(A61K31/4709)

Novel pyrrole compounds, synthesis method thereof and pharmaceutical compositions containing same // 2607788
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) possessing inhibitory activity on Bcl-2 family proteins. In formula (I) (I) A1 is hydrogen, (C1-C6)polyhaloalkyl group or (C1-C6)alkyl group, A2 is hydrogen, (C1-C6)polyhaloalkyl group, (C1-C6)alkyl group or cycloalkyl group, T denotes a hydrogen atom, (C1-C6)alkyl group, optionally substituted with one-three halogen atoms, group (C1-C4)alkyl-NR1R2 or group (C1-C4)alkyl-OR6, R1 and R2 each independently from each other is a hydrogen atom or (C1-C6)alkyl group, or R1 and R2 form with a nitrogen atom bearing them, heterocycloalkyl, R3 is (C1-C6)alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R4 is an aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R5 is hydrogen or halogen atom, R6 is a hydrogen atom or a linear or branched (C1-C6)alkyl group, Ra, Rb, Rc and Rd each independently from other represents hydrogen, linear or branched (C1-C6)alkyl, halogen atom, a linear or branched (C1-C6)alkoxy group, hydroxy group, R7-CO-NH-(C0-C6)alkyl-, R7-SO2-NH-(C0-C6)alkyl-, R7-NH-CO-NH-(C0-C6)alkyl-, R7-O-CO-NH-(C0-C6)alkyl-, or substitutes of pair (Rb, Rc) form together with carbon atoms carrying them, a ring consisting of 5–6 ring members, which may contain 1–2 oxygen atoms, R7 is hydrogen, linear or branched (C1-C6)alkyl, aryl or heteroaryl. Invention also relates to methods of producing compounds of formula (I), to a pharmaceutical composition, use of a pharmaceutical composition for preparing a drug, use of compound of formula (I) for preparing a drug.EFFECT: obtaining novel compounds of formula (I) possessing inhibitory activity on Bcl-2 family proteins.37 cl, 2 tbl, 473 ex
Compounds having antagonistic activity towards muscarinic receptors and agonist activity to beta2-adrenoreceptors // 2606121
FIELD: chemistry.SUBSTANCE: present invention relates to compounds of general formula (I), acting as muscarinic receptors antagonists or beta2-adrenoreceptors agonists, as well as to pharmaceutical compositions based thereon and to therapeutic applications for preparing a medicine to prevent and treat diseases, such as asthma, chronic bronchitis, etc.EFFECT: obtained are novel compounds of formula (I) having activity towards muscarinic receptors or beta2-adrenoreceptors.13 cl, 5 tbl, 39 ex, 2 dwg

Quinoline and quinoxaline derivatives effective as cysteinyl-leukotriene antagonists // 2605929
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a heterocyclic compound of formula (IA) or to a pharmaceutically acceptable salt thereof, where in each case R1 and R3 are independently selected from a group comprising hydrogen, halogen, -OH, -C1-2alkyl, -O-C1-2alkyl, -O-C1halogenalkoxy, -N(C1alkyl)2; R2 represents hydrogen; W represents a group selected from -CH= or -N=; X represents a group selected from -CH=CH- or -N=CH-, where nitrogen from -N=CH- is directly bonded with ring 'a'; Y represents a group selected from -CH=CH- or -C≡C-; Z denotes a bond or group selected from -(CH2)n- and -CH=CH-; A is a group selected from -OR, -O(CH2)nphenyl, -O(CH2)nthiophene; P is selected from a group comprising -O-; Q is a group selected from -COOH; where R is selected from a group comprising hydrogen, -C1-6alkyl, -C3-6cycloalkyl, -C1alkyl (C3-6cycloalkyl), -C3-6alkenyl and -C3-6alkynyl; 'n' in each case represents an integer, selected from 1, 2 or 3; 'm' in each case represents an integer, selected from 0-3, inclusive. Invention also relates to a compound of formula (Id), where radicals are described in patent claim.EFFECT: obtaining novel heterocyclic compounds effective as antagonists of cysteinyl-leukotriene.9 cl, 1 dwg, 2 tbl, 67 ex

3-carboxy-4-aminoquinoline derivates, useful as sweet taste modifiers // 2605549
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry and specifically to novel quinoline derivatives of general formula (IIIb) or ingestible salt thereof, where A is NH2; B is C1-C4 alkyl; C is -CO2R7; R7 is hydrogen; L1 is C1-C8 alkylene, C6-cycloalkylene or -CH2-C6-cycloalkylene; L2 is -O-, NR34-C(O)-, -C(O)-NR34-, -(3-6-member heterocyclylene-C(O))-group, where heterocyclylene contains one nitrogen atom; R33 is C1-C6 alkyl, optionally substituted C1-C6 alkoxy or hydroxy, C3-C10 carbocyclyl, optionally substituted with one C1-C6 alkoxy, C6-C10 aryl, optionally substituted with one or two substitutes, selected from -OH, halogen, -C(=O)NH2, -C(=O)NHC1-6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-OH and O-C1-C6 alkyl-OH, C6-C10 aryl C1-C4 alkyl, optionally substituted C1-C6 alkoxy, 5-10-member heterocyclyl containing 1 or 2 oxygen atoms, pyridine or pyridine-C1-C4 alkyl; and R34 is hydrogen. Invention also relates to quinoline derivatives of formula (IIIc) and (IIIc'), specific quinoline derivatives, ingestible composition based on compounds of formula (IIIb), (IIIc) and (IIIc'), method of enhancing sweet taste of ingestible composition, method of producing intermediate compounds of formulae (IV) and (IVc).EFFECT: novel quinoline derivatives, useful as sweet taste modifiers.23 cl, 23 tbl, 133 ex, , ,

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

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

New substituted quinoline compounds as inhibitors of s-nitrozoglutation-reductase inhibitors // 2599144
FIELD: chemistry.SUBSTANCE: invention is related to organic chemistry and specifically to novel quinoline derivatives of general formula I or pharmaceutically acceptable salts, stereoisomers or N-oxides, where m = 0 and 1; R1 is independently selected from a group consisting of chlorine, fluorine and bromine; R2b and R2 c are independently selected from a group, consisting of hydrogen, halogen, C1-C3 alkyl, fluorinated C1-C3alkyl, cyano and N (CH3)2; X is selected from a group consisting of n is selected from a group consisting of 0 and 1; R3 is independently selected from a group consisting of halogen, C1-C3 alkyl, fluorinated with1-C3 alkyl, cyano, C1-C3alkoxy and NR4R4′, where R4 and R4′ are independently selected from a group consisting of C1-C3 alkyl; and a is selected from a group consisting of .Invention is also related to the use of formula I, pharmaceutical composition based on the compound of formula I, method of treating pulmonary disorders and inflammatory diseases based on use of the compound of formula I, and a method of producing a pharmaceutical composition based on the compound of formula I.EFFECT: technical result is obtaining novel quinoline derivatives, useful as inhibitors of S-nitrozoglutation reductase (GSNOR).17 cl, 64 ex

Triazolopyrine compounds as kinase inhibitors pim // 2598846
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula I, their stereoisomers and pharmaceutically acceptable salts thereof, in which R1, R2, R3, R4 and R10 assume values given in the patent claim. Declared compounds are inhibitors of kinase tyrosine kinases PIM-1, and/or PIM-2, and/or PIM-3 and can be used in treating diseases mediated by said kinase. Invention also relates to a pharmaceutical composition based on them, methods of producing the declared compounds and an intermediate compound used in production of the declared compounds.EFFECT: disclosed are compounds of Formula I, their stereoisomers and pharmaceutically acceptable salts.56 cl, 6 tbl, 11 ex biological researches (A-K), 6 receptions of, 328 ex

Quinoline-2-amine derivatives, useful for treating aids // 2598845
FIELD: chemistry.SUBSTANCE: present invention relates to organic chemistry, namely to new quinoline-2-amine derivatives of general formula (I) or pharmaceutically acceptable salts thereof, where X represents CR0 or N, i.e. together with the ring it belongs to it forms respectively a benzene or a pyridine group, R0, R1, R2, R3, R4, R7 and R8 independently represent a hydrogen atom , a halogen atom or a group selected from a (C1-C5)alkyl group, a (C1-C5)fluoroalkyl group, a (C1-C5)alkoxy group, a (C1-C5)fluoroalkoxy group, a -NRaRb group, a -NRa-SO2-NRaRb group, a -NRa-SO2-Ra group and may additional represent a group selected from (IIa) or (IIIa); A represents an oxygen atom, B is a covalent bond, n equals 1, 2 or 3, m equals 1, 2 or 3, R, R′, Rand R andb independently represent a hydrogen atom or (C1-C5)alkyl group, R and R′ can further form with a nitrogen atom, to which they are bonded, saturated 5-or 6-member heterocycle, possibly containing one more heteroatom O, R5 is a hydrogen atom or (C1-C5)alkyl group, R10 is a hydrogen atom or a chlorine atom, and R11 is a hydrogen atom under the conditions specified in CL. 1. Invention also relates to specific quinoline-2-amine derivatives and a pharmaceutical composition based on the compound of formula (I).EFFECT: technical result: there are new quinoline-2-amine derivatives, useful for treating AIDS.14 cl, 2 tbl, 6 ex , ,

Substituted benzamide derivatives // 2595902
FIELD: chemistry.SUBSTANCE: invention relates to compound of formula (I), where R is hydrogen or C1-7alkyl; R1 represents -(CH2)n-(O)o-5-7-member heterocycloalkyl, containing 1-2 heteroatoms selected from N and O, except for piperazine, where said heterocycloalkyl group optionally substituted with C1-7alkyl, hydroxy or halogen; n equals to 0, 1 or 2; o equals to 0 or 1; R2 represents CF3, C3-6-cycloalkyl, possibly substituted C1-7alkoxy or halogen, or represents indane-2-yl, or is 6-member heterocycloalkyl, containing 1-2 heteroatoms selected from N and O, optionally substituted with pyrimidinyl, or is 5-6 mono- or 9-10-member bicyclic heteroaryl containing 1-2 heteroatoms selected from N, O and S, where the heteroaryl is not thiazol and where said aromatic ring, is possibly substituted with one or two substitutes selected from C1-7alkyl, halogen, 5-6-member heteroaryl containing 1-2 heteroatoms selected from N and O, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2Cl)(CH3), S-C-1-7alkyl, C1-7alkoxy, CH2-C-1-7alkoxy, C2-7alkynyl or cyano, or substituted with -C(O)-phenyl, -O-phenyl, -O-CH2-phenyl, phenyl, and where said phenyl ring may be substituted with halogen, -C(O)OH or -C(O)O-C-1-7alkyl, or said aromatic ring, is possibly substituted with 5-6-member heterocycloalkyl, containing 1-2 heteroatoms selected from N and O, OCH2-oxetane-3-yl or O-tetrahydropyran-4-yl, possibly substituted C1-7alkyl; X is bond, -CH2NH-, -CHR″-, -(CHR″)q-O-, -O-(CHR″)q- or -(CH2)2-; Y is bond; R″ is hydrogen, C1-7alkyl, CF3, C1-7alkoxy; q is equal to 0, 1, 2 or 3; or pharmaceutically acceptable acid addition salt thereof, except for compounds specified in patent claim. Invention also relates to specific compounds specified in patent claim. Compounds are intended for producing medicinal agents, showing affinity to TAAR1.EFFECT: technical result: benzamide derivatives having high affinity to receptors associated with TAAR1 trace amines.9 cl, 1 tbl, 323 ex

Substituted 2-oxy-quinoline-3-carboxamides as kcnq2/3 modulators // 2595894
FIELD: chemistry.SUBSTANCE: invention relates to substituted 2-oxy-quinoline-3-carboxamides of general formula (I) in form of free compounds or salts of physiologically acceptable acids or bases, where R1 is C1-6-aliphatic residue; 6-member unsubstituted or mono- or disubstituted aryl or unsubstituted 5-member heteroaryl, selected from a thienyl; R2 is CF3; C1-4-aliphatic residue; O-C1-4-aliphatic residue; R3, R4, R5 and R6 each independently represent H; F; Cl; Br; I; CN; CF3; R7 is C1-6-aliphatic residue, unsubstituted or mono- or trisubstituted; where "aliphatic residue" in each case may be branched or straight, saturated, where "mono- or trisubstituted" with respect to "aliphatic residue" relates, in relation to corresponding residues, to substitution of one or three hydrogen atoms, each independently from other, with at least one substitute selected from a group which includes F, Cl, Br, I, OH, O-C1-4-aliphatic residue, where "mono- or disubstituted" with respect to "aryl" relates, in relation to corresponding residues, to substitution of one or two hydrogen atoms, each independently from other, with at least one substitute selected from a group which includes F, Cl, Br, I, OH, O-C1-4-aliphatic residue C1-4-aliphatic residue. Invention also relates to a pharmaceutical composition based on compound of formula (I) and a method of treating and/or preventing diseases mediated by channels KCNQ2/3 K+.EFFECT: obtaining novel 2-oxy-quinoline-3-carboxamide derivatives having useful biological activity.8 cl, 2 tbl, 53 ex

Pi3-kinase inhibitors and use thereof // 2595718
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds which are irreversible PI3-kinase inhibitors, and conjugates containing one or more PI3-kinases, containing cysteine residue, which is covalently and irreversibly boned with PI3-kinase inhibitor. Invention also discloses pharmaceutical compositions containing said compounds.EFFECT: compounds are intended for treating disorders and diseases associated with PI3-kinase.19 cl, 16 dwg, 26 tbl, 52 ex

Catechol-o-methyl transferase inhibitors and use thereof in treating psychotic disorders // 2586974
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to derivatives of 4-pyridinone formula I or pharmaceutically acceptable salts thereof, where A is hydrogen, B(OH)2, halogen, C(O)NH(CH2)nC(O)N(R3)2; X is hydrogen or halogen; Y denotes phenyl, benzimidazolil, benztiazolil, benzoksazolil, benzpiperidinil, quinolyl, indolyl, indazolyl or pyridyl, each optionally substituted with 1-3 groups Ra, provided that Y denotes phenyl, then at least one of said Ra selected from OCF3, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)n(C)6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, where said heterocyclic ring and aryl optionally substituted with 1-3 groups Rb; R1 represents hydrogen, NR2R3, Si(CH3)3, (CH2)nC6-10aryl, C2alkenyl or C1-4alkyl, said alkyl and alkenyl optionally substituted with 1-3 groups of halogen, OH, C1-6alkyl, O-C1-6alkyl, NR2R3, SOR2, NHSO2R2, CF3, C6-10aryl, heterocyclyl, -C≡C-C6-10aryl, C(O)NR2R3, wherein said aryl and heterocyclyl optionally substituted with 1-2 groups Ra; R2 and R3 independently denote H, C1-6alkyl, (CH2)nheterocyclyl, (CH2)nC6-10aryl, wherein said aryl optionally substituted by group Ra or R2 and R3 together with nitrogen atom to which they are bonded, form a 6-member ring, which contains oxygen; Ra is C1-6alkyl, halogen, CF3, OCF3, C3-6cycloalkyl, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, CN, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)nC6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, wherein said heterocyclyl and aryl optionally substituted with 1-3 groups Rb; Rb is C1-6alkyl, halogen, CHF2, oxo (=O), N(R2)2, CH2OH, S(O)2NR2R3, (CH2)nC6-10aryl, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, OR2, C3-6cycloalkyl, CF3 or CN; and n equals 0-3; and where heterocycle is aromatic or saturated or partially saturated monocyclic or bicyclic ring containing 5-10 atoms, among which 1-4 atoms are heteroatoms selected from nitrogen, oxygen and sulphur. Invention also relates to pharmaceutical composition based on compound of formula I, method of treating and/or preventing neurological and psychiatric disorders and method of intensifying action of antipsychotic agent based on use of compound of formula I.EFFECT: new compounds are prepared effective in treating diseases associated with catechol-O-methyltransferase (COMT).52 cl, 1 tbl, 17 ex

Synthesis and anticancer activity of derivatives of aryl and heteroaryl quinolines // 2584688
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I and pharmaceutically acceptable salts thereof , where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 is (C1-C6)alkoxy, hydroxyl or OR8; R6 is hydroxyl or (C1-C6)alkoxy; R7 represents hydrogen, hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents a RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion; or where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 represents hydrogen, (C1-C6)alkoxy, hydroxyl or OR8; R6 is (C1-C6)alkoxy; R7 is hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents PO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion. Disclosed compounds have anti-cancer activity. Invention also relates to compounds of formula I, radicals of which are presented in patent claim and to using pharmaceutical composition containing effective amount of compound of invention for treating cancer.EFFECT: technical outcome is new compounds possessing anticancer activity.17 cl, 23 dwg, 7 tbl, 4 ex

Pharmaceutically acceptable salt (e)-n-[4-[[3-chloro-4-(2-pyridylmethoxy) phenyl] amino] -3-cyano-7-ethoxy-6-quinolyl] -3-[(2r)- 1- methylpyrrolidin-2-yl] prop-2-enamide, method for production and use thereof in treating cancer // 2583056
FIELD: pharmaceutics.SUBSTANCE: invention relates to a pharmaceutically acceptable salt of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide (formula (I)), where n equals 1, 2 or 3; and M is a molecule of acid, where said salt is selected from group consisting of hydrochloride, para-toluene sulphonate, methanesulphonate, maleate, succinate and L-malate. Invention also relates to method of producing salt of formula (I), pharmaceutical composition based on salt compound of formula (I) and use of salt compound of formula (I).EFFECT: novel salt of compound of formula (I) effective in treating cancer.10 cl, 7 tbl, 13 ex
Heteroarylsulphonamide derivatives, production and use thereof for human treatment // 2582995
FIELD: chemistry.SUBSTANCE: invention relates to geteroarilsulfonamide derivatives of formula I, where R1 is a substituent of the phenyl nucleus X selected from the group consisting of: hydrogen, F, Cl, Br, trifluoromethyl, trifluoromethoxy group, a linear or branched C1-C4-alkyl, linear or branched C1-C4 alkoxy group; n is 0, 1 or 2; A is oxygen or sulfur; D is -C (=O)-, -CH2O- or -O-; B is a nitrogen atom if n = 1 or 2, and D is -C(=O) -, or B is CH, if n = 0, and Dis -CH2O-, or if n = 1, D is -O-; R2 is hydrogen, and HetAr is pyridyl or quinolyl, optionally containing a substituent which is a linear or branched C1-C4-alkyl or trifluoromethyl; or pharmaceutically acceptable salts thereof. Invention also relates to the methods for producing compounds of formula I and to the pharmaceutical composition containing a therapeutically effective amount of the compound of formula I. EFFECT: technical result is geteroarilsulfonamide derivatives of formula I, with blocking activity to Kv1,5 potassium channels.12 cl, 1 tbl, 35 ex
Quinoline derivatives and melk inhibitors containing same // 2582610
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to a heterocyclic compound of general formula (I) or its pharmaceutically acceptable salt thereof, where: R1 is C1-C6 alkyl sulphonyl or -CO-R5, where R5 is C1-C-6 alkyl or C3-C5 cycloalkyl; R2 represents phenyl which can contain group substitute selected from group of substitutes C, or -NR6AR7A, where R6A is hydrogen atom and R7A is -(CH2)n-R10A (where n equals whole number from 0 to 2 and R10A represents mono- or tricyclic C3-C10 cycloalkyl, which can contain group substitute selected from group of substitutes D, phenyl, which can contain group substitute selected from a group of substitutes E, aliphatic heterocyclic group which is selected from piperidinil, piperazinil and azabicyclooctanil and can be substituted C1-C-6 alkyl, aromatic heterocyclic group which is selected from a pyridinyl, pyrimidinyl and pirazolil and can contain group substitute selected from a group of substitutes I), or R6A and R7A is formed with adjacent nitrogen atom aliphatic heterocyclic group that is selected from piperidinil and piperazinil and may contain group substitute selected from a group of substitutes F; R3 is C6-C10 aryl, which can contain group substitute selected from a group of substitutes G, or aromatic heterocyclic group which is selected from a pyridinyl, pyrimidinyl, tiofenil, isoxazolyl, pyrrolyl and pirazolil and can contain group substitute selected from a group of substitutes H; R4 is hydrogen atom or halogen; R is hydrogen atom or halogen; and R101 is hydrogen atom; where said substitutes C - I are one-three substitutes are given in claim. Invention also relates to pharmaceutical composition, an inhibitor of MELK, agent, which simulates the expression MELK, anticancer agent based on compounds of formula (I), method of treating and/or preventing diseases, which includes MELK overexpression, using compound of formula (I).EFFECT: obtained are novel heterocyclic compounds effective as anti-tumour agent.19 cl, 4 tbl, 1200 ex

Substituted 2-oxo- and 2- thioxo- dihydroquinoline-3-carboxamides as kcnq2/3 modulators // 2581362
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to derivative 2-oxo- and 2-thioxodihydroquinoline-3-carboxamides of formula in the form of free compounds, or in the form of salts of physiologically acceptable acids or bases, wherein X means O or S, R1 represents an unsubstituted C1-7-aliphatic residue; or aryl specified in phenyl unsubstituted or monosubstituted by at least one substitute specified in a group, which contains F, Cl, Br; R2 represents CF3; C1-4-aliphatic residue or O-C1-4-aliphatic residue, wherein C1-4 aliphatic residue in each case is unsubstituted; each R3, R4, R5 and R6 independently represents H; F; Cl; Br; CN; CF3; OCF3; provided at least one of R3, R4, R5 and R6 does not represent H; R7 represents C1-7-aliphatic residue unsubstituted, or mono- or disubstituted; or 6-merous heterocycloaliphatic residue specified in tetrahydropyrane; wherein the 'aliphatic residue' in each case can be branched or unbranched, saturated; wherein 'mono- or disubstituted' in relation to the 'aliphatic residue' refers in the view of respective residues or groups, to substitution of one or two hydrogen atoms specified in one or two hydrogen atoms, each independently, by at least one substitute specified in a group, which contains OH, O-C1-4-aliphatic residue, COOH or C(=O)-O-C1-4-aliphatic residue. The invention also refers to a pharmaceutical composition based on the compound of formula (I).EFFECT: new compounds effective in treating and/or preventing diseases mediated by KCNQ2/3 K+ canals are produced.8 cl, 2 tbl, 45 ex

Eye medicinal film with moxifloxacin // 2581025
FIELD: medicine.SUBSTANCE: invention refers to medicine, particularly to ophthalmology, and can be used in preoperative and postoperative prevention and treatment of infectious inflammatory complications following abdominal operations on eyeball. Eye film comprises polyvinyl alcohol, dihydroquercetin as an active substance of vegetable origin, moxifloxacin as an antibiotic. Invention increases range of therapeutic action of film by giving it strong antioxidant, anti-inflammatory, immunomodulatory properties, provides long-term effect eye film.EFFECT: eye medicinal films with moxifloxacin are easy to use, have prolonged antimicrobial, antioxidant, immunomodulatory, anti-inflammatory properties.1 cl, 1 dwg

Aminopyrazole derivative // 2580543
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound, which has formula presented below, or a pharmaceutically acceptable salt thereof. This compound can inhibit fibroblast growth factor receptor (FGFR) kinases in tumour tissues. In formula (I) A means a heteroaryl specified in indole, azaindole, benzofuran, benzothiophene, benzorhiazole, quinoline and pyrrole, or a benzene ring; R1 particularly means hydrogen, hydroxy, halogen, cyano, C1-4 haloalkyl, C1-6 alkyl, C2-6 alkinyl; R2 particularly means hydrogen, hydroxy, halogen, cyano, C1-4 haloalkyl, C1-6 alkyl, C2-6 alkinyl, C3-7 cycloalkyl, phenylC1-4 alkyl, or R1 and R2 together with a nitrogen atom connected thereto form a 5-6-merous heterocyclyl group containing two oxygen atoms optionally substituted by a halogen; R3 means H, C1-5 alkyl group, phenylC1-5 alkyl group or C1-4 haloalkyl group; and R4 means H or halogen.EFFECT: invention refers to a pharmaceutical composition and an agent for FGFR inhibition, an agent for preventing or treating a malignant new growth, a method for preventing or treating malignant new growths, and the use of the compounds for producing a medicinal agent for preventing or treating malignant new growths.10 cl, 35 tbl, 246 ex

1-hydroxyimino-3-phenyl-propanes // 2579114
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to 1-hydroxyimino-3-phenyl-propane derivatives of formula I, wherein R1 represents -(CH2)m-phenyl, m is equal to 0, and phenyl is substituted by 1-3 groups independently specified in C1-7-alkyl or hydroxy, or -(CH2)n-heteroaryl, wherein n is equal to 0 or 1, and heteroaryl is specified in pyridine, 1H-pyridin-2-one, 1-oxy-pyridine, 1H-pyrimidin-2-one, quinoline and pyrazine, and is ubsubstituted or substituted by 1-3 groups specified in the patent claim; R2 represents hydrogen or C1-7-alkyl, or when R4 represents hydrogen, R2 represents phenyl optionally substituted by C1-7-alkyl; R3 represents hydrogen; R5 represents hydrogen or hydroxy; or R3 and R5 are substituted by a double bond; R4 is specified in a group consisting of C1-7-alkyl, C3-7-cycloalkyl, C2-7-alkenyl, halogen-C1-7-alky, optionally substituted phenyl, optionally substituted phenyl-C1-7-alkyl, 5-9-merous heteroaryl containing 1-2 heteroatoms specified in N and S optionally substituted by C1-7-alkyl or oxo, and piperidinyl optionally substituted by C1-7-alkyl, or R4 and R5 together with a carbon atom to which they are attached, form a C3-7-cycloalkyl ring; R6 represents hydrogen halogen; or R4 and R6 together with a carbon atom to which they are attached, form a cyclic group G , wherein m represents 0 or 2; R7 - R9 are those as specified in the patent claim; R10 is specified in hydrogen, halogen and C1-7-alkyl; or their pharmaceutically acceptable salts. The invention also refers to specific compounds specified in cl. 19 of the patent claim, a method for producing the compounds I, a pharmaceutical composition, a method of treating diabetes and using the compounds for producing a medicinal agent.EFFECT: 1-hydroxyimino-3-phenyl-propane derivatives possessing GPBAR1 agonist activity and effective in treating diabetes.26 cl, 516 ex

Compounds applicable for treating aids // 2575845
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to using a compound of formula or any of its pharmaceutically acceptable salts, wherein means an aromatic ring, wherein V represents C or N, and when V represents N, V is found in meta- or para-position to Z, R independently represents a hydrogen atom, halogen atom or group specified in -CN group, hydroxyl group, -COOR1 group, (C1-C3)fluoralkyl group, (C1-C3)fluoralkoxy group, -NO2 group, -NR1R2 group, (C1-C4)alkoxy group, phenoxy group and (C1-C3)alkyl group, wherein the above alkyl is optionally monosubstituted by a hydroxyl group, R1 and R2 independently represent a hydrogen atom or (C1-C3)alkyl group, n is equal to 1, 2 or 3, n′ is equal to 1 or 2, R′ represents a hydrogen atom, halogen atom or group specified in (C1-C3)alkyl group, -NO2 group, -NR1R2 group, morpholinyl group, N-methylpiperazinyl group, (C1-C3)fluoralkyl group and (C1-C4)alkoxy group, R″ represents a hydrogen atom, Z, Y, X, W, T and U represent N or C, and wherein at most four of V, T, U, Z, Y, X and W groups represent N, and at least one of T, U, Y, X and W groups represents N, for producing a medicinal preparation for preventing, inhibiting or treating AIDS. The invention also refers to using specific compounds, new quinoline derivatives, a pharmaceutical composition based on the new quinoline derivatives.EFFECT: new quinoline derivatives are produced, and new biological activity of known compounds is stated.15 cl, 2 tbl, 11 ex

Aryl-substituted carboxamide derivatives as calcium or sodium channel blockers // 2575168
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to aryl-substituted carboxamide derivatives of formula (I)or their pharmaceutically acceptable salts, wherein in formula (I) R represents hydrogen; R1 is independently specified in a group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -On-C1-6 alkyl, wherein alkyl is unsubstituted or substituted by one or more substitutes optionally specified in R7, (5) -On-heterocylic group specified in piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl and oxetanyl; n has the value of 0 or 1; when n has the value of 0, a chemical bond is present instead of On; p has the value of 1 or 2; when p is equal to two, R1 can be identical or different from each other; R2 represents C1-6 alkyl, which is unsubstituted or substituted by one or more substitutes, independently specified in R7; or R2 together with R1 forms C3-C6 cycloalkyl; X represents 1,2-C3 cycloalkylene; W, Y and Z are independently specified in nitrogen atom or carbon atom; at least one of W, Y and Z represents nitrogen, and simultaneously W, Y and Z are other than carbon; R3, R4, R5 and R6 are such as presented in the patent claim; Ar means aryl, which represents mono- or bi-carbocyclic or mono or bi-heterocyclic ring containing 0-3 heteroatoms specified in O, N and S, including phenyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyridyl, piperidinyl, pyrimidinyl, isooxazolyl, triazolyl, tetrahydronaphthyl, benzofuranyl, benzothiophenyl, indolyl, benzoimidazolyl, quinolyl, isoquinolyl, quinoxalinyl, pyrazolo [1,5-a] pyridyl, thieno [3,2-b] pyrrolyl, wherein aryl is optionally substituted by 1-3 substitutes specified in the patent claim. Also the invention refers to compounds of formula (II)and their aryl-substituted carboxamide derivatives specified in cl. 3 of the patent claim, a pharmaceutical composition, a method of treating and using.EFFECT: aryl-substituted carboxamide derivatives exhibiting blocking activity on T-type calcium channels or voltage-dependent channels.10 cl, 6 tbl, 464 ex

Pharmaceutically active compounds as axl inhibitors // 2573834
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of structural formula (I) possessing inhibitory activity on the TAM family of receptor tyrosine kinases (RTKs). In formula (I) A represents C-R10; B represents C-R11, N; R1, R4 are independently specified in -H, -F, -Cl, -Br, -I, -OH, -NH2, -OCH3, -OC2H5, -OC3H7, -OCH(CH3)2, -NO2, -CHO, -COCH3, -COC2H5, -COC3H7, -O-cyclo-C3H5, -OCH2-cyclo-C3H5, -O-C2H4-cyclo-C3H5, -OCF3, -OC2F5, -CH2F, -CHF2, -CF3, -CH2Cl, -CH2Br, -CH2I, -CH2-CH2F, -CH2-CHF2, -CH2-CF3, -CH2-CH2Cl, -CH2-CH2Br, -CH2-CH2I, cyclo-C3H5, -CH2-cyclo-C3H5, -CH3, -C2H5, -C3H7, -CH(CH3)2, -C4H9, -CH2-CH(CH3)2, -CH(CH3)-C2H5, -C(CH3)3, -CH=CH2, -CH2-CH=CH2, -C(CH3)=CH2, -CH=CH-CH3; R2 are R3 are independently specified in -O-R18, -O-CR73R74-R18, -O-CR73R74-CR75R76-R18, -O-CR73R74-CR75R76-CR77R78-R18, -O-CR73R74-CR75R76-CR77R78-CR79R80-R18; R5 and R6 represent -H; R7, R8, which can be identical or different from each other, represent -H, -F, -Cl, -Br, -I, -CN, -NO2, -CH3, -C2H5, -C3H7, -CH(CH3)2, cyclo-C3H5, -CH2-cyclo-C3H5, -OCH3; R9 represents -H. The radical values D, R10, R11, R18, R73-R80 are presented in the patent claim. The invention also refers to a pharmaceutical composition containing the above compound.EFFECT: producing the compounds possessing the inhibitory activity on the TAM family of receptor tyrosine kinases (RTKs).14 cl, 3 tbl, 106 ex

Quinolyl-containing compound of hydroxamic acid, method for thereof obtaining and application in treatment of diseases, caused by abnormal proteinkinase and/or hystone deacetylase activity // 2573633
FIELD: chemistry.SUBSTANCE: claimed invention relates to field of organic chemistry, namely to novel quinolyl-containing compounds of hydroxamic acid of general formula (I), wherein each of V1 and V2 independently represents halogen; one of R and R' represents group Q, containing hydroxamic acid, and the other represents methoxy, wherein group Q, containing hydroxamic acid, is represented by formula ; A represents O; L represents C1-6alkyl; J represents NH, piperidinyl, or J is absent; X is absent; Y represents C1-6alkyl, or Y is absent. The invention also relates to method for obtaining formula (I) compound, pharmaceutical composition, based on formula (I) compound and its application for treatment of diseases, caused by proteinkinase and/or histone deacetylase activity.EFFECT: novel compounds, which can be applied in cancer treatment, have been obtained.25 cl, 7 dwg, 7 tbl, 45 ex

Derivatives of (4-methylsulphonylaminophenyl)-quinoline, useful in treatment of hepatitis c // 2572835
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to compound, selected from the group of N-{4-[7-tert-butyl-8-methoxy-5-(2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-2-yl]phenyl}-methanesulphonamide; N-{4-[7-tert-butyl-8-methoxy-5-(6-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-2-yl]-phenyl}- methanesulphonamide; and N-{4-[7-tert-butyl-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-8-methoxy-quinolin-2-yl]-phenyl}- methanesulphonamide; or to its pharmaceutically acceptable salt. The invention also relates to application of said compound for treatment or prevention of infection with hepatitis C virus (HCV) and for manufacturing thereof based medication.EFFECT: novel compounds, possessing useful biological activity have been obtained.5 cl, 2 tbl, 6 ex

Oxazoline derivatives for treating cns disorders // 2569887
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formulawherein Ra represents hydrogen or C1-7alkyl; R1 represents groups and or may be specified in a group consisting of , wherein R8 represents hydrogen, halogen or aryl optionally substituted by halogen; X represents a bond, -(CH2)n-, -CHRCH2-, -CHR(CH2)2-, -O-CHRCH2- or -(C3cyclopropyl)-CH2-CH2-, and R represents C1-7alkyl or C1-7alkyl substituted by halogen; R2 represents a) C1-7alkyl; b) hydrogen; c) NH-phenyl optionally substituted by one or more substitutes specified in halogen or C1-7alkyl substituted by halogen; d) NH-6-merous heteroaryl containing 1 or 2 heteroatoms N optionally substituted by one or more substitutes specified in halogen or C1-7-alkyl substituted by halogen; e) (CR'R")m-C3-6-cycloalkyl optionally substituted by halogen, C1-7alkyl, C1-7alkyl substituted by halogen, halogen-substituted phenyl or heteroaryl, which represents pyridine; f) 6-merous heterocycloalkyl containing 1 or 2 heteroatoms specified in N and O, optionally substituted by halogen or C1-7alkyl substituted by halogen; g) (CR'R")m-5-6-merous monocyclic or 9-10-mrous bicyclic heteroaryl containing 1-3 heteroatoms specified in N, S and O, optionally substituted by halogen, C1-7alkoxy, C1-7alkyl, substituted by halogen, C1-7alkoxy substituted by halogen, C1-7alkyl, C3-6-cycloalkyl, NHC(O)-C1-7alkyl, cyano, S(O)2-C1-7alkyl, NR6R7 or 5-6-merous heteroaryl containing 1 or 2 heteroatoms, N or 6-merous heterocyclyl containing 1 or 2 heteroatoms specified in N, O and S, wherein S is optionally specified by two oxygen molecules, which is optionally substituted by halogen; h) (CR'R")m-phenyl optionally substituted by halogen, C1-7alkyl substituted by halogen, C1-7-alkoxy substituted by halogen, C1-7alkyl, C2-7alkinyl, C1-7alkoxy, CH2-C1-7alkoxy or cyano; i) -O(CH2)o-phenyl optionally substituted by halogen, C1-7alkoxy or C1-7alkyl substituted by halogen; R' and R" independently represent hydrogen, C1-7alkoxy or C1-7alkyl; or together with atom C may form C3-6-cycloalkyl group; R3 represents phenyl or 10-merous heteroaryl containing 1 heteroatom N, wherein the above aromatic rings are optionally substituted by one or more substitutes specified in halogen or C1-7alkoxy; R4 represents C1-7alkyl, phenyl or 6-merous heteroaryl containing 1 heteroatom N, wherein the above aromatic rings are optionally substituted by one or more substituted specified in halogen, cyano or C1-7alkoxy; R5 represents hydrogen, C1-7alkyl or phenyl substituted by halogen; R6/R7 independently represent hydrogen, C1-7alkyl or (CH2)2-O-C1-7alkyl; m equals to 0, 1 or 2; n equals to 1, 2 or 3; o equals to 0 or 1; p equals to 0, 1 or 2; or their pharmaceutically acceptable acid addition salt. The invention also refers to compounds which represent 4-[2-((S)-2-amino-4,5-dihydrooxazol-4-yl)-ethyl]-N-(4-chlor-phenyl)-benzamide or (S)-4-(2-(2-amino-4,5-dihydrooxazol-4-yl)-ethyl)-N-(5-ethynylpyridin-2-yl)benzamide. The compositions according to the invention are applicable to produce a pharmaceutical composition having a high affinity to trace amine associated receptors.EFFECT: oxazoline derivatives applicable in treating depression, bipolar disorder, attention deficit/hyperactivity syndrome (ADHD), psychotic disorders, schizophrenia, Parkinson's disease, migraine and addictive substance abuse.23 cl, 1 tbl, 233 ex

Pharmaceutical compositions // 2568882
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to the pharmaceutical industry and represents a pharmaceutical composition for the treatment of a respiratory, inflammatory or obstructive disease of the respiratory tract, containing R(+) budesonide and one or more beta2-agonists, selected from albuterol, levoalbuterol, terbutaline, pirbuterol, procaterol, metaproterenol, fenoterol, bitolterol, mesylate, ritodrine, arformoterol, carmoterol, bambuterol, clenbuterol, indacaterol, milveterol, vilanterol or olodanterol, and optionally one or more pharmaceutically acceptable excipients.EFFECT: introduction of the claimed combination one time per day and reduction of side effects in the treatment of respiratory, inflammatory or obstructive diseases of the respiratory tract are provided.39 cl, 30 ex

Solid forms of n-(4-(7-azabicyclo[2,2,1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide // 2568608
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to novel solid forms of N-(4-(7-azabicyclo[2,2,1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide (A-HCl forms, B forms, B-HCl forms). The invention also relates to pharmaceutical compositions based on A-HCl forms, or B forms, or B-HCl forms, or combinations thereof; a method of treating diseases caused by CFTR mutations; a method of modulating CFTR activity in a biological sample.EFFECT: obtaining novel stable solid forms of N-(4-(7-azabicyclo[2,2,1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide, having biological activity.32 cl, 24 dwg, 13 tbl, 8 ex

Substituted quinoline compounds and methods of their application // 2568258
FIELD: medicine, pharmaceutics.SUBSTANCE: claimed invention relates to novel substituted quinolines of general formula (I), where R1 stands for hydroxyC2-6 alkoxy and R2 is H, C1-10alkoxy or hydroxyC1-10alkoxy; R3 is H or F, R4 is H, F, Cl, Br, I or CN; and X is CH or N, or to their stereoisomers, tautomers, or pharmaceutically acceptable salts. Invention also claims pharmaceutical compositions, which include such compounds and methods of applying compounds and compositions in treatment of hyper-proliferative disorders in mammals, especially humans.EFFECT: claimed compounds inhibit activity of protein- and tyrosinkinase and cell activity, such as proliferation, differentiation, apoptosis, migration and invasion.15 cl, 3 dwg, 2 tbl, 18 ex

Compounds suitable for cancer treatment // 2567752
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to application of formulacompound,where stands for aromatic ring, where V represents C or N and, where V represents N, V is in meta- or para-position to Z, R independently represents hydrogen atom, halogen atom or group, selected from group -CN, hydroxyl group, group -COOR1, (C1-C3)fluoroalkyl group, (C1-C3)fluoroalkoxy group, group -NO2, group -NR1R2, (C1-C4)alkoxy group, phenoxy group and (C1-C3)alkyl group, where said alkyl is possibly monosubstituted with hydroxyl group, R1 and R2 independently represent hydrogen atom or (C1-C3)alkyl group, n equals 1, 2 or 3, n' equals 1 or 2, R' represents hydrogen atom, halogen atom or group, selected from (C1-C3)alkyl group, group -NO2, group -NR1R2, morpholinyl group, N-methylpiperazinyl group, (C1-C3)fluoroalkyl group and (C1-C4)alkoxy group, R" represents hydrogen atom, Z, Y, X, W, T, U independently represent N or C, and where maximum four of groups V, T, U, Z, Y, X and W represent N, and at least one of groups T, U, Y, X and W represents N, or any of its pharmaceutically acceptable salts for obtaining medication for prevention, inhibition or treatment of cancer. Invention also relates to application of particular compounds, to novel quinoline and isoquinoline derivatives, pharmaceutical composition based on novel quinoline and isoquinoline derivatives.EFFECT: obtained are novel quinoline and isoquinoline derivatives, and novel biological activity of known compounds is discovered.10 cl, 2 tbl, 6 ex

Azabicyclocompound and its salt // 2565078
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to novel azabicyclic compounds, represented by the given below general formula, or to their pharmaceutically acceptable salts. The said compounds demonstrate inhibition activity with respect to HSP90 and action inhibiting cellular proliferation. In formula (I) X1 represents CH or N; one of X2, X3 and X4 represents N, and the others represent CH; one or two of Y1, Y2, Y3 and Y4 represent C-R4, one of the remaining ones represents CH or N and the remaining one represents CH; R1 represents a monocyclic group optionally substituted 5- or 6-membered unsaturated heterocyclic group, which contains from 1 to 2 heteroatoms, selected from N, S and O, or an optionally substituted 9- or 10-membered bicyclic unsaturated heterocyclic group, which contains from 1 to 2 heteroatoms, selected from N, S and O, where the possible substituent is determined in the formula of the invention; R2 represents a hydrogen atom, an optionally substituted with halogen atoms alkyl group, containing from 1 to 6 carbon atoms, or an alkenyl group, containing from 2 to 6 carbon atoms; and R3 represents CO-R5; R4 are similar or different and represent a hydrogen atom, a halogen atom, a cyanogroup, an alkyl group, which contains from 1 to 6 carbon atoms, optionally substituted with a mono- or di(C1-C6-alkyl)aminogroup or a morpholine group, a cycloalkyl group, which contains from 3 to 7 carbon atoms, an alkenyl group, which contains from 2 to 6 carbon atoms, an alkoxygroup, which contains from 1 to 6 carbon atoms, a phenyl group, -N(R6)(R7), -S-R8 or -CO-R9; R5 represents an aminogroup or mono- or di(C1-C6alkyl)aminogroup; R6-R9 have values, given in the invention formula.EFFECT: invention relates to the pharmaceutical product, pharmaceutical composition and method of treating a cancer disease.11 cl, 3 tbl, 191 ex

4-phenoxy-nicotanimides or 4-phenoxy-pyrimidine-5-carboxamides // 2565077
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula I wherein A1 represents CR13; A2 represents CR14 or N; R1 and R2 are independently specified in hydrogen, halogen, and halogen-C1-7-alkyl; R13 and R14 are independently specified in hydrogen, C1-7-alkyl, halogen, halogen-C1-7-alkyl and C1-7-alkoxy; R3 is specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxy, piperidinyl and -NR15R16, wherein R15 and R16 are independently specified in hydrogen, C1-7-alkyl and C3-7-cycloalkyl; R4 is specified in hydrogen and C1-7-alkyl; or R3 and R4 or R3 and R14 together represent -X-(CR17R18)n- and form a part of the ring, wherein X is specified in -CR19R20- and -NR21-; R17, R18, R19, R20 are hydrogen; R21 is specified in hydrogen, C1-7-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-7-alkyl, wherein C3-7-cycloalkyl is substituted or not by C1-7-alkoxycarbonyl, and C1-7-alkylsulphonyl; and n represents 1, 2 or 3; B1 represents N or N+-O-; B2 represents CR7 or N; R5, R6 and R7 are independently specified in hydrogen, halogen and C1-7-alkyl; and R8, R9, R10, R11 and R12 are those as presented in the patent claim. The compound also refers to pharmaceutically acceptable salts of the compounds of formula I and to pharmaceutical compositions possessing GPBAR1 receptor agonist activity.EFFECT: compounds of formula I as GPBAR1 agonists.20 cl, 85 ex

Sulphonamide compounds possessing trpm8 antagonist activity // 2563030
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new sulphonamide compounds of the structure as follows or to its pharmaceutically acceptable salt, wherein a bicyclic aromatic heterocycle consisting of pyridine condensed with benzene; one of Y and Z is CR2d, whereas the other one is a chemical bond; the ring B is (a) mono- or bicyclic aromatic hydrocarbon having 6-11 carbon atoms as circular atoms; (b) 5-11-merous mono- or bicyclic aromatic heterocycle containing carbon atoms and 1-4 heteroatoms specified in oxygen, sulphur and nitrogen atoms; or (c) 4-12-merous mono- or bicyclic non-aromatic heterocycle containing carbon atoms and 1-4 heteroatoms specified in oxygen, sulphur and nitrogen atoms; ring C: benzene, R1: (a) H; (b) C1-C6alkyl, which can be optionally substituted by 1-3 groups specified in halogen, oxo and hydroxy; (c) C3-C7cycloalkyl; (d) C1-C6alkoxy group; or (e) halogen; each of R2a, R2b, R2c and independently represents(a) H; (b) C1-C6 alkyl, which can be optionally substituted by 1-3 groups specified in C1-C6alkoxy group, halogen and hydroxy; (c) C3-C7cycloalkyl; (d) C1-C6alkoxy group; (e) phenyl; (f) 6-merous monocyclic aromatic heterocyclic group containing carbon atoms and 1-4 heteroatoms specified in oxygen, sulphur and nitrogen atoms; (g) 5-merous monocyclic non-aromatic heterocyclic group containing carbon atoms and 1-4 heteroatoms specified in oxygen, sulphur and nitrogen atoms; or (h) halogen, each of R3a, R3b, R3c and R3d independently means (a) H; (b) C1-C6alkyl, which can be optionally substituted by 1-7 groups specified in C3-C7cycloalkyl (wherein cycloalkyl can be optionally substituted by 1 group specified in C1-C6alkyl and C1-C6halogenalkyl), C1-C6alkoxy group, C1-C6halogenoalkoxy, halogen and hydroxy; (c) C3-C7cycloalkyl; (d) C1-C6alkoxy group, which can be optionally substituted by 1-3 groups specified in C3-C7cycloalkyl, C1-C6alkoxy group and halogen; (e) C3-C7cycloalkoxy group; (f) phenyl, which can be optionally substituted by 1 group specified in halogen; (g) 6-merous monocyclic aromatic heterocyclic group containing carbon atoms and 1-4 heteroatoms specified in oxygen, sulphur and nitrogen atoms; (h) phenoxy group; (j) halogen; or (k) hydroxy, each of R5 and R6: H, n means 0 or 1, X is (a) a carboxy group; (b) C1-C6alkoxycarbonyl; (c) hydroxy-C1-C6-alkyl, (d) aminocarbonyl, wherein a nitrogen atom can be optionally substituted by one group specified in C1-C6alkyl, C1-C6alkoxy group and nitrile; or (e) C2-C7alkanoyl. The invention also refers to a pharmaceutical composition based on the declared compound and to using the declared compound.EFFECT: produced are new sulphonamide compounds possessing TRPM8 antagonist activity.16 cl, 20 tbl, 242 ex

Derivatives of chinolinesulphonamides and their application for modulation of pkm2 activity // 2561132
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to heterocyclic compounds of general formula (I) and to their pharmaceutically acceptable salts, where each W, X, Y and Z represents CH; each W, X and Y represents CH and Z represents N or each W, X and Z represents CH and Y represents N; D and D1 are independently selected from bond or NRb; A represents chinolinyl; L is bond, -C(O)-, -(CRcRc)m-, -OC(O)-, -(CRcRc)m-OC(O)-, -(CRcRc)m-C(O)-, -NRbC(S)- or -NRbC(O)- (where point of binding to R1 is on the left side); R1 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, aryl (where aryl represents phenyl or naphthyl), heteroaryl (where heteroaryl represents 5-10-membered mono- or bicyclic aromatic ring with 1-3 heteroatoms, selected from nitrogen and sulphur) and heterocyclyl (where heterocyclyl represents tetrahydrofuranyl or azetidinyl) each of which is substituted with 0-5 substituents Rd; each R3 is independently selected from halo-C1-alkyl, C1-C6 alkyl, hydroxyl and -ORa; each Ra is independently selected from C1-C6 alkyl and acyl (where acyl represents -C(O)CH3), hydroxy-C1-C2 alkyl; each Rb is independently selected from hydrogen and C1-C6 alkyl; each Rc is independently selected from hydrogen, C1-C6 alkyl or two Rc, taken together with atoms of carbon, which they are bound to, form C3-cycloalkyl; each Rd is independently selected from halo-C1-alkyl, halo-C1-alkoxy, C1-C6 alkyl, C2-C6 alkinyl, cyano, hydroxyl, -C(O)Ra, -OC(O)Ra, -C(O)ORa, -SRa, -NRaRb and -ORa; n equals 0 or 1; m equals 1, 2 or 3; h equals 1 or 2 and g equals 1. Invention also relates to particular compounds, pharmaceutical composition, based on formula (I) compound and method of modulating PKM2 activity.EFFECT: novel heterocyclic compounds, useful for modulating PKM2 activity, have been obtained.46 cl, 1 dwg, 2 tbl, 2 ex

Compounds and methods for using // 2561109
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound or its pharmaceutically acceptable salt; the compound is a) described by Formula wherein R1 is absent; the index n means an integer from 0 to 2; when n = 0, then X1 means -CH2-; X1 means a member specified in a group consisting of -CH2-, -O-, -N(H)- and -N(Ra)-, wherein Ra is specified in a group consisting of C1-6alkyl; each X2a, X2b and X2c is independently specified in a group consisting of C(H); A means a member specified in a group and (aa), wherein R3 is independently specified in a group consisting of halogen and -Rg, wherein Rg is specified in a group consisting of C1-4alkyl; B means a member specified in a group of compounds and (aaa), wherein R4a is absent; L is absent or means a member specified in a group consisting of C6arylene-C1-6heteroalkylene, C1-6heteroalkylene, C1-6alkylene, C2-6alkenylene, C2-6alkynylene and -O-; heteroalkylene contains 1 or 2 heteroatoms specified in a group consisting of N, O or S; E means hydrogen or halogen; or alternatively, E is specified in a group consisting of phenyl, C5-6heteroaryl; C5-6heteroaryl is specified in a group consisting of pyrazol, pyridine and pyrazine, C3-7heterocycloalkyl; C3-7heterocycloalkyl is specified in a group consisting of morpholine, pyrrolidine, piperidine and piperazine, and C3-7cycloalkyl, and if so required 1 ring independently specified in a group consisting of a 5-merous heterocyclic ring containing 2 O heteroatoms, a benzene ring and a 5,6-merous heteroaromatic ring containing 2 N heteroatoms can be condensed with E; E and 1 ring condensed with E if so required are independently protected 0 to 5 times by substitutes R6 specified in a group consisting of halogen, -NRpRq, -ORp, -C(O)ORp, -NRpC(O)ORr, -S(O)2Rr, -Rr, -Rs, =O, -Z1-NRpRq and -Z1-Rs; Z1 means C1-6alkylene; each Rp and Rq are independently specified in hydrogen and C1-6alkyl; Rr is specified in a group consisting of C1-6alkyl and phenyl; Rs is specified in a group consisting of phenyl and pyrazole, and 1 pyrimidine ring can be condensed with Rs. Or the compound b) is specified in a group consisting of 2-(1-(benzo[d]thiazol-2-ylcarbamoyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)-N,N-dimethylthiazol-4-carboxamide, 2-(1-(benzo[d]thiazol-2-ylcarbamoyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-fluorophenoxy)thiazol-4-carboxamide and N-(benzo[d]thiazol-2-yl)-6-(6-(methylsulphonylcarbamoyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide. The invention also refers to specific compounds. The compounds according to the inventions are applicable for a pharmaceutical composition having BCl-XL antiapoptosis protein inhibitory activity. The pharmaceutical composition contains a therapeutically effective amount of the composition of formula a) or b), or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable diluent, carrier or excipient.EFFECT: new compounds inhibiting BCl-XL antiapoptosis protein.21 cl, 2 tbl, 7 dwg, 66 ex

Antibacterial pharmaceutical composition and method for preparing it // 2561037
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to medicine and concerns a pharmaceutical composition in the form of a film-coated tablet. As an active substance, the composition contains moxifloxacin hydrochloride in a therapeutically effective amount, and auxiliary ingredients, i.e. silicon dioxide, sodium croscarmellose, an excipient and a lubricant, but it is free from lactose. The excipient represents microcrystalline cellulose or its combination with magnesium carbonate basic. A method for producing the composition involves mixing powders of moxifloxacin hydrochloride, excipient, silicon dioxide, moisturising, granulating, drying, lubricating, tabletting and coating.EFFECT: preparation is applicable to control bacterial infections and possesses stability, adequate strength, good appearance and high release rate.7 cl, 1 tbl, 6 ex

Pharmaceutical composition of moxifloxacin and method for producing it // 2558932
FIELD: medicine.SUBSTANCE: as a binding agent, the composition contains completely pregelatinised corn starch; as a filling agent, it contains microcrystalline cellulose; a disintegrating agent is sodium croscarmellose, and a lubricant is magnesium stearate. A completely pregelatinised corn starch/microcrystalline cellulose ratio makes 0.4. The composition can be presented in the form of tablets or Vivacoat-coated tablets. What is also presented is a method for producing the pharmaceutical composition. The composition is applicable for treating bacterial infections in mammals.EFFECT: moxifloxacin tablets are lactose-free and characterised by adequate mechanical strength, hardness, stability and release properties.4 cl, 5 tbl

odulators of atp-binding cassette transporters // 2556984
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula A-I, where G1 stands for hydrogen atom or R'; G2 stands for halogen atom, CN, CF3, isopropyl or phenyl, where said isopropyl or phenyl is optionally substituted with up to three substituents, independently selected from WRW; G3 stands for isopropyl or (C3-C10)cycloaliphatic ring, where said G3 is optionally substituted with up to three substituents, independently selected from WRW; W stands for bond or (C1-C6)alkylidene chain, where up to two methylene groups of W residue are optionally and independently substituted for -CO2- or -O-; RW stands for R'; and R' is independently selected from hydrogen atom or (C1-C8)alkyl group. Invention also relates to method of obtaining compound of formula FF (stands for bromine atom, fluorine atom or tret-butyl; G3 stands for tret-butyl) by hydrogenation of respective nitrocompound in presence of palladium catalyst and to methods of obtaining C-9 and 433 compounds, which include stage of hydrogenation of respective nitrocompound in presence of palladium catalyst as intermediate stage.EFFECT: formula A-I compounds, which are intermediate for synthesis of modulators of ATP-binding cassette ("ABC") transporters.35 cl, 4 tbl, 80 ex

Aminopyrazol triazolothiadiazole c-met protein kinase inhibitors // 2552993
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula , wherein R1 represents methyl or ethyl, R2 represents hydrogen, fluorine or methyl, R3 represents hydrogen, fluorine or methyl, each R4 represents hydrogen and R5 represents hydrogen, methyl. The invention also refers to a pharmaceutical composition for treating or relieving a degree of severity of a proliferative disorder by means of compounds of formula (I).EFFECT: compounds are effective in preparing a drug for treating or reducing a degree of severity of metastatic cancer, glioblastoma, gastric carcinoma or cancer specified in colon cancer, breast cancer, prostate cancer, cerebral cancer, liver cancer, pancreatic cancer or lung cancer and hepatocellular carcinoma.16 cl, 4 tbl, 6 ex

odulators of atp-binding transporters // 2552353
FIELD: medicine.SUBSTANCE: invention relates to a method of treatment or relieving the severity of cystic fibrosis in a patient, where the patient has the cystic fibrosis transmembrane receptor (CFTR) with R117H mutation, including a stage of introduction to the said patient of an effective quantity of N-(5-hydroxy-2,4-ditert-butyl-phenyl)-N-methyl-4-oxo-1H-quinoline-3-carboxamide.EFFECT: elaborated is the method of treating cystic fibrosis, based on the application of N-(5-hydroxy-2,4-ditert-butyl-phenyl)-N-methyl-4-oxo-1H-quinoline-3-carboxamide.3 cl, 4 tbl, 30 ex

Pde10 inhibitors and compositions containing them and methods // 2545456
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.EFFECT: compounds of formula (I) as PDE10 inhibitors.39 cl, 13 ex, 2 tbl, 77 dwg

N1/n2-lactam acetyl-coa-carboxylase inhibitors // 2540337
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formula or its pharmaceutically acceptable salt, wherein G represents a group of formula or R1 represents isopropyl or tert-butyl; R2 represents naphthyl, quinolinyl or isoquinolinyl, R2 is optionally independently substituted by one-two groups of methyl, methoxy or chloro; R3 represents hydrogen. The invention also refers to a pharmaceutical composition containing the compound of formula (I).EFFECT: compounds of formula (I) as acetyl-CoA-carboxylase(s) inhibitors.6 cl, 10 dwg, 7 tbl, 125 ex

Bicyclic nitrogen-containing heterocyclic compounds, useful in treatment of hepatitis c // 2540332
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to novel heterocyclic compounds of general formula (I) or to their pharmaceutically acceptable salts, where X1 stands for N and X2, X3 and X4 stand for CR5; or X1 and X2 stand for N and X3 and X4 stand for CR5; or X1, X2 and X4 stand for CR5, and X3 stands for N; or X1, X2, X3 and X4 stand for CR5; R1 stands for (a) heteroaryl radical, selected from the group, including pyridinyl, 2-oxo-1,2-dihydropyridin-3-yl, 2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl, said heteroaryl optionally contains as substituents halogen, C1-C6-alkyl, C1-C6-hydroxyalkyl, C1-C3-alkoxy-C1-C3-alkyl, C1-C6-alkoxygroup, or (b) heterocyclic radical, selected from the group, including 2-oxotetrahydropyrimidin-1-yl, 2,6-dioxotetrahydropyrimidin-1-yl, 2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl and 2,4-dioxotetrahydropyrimidin-1-yl; R2 stands for hydrogen or C1-C6-alkoxygroup; R3 stands for (a) phenyl, (b) pyridine, where said phenyl or said pyridine independently optionally contain 1-3 substituents, selected from the group, including halogen, (CH2)nNRcRd, or (c) NRaRb, (d) hydrogen, (e) halogen; Ra and Rb together with nitrogen atom, which they are bound to, form cyclic amine, containing from 3 to 5 carbon atoms, independently substituted with group (CH2)nNReRf; Rc and Rd independently stand for hydrogen, SO2R8, where R8 stands for C1-C6-alkyl; Re and Rf independently stand for hydrogen, SO2R8, where R8 stands for C1-C6-alkyl; R4 stands for CF3, CH2CF3 or CR4aR4bR4c, where (i) R4a, R4b and R4c are independently selected from the group, including C1-C3-alkyl, CD3; or (ii) taken together R4a and R4b form C2-C4-alkylene and R4c stands for cyanogroup or C1-C2-fluoroalkyl; R5 in each case independently stands for hydrogen, halogen, C1-C6-alkoxygroup or C1-C6-alkyl; n in each case independently equals 0-3. Invention also related to method of treating infection with hepatitis C virus, method of inhibiting HCV replication, application of formula (I) compound and based on it pharmaceutical composition.EFFECT: novel heterocyclic compounds of formula (I), possessing useful biological activity are obtained.24 cl, 3 tbl, 43 ex

Amorphous salt of macrocyclic hcv inhibitor // 2536868
FIELD: chemistry.SUBSTANCE: invention relates to a sodium salt of formula I compound in the solid amorphous form. The sodium salt of formula (I) compound is obtained by (a) the preparation of a mixture of the formula I compound in a non-aqueous solvent and a water solution of sodium hydroxide; and (b) drying by spraying of the mixture (a) in a spray-drying device. The stage (a) includes mixing the sodium hydroxide solution with the said solvent and further addition of the formula I compound. The solvent is represented by halogen-containing hydrocarbon. The invention also relates to a pharmaceutical composition, possessing HCV inhibiting properties, including sodium salt of the formula I compound in the amorphous form, and a pharmaceutically acceptable carrier.EFFECT: sodium salt of the formula (I) compound for application as HCV inhibitor and medication for HCV treatment.10 cl, 7 dwg, 3 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

New phenylamide or pyridylamide derivatives and using them as gpbar1 agonists // 2533887
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new phenylamide or pyridylamide derivatives of formula or their acceptable salts, wherein A1 is CR12 or N; A2 is CR13 or N; R1 and R2 are independently specified in hydrogen, C1-7-alkyl, halogen and C1-7-alkoxygroup; R12 and R13 are independently specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, amino group and C1-7-alkylsulphanyl; R3 is specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, cyano group, C3-7-cycloalkyl, five-merous heteroaryl and phenyl; R4 is specified in methyl and ethyl; or R3 and R4 together represent -X-(CR14R15)n- and form a part of the ring, wherein X is specified in -CR16R17-, O, S, C=O; R14 and R15 are independently specified in hydrogen or C1-7-alkyl; R16 and R17 are independently specified in hydrogen, C1-7-alkoxycarbonyl, heterocyclyl substituted by two groups specified in a halogen, or R16 and R17 together with an atom C, which they are attached to, form =CH2 group; or X is specified in a group NR18; R14 and R15 are hydrogen; R18 is specified in hydrogen, C1-7-alkyl, halogen-C1-7-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-7-alkyl, heterocyclyl, heteroaryl-C1-7-alkyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkylcarbonyloxy-C1-7-alkyl, phenyl, wherein phenyl is unsubstituted, phenylcarbonyl, wherein phenyl is substituted by C1-7-alkoxycarbonyl, and phenylsulphonyl, wherein phenyl is substituted by carboxyl-C1-7-alkyl, or R18 and R14 together represent -(CH2)3- and form a part of the ring, or R18 together with R14 and R15 represent -CH=CH-CH= and form a part of the ring; and n has the value of 1, 2 or 3; B1 represents N or CR19 and B2 represents N or CR20, provided no more than one of B1 and B2 represents N; and R19 and R20 are independently specified in a group consisting of hydrogen and halogen-C1-7-alkyl; R5 and R6 are independently specified in a group consisting of hydrogen, halogen and cyano group; and one-three, provided R4 represents methyl or ethyl, two of the residues R7, R8, R9, R10 and R11 are specified in C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, cyano group, C1-7-alkoxycarbonyl, hydroxy-C3-7-alkynyl, carboxyl-C1-7-alkyl, carboxyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkynyl, C1-7-alkoxycarbonyl-C1-7-alkylaminocarbonyl, carboxyl-C1-7-alkylaminocarbonyl-C1-7-alkyl, carboxyl-C1-7-alkyl-(C1-7-alkylamino)-carbonyl-C1-7-alkyl, phenyl-carbonyl, wherein phenyl is unsubstituted, phenyl-C1-7-alkyl, wherein phenyl is substituted by 1-2 groups specified in a halogen, C1-7-alkoxygroup, carboxyl, phenyl-C2-7-alkynyl, wherein phenyl is substituted by 2 groups specified in halogen, carboxyl or C1-7-alkoxycarbonyl, and pyrrolidine carbonyl-C1-7-alkyl, wherein pyrrolidinyl is substituted by carboxyl, and the other R7, R8, R9, R10 and R11 represent hydrogen; the term 'heteroaryl' means an aromatic 5-merous ring containing one or two atoms specified in nitrogen or oxygen; the term 'heterocyclyl' means a saturated 4-merous ring, which can contain one atom specified in nitrogen or oxygen. Besides, the invention refers to a pharmaceutical composition based on the compound of formula I.EFFECT: there are prepared new compounds possessing the GPBAR1 agonist activity.21 cl, 1 tbl, 190 ex

New benzene sulphonamide compounds, methods for preparing and using them in therapy and cosmetics // 2528826
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new benzene sulphonamide compounds, wherein the compounds are specified in a group of the following compounds, including additive salts with pharmaceutically acceptable acid, additive salts with pharmaceutically acceptable base and enantiomers of these compounds: 1) 3-[(4-but-2-inyloxybenzenesulphonyl)-methylamino]-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 2) (S)-3-(4-but-2-inyloxybenzenesulphonylamino)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 3) (S)-3-(4-benzyloxybenzenesulphonylamino)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 4) (S)-3-[(4-benzyloxybenzenesulphonyl)-methylamino]-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 5) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 6) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(naphthalen-1-ylmethoxy)-benzenesulphonylamino]-propionamide, 7) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-(4-propoxybenzenesulphonylamino)-propionamide, 8) (S)-3-[4-(3-cyanobenzyloxy)-benzenesulphonylamino]-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 9) (S)-3-[4-(4-cyanobenzyloxy)-benzenesulphonylamino]-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 10) benzyl-4-{(S)-1-hydroxycarbamoyl-2-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-entyl}-piperazine-1-carboxylate, 11) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-phenylpiperidin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 12) (R)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 13) (S)-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-2-piperazin-1-ylpropionamide, 14) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide hydrochloride, 15) tert-butyl-3-{4-[(S)-2-hydroxycarbamoyl-2-(4-methanesulphonylpiperazin-1-yl)-ethylsulphamoyl]-phenoxymethyl}-2-methylindole-1-carboxylate difluoroacetate, 16) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(quinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 17) (S)-2-(4-benzylpiperazin-1-yl)-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 18) (S)-2-[4-(4-fluorobenzyl)-piperazin-1-yl]-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino-propionamide, 19) (S)-2-(4-ethulpiperazin-1-yl)-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 20) (S)-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-2-[4-(4-trifluoromethylbenzyl)-piperazin-1-yl]-propionamide, 21) (S)-N-hydroxy-2-[4-(4-methylbenzyl)-piperazin-1-yl]-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 22) (S)-3-[4-(benzoisoxazol-3-ylmethoxy)-benzenesulphonylamino]-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-propionamide, 23) (S)-N-hydroxy-2-(4-isobutyrylpiperazin-1-yl)-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 24) (S)-N-hydroxy-2-[4-(2-methylpropane-1-sulphonyl)-piperazin-1-yl]-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-propionamide, 25) (S)-N-hydroxy-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-trifluoromethylpyrazolo[1,5-a]pyridin-3-ylmethoxy)-benzenesulphonylamino]-propionamide, 26) (S)-N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)-benzenesulphonylamino]-2-[4-(propane-2-sulphonyl)-piperazin-1-yl]-propionamide, and 27) (S)-2-(4-benzylpiperazin-1-yl)-N-hydroxy-3-[4-(2-trifluoromethylpyrazolo[1,5-a]pyridin-3-ylmethoxy)-benzenesulphonylamino]-propionamide. The invention also refers to pharmaceutical and cosmetic compositions on the basis of the above compounds possessing TNFα-converting enzyme (TACE) activity.EFFECT: there are prepared new compounds and compositions on the basis thereof which can be used in medicine and veterinary science for treating rheumatoid arthritis, non-insulin dependent diabetes mellitus, Crohn's disease or inflammatory skin disease.35 cl, 28 ex

New pyrazole-3-carboxamide derivative possessing antagonist activity on 5-нт2в receptor // 2528406
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula (I), wherein A means morpholinyl, 1,4-oxazepamyl, piperidinyl, pyrrolidinyl or azetidinyl which is bound to N; R1 means C1-C6-alkyl group; R2 means bicyclic aryl group specified in 1H-indolyl, 1H-pyrrolo[3,2-b]pyridyl, quinolyl, naphthyl, 1H-pyrrolo[2,3-b]pyridyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, benzo[b]thiophenyl, imidazo[1,2-a]pyridyl, benzo[b]thiazolyl, 5H-pyrrolol[2,3-b]pyrazinyl and quinoxalinyl which can be substituted by R4; R3 means hydrogen or halogen atom; R4 means C1-C6-alkyl group, C1-C6-halogenalkyl group, OR1A, halogen, -(CH2)aOH, CN, NHCOR1A, SO2R1A or NHSO2R1A; R5 means C1-C6-alkyl group, -(CH2)aOH, -(CH2)aOR1B, halogen or CONH2; provided p is a plural number, R5 can be identical or different, or R5 can be combined with another R5; each of R1A and R1B independently means C1-C6-alkyl group; a is equal to 0, 1 or 2; n is equal to 1 or 2; p is equal to 0, 1, 2, 3, 4 or 5. Besides, the invention refers to intermediate compounds of formulas (IA) and (IB) for preparing the compounds of formula (I), to a preventive or therapeutic agent containing the compounds of formula (I), pharmaceutical compositions, using the compounds of formula (I) and to a method for preventing or treating diseases.EFFECT: compounds of formula (I) as selective 5-HT2B receptor antagonists.11 cl, 1 dwg, 18 tbl, 88 ex

Apoptosis-inducing preparations for treatment of cancer and immune and autoimmune diseases // 2527450
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to compound of formula or to its therapeutically acceptable salt, where A1 represents N or C(A2); A2 represents H; B1 represents H, OR1 or NHR1; D1 represents H; E1 represents H; Y1 represents CN, NO2, F, Cl, Br, I, R17 or SO2R17; R1 represents R4 or R5; Z1 represents R26 or R27; Z2 represents R30; Z1A and Z2A both are absent; L1 represents R37; R26 represents phenylene; R27 represents indolyl; R30 represents piperasinyl; R37 represents R37A; R37A represents C2-C4 alkylene; Z3 represents R38, R39 or R40; R38 represents phenyl; R39 represents benzodioxilyl; R40 represents C4-C7cycloalkenyl, heterocycloalkyl, which represents monocyclic six- or seven-member ring, containing one heteroatom, selected from O, and zero of double bonds, or azaspiro[5.5]undec-8-ene; the remaining values of radicals are given in i.1 of invention formula. Invention also relates to pharmaceutical composition, based on claimed compound.EFFECT: novel compounds, which can be applied in medicine for treatment of diseases, in the process of which anti-apoptotic Bcl-2 protein is expressed, are obtained.8 cl, 2 tbl, 411 ex
 
2551106.
Up!