Connections of substituted triazolbronic acid

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): , wherein the residues R1, R1' and R1ʺ independently represent hydrogen, alkoxy, halogen or -CF3 group. The residue R2 it represents C1-7alkyl or phenyl, or a pharmaceutically acceptable salt thereof. Also pharmaceutical composition, using the compounds of formula I, and method of treatment are provided.

EFFECT: compounds of formula I are inhibitors immunoproteasomal subunit LMP7, and may be useful in the treatment of inflammatory diseases and disorders such as rheumatoid arthritis, lupus and irritable bowel syndrome.

13 cl, 1 tbl, 5 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing compounds of formula where R1a and R1b are selected from H and F and one of R1a and R1b is F, Het is tetrazolyl, optionally substituted with methyl, R2 is selected from benzyl and C1-C6 alkyl, optionally substituted with a halogen or C1-C4 alkyloxy. The present method includes combining compounds and where X is selected from Cl, Br, I and trifluoromethanesulphonate, Y is selected from BF3 and BR3R4, R3 and R4 are selected from OH, C1-C6monoalcohols and C1-C6diatomic alcohols, or where R3 and R4 together with B, to which they are attached, form a cyclic boronate optionally substituted with methyl.

EFFECT: obtaining oxazolidinones.

22 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing carbonyl derivatives of 5,10,15,20-tetraphenylporphyrin of formula I where R is o-carborane or m-carborane, which are obtained by reacting mercaptocarborane with 5,10,15,20-tetra(n-trifluoromethanesulphonylmethyloxyphenyl)porphyrin in palladium catalysis conditions while boiling in anhydrous toluene while stirring in an atmosphere of an inert gas at room temperature. The method includes successively adding diisopropylethylamine (DIPEA), the corresponding mercaptocarborane, 1,1'-bis(diphenyl-phosphino)ferrocene (dppf) and tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), followed by boiling the reaction mixture in an Ar atmosphere for a few hours, separating the finished products using know techniques; 5,10,15,20-tetra(n-trifluoromethanesulphonylmethyloxyphenyl)porphyrin is obtained by reacting 5,10,15,20-tetrahydroxyporphyrin with a trifluoromethanesulphonic acid anhydride in a medium of methylene chloride in an atmosphere of an inert gas.

EFFECT: obtaining novel carbonyl derivatives of 5,10,15,20-tetraphenylporphyrin, which can be used as anti-tumour agents in boron neutron capture therapy and photodynamic therapy of cancerous diseases.

1 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula: or its pharmaceutically acceptable salts. Values of radicals are as follows: Ra represents member, selected from CN, C(O)NR1R2, C(O)OR3; R1 and R2 represent H, R3 represents H or unsaturated C1-C10 alkyl; X represents member, selected from N, CH and CRb, Rb represents member, selected from halogen, substituted or non-substituted C1-C10 alkyl, C(O)OR4, OR4, NR4R5, where R4 and R5represent members, independently selected from H, substituted or non-substituted C1-C10 alkyl, substituted or non-substituted C1-C10 heteroalkyl, containing at least 1 heteroatom, where heteroatom represents O or N, and heteroatom can take any internal position in heteroalkyl group or take the position, through which alkyl group is bound to the remaining part of molecule, non-substituted C3-C10 cycloalkyl, pyridyl, substituted with CN group, or independently represents ; and , where alkyl and heteroalkyl substituents are independently selected from the group, including: -R', =O, -CO2R', -OR', -OC(O)R', -NR"C(O)R', -NR'R", -CONR'R", pyridyl, halogen, , 4-methylpiperazinyl, 4-methylpiperidinyl, in quantity from 0 to 3; and where R' and R" are independently selected from the group, including hydrogen, non-substituted phenyl, non-substituted C1-C10 alkyl, C1-C10 alkoxy, on condition that R4 and R5, together with atoms to which they are bound, are optionally combined with formation of 4-8-membered non-substituted heterocycloalkyl ring, containing 1-2 heteroatoms, selected from N and O. Also claimed are pharmaceutical compositions, method of treating state, mediated by phosphodiesterase (FDE), a method of FDE inhibition.

EFFECT: invention makes it possible to obtain compounds, capable of inhibiting phosphodiesterase.

134 cl, 141 dwg, 2 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: claimed is a method of obtaining oligoborosilazanes by the interaction of oligosilazanes, which do not contain alkyl radicals at a nitrogen atom, with an aminoborane complex, which does not contain alkyl radicals at a nitrogen atom, with the ratio of silazane to a boron-containing modifier from 3 to 18, with carrying out the process at a temperature of 40-140°C in a mixture of toluene with diglyme or benzene with diethyl ether with the molar ratio from 1:1 to 1:33.

EFFECT: method makes it possible to obtain oligoborosilazanes with the given molecular weight with high output, which is reached due to the step-by-step thermal processing of the reaction mixture at an increased temperature.

2 cl, 4 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to porous crystalline materials. A porous crystalline material having a tetrahedral framework comprising the general structure M1-IM-M2, wherein M1 comprises a metal having the first valency, M2 comprises a metal having the second valency different from the first valency, and IM is imidazolate or a substituted imidazolate linking moiety. One or more of the following conditions is met: M1 comprises a monovalent metal, and M2 comprises a trivalent metal; M1 is Li+; and M2 is B3+. Also claimed is a gas adsorption method, a method of separating gas from a fluid stream containing the gas.

EFFECT: adsorbents with an improved gas uptake on a gravimetric basis.

28 cl, 3 dwg, 8 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining hydrochloride of tertbutyl ester of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid (I). Method includes reduction of tertbutyl ester of (4-fluoro-3-pyridin-4-yl-benzyl) carbamic acid under conditions of reducing hedrogenisation and then HCl processing with output of hydrochloride of tertbutyl esther of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid. Also claimed are methods of obtaining intermediate products, namely 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid and tertbutyl ester of (4-fluoro-3-pyridin-4-yl)benzyl-carbamic acid.

EFFECT: invention makes it possible to considerably simplify obtaining hydrochloride of tertbutyl esther of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid.

30 cl, 1 ex

FIELD: biotechnologies.

SUBSTANCE: invention relates to a method of obtaining of unsubstituted alkyl ammonium and alkyl guanidine 7,8(7,9)-dodeca hydro dicarbo nido undecaborates. The method comprises interaction of unsubstituted o(m)-carboranes with alkylamines and alkyl guanidines in the medium of the lower aliphatic alcohols. Meanwhile the process is performed at combined effect of catalyser and ultrasonic activisation at the temperature 60-80°C in the medium of the lowest aliphatic alcohols or respective water and alcohol mixes. The catalysers are fluorides of alkali metals, ammonium fluorides of or ammonium tetraalkyl fluorides.

EFFECT: invention allows to simplify the named compounds and to increase their yield.

6 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining monohalogenderivatives of 1,2-, 1,7-, 1,12-dicarba-closo-dodecarboranes(12). Method includes interaction of o(m,p)-carboranes with halogenating agents. As the latter used are N-halogenimides (amides): N-halogen-succinimides, 1,3-dihalogen-5,5-dimethylhydantoins, trihalogen-isocyanuric acids, N-halogen-arylsulfonamides and their sodium salts, N-halogenphthalimides, where halogen = Cl, Br, I; aryl = phenyl, p-tolyl, in the medium of acidic organic solvent. As solvent applied are monobasic liquid organic acids of aliphatic series R-COOH, where R=H, CnH2n+1, CnF2n+1, n=1-3. The process is carried out with application of ultrasound activation at temperature 60-80°C for 3-5 hours.

EFFECT: invention makes it possible to reduce energy consumption.

15 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining of monohalogen-derivatives of 1,2-,1,7-,1,12-dicarba-closo-dodecaboranes(12). Method includes interaction of o(m,p)carboranes with halogenating agents; as halogenating agents used are N-halogenimides (amides): N-halogen-succinimides, 1,3-dihalogen-5,5-dimethylhydantoins, trihalo-isocyanuric acids, N-halogenaryl-sulfonamides and their sodium salts, N-halogenphthalimides, where halogen= Cl, Br, I; aryl = phenyl, p-tolyl, in medium of acidic organic solvent. As solvent applied are liquid organic monobasic acids of aliphatic series R-COOH, where R=H, CnH2n+1, CnF2n+1, n=1-3. the process is carried out with application of ultrasound activation in presence of catalyst, as catalyst used are strong acids: sulfuric (H2SO4), methanesulfonic (CH3SO2OH) and trifluoromethanesulfonic (CF3SO2OH) in amount 0.1-1.0 mol %. The process is carried out at temperature 20-50°C for 2-4 hours.

EFFECT: invention makes it possible to reduce energy consumption.

15 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining pyridinates of 1-fluoro(chloro)-3-alkyl(aryl)borolanes of general formula (1), where R=Bu, X=F (a); R=Hex, X=F (b); R=Hex, X=Cl (c); R=Bn, X=Cl (d). The method includes the interaction of unsaturated compounds, selected from the group of hex-1-ene, oct-1-ene or allylbenzene, with triethylaluminium (AlEt3) in the presence of a catalyst (Cp2ZrCl2) in a ratio of 10:12:0.5 in hexane in an atmosphere of inert gas with mixing for 7 h, addition of boron trifluoride etherate (BF3·Et2O) or boron chloride (BCl3) and pyridine in a double with respect to AlEt3 amount, following mixing at room temperature for 30-60 min.

EFFECT: obtained compounds can be applied as components of catalytic systems in processes of oligo- and polymerisation of olefin, diene and acetylene hydrocarbons, as well as in fine organic and organometallic synthesis.

1 ex

FIELD: veterinary medicine.

SUBSTANCE: treatment is carried out with an aqueous solution of the preparation "Biopag-D" at a concentration of 4-2% by drifting animals through the baths with the solution having the immersion depth up to the carpal joint.

EFFECT: invention enables to treat efficiently and stress-free and prevent treatment of diseases of hooves and dew claws of animals.

3 cl, 5 dwg, 4 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: stimulating the excised liver regeneration is ensured by a 70% hepatectomy into a laboratory animal on the second day of the experiment. A liver regeneration stimulator is presented by L-norvaline administered intragastrically in a daily dose of 10.0 mg/kg every 46 hours for the first 7 days of the experiment.

EFFECT: method provides the effective stimulation of the excised liver regeneration evidenced by reducing the animals' lethality, improved hepatic microcirculation, reduced manifestation of cytolysis and enhanced synthetic function of the liver.

2 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapeutic dentistry, and can be used for the local treatment of chronic gingivitis caused by tobacco smoking in young individuals. That is ensured by a preparatory procedure of luminal-dependent chemiluminescence of the oral fluid aiming at a maximum burst and a glow light sum. If the maximum burst falls within the range of 3.3 to 18.15 standard units, whereas the glow light sum ranges from 8.2 to 40 standard units, an antioxidant therapy is conducted by using a transverse gingival mucosa electrophoresis on 5% aqueous propolis by means of jaw electrodes in a tray at a current intensity of 0.5-1 mA and an exposure of 8-10 minutes. A polarity is alternated with a positive pole to be taken the first. The therapeutic course makes 4 procedures every second day. Colgate Propolis Toothpase and Mouthwash are used additionally during 30 days. If the maximum burst is from 0.8 to 1.24 standard units, whereas the glow light sum ranges from 3.34 to 7.5 standard units, a pro-oxidant therapy is required by using an exposure to magnetic infrared laser (MIL) light covering a projection of gums and generated by Optodan laser with a periodontal attachment The exposure parameters: 2-2,000 Hz in segments, 2 minutes per each segment, no more than 12 minutes per 1 procedure. The therapeutic course makes 4 procedures every second day. Parodontax Toothpase and Mouthwash are used additionally during 12 days.

EFFECT: method simplifies and reduces the length of the treatment in the given category of patients.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to oxazolopyramidine compounds of formula I, where A represents O; R1 is selected from phenyl or pyrimidine, which are optionally substituted with R11; R2 represents phenyl, which is optionally substituted wby 1-3 ring carbon atoms with similar or different substituents R22, R11 represents halogen; R22 is selected from hydroxy group, (C1-C4)-alkyl, which is optionallysubstituted with 1-3 atoms of fluorine, (C1-C4)-alkyloxy, (C1-C4)-alkyl-S(O)m-; m equals 2. Invention also relates to pharmaceutical composition, which contains formula I compounds, and to method of obtaining formula I compounds.

EFFECT: formula I compounds, intended for activation of EDG-1 receptor and applied for wound healing.

15 cl, 2 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to oxazolopyramidine compounds of formula (I), where A represents O; X represents (C1-C6)-alkanediyl or (C1-C6)-alkanediyloxy, where oxygen atom of (C1-C6)-alkanediyloxy is bound to group R2; Y represents pyrrolidinyl; R1 represents (C1-C4)-alkyl; R2 represents phenylene, optionally substituted by one or two carbon atoms in ring with similar or different substituent R22; R3 is selected from group, which consists of cycloalkyl-CuH2u-, where u equals 1; radical of saturated 3-10-member monocyclic ring, phenyl or pyridyl, where ring radical is optionally substituted by one or two carbon atoms of ring with substituent R31; R4 represents hydrogen; R22 represents (C1-C4)-alkyl; R31 is selected from group, which consists of halogen and (C1-C4)-alkyl. Invention also relates to (S)-l-[2-(2,6-dimethyl-4-{5-[methyl-(3,3,3-trifluoropropyl)amino]-7-propoxyoxazolo[5,4-d]pyrimidine-2-yl}phenoxy)acetyl]pyrrolidine-2-carboxylic acid, pharmaceutical composition and to method of obtaining compounds of formula (I) .

EFFECT: compounds of formula (I), intended for activation of EDG-1 receptor and applied for wound healing.

16 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to veterinary and can be applied in animal-breeding for stimulation of metabolic processes, and growth activity of calves. Medication for stimulation of metabolic processes and growth activity of calves includes succinic acid as energetic stimulator, with application of citric acid as activator of succinic acid, beetroot molasses as carbon component, and methionine and sodium chloride as stimulators of digestion system.

EFFECT: application of invention makes it possible to ensure expressed acceleration of growth energy in early postnatal period.

3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: cytoflavin is administered into laboratory animals (rats) daily immediately before overheating in an air laboratory thermostat at +40±1-2°C for 45 minutes. The preparation is administered intraperitoneally in a dose of 100 mg/kg of body weight for 14 days.

EFFECT: higher body adaptability by increasing antioxidant activity and reducing a rate of lipid peroxidation products accumulation with underlying thermal exposure.

4 tbl

FIELD: medicine.

SUBSTANCE: minor amputation of the foot with the further necrectomy is performed. After the application of an antimicrobial bandage and drainage, the wound is hermetised from the environment by the creation of a negative pressure above the wound in a combination with drug treatment. The reatment is performed in two steps. At the first step the wound with the antimicrobial bandage and drainage is first hermetised from above with an adhesive film, with the creation and support of the negative pressure not lower than 80 mm Hg. Urokinase 500000 U is additionally introduced daily intravenously by drop infusion per 100 ml of physiological solution, Vessel-Due-F in a dose of 600 LU per 100 ml of physiological solution and VAP 20 - alprostadil in a dose of 40 mcg per 100 ml of physiological solution. In addition Antistax in capsules is introduced to the patient. At the second stage active 24-hour vacuum aspiration with the change of the negative pressure from 10 to 80 mm Hg within a day is carried out. Additionally introduced is Vessel-Due-F in a dose of 1 capsule with 250 LU 2 times per day between meals and Antistax. At the first and second stages Antistax is introduced in a dose of 2 capsules in the morning 30-40 minutes before meal, daily. Duration of each stage constitutes not less than 7 days.

EFFECT: increase of the treatment efficiency due to the complete and timely purification of the wound from pathological exudates, elimination of the progression of the purulent-necrotic process, increase of the regenerative activity of tissues, activation of local immunity, recovery of microcirculation and oxygenation of the affected tissues.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves professional oral hygiene is carried out consisting in ultrasonic removal of supra- and subgingival dental deposits and polishing of supragingival teeth. Bite splinting and recovery of dentition integrity may be required. After dissecting a mucoperiosteal flap according to the known technique, an incision area is sanitated by means of a photodynamic therapy (PDT). The PDT is conducted with the use of a diode laser at wave length 660±5 nm and emitting power 0.5-1.0 Wt. The photosensitiser "Photoditasin" in the form of 0.5% gel is introduced by means of a cannula into dental gaps, under the dissected segments of the flap and onto the mucosal tissue for 5 minutes. The photosensitiser is washed out, and the gingival pockets are repeatedly exposed to laser light for 2-3 min in the same environment. Sterile osteoplastic material is introduced into bone defects, and the flap is sutured together.

EFFECT: effective cleansing of the surgical area, eliminating the periodontal inflammation, stimulating tissue osteogenesis and regeneration, stabilising the processes of bone tissue absorption of alveolar interdental septa and preserving the tissues.

2 cl, 1 ex

FIELD: medicine.

SUBSTANCE: to correct pathologic changes in the condition of viable offspring under a cytostatic impact the medication glutoxim is introduced to female rats in a dose of 50 mcg/kg 5 days before and 5 days after the introduction of the cytostatic medication vepesid. The latter is introduced once intravenously in a maximal tolerable dose, equal to 30 mg/kg. It has been established that glutoxim can be applied as means for the correction of pathologic changes in the viable offspring of rats, obtained from coupling 3 months after the cytostatic impact.

EFFECT: application of glutoxim as the means of corrective therapy makes it possible to increase efficiency and reduce its side effects.

6 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to biotechnology and provides a α1,6-glucan-containing compound of Helicobacter pylori. The present invention also discloses a conjugate for inducing immune response against H.pylori, which contains said compound conjugated with a carrier protein. The present invention also discloses an immunogenic composition, use of said composition and a method of inducing immune response against H.pylori using said composition. The present invention also discloses immune serum for neutralising H.pylori in mammals, which is obtained by immunising said mammal with an immunogenic composition containing said immunogenic composition. The present invention discloses an antibody which recognises said α1,6-glucan-containing compound of H.pylori, use of said antibody and a method of inducing complement-mediated bacteriolysis of H.pylori strains which express α1,6-glucan using said antibody.

EFFECT: invention improves the effectiveness of immunogenic compositions against Hpylori.

27 cl, 8 dwg, 21 tbl, 11 ex

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