5(6)-nitro-1-(thietanyl-3)-2-ethoxybenzimidazole, inhibiting peroxidation of lipids
SUBSTANCE: invention relates to field of organic chemistry, namely to novel compound - 5(6)-nitro-1-(thietanyl-3)-2-ethoxybenzimidazole, inhibiting peroxidation of lipids.
EFFECT: novel compound, possessing useful biological properties, has been obtained.
2 cl, 1 dwg, 2 ex
The present invention relates to organic chemistry and medicine, namely to a new connection - 5(6)-nitro-1-(titanyl-3)-2-ethoxybenzothiazole, inhibitory lipid peroxidation (LPO).
As the agents involved in the inhibition of PAUL, known drugs such as vitamin E (α-tocopherol), vitamin C (ascorbic acid), β-carotene, the enzyme superoxide dismutase, as well as BHT (2,6-di-tert-butyl-4-METHYLPHENOL) and Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) [the State register of medicines. Vol. 1, Wiley, 2004, pp. 103, 123, 142, 203, 290].
As a prototype and comparison drug taken Dibazol: 2-(Phenylmethyl)-1H-benzimidazol, as the closest analogue of the chemical structure used in medical practice [Register of medicines [Electronic resource]. - Access mode: http://www.reles.ru/cat/drugs/Bendazol/. Reference date: 07.05.2014].
The object of the invention is to expand the Arsenal of biologically active substances, including having the property to inhibit the FLOOR.
The technical result - obtaining biologically active substances, inhibitory FLOOR.
Summary of the invention 5(6)-nitro-1-(titanyl-3)-2-ethoxy-benzimidazole of formula (I):
inhibits lipid peroxidation.
This compound and its properties are described in the literature.
Approx�R 1. The synthesis of the claimed compounds
Synthesis of 5(6)-Nitro-1-(titanyl-3)-2-ethoxybenzothiazole carried out by the method [Kataev, V. A., Khaliullin, A. N., Spirihin L. V., Gailunas I. A. Synthesis and isomerism of the products of the interaction 5(6)-nitro-2-chlorobenzimidazole with epimyocardium (article) //Russian Journal of organic chemistry 2002. - T. 38. - No. 10 - p. 1560-1562]. In 50 ml of anhydrous ethanol was dissolved 0.28 g (12 mmol) of metallic sodium. To the resulting solution was added 2.70 g (10 mmol) of 5(6)-nitro-1-(titanyl-3)-2-chlorobenzimidazole, boil for 5 hours. After cooling to 5-10°C, the solution was filtered, the filtrate neutralized with dilute acetic acid to pH 6-7 and evaporated. The rest is filled with water, the precipitate was filtered off, purified by crystallization from aqueous ethanol (1:1).
Yield 53%, Rf0,45. T a MP 182-184°C.
Found, % : 49,9 (C), And 4.2 (H), And 15.7 (N).
Calculated, %: 49,8 (C), And 4.2 (H) Of 15.8 (N).
Assessment of the lower level FLOOR
The effect of the claimed compounds and product comparison on the processes of free radical oxidation (fro) in model systems in vitro was studied using a rapid method for determination of antioxidant activity, based on the detection of chemiluminescence (CHL) - the glow arising from the interaction of free radicals [Farkhutdinov R. R. research Methods chemiluminescence of biological material on chemilumi�the ETP CL-003. / R. R. Farkhutdinov, S. I. Tevdoradze // Methods for evaluation of antioxidant activity of biologically active substances of therapeutic and prophylactic purposes: Sat. Dokl. scientific. practical. of the seminar. M., 2005. - S. 147-154.].
Registration of luminescence was carried out on the device HL-003 (Russia). CL model systems were characterized by spontaneous glow, fast flash, and then a slow-paced flash. The most informative characteristics of CL were the sum of the luminescence is determined by the radiation intensity, and amplitude maximum luminescence.
To assess the impact on the processes of SRO in vivo studies were carried out on model systems in which the flow of the reaction FLOOR.
The influence of the studied compounds on PAUL studied in the chicken yolk lipids, similar in composition to the blood lipids. Lipids were obtained by homogenization of chicken yolk in phosphate buffer in the ratio 1:5 and then diluted 20-fold, were selected by Adding 10 ml. in 1 ml of 50 mm solution of Fe2+led to the initiation of the oxidation of unsaturated fatty acids, which was accompanied by chemiluminescence. The illumination intensity was judged on the process FLOOR.
Drugs were added to the model system at concentrations corresponding to therapeutic dose prescribed drugs - Dibazol. As control was used a model system, in �which is the test preparations were added to 0.9% saline in the same volume.
The invention is illustrated in the figure, which shows the effect of the claimed compounds and Dibazol on the SRO processes in the model system of lipid peroxidation, where To control, I - the claimed compound II - product comparison Dibazol.
In the model system of liposomes tested compound inhibited the spontaneous level of illumination, reduced flash and the CL light sum (figure). Thus, the antioxidant activity of compound (I) induced when the FLOOR is higher than the reference drug - Dibazol.
1. 5(6)-nitro-1-(titanyl-3)-2-ethoxybenzylidene formula:
2. A substance according to claim 1, inhibiting lipid peroxidation.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to novel compounds of general formula (I) or their pharmaceutically acceptable salts, which possess properties of RNA-polymerase inhibitor, in particular HCV inhibitor. Such disease can be hepatitis C. In formula (I)
is selected from the group, including simple carbon-carbon bond and double carbon-carbon bond; R1 represents hydrogen atom; R2 represents hydrogen atom; R3 represents hydrogen atom; R4 is selected from the group, including
R5 is selected from the group, including hydrogen atom, C1-C6alkyl and C1-C6alkyloxy; R6 is selected from the group, including hydrogen atom, C1-C6alkyl and C1-C6alkyloxy; R7 is selected from the group, including hydrogen atom, phenyl, 5-membered heterocycle, carbocycle with 2 condensed cycles, where 5-membered heterocycle contains at least 1 heteroatom, selected from the group, consisting of N, O and S, and where phenyl, heterocycle and carbocycle with 2 condensed cycles are optionally substituted with at least one of RJ and RK.
EFFECT: compounds can be used for treatment of disease, which can be treated by HCV inhibition.
21 cl, 2 tbl, 7 ex
SUBSTANCE: invention relates to a method of producing pyrazoline carboxamidine derivatives of formula . Said compounds are known as powerful 5-HT6 antagonists. The disclosed method comprises reacting a corresponding substituted 4,5-dihydro-(1H)-pyrazole or an isomer thereof with isothiocyanate R6-N=C=S to obtain an amide of substituted 4,5-dihydro-(1H)-pyrazole-1-carbothioic acid or tautomeric substituted 4,5-dihydro-(1H)-pyrazole-1-carboxymidothioic acid . The obtained intermediate compounds are reacted with a corresponding alkylating agent to obtain an intermediate S-alkylated compound . Said intermediate compound is reacted with a sulphonamide derivative R7SO2NH2 and the target compound of formula (I) is separated from the reaction mixture. The invention also relates to novel intermediate products (IIIa), (IIIb) and (IV). Symbols given in the formulae have values given in the description.
EFFECT: providing an alternative method which improves atom efficiency of synthesis of desired compounds with higher output compared to existing methods for synthesis of said compounds.
8 cl, 1 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to organic chemistry, namely to compounds of formula (I), wherein R1 and R2 independently represent C6-C10 aryl optionally substituted by -OH, halogen, -OC1-C3 alkyl, -NO2, -CF3 or C1-C3 alkyl, or 5- or 6-merous heteroaryl containing one heteroatom specified in N, S and O; A and M independently represent a methylene group or a single bond; an adjacent aromatic cycle is attached directly to an amide group; the group Y=Z represents together and irregularly oxygen atom (-O-), cis-vinylidene group (-CH=CH-), iminogroup (-N=CH- or -CH=N-) or methylene group with sp2-hybridised carbon atom (=CH-); X irregularly represents methine group (=CH-), cis-vinylidene group (-CH=CH-) or carbon atom (=N-), and W represents hydroxyl group (-OH), C1-C6 alkyl optionally substituted by -SH, 5- or 6-merous heteroaryl containing 1 to 2 nitrogen heteroatoms, or C6-C10 aryl, optionally substituted by -SH, -NH2, and their pharmaceutically acceptable salts.
EFFECT: described are the methods for preparing the compounds, using as a drug for treating cancer and the based pharmaceutical composition.
14 cl, 6 tbl, 49 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.
EFFECT: there are prepared new quinolin-4-one derivatives effective in treating neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases caused by mitochondrial dysfunction.
18 cl, 1 tbl, 257 ex
SUBSTANCE: invention relates to organic chemistry, namely to mixture of E- and Z-isomers of (4-bromophenyl)ethylidene hydrazide of 2-[6-methyl-1-(thiethan-3-yl)uracyl-3-yl]acetic acid in molar ratio 3.5:1 of general formula: .
EFFECT: obtained is novel mixture of isomers, demonstrating hypotensive activity.
2 cl, 4 tbl, 4 ex
SUBSTANCE: invention relates to 2-bromo-1-(thietanyl-3)imidazole-4,5-dicarboxylic acid derivatives of formula Ia, b where R is COOK (Ia) or (Ib)
EFFECT: obtaining novel heterocyclic compounds having antidepressant activity.
4 cl, 1 tbl, 5 ex
SUBSTANCE: invention relates to a novel 6-methyl-1-(1-oxothietan-3-yl)uracil in the form of a mixture of cis- and trans-isomers in molar ratio of 10:1.
EFFECT: compound exhibits hypotensive activity and corresponds to said formula.
2 cl, 2 tbl, 4 ex
SUBSTANCE: invention relates to a method of obtaining chiral heterocyclic ligands based on 1,2-diaminocyclohexane, which contain heterocyclic fragments: thienyl-2-, thienyl-3-, furyl-2-, 5-methylfuryl-2-, (2,2'-bithiophen)-5-yl-, 5-(4'-methylcyclohex-1'-en-1'-yl)thiophene-2-, which can be included into a structure of complexes for carrying out enantioselective reactions and asymmetric catalysis, as well as possess luminescence properties. The method is realised due to the application of available reagents, application of an acceptable molar ratio of reagents, considerable reduction of the total time of the reaction, the reduction of production costs is achieved due to the simplification of the reactor scheme and the time of the reaction carrying out.
EFFECT: simplification of the technological process.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to compounds of formulas I, II, III, IV, V, VIII or to their pharmaceutically acceptable salts, wherein: Z represents , or phenyl; D represents or ; X represents N(R9), O, S, S(=O) or S(O)2; each Y independently represents O or S; G represents or ; the other radical values are described in the patent claim. The invention also refers to pharmaceutical compositions based on the above compounds.
EFFECT: there are prepared new compounds and based compositions which can find application for treating malaria or eliminating or inhibiting the growth of Plasmodium species.
30 cl, 3 tbl, 23 ex
SUBSTANCE: method includes synthesis of o-phenylenediamine (o-PDA) dihydrochloride first by dissolving o-PDA in hydrochloric acid solution, filtering the obtained solution and vacuum evaporation to a dry residue which is dried at 105-110°C; mixing the dry o-PDA dihydrochloride with urea, heating the obtained mixture on a paraffin bath to 150°C, cooling the obtained melt, grinding and dissolving in a warm diluted sodium hydroxide solution, filtering, adding hydrochloric acid to the filtrate until neutralisation, filtering out the precipitated benzimidazolone-2, purifying by recrystallising from ethanol; adding phosphorus oxychloride to the benzimidazol-2one, adding concentrated hydrochloric acid, heating at 145-150°C for 4 hours, stirring after cooling the mixture and pouring on ice, filtering out the reaction mixture, neutralising the filtrate with 10 ammonia solution to pH 7-8, filtering the 2-chlorobenzimidazole precipitate, drying at 60°C, recrystallising from a mixture of ethanol and water in ratio of 1:1; synthesis of 2-chloromethylthiirane by mixing epichlorohydrin and ethanol, cooling to 0°C, adding ground thiourea, mixing for 60 minutes at 0-5°C, slowly raising temperature to 20°C for 60 minutes and stirring at said temperature for 3 hours, filtering, pouring the filtrate in three portions into a separating funnel containing 3 litres of water, collecting the organic layer, washing with water, filtering, drying the filtrate, adding anhydrous calcium chloride, filtering and vacuum distillation. Further, the method includes synthesis of 1-(thietanyl-3)-2-chlorobenzimidazole by adding 2-chlorobenzimidazole to aqueous potassium hydroxide solution, heating to 70°C and adding 2-chloromethylthiirane, stirring the reaction mixture at said temperature until achieving pH≤7, filtering out the filtrate, washing with diethyl ether, 10% potassium hydroxide solution, water, drying, purifying by crystallisation from a mixture of ethanol and water in ratio of 1:1, separating the organic and aqueous layers, adding hydrochloric acid solution to the aqueous solution to pH 5-6, filtering out the precipitate, washing with water and drying. Further, 2-[1-(1,1-dioxothietanyl-3)benzimidazolyl-2-thio]acetic acid is obtained using thioglycolic acid solution and potassium hydroxide solution in distilled water, boiling for 30 minutes, cooling to room temperature, filtering the solution, acidifying the filtrate with hydrochloric acid to pH 3-4, filtering out the precipitate, washing with water and drying. The end product is obtained by adding potassium hydroxide to a solution of 2-[1-(1,1-dioxothietanyl-3)benzimidazolyl-2-thio]acetic acid in ethanol, boiling the mixture for 45 minutes, cooling, filtering out the filtrate and drying.
EFFECT: novel method of producing a compound, which increases the output of the end product while reducing the time and cost of production.
SUBSTANCE: invention represents a mixture of two structural isomers: 2,6-di(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-4-methylphenol and its diastereomers, and 2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)-6-(2,2,1-trimethylbicyclo[2.2.1]hept-5-yl)-4-methylphenol, and their diastereomers with the ratio of the first and second structural isomer isomers from 60:40 wt % to 95:5 wt %.
EFFECT: extension of the arsenal of means, possessing simultaneously haemorheological, anti-aggregate, anti-thrombogenic, retinoprotecting, endothelium-protecting, neuroprotecting, anti-arrhythmia and anti-ischemic activity, enhancing the cerebral blood flow.
4 dwg, 20 tbl, 6 ex
SUBSTANCE: what is presented is using Histochrom (same as echinochrome A or pentahydroxyethyl naphthoquinone) as an agent able to prevent pulmonary fibrosis developed under cytostatic agents. The invention can be used for the pharmacological prevention and correction of the pulmonary tissue disorders caused by administering the cytostatic agents.
EFFECT: preventing hypertrophy of interalveolar connective tissue in the lungs associated with administering bleomycin.
4 dwg, 1 tbl
SUBSTANCE: drops possessing antiviral and immunomodulatory effects characterised by the fact that they represent a 95% ethanol infusion of wild strawberry leaves and fruit specified in: red raspberry fruit, mountain ash fruit, bilberry fruit, blood-red hawthorn fruit, cinnamon rose fruit; 15-25 mg of the substance in 1 ml of the infusion.
EFFECT: drops possess pronounced antiviral and immunomodulatory effects.
15 tbl, 5 ex
SUBSTANCE: melanin having water-solubility of at least 80% and an paramagnetic centre concentration of at least 8·1017 spin/g is administered orally into the animals having been exposed to the radiation in a dose high enough to cause a spinal radiation injury; melanin is administered after dissolved in distilled water in the effective concentration. Melanin water is used as drinking water for the mice having been exposed to single and fractionated acute radiation, which is able to cause acute radiation disease. Melanin water is taken from the 1st to 30th day following the single radiation, or from the 1st day of the fractionated radiation to the 30th day on completion of the radiation.
EFFECT: higher survival rate, faster recovered haemopoiesis, body weight and orientation and motion activity.
7 tbl, 5 ex
SUBSTANCE: invention provides a composition having antioxidant properties in the form of a tablet, comprising an active agent based on nicotinamide adenine dinucleotide in reduced form (NADH) and inert filling agents, characterised by that the active ingredient is a complex which is a mixture of 10 wt % NADH with 63 wt % vegetable fats, 17 wt % beeswax and 10 wt % chlorophyll, and the inert filling agents are in the form of microcrystalline cellulose, Macrogol 6000, intense sweetener and a food flavourant.
EFFECT: invention provides a new tablet form of NADH.
SUBSTANCE: invention refers to a pharmaceutical composition with anti-ischemic and antioxidant activity in the form of tablets or capsules, and a method for preparing it. The composition contains 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid in an amount of 40 to 80 wt %, an amino-containing compound and pharmaceutically acceptable excipients. The amino-containing compound is specified in a group of trometamol, methyl glucamine and L-lysine; 1 mole of 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid is accounted for 0.05 to 0.25 mole of the above amino-containing compound. The composition also contains lactose, microcrystalline cellulose, calcium stearate and other pharmaceutically acceptable excipients. According to the method for preparing the composition, taking 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid and amino-containing compound in molar ratio 1:0.05 to 1:0.25, pre-mixing, moisturising with a aqueous or alcohol solution of a binding agent, adding pharmaceutically acceptable excipients in such an amount to provide the content of 4-((3-oxo-3-ethoxypropanoyl)amino)benzoic acid from 40 to 80 wt %, granulating the mixture, drying and producing tablets or capsules according to the known technique.
EFFECT: implementing the above application.
6 cl, 7 tbl, 4 ex
SUBSTANCE: claimed is the application of 5(6)-nitro-1-(1,1-dioxothietanyl-3)-2-chlorobenzimidazole of formula (I) , earlier known as the means with broncholytic and spasmolytic activity, as the means, inhibiting peroxide oxidation of lipids.
EFFECT: realisation of the claimed purpose.
SUBSTANCE: claimed is the application of 5(6)-nitro-2-chloro-benzimidazole of formula (I) as the preparation, inhibiting peroxide oxidation of lipids.
EFFECT: achievement of the claimed purpose, activity of the said formula compound is higher than of the comparison medication dibazole.
SUBSTANCE: method for preparing an agent possessing anti-inflammatory, diuretic and antioxidant activity, involving milling Spiraea salicifolia shoots representing a mixture of leaves, blossom and shoots, extracting them three times by gradual maceration, mixing in infusing, filtering, condensing, separating, drying in the certain environment.
EFFECT: agent shoes the pronounced anti-inflammatory, diuretic and antioxidant activity.
2 dwg, 12 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and can be used as a hepatotrophic, lipotropic agent in gastroenterology, as well as for treating cardiac and cerebral atherosclerosis, in neurology in the lower extremity artery diseases (endarteritis). The agent contains tabletted powders of diisopropylammonium dichloroacetate, microcrystalline cellulose, lactose and excipients presented by Aerosil, Primogel and calcium stearyl fumarate.
EFFECT: agent possesses no toxicity, has the high adsorption properties, the apparent anti-inflammatory action, and provides metabolism and the liver regeneration.
3 tbl, 2 ex
SUBSTANCE: albendazole is added in small portions to the suspension of sodium alginate in hexane in the presence of the preparation E472c while stirring, carbon tetrachloride is poured, the resulting suspension is filtered and dried at room temperature.
EFFECT: simplifying the process of production of the said capsules, the reduction of losses, and increase in the yield by weight.