3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-triftoratsetatov) indole-3-ylmethyl]-n-(2-methylphenylsulfonyl)benzamide or its pharmaceutically acceptable salt as antagonists of leukotriene and intermediates for their production

 

(57) Abstract:

Usage: in medicine as leukotriene antagonists the invention: product - h 3-methoxy-4-{methyl-5-(2-methyl - 4,4.4-triftoratsetatov)indole-3-ylmethyl-M-(2-methylphenylsulfonyl)benzamide f-PI I: SN AXIS CF-CH-CH(CH,)NHC(0; o BF SN F N Oga yield 57%, CCI 147-149°C. Z-Methoxy-4-N-methyl-5- (2-methyl-4,4,4-triftoratsetatov)indole-3-illip the benzoic kislota-ly ll fH3 fi NT X And CF3-CH2-CH(CH3)NHC(0: OORn R is H or easy removable protective group, yield 88%, 2-Methyl-4.4,4-triptorelin hydrochloride CF-CH-CH(CH JNH-HCI. BF C5HiiCtF3N IHAD 79%1 sh 45 2255 °C Reagent 1: substance f-crystals II, where R - N. Reagent 2 connection CFT-PI lit ,, 22 reaction Conditions in the presence of a dehydrating reagent-dicyclohexylcarbodiimide. in Federal organic solvent 3 and 3 AP.f-crystals :(0)-NHSO-K . ve §

 

Same patents:

FIELD: medicine.

SUBSTANCE: it is suggested to apply tris-(2-hydroxyethyl)ammonium salt of 1-benzylindolyl-3-thioacetic acid earlier known as a stabilizer of cell membrane as preparation to treat autoimmune diseases. The property of the above-mentioned salt to inhibit T-dependent activation of B-lymphocytes, under conditions of decreased medullary function and body leukopenia should enable to develop new pharmacological preparation for treating autoimmune diseases, such as, for example, systemic lupus, rheumatoid polyarthritis, transplant's detachment at transplanting either organs or bony marrow.

EFFECT: higher efficiency of application.

4 ex, 3 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of indol-3-yl of the formula (I):

wherein each A and B represents independently of one another oxygen atom (O), NH, CONH, NHCO or a direct bond; X means (C1-C2)-alkylene or a direct bond; R1 means hydrogen atom (H); R2 means hydrogen atom (H); R3 means NHR6, -NR6-C(=NR6)-NHR6, -C(=NR6)-NHR6, -NR6-C(=NR9)-NHR6, -C(=NR9)-NHR6 or Het1; each R4 and R5 represents independently of one another hydrogen atom (H); R7 means -(CH2)o-Ar, Het, OR6; R6 means hydrogen atom (H); R7 means (C1-C10)-alkyl, (C3-C10)-cycloalkyl; R8 means Hal, NO2 (nitro-group), CN (cyano-group), Z, -(CH2)o-Ar, COOR1, OR1, CF3, OCF3, NHR1; R9 means CN or NO2; Z means (C1-C6)-alkyl; Ar means aryl that can represent unsubstituted, monosubstituted, or polysubstituted R8; Hal means F, Cl, Br, J; Het means saturated, partially or completely saturated monocyclic or bicyclic heterocyclic radical comprising from 5 to 10 ring members wherein 1 or 2 nitrogen atom (N) and/or 1 or two sulfur atom (S) present, and heterocyclic radical can be monosubstituted with phenyl; Het1 means saturated, partially or completely unsaturated monocyclic or bicyclic heterocyclic radical comprising from 5 to 10 ring members and from 1 to 4 nitrogen atoms (N) that can be unsubstituted or monosubstituted NHX, or oxo-group; n = 0, 1 or 2; m = 0, 1, 2, 3, 4, 5 or 6; o means 0, 1 or 2; and their physiologically acceptable salts and solvates. Compounds of the formula (I) elicit intergin-inhibitory effect that allows their using as components of pharmaceutical composition. Also, invention describes intermediate compounds.

EFFECT: valuable medicinal properties of compounds.

11 cl, 4 sch, 1 tbl, 34 ex

FIELD: medicine, arthrology, pharmacy.

SUBSTANCE: agent comprises glucosamine salt as saccharide, dimethylsulfoxide, ointment base and ibuprofen or nimesulide, or piroxicam, or meloxicam, or diclofenac salt, or indometacin, or ketoprofen as a nonsteroid anti-inflammatory agent. Glucosamine hydrochloride, glucosamine sulfate sodium, potassium or calcium salt is used as glucosamine, and diclofenac potassium or sodium salt is used as diclofenac salt. New ointment shows high perfusion rate of active substances to the articulation zone and enhanced effectiveness. Invention expands assortment of agents used in treatment of articulations.

EFFECT: improved, enhanced and valuable medicinal properties of agent.

2 cl, 14 ex

FIELD: medicine, arthrology, pharmacy.

SUBSTANCE: invention relates to agents of topical applying used in treatment of articulation diseases. Proposed agent comprises mixture of chondroitin sulfate and glucosamine salts as a saccharide, the compound taken among the group nonsteroid anti-inflammatory agents, in particular, ibuprofen or nimesulid, or piroxicam, or meloxicam, or diclofenac salt, or indometacin, or ketoprofen, dimethylsulfoxide and an ointment base taken in the definite ratio of components. Invention provides enhancing effectiveness due to the content a mixture of low-molecular and high-molecular saccharides in it that results to increasing diffusion rate of active component to the articulation zone and also the compound taken among the group of nonsteroid anti-inflammatory agents. The combined using these agents provides the curative synergetic effect.

EFFECT: improved and valuable medicinal properties of agent.

2 cl, 14 ex

FIELD: chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to manufacturing solid medicinal formulations of preparations. Invention proposes a medicinal formulation consisting of a core comprising the following components: indometacin, lactose, calcium phosphate, hydroxypropylcellulose, magnesium stearate, sodium croscarmellose and envelope comprising collicute MAE 100P, propylene glycol, pigment titanium dioxide, talc, collidon-30, brown sycovite-70. Also, invention discloses a method for preparing the formulation. Invention provides enhancing stability of envelope to effect of stomach juice, rapid and complete release of active substance, simultaneous simplifying the process of applying the envelope for a single step.

EFFECT: improved and valuable pharmaceutical properties of formulation.

3 cl, 1 tbl

FIELD: medicine, neurooncology.

SUBSTANCE: one should carry out chemotherapy and irradiation till radical dosage. Moreover, 2-3 d before the onset of radiation therapy and during the whole course of irradiation one should indicate the intake of indometacin at daily dosage being 300 mg, and 8-14 d before the end of therapy course or the stage of radiation therapy it is necessary to conduct chemotherapeutic cycle with vincristine at total dosage being 4 mG and lomustine at total dosage 160-240 mg. At performing a split course of irradiation the intake of indometacin should be indicated between the stages. The innovation enables to increase radio sensitivity of malignant tumor, suppress angiogenesis, proliferative activity and increased cytotoxic activity of chemopreparations.

EFFECT: higher efficiency of therapy.

1 cl, 3 ex

FIELD: medicine.

SUBSTANCE: method involves intragastrically introducing indometacin to rats at a dose of 4.5-5 mg/kg of mass after holding the animals without food and water during 5 days.

EFFECT: enhanced effectiveness of bleeding and perforating ulcer formation.

2 tbl

FIELD: medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to composition possessing an anti-inflammatory effect and useful for oral administration in form of emulsion preliminary concentrate. Composition comprises NO-releasing nonsteroid anti-inflammatory drug, surface-active substance, oil or semisolid fat and forms in situ emulsion of type oil-in-water after contact with aqueous medium, such as gastroenteric fluid. Also, invention relates to a medicinal formulation based on thereof, oral emulsion, set based on thereof and a method for treatment of inflammation and pain. Proposed compositions possess the improved availability.

EFFECT: improved and valuable properties of composition.

40 cl, 1 tbl, 20 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new amide derivatives of carboxylic acid that are antagonists of NMDA receptors of the formula (I): , wherein one radical among R1, R2, R3 and R4 represents -OH or NH2-group and others are hydrogen atoms; or two adjacent groups R1, R2, R3 and R4 in this case in common with one or more similar or different additional heteroatoms and -CH= and/or -CH2-groups form 5-6-membvered homo- or heterocyclic ring but preferably pyrrole, pyrazole, imidazole, oxazole, oxooxazolidine or 3-oxo-1,4-oxazine ring; two other groups among R1, R2, R3 and R4 radicals represent hydrogen atoms; R5 and R6 in common with nitrogen atom between them form saturated or unsaturated 4-6-membered heterocyclic ring that is substituted with phenoxy-, phenyl-[(C1-C4)-alkoxy]-, phenoxy-[(C1-C4)-alkyl]-, benzoyl-group optionally substituted in aromatic ring with one or more halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; X and Y mean independently oxygen, nitrogen atom or group -CH=, and to their salts formed with acids and bases. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical compositions showing activity as selective antagonists of NR2B receptor based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of the following diseases: chronic neurodegenerative diseases, chronic painful states, bacterial and viral infections.

EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.

11 cl, 2 tbl, 27 ex

FIELD: pharmaceutical technology, pharmacy.

SUBSTANCE: method involves addition sugar-alcohol and/or saccharide showing melting point by 5°C lower or above as compared with the first mentioned sugar-alcohol and/or saccharide to sugar-alcohol and/or saccharide followed by combined treatment of prepared powder by pressing and heating. Invention allows preparing medicinal compositions decomposing in mouth cavity rapidly being without water and showing light using owing to the presence of sufficient strength in preparing, transport in usual using. Method involves mixing, pressing and heating components that represent two or more sugar-alcohol and/or saccharide and active component wherein difference between melting points of one among two or more indicated sugar-alcohol and/or saccharide that shows the higher content and any remaining indicated two or more sugar-alcohol and/or saccharide is 5°C or above. Invention provides preparing strength rapidly soluble tablets.

EFFECT: improved preparing method, improved pharmaceutical properties of composition.

30 cl, 12 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing engine fuel, more specifically to a catalyst process of producing diesel fuel with improved temperature characteristics from crude oil. A method is described for preparing a catalyst for producing diesel fuel from natural raw material based on crystalline silico aluminophosphates with zeolite-like structure of the SAPO-31 type by preparing an aqeous reaction mixture which contains an aluminium source, phosphoric acid and a silicon source, as well as an organic structure forming compound, and with total composition expressed in molar ratios: R/Al2O3=0.5-2.0, P2O5/Al2O3=0.8-1.2, SiO2/Al2O3=0.05-1.5, H2O/Al2O3=15-200, where: R is an organic structure forming compound, which is a separate di-n-butylamine or a mixture of di-n-butylamine with di-n-propylamine, taken in molar ratio of 1:2, with subsequent crystallisation of the prepared mixture in hydrothermal conditions, necessary for formation of zeolite-like crystals with SAPO-31 structure, filtration, washing, drying, calcination and further introduction of a modifying group VIII metal. Also described is a method of producing diesel fuel from natural raw material at high temperature and hydrogen pressure in the presence of a catalyst, where the process is carried out in a single step and the catalyst used is crystalline silico aluminiumphosphate with a zeolite-like SAPO-31 structure, modified by a group VIII metal, obtained using the above described method.

EFFECT: high catalyst activity during hydrogenation of unsaturated hydrocarbons and ether bonds, as well as in decarbonation reactions and isomerisation formed paraffins with normal structure with high selectivity towards isomer products and with reduced formation of heavy compounds and cracking starting material; process of producing diesel fuel is carried out in a single step.

5 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to catalysts, specifically to a catalyst for synthesis of 1-(dimethylamino)-3-alkyl-2-propines. The invention describes a method for synthesis of 1-(dimethylamino)-3-alkyl-2-propines through aminomethylation of 1-alkynes using bisamine (N,N,N1,N1-tetramethylmethanediamine) in an argon atmosphere in the presence of a catalyst in form of 6-hydrous samaric nitrate Sm(NO3)2*6H2O.

EFFECT: said catalyst does not form explosive acetylides during aminomethylation of 1-alkynes in the presence of bisamine.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: described is a catalyst for producing diesel fuel from natural raw material based on crystalline silico aluminophosphate with a zeolite-like structure of the SAPO-31 type, which is modified with a group VIII metal, where degree of dispersion of the group VIII metal in the catalyst composition is higher than 14%. The catalyst is prepared by saturating the starting calcined material, crystalline silico aluminophosphate with a zeolite-like structure of the SAPO-31 type with a solution of a platinum and/or palladium compound such that the amount of metal in the end product is not more than 10.0 wt %, followed by drying and oxidative treatment at temperature not higher than 500°C, while raising temperature in the furnace at a rate not higher than 20°C. The process of producing diesel fuel takes place at temperature not higher than 400°C, pressure not higher than 10 MPa, mass rate of feeding the raw material not higher than 10 h-1, volume ratio of hydrogen to material not higher than 5000, in the presence of the disclosed catalyst in a single step.

EFFECT: high stability of the action of the catalyst for single-step hydrotreatment of natural raw material.

6 cl, 1 tbl, 8 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to compounds of formula I ,

where R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30), and R(31) are disclosed in claims. Compound of present invention are particularly useful as new antiarrythmia bioactive substances, in particular for treatment and prophylaxis of atrial arrhythmia (e.g., atrial fibrillation or auricular flutter).

EFFECT: higher efficiency.

13 cl, 18 ex, 1 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to (R)-enantiomers of 2-arylpropionamides of the formula (Ia): and their pharmaceutically acceptable salts wherein Aryl represents phenyl group substituted with a group chosen from isopropyl, acetyl, (2'',6''-dichlorophenyl)amino-group, α-hydroxyisopropyl, (R,S)-α-hydroxybenzyl and its individual R-isomers, (R,S)-(α-methylbenzyl) and its individual R-isomer and (R,S)-α-hydroxy-α-methylbenzyl and its individual R-isomer; R represents hydrogen atom (H) or (C1-C4)-alkyl; R' represents the following groups: -amino acid residue consisting of linear or branched (C1-C6)-alkyl substituted with carboxy-group -CO2H; -residue of the formula: -CH2-CH2X-(CH2-CH2O)nR wherein R has abovementioned values; n means a whole number from 0 to 1 while X represents oxygen atom; -heteroaryl chosen from the group consisting of 2-pyrimidinyl or 4-pyrimidinyl. Also, invention proposes a pharmaceutical composition inhibiting of interleukin-8-induced chemotaxis of neutrophiles and comprising as an active components (R)-enantiomers of 2-arylpropionamides of the formula (I) and their pharmaceutically acceptable salts in mixture with a suitable carrier. Also, invention proposes a method for preparing compounds of the formula (Ia). Also, invention proposes (R)-enantiomers of 2-arylpropionic acids of the formula (Va) given in the invention description and their pharmaceutically acceptable salts. Proposed (R)-2-arylpropionamides are useful in prophylaxis and treatment of tissue damage caused by enhanced accumulation of polymorphonuclear neutrophiles in the inflammation sites.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

13 cl, 6 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: method of detecting a compound which is a noncompetitive inhibitor of human immunodeficiency virus (HIV) protease (SEQ ID No:1) involves detection using alanine scanning methods and molecular docking of the compound at least with one atom of an amino acid residue selected from a group consisting of Asn98, Phe99, Asp29, Asp30, Arg8, Gly49, Gly51 and Gly52 SEQ ID NO:1, at a distance of not more than 5 Å.

EFFECT: increased effectiveness of the compounds.

4 cl, 2 dwg, 4 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of (R)-2-arylpropionamides of general formula I, in which Ar is phenyl group, substituted in 3(meta) position by group R1, selected from: linear or branched C1-C8-alkanoyl, C3-C6- cycloalkanoyl, heteroarylcarbonyl, C1-C6-alkylaminocarbonyl, arylaminocarbonyl, C1-C6-alkylamino, C1-C6-acylamino, arylamino, benzoylamino, aryloxy, heteroaryl, C1-C6-alkoxycarbonyl, C6-aryloxycarbonyl, C1-C8-alkansulfonyl, arylsulfonyl, or 3,4-dihydro-1H-quinolyl-2-on; R is selected from: -H, OH; - heteroaryl group is selected from: pyridine, pyrimidine, pyrrole, thiophene, furan, indole, thiazole, oxazole; - α or β carboxyl residue can consist of straight or branched C1-C6-alkyl, C3-C6-cycloalkyl, optionally substituted with other carboxyl (COOH) group; - residue with formula SO2Rd, in which Rd is C1-C6-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl or pyridyl, on condition that compounds of formula I are not the following compounds: (R)-2-(3-phenoxyphenyl)-propanoyl-phenylglycine; (R)-2-( phenoxyphenyl)-propanoyl-glycine; (R)-2-[(3'-acetyl)phenyl]-R-4''-pyrimidyl)propionamide. Invention also relates to method of obtaining formulaI compound and application of formula I compound for preparation of medications for treatment of diseases including C5a induced hemotaxis of human PMNs.

EFFECT: obtained are novel derivatives of (R)-2-arylpropionamide, possessing useful biological properties.

9 cl, 3 dwg, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining secondary amides. Method is realised by carbonylation of respective tertiary amines by means of carbon monoxide in presence of catalyst, containing less than 750 parts per million (ppm) of palladium, and halogen-containing promoter.

EFFECT: increased catalytic activity of catalyst with reduction of palladium concentration and increase of reaction selectivity.

39 cl, 7 tbl

FIELD: food industry.

SUBSTANCE: present invention relates to food industry, namely to using the compound of formula (I)

in the form of one of its stereoisomers or a mixture of the latter, where n is an integer from 0 to 2, dotted line denotes a single or double carbon-carbon bond. Each separately taken from R1-R4 is a hydrogen atom or denotes R5 or OR5 group. R5 is C1-C5 alkyl group. Optionally, one of the groups R1-R4 is -OH group, and/or R1 and R2, taken together, and/or R3 and R4, combined, represent OCH2O group provided that the said groups, combined, are adjacent substitutes of phenyl group, as an ingredient, imparting, reinforcing, improving or modifying taste of kokumi or umami flavored product. Invention relates to a compound of formula

where R3 denotes a hydrogen atom or C1-3-alkyl group, a R4 denotes C1-3-alkyl group or OR6 group, where R6 is C1-C-3-alkyl group. Invention relates to flavor-modificative composition which contains an ingredient imparting or modifying taste, at least one compound of formula (II), at least one ingredient selected from a group consisting of carrier aroma and flavoring base, and, optionally, at least one aromatic adjuvant.

EFFECT: invention relates to flavored product containing at least one compound of formula (II) and a food base.

13 cl, 21 tbl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a new compound of the general formula (2) and a method for its preparing wherein R1 represents hydrogen atom or salt-forming metal; R2 represent a direct or branched (C1-C7)-halogenalkyl group; m represents a whole number from 2 to 14; n represents a whole number from 2 to 7; A represents a group taken among the following formulae: (3) , (4) ,

(5) ,

(6) ,

(17) , (18) , (19) , (20) , (23) , (25) and (26) wherein R3 in formula (6) represents a direct or branched group (C1-C5)-alkyl group; R8 in formulae (18) and (20) represents a direct or branched (C1-C5)-alkyl group, a direct or branched (C2-C5)-alkenyl group or a direct or branched (C2-C5)-alkynyl group; in formula (23) each R21, R22, R23 and R24 represents independently hydrogen atom, a direct or branched (C1-C5)-alkyl group, a direct or branched (C1-C7)-halogenalkyl group, halogen atom or acyl group; in formulae (25) and (26) X represents halogen atom; or enantiomers of compound, or hydrates, or pharmaceutically acceptable salts of compound, or its enantiomers. Also, invention relates to a pharmaceutical composition containing indicated compound as an active component and to a therapeutic agent used against breast cancer based on thereof.

EFFECT: valuable medicinal properties of compounds.

10 cl, 2 tbl, 39 ex

Up!