Ethyl 1'-benzyl-3,3-dimetnyl-1,2'-dioxo-5'-phenyl-1'2,2',3,4,10-hexahydro-1h-spiro[acridine-9,3'-pyrrol]-4'-carboxylates and synthesis method thereof

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, and more specifically to novel ethyl 5-R1-7-R2-1'-benzyl-3,3-dimethyl-1,2' -dioxo-5'-phenyl- 1',2,2',3,4,10-hexahydro-1H-spiro[acridine-9,3'-pyrrol]-4'-carboxylates of formula , where R1=H, Me; R2=H, OMe; R3=H, Me, OMe, Br, and to a method for synthesis of the said compounds.

EFFECT: obtaining novel compounds which can be used as primary products for synthesis of novel heterocyclic systems and in pharmacology as compounds with analgesic activity.

5 cl, 1 tbl, 3 ex

 

The invention relates to the field of organic chemistry, namely to new individual compounds of class Spiro[acridine-9,3'-pyrrole] and to the way they are received, which can be used as starting products for the synthesis of new heterocyclic systems.

Known structural analogues of the claimed compounds - 6,6-dimethyl-1-n-methoxyphenyl-2,4-dioxo-2,3,4,5,6,7-hexahydro-1H-indole-3-Spiro-2'-(3-benzoyl-5-oxo-4-phenylamino-2,5-dihydrofuran), which is the product of interaction of 4-benzoyl-1-phenyl-5-methoxycarbonyl-2,3-dihydro-2,3-pyrrolidine with 5,5-dimethyl-3-n-methoxyphenyl-2-cyclohexen-1-one produced according to the following scheme (Unibanco, Annalies // Zhur.org.chem.., 2006, V.42, Vol.5, s):

The disadvantages of this method include the inability to obtain ethyl 1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylates.

Object of the invention is to develop a simple method of synthesis is not described in the literature ethyl 1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylates.

The task is carried out by boiling solution of ethyl 1-benzyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylate (I) and 3-(arylamino)-5,5-dimethylcyclohex-2-nonami (IIA, b) in a ratio of 1:1 according to the following scheme:

The process is conducted at a temperature 139-140°C, and as solvents are used as absolutemorp-xylene.

From the patent and technical literature were not identified methods of obtaining substituted ethyl 1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylates having similar characteristics with the claimed method, and it has not been used for the original products, solvents in which the reaction takes place, and the temperature, on what basis is it possible to make a conclusion on the compliance of the claimed technical solution the criterion of "novelty" and "inventive level.

The invention is illustrated by the following examples.

Example 1. Ethyl 1'-benzyl-3,3,7-trimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylate (IIIB).

A solution of 1.0 mmol of the compound (I) and 1.0 mmol of enamine (IIB) in 15 ml of absolutem-xylene was boiled for 5 h, cooled, precipitated precipitate was filtered. The yield was 73%. TPL 263-264°C (from toluene). The compound (IIIB), C35H34N2O4.

Found, %: C 76.75; N, 6.39; N, 5.03.

Calculated, %: C 76.90; N, 6.27; N, 5.12.

The compound (IIIB) is a colourless, crystalline substance, soluble in DMSO and DMF, difficultly soluble in the usual organic solvents, insoluble in water and alkanes. Stable when stored under normal conditions

In the IR spectrum of compound (IIIB), filmed in paste form in vaseline oil, there are bands of stretching vibrations of NH group at 3264 cm-1, lactam and ester carbonyl band at 1687 cm-1and ketone groups at 1624 cm-1.

In the PMR spectrum of the compound (IIIB), recorded in solution in DMSO-d6besides the signals of the protons of aromatic rings and related groups, there are two singlet protons of two methyl groups at 0.99 and 1.08 ppm, doublet signals of four nonequivalent protons of methylene groups2H2and4H2in the field 2.06-2.55 ppm, with a characteristic constants of spin-spin interaction (J 16.0 and 16.4 Hz), broadened singlet proton of NH group at 9.62 ppm and a triplet and multiplet signals of the protons of the ethyl group ethoxycarbonyl substituent at 0.74 and 3.59 ppm, respectively.

Example 2. Ethyl 1'-benzyl-3,3-dimethyl-7-methoxy-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylate (V).

A solution of 1.0 mmol of the compound (I) and 1.0 mmol of enamine (IIB) in 15 ml of absolutem-xylene was boiled for 6 h, cooled, precipitated precipitate was filtered. Yield 78%. TPL 268-269°C (from toluene). Connection (V) C35H34N2O5.

Found, %: C 74.80; H 6.03; N, 5.00.

Calculated, %: C 74.71; H 6.09; N, 4.98.

Connection (V) - a colorless crystal of the economic substance soluble in DMSO and DMF, difficultly soluble in the usual organic solvents, insoluble in water and alkanes. Stable when stored under normal conditions.

In the IR spectrum of compound (V)filmed in paste form in vaseline oil, there are bands of stretching vibrations of NH group at 3256 cm-1, lactam and ester carbonyl band at 1687 cm-1and ketone groups at 1626 cm-1.

In the PMR spectrum of the compound (V)recorded in solution in DMSO-d6besides the signals of the protons of aromatic rings and related groups, there are two singlet protons of two methyl groups at 0.99 and 1.08 ppm, doublet signals of four nonequivalent protons of methylene groups2H2and4H2in the field 2.06-2.55 ppm, with a characteristic constants of spin-spin interaction (J 16.4 and 16.6 Hz), broadened singlet proton of NH group at 9.63 ppm and a triplet and multiplet signals of the protons of the ethyl group ethoxycarbonyl substituent at 0.74 and 3.60 ppm, respectively.

The proposed method is simple, one-step and allows you to get not described in the literature ethyl 5-R1-7-R2-1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4-carboxylates (IIIA-e) in good yields, which will be used as the source p is the FL for the synthesis of heterocyclic systems, and pharmacology as potential medicines.

Example 3. Pharmacological study of ethyl 1'-benzyl-3,3,7-trimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylate (IIIB) and ethyl 1'-benzyl-7-bromo-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylate (G) and the presence of analgesic activity.

Evaluation of the analgesic properties of the compounds (IIIB, g) studied in outbred mice weighing 18-22 grams method of thermal stimulation "hot plate" Eddie and Leimbach (N.B. Eddy, Leimbarh D.J. Pharmacol and.. Gher. 1953., 385-393). As the comparison drug used analgin.

Studies have shown (see table), which is compound (IIIB, g) have a fairly strong analgesic activity. Data on pharmacological activity of analogues of the claimed compounds in the available literature no.

Analgesic activity of compounds (IIIB, g)
No. of connectionsDose, mg/kgDefensive reflex through
2 hours2.5 hours
Control 2% krahm. mucus50 10,6±1,21
Analgin93 (U50)12,8±1,916,3±3,0
IIIb5021,20±0,71
G5023,98±0,77

1. Ethyl 5-R1-7-R2-1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylates of the formula

where R1- H, Me; R2- H, OMe; R3- H, Me, OMe, Br.

2. Ethyl 1'-benzyl-7-bromo-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylate of the formula

possessing analgesic activity.

3. The way to obtain ethyl 5-R1-7-R2-1'-benzyl-3,3-dimethyl-1,2'-dioxo-5'-phenyl-1',2,2',3,4,10-hexahydro-1H-Spiro[acridine-9,3'-pyrrole]-4'-carboxylates of General formula

characterized in that ethyl 1-benzyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates are subjected to interaction with 3-(arylamino)-5,5-dimethylcyclohex-2-tonami in inert aprotic solvent, followed by separation of the target about the of aktov.

4. The method according to claim 3, wherein the process is conducted at a temperature 139-140°C.

5. The method according to claim 3 or 4, characterized in that the solvent used absolute m - or p-xylene.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-thio-D-glucitol compounds of formula I or to pharmaceutically acceptable salts thereof or hydrates of the compound or salts: , [where R1, R2, R3 and R4 are identical or different, and each is a hydrogen atom, C1-C6-alkyl group), A is -(CH2)n-, -CONH(CH2)n-, -O- or -(CH2)nCH=CH- (where n is an integer from 0 to 3, Ar1 is an arylene group, heteroarylene group, which is an unsaturated 5-9-member mono- or bicyclic group, containing 1-2 heteroatoms, selected from S and N, Ar2 is an aryl group or heteroaryl group which is an unsaturated 5-9-member mono- or bicyclic group containing 1-2 heteroatoms selected from O, S and N, and R5, R6, R7, R8, R9 and R10 are identical or different, and each is (i) a hydrogen atom, (ii) a halogen atom, (iii) a hydroxyl group, (iv) C1-8-alkyl group, optionally substituted with hydroxyl group(s), (v) -(CH2)m-Q {where m is an integer from 0 to 4, and Q is -CO2H, -ORc1, -CO2Ra3, -SRe1, -NHRa6 or -NRa7Ra7 (where each of Ra3, Ra6 and Ra7 is a C1-6-alkyl group, Rc1 is a C1-6-alkyl group, and Rc1 is a C1-6-alkyl group)}, (vi) -O-(CH2)m'-Q' {where m' is an integer from 1 to 4, and Q' is a hydroxyl group,-CO2H, -CO2Ra8, -CONRa10Ra10, -NRa12Ra12 (where each of Ra8, Ra10 and Ra12 is a C1-6-alkyl group)}, (vii) -ORf {where Rf is C3-7-cycloalkyl group or tetrahydropyranyl group)}, (viii) morpholine group, (ix) phenyl group, (x) pyridyl group]. The invention also relates to 1-thio-D-glucitol compounds of formulae IA, II, III, IV, to a pharmaceutical agent, to methods of obtaining 1-thio-D-glucitol compounds, as well as to compounds of formulae XIII, XIV.

EFFECT: obtaining novel biologically active compounds which are inhibitors of sodium-dependent co-transporter-2-glucose.

25 cl, 140 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: in formula (1), R1 is di-C1-6alkoxyphenyl group; A is one of the following groups (i)-(vi); (i) -CO-B-, where B is C1-6alkylene group; (ii) -CO-Ba-, where Ba is C2-6alkenylene group; (iii) -CH(OH)-B-; (iv) -COCH((C)OOR3)-Bb-, where R3 is C1-6alkyl group and Bb is C1-6alkylene group. Values of the other radicals are specified in the patent claim. Invention also concerns the pharmaceutical composition exhibiting properties of a phosphodiesterase PDE4 inhibitor containing the compound under the invention; the phosphodiesterase 4 inhibitor containing as an active component the compound of the invention; preventive or therapeutic preparation for atopic dermatitis containing as an active component the compound of the invention.

EFFECT: higher effectiveness of application of the compound.

8 cl, 24 tbl, 262 ex

FIELD: pharmacology.

SUBSTANCE: invention deals with formula I compounds and their sals pharmaceutically relevant in the capacity of phosphatidylinositol 3-kinase inhibitors, their preparation method as well as their application for production of a pharmaceutical preparation, a pharmaceutical compounds based thereon and a therapy method envisaging their application. In a formula compound R1 is represented by aminocarbonyl, non-obligatorily displaced with nitrile, or R1 is represented by C1-C8-alkylcarbonyl that is non-obligatorily displaced with hydroxi, carboxi, C1-C8-alcoxicarbonyl, nitrile, phenyl, C1-C8-halogenalkyl or C1-C8-alkyl, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkyl aminocarbonyl alkylcarbonyl that is non-obligatorily displaced with halogen, hydroxi, C1-C8-alkylanimo, di(C1-C8-alkyl)amino, carboxi, C1-C8-alcoxicarbonyl, nitrile, C1-C8-halogenalkyl or C1-C8-alkyl, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkylaminocarbonyl, non-obligatorily displaced with C1-C8-cycloalkyl or R1 is represented by C1-C8-alkylcarbonyl or C1-C8-alkylaminocarbonyl, each of them non-obligatorily displaced with C1-C8-alcoxi, non-obligatorily displaced with hydroxi or R1 is represented by C1-C8-alkylaminocarbonyl, displaced with phenyl, additionally displaced with hydroxi or R1 is represented by C1-C8-alkylcarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-4 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with C1-C8-alkyl on condition that the 6-membered heterocyclic ring is no 1-piperidyl or R1 is represented by C1-C8-alkylaminocarbonyl that is non-obligatorily displaced with a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring is non-obligatorily displaced with C1-C8-alkyl or R1 is represented by -(C=O)-(NH)a-Het, where a stands to denote 0 or 1 and Het stands to denote a 4-, 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) where the ring is non-obligatorily displaced with hydroxi, C1-C8-alkyl, C1-C8-alcoxi or a 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen or R1 is represented by -(C=O)-(NH)b-T, where b stands to denote 0 or 1 and T stands to denote C3-C8-cycloalkyl that is non-obligatorily displaced with hydroxi or C1-C8-alkyl displaced with hydroxi or R1 is represented by -(C=O)-(NH)b-T, where b stands to denote 1 and T stands to denote phenyl that is non-obligatorily displaced with C1-C8-alkyl or C1-C8-alkyl displaced with hydroxi, R2 is represented by C1-C3-alkyl; one of R3 and R4 is represented by R6 while the other is represented by R7; R5 is represented by hydrogen or a halogen; R6 is represented by hydrogen, hydroxi, amino, -SOR8, -SO2R8, -SO2NH2, -SO2NR9R10, -COR8, -CONHR8, -NHSO2R8, nitrile, carboxi, -OR8 or C1-C8-halogenalkyl; R7 is represented by hydrogen, R11, -OR11, halogen, -SO2R8, ciano or C1-C8-halogenalkyl or, when R4 is represented by R7, R7 may equally be represented by -NR12R13; R8 and R11 are independently represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with hydroxi, nitrile, amino, C1-C8-alkylamino or di(C1-C8-alkyl)amino; any R9 is represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with hydroxi, C1-C8-alcoxi, nitrile, amino, C1-C8-akrylamino, di(C1-C8-alkyl)amino or 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatom(s) selected from among the group consisting of oxygen and nitrogen where the ring where the ring is non-obligatorily displaced with C1-C8-alkyl, and R10 is represented by hydrogen or C1-C8-alkyl or R9 and R10 together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C1-C8-alkyl; any R12 is represented by C1-C8-alkyl or C3-C8-cycloalkyl, non-obligatorily displaced with amino, C1-C8-alkylamino or di(C1-C8-alkyl)amino and R13 is represented by halogen or C1-C8-alkyl or R12 and R13 together with the nitrogen atom they are connected to form a 5- or 6-membered heterocyclic ring that has 1-2 cyclic nitrogen heteroatoms where the ring is non-obligatorily displaced with C1-C8-alkyl.

EFFECT: proposed compounds are to be utilised for treatment of diseases mediated by phosphatidilinozitol 3-kinase such as allergy, psoriasis, diabetes, atherosclerosis, diabetes, cancer.

19 cl, 3 tbl, 181 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: invention claims compounds of the formula (I) with radicals as described in the claim, and medicine with inhibition effect on glycine absorption, based on compound of the formula (I) .

EFFECT: medicine for diseases treatment where glycine absorption inhibition can be effective.

21 cl, 1 tbl, 173 ex

FIELD: chemistry.

SUBSTANCE: there are disclosed 1-(2-aminobenzol)piperazine derivatives of formula (I) and pharmaceutically acceptable acid-additive salts with radical values specified in patent claim. The compounds are characterised with inhibiting effect on glycine I carrier. There is also disclosed medical product based on the compounds of formula (I).

EFFECT: compound can be used for treatment of the diseases associated with glycine uptake inhibition.

12 cl, 5 tbl, 396 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

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

7 cl, 1 tbl, 144 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, CaH2a+1 wherein one or more atoms H are substituted with F, -NR11R12 or -SOj-R15 wherein a = 1-8; R11 and R12 mean independently of one another H, CeH2e+1 or CrrH2rr-1 wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means CkH2k+1 wherein k = 1-8; R5 means CpH2p+1 or CssH2ss-1; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SOwR23, -NR32COR30, NR32CSR30, -NR32SObbR30, H, F, Cl, Br, -OH, -NH2, CeeH2ee+1, -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or CzH2z+1, CzzH2zz-1 wherein z = 1-8; zz = 3-8 wherein in CzH2z+1 and CzzH2zz-1 one or more H atoms are substituted with fluorine atom and one or more CH2-groups are substituted with -C(=O) or NR27 wherein R27 means H or CaaH2aa+1 wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, CccH2cc+1, CyyH2yy-1, pyrrolydinyl, piperidinyl wherein in their cycles CH2-group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or ChH2h+1 wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group ChH2h+1 one or more hydrogen atoms are substituted with fluorine atom, and in the groups CccH2cc+1 and CyyH2yy-1 one or more hydrogen atoms can be substituted with fluorine atom, and CH2-group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO2CH3; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, CooH2oo+1 wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO2 or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, CuuH2uu+1 or -COR72 wherein uu = 1-8; R72 means H, CvvH2vv+1 wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, CttH2tt+1 or -C(NH)NH2 wherein tt = 1-8 and wherein in the group CttH2tt+1 one or more CH2-groups can be substituted with NR44 wherein R44 means CggH2gg+1 wherein gg = 1-8; R42 means H or ChhH2hh+1 wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -OvSOwR23, -NR32COR30, -NR32CSR30 and -NR32SObbR30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

21 cl, 15 tbl, 221 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to compounds of general formula (II) and pharmaceutically acceptable salts thereof, and to use and a pharmaceutical composition based on the said compounds. In formula (II) compounds, A is a heteroaromatic 5-member cyclic system containing one group X selected from a group consisting of S and O; Z1 and Z2 independently represent O; R2 is OR6; R6 is H; R8 is hydrogen or (C1-C6)alkyl; E is phenyl which is optionally substituted with 1-4 substitutes in form of halogen; Y is phenyl which is optionally substituted with 1-2 substitutes selected from halogen, (C1-C6)alkoxy or halogen((C1-C6))alkyloxy; m equals 0; n equals 0; q equals 0; t equals 0; or pharmaceutically acceptable salts thereof.

EFFECT: obtaining aromatic compounds of formula (II) for inhibiting dehydroorotate dehydrogenase.

6 cl, 22 ex

FIELD: medicine.

SUBSTANCE: there are offered versions of a pharmaceutical liquid suspension dosage form containing NSAID and/or acetaminophen particles. Said particles are coated with one layer of the controlled release composition. There is offered a method of pain management in a mammal that implies introduction of said dosage form in an effective amount to ensure pain relief within 12 hours following introduction of the dosage form. There is also offered the method of administering acetaminophen and/or NSAID as a liquid suspension pharmaceutical dosage form to a mammal whereat the mammal takes a controlled release dose of said substance over 12 hours after introduction of the dosage form where acetaminophen and/or NSAID are not additionally taken during said 12-hour period.

EFFECT: therapeutic effect of the dosage form lasts within 8 hours following its initial introduction to the mammal.

16 cl, 6 ex, 1 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: there are selected strains Lactobacillus capable to raise IL-10 level and simultaneously to reduce TGF-beta-2 level in human breast milk to be applied with the products containing cells of selected strains to improve human milk for breast feeding. Selected strains and said products containing cells of selected strains are applied to increase of levels of anti-inflammatory cytokine IL-10 in human breast milk and reduce risk of allergy development in a breast-fed infant, to improve anti-inflammatory activity of human breast milk and to reduce simultaneously causal factors.

EFFECT: invention provides decreased TGF-beta-2 level in milk that leads to reduced risk of mastitis development in a nursing mother.

22 cl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention covers medical products which contain pharmacologically acceptable liquid crystals and their derivatives of general structural formula: , where X represents a group -CH=N-, while Y and Z are alkyl or alkoxyl group and are taken in a daily dose in amlount 355 mcg to 10 g a day.

EFFECT: medical products under the invention exhibit antiinflammatory, immunomodulatory, analgetic (anaesthetising) and antineoplastic action when administered in optimal doses without foreign substances.

11 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (XXI) where values of R1, Y, Ra and Rb are given in subparagraphs 1 and 2 of the formula of invention, as phosphatidylinositol-3-kinase inhibitors, a pharmaceutical composition based on said compounds and their use.

EFFECT: compounds can be used for treating and preventing diseases mediated by phosphatidylinositol-3-kinase.

5 cl, 5 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: described are spirocyclic derivatives of cyclohexane of general formula . Values of radicals are given in the formula of invention. The compounds have affinity to the ORL1 receptor and can be used for treating abstinence syndrome (withdrawal syndrome) and pain. Also described is a medicinal agent and use of formula (I) compounds for preparing respective medicinal agents.

EFFECT: increased effectiveness of using the compounds.

13 cl, 17 ex, 1 dwg

FIELD: veterinary science.

SUBSTANCE: agent for prevention of development and treatment of inflammatory processes in animals is represented by a medication, for preparation of which the mixture of the following components ground to fine and ultrafine particles, which are treated with beams of ultraviolet lamps is placed into dry sterile reservoir made of dark glass, such as medicinal plants at their ratio in powder of 25.0 g (by 1.25 wt %): dry leaves, stems, flowers of peppermint, dry flowers of wild chamomile, dry leaves of costmary anthodes, dry leaves, stems, flowers, fruit of plaster clover, dry herb of touch-and-heal, dry flowers of pot marigold (calendula), dry herb of yarrow, dry herb of thyme, dry leaves, stems, flowers, fruit of killwort, dry leaves of eucalyptus, dry leaves and anthodes of foalfoot, dry leaves of garden sage, dry leaves of stinging nettle, dry herb of lady's thumb, dry flowers of densely flowered mullein corolla (dense mullein), ground fruit of anis and fruit of cinnamon rose, ground kernels of walnut fruit, seedless pulp of sea-buckthorn (if not available, sea-buckthorn oil), vegetable raw materials with weight of 500.0 g (25 wt %) is mixed with 1500.0 g (75 wt %) of vegetable oil (corn, sunflower-seed, olive). After maintenance at room temperature and permanent mixing during 10 days, dark glass reservoir with mixture is placed into water bath for 5 days at the temperature of up to 40°C. Oil infusion is separated from vegetable raw materials, preserved at the temperature of 2-4°C in dark glass reservoirs or in dark room.

EFFECT: improved efficiency of treatment and prophylactics.

3 cl

FIELD: medicine.

SUBSTANCE: invention relates to chemical-pharmaceutical industry and medicine, namely to pharmaceutical solution of meloxicam for parenteral introduction in therapeutically effective quantity for treatment of rheumatoid arthritis, osteoarthritis, arthrosis, inflammatory and degenerative diseases of joints, which are accompanied with pain syndrome, which contains meloxicam and pharmaceutically acceptable excipients and auxiliary substances, which differs by the fact that it additionally contains glycine, with quantitative ratio of meloxicam and glycine 0.05-0.2 wt %: 0.05-0.1 wt % respectively.

EFFECT: high efficiency with higher safety with respect to development of gastro-intestinal side effects, high stability during storage.

11 cl, 1 tbl, 2 ex

FIELD: veterinary science.

SUBSTANCE: preparation for treatment of serous and catarrhal inflammation of mammary gland in cows in the form of ointment consists of filler containing lanolin, vaseline and vegetable oil, and active substance - resorcin and boric acid, at the following ratio of components, wt %: Lanolin 35-40; Resorcin 2-4; Boric acid 1.5-2.5; Vaseline 35-45; Vegetable oil - the rest.

EFFECT: broader range of preparation therapeutic action.

5 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to method of enhancing prolonged februfungal action, increase of februfungal activity and reduction of toxicity of salicylates by introduction in therapeutic dose as salicylate of allyl ether of acetylsalicylic acid. Introduction of allyl gragment into carboxyl group of acetylsalicylic acid molecule allows to enhance prolonged februfungal action and reduce toxicity of acetylsalicylic acid.

EFFECT: application of allyl ether of acetylsalicylic acid as antipyretic will allow to reduce therapeutic dose of acetylsalicylic acid and reduce risk of development of side effects connected with intake of salicylates.

1 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 11b-(het)aryl-2,3,6,11b-tetrahydrooxazolo[2',3':2,1]pyrrolo [3,4-b]quinolin-5,11-diones with general formula 1 R1=Ar, Het; R2=H, Alk, OAlk, halogen; R3 - H, Alk, OAlk, halogen; R4=H, Alk, OAlk, halogen and to a synthesis method which involves reacting initial 3-(het)aroyl-4-oxo-1,4-dihydro-2-quinolincarboxylate with monoethanolamine in ratio 1:1 in methanol, ethanol, tetrahydrofuran, toluene, dioxane while heating in the presence or absence of acetic acid for 2-24 hours (control using thin-layer chromatography).

EFFECT: formula 1 compounds have potential for use as low-toxicity substances with biological activity, for example antimicrobial, antiviral and anticonvulsant; method of producing formula 1 compounds is easy to implement, safe, does not require special conditions, allows for obtaining substances which can not be produced using other methods.

2 cl, 10 ex

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