Ortho-condensed systems (C07D471/04)

Fluorine-9-methyl-β-carbolines // 2642785
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of the general formula (I) , where R1 is -F, and R2 is -H or -F, or R1 is -H, and R2 is -F; which can be used as a medicine for treatment of diseases and/or injuries of the inner ear.EFFECT: increased efficiency of compounds.10 cl, 30 dwg, 1 tbl, 9 ex
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
ethod for obtaining of n-aryl-substituted 3h-imidazo[4,5-b] pyridines // 2642456
FIELD: pharmacology.SUBSTANCE: invention relates to a method of obtaining N-aryl-substituted 3H-imidazo[4,5-b] pyridines, formula shown below, where R=H, OCH3, CH3, Cl, involving nucleophilic substitution of the chlorine atom in 2-chloro-3-nitro-6-R-pyridine in a reaction with imidazole, deoxidizing isomerization recycling of N-(3-nitro-6-R-pyrid-2-yl) benzimidazoles. Nucleophilic substitution is carried out in DMF in the presence of K2CO3 for 1 hour at a temperature of 50°C and molar ratio of 2-chloro-3-nitro-6-R-pyridine:benzimidazole:K2CO3=1:1:1.5, deoxidizing isomerization recycling of N-(3-nitro-6-R-pyrid-2-yl)benzimidazoles is performed by SnCl2⋅2H2O at a temperature of 80°C for 20 h in a mixture of isopropanol and 18% hydrochloric acid taken in a volumetric ratio of 1:1, and molar ratio of 1-(3-nitro-6-R-pyridine-2-yl)-1H-benzimidazole : SnCl2⋅2H2O=1:3.5.EFFECT: method is developed for preparation of these derivatives, which can be used as precursors for drugs.8 ex
3-aminocyclopentancarboxamide derivatives // 2641913
FIELD: chemistry.SUBSTANCE: invention relates to the individual compounds selected from the group: 4-(1,3-benzoxazole-2-yl)]-N-[(1R,3S)-3-(ethylcarbamate)cyclopentyl]-N-methylbenzamide, N-((1R,3S)-3-ethylcarbamoylcyclopentyl)-N-methyl-4-(1-methyl-1H-benzoimidazol-2-yl)-benzamide, 4-benzothiazol-2-yl-N-((1R,3S)-3-ethylcarbamoylcyclopentyl)-N-methylbenzamide, ((1R,3S)-3-ethylcarbamoylcyclopentyl)-methylamide4'-[(R)-(tetrahydrofuran-3-yl)oxy]-biphenyl-4-carbon acid, 4-benzoxazole-2-yl-N-((1R,3S)-3-isopropylcyclopentadienyl)-N-methylbenzamide, and other compounds that are specified in the claims. The invention also relates to medicinal means having an inhibiting activity against fatty acid synthase (FAS) containing therapeutically effective amount of the compound of the invention.EFFECT: new compounds are obtained that have an inhibiting activity against the synthesis of fatty acids.2 cl, 2 tbl, 12 ex

ethod of producing (1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4as,7as)-octahydro-6h-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid // 2641699
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to the method of producing (1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo [3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid of the formula (6), which comprises adding tert-butyl octahydro-1H-pyrrolo [3,4b] pyridine-1-carboxylate into a compound of the formula to form a compound of the formula , reacting the compound (2) with triethylorthoformate in acetic anhydride to form a compound of the formula , attaching a cyclic amine to the compound of the formula (3) to form a compound of the formula ; cyclizing a compound of the formula (4) under alkaline conditions to form a compound of the formula ; cleaving the Boc protecting group from the compound of the formula (5) to form the final compound of the formula .EFFECT: improved method of producing acid of the formula, the method is characterized by its simplicity, economy, and low environmental risk.5 cl, 5 dwg, 5 ex
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

Derivatives of azaindasole or diazaindasole type for pain treatment // 2640046
FIELD: pharmacology.SUBSTANCE: invention relates application of a compound of formula for treatment or prevention of pain associated with at least one Trk protein. The radicals and symbols in formula (I) have the definitions indicated in the claims. The invention also relates to a pharmaceutical composition comprising a compound of formula (I) as an active substance.EFFECT: compound application efficiency increase.15 cl, 6 dwg, 1 tbl, 35 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
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

Crystalline forms of grapiprant // 2638931
FIELD: pharmacology.SUBSTANCE: invention relates to the crystalline form of grapiprant selected from the group consisting of Form X, Form X2, Form X3, Form F, Form K, Form L, Form M and Form N.EFFECT: new crystalline form of grapiprant, as well as pharmaceutical compositions suitable for treatment of pain, inflammation, arthritis and cancer, and methods to obtain them.8 cl, 13 tbl, 23 dwg, 12 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
Enzymes inhibition // 2638537
FIELD: pharmacology.SUBSTANCE: invention relates to the compound of the formula or its pharmaceutically acceptable salt. In the formula (I) R1 represents -CN; R2 is selected from (C1-C4)haloalkyl, (C1-C4)haloalkoxy; W represents the (i) 5-membered heteroaryl ring, where two or three ring-atoms represent the hetero-atom N, optionally substituted by one group, which is selected from the (C1-C4) alkyl, the group -NHR18, and from the group -COOR28; or (iii) phenyl group; R3 represents the group -CH2-R23; R5 represents the hydrogen; R6 represents the hydrogen; A1 represents the group -CR7=; A2 represents the group =CR8- or the group =N-; A3--A4 represents the group, which is selected from the group -CR4=N-, the group -CR4=CR9- and the group NR17-CO-; R4 represents the group, which is selected from the hydrogen, the (C1-C4) alkyl, -NR10R11, -NHCOR12, -NHCOO-R13, -NHCONR27-R14, the (C1-C4)alkoxy, -NH(CH2)n-SO2(C1-C4)alkyl, -(NH)q(CH2)n-(C6H4)-SO2(C1-C4)alkyl, -NHSO2(C1-C4) alkyl and -(NH)r(CH2)nCONR15R16; the other chemical groups value is indicated in the invention formula. The invention also relates to the pharmaceutical composition and to the method of the disease or state treatment, where HNE is implicated.EFFECT: there are new compounds of the formula that offer the inhibitors' properties of the human neutrophil elastase.14 cl, 97 ex

Solid forms of inner salt pyridopyrimidine // 2638137
FIELD: chemistry.SUBSTANCE: invention relates to polymorph of inner salt 1-[(2-chlor-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4N-pyrido[1,2-a]pyrimidine designated as form A, characterized by powder diffraction roentgenogram taken with the use of Cu(Kα1) radiation at room temperature, having, at least, the position of reflections 2θ: 8.036, 9.592, 13.719, 14.453, 17.07, 23.092, 24.027, 24.481, 29.743, 31.831. Polymorphic form A is produced by the formation of a suspension of toluene with one or more solid forms of the inner salt 1-[(2-chlor-5-thiazolyl) methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4N-pyrido[1,2-a]pyrimidine selected from the group: (i) polymorphic form B of the inner salt 1-[(2-chlor-5-thiazolyl) methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4N-pyrido[1,2-a]pyrimidine characterized by the powder diffraction roentgenogram taken with the use of Cu(Kα1) radiation at room temperature, having, at least, the position of reflections 2θ: 6.654, 9.41, 10.983, 11.986, 15.513, 21.225, 22.012, 25.638, and 28.545 40.244, and (ii) a mixture of (i) polymorphic form A of the inner salt 1-[(2-chlor-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4N-pyrido[1,2-a]pyrimidine. The resulting slurry is cured and optionally, if necessary, seed crystals of the polymorphic form A are added according to cl. 1, and/or the slurry is mixed and heated to a temperature of 90°C to 110°C, while the transformation of the solid forms of the inner salt of 1-[(2-chloro-5-thiazolyl)methyl]-3-(3,5-dichlorophenyl)-2-hydroxy-9-methyl-4-oxo-4N-pirido[1,2-a]pyrimidine in polymorphic form A. Also, the versions of the method of producing polymorphic form A of the invention are proposed. The polymorphic form A of the invention is intended to control insect pests.EFFECT: polymorphic form of the inner salt has improved stability properties, filterability, solubility.9 cl, 2 dwg, 16 tbl, 18 ex
Pyrazolo [3,4-c] pyridines and methods of application thereof // 2638116
FIELD: pharmacology.SUBSTANCE: subject of the invention is pyrazolo [3,4-c] pyridines of the formula I ,including their stereoisomers, geometric isomers, tautomers and pharmaceutically acceptable salts, wherein R1 and R2 have the values disclosed in the claims. These compounds are useful for inhibiting Pim-kinases and for treating disorders such as cancer, mediated by Pim-kinase. Methods for using compounds of formula I for in vitro, in situ and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells or related pathological conditions are disclosed.EFFECT: increased application effeciency.4 cl, 3 tbl, 328 ex
Pyrazolaminopirimidine derivatives as leucine-repeating kinase 2 (lrrk2) modulators for treatment of parkinson disease // 2637948
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula or to their pharmaceutically acceptable salts, wherein X, R1, R2, R3 and A are as defined in the claims. The compounds of formula (I) are modulators of leucine-repeating kinase 2 (LRRK2) modulators.EFFECT: application fortreatment of diseases associated with the LRRK2 receptor, such as Parkinson's disease.20 cl, 2 tbl, 53 ex
Kinase inhibitors // 2637944
FIELD: pharmacology.SUBSTANCE: invention relates to the compound, which is selected from the group consisting of: 1-{3-tert-Butyl-1'-[2-(4-hydroxy-piperidin-1-yl)-ethyl]-1'H-[1,4']bipyrazolyl-5-yl}-3-{4-[3-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-yloxy]-1,2,3,4-tetrahydro-naphthalin-1-yl}-urea formiate; 1-(3-tert-Butyl-1'-{2-[(2-methoxy-ethyl)-methyl-amino]-ethyl}-1'H-[1,4']bipyrazolyl-5-yl)-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalin-1-yl}-urea; 1-[3-tert-Butyl-1'-(2-dimethylamino-ethyl)-1'H-[1,4']bipyrazolyl-5-yl]-3-[4-(3-dimethylamino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalin-1-yl]-urea formiate; 1-[3-tert-Butyl-1'-(2-dimethylamino-ethyl)-1'H-[1,4']bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-yloxy]-1,2,3,4-tetrahydro-naphthalin-1-yl}-urea formiate; 1-[3-tert-Butyl-1'-(3-dimethylamino-propyl)-1'H-[1,4']bipyrazolyl-5-yl]-3-{4-[3-(2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-yloxy]-1,2,3,4-tetrahydro-naphthalin-1-yl}-urea formiate; the other compounds are indicated in the formula of invention. The invention also relates to the pharmaceutical composition, to the method of disease or conditions treatment in human, which has a positive result from the inhibition of the p38 MAP kinase activity and to the compound application in the manufacture of the medicinal agent.EFFECT: new compounds are obtained, which have the inhibitory action in regard to the p38 mitogen-activated protein kinase activity.11 cl, 30 ex

Aminopyrimidine kinase inhibitors // 2636589
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula 2 , wherein independently for each case R1 is hydrogen; each R2 and R3 is independently selected from the group consisting of hydrogen; (C1-C6)alkyl, optionally substituted with OH; heteroaryl containing 6 atoms in the ring, 1 atom of which is N, and the remaining ones are C atoms (pyridine); heterocyclyl containing 5 or 6 ring atoms, 1 atom of which is N and the remaining ones are C atoms (piperidine or pyrrolidine) optionally substituted by a group selected from methyl, phenyl, pyridinylmethyl, quinolinylmethyl, pyridinylmethyl, piperidinylmethyl or azetidinylmethyl; aryl (C1-C6)alkyl, wherein aryl contains 6 ring atoms, optionally substituted amino or CH2NH2, where (C1-C6)alkyl is optionally substitutedby OH; heteroaryl (C1-C6)alkyl, wherein heteroaryl contains 5 to 9 ring atoms, of which 1 to 2 are heteroatoms selected from N and S, and the remaining atoms are C atoms (indole, pyridine, thiophene, benzimidazole, pyrazole), wherein heteroaryl is optionally is replaced by ethyl; heterocycle (C1-C6)alkyl, wherein the heterocycle contains 6 ring atoms, 1 atom of which is N and the remaining ones are C atoms (piperidine) optionally substituted by methyl; and - [C(R4)2]p-R5, or R2 and R3 are joined together to form an optionally substituted heterocyclic ring containing 5-10 atoms, of which 1 to 2 are heteroatoms selected from N and O, and the remaining ones are C atoms; R20 is selected from the group consisting of hydrogen; heterocyclyl containing 6 ring atoms, 1 atom of which is a heteroatom selected from N, and the remaining atoms are C atoms (piperidinyl); halogen (C1-C6)alkyl; trifluoromethyl; fluorine (C1-C6)alkyl; -O-[C(R4)2]p-R5; -OR16, where R16 is methyl; and amino, which is -N(R50)(R51), where each R50 and R51 is independently hydrogen, (C1-C6)alkyl, optionally substituted by methoxy, or - (CH2)m-R61, where R61 is an aryl containing 6 ring atoms, and m is an integer from 1 to 8. The invention also relates to specific compounds as defined in the claims. The compounds of the invention are for cancer treatment or effect on apoptosis, by administration of a therapeutically effective amount of a compound to a mammal in need thereof.EFFECT: aminopyrimidine compounds for cancer treatment.24 cl, 30 tbl, 251 ex, 53 dwg
New tetrahydropyrimidine connection or its salt // 2636310
FIELD: pharmacology.SUBSTANCE: invention relates to a new tetrahydropyridopyrimidine compound of the general formula (I) or a pharmaceutically acceptable salt thereof. The compounds possess an inhibitory activity against the androgen receptor (AR) and can be used to treat a tumour associated with activity (AR). In the general formula ,X is a halogen atom or halogen-C1-3an alkyl group; R is a phenyl group which is substituted by R1 and can also be substituted by R2, or a 5- or 6-membered heteroaryl group which contains 1 to 3 heteroatoms selected from a nitrogen, oxygen or sulfur atom and which is substituted by R1 and can also be substituted by R2; R1 represents a hydrogen atom, a phenyl group, a hydroxy-C1-6alkyl group, hydroxy-C3-7cycloalkyl group,C1-6an alkoxy group which may be substituted by Ra, C3-7 a cycloalkylaminosulfonyl group, a (6-7) membered monocyclic heterocycloalkylsulfonyl group, with two nitrogen atoms or a nitrogen atom and an oxygen atom in the ring; halogen-C1-3alkoxycarbonylamino group, halogen-C1-3alkylcarbonylamino group, a (5-7)membered monocyclic heterocycloalkanecarbonyl group,containing a nitrogen atom in the ring, and substituted with hydroxy-C1-6alkyl group, or - (CH2)n-C(=O)-NHRf; R2 is a hydrogen atom, a halogen atom or a halogen-C1-3an alkyl group; Ra is C1-6alkylpyrazolyl group, a triazolyl group, a tetrazolyl group or a C1-6 alkylsulfonylpiperazinyl group; Rf is halogen-C1-3alkyl group, hydroxy-C1-6alkyl group, hydroxy-C3-7cycloalkyl group, hydroxy-C3-7cycloalkyl-C1-6alkyl group C1-6alkyl group, substituted by Rfa; Rfa is C a 1-6alkylpyrazolyl group, halogen-C1-3alkylthiazolyl group, an oxadiazolyl group or a halogen-C1-3alkyloxadiazolyl group; and n is an integer from 0 to 3.EFFECT: obtaining of a new compound.20 cl, 5 tbl, 63 ex
Imidzol derivative condensed heterocycle having active ampk effect // 2635662
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of the formula (I), or a pharmaceutically acceptable salt thereof, wherein the group represented by the formula is a group represented by the formula: ; R1, in each case, independently, is halogen, unsubstituted alkyl, substituted alkenyl, substituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or substituted amino; wherein the said radical values are disclosed in the invention formula; m is an integer of 2 or 3; R2 is hydrogen; X is -O-; and Y is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; where the said values of the radical are disclosed in the invention formula. The invention also relates to the pharmaceutical composition based on a compound of theformula (I) and the method of preventing or treating diabetes based on the compound use of the formula (I). .EFFECT: new compounds have been produced that have an activating effect on adenosine monophosphate-activated protein kinase.18 cl, 87 tbl, 24 ex
Intermediate chemical compounds and methods for producing compounds // 2635359
FIELD: chemistry.SUBSTANCE: invention relates to the method for producing 5-bromo-4-chloro-3-nitro-1H-pyrrolo[2,3-b]pyridine of formula comprising the step of bromination of 4-chloro-3-nitro-1H-pyrrolo [2,3 -b] pyridine of formula with a brominating agent to give 5-bromo-4-chloro-3-nitro-1H-pyrrolo[2,3-b]pyridine of formula I. Bromination is carried out at 25°C using acetic acid as a solvent.EFFECT: improving the compound properties.6 cl, 1 ex
Bruton's tyrosine kinase inhibitors // 2634723
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of general formula I: , as well as to pharmaceutical compositions based thereon, and to application for treatment of inflammatory or autoimmune diseases associated with aberrant B-cell proliferation.EFFECT: new compounds with inhibitory activity against Btk are obtained.27 cl, 2 tbl, 34 ex
Fluoroquinolones based on 4-deoxypyridoxine // 2634122
FIELD: pharmacology.SUBSTANCE: invention relates to new fluoroquinolone derivatives of the general formula (I), where R1 = ; R2 = H; R3 = ; or R1 = C2H5; R2 = H; R3 = ; or R1 = C2H5; R2 = F; R3 = ; or R1 = ; R2 = OCH3; R3 = .EFFECT: new fluoroquinolone derivatives with antibacterial activity.2 tbl, 6 ex

Solid dispersions produced by melt extrusion and containing apoptosis-inducing agent // 2633353
FIELD: pharmacology.SUBSTANCE: dispersion includes a compound of Formula I , where the value of R0, R1, R2, R3, R4, A, B, R5, X, Y and R6 groups is determined in the claims, or a pharmaceutically acceptable salt thereof. The compound of Formula I or its pharmaceutically acceptable salt are dispersed in a solid matrix which contains (a) at least one pharmaceutically acceptable water-soluble polymer carrier, and (b) at least one pharmaceutically acceptable surfactant. At least 5% of the compound of Formula I or its pharmaceutically acceptable salt is presented in the crystalline form, as studied by X-ray diffractometry. The compound or its pharmaceutically acceptable salt is presented in an amount equal to an amount of the parent compound from approximately 5% to approximately 40% by weight; at least one pharmaceutically acceptable water-soluble polymer carrier is presented in an amount from approximately 40% to approximately 85% by weight, and at least one pharmaceutically acceptable surfactant is presented in an amount from approximately 5% to approximately 20% by weight. A compound of Formula I in which R0 is chlorine, R1 and R2 are H, R3 and R4 are methyl, A is N, B is CH, R5 is nitro, X is -NH-, Y is - (CH2)n-, where n=1 , and R6 is selected from the group consisting of tetrahydropyranyl and 4-hydroxy-4-methylcyclohexyl, is excluded from the scope of the compound of Formula I. Methods for preparation of a solid dispersion suitable for oral delivery, a pharmaceutical dosage form and a solid dispersion for use as a medicament are also proposed.EFFECT: solid dispersion is applicable for oral administration to the patient in need of treatment of a disease characterised by overexpression of one or more Bcl-2 family antiapoptotic proteins.51 cl, 1 dwg, 17 tbl, 19 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
Substituted derivatives of 3-heteroaroylaminopropionic acid and their application as drugs // 2632897
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula I in any of its stereoisomeric forms or a physiologically acceptable salt thereof, wherein A is selected from the group consisting of C(R1) and N; D is selected from the group consisting of C(R2) and N; E is selected from the group consisting of C(R3) and N; L is selected from the group consisting of C(R4); where at least one and not more than two of A, D, E or L is N; G is selected from the group consisting of R71-O-C(O)-;R1 is selected from the group consisting of hydrogen, halogen; R2 is selected from the group consisting of hydrogen, halogen, (C1-C7)-alkyl, Het2 and Ar-CsH2s-, where s is 0; R3 is selected from the group consisting of hydrogen, Het2, R11-O-; R4 and R10 are selected from the group consisting of hydrogen, halogen; provided that one of the R2, R3 is a cyclic substituent; R11 is selected from the group consisting of hydrogen, R14; R12 and R13 are hydrogen; R14 is (C1-C10)-alkyl optionally substituted by one substituent, which is an oxo group; R30 is selected from the group consisting of R31, R32-CuH2u-, where u is 0; R31 is (C1-C10)-alkyl; R32 is phenyl, wherein phenyl is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O-, CF3-; R40, R50, R60 and R71 are hydrogen; Ar, independently of other Ar groups, is selected from the group consisting of phenyl and aromatic 5-membered or 6-membered monocyclic heterocycle which includes one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and is bonded through the carbon atom of the ring, wherein phenyl and heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, HO-(C1-C6)-alkyl, Het4, (C1-C6)-alkyl-O-, -CF3, -CO-(C1-C6)-alkyl, -CO-NR12R13 and NC-; and wherein phenyl can be substituted with -CH=CH-CH=CH-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O- or -N((C1-C3)-alkyl) -CH=CH-; Het2 is a saturated 5-membered - 6-membered monocyclic heterocycle that includes a nitrogen atom in the ring through which Het2 is attached and optionally one other ring heteroatom selected from the group consisting of nitrogen and oxygen; Het4, regardless of other Het4 groups, is a saturated or unsaturated 4-membered to 5-membered monocyclic heterocycle that includes one to three ring heteroatoms selected from the group consisting of nitrogen and oxygen which is optionally substituted by one or more identical or different substituents selected from the group consisting of (C1-C4)-alkyl, HO-, (C1-C4)-alkyl-O-. Compounds of formula are obtained by the reaction of a compound of formula II with a compound of formula III, where the A, D, E, L, G, R10, R30, R40, R50 and R60 groups such as defined above for compounds of formula I, and additional functional groups may be present in protected form or in the form of a precursor group, and group J in the compound of formula II is HO-, (C1-C4)alkyl-O- or halogen.EFFECT: substituted derivatives of 3-heteroaroylaminopropionic acid for application as a pharmaceutical agent for catheptase protease A inhibition.10 cl, 1 tbl, 620 ex
Substituted triazolopyridines and their applicaion as tyrosine threonine kinase (ttk) inhibitors // 2632464
FIELD: chemistry.SUBSTANCE: invention relates to a compound of general formula (I) where R1 means where * indicates the place of this group attachment to the rest of the molecule; R2 means where * indicates the place of this group attachment to the rest of the molecule; R3 means a hydrogen atom; R4 means a hydrogen atom; R5 means a hydrogen atom; R5a means a group selected from (C1-C4)-alkoxy-, halo-(C1-C4)-alkoxy groups; R5b means a group selected from -C(═O)N(H)R8 , -C(=O)NR8R7, -N(R7)C(=O)OR8, R7-S(=O)2-; R6 means , where * indicates the place of this group attachment to the rest of the molecule; R7 means a (C1-C3)-alkyl group; R8 means a hydrogen atom or a (C1-C6)-alkyl group. This (C1-C6)-alkyl group is optionally substituted once or repeatedly by a halogen atom; or R7 and R8 together with the moiety of the molecule to which they are attached, represent a 4 to 6-membered heterocyclic ring which is optionally substituted once or repeatedly by the same or different halogen atom; R9 means a group selected from (C1-C3)-alkyl, hydroxy-(C1-C3)-alkyl group, -N(H)R8; and Q is CH. The invention also relates to methods for the preparation of a general formula (I) compound, application of the compound of the invention as an Mps-1 kinase inhibitor, and application of the compound of the general formula (7) for preparation of a compound of the general formula (I).EFFECT: new compounds of general formula I having the properties of Mps-1 kinase inhibitor are obtained.10 cl, 99 ex, 8 tbl
ethod for production of 4-benzyl-1-phenethyl-piperazin-2,6-dione, intermediate compound and method for its production // 2631323
FIELD: pharmacology.SUBSTANCE: invention relates to a formula III compound or pharmaceutically acceptable salts thereof, which is a new key intermediate in schistosomicide praziquantel synthesis. The invention also relates to a method for production of formula III compound, method for production of formula IV compound and application of formula III compound or its pharmaceutically acceptable salts to obtain schistosomicide praziquantel.EFFECT: improved method.12 cl, 15 ex
[1,2,4] triazolopiridines and their application as inhibitors of phosphodiesterase // 2630699
FIELD: chemistry.SUBSTANCE: invention relates to a compound of general formula (I) in which R is a branched butyl. The invention also relates to a pharmaceutical composition having a phosphodiesterase inhibitory activity, to the use of a compound for the preparation of a pharmaceutical composition, and to a method of treating or reducing the intensity of a disease, disorder or condition susceptible to a PDE4 inhibitory activity.EFFECT: new compound of general formula I, having a phosphodiesterase inhibitory activity, was obtained.10 cl, 4 ex
Compounds // 2630677
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the general formula ,where Cyc1 is imidazolyl or triazolyl; Cyc2 is phenyl; Cyc3 is phenyl or 5-10 membered heteroaryl containing 1 heteroatom selected from S and N; R1 is halogen; s is equal to 0 or 1, R2 is hydrogen; R3 is hydrogen, C1-8 alkyl or C1-8 alkyl which is substituted by a group selected from pyridyl or -OC1-8 alkyl; Y is N or C (R5); R4 is hydrogen or C1-4 alkyl; R5 is hydrogen or halogen; or R3 and R4 can be taken together to form C2 alkylene; where one carbon of the alkylene chain can be replaced by sulfur; R6 is C1-8 alkyl, Cyc10, halogen or Cyc10 substituted by halogen or cyano, wherein Cyc10 is a 5-membered heteroaryl containing 3-4 nitrogen atoms; m is equal to 2, where each R6 can be the same or different; R7 is halogen, -NH2, -COOR48, -NHC (O) O-C1-8 alkyl, -NHC (O) O-C1-4 alkylene-OC1-8 alkyl; R48 is hydrogen or C1-8 alkyl; n is equal to 1 or 2, where n is an integer 2, each R7 can be the same or different; and R62 is hydrogen, their pharmaceutically acceptable salts or solvates thereof.EFFECT: compounds are factor XIa inhibitors, so they can be used to prevent or treat thromboembolic diseases.15 cl, 3 tbl, 927 ex
Pyrollo [2,3-b]pyridine derivatives as protein kinase inhibitors // 2629999
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula which exhibits activity against protein kinases, as well as to methods of its preparation and pharmaceutical compositions.EFFECT: increased compound activity.15 cl, 8 tbl, 9 ex

Contrast agent for myocardial perfusion visualization // 2629840
FIELD: medicine.SUBSTANCE: compounds and methods for myocardial perfusion visualization are described, comprising administration of a compound associated with visualization moiety, wherein the said compound binds to the mitochondrial complex I (MC-I), and patient scanning by diagnostic imaging. The invention also relates to kits containing the said compound or precursor compounds, associated or not with the visualization moiety.EFFECT: visualization compounds make an important diagnostic marker available for myocardial perfusion visualization.7 cl, 1 dwg, 1 ex
Derivatives of 1,5- and 1,7-naphthyridine useful in treatment of fgfr-mediated diseases // 2629194
FIELD: chemistry.SUBSTANCE: invention relates to a novel derivative of 1,5- and 1,7-naphthyridine of the formulas or , as well as to its tautomeric or isomeric form, and a pharmaceutically acceptable salt, wherein X1 is N and X2 is CR3a or X2 is N and X1 is CR3a; Each R2 is independently selected from halogen and C1-4alkoxy; Y is -E-D; D is a 5- or 6-membered aromatic monocyclic heterocyclyl containing one or two N atoms, wherein said heterocyclyl may be optionally substituted with one or two R1 groups; E is a chain; R1 is C1-6alkyl; R3a is hydrogen or chlorine; R3 is C2-6alkynyl, halo C1-6alkyl, hydroxyC1-6alkyl, cyano C1-6alkyl, C1-6alkoxyC1-6alkyl, C1-6alkyl, substituted R9, C1-6alkyl substituted with -NR10R11, C1-6alkyl substituted with -C(=O)-NR10R11, R13; R9 is a 5- or 6-membered saturated or aromatic monocyclic heterocyclyl containing one, two or three heteroatoms selected from N or O, wherein mentioned 5- or 6-membered monocyclic heterocyclyl is optionally and independently substituted with 1 or 2 substituents, wherein each substituent is independently selected from =O, C1-4alkyl, -S(=O)2-NR14R15 and phenyl C1-6alkyl; R10 and R11 are each independently hydrogen, C1-6alkyl, C1-6alkyl substituted with -NR14R15; R13 is a saturated 6-membered monocyclic heterocyclyl containing one N atom; R14 and R15 are each independently hydrogen or C1-4alkyl; N is independently an integer of 2, 3 or 4. The invention also relates to a pharmaceutical composition based on a compound of formulas (IA) or (IB), the use of mentioned compound, a method for treating or preventing a condition mediated by FGFR kinase, a product based on a compound of formulas (IA) or (IB).EFFECT: new naphthyridine derivatives, useful in the treatment of cancer, have been obtained.36 cl, 4 tbl, 38 ex
Polymorphs of arry-380, selective inhibitor of erb2, and pharmaceutical compositions containing them // 2629116
FIELD: chemistry.SUBSTANCE: invention relates to the polymorphs N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine. The invention also relates to a process of preparation of mentioned polymorphs, a pharmaceutical composition comprising mentioned polymorphs, a method for treating a hyperproliferative disease, and the use of mentioned polymorphs. As a result, polymorphic forms of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine having various physical properties in the solid state.EFFECT: possibility of improving the performance characteristics of the product.136 cl, 58 dwg, 29 tbl, 31 ex

Aminomethyl quinolones useful ifor treatment of jnk-mediated disorder // 2629111
FIELD: chemistry.SUBSTANCE: invention relates to new aminomethyl quinolone derivative of formula (I) or its pharmaceutically acceptable salt, where R is -C(=O)A, -C(=O)OA, -C(=O)NHA, -C(=N-C≡N)A, -C(=N-C≡N)NHA or A; A is C1-6-alkyl, phenyl, lower cycloalkyl, adamantyl, heterocycloalkyl selected from benzodioxin, pyrrolidine, piperidine, morpholine or piperazine, heteroaryl selected from pyridine, pyrazole, thiazole, triazole or pyrimidine or bicyclic heteroaryl selected from quinoline, quinazoline, indole, benzothiazole, benzoimidazole or imidazopyridine optionally substituted with one or two A1; each A1 independently represents A2 or A3; each A2 is independently halo or oxo; each A3 is independently C1-6-alkyl, C1-6-alkoxy, phenyl, benzyl, heterocycloalkyl selected from morpholine, piperidine, diazepane, pyrrolidine, azepane or piperazine, bicyclic heterocycloalkyl selected from benzodioxole or diazobicycloheptane, heteroaryl selected from oxazole, triazole, pyrazole, imidazole, thiadiazole, oxadiazole, thiazole or tetrazole, amino, C1-6-alkylamino, C1-6-dialkylamino, amido, C1-6-alkyl ester group, sulfonyl, sulfonamido, -C(=O) or -C(═O)O, optionally substituted by one, two or three groups, selected from halo, hydroxy, C1-6-alkylamino, C1-6-alkyloxy, C1-6-alkyl, C1-6-alkoxy, phenyl, hydroxycycloalkyl wherein cycloalkyl is adamantyl, amino, C1-6-alkylamino, C1-6-dialkylamino, t-butyl complex of carbamic acid ester, (C1-6-alkyl) sulfonyl-piperidinyl or hydroxy- (C1-6-alkyl); R' is H or methyl; X is CX'; X' is H or halo; X1 is H, 2-oxazolyl, dimethylamido or C1-6-alkyl ester group; Y is CH or N; and Y1 is H, halo, C1-6- alkoxy or halo (C1-6alkyl). The invention also relates to particular aminomethyl quinolone derivatives and to the use of said aminomethyl quinolone derivatives.EFFECT: obtained new aminomethyl quinolone derivatives, useful in the treatment of JNK-mediated disorder.15 cl, 2 tbl, 211 ex
Apoptosis-inducing means for treatment of malignant tumour and immune and autoimmune diseases // 2628885
FIELD: pharmacology.SUBSTANCE: invention relates to application of a combination of a formula (III) compound with one or more additional drugs for the manufacture of a drug for use in therapy that inhibits the activity of anti-apoptotic Bcl-2 proteins. The radical values are set forth in claim p.1.EFFECT: increased efficiency of compounds.16 cl, 6 tbl, 19 ex

Amide compounds, methods for production, application as means for treatment and prevention of diseases caused by rna-containing viruses // 2628800
FIELD: pharmacology.SUBSTANCE: compounds of the invention are intended for manufacture of a pharmaceutical composition, kit or drug. The invention also relates to a process for preparation of compounds of the invention (versions). Compounds of the invention are intended for use in the prevention or treatment of diseases caused by RNA-containing viruses belonging to enteroviruses, metapneumoviruses or pneumoviruses.EFFECT: amide compounds for treatment or prevention of diseases caused by RNA-containing viruses.26 cl, 8 tbl, 5 ex

Bicyclic piperazine compounds // 2628616
FIELD: pharmacology.SUBSTANCE: invention relates to new bicyclic piperazine compounds of formula , as well as to pharmaceutically acceptable salts thereof.EFFECT: new compounds of formula I have been obtained that have modulating activity against Bruton tyrosine kinase, that can be used to prepare pharmaceutical compositions, as well as for treatment of immune disorders such as inflammation mediated by kinase.17 cl, 15 dwg, 2 tbl, 131 ex

Salts and crystalline forms of apottosis-inducing agent // 2628560
FIELD: pharmacology.SUBSTANCE: invention relates to a compound having the systematic name 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy) benzamide (compound 1) in the form of a free base crystalline anhydrate, a free base hydrate of crystalline form, a solvate of crystalline form, a hydrochloride salt of crystalline form, or a sulfate salt of crystalline form. The invention also relates to a pharmaceutical composition having an inhibitory activity against anti-apoptotic proteins of the Bcl-2 family comprising a therapeutically effective amount of the compound of the invention and one or more pharmaceutically acceptable excipients.EFFECT: crystalline forms of compound 1 suitable for use as an active pharmaceutical ingredient.21 cl, 14 dwg, 14 tbl, 17 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
Compounds of pyridazinamide and their use as synthetic syneckinasis inhibitors (syk) // 2627661
FIELD: chemistry.SUBSTANCE: invention relates to novel pyridazinamides of the formula I , where all variable substituents are defined in the claims, and their pharmaceutically acceptable salts, as well as a pharmaceutical composition based on them.EFFECT: compounds of the formula are SYK inhibitors and are useful for the treatment of autoimmune and inflammatory diseases.10 cl, 1 tbl, 43 ex
Heterocyclyl pyridinylpyrazoles // 2627272
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclylpyridinylpyrazoles of the formula (I), in which R1-R5, X1, U, Q, W, a, b and n have the values defined as defined in the invention formula and their agrochemically active salts. Compounds of formula (I) can be used to control phytopathogenic harmful fungi in agriculture, horticulture, forestry, livestock, materials protection, household and hygiene, and to reduce the content of mycotoxins in plants and parts of plants. The invention also relates to the use of compounds of formula (I) and to method and composition for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on plant seeds.EFFECT: decrease the content of mycotoxins in plants and parts of plants.10 cl, 7 tbl, 31 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
Adamantyl derivatives useful for treatment of jnk-mediated disorder // 2626890
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to the heterocyclic compound of I formula or a pharmaceutically acceptable salt thereof, wherein R represents phenyl optionally substituted with one or more R'; R' is halo or methoxy; X represents CH; X1 represents C(=O)OCH3; Y represents N; Y1 It is OH, N(Y1')2, NHS(=O)2Y1', NHC(=O)Y1', NHC(=O)C(CH3)2OH or NHC(=O)C(CH3)2OC(=O)Y1'; each Y1' independently represents H, C1-6-alkyl or lower cycloalkyl; Y2 It is H. The invention also relates to formula I based on the compound of the pharmaceutical composition and the use thereof.EFFECT: new heterocyclic compounds useful for treating JNK-mediated disorder are obtained.12 cl, 5 tbl, 31 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
8-carbamoyl-2-(2,3-di-substituted pyrid-6-yl)-1,2,3,4-tetrahydroisoquinoline derivatives as apoptosis-inducing agents for cancer treatment // 2625315
FIELD: pharmacology.SUBSTANCE: invention relates to organic chemistry, namely a heterocyclic compound of formula (I) or to a therapeutically acceptable salt thereof, where X is benzo[d]thiazolyl, thiazolo[5,4-b]pyridinyl, thiazolo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, thiazolo[5,4-c]pyridinyl, thiazolo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl or imidazo[ 1,2-b]pyridazinyl; Y1 means pyrrolyl, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with 1 or 2 substituents independently selected from R5, CN and Cl; L1 is selected from (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-S-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; Y2 means mono- or tricyclic C8-C10-cycloalkyl, spiro[2.5]octyl, spiro[3.5]nonyl, oxatricyclo[3.3.1.13,7]decyl or azabicyclo[3.2.1]octyl; where Y2 is optionally substituted with 1, 2 or 3 substituents independently selected from R8, OR8, SO2R8, CO(O)R8, OH and Br; Z1 is selected from , R1 and R3 are absent; R2 is deuterium or C1-C6-alkyl; R5 is C1-C6-alkyl; R6A is selected from hydrogen and C1-C6-alkyl; each R6 and R7 are hydrogen; R8 is selected from the group consisting of C1-C3-alkyl, morpholinyl and dioxydothiomorpholinyl; where R8, meaning C1-C6-alkyl, is optionally substituted with a substituent selected from R16, OR16, SO2R16 and NHR16; Rk is selected from C1-C6-alkyl, morpholinyl, cyclopropyl and C1-haloalkyl; R16 Is selected from C1-C4-alkyl, phenyl, morpholinyl and tetrahydropyranyl; where R16, meaning C1-C4-alkyl, is optionally substituted with 1 substituent selected from OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s, m and p is 0; r is 0 or 1; N is 0, 1, or 2. The invention also relates to specific compounds, pharmaceutical compositions based on these compounds and a method for treatment of these diseases.EFFECT: new heterocyclic compounds are obtained, that are useful for treatment of some cancers.16 cl, 3 tbl, 86 ex
Hydinine derivatives as inheritors of ferment pde10a // 2624440
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to heterocyclic compounds selected from 7-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline and 6-[2-(5,8-dimethyl[1,2,4]triazolo[1,5-a]pyrazin-2-yl)-ethyl]-[1,3]dioxolo[4,5-g]quinoline and the pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions on the basis of one of these compounds and the use of these compounds.EFFECT: obtained new heterocyclic compounds useful in the treatment of a neurodegenerative or psychiatric disorder.10 cl, 1 tbl, 2 ex
Kinase inhibitors // 2623734
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof which have an inhibitory activity against p38 MAP kinase. In formula (I), W is NH, Y is selected from the -O (CR3R4)n- group, where n is 0, R1 is (IIb) group , X1 is -(CH)-, R9 is C1-C6alkyl, C3-C6cycloalkyl or phenyl optionally substituted with halogen atoms, R12 is a hydrogen atom, A is a bivalent cycloalkylene radical having 5, 6 or 7 ring atoms, wherein the said cycloalkylene ring is attached to W and Y and fused to a phenyl ring, wherein such phenyl ring is optionally substituted with one or two R27 groups, R27 is selected from halogen, R2 is a radical of formula (IVb) or (IVc) where R17 is selected from a single electron pair, hydrogen or aryl, where any such aryl may be optionally substituted by a C1-C6alkyl or C3-C7cycloalkyl; or R17th is a group of general formula (V) R20 is selected from the group consisting of -CH3 or -C2H5; R21 is -CH3 or -C2H5; R18 is selected from the group consisting of a single electron pair, hydrogen, aryl, heteroaryl, -(C1-6alkyl), -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6alkyl) and (C5-C7heterocycloalkyl)-(C3-C6cycloalkyl) group, R19 Is selected from -CF3, z1, z2, z3 and z4 are independently selected from the group consisting of C, N, O, -CH- and -NH- groups, in such combination that the resulting ring is an aromatic system, T is -CR28=; R28 is halogen; R22 is H or halogen. The invention also relates to a pharmaceutical composition comprising the said compounds, a method for treatment of diseases which benefit from p38 MAP kinase inhibition, and their application for manufacture of a medicament for treatment of such diseases.EFFECT: increased efficiency of compounds application.14 cl, 2 tbl, 35 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

Crystalline form of compound used as a mineralocorticoid receptor antagonist and the method of its production // 2622105
FIELD: chemistry.SUBSTANCE: invention relates to crystalline forms I and II of compound 2-chloro-4-[(3S,3aR)-3-cyclopentyl-7-(4-hydroxy-1-carbonyl)-3,3a, 4.5-tetrahydro-2H-pyrazolo[3.4-f]quinolin-2-yl]benzonitrile of formula (I), used as a mineralocorticoid receptor antagonist. Crystalline forms have characteristic peaks of powder X-ray diffraction pattern specified in the claims. The invention also relates to processes for preparing crystalline forms I and II and the use of the obtained crystal forms in the manufacture of medicaments for the treatment and/or prevention of kidney damage or cardiovascular diseases.EFFECT: obtained crystalline form the compound of formula amorphous form of its superior stability, not only at high temperature and humidity, and light conditions.16 cl, 4 dwg, 4 tbl, 10 ex

Application of adamantane indole and their hydrochlorides as cholinesterase inhibitors and nmda-receptors blockers // 2621348
FIELD: pharmacology.SUBSTANCE: invention relates to application of adamantane-containing indoles and their hydrochlorides of general formula where R1, R2, R3, R4 may be the same or different and independently represent H, F, Cl, Br, (C1-C6) alkyl, (C1-C6) alkoxy; R5, R6 may be the same or different and independently represent H, (C1-C6) alkyl, ONO2; X represents CH2CH(OH)CH2 or CH2CH2C(O); Z=no, Cl; R7, R8, R9, R10 may be the same or different and independently represent H, F, Cl, Br, (C1-C6) alkyl, (C1-C6) alkoxy; R11, R12, R13, R14, R15, R16, R17, R18 may be the same or different and independently represent H, (C1-C6) alkyl, as a cholinesterase inhibitors and NMDA receptors blockers, and can be used as new drugs that interact with several targets responsible for improval of memory and cognitive functions, weakening of which has various origin, including dementias of various origins, especially due to neurodegenerative diseases, such as Alzheimer's disease.EFFECT: increased compound application effeciency.15 cl, 1 dwg, 1 tbl, 3 ex
 
2550950.
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