Ortho-condensed systems (C07D471/04)

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
Quaternary ammonium salts based on derivatives of vitamin b6 // 2607522
FIELD: medicine.SUBSTANCE: invention relates to novel derivatives of vitamin B6 of general formula (I) with high antibacterial activity. ,where at R1=R4=N+(CH3)2C8H17, R2+R3=-C(CH3)2O-, R5=H, n=2, m=0; at R1=R4=N+(CH3)2C12H25, R2+R3=-C(CH3)2O-, R5=H, n=2, m=0; at R1=R4=N+(CH3)2C18H37, R2+R3=-C(CH3)2O-, R5=H, n=2, m=0; at R1=R4=N+(CH3)2C8H17, R2=R5=H, R3=OH, n=2, m=1; at R1=R4=N+(CH3)2C12H25, R2=R5=H, R3=OH, n=2, m=1; at R1=R4=N+(CH3)2C18H37, R2=R5=H, R3=OH, n=2, m=1; at R1=R5=H, R2+R3=-CH(C2H5)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(C3H7)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(C4H9)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(C(CH3)3)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(C8H17)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(CH2CH(CH3)C9H19)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH2O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-C(cycle-C4H8)O-, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R5=H, R2+R3=-CH(C3H7)O-, R4=N+(CH3)2C8H17, n=1, m=0; at R1=R5=H, R2+R3=-CH(C3H7)O-, R4=N+(CH3)2C12H25, n=1, m=0; at R1=R5=H, R2+R3=-CH2O-, R4=N+(CH3)2C8H17, n=1, m=0; at R1=R5=H, R2+R3=-CH2O-, R4=N+(CH3)2C12H25, n=1, m=0; at R1=R5=H, R2+R3=-C(CH3)2O-, R4=N+(CH3)2C12H25, n=1, m=0; at R1=R2=R5=H, R3=OH, R4=N+(CH3)2C12H25, n=1, m=1; at R1=R3=R5=H, R2=C(O)CH3, R4=N+(CH3)2C8H17, n=1, m=0; at R1=R3=R5=H, R2=C(O)CH3, R4=N+(CH3)2C12H25, n=1, m=0; at R1=R3=R5=H, R2=C(O)CH3, R4=N+(CH3)2C18H37, n=1, m=0; at R1=R2=R3=R5=H, R4=N+(CH3)2C8H17, n=1, m=1; at R1=R2=R3=R5=H, R4=N+(CH3)2C12H25, n=1, m=1; at R1=R2=R3=R5=H, R4=N+(CH3)2C18H37, n=1, m=1; at R1=N+(CH3)2C8H17, R2+R3=-C(CH3)2O-, R4+R5=-OC(CH3)2OCH2-, n=1, m=0; at R1=N+(CH3)2C18H37, R2+R3=-C(CH3)2O-, R4+R5=-OC(CH3)2OCH2-, n=1, m=0; at R1=N+(CH3)2C8H17, R2+R3=-C(CH3)2O-, R4=OH, R5=CH2OH, n=1, m=1; at R1=N+(CH3)2C18H37, R2=H, R3=R4=OH, R5=CH2OH, n=1, m=1.EFFECT: invention can be used in medicine and veterinary science.1 cl, 2 tbl, 30 ex
Substituted n2-(4-amino-2-methoxyphenyl)-n4-[2-(dimethylphosphoryl)-phenyl]-5-chloro-pyrimidine-2,4-diamines as modulators of alk and egfr, applicable for treating cancer // 2607371
FIELD: chemistry.SUBSTANCE: invention relates to novel substituted N2-(4-amino-2-methoxyphenyl)-N4-[2-(dimethylphosphoryl)-phenyl]-5-chloro-pyrimidine-2,4-diamines of general formula 1 and their stereoisomers, N4-[2-(dimethylphosphoryl)-phenyl]-N2-{4-[4-(1-methyl-1,8-diaza-spiro[4.5]dec-8-yl)-piperidin-1-yl]-2-methoxyphenyl}-5-chloro-pyrimidine-2,4-diamine and their pharmaceutically acceptable salts. Compounds have anti-cancer effect and can be used for preparing a drug for preventing or treating cancer, in particular, non-small cell lung cancer (NSCLC), including with metastases in brain. In compounds of general formula 1 1, R denotes a substitute, selected from a series (a)-(o): (a)-(c), (e)-(i), (k)-(l), (m)-(o), in which R2, R3, R4 and R5 are optionally identical C1-C4alkyls; n is an optionally identical number 1 or 2; arrow indicates binding point of substitute. Invention also relates to a method of producing compounds of formula 1.EFFECT: method comprises reacting compounds of general formula 2, 1_1(17) where R is a substitute selected from corresponding substitutes given above, with N-[2-(dimethylphosphoryl)phenyl]-2,5-dichloro-pyrimidine-4-amine of formula 1_1(17).12 cl, 2 tbl, 4 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
Fused heterocyclic compound and use thereof for pest control // 2606119
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a novel heterocyclic compound of general formula (1) or N-oxide thereof, where A1: -NR7-, O or S, A2: =CR8-, A3: N or =CR9-, R1 is C1-C4 alkyl, optionally substituted with 3 atoms or Groups X, or C3-C6 cycloalkyl group, R2, R3 and R4 are identical or differ from each other and each denotes C1-C2 alkyl optionally substituted with 3–5 atoms or Groups X, 6-member heterocycle -OR10, -NR10C(O)R11, cyano group, a halogen atom or a hydrogen atom, R5 and R6 are identical or differ from each other and each denotes C1-C6 alkyl substituted with 3–5 atoms or Groups X, -OR10, -S(O)mR10, -CO2R10, -C(O)NR10R11, -SF5, cyano group, halogen atom or hydrogen atom (where R5 and R6 cannot simultaneously represent hydrogen atom), R7 represents C1-C6 alkyl, optionally substituted with 3 atoms or Groups W, C1-C6 alkyl, substituted with one phenyl group (where phenyl group is substituted with one atom or Group Z), C1-C6 alkyl substituted with one 5-member heterocycle (where 5-member heterocyclic group is thiazolyl, substituted with one atom or a group selected from Group Z), or a hydrogen atom, R8 and R9 are identical or differ from each other and each denotes C1-C6 alkyl substituted with 3 halogen atoms, -OR10, -S(O)mR10, -NR10R11, cyano group, a halogen atom or a hydrogen atom, R10 and R11 are identical or differ from each other and each denotes C1-C6 alkyl, optionally substituted with 3–5 atoms or Groups X, phenyl group, each m independently equals 0, 1 or 2 and n equals 0, 1 or 2, where in -S(O)mR10 R10 is different from a hydrogen atom, when m equals 1 or 2, Group X: C1-C6 alkoxy group, hydroxy group and a halogen atom, Group Z: C1-C6 alkoxy group, halogen atom, Group W: halogen atom. Invention also relates to a composition for pest control, a pest control method and intermediate compounds.EFFECT: obtaining novel compounds effective for pest control.24 cl, 71 tbl, 83 ex (1)

Neprilysin inhibitors // 2605557
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I, where R1 is -OR7; R2 is H; X is selected from a pyrazole, triazole, benzotriazole, tetrazole, oxazole, isoxazole, thiazole, pyridazine, pyrimidine and pyridyl triazole; R3 is absent or is selected from H; halogen; -C0-5alkylene-OH; -C1-6alkyl; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; phenyl, optionally substituted with one or two groups independently selected from halogen, -OCH3, -NHC(O)CH3 and phenyl; naphthalenyl; pyridinyl; pyrazinyl; and R3, when present, is bonded to carbon atom; R4 is selected from H; -OH; -C1-2alkylene-COOR35; -pyridinyl; and phenyl or benzyl, optionally substituted by one or more groups selected from halogen and -OCH3; and R4, when present, is bonded to carbon atom or a nitrogen atom; a equals 0 or a equals 1; and R5 is selected from halogen and -CN; b is equal to 0 or 1, and R6 is selected from Cl, F, -OH, -CH3, -OCH3 and -CF3; or b is equal to 2, and R6 each is independently selected from halogen, -OH, -CH3, or -OCH3, or b is equal to 3, and R6 each is independently selected from halogen or -CH3; R7 is selected from H, -C1-8alkyl, -C1-3alkylene-C6-10aryl, -C0-6alkylene morpholinyl or dioxol-2-one methyl, of formula (a); or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are obtained by condensation of compound of formula 1 with a compound of formula 2, where P1 is H or tert-butoxycarbonyl; and wherein method further includes removal of protective group of compound of formula 1, when P1 is tert-butoxycarbonyl. Also compound of formula (I) is obtained by removing protective group of compound of formula (6) or salt thereof; where R1P is -O-P3, where P3 is methyl. Invention also relates to intermediate compounds of formulae (1) and (6). Compounds of formula (I) are intended for inhibiting neprilysin activity.EFFECT: compounds having neprilysin inhibiting activity.19 cl, 9 ex,(а), ,

Pirazoloqinoline derivative // 2605096
FIELD: pharmaceutics.SUBSTANCE: invention relates to composition presented by formula (I) or its pharmaceutically acceptable salt, where R1 is hydrogen atom; R2 is aromatic ring group defined in claim, R3 is hydrogen or fluorine atom, R4 is hydrogen atom; R5 is oxepanyl group, etc.; R6 is hydrogen atom. Disclosed composition exhibits PDE9-inhibiting action. Therefore, intracerebral proteins concentration increase is possible. PDE9-inhibitory action and cGMP increase leads to improvement of training course and memory development.EFFECT: composition of formula (I) can be used as therapeutic agent against cognitive dysfunctions accompanying Alzheimer's disease.19 cl, 1 dwg, 12 tbl, 63 ex (I)

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),

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

New compounds for treating diseases, associated with amyloid or amyloid-like proteins // 2603008
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula (I) possessing properties of aggregation of Aβ1-42, pharmaceutical composition, based thereon, use thereof, method of treating using them, kit for detecting or diagnosing diseases, method of reducing deposits of β-amyloid plaques and method of maintaining or improving cognitive abilities. In general formula (I) A there are selected from group, consisting of (i), (ii), (iii), (iv), (v), (vi) and (viii), L1 is selected from group, consisting of (a), B is selected from group, consisting of (ix), (x), (xi), (xii), (xiii), where R1, R2 and R3 are selected from group of hydrogen, halogen, CN, -CONR30R31, -N(R30)-C(O)-R31, alkyl, -O-alkyl, -C(O)O-alkyl, 6-membered heterocycle with 1-2 heteroatoms, selected from N and O, fluoroalkyl, where the heterocycloalkyl can be optionally substituted with acetyl or methyl group, or, if any of these groups R1/R2/R3 are adjacent, they can be taken together and form 5-8-member ring, containing carbon atoms and optionally one or two heteroatoms, selected from O, S or N, and where 5-8-member ring can be substituted with NR20R21 or -O-alkyl, where alkyl can be substituted with F, methoxy or SO2Me; Ra is selected from hydrogen, alkyl; Rb is selected from hydrogen, halogen, CONR30R31; R30, R31, R20 and R21 are selected from hydrogen, alkyl; X and Y are selected from CRb and N; p equals to 0, 1 or 2.EFFECT: compounds can be used for treating of group of violations and disorders, associated with amyloid protein, such as Alzheimer's disease, and diseases or conditions, associated with amyloid-like proteins, as well as for treating eye diseases, associated with pathological abnormalities/changes in visual system tissues.36 cl, 12 dwg, 10 tbl, 219 ex A-L1-B (I), , , , , , and ,, , , and ,

Diamides of 4,7-disubstituted 1,10-phenanthroline-2,9-dicarboxylic acids, synthesis method thereof and extraction mixture based thereon // 2601554
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to diamides of 4,7-disubstituted 1,10-phenanthroline-2,9-dicarboxylic acids, where R is radical selected from lower alkyls group or aryl containing 6 carbon atoms, and X denotes n-pentoxy, chlorine or phenyl. Invention also relates to a method of producing said dicarboxylic acid diamides, to intermediate compound - 4,7-di-pentoxy-1,10-phenanthroline-2,9-dicarboxylic acid and method for production thereof, extraction mixture based on diamine of 4,7-disubstituted 1,10-phenanthroline-2,9-dicarboxylic acids.EFFECT: produced novel diamides of dicarboxylic acids for use during extraction and concentration of radionuclides.6 cl, 3 tbl, 3 ex

Azaindazole or diazaindazole derivatives as medicine // 2600976
FIELD: chemistry.SUBSTANCE: invention relates to a compound of general formula (I) or a pharmaceutically acceptable salt thereof, in which radicals and symbols assume values given in patent claim. Compound of formula (I) is a kinase inhibitor, such as ALK Abl and/or c-Src.EFFECT: invention also relates to its use as a drug for treating cancer, inflammation and neurodegenerative diseases, such as Alzheimer's disease, to its use as an inhibitor of said kinases, to a pharmaceutical composition containing said compound, and to methods of its production.16 cl, 20 tbl, 35 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

2-arylimidazo[1,2-b]pyridazine,2-phenylimidazo[1,2-a]pyridine and 2-phenylimidazo[1,2-a]pyrazine derivatives // 2598385
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula or a pharmaceutically acceptable salt thereof. Disclosed compounds have inhibitory activity on Hedgehog pathway activation and can be effective in treating pancreatic cancer or prostate cancer. In formula R1 is a pyridyl, optionally substituted in position where substitution is possible with one or more R8; R2 is CN, C1-C6 alkyl, C3-C-8 cycloalkyl, phenyl, 5-6-member heteroaryl, where 1-2 members are heteroatoms selected from N and O, 4-5-member heterocyclyl, where 1 member is a heteroatom selected from a group consisting of N, where each alkyl, cycloalkyl, phenyl or heterocyclyl group is optionally substituted in position where substitution is possible with one or more R10; R3 is halogen, C1-C-6 alkyl, C1-C6 haloalkyl or C3-C8 cycloalkyl; A is a bond,-N(R7)-, -N(R7)C(O)-, N(R7)C(O)N(R7)-, -C(O)O-, -S(O)2N(R7)- or-N(R7)S(O)2-; each R5 is independently hydrogen, C1-C6 alkyl; each Z is independently CR6; each R6 is independently hydrogen, halogen. Invention also relates to a pharmaceutical composition containing disclosed compound, a method of inhibiting Hedgehog signaling pathway and use of compounds.EFFECT: technical result is obtaining novel compounds having inhibitory activity on Hedgehog pathway activation.19 cl, 3 dwg, 5 tbl, 706 ex

Solid dispersions containing agents causing apoptosis // 2598345
FIELD: medicine.SUBSTANCE: invention relates to a solid dispersion for apoptosis induction. Dispersion contains a compound of formula I , where: R0 denotes chlorine; R1 and R2 denote H; R3 and R4 denote methyl; A1 denotes N and A2 denotes CH; R5 denotes nitro; X denotes -NH-; Y denotes -(CH2)n-, where n=1; and R6 is selected from a group consisting of tetrahydropyranyl and 4-hydroxy-4-methylcyclohexyl; or its pharmaceutically acceptable salt. Herewith the compound of formula I or its pharmaceutically acceptable salt are dispersed in a solid matrix, which contains (a) at least one pharmaceutically acceptable water-soluble polymer carrier and (b) at least one pharmaceutically acceptable surfactant. Water-soluble polymer carrier is selected from a group consisting of homopolymers and copolymers of N-vinillactams, cellulose esters, cellulose ethers, polyalkylene oxides with high molecular weight, polyacrylates, polymethacrylates, polyacrylamides, vinyl acetate polymers, grafted copolymers of ethylene glycol, polyvinyl caprolactam and polyvinyl acetate, oligo- and polysaccharides and mixtures thereof. Surfactant is selected from a group consisting of polyoxyethylene glycerides, monoesters of sorbitan fatty acids, polysorbates, α-tocopheryl-polyethylene glycol succinate (TPGS) and their mixtures. Also not more than 5 % of the compound of formula I or its pharmaceutically acceptable salt in a solid dispersion is in crystalline form as per X-ray diffraction analysis data. Also described are: a method of producing the solid dispersion, orally delivered pharmaceutical dosage form.EFFECT: solid dispersion is suitable for oral use by a person who needs it for treating a disease characterized by overexpression of one or more antiapoptosis proteins from the Bcl-2 family, for example, cancer.44 cl, 2 tbl, 17 ex

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

Derivatives of 7-(heteroaryl-amino)-6,7,8,9-tetrahydropyrido[1,2-a]indole-acetic acid and use thereof as prostaglandin d2 receptor modulators // 2596823
FIELD: chemistry.SUBSTANCE: invention relates to derivatives of 7-(heteroaryl-amino)-6,7,8,9-tetrahydropyrido[1,2-a]indole-acetic acid with formula (I) or pharmaceutically acceptable salt of such compound, where R1 and R2 represent independently of each other hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy group, halogen, trifluoromethoxy group or trifluoromethyl; R3 represents hydrogen, (C1-C4)alkyl, (C1-C2)alkoxy-(C2-C3)alkyl, (C1-C4)fluoroalkyl or (C3-C6)cycloalkyl-(C1-C2)alkyl; and R4 represents heteroaryl group, which is unsubstituted or mono-substituted, where substitutes are independently selected from group comprising halogen, (C1-C4)alkyl, (C3-C6)cycloalkyl, (C1-C4)alkoxy group, (C1-C4)fluoroalkyl and phenyl; where term "heteroaryl" denotes 5-10-member monocyclic or bicyclic aromatic ring containing one nitrogen atom and optionally one additional heteroatom selected from oxygen, nitrogen and sulphur. Invention also relates to the pharmaceutical composition based on compound with formula (I) and application of compound with formula (I).EFFECT: obtaining new heterocyclic compounds having antagonistic activity in relation to CRTH2 receptor.17 cl, 19 dwg, 51 ex

N-heteroaryl compounds // 2596185
FIELD: pharmaceutics.SUBSTANCE: invention relates to N-heteroaryl compounds and pharmaceutically acceptable salts, solvates or N-oxides of general formula (I), where R1: halogen, C1-C6-alkyl, C1-C6-alkyloxy, C1-C6-alkylthio, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy-C-1-C6-alkyl, C1-C6-alkyl-carbonyl, SF5, C1-C6-alkylsulphonyl, wherein each carbon-containing radical is optionally substituted with one or more halogen atoms, R2: hydrogen, C1-C6-alkyl, R3, R4 and R7 hydrogen, C1-C6-alkyl, R5: hydrogen, C1-C6-alkyl, C1-C6-acyl or C1-C6-alkyloxycarbonyl, R6: hydrogen, C1-C6-alkyl, C1-C6-alkyloxycarbonyl, phenyl, phenyl-C1-C6-alkyl, n=1-3, X: carbonyl, thiocarbonyl or sulphonyl group, A is a bond, E is a bond or NR9, where R9 - hydrogen, B is N, D is N or CR11, where R11 - hydrogen, Y1 is C or N, where C is substituted with R12, which is hydrogen, C1-C6-alkyl, C1-C6-galoalkilom, nitro, Y2 is C or N, where C is substituted with R13, which is hydrogen, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, nitrilo, di(C1-C6-alkyl)amino, N-pyrrolidinyl, C1-C6-alkylthio, C1-C6-alkylcarbonyl, aminocarbonyl, C1-C6-alkylamino-carbonyl, C1-C6-alkoxycarbonyl, Y3 is C, where C is substituted with R14, which is hydrogen, C1-C6-alkyl, C1-C6-alkoxy, amino, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, C1-C6-alkylcarbonyl, 1,3-dioxolane, which is unsubstituted or substituted with C1-C6-alkyl, Y4 is C or N, where C is substituted with R15, which is hydrogen, C1-C6-alkyl, wherein two of Y1, Y2 and Y4 can represent N, or Y3 and Y4 are bonded to form a ring system, selected from phenyl, thiophene, imidazole, pyridine, furan, 1,4-dioxane, triazole, and where at least one of B and D is a nitrogen atom. Invention also relates to a pharmaceutical composition based on compound of formula (I), intermediate compounds of formulae (1-IV), (3-IV), (4-II), method of treating helminth infection, compounds of formula (Ia), use of formula (I) and (Ia).EFFECT: obtaining novel compounds effective in treating parasitic infections.23 cl, 3 tbl, 18 ex

Nitrogen-containing saturated heterocyclic compounds // 2595136
FIELD: pharmaceutics.SUBSTANCE: invention relates to a compound of formula [I] and its pharmaceutically acceptable salts thereof. Compound of formula [I] possesses renin-inhibitory activity. In formula [I] R1 is C3-6-cycloalkyl group; R denotes lower alkyl group or makes 5-6-member ring by binding with R22 at each end; T is a carbonyl group; Z is -O-, -NH- or single bond; and R3, R4, R5 and R6 are a hydrogen atom. Invention also relates to a pharmaceutical composition containing a compound of the invention, and to a compound of formula [II].EFFECT: obtaining novel compounds of formula [I], having renin inhibitory activity.11 cl, 93 tbl, 422 ex

Agents causing apoptosis and intended for treating cancer, immune and autoimmune diseases // 2594282
FIELD: chemistry. SUBSTANCE: invention refers to heterocyclic compounds of formula (I) or to therapeutically acceptable salt thereof, where X represents benzo [d] thiazolyl, optionally substituted with one or two R4; Y1 represents a pirrolil, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with one or two substitutes independently selected from a group consisting of R5, CO(O)R5, CO(O)H and CN; L1 selected from group comprising (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-C(O)-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; and Y2 is selected from a group consisting of C3-4 alkyl with branched chain, C5-7 cycloalkyl, C6-7 cycloalkyl, phenyl, piperidinyl, morpholinyl and tetrahydropiranyl; where the phenyl is optionally condensed with benzene; where Y2 optionally substituted with one, two or three substitutes independently selected from a group consisting of R8, OR8, SO2R8, CO(O)R8, NHR8, N(R8)2, C(O)H, OH, CN, NO2, F, Cl, Br and I; or L1 represents a bond; and Y2 is selected from a group consisting of C5 cycloalkyl, phenyl, tetrahydropiranyl and piperidinyl; where C5 cycloalkyl and tetrahydropiranyl presented by Y2 are optionally condensed with benzene; Z1 is selected from group consisting of or ; R1, R2 and R3 are absent; R4, in each case is independently selected from group consisting of OR12 and halogen; R5, in each case is independently selected from group consisting of C1-6 alkyl, C1-6 hydroxyalkyl, phenyl and cyclopropyl; R6A represents C1-6 alkyl; each R6 and7, in each case are independently selected from group consisting of hydrogen, R15 and CO(O)R15; R8, in each case is independently selected from group consisting of C1-6 alkyl, C2-6 alkynyl, phenyl, piperidinyl and morpholinyl; where R8 C1-6 alkyl and C2-6 alkynyl are optionally substituted with one, two or three substitutes independently selected from a group consisting of R16, OR16, SO2R16, C(O)R16, NHR16, N(R16)2, OH and F; where R8 phenyl is optionally substituted with one Cl; Rk, in each case represents C1-6 alkyl; R12 is C1-4 alkyl; R15, in each case is independently selected from a group consisting of C1-4 alkyl and phenyl; where R15 C1-4 alkyl is optionally substituted with one substitute selected from a group consisting of C1-4 alkoxy, morpholinyl and C6cycloalkyl; R16, in each case is independently selected from a group consisting of C1-4 alkyl, C1-4 hydroxyalkyl, phenyl, tetrahydropiranyl, morpholinyl, 1,4-dioxanyl, dioxydotiomorfolinyl and pyridinyl; q equals to 1, 2 or 3; s, r, m, n and p equals to 0; or where the compound is selected from a group specified in item 1. Invention also relates to pharmaceutical composition based on the above compounds and method of cancer treating. EFFECT: technical result allows obtaining new heterocyclic compounds effective in cancer treating. 9 cl, 3 tbl, 188 ex

Azaindoles as glucokinase activators // 2593369
FIELD: pharmaceutics. SUBSTANCE: invention relates to compounds of formula (I): where: R1 is phenyl, unsubstituted or mono-or disubstituted independently halogen, cyano, C1-6 alkyl, alkoxy, -SO2CH3, -CF3, -C(CH3)2OH, -CH(CH3)OH, -C(CH3)(C(CH3)2)OH, -SO2(CH2)2OH, -NH(SO2CH3), -C(O)CH3, -C(CH2CH3)2OH, -N(CH3)2, -SO2CH(CH3)2, -SO2(CH2)2OCH2CH3, -SO2(CH2)2N(CH3)2, pyrasol or -SO2(CH2)2-morpholinium, 6-member heteroaryl containing 1 N heteroatom, unsubstituted or substituted C1-6 alkyl, alkoxy or -SO2CH3, or 2,3-dihydrobenzo[1,4]dioxine-6-yl; R2 is C1-6 alkyl, 5-6-member heterocycloalkyl, containing 1 heteroatom selected from O, N, or C3-6-cycloalkyl, unsubstituted or substituted (=O); R3 is hydrogen, halogen, acyl group, cyano, C1-6 alkyl, unsubstituted or mono-, di- or three-substituted independently hydroxy, alkoxy, halogen, C1-6 alkyl, cyano, (=O) or -N(CH3)2, -OCH3, -OCH2C(O)N(CH3)2, -O(CH2)2OCH3, -O(CH2)2N(CH3)2, -OCH(CH3)2, -OC(CH3)2CH2OH, -OCH2CH2OH, -OC(CH3)2C(O)OCH2CH3, -OC(CH3)2C(O)OH, -CH2OC(O)CH2N(CH3)2, -NHC(O)CH2N(CH3)2 or -SO2-C1-6 alkyl; connection between C1 and C2 is single or double bond; X1 represents hydrogen, hydroxy, alkoxy or is absent, if the relationship between C1 and C2 is a double bond; and X2 represents hydrogen or is absent, if the relationship between C1 and C2 is double bond, as well as their pharmaceutically acceptable salts. EFFECT: mentioned compounds and containing them pharmaceutical compositions are effective for treating metabolic diseases and disorders, such as, for example, type II diabetes mellitus. 35 cl, 4 tbl, 141 ex

Substituted n-(1h-indazole-4-yl) imidazole [1,2-a]pyridine-3- carboxamide compounds as inhibitors of tyrosine kinase type iii receptor // 2591195
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts, where R1, R2, R3, R4, R5 and R6 have values specified in patent claim. Compound of formula I are inhibitors of tyrosine kinase of type III, and, in particular, cFMS. They are effective in treating fibrosis, bone diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in mammal.EFFECT: invention also relates to methods of producing compounds of formula I, pharmaceutical compositions containing them and methods of treating said diseases.47 cl, 1 tbl, 161 ex

Novel 4-amino-n-hydroxybenzamides as hdac inhibitors for treating cancer // 2591190
FIELD: pharmaceutics.SUBSTANCE: invention relates to the HDAC inhibitors of formula (I) or pharmaceutically acceptable salts, esters or stereoisomers, where R1 represents hydrogen or halogen; R2 represents hydrogen, C1-4-alkyl; R3 is phenyl, unsubstituted or substituted with one or two or three times a halogen, C1-4-alkyl, C1-4-alkoxy, C1-4-alkylsulfonyl, cyano, trifluoromethyl, phenyl, phenoxy, pirrolyl, imidazonyl, oxazolyl or di C1-4-alkylamino-C1-4-alkoxy; naphthalenyl; quinolinyl; C3-7-cycloalkyl; phenylalkyl, where phenyl may not be substituted by or once or twice substituted by halogen, C1-4-alkoxy, phenyl; naftalinilalkyl; phenylcycloalkyl; pyrimidinyl; phenylsulfonyl, where phenyl may not be substituted by or once or twice substituted by halogen, phenyl; or phenylcarbonyl, where phenyl may not be substituted by or once or twice substituted by halogen, C1-4-alkoxy; R4 is hydrogen or C1-4-alkyl; Y represents -CH2- or -C=O; or R4 and Y together with carbon atom to which R4 is connected, can form a phenyl ring or a pyridine ring, which may not be substituted with or substituted with halogen; provided that R2 is C1-4alkyl; A represents -C=O, -CH2- or -CH-alkyl, provided that a and Y simultaneously does not represent -C=O.EFFECT: presented are pharmaceutical compositions of these compounds and use thereof as drug for treating cancer.14 cl, 3 tbl, 101 ex

Quinoxalines and azaquinoxalines as crth2 receptor modulators // 2589709
FIELD: chemistry.SUBSTANCE: invention relates to compound of formula (IC) and pharmaceutically acceptable salts thereof. Disclosed compounds have properties of CRTH2 receptor modulators. In formula (IC) R1 represents -C(O)-N(R6a)(R6b); I) R6a is H, and R6b represents a) -Q-RAH, where RAH is phenyl, and where RAH is unsubstituted or substituted with one fragment R8, selected from group consisting of fluorine and -CN; Q is selected from group consisting of (i) link; (ii) , where Re denotes H, and R(f) is H or methyl; b) -Q-RHC, where RHC is C5-C6 cycloalkyl, where said C5-C6 cycloalkyl forms condensed cycle with benzene ring and where RHC is unsubstituted or substituted with 1-2 fragments of R12, independently selected from group consisting of halogen and -CN; II) or R6a and R6b together with N atom to which they are bonded form R6h, where R6h is pyrrolidinyl, piperidinyl or piperazinyl, where R6h is substituted with -Z-RCY, Z is bond and RCY is unsubstituted phenyl or phenyl, substituted with 1-2 fragments of R10, selected from group consisting of halogen and -CN; R6H optionally substituted with 1-2 fragments in R9, where each fragment R9 is independently C1-C3 alkyl, halogen or -CN, and R2 is unsubstituted phenyl. Invention also relates to pharmaceutical composition for treating asthma or allergic rhinitis and method of treating asthma or allergic rhinitis.EFFECT: technical result is obtaining novel compounds which can be used to treat asthma or allergic rhinitis.10 cl, 2 tbl, 44 ex

Derivatives of 4-hydroxy-1,2,3,4-tetrahydronaphthalene-1-yl-urea and their use in treatment, inter alia, diseases of respiratory tract // 2586333
FIELD: chemistry.SUBSTANCE: invention relates to individual compounds comprising 4-hydroxy-1,2,3,4-tetrahydronaphthalene-1-yl-urea, and pharmaceutically acceptable salts thereof. Compounds of invention have properties of inhibitor of p38 MAP kinase. Invention also relates to pharmaceutical composition, to method for inhibiting p38 MAP kinase and to use of compounds in manufacture of medicament.EFFECT: Technical result provided new compounds having properties of inhibitor of p38 MAP kinase, which are useful as anti-inflammatory agents in treatment of diseases of respiratory tract.9 cl, 3 tbl, 34 ex

Urea derivatives and therapeutic use thereof in treating, among other things, respiratory tract diseases // 2586223
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) or its pharmaceutically acceptable salt thereof, wherein R1 represents radical of formula (IA), (IB), or (IC), wherein R4b is C1-C6 alkyl, C3-C6 cyclo alkyl, phenyl, which is optionally substituted 1-2 substitutes selected from halogen, hydroxy or O-benzyl; or radical of formula (IIa) or (IIb), wherein n equals 1 or 2; and R3 and R4 are independently h or C1-C6 alkyl; R3b is optionally substituted C1-C-6 alkyl, wherein substitute is selected from (C1-C6) alkoxy; y represents-O-; A is a cyclo-alkylene radical, having 5, 6 or 7 atoms of ring condensed with phenyl ring; R2 represents radical of formula (IIIa), (IIIb), (IIIc), wherein q is equal to 0, 1, 2 or 3; R7 is -CH3; R8 is -CH3 or C2H5 and each presence R6 is independently H, C1-C6 alkyl. Invention also relates to pharmaceutical composition inhibiting activity of MAP-kinase p38 containing effective amount of compound of formula I, together with one or more pharmaceutically acceptable carriers.EFFECT: technical result is compound for use in treating disease or condition, which has positive result of MAP-kinase p38 inhibiting.11 cl, 2 tbl, 22 ex (I) (IA) (IB) (IC) (IIa) (IIb) (IIIa) (IIIb) (IIIc)

Tetracyclic compounds // 2585622
FIELD: organic chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a particular 9-ethyl-6,6-dimethyl-8-(4-morpholine-4-yl-piperidine-1-yl)-11-oxo-6,11-dihydro-5H-dihydro-5H-benzo [b]carbazole-3-carbonitrile . Invention also relates to a medicament, an ALK inhibitor and pharmaceutical composition based on particular benzo-carbazole derivative.EFFECT: novel benzo-carbazole derivatives which are useful in treating cancer are obtained.7 cl, 49 tbl, 1218 ex

Agonists of protein tyrosine phosphatase-1 containing homology-2 src domain, and methods of treating using said agonists // 2584986
FIELD: pharmaceutics.SUBSTANCE: in formula I R1 and R3 independently represent hydrogen, and R2 represents , , , , or R1 independently represents hydrogen, R3 is methyl, and R2 represents or or R2 and R3 independently represent hydrogen, and R1 is . Invention also refers to pharmaceutical compositions containing said compound, a method for increasing Src homology-2 containing proteintyrosinephosphatase-1 (SHP-1) expression in a cell, method of treating diseases or pathological condition characterised by low expression SHP-1, and to use of said compounds for preparing a drug for treating diseases or pathological condition characterised by low expression of SHP-1.EFFECT: disclosed are novel compounds of formula I, having Src homology-2 containing protein tyrosine phosphatase-1 (SHP-1) agonist activity.11 cl, 6 tbl, 23 dwg, 2 ex
Some chemical compounds, compositions and methods // 2582676
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to new compounds of formula V-A or their pharmaceutically acceptable salts possessing the properties of PI3-kinase (phosphatidylinositol-3-kinase) activity inhibitors. The compounds can find application for treating diseases and conditions associated with PI3-kinase activity, particularly in a T-cell, B-cell, mastocyte, dendritic cell, or neutrophil. This disease represents one or more diseases specified in cancer, a bone disorder, inflammatory disease, immune disease, respiratory disease or thrombosis. Cancer represents leukaemia or lymphoma, or cancer is specified in acute myeloid leukaemia, chronic lymphocytic leukaemia and multiple myeloma, where lymphoma represents non-Hodgkin lymphoma; an inflammatory or immune disorder is asthma, allergy, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, or graft-versus-host disease. The compound of formula V-A, or its pharmaceutically acceptable salt, or a composition can be used in a combination with rapamycin. In formula V-A:B represents a group of formula wherein Wc represents phenyl, 6-merous heterocyclyl with one heteroatom specified in oxygen or nitrogen, or C3-C6cycloalkyl; q is equal to 0 or 1; R1 represents hydrogen, C1-C4alkyl or halogeno; R2 represents halogeno or C1-C4alkyl optionally substituted by halogeno; R3 represents halogeno; R9 represents hydrogen or C1-C4alkyl.EFFECT: producing the new compounds for treating the diseases or conditions associated with PI3-kinase activity.62 cl, 19 dwg, 6 tbl, 55 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

Inhibitors of akt activity // 2579513
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula , where each R1 and R2 is independently selected from hydrogen, C1-C10alkyl, optionally substituted OH and OR3, where R3 represents C1-C10alkyl, or R1 and R2 together represent oxo or optionally C1-C10alkyl O-substituted oxime; W represents O, NR′ or CRaRb, where R′ represents either hydrogen, or C1-C10alkyl; X is either absent or represents CR4R5, where each Ra, Rb, R4 and R5 are independently selected from substituents, given for R1 and R2; Y and Z independently represent substituted or non-substituted nitrogen or carbon (substituents for which are given in i. 1 of the invention formula), or Y and Z together form optionally substituted pyrazolyl, imidazolyl, pyriminidyl, 1,2,4-triazolyl (substituents for which are given in i. 1 of the invention formula); R7a and R7b represent H; R6a and R6b represent H or R6a and R6b can be combined with formation of C3-C6cycloalkyl, optionally substituted with one or two substituents, selected from C1-C6alkyl and OH; Cy is selected from C1-6alkyl(C3-C8)cycloalkyl, phenyl, pyridinyl and thienyl; m equals 0 or 1; R8 represents F. the invention also relates to particular compounds, given in i. 1 of the invention formula, to pharmaceutical composition and method for treating malignant tumour.EFFECT: novel methods for Akt inhibition.19 cl, 1 dwg, 153 ex

Novel conjugates of cc-1065 analogues and bifunctional linkers // 2578719
FIELD: chemistry.SUBSTANCE: invention relates to the conjugate of formula (III) or to a pharmaceutically acceptable salt thereof, where the group V2 is selected from an anti-CD19 antibody, an anti-CD22 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD56 antibody, an anti-CD70 antibody, an anti-CD74 antibody, an anti-CD138 antibody, an anti-CLL-1 antibody, an anti-5T4 antibody, an anti-CD303 antibody, an anti-Tag 72 antibody, an anti-Lewis A like carbohydrate antibody, an anti-EphB3 antibody, an anti-HMW- MAA antibody, an anti-CD38 antibody, an anti-Cripto antibody, an anti-EphA2 antibody, an anti-GPNMB antibody, an anti-integrin antibody, an anti-MN antibody, an anti-Her2 antibody and an anti-PSMA antibody, or from an epitope-binding fragment; each L2 is independently a linker group: ; each L is selected from structures indicated in claim 1; each V1 is selected from valylcitrulline, valyllysine, phenylalanyllysine, alanylphenylalanyllysine, and D-alanylphenylalanyllysine; each Y is the self-eliminating spacer system which consists of 1 or more self-elimination spacers and is linked to V1, optionally L and Z; p equals 1, z equals q; q ranges from 1 to 4; z equals a positive integer equal to or less than the total number of binding sites for Z; each Z is independently a compound selected from a group consisting of the structures given in claim 1; each Z is linked to Y by an OH group through an ω-amino amino carbonyl cyclisation spacer which is part of Y; where the spacer Y is , and where the ω-amino amino carbonyl cyclisation spacer A is selected from the structures indicated in claim 1. The invention also relates to the intermediate compound of formula (IV) and use of the conjugate of formula (III).EFFECT: obtaining the conjugate of a DNA-alkylating agent and the system of bifunctional linkers, having anti-tumour activity.12 cl, 7 dwg, 16 ex

Solid dispersions produced by melt extrusion and containing apoptosis-inducing agent // 2577859
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a solid dispersion for apoptosis induction. The dispersion contains a compound of formula I , where: R0 means chlorine; R1 and R2 mean H; R3 and R4 mean methyl; A1 means N, and A2 mean CH; R5 means nitro; X means -NH-; Y means -(CH2)n-, where n = 1; and R6 is specified in a group consisting of tetrahydropyranyl and 4-hydroxy-4-methylcyclohexyl; or its pharmaceutically acceptable salt. The compound of Formula I or its pharmaceutically acceptable salt are dispersed in a solid matrix which contains (a) at least one pharmaceutically acceptable water-soluble polymer carrier, and (b) at least one pharmaceutically acceptable surfactant. At least 5% of the compound of Formula I or its pharmaceutically acceptable salt is presented in the crystalline form if studied by X-ray diffractometry. The compound or its pharmaceutically acceptable salt is presented in an amount equal to an amount of a parent compound from approximately 5% to approximately 15% by weight; at least one pharmaceutically acceptable water-soluble polymer carrier is presented in an amount from approximately 70% to approximately 85% by weight, and at least one pharmaceutically acceptable surfactant is presented in an amount from approximately 5% to approximately 15% by weight. There are also presented a method for producing dispersion and a pharmaceutical dosage form applicable for oral delivery.EFFECT: solid dispersion is applicable for oral administration in the patient in need of treating a disease characterised by overexpression of one or more Bcl-2 family antiapoptotic proteins, eg cancer.44 cl, 1 dwg, 17 tbl, 19 ex

Crystalline form of compound of pyrimido [6, 1-a] isoquinolin-4-one // 2577541
FIELD: chemistry.SUBSTANCE: present invention relates to a novel crystalline Polymorph of N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]isoquinoline-3(4H)-yl]ethyl}urea. Said compound can be used in treating asthma, allergic asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or respiratory distress syndrome. Crystalline structure of said Polymorph has x-ray powder diffraction diffractogram containing characteristic peaks in units 2θ, at 10.1°, 12.9°, 15.3° and 17.6°, and following structural parameters, obtained by single crystal analysis Temperature123 (2) KWave length 0.71073 ÅCrystalline circuittriclinicSpatial groupP-1Dimensions of elementary cella = 8.1246 (4) Åα = 91.583(4)°.b = 11.4573 (5) Åβ = 90,299(4)°.c = 13.2398 (6) Åγ = 99.628(4)°.volume1214.56 (10) Å 3Z 2At that, at least 95 % of polymorph is in thermodynamically stable polymorphic form. Invention also relates to method of producing said crystalline polymorph. Method involves (a) combining N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a] isoquinoline-3(4H)-yl]ethyl}urea with solvent to form mixture, (b) heating mixture at temperature in range of 45-121 °C during time, suitable for formation of said polymorph, and slow cooling to temperature in range of 30-40 °C, under conditions suitable for formation of said polymorph; and (c) filtering and drying. Method may further include stage of mixture filtration after step (a). As solvent DMSO, ethanol, methanol, isopropyl alcohol, hexanes, pentane, ethyl acetate, dichloromethane or chloroform can be used.EFFECT: said mixture is retained at or above temperature of about 50 °C for about 24-96 hours.19 cl, 22 dwg, 15 tbl, 13 ex

Antiinfective compounds // 2576662
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to heterocyclic compounds of formula Ib and its pharmaceutically acceptable salts, wherein X, Y and Z represent CH; o is equal to 1; n is equal to 0; m is equal to 1 or 2; A represents C=O; W represents NH; in each specific case, R2 is independently specified in a group consisting of C1-C10 alkyl; in each specific case, R3 is independently specified in a group consisting of halogen, C1-C10 alkyl optionally substituted by halogen; OR6, -NO2, heteroaryl representing pyridyl; in each specific case, R6 is independently specified in a group consisting of C1-C10 alkyl and C1-C10 halogenalkyl; R10 represents a fragment specified in a group consisting of wherein m' is equal to 0, 1, 2, 3 or 4; in each specific case, R11 is independently specified in a group consisting of hydrogen and C1-C10 alkyl; in each specific case, R12 is independently specified in a group consisting of hydrogen, C1-C10 alkyl optionally substituted by OR8 group, heterocyclyl representing morpholinyl, or by hydroxyl; C3-C10 cycloalkyl, C1-C10 halogenalkyl, hydroxyl, -OR14, C(O)R14, -C(O)N(R14)2, phenyl optionally substituted by halogen, -N(R8)C(O)R8 group or OR8 group; benzyl optionally substituted by halogen or OR8 group; in each specific case, R14 is independently specified in a group consisting of hydrogen, C1-C8 alkyl; phenyl optionally substituted by halogen, C1-C3 halogenalkyl or OR8 group, benzyl optionally substituted by halogen; in each specific case, R8 is independently specified in a group consisting of hydrogen, C1-C10 alkyl, C1-C3 halogenalkyl, C3-C7 cycloalkyl, phenyl substituted by halogen or OR8 group. The invention also refers to specific compounds, using the above compounds, a pharmaceutical composition based on the compound of formula EFFECT: activity of certain known compounds has been examined, and the new compounds possessing inhibitory activity on mycobacterial growth have been produced.10 cl, 3 dwg, 2 tbl, 3 ex

Condensed heterocyclic derivatives as s1p modulators // 2576660
FIELD: chemistry.SUBSTANCE: invention relates to condensed heterocyclic derivative of formula (I), selected from structures A, B, C, D and E, where R1 is selected from (1-4C)alkyl; (3-6C)cycloalkyl; indanyl, optionally substituted with halogen; phenyl, optionally substituted with one-three substituents, independently selected from halogen, cyano, (1-4C)alkyl, optionally substituted with one or several fluorine atoms, (1-4C)alkoxy, optionally substituted with one or several fluorine atoms; pyridyl, optionally substituted with one halogen atom; Z represents linker group -W-(Cn-alkylene)-T-, where W is bound with R1 and is selected from bond, -O-, -S-, -SO2-, -NH-,-CH=CH-, -C≡C- and trans-cyclopropylene; n represents integer number from 0 to 2, T is bound with phenylene fragment and is selected from bond, -O-, -S-, -SO2-, -NH-, -CO-, -C=C-, -C≡C- and trans-cyclopropylene; R2 represents H or one or two substituents, independently selected from halogen, (1-4C)alkyl, optionally substituted with one-three halogen atoms, or (104C)alkoxy; X is selected from C or N; if X represents C, R3 is selected from H and (1-4C)alkyl, in other case R3 is absent; Y is selected from NH, O and S; R4 represents (1-4C)alkylene-R5 where one or several carbon atoms in alkylene group can be independently substituted with one or two halogen atoms or (CH2)2, with formation of cyclopropyl part, R5 represents -COOH. The invention also relates to pharmaceutically acceptable salts of formula (I) compounds, pharmaceutical composition, containing formula (I) compounds, and application of formula (I) compounds for medication manufacturing.EFFECT: formula compounds, demonstrating properties of receptor S1P agonists.24 cl, 1 dwg, 1 tbl

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

3,5-disubstituted alkynylbenzene compound and salt thereof // 2576384
FIELD: chemistry.SUBSTANCE: invention relates to a compound of structural formula having FGFR kinase inhibiting activity. In formula (I) R1 are identical or different from each other, and each is C1-C6alkyl; X1 and X2 are independently N or CH; R2 is hydrogen, C2-C6alkynyl, -C(=O)ORx, -C(=O)N(Rx)(Ry), hydroxy-C1-C6alkyl, di(C1-C6alkyl)amino-C1-C6alkkyl or a monocyclic or bicyclic C2-C9heteroaryl group containing 1-3 identical or different heteroatoms selected from a nitrogen, oxygen and sulphur atom, optionally containing R3; and R3 is C1-C6alkyl or di(C1-C6alkyl)amino-C1-C6alkyl; Z is -C(R4)=C(R5)(R6) or -C≡C-R7; Rx and Ry are identical or different from each other, and each is hydrogen, C1-C6alkyl, C3-C10cycloalkyl, di(C1-C6alkyl)amino-C1-C6alkyl or C1-C6alkoxy-C1-C6alkyl; l is an integer from 0 to 3; m is an integer from 1 to 3; and n is an integer from 0 to 2. Values of radicals Y, R4-R7 are given in the claim. The invention also relates to a pharmaceutical composition containing said compound, an anti-tumour agent and a tumour treatment method.EFFECT: improved properties of compounds.15 cl, 5 tbl, 73 ex

Novel methods of producing propane-1-sulphonic acid {3-[5-(4-chloro-phenyl)-1h-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide // 2575478
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing a compound of formula 1, , which includes a Suzuki-Miyaura reaction, followed by Friedel-Crafts acylation, where a compound of formula 2 reacts in the presence of a palladium catalyst, a base and a compound of formula 3 (1st Suzuki-Miyaura reaction) to obtain a compound of formula 4 , the compound of formula 4 further reacts in the presence of a halogenating agent to obtain a compound of formula 5 , where X is I (5a) or Br (5b); and the compound of formula 5 further reacts in the presence of either a compound of formula (D) , or a compound of formula 7 (Sonogashira reaction), to obtain a compound of formula 8 , which further reacts in the presence of a compound of formula 9 and under Friedel-Crafts acylation conditions to obtain a compound of formula 1, where all R1, R2, R3 and R4 represent a methyl, or together with carbon atoms with which they are bonded form a phenyl ring; and R5 is -(C1-C6)alkyl.EFFECT: novel method of producing a compound of formula 1 with high output.4 cl, 9 ex

ethod of obtaining derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines, which contain functional group in position 2 // 2575174
FIELD: chemistry.SUBSTANCE: invention relates to novel method for synthesis of derivatives of 5,6-dihydropyrrolo[2,1-a]isoquinolines, which contain functional group in position 2. Method consists in the fact that 6,7-diethoxy-3,4-dihydro-1-(3,4-diethoxybenzoyl)isoquinoline is dissolved in trifluorethanol with further addition of acrolein, or croton aldehyde, or cinnamon aldehyde, or acrylonitrile and mixing at temperature +70°C, residue, obtained after reaction completion and removal of reagents, is crystallised in mixture of ether with hexane. , 1 R=H, X=CHO; R=CH3, X=CHO; R=C6H5, X=CHO; R=H, X=CN.EFFECT: increase of prime yield.4 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

New hydroxamic acid derivative // 2575129
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formula [1] or its pharmaceutically acceptable salt, wherein R1 are R2 identical or different, and each of them represents a hydrogen atom, C1-6alkyl group, C3-8cycloalkyl group or C1-6alkoxy group (C1-6alkyl group, C1-6alkoxy group and C3-8cycloalkyl group can be substituted by 1-3 substitutes, which are identical or different from a halogen atom, C1-6alkoxy group); R3 represents a hydrogen atom or C1-6alkyl group; R4 represents a hydrogen atom, C1-6alkyl group, C3-8cycloalkyl group (which can be substituted by substitutes specified in the patent claim), a heterocyclic group specified in pyridine; A1 represents a bivalent aryl group, a bivalent heterocyclic group specified in pyridyl, pyrazinyl, thiophenyl, or C3-8cycloalkylene group (bivalent aryl group can be substituted by 1-4 substitutes, which are identical or different from the following group of substitutes Ra, which are specified in the patent claim); L represents -C≡C-, -C≡C-C≡C-, -C≡C-(CH2)m-O-, CH=CH-, -CH=CH-C≡C-, -C≡C-CH=CH-, -O-, -(CH2)m-O-, -O-(CH2)m-, C1-4alkylene group or a bond; m means 1, 2 or 3; A2 represents a bivalent aryl group, a bivalent heterocyclic group (presented in the patent claim), C3-8cycloalkylene group, C3-8cycloalkenylene group, C1-4alkylene group or C2-4alkenylene group (which can be substituted by 1-4 substitutes, which are identical or different and specified in a group of substitutes Rb, which is specified in the patent claim); W represents R6-X1-, R6-X2-Y1-X1-, R6-X4-Y1-X2-Y3-X3-, Q-X1-Y2-X3- or Q-X1-Y1-X2-Y3-X3-; Y2, Y1, Y3, n, X1, X3, X2, X4, Q, R6, R7, R8 and R9 are presented in the patent claim. The compounds of formula [1] possess antimicrobial activity on gram-negative bacteria by LpxC inhibition.EFFECT: hydroxamic acid derivatives possessing uridyldiphospho(UDP)-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) inhibition activity.25 cl, 107 tbl, 36 ex

New amide derivatives and using them as medicinal product // 2574409
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to an amide derivative of formula (I)exhibiting the property of inhibiting proMMP-9 production, as well as to a based pharmaceutical composition and medicinal product on it's base and an agent for inhibiting MMP-9 production. In general formula (I), A represents phenylene or 6-merous heteroarylene presented by the following formula R1 represents C1-C6alkyl or C3-C6cycloalkyl; R2 represents aC1-C6alkyl optionally substituted by a halogen atom, or C3-C6cycloalkyl; R3 represents a hydrogen atom or C1-C6alkyl; each R4a, R4b and R4c represents a hydrogen atom; W represents a bond, C1-C6alkylene or C3-C6cycloalkyldiene; X represents a nitrogen atom (if Y represents a bond, The nitrogen atom can be oxidised to form N-oxide); Y represents a bond; m is equal to 1 or 2; Z1 represents a carbon atom or a nitrogen atom, each Z2 and Z3 represents a carbon atom; Ra and Rb together with an adjacent atom form a nitrogen-containing cyclic group presented below: , or , which is optionally substituted by C1-C6alkyl optionally substituted by a hydroxyl group or C1-C6alkoxy or oxo.EFFECT: producing new amide derivatives.12 cl, 5 tbl, 843 ex

Apoptosis-inducing agents for treating malignant tumours and immune and autoimmune diseases // 2573832
FIELD: chemistry.SUBSTANCE: invention relates to 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(trans-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulphonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide and a pharmaceutical composition containing a therapeutically effective amount of said compound. As a result, 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(4-{[(trans-4-hydroxy-4-methylcyclohexyl)methyl]amino}-3-nitrophenyl)sulphonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide is obtained, which inhibits anti-apoptotic protein Blc2 activity.EFFECT: high activity.2 cl, 5 tbl, 378 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

Novel naphthyridine derivatives and thereof application as kinase inhibitors // 2573390
FIELD: chemistry.SUBSTANCE: invention relates to naphthyridine derivatives of general formula I in which R1-R6 substituents have the following values: R1 represents NR7R8, R2 represents hydrogen, and R3 represents hydrogen, where R7 represents hydrogen, and R8 can represent -C(Y)NR9R10, where Y represents O, S, and R9 hydrogen and R10 can represent (i) non-substituted saturated C1-6-alkyl, possibly substituted with non-substituted C6-aryl, (ii) non-substituted C6-aryl, R4 represents hydrogen, R5 can represent (i) C6-aryl, substituted with saturated C1-6-alkoxy or hydroxyl, (ii) C5-heteroaryl, containing 2 nitrogen atoms, substituted with saturated C1-6-alkyl, (iii) NR15R16, where R15 represents hydrogen, and R16 represents C6-aryl, substituted with saturated C1-6-alkoxy, and R6 represents hydrogen; and their physiologically acceptable salts, which are kinase modulators.EFFECT: obtaining novel compounds.12 cl, 1 tbl, 10 ex

Novel crystalline acid-addition salts of tricyclic derivative or their hydrates and method for thereof obtaining // 2572820
FIELD: chemistry.SUBSTANCE: invention relates to novel crystalline acid-addition salt of tricyclic derivative in form of its hydrate, represented by the following chemical formula 2: , method for thereof obtaining, and based on its pharmaceutical composition for prevention and treatment of diseases, caused by PARP overactivity.EFFECT: obtained is novel crustalline acid-addition salt of tricyclic derivative in form of its hydrate, which is stable with respect to hygroscopicity and therefore useful in supporting quality in medication obtaining.4 cl, 3 dwg, 2 tbl, 22 ex

Tetrahydrocarboline derivative // 2572818
FIELD: chemistry.SUBSTANCE: claimed invention relates to field of organic chemistry, namely to novel heterocyclic compounds of general formula (I) and to its pharmaceutically acceptable salt or its solvate, where R1 represents halogen atom, C1-4 alkyl group, C1-4 alkoxygroup, C1-4 halogenalkyl group, cyanogroup, carbamoyl group, R2 represents hydrogen atom, R3 represents C1-4 alkyl group, R4 represents hydrogen atom or C1-4 alkyl group, ring A represents (i) C3-6 monocyclic carbon ring, including phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclohexene, (iii) 5-6-membered monocyclic heterocyclic ring, containing one-two heteroatoms, selected from oxygen atom, nitrogen atom and sulphur atom, including thiophene, furan, isoxazole, imidazole, pyrazole, thiazole, pyridine or (iv) 9-membered bicycic heterocyclic ring, including indole, X represents nitrogen atom or carbon atom, T represents bond or linear C1-4 alkylene group, C2-4 alkenylene group or C2-4 alkinylene group, optionally substituted with two R5 (where R5 represents C1-4 alkyl group or aminogroup), U represents (i) methylene group, (ii)oxygen atom, (iii) -NR6- (where R6 represents hydrogen atom or methyl group) or (iv) 3-6-membered monocycle, including cyclobutane, cyclopentane, cyclohexane, phenyl, thiophene, pyrrolidine, pyrazole, imidazole, triazole, oxazole, piperazine, piperidine, tetrahydropyridine C7-8 bridge carbon ting, including bicyclooctane, bicycloheptane and imidazolidine, optionally substituted with one-three R7 (where R7 represents halogen atom, C1-4 alkyl group; hydroxygroup, C1-4 alkoxygroup or benzyloxy group), Y represents (i) bond or (ii) linear C1-3 alkylene group, optionally substituted with one or two R8 (where R8 represents methyl group), W represents bond or linear C1-3 alkylene group; Z represents methylene group, oxygen atom or sulphur atom, q represents integer number 1, r represents integer number from 0 to 5, and t represents integer number from 0 to 2, on condition that groups, represented by set R1, R2, R3, R5, R7 and R8, can be similar or different, respectively, and two R3 or R5, bound with one and the same carbon atom, can be taken together with carbon atom with formation of C3cycloalkyl, respectively. Invention also relates to pharmaceutical composition, pharmaceutical preparation and ENPP2 inhibitor, based on formula (I) compound.EFFECT: novel compounds, possessing inhibiting activity with respect to ENPP2, have been obtained.29 cl, 2 dwg, 3 tbl, 937 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
 
2551339.
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