each case Ra independently represents hydrogen, (C1-C6)alkyl; and said Rb and Rc, together with a nitrogen atom with which they are bonded, optionally form 5-6-member heterocycle, containing 1-2 heteroatoms selected from O and N, where heterocycle is optionally substituted with (C1-C4)alkyl; provided that if R5 and R6 denote H or methyl, then Q is not H.EFFECT: obtaining novel compounds of formula.19 cl, 5 tbl, 73 ex

Substituted aminobutyric derivatives as neprilysin inhibitors // 2604522
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I, where R1 denotes -OR7; R2a is selected from -CH2OH, -CH2OP(O)(OH)2 and -CH2OC(O)CH(R37)NH2; or R2a together with R7 forms -CH2O-CR18R19-; R2b is selected from H and -CH3; Z denotes -CH-; X is selected from a pyrazole, imidazole, triazole, benzotriazole, oxazole, isoxazole, pyrimidine, pyridazine, benzimidazole, pyran and triazolo[4,5-b]pyridine; R3 is absent or is selected from H; halogen; -C0-5alkylene-OH; -C-1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C(O)NR22R23; =O; phenyl, optionally substituted with one or two groups, independently selected from halogen; and pyridinyl; R4 is absent or is selected from H; -OH; halogen; -C1-6alkyl; -CH2OC(O)CH(R36)NH2; -CH[CH(CH3)2]-NHC(O)O-C1-6alkyl; and phenyl or benzyl; a = 0; b = 0 or an integer from 1 to 3; each R6 is independently selected from halogen; R7 is selected from H, -C1-8alkyl,-C1-3alkylene-C6-10aryl, [(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C1-6alkylene-NR12R13, -C1-6alkylene-C(O)R31, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl; structural formulae (a1), (a2), (a3) and (a4); R10 is selected from -C1-6alkyl, -O-C1-6alkyl, -C3-7cycloalkyl, -O-C3-7cycloalkyl and -CH[CH(CH3)2]-NH2; and R12 and R13 are independently selected from H, -C1-6alkyl and benzyl, or R12 and R13 together form -(CH2)5- or -(CH2)2O(CH2)2-; R31 is selected from -O-benzyl and -NR12R13; and R32 denotes -C1-6alkyl; R18 and19 are independently selected from H and -C1-6alkyl; R20 is selected from H and -C1-6alkyl; R21 denotes H; R22 and R23 are independently selected from H, -C1-6alkyl, -(CH2)2OCH3 and -C0-1alkylene-C3-7cycloalkyl; or R22 and R23 together form a saturated -C3-5heterocycle, selected from azetidine or pyrrolidine; and optionally containing an oxygen atom in ring; R36 is selected from H, -CH(CH3)2, phenyl and benzyl; and R37 is selected from H and -CH(CH3)2; and where methylene linker on biphenyl can be substituted with one or two -C1-6alkyl groups; or a pharmaceutically acceptable salt thereof. Invention relates to a method of producing a compound of formula I by combining a compound of formula 1 with a compound of formula 2. Invention also relates to an intermediate compound of formula 1, intended for use in synthesis of compound of formula I, where P1 denotes H or tert-butoxycarbonyl; or HCl salt thereof. Compounds of formula I are intended for preparing a pharmaceutical composition, possessing inhibitory activity on neprilysin (NEP).EFFECT: technical result is aminobutyric derivatives as neprilysin (NEP) inhibitor, for treating hypertension, cardiac failure or kidney disease.17 cl, 20 ex, (а1), (а2),(а3) and (а4),

Pyrazine derivatives used as atr kinase inhibitors // 2604066
FIELD: chemistry.SUBSTANCE: present invention relates to pyrazine compounds , used as inhibitors of ATR protein kinase, pharmaceutical compositions containing compounds according to invention, and use of compounds according to present invention to increase cell sensitivity to DNA damaging agents and as a radio-sensitiser and a chemo-sensitiser.EFFECT: high sensitivity of cells to DNA damaging agents, radio-sensitiser and chemo-sensitiser.115 cl, 98 dwg, 18 tbl, 77 ex

New derivatives of 3,3-dimethyltetrahydroquinoline // 2603276
FIELD: chemistry.SUBSTANCE: invention is related to organic chemistry and specifically to new tetrahydroquinolin derivatives of general formula (I) or pharmaceutically acceptable salts or esters where R1 represents hydrogen, halogen, carboxyl, alkoxycarbonyl, alkilsulphonylaminocarbonyl or cycloalkylalkilsulphonylaminocarbonyl; R2 represents hydrogen, halogen or carboxyl; R3 represents hydrogen, halogen, carboxyl, halogenalkyl, cyano, alkoxycarbonyl, alkylsulphonyl, alkylsulphonylaminocarbonyl, cycloalkylalkilsulphonylaminocarbonyl, carboxylalkylamino(alkyl)carbonyl, alkyl(hydroxy)pyrrolidinylcarbonyl or carboxylpyrrolydincarbonyl; R4 is hydrogen, carboxyl, alkilsulphonylaminocarbonyl or cycloalkylalkilsulphonylaminocarbonyl; R5 is pyridinyl, substituted pyridinyl, morphonylpyrinidil, phenyl or substituted phenyl, where substituted pyridinyl and substituted phenyl represent pyridinyl and phenyl, substituted with one or two substitutes given in the patent claim; where the alkyl, one or in combination, is saturated alkyl group with linear or branched chain containing 1 to 6 carbon atoms; alkoxy, one or in combination, denotes a group of alkyl-O-, where the alkyl such as defined above; cycloalkyl, one or in combination, relates to saturated carbon ring, containing from 3 to 6 carbon atoms; provided that 3,3-dimethyl-2-phenyl-1,2,3,4,6-hydroxyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinline is excluded. Invention is also related to specific compounds, pharmaceutical composition based on compound of formula (I), use of formula (I) and a method of treating or preventing diseases based on use of compounds of formula (I).EFFECT: technical result is obtaining novel tetrahydroquinolin derivatives, useful as activator AMR-activated protein kinase (AMPK).17 cl, 236 ex

Pyrazole derivatives // 2600983
FIELD: chemistry.SUBSTANCE: pyrazole derivatives are disclosed, which are encompassed by formula (I), in which radicals and groups are defined in patent claim and which are suitable for treating disorders mediated by peripheral cannabinoid 1 receptor 1.EFFECT: invention also discloses pharmaceutical compositions and methods related to use of said compounds.29 cl, 11 ex

Cyanoquinoline derivatives // 2600928
FIELD: chemistry.SUBSTANCE: invention relates to novel cyanoquinoline derivatives of general formula I, as well as to stereoisomers, cis-trans-isomers or pharmaceutically acceptable salts thereof, where R1 is selected from a group consisting of 4-bromobut-2-enamide, 4-(dimethylamino)but-2-enamide, acrylamido, but-2-enamide, 3-methylbut-2-enamide, 2-(1-tert-butoxycarbonylpiperidin-4-ylidene) acetamide, 2-(piperidin-4-ylidene)acetamide, 2-(1-methylpiperidin-4-ylidene) acetamide, 2-(1-ethylpiperidin-4-ylidene) acetamide, 2-(1-benzylpiperidin-4-ylidene) acetamide, 2-(1-(2-methoxyethyl) piperidin-4-ylidene)acetamide, 2-(1-(2-methoxycarbonylmethylene)piperidin-4-ylidene)acetamide, 2-(1-isopropylpiperidin-4-ylidene) acetamide, 2-(1-(2-hydroxyethyl)piperidine-4-ylidene)acetamide, 2-(pyrrolidin-3-ylidene)-acetamide, N-(N-(2-(2-(dimethylamino)ethoxy)ethyl)amino)fumaramide, 2-(1-(2-(2-(2-hydroxyethoxy)ethylamino)acetyl) piperidin-4-ylidene)acetamide, 2-((1-methylsulphonyl)piperidin-4-ylidene) acetamide, 4-(piperidin-1-yl)but-2-enamide, 4-(morpholin-4-yl)but-2-enamide, 4-(tert-butylamino)but-2-enamide, 4-(benzylamino)but-2-enamide, 4-(6-hydroxyhexylamino)but-2-enamide, 4-(N-methylbenzylamino)but-2-enamide, 4-(diethylamino)but-2-enamide, 4-(2-methoxyethylamino)but-2-enamide, 4-(diethanolamino)but-2-enamide, 4-(N-methylmethoxyethylamino) but-2-enamide, 4-(N-methyl-ethanolamino)but-2-enamide, 4-(dimethoxyethylamino)but-2-enamide, 4-(N-methyl-6-amino-1-hexanolyl)but-2-enamide and propylamide; one of R2 and R3 is H, while other is selected from unsubstituted C6-aryl-C1-2-alkyl, substituted with 1-2 substitutes or unsubstituted C6-aryl and substituted with 1 substitute or unsubstituted 6-9-member heteroaryl, where, when R2 or R3 is selected from a substituted C6-aryl, substitute is selected from C2-C6-alkynyl, halogen, C6-aryl-C1-alkyloxy (where said C6-aryl can be substituted with 1 substitute selected from halogen, cyano, C1-C6 alkyl, C1-C-6 alkoxy), and 6-member heteroaryl-C-1-alkyloxy, and when R2 or R3 are selected from a substituted heteroaryl, substitute is selected from a group comprising C6-aryl-C1-alkyl (where said C6-aryl is optionally substituted with 1 substitute selected from halogen and cyano, methoxy group), C6-arylamido (where the said C6-aryl can be unsubstituted or substituted with 1 dimethylamino group), C6-arylsulphonylamino, C5-heteroarylamido, C6-cycloalkylamido, C6-arylaminocarbonyl (where said C6-aryl is substituted with 1 methoxy group), C6-aryl-C1-alkyloxy and C6-aryloxy; or R2 and R3, together with a nitrogen atom to which they are bonded, form a substituted or unsubstituted 9-10-member heterocyclyl, where heterocycyl substitutes are selected from halogen, C1-C-6 alkyl, CF3, C6-aryl-C1-alkoxy, -COOMe, -CH2OH and pyrrolyl; and R4 is substituted with 1 methyl or unsubstituted 5-6-member heterocyclyl or unsubstituted 6-member heteroaryl. Invention also relates to specific compounds, pharmaceutical composition based on compound of formula I and use of formula I.EFFECT: technical result is obtaining novel cyanoquinoline derivatives which are useful in treating tumours.33 cl, 20 tbl, 228 ex
 
2550919.
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