Containing three or more hetero rings (C07D405/14)

Heterocyclic compounds useful as pdk1 inhibitors // 2615130
FIELD: chemistry.SUBSTANCE: present invention relates to novel compounds of general formulae II, III, IV and V, where values of radicals are given in description, or pharmaceutically acceptable salts thereof, which can be used as PDK1 inhibitors.EFFECT: present invention also relates to pharmaceutical compositions based thereon and to methods of treating cancer, mediated by protein kinase PDK1.32 cl, 2 tbl, 445 ex
Novel pyrazine derivatives // 2612138
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I), a pharmaceutically acceptable salt or ester thereof. Compounds of formula (I) modulate activity of cannabinoid receptor 2 (CB2). . In formula (I) R1 is a halophenyl or C3-C6-cycloalkyl-C1-C6-alkoxy; R2 is a C3-C6-cycloalkyl, azetidinyl or difluoroazetidinyl; one of R3 and R4 is hydrogen, and other is -(CR5R6)-R7 or -A-R7; or R2 is a C3-C6-cycloalkyl, and R3 and R4 together with a nitrogen atom, to which they are bonded, form piperidinylamine; R5 and6 are independently selected from hydrogen, C1-C6-alkyl, halogen-C1-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C6-alkyl, phenyl, phenyl-C1-C6-alkyl and halophenyl; or R5 and6 together with carbon atom, to which they are bonded, form C3-C6-cycloalkyl or oxetanyl; R7 is cyano, carboxy, 5-methyl-[1,2,4]oxadiazol-3-yl, 5-amino-[1,2,4]oxadiazol-3-yl, thiazolyl, C1-C6-alkylthiazolyl, pyridinyl, C1-C6-alkylaminocarbonyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, aminocarbonyl, C1-C6-alkoxycarbonyl, di-C1-C6-alkylaminocarbonyl, phenyl-C1-C6-alkyl, pyridinyl-C1-C6-alkyl, halogen-C1-C6-alkylaminocarbonyl, 5-phenyl-2-methyl-oxazol-4-yl-alkyl, aminocarbonyl-C1-C6-alkyl or halogen; and A is cyclohexyl or thiophenyl, under condition specified in patent claim. Invention also relates to individual compounds, pharmaceutical composition, use of compounds and to a method of modulating CB2 receptor activity.EFFECT: technical result is obtaining novel compounds of formula (I) modulating activity of cannabinoid receptor 2 (CB2).19 cl, 111 ex

Pyrimidine gyrase and topoisomerase iv inhibitors // 2609259
FIELD: chemistry.SUBSTANCE: invention relates to a novel compound of formula (I) or a pharmaceutically acceptable salt thereof, which having gyrase MIC and topoisomerase IV inhibiting properties and can be used for treating bacterial infections, mediated by one or more bacteria from Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus aureus, Clostridium difficile, Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Mycobacterium avium complex, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium ulcerans, Chlamydophila pneumoniae, Chlamydia trachomatis, Haemophilus influenzae, Streptococcus pyogenes or β-haemolytic streptococci. Infections are infections of lower and upper airway, ear infections, pleuropulmonary and bronchial infections, infections of urinary tract, intraabdominal infections, cardiovascular infections, blood poisoning, sepsis, bacteriaemia, CNS infections, skin and soft tissue infection, gastro-intestinal infections, infections affecting bones and joints, genital infections, eye infections or granulomatous infections, uncomplicated skin and skin structure infections (uSSSI), catheter infections, pharyngitis, sinusitis, etc. In formula (I) R is hydrogen or fluorine; X is hydrogen, -PO(OH)2, -PO(OH)O-M+, -PO(O-)2⋅2M+ or -PO(O-)2⋅D2+; M+ is a pharmaceutically acceptable univalent cation, such as Li+, Na+, K+, N-methyl-D-glucamine and N(R9)4+, where each R9 is independently hydrogen or C1-C4 alkyl group; D2+ is a pharmaceutically acceptable divalent cation, such as Mg2+, Ca+2 and Ba2+.EFFECT: novel compounds.21 cl, 2 dwg, 27 tbl, 39 ex
Novel pyrrole compounds, synthesis method thereof and pharmaceutical compositions containing same // 2607788
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) possessing inhibitory activity on Bcl-2 family proteins. In formula (I) (I) A1 is hydrogen, (C1-C6)polyhaloalkyl group or (C1-C6)alkyl group, A2 is hydrogen, (C1-C6)polyhaloalkyl group, (C1-C6)alkyl group or cycloalkyl group, T denotes a hydrogen atom, (C1-C6)alkyl group, optionally substituted with one-three halogen atoms, group (C1-C4)alkyl-NR1R2 or group (C1-C4)alkyl-OR6, R1 and R2 each independently from each other is a hydrogen atom or (C1-C6)alkyl group, or R1 and R2 form with a nitrogen atom bearing them, heterocycloalkyl, R3 is (C1-C6)alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R4 is an aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R5 is hydrogen or halogen atom, R6 is a hydrogen atom or a linear or branched (C1-C6)alkyl group, Ra, Rb, Rc and Rd each independently from other represents hydrogen, linear or branched (C1-C6)alkyl, halogen atom, a linear or branched (C1-C6)alkoxy group, hydroxy group, R7-CO-NH-(C0-C6)alkyl-, R7-SO2-NH-(C0-C6)alkyl-, R7-NH-CO-NH-(C0-C6)alkyl-, R7-O-CO-NH-(C0-C6)alkyl-, or substitutes of pair (Rb, Rc) form together with carbon atoms carrying them, a ring consisting of 5–6 ring members, which may contain 1–2 oxygen atoms, R7 is hydrogen, linear or branched (C1-C6)alkyl, aryl or heteroaryl. Invention also relates to methods of producing compounds of formula (I), to a pharmaceutical composition, use of a pharmaceutical composition for preparing a drug, use of compound of formula (I) for preparing a drug.EFFECT: obtaining novel compounds of formula (I) possessing inhibitory activity on Bcl-2 family proteins.37 cl, 2 tbl, 473 ex
Sulfonamide derivative and medicinal use thereof // 2607081
FIELD: chemistry; pharmaceutics.SUBSTANCE: invention relates to novel sulfonamide derivatives of general formula (1) or pharmaceutically acceptable salts thereof, possessing the properties of inhibition integrin α4β7. In general formula (1) (1), A means a group presented by general formula (2-1) or (2-2) , where Arm is a 5- or 6-member aromatic ring, containing 0, 1 or 2 heteroatoms, selected from nitrogen atoms, R1 and R11, each, independently, represents any substitute selected from a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, mono- or di-lower alkylamino group, R12, R13 and R14, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group, lower alkoxy group, amino group, lower alkylamino group, low di(alkyl)amino group or (lower alkylamino)lower alkyl group, R2 and R3, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group or lower alkoxy group, B is represents any substitute selected from lower alkoxy group, optionally substituted by hydroxyl group, lower alkyl group, mono- or di-lower alkylamino group; C3-C6cyclic alkoxy group and/or 6-member(s) heterocyclic(s) group (groups) with an oxygen atom, sulphur atom or a nitrogen atom as heteroatom, hydroxyl group, R41 is represents a hydrogen atom or lower alkyl group, a, b, c and d, each, independently, represents C-R31, C-R32, C-R33 and C-R34 respectively, but one or two of a, b, c and d, each, can be a nitrogen atom, R31, R32, R33 and R34, each, independently, represents any substitute selected from a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, provided that any R31, R32, R33 and R34 represents a halogen atom or lower alkyl group, e, f, g and h, each, independently, represents C-R35, C-R36, C-R37 and C-R38 respectively, however, one or two of e, f, g and h, each, can be a nitrogen atom, R35, R36, R37 and R38, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group or lower alkoxy group, D represents a phenyl group or a 5 -or 6-member aromatic heterocyclic group, containing a nitrogen atom, an oxygen atom or sulphur atom, optionally containing a substitute(s), selected from a group consisting of hydroxyl groups, lower alkyl groups, lower alkoxy groups, E is a 5- or 6-member heterocyclic group with 1-4 heteroatoms, selected from nitrogen atoms, an oxygen atom and sulphur atom in the cycle, optionally containing a substitute(s), selected from a group consisting of halogen atoms, hydroxyl groups, lower alkyl groups, lower alkoxy groups, amino groups, 4- or 6-member cyclic amino groups, carboxyl groups and lower alkoxy-carbonyl groups; aminocarbonyl group, optionally containing a substitute(s) selected from the group, consisting of hydroxyl groups, lower alkyl groups, lower alkoxy groups, 5- or 6-member heterocyclic groups, containing 1, 2, 3 or 4 heteroatoms, selected from a group consisting of oxygen atoms, sulphur atoms and nitrogen atoms as a component(s) ring atom(s), and substituted by heterocycle of lower alkyl groups, where heterocycle means a 5- or 6-member heterocyclic groups, containing 1, 2, 3 or 4 heteroatoms, selected from group consisting of oxygen atoms, sulphur atoms and nitrogen atoms as a component(s) ring atom(s); hydrogen atom, hydroxyl group, lower alkyl group, lower alkoxy group, amino group, lower alkyl-carbonyl group, lower alkyloxy-carbonyl group or a lower alkylaminoalkilen group, and provided that the lowest alkyl-carbonyl group and the lowest alkyloxycarbonil group can be, each of which, are connected to a phenyl group, presented D, to form condensed ring.EFFECT: compounds can be used for treating or preventing an inflammatory disease, in which the pathological condition associated with indirect by integrins α4β7 adhesion process.15 cl, 2 tbl, 258 ex
Pyrrolidinyl urea and pyrrolidinyl thiourea compounds as trka kinase inhibitors // 2606131
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula I given below, or to their stereoisomers, tautomers or pharmaceutically acceptable salts thereof. R1, R2, Ra, Rb, Rc, Rd, X, Y, B, and ring C are as defined by the invention formula. Wherein the Y-B moiety and the NH-C(=X)-NH moiety are in the trans configuration.EFFECT: compounds of formula I are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.56 cl, 31 tbl, 649 ex

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

ethod of producing chiral hydrazides // 2588570
FIELD: chemistry.SUBSTANCE: invention relates to methods of producing chiral compounds, particularly to method of producing chiral compound of formula (II). Method involves reaction of chiral compound of formula (I) with H2N-NH-CHO in solvent to obtain compound of formula (II). In formulae (I) and (II) Y denotes substituted or unsubstituted aryl fragment, wherein substituted aryl fragment contains 1, 2 or 3 substitutes, which are selected from group comprising halogen, alkyl and C1-C6alkoxy group. Invention also relates to methods of producing chiral compounds of formulae (III)-(V) using method of producing chiral compound of formula (II), chiral compounds of formulae (II)-(V) and use thereof to obtain fungicidal agent, preferably of posaconazole.EFFECT: in formulae (III)-(V) Y has value specified for compounds of formulae (I) and (II); Raa, Rbb and Rcc can be identical or different and denote alkyl or aryl residue; R1 denotes an alkyl residue.31 cl, 2 dwg, 3 ex

Novel triazole compounds // 2588137
FIELD: pharmaceuticals.SUBSTANCE: invention relates to compounds of formula (I), pharmaceutically acceptable salts and esters. Compounds of formula (I) have affinity and selectivity for GABA A α5 receptor. In formula X is N or CH; R1, R2 - C1-C7-alkyl, phenyl substituted by 1 halogen, wherein one of substituents R1 and R2 is an alkyl group; R3 - haloC1-C7-alkyl, nitro, -C(O) R4, -C(O) NR5R6; R4 - C1-C7-alkyl, hydroxy, C1-C7-alkoxy; R5 - hydrogen, C1-C7-alkyl, haloC1-C7 alkyl hydroxyC1-C7-alkyl, -(CH2)n-C3-C8 cycloalkyl, - (CH2)n- (4-6 membered heterocycloalkyl with 1 heteroatom selected from O), wherein heterocycloalkyl is optionally substituted with one C1-C7-alkyl group; n is an integer ranging from 0 to 1; R6 - hydrogen, C1-C7-alkyl; or R5 and R6 together with nitrogen to which they are attached form a bicyclic 7-membered heterocycloalkyl with additional heteroatom selected from O, 6-membered heterocycloalkyl with additional heteroatom selected from O, S, wherein heterocycloalkyl is optionally substituted by one or more oxo groups. Invention also relates to a pharmaceutical composition comprising a compound of invention in an effective amount, to a method for treating or preventing diseases associated with GABA A α5 receptor, use of compounds for preparation of medicaments and use of compounds for treating or preventing diseases associated with GABA A α5 receptor.EFFECT: technical result is obtaining novel compounds having affinity and selectivity for GABA A α5 receptor.23 cl, 1 tbl, 53 ex

Diaminopyrimidine derivatives and methods for production thereof // 2587493
FIELD: pharmaceutics.SUBSTANCE: present invention relates to a novel diaminopyrimidine derivative formula 1 or pharmaceutically acceptable salts thereof possessing properties of agonist of 5-HT4 receptors. In formula 1 (Formula 1)R1 denotes a phenyl group substituted with one or more substitutes selected from a group consisting of hydroxy, amino, halogen, cyano, nitro, C1-5alkyl (where C1-5alkyl is optionally substituted with halogen), C1-5alkoxy, C1-5alkylthio, C1-5alkoxycarbonyl, aminosulphonyl and benzyloxycarbonylamino; or heteroaryl group selected from a group comprising pyridinyl, quinolinyl, chromenonyl, indolyl, indolinyl and benzimidazolyl, wherein heteroaryl group can be optionally substituted with one or more substitutes selected from a group consisting of C1-5alkyl (where C1-5alkyl is optionally substituted with halogen) and acetyl, R2 denotes hydrogen; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of hydroxy, C1-5alkoxy, benzylamino (where benzylamino is optionally substituted by halogen), phenylamino, C1-5alkylamino, C3-6cycloalkylamino and hydroxy-C1-5alkylamino; C1-5alkoxycarbonyl group or formyl group, R3 denotes hydrogen, hydroxyl group; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of C1-5alkoxycarbonylamino and di-C1-5alkylamino, or group selected from a group consisting of following formulae A, B, D and E (where symbol * in formulae A, B, D and E denotes position of attachment of said group of compounds of formula 1),R4 denotes hydrogen, R5 denotes C1-5alkyl group, optionally substituted phenyl or C2-6alkenyl group, optionally substituted phenyl or C3-6cycloalkyl, R6 denotes C1-10alkyl group, optionally substituted with a substitute selected from a group consisting of hydroxy, halogen, C1-5alkoxy, amino, C1-5alkoxycarbonylamino, benzyloxycarbonylamino, di-C1-5alkylamino, C1-5alkoxy-C1-5alkyloxy, phenoxy, benzyloxy, phenyl (where phenyl is optionally substituted with one or more substitutes selected from a group consisting of halogen, amino and C1-5alkoxy), thiophenyl, pyridinyl, piperidinyl, piperazinyl (where piperazinyl is optionally substituted with benzyl) and acetyl; C3-6cycloalkyl group; piperidinyl group; C1-10alkenyl group, optionally substituted phenyl; trifluoromethyl group, trifluoroethyl group or a phenyl group optionally substituted with halogen, R7 denotes hydrogen, R8 and R9 each independently denote hydrogen; C1-10alkyl group, optionally substituted with substitute selected from a group consisting of amino, C1-5alkoxycarbonylamino, hydroxy, C1-5alkylthio, C3-10cycloalkyl, phenyl (where phenyl is optionally substituted with one or more substitutes selected from a group consisting of hydroxy, C1-5alkyl, mono-or di-C1-5alkylamino, trifluoromethyl, halogen, C1-5alkoxy C1-5alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where furanyl is optionally substituted with mono-or di-C1-5alkyl), pyridinyl and benzyloxy; piperidinyl group, optionally substituted benzyl, benzoyl, C1-5alkyl or C1-5alkylcarbonyl; azetidinyl group, optionally substituted C1-5alkoxycarbonyl; C1-5alkylsulphonyl group or C3-10cycloalkyl group.EFFECT: invention relates to use of formula 1 or its pharmaceutically acceptable salt for preparing a drug for preventing or treating gastrointestinal motility dysfunction; gastrointestinal motor dysfunction is gastroesophageal reflux disease (GERD), lock (constipation), irritable bowel syndrome (IBS), dyspepsia, postoperative intestinal obstruction, prolonged gastric emptying, gastroparesis, intestinal pseudo-obstruction,drug-induced delayed transit content over colon or diabetic gastroparesis.9 cl, 54 tbl, 495 ex

ethod of producing chiral triazolones // 2585760
FIELD: chemistry.SUBSTANCE: invention relates to method of producing compound of formula (IVb), involving (1.1) using compound of formula (Ia) or salts thereof (Ia) (1.2) using phosgene derivative of formula (IIb) (IIb), wherein Y1N-and Y2N-denote identical or different optionally substituted nitrogen-containing heterocyclic fragments, preferably selected from group comprising imidazolyl and benzimidazolyl; (1.3) using compound of formula (III) or salts thereof (III), in which R1 denotes ethyl, and in which R denotes h; (2) mixing and introduction into reaction of compounds of formulae (Ia), (IIb) and (III) in solvent in any order to obtain reaction mixture containing Chiral compound of formula (IVb) (IVb). Invention also relates to chiral compound of formula (IVb), to optionally crystalline chiral compound of formula (IVb) and to compound of formula (IIc) (IIc) to obtain compound of formula (IVb) or formula (IVd). EFFECT: technical result is new non-toxic method of producing compound of formula (IVb).29 cl, 5 dwg, 6 ex

Cleaning of posaconazole and intermediate products for synthesis of posaconazole // 2585683
FIELD: chemistry.SUBSTANCE: present invention relates to method of producing hydrochloride salt (HCl) of compound of formula (I), wherein Y1 and Y2 independently denote F or Cl, preferably F, wherein said compound of formula (I) contains a cis-isomer and trans-isomer, which involves (1) using compound of formula (I), contained in first suitable solvent; and (2) treating compound of formula (I) contained in first suitable solvent, with help of HCl, contained in second suitable solvent to obtain HCl salt of compound of formula (I).EFFECT: invention also relates to crystalline hydrochloride salt (HCl) containing cis-isomer (II) and trans-isomer (III), use of said salt for preparing fungicide and to use of method for cleaning of mixture of diastereomers cis-isomer (II) and trans-isomer (III).32 cl, 1 dwg, 6 ex (I) (II) (III)

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
Sgc stimulators // 2582679
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula IA or IB or their pharmaceutically acceptable salts. The compounds of formula IA or IB possess sGC-stimulating activity. In formulas IA and IB , a circled B symbol means B ring, and B ring represents phenyl; n is equal to an integer specified in 0 to 1; each JB is independently specified in halogen; X is specified in N or C-H; D ring represents a 6-merous ring having X in formula IA, or a 5-merous ring having Y in formula IB; each Y is independently specified in C-H, C, N, O or S and independently substituted by JD when Y represents C or N; each of bonds between the two neighbouring atoms Y or between neighbouring Y and N in formula IB independently represents a single or double bond depending on whether Y is C, N, O or S, and D ring is aromatic; m is equal to an integer specified in 0 to 3; each JD is a substituted on a halogen or nitrogen atom of the ring and independently specified in halogen, -C(O)N(RD)2, -N(RD)2, -N(Rd)C(O)RD, -N(Rd)C(O)ORD, a 4-8-merous heterocyclic ring, wherein each specified 4-8-merous heterocyclic ring contains 1 to 2 heteroatoms independently specified in O, N or S; RC is specified in halogen, -CN, C1-6alkyl or C ring. The invention also refers to individual compounds and a pharmaceutical composition containing the compound of the invention or its pharmaceutically acceptable salt in an effective amount.EFFECT: produced are the new compounds of formula IA or IB possessing sGC-stimulating activity.58 cl, 6 tbl, 12 ex
Triazole derivatives as gaba receptor ligands // 2582337
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts. The compounds of formula (I) possess GABA A α5 receptor affinity and selectivity. In formula A represents -CH2-O- or -CH=CH-; X represents S or CH; Y represents O, NR9 or CR9, provided X represents S, then Y represents CR9, and if X represents CH, then Y represents O or NR9; each of u and v represents a single bond or double bond provided both u and v are other than double bonds, and both are other than single bonds; R1, R2 represent C1-7-alkyl, phenyl, optionally substituted halogeno, or 6-merous heteroaryl containing one ring N heteroatom; one of R1 and R2 represents C1-7-alkyl; R3 represents -C(O)NR5R6. The invention also refers to pharmaceutical compositions containing an effective amount of the compound of the invention and using the compounds for producing medicinal products.EFFECT: new compounds of formula (I) possessing GABA A α5 receptor affinity and selectivity are produced.16 cl, 1 tbl, 11 ex

Triazole derivatives and application thereof in neurological diseases // 2581504
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts and esters. The compounds of formula (I) possess GABA A α5 receptor affinity and selectivity. In formula A represents -CH2-O-, -CH=CH- or -C≡C-; X represents N or CH; Y represents N or CR9; Z represents N or CR10; R1, R2 represent C1-7-alkyl, phenyl optionally substituted by one halo, or 6-merous heteroaryl containing one ring N heteroatom optionally substituted by one halo, wherein one of R1, R2 represents C1-7-alkyl; R3 represents halo, -C(O)R4 or -C(O)NR5R6. The invention also refers to a pharmaceutical composition containing the compound of the invention in an effective amount and the use of the compounds to produce medicinal products.EFFECT: new compounds of formula (I) possessing GABA A α5 receptor affinity and selectivity are produced.24 cl, 1 tbl, 84 ex

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

Obtaining intermediate products for synthesis of posaconazole // 2580318
FIELD: chemistry.SUBSTANCE: claimed invention relates to method for obtaining chiral compound of formula or its salt, where Y1 and Y2 independently stand for F or Cl, preferably F, as well as to crystalline chiral compound of formula (IX) or its salt, in which from 80 to 95%, preferably from 85 to 95% of molecules of said crystalline compound or its salt are contained in form of cis-isomer of formula or its salt and from 20 to 5%, preferably from 15 to 5% of molecules of said crystalline compound or its salt are contained in form of trans-isomer of formula or its salt, and to its application for obtaining fungicidal preparation.EFFECT: increase of method efficiency.23 cl, 5 dwg, 2 tbl, 2 ex

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

Novel nicotinamide derivative or its salt // 2576623
FIELD: chemistry.SUBSTANCE: invention relates to nicotinamide derivative, represented by the following formula wherein R1 represents substituent, represented by the following formula R3 represents hydrogen atom or C1-6 alkyl, C3-8 cycloalkyl, phenyl, pyridyl or thienyl groups, each of which optionally contains substituent, selected from the group of substituents α1-1; group of substituents α1-1: halogen atom and C1-6 alkyl, C3-8 cycloalkyl, C1-6 alkoxy, C1-6 alkylthio, phenyl and pyrazolyl groups, each of which optionally contains halogen atom. R4 represents hydrogen atom, C1-6 alkyl group or C3-8 cycloalkyl group, R5 represents hydroxygroup, halogen atom or C1-6 alkyl or C1-6 alkoxy group, each of which optionally contains phenyl group, n represents integer number from 0 to 2, when n has value 2, R5 can be similar or different from each other and two R5, together with carbon atom, which they are bound to, can form C3-8 cycloalkane ring, X1 represents oxygen atom or -N(R6)- (wherein R6 represents hydrogen atom or acyl group), "*" represents binding site and R2 represents pyridyl, indazolyl, phenyl, pyrazole pyridyl, benzisoxazolyl, pyrimidinyl or quinolyl group, each of which optionally contains substituent, selected from the group of substituents α2-1;group of substituentsα2-1: halogen atom and C1-6 alkyl, C3-8 cycloalkyl, C1-6 alkoxy, (di) C1-6 alkylamino, acyl, pyrazolyl, triazolyl, morpholinyl and pyrrolizyl groups, each of which optionally contains substituent, selected from the group of substituents β2-1;group of substituents β2-1: halogen atom, oxo and C1-6 alkyl and C1-6 alkoxy groups.EFFECT: compounds possess excellent Syk-inhibiting activity.19 cl, 8 tbl

Compounds for treating clostridium difficile associated diseases // 2575477
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to a bibenzoimidazol derivative of general formula wherein R1 is pyridyl; R2 represents an aromatic 9-merous bicyclic ring system, wherein one or two carbon atoms can be substituted by N, O, or S; or to its pharmaceutically acceptable salt, hydrate or solvate. The invention also refers to a combination based on the compound of formula (I) and an additional specified agent, a pharmaceutical composition based on the compound of formula (I), a method of treating Clostridium difficile infection and a method of eliminating Clostridium difficile bacterium.EFFECT: produced are new bibenzoimidazol derivatives possessing effective biological properties.14 cl, 2 tbl, 2 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

Isoindolinone-based phosphatidylinositol-3-kinase inhibitors // 2573569
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to pharmaceutically acceptable compositions containing the above compounds, and to methods for using the compositions for treating various diseases, conditions or disorders.EFFECT: invention refers to the compounds applicable as PI3K, particularly PI3Kγ inhibitors.18 cl, 2 tbl, 26 ex

Kibdelos porangium extracts as antibacterial agents // 2572621
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to an antibacterial composition containing one or more refined compounds specified in compounds of formula:, wherein R1 and R2 are independently specified in a group consisting of hydrogen and halogen; and R3 are specified in a group consisting of hydrogen and C1-C6alkyl; and formula , wherein: R1 and R2 are independently specified in a group consisting of hydrogen and halogen; and R3 represents hydrogen, and pharmaceutically acceptable salts. These compositions are acceptable in treating and/or preventing bacterial infections and associated diseases and conditions in humans and animals. The invention also refers to a method for producing these compositions by fermentation and precipitation, partial synthesis and complete synthesis; to methods for bacterial growth inhibition, as well as to biologically pure cultures of bacterial strains, which are used to produce these compounds.EFFECT: producing the compositions, which are acceptable in treating and/or preventing bacterial infections and associated diseases and conditions in humans and animals.20 cl, 3 dwg, 3 tbl, 3 ex

N-[(1h-pyrazol-1-yl) aryl]-1h-indole or 1h-indazole-3-carboxamide derivatives, producing and using them as p2y12 antagonists // 2572593
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to compounds characterised by general formula (I), wherein A represents an aromatic diradical specified in groups having formulas such as below whereas the other radical and groups have values presented in the patent claim.EFFECT: invention refers to methods for producing the compounds of formula (I) , pharmaceutical composition containing them, and using them as P2Y12 antagonists for treating cardiovascular diseases.14 cl, 16 tbl, 21 ex

3-acylaminopyridin derivatives, applicable as serine-threonine proteinkinase gsk3b inhibitors, as medications for type ii diabetes treatment // 2570907
FIELD: chemistry.SUBSTANCE: invention relates to 3-acylaminopyridin-2(1H)-one and its novel derivatives, which can be potential medications for treatment of type II diabetes. , wherein X - -(CH2)n-n=0-2, -CH(OCH3)-, -CH=CH-; Y - 1-adamantyl, 4-isopropylphenyl,3-(methoxymethyl)-4-methoxyphenyl, 3-(4-methyl-1H-pyrazol-1-yl)methyl-4-methoxyphenyl, 4-(difluoromethoxy)phenyl, 3,5-dimethylisoxazol-4-yl, 3,5-dimethyl-4-nitro-1H-pyrazol-1-yl, 3-trifluoromethyl-1H-pyrazol-1-yl, 1-ethyl-3-trifluoromethyl-1H-pyrazol-5-yl, 1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl; Z - 4 pyridyl, bromine.EFFECT: obtaining medication for treating diabetes.4 cl, 2 dwg, 3 tbl, 21 ex

Azetidinyl diamides as monoacylglicerol lipase inhibitors // 2569298
FIELD: chemistry.SUBSTANCE: invention relates to formula (I) compounds, where Y and Z are independently selected from group a) or b) in such a way that one of Y or Z is selected from group a) and the other is selected from group b); group a) represents i) substituted C6-10aryl; ii) C3-8cycloalkyl, optionally substituted with one or two substituents, representing fluorine; iii) trifluoromethyl; or iv) heteroaryl, selected from the group, consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyrimidinyl, isoxazolyl, benzothienyl, thieno[3,2-b]thiophen-2-yl, pyrazolyl, triazolyl and [1,2,3]thiadiazolyl; where C6-10aryl is substituted, and heteroaryl is optionally substituted with one substituent, selected from the group, consisting of fluorine, chlorine, bromine, C1-4alkyl, C1-4alkoxy and C1-4alkylcarbonylamino; group b) represents i)C6-10aryl; ii) heteroaryl, selected from the group, consisting of thiazolyl, pyridinyl, indolyl, indazolyl, benzoxazolyl, benzothiazolyl, benzofuranyl, benzothienyl, 1H-pyrrolo[3,2-b]pyridin-5-yl, 1H-thieno[2,3-c]pyrazol-5-yl, 1H-pyrrolo[2,3-b]pyridine-5-yl, 1H-pyrazolo[3,4-b]pyridine-5-yl, furo[2,3-b]pyridine-2yl, furanyl, [1,2,3]triazolyl, thienyl, oxazolyl, [1,3,4]oxadiazol-2-yl, pyrrolyl, pyrazolyl and benzimidazolyl; iii) 2,3-dihydro-1H-indolyl; vi) 1-(2,4-dichlorophenyl)-4,5,6,7-tetrahydro-1H-indazol-3-yl; or ix) diphenyl-1H-pyrazol-3-yl; in which each phenyl is optionally substituted with one or two substituents, representing chlorine, and in which said pyrazolyl is optionally substituted with one substituent, representing methyl, where C6-10aryl, 2,3-dihydro-1H-indolyl and heteroaryl from group b) are optionally independently substituted with one or two substituents, selected from the group, consisting of bromine, chlorine, fluorine, iodine, C1-4alkyl, C1-4alkoxy and trifluoromethyl; and where C6-10aryl and heteroaryl are substituted with one additional substituent, selected from the group, consisting of i) C6-10aryl; ii) heteroaryl, selected from the group, consisting of thienyl, quinolinyl, pyridinyl, isoxazolyl, benzimidazolyl, pyrrolyl, furanyl and pyrazolyl; where said heteroaryl is optionally substituted with one phenyl substituent, with said phenyl substituent being optionally substituted with one or two chlorine substituents or trifluoromethyl; and where phenyl of C6-10aryl and heteroaryl are optionally independently substituted with one or two substituents, selected from the group, consisting of C1-4alkyl; cyanomethyl; C1-4alkoxy; from one to three substituents, representing fluorine or chlorine; trifluoromethy; trifluoromethoxy; C1-4alkylcarbonyl; C1-4alkoxycarbonyl(C2-4)alkenyl; cyano(C2-4)alkenyl; (2-cyano)ethylaminocarbonyl; cyano; carboxy; aminocarbonyl, formyl, nitro, bromine, hydroxyl; and NRcRd, in which Rc represents hydrogen or C1-6alkyl and in which Rd represents hydrogen,C1-6alkyl, di(C1-4alkyl)aminosulphonyl and C1-4alkylsulphonyl; s equals 0, 1 or 2; R1 represents C6-10aryl, C1-3alkyl; or its pharmaceutically acceptable salts. Formula (I) compounds are used for manufacturing pharmaceutical composition, possessing inhibiting activity with respect to monoacylglicerol lipase (MGL), containing therapeutically effective quantity of formula (I) compound and at least one pharmaceutically acceptable carrier, pharmaceutically acceptable excipient and pharmaceutically acceptable diluent.EFFECT: compounds, intended for treatment of inflammatory pain.20 cl, 7 tbl, 131 ex

Triazine derivative and pharmaceutical composition including it, possessing analgesic activity // 2565073
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to formula (VIII) compounds and their pharmaceutically acceptable salts. Invention compound possess antagonistic effect with respect to P2X3 and/or P2X2/3 receptor. In formula (VIII) Z1 and Z2, each independently represent oxygen atom or sulphur atom; D ring represents benzene ring, pyridine ring, pyrimidine ring, pyrazine ring or pyridazine ring; B ring represents 6-membered aromatic heterocyclic ring with 1-3 nitrogen atoms, 5-membered aromatic heterocyclic ring with one nitrogen atom and one oxygen atom, one sulphur atom, one nitrogen atom and one sulphur atom, one oxygen atom, two nitrogen atoms, one oxygen atom and two nitrogen atoms, one sulphur atom and two nitrogen atoms, four nitrogen atoms or three nitrogen atoms, or non-substituted 9-membered condensed aromatic heterocyclic ring with one nitrogen atom and one oxygen atom or two nitrogen atoms. Values of other radicals are given in invention formula.EFFECT: invention relates to formula (IX) compounds, formula (VII) compounds, formula (X) compounds, structural formulae and values of radicals of which are given in invention formula, to pharmaceutical composition, possessing antagonistic effect with respect to P2X3 and/or P2X2/3 receptor, to method of treatment and/or prevention of disease, associated with P2X3 and/or P2X2/3 receptor, to pharmaceutical composition, possessing analgesic effect and to method of obtaining formula (VIII) compound.34 cl, 586 tbl, 107 ex

Novel solvate crystals // 2563631
FIELD: chemistry.SUBSTANCE: invention relates to crystals of solvate of trityl olmesartan medoxomil with acetone, which comprise 1 mol of acetone per 1 mol of of trityl olmesartan medoxomil, versions of methods of thereof obtaining, as well as to method of obtaining olmesartan medoxomil with application of crystals of solvate of trityl olmesartan medoxomil with acetone.EFFECT: obtaining olmesartan medoxomil with lower content of admixtures in synthesis with application of crystals of solvate of trityl olmesartan medoxomil with acetone.15 cl, 7 dwg, 5 ex

Pyrrolidine derivatives as nk-3 receptor antagonists // 2561271
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula and its pharmaceutically active salts; R1 represents hydrogen, halogen; n represents 1 or 2, if n represents 2, then R1 can be different; R2 represents C2-7-alkyl or C3-6-cycloalkyl; R3 represents the group wherein X represents CH; R5 represents hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, S(O)2-lower alkyl, -C(O)-CH2-CN, or represents -C(O)-C3-6-cycloalkyl, wherein the cycloalkyl groups can be optionally substituted by a lower alkyl, -CH2-O-lower alkyl, lower alkoxy, CF3, halogen or cyano, or represents -C(O)-(4-6-merous heterocycloalkyl containing 1 heteroatom specified in O, N), or represents -C(O)-(6-merous heteroaryl containing 1-2 heteroatoms N), or represents 6-merous heteroaryl containing 1-2 heteroatoms N, or represents -C(O)-phenyl, wherein heterocycloalkyl, heteroaryl or phenyl groups are optionally substituted by halogen, lower alkyl, =O, lower alkyl substituted by a halogen, lower alkyl substituted by hydroxy, -C(O)-CH2-N(di-lower alkyl), C(O)NH2, -O-C(O)-lower alkyl, C(O)-lower alkyl, S(O)2-lower alkyl or cyano; R4 represents phenyl substituted by a halogen. The invention also refers to the compound [(3S,4R)-4-(4-chloro-3-fluoro-phenyl)-1-(1-isopropyl-6-oxo-piperidin-3-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester; to a medicinal product possessing properties of an NK-3 receptor antagonist, containing one or more compounds of the inventions, and to the use of the compounds for preparing the medicinal product.EFFECT: there are prepared new compounds, which possess the properties of the NK-3 receptor antagonist.8 cl, 1 tbl, 126 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

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

Heteroaromatic and aromatic piperazinyl azetidinyl amides as monoacylglycerol lipase inhibitors // 2558141
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C1-4alkyl, trifluoromethyl, C1-4alkoxy, C1-4alkylthio, nitro and cyano; r=1-2; R2 is absent or is an oxo-group; Z is: (a) phenyl substituted with NRaRb; where Ra is: H or C1-4alkyl; where Rb is: C1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, Ra and Rb are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C1-3)alkyl, phenyl(C1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C1-6alkyl, C1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C1-6alkyl, phenyl and NRcRd; where Rc: H or C1-4alkyl; where Rd is: C1-4alkyl or C1-6cycloalkyl(C1-4)alkyl; and where the C1-2alkyl of phenyl(C1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C5-8cycloalkyl; where the C5-8cycloalkyl is optionally substituted with one C1-6alkyl substitute; (j) benzene ring-condensed C5-8cycloalkyl or benzene ring-condensed C5-8cycloalkyl(C1-4)alkyl; where said C5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C1-4alkyl, trifluoromethyl, C5-8cycloalkyl, phenyl, phenyl(C1-2)alkoxy, phenyl(C2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C1-4alkyl, C1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.21 cl, 5 tbl, 11 ex

Indole derivative and its pharmaceutical application // 2556216
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to compound, represented by the following formula , or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).32 cl, 86 tbl, 387 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

Chromone derivatives, method for preparing them and therapeutic uses thereof // 2545214
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new chromone derivatives of general formula , wherein: R1 represents one or more identical or different substitutes on a benzene ring, each of which independently represents a hydrogen atom, or a halogen atom, or C1-4 alkoxy group, or OH group. or group -O(CH2)nO-, wherein n=1 or 2, R2 represents a hydrogen atom, or C1-4 alkyl group; A and B independently represent either a nitrogen atom, or a carbon atom; R3 represents a hydrogen atom or one or more identical or different substitutes specified in a group consisting of: a halogen atom, C1-4 alkyl group, C1-4 alkoxy group, group -O(CH2)nO-, wherein n=1 or 2, group NO2, group NHSO2R4, group NHR5, OH group, C1-4 halogenoalkyl group, CN group, or R3 makes a ring condensed with a benzene ring bearing it, specified in a group consisting of indole, benzimidazole, carbostyril, benzoxazolone and benzoxazolone and benzimidazolone, R4 represents C1-4 alkyl group, or C1-4 dialkylamino group, or C1-4 alkoxyalkyl group, or C1-4 dialkylaminoalkyl group, R5 represents a hydrogen atom, or C1-4 alkylcarbonyl group, or C1-4 alkoxycarbonyl group, and to its pharmaceutically acceptable salts, as well as to methods for preparing them, and to based pharmaceutical compositions, and to using them as a therapeutic agent for central nervous system disorders, as long as they possess the D3 dopaminergic ligand properties.EFFECT: preparing the compositions for treating central nervous system disorders, as long as they possess the D3 dopaminergic ligand properties.17 cl, 1 dwg, 2 tbl, 33 ex

Pyrazines applicable as delta-opioid receptor modulators // 2543484
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to pyrazine derivatives of formula I, as well as to their enanthiomers, diastereomers and pharmaceutically acceptable salts, wherein R1 is specified in a group consisting of ii) pyridinyl optionally having one substitute specified in a group consisting of C1-4alkoxy and cyano; and iii) pyrimidin-5-yl; or R1 optionally represents methoxymethyl, when Y represents ethinyl; Y represents ethinyl or a bond; R2 represents phenyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxol-5-yl, indolyl or pyridinyl substituted by methyl, phenyl has one to two substitutes independently specified in a group consisting of C1-4alkyl, C1-4alkoxy, fluorine, chlorine, cyano, cyanomethyl, difluoromethyl, trifluoromethyl and hydroxy; or R2 represents phenyl having one C1-4alkylcarbonylamino or 1H-imidazol-1-yl substitute; X represents O or CH2; L is absent, and R3 represents 4-aminocyclohexyl, or L represents methylene, while R3 is specified in a group consisting of i) pyrrolidin-2-yl; ii) 1-aminoeth-1-yl; and iii) 1-aminocyclopent-1-yl; or R3 is combined into one cycle with L nitrogen atom to which L is attached to form piperazinyl. Besides, the invention refers to specific compounds, a pharmaceutical compound based on a compound of formula I, a method of treating pain and some neurodegenerative diseases.EFFECT: there are produced new pyrazine derivative effective in treating pain and some neurodegenerative diseases.21 cl, 3 tbl, 13 ex

Bcl-2-selective apoptosis-inducing agents for treating caner and immune diseases // 2542994
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to specific compounds or to their therapeutically acceptable salt presented in the patent claim and representing sulphonyl benzamide derivatives. The invention also refers to a pharmaceutical composition inhibiting the activity of anti-apoptotic proteins of the family Bcl-2, containing an excipient and an effective amount of a specific sulphonyl benzamide derivative.EFFECT: sulphonyl benzamide derivatives inhibiting the activity of anti-apoptotic Bcl-2 proteins.2 cl, 3 tbl, 558 ex

3-benzofuranylindol-2-one derivatives substituted in position 3, preparing and using them in therapy // 2542991
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new 3-benzofuranylindol-2-one derivatives substituted in position 3 of formula wherein: R1 means a hydrogen atom; R2, R3, R4 equal or different, found in any accessible position of the phenyl ring, means independently a hydrogen atom or a halogen atom; R5 means (C1-6) alkyl group; n means 1; in the form of the base or acid-additive salt, as well as to a therapeutic agent and a pharmaceutical composition based on the above compounds possessing the ghrelin receptor antagonist activity, and to using this compounds for preparing the therapeutic agent for preventing or treating obesity, diabetes, appetite disorders and overweight.EFFECT: preparing the therapeutic agent used for preventing or treating obesity, diabetes, appetite disorders and overweight.8 cl, 1 ex

Substituted 3-benzofuranyl-indol-2-one-3-acetamidopiperazines derivatives, preparing and using them in therapy // 2542980
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new 3-benzofuranyl-indol-2-one-3-acetamidopiperazine derivatives of formula , wherein: R1 means hydrogen atom; R2, R3, R4 are identical or different, found in any accessible position of phenyl nucleus; they independently mean hydrogen atom and halogen atom; R5 and R6 are identical or different, mean hydrogen atom, (C1-6) alkyl group; R7 means (C1-6) alkyl group; R8 and R9 found in any accessible position of piperazine nucleus, mean hydrogen atom, or (C1-6)alkyl group; at least one of R8 and R9 is differed from H; n means 1; which are present in the form of a base or an acid addition salt, as well as to methods for preparing these compounds, a therapeutic agent or a based pharmaceutical composition for treating obesity, diabetes, appetite disorder and overweight and to therapeutic use of these compounds.EFFECT: preparing the compounds for treating obesity, diabetes, appetite disorder and overweight and to therapeutic use of these compounds.10 cl, 3 ex

Black pigment dispersion // 2541013
FIELD: chemistry.SUBSTANCE: invention refers to pigment dispersion that can find application in electrophoretic displays. The dispersion contains α) a bis-(oxodihydroindolilene)benzodifuranone colouring agent of formula I wherein R1-R10 have values specified in cl.1, β) a special polymer dispersing agent containing modified poly(meth)acrylates, and γ) a solvent applicable for dispersions used in the electrophoretic displays. There are also described new colouring agents of bis-(oxodihydroindolilene)benzodifuranone compounds, dispersing agents and the electrophoretic display comprising these agents.EFFECT: presented colouring agents have low conductivity and using them as black pigments in the electrophoretic displays enables reducing energy consumption as compared to using state-of-art carbon black.11 cl, 1 dwg, 1 tbl, 11 ex

Bis-benzimidazole derivatives as hepatitis c virus inhibitors // 2540897
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to bis-benzimidazole derivatives of formula I and their optional stereoisomers, pharmaceutically acceptable salts and solvates, wherein R and R' are independently specified in -CR1R2R3, phenyl substituted by 1 substitute specified in halogen; and tetrahydrofuranyl, wherein R1 is specified in C1-4alkyl optionally substituted by methoxy, hydroxyl or dimethylamino; C3-6cycloalkyl; phenyl optionally substituted by 1, 2 or 3 substitutes optionally specified in halogen, C1-4alkoxy, trifluoromethoxy, or 2 substitutes on adjoining atoms of the ring form 1,3-dioxolane group; benzyl substituted by halogen or methoxy; pyridinyl; indolyl; pyridinylmethyl or indolylmethyl; R2 is specified in hydrogen, hydroxyl, di-C1-4alkylamino, (C3-6cycloalkyl) (C1-4alkyl)amino, C1-4alkylcarbonylamino, phenylamino, C1-4alkyloxycarbonylamino, (C1-4alkyloxycarbonyl)(C1-4alkyl)amino, C1-4alkylaminocarbonylamino, tetrahydro-2-oxo-1(2H)-pyrimidinyl, pyrrolidin-1-yl, piperidin-1-yl, 3,3-difluoropiperidin-1-yl, morpholin-1-yl, 7-azabicyclo[2.2.1]hept-7-yl and imidazol-1-yl; and R3 represents hydrogen or C1-4alkyl or CR2R3 together form carbonyl; or CR1R3 form cyclopropyl group. The invention also refers to a pharmaceutical composition based on a compound of formula I.EFFECT: there are prepared bis-benzimidazole derivatives possessing the inhibitory activity on hepatitis C virus.9 cl, 4 tbl, 3 ex

Phenylethynyl derivatives as hepatitis c virus inhibitors // 2538507
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclic compounds of general formula I or to pharmaceutically acceptable salts or solvates or stereoisomers thereof, where R and R* are each independently -CR1R2R3, C1-4alkylamino, benzylamino, C6-10arylamino, heteroC4-7cycloalkyl containing 1 heteroatom selected from O; where R1 is selected from C1-4alkyl; phenyl, optionally substituted with 1, 2 or 3 substitutes independently selected from halogen, C1-4alkyl, C1-4alkoxy, trifluoromethoxy or 2 substitutes at neighbouring ring atoms, which form a 1,3-dixolane group; benzyl, optionally substituted with a halogen or methoxy; phenylsulphonylmethyl; C3-5heteroaryl containing 1 to 2 heteroatoms independently selected from N and O; C3-5heteroarylmethyl containing 1 to 2 heteroatoms selected from N and C3-6cycloalkyl; R2 is selected from hydrogen, hydroxyl, di-C1-4alkylamino, C1-4alkylcarbonylamino, C1-4alkyloxycarbonylamino, C1-4alkylaminocarbonylamino, piperidin-1-yl or imidazol-1-yl; R3 is hydrogen or, alternatively, R2 and R3 together form an oxo group; or R1 and R3 together form cyclopropyl; under the condition that if one of R and R* is -CH(C6H5)N(CH3)2, the other cannot be -CH(C6H5)NHC(=O)OCH3; and if R and R* are identical, R1 is not phenyl, when R2 is hydroxyl, acetylamino, methoxycarbonylamino or tert-butoxycarbonylamino, and R3 is hydrogen; and R1 is not C1-4alkyl, when R2 is C1-4alkyloxycarbonylamino, and R3 is hydrogen. The invention also relates to a pharmaceutical composition based a compound of formula I and use thereof.EFFECT: obtaining novel compounds which are useful in preventing or treating HCV infection.9 cl, 2 tbl, 3 ex

Heteroaryl compounds and using them // 2536584
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of structural formula possessing inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases. In formula (I-b), ring A and ring B represents phenyl; Ry represents -CN, -CF3, C1-4 aliphatic group, C1-4 halogenaliphatic group, -OR, -C(O)R or -C(O)N(R)2; each group R independently represents hydrogen or a group specified in C1-6 aliphatic group optionally containing a substitute presented by halogen, -(CH2)0-4R°, -(CH2)0-4OR°, -(CH2)0-4N(R°)2, -(CH2)0-4N(R°)C(O)OR°, -(CH2)0-4C(O)R°, -(CH2)0-4S(O)2R°, or 5-6-merous substituted or aryl ring containing 1-2 heteroatoms independently specified in nitrogen or oxygen optionally substituted by group =O, -(CH2)0-4R°, -(CH2)0-4N(R°)2 or -(CH2)0-4OR°; phenyl; 5-6-merous heterocyclic ring containing 1-2 heteroatoms independently specified in nitrogen, oxygen or sulphur optionally substituted by group -(CH2)0-4R°, -(CH2)0-4OR° or =O; or 6-merous monocyclic heteroaryl ring containing 1 nitrogen atom; W1 and W2 represent -NR2-; R2 represents hydrogen, C1-6aliphatic group or -C(O)R; m and p are independently equal to 0, 1, 2, 3 or 4; Rx is independently specified in -R, -OR, -O(CH2)qOR or halogen, wherein q=2; Rv is independently specified in -R or halogen; R1 and R° radical values are presented in the patent claim. The invention also refers to a pharmaceutical composition containing the above compounds.EFFECT: preparing the compounds possessing the inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases.17 cl, 25 dwg, 20 tbl, 286 ex

Isatin derivatives applicable as imaging in vivo agents // 2535975
FIELD: medicine, pharmaceutics.SUBSTANCE: there are described new isatin-5-sulphonamide derivatives of general formula or their physiologically acceptable salts, wherein R represents phenyl, 3-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, tetrahydropyranyl, diazine or triazolyl methyl optionally substituted by one C1-6alkyl, which can be additionally substituted by one halogen; R' represents phenyl optionally substituted by one or two halogens, or triazolyl optionally substituted by one C1-6alkyl which can be additionally substituted by one halogen; provided R means phenyl, R' represents optionally substituted triazolyl, pharmaceutical compositions containing the above derivatives, using them as molecular imaging agents, using them in diagnosing or treating diseases or disorders related to apoptosis dysregulation, methods for synthesis of the above derivatives, methods for molecular imaging of caspase activity and apoptosis, and methods for assessing the therapeutic exposure of the analysed compound on caspase activity.EFFECT: new isatin-5-sulphonamide derivatives are described.27 cl, 26 dwg, 4 tbl, 11 ex

Apoptosis-inducing agents for treatment of cancer and immune and autoimmune diseases // 2535203
FIELD: medicine, pharmaceitics.SUBSTANCE: invention relates to particular derivatives of N-(phenylsulphonyl)benzamide, given in i.1 of the invention formula. The invention also relates to a pharmaceutical composition, possessing an inhibiting activity with respect to anti-apoptotic proteins Bcl-2, containing an effective quantity of one of the said compounds or a therapeutically acceptable salt of such a compound.EFFECT: N-(phenylsulphonyl)benzamide derivatives as inhibitors of the anti-apoptotic proteins Bcl-2.2 cl, 2 tbl, 458 ex

Synthesis of resorcylic acid lactones used as therapeutic agents // 2534527
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new macrocyclic compounds of formula or their tautomer, pharmaceutically acceptable salt, solvate or ester, wherein: X represents O or NR; Y represents -O-(CH2)mCOOR or -O-(CH2)mCON(R)2, wherein groups related to a nitrogen atom, can be in a Z- or E-configuration; R1 and R2 independently represent hydrogen or halogen; R3, R4, R5, R6, R7, R8, R9 and R10 independently represent hydrogen, alkyl, OR, -O(CH2)mC(O)(CH2)pN(R)2, -O(CH2)mN(R)C(O)(CH2)pOR, -(CH2)mN3 or -O(CH2)mN3; and each R independently represents R11, hydrogen, alkyl, alkylamino, dialkylamino, alkoxycarbonyl, phenyl or a protective group; or two R on the same nitrogen are taken together with nitrogen for producing a 5-6-merous heterocyclic or heteroaryl ring; wherein the group contains more than one substitute R; wherein R is optionally substituted, and each R can be identical or different, and wherein the protective group is specified in ethoxymethyl, methoxymethyl, tert-butyldimethylsilyl (TBS), phenylmethylsilyl, trimethylsilyl (TMS), 2-trimethylsilyl ethoxymethyl (SEM), 2-trimethylsilylethyl, benzyl and substituted benzyl; R11 represents a group , wherein Z represents an inorganic or organic counter-ion specified in a halogen, -O-alkyl, toluene sulphonate, methylsulphonate, sulphonate, phosphate, formiate or carboxylate; n represents 0, 1 or 2; m and p independently represent 0, 1 or 2; and dashed lines mean either a single, or a double bond, wherein the necessary conditions of the valence are observed by additional hydrogen atoms; and wherein in formula I′, when n represents 1, and X represents O, and the double bond is present between the carbon atoms having R9 and R10, then at least one of R5, R6, R7, R8, R9 or R10 are other than hydrogen; and wherein in formula I′, when n represents 1, and X represents O, and the bond between the carbon atoms having R9 and R10, represents the single bond, then at least one of R5, R6, R7 or R8 is other than hydrogen. The invention also refers to pharmaceutical compositions containing these compounds, using them and methods of treating diseases mediated by kinases and a heat-shock protein 90 HSP90.EFFECT: preparing the new macrocyclic compounds.28 cl, 5 dwg, 3 tbl, 9 ex

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

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

Quinazolinones as prolyl hydroxylase inhibitors // 2528412
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to quinazolinone compounds of formula (I) and its pharmaceutically acceptable salts, wherein n is equal to 0 to 3, and R1 is defined as stated in the patent claim. The above compounds are prolyl hydroxylase inhibitors and can be used in pharmaceutical compositions and methods of treating pathological conditions, disorders and conditions mediated by prolyl hydroxylase activity.EFFECT: compounds can be administered into the patient for treating, eg anaemia, vascular diseases, metabolic disorders, as well as for wound healing.22 cl, 2 tbl, 211 ex
 
2551145.
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