Quinolines and isoquinolines (A61K31/47)

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

New derivative of 3-(4-(benzyloxy)phenyl)hex-4-ine acid, method for its production and pharmaceutical composition for metabolic disease prevention and treatment including it as effective ingredient // 2628077
FIELD: pharmacology.SUBSTANCE: invention relates to a compound represented by formula 1, its optical isomer or a pharmaceutically acceptable salt thereof: [Formula 1] , as well as to methods for its preparation and a pharmaceutical composition based on it.EFFECT: new connections are obtained, with the ability to activate the GPR40 enzyme, suitable for use for metabolic disease prevention or treatment.10 cl, 7 tbl, 77 ex, 2 dwg
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

Derivatives of hinoline, visualizing tau protein // 2627694
FIELD: pharmacology.SUBSTANCE: invention relates to a new quinoline derivative of formula (I) or a pharmaceutically acceptable salt thereof, wherein A is or , R1 is halogen or , in which R4 and R5 each independently represents hydrogen, a lower alkyl group, or R4, R5 and the nitrogen atom to which they are attached together form a 6-member nitrogen-containing aliphatic ring (where the nitrogen atom may be substituted by a lower alkyl group), or R4 and the nitrogen atom to which it is attached together with ring A form a 10-membered nitrogen-containing fused bicyclic ring (one carbon atom constituting the nitrogen-containing condensed bicyclic ring can be replaced by the oxygen atom), and R5 is a lower alkyl group where a line crossed by a dashed line means a bond of the above general formula with another structural moiety, R2 or R3 each independently represents NRaRb or -O-lower alkyl group (each alkyl group may be substituted with 1 to 2 substituents selected from halogen, hydroxy groups), ring A is unsubstituted or substituted by R6 (where R6 is one substituent selected from halogen and an -O-lower alkyl group (each alkyl group may be substituted with 1 to 2 substituents selected from halogen, hydroxy, Ra and Rb each represents hydrogen or a lower alkyl group, m and n denote an integer from 0 to 1, wherein at least one of R2, R3 and R6 is an -O-lower alkyl group substituted with one hydroxy group and one halogen. The invention also relates to a pharmaceutical composition, a composition for conformational disease diagnosis, treatment or prevention, a diagnostic kit based on a compound of formula (I), a method of treatment, a method for detection or staining of a protein-layer β-structure, a process for preparation of a compound of formula (I) and intermediates.EFFECT: new compounds are obtained that can be used to diagnose and treat conformational diseases, in particular, a disease having such a cardinal symptom as intracerebral accumulation of tau protein, for example, Alzheimer's disease.17 cl, 29 dwg, 26 tbl, 2 ex
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
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
Quinolines as fgfr kinase modulators // 2625303
FIELD: pharmacology.SUBSTANCE: invention related to a new quinoline derivative of formula (I), where W us -N(R3)- or -C(R3aR3b)-; each R2 is independently selected from halogen, C1-4alkoxy, Y is -E-D; D is phenyl or 5-6-membered monocyclic heterocyclyl, containing one or two heteroatoms selected from N or O, wherein the mentioned heterocyclyl can be optionally substituted with one group of R1; E is a link; R1 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyl which is substituted with -S(=O)2-C1-6alkyl, R6; R3a is hydroxyl, hydroxyC1-6alkyl, cyanoC1-6alkyl, C1-6alkyl which is substituted with -NR10R11, C1-6alkyl which is substituted with -C(=O)-NR10R11; R3b is hydrogen; or R3a and R3b are combined to obtain =O or to obtain =CH-C0-4alkyl which is substituted with R3c; R3c is cyano; R3 is C2-6alkynyl, hydroxyC1-6alkyl, hydroxyhaloC1-6alkyl, C1-6alkyl which is substituted with R9, C2-6alkynyl which is substituted with R9, C1-6alkyl which is substituted with -NR10R11; R6 is 6-membered monocyclic heterocyclyl, containing one O atom; R9 is 5- or 6-membered monocyclic heterocyclyl, containing one or two heteroatoms, seleceted from N or O, each is optionally and each is independently substituted with substitute selected from =O, C1-4alkyl, C1-4alkoxy, S(=O)2-NR14R15, C1-4alkyl which is substituted with -NH-S(=O)2-haloC1-4alkyl, 6-membered aromatic monocyclic heterocyclyl, containing two N atoms, wherein the mentioned heterocyclyl is optionally substituted with R16; each R10 and R11 independently represent hydrogen, C1-6alkyl, haloC1-6alkyl; each R14 and R15 independently represent C1-4alkyl; R16 is C1-4alkoxy; n independently represent a whole number equal to 2, 3 or 4; as well as to its pharmaceutically acceptable salt and to any tautomeric or stereochemically isomeric form thereof. The invention also relates to pharmaceutical compositions based on compound of formula (I), application of the compound of formula (I), method for the prevention or treatment of a disease and product based on the compound of formula (I).EFFECT: new quinoline derivatives are obtained, useful in the treatment of diseases mediated by FGFR kinase.30 cl, 2 tbl, 35 ex

2-quinaldicarboxylic acid derivatives and their anti-influenza activity // 2624906
FIELD: pharmacology.SUBSTANCE: agent is amino acid derivatives of 2-quinaldicarboxylic acid: 2-quinaldine-seryl methyl ester (Qln-Ser), 2-quinaldine-tryptophanyl methyl ester (Qln-Trp) and 2-quinaldine-alanyl-proline-1(1-adamantyl)ethylamide (Qln-APR), and can be used for development of new antiviral drugs. The invention also relates to a new compound - 2-quinaldine-alanyl-proline-1(1-adamantyl)ethylamide (Qln-APR).EFFECT: increased antiviral activity of derivatives against influenza A viruses and acting on strains resistant to rimantadine and amantadine.3 cl, 7 dwg, 4 tbl, 6 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
Heterocyclic compounds and their application as glycogen synthase kinase-3 inhibitors // 2623427
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of formula , where A represents NRB, where RB represents hydrogen; X1 and X2 represent CR2 and X3, X4, X5 and X6 represent CR3 or CR4, or X1 and X2 represent CR2, X3 represent N, and X4, X5 and X6 represent CR3; Y1, Y2, Y3 and Y4 represent CR4 or CR5 or Y2 represents N, and Y1, Y3 and Y4 represent CR5; provided that no more than one of Y1, Y2, Y3 and Y4 represents CR4; and provided that one of Y1, Y2, Y3 and Y4 represents CR4 or C-CF3, if none of X3, X4, X5 and X6 represents CR4; R1 represents hydrogen; each R2 represents hydrogen; each R3 is independently selected from the group consisting of hydrogen, CN, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy and C1-C6-haloalkoxy; R4 represents a C-linked saturated or partially unsaturated monocyclic 5- or 6-member heterocyclic ring containing one heteroatom selected from O and N, as ring members, wherein the heterocyclic ring optionally has one N-linked substituent R8; R5 is selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C6-haloalkyl and C3-C7-cycloalkyl; and R8 is selected independently on the case from the group consisting of C1-C6-alkyl, C1-C6-haloalkyl and C1-C6-alkoxycarbonyl. The invention also relates to pharmaceutical compositions based on a formula (I) compound, formula (I) compound application, a method of treatment of diseases susceptible to treatment by a compound that modulates the activity of 3β glycogen synthase kinase.EFFECT: new heterocyclic compounds useful for treatment of neurodegenerative disorders or inflammatory diseases are obtained.25 cl, 2 tbl, 70 ex

Combined composition of substances with complex pharmacological activity // 2622991
FIELD: pharmacology.SUBSTANCE: invention relates to a combined composition having radioprotective and antiradiation activity. This composition contains (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide and (3aS)-2-[(3S)-1-azabicyclo-[2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1-oxo-1H-benz[de]isoquinoline.EFFECT: invention provides an expressed decrease in the manifestation of primary radiation exposure symptoms when affected by various doses of ionizing radiation.2 cl, 2 dwg, 7 tbl, 7 ex
Azole derivatives // 2622639
FIELD: pharmacology.SUBSTANCE: invention relates to azole derivative of formula (I) or its pharmaceutically acceptable salt, wherein R1 is hydrogen atom or C1-5alkyl; R2 is hydrogen atom or C1-5alkyl; R3 is phenyl or pyridyl (where phenyl or pyridyl is optionally substituted with one or two fragments selected from the group consisting of C1-5alkoxy, halogen and trifluoromethyl atoms); each of R4 and R5, which can be the same or different, represent hydrogen atom or C1-5alkyl (where C1-5alkyl is optionally substituted with one fragment selected from the group consisting of hydroxy and C1-5alkoxy), or R4 and R5 together with nitrogen atom joining them form 4-7-membered saturated or unsaturated heterocycle, optionally compirsing one cyclic nitrogen, oxygen or sulfur atom, aside from the mentioned above joining nitrogen atom (where 4-7-membered saturated and unsaturated heterocycle is optionally substituted with one or two fragments, selected from the group consisting of hydroxy C1-5alkyl (where C1-5 alkyl is optionally substitued with one or two hydroxyl group), C1-5alkoxy, halogen atoms, cyano, C2-5alkanoyl, aminocarbonyl, mono-C1-5alkylaminocarbonyl, di-C1-5 alkylaminocarbonyl, trifluoromethyl, amino, mono-C1-5alkylamino, di-C1-5alkylamino and C2-5alkylamino, wherein the mentioned 4-7-membered saturated or unsaturated heterocycle optionally has C1-5alkylene fragment, joining two different cyclic carbon atoms), or form 2-oxa-6-azaspiro[3.3]hept-6-yl or 7-oxa-2-azaspiro[3.5]non-2-yl; azole cycle represented by formula (α) has any structure of group (II) formula, contained in invention formula, and wherein Ry is hydrogen atom or C1-5alkyl; X1 and X2 are such that: (i) if X1 means an ordinary link or fragment -CO-, X2 means -C1-5alkylene- or -O-C1-5alkylene-; and (ii) if X1 means a fragment -CONRx1-, X2means an ordinary link; Rx1 is hydrogen atom or C1-5alkyl; and cycle A is benzol cycle, pyridine cycle (where benzol cycle is optionally substituted with one or two fragments, selected from the group consisting of halogen atoms and C1-5alkoxy), 5-6-membered saturated or partly unsaturated heterocycle, containing one or two nitrogen atoms (where 5-6-membered saturated or unsaturated heterocycle is optionally substituted with one oxo group) or C3-7cycloalkane. The invention also relates to a pharmaceutical composition having antagonistic effect against V1b arginine-vasopressin receptor, and to agent for treating or preventing mood disorders, anxiety disorders or drug addiction, comprising azole derivative of formula (I) or its pharmaceutically acceptable salt as an active agent.EFFECT: azole derivative having antagonistic effect against V1b arginine-vasopressin receptor.12 cl, 22 tbl, 361 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
Heterobicyclic derivatives as hcv inhibitors // 2621734
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclic compound of formula (I) or to pharmaceutically acceptable salt thereof, wherein Y is CH, N or CR4; W is carbonyl, sulfonyl or CR5R6; is or is independently selected from the group containing R and R' independently selected from -CR1R2R3, where R1 is selected from C1-4alkyl; R2 is C1-4alkyloxycarbonylamino; R3 is hydrogen; R4 is hydrogen or fluorine; CR5R6 together form oxetane. The invention also relates to pharmaceutical composition based on compound of formula (I), its use and product on its base.EFFECT: obtaining novel heterocyclic compounds, useful in the treatment of HCV infections.14 cl, 2 tbl

aleate salts of (e)-n-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and their crystal form // 2621719
FIELD: chemistry.SUBSTANCE: method of increasing neratinib oral absorption incudes neratinib administering to a patient in the form of maleate salt, where the neratinib maleate salt is a crystalline monohydrate of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide maleate (Form II). The invention also relates to a method for cancer treatment including neratinib administering to a patient in the form maleate salt (Form II).EFFECT: increased oral absorption and cancer treatment based on the use of a crystal form of neratinib maleate salt.7 cl, 8 dwg, 11 tbl, 2 ex
Pharmaceutical compositions comprising camptothecin derivative // 2620331
FIELD: pharmacology.SUBSTANCE: composition comprising 7-tret-butoxyiminomethyl camptothecin, as an active agent, and a carrier comprising a lipophilic component, a surfactant, a hydrophilic component and a co-solvent. The lipophilic component is a propylene glycol monoester of caprylic acid. The surfactant is vitamin E TPGS. The hydrophilic component is PEG 400. The co-solvent is ethanol. Also, a method for composition preparation and a method of treatment are disclosed.EFFECT: increased bioavailability of 7-tret-butoxyiminomethyl camptothecin.5 cl, 6 ex
ethod for neuralgia treatment // 2619344
FIELD: medicine.SUBSTANCE: for neuralgia treatment, a drug complex is used, where one of non-steroidal anti-inflammatory compounds drugs is applied as the basic analgesic agents, namely - ketorolac tromethamine at a dose of 15-75 mg, or sodium metamizole at a dose of 500-2500 mg, or the ketoprofen at a dose of 50-250 mg, or dexketoprofen at a dose of 25-125 mg, or lornoxicam at a dose of 4-20 mg, cyanocobalamin at a dose of 500-2500 mcg is used as an adjuvant analgesic agent, and drotaverine hydrochloride at a dose of 10-50 m is used as a myotropic spasmolytic action, that are administered intravenously with distribution of the said doses by one or two daily injectios, course of treatment lasts 1-10 days.EFFECT: method allows to ensure complete elimination of the pain syndrome after the course of treatment, the possibility of pain syndrome elimination with a single administration of drugs with obtaining of a momentary stable analgesic effect by eliminating the protective muscular tension in the affected nerve zone at method safety.2 tbl, 125 ex

Crystalline solvates of hydrochloride 6-(piperidin-4-yloxy)-2h-isoquinolin-1-one // 2619129
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, in particular to crystalline dihydrate 6-(piperidin-4-yloxy)-2H-isoquinolin-1-one of formula and a solid pharmaceutical composition thereof.EFFECT: obtained crystalline hydrochloride dihydrate, having better stability and hygroscopicity, which is preferable in obtaining the medicinal product based on it.16 cl, 14 dwg, 1 tbl

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
4-aminoquinoline-3-carboxylic acid derivatives and compositions containing them for enhancing sweet taste // 2617700
FIELD: chemistry.SUBSTANCE: invention relates to a new derivative of quinoline of formula (I) (I)or its salt suitable for internal use, where R1 and R2 represents hydrogen; L represents a C1-C7 alkylene, C3-C6 cycloalkylene or -(CH2)1-3-(C3-C6) cycloalkylene; M represents -NR4-C(O)- or -C(O)-NR4-; when M represents -NR4-C(O)-, R4 represents hydrogen; or alternatively R4 represents a C1-C3 alkilinity linker, where the specified alkilinity linker and from 2 to 5 atoms of L, together with the nitrogen to which they are attached, form a 5-8-membered monocyclic, bicyclic or bridged heterocyclic ring that is optionally substituted and contains one hetero-atom representing a nitrogen atom; and R3 represents a C1-C6 alkyl, a substituted C1-C3 alkyl, a C3-C6 cycloalkyl, a substituted C3-C6 cycloalkyl, a 6-membered heterocyclyl containing one oxygen atom, or a substituted 6-membered heterocyclyl containing one nitrogen atom; when M represents -C(O)-NR4-, R4 represents hydrogen; or alternatively R4 and R3 together with the nitrogen to which they are attached form a 5-6-membered monocyclic heterocyclic ring which contains one nitrogen atom; where in the group indicated as substituted, one substituent is selected from the group consisting of the following substituents: -NH2, a hydroxyl, a C1-6 alkoxy, a C1-6 alkyl, a 6-membered heterocyclyl containing one or two atoms selected from N and O, a C3-4 cycloalkyl, and C(=O)NRaRa, where each Ra independently means hydrogen or a C3-6 cycloalkyl; provided that the compounds of the formula (I) cannot represent compounds mentioned in claim 1. The invention also relates to a composition based on a compound of the formula (I) and methods for enhancing the sweet taste.EFFECT: new quinoline derivatives useful as sweet taste modifiers are obtained.31 cl, 24 tbl, 24 ex
Solid dosage forms with choline-positive action based on 9-butylamino-3,3-dimethyl-1,2,4-trihydroacridine // 2616247
FIELD: pharmacology.SUBSTANCE: solid dosage form comprising of 9-butylamino-3,3-dimethyl-1,2,4-trihydroacridine, calcium stearate, dicalcium phosphate dihydrate, polyvinyl pyrrolidone, sodium dodecyl sulfate, talc, milk sugar in a certain weight ratio is described. A method for preparing said solid dosage form is shown.EFFECT: invention provides a high tablet hardness, required disintegration and high bioavailability of the active ingredient, ease of manufacture of proposed tablets.1 tbl
Amorphous (5-fluoro-2-methyl-3-quinolin-2-ylmethylindol-1-yl)-acetic acid // 2616000
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a stable solid dispersion (5-fluoro-2-methyl-3-quinolin-2-ylmethylindol-1-yl)-acetic acid (Compounds 1), containing amorphous (5-fluoro-2-methyl-3-quinolin-2-ylmethylindol-1-yl)-acetic acid (Compound 1) or its pharmaceutically or veterinarily acceptable salt and polymer, selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (PVP-VA), hydroxypropyl methylcellulose (HPMC) and hypromellose acetate succinate (HPMC AS) and their mixtures. Invention also relates to a method of producing said stable solid dispersion, its application, method of treating said diseases and pharmaceutical composition based on stable solid dispersion.EFFECT: obtaining a stable solid dispersion based on amorphous compound 1 and polymer, useful for treating or preventing diseases mediated by prostaglandin D2 (PGD2) or other agonists, acting on CRTH2 receptor.22 cl, 17 dwg, 15 tbl, 13 ex
Tetrahydroquinoline derivatives as activators of ampk // 2615758
FIELD: chemistry.SUBSTANCE: invention relates to a new tetrahydroquinoline derivative of formula or its pharmaceutically acceptable salt, wherein R1: hydrogen, lower alkyl, halogen or carboxy; R2: hydrogen, lower alkyl, halo-lower alkyl, halogen, cyano, or carboxy; R3 and R4: lower alkyl; R5 and R6 are selected from hydrogen, carboxy-lower alkylamino, carboxycyclopropylamino, lower alkylsulfonylamino, phenylsulfonylamino, halophenylsulfonylamino, lower alkylphenylsulfonylamino, halophenylkarbonilamino, piridinilsulfonilamino, lower alkylaminosulfonyl and halophenylaminosulfonyl; with the provision that both R5 and R6 do not simultaneously represent hydrogen; R7: hydrogen or lower alkyl. The invention also relates to the pharmaceutical composition based on the compound of the formula (I) and to the application of the compound of the formula (I).EFFECT: invention provides obtaining new tetrahydroquinoline derivatives useful as an activator of AMP-activated protein kinase (AMPK).20 cl, 1 tbl, 94 ex

7-{(3s,4s)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidin-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid crystal // 2615509
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, in particular, to a hydrochloride salt crystal, a hydrochloride salt hydrate crystal and methane sulphonate salt crystal 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidin-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. Invention also relates to an antibacterial pharmaceutical preparation based on said crystal, a method of producing said crystals.EFFECT: technical result: obtained crystals have high solubility in water, as well as high storage stability.19 cl, 6 dwg, 4 tbl, 13 ex

Stable pharmaceutical composition for oral administration comprising levocetirizine, or pharmaceutically acceptable salt thereof and montelukast or pharmaceutically acceptable salt thereof // 2614382
FIELD: medicine, pharmacy.SUBSTANCE: this present invention relfers to a pharmaceutical composition in the form of a capsule for oral administration for asthma or allergic rhinitis prevention or treatment. The composition comprises: (a) the first fraction of particles in the form of mini-pill comprising levocetirizine, or pharmaceutically acceptable salt thereof and organic acid; and (b) the second fraction of particles in the form of mini-pill comprising montelukast or pharmaceutically acceptable salt thereof. The organic acid is citric acid, tartaric acid, succinic acid or ascorbic acid. The organic acid is present in the amount of 100 parts by weight per 100 parts of levocetirizine. The said first and second particle fractions are physically separated and filled into the capsule. A method for pharmaceutical capsule composition production is also described. The pharmaceutical composition of this invention inhibits the production of related contaminants of levocetirizine and montelukast and provides good stability.EFFECT: invention expands the product range of drugs for allergic rhinitis or asthma prevention or treatment.9 cl, 3 dwg, 4 tbl, 6 ex
Gelatine capsule of selective vessel destruction in tumours // 2613146
FIELD: medicine.SUBSTANCE: gelatine capsule of selective vessel destruction in tumours relates to field of pharmaceutics and medicine, in particular to oncology, and deals with novel medications, mechanism of action of which consists in their destruction of already existing vessels inside tumour, preventing in such way supply of blood and oxygen, vital for survival of solid tumours with dimensions exceeding 1 mm. The capsule contains approximately 250-900 mg of pharmaceutical composition, which contains anti-tumour compound 7-methoxy-4-nitro-3-(p-methoxyphenyl)isoquinolinone 16-18 wt %, crospovidone 5-8 wt %, hypromellose 2-3 wt %, polysorbate 80 - 1-2 wt %, sodium laurylsulphate 0.7-1.2 wt %, the remaining part - mannitol, in gelatine capsule.EFFECT: invention solves the task of creating novel peroral anti-tumour medication for prevention or treatment of benign or malignant tumours, independently on their origin or size, within the framework of treating mammals, in particular humans, resistant to traditional treatment.3 cl, 1 tbl

New rebamipide prodrugs, method for their preparation and application // 2612509
FIELD: biotechnology.SUBSTANCE: invention relates to a compound of formula 1 that is a new rebamipide prodrug, and to the pharmaceutical composition thereof.EFFECT: new rebamipide prodrug with absorption rate 25 times higher than that of rebamipide, which can be used for prevention or treatment of gastric ulcer, acute gastritis, chronic gastritis, xerophthalmia, cancer, osteoarthritis, rheumatoid arthritis, or obesity.7 cl, 3 tbl, 204 ex, 1 dwg
ethod of increasing the efficiency of treatment of patients with tuberculosis // 2611398
FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to phthisiology, and can be used to improve the efficiency of treatment of patients with tuberculosis. Method includes the determination of the degree of patient’s medication adherence through his questioning, which is performed at the beginning of the main course of treatment. Stens are determined and after its determination diagnose the factors affecting the level of adherence, and then the prediction of medication adherence is determined: if total score is from 35 points and more, 1–2 stens mark the unsatisfactory medication adherence, if it is 16–34 points, 3–5 stens mark satisfactory medication adherence, if it is 4–15 points, 6–8 stens mark good medication adherence, if it is up to 3 points, 9–10 stens mark medication adherence. In case of unfavorable prognosis at 1–5 stens prescribe cycloferon immunomodulator and methods of psychotherapy, as well as the chemotherapy regimen correction is carried out by changing the method of administration of etiotropic drugs, and at a satisfactory medication adherence etiotropic drugs are administered parenterally, and at unsatisfactory medication adherence etiotropic drugs are administered parenterally and inhalationly.EFFECT: use of invention improves efficiency of treatment of patients with tuberculosis by determining the degree of patient’s medication adherence for further treatment correction.1 cl, 2 ex
ethod for production of antiparasitic long acting preparation for animals // 2611387
FIELD: veterinary medicine.SUBSTANCE: praziquantel, ivermectin, copolymer of lactic and glycolic acids are mixed with a solvent with the following ingredient ratio (in wt %): praziquantel - 1.0-15.0, ivermectin - 0.5-8.0, copolymer of lactic and glycolic acids - 6.0-16.5, solvent - the rest. At that,praziquantel and ivermectin are the first to be dissolved in the solvent. The solution is then purged with argon or nitrogen and placed in an ultrasonic bath. The mixture is kept in the ultrasonic bath for 50-60 minutes till complete dissolution of the components. Then the copolymer of lactic and glycolic acids is added. For complete copolymer dilution, the obtained mixture is kept for 4-5 hours with occasional stirring at the rotation speed of 1600-2000 rpm. Then, the resulting solution is subjected to sterile filtration, dispensed into vials and sealed.EFFECT: method can reduce loss of active ingredients during manufacture and provide a harmless, non-toxic, sterile and effective long-acting drug for treating animals against a wide range of parasitic infections.5 cl, 8 ex

Pharmaceutical composition for treating, preventing or relieving movement disorders and its application // 2611376
FIELD: medicine.SUBSTANCE: group of inventions relates to treatment of movement disorders. Application of composition is proposed, which contains zolmitriptan or its pharmaceutically acceptable salt and 5-HT-receptor agonist buspirone or its pharmaceutically acceptable salt for treating, preventing or relieving movement disorders and use of set containing pharmaceutical composition of zolmitriptan or its salt and pharmaceutical composition of 5-HT-receptor agonist buspirone or its salt, at same prescription.EFFECT: technical result is increased efficiency of combined treatment in part of manifestations of delayed dyskinesia and relief of symptoms of Parkinson's disease in its model in rats.13 cl, 4 dwg, 9 ex
Quinoline carboxamide and quinoline carbonitrile derivatives as mglur2 negative allosteric modulators, compositions and use thereof // 2610262
FIELD: pharmaceutics.SUBSTANCE: invention relates to organic chemistry, namely, to quinoline carboxamide derivatives of following structures. Invention also relates to pharmaceutical composition based on one of said compounds, use of said compounds for treating diseases or disorders mediated by mGluR2, such as Alzheimer's disease, cognitive disorder, schizophrenia, mood disorders, painful disorders, and sleep disorders.EFFECT: novel quinoline carboxamide derivatives with useful biological properties.25 cl, 8 tbl, 310 ex
ethod of treating placental insufficiency in pregnant women suffering from vaginal dysbiosis // 2610061
FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to maieutics, and can be used for treating placental insufficiency in pregnant women suffering from vaginal dysbiosis. For this purpose it is combined with complex drug-induced and laser therapy. During 6 days daily pregnant vaginal sanitation with 0.01 % miramystine for 5 minutes. Tablets of fluomizine are introduced at bedtime. Optimum dose of laser exposure is selected based on parameters of ultrasonic examination, doplerography examination and cardiotocography of foetus. In disturbed uterine-placental perfusion of 1a degree, delay of intrauterine growth retardation on 1 week, sum of Fisher indicators of 7 points daily percutaneous exposure on median cubital vein at wave length of 905 nm, frequency 1000 Hz, radiation power 50 W, for 2 minutes, therapeutic course is 5 procedures. In disturbed uterine-placental perfusion 1b degree, gestational delay of 2 weeks and sum of Fisher indicators of 6-7 points daily percutaneous exposure on ulnar vein with laser device at wave length of 905 nm, frequency 1,000 Hz, radiation power 50 W, for 5 minutes, daily therapeutic course is 7 procedures. In disturbed uterine-placental perfusion of 2 degree, delay of intrauterine growth retardation of 3 weeks, evaluation by Fischer of 6 points daily percutaneous exposure on anterior abdominal wall within projection of placenta wavelength 905 nm, frequency 1,000 Hz, power 65 W, for 6 minutes. Daily therapeutic course is 10 procedures.EFFECT: method provides higher clinical effectiveness, reduced length of treatment, reduced drug load on body of pregnant woman.1 cl, 3 tbl, 3 ex
ethod of treating children with acute respiratory infections accompanied with secondary immune deficiency // 2609865
FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to clinical Immunology and allergology, and can be used for treating children suffering frequent episodes of acute respiratory infections accompanied secondary immune deficiency. Method involves the intranasal introduction of "Grippferon" during 5 days a week with underlying nebulization through face mask with 12.5 % solution of "Cycloferon" – 2 ml, 2 times a week and application of medical pepper of patch on skin in projection of thymus, that is performed 2 times a week for time, when in last 3 months episodes of acute respiratory infections are not registered or only one episode is registered.EFFECT: use of invention increases efficiency of antirecurrent therapy of frequent recurrent ARI episodes.1 cl, 1 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

Serotonin 5-ht3 receptor antagonists for application in treatment of lesional vestibular disorders // 2608458
FIELD: medicine.SUBSTANCE: invention relates to medicine and consists in application of serotonin 5-HT3 receptor antagonist for treatment of damages during vestibular disorders, wherein, mentioned damage is characterized by damage of internal ear cells and/or vestibular nerve cells, wherein, serotonin 5-HT3 receptor antagonist is selected from a group comprising ondansetron, palonosetron, tropisetron, lerisetron, alosetron, granisetron, dolasetron, bernesetron, ramosetron, azasetron, itasetron, zakoprid and cilansetron; and mentioned serotonin 5-HT3 receptor antagonist is introduced to the patient, at least during 5 days.EFFECT: treatment of damages during vestibular disorders.4 cl, 4 ex, 6 dwg

Deuterium-enriched 4-hydroxy-5-methoxy-n,1-dimethyl-2-oxo-n-[(4-trifluoro-methyl)phenyl]-1,2-dihydroquinoline-3-carboxamide // 2608306
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to deuterium-enriched 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[(4-trifluoromethyl)-phenyl]-1,2-dihydroquinoline-3-carboxamide. Invention also relates to a pharmaceutical composition based on deuterium-enriched carboxamide, method for production thereof and method of treating malignant hyperproliferative disorder or autoimmune disease, based on use of deuterium-enriched carboxamide.EFFECT: technical result is obtaining deuterium-enriched 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[(4-trifluoromethyl)-phenyl]-1,2-dihydroquinoline-3-carboxamide, having useful biological properties.25 cl, 7 dwg, 10 tbl, 1 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

Combined anticancer therapy // 2607596
FIELD: medicine.SUBSTANCE: present invention relates to combined therapy with {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4difluorophenyl} amide of propane-1-sulphonic acid (compound 1) or its pharmaceutically acceptable salt and EGFR inhibitor, selected from erlotinib and cetuximab, for treating cancer, containing b-Raf with V600 mutation, namely colorectal cancer, melanoma and thyroid cancer.EFFECT: combination of compound 1 with EGFR inhibitor leads to improved anti-tumor effects, which considerably exceed the results, obtained for each compound separately, without increasing the toxicity.20 cl, 6 ex, 15 tbl, 9 dwg

Encapsulated dosage form, containing montelukast and levocetirizine // 2606857
FIELD: pharmaceutics.SUBSTANCE: invention relates to capsule dosage form for preventing or treating allergic rhinitis and asthma, which consists of two separate layers: (1) montelukast layer, containing montelukast or its pharmaceutically acceptable salt; and (2) levocetirizine layer, containing levocetirizine or its pharmaceutically acceptable salt, in which said montelukast layer and levocetirizine layer contain water in amount of 5 % and less; and their production method.EFFECT: encapsulated dosage form, according to invention, can completely separate two active ingredients, minimizing so reaction activity between them and improving stability of product with respect to ageing effect and thus optimizing therapeutic action.20 cl, 5 tbl, 9 ex
Compounds having antagonistic activity towards muscarinic receptors and agonist activity to beta2-adrenoreceptors // 2606121
FIELD: chemistry.SUBSTANCE: present invention relates to compounds of general formula (I), acting as muscarinic receptors antagonists or beta2-adrenoreceptors agonists, as well as to pharmaceutical compositions based thereon and to therapeutic applications for preparing a medicine to prevent and treat diseases, such as asthma, chronic bronchitis, etc.EFFECT: obtained are novel compounds of formula (I) having activity towards muscarinic receptors or beta2-adrenoreceptors.13 cl, 5 tbl, 39 ex, 2 dwg

Quinoline and quinoxaline derivatives effective as cysteinyl-leukotriene antagonists // 2605929
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a heterocyclic compound of formula (IA) or to a pharmaceutically acceptable salt thereof, where in each case R1 and R3 are independently selected from a group comprising hydrogen, halogen, -OH, -C1-2alkyl, -O-C1-2alkyl, -O-C1halogenalkoxy, -N(C1alkyl)2; R2 represents hydrogen; W represents a group selected from -CH= or -N=; X represents a group selected from -CH=CH- or -N=CH-, where nitrogen from -N=CH- is directly bonded with ring 'a'; Y represents a group selected from -CH=CH- or -C≡C-; Z denotes a bond or group selected from -(CH2)n- and -CH=CH-; A is a group selected from -OR, -O(CH2)nphenyl, -O(CH2)nthiophene; P is selected from a group comprising -O-; Q is a group selected from -COOH; where R is selected from a group comprising hydrogen, -C1-6alkyl, -C3-6cycloalkyl, -C1alkyl (C3-6cycloalkyl), -C3-6alkenyl and -C3-6alkynyl; 'n' in each case represents an integer, selected from 1, 2 or 3; 'm' in each case represents an integer, selected from 0-3, inclusive. Invention also relates to a compound of formula (Id), where radicals are described in patent claim.EFFECT: obtaining novel heterocyclic compounds effective as antagonists of cysteinyl-leukotriene.9 cl, 1 dwg, 2 tbl, 67 ex
Injection preparation based on drotaverine and preparation method thereof // 2605826
FIELD: pharmaceutics.SUBSTANCE: invention relates to pharmaceutical industry and represents pharmaceutical preparation in form of solution for intravenous and intramuscular administration, containing drotaverine hydrochloride, sodium disulphite, buffer agent and solvent. According to invention, preparation as buffer agent contains ammonium acetate and 30 % aqueous solution of acetic acid, and solvent is 95 % ethanol and water for injections highly purified in following proportions: drotaverine hydrochloride (in terms of anhydrous substance) - 18-22 mg, sodium disulphite - 0.9-1.1 mg, ethanol 95 % (in terms of anhydrous) - 0 59.4-72.6 mg, ammonium acetate - 0.66-1.0 mg, 30 % aqueous solution of acetic acid - 0.54-1.0 mg, water for injections - up to 1.0 ml, pH - 4.0-5.5, as well as method of producing of preparation.EFFECT: invention provides high stability of preparation and maintaining pH in process of storage.3 cl, 4 ex

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

Nuclear receptor binding agents // 2604666
FIELD: medicine.SUBSTANCE: group of inventions relates to medicine, namely, to gastrology and endocrinology, and can be used for prevention, treatment, delay of the onset, reduction of the incidence or reduction of the severity of a condition associated with high fat diet consumption, fatty liver infiltration, post-menopausal obesity, to increase energy consumption in a patient, to increase lean body mass. For this purpose, the patient in need thereof, administering a therapeutically effective amount of an estrogen receptor ligand compound, wherein the compound represents 4-bromo-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinoline-1-(2H)-on (12u) or 4-cyano-6,8-dihydroxy-2-(4-hydroxyphenyl)isoquinoline-1-(2H)-on (14m).EFFECT: group of inventions provides increase in treatment efficacy of said states within its safety.13 cl, 10 tbl, 33 dwg, 41 ex

Novel class of selective agonists of somatostatin receptors // 2603962
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I or its pharmaceutically acceptable salt, wherein R1, R5 are independently selected from H; R2, R3 and R4 are selected from H and ring A, wherein one of R2, R3 or R4 independently represents ring A; ring A is a 6-member monocyclic or 10-member bicyclic aromatic ring which optionally contains 1 heteroatom, which is N, wherein ring A can be optionally substituted with 1-3 substitutes independently selected from halogen, OH, COOH, C1-C6-alkyl, C1-C6-alkoxy, -C(O)C1-C6-alkyl, -NO2; ring B is a 5-6-member non-aromatic ring, optionally containing 1 heteroatom, which is O, wherein ring B can be optionally substituted with 1-3 substitutes independently selected from -C1-C6-alkyl, -C(O)C1-C6-alkyl, -C1-C6-alkoxy; R6 is selected from H or C1-C6-alkyl, R7 denotes H or-(Z)m-(D)p, where independently m=0-1, p=0-1, wherein m=p=0 does not hold; Z is selected from C1-C6-alkyl; D is a 5-6-member non-aromatic ring, optionally containing one N heteroatom, wherein ring D can be optionally substituted with one substitute selected from C1-C6-alkyl, C1-C6-alkoxy. Compound of formula I or pharmaceutically acceptable salt thereof are intended for use as sst4 receptor agonist for preparing a pharmaceutical composition for treating and/or preventing a pathological condition or disease involving somatostatin receptors subtype 4 (sst4). Invention also relates to a pharmaceutical composition for treating and/or preventing a pathological condition or disease, treatment and/or prevention of which requires use of somatostatin receptor agonist subtype 4 (sst4), containing a therapeutically effective amount of compound of formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, solvent and/or filler.EFFECT: chemical compounds, which are selective agonists of human sst4 receptors.15 cl, 4 dwg, 3 tbl, 6 ex

Aerosolized fluoroquinolones and uses thereof // 2603638
FIELD: medicine.SUBSTANCE: invention relates to using levofloxacin or ofloxacin in a dose from 20 mg to 400 mg per day for treating microbial infection in the patient.EFFECT: technical outcome: invention relates to the use of levofloxacin or ofloxacin in effective dosages for treating a microbial infection.14 cl, 53 dwg, 37 tbl, 13 ex

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

Combination of sirosingopin and mitochondrial inhibitors for treatment of cancer and for immunosuppression // 2602937
FIELD: medicine.SUBSTANCE: group of inventions is related to medicine, pharmacology, pharmaceutics, and involves a pharmaceutical composition and combination of sirosingopin (SS) and mitochondrial inhibitor (MI), where the said mitochondrial inhibitor represents metformin or fenformin. Ratio of the amount of (wt/wt) CC and MI can range from 1 to 10-1 to 1000. This combination can be used in treating such types of cancer as carcinoma, sarcoma, leukaemia, myeloma, lymphoma, various types of cancer of the nervous system or autoimmune diseases of skin, nervous system, connective tissue, muscles, blood, bone tissue and internal organs, as immunosuppressive therapy. Group of inventions also includes the method of determining if the cancer cell is sensitive to the SS. For this purpose, (a) a suspension of single cells cultivated cancer cells in acceptable media is received; (b) the cancer cell is incubated with SS; (c) the cancer cell obtained at step (b) is incubated with positively charged fluorescent dye; (d) the fluorescence excited intensity is measured; and (e) fluorescence intensity, measured at step (d) is compared with the intensity of fluorescence of the cancer cell to be incubated only with positively charged fluorescent dye. Relative increase in fluorescence intensity of cancer cells, preliminary incubated with SS, means that cells are sensitive to treatment with SS. Group of inventions also includes a method of treating cancer or autoimmune disease by administration of a combination or a composition of SS and the said MI to a warm-blooded animal in the amount effective with respect to the aforementioned disease.EFFECT: said combination and composition provide a synergetic effect when used regarding the aforementioned disorders, the prognosis of which, in its turn, can be provided for implementation of the above method for prognosis of cancer cell sensitivity to SS.14 cl, 12 dwg, 1 ex, 1 tbl

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
 
2551099.
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