(A61K31/5377)

Chloride 4-[(1e)-1-(6-chloro-4-oxo-4n-chromen-3-yl)-4-methylpent-1-en-3-yl]morpholine-4-yl, method of producing thereof and its antituberculosis effect // 2613633
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to chloride 4-[(1E)-1-(6-chloro-4-oxo-4H-chromen-3-yl)-4-methylpent-1-en-3-yl]morpholine-4-yl of formula I and method of producing thereof.EFFECT: new heterocyclic compound, may be used as a potential antituberculosis drug.3 cl, 5 dwg, 2 tbl, 2 ex
Dispiropyrrolidine derivatives // 2612534
FIELD: chemistry.SUBSTANCE: invention relates to a dispiropyrrolidine derivative of general formula (1), where ring A is a spiro compound 4-6-member saturated hydrocarbon ring, which can contain one or more substitutes, ring B is a benzene ring which can contain one or more substitutes, or a pyridine ring, which can contain one or more substitutes, R1 is an aryl group which can contain one or more substitutes, or heteroaryl group, which can contain one or more substitutes, R2 is a hydrogen atom; and R3 is a group presented by general formulae (2), (3) or (4), which inhibits protein interaction between Mdm2 and p53 protein and has antitumour activity.EFFECT: dispiropyrrolidine derivatives are disclosed.29 cl, 199 ex R3 :
Substituted dihydropyrazolones for treating cardiovascular and hematologic diseases, use thereof, drug and method of treating and/or preventing // 2611012
FIELD: chemistry; pharmaceutics.SUBSTANCE: present invention relates to use of dihydropyrazolone derivatives of formula (I), in which radicals and symbols are defined in p. 1 of patent claim.EFFECT: making drug for treating and/or preventing cardiac diseases of blood circulation, cardiac failure, anemia, chronic diseases of kidneys and renal failure, as well as medicinal agent containing said dihydropyrazolone derivatives, and method of treating and/or preventing said diseases in human and animals.4 cl, 10 tbl, 180 ex
orpholino-substituted derivatives of bicyclic pyrimidine urea or carbamate as mtor inhibitors // 2609208
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts . In formula (I) m is equal to 1; o equals 1 or 2; each R1 is independently selected from group consisting of H and unsubstituted C1-6alkyl; two R1 are possibly combined to form, together with ring, to which they are bonded, 8-oxa-3-azabicyclo[3.2.1]octane-3-yl or 3-oxa-8-azabicyclo[3.2.1]octane-8-yl ring; T1 is phenyl, where T1 is substituted by group N(R5a)C(O)N(R5bR5) and T1 is optionally additionally substituted with one or more R6, which are identical or different; R6 is halogen; each of R5a, R5b represents H; R5 represents H; T2; and C1-6alkyl, where C1-6alkyl is optionally substituted with one or more R8, which are identical or different; R8 represents halogen or OR9; R9 represents H; T2 is unsubstituted and selected from group consisting of phenyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl or tetrahydrofuranyl; Ra and Rb are selected to obtain one of formulae (Ik)–(Ip) or Ra, Rb, T1 are selected to obtain formula (Iq) R14, R14a, R14b, R14c are independently selected from group consisting of H; halogen or unsubstituted C1-6alkyl. Compounds of formula (I) possess mTOR inhibiting activity. Invention also relates to pharmaceutical composition containing compounds of formula (I), use of compounds for making drug and to method of treating.EFFECT: novel compounds of formula (I) are obtained, which have mTOR inhibitor activity, which can be used for treating or preventing mTOR related diseases and disorders.16 cl, 15 tbl, 82 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
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

Aromatic derivatives of sulfanilamides carbonic anhydrase ii (ca ii) inhibitors, methods for production and use thereof // 2607630
FIELD: chemistry.SUBSTANCE: present invention relates to novel aromatic sulphonamide derivatives, general formula 1 and pharmaceutically acceptable salts thereof, which are selective inhibitors of carbonic anhydrase II (CA II). Substituted sulphonamides correspond to general formula 1 ,where A is phenyl or thiophene; R1 is C1-C5alkyl, C-3C6cycloalkyl, -C(O)R3; provided that R1 is not methyl, when A is phenyl, R2 represents hydrogen; R3 is a 5-6 member heterocyclyl with one or two heteroatoms, selected from nitrogen or oxygen atoms; R2 is C1-C3alkyl, C1-C3alkoxy. Invention also relates to a method of producing compounds of general formula 1. Method involves two stages: a) sulphochlorination of corresponding oxazole derivative of general formula 5 (a-o) or 6 (a-j) with a mixture chlorosulphonic acid and thionyl chloride to produce intermediate sulphochlorides of formula 7 (a-o) or 8 (a-j), respectively, and b) with subsequent conversion of obtained sulphochlorides into primary sulphamides of formula 9 (b-o) or 10 (a-j) by reacting with ammonia according to following scheme ,where ,where R1 is C1-C5alkyl, C3-C6cycloalkyl; NR'Rʺ is a morpholine or pyrrolidine.EFFECT: compounds can be used for treating glaucoma, in particular, open-angle glaucoma, and other diseases caused by high intraocular pressure, age-related macular degeneration, diabetic macular edema, diabetic retinopathy, hypertensive retinopathy and retinal vasculopathy mediated by activity of carbonic anhydrase II.11 cl, 2 dwg, 2 tbl, 57 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
Novel immune system modulators related applications // 2606114
FIELD: chemistry.SUBSTANCE: invention relates to novel compounds of formula I or a pharmaceutically acceptable salt thereof, which possess properties of TOLL-like receptor (TLR9) inhibitor and can be used for treating autoimmune diseases, mediated by TLR9 activity. Diseases can be selected from cutaneous and systemic lupus erythematosus, insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, atherosclerosis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, autoimmune hemolytic anemia, Behget's syndrome, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia, myasthenia gravis, pernicious anemia, polyarteritis nodosa, polymyositis/dermatomyositis, primary biliary sclerosis, sarcoidosis, sclerosing cholangitis, Sjogren's syndrome, systemic sclerosis (scleroderma and CREST syndrome), Takayasu's arteritis, temporal arteritis, and Wegener's granulomatosis. In Formula I X is absent or denotes aryl; Q is H, (CH2)qNR1R2, SR1 or CR1R2R2', where q is equal to 0 or 1; R1, R2 and R2', each independently, represent hydrogen, C1-C12 alkyl, or R1 and R2 together with a nitrogen atom, with which they are bonded form a 6-member heterocycle, containing two nitrogen atoms or a nitrogen atom and an oxygen atom, which can be optionally substituted with (C1-C4)alkyl or (CH2)pORa, where p is equal to 2-4; R7 is NR3R4; R3 and R4, each independently represent (C1-C12)alkyl, or R3 and R4, together with a nitrogen atom with which they are bonded, form or 6-member heterocycle containing 1-2 heteroatoms selected from a group consisting of O and N, and which can be optionally substituted with (C1-C4)alkyl; Y is NR11, where R11 is hydrogen or (C1-C12)alkyl; L is an alkyl or alkenyl, each containing from 2 to 10 carbon atoms; R5 is hydrogen, halogen, CF3, ORa, SRa, NRbRc or NH(CH2)pNRbRc; R6 is a halogen, (C1-C12)alkyl, CF3, phenyl, phenyl substituted with halogen, CN or CF3, or NH(CH2)pNRbRc; in each case Ra independently represents hydrogen, (C1-C6)alkyl; and said Rb and Rc, together with a nitrogen atom with which they are bonded, optionally form 5-6-member heterocycle, containing 1-2 heteroatoms selected from O and N, where heterocycle is optionally substituted with (C1-C4)alkyl; provided that if R5 and R6 denote H or methyl, then Q is not H.EFFECT: obtaining novel compounds of formula.19 cl, 5 tbl, 73 ex

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

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

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

Pyrazole derivatives // 2600983
FIELD: chemistry.SUBSTANCE: pyrazole derivatives are disclosed, which are encompassed by formula (I), in which radicals and groups are defined in patent claim and which are suitable for treating disorders mediated by peripheral cannabinoid 1 receptor 1.EFFECT: invention also discloses pharmaceutical compositions and methods related to use of said compounds.29 cl, 11 ex

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

Imidazopyrazines // 2600327
FIELD: pharmaceutics.SUBSTANCE: invention relates to novel compounds of formula I and pharmaceutically acceptable salts thereof, in which values for groups R1, R2, R3, R4 and X are defined in patent claim. Invention also relates to pharmaceutical compositions, having activity of inhibitor of Fms-like tyrosine 3 (FLT3) containing said compounds and pharmaceutically acceptable salts thereof.EFFECT: invention relates to use of said compounds and pharmaceutical compositions for treating, controlling or relieving symptoms of AML (acute myeloid leukaemia).35 cl, 93 ex, 1 tbl

Novel fused pyrimidine derivatives for inhibition of tyrosine kinase activity // 2598852
FIELD: chemistry.SUBSTANCE: present invention relates to a novel fused pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof, having Bruton's tyrosine kinase inhibitory activity (ECT). Compounds can be used for preparing a drug for preventing or treating Bruton's tyrosine kinase mediated cancers and tumours, such as leukaemia, lymphoma, B-cell lymphoma, T-cell lymphoma, myeloma, acute lymphoid leukaemia (ALL), chronic lymphoid leukaemia (CLL), etc; inflammatory diseases, such as arthritis, rheumatoid arthritis, spondyloarthropathy, gouty arthritis, osteoarthritis, Still's disease, other arthritic conditions, lupus, etc; autoimmune diseases and immunologically mediated diseases, including Sjorgen's syndrome, autoimmune thyroiditis, hives, multiple sclerosis, sclerodermatitis, rejection of transplanted organs, heterotransplantation, idiopathic thrombocytopenic purpura (ITP), Parkinson's disease, Alzheimer's disease, associated with diabetes disease, pelvic inflammation, allergic rhinitis, allergic bronchitis, Hodgkin disease, non-Hodgkins lymphoma, multiple myeloma, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), diffuse large B-cell lymphoma, follicular lymphoma, etc. In compounds of formula (I).W is O; X is NH, O, SO or SO2; Y denotes a hydrogen atom, halogen atom, C1-6alkyl or C1-6alkoxy, each of A and B independently denotes a hydrogen atom, halogen atom or di(C1-6alkyl)aminomethyl; Z is selected from a group consisting of formulae Z2, Z4, Z28, Z61, Z100, Z113, Z138, Z164, Z168 and Z189 .EFFECT: treating different diseases.10 cl, 3 dwg, 19 tbl, 237 ex

Chromenone compounds as pi3-kinase inhibitors for treating cancer // 2598028
FIELD: pharmaceutics.SUBSTANCE: invention relates to chrome neon compounds with formula I possessing properties of PI3-kinase enzymes inhibitor or its pharmaceutically acceptable salts, pharmaceutical compositions based on them. In general formula I R1 represents C1-4alkyl, possibly substituted hydroxy; R2 represents C1-4alkyl; or R1 and R2 form together 4-6-member nitrogen-containing heterocyclic ring system which optionally contains 1 additional heteroatom selected from oxygen and sulphur, where sulphur ring atom is optionally oxidated with formation of S-oxide(-s), where said ring is possibly substituted with hydroxy; R3 and R5 are independently selected from H, halogen, C1-3alkoxy and cyano; R4 represents H or fluorine; n equals to 0 or 1.EFFECT: prevention and treatment of tumours sensitive to inhibition of PI3-kinase enzymes.15 cl, 4 dwg, 3 ex, 1 tbl

Drug for prevention and treatment of diabetes // 2597848
FIELD: medicine.SUBSTANCE: group of inventions is related to medicine and pharmacology. One proposes application of afobazole {5-ethoxy2-[2-(morpholino)ethylthio]-benzimidazole dihydrochloride}, anxiolytic, as an agent for preventing and treating diabetes and use of the main metabolite afobazole, connection of m-11, 2-[2-(3-oksomorfolin-4-YL) ethylthio]-5-ethoxybenzimidazole also as an agent for preventing and treating diabetes. It is shown that afobazole and connection of the m-11 inhibit depeptidylpeptidase-IV (DPP-4), without affecting other activity prolin specific enzymes. Hypoglycemic activity of afobazole can be caused by not only starting substance and its main metabolite. Set of obtained results combined with multiple clinical data on good tolerance this anxiolytic make it possible to consider application according to the new reading-as an agent preventing developing diabetes.EFFECT: technical result: afobazole provides manifested hypoglycemic effect on the background hyperglycemia and tolerance to glucose load; the main metabolite afobazole, connection of m-11, exhibits angihyperglycemic effect, the intensity of which is lower than for afobazole.2 cl, 5 tbl, 2 dwg

Use of compounds of 1,3,4-thiadiazine class as agent for correction of experimental alloxan diabetes // 2597764
FIELD: medicine.SUBSTANCE: invention relates to medicine, in particular to experimental pharmacology, novel biologically active compounds of general formula I, representing 2-morpholino-5-phenyl-6H-1,3,4-thiadiazin, hydrobromide (L-17); 2-morpholino-5-(4′-fluorophenyl)-6H-1,3,4-thiadiazin, hydrobromide (L-31), or general formula II: 2-amino propyl morpholino-5-phenyl-6H-1,3,4-thiadiazin, dihydrobromide (L-14); 2-amino propyl morpholino-5-(4′-fluorophenyl)-6H-1,3,4-thiadiazin, dihydrobromide (L-91) as agent for correction of experimental alloxan diabetes mellitus.EFFECT: technical outcome is above compounds at intramuscular introduction in dosage of 40 mg/kg have antidiabetics action in development of alloxan diabetes in rats.1 cl, 2 dwg, 1 tbl

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

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

Composition of nanostructured aprepitant, synthesis method thereof and pharmaceutical compositions containing same // 2595841
FIELD: nanotechnology.SUBSTANCE: present invention is aimed at nanostructured aprepitant composition, method for production thereof and pharmaceutical compositions containing same. Nanoparticles of aprepitant according to invention have an average particle size of less than about 200 nm. Aprepitant is a chemical compound that belongs to a class of drugs called substance P antagonists (SPA). Its effect is mediated by action on neurokinin 1 receptor. Aprepitant is manufactured by Merck & Co. under brand name Emend for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting.EFFECT: stable nanostructured particles of invention are presented by increased solubility, dissolution rate, permeability and bioequivalent or enhanced biological performance characterised by significantly decreased food effect compared to reference and marketed drug.7 cl, 5 dwg, 6 ex

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

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

Pharmaceutical composition for oral administration with improved solubility and/or absorbability // 2589701
FIELD: pharmaceutics.SUBSTANCE: present invention relates to a pharmaceutical composition for oral administration containing 4-((1-methyl pyrrole-2-yl)carbonyl)-N-(4-(4-morpholine-1-yl-carbonylpiperidin-1-yl)phenyl)-1-piperazincarboxamide, its salt or solvate as active pharmaceutical ingredient and fumaric acid as acid additive. Fumaric acid is contained in an amount of 0.25 to 5 weight fractions on the weight ratio of 4-((1-methyl pyrrole-2-yl)carbonyl)-N-(4-(4-morpholine-1-yl-carbonylpiperidin-1-yl)phenyl)-1-piperazincarboxamid.EFFECT: also described is method of stabilization, improve solubility and improved intestinal absorption of 4-((1-methyl pyrrole-2-yl)carbonyl)-N-(4-(4-morpholine-1-yl-carbonylpiperidin-1-yl)phenyl)-1-piperazincarboxamide by adding of fumaric acid to pharmaceutical composition.12 cl, 5 dwg, 8 tbl, 9 ex

Pharmaceutical compositions // 2589699
FIELD: medicine; pharmaceuticals.SUBSTANCE: group inventions relates to local pharmaceutical compositions for treating hyperproliferative skin disease, Gorlin syndrome, basal cell carcinoma, sebaceous hyperplasia or psoriasis comprising N-[6-((2R,6S)-2,6-dimethylmorpholino)pyridin-3-yl]-2-methyl-4'-trifluoromethoxy)biphenyl-3-carboxamide, a solvent mixture consisting of dimethylisosorbide, propylene glycol, diisopropyl adipate and benzyl alcohol, an oil phase, antioxidants, texture enhancers, surfactants and preservatives. In addition, group of inventions relates to a method of treating a hyperproliferative skin disease, Gorlin syndrome, basal cell carcinoma, sebaceous hyperplasia or psoriasis using disclosed compositions.EFFECT: group of inventions provides compositions that effectively deliver active agent into skin, limiting systemic exposure, skin permeability is maintained at acceptable levels, favorable from standpoint of patient tolerance and stable.5 cl, 3 dwg

Pyrrolo[2,1-f][1,2,4]triazine compound, method for production and use thereof // 2589053
FIELD: chemistry.SUBSTANCE: invention relates to pyrrolo[2,1-f][1,2,4]triazine compound of general formula I, its isomer, pharmaceutically acceptable salt, ester or hydrate. Compound of general formula I possess properties of PI3K kinase activity. In general formula I X is CH or N; R1 is -NR5R6; R2 is ; R3 is -NH2, -NHC(O)NHR11, -NHC(O)OR11, -NHC(O)R11, -CH2OH, -CH2S(O)2R12 or -CH2NHS(O)2R12; R4 is H or CF3. Invention also relates to a method of producing pyrrolo[2,1-f][1,2,4]triazine compounds of general formula I and use thereof in preparing drugs for treating a disease associated with phosphatidylinositol 3-kinase and inhibitor of rapamycin target protein.EFFECT: technical result is obtaining novel pyrrolo[2,1-f][1,2,4] triazine compound of general formula I, having PI3K kinase activity inhibitor properties.11 cl, 2 dwg, 5 tbl, 39 ex

Niacin mimetics and method for use thereof // 2588133
FIELD: pharmaceutics.SUBSTANCE: in the general formula (I) R represents hydrogen, C1-6alkyl, fused bicyclic or arylalkenylaryl.EFFECT: pharmaceutical composition based on compounds of formula (I); a method of treating hyperlipidaemia and hypercholesterolaemia, as well as a method of increasing serum level of high density lipoprotein (HDL) and a method of reducing low density lipoprotein (LDL) using same.14 cl, 23 dwg, 8 tbl, 8 ex

Diaminopyrimidine derivatives and methods for production thereof // 2587981
FIELD: pharmaceutics.SUBSTANCE: present invention relates to a novel compound of diaminopirimidine formula 1 or its pharmaceutically acceptable salts possessing the properties of 5-HT4 receptors agonist. In formula 1 (Formula 1)R1 denotes a phenyl group substituted with one or more substitutes selected from a group consisting of hydroxy, amino, halogen, cyano, nitro, C1-2alkyl (where C1-2alkyl optionally substituted with halogen), C1-5alkoxy,C1-5alkylthio, C1-5alkoxycarbonyl and aminokarbonil, or heteroaryl group selected from a group consisting of furanyl, pyrrolyl, tiofenil, hinolinil, hromenonil, indolil, benzimidazole-4-yl, benzimidazole-5-yl, benzimidazole-6-yl, benzimidazole-7-yl and indazolil, herewith the heteroaryl group can be optionally substituted with one or more substitutes selected from a group consisting of C1-5alkyl (where C1-5alkyl optionally substituted with halogen) and C1-5alkoxy, R2 denotes a nitrogen-containing cyclic group selected from a group consisting of the following formulae from A to D (where * symbol in A-D formulae denotes the position of this group attachment to a compound of formula (1))R3 denotes C1-5alkyl group, optionally substituted by phenyl, R4 denotes hydrogen, C1-5alkyl group optionally substituted with a substitute selected from a group consisting of hydroxy, C1-5alkylamino, pyrrolidinyl and hydroxy-C-1-5alkylamino; C1-5alkoxycarbonyl group or amin-carbonyl group, R5 denotes hydrogen, hydroxyl group; C1-5alkoxy group; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of amino and C1-5alkoksikarbonilamino; or group selected from a group consisting of the following formulae of E to I (where * symbol in E-I formulae is the position of this group attachment to one of the of A-D formula compounds),R6 means hydrogen, hydroxyl group or C1-5alkyl group optionally substituted with hydroxy, X denotes -CH(R7)-, -C(=O)-, -N(R8)- or -O-, R7 means hydrogen; hydroxyl group; amino-carbonyl group; phenyl group or C1-5alkyl group optionally substituted with hydroxy, R4 and R5, R5 and R6, R4 and R6 or R5 and R7 may be interconnected while forming 5- or 6-element ring; the said ring may be carbocyclic or additionally contain an oxygen atom as a heteroatom, R8 denotes hydrogen or C1-5alkyl group. Values of R9-R12 radicals are given in the patent claim.EFFECT: invention relates to the use of formula 1 or its pharmaceutically acceptable salt for preparing a drug in order to prevent or treat gastrointestinal motility dysfunction; Gastrointestinal motor dysfunction is gastroesophageal reflux disease (GERD), a lock (constipation), an irritable bowel syndrome (IBS), dyspepsia, postoperative intestinal obstruction, prolonged gastric emptying, gastroparesis, intestinal pseudo-obstruction, content transit deceleration over the colon induced by medicines or diabetic gastroparesis.8 cl, 38 tbl, 355 ex

Use of sigma ligands from pain in bone cancer // 2585095
FIELD: medicine.SUBSTANCE: group inventions relates to prophylaxis and/or treatment of pain associated with bone cancer. Disclosed is use of a sigma-ligand, which is a 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine, a salt or stereoisomer thereof for prevention and/or treatment of pain associated with bone cancer; use of same compound for production of a medicament for same purpose, a method of treating pain associated with bone cancer and use of a combination of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine, or a salt or stereoisomer thereof and an opiate or opioid compound for prevention and/or treatment of pain associated with bone cancer.EFFECT: technical result consists in implementing claimed devices and synergistically analgesic effect of morphine on cancer pain model.7 cl, 3 dwg
Sgc stimulators // 2582679
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula IA or IB or their pharmaceutically acceptable salts. The compounds of formula IA or IB possess sGC-stimulating activity. In formulas IA and IB , a circled B symbol means B ring, and B ring represents phenyl; n is equal to an integer specified in 0 to 1; each JB is independently specified in halogen; X is specified in N or C-H; D ring represents a 6-merous ring having X in formula IA, or a 5-merous ring having Y in formula IB; each Y is independently specified in C-H, C, N, O or S and independently substituted by JD when Y represents C or N; each of bonds between the two neighbouring atoms Y or between neighbouring Y and N in formula IB independently represents a single or double bond depending on whether Y is C, N, O or S, and D ring is aromatic; m is equal to an integer specified in 0 to 3; each JD is a substituted on a halogen or nitrogen atom of the ring and independently specified in halogen, -C(O)N(RD)2, -N(RD)2, -N(Rd)C(O)RD, -N(Rd)C(O)ORD, a 4-8-merous heterocyclic ring, wherein each specified 4-8-merous heterocyclic ring contains 1 to 2 heteroatoms independently specified in O, N or S; RC is specified in halogen, -CN, C1-6alkyl or C ring. The invention also refers to individual compounds and a pharmaceutical composition containing the compound of the invention or its pharmaceutically acceptable salt in an effective amount.EFFECT: produced are the new compounds of formula IA or IB possessing sGC-stimulating activity.58 cl, 6 tbl, 12 ex
Pyrazole compounds as sigma receptor inhibitors // 2582338
FIELD: medicine.SUBSTANCE: invention refers to compounds of general formula (1) shown below, or their pharmaceutically acceptable salts having pharmacological activity towards sigma receptor, to methods for producing these compounds and to pharmaceutical compositions containing them, and to using them for treating and/or preventing sigma receptor-related diseases. In the compounds of formula (I), R1 represents phenyl substituted by halogen atoms; naphthyl; C5-6 cycloalkyl; or quinolyl; R2 and R3 are independently specified in H and C1-6 alkyl group; R4 and R5 together with the nitrogen atom to which they are attached, form a substituted or unsubstituted 5-6-merous heterocyclyl group with one or two heteroatoms specified in O or N, wherein the substitute is specified in C1-6alkyl and C1-6alkanoyl; X represents an oxygen atom or a CH2 group; m is specified in 1, 2, 3 and 4; and n is specified in 1, 2, 3 and 4.EFFECT: higher efficacy.13 cl, 2 tbl, 50 ex

Aminopyrazole derivative // 2580543
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound, which has formula presented below, or a pharmaceutically acceptable salt thereof. This compound can inhibit fibroblast growth factor receptor (FGFR) kinases in tumour tissues. In formula (I) A means a heteroaryl specified in indole, azaindole, benzofuran, benzothiophene, benzorhiazole, quinoline and pyrrole, or a benzene ring; R1 particularly means hydrogen, hydroxy, halogen, cyano, C1-4 haloalkyl, C1-6 alkyl, C2-6 alkinyl; R2 particularly means hydrogen, hydroxy, halogen, cyano, C1-4 haloalkyl, C1-6 alkyl, C2-6 alkinyl, C3-7 cycloalkyl, phenylC1-4 alkyl, or R1 and R2 together with a nitrogen atom connected thereto form a 5-6-merous heterocyclyl group containing two oxygen atoms optionally substituted by a halogen; R3 means H, C1-5 alkyl group, phenylC1-5 alkyl group or C1-4 haloalkyl group; and R4 means H or halogen.EFFECT: invention refers to a pharmaceutical composition and an agent for FGFR inhibition, an agent for preventing or treating a malignant new growth, a method for preventing or treating malignant new growths, and the use of the compounds for producing a medicinal agent for preventing or treating malignant new growths.10 cl, 35 tbl, 246 ex

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

ethod for obtaining 5-chloro-n-(5s)-2-oxo-3-[4-(3-oxo-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophenecarboxamide in modification ii (versions) // 2578602
FIELD: chemistry.SUBSTANCE: invention relates to method for obtaining 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide, represented by formula, in modification II (thereof versions). Method for obtaining formula (I) in modification II, characterised by the following spectral data in nearest IR region [cm-1]: 4086, 4228, 4418, 4457, 4634, 4905, 5846, 5911, 6026, 6081, 6582, consists in the fact that compound of formula (I) in modification I, characterised by the following spectral data in nearest IR region [cm-1]: 4082, 4142, 4170, 4228, 4299, 4376, 4429, 4479, 4633, 4791, 4877, 4907, 5081, 5760, 5885, 6002, 6441, 6564, 8473, 8833, is dissolved in inert solvent, selected from the group, including acetone, tetrahydrofuran, 1-pentanol and their mixtures, and compound is precipitated by addition of n-heptane additive at temperatures within from 0 to 80°C. Method for obtaining compound of formula (I) in modification II, is also realised by dissolution of compound (I) in modification I in 1,4-dioxane, with exposure of solution at temperature within from 30°C to temperature of solvent reflux till complete solvent evaporation. Method for obtaining compound of formula (I) in modification II is realised by suspending compound (I) in modification I in ethanol with mixing or shaking suspension at temperature within from 20 to 25°C until transformation into modification II occurs.EFFECT: obtaining 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide, represented by formula , in modification II, possessing high solubility.4 cl, 12 dwg, 7 tbl, 2 ex

Substituted azol derivatives, pharmaceutical composition containing these derivatives, and methods of treating parkinson's disease with using these derivatives // 2578596
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a substituted azol derivative presented by the following formula (I)3-(4-benzyloxy-3,5-dimethyl-phenyl)-isoxazol-5-ylmethyl ester of carbamic acid, 3-(4-prop-2-inyl-oxyphenyl)-isoxazol-5-ylmethyl ester of carbamic acid or 2-{[3-(4-benzyloxy-phenyl)-isoxazol-5-ylmethyl]-amino}-propionamide or its pharmaceutically acceptable salt, wherein R is specified in a group consisting of C4-C15 arylalkyl unsubstituted or substituted by at least one substitute specified in a group consisting of halogen, trifluoromethyl, trifluoralkoxy, -NO2, C(=O)OCH3, linear or branched C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyloxy, benzyloxy, -C(=O)H, -OH and -C=N-OH; C4-C15 heteroarylalkyl unsubstituted or substituted by at least one substitute specified in a group consisting of halogen, C(=O)OCH3, linear or branched C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenyloxy, benzyloxy; linear, branched or cyclic C1-C10 alkyl substituted by at least one substitute specified in a group consisting of C1-C3-alkyloxy, C1-C3 alkylthio, carbamate, tert-butyl-OC(=O)NH-, -NH3 +, -NH2, -OH, -C(=O)OCH2CH3, -NHC(=O)NH2, trifluoromethylsulphanyl, trifluoromethyl and -CN; wherein when R represents C4-C15-heteroarylalkyl, a heteroaryl group is specified in a group consisting of imidazol, chlorthiophen, benzothiazol, pyridine, quinoline, benzotriazol, isoxazol, furan, N-oxopyridine, N-methylpyridine and benzo[1,3]dioxol, and when R means C4-C15 arylalkyl, wherein aryl is specified in a group consisting of phenyl, phenyloxy, benzyloxy and naphthalinyl, Y is specified in a group consisting of O and N - R1, R1 means a substitute specified in a group consisting of H and linear or branched C1-C3 alkyl; R2 is specified in a group consisting of H and halogen; A is specified in a group consisting of O and S; B represents C; Z is specified in a group consisting of imidazol, pyrrolidine and tetrazol unsubstituted or substituted by at least one substitute specified in a group consisting of OH, carbamate, linear or branched C1-C4 alkyl, halogen, NO2, CF3, CN and phenyl; -OC(=O)NR3R4; NC(=NH)NH2 and -NC(=O)NH2; each of R3 and R4 is independently specified in a group consisting of H; C1-C5 alkyl unsubstituted or substituted by at least one substitute specified in a group consisting of NH2 and NR7R8; piperidine, piperazine and diazepane unsubstituted or substituted by C1-C3 alkyl, or R3 and R4 together can form piperidine, piperazine, imidazol, pyrrolidine, triazol, tetrazol, diazepane or morpholine unsubstituted or substituted by C1-C3 alkyl; each of R7 and R8 means at least one substitute independently specified in a group consisting of H and linear or branched C1-C3 alkyl; each m and n independently means 0 or 1. The compounds according to the inventions are active to treat Parkinson's disease.EFFECT: azol derivatives as a monoamine oxidase B (MAOB) inhibitor.18 cl, 4 tbl, 207 ex

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

Crystalline anhydrous γ-modification of 4-(3'-chlor-4'-fluoranilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline, method for producing it and based pharmaceutical composition // 2577518
FIELD: medicine.SUBSTANCE: invention concerns the new crystalline anhydrous γ-modification of 4-(3'-chlor-4'-fluoranilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline (international nonproprietary name is Gefinitib), which is characterised by the definite set of diffraction peaks (d, Å) and their intensity (Irelative, %) specified in cl.1 of the patent claim. The invention also refers to a method for producing and using it for preparing the pharmaceutical composition which is applicable in the pharmaceutical industry and medicine as a selective tyrosine kinase inhibitor for treating oncology diseases. The produced crystalline γ-modification of Gefinitib represents a white or off-white powder, odour-free, soluble in dimethyl sulphoxide, poorly soluble in ethanol and methanol, practically insoluble in water.EFFECT: higher biological activity.4 cl, 7 dwg, 3 tbl, 5 ex

Pharmaceutical composition in form of gel-like ophthalmic drops for treating glaucoma // 2576778
FIELD: medicine.SUBSTANCE: pharmaceutical composition for treating glaucoma contains timolol, a preserving agent, hyaluronic acid and/or carbomer and water. The preserving agent is specified in a group of: boric acid, polyhexanide, cetylpyridinium chloride. The composition contains the ingredients in the declared amounts.EFFECT: using the invention enables increasing the therapeutic effectiveness in glaucoma by the prolonged complex action of the ophthalmic drops, as well as by the prolonged time of preparation contact with the cornea that decreases a rate of preparation administration and length of the therapeutic course.1 ex

ethod for obtaining pyrimidine derivatives // 2576619
FIELD: chemistry.SUBSTANCE: invention relates to crystalline form of monohydrochloride salt of formula A compound in polymorphic form A, where said monohydrochloride salt has in diffraction of X-rays peak at diffraction angle 2θ 9.9±0.3° and 20.0±0.3°.EFFECT: said crystalline form has low moisture-absorption in comparison with free base and monohydrate monochloride, which makes it possible to provide composition stability with low risk of chemical destruction.4 cl, 10 tbl, 14 dwg, 16 ex

Compounds, compositions and methods suitable for cholesterol mobilisation // 2576402
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a novel heterocyclic compound of general formula (II) or to a pharmaceutically acceptable salt, where each R9 is -H; each R10 is independently -H, -OH, NH(methyl), -N(methyl)(methyl) or -O-methyl; each of Q1, Q2 and Q3 is independently CR10 or N; X is CHR10 or O; and each m is 1. The invention also relates to a pharmaceutical composition based on a compound of formula (II), a treatment method based on the use of a compound of formula (II), and a method of determining the level of activity of P2Y13 in a subject, based on the use of a compound of formula (II).EFFECT: obtaining novel compounds having agonistic activity with respect to the P2Y13 receptor.18 cl, 28 dwg, 4 tbl, 20 ex

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

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

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

Azole derivative // 2573634
FIELD: medicine.SUBSTANCE: invention relates to compound of structural formula (1), which possesses inhibiting activity with respect to rotamase «FKBP12». In formula R1 represents formulae or X represents -(CH2)m-X1-(CH2)n-; X1 represents bond, -O-, -NRaC(=O)-, -C(=O)NRb-, -NRcS(=O)2- or -S(=O)2NRd-; Ra, Rb, Rc and Rd, each can be similar or different and represent hydrogen atom or C1-6alkyl group; m and n, each, can be similar or different and represent integer number 0-3; R2 represents phenyl group, pyridyl group, pyridazyl group, pyrimidyl group or pyrazinyl group. Values of ring A radical and substituents of R2 radical are disclosed in invention formula. Invention also relates to pharmaceutical preparation, which contains claimed compound, and to medication for prevention of treatment of alopecia.EFFECT: increase of treatment efficiency.12 cl, 3 dwg, 1 tbl, 24 ex

Composition containing tetracyclic compounds // 2573392
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a pharmaceutical composition for oral administration, applicable for preventing and/or treating cancer, depression and a cognitive impairment, containing a substance described by formula (I), a pharmaceutically acceptable carrier and a dissolution agent.EFFECT: producing new composition.12 cl, 30 dwg, 46 tbl, 467 ex

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

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

Oxazoline derivatives for treating cns disorders // 2569887
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a compound of formulawherein Ra represents hydrogen or C1-7alkyl; R1 represents groups and or may be specified in a group consisting of , wherein R8 represents hydrogen, halogen or aryl optionally substituted by halogen; X represents a bond, -(CH2)n-, -CHRCH2-, -CHR(CH2)2-, -O-CHRCH2- or -(C3cyclopropyl)-CH2-CH2-, and R represents C1-7alkyl or C1-7alkyl substituted by halogen; R2 represents a) C1-7alkyl; b) hydrogen; c) NH-phenyl optionally substituted by one or more substitutes specified in halogen or C1-7alkyl substituted by halogen; d) NH-6-merous heteroaryl containing 1 or 2 heteroatoms N optionally substituted by one or more substitutes specified in halogen or C1-7-alkyl substituted by halogen; e) (CR'R")m-C3-6-cycloalkyl optionally substituted by halogen, C1-7alkyl, C1-7alkyl substituted by halogen, halogen-substituted phenyl or heteroaryl, which represents pyridine; f) 6-merous heterocycloalkyl containing 1 or 2 heteroatoms specified in N and O, optionally substituted by halogen or C1-7alkyl substituted by halogen; g) (CR'R")m-5-6-merous monocyclic or 9-10-mrous bicyclic heteroaryl containing 1-3 heteroatoms specified in N, S and O, optionally substituted by halogen, C1-7alkoxy, C1-7alkyl, substituted by halogen, C1-7alkoxy substituted by halogen, C1-7alkyl, C3-6-cycloalkyl, NHC(O)-C1-7alkyl, cyano, S(O)2-C1-7alkyl, NR6R7 or 5-6-merous heteroaryl containing 1 or 2 heteroatoms, N or 6-merous heterocyclyl containing 1 or 2 heteroatoms specified in N, O and S, wherein S is optionally specified by two oxygen molecules, which is optionally substituted by halogen; h) (CR'R")m-phenyl optionally substituted by halogen, C1-7alkyl substituted by halogen, C1-7-alkoxy substituted by halogen, C1-7alkyl, C2-7alkinyl, C1-7alkoxy, CH2-C1-7alkoxy or cyano; i) -O(CH2)o-phenyl optionally substituted by halogen, C1-7alkoxy or C1-7alkyl substituted by halogen; R' and R" independently represent hydrogen, C1-7alkoxy or C1-7alkyl; or together with atom C may form C3-6-cycloalkyl group; R3 represents phenyl or 10-merous heteroaryl containing 1 heteroatom N, wherein the above aromatic rings are optionally substituted by one or more substitutes specified in halogen or C1-7alkoxy; R4 represents C1-7alkyl, phenyl or 6-merous heteroaryl containing 1 heteroatom N, wherein the above aromatic rings are optionally substituted by one or more substituted specified in halogen, cyano or C1-7alkoxy; R5 represents hydrogen, C1-7alkyl or phenyl substituted by halogen; R6/R7 independently represent hydrogen, C1-7alkyl or (CH2)2-O-C1-7alkyl; m equals to 0, 1 or 2; n equals to 1, 2 or 3; o equals to 0 or 1; p equals to 0, 1 or 2; or their pharmaceutically acceptable acid addition salt. The invention also refers to compounds which represent 4-[2-((S)-2-amino-4,5-dihydrooxazol-4-yl)-ethyl]-N-(4-chlor-phenyl)-benzamide or (S)-4-(2-(2-amino-4,5-dihydrooxazol-4-yl)-ethyl)-N-(5-ethynylpyridin-2-yl)benzamide. The compositions according to the invention are applicable to produce a pharmaceutical composition having a high affinity to trace amine associated receptors.EFFECT: oxazoline derivatives applicable in treating depression, bipolar disorder, attention deficit/hyperactivity syndrome (ADHD), psychotic disorders, schizophrenia, Parkinson's disease, migraine and addictive substance abuse.23 cl, 1 tbl, 233 ex

Compositions for kinase cascade modulation and methods of their application // 2569299
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to polymorph of mesylate salt of 2-(5-(4-(2-morpholinethoxy)phenyl)pyridine-2-yl)-N-benzylacetamide, possessing properties of Syk inhibitor, method of its synthesis, based on it pharmaceutical composition and its application for treatment and prevention of cell proliferation.EFFECT: obtaining composition, possessing properties of Syk inhibitor.17 cl, 10 tbl, 28 dwg, 32 ex
 
2551315.
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