(A61K31/5377)

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
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

New pyrazole derivative // 2625790
FIELD: pharmacology.SUBSTANCE: in particular, invention relates to a compound represented by the following general formula (I): [wherein Ar1 is 2-methoxy-4-(2-pyridylmethoxy)phenyl, etc. and Ar2 is 1H-indole-6-yl group, etc.] or to salt thereof.EFFECT: increased efficiency of treatment.19 cl, 4 dwg, 1 tbl, 112 ex
Combined drug of anxiolithic, stress-protector, nootropic and antioxidant action // 2625754
FIELD: pharmacology.SUBSTANCE: invention is a combined drug of anxiolytic, stress-protective, nootropic and antioxidant action containing tryptophan, characterised by additional content of tiotriazoline at a quantitative ratio: tryptophan ranging from 1 to 7 wt parts per 1 wt part of thiotriazoline.EFFECT: agent has a higher anxiolytic and antioxidant activity compared to the known agents and has additional nootropic and stress-protective action.3 cl, 5 tbl, 2 ex
Bimatoprost and thymolol solutions not containing conservants // 2624534
FIELD: pharmacology.SUBSTANCE: invention relates to a composition of bimatoprost and timolol containing no preservatives to reduce intraocular pressure in a human, containing the following composition: 0.03% w/o bimatoprosta; 0.5% w/o timolol; 0.268% w/o sodium phosphate dibasic heptahydrate; 0.014% w/o citric acid monohydrate; 0.68% w/o sodium chloride and water, and having a pH of 7.3. The invention provides a formulation that does not contain any antimicrobial preservative that is stable in solution for a long time at ambient temperature and is also stable in the plastic packaging in which it is usually stored.EFFECT: compositions of the invention are more effective in treating increased IOP than compositions with preservatives, and have a lower risk of side effects.8 cl, 1 tbl

2-carboxamide cycloamino urea derivatives in combination with hsp90 inhibitors for treating proliferative diseases // 2624493
FIELD: pharmacology.SUBSTANCE: proposed: a pharmaceutical combination for treating melanoma comprising: (a) 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl) pyridin-4-yl] thiazol-2-yl}amide) (S)-pyrrolidine-1,2-dicarboxylic acid (compound A) or its pharmaceutically acceptable salt; and (b), at least, one Hsp90 inhibitor, representing ethylamide 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethyl-phenyl) isoxazole-3-carboxylic acid (AUY922) or its pharmaceutically acceptable salt; the use of the said combination for manufacturing drugs to treat melanoma and corresponding method for treating melanoma.EFFECT: synergistic effect of the compound combinations in reducing the tumour volume.4 cl, 9 dwg, 2 tbl, 6 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

Compound 8-fluorophthalazine-1(2h)-one as inhibitors of bruton tyrosine kinase // 2622391
FIELD: pharmacology.SUBSTANCE: compounds of 8-fluorophthalazine-1(2H)-ones of formula II are proposed, wherein one of X1, X2 and X3 represent N, and the other symbols have meanings defined in claim 1 of the invention formula, or stereoisomers, gautomers and pharmaceutically acceptable salts thereof. The compounds proposed inhibit the kinase Btk (Bruton tyrosine kinase) and can be used to treat immune disorders, such as inflammation, mediated by kinase Btk.EFFECT: increased efficiency while using the compounds of formula II for the diagnosis and treatment in vitro, in situ and in vivo such disorders in mammalian cells, or associated pathological conditions.25 cl, 8 dwg, 2 tbl, 69 ex
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

Apoptosis inducing agents selective for bcl-2 for cancer and immune diseases treatment // 2621052
FIELD: pharmacy.SUBSTANCE: invention relates to specific heterocyclic compounds containing the sulphonyl amino carbonyl group. The invention also relates to a pharmaceutical composition based on this compound.EFFECT: new heterocyclic compounds with inhibitory activity in terms of anti-apoptotic Bcl-2 proteins are obtained.2 cl, 3 tbl, 481 ex
Heterocyclic derivatives as receptors associated with tracer amines (taars) // 2621050
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula and to pharmaceutical compositions based thereof.EFFECT: new compounds are obtained with an affinity for the receptors to TAAR1 and can be used to treat depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity disorder, disorders caused by stress, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, malnutrition, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, temperature homeostasis disorders, sleep disturbance, circadian dysregulation and cardiovascular disorders.23 cl, 16 dwg, 1 tbl, 55 ex
Pyrazole quinolinone derivatives, their preparation and therapeutic application // 2621037
FIELD: pharmacy.SUBSTANCE: invention relates to compounds according to formula (I) , wherein R1, R2 and R3 are as defined in claim cl. 1. The compounds of this invention are reversible and selective inhibitors of type 2 methionine aminopeptidase (MetAP2). The invention also relates to intermediates for preparing the compounds of formula (I), drug and pharmaceutical compositions based on the compounds of formula (I) and their therapeutic application.EFFECT: increased efficiency of compounds application.24 cl, 2 tbl, 25 ex

Phenyl derivatives // 2619105
FIELD: chemistry.SUBSTANCE: invention relates to new compounds of general formula containing two cyclic groups, especially where M1 - Ring 1 and M2 - Ring 2, each independently represents a phenoxy group. The compounds have high antagonistic activity against human S1P2.EFFECT: invention due to its properties can be used as a therapeutic agent for the treatment of S1P2-mediated diseases such as diseases, resulting from vasoconstriction, fibrosis and respiratory diseases.8 cl, 6 dwg, 5 tbl, 45 ex
Bruton's tyrosine kinase inhibitors // 2618529
FIELD: pharmacy.SUBSTANCE: invention relates to a compound of general formula I, below, or a pharmaceutically acceptable salt thereof. In the formula I compound, X is halogen; Y is H or lower alkyl; R is -R1-R2-R3; R1; R1 is pyridyl; R2 is -C (= O) or is absent; R3 is morpholinyl or pyrrolidinyl, optionally substituted by a lower alkyl. The above compounds are used to modulate OMB activity and treat diseases associated with excessive OMB activity. Furthermore, these compounds are used for treatment of inflammatory and autoimmune diseases associated with aberrant B-cell proliferation, such as rheumatoid arthritis. The invention also relates to the pharmaceutical composition comprising a compound of formula I and at least one carrier, diluent or excipient.EFFECT: increased efficiency of compounds application.20 cl, 2 tbl, 7 ex
Phenylpyrrole derivative // 2618228
FIELD: pharmacy.SUBSTANCE: invention relates to new derivatives of formula (I) Q: (A) or (B) phenylpyrrole, or pharmaceutically acceptable salts thereof, which are useful for prevention or treatment of diseases such as dementia, Alzheimer's disease, attention deficit, hyperactivity disorder, schizophrenia, epilepsy, "central" cramp, obesity, diabetes, hyperlipidemia, narcolepsy, idiopathic hypersomnia, behavior-induced insufficient sleep syndrome, sleep apnea syndrome, circadian rhythm, parasomnia, sleep-related traffic violation, insomnia and depression, or allergic rhinitis.EFFECT: increased compound application effeciency.13 cl, 3 tbl, 10 ex

Pyrazole compound and its pharmaceutical use // 2617678
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to a compound of general formula or pharmaceutically acceptable salt thereof. In formula (I) Cy represents phenyl, C3-8 cycloalkyl or C3-8 cycloalkenyl , Cya is a heterocyclic group with the structure given in the invention formula, R1a and R2b are groups defined in the formula. The objects of invention are also the pharmaceutical composition and the agent based on formula (I) compound, the method of diabetes treatment and prevention and compound application.EFFECT: invention is SGLT1 inhibitor and can be used to treat or prevent diabetes.24 cl, 4 tbl, 605 ex
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
 
2551256.
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