Ortho-condensed systems (C07D471/04)

Salts and crystalline forms of apottosis-inducing agent // 2628560
FIELD: pharmacology.SUBSTANCE: invention relates to a compound having the systematic name 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy) benzamide (compound 1) in the form of a free base crystalline anhydrate, a free base hydrate of crystalline form, a solvate of crystalline form, a hydrochloride salt of crystalline form, or a sulfate salt of crystalline form. The invention also relates to a pharmaceutical composition having an inhibitory activity against anti-apoptotic proteins of the Bcl-2 family comprising a therapeutically effective amount of the compound of the invention and one or more pharmaceutically acceptable excipients.EFFECT: crystalline forms of compound 1 suitable for use as an active pharmaceutical ingredient.21 cl, 14 dwg, 14 tbl, 17 ex
Compound as wnt signal inhibitor, its compositions and application // 2627712
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of the general formula (I) or an N-oxide thereof, wherein X1, X2, X3 and X4 independently represent CR4 or N, where 0 or 1 of X1-X4 can be N; Y1, Y2 and Y3 are hydrogen; R1 is selected from hydrogen, , C6 aryl, 6-member heterocycloalkyl containing 2 heteroatoms selected from N and O, and 5- or 6-member heteroaryl containing 1-4 heteroatoms selected from N, O and S, wherein each of C6 aryl, 6-member heterocycloalkyl and 5- or 6-member heteroaryl may be optionally substituted with one R4; R2 is selected from hydrogen, halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl and 6-member heteroaryl may be optionally substituted with one R4. If X5 is N, R2 is selected from halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl, and 6-member heteroaryl may be optionally substituted with one R4; each R4 Is independently selected from hydrogen, halogen, cyano, oxo, C1-6 alkoxy, -C(O)OR5, -C(O)R5, C1-6 alkyl. Moreover , C1-6 alkyl may be optionally substituted with 1 to 3 substituents selected from halogen and cyano; R5 is C1-6 alkyl; and where the central structure of Formula I, limited by X5, X6, X7 and X8, is: or The invention also relates to particular compounds, a method for inhibiting the secretion of WNT signalling in a cell, use of a compound of formula (I), a method for treatment of a disorder mediated by WNT. .EFFECT: new heterocyclic compounds have been obtained that are useful for treatment of cancer, fibrosis and osteoarthritis.22 cl
Compounds of pyridazinamide and their use as synthetic syneckinasis inhibitors (syk) // 2627661
FIELD: chemistry.SUBSTANCE: invention relates to novel pyridazinamides of the formula I , where all variable substituents are defined in the claims, and their pharmaceutically acceptable salts, as well as a pharmaceutical composition based on them.EFFECT: compounds of the formula are SYK inhibitors and are useful for the treatment of autoimmune and inflammatory diseases.10 cl, 1 tbl, 43 ex
Heterocyclyl pyridinylpyrazoles // 2627272
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclylpyridinylpyrazoles of the formula (I), in which R1-R5, X1, U, Q, W, a, b and n have the values defined as defined in the invention formula and their agrochemically active salts. Compounds of formula (I) can be used to control phytopathogenic harmful fungi in agriculture, horticulture, forestry, livestock, materials protection, household and hygiene, and to reduce the content of mycotoxins in plants and parts of plants. The invention also relates to the use of compounds of formula (I) and to method and composition for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on plant seeds.EFFECT: decrease the content of mycotoxins in plants and parts of plants.10 cl, 7 tbl, 31 cl
Aza-aryl-1-h-pyrazol-1-yl-sulphonamides // 2627268
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) ,in which radicals and characters have values specified in the claims and their versions. The proposed compounds act as potent antagonists of CCR (9) receptor. Animal testing has shown that these compounds are useful for treatment of inflammation, disease with a hallmark for CCR (9). The compounds as a whole are arylsulfamide derivatives and are used in pharmaceutical compositions, methods for treatment of CCR (9) mediated diseases and as a control in assays for identification of CCR (9) antagonists.EFFECT: increased efficiency of compounds application.26 cl, 2 tbl, 33 ex
Adamantyl derivatives useful for treatment of jnk-mediated disorder // 2626890
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to the heterocyclic compound of I formula or a pharmaceutically acceptable salt thereof, wherein R represents phenyl optionally substituted with one or more R'; R' is halo or methoxy; X represents CH; X1 represents C(=O)OCH3; Y represents N; Y1 It is OH, N(Y1')2, NHS(=O)2Y1', NHC(=O)Y1', NHC(=O)C(CH3)2OH or NHC(=O)C(CH3)2OC(=O)Y1'; each Y1' independently represents H, C1-6-alkyl or lower cycloalkyl; Y2 It is H. The invention also relates to formula I based on the compound of the pharmaceutical composition and the use thereof.EFFECT: new heterocyclic compounds useful for treating JNK-mediated disorder are obtained.12 cl, 5 tbl, 31 ex

New pyrazole derivative // 2625790
FIELD: pharmacology.SUBSTANCE: in particular, invention relates to a compound represented by the following general formula (I): [wherein Ar1 is 2-methoxy-4-(2-pyridylmethoxy)phenyl, etc. and Ar2 is 1H-indole-6-yl group, etc.] or to salt thereof.EFFECT: increased efficiency of treatment.19 cl, 4 dwg, 1 tbl, 112 ex
8-carbamoyl-2-(2,3-di-substituted pyrid-6-yl)-1,2,3,4-tetrahydroisoquinoline derivatives as apoptosis-inducing agents for cancer treatment // 2625315
FIELD: pharmacology.SUBSTANCE: invention relates to organic chemistry, namely a heterocyclic compound of formula (I) or to a therapeutically acceptable salt thereof, where X is benzo[d]thiazolyl, thiazolo[5,4-b]pyridinyl, thiazolo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, thiazolo[5,4-c]pyridinyl, thiazolo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl or imidazo[ 1,2-b]pyridazinyl; Y1 means pyrrolyl, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with 1 or 2 substituents independently selected from R5, CN and Cl; L1 is selected from (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-S-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; Y2 means mono- or tricyclic C8-C10-cycloalkyl, spiro[2.5]octyl, spiro[3.5]nonyl, oxatricyclo[3.3.1.13,7]decyl or azabicyclo[3.2.1]octyl; where Y2 is optionally substituted with 1, 2 or 3 substituents independently selected from R8, OR8, SO2R8, CO(O)R8, OH and Br; Z1 is selected from , R1 and R3 are absent; R2 is deuterium or C1-C6-alkyl; R5 is C1-C6-alkyl; R6A is selected from hydrogen and C1-C6-alkyl; each R6 and R7 are hydrogen; R8 is selected from the group consisting of C1-C3-alkyl, morpholinyl and dioxydothiomorpholinyl; where R8, meaning C1-C6-alkyl, is optionally substituted with a substituent selected from R16, OR16, SO2R16 and NHR16; Rk is selected from C1-C6-alkyl, morpholinyl, cyclopropyl and C1-haloalkyl; R16 Is selected from C1-C4-alkyl, phenyl, morpholinyl and tetrahydropyranyl; where R16, meaning C1-C4-alkyl, is optionally substituted with 1 substituent selected from OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s, m and p is 0; r is 0 or 1; N is 0, 1, or 2. The invention also relates to specific compounds, pharmaceutical compositions based on these compounds and a method for treatment of these diseases.EFFECT: new heterocyclic compounds are obtained, that are useful for treatment of some cancers.16 cl, 3 tbl, 86 ex
Hydinine derivatives as inheritors of ferment pde10a // 2624440
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to heterocyclic compounds selected from 7-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline and 6-[2-(5,8-dimethyl[1,2,4]triazolo[1,5-a]pyrazin-2-yl)-ethyl]-[1,3]dioxolo[4,5-g]quinoline and the pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions on the basis of one of these compounds and the use of these compounds.EFFECT: obtained new heterocyclic compounds useful in the treatment of a neurodegenerative or psychiatric disorder.10 cl, 1 tbl, 2 ex
Kinase inhibitors // 2623734
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof which have an inhibitory activity against p38 MAP kinase. In formula (I), W is NH, Y is selected from the -O (CR3R4)n- group, where n is 0, R1 is (IIb) group , X1 is -(CH)-, R9 is C1-C6alkyl, C3-C6cycloalkyl or phenyl optionally substituted with halogen atoms, R12 is a hydrogen atom, A is a bivalent cycloalkylene radical having 5, 6 or 7 ring atoms, wherein the said cycloalkylene ring is attached to W and Y and fused to a phenyl ring, wherein such phenyl ring is optionally substituted with one or two R27 groups, R27 is selected from halogen, R2 is a radical of formula (IVb) or (IVc) where R17 is selected from a single electron pair, hydrogen or aryl, where any such aryl may be optionally substituted by a C1-C6alkyl or C3-C7cycloalkyl; or R17th is a group of general formula (V) R20 is selected from the group consisting of -CH3 or -C2H5; R21 is -CH3 or -C2H5; R18 is selected from the group consisting of a single electron pair, hydrogen, aryl, heteroaryl, -(C1-6alkyl), -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(C1-C6alkyl) and (C5-C7heterocycloalkyl)-(C3-C6cycloalkyl) group, R19 Is selected from -CF3, z1, z2, z3 and z4 are independently selected from the group consisting of C, N, O, -CH- and -NH- groups, in such combination that the resulting ring is an aromatic system, T is -CR28=; R28 is halogen; R22 is H or halogen. The invention also relates to a pharmaceutical composition comprising the said compounds, a method for treatment of diseases which benefit from p38 MAP kinase inhibition, and their application for manufacture of a medicament for treatment of such diseases.EFFECT: increased efficiency of compounds application.14 cl, 2 tbl, 35 ex
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

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

Application of adamantane indole and their hydrochlorides as cholinesterase inhibitors and nmda-receptors blockers // 2621348
FIELD: pharmacology.SUBSTANCE: invention relates to application of adamantane-containing indoles and their hydrochlorides of general formula where R1, R2, R3, R4 may be the same or different and independently represent H, F, Cl, Br, (C1-C6) alkyl, (C1-C6) alkoxy; R5, R6 may be the same or different and independently represent H, (C1-C6) alkyl, ONO2; X represents CH2CH(OH)CH2 or CH2CH2C(O); Z=no, Cl; R7, R8, R9, R10 may be the same or different and independently represent H, F, Cl, Br, (C1-C6) alkyl, (C1-C6) alkoxy; R11, R12, R13, R14, R15, R16, R17, R18 may be the same or different and independently represent H, (C1-C6) alkyl, as a cholinesterase inhibitors and NMDA receptors blockers, and can be used as new drugs that interact with several targets responsible for improval of memory and cognitive functions, weakening of which has various origin, including dementias of various origins, especially due to neurodegenerative diseases, such as Alzheimer's disease.EFFECT: increased compound application effeciency.15 cl, 1 dwg, 1 tbl, 3 ex
Heterocyclic derivatives as receptors associated with tracer amines (taars) // 2621050
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula and to pharmaceutical compositions based thereof.EFFECT: new compounds are obtained with an affinity for the receptors to TAAR1 and can be used to treat depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder, disorders caused by stress, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, malnutrition, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, temperature homeostasis disorders, sleep disturbance, circadian dysregulation and cardiovascular disorders.23 cl, 16 dwg, 1 tbl, 55 ex
Pyrazole quinolinone derivatives, their preparation and therapeutic application // 2621037
FIELD: pharmacy.SUBSTANCE: invention relates to compounds according to formula (I) , wherein R1, R2 and R3 are as defined in claim cl. 1. The compounds of this invention are reversible and selective inhibitors of type 2 methionine aminopeptidase (MetAP2). The invention also relates to intermediates for preparing the compounds of formula (I), drug and pharmaceutical compositions based on the compounds of formula (I) and their therapeutic application.EFFECT: increased efficiency of compounds application.24 cl, 2 tbl, 25 ex
ethod for prepairing derivatives of 2-phenyl [1,2,4] triazolo [1,5-a] pyridine // 2620379
FIELD: chemistry.SUBSTANCE: invention relates to the method for prepairing derivatives of 2-phenyl [1,2,4] triazolo [1,5-a] pyridine of the formula or its salts, wherein R1 represents hydrogen, halogen, an optionally protected hydroxy group or an optionally protected amino group and R2 represents hydrogen or halogen comprising reacting the pyridine compound of the formula or its salt with benzonitrile in the presence of Cu-catalyst, a 1,10-phenanthroline derivative, and the mixtures of O2/N2 characterized in that no other solvents other than benzonitrile participating in the reaction thereof, are not applicable.EFFECT: new method for preparing a compound of the formula I, applicable on a large scale, is proposed.13 cl, 1 tbl, 8 ex

Solid forms of selective cdk4/6 inhibitor // 2619944
FIELD: pharmacology.SUBSTANCE: invention relates to the crystalline free base of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a polymorphic form A with a specific surface area less than or equal to 2 m2/g and a powder X-ray diffraction pattern containing peaks with diffraction angles (2θ) 8.0±0.2, 10.1±0.2 and 11.5±0.2, as well as to pharmaceutical compositions based thereon.EFFECT: free base with larger particle size and improved physicochemical properties is obtained, which can be used for treatment of cell-proliferative diseases such as cancer.13 cl, 9 dwg, 13 tbl, 7 ex
Substituted imidazopyridinyl-amino-pyridine compounds, useful for treatment of cancer // 2619463
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of formula (I) or a pharmaceutically acceptable salt or ester, wherein X1: N and X2: CRx; Rx, R1 and R3: H, halogen, nitro, C1-C6alkyl, C1-C6alkyl, substituted by three halogen atoms, C1-C6alkoxy, amino, C6-C10-aryl, C6-C10-aryl substituted by 1-2 substituents selected from hydroxyl, halogen, cyano, amino, di-C1-C6alkilamino, C1-C6alkyl, C1-C6alkyl substituted by hydroxyl or amino, C1-C6alkoxy, C1-C6alkoxy substituted by three halogen atoms, C1-C6alkilkarbonyl, C1-C6alkoxykarbonyl, carboxyl, aminocarbonyl, C1-C6alkilaminokarbonyl, C1-C6alkilkarbonylamino, C1-C6alkilsulfinyl, 5-x heteroaryl containing 2 atom of N, and 5-x or 6-x heterocycle Containing 1-2 heteroatoms selected from N and O, Heteroaryl containing one or two 5-x or 6-x rings and 1-2 heteroatoms selected from N, O and S, heteroaryl containing one or two 5-x or 6-x rings and 1-2 heteroatoms selected from N and O, substituted by 1 or more substituents selected from hydroxyl, halogen, amino, C1-C6alkylcarbonyl, carboxyl, C1-C6alkyl and a 6-x heterocycle containing 2 heteroatoms selected from N and O, C3-C6 saturated carbocycle or 6-membered A heterocycle containing 1 N atom; X or y is 0 or 1; Rp1: halogen; Rp2: C1-C6alkyl or 5-x heteroaryl containing 2 heteroatoms selected from N and O; Rn5 and Rn6: H or S(O)2R8; R8: H or C1-C6alkyl; R: H, halogen, C1-C6alkyl, C1-C6alkyl, substituted by amino, C1-C6alkoxy, amino, 5-x heteroaryl containing 2-3 heteroatoms selected from N, C3-C6saturated carbocycle, C3-C6 saturated carbocycle substituted by one A substituent selected from amino, C1-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, carboxyl, and aminocarbonyl, a heterocycle containing one 4-x or 6-x ring and 1-2 heteroatoms selected from N, A heterocycle containing one 4-, 5-x or 6-x ring and 1-2 heteroatoms selected from N, O and S substituted with one substituent selected from methyl and amino or Q-T; Q: connection or C1-C6alkyl linker; T: NRn1Rn2, C(O)Ro, or S(O)2Rs; Rn1: H; Rn2: H, C1-C6alkyl, C1-C6alkyl substituted by C6-C10aryl, C(O)R4, C(O)OR4, C(O)NR4'R4, or S(O)2R5 or Rn1 and Rn2, together with the nitrogen atom to which they are attached form a 6-x ring, which optionally contains 1 additional O atom; R4, R4', and R5: H, C1-C6alkyl, C1-C6alkyl substituted by 1-2 substituents independently selected from C6-C10aryl, 5-x or 6-x heteroaryl containing 1 to 4 N atoms and C3 to C6 saturated carbocycle, C6-C10aryl, C6-C10aryl substituted by 1-2 substituents independently selected from halo, cyano, C1-C6alkyl, C1-C6alkyl substituted with three halogen atoms or with one phenyl, C1-C6alkoxy, C1-C6alkoxy substituted with three atoms of halogen, C1-C6alkilamino, di-C1-C6alkilamino, C6-C10arilkarbonyl wherein aryl is substituted by halogen, C1-C6alkoksikarbonyl, C1-C6alkilkarbonylamine, C6-C10-aryl and 5-h ennogo heteroaryl containing 1 or 2 N atoms, heteroaryl containing one or two 5-x or 6-x rings and 1-2 heteroatoms selected from N, O and S, heteroaryl containing one or two 5- or 6-membered rings and 1-2 heteroatoms selected from N, O and S, substituted with 1 or 2 substituents independently selected from halogen and C1-C6 alkyl, or C3-C6 saturated carbocycle; Ro: C6-C10aryl, NRo1Ro2, or ORo3; Rs: a 6-x heterocycle containing 1 N atom, or NRs1Rs2; Ro1 and Ro2: H, C1-C6alkyl, C1-C6alkyl substituted by 1 substituent selected from C3-C8 saturated carbocycle, C6-C10 aryl, and C1-C6alkylcarbonylamino, C6-C10aryl, C6-C10aryl substituted by one or two substituents, Independently selected from halogen, cyano, C1-C6alkyl, C1-C6alkoxy and C1-C6alkylcarbonylamino, heteroaryl containing one or two 5-x or 6-x rings and 1 heteroatom selected from N or O, heteroaryl containing one or two 5-x or 6-x rings and 1-2 heteroatoms selected from N and S substituted with one substituent selected from halogen and C1-C6alkyl or C3-C6 A saturated carbocycle; Ro3: H or C1-C6alkyl; And Rs1 and Rs2: H or C1-C6alkyl. The invention also relates to specific compounds, pharmaceutical compositions based on compounds of formula (I) a method of treating a cell proliferative disorder.EFFECT: obtaining novel heterocyclic compounds, useful in the treatment of bacterial infections.21 cl, 4 tbl, 134 ex
Novel condensed pyridine derivatives used as c-met tyrosine kinase inhibitors // 2619130
FIELD: chemistry.SUBSTANCE: compounds have c-Met inhibiting properties. In the formula I B is absent, represents O, S, OCH2 or SCH2; each of the R1, R2, R3 and R4 independently represents hydrogen, halogen, unsubstituted C1-6alkyl, C1-6alkyl substituted by hydroxyl or 3-6 membered heterocyclyl with one heteroatom selected from N; carbamoyl; R1 and R2 or R3 and R4 form = O or cyclopropyl together; A represents N or CH; n equals 0, 1 or 2; each of the R5 independently represents halogen or unsubstituted C1-6alkyl; Z is NHR6 or is represented by formula II , where each of the R18 and R19 independently represents an unsubstituted C1-8alkyl or phenyl substituted by halogen; R6 is represented by formula , when R6 represented by formula VII, B represents O, S,OCH2 or SCH2; B1 represents where each of the Q1 independently represents C(R7)2; B2 represents NHQ2, and Q2 represents phenyl substituted by halogen; Q3 represents hydrogen or phenyl substituted by halogen; each of the R7, R8, R9 and R10 independently represents hydrogen or phenyl substituted by halogen. The invention also relates to a pharmaceutical composition, to use of pharmaceutical composition to prepare a medical agent; to use of a compound to prepare a medical agent.EFFECT: obtaining novel condensed derivatives of formula I, having a high inhibitory activity on c-Met.36 cl, 2 tbl, 73 ex

N-piperidin-3-yl-benzamide derivatives for cardiovascular diseases treatment // 2618628
FIELD: pharmacology.SUBSTANCE: invention relates to substituted amide compounds of formula pharmaceutical compositions containing such compounds and application of such compounds for lowering plasma lipid levels, such as low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides, and thus, for treatment of diseases exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in mammals, including humans.EFFECT: increased efficiency of compounds application.42 cl, 10 dwg, 55 ex
New compounds and compositions for nampt inhibition // 2617988
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to the compound of IIB formula, or its pharmaceutically acceptable salts in which R represents a bicyclic nine-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, wherein the said heteroaryl may be substituted by one or more substituents selected from the group consisting of oxo and halo; R1 is -NHR4 and R4 is 3-10 membered cycloalkyl, aryl selected from phenyl and tetrahydronaphthalene, or 9-10 membered heteroaryl containing 1 or 2 heteroatoms selected from N and O; 3-10 membered cycloalkyl; aryl selected from phenyl and naphthalenyl; or 5-10-membered monocyclic or bicyclic heteroaryl comprising one or two heteroatoms selected from N, O and S; R2 and R3 are hydrogen; values of other substitutes are specified in the invention formula; or where the compound is selected from a group consisting of compounds specified in the invention formula. Invention compounds have properties of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor. The invention also refers to individual compounds selected from the group indicated in the invention formula, to the pharmaceutical composition, method of treatment, compounds application and application of the pharmaceutical composition.EFFECT: invention provides new compounds of IIB formula, with the properties of nicotinamide phosphoribosyltransferase inhibitor which can be used for hyperproliferative disorders treatment.33 cl, 4 tbl, 25 ex
Novel compounds and compositions for inhibiting nampt // 2617643
FIELD: chemistry.SUBSTANCE: present invention relates to compounds of formula II: .EFFECT: novel compounds of formula II are obtained, which can be used in method of inhibiting nicotinamide-phosphoribosyltransferase "NAMPT", as well as pharmaceutical compositions based thereon.17 cl, 3 tbl, 11 ex
Novel compounds and compositions for inhibiting nampt // 2617424
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula IIIA .EFFECT: obtaining novel compounds of formula IIIA, as well as compositions based thereon for inhibiting NAMPT, described is use of compounds for preparing a drug for treating cancer.21 cl, 3 tbl, 20 ex, 3 dwg

Pyridone and aza-pyridone compounds and methods of use // 2617405
FIELD: chemistry.SUBSTANCE: invention relates to a compound selected from formula I, or its stereoisomers, or pharmaceutically acceptable salts thereof, where R1 is optionally substituted C1-C3 alkyl; R2, R3 and R4 are independently selected from H, F, Cl; R5 is selected from (i) optionally substituted C6-C20 aryl, selected from phenyl; (ii) optionally substituted C5-C20 heteroaryl, selected from pyrazolyl, pyridinyl, pyrimidinyl, tetrahydroisoquinolinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 4,6,7-trihydropyrazolo[3,2-c][1,4]oxazinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 2,3-dihydro-1H-isoindolyl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinyl; (iii) optionally substituted -(C6-C20 aryl)-(C3-C20 heterocyclyl), where heterocyclyl is selected from azetidinyl, piperidinyl, morpholino, piperazinyl; (iv) optionally substituted -(C5-C20 heteroaryl)-(C3-C20 heterocyclyl), where heteroaryl is selected from pyridinyl and pyridazinyl and heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,4-diazepanyl, 2,6-diazaspiro[3.3]heptanyl, 7,9-diazabicyclo[3.3.1]nonanyl, hexahydropyrrolo[3,4-c]pyrrolyl, morpholino; (v) optionally substituted -(C5-C20 heteroaryl)-(C1-C6 alkyl), where heteroaryl is selected from pirazolyl and pyridinyl; or (vi) optionally substituted -(C5-C20 heteroaryl)-C(=O)-(C3-C20 heterocyclyl), selected from (pyridinyl)-C(=O)-(morpholino); R6 represents H or C1-C3 alkyl; Y1 and Y2 are independently selected from CR6 and N; where C1-C3 alkyl, C3-C20 heterocyclyl, C6-C20 aryl and C5-C20 heteroaryl optionally substituted with one to three groups, independently selected from D, F, Cl, Br, I, -CH3, -CH2CH3, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH, -C(CH3)2OH, -CH2F, -OC(O)CH3, -COCH3, -NHCH3, -N(CH3)2, =O, -OH, -OCH3, -OCH2CH2N(CH3)2, -OP(O)(OH)2, -CH2OCH3, cyclopropyl, azetidinyl, 1-(methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, oxetanyl and morpholino; where group (a), formed Z1, Z2, Z3, Z4, Z5, X and NC(O), forms structure, given in claim, and wherein wavy line indicates bonding point. Invention relates to a pharmaceutical composition for treating a condition, mediated by Bruton's tyrosine kinase, containing a compound of formula (I) and a pharmaceutically acceptable carrier, lubricant, a diluent or filler. Compounds of formula (I) are intended for use as a drug for treating cancer, mediated by Bruton's tyrosine kinase.EFFECT: pyridone and aza-pyridone compounds for treating disorders mediated by Bruton's tyrosine kinase (Btk).20 cl, 9 dwg, 4 tbl, 907 ex (а)
Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors // 2617401
FIELD: chemistry.SUBSTANCE: invention relates to compounds of general formula (I) (I), where: R1 and R2, which can be identical or different, independently selected from a group consisting of: - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl; - (C1-C6)halogenalkyl; - (C3-C7)cycloalkyl and - (C3-C7)heterocycloalkyl, containing heteroatom O; R3 represents hydrogen, (C1-C6)alkyl or (C1-C3)alkylthio(C1-C6)alkyl; A is a partially unsaturated or unsaturated bicyclic ring system consisting of two condensed monocyclic ring systems B and C, presented in cl. 1 of formula, where ring C is a monocyclic aryl or monocyclic heteroaryl ring system, ring B is a 5- or 6-member heterocycloalkyl group, zero of Y groups is bonded to ring C, n of groups Y is bonded to ring B, and n is an integer from 1 to 3; and where ring B and C optionally contains additional heteroatoms in amount of 1 to 4, selected from N, O or S; p is an integer from 0 to 3; Y denotes oxo group; K is selected from a group consisting of: - (C1-C6)alkyl, optionally substituted with one (C3-C7)cycloalkyl group; - (C3-C6)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; - (C3-C6)heterocycloalkyl containing 1 or 2 heteroatoms selected from N or O, optionally substituted with one or more (C1-C6)alkyl group; - (C1-C4)halogenalkyl; - OR4, where R4 selected from a group consisting of: - H; - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl or heteroaryl; - halogen atoms; - CN; - NO2; - NR5R6, where R5 and R6, which can be identical or different, independently selected from a group consisting of: - H; - OH; - (C1-C4)alkyl-NR7R8, where R7 and R8, which can be identical or different, independently selected from a group consisting of: H; (C1-C6)alkyl, possibly substituted (C1-C6)alkoxyl; and (C1-C6)alkyl-NR9R10, where R9 and R10, which can be identical or different, represent H or (C1-C6)alkyl; or they form together with a nitrogen atom to which they are bonded, (C3-C6)heterocycloalkyl ring containing 1 or 2 heteroatoms, selected from N, O or S, optionally substituted (C1-C6)alkyl or (C1-C6)alkylcarbonyl group; -(C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl or heteroaryl, (C3-C6)heterocycloalkylcarbonyl containing 1 or 2 heteroatoms selected from N or O, heteroarylcarbonyl, wherein all of them may further be substituted with one or more (C1-C6)alkyl, (C1-C6)halogenalkyl or (C1-C6)alkoxyl groups, which are identical or different and are selected independently; - SO2R11, where R11 represents (C1-C6)alkyl; - C(O)R12, where R12 is (C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl; - (C1-C4)alkyl-NR13R14, where R13 and R14, which can be identical or different, are independently selected from a group consisting of groups: - SO2(C1-C6)alkyl, H, (C1-C6)alkyl and (C3-C7)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; and - SO2NR15R16, where R15 and R16, which can be identical or different, independently represent H or (C1-C6)alkyl; where groups with R4 at R16 have similar or different values in each case, if they are present in more than one group; and where heteroaryl is a mono- or bicyclic ring system with 5–10 ring atoms, containing 1 or 2 heteroatoms selected from N, O or S; or its pyridine-N-oxides, pharmaceutically acceptable salts or solvates. As well as to methods of producing such compounds, compositions containing them and their therapeutic application as inhibitors of phosphodiesterase 4 (PDE4) enzyme.EFFECT: disclosed are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors.16 cl, 16 tbl, 52 ex
Antibiotic derivatives of 2-oxo-oxazolidine-3, 5-diyl // 2616609
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula I or pharmaceutically acceptable salts possessing antibacterial action, , wherein R1a represents H or carboxy and R1b represents H, or R1a and R1b represent together or group *-C(O)-NH-S-# or group *-C(OH)=N-S-# in which "*" is connection point of R1a and "#" is connection point of R1b; R2 represents H, (C1-C3)alkyl, hydroxy-(C1-C3)alkyl, benzyl or (C3-C5)cycloalkyl; R3 represents H or halogen; U is N or CR4; wherein R4 represents H or (C1-C3)alkoxy; A represents CH, B represents NH and m is 1 or 2 and n is 1 or 2; or A is N, B is absent, m is 2 and n is 2; Y represents CH or N; and Q represents O or S. Invention also relates to pharmaceutical composition.EFFECT: novel compounds are obtained, which can be used for preventing or treating bacterial infections.15 cl, 25 ex

Solid forms of nematocidal sulfonamides // 2615139
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to polymorphous form A and polymorphous form TS 8-chloro-N - [(2-chloro-5-methoxyphenyl) sulfonyl] -6- (trifluoromethyl) imidazo [1,2- a] pyridine-2-carboxamide (compound 1).EFFECT: invention provides obtaining polymorphous forms of the compounds of nematicidal sulfonamides with different resistance in the compositions.2 cl, 1 dwg, 26 tbl, 23 ex
Compounds for metabolic syndrome treatment // 2615136
FIELD: pharmacy.SUBSTANCE: invention relates to new compounds of formula I .EFFECT: new compound of formula I are obtained, their application for metabolic syndrome, metabolic disease or metabolic disorders treatment is proposed.16 cl, 8 tbl, 37 ex, 8 dwg

Heterocyclic compounds useful as pdk1 inhibitors // 2615130
FIELD: chemistry.SUBSTANCE: present invention relates to novel compounds of general formulae II, III, IV and V, where values of radicals are given in description, or pharmaceutically acceptable salts thereof, which can be used as PDK1 inhibitors.EFFECT: present invention also relates to pharmaceutical compositions based thereon and to methods of treating cancer, mediated by protein kinase PDK1.32 cl, 2 tbl, 445 ex
1-imino-2,3,4,5-tetrahydro-1h-pyrrolo[3,4-c]pyridine-3,4-diones // 2613967
FIELD: chemistry.SUBSTANCE: invention relates to methods of obtaining new functionally substituted fused heterocyclic molecules -1-imino-2,3,4,5-tetrahydro-1H-pyrrolo[3,4-c]pyridine-3,4-diones of the formula (I) wherein R1=R2=Me (1a); R1=Me, R2=Et (1b); R1+R2=(CH2)4 (1c); R1+R2=(CH2)5 (1d); R1+R2=(CH2)6 (1e), which may be employed as biologically active compounds in organic synthesis and as fluorescent dyes. The production method consists in suspending the corresponding 2-oxo-4-cyano-1,2-dihydropyridine-3-carboxamide in ethanol, followed by the addition of aqueous ammonia solution with the concentration of 20%, after which the reaction mass is boiled for 30 minutes to obtain the desired product.EFFECT: new compounds with useful biological activity are obtained.5 ex
2-(azaindol-2-yl)benzimidazole derivatives as pad4 inhibitors // 2611010
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to 2-(azaindol-2-yl)benzimidazole derivatives of formula (I) or a pharmaceutically acceptable salt thereof, where R1 is hydrogen; R2 is hydrogen, perhalomethylC0-5alkyl-O- or C1-6alkoxy; R3 is C1-6alkyl or C1-6alkoxyC1-6alkyl; R4 is C1-6alkyl, perhalomethylC1-6alkyl or unsubstituted C3cycloalkylC1-6alkyl; A is C-R5 or N; B is C-R6 or N; D is C-R7 or N; provided that one of A, B and D is N; R5, R6 and R8 are hydrogen; R7 is hydrogen, C1-6alkoxy or hydroxy; R9 is hydrogen or hydroxy; R10 is hydrogen or C1-6alkyl. Invention also relates to specific derivatives of 2-(azaindol-2-yl)benzimidazole and a pharmaceutical composition based on compound of formula (I).EFFECT: novel derivatives of 2-(azaindol-2-yl)benzimidazole, useful as PAD4 inhibitors are obtained.10 cl, 30 ex

Use of sigma ligands in diabetes type-2 associated pain // 2608943
FIELD: chemistry.SUBSTANCE: invention relates to use of a sigma ligand, which is a 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine or a pharmaceutically acceptable salt thereof.EFFECT: prevention and/or treatment of pain associated with type 2 diabetes and related symptoms.6 cl, 9 dwg, 4 ex

Use of adamantane-containing indoles and their hydrochlorides as cytoprotectors and for treating and preventing diseases associated with increase in cytosolic calcium concentration and pharmacological agent based thereon // 2608737
FIELD: chemistry; pharmacology.SUBSTANCE: invention relates to use of adamantane-containing indole derivatives and their hydrochlorides of general formula 1, where R1, R2, R3, R4 can be identical or different and independently represent H, F, Cl, Br, (C1-C6)alkyl, (C1-C6)alkoxy; R5, R6 can be identical or different and independently represent H, (C1-C6)alkyl, ONO2; X is CH2CH(OH)CH2 or CH2CH2C(O); Z = no, Cl; as cytoprotectors in treating and preventing of diseases associated with increase in cytosolic calcium concentration.EFFECT: treatment and prevention of diseases associated with increase in cytosolic calcium concentration.31 cl, 9 dwg, 8 ex ,

Adamantane-containing indoles and their hydrochlorides with microtubules stabilizing property, methods of their production, pharmacological agent based thereon and method of treating and preventing diseases associated with microtubule system disorders // 2608631
FIELD: chemistry; medicine.SUBSTANCE: invention relates to novel adamantane-containing indoles and their hydrochlorides of general formula 1, in which R1, R2, R3, R4 can be identical or different and independently represent H, F, Cl, Br, (C1-C6)alkyl, (C1-C6)alkoxy; R5, R6 can be identical or different and independently represent H, (C1-C6)alkyl, ONO2; X is CH2CH(OH)CH2 or CH2CH2C(O); Z = no, Cl; R7, R8, R9, R10 can be identical or different and independently represent H, F, Cl, Br, (C1-C6)alkyl, (C1-C6)alkoxy; R11, R12, R13, R14, R15, R16, R17, R18 can be identical or different and independently represents H, (C1-C6)alkyl.EFFECT: compounds possess microtubules stabilization property and may be used for treating or preventing diseases related to disturbed microtubule system, for example, such as hyperproliferative manifestations and neurodegenerative disorders.22 cl, 7 dwg, 54 ex ,

Imidazo[1,2-a]pyridine compounds, synthesis thereof and methods of using same // 2608611
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to novel imidazole derivatives of formula given below or pharmaceutically acceptable salt thereof, where Y denotes CH or N; R1 is: -alkyl containing 1-2 carbon atoms; - substituted alkyl containing 1-3 carbon atoms, which includes 1-3 substitutes, selected from a heteroaryl (selected from pyridine, thiazole furan), phenyl, halogen, wherein said heteroaryl and phenyl are substituted with 1-3 substitutes, selected from halogen, -OQ10, methylsulphonyl group, fluorophenox group and Q15; wherein Q10 is an alkyl containing 1-3 carbon atoms, and Q15 is hydrogen, alkyl containing 1-2 carbon atoms, which can be substituted with three halogen atoms; - cycloalkyl containing 3-6 carbon atoms; - amide (-CONH2) or alkyne containing 2-4 carbon atoms; -halogen; -phenyl; -substituted phenyl, containing 1-2 substitutes, selected from trifluoromethylphenoxy group, -OQ10, halogen, thiomorpholine; wherein Q10 is an alkyl, containing one carbon atom; -benzotriazole; R2 is: -alkyl, containing one carbon atom; -substituted alkyl, containing one carbon atom, containing 1-3 substitutes, selected from halogen and phenyl; -phenyl; R3 is -COW, where W is OR1, NHR1 or NR1R2. Invention also relates to a pharmaceutical composition based on a condensed imidazole derivative and use of said compound.EFFECT: technical result is obtaining novel condensed imidazole derivatives, useful in treatment or prevention of tuberculosis.19 cl, 4 dwg, 5 tbl

Substituted polycyclic carbamoyl pyridone derivative prodrug // 2608519
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts thereof, which have inhibitory effect on cep-dependent endonuclease. In formula (I) , PR represents a group selected from -C(=O)-PR0, -C(=O)-PR1, -C(=O)-L-PR1, -C(=O)-L-O-PR1, -C(=O)-L-O-L-O-PR1, -C(=O)-O-PR2, -C(=O)-N(PR2)2, -C(=O)-O-L-O-PR2, -CH2-O-PR3, -CH2-O-L-O-PR3, -CH2-O-C(=O)-PR3, -CH2-O-C(=O)-O-PR3, -CH(-CH3)-O-C(=O)-O-PR3, -CH2-O-C(=O)-N(-K)-PR3, -CH2-O-C(=O)-O-L-O-PR3, -CH2-O-C(=O)-O-L-N(PR3)2, -CH2-O-C(=O)-N(-K)-L-O-PR3, -CH2-O-C(=O)-N(-K)-L-N(PR3)2, -CH2-O-C(=O)-O-L-O-L-O-PR3, -CH2-O-C(=O)-O-L-N(-K)-C(=O)-PR3, -CH2-O-P(=O)(-OH)2, -CH2-O-P(=O)(-OBn)2, -CH2-PR4, -C(=N+PR52)(-NPR52); R1a – hydrogen, halogen, carboxy, lower alkyl, possibly containing substituent C, lower alkyl carbonyl, possibly containing substituent C, or -Z-N(RA1)(RA2), R2a – hydrogen or lower alkyl, possibly containing substituent C; R3a – hydrogen, lower alkyl, possibly containing substituent C, a carboxylic group, possibly containing substituent C, carbocycle-lower alkyl, possibly containing substituent C, carbocycloksi-lower alkyl, possibly containing substituent C, heterocyclic group, possibly containing substituent C, or heterocycle-lower alkyl, possibly containing substituent C, or B1, or B2 represents a CR5aR6a, and the other represents a NR7a, or B1 represents a CR8aR9a and B2 represents a CR10aR11a. Values of other radicals are given in the patent claim. Invention also refers to pharmaceutical compositions.EFFECT: obtained new compounds of formula (I) possessing inhibitory activity against the cep-dependent endonuclease and which can be useful in treating influenza.10 cl, 4 dwg, 35 tbl, 1035 ex
Compounds useful as trpm8 modulators // 2608109
FIELD: chemistry.SUBSTANCE: present invention relates to novel compounds of structural formula (II) and structural formula (III) or to salts thereof, compositions for inducing cooling effect, containing a compound having structural formula (I), formula (II) and formula (III), or salt thereof, a method of modulating agonistic activity of transient receptor potential melastatin 8 (TRPM8) channel and to a method of inducing a cooling sensation in a human or animal (versions).EFFECT: novel compounds.27 cl, 10 tbl, 253 ex
Novel pyrrole compounds, synthesis method thereof and pharmaceutical compositions containing same // 2607788
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) possessing inhibitory activity on Bcl-2 family proteins. In formula (I) (I) A1 is hydrogen, (C1-C6)polyhaloalkyl group or (C1-C6)alkyl group, A2 is hydrogen, (C1-C6)polyhaloalkyl group, (C1-C6)alkyl group or cycloalkyl group, T denotes a hydrogen atom, (C1-C6)alkyl group, optionally substituted with one-three halogen atoms, group (C1-C4)alkyl-NR1R2 or group (C1-C4)alkyl-OR6, R1 and R2 each independently from each other is a hydrogen atom or (C1-C6)alkyl group, or R1 and R2 form with a nitrogen atom bearing them, heterocycloalkyl, R3 is (C1-C6)alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R4 is an aryl group or heteroaryl group, wherein one or more carbon atoms of previous groups or their possible substitutes can be deuterated, R5 is hydrogen or halogen atom, R6 is a hydrogen atom or a linear or branched (C1-C6)alkyl group, Ra, Rb, Rc and Rd each independently from other represents hydrogen, linear or branched (C1-C6)alkyl, halogen atom, a linear or branched (C1-C6)alkoxy group, hydroxy group, R7-CO-NH-(C0-C6)alkyl-, R7-SO2-NH-(C0-C6)alkyl-, R7-NH-CO-NH-(C0-C6)alkyl-, R7-O-CO-NH-(C0-C6)alkyl-, or substitutes of pair (Rb, Rc) form together with carbon atoms carrying them, a ring consisting of 5–6 ring members, which may contain 1–2 oxygen atoms, R7 is hydrogen, linear or branched (C1-C6)alkyl, aryl or heteroaryl. Invention also relates to methods of producing compounds of formula (I), to a pharmaceutical composition, use of a pharmaceutical composition for preparing a drug, use of compound of formula (I) for preparing a drug.EFFECT: obtaining novel compounds of formula (I) possessing inhibitory activity on Bcl-2 family proteins.37 cl, 2 tbl, 473 ex
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
 
2551183.
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