Biphenyl derivatives and application thereof in treating hepatitis c
SUBSTANCE: invention refers to a compound which represents a biphenyl derivative of formula . What is also described is a pharmaceutical composition for treating or relieving HCV on the basis of said compound.
EFFECT: higher efficacy of the composition.
3 cl, 265 ex
The text descriptions are given in facsimile form.
2. The pharmaceutical composition intended for the treatment or relief of HCV, comprising the compound according to claim 1 and a pharmaceutically acceptable diluent or carrier.
3. The use of compounds according to claim 1 for the manufacture of a medicinal product intended for use for the treatment or relief of HCV.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to N-(2-thiazolyl)amide derivatives of formula wherein R1 and R2 are independently selected from H, -NO2, fluorine, chlorine and iodine, provided at least one of R1 and R2 is different from H; m is equal to 1 or 2, or to its pharmaceutically acceptable salts.
EFFECT: invention refers to a method for preparing said compounds, based pharmaceutical composition and applying them for preparing a drug for treating or preventing GSK-3 mediated diseases or conditions, especially neurodegenerative diseases, such as Alzheimer's disease or insulin-independent diabetes.
24 cl, 3 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to 5-amino-3-(2-aminopropyl)-[1,2,4]thiadiazole derivatives of general formula wherein R1, R2, R3 can be identical or different independently means hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, heteroaralkyl (wherein 5- or 6-member N-, O- or S-heteroaromatic cycle), cycloalkyl, 2,2,6,6-tetramethyl-piperidin-4-yl, and also R1+R2 can mean heterocycle specified in optionally substituted pyrrolidine, piperidine, azepane, piperazine, morpholine wherein optional substitutes can be hydroxyl, cyanogroup, halogens, alkyls, lower alkoxy groups, lower alkothio groups, trihalogen methyl, sulphamide, optionally substituted amino groups (amino, dimethyl amino, diethyl amino) provided R1=H, R2 is different from hydrogen or methyl.
EFFECT: there are produced new compounds which can find application in medicine as the substances possessing neuromodulatory activity.
2 cl, 3 ex
SUBSTANCE: invention relates to compounds of general formula (I) and pharmaceutically acceptable salts thereof, where Ar denotes a phenyl group substituted with piperazine or benzo[d]thiazole, with a phenyl part bonded to B, where the piperazine or benzo[d]thiazole can be unsubstituted or substituted with substitutes selected from alkyl or acetyl; B denotes -O-; R1 denotes hydrogen; R2 denotes S(O)2R4 or C(O)(CH2)n-C(O)OR5; R3 denotes halogen; R4 denotes an aryl which can be unsubstituted or substituted with substitutes selected from a group comprising halogen, alkyl, fluoroalkyl, alkoxy and trifluoromethoxy; R5 denotes hydrogen; n is a whole number from 1 to 3. The invention also relates to a method of producing said compounds and a pharmaceutical composition for treating metabolic disorders associated with insulin resistance or hyperglycaemia, based on said compounds.
EFFECT: novel compounds are obtained, which can be used in medicine to treat type 2 diabetes, obesity, glucose intolerance, dyslipidaemia, hyperinsulinaemia, atherosclerotic disease, polycystic ovary syndrome, coronary artery disease, hypertension or non-alcoholic fatty liver disease.
28 cl, 3 dwg, 4 tbl, 22 ex
SUBSTANCE: invention relates to a method of producing amide-containing 1,3,5-dithiazinanes of general formula , where R=H (Ia), CH3 (Ib). The method is realised by reacting hydrogen sulphide-saturated aldehyde (formal or acetic) with a mixture of isonicotinic acid hydrazide - BuONa (1:3, pH>11.5). The process is carried out at ratio hydrazide: aldehyde: H2S equal to 1:3:2, at temperature 40°C while stirring constantly for 4 hours, followed by neutralisation with a calculated quantity of dilute HCl and purification via column chromatography on SiO2. The substances obtained using the disclosed method can be used as radiation protection, antitumour and diuretic agents, as well as selective sorbents and extractants of noble and precious metals.
EFFECT: obtaining amide-containing 1,3,5-dithiazinanes of general formula (I).
SUBSTANCE: invention relates to derivatives of 1,3,4-thiadiazolines (I), thiadiazinones (II) and thiadiazepines (III), obtained based on thiohydrazides of oxamic acids, which can be used to inhibit pathogenic bacteria, and can particularly affect type III secretion system in pathogens, having general formula:
, , ,
where R denotes H; R1 denotes H, pyridinyl; phenyl, substituted with alkyl C1-C5, Hal, CF3; a group , where X denotes S, substituted with alkyl C1-C5, COOR4; R2, R3 denotes alkyl C1-C5, pyridinyl, phenyl, substituted Hal, OH, OR4, a R4 denotes unsubstituted alkyl C1-C4.
EFFECT: obtaining compounds which can be used to inhibit pathogenic bacteria.
2 cl, 2 dwg, 6 tbl, 21 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.
EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.
13 cl, 1 tbl, 31 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to compounds of formula
where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.
EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.
12 cl, 13 ex
SUBSTANCE: invention relates to a novel compound of general formula I
and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.
EFFECT: novel dipeptidyl peptidase IV inhibitors.
10 cl, 1 tbl, 43 ex
SUBSTANCE: invention refers to new indazole derivants with the formula (1.0) or to their pharmaceutically acceptable salts and isomerides that act as inactivators in relation to ERK2. In formula (1.0): meanings of the chemical groups Q, R1, R2 are given in the invention formula. The invention also refers to the pharmaceutical composition containing the mentioned compounds and to application of the compounds with the formula (1.0) for production of crude drugs used in malignant growth treatment.
EFFECT: application of the compounds for production of crude drugs used in malignant growth treatment.
65 cl, 611 ex, 27 tbl
SUBSTANCE: compounds can be used to treat such diseases as hypertension, congestive heart failure, cardiac hypertrophy and others. In formula I R1 denotes a) cyclohexyl or trifluoromethyl; or b) phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 2-imidazolyl, 2-thiazolyl, 2-benzothienyl, 4-benzofuryl, 4-benzothienyl, 7-benzofuryl, 2,3-dihydro-7-benzofuryl, 7-benzothienyl, 1,3-benzodioxol-4-yl, 7-indazolyl, or 8-quinolinyl, optionally substituted with 1-3 substitutes, and X and Y each denotes a single bond; R2 denotes methyl, ethyl, propyl, butyl, pentyl, hexyl, 5-pentenyloxy, 3,33-trifluoropropyl, 4,4-difluoropentyl, 3-(cyclopropyl)propyl, 4-(cyclopropyl)butyl, 3-hydroxypropyl, 4-hydroxybutyl, 4-hydroxypentyl, 4-hydroxyhexyl, 5-hydroxyhexyl, 2-hydroxyethoxy etc, given in the claim; R3 denotes H, F, OH, methoxy, ethoxy, 3-hydroxypropoxy, acetylamino, propionylamino, (2-methylpropionyl)amino, or butanoylamino; A denotes 2,4-disubstituted morpholine with R1XCR2R3Y, bonded on the second position and Q bonded on the fourth position, 1,3-disubstituted piperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-dibustituted-3-methylpiperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-disubstituted benzene or 1,3-disubstituted cyclohexane; Q denotes Q1, Q2, Q4, Q5, Q9, or Q10 given in the claim, to which A and N are bonded on cut-off bonds, R4 denotes H or methyl.
EFFECT: obtaining novel compounds having aspartic protease inhibitor properties, particularly renin inhibitor.
10 cl, 1 tbl, 166 ex
SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.
EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.
11 cl, 38 ex, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: there are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula
, where R1 means C1-C4alkyl, R2 and R3 mean halogen, R4 is selected from the group consisting of 2-furanyl, 3-furanyl, 2-thiophen, 3-thiophen, phenyl, benzyl, 2-benzofuranyl, etc., R5 is selected from the group consisting of hydrogen and R6, R6 means a subgroup of general formula
which are antagonists of tachykinin receptors. Also, there are described pharmaceutical compositions containing such compounds, and methods for making such compounds and intermediate products for making the compounds according to said methods.
EFFECT: preparation of new compounds.
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to compound of general formula (I) or its pharmaceutically acceptable salt, mediated by glutamate receptor, and to based on them pharmaceutical composition. (I), where R1 stands for C1-6alkyl; R2 and R3 stand for hydrogen; p stands for 0; n stands for 1; R5 and R6 stand for hydrogen, and Het stand for thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, imidozolyl, each of which can be substituted with one or two groups, independently selected from the list, which consists of C1-6alkyl, C1-6alkoxy, acetyl, halogen, halogenC1-6alkyl, cyano.
EFFECT: creation of compound which has property to enhance response reaction.
4 cl, 2 tbl, 6 dwg, 38 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to novel compounds of formula (1) , in form of trans- or cis-isomers, or their mixture, where R1 is selected from , and ; R7 stands for lower alkyl; R8 stands for lower alkyl; X represents >C=O or >SO2; R9 and R11 represent hydrogen or together form double bond; R10 and R12 are independently selected from hydrogen or lower alkyl; m stands for 1 or 2; n stands for 0, 1 or 2 and their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition and to application of said compounds, as well as compounds of formula (I), where R1 represents (R2, R3, R4, R5 and R6 each is independently selected from hydrogen, lower alkyl, lower alkoxy group or halogen; on condition that R2, R3, R4, R5 and R6 do not represent hydrogen), for treatment and/or prevention of DPP-IV-associated diseases.
EFFECT: obtaining novel compounds for treatment and/or prevention of DPP-IV-associated diseases.
14 cl, 1 tbl, 33 ex
SUBSTANCE: invention relates to novel bioisosteres of actinonin of general formula (I) , as well as to pharmaceutically acceptable salts thereof and pharmaceutical compositions based on said compounds, with peptide deformylase (PDF) inhibitory activity, as well as to use of the compounds or pharmaceutical compositions based on said compounds to prepare medicinal agents. In general formula (I) R1 is a hydrogen atom, R2 is a hydrogen atom, (C1-C6)alkyl residue, hetero(C1-C6)alkylphenyl residue, where the heteroatom is sulphur, R3 is a hydrogen atom, R4 is (C1-C6)alkyl residue, (C3-C7)cycloalkyl residue, R6 is a hydrogen atom, n is 1, 2 or 3. Values of substitute R5 are given in the formula of invention.
EFFECT: new compounds have useful biological activity.
8 cl, 1 ex
SUBSTANCE: invention relates to N-substituted aniline and diphenylamine analogues, chosen from 3,4-bisdifluoromethoxy-(3-carboxyphenyl)-N-(5-(2-chloropyridinylmethyl))-aniline, 3,4-bisdifluoromethoxy - N-(3-carboxyphenyl) - N-(3-(2-chloropyridylmethyl))-aniline, 3,4 - bisdifluoromethoxy - N-(3-carboxyphenyl) - N-(4-(3,5-dimethylisoxazolylmethyl)) aniline, 3 - cyclopentyloxy - 4-methoxy - N-(3-aminocarbonylphenyl) - N-(3-pyridylmethyl) aniline and other compounds given in paragraph 1 of the formula of invention and to their pharmaceutically acceptable salts as inhibitors of PDE4 enzyme.
EFFECT: compounds can be used for treating and preventing diseases caused by activity of the PDE4 enzyme.
15 cl, 8 dwg, 58 ex
SUBSTANCE: there is disclosed method of producing (+)duloxetine or its acid-additive salt, including (i) isolation of racemic (±)duloxetine with chiral acid thus producing chiral acid salt and (+)duloxetine, essentially free from (-)duloxetine; and (ii) if desired, transformation of the salt produced at the stage (i) into free base or other acid-additive salt if reasonable. Additionally, method of producing (+)duloxetine or its acid-additive salt can include intermediate process stage that is O-alkylilation enabled with the base or phase-transfer catalyst added.
EFFECT: specified method allows for production of receive enantiomer-pure (+)duloxetine.
17 cl, 5 ex
SUBSTANCE: present invention pertains to a new derivative of cyclic amine or its salts with the following formula (I): (where symbols stand for the following: A: 5-8-member cyclic amine, which may contain a double bond, a bridged structure and may contain substitutes R7-R11 in the ring, or -NH2, -NH(inferior alkyl), -N(inferior alkyl)2 or ) morpholin-1-yl; ring B: benzole, thiophene, furane, pyrrole, 5-7-member cycloalkane or 5-7-member cycloalkene; X1: a bond or inferior alkylene; X2: -(CR12R13)n-, -N(R14)-, -N(R14)CO-, -CON(R14)-, -CO-, -CH(OH)-, -N(R14)- (CR12R13)n-, (CR12R13)n-N(R14)-, -CON(R14)-(CR12R13)n-, -n(R14)CO-(CR12R13)n-, -(CR12R13)n-N(R14)CO-, -(CR12R13)n-CON(R14)-, -CO-(CR12R13)n- or -(CR12R13)n-CO-; Y1: -OH, -O-inferior alkyl, NH2 or -N3; R1 and R2: are identical or different and stand for a halogen atom, inferior alkyl or inferior alkylene-OH; R3-R6: are identical or different and stand for a hydrogen atom, a halogen atom, inferior alkyl, inferior alkenyl, inferior alkynyl, -O-inferior alkyl, -OH, -NH2, -NH(inferior alkyl), -N(inferior alkyl)2, -NH-CO- inferior alkyl, -N(inferior alkyl)-CO- inferior alkyl, -CN-, -NO2, -CF3, -O-inferior alkylene-OH, -inferior alkylene-OH, -inferior alkylene-halogen, -inferior alkylene-O-inferior alkyl, -CO-5-8-member cyclic amine, -COOH-inferior alkyl, -COO-inferior alkylene-aryl, pyridine, thiophene, -inferior alkylene-morpholine, aryl, which may contain a substitute: -O-inferior alkyl or -CF3; R7: hydrogen atom, inferior alkyl, -inferior alkylene-aryl or -inferior alkylene-pyridine: R7 is substitute on the nitrogen atom of the cyclic amine; R8-R14: are identical or different and stand for a hydrogen atom or inferior alkyl; n: is an integer, equal to 1, 2 or 3; where R5 and R6, R4 and R5 or R3 and R4 can form an inferior alkylene together, -O-inferior alkylene-O-, -O-inferior alkylene-, -inferior alkylene-O-, -C(R15)=C(R16)-O-, -O-C(R15)=C(R16)-, -C(R15)=C(R16)-C(R17)=C(R18)-; R3 and Y1 together can form -O-inferior alkylene-O- or -inferior alkylene-O-; R1 and Y1 together can form -inferior alkylene-O-; and Y1 and a branch on - X1-A together can form -O- or -O-inferior alkylene; R15-R18 stand for a hydrogen atom, under the condition that, 6-chloro-2,2-dimethyl-1-(1-methyl-4-piperidinyl)indan-1-ol is not included in the group of compounds). The invention also pertains to a derivative of cyclic amine or its salts with formula (II), to a derivative of cyclic amine or its salts with formula (III), to pharmaceutical composition, as well as their use.
EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on these compounds, with antagonist effect on NMDA receptors NMDA.
7 cl, 160 ex, 45 tbl
SUBSTANCE: method of enantiomeric obtaining aminoalcohols of formula I in which R1, R2 and n have values given in invention formula, lies in enantioselective hydration of aminoketones in presence of non-racemic catalyst, representing complex of transitive metal, which contains one or more metals and its salts, selected from group, including rhodium, iridium, ruthenium and palladium, in which transitive metal forms complex with chiral diphosphine ligand A.
EFFECT: improvement of synthesis of aminoalcohols, which are acceptable as precursors for obtaining anti-depressants.
11 cl, 6 ex
FIELD: medicine; pharmacology.
SUBSTANCE: invention refers to new compositions of general formula (I): where R1 and R2 mean H; R3 means H; R4 means lower alkyl; n is equal to 1-6; X means O; formula group =N-D (where D means H, lower alkyl); Y means ethylene group, ethynylene group, formula group -E-CH2 - (where E means carbonyl, formula group -CH(OH)-), C6-C10arylen C6-C10arylen group substituted with 1-3 substitutes, selected from Group (a) of substitutes; Z means single bond, C1-C10alkylen group or C1-C10alkylen group containing oxygen atom in specified carbon chain or on the end of specified carbon chain; R5 means H, C3-C10cycloalkyl group, C6-C10aryl, C6-C10aryl group substituted with 1-3 substitutes selected from Group (a) of substitutes; R6 and R7 are identical or different and represent each H, lower alkyl; Group (a) of substitutes represents group consisting of halogen, lower alkyl group, halogenated lower alkyl group, lower alkoxy group, lower alkylthio group; provided when R5 represents H, Z represents branched C1-C10alkylen group or C1-C10alkylen group containing oxygen atom in specified carbon chain or on the end of specified carbon chain, or it pharmacologically acceptable salt.
EFFECT: high immunosuppressive activity of compounds and their effective application for pharmaceutical compositions and for methods of preventive rheumatoid arthritis treatment.
51 cl, 13 tbl, 91 ex
SUBSTANCE: method involves extraction of green Siberian cedar wood with a hydrocarbon solvent (petroleum ether), followed by treatment of the extract with aqueous solutions of a weak inorganic base and a strong organic base to obtain salts of weak carboxylic acids, acidification of the solution of salts of weak carboxylic acids with mineral acid and extraction of weak acids with petroleum ether, followed by cooling down the extract in order to separate coloured and polar impurities from the lambertian acid concentrate. The lambertian acid is purified through crystallisation of diethylammonium salt, followed by acidification.
EFFECT: obtaining a product of better quality.
1 cl, 2 ex