(A61K31/517)

Comt inhibitors // 2642779
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of the formula (I) and their pharmaceutically acceptable salts which have the properties of a catechol-O-methyltransferase (COMT) inhibitor. In the compound of the formula (I) , where R1 is hydrogen, methyl, Br, F or Cl; R2 is hydrogen, lower alkyl, Br, I, C3-6cycloalkyl, C(O)O-lower alkyl, C(O)NH-lower alkyl substituted by halogen, C(O)(morpholine) or is 3,4-dihydronaphthalen-2-yl optionally substituted by lower alkyl, 1,2,3,4-tetrahydronaphthalen-2-yl, 2,3-dihydrobenzofuran-6-yl, 1-methyl-2,3-dihydro-1H-indolin-5-yl, 1-methylindolin-5-yl, tetrahydropyran-4-yl, 3,6-dihydro-2H-pyran-4-yl, 2-isopropyl-1,2,3-tetrahydroisoquinolin-5-yl, 2,3-dihydro- dimethyl[1,4]dioxin-6-yl, benzo[1,3]-dioxol-5-yl, 1,2,3,4-tetrahydroisoquinolin-7-yl optionally substituted by lower alkyl, cyclohexenyl, morpholinyl, 4-methylpiperazinyl, naphthalen-1-yl, naphtalen-2-yl, or represents (CHR)n-phenyl optionally substituted by one to five substituents R4, where R4 is F, Cl, CN, CH2-CN, lower alkyl, hydroxy, lower alkyl, substituted hydroxy, lower alkoxy, (CH2)1.2-lower alkoxy, S-lower alkyl, (CH2)1.2-S-lower alkyl, -CH2)1.2-S (O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2-di-lower alkylamino, -S(O)2-piperidinyl, lower alkyl substituted by halogen, -N=N-phenyl, di-lower alkylamino, (CH2)1.2-di-lower alkylamino, (CH2)2-NH-lower alkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, CH(CH3) C(O)O-lower alkyl, O-phenyl, O-benzyl, phenyl, optionally substituted CF3, SF5, benzyl, C(O)-lower alkyl, C(O)-phenyl, C(O)-morpholinyl, C(O)-4-methylpiperazinyl, C(O)-di-oxothiomorpholinyl, C(O)-piperidinyl, optionally substituted by F, C(O)-NH-(CH2)2-morpholinyl, C(O)-NR-(CH2)2-NR2, C(O)-N-di-lower alkyl, CH2-O-(CH2)2-4-methylpiperazinyl, CH2-O-(CH2)2-di-alkylamino, CH2-O-(CH2)2-pyrrolidinyl, CH2-O-(CH2)2-morpholinyl, CH2-O-(CH2)2-piperidinyl optionally substituted by lower alkyl substituted by halogen or lower alkyl, (CH2)3,4-pyrrolidinyl, (CH2)2,3-di-lower alkylamino, morpholinyl, CH2-morpholinyl, CH2-piperazine substituted by lower alkyl, -S(O)2-piperazine substituted by lower alkyl, CH2-O-C(O)-piperazine substituted by lower alkyl, pyrazolyl or (CH2)1,2-lower alkoxy; R is hydrogen, lower alkyl or hydroxyl; n is 0, 1, 2, or 3; or R2 is C(O)-phenyl optionally substituted by lower alkyl; or is -O-phenyl optionally substituted by F; or is CH=CH-phenyl optionally substituted by lower alkyl; or is C≡C-phenyl; or R2 is a heteroaryl selected from the group consisting of pyrazolyl, thiazolyl, pyridinyl, pyrimidinyl, imidazolyl, isoxazolyl, isothiazolyl, thiophenyl, 1-thia-3,4-diazolyl, imidazo[1,2-a]pyridinyl, indazolyl, quinolinyl or isoquinolinyl, and the said groups are optionally substituted by R5, where R5 is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, hydroxy, (CH2)1.2-lower alkoxy, CH2-di-lower alkylamino, di-lower alkylamino, morpholinyl, piperazinyl, pyrrolidin-1-yl, C(O)-piperidinyl, C(O)-4-methylpiperazinyl, phenyl optionally substituted by halogen, pyridinyl, S(O)2N(CH3)2, C(O)O-lower alkyl, NHC(O)-lower alkyl, or is C(O)-heteroaryl selected from pyridinyl and thiophenyl, where heteroaryl groups are optionally substituted by lower alkyl, n is 0, 1, 2 or 3; R3 is hydrogen, methyl, Br, F, Cl, CF3, nitro, amino, cyano, NHC(O)-phenyl, or is 1-methyl-1,2,3,6-tetrahydropyridinyl, or is pyridinyl optionally substituted by methyl or morpholinyl, or is phenyl optionally substituted by methyl , SO2CH3, CF3, CN, F or C(O)N (di-lower alkyl).EFFECT: compounds can be used to treat Parkinson's disease, depression, cognitive impairment and motor symptoms, resistant depression, cognitive impairment, mood and negative symptoms of schizophrenia.16 cl, 2 tbl, 256 ex

Salts of 4-((2-(6-(4-methylpiperazine-1-carbonyl)-naphthalen-2-yl)ethyl) amino)quinazoline-6-carbonitrile and pharmaceutical composition // 2641001
FIELD: pharmacology.SUBSTANCE: invention relates to the salts of 4-((2-(6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl)ethyl)amino)quinazoline-6-carbonitrile, which have the properties of a cyclin-dependent CDK8/CDK19 kinase inhibitor, and to pharmaceutical compositions comprising these salts, and to the use of such salts or such compositions for treatment of diseases or disorders mediated by the cyclin-dependent CDK8/19 kinase.EFFECT: new salts are obtained, which have improved solubility compared to the free base.13 cl, 5 tbl, 23 ex, 5 dwg
Heterocyclic compounds, effective for kinase inhibition // 2640862
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I)or a pharmaceutically acceptable salt thereof, wherein Q is O; W is phenyl; X is absent; Y is NH; Z1 and Z2 are N; Z3 is NR5, where R5 is hydrogen; R1 is pyridine or pyrimidine; optionally substituted with C1-C6alkyl, C1-C6alkoxy, -NR10R11 or -SOmR12, where R10 and R11 are hydrogen, R12 is C1-C6alkyl; and m is 0; R3 is C1-C6alkyl; R2 is C1-C6alkyl when p is 1; or one R2 is C1-C6alkyl and one R2 is halogen when p is 2; or one R2 and R3 combined with formation of a five- to seven-membered carbocycle; R4 is hydrogen; p=1 or 2; and n is 1.EFFECT: heterocyclic compounds designed for cancer treatment.12 cl, 1 tbl, 8 ex
Pharmaceutical compositions of substituted quinazolinones // 2640115
FIELD: pharmacology.SUBSTANCE: composition according to this invention contains an active ingredient selected from a series of substituted quinazolinones and their pharmaceutically acceptable salts, stereoisomers, tautomers or hydrates, and additionally contains approximately 10 wt % to approximately 85 wt % of microcrystalline cellulose; approximately 4.0 wt % of sodium starch glycolate; approximately 0.5 wt % of magnesium stearate; and approximately 2.5 wt % of colloidal silicon dioxide; and prepared for peroral introduction and immediate release.EFFECT: creation of new compounds that increase the bioavailability of substituted quinazolinones while maintaining stability, possibility of treatment and prevention of the abovementioned diseases.15 cl, 1 tbl, 1 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
Stabilized pemetrexede composition // 2636783
FIELD: pharmacology.SUBSTANCE: invention refers to cancer pemetrexed compositions in an airtight container that contains pemetrexed or its pharmaceutically acceptable salt, as the active ingredient, as well as N-acetyl-L-cysteine and sodium citrate, where this the composition has gaseous oxygen content of 3% vol./vol. in the container free space or less relative to the total amount of free space.EFFECT: invention implementation allows to obtain a stable pemetrexed composition.7 cl, 14 tbl, 39 ex, 1 dwg
Biomarkers for prediction of sensitivity to antitumor treatment // 2635193
FIELD: pharmacology.SUBSTANCE: invention is intended for treatment of cancer in a patient having AKT1 mutation at position L52 or D323. The presence of L52 or D323 mutation in the patient's AKT1 gene is determined. A patient with such mutation receives (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one or a pharmaceutically acceptable salt thereof.EFFECT: invention provides effective cancer treatment.17 cl, 18 dwg, 3 tbl, 4 ex

Pharmaceutical composition including amide derivative, inhibiting cancer cells growth, and non-metal salt lubricant // 2632099
FIELD: pharmacology.SUBSTANCE: invention is a pharmaceutical composition containing a substance of formula (I) , or a pharmaceutically acceptable salt thereof and a lubricant other than a metal salt, as well as a method to obtain a preparation of this pharmaceutical composition.EFFECT: invention allows to improve the stability of a pharmaceutical composition containing an amide derivative of formula (I) and to increase the shelf life without qualitative changes over time.17 cl, 4 dwg, 9 tbl, 8 ex

Combinations of akt inhibitor compounds and abiraterone, and application methods // 2631240
FIELD: pharmacology.SUBSTANCE: invention relates to a new combination of a) a formula Ia compound or a pharmaceutically acceptable salt thereof, and b) abiraterone or a pharmaceutically acceptable salt thereof in a therapeutically active amount. The combination can be used to treat prostate cancer. The invention also relates to a method for prostate cancer treatment using this combination. The formula Ia compound corresponds to the structural formula A combination is preferred where the formula Ia compound and abiraterone are at a ratio of 1:5 (mg/kg). It is desirable to use abiraterone acetate as a pharmaceutically acceptable salt of abiraterone. The combination is used when the cancer is associated with a PTEN mutation or with AKT overexpression or amplification with PI3K mutation, with Her2/ErbB2 mutation. It is preferable to use the combination if the cancer associated with the PTEN mutation is prostate cancer with zero PTEN status.EFFECT: combination has increased activity and allows to significantly reduce the tumour volume in comparison with the control sample.14 cl, 2 dwg, 2 tbl, 15 ex

Histones deacetylases (hdacs) inhibitors // 2629947
FIELD: pharmacology.SUBSTANCE: invention relates to a new compound of formula X or a pharmaceutically acceptable salt thereof which have the properties of a histone deacetylase (HDAC) inhibitor. The compounds can be used as active agents for pharmaceutical compositions suitable for use in the treatment of a tumour disease associated with impaired HDAC activity. Such a disease can be pancreatic carcinoma, hepatocellular carcinoma, colon tumours, mammary tumours, prostate tumours, lymphomas and skin tumours. In particular, tumour diseases can be melanoma and basal carcinomas, large-cell lung cancer, lung adenocarcinoma, small cell lung cancer, stomach cancer, ovarian adenocarcinoma, promyelocytic leukemia, chronic myelocytic leukemia or acute lymphocytic leukemia. In the formula (I) R1 is hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl; R2 is (C6)aryl, (C6)aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, wherein heteroaryl is a 5-membered monocyclic ring system containing one heteroatom in the ring selected from nitrogen, wherein the said system is fused to a benzene ring, halo(C6)aryl(C1-C6)alkyl or (C1-C6)alkoxy(C6)aryl(C1-C6)alkyl; R3 is N-hydroxyamino-oxo(C2-C6)alkenyl; R4 is hydrogen, N-hydroxyamino-oxo(C2-C6)alkenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; R5 is hydrogen, halogen, N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene or (2E)-3-N-(2-aminophenyl)-3-oxo-propenyl; and R6 is hydrogen, N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonylphenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (II) each of R1, R2, R5 and R6 is as defined in (I) above; R3 is hydrogen or N-hydroxyamino-oxo(C2-C6)alkenyl; and R4 is N-hydroxyamino-oxo(C2-C6)alkenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (III) each of R1, R2, R4 and R6 is as defined in (I) above; R3 is as defined in (II) above; and R5 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene or (2E)-3-N-(2-aminophenyl)-3-oxo-propenyl; or (iv) each of R1, R2, R4, R5 is as defined in (I) above; R3 is as defined in (II) above; and R6 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonylphenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (V) each of R1, R2, R5 and R6 is as defined in (III) above; R3 is hydrogen; and R4 is a halogen.EFFECT: increased efficiency of treatment.15 cl, 1 dwg, 1 tbl, 6 ex
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

Selective and reversible ubiquitin-specific protease 7 inhibitor // 2622640
FIELD: pharmacology.SUBSTANCE: viral infections and diseases are selected from viral infections of Herpes simplex-1 or -2, hepatitis A, hepatitis C, SARS of coronavirus infection and disease, Epstein-Barr virus, rhinovirus infections and diseases, adenovirus infections and diseases, poliomyelitis. In the formula each identical or different R1 is selected from the group consisting of halogen, linear or branched (C1-C6)alkyl, OR; L1 is a linear or branched (C1-C6)alkylene; Q is 0, 1, 2, 3 or 4; X' is CR7; R7 is OR; N is 0, 1 or 2; P is 1, 2 or 3; R3, R4, R8' and R8 each represents H; A is -C (O)-; L2 is linear or branched (C1-C6) alkylene, optionally interrupted by at least one O; R6 is selected from the group consisting of aryl, heteroaryl, cycloalkyl, H, wherein aryl, heteroaryl, cycloalkyl is mono- or polycyclic and is optionally substituted by halogen, OR; each R, identical or different, is independently selected from H, linear or branched (C1-C6)alkyl. At that, "aryl" means an aromatic monocyclic hydrocarbon ring system of 6 carbon atoms, "cycloalkyl" means a non-aromatic, monocyclic, hydrocarbon ring of 3-10 carbon atoms; "heteroaryl" means a 5-membered aromatic mono-heterocyclic ring. The invention also relates to versions of the for preparation of compounds.EFFECT: compounds can be used to prepare a drug for treatment or prevention of cancer and metastases, viral infections and diseases, or viral infectivity, or latency mediated by ubiquitin-specific proteases activity.19 cl, 6 dwg, 4 tbl, 14 ex
Heterobicyclic derivatives as hcv inhibitors // 2621734
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclic compound of formula (I) or to pharmaceutically acceptable salt thereof, wherein Y is CH, N or CR4; W is carbonyl, sulfonyl or CR5R6; is or is independently selected from the group containing R and R' independently selected from -CR1R2R3, where R1 is selected from C1-4alkyl; R2 is C1-4alkyloxycarbonylamino; R3 is hydrogen; R4 is hydrogen or fluorine; CR5R6 together form oxetane. The invention also relates to pharmaceutical composition based on compound of formula (I), its use and product on its base.EFFECT: obtaining novel heterocyclic compounds, useful in the treatment of HCV infections.14 cl, 2 tbl
Derivatives of 5-substituted quinazolinone, compositions containing them and methods of application thereof // 2617989
FIELD: pharmaceutics.SUBSTANCE: compounds of formula (I) R1 is halogen atom; (C1-C6) alkyl, optionally substituted with one or more halogen atoms; (C1-C6) alkoxy group, optionally substituted with one or more halogen atoms, or -(CH2)nNHRa, where Ra represents hydrogen atom; -C(O)-(CH2)n-phenyl or -C(O)-(CH2)n-pyridyl, where phenyl is optionally substituted with one or more substitutes of halogen atom; -SCF3; (C1-C6)alkyl, optionally substituted with one or more halogen atoms, or (C1-C6)alkoxy group, optionally substituted with one or more halogen atoms; -C(O)-(C1-C8)alkyl, where alkyl is optionally substituted with one or more halogen atoms; -C(O)-(CH2)n-(C3-C10-cycloalkyl); -C(O)-(CH2)n-NRbRc, where Rb and Rc are hydrogen atoms independently of each other; (C1-C6)alkyl; or phenyl, optionally substituted with one or more substitutes of halogen atom or (C1-C6)alkyl; -C(O)-(CH2)n-O-(C1-C6)alkyl; or -C(O)-(CH2)n-O-(CH2)n-phenyl; R2 is hydrogen atom; OH; phenyl or (C1-C6) alkyl, optionally substituted with one or more halogen atoms; R3 is hydrogen atom; or (C1-C6) alkyl; and n takes values 0, 1 or 2.EFFECT: method is disclosed of treating or controlling diseases or disorders, such as cancer involving administering 5-substituted quinazoline compound of formula (I) or its pharmaceutically acceptable salt, solvate or stereoisomer.32 cl, 59 ex
Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors // 2617401
FIELD: chemistry.SUBSTANCE: invention relates to compounds of general formula (I) (I), where: R1 and R2, which can be identical or different, independently selected from a group consisting of: - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl; - (C1-C6)halogenalkyl; - (C3-C7)cycloalkyl and - (C3-C7)heterocycloalkyl, containing heteroatom O; R3 represents hydrogen, (C1-C6)alkyl or (C1-C3)alkylthio(C1-C6)alkyl; A is a partially unsaturated or unsaturated bicyclic ring system consisting of two condensed monocyclic ring systems B and C, presented in cl. 1 of formula, where ring C is a monocyclic aryl or monocyclic heteroaryl ring system, ring B is a 5- or 6-member heterocycloalkyl group, zero of Y groups is bonded to ring C, n of groups Y is bonded to ring B, and n is an integer from 1 to 3; and where ring B and C optionally contains additional heteroatoms in amount of 1 to 4, selected from N, O or S; p is an integer from 0 to 3; Y denotes oxo group; K is selected from a group consisting of: - (C1-C6)alkyl, optionally substituted with one (C3-C7)cycloalkyl group; - (C3-C6)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; - (C3-C6)heterocycloalkyl containing 1 or 2 heteroatoms selected from N or O, optionally substituted with one or more (C1-C6)alkyl group; - (C1-C4)halogenalkyl; - OR4, where R4 selected from a group consisting of: - H; - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl or heteroaryl; - halogen atoms; - CN; - NO2; - NR5R6, where R5 and R6, which can be identical or different, independently selected from a group consisting of: - H; - OH; - (C1-C4)alkyl-NR7R8, where R7 and R8, which can be identical or different, independently selected from a group consisting of: H; (C1-C6)alkyl, possibly substituted (C1-C6)alkoxyl; and (C1-C6)alkyl-NR9R10, where R9 and R10, which can be identical or different, represent H or (C1-C6)alkyl; or they form together with a nitrogen atom to which they are bonded, (C3-C6)heterocycloalkyl ring containing 1 or 2 heteroatoms, selected from N, O or S, optionally substituted (C1-C6)alkyl or (C1-C6)alkylcarbonyl group; -(C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl or heteroaryl, (C3-C6)heterocycloalkylcarbonyl containing 1 or 2 heteroatoms selected from N or O, heteroarylcarbonyl, wherein all of them may further be substituted with one or more (C1-C6)alkyl, (C1-C6)halogenalkyl or (C1-C6)alkoxyl groups, which are identical or different and are selected independently; - SO2R11, where R11 represents (C1-C6)alkyl; - C(O)R12, where R12 is (C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl; - (C1-C4)alkyl-NR13R14, where R13 and R14, which can be identical or different, are independently selected from a group consisting of groups: - SO2(C1-C6)alkyl, H, (C1-C6)alkyl and (C3-C7)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; and - SO2NR15R16, where R15 and R16, which can be identical or different, independently represent H or (C1-C6)alkyl; where groups with R4 at R16 have similar or different values in each case, if they are present in more than one group; and where heteroaryl is a mono- or bicyclic ring system with 5–10 ring atoms, containing 1 or 2 heteroatoms selected from N, O or S; or its pyridine-N-oxides, pharmaceutically acceptable salts or solvates. As well as to methods of producing such compounds, compositions containing them and their therapeutic application as inhibitors of phosphodiesterase 4 (PDE4) enzyme.EFFECT: disclosed are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors.16 cl, 16 tbl, 52 ex

Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)piperidine-2,6-dione derivatives and their pharmaceutical compositions and use // 2611007
FIELD: pharmaceutics.SUBSTANCE: invention relates to polymorphous solid crystalline forms 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)piperidine-2,6-dione of following structural formula. Solid crystalline forms of compound corresponding to structural formula , represent crystalline form A1 of hydrochloride salt of said compound with indications of powder x-ray peak at approximately 8.6, 13.1, 20.5 and 26.3 degrees 2θ; either crystalline form of A monohydrate of said compound, having powder x-ray, including peaks at approximately 14.6, 15.6, 16.7, 21.9 and 30.0 degrees 2θ; crystalline form B, having powder x-ray, including peaks at approximately 10.6, 14.7, 19.1 and 25.9 degrees 2θ; crystalline form C with powder x-ray, including peaks at approximately 10.8, 15.1, 25.1 and 26.6 degrees 2θ; crystalline form E hydrate with powder x-ray, including peaks at approximately 7.3, 14.6, 22.0, 30.0 and 37.0 degrees 2θ; crystalline form F, having powder x-ray, including peaks at approximately 14.5, 15.7, 22.7 and 29.9 degrees 2θ. Invention covers also data of differential scanning calorimetry, thermogravimetric analysis data, indices of hygroscopicity and stability of obtained solid crystalline forms. Invention also relates to pharmaceutical composition containing therapeutically effective amount of solid shape and pharmaceutically acceptable carrier, thinner or excipient.EFFECT: compound possesses properties of TNF-α and can be used for treating various forms of cancer, angiogenesis, macular degeneration and associated syndrome, pain and other disorders and diseases associated with TNF-α.42 cl, 23 dwg, 10 tbl, 4 ex
Thiazolpyrimidines // 2610840
FIELD: pharmaceutics.SUBSTANCE: invention relates to compound of formula I, where R1 is phenyl optionally including from 1 to 3 of following groups as substitutes: C1-6-haloalkyl, C1-6-alkoxy group, C1-6-alkylsulphonyl or R1'; R1' represents pyrrolidinyl or spiroheterocycloalkyl selected from 8-oxy-3-azabicyclo[3.2.1]octane derivatives or 2-oxy-6-azaspiro[3.3]heptane, each of them optionally contains R1ʺ as substitute; R1ʺ is C1-6-alkyl; B is phenyl, pyridinyl, pyrrolidinyl or piperidinyl; X is OH, C1-6-alkoxy group, NHC(=O)Y, C(=O)NH2, C(=O)NHY, C(=O)X', C(=O)Y, CH2NHY, CH2CH2Y, CF=CHY, CH=CHY, CH2OH, C(=O)NHCH2CH2N(CH3)2 or C(=O)NHCH2CH2Y; X' is OH or C1-6-alkoxy group; Y is heterocycloalkyl, consisting of one ring containing from 5 to 7 ring atoms and containing 1 or 2 N atoms, phenyl or monocyclic or bicyclic heteroaryl containing from 6 to 9 ring atoms, containing at least one aromatic or partially unsaturated ring containing from 5 to 6 ring atoms including 1 or 2 N atoms, each of them optionally contains one or two substitutes Y3; Y3 is hydroxy group, C1-6-alkyl, C1-6-alkoxy group, oxo group, amino group, amide group, C(=O)NH(CH3), C(=O)OH, C(=O)OY4 or heteroaryl, selected from oxadiazolyl or triazolyl, possibly containing one or two C1-6-alkyl groups as substitute, oxo groups or SH; Y4 is C1-6-alkyl; or its pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition with inhibiting activity in relation to splenic tyrosine kinase (SYK), including therapeutically effective amount of compound of formula I, mixed with at least one pharmaceutically acceptable carrier, excipient or thinner.EFFECT: thiazolpyrimidines effective in treating disorders associated with SYK.14 cl, 2 tbl, 68 ex

Combined anticancer therapy // 2607596
FIELD: medicine.SUBSTANCE: present invention relates to combined therapy with {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4difluorophenyl} amide of propane-1-sulphonic acid (compound 1) or its pharmaceutically acceptable salt and EGFR inhibitor, selected from erlotinib and cetuximab, for treating cancer, containing b-Raf with V600 mutation, namely colorectal cancer, melanoma and thyroid cancer.EFFECT: combination of compound 1 with EGFR inhibitor leads to improved anti-tumor effects, which considerably exceed the results, obtained for each compound separately, without increasing the toxicity.20 cl, 6 ex, 15 tbl, 9 dwg

Crystalline γ-modification of n-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinoline amine of bis (4-methylbenzenesulfonate) monohydrate, method of its production and pharmaceutical composition based thereon // 2603943
FIELD: pharmaceutics.SUBSTANCE: invention relates to novel crystalline anhydrous modification N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinoline amine of bis (4-methylbenzenesulfonate) monohydrate (lapatinib ditosylate monohydrate), in particular γ-modification, characterized by certain set of diffraction maxima (d, Å) and their intensity (Irelative, %) and certain thermal effects and their temperatures on curve of differential scanning calorimetry, as well as to method of its production and use in pharmaceutical compositions as reversible selective inhibitor of intracellular tyrosine kinase receptor of epidermal growth factor for treating advanced and/or metastatic breast cancer.EFFECT: increased biological activity.4 cl, 5 dwg, 3 tbl, 4 ex

Combined c-met and egfr antagonists therapy // 2601892
FIELD: biology.SUBSTANCE: present invention relates mainly to molecular biology and medicine. In particular, the invention relates to a combined therapy of pathological conditions, such as cancer.EFFECT: method of treating cancer involves introduction of therapeutically effective amount of c-met antagonist and EGFR antagonist.5 cl, 9 tbl, 9 ex, 25 dwg

Ipp complex as marker for erlotinib treatment // 2600828
FIELD: medicine.SUBSTANCE: present group of inventions relates to medicine. Disclosed is method for prediction of reaction of patient suffering non-small cell lung cancer (NSCLC), to treatment with erlotinib hydrochloride, which involves determining ILK gene expression level in sample of patient's tumour, and comparison of ILK gene expression levels with ILK gene expression levels in tumours of patient population, whereon above treatment has not produced favourable clinical effect, and if ILK gene expression level 0.93 times less in patient's tumour sample, then treatment will produce favourable clinical effect on such patient, which does not respond to gefitinib therapy. Disclosed is employing ILK gene for prediction of NSCLC patients response to erlotinib hydrochloride treatment, and use of erlotinib hydrochloride for NSCLC treatment.EFFECT: presented group of inventions provides effective prediction of patient's response to erlotinib hydrochloride treatment.4 cl, 7 dwg, 1 ex

Substituted 4-(selenophen-2(or 3)-ylamino) pyrimidine compounds and methods of use thereof // 2597609
FIELD: chemistry.SUBSTANCE: present invention relates to selenophen compound of formula or its pharmaceutically acceptable salt, solvate or hydrate. Ring A is a conjugated benzene ring; 6-member aromatic conjugated ring containing one nitrogen atom; 5-member aromatic conjugated ring containing one or two heteroatoms selected from oxygen, nitrogen,sulfur and selenium, provided that there is no more than one oxygen atom or sulphur or selenium; such rings include pyridine, pyridazine, pyrazine, pyrimidine, thiophene, furan, pyrrole, selenophen, imidazole, pyrazole, oxazole, isoxazole, thiazole and isothiazole; where ring A is substituted with one, two or more groups independently selected from hydrogen, amino, thiol, C1-6alkyl and C1-6alkoxy. Y represents N. X represents O or NR6, where R6 is selected from hydrogen, C1-6alkyl and galogenoC1-6 alkyl. X can be connected in 2-m, or in 3-m position selenophen ring. R1, R2, R3 and R4 independently selected from hydrogen, nitro, C1-6alkyl, C1-4alkoxycarbonyl, aminokarbonyl and aminoC1-6 alkyl. Also disclosed is a group of specific compounds, methods of producing selenophen compounds and pharmaceutical composition.EFFECT: present invention enables to obtain selenophen compounds used for treating, inhibiting or controlling a cell proliferative disorder in a warm-blooded animal.29 cl, 1 dwg, 2 tbl, 31 ex

Selective histamine h4 receptor antagonists for treating vestibular disorders // 2589846
FIELD: medicine.SUBSTANCE: group of inventions relates to treatment and/or prevention of vestibular disorders. Disclosed is use of a selective antagonist of H4 histamine receptors, selected from a group consisting of 1-[(5-chloro-1H-benzimidazol-2-yl)carbonyl]-4-methylpiperazine, 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine, 4-((3R)-3-aminopyrrolidin-1-yl)-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine, or cis-4-(piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine for treatment and/or prevention of vestibular disorders and composition for same purpose containing said compounds.EFFECT: technical result consists in reducing rate of spontaneous nystagmus and reduced excitability of vestibular neurons.6 cl, 4 dwg

Use of 2-carboxamide-cycloamino urea derivatives in treatment of egfr-dependent diseases or diseases with acquired resistance to agents targeted at egfr-family members // 2589695
FIELD: medicine.SUBSTANCE: disclosed is a group of inventions relates to treatment of malignant tumours. Disclosed are: use of 2-amide-1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)pyridin-4-yl]thiazol-2-yl}amide) (S)-pyrrolidine-1,2-dicarboxylic acid or its salt for production of pharmaceutical compositions for treating a malignant tumour, combination of said compound with EGFR-modulators for said use, method of treating said disease using said compound and pharmaceutical compositions for treating said disease.EFFECT: technical result is shown tumour regression under action of disclosed compound, synergetic anti-cancer action of said compound in combination with EGFR-modulator.10 cl, 7 dwg, 3 tbl, 6 ex

N-hydroxy-benzamides for treating cancer // 2577861
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula wherein X represents -CH2-, an oxygen atom or -NR4; R1 represents a hydrogen atom or halogen atom; R2 represents a hydrogen atom or C1-C6-alkyl provided X represents -CH2- or an oxygen atom; R3 represents phenyl substituted once or twice by a halogen atom, nitro, cyano; pyridin-2-yl unsubstituted or substituted once by nitro; pyrimidin-2-yl unsubstituted or substituted once or twice by C1-C6-alkyl, trifluoromethyl, C1-C6-alkoxy, phenoxy, pyridinyl, C1-C6-alkylpyridinyl, C1-C6-alkoxypyridinyl, halogenopyridinyl, morpholinylpyridinyl, naphthyl, quinolinyl, phenyl or substituted phenyl, wherein the substituted phenyl represents phenyl substituted once or twice by C1-C6-alkyl, a halogen atom, C1-C6-dialkylamino, C1-C6-alkoxy, trifluoromethyl or phenoxy; quinazolin-2-yl substituted once by a halogen atom; phenylcarbonyl substituted once or twice by a halogen atom, trifluoromethyl, C1-C6-alkoxy or phenyl; pyridinyl alkenyl carbonyl, wherein alkenyl contains from 1 to 6 carbon atoms; pyridinyl alkoxycarbonyl, wherein alkoxy contains from 1 to 6 carbon atoms; phenylsulphonyl, wherein phenyl is substituted once or twice by a halogen atom, trifluoromethyl, trifluormethoxy, C1-C6-alkoxy; or pyridinyl sulphonyl; R4 represents a hydrogen atom or C1-C6-alkyl; or their pharmaceutically acceptable salts. The invention also refers to a pharmaceutical compositions containing the above compounds, and using the compounds of formula (I) for producing a medicinal product and for treating cancer.EFFECT: compounds of formula (I) possessing HDAC6 or HDAC8 inhibitory activity.19 cl, 2 dwg, 3 tbl, 69 ex

Pharmaceutical composition including amide derivative or pharmaceutically acceptable salt thereof // 2575829
FIELD: chemistry.SUBSTANCE: pharmaceutical composition includes a compound of formula (I) or a pharmaceutically acceptable salt thereof, an acid additive and inert filler. As the acid additive alginic acid or silicon dioxide is used.EFFECT: enhanced storage stability of the specified composition.9 cl, 19 ex, 7 tbl, 4 dwg

Antiviral heterocyclic compounds // 2572558
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new compounds of formula (I), which possess the properties of HCV NS5B RNA-polymerase inhibitor. The compounds may be used for treating or preventing an infection caused by hepatitis C virus (HCV). In formula (I), X represents CH or N, R1 is specified in a group consisting of R1a, R1c: wherein R1a is optionally substituted by C1-6alkyl, C1-6alkoxy or hydroxy, and wherein R1c is optionally substituted by C1-6alkyl; R2 represents (a) aryl specified in phenyl, or (b) NRaRb, wherein the above aryl is optionally substituted by (CH2)nNRcRd; Ra and Rb together with a nitrogen atom, to which they are attached, represent 5-merous heterocyclic amine substituted by (CH2)nNRcRd group, wherein n means a number from zero to two; Rc and Rd independently represent hydrogen, O2SR4, wherein R4 represents C16alkyl; R3 represents CR4aR4bR4c, wherein: 1) R4a, R4b and R4c are independently specified in C1-3alkyl.EFFECT: producing the compounds for treating or preventing an infection caused by hepatitis C virus (HCV).14 cl, 2 tbl, 9 ex

Purine derivatives applicable for treating fap-related (fibroblast activator protein) diseases // 2569749
FIELD: medicine, pharmaceutics.SUBSTANCE: invention concerns using a compound representing 1-[(4-methylquinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)-xanthine or its salt for producing a pharmaceutical composition applicable for treating hyperproliferative diseases responding to FAP (fibroblast activator protein) inhibition specified in a group consisting cirrhosis, or healing wounds, treating acne and proliferative skin diseases, such as e.g. psoriasis.EFFECT: invention refers to using the substances, which possess an inhibitory ability for treating hyperproliferative diseases.4 cl

New nicotinamide derivative or salt thereof // 2560163
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to nicotinamide derivatives of formula (I) exhibiting the property of Syk-kinase inhibitor and to a based pharmaceutical composition. In general formula R1 means halogen atom; R2 means a substitute presented by formula as follows and R3 means a pyridyl group presented by formulas as follows (VIII-1) or (VIII-2); R4 and R5 mean hydrogen atom. The other radicals are presented in the patent claim.EFFECT: producing new nicotinamide derivatives.13 cl, 2 dwg, 25 tbl, 47 ex

Crystalline forms of 6-(1h-imidazol-1-yl)-2-phenylquinazoline and its salts // 2557547
FIELD: chemistry.SUBSTANCE: invention relates to novel crystalline forms of 6-(1H-imidazol-1-yl)-2-phenylquinazoline of formula (I) in form of salt, selected from hydrochloride, (L)-tartrate and maleate. Compounds possess strong analgising action and can be applied in therapy in treatment of pain in case of such diseases as rheumatoid arthritis, osteoarthritis, pathologies of inflammatory diseases, gastrointestinal tract diseases, etc. Each crystalline form of salt is characterised by spectrum of X-ray powder diffraction (XRPD). Crystalline form of hydrochloride is also characterised by melting point with decomposition at approximately 240°C. Crystalline form of (L)-tartrate and crystalline form of maleate are also characterised by DSC thermograms and FTIR spectra. Crystalline form of maleate is additionally characterised by triclinic system with parameters of crystalline cell a = 8.9412 (5) E, b = 9.8081 (5) E, c = 10.5922 (6) E, α: 90.517° (4), β = 101.969° (5), γ = 99.132° (4), V = 896.34 (8) E3, space group P-1.EFFECT: salts possess improved solubility, bioavailability and stability.3 cl, 66 dwg, 19 tbl, 65 ex

Pharmaceutical composition containing n-[3-chlor-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5[[[2-(methylsulphonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine // 2548757
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to a pharmaceutical composition containing N-[3-chlor-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5[[[2-(methylsulphonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine or its pharmaceutically acceptable salt as an active pharmaceutical ingredient in an amount of more than 60 wt % to less than 85 wt % as related to total weight of the composition. The active pharmaceutical ingredient is characterised by a wetting angle of less than 55°.EFFECT: method for preparing the pharmaceutical composition involves the stage of grinding or milling the above pharmaceutical ingredient in the presence of one or more excipients.7 cl, 7 dwg, 5 tbl, 6 ex

Derivatives of 6-amino quinazoline or 3-cyanoquinoline, methods of their production and their application as inhibitors of receptor tyrozine kinases egfr or her-2 // 2536102
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to heterocyclic compound of formula (I) or its racemate, enantiomer, diastereoisomer and their mixture, as well as to their pharmaceutically acceptable salt, where A is selected from the group, consisting of carbon atom or nitrogen atom; when A represents carbon atom, R1 represents C1-C6-alkoxyl; R2 represents cyano; when A represents nitrogen atom, R1 hydrogen atom or C1-C6-alkoxyl; where said C1-C6-alkoxyl is optionally additionally substituted with one C1-C6-alkoxyl group; R2 is absent; R3 represents radical, which has the formula given below: or , where D represents phenyl, where phenyl is optionally additionally substituted with one or two halogen atoms; T represents -O(CH2)r-; L represents pyridyl; R4 and R5 each represents hydrogen atom; R6 and R7 each is independently selected from hydrogen atom or hydroxyl; R8 represents hydrogen atom; R9 represents hydrogen atom or C1-C6-alkyl; r equals 1 and n equals 2 or 3. Invention also relates to intermediate compound of formula (IA), method of obtaining compound of formulae (I) and (IA), pharmaceutical composition based on formula (I) compound and method of its obtaining and to application of formula (I) compound.EFFECT: novel heterocyclic compounds, inhibiting activity with respect to receptor tyrosine kinases EGFR or receptor tyrosine kinases HER-2 are obtained.18 cl, 12 ex, 4 tbl

Quinazoline compounds // 2530887
FIELD: chemistry.SUBSTANCE: invention relates to (3aR,6aR)-N-(4-(3-ethylphenylamino)-7-methoxyquinazolin-6-yl)-1-methylhexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxamide or its pharmaceutically acceptable salt, as well as to a pharmaceutical composition for treatment of the cancer disease, sensible to inhibition of hyper-expression and/or hyperactivity of a receptor of an epidermal growth factor, which contains the claimed compound, a method of the cancer disease treatment, a method of inhibition and to the application of the claimed compound for a drug preparation.EFFECT: (3aR,6aR)-N-(4-(3-ethylphenylamino)-7-methoxyquinazoline-6-yl)-1-methylhexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxamide, which shows an inhibition activity to hyperexpression and/or hyperactivity of the epidermal growth factor receptor.12 cl, 4 tbl, 7 ex

Jak kinase-modulating quinazoline derivatives and methods of applying thereof // 2529019
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula (I) , where R1 and R2 have the following values: (i) R1 and R2 together form =O; (ii) R1 and R2 together with carbon atom, which they are bound with, form duoxacycloalkyl; R1 represents hydrogen or halogen; and R2 represents halogen; (iv) R1 represents C1-6alkyl, where alkyl is optionally substituted with cyano, -RxS(O)qRv or -RxNRyRz; and R2 represents hydrogen; (v) R1 represents -OR12 or -NR13R14; and R2 represents hydrogen, deutero or phenyl, which is optionally substituted with halogen; R3 represents hydrogen, halogen, C1-6alkyl, cyano, halogen C1-6alkyl, C3-10cycloalkyl or C1-6alkoxy; R4 and R5 represent hydrogen; R6 is independently selected from halogen, C1-6alkyl, halogenC1-6alkyl, -RxOR18 and -RxS(O)qRv; R7 independently represents halogen or -RxORw; R12 is selected from hydrogen and C1-6alkyl, R13 represents hydrogen; R14 is selected from hydrogen, C3-10cycloalkyl, -C(O)Rv and -C(O)ORw; R18 represents hydrogen, C1-6alkyl, or pyperidinyl, where R18 is optionally substituted with 1-3 Q1 groups, each Q1 is independenly selected from hydroxyl, C1-6alkoxy, C1-6alkoxycarbonyl, carboxyl and morpholinyl; Rx independently represents C1-6alkylene or simple bond; Rv and Rw represent hydrogen or C1-6alkyl; Ry and Rz represent hydrogen; n has value 0-4; p has value 0-5; and each q independently has value 0, 1 or 2. Invention also relates to compounds of formula (II) , where substituents have values, given in the invention formula, to pharmaceutical composition, possessing inhibiting activity with respect to JAK kinases, containing compounds of formula (I) or (II), methods of treating JAK-modulated disease, and application of compounds of formula (I) or (II).EFFECT: compounds of formula (I) or (II) as inhibitors of JAK kinases.32 cl, 6 dwg, 2 tbl, 84 ex

Quinazolinones as prolyl hydroxylase inhibitors // 2528412
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to quinazolinone compounds of formula (I) and its pharmaceutically acceptable salts, wherein n is equal to 0 to 3, and R1 is defined as stated in the patent claim. The above compounds are prolyl hydroxylase inhibitors and can be used in pharmaceutical compositions and methods of treating pathological conditions, disorders and conditions mediated by prolyl hydroxylase activity.EFFECT: compounds can be administered into the patient for treating, eg anaemia, vascular diseases, metabolic disorders, as well as for wound healing.22 cl, 2 tbl, 211 ex

Combinations of inhibitors of phosphoinositide 3-kinase and chemiotherapeutic agents and methods of application // 2523890
FIELD: medicine, pharmaceutics.SUBSTANCE: claimed is a group of inventions, which includes a method of treating a hyperproliferative disorder by introduction to a mammal of a therapeutic combination in the form of a combined composition or by alternation, and the therapeutic combination contains a therapeutically effective quantity of formula compound 4-(2-(1H-indasol-4-yl)-6-((4-(methylsulphonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine, or formula (S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one, or their stereoisomers, geometrical isomers, tautomers, or their salts and a therapeutically effective quantity of a chemiotherapeutic agent, selected from erlotinib, docetaxel, 5-FU, gemcitabine, PD-0325901, cisplatin, carboplatin, paclitaxel, bevacizumab, trastuzumab, pertuzumab, temozolomide, tamoxifen, doxorubicin, Akti-1/2, HPPD, rapamycin and lapatinib; a pharmaceutical composition of the same purpose and composition, application of the said therapeutic combination for manufacturing of medication for treatment of cancer, selected from breast cancer, cervical cancer, cancer of large intestine, endometrium, glioma, lung cancer, melanoma, ovarian cancer, cancer of pancreas and prostate, a product for treatment of a hyperproliferative disorder, including the said composition and an instruction and the product, containing the said combination for separate, simultaneous or successive application in treatment of a hyperproliferative disorder.EFFECT: synergism of suppression of cell proliferation and regression of forms of cancer mentioned above.45 cl, 52 dwg

Compounds inhibiting (blocking) bitter taste, methods for use and production thereof // 2522456
FIELD: chemistry.SUBSTANCE: invention relates to a compound of general formula (I) or pharmaceutically acceptable salts thereof, where Alk is an C1-C6alkyl group; G is C=O and Q is CR51R52 or NR51, where R51 and R52, being identical or different, independently denote H, C1-C6alkyl, optionally substituted with a substitute selected from a group comprising carboxy, phenoxy, benzyloxy, C1-C6alkoxy or hydroxy; C3-C6cycloalkylC1-C6alkyl; phenylC1-C6alkyl, optionally substituted with a halogen; phenylamidoC1-C6alkyl; phenylC1-C6alkylamidoC1-C6alkyl, optionally substituted with a C1-C6alkoxy group; or R51 and R52, together with a carbon atom with which they are bonded form a C=O or C2-C6alkenyl group, optionally substituted with a phenyl; M1 is CR49, where R49 is H; M2 is CR50, where R50 is H; R38 is H, C1-C6alkyl, substituted with a phenoxy group; C3-C6cycloalkylC1-C6alkyl; arylC1-C6alkyl, optionally substituted with 1 or 2 substitutes selected from a group comprising C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxycarbonyl, carboxyl, N-methylamido, hydroxy, C1-C6alkoxyC1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulphanyl, cyano, halogen, perfluoroC1-C6alkyl, nitro, formyl, hydroxyC1-C6alkyl and amino, wherein the aryl moiety is a phenyl or naphthyl; and heteroarylC1-C6alkyl, where the heteroaryl moiety is pyridinyl, optionally substituted with 1 or 2 groups selected from C1-C6alkoxy or hydroxyC1-C6alkyl, pyrazolyl or isoxazolyl, substitute with 1 or 2 C1-C6alkyl groups; R47 and R48 is C1-C6alkyl. The invention also relates to specific compounds, a method of reducing or weakening bitter taste, a composition of a food/non-food product or beverage or drug for reducing or lightening bitter taste and a method of producing a compound of formula (I).EFFECT: obtaining novel compounds which are useful as bitter taste inhibitors or taste modulators.37 cl, 6 dwg, 12 tbl, 186 ex

Hydroxylated pyrimidyl cyclopentane as proteinkinase (act) inhibitor // 2520735
FIELD: chemistry.SUBSTANCE: invention relates to a novel compound, corresponding to formula I, and its pharmaceutically acceptable salts, possessing properties of a proteinkinase ACT inhibitor. The invention also relates to a pharmaceutical composition, containing efficient amount of the said compound, and a set for treatment of pathological state, mediated by proteinkinase ACT, which includes: a) one pharmaceutical composition, containing the compound by i.1 and b) an instruction for its application. Formula I compound corresponds to the structural formula: i.e. (S)-2-(4-chloro-3-fluorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-((1R,4S)-4-methoxycyclohexylamino)propan-1-one.EFFECT: compound can be used as a medication for treatment of pathological states, mediated by proteinkinases ACT, such as inflammation, hyperproliferative, such as cancer, cardiovascular, neurodegenerative, gynaecological or dermatological disease or disorder.9 cl, 1 ex

Quinazolinone, quinolone and related analogues as sirtuin modulators // 2519779
FIELD: chemistry.SUBSTANCE: invention relates to a compound of structural formula or a salt thereof, where each of Z1, Z2 and Z3 is independently selected from N and C(R9), where not more than one of Z1, Z2 and Z3 is N; each R9 is hydrogen; and is a second chemical bond between either W2 and C(R12), or W1 and C(R12); W1 is -N=, and W2(R14) is selected from -N(R14)- and -C(R14)=, such that when W1 is -N=, W2(R14) is -N(R14)- and is a second chemical bond between W1 and C(R12); R11 is selected from phenyl and a heterocycle which is selected from a saturated or aromatic 5-6-member monocyclic ring, which contains one or two or three heteroatoms selected from N, O and S, or an 8-member bicyclic ring which contains one or more heteroatoms selected from N, O and S, where R11 is optionally substituted with one or two substitutes independently selected from halogen, C1-C4 alkyl, =O, -O-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from -C1-C4alkyl; or two R13 together with a nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, optionally containing an additional heteroatom selected from NH and O, where if R13 is an alkyl, the alkyl is optionally substituted with one or more substitutes selected from -OH, fluorine, and if two R13 together with the nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, the saturated heterocycle is optionally substituted on any carbon atom with fluorine; R12 is selected from phenyl, a 4-6-member monocyclic saturated ring and a heterocycle, which is selected from an aromatic 5-6-member monocyclic ring which contains one or two heteroatoms selected from N and S, where R12 is optionally substituted with one or more substitutes independently selected from halogen, -C≡N, C1-C4 alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen, C1-C4 alkyl, C1-C4 fluorine-substituted alkyl, C1-C4 alkyl-N(R13)(R13), C1-C4 alkyl-C(O)-N(R13)(R13); and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, -NH-S(=O)2-†, where † denotes the point where X1 is bonded to R11. The invention also relates to a pharmaceutical composition having sirtuin modelling activity based on said compounds.EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a subject suffering from or susceptible to insulin resistance, metabolic syndrome, diabetes or complications thereof.18 cl, 2 tbl, 52 ex

Combinations of antibody drug conjugates and chemotherapeutic compounds and methods for using // 2510272
FIELD: medicine, pharmaceutics.SUBSTANCE: group of inventions refers to medicine, namely to oncology, and can be used for treating hyperproliferative disorders. That is ensured by administering a therapeutic combination in the form of a combination composition or alternatively in a mammal. The therapeutic combination comprises Trastuzumab-MCC-DMl and a chemotherapeutic compound specified in GDC-0941 and GNE-390. A pharmaceutical composition for treating a hyperproliferative disorder contains Trastuzumab-MCC-DMl and the chemotherapeutic compound specified in GDC-0941 and GNE-390.EFFECT: group of inventions provides the synergetic effect of administering the therapeutic combination: the antibody drug conjugate of Trastuzumab-MCC-DMl and the chemotherapeutic compounds GDC-0941 and GNE-390.16 cl, 40 dwg, 5 ex

1h-quinazoline-2,4-diones // 2509764
FIELD: chemistry.SUBSTANCE: invention relates to N-[2,4-dioxo-6-(tetrahydrofuran-2-yl)-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]methanesulphonamide and N-[6-(1-isopropoxyethyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H- quinazolin-3-yl] methanesulphonamide, having antagonistic activity on the AMPA receptor. The invention also relates to a pharmaceutical composition.EFFECT: use of said compounds to produce drugs for treating AMPA mediated conditions and primarily for treating epilepsy or schizophrenia.6 cl, 81 ex

Phenoxypyridinylamide derivatives, and their use in treatment of pde4-mediated disease states // 2509077
FIELD: biotechnologies.SUBSTANCE: invention refers to a compound of formula (I): , where R1 represents NR7C(O)R8 or NR9R10; R2 represents hydrogen; R3 represents halogen; R4 represents hydrogen, halogen, cyano, hydroxy, C1-4alkyl, C1-4alkoxy, CF3, OCF3, C1-4alkylthio, S(O)(C1-4alkyl), S(O)2(C1-4alkyl), CO2H or CO2(C1-4alkyl); R5 represents C1-6alkyl (replaced with NR11R12 or heterocyclyl that represents nonaromatic 5-7-membered ring containing 1 or 2 heteroatoms independently chosen from a group containing nitrogen, oxygen or sulphur); R6 represents hydrogen, halogen, hydroxy, C1-4alkoxy, CO2H or C1-6alkyl (possibly replaced with NR15R16 group, morpholinyl or thiomorpholinyl); R7 represents hydrogen; R8 represents C3-6cycloalkyl (possibly replaced with NR24R25 group), phenyl or heteroaryl, which represents aromatic 5- or 6-membered ring containing 1 to 3 heteroatoms independently chosen from the group containing nitrogen, oxygen and sulphur, and which is probably condensed with one 6-membered aromatic or nonaromatic carbocyclic ring or with one 6-membered aromatic heterocyclic ring, where the above 6-membered aromatic heterocyclic ring includes 1 to 3 heteroatoms independently chosen from a group containing nitrogen, oxygen and sulphur; R9 represents hydrogen or C1-6alkyl (possibly replaced with pyrazolyl); R10 represents C1-6alkyl (possibly replaced with phenyl or heteroaryl group, which represents aromatic 5- or 6-membered ring containing 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur, and which is possibly condensed with one 6-membered heterocyclic ring, where the above 6-membered aromatic heterocyclic ring contains 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur; where the above phenyl and heteroaryl groups in R8, R9 and R10 are possibly independently replaced with the following group: halogen, hydroxy, C(O)R42, C1-6alkyl, C1-6hydroxyalkyl, C1-6halogenoalkyl, C1-6alkoxy(C1-6)alkyl or C3-10cycloalkyl; unless otherwise stated, heterocyclyl is possibly replaced with group of C1-6alkyl, (C1-6alkyl)OH, (C1-6alkyl)C(O)NR51R52 or pyrrolidinyl; R42 represents C1-6alkyl; R12, R15 and R25 independently represent C1-6alkyl (possibly replaced with hydroxy or NR55R56 group); R11, R16, R24, R51, R52, R55 and R56 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts.EFFECT: new compounds are obtained, which can be used in medicine for treatment of PDE4-mediated disease state.10 cl, 2 tbl, 202 ex

Positive allosteric modulators of m1 receptors based on pyranyl aryl methylbenzoquinazolinone // 2507204
FIELD: chemistry.SUBSTANCE: invention relates to novel pyranyl aryl methylbenzoquinazolinone compounds of formula (I), which are positive allosteric modulators of the M1 receptor and which can be used to treat diseases associated with the M1 receptor, such as Alzheimer's disease, schizophrenia, pain disorders or sleep disturbance. In formula (I) X-Y are selected from a group comprising (1) -O-CRARB-, (2) -CRARB-O-, (3) -CRARB-SRC-, (4) -CRARB-NRC- and (5) -NRC-CRARB-, where each RA and RB is a hydrogen atom, and RC is selected from a group comprising (a) hydrogen, (b) -C(=O)-C1-6alkyl, (c) -C1-6alkyl, (d) -C(=O)-CH2-C6H5, (e) -S(=O)2-C1-6 alkyl, R1 is a hydroxy group, R2 is selected from a group comprising (1) -phenyl, (2) - heteroaryl, where the phenyl or heteroaryl group R2 is optionally substituted; the rest of the values of the radicals are given in the claim.EFFECT: obtaining novel pyranyl aryl methylbenzoquinazolinone compounds.28 cl, 12 tbl, 37 ex

Quinazoline derivatives, possessing antidepressant, anxiolytic and nootropic activity // 2507199
FIELD: chemistry.SUBSTANCE: invention relates to novel medication possessing antidepressant, anxiolytic and nootropic activity, which represents compound of general formula where: X is NH or 1,4-piperasino; R1=H or CH3; R2=H, OCH3 or N(CH3)2.EFFECT: on experimental models in vivo compounds, possessing original spectrum of psychotropic action, exceed medications of different pharmacological groups - aphobazolum, melipramin, phenotropil, diazepam in complex of useful qualities, and can be applied in treatment of patients with anxiety and depressive disorders.4 tbl, 8 ex

Quinazoline derivatives, possessing nootropic and antihypoxic activity // 2507198
FIELD: chemistry.SUBSTANCE: invention relates to novel medication, possessing nootropic and antihypoxic activity, which represents arylamides of 2-[4-oxo-3(4H)quinazolinyl]acetic acid of general formula where R=o-CH3, n-CH3 or 2,3-phenylene. Compounds demonstrated original spectrum of psychotropic action, exceeding in complex of useful properties medications of different pharmacological groups - piracetam, phenibut, phenotropil, mexidol, on experimental models in vivo.EFFECT: compounds can be widely applied in treatment of patients with organic affection of brain.3 tbl, 5 ex

Quinazoline derivatives // 2506261
FIELD: chemistry.SUBSTANCE: claimed invention relates to novel quinazolina derivatives, which have benzofurane substituent of formula: in which each of R1, R2, R5, R8, R9 and R10 represent H, R3 and R4 similarly represent alkoxy or methoxyethoxy group; R6 represents alkyl; R7 represents-C(O)NRaRb, and each of Ra and Rb independently represents H, alkyl, ethyl, substituted with diethylaminogroup, C3-C6cycloalkyl, or Ra and Rb together form cycloalkyl; Z represents N; X represents O, S or NR, where R represents H or alkyl.EFFECT: invention relates to pharmaceutical composition, inhibiting KDR, based on said compounds, method of treating associated with angiogenesis disorder, representing cancer, age-related macular degeneration or chronic inflammatory disease, and method of inhibiting activity of growth factor of vessel endothelium.18 cl, 6 ex

Quinazoline derivatives inhibiting egfr activity // 2505534
FIELD: chemistry.SUBSTANCE: invention relates to novel quinazoline derivatives of formula , where each of R1, R2 and R5, independently, represents H; one of R3 and R4 represents where n - 1 or 2; each Ra represents H, C1-10alkyl, optionally substituted with substituent, selected from group, including C1-10alkoxy, C1-10alkansulfonyl carboxy-group, 5-6-membered monocyclic heterocycloalkyl, which has one or several heteroatoms, selected from O and N, where N atom can be substituted with C1-10alkyl, phenyl, optionally substituted with halogen, 5-6-membered monocyclic heteroaryl, which has one or several heteroatoms, selected from N and S, 7-membered bicyclic heterocycloalkyl, which has 2 N atoms; C2-10alkenyl; C2-10alkinyl; cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms; each of Rb and Rc, independently, represents H or C1-10alkyl, optionally substituted C1-10alkoxy, or Rb and Rc, together with atom of nitrogen, with which they are bound, form bicyclic ring of the following formula: , where each of m1, m2, m3, and m4 is 0, 1 or 2; A is CH; B is NR, where R is H or C1-10alkyl; and each of Ri, Rii, Riii, RiV, Rv, Rvi, Rvii and Rviii is H; or 6-7-membered monocyclic heterocycloalkyl, containing 1-2 N atoms, optionally substituted with substituent, selected from group, including hydroxy, C1-10alkyl, optionally substituted C1-10alkoxy, C1-10alkyl, optionally substituted with C3-6cycloalkyl; and each of Rd, Re, independently represents H, C2-10alkenyl; C2-10alkinyl; or C1-10alkyl, optionally substituted with substituent, selected from group, including C1-10alkyloxy, hydroxy, CN, 5-6-membered monocyclic heterocycloalkyl, which has 1 or 2 N atoms, optionally substituted with C1-10alkyl, halogen or 5-6-membered heterocycloalkyl, which has 1 N atom, phenyl, optionally substituted with halogen, cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms, 5-6-membered monocyclic heteroaryl, which has one or 2 N atoms; or Rd and Re, together with nitrogen atom, with which they are bound, form 5-6-membered saturated heterocycloalkyl, which has 1-2 heteroatoms, selected from N and O, optionally substituted with substituent, selected from group, including C1-10alkyl (which is optionally substituted with C3-6cicloalkyl, C1-10alkoxy, halogen), 5-membered heterocycloalkyl, which has one N atom, halogen, C1-10alkansulfonyl, C1-10alkylcarbonyl, optionally substituted with halogen, or Rd and Re, together with nitrogen, with which they are bound, form 7-10-membered, saturated, bicyclic heterocycloalkyl, containing 1-2 heteroatoms, selected from N and O, optionally substituted with C1-10alkyl; and the other of R3 and R4 represents H, halogen or C1-10alkoxy; X represents NRf, where Rf represents phenyl, substituted with C2-4 alkinyl; and Z represents N. Invention also relates to particular quinazoline derivatives, based on it pharmaceutical composition, and to method of cancer treatment.EFFECT: novel quinazoline derivatives, inhibiting EGFR activity are obtained.11 cl, 171 ex

Hydroxylated pyrimidylcyclopentanes as protein kinase (akt) inhibitors // 2504542
FIELD: chemistry.SUBSTANCE: invention concerns novel hydroxylated pyrimidylcyclopentanes of general formula I and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition containing an effective amount of a compound of formula I, use of the compounds to produce a drug for therapy of protein kinase AKT mediated pathological conditions such as a hyperproliferative disease, particularly cancer. In formula (I):, R1 is C1-C6 alkyl containing one substitute OH; R2 is hydrogen or F; and R3 is O or CF3. The subject of the invention is a kit containing a pharmaceutical composition and directions for use thereof.EFFECT: compounds have protein kinase AKT selective inhibitor properties.15 cl, 3 ex

Antifungal crystalline compounds // 2500679
FIELD: chemistry.SUBSTANCE: described are novel crystalline forms of (1R,2R)-7-chloro-3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]quinazolin-4(3H)-one: Form I, Form II, Form III, Form IV and Form VI, each characterised by X-ray powder diffraction (XRPD) data and infrared spectrum data, and a method of producing crystalline Form VI. The preferred form is Form VI, which has antifungal and antimicrobial activity, has the least impurity content, the highest uniform quality of the product, the highest uniform physical characteristics, including colour, rate of dissolution, easiness of handling and longest stability compared to the amorphous form.EFFECT: improved properties of the compound.19 cl, 22 ex, 25 tbl, 23 dwg

Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine // 2498804
FIELD: medicine, pharmaceutics.SUBSTANCE: group of inventions refers to medicine, more specifically to oncology and concerns using neranitib and capecitabine in a combination for treating a new growth (breast cancer); wherein neranitib is administered in the approximate amount of 240 mg a day, and capecitabine is administered in the approximate amount of 1500 mg a day. There are also presented: a pharmaceutical composition, a kit and a method of treating breast cancer which involves administering neranitib and capecitabine.EFFECT: group of inventions provides a synergetic effect of administering neranitib in the approximate amount of 240 mg a day and capecitabine in the approximate amount of 1500 mg a day in a combination for treating new growths.19 cl, 2 tbl, 4 ex
 
2550958.
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