Method for preparing conjugate of (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde and 20-hydroxyecdysone and using it as antioxidant agent inhibiting lipid peroxidation process. RU patent 2490267.
 Compounds applicable for neurodegenerative disorders / 2461562Present invention describes compounds applicable for treating or relieving a neurodegenerative disorder. There are also described methods of treating or relieving said disorders with said method involving the introduction a compound according to the present invention or a composition containing said compound in a patient. |
 Method of producing methyl-regrouped ecdysteroid 2,3:20,22-diacetonide-9α,13α -epoxy-14β -methyl-13-demethyl-14-desoxy-7,8-dihydro-20-hydroxyecdysone / 2443709Invention relates to a method of producing a novel compound, a derivative of diacetonide 20-hydroxyecdysone with a novel regrouped 18-methyl group. Described is a method of producing a C27-steroid with a regrouped methyl group via hydrogenation over a palladium catalyst (10% Pd/C) in a solution of an alcohol (preferably methanol) in the presence of an alcoholate of an alkali metal (preferably sodium methylate), diacetonide 9α, 14α-epoxy-14-desoxy-20-hydroxyecdysone or diacetonide 14α-hydroperoxy-20-hydroxyecdysone, or Δ8(14) - 14-desoxy-20-hydroxyecdysone, followed by treatment of the reaction mixture with ammonium chloride solution and extraction of the desired 2,3:20,22-diacetonide 9α, 13α-epoxy-14β-methyl-13-demethyl-14-desoxy-7,8-dihydro-20-hydroxyecdysone using known techniques with output of 60-65%. |
 Compounds, useful for treatment of neurodegenerative malfunctions / 2440367Invention also describes methods of treatment or reduction of such malfunctions severity, including introduction into patient's organism of compound according to claimed invention or composition, which contains it. |
 17β-hsd1 and sts inhibitors / 2412196Invention describes substituted derivatives of steroids which are selective inhibitors of type I 17β-hydroxysteroid dehydrogenase 17β-HSD1 and which can also be steroid sulphatase inhibitors, as well as salts thereof, pharmaceutical agents containing said compounds. The invention also describes use of said novel substituted derivatives of steroids for treatment, especially their use in treating or preventing steroid hormone dependent diseases or disorders, such as those for which inhibition of the 17β-HSD1 and/or STS is necessary and/or for which reduction of concentration of endogenic 17β-oestradiol is necessary. |
 Method of producing timosaponin bii / 2395518Invention describes a method of producing Timosaponin BII, which uses traditional Chinese medicinal agent Rhizoma Anemarrhenae or Anemarrhena asphodeloides Bge coronal root as raw material and involves extraction of Timosaponin BII using one or more processes selected from solvent extraction, polymer resin adsorption, polyamide chromatography, inverted phase column chromatography, column chromatography with Sephadex LH-20 etc, combined with the corresponding method of drying, e.g. low pressure drying, freeze drying, spray drying etc. |
 Uniformly tritiated triterpene glycosides of holothurians cucumaria / 2351606Invention refers to production of new tritiated analogues of physiologically active compounds - triterpene glycosides of holothurians Cucumaria of formula: . |
 Method for obtaining frondoside a and method of immune system stimulation for mammals / 2339644Extraction of dried cook water of sea cucumber Cucumaria frondosa or dried powder tissues of Cucumaria frondosa by chloroform and methanol mix is performed during boiling with reflux condenser to obtain organic extract; extract is evaporated, evaporated extract is re-dissolved in water, obtained colloid solution is decanted, ethylacetate is added to solution, water phase is decanted and undergoes chromatography in teflon or silica gel columns. Immune system activity of mammals, including lizosomic activity, phagocitosis and active oxygen form generation in macrophags of mammals, infected with bacterial cells, viruses and protozoa, is stimulated by oral, intraperitoneal or intramuscular or combined introduction of frondosite A dosage of 1 to 15 mcg/kg, preferably 10 mcg/kg. |
 Method of stereo-specific reduction of sapogenine-3 / 2326890Described method of stereo-specific production of 3(3-hydroxy-5β-H steroid sapogen or its derivatives by reduction of 3-keto,5β-H-steroid sapogenine with steric unfavoured organ-borane. 3β-Hydroxy,5β-H- steroid sapogenine or its derivative can be produced by reduction of 3-keto,5β-H- steroid sapogenine with relatively high steric unfavoured organ-borane reagent used as reducing agent, or by SN2 transformation of 3α-hydroxy,5β-H- steroid sapogenine or its derivative. Method represents easy way of steroid sapogenine production, such as sarsasapogenine, epysarsasapogenine, smylagenine, epysmylagenine andtheir esters using available or easy-made original substances (e.g., diosgenone, preferably of diosgenine). |
 Derivatives of 5b-sapogenin and pseudo sapogenin and application for dementia medical treatment / 2325396Invention discovers derivatives of 5β-sapogenin and pseudo sapogenin of general formula or , where in general formula I or II: R1 R2, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and R15 if available-H, independently R1 and R13-OH or R3-OH, =O or OR, where R - optionally substituted alkyl; lower acyl optinally substituted with carbamonyl or amino or lower alkoxycarbamonyl; lower alkoxycarbamonyl; R14 lower alkyl, optionally double bond with the exception of smylagenin and those compounds of formula I where simultaneously R1= R2= R4= R5= R6= R7= R8=R9= R10= R11= R12= R13=H, R3=β OH, R14=CH3, and methyl in C20 condition has α-orientation and C25 has S-configuration. |
 Derivatives of sapogenin, their synthesis, using and method based on their using / 2311423Invention discloses derivatives of steroid sapogenins of the general formula (I): wherein R means alkylcarbonyl, alkoxycarbonyl substituted possibly with amino-group and others under condition that R is not acetyl and R is not ethoxycarbonyl if C3 is in S and C25 in R-configurations simultaneously; R is nor succinyl if C3 and C25 are in S-configuration simultaneously, or C3 R(α) or S(β), and C25 in R-configuration. Also, invention discloses using these compounds in treatment of cognitive dysfunction, noncognitive neurodegeneration, noncognitive neuromuscular degeneration and loss of receptors in absence of cognitive, nervous and neuromuscular insufficiency. Also, invention discloses methods for synthesis of these compounds, treatment and pharmaceutical composition containing thereof. |
 Amide compound / 2479576Compounds exhibit antagonistic activity towards the EP4 receptor, which enables use thereof as an active ingredient in a pharmaceutical composition for treating chronic kidney disease or diabetic nephropathy. |
 Novel condensed pyrrole derivatives / 2434853Invention relates to compounds of formula (1) (lb) in which A denotes a benzene ring; Ar denotes naphthalenyl which optionally contains 1-3 substitutes independently selected from a group comprising C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, hydroxy group, C1-C6alkoxy group, halogen, heteroalkyl, heteroalkoxy group, nitro group, cyano group, amino- and mono- or di- C1-C6alkyl-substuted amino group; R1 denotes hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy group, carboxy group, heteroalkyl, hydroxy group optionally substituted with heterocyclylcarbonyl-C1-C6alkyl or R1 denotes N(R')(R")-C1-C6alkyl or N(R')(R")-carbonyl- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, heteroalkyl, phenyl-C1-C6alkyl; or R1 denotes R'-CO-N(R")-C1-C6alkyl, R'-O-CO-N(R")- C1-C6alkyl- or R'-SO2-N(R")- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cyclalkyl, C3-C7cycloalkyl- C1-C6alkyl or optionally substituted phenyl; R2, R2' and R2" independently denote hydrogen, halogen, cyano group, C1-C6alkyl, halogenated C1-C6alkyl or C1-C6alkoxy group; n equals 1; and pharmaceutically acceptable salts thereof. The invention also relates to use of compounds in any of claims 1-9, as well as to a pharmaceutical composition. |
 Synthesis of protease inhibitor precursor / 2421459Invention relates to a compound of formula (I) or stereoisomer thereof, or salt thereof, as well as synthesis method thereof and intermediate compounds of formulae (II) and (III) used in this method. |
 Dpp-iv inhibitor containing beta amino group, method for making thereof and pharmaceutical composition containing it for prevention and treatment of diabetes or obesity / 2419615Invention refers to a compound of formula |
 New antagonists nk1 and nk2 / 2419609There are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula |
 Method of nebivolol racemate obtainment / 2392277Invention refers to novel method of obtaining [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyrane-2-methanol] racemate of the formula (I) (nebivolol) and its pharmaceutically acceptable salts , involving stages indicated in the claim, and to intermediate compounds and methods of obtainment thereof. |
 Derivatives of benzo {b} {1, 4} dioxepin / 2350610New derivatives of benzo {b} {1, 4} dioxepin formulas (I) where B, X, Y, Z, R1 and R2 accept the value specified in the description of the invention, and also them pharmaceutically comprehensible salts. |
 Macrocyclic compounds, medicinal agents based on them and their use / 2347784Present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases. |
 New physiologically active substances / 2338741Invention pertains to new compounds with general formula (I) , and their salts used in pharmacology, and their hydra as well as others, where W represents or and R3, R7, R16, R17, R20, R21 and R21 are identical or different and each of them represents a hydrogen atom or assumes other values, given in the formula of invention. The invention also relates to pharmaceutical compositions and medicinal preparations based on these compounds, cultures, used for obtaining them, methods of inhibition and treatment and use. |
 General synthesis of myriaporones / 2328492Invention relates to the compounds with formula , where R, selected from H, SiR'3, SOR', SO2R', C(=O)R' or not necessarily substituted C1-C6alkyl; R' is selected from the C1-C6alkyl group; R" is selected from CH2OR, C1-C6alkyl, C1-C6halogenalkyl, C2-C6alkenyl or C1-C6alkylidene; substitutes are the alkoxigroup. The invention also relates to the compounds with the formula , , , , where R1, R2, R4 and R6 are selected from PMB, benzyl, 2,6-dimethylbenzyl, o-nitrobenzyl, 2,6-dichlorbenzyl, 3,4-dichlorbenzyl, TBS, TES, TBDPS, TIPS and TMS; R5 is selected from OR', N(R')2, N(R')(C1-C4alkoxi); and -R' is selected from C1-C6alkyl and C7-C10aralkyl, L is the stereospecific leaving group. The method for synthesis of the compound with formula 5 is invented, which includes removal of the protective groups from the precursor's hydroxyl groups. The methods for producing the compounds with the formulas 14 and 26 are invented, which include the precursor's tailing by interacting with CH3C(O)R5, where R5 is the group selected from OR', N(R')2, N(R')(C1-C4alkoxi); and R' is C1-C6alkyl and C7-C10aralkyl. The method for producing the compounds with the formulas 19 and 30 , which include the precursor's tailing by interacting with ethylmagnesiumbromide. The pharmaceutical composition based on the compound with the formula I with the cytotoxic activity is invented. |
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Method of dog's hepatosis therapy / 2490018 Invention refers to veterinary science, and may be used for dog's hepatosis therapy. The method for dog's hepatosis therapy involves using a hepatoprotector, a microelement and herbal tea; the hepatoprotector is presented by the preparation Ursosan containing 250 mg of ursodeoxycholic acid; the microelement is selenium, and herbal tea is aqueous-alcoholic extract of camomile blossom clusters and birch buds used sequentially orally: Ursosan 10 mg per 1 kg of animal's body weight, selenium 3 mg per 1 kg of animal's body weight, aqueous-alcoholic extract of camomile blossom clusters and birch buds 1 ml per 1 kg of animal's body weight for 30 days every 12 hours. |
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to organic chemistry and chemistry of natural products, more specifically to a method for preparing a new compound, a 20-hydroxyecdysone derivate conjugated with a short-chain vitamin E analogue, promising for medicine and pharmacology, namely to a method for preparing a 20-hydroxyecdysone conjugate by a reaction thereof with (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetaldehyde in ethyl acetate at room temperature in the absence of an acid catalyst (TsOH or phosphonomolybdic acid) for 24 h, debenzylation of the prepared intermediate conjugate in the ethanol solution in the presence of the catalyst Pd-C. The invention also refers to using such compound as an antioxidant agent inhibiting the lipid peroxidation process.
EFFECT: prepared hybride compounds appears to be promising in medicine and pharmacology as the new geroprotective antioxidants.
3 cl, 3 tbl, 3 ex
The invention refers to the organic chemistry and chemistry of natural compounds, specifically, method of production of new compounds derived 20- conjugated with analogue of vitamin E, perspective for medicine and pharmacology.
Ecdysteroids - molting hormones and insect metamorphosis - are widespread and varied class of steroid compounds in nature. Detection of hormones of insects in many plants, and in some kinds of 2-3% of the dry weight is allowed to allocate these connections to study their properties and chemical transformations [ A.A., Kovganko N.V. Ecdysteroids: chemistry and biological activity II Minsk: Science and technology, 1989, 327 S.].
It is established that ecdysteroids have a wide range of biological properties, representing practical interest for medicine, and belong to low-toxic compounds [Cheeses V.N., Z.A. effect of phytoecdysteroids and toxic lesions of the kidneys in the experiment // . and the wedge. ., 2001, №4, p.56-58; Cheese V.N., GA, Z.A. The impact of phytoecdysteroids and bemythyl on functional, metabolic and immunobiological characteristics of performance of the experiment. // . and the wedge. ., 2008, №5, pp. 40-43; GA, Cheese V.N., Z.A. Immunomodulating and stress-protective activity of phytoecdysteroids ecdysone and when stress in mice. // Chemical-pharmaceutical magazine, 2010, V.44, №1, p.9-11]. A number of modelling experiments shows that a 20- (the most common and affordable ) and its derivatives manifests expressed antioxidant properties comparable with and [Kuzmenko A.I., Morozova R.P., Nikolaenko I.A., Donchenko G.B. // Military-effect. log., 1999, №3, p.35; Volodin V.V., Shirshov T.I., S.A. Burtsev, Melnik M.V. // Rast. Resources., 1999, the so-35, №2, p.76; Kuzmenko A.I., Morozova R.P., Nikolaenko I.A., V. Donchenko // Ukr. biochem. log., 1999, .71, №2, p.69; N.P. Konovalova, I. Mitrokhin, L.M. Volkov, L.I. Sidorenko, I. Todorov. // Izv. An. Ser. Biol., 2002, №6, .650; Kuzmenko A.I., Morozova R.P., Nikolaenko I.A., V., Kholodova .. // Biochemistry, 1997, .62, №6, .712]. Describes how to use in practical medicine of the medicinal product, developed on the basis of 20- («ecdysten») as the drug of correction of the impaired metabolic processes in the human organism during the treatment of various diseases [Cheeses V.N., FOR., Komarin A.S. and other Experimentally-clinical evaluation of the effectiveness of the application of ekdistena for treatment of hepatitis // . and the wedge. ., 2004, №5, p.56-59; Cheese V.N. : biological effects in the body of the higher animals and prospects of use in medicine. // . and the wedge. ., 2008, №5, pp. 40-43].
Recently in medical chemistry best direction in the creation of medicines is conjugates by chemical combinations of molecules with specific properties. Received conjugates (hybrid molecules) are either to a synergistic effect or have an effect of prolonged action in the body, or severely affect the target organ.
Closest to the proposed invention is a method of molecular conjugation of vitamins C and analogue of vitamin E recognized natural antioxidants interaction of vicinal group of ascorbic acid and aldehyde function component (analogue of vitamin E) during the catalysis n-TsOH. The reaction was carried out in benzene by heating for 8 hours, and the output produced conjugate amounted to 55%. The resulting synthetic conjugate showed interesting properties. Possessing antioxidant activity commensurate with natural a-tocopherol or L-ascorbic acid, he is able to catch free radicals in both hydrophilic and tissues of the body, increasing the immune status [Manfredini S., Vertuani S., Manfredi B., Rossoni G., Calviello G., Palozza P Novel antioxidant agents deriving from molecular combinations of vitamins C and E analogues.// Biorganic and Medicinal Chem., 2000, 8, p.2791-2801].
Conjugates of ecdysteroids with analogues of vitamin E or other unknown. The objective of the invention was the way to get a new hybrid antioxidants on the basis of synthetic combination of natural - 20- and C 2-analogue α-tocopherol.
Solution of the problem has been achieved by the interaction of the 20- (1) with the stoichiometric number (6-hydroxy-2,5,7,8--2-yl)acetaldehyde (2) in ethyl acetate in the presence of a catalytic amount of steam- TsOH (10% by weight of ) at room temperature (about 20 C) within 24 hours. With the release of 62% is formed bis-conjugated adduct (3). If n-TsOH replace the other catalyst, for example, acid (FMK), the response time increases.
6- conjugate (3) smoothly flows in hydrogenizing in the solution of ethanol in the presence of a catalyst Pd-C and leads to a corresponding connection (4) with free phenolic groups.
Connections 3, 4 are new. Their structure is proved by NMR 1H and 13 C. For the connection of 4 was shot mass spectrum MALDI-TOF and registered ion [M+H] + . NMR 1H and 13C production of hybrid connections 3, 4 clear signals of all atoms of carbon and hydrogen and fragments of molecules.
The resulting conjugate with C 2-analogue of vitamin E 4 is promising for use as with adaptogenic and geroprotective drug for conditions associated with the activation of the processes of peroxide oxidation in the body.
The essence of the method is demonstrated by the following examples.
Example 1. 2,3:20,22-Bis-O-[2-(6-benzyloxy-2,5,7,8--2-yl)]-20- (3). To a solution of 0.20 g (0.42 mmol) connection 1 in 3 ml EtOAc solution 0.28 g (0.83 mmol) aldehyde 2 3 ml EtOAc and added 0.02 g TsOH, the reaction mixture was stirred for 24 hours at room temperature and . Balance in column (20 g SiO 2 eluent - CHCl 3 ). Got 0.29 g (62%) connections 3, R f 0.56 (CHCl 3-MeOH, 20:1), .. 128-130°C, [α] D 20 +20.7 degrees (with 2.03, CHCl 3 ). NMR spectrum 1 N (CDCl 3 ), coth ppm, J, Hz: 0.90 (3H, H 3 C 18 ), 1.00 (3H, N 3 19 ), 1.17 (3H, N 3 WITH 21 ), 1.27 (3H, H 3 C 26 ), 1.28 (3H, H 3 C 27 ), 1.37 (6N, CH 3-2' and CH 3-C 2" ), 2.11, 2.18 and 2.24 (18, 6 CH 3-Ar), 2.63 m (4H, H 2 C 4' and H 2 C 4" ), 3.62 m (1W, HC 22 ), 4.10 m (1W, HC 2 ), 4.14 m (1W, NA 3 ), 4.71 (4H, OCH 2 Ph), 5.18 .. (1H, NA 2"" , 1/2 w =13.0 Hz), 5.24 .. (1H, NA 2"' , 1/2 w =13.0 Hz), 5.85 with (1H, NS 7 ), 7.35-7.50 m (10H, N-Ar). NMR-spectrum of 13 (CDCl 3 ), coth ppm: 11.92, 12.01 and 12.89 (6 IU-Ar), 17.00 (18 ), 20.56 (19 ), 20.56 (4' 4" ), 21.50 (C 11 ), 23.04 (16 C ), 23.61 (21 C ), 24.80 (MeC 2' ), 24.97 (MeC 2" ), 26.68 (With 23 ), 29.47 (26 and 27 ), 30.86 (15 ), 30.94 (C 4 ), 31.74 (3' ), 31.85 (3" ) 34.00 (12 ), 34.71 (9 ), 37.82 (1 ), 38.40 (10 ), 41.41 (24 ), 45.53 (13 ), 47.36 (5 ), 49.74 (Since 1"' , 17 ), 50.83 (1"" ), 70.48 (With 25 ), 73.36 (2' 2" ), 74.75 (OCH 2 Ph), 76.75 (3 ), 77.07 (C 2 ), 83.55 (20 ), 83.85 (22 ), 84.86 (14 ), 101.41 and 101.63 (With 2"" ), 102.00 (With 2"' ), 117.41 (C 8a' ), 117.49 (C 8a" ), 121.43 (7 ), 123.04 (With 8' 8" ), 126.06 (7' 7" ), 127.74, 127.76 and 128.47 (Ph), 128.055 (5' , With 5" ), 137.97 (co 2), 147.48 (C 4a' ), 147.60 (C 4a ), 148.39 (6' 6" ), 163,23 (8 ), 202.62 (6 ).
Example 2. To a solution of 0.20 g (0.42 mmol) connection 1 in 3 ml EtOAc solution 0.28 g (0.83 mmol) aldehyde 2 3 ml EtOAc and added 0.02 g PMK, the reaction mixture was stirred 54 hours at room temperature and . Further processed as described in example 1. Got 0.29 g (61%) connections 3 identical obtained in example 1.
2,3:20,22-Bis-O-[2-(6-hydroxy-2,5,7,8--2-yl)]-20- (4). Through suspension 0.28 g (0.25 mmol) connections 3 and 0.07 g catalyst (10% Pd-C) in 5 ml abs. methanol missed hydrogen (control of the TLC, about 3 hours). The catalyst was filtered, filtrate . Balance column (15 g SiO 2 eluent - CHCl 3 ). Got 0.23 g (96%) connections 4, .. 130-134°[α] D 20 +24.5 degrees (with 1.82, CH 2 Cl 2 ). NMR spectrum 1 N (CDCl 3 ), coth ppm, J, Hz: 0.81 (3H, H 3 C 18 ), with 0.97 (3H, H 3 C 19 ), with 1.15 (3H, N 3 WITH 21 ), 1.26 (6N, N 3 26 N-3 of 27 ), 1.33 (3H, CH 3 2' ), 1.34 (3H, CH 3 2" ), 2.11, 2.16 and 2.18 (18, 6 CH 3-Ar)2.62 (4H, CH 2 4' and CH 2 4" ), 3.59 m (1W, WITH 22 ), 4.12 m (1W, HC 2 ), 4.46 m (1W, HC 3 ), 5.14 .. (1H, HC 2"" ), 5.21 .. (1H, HC 2"' ), 5.82 (1H, HC 7 ). NMR-spectrum of 13 (CDCl 3 ), coth ppm: 11.32, 11.85 and 12.26 (Me-Ar), 16.97 (18 ), 20.63 (19 ), 20.63 (4' 4" ), 21.46 (11 ), 23.00 (16 ), 23.53 (21 ), 24.37 (2 Months' ), 24.64 (2 Months" ), 26.65 (23 ), 29.43 (26 and 27 ), 30.82 (15 ), 30.92 (4 ), 31.65 (3' ), 31.95 (3" ) 33.16 (12 ), 34.69 (9 ), 37.80 (1 ), 38.37 (10 .), 41.38 (24 ), 45.42 (13 ), 47.33 (5 ), 49.71 (17 ), 50.90 (Since 1"' and 1"" ), 70.51 (25 ), 73.05 (2' ), 73.32 (2" ), 76.73 (3 ), 77.05 (2 ), 83.59 (20 ), 83.83 (22 ), 84.80 (14 ), 101.44 and 101.66 (1H, WITH 2"" ) 102.01 (1H, WITH 2"' ), 117.10 (C 8a' and C 8a" ), 118.71(C 5' and 5 C" ), 121.38 (With 8' 8" , 7 ), 122.64 (7' 7" ), 144.81 (C 4a' and C 4a ), 145.11 (6' ), 163.21 (8 ), 203.01 (6 ). MALDI-TOF MS: m/z 942.360 [M+H] + . Calculated for (57 C H 80 11 O +H) 942.248.
For (4) has been studied the influence on the processes of lipid peroxidation (LPO) in experiments in vitro on liver homogenate. In experiments t vivo in intact animals determined the extent of accumulation of malondialdehyde (MDA) in the liver enzymes of antioxidant system - catalase and superoxide dismutase. In animals with acute experimental hepatitis b liver homogenate determined the content of diene conjugates (NAM), malondialdehyde and reduced glutathione.
The biological activity of the drug (4) demonstrated by the following examples.
Example 1. Experiments were carried out in the in vitro system on liver normal animals (rats-males - 160-180 g). The processes of lipid peroxidation (LPO) activated by the addition of iron (II) (1·10 -4 M) and ascorbic acid (2·10 -4 M). One of the final Pol products - malonic dialdehyde (MDA) was determined in the reaction with acid.
Experiments have shown pronounced inhibitory effect connections 4 on the processes FLOOR, which is manifested in the suppression of the reactions of formation of MDA by 94.2%. The corresponding effect of vitamin E (used pharmaceutical preparation tocopherol in the final concentration of 1·10 -4 g/ml) and ecdysone was 83.3 and 27.8% respectively (see table 1).
Example 2. Male rats (160-180 g) orally for 7 days injected the compound 4 (5 mg/kg), (5 mg/kg) and vitamin E (50 mg/kg). The dose of previously identified as the most optimal). After the experiment, the animals were slaughtered (under light ether anesthesia). In the liver of animals was determined MDA [Steel I.D., this year Methods of determination of malondialdehyde using acid // Modern methods in biochemistry, Ed. by V.N. Orekhovich, M, 1977, p.66-68] and activity of antioxidant enzymes catalase and superoxide dismutase (SOD) on methods [Korolyuk M.A., L.I. Ivanov, Mayorova, ETC etc. Method for determining the activity of catalase // lab. case, 1988, №1, p.16-19] and [Dubinin E.E., Salnikova L.A., L. F. Efimova Activity and range of erythrocyte superoxide dismutase and human plasma // lab. case, 1983, №10, p.30-33].
The research showed that, as in vitro experiments, the introduction of connections 4 in the body of animals leads to inhibition of lipid peroxidation, as evidenced by the lowering of the liver MDA by 42% in comparison with the intact group. With the introduction of ecdysone and vitamin E content of MDA in the liver is reduced to only 17.9% to 30% (table 2). In case of introduction of a connection 4 also noted a more pronounced increase in the activity of enzymes that determine the state of the antioxidant protection of the organism (table 2).
Table 2
Comparative effect connections 4, ecdysone and vitamin E on some indices of antioxidant system, the level of MDA in the liver of rats (Pitch m, n=8).
Substance
Catalase, mmol/min/g protein
Effect,%
SOD, EUR/min/mg protein
Effect,%
HMM, nmol/mg protein
Effect,%
Vitamin E
16.8±0.74
+6.3
1.78±0.16
+12.6
0.562±0.028 1
-30
Connection 4
19.4±1.04 1
+22.07
2.10±0.20 1
+32.9
0.424±0.022 1,2,3
-42
17.11±0.98
+8.3
1.91±0.18
+20.9
0.600±1 0.030
-17,9
Control
15.8±0.98
-
1.58±0.12
-
0.731±0.04
-
Note. Designation reliability are the same as in table 1.
Example 3. Experiments were performed on rats-males weighing 180-200, Liver damage they caused by the introduction of SSC (for the 0.4 ml of 50% oil solution per 100 g body weight daily for 4 days) [Levshin B.I., Experimental pharmacotherapy selenium and toxic liver damage: Avtoref. dis. Dr. med. Sciences., Kharkov, 1973]. It is known that the CCl 4 is a strong prooxidants. Beginning with the 2nd day of the introduction of CCl 4 , orally to rats at a special probe is introduced inside (5 mg/kg), junction 4 (5 mg/kg) and vitamin E (50 mg/kg) dose picked as the most effective in the preliminary experiments).
After 3 days after the re-introduction of drugs animals (2 hours after the last injection) rats scored (under light ether anesthesia). Severity of the processes of lipid peroxidation (LPO) was judged on the content of diene conjugates (DC), malonic dialdehyde (MDA) and reduced glutathione in the liver homogenate. The content of diene conjugates and reduced glutathione was determined by the method of [Steel I.D. The method of determining the process of diene conjugation of unsaturated higher fatty acids // Modern methods in biochemistry, Ed. by V.N. Orekhovich, M, 1977, p.63-64] and [Smirnov V.V. Glutathione - dependent antioxidant system of the brain with craniocerebral injury // Dis. kand. honey. Sciences., St. Petersburg, 1995, 153 C.]. The experiments showed that the introduction of rats CCl 4 led to a sharp activation FLOOR, as evidenced by increase in DK, MDA (164.8-69.7%) and a decrease of restored glutathione (51.4%) in liver. Connection 4 and in these experiments showed expressed an antioxidant effect, significantly more superior to the action of ecdysone and vitamin E. Under the influence of connection 4 contents DK and the MDA in the liver of rats with CCl 4 - hepatitis was lower by 53.5 and 36.9% and 23.1 7.1% (p>0.05) higher than in intact animals. lowered the content of the CD and MDA only 29.5 and 20.9%. Vitamin E had also expressed effect, but in this case, the contents of the CD and MDA decreased only by 41.5 and 26.8%. Connection 4 showed also expressed effect. And in this case, the connection 4 acted more pronounced than actually and vitamin E (table 3).
Thus, the connection of 4 has a strong antioxidant effect, that opens up the prospect of its use in a number of diseases, based on activation of lipid peroxidation processes.
Table 3
Antioxidant activity of connections 4 in comparison with and vitamin E lesion of the liver of rats CCl 4 (Pitch m, n=8).
Experiment conditions
DK, mmol/g
Effect,%
HMM, nmol/mg protein
Effect,%
Glutathione SH, mkmol/mg
Effect,%
In intact animals
0.182±0.012
0.700±0.032
8.76±0.32
Control (CCl 4 - hepatitis)
0.482±0.036 1
1.188±0.094 1
4.26±0.22 1
CCl 4 + drug (4)
0.224±0.014 1,2
-53.5
0.750±0.034 2
-36.9
8.24±0.30 2
+93.4
CCl 4 +
0.340±0.020 1,2,3
-29.5
0.940±0.052 1,2,3
-20.9
6,94±0.32 1,2,3
+62-9
CCl 4 + vitamin E
0.282±0.018 1,2,3
-41.5
0.870±0.038 1,2,3
-26.8
6.30±0.24 1,2,3
+47.8
Note. 1 - significantly compared to control animals, 2 - relative to the control, 3 - on a group of animals treated with the background of the CCl 4 connection 4 (p>0.05).
In the result of the performed testing connection 4 showed higher antioxidant activity compared with vitamin E and 20- ().
1. The method of obtaining conjugate (6-hydroxy-2,5,7,8--2-yl)acetaldehyde with 20-, wherein the 20- interacts with the stoichiometric quantity of 6-hydroxy-2,5,7,8--2-yl) in ethyl acetate in the presence of acid catalyst at a temperature ~20 C for 24 h, with a subsequent received intermediate conjugate solution in ethanol in the presence of a catalyst Pd-C.
2. The method according to claim 1, characterized in that in the capacity of an acid catalyst used pair- (TsOH) or acid (FMF) in the amount of 10% by weight .
3. The conjugate (6-hydroxy-2,5,7,8--2-yl)acetaldehyde with 20- as an antioxidant, inhibiting lipid peroxidation.