Derivatives of 3-(6`-methoxypropanol-3`)-2-acetylfuran-2 - carboxylic acid, which has anti-allergic activity
(57) Abstract:Use in medicine to create a drug that has anti-allergic activity. The inventive product: derivatives of 3-( 6-methoxypropanol - 3 ) -2-acetylfuran-2-carboxylic acid, namely ethyl ester of 3-(6 - methoxypropanol-3) -2-acetylfuran-2-carboxylic acid. C17H16O6. So pl. 206°C and about-anized 3-(6 - methoxypropanol-3) -2-acetylfuran-2 - carboxylic acid. C22H19NO6. So pl. 263°C. Inhibit the reaction of passive cutaneous anaphylaxis 32.2 52.9 per cent of Reagent 1: 6-methoxypropan-3-aldehyde. Reagent 2: acetoacetic ester or o-anisidin acetoacetic acid. The process conditions in the environment of pyridine under heating. table 1. The invention relates to chemical-pharmaceutical industry, namely to new biologically active substances on the basis of which can be created drugs that have anti-allergic activity.The claimed compounds are new derivative chromone, namely Amida and esters of 3-(chromosol-3l)-2-acetylfuran-2-carboxylic acid formula
< / BR>where I R OS2H5< / BR>II R=-
The claimed compounds, their properties and biological aktivnost are drug sodium cromoglycate (Intal) disodium salt of 1,3-bis-(2-carboxyphenyl-5-oxy)-2-oxoprop, having antiallergic activity 
< / BR>The purpose of the invention to provide new derivatives of chromone with more pronounced in comparison with the prototype of the INTA, antiallergic activity.The goal has been achieved by the synthesis of compounds of the formula
< / BR>where I R COC2H5< / BR>II R is obtained by condensation of 6-methoxypropan-3-aldehyde with ethyl ether or o-methylaniline acetoacetic acid.P R I m e R 1. Ethyl ester of 3-(6l-methoxypropanol-3l)-2-acetylfuran-2-Carbo - new acid.To a solution 2,04 g 6-methoxypropan-3-aldehyde in 15 ml of dry pyridine are added dropwise of 1.26 ml (0.01 mol) of fresh acetoacetic ester. The mixture is heated on a water bath at a temperature of 60aboutC for 2.5 h, then cooled and poured into ice water, acidified with hydrochloric acid. The precipitate is filtered off and, after recrystallization from toluene obtain 2.15 g of white crystalline powder. Exit 68% of theoretical. So pl. 206aboutC.Found, 64,12; N 4,82;
Calculated With 64,56; N 5,06; 30,38.The IR-spectrum, liquid paraffin, 1740, 1700, 1635 (cm-1).P R I m m e R 2. o-Anisidin 3-(6lIDA and 1,91 g o anisidine acetoacetic acid are dissolved in 20 ml of dry pyridine and heated on water bath for 4 hours After cooling, the reaction mixture is poured into ice water, acidified with hydrochloric acid, the precipitated precipitate is filtered off. After recrystallization from isopropyl alcohol get 2,75 g yellow powder. The yield was 73% of theoretical. So pl. 263aboutC.Found, 69,62; H 5,15; N A 3.87
Calculated With 70,03; N 5,04; N 3,71.The IR-spectrum, liquid paraffin, 3300, 1700, 1675, 1645 (cm-1)
Research anti-allergic effects of the substances was carried out on the model reaction of passive cutaneous anaphylaxis (Russian perfumery-cosmetic Association), mediated by antibodies of class IgE  which is one of the most frequently used methods for the evaluation of anti-allergic activity of the compounds.Serum containing specific homotaurine antibodies, received the third week after sensitization of mice CBA with ovalbumin (0.5 μg) with aluminum hydroxide (2.5 mg/mouse). The resulting serum at a dilution of 1: 200 was injected intradermally in 6 clipped skin of the back of white rats-males line Wisar (160-180 g) in the amount of 590 mm. After 24 h, rats intravenously injected resolving dose of ovalbumin (1 mg/kg) in 1 ml of 0.5% solution of the dye Evans blue in saline. After 30 min the rats under ether Nadom at 37aboutC for 4 days. The amount of dye in extravasate was determined spectrophotometrically at 600 nm on a calibration curve.The analyte was injected at a dose of 10 mg/kg over 90 min to a resolution of the dose of antigen. As a comparison object used antiallergic drug sodium cromoglycate (Intal), which are similar in structure (derived chromone) and action, and diasorin (similar compared  sodium cromoglycate was administered at a dose of 50 mg/kg (5 times greater than the analyte, as in the dose of 10 mg/kg expressed anti-allergic actions, he has not shown) intraperitoneally for 90 min to resolving dose. Control rats were injected intraperitoneally with saline. The percentage of inhibition of the reaction was calculated by the formula a 100 A 100 a percentage of inhibition of the Russian perfumery-cosmetic Association,
With mcg Evans blue in the skin of rats treated with the drug,
In mcg Evans blue in the skin of control rats.The results of the experiments are processed statistically  and is shown in the table.Determination of acute toxicity and calculations LD50carried out according to the method of Cerberus  White mice weighing 18-20 g were injected intraperitoneally 0.5 ml of the suspension of the substances under study, prepared the x substances is more than 1300 mg/kg, therefore, these compounds belong to the class of practically non-toxic substances.The results of these studies show that the claimed compounds 1 and 2 have a pronounced anti-allergic action, exceeding the activity of a drug cromolyn sodium introduced at a dose 5 times higher compared to the doses of the compounds under study. The substance 2 is superior in activity diasorin.This indicates the feasibility of further research of these substances with the aim of creating effective medicines. Derivatives of 3-( 6-methoxypropanol - 3)-2-acetylfuran-2-carboxylic acid formula
< / BR>where R OC2H5or
< / BR>having antiallergic activity.
Y is a bond or-O-;
p = 1-16; and
Z is-H or-G-Q, where G is a simple bond or-CH= CH-;
and Q is phenyl, substituted C1-C3the alkoxy group
where I R1= -OH
R2= --CH3R3= - OH
II R1= -H; R2= -C1; R3= -OH
III R1= -O--CH3; R2= -H;
R3= -Nhaving antiallergic activity, which can be used in medicine
FIELD: organic synthesis.
SUBSTANCE: invention provides compounds of general formula I:
, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.
EFFECT: increased choice of cysteine protease inhibitors.
34 cl, 1 tbl, 13 ex
FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of sulfonamides of the formula (I) or their pharmaceutically acceptable salts wherein R1 means -OH or -NHOH; R2 means hydrogen atom; R3 means alkyl, alkoxyalkyl, arylalkyl, pyridylalkyl or morpholinylalkyl; A means piperidyl or tetrahydrofuranyl; n = 0; E means a covalent bond; (C1-C4)-alkylene, -C(=O)-, -C(=O)O- or -SO2-; X means hydrogen atom, alkyl, aryl, arylalkyl, alkoxyalkyl, morpholinyl or tetrahydropyranyl; each among G and G' means -C(R5)=C(R5') wherein R5 and R5' mean hydrogen atom; M means the group -CH-; z means the group -(CR7R7')a-L-R8 wherein a = 0 and each among R7 and R7' means hydrogen atom; L means a covalent bond; R8 means halogen atom or alkoxy-group. Compounds of the formula (I) are inhibitors of metalloproteases and can be used for treatment of arthritis, cancer tumors and other diseases.
EFFECT: valuable medicinal properties of compounds.
15 cl, 7 tbl, 56 ex
SUBSTANCE: before applying substitute hormonal therapy (SHT) on should evaluate antithrombogenic activity of vascular wall in women. For this purpose one should determine quantitative values of ADP-induced aggregation of thrombocytes, activity of antithrombin III in blood and fibrinolytic blood activity both before and after "cuff"-test. Then one should detect the indices calculated as the ratio of mentioned values both before and after carrying out the mentioned test. If mentioned indices are decreased against the norm by 20-40% women should be prescribed to undergo SHT at additional introduction of aspirin and supradin. The method provides prophylaxis of cardio-vascular diseases in this category of female patients due to correcting affected functional activity of vascular endothelium.
EFFECT: higher efficiency of prophylaxis.
1 cl, 1 ex, 4 tbl
FIELD: medicine, natural compounds.
SUBSTANCE: larch wood is saturated with water and extraction with ethyl acetate is carried out. Prepared extract is treated with hot water and this process is combined with distilling off a solvent. Then water-insoluble resin impurities are separated and crude product is isolated by crystallization and recrystallized. Invention provides simplifying the process.
EFFECT: improved preparing method.
FIELD: medicine, pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to compositions used for treatment and/or prophylaxis of chlamydium infections caused by C. pheumoniae. Pharmaceutical composition used for treatment and/or prophylaxis of chlamydium infection caused by C. pneumoniae comprises the taken phenolic compound, or extract, or fraction, or incomplete fraction comprising the taken phenolic compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction obtained from plants and comprising indicated compound or corresponding synthetic compound on C. pneumoniae represents the definite percent of inhibition for formation of inclusions. The composition useful for health eliciting an anti-chlamydium effect with respect to C. pneumoniae comprises the taken phenolic compound or extract, or fraction, or incomplete fraction containing indicated compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent for inhibition in formation of inclusions. Also, invention relates to applying the composition useful for health in preparing foodstuffs or as supplements for nutrition for every day. Also, invention relates to applying phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound or mixture of indicated compounds obtained from plants in manufacturing a medicinal agent used for treatment and/or prophylaxis of chlamydium infections caused by C. pneumoniae. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent in inhibition in formation of inclusions. Compositions promote to effective prophylaxis and treatment of chlamydium infections caused by C. pneumoniae.
EFFECT: valuable medicinal properties of compounds.
21 cl, 1 dwg, 1 tbl, 6 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to new compounds of coumarone class, namely, to 6-nitro-2-iminocoumarin 3-carboxylic acid 4-toluidide silver salt of the formula (1): that elicits an antibacterial effect and can be used in medicine. Invention provides preparing a new compound eliciting an antibacterial effect with respect to S. aureus, E. coli, and C. albicans with mononuclear cells values 0.25; 0.5 and 7.8 mcg/ml, respectively, and with acute toxicity value LD50 for these compounds 2 460 ± 230 mg/kg.
EFFECT: valuable properties of compound.
1 cl, 1 tbl, 2 ex
FIELD: organic chemistry, medicine, pharmacology.
SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):
and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:
wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.
EFFECT: improved preparing methods, valuable medicinal properties of compounds.
22 cl, 1 tbl, 2 sch, 78 ex
SUBSTANCE: the present innovation deals with phospholipid complexes of proanthocyanidine A2 and pharmaceutical compositions upon their basis as antiatherosclerotic agents, those for preventing and treating myocardial and cerebral infarction. Phospholipids of the above-mentioned complex should be preferably chosen out of lecithins, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine. The innovation provides the preparation to treat the above-mentioned diseases due to decreasing the quantity and burden of atheromatous plaque, decreased obstruction of carotid arteries and decreased thickness of vascular walls.
EFFECT: higher efficiency of prophylaxis and therapy.
9 cl, 11 dwg, 6 ex, 2 tbl