(A61K31/497)

2-aminopyrasine derivatives as csf-1r kinase inhibitors // 2642777
FIELD: pharmacology.SUBSTANCE: invention relates to a compound that is an amino acid or ester of an amino acid of formula , or a pharmaceutically acceptable salt thereof, which has an inhibitory activity against CSF-1R kinase. In formula (I), ring A is a phenyl group; R1 and R2 independently represent a hydrogen atom, a halogen atom or an unsubstituted C1-4 alkyl; n is 1; X is NH; V is -N=, W is -C(Z)=; Z represents a hydrogen atom, a fluorine atom, a chlorine atom or unsubstituted C1-3 alkyl; ring B is a 1,4-phenylene, 1,3-phenylene or pyridinyl group; [Linker] is a -(CH2)m-X1-(Alk1)x-Y1 group, where m is 0, 1, 2 or 3; x is 0 or 1; Alk1 is an unsubstituted C1-3 alkylene group; X1 and Y1 independently represent a bond, -O-, -S-, -NR7th-, -C(=O) - or -C(=O)NR5-, where R5 is a hydrogen atom or C1-4 alkyl and R7 is a hydrogen atom, unsubstituted C1-4 alkyl or -C(=O)CH3; R is a group of formula or , in which R8 is a -COOH group or an ester group of the formula -(C=O)OR14, where R14 is R15R16R17C-, where any R15 represents a hydrogen atom or C1-3alkyl-(Z1)a-[(C1-C3)alkyl]b-, where a and b are independently 0 or 1, Z1 is -O-, -S- or -NH-, R16 and R17 independently represent a hydrogen atom or C1-3 alkyl- or R15 and R16, taken together with the carbon atom to which they are attached, form a 3-7-membered cycloalkyl ring; and R17 represents a hydrogen atom; where (i) R9 and R10 are side chains of natural amino acids, (ii) one of R9 and R10 represents a hydrogen atom or unsubstituted C1-4 alkyl, and the other is an unsubstituted C1-6 alkyl group or C1-6 alkyl group substituted by a C1-4 alkoxy group, or (iii) R9 and R10, taken together with the carbon atom to which they are attached, form a saturated spiro-cyclobutyl ring; R11 represents a hydrogen atom or an unsubstituted C1-2alkyl group; ring D is a 5- to 7-membered saturated heterocyclyl group with at least one nitrogen atom in the ring. The invention also relates to a pharmaceutical composition, a method of treatment or prevention of diseases or disorders mediated by CSF-1R kinase, as well as application of the said compounds for preparation of a medicament useful for treatment of such diseases.EFFECT: increased application efficiency.18 cl, 59 ex
Amide derivatives as grp119 agonists // 2642429
FIELD: pharmacology.SUBSTANCE: invention relates to an amide derivative of the following formula 1, its stereoisomers or its pharmaceutically acceptable salts of formula 1, wherein X1, X2, X3, X4, X5, X6, X7 and X8 each independently is C or N; R1 is -F or -C1-3-perfluorinated alkyl; R2 and R3 each is independently selected from the group consisting of halogen, -C1-5-alkyl and C3-6-cycloalkyl, wherein -C1-5-alkyl and C3-6cycloalkyl independently of one another may be unsubstituted or substituted by halogen, -CN, -OC1-5-alkyl or-C1-5-alkyl, or R2 and R3 together with the carbon atom to which they are attached, can form C3-6-cycloalkyl, where C3-6cycloalkyl may be unsubstituted or substituted by halogen, -OC1-5-alkyl or -C1-5-alkyl; R4 and R5 each independently is H, halogen or -C1-5-alkyl; R6 and R7 each independently is H, halogen, -C1-5-alkyl or -CN; R8 means methyl; R9 means H, halogen or OH; and m is 1 or 2. The invention also relates to individual compounds and to a pharmaceutical composition.EFFECT: new compounds of formula 1 are obtained that have the properties of GPR119 agonists, which can be used in diabetes mellitus treatment.7 cl, 15 tbl
5-(pyridine-2-ylamino)-pyrasin-2-carbonitrile compounds and their therapeutic application // 2641693
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula , as well as to pharmaceutical compositions based thereon for use in the treatment of a disease or condition mediated by SNK1.EFFECT: new compounds are obtained that inhibit the kinase function of kinase 1 of the control point.37 cl, 2 dwg
Partly saturated nitrogen-containing heterocyclic compound // 2641291
FIELD: chemistry.SUBSTANCE: invention relates to a compound of the formula (I'), (wherein W represents the formula -CR11R12CR13R14-; R11 represents a hydrogen atom, a fluorine atom, C1-4 alkyl or phenyl; R12 represents a hydrogen atom, a fluorine atom or C1-4 alkyl; provided that R11 and R12, together with the adjacent carbon atom, optionally form C3-8 cycloalkane or tetrahydropyran; R13 represents a hydrogen atom, a carbamoyl, C1-4 alkyl (C1-4 alkyl is optionally substituted by one group selected from the group consisting of hydroxy, C1-3 alkoxy and di-C1-3 alkylamino), halo-C1-4 alkyl, phenyl, pyridyl, benzyl or phenethyl; R14 represents a hydrogen atom, C1-4 alkyl or halogen-C1-4 alkyl; Y represents a single bond or C1-6 alkanediyl (C1-6 alkanediyl is optionally substituted by one hydroxy group and one of the carbon atoms in C1-6 alkanediyl is optionally substituted by cycloalkpropane-1,1-diyl); R2 represents a hydrogen atom, C1-6 alkyl, C3-8 cycloalkyl {C3-8 cycloalkyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl (C1-6 alkyl is optionally substituted by one phenyl group), phenyl (phenyl is optionally substituted by one halogen atom), C1-6 alkoxy [C1-6 alkoxy is optionally substituted by one group selected from the group consisting of C3-8 cycloalkyl, phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom and C1-6 alkyl) and pyridyl (pyridyl is optionally substituted by one halogen atom)], C3-8 cycloalkoxy, phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl) and pyridyloxy (pyridyloxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl)}, phenyl (phenyl is optionally substituted by one to three groups that are the same or different and which are selected from the group of α3 substituents), naphthyl, indanyl, tetrahydronaphthyl, pyrazolyl [pyrazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl (phenyl optionally substituted by one C1-6 alkyl)], imidazolyl [imidazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl], isoxazolyl [isoxazolyl is optionally substituted by one phenyl group (phenyl is optionally substituted by one halogen atom)], oxazolyl [oxazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl and phenyl], thiazolyl [thiazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl, phenyl and morpholino], pyridyl (pyridyl is optionally substituted by one or two groups that are are the same or different and are selected from the group of α5 substituents), pyridazinyl [pyridazinyl is optionally substituted by one C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl group)], pyrimidinyl [pyrimidinyl is optionally substituted by one group selected from the group consisting of halogen-C1-6 alkyl, C3-8 cycloalkyl, phenyl and phenoxy (phenoxy is optionally substituted by one C1-6 alkyl)], pyrazinyl [pyrazinyl is optionally substituted by one group selected from the group consisting of C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl), and phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl and C3-8 cycloalkyl)], benzothiophenyl, quinolyl, methylenedioxyphenyl (methylenedioxyphenyl is optionally substituted by one or two fluorine atoms), azetidinyl (azetidinyl is optionally substituted with one pyrimidinyl group), piperidinyl (piperidinyl is optionally substituted by one group selected from the group consisting of pyrimidinyl, phenyl-C1-3 alkyl, C3-8 cycloalkyl-C1-3 alkylcarbonyl and phenyl-C1-3 alkoxycarbonyl) or the following formula (I") -CONR5CH2-R6 (I") [wherein in formula (I") R5 represents a hydrogen atom or C1-3 alkyl and R 6 is phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom, halogen-C1-6 alkyl and phenyl)], Y4 represents C1-4 alkanediyl; R3 represents a hydrogen atom or methyl; R4 represents -COOH or -CONHOH).EFFECT: compound has a superior PHD2 inhibitory effect.16 cl, 28 tbl, 11 ex

Azadecalins condensed with heteroarylketones - glucocorticoid receptor modulators // 2639867
FIELD: medicine.SUBSTANCE: invention provides azadecalin compounds of formula ondensed with heteroarylketones, which are modulators of glucocorticoid receptors. The radicals and symbols in formula I have the definitions given in the claims. In some embodiments of the present invention, pharmaceutical composition is provided comprising a pharmaceutically acceptable excipient and a compound of formula (I). In some embodiments of the present invention, a method is provided for modulation of glucocorticoid receptors that comprises glucocorticoid receptors contacting with a compound of formula I, thereby modulating the glucocorticoid receptors, as well as a method for treatment of diseases by glucocorticoid receptors modulation, which comprises administration of a therapeutically effective amount of a formula I compound to a subject in need thereof, as a result, disease treatment takes place.EFFECT: increased efficiency of treatment.24 cl, 2 dwg, 1 tbl, 22 ex
Heterocyclic amines and their application // 2632900
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein W is S; Y is N; X is N; R1 is selected from (a) C1-C6 alkyl optionally substituted with amino, methylamino, dimethylamino, C1-C6 alkoxy or isoindolyl; (B) -NR8R7, -CH2NR7R8, where R7 and R8 are joined to form optionally substituted C3-C7 non-aromatic ring which is pyrrolidine, morpholine, piperazine, piperidine, 1,4-diazepane, azepane, azetidine, 2-azabicyclo[2.2.1]heptane or 2,5-diazabicyclo[2.2.1]heptane and optionally substituted by one or more C1-C6alkyl, C1-C6alkoxy, methoxyethyl, 1-methoxypropane, isopropyloxymethyl, isopropyloxyethyl, -C(O(CH2)-methyl, -C(O)(CH2)-O-isopropyl, C1-C6haloalkyl, -S(O)2-methyl, -S(O)2-isopropyl, oxo, -C(O)(C1-C2)alkyl-N(methyl)2, -C(O)(C2)alkyl-(pyrrolidine), t-butyl-C(O)- or phenyl; or (c) -O-(tetrahydro-2H-pyran); each of R2, R3 and R5 are hydrogen; R4 is selected from C3-C6cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and optionally substituted heteroaryl selected from pyridine, pyrazole, pyridazine, pyrimidine. The said heteroaryl is optionally substituted with 1 to 2 substituents selected from C1-C6 alkyl and CN. The invention also relates to specific compounds as defined in the claims. The compounds of the invention are intended for the manufacture of a pharmaceutical composition having an inhibitory activity against an interleukin 1 receptor associated kinase 1 (IRAK-1) and an interleukin 1 receptor associated kinase 4 (IRAK-4). The compounds of the invention are also useful in a method for treatment of a disorder sensitive to inhibition of IRAK-1-mediated signalling.EFFECT: heterocyclic amines having inhibitory activity against an interleukin 1 receptor associated kinase 1 and interleukin 1 receptor associated kinase 4.24 cl, 4 tbl, 431 ex
Amide derivatives as ttx-s blockers // 2632899
FIELD: chemistry.SUBSTANCE: invention relates to the amide derivatives of formula ,where A is selected from the group consisting of phenyl, benzoimidazolyl, dihydroisoquinoline, indole, indazole, pyrazolyl, pyrazinyl, pyridazinyl, pyridyl, chinoline, sochinila and thiazolyl; B is selected from the group consisting of chemical bond, -C1-6alkylene-, -O-C1-6alkylene- and -NR7-; W is hydrogen or C1-6 alkyl; Z represents a nitrogen atom or CH; R1 represents a fluorinated substituent, independently selected from the group consisting of -CF3, -CHF2, -OCF3, -OCHF2, -OCH2CHF2, -OCH2CF3, -OCF2CHF2, -OCF2CF3, -OCH2CH2CF3, -OCH(CH3)CF3, -OCH2C(CH3)F2, -OCH2CF2CHF2, -OCH2CF2CF3, -OCH2CH2OCH2CF3, -NHCH2CF3, -SCF3, -SCH2CF3, -CH2CF3, -C (CH3)2CF3, -CH2CH2CF3, -CH2OCH2CF3, -OCH2CH2OCF3, 4,4-difluoropiperidino and (4-fluorobenzyl) oxy; R2 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -On-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, (7) -On-phenyl or -On-naphthyl, where specified phenyl or naphthyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, and (10) -NR8R9; where n represents 0 or 1; if n=0, a chemical bond is present instead of-On-; p represents 1, 2, 3, or 4; if p is two or more than two, R2 may be the same or different; R3 and R4 independently represent hydrogen or C1-6 alkyl; R5 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) -On-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, where n represents 0 or 1; if n=0, a chemical bond is present instead of -On-; q represents 1, 2, or 3; if q is equal to two or more than two, R5 may be the same or different; R6 independently represents hydrogen, C1-6 alkyl, C2-6alkenyl, C3-7 cycloalkyl, phenyl, or heterocyclic group, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C1-6alkyl and -O-C1-6 alkyl; R7 is selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -(C=O)m-Ol-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R10, (9) -(C=O)m-Ol-heterocyclic group, where this heterocyclic group is unsubstituted or substituted by one or more of the substituents independently selected from R10, and (11) -NR8R9, where l=0 or 1 and m=0 or 1; if l=0 or m=0, a chemical bond is present instead of-Ol- or -(C=O)m -, and if l=0 and m=0, a chemical bond is present instead of -(C=O)m-Ol-; R8 and R9independently represent hydrogen or C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C1-6alkyland -O-C1-6 alkyl; or R8 forms a 4-7-membered ring with R9, which may contain a nitrogen atom, an oxygen atom, a sulfur atom, a carbonyl or a double bond, where a 4-7-membered ring is not optionally substituted with 1-6 substituents independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, (3) halogen, (4) C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R10, and (6) -O-C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R10; R10 is independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, and (3) halogen, which possess activity relative to blocking the potential-dependent sodium channels, such as TTX-S.EFFECT: method for producing amido derivatives is improved.14 cl, 3 tbl

Aminomethyl quinolones useful ifor treatment of jnk-mediated disorder // 2629111
FIELD: chemistry.SUBSTANCE: invention relates to new aminomethyl quinolone derivative of formula (I) or its pharmaceutically acceptable salt, where R is -C(=O)A, -C(=O)OA, -C(=O)NHA, -C(=N-C≡N)A, -C(=N-C≡N)NHA or A; A is C1-6-alkyl, phenyl, lower cycloalkyl, adamantyl, heterocycloalkyl selected from benzodioxin, pyrrolidine, piperidine, morpholine or piperazine, heteroaryl selected from pyridine, pyrazole, thiazole, triazole or pyrimidine or bicyclic heteroaryl selected from quinoline, quinazoline, indole, benzothiazole, benzoimidazole or imidazopyridine optionally substituted with one or two A1; each A1 independently represents A2 or A3; each A2 is independently halo or oxo; each A3 is independently C1-6-alkyl, C1-6-alkoxy, phenyl, benzyl, heterocycloalkyl selected from morpholine, piperidine, diazepane, pyrrolidine, azepane or piperazine, bicyclic heterocycloalkyl selected from benzodioxole or diazobicycloheptane, heteroaryl selected from oxazole, triazole, pyrazole, imidazole, thiadiazole, oxadiazole, thiazole or tetrazole, amino, C1-6-alkylamino, C1-6-dialkylamino, amido, C1-6-alkyl ester group, sulfonyl, sulfonamido, -C(=O) or -C(═O)O, optionally substituted by one, two or three groups, selected from halo, hydroxy, C1-6-alkylamino, C1-6-alkyloxy, C1-6-alkyl, C1-6-alkoxy, phenyl, hydroxycycloalkyl wherein cycloalkyl is adamantyl, amino, C1-6-alkylamino, C1-6-dialkylamino, t-butyl complex of carbamic acid ester, (C1-6-alkyl) sulfonyl-piperidinyl or hydroxy- (C1-6-alkyl); R' is H or methyl; X is CX'; X' is H or halo; X1 is H, 2-oxazolyl, dimethylamido or C1-6-alkyl ester group; Y is CH or N; and Y1 is H, halo, C1-6- alkoxy or halo (C1-6alkyl). The invention also relates to particular aminomethyl quinolone derivatives and to the use of said aminomethyl quinolone derivatives.EFFECT: obtained new aminomethyl quinolone derivatives, useful in the treatment of JNK-mediated disorder.15 cl, 2 tbl, 211 ex
Compound as wnt signal inhibitor, its compositions and application // 2627712
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of the general formula (I) or an N-oxide thereof, wherein X1, X2, X3 and X4 independently represent CR4 or N, where 0 or 1 of X1-X4 can be N; Y1, Y2 and Y3 are hydrogen; R1 is selected from hydrogen, , C6 aryl, 6-member heterocycloalkyl containing 2 heteroatoms selected from N and O, and 5- or 6-member heteroaryl containing 1-4 heteroatoms selected from N, O and S, wherein each of C6 aryl, 6-member heterocycloalkyl and 5- or 6-member heteroaryl may be optionally substituted with one R4; R2 is selected from hydrogen, halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl and 6-member heteroaryl may be optionally substituted with one R4. If X5 is N, R2 is selected from halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl, and 6-member heteroaryl may be optionally substituted with one R4; each R4 Is independently selected from hydrogen, halogen, cyano, oxo, C1-6 alkoxy, -C(O)OR5, -C(O)R5, C1-6 alkyl. Moreover , C1-6 alkyl may be optionally substituted with 1 to 3 substituents selected from halogen and cyano; R5 is C1-6 alkyl; and where the central structure of Formula I, limited by X5, X6, X7 and X8, is: or The invention also relates to particular compounds, a method for inhibiting the secretion of WNT signalling in a cell, use of a compound of formula (I), a method for treatment of a disorder mediated by WNT. .EFFECT: new heterocyclic compounds have been obtained that are useful for treatment of cancer, fibrosis and osteoarthritis.22 cl
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

Composition and method of autoimmune diseases treatment // 2621129
FIELD: pharmacy.SUBSTANCE: combination of antibiotics containing rifabutin, clarithromycin and clofazimine for treatment of autoimmune diseases such as multiple sclerosis.EFFECT: increased efficiency of treatment.16 cl, 5 tbl, 12 dwg
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

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), ,

Pyrazine derivatives used as atr kinase inhibitors // 2604066
FIELD: chemistry.SUBSTANCE: present invention relates to pyrazine compounds , used as inhibitors of ATR protein kinase, pharmaceutical compositions containing compounds according to invention, and use of compounds according to present invention to increase cell sensitivity to DNA damaging agents and as a radio-sensitiser and a chemo-sensitiser.EFFECT: high sensitivity of cells to DNA damaging agents, radio-sensitiser and chemo-sensitiser.115 cl, 98 dwg, 18 tbl, 77 ex

Piperidine derivatives as gpr119 agonists // 2603346
FIELD: chemistry.SUBSTANCE: invention relates to a piperidine derivative of formula 1, stereoisomers or pharmaceutically acceptable salts thereof. Compounds of formula 1 have GPR119 agonist properties. In formula 1 [formula 1] W is O or N-Rh group; Ra, Rb and Rh each independently is H or C1-3 alkyl group; Rc is -F or -C1-3 hyperfluoride alkyl group; Rd and Re are each independently selected from a group consisting of H, halogen, -C1-5 alkyl group; or Rd and Re are combined to form a -C3-7 cycloalkyl group; selected from a group consisting of: , where Rf1 and Rf2 are each independently H, halogen or -CN group; selected from a group consisting of: , where Rk1 and Rk2 are each independently H, -CN Group, halogen or -C1-5 alkyl(OH) group; is ; Q is H, -S(O)R1 group, -S(O)2R1 group, -C(O)R1 group, -C(O)OR1 group, -C(O)NHR1 group, -C(O)NR2R3 group, -S(O)2NHR1 group, -S(O)2NR2R3 group or . Invention also relates to a pharmaceutical composition.EFFECT: novel piperidine derivatives of formula 1, which control GPR119 activity, are obtained.8 cl, 183 tbl, 131 ex

ethod of producing n-[5-(3,5-diftorbenzil)-1h-indazole-3-yl]-4-(4-methylpiperazine-1-yl)-2-(tetrahydropyran-4-ylamino)benzamide // 2602071
FIELD: pharmaceutics.SUBSTANCE: invention relates to novel crystalline forms of N-[5-(3,5-diftorbenzil)-1H-indazole-3-yl]-4-(4-methylpiperazine-1-yl)-2-(tetrahydropyran-4-ylamino)benzamide (Formula 1), namely forms 1 and 2, synthesis methods thereof, as well as to pharmaceutical compositions containing them.EFFECT: invention can be used as ALK inhibitor in treating the diseases caused by deregulated kinase activity.16 cl, 8 dwg, 4 tbl, 7 ex (I)

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

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

Phenicol antibacterial agents // 2593204
FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula I or its pharmaceutically acceptable salts, where grouping Het denotes a pyridinyl or thiazolyl; each of R1 and R2 represents H; each R3 and R4 independently denotes H, -C1-8alkyl or R3 and R4, taken together, form C3-6cycloalkyl; W represents -H, -PO(OH)2 or -CH2OPO(OH)2; each of X and Y denotes chlorine or each of X and Y denotes fluorine, and Z is H. EFFECT: compounds of formula I are used in method of controlling and treating infections in livestock, which involves administering animal with therapeutically effective amount of compound of formula I or its pharmaceutically acceptable salt. 8 cl, 3 tbl, 161 ex

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

Dihydrooxazole-2-amine derivatives // 2587512
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I), in which R1 is hydrogen or lower alkyl; R2 represents hydrogen or represents heteroaryl, selected from a pyridinyl, containing as a substitute cyano group; R3 represents hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy group, lower alkoxy group, substituted with halogen, cyano group, S-lower alkyl, S(O)-lower alkyl, S(O)2-lower alkyl, C(O)-lower alkyl or C3-6-cycloalkyl; R4 is hydrogen or lower alkyl; 6-member aromatic ring, possibly containing (N), is a phenyl or pyridinyl, in which N atom can be in different positions; X is a bond or -CH(CF3)-; Ar denotes aryl or heteroaryl, selected from phenyl, naphthyl, quinolinyl, pyridinyl, pyrimidinyl, pyrazinyl, possibly containing one or more as a substitute R3. Invention also relates to a pharmaceutical composition having high affinity for trace amine receptors (TAAR1), containing as an active ingredient a compound of formula (I) and a pharmaceutically acceptable carrier.EFFECT: dihydrooxazole-2-amine derivatives, having high affinity for trace amine receptors (TAAR1), used as therapeutically active substance.14 cl, 1 tbl, 75 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 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

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

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

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

8-azabicyclo[3,2,1]octan-8-carboxamide derivative // 2574597
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula and their pharmaceutically acceptable salts having the property of 11β dehydrogenase hydroxysteroid type 1 (11βHSD1) inhibitor, based medicinal and therapeutic agents, a method for prevention or treatment with using them, and using them for treating 11βHSD1-mediated diseases, such as type 2 diabetes mellitus, impaired glucose tolerance, hyperglycemia, insulin resistance, lipid dismetabolism, hypertension, arterial sclerosis, angiosclerosis, etc. In formula (1) A represents a group, which is presented by formula ; R1a and R1b are identical or different, and each independently represents C1-6 alkyl, which can be optionally substituted by 1-3 halogen atoms; each of m and n independently represents an integer from 0 to 5; X1 represents hydroxyl or aminocarbonyl; Z1 represents a single bond, oxygen atom, sulphur atom, -SO-, -SO2- or -N(R3)-; R2 represents optionally substituted C1-6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted C6-10 aryl, optionally substituted C7-16 aralkyl, optionally substituted 3-7-merous heterocycle, optionally substituted 3-7-merous heterocyclic C1-6 alkyl, optionally substituted 5-12-merous mono- or polycyclic heteroaryl, optionally substituted 5-12-merous mono- or polycyclic heteroaryl-C1-6 alkyl, or optionally substituted 5-7-merous cyclic amino group; R3 represents C1-6 alkyl, C3-7 cycloalkyl, C6-10 aryl, or C7-16 aralkyl; or its pharmaceutically acceptable saly.EFFECT: producing the pharmacologically acceptable salts possessing the property of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) inhibitor.42 cl, 47 tbl, 438 ex

Dipeptidyl peptidase-iv inhibitors // 2574410
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formula , its stereoisomers or pharmaceutically acceptable salts, wherein Y means -CH2-, -CHF- or -CF2-; m = 1, n = 1 or 2, and p represents integers optionally specified in 0, 1 or 2; X means a bond, C1-C5-alkylene or -C(=O)-; R1 means hydrogen, groups specified in alkyl, -S(O)PR10, -NR10S(O)pR11, -CN, -NR10R11, -NR10COR11 or 5-6-merous heterocyclic rings with 1-4 heteroatoms specified in N, O and S, which is optionally substituted by alkoxy, hydroxy, hydroxyalkyl, halogenalkyl, cycloalkyl, aryl, arylalkyl, 6-merous heteroaryl cycle with 1-2 nitrogen atoms or one or more oxo, alkyl, halogen; the substitutes are optionally additionally substituted by one or more halogen atoms; R2, R3 and R4 independently mean hydrogen or alkyl; R2 and R4 may be combined to form an optionally substituted 6-7-merous cycle with 1 heteroatom specified in N and O, wherein the substitutes are specified in one or more oxo or alkyl; R5 means hydrogen or alkyl group; R6 means hydrogen or alkyl; R7 means hydrogen or alkyl; R8 means -CN; R10 and R11 independently mean hydrogen or optionally substituted groups specified in alkyl, cycoalkyl, cycloalkylalkyl, aryl, arylalkyl and 6-merous heterocyclyl with one nitrogen atom; when groups R10 and R11 are substituted with the substitutes representing one or more substitutes specified in halogens, cyano, oxo (=O), thioxo (=S), thioalkyl, amino, alkyl, halogenalkyl and -SO2Ra; wherein Ra means alkyl; the above groups represent C1-C6 alkyl groups; the above cycloalkyl groups represent C3-C10 cycloalkly groups; the above aryl groups represent C6-C10 aryl groups; the above halogens are specified in fluorine, chlorine bromine and iodine. The compounds of formula (I) are produced by binding the compound of formula , which is presented in the free, saline or protected form, with the compound of formula , wherein L means leaving groups specified in chlorine, bromine, iodine, tosylates, mesylates, triflates; PG means hydrogen or protective groups containing acetyl, trifluoracetyl, arylsulphonyl, nosyl, tosyl, -Boc or -CBz. The invention also refers to intermediate compounds of formula (II). The compounds of formula (I) aim at treating diseases controlled or normalised by DPP-IV inhibition.EFFECT: dipeptidyl peptidase (DPP-IV) inhibitors effective for treating conditions controlled or normalised by DPP-IV inhibition, particularly type II diabetes mellitus.19 cl, 2 tbl, 83 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

Novel cyclopentane derivatives // 2572555
FIELD: medicine, pharmaceutics.SUBSTANCE: claimed invention relates to compounds of formula where A1 and R1, R2, R3, R4 and R5 are determined in invention formula, which are preferable inhibitors of cathepsin cycteinprotease, in particular cathepsin S or L cycteinprotease, which makes them useful as medications, especially for treatment of diabetes, atherosclerosis, aneurism of abdominal aorta, peripheral arterial disease or diabetic nephropathy.EFFECT: invention relates to methods of obtaining claimed compounds, thereof-containing pharmaceutical composition and thereof application.24 cl, 1 tbl, 255 ex

New antithrombotic agent // 2570426
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula or their pharmaceutically acceptable salts, wherein Xa represents N or CH; R1e represents C1-6-alkyl optionally substituted by aryl specified in phenyl, naphthyl, fenanthryl and anthryl, or by halogen; C1-6-alkoxy optionally substituted by aryl specified in phenyl, naphthyl, fenanthryl and anthryl, by halogen or C3-8-cycloalkyl; C2-6-alkenyl; C3-8-cycloalkyl; or halogen; R1f represents hydrogen, C1-6-alkyl, C1-6-alkoxy, hydroxyl, cyano or halogen; R21 represents 5-10-merous heteroaryl, which has 1-3 heteroatoms specified in nitrogen, oxygen or sulphur, and which can be substituted by identical or different 1-3 groups specified in the patent claim; R31 represents 6-merous heteroaryl, which has 1 or 2 nitrogen atoms, and which can be substituted by identical or different 1-3 groups specified in the patent claim. The invention also refers to an antithrombotic agent and a medicinal product containing the compounds of formula IIa as an active ingredient, to a method for preventing thrombocyte aggregation, and a method for preventing or treating ischemic stroke, acute coronary syndrome, microvascular dysfunction, peripheral arterial disease, arteriosclerosis obliterans, ischemic heart disease, thrombotic microangiopathy, or unstable or stable angina.EFFECT: compounds of formula IIa exhibiting the inhibitory activity on thrombocyte aggregation.18 cl, 34 tbl, 192 ex

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

Cyclopentylacrylamide derivative // 2565070
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to compound, represented by general formula or its pharmaceutically acceptable salt, in which R1 and R2 independently represent hydrogen atom, C1-C6alkylsulphonyl group, which includes cyclopropylsulphonyl group, or C1-C6alkoxy- C1-C6alkylsulphonyl group, and A is selected from group which includes: thiazolyl group, 1,2,4-thiadiazolyl group, pyrazolyl group, pyridyl group, pyrazinyl group, isooxazolyl group, benzothiazolyl group and thiazolo[5,4-b]pyridyl group, and A can be mono-substituted by substituent, selected from group, which includes halogen atom; C1-C6alkyl groups, optionally substituted with halogen atom or hydroxyl group; C1-C6alkoxyl groups, optionally substituted with halogen atom or hydroxyl group; C1-C3alkoxy-C1-C2alkoxyl groups; C1-C3alkoxycarbonyl-C1-C2alkoxyl groups; C1-C6alkylsulphanyl groups; C1-C6amino-alkylsulphanyl group, optionally substituted with C1-C3alkyl group; C1-C6alkylsulphanyl-C1-C6alcoxyl groups; phenyl group; 1,3-dipxolane, substituted with two C1-C6alkyl groups; piperazinesulphonyl is substituted with methyl group; 1,3-dioxolanemethyl, substituted with two methyl groups; piperazinemethyl, substituted with methyl group; tetrahydropyranyloxy-C1-C3alkoxy group; aminosulphonyl groups, optionally substituted with C1-C3alkyl group; C1-C6 hydroxyalkylsulphanyl groups; -(O)(CH2)C(O)O-C1-C6alkyl group; -C(O)O-C1-C6 alkyl group; as well as groups, represented by general formula -(CH2)mP(O)R4R5 (where R4 and R5 independently represent C1-C3alkoxyl group; m is integer number from 0 to 1). Compound of formula (1) is intended, as active ingredient, for production of pharmaceutical composition, which has effect for activation of glucokinase (GK) or hypoglycaemic action. Invention also relates to intermediate compounds, represented by formula in which R1 and R2 independently represent hydrogen atom, C1-C6alkylsulphonyl group, which includes cyclopropylsulphonyl group, or C1-C6alkoxy-C1-C6alkylsulphonyl group.EFFECT: acrylamide compounds as glucokinase activator for treatment of diabetes.21 cl, 38 tbl, 55 ex

Identification of lkb1 mutation as prognostic biomarker of sensitivity to tor-kinase inhibitors // 2565034
FIELD: medicine, pharmaceutics.SUBSTANCE: group of inventions relates to medicine and can be used for application of TOR-kinase inhibitor for obtaining medication for treatment of non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers syndrome. For this purpose effective quantity of TOR-kinase inhibitor, representing 7-(6-(2-hydroxypropan-2-yl)pyridine-3-yl)-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or 1-ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridine-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one or its pharmaceutically acceptable salt is introduced to patient. Pharmaceutical composition and sets for treatment of diseases, application for prediction of probability of patient's response to therapy with TOR-kinase inhibitor, application for prediction of therapeutic efficiency of treatment with TOR-kinase inhibitor are also claimed. EFFECT: group of inventions provides diagnostics and treatment of non-small lung carcinoma, cervical cancer, Peutz-Jeghers syndrome, which are characterised by absence or mutation of gene or protein LKB1 and/or AMPK in comparison with wild type.25 cl, 7 dwg

Substituted pyrrolidin-2-carboxamide // 2564022
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to specific derivatives of pyrrolidine-2-carboxamides specified in point 1 of the patent claim, and their pharmaceutically acceptable salts. The invention also refers to a pharmaceutical composition inhibiting the p53 and MDM2 reaction and to using the above compounds for treating cancer.EFFECT: derivatives of pyrrolidine-2-carboxamide as p53 and MDM2 protein reaction inhibitors applicable for treating cancer.11 cl, 475 ex

Spiro amino compounds applicable for treating sleep disorders and drug addiction // 2562609
FIELD: medicine, pharmaceutics.SUBSTANCE: invention related to a spiro amino compound of formula,wherein m represents 1 or 2 or 3, n represents 1 or 2, R is specified in a 6-merous aromatic ring and a 5-merous heteroaromatic ring containing 1 to 2 heteroatoms specified in S and N; this ring is substituted by one or two substitutes specified in a group consisting of (C1-C3)alkyl, halogen atom, (C3-C5)cycloalkyloxygroup, phenyl optionally substituted by one or more halogen atoms, 5- or 6-merous heterocycle containing at least one nitrogen atom specified in 1,2,3-triazole, pyrimidine, pyridine, and pyrazine; P represents a substitute Q, wherein Q is specified in a group consisting of phenyl, pyridyl, pyrimidyl; Q is optionally substituted by one or more substitutes specified in a group consisting of (C1-C3)alkyl, halogen, trifluoromethyl, methylcarboxygroup. The invention also refers to a spiro amino compound of formula (VI), wherein m represents 1 or 3, n represents 1 or 2, R represents phenyl substituted by the substitute cyclopropyl (C1-C3)alkoxy, P represents a substitute Q, wherein Q is specified in a group consisting of phenyl, pyridyl, pyrimidinyl; Q is optionally substituted by one or more substitutes specified in a group consisting of (C1-C3)alkyl, halogen, trifluoromethyl and methylcarboxygroup. The compounds of formula IV are applicable to produce a drug preparation for treating the pathologies, which require an orexin receptor 1 antagonist to be applied.EFFECT: spiro amino compounds possessing the orexin receptor agonist activity.19 cl, 99 ex

Application of antagonists of opioid receptors in case of gastrointestinal tract diseases // 2561873
FIELD: medicine.SUBSTANCE: group of inventions relates to medicine, namely to method of treatment or prevention of opioid-induced constipation or opioid-induced intestine dysfunction in patients without reduction of mediated opioid anaesthesia or development of symptoms of central opioid withdrawal, associated with activation of opioid receptors on periphery. For this purpose effective quantity of 5-(2-methoxy-4-{[2-(tetrahydropyran-4-yl)-ethylamino]methyl}-phenoxy)pyrazine-2-carboxamide (Compound I) or its pharmaceutically acceptable salt is introduced to patient.EFFECT: group of inventions provides treatment or prevention of frequent side effects in patients who have taken opioids for several days.12 cl, 9 dwg, 1 tbl, 3 ex

Anticancer agent involving combinations of kinase inhibitory compounds // 2560683
FIELD: medicine, pharmaceutics.SUBSTANCE: presented is a group of inventions involving an anticancer agent for combined application of a compound representing N-(2-fluor-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide or its pharmaceutically acceptable salt of formula (I), and the compound 4-[3-chlor-4-(cyclopropylamino-carbonyl)amino-phenoxy]-7-methoxy-6-quinolinecarboxamide or its pharmaceutically acceptable salt of formula (II), (versions), an anticancer pharmaceutical composition containing the compound of formula (I) and the compound of formula (II), as well as a method of treating cancer. The compound of formula (I) , the compound of formula (II) .EFFECT: excellent anticancer effect on various types of cancer as compared to using the declared compounds separately.5 cl, 5 dwg, 5 tbl

Quinolone analogues and related methods // 2549895
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formula , wherein A and V independently represents H or a halogen; Q is absent; R4 independently represents H, a C1-C6 alkyl or C3-C6 cycloalkyl; R7 represents H; and R8 represents a C1-C10 alkyl substituted by OH or C1-C6 alkoxy; or C1-4 alkyl substituted by a 5-6-merous aromatic heterocyclic ring containing 1-2 heteroatoms specified in N and S, wherein the above aromatic heterocyclic ring is optionally substituted by a C1-C10 alkyl; or in -NR7R8, R7 and R8 together with N can form an optionally substituted azacyclic ring containing where applicable an additional heteroatom specified in H, O and S, as a cycle member, optionally substituted by a C1-C10 alkyl, which is substituted by a C1-C6 alkoxy; m is equal to 0; n is equal to 0. The invention also refers to a compound of formula (wherein the substitutes are those as specified in the patient claim), to a pharmaceutical composition containing a therapeutically effective amount of the compounds of formula (VIII), and to a method of treating or relieving a cell-proliferative disorder.EFFECT: compound of formula (VIII) inhibiting cell proliferation or cell apoptosis.12 cl, 1 dwg, 14 tbl, 55 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

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

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

Bruton's tyrosine kinase inhibitors // 2542585
FIELD: medicine.SUBSTANCE: present invention refers to compounds having formula III such as below, wherein: Q represents C(Y3) or N; R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl or heterocyclyl each of which is optionally substituted by one or more C1-6alkyls, hydroxyC1-6alkyls, oxogroups or halogenC1-6alkyls; R2 represents -C(=O), -O, -C(R2')2, -C(R2')2C(=O), -C(R2')2C(=O)NR2', C(R2')2 N(R2')C(=O), -C(=NH), -C(R2')2NR2' or -S(=O)2; each R2' independently represents H or C1-6alkyl; R3 represents H or R4; R4 represents C1-6alkyl, C1-6alkoxygroup, aminogroup, C1-6alkylaminogroup, di(C1-6alkyl)aminogroup, heterocyclyl, C1-10alkylheterocycloalkyl, heterocycloalkylC1-10alkyl each of which is optionally substituted by one or more C1-6alkyls, C1-6alkylaminogroups, di(C1-6alkyl)aminogroups, hydroxygroups, hydroxyC1-6alkyls, C1-6alkoxygroups, oxogroups or halogenC1-6alkyls; X represents CH; X' represents CH; and the rest symbols have values as specified in the patent claim. The compounds of formula III inhibit Bruton's tyrosine kinase (Btk). There are also described compositions containing the compounds of formula III, and at least one carrier, thinner or excipient, and a method for producing the compound of formula X in accordance with the following procedure.EFFECT: compositions are effective for modulating Btk activity and treating diseases related to Btk hyperactivity, and can be used for treating inflammatory and autoimmune diseases related to disturbed B-cell proliferation, such as rheumatoid arthritis.22 cl, 2 tbl, 260 ex

Nitroimidazooxazine and nitroimidazooxazole analogues and use thereof // 2540860
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.EFFECT: obtaining novel compounds with useful biological activity.7 cl, 21 dwg, 3 tbl

Compound with successive aricyclic structure, possessing activity of inhibiting acycloenzyme a diacylglycerolacyltransferase (dgat1) // 2538964
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclic compound of formula or to its pharmaceutically acceptable salt, where Alk represents linear C1-6 alkylene group, branched C1-6 alkylene group or C1-6 alkylene group, which has ring structure, where part of carbon atoms, constituting ring structure can be optionally substituted with oxygen atom, in ring X, X1 represents N or CRX1, X2 represents N or CRX2, X3 represents CRX3, X4 represents N or CRX4, where RX1, RX2, RX3 and RX4 each independently represents hydrogen atom; linear or branched C1-6alkyl group; linear or branched C1-6alcoxygroup; or halogen atom, in ring Y, Y1 represents CRY1, Y2 represents N or CRY2, Y3 represents N or CRY3, Y4 represents N or CRY4, RY1, RY2, RY3 and RY4 each independently represents hydrogen atom; linear or branched C1-6alkyl group, which can be substituted with halogen atom(s); C3-7alkyl group, which has ring structure; linear or branched C1-6alkoxygroup; halogen atom or cyanogroup, in ring Z, RZ represents linear or branched C1-6alkyl group, which can be substituted with halogen atom(s), or C3-7alkyl group, which has ring structure, which can be substituted with halogen atom(s). Invention also relates to particular compounds, DGAT1 inhibitor based on formula (I) compound, application of formula (I) compound, method of prevention or treatment of diseases, mediated by DGAT1 inhibition.EFFECT: obtained are novel compounds, possessing useful biological activity.19 cl, 19 tbl, 149 ex

Aminopyrazine derivatives and medications // 2535217
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to novel compounds of general formula [1] or their pharmaceutically acceptable salts, which possess properties of an inhibitor of the JAK2 thyrokinase activity. In general formula radicals are selected from group (I) or (II). In group (I) X represents CH or N; R1 represents a halogen atom and R2 represents H, a halogen atom, CN, or is selected from the groups of formulas , or a group -ORP or 5-6-membered heteroaryl, containing 1-4 nitrogen atoms and optionally additionally containing an oxygen or sulphur atom or containing an oxygen atom as a heteroatom, optionally substituted; or (II) X represents -CRA; and RA represents a group of formula , RB represents (a) amino, optionally substituted with one or two groups, selected from the group, consisting of C1-6alkyl, C3-6cycloalkyl, (C3-6cycloalkyl)C1-6alkyl and C1-3alcoxyC1-3alkyl, (b) C1-3alcoxy, (c) hydroxy or (d) a 5-6-membered saturated cyclic amino group, which additionally can contain a heteroatom, selected from an oxygen atom; R1 represents a halogen atom and R2 represents H; R3 -R5 have values given above. Other values of the radicals are given in the invention formula.EFFECT: compounds can be applied for the prevention or treatment of cancer, for instance hematologic cancer disease or a solid form of cancer, inflammatory disorder, for instance, rheumatoid arthritis, inflammatory intestinal disease, osteoporosis or multiple sclerosis and angiopathy, for instance, pulmonary hypertension, arteriosclerosis, aneurism or varicose veins.14 cl, 19 tbl, 234 ex

Oxyindole derivatives possessing agonist activity on motilin receptor // 2533116
FIELD: medicine, pharmaceutics.SUBSTANCE: group of inventions refers to new oxyindole derivatives of formula (I) or their pharmaceutically acceptable salts, based pharmaceutical compositions and using them for treating various disorders, which are mediated through the motilin receptor (GPR38). In general formula I, R1 means hydrogen, C1-C4alkyl or C3-C7cycloalkyl; R2 means C1-C4alkyl or C3-C7cycloalkyl; or R1 and R2 together with atoms which they are bound to, form a 3-6-merous ring, which can contain oxygen; R3 and R4 mean hydrogen or C1-C4alkyl; R5 means hydrogen or C1-C4alkyl; R6 and R7 mean hydrogen, C1-C4alkyl or C1-C4alkoxy C1-C4alkyl; or R6 and R7 together with a nitrogen atom which they are bound to, form a 4-6-merous ring, which can contain nitrogen or oxygen; the 4-6-merous ring is optionally substituted by 1-4 substitutes specified in a group consisting of C1-C4alkyl, amino, C1-C4alkylamino and di(C1-C4alkyl)amino; A means or , wherein p, q and r independently have the values of 0, 1 or 2; R8 and R9 mean hydrogen or C1-C6alkyl; wherein alkyl is optionally substituted by hydroxy, C1-C4alkyl, amino, C1-C4alkylamino and di(C1-C4alkyl)amino; or R8 and R9 can be combined to form a C3-C7-merous ring; or R8 and R9 can be independently combined with one or both R8 and R9 groups to form alkylene bridges between terminal nitrogen and an alkyl part of R8 or R9 groups; the bridge contains 1 to 5 carbon atoms; the above bridge is optionally substituted by 1-4 C1-C4 alkyl groups; W means N-R10, the above R10 means hydrogen or C1-C4alkyl; X means C0-C4alkylene or C0-C4alkylene-K-C0-C4alkylene, wherein K means -O- and wherein alkylene is optionally substituted by C1-C4alkyl; Y means hydrogen or a 5-10-merous ring; the above ring is optionally substituted by hydroxyl, halogen, halogen C1-C4alkyl, C1-C4alkyl or C1-C4alkoxy; provided X means C0, Y means other than hydrogen; Z means halogen or C1-C4alkyl; m has the value of 0, 1, 2, 3 or 4; n has the value of 0, 1 or 2.EFFECT: preparing the new oxyindole derivatives.10 cl, 15 tbl, 99 ex

Diaminoheterocyclic carboxamide compound // 2526253
FIELD: medicine, pharmaceutics.SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.16 cl, 201 tbl, 582 ex

Pharmaceutical composition based on 6-[(4-methyl-1-1-piperazinyl)methyl]-indolo[1',7':1,2,3]pyrrolo[3',4':6,7]azepino[4,5-b]indole-1,3(2h,10 h)-dione as anti-tumour medication // 2523387
FIELD: chemistry.SUBSTANCE: claimed is a pharmaceutical composition, which contains as minimum one active component - a pharmaceutically acceptable salt of 6-[(4-methyl-1-1-piperazinyl)methyl]-indolo[1',7':1,2,3]pyrrolo[3',4':6,7]azepino[4,5-b]indole-1,3(2H,10 H)-dione of formula (I), in particular mesylate of 6-[(4-methyl-1-1-piperazinyl)methyl]-indolo[1',7':1,2,3]pyrrolo[3',4':6,7]azepino[4,5-b]indole-1,3(2H,10 H)-dione of formula (1) and as minimum one auxiliary substance.EFFECT: demonstrated suppression of growth of adenocarcinoma and melanoma tumour.2 tbl
 
2551075.
Up!