Condensed carbocycle substituted dihydroimidazole derivatives used for pain control or management of glaucoma-like conditions

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a method of intraocular pressure reduction and to a method of pain control involving the administration of a therapeutic compound representing , or its tautomer or stereoisomer forms wherein X represents NH; n is equal to 2 or 3; Ra, Rb, Rc and Rd represent stable functional groups independently consisting of: 0 to 4 carbon atoms, 1 to 9 hydrogen atoms; and Re represents H or C1-4alkyl. Furthermore, the invention refers to a compound represented by formula , or to its tautomer or stereoisomer form.

EFFECT: new compound is prepared; besides, the known compounds to be applied in pain and glaucoma control are studied.

8 cl, 1 tbl

 

Prior art

There is a continuing need in the alpha-adrenergic compounds for the treatment of pain, glaucoma and other conditions.

Description of the invention

This document describes the connection that has the following structure:

where X represents O, S or NH;

n is 2 or 3;

Ra, Rb, Rcand Rdrepresent a stable functional groups independently comprising from 0 to 4 carbon atoms, from 0 to 10 hydrogen atoms, from 0 to 2 oxygen atoms, from 0 to 1 sulfur atom, from 0 to 1 nitrogen atom, 0 to 3 fluorine atoms, from 0 to 1 chlorine atom and from 0 to 1 bromine atom; and

Rerepresents N or C1-4alkyl.

These compounds are effective for treatment of pain, glaucoma and for lowering intraocular pressure. The connection is included in the dosage form or drug and administered to the mammal in need. For example, for the treatment of glaucoma or lowering of intraocular pressure can enter the liquid composition in the form of eye drops. If any of these conditions, you can also enter a solid dosage form. The prior art known to other types of dosage forms and drugs, which can also be applied in this case.

For descriptive purposes, those who mines "to expose", "treating" or "treatment" refer to the use of compounds of the composition, therapeutically active agent or drug to diagnose, treat, cure, relief, treatment, prevention of disease or other undesirable condition.

Unless otherwise stated, references to the connection should be interpreted in a broad sense, including pharmaceutically acceptable salts, prodrugs, tautomers, alternate solid forms, as well as non-covalent complexes chemical object depicted structures or chemical names.

Pharmaceutically acceptable salt is any salt of the parent compound, suitable for administration to an animal or person. To the pharmaceutically acceptable salt is any salt that can be formed in vivo by injection of acid, any salt or prodrug, which is converted to the acid or salt. Salt includes one or more ionic forms of connection, such as the conjugate acid or base, associated with one or more corresponding counterions. Salts can be formed from or include one or more deprotonated acidic groups (e.g. carboxylic acids), one or more protonated basic groups (e.g. amines), or both types of groups at the same time (for example, zwitter-ions).

Prole the arstvo represents a connection, passing in the form of a therapeutically active compound after administration. Without limiting the scope of the present invention, the conversion may occur under the action of hydrolysis of ester group or any other biologically labile group. Receipt of prodrugs is well known in the prior art. For example, in Chapter ((Prodrugs and Drug Delivery Systems" ("Prodrugs and systems for drug delivery") from the book by Richard B.Silverman, Organic Chemistry of Drug Design and Drug action (Organic chemistry of drug development and their impact), 2d Ed., Elsiever Academic Press: Amsterdam, 2004, p.p.496-557 proposed a more detailed description on this issue.

The tautomers are isomers that are in dynamic equilibrium with each other. For example, the tautomers can be related to the mechanism of proton transfer, hydrogen atom or hydride ion. Examples of tautomers below.

Except when stereocilia marked explicitly, understand that the structure includes all possible stereoisomers, both pure and any possible mixture.

Alternative solid forms are solid forms other than those which are formed as a result of application of the methods described in this document. For example, alternative solid forms can be polymorphic forms, a variety of the types of amorphous solid forms, vitreous education and the like.

Nequalities complexes are complexes formed between the compound and one or more additional chemical fragments, without the formation of covalent bonds between the compound and these additional chemical fragments. They may be or may not be characterized by a certain ratio connection and additional chemical fragments. Examples of such complexes are solvate, hydrates, complexes with charge transfer and the like.

X represents O, S or NH. So, suggest connections that meet any of the structures described below.

Since n equals 2 or 3, also provides compounds that meet any of the following structures.

The connection part

attached to one of the non-aromatic carbon atoms of the ring system. In other words, the assumed connection described by the structures shown below:

Ra, Rb , Rcand Rdrepresent a stable functional groups independently comprising from 0 to 4 carbon atoms, from 0 to 10 hydrogen atoms, from 0 to 2 oxygen atoms, from 0 to 1 sulfur atom, from 0 to 1 nitrogen atom, 0 to 3 fluorine atoms, from 0 to 1 chlorine atom and from 0 to 1 bromine atom.

Taking into account limitations (for example, restrictions on the number of atoms) examples of groups Ra, Rb, Rcand Rdinclude, but are not limited to:

- hydrocarbon, indicating a functional group containing only atoms of carbon and hydrogen, including, but not limited to, the following:

(a) alkyl, which represents hydrocarbon that does not contain double or triple links, including but not limited to:

linear alkyl, for example methyl, ethyl, n-propyl, n-butyl, and others;

branched alkyl, such as ISO-propyl, tert-butyl and other branched butyl isomers, and the like;

- cycloalkyl, such as cyclopropyl, cyclobutyl etc.;

- combinations of linear, branched and/or cyclic Akilov,

b) alkenyl, for example hydrocarbon containing 1 or more double bonds, including linear, branched, or cyclic of alkenyl,

in) quinil, for example hydrocarbon containing one or more triple relations, including linear, branched, or cyclic alkinyl,

d) combine the tion of alkyl, alkenyl and/or quinil:

- alkyl-CN, such as-CH2-CN, -(CH2)2-CN; -(CH2)3-CN and the like;

- hydroxyalkyl, i.e. alkyl-OH, such as hydroxymethyl, hydroxyethyl and the like;

- simple ester substituents, including-O-alkyl, alkyl-O-alkyl and the like;

- thioester deputies, including-S-alkyl, alkyl-B-alkyl and the like;

- amine substituents, including-NH2, -NH-alkyl, -N-alkyl1alkyl2(i.e. alkyl1and alkyl2are the same or different, and both are attached to the N atom), alkyl-NH2, alkyl-NH-alkyl, alkyl-N-alkyl1alkyl2and the like;

- aminoalkyl, i.e. alkyl-amine, such as aminomethyl (-CH2-Amin), aminoethyl and the like;

- hard-ether substituents, including-CO2-alkyl, -CO2-phenyl and the like;

- other carbonyl substituents, including aldehydes, ketones, such as acyl (i.e.), and the like, in particular, refers to such deputies as acetyl, propionyl and benzoyl;

- fully or partially fluorinated hydrocarbons, such as-CF3, -CH2CF3and the like, as well as

- CN;

- the possible combinations of the above substituents, with regard to specified restrictions;

in another case, a Deputy may be is-F, -Cl, -Br or-I.

In particular, imply alkali containing from 1 to 4 carbon atoms:

Ra, Rb, Rcand Rdare stable, i.e. they must remain sufficiently stable to be stored in the vial at room temperature at normal atmospheric pressure for at least 12 hours, or to be sufficiently stable for any purpose described in this document.

If Ra, Rb, Rcor Rdis a salt, for example carboxylic acid or amine, the counterion of the specified salt, i.e. ion unrelated covalent bond with the remainder of the molecule, not considered when counting the number of atoms in the functional group. So, for example, saltconsists of 1 carbon atom and 2 oxygen atoms, i.e. the sodium atom is not considered. In another example, saltconsists of 2 carbon atoms, 1 nitrogen atom and 7 hydrogen atoms, that is, a chlorine atom are not taken into consideration.

In another embodiment, each of Ra, Rb, Rcand Rdindependently represents-H, alkyl containing from 1 to 4 carbon atoms, -F, -Cl, -Br, -CH2OH amine containing from 0 to 4 carbon atoms, -CH2CN, -CF3or acyl containing from 1 to 4 carbon atoms.

In another embodiment, each of Ra, Rb, Rcand R dindependently represents-H, -F, -Cl, -Br, CH3, -NHCH3or-CF3.

Re represents H or C1-4alkyl, i.e. methyl, ethyl, n-propyl ISO-propyl and butyl isomers. Reattached to one of the non-aromatic carbon atoms in the ring system. So, it refers to the connection described by any of the structures shown below.

In one of the embodiments n is 2.

In another embodiment n is equal to 3.

In another embodiment X represents O.

In another embodiment X represents S.

In another embodiment X represents NH.

In another embodiment, each of Ra, R0, Rcand Rdindependently selected from H, methyl, ethyl,3the alkyl and C4of alkyl, F, Cl, Br, -CH2HE, -CH2NH2, -CHNH(C1-4the alkyl), -CN(C1-4alkyl)2, -CH2CN and CF3.

In another embodiment, each of Ra, Rb, Rcand Rdindependently selected from H, methyl, ethyl, F, Cl, Br, -CH2CN and CF3.

In another embodiment Rerepresents H.

In another embodiment Rerepresents methyl.

In another embodiment the compound has the following structure:

Another embodiment is a method of reducing intraocular pressure, enabling the th introduction of the compounds according to the invention to the mammal in need.

Another embodiment is a method of treating pain, comprising introducing the compound according to the invention to the mammal in need.

Below are some hypothetical examples of suitable compounds.

Other suitable compounds include:

(4,5-dihydro-1H-imidazol-2-yl)-(1,2,3,4,-tetrahydro-naphthalene-1-yl)amine, [(1S)-(4,5-dihydro-1H-imidazol-2-yl)-(1,2,3,4,-tetrahydro-naphthalene-1-yl)]amine, and (4,5-dihydro-1H-imidazol-2-yl)-(5,7-dimethyl-1,2,3,4,-tetrahydro-naphthalene-1-yl)amine.

The synthesis methods

A solution of 5,7-dimethyl-3,4-dihydro-2H-naphthalene-1-it (commercially available, 12.3 g, 28, 3 mmol) (Intermediate 4) in isopropanol (100 ml) was treated with cyanoborohydride sodium (9,01 g, 143,5 mmol) and ammonium acetate (47,4 g, 615 mmol), the reaction mixture is boiled under reflux for 16 hours. The mixture was podslushivaet sodium hydroxide (10 ml). The precipitate was isolated by conventional water extraction to obtain (6.5 g, 37,1 mmol) (intermediate 5). The compound (500 mg, 5.7 mmol) (intermediate 5) and 4,5-dihydro-1H-imidazol-2-sulfonic acid (940 ml, 6.3 mmol) in 2-butanol (30 ml) Ki is atili under reflux for 24 hours. The mixture is evaporated under reduced pressure. The resulting substance was purified by chromatography on silica gel with 5% NH3-MeOH:CH2Cl2obtaining (90 mg, 3.7 mmol, 36%) (4,5-digdia-1 H-imidazol-2-yl)-(5,7-dimethyl-1,2,3,4-tetrahydro-naphthalene-1-yl)amine (904).

Similar procedure as for904used for other connections.

(4,5-dihydro-1H-imidazol-2-yl)-(1,2,3,4,-tetrahydro-naphthalene-1-yl)amine,639:

1H NMR (CD3OD, 300 MHz): δ=7,26-7,14 (m, 4H)and 4.65 (t, J=6.0 Hz, 1H), 3,74 (s, 4H), 2,65-2,90 (m, 2H), 1,86-of 2.08 (m, 3H), of 1.42 to 1.47 (m, 1H).

[(1S(4,5-dihydro-1H-imidazol-2-yl)-(1,2,3,4-tetrahydro-naphthalene-1-yl)]amine,323:

1H NMR (CD3OD, 500 MHz): δ=7,06-7,37 (m, 4H)and 4.65 (t, J=5.0 Hz, 1H), 3,74 (s, 4H), 2,72 are 2.98 (m, 2H), 1.77 in-of 2.23 (m, 3H), of 1.44 to 1.48 (m, 1H).

(4,5-dihydro-1H-imidazol-2-yl)-(5,7-dimethyl-1,2,3,4-tetrahydro-naphthalene-1-yl)amine,904:

1H NMR (CD3OD, 500 MHz): δ=6,94 (d, 2H), br4.61-of 4.67 (m, 1H), 3,90 (s, 4H), 2,63-2,60 (m, 2H), 1,82-to 1.98 (m, 4H), of 2.28 (s, 3H), of 2.28 (s, 3H).

Data for biological studies

The analysis, called " technology selection and amplification receptors (RSAT)

In the analysis RSAT measure receptor-mediated loss of contact inhibition, which results in selective proliferation of cells containing the receptor, in a mixed population of confluent cells. The increase in the number of cells evaluated using appropriate transfe the new marker gene, such as the gene for β-galactosidase activity, which can be easily determined in 96-well pad. The receptor activates the G protein, Gq, cause this response. Alpha2receptors, which are usually associated with Gi, activate response RSAT co-expression of the hybrid protein Gq, which is the domain of pattern recognition receptor Gi, called Gq/i5.

Cells NIH-3T3 were seeded with a density of 2×106cells in a Cup with a diameter of 15 cm and is supported on the environment Dulbecco, which is a modification of eagle medium with addition of 10% calf serum. The next day cells cotransfected by precipitation of calcium phosphate with plasmids the mammalian expression, encoding the p-SV-β-galactosidase (5-10 µg), receptor (1-2 µg) and protein G (1-2 µg). 40 µg DNA Molok salmon can also be incorporated into the mixture for transfection. Fresh medium was added on the following day, and after 1-2 days, the cells harvested and frozen in 50 aliquot for analysis. Cells are thawed and add 100 ál of cells to 100 ál aliquot of various concentrations of drugs in triplicate in 96-well pad. Incubation is carried out in a period of 72-96 hours at 37°C. After washing with phosphate-saline buffer solution to determine the enzymatic activity of β-galactosidase by adding 200 μl of chromogenic substrate (consisting of 3.5 mm o-nitrophenyl-β-D-galactopyranoside and 05% nonidet the P-40 in phosphate-saline buffer solution), incubation overnight at 30°C and measuring optical density at 420 nm. Absorption is a measure of the enzymatic activity, which depends on the number of cells and reflects mediated by receptors of cell proliferation. Efficiency or internal activity is calculated as the ratio of maximum effect of the medicinal product to the maximum effect standard full agonists for each receptor subtype. Brimonidine, also called UK14304, the chemical structure of which is shown below, is used as the standard agonist for alpha2Aalpha2Band alpha2Cthe receptors. ES represents the concentration at which the effect of the medicinal product is half of its maximum effect.

The RSAT results of the analysis with several typical compounds according to the invention described in Table 1 together with the chemical formulas of these typical compounds. Size EU50are nanomolar. N.O. means "not defined" at concentrations less than 10 micromol. VA stands for "internal activity".

Table 1
StructureAlpha 2BAlpha 2C Alfa-2A
37179The concentration is
(84)(50)(25)
49308 (42)Concentration (12)
(102)
68The concentration is1622
(80)(4)(35)

Ways to develop the formulas for these compounds are well known in the prior art. For example, in U.S. patent No. 7141597 (in particular, from column 10, line 27 to column 14, line 47) contains information that can be used as a General guide. Similar information on this issue is also found in numerous other sources. The biological activity of the compounds described herein (e.g., Table 1), the can is to be used as additional General guidance on the selection dosages, depending on the particular application of the connection.

The above description explains the specific methods and compositions that can be applied to embodiments of the present invention, and represent the best the proposed method. However, for professionals in the art it is obvious that you can get additional compounds with the desired pharmacological properties similar way and that the described compounds can also be obtained from other source compounds with other chemical reactions. You can also get other pharmaceutical compositions and use them to produce essentially the same result. So, in spite of the above detailed description in this document should not be construed as limiting the scope of the invention or scope of the present invention should be determined solely by the formula.

1. A method of reducing intraocular pressure comprising introducing the compound to a mammal in need where the compound represented by formula

or its tautomeric or stereoisomeric form,
where X represents NH;
n is 2 or 3;
Ra, Rb, Rcand Rdrepresent a stable functional groups independently comprising from 0 to 4 carbon atoms, 1 is about 9 hydrogen atoms; and
Rerepresents N or C1-4alkyl.

2. A method of treating pain, comprising the introduction of a therapeutic compound to a mammal in need where the compound represented by formula

or its tautomeric or stereoisomeric form,
where X represents NH;
n is 2 or 3;
Ra, Rb, Rcand Rdrepresent a stable functional groups independently comprising from 0 to 4 carbon atoms, from 1 to 9 hydrogen atoms; and
Rerepresents N or C1-4alkyl.

3. The method according to claim 1 or 2, where each Ra, Rb, Rcand Rdindependently selected from H, methyl, ethyl,3the alkyl and C4the alkyl.

4. The method according to claim 1 or 2, where each Ra, Rb, Rcand Rdindependently selected from H, methyl, ethyl.

5. The method according to claim 4, where Rerepresents N.

6. The method according to claim 4, where Rerepresents methyl.

7. The method according to claim 1 or 2, where the compound represented by formula

or is its tautomeric or stereoisomeric form.

8. The compound represented by formula
or its tautomeric or stereoisomeric form.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention concerns method of obtaining heterocycles of formula I , where X, A, R10-R17 are as defined in point 1 of the claim, while a) isothiocyanate of formula II is transformed into thiourea of formula IV by interaction with primary amine of formula III, and b) thiourea of formula IV is transformed into compound of formula I by interaction with sulfochloride R6SO2Cl in the presence of a base, where A, X, n, m and R10 to R17 in compounds of formulae II, III and IV are as defined in formula I, and R6 is (C1-C4)-alkyl, trifluoromethyl or phenyl non-sustituted or substituted by methyl, trifluoromethyl, F, CI, Br or polymer carreir. The transportation is shown by combination formulae

EFFECT: new multipurpose synthesis technique for heterocyclic compounds of the general formula I.

8 cl, 31 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel imidazoline-2-yl-aminophenylamides of the formula (I): wherein R1 means phenyl optionally substituted with one, two or three substitutes chosen independently from group comprising alkyl, alkenyl, alkoxy-group, optionally substituted aryl, optionally substituted aryloxy-, aralkyloxy-group, halogen atom, halogenalkyl, halogenalkoxy-, hydroxy-group, hydroxyalkyl, alkylsulfonyl, alkoxyalkyloxy-, hydroxyalkyloxy-, cyano-, hydroxy-group, cycloalkyl, cycloalkyloxy-, cycloalkylalkoxy-, amino-, alkylamino-, dialkylamino-group, optionally substituted heterocyclyl, optionally substituted heterocyclyloxy-group, optionally substituted heterocyclylsulfonyl, optionally substituted heterocyclylalkyloxy-group, sulfamoyl, alkylsulfamoyl, dialkylsulfamoyl; R2 means hydrogen atom; A means -C(O)-NRa-(CRbRc)n- or -NRa-C(O)-(CRbRc)n-; n = 1-6; each among Ra, Rb and Rc means independently hydrogen atom or alkyl, or their pharmaceutically acceptable salt or solvates, and to compounds of the formula (II): wherein R1, R2, Rb, Rc and A have above given values; each R3 and R4 means independently hydrogen atom or alkoxycarbonyl; Ra means hydrogen atom, alkyl or cycloalkyl. These compounds are effective modulators of IP receptors and firstly antagonists of IP receptors. Except for, invention involves pharmaceutical compositions containing indicated compounds.

EFFECT: valuable biological and medicinal properties of compounds and pharmaceutical composition.

11 cl, 1 tbl, 10 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds 2,6-di-tert.-butyl-4-{2-[2-(methylamino)ethyl]-1,3-thiazole-4-yl}phenol, 2,6-di-tert.-butyl-4-[4-(hydroxymethyl)-1,3-oxazole-2-yl]phenol, 4-methylphenyl-2-[4-(1,1-biphenyl-4-yl)-1H-imidazole-2-yl]ethylcarbamate and others or their pharmaceutically acceptable salts. Also, invention relates to using these compounds for preparing a medicinal agent possessing one of the following three activities: inhibition of monoamine oxidases activity, inhibition of lipids peroxidation and modulating activity with respect to sodium channels. Proposed derivatives of thiazole, oxazole or imidazole possess one of the following species of pharmacological activity: inhibition of monoamine oxidases activity, inhibition of lipids peroxidation and modulation of sodium channels.

EFFECT: valuable biochemical and biological properties of derivatives.

34 cl, 119 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 2-phenylaminoimidazoline phenylketone that can be used as IP antagonists. Invention describes 2-phenylaminoimidazoline phenylketone of the general formula (I): wherein R1 mean optionally substituted aryl wherein R1 is optionally substituted with 1, 2 or 3 substitutes chosen independently from series including alkoxy-group, aryl aryloxy-, aralkyloxy-group, halogen atom, ethylenedioxy-group or optionally substituted heterocyclyl that means a monovalent saturated carbocyclic radical comprising from 3 to 7 atoms in cycle and comprising one or two heteroatoms chosen independently from nitrogen and oxygen atoms, and can be optionally substituted with one or more substitutes chosen independently from alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl sulfonyl, furanyloxy-group; R2 means hydrogen atom; A means -C(O)-(CH2)n- or -C(O)-CH2-O-; index n means a whole number from 2 to 6, or its pharmaceutically acceptable salt or solvate. Invention provides preparing novel compounds showing useful biological properties.

EFFECT: valuable properties of compounds.

16 cl, 1 tbl, 23 ex

The invention relates to derivatives of 2-(arylvinyl)aminoimidazole formula I, where R1denotes a group of formula (A), (B) or (C), a R2, R3, R4, R5, R6and X are such as defined in the claims

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) or to its stereoisomers, or to a pharmaceutically acceptable salt, wherein Ra represents H or (C1-C6)alkyl; Rb is specified in an optionally substituted group consisting of -(CH2)n-aryl, -CH(CH3)-aryl, -(CH2)n-arylaryl, -(CH2)n-arylheteroaryl, -(CH2)n-(C3-C8) cycloalkyl, -(CH2)n-heteroaryl, -(CH2)n-heterocyclyl and -(C3-C8) cycloalkylaryl; or Ra and Rb taken together with a nitrogen atom form 2,3-dihydro-1H-isoindolyl, decahydroisoquinolinyl, optionally substituted piperidinyl or optionally substituted pyrrolidinyl; Y is specified in an an optionally substituted group consisting of 5,6,7,8-tetrahydro[1,6]naphthyridinyl, -NH-(CH2)n-heterocyclyl, wherein NH is attached to carbonyl, and -heterocyclylaryl, wherein heterocyclyl is attached to carbonyl; and n is equal to 0, 1 or 2; wherein each heterocyclyl represents an independent non-aromatic ring system containing 3 to 12 ring atoms, and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; wherein each heteroaryl represents an independent non-aromatic ring system containing 3 to 12 ring atoms and at least one ring atom specified in a group consisting of nitrogen, oxygen and sulphur; and wherein the optional substitutes are independently specified in a group consisting of C1-C6-alkyl, C1-C6-alkoxy, halogen, CN, CF3, OCF3, NH2, NH(CH3), N(CH3)2, hydroxy, cyclohexyl, phenyl, pyrrolidinyl, -C(O)-piperidinyl, -N(H)-C(O)-C1-C6-alkyl and N(H)-S(O)2-C1-C6-alkyl. The invention also describes a pharmaceutical composition having chemokine receptor antagonist activity and a method of treating such diseases, such as rheumatoid arthritis, psoriasis, lupus, etc.

EFFECT: there are prepared and described new chemical compounds that can be used as chemokine receptor antagonists and, as such, may be used in treating certain pathological conditions and diseases, particularly inflammatory pathological conditions and diseases and proliferative disorders and conditions, eg rheumatoid arthritis, osteoarthritis, multiple sclerosis and asthma.

23 cl, 59 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, biotechnology, as well as to pharmaceutical, food and cosmetic industries, and concerns an agent made of sea urchin viscera being waste after edible gonads have been separated. The agent with anti-inflammatory and immunotropic activity is characterised by the fact that it represents an alcoholic extract prepared of sea urchin viscera after gonad separation, containing 10-15% of peptides, 35-45% of amino acids, 4-8% of phospholipids, trace substances, and has the following characteristics: molecular weight of the peptide fractions as determined by polyacrylamide gel electrophoresis is 19-15 kDa, 6-3,5 kDa and less than 3.5 kDa. The agent is prepared by separating gonads from sea urchins, taking the viscera, extraction in ethanol in ratio 1:1-3 at temperature 0 to plus 10°C for 2 h to 10 days, separation of a liquid portion to produce a water-alcohol extract, alcohol distillation, and drying.

EFFECT: invention provides preparing the safe agent with the evident therapeutic effect.

3 cl, 7 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is an antimicrobial, anti-inflammatory and analgesic agent of a benzamidine derivative of empirical formula (C13H11N3O2), namely N-4-nitrophenylbenzamidine (I) as an active substance. It is shown that N-4-nitrophenylbenzamidine is low-toxic; it possess antimicrobial (on Gram-positive and Gram-negative bacteria), anti-inflammatory and analgesic activity.

EFFECT: these properties make it possible to suggest that N-4-nitrophenylbenzamidine may be used in medicine, as an ingredient of the drug preparation for specified application.

2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention discloses a product of modification of sulphanilic acid, and specifically n-(1,5-dihydro-3-methyl-8-R1-8-R2-9-hydroxy-[1,3]dioxepino[5,6-c]pyridinyl-6-azo)phenylsulphonic acid and salt forms thereof of general formula I: , where R1, R2 are selected from a group comprising: a hydrogen atom, methyl, a linear or branched alkyl or R1 and R2 together form a spirocycloalkyl group. Compounds of formula (I) have antibacterial activity, are more efficient with respect to both gram-negative bacteria Proteus vulgaris, Pseudomonas aeroginosa and gram-positive bacteria Staphylococcus aureus, and can be used in medicine and veterinary.

EFFECT: improved properties.

1 cl, 1 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to novel pyridyloxy derivatives or its pharmaceutically acceptable ester or a pharmaceutically acceptable salt of the mentioned derivatice or ester of general formula (I), wherein R represents a pyridyl group substituted by 1-3 groups independently specified in a group of substitutes A; the group of substitutes A represents a group comprising halogen atom, C1-C6 alkyl group and C1-C6 alkoxy group, and Me represents a methyl group. Also, the invention refers to specific compounds of formula (I), to a pharmaceutical composition and a receptor-γ activator/modulator on the basis of a compound of formula (I), to a method of treating and/or preventing a disease.

EFFECT: there are prepared novel pyridyloxy derivatives effective in treating the disease mediated by peroxisome proliferator activated receptor-γ (PPAR) γ.

37 cl, 2 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new lipid compound of general formula , wherein n=0; R1 and R2 are identical or different, and may be specified in a group of substitutes consisting of a hydrogen atom, a C1-C7alkyl group, a halogen atom and a C1-C7alkoxy group; X represents COR3 or CH2OR4, wherein R3 is specified in a group consisting of hydrogen, hydroxy, C1-C7alkoxy and amino; and R4 is specified in a group consisting of hydrogen, C1-C7alkyl or C1-C7acyl, Y represents C9-C21 alkene with one or more double bonds in E- or Z-configurations with the chain Y being unsubstituted and containing a double bond in the ω-3 position; provided R1 and R2 cannot simultaneously represent a hydrogen atom.

EFFECT: invention refers to pharmaceutical compositions containing the lipid compounds which are used for treating and/or preventing the conditions related to high NFkB functions, treating and/or preventing an inflammatory disease or a condition, lower plasma insulin and/or blood glucose levels, treating insulin resistance, treating and/or preventing peripheral tissue insulin resistance and/or diabetic condition, eg type 2 diabetes mellitus.

45 cl, 1 tbl, 1 dwg, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new N-aryl-2,3-diaroyl-8,10-dimethylpyrido[2',3':3,4]pyrazolo[1,5-α]pyrimidine-4-carboxamides of formula I possessing analgesic activity, and to a method for preparing them. In formula I Ar1=Ph, C6H4Me-4, C6H4OMe-4; Ar2-Ph, C6H4Me-4, C6H3(Me)2-2,5. The method for preparing said compounds consists in a reaction of 1-aryl-4,5-diaroyl-1H-pyrrol-2,3-diones with 3-amino-4,6-dimethyl-2H-pyrazolo[3,4-6]pyridine at temperature 108-110°C in an absolute toluene medium.

EFFECT: there are prepared the compounds possessing analgesic activity.

4 cl, 1 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to tricyclic spiro-derivatives of formula (I') wherein: R1 means H, C1-C6-alkyl, C1-C6-alkoxy, halogen-C1-C6-alkyl, halogen-C1-C6-alkoxy, halogen; m is equal to 0-4; R2 means A; A means , : n is equal to 1-4; R4 means C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C6-C10-aryl, 5, 6-member heteroaryl containing one, two and three heteroatoms independently specified in N, O, S, which may be condensed with a benzene ring; R4 may be substituted by one or more groups R6; R6 means C1-C6-alkyl, C1-C6-alkoxy, C6-C10-aryl, C6-C10-aryl-C1-C6-alkyl, C3-C8-cycloalkyl, CN, halogen, aminocarbonyl, C1-C6-acylamino, C1-C6-alkylsulphonyl, trihalogen-C1-C6-alkyl, -O-phenyl wherein phenyl may be substituted by one or two substituted specified in halogen, C1-C6-alkoxy; R7 means H, and C1-C6-alkyl; R means B; B means: , n is equal to 1-4; R5 means COOH, tetrazole; X means CH2, NH; Y means C(O); Z means C(O); as well as its geometric isomers, optically active forms, such as enantiomers, diastereomers, its racemate forms, or its pharmaceutically acceptable salts.

EFFECT: compounds are used for treating and/or preventing allergic diseases, inflammatory dermatoses and other diseases with an inflammatory component.

23 cl, 3 tbl, 125 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to dimethyl 4-acyl-1-hydroxy-3-methyl-7-oxo-6-phenyl-2,6-diazabicyclo[3.2.1]oct-3-ene-5,8-dicarboxylates of formula wherein Ar=Ph, C6H4Me-4, C6H4OMe-4, C6H4C1-4, C6H4Br-4; R=Me, Ph, as well as to a method for preparing them by setting a benzene solution of 1-aryl-4,5-bis(methoxycarbonyl)-1H-pyrrol-2,3-dions and 4-aminopent-3-en-2-one or 3-amino-1-phenylbut-2-en-1-one at room temperature.

EFFECT: compounds may be used as raw products for synthesis of new heterocyclic systems in pharmacology as potential drug preparations possessing analgesic activity.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to veterinary science, and concerns treating corneal diseases in dogs. For this purpose, mesenchymal cord and placental stem cells received after easy human delivery are used. The mesenchymal stem cells are introduced retrobulbarly in saline solution 1-2 ml containing 0.075-0.20×106 cell/kg. The cells are introduced 1-2 times annually.

EFFECT: method provides the effective treatment of corneal diseases in dogs by creating the depot stem cells in a close proximity to the lesion.

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and is intended for treatment of inflammatory and trophic cornea diseases. For this purpose silicone-hydrogel soft contact lens, covered from inner surface by silico-dried amnion, is placed on cornea. Amnion with diameter smaller than lens diameter is used. Amnion is fixed on lens by means of polyacrylamide film, saturated with medication. As such means, used is antibacterial, anti-inflammatory, regenerating medication.

EFFECT: method ensures elimination of amnion dislocation under lens and reduction of time of corneal defect epithelisation, which increases treatment efficiency.

3 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly ophthalmology, and aims at conservative treatment of dacryostenosis. Ofloxacin ophthalmic gel is introduced into a lachrymal duct. Ofloxacin ophthalmic gel 3ml is introduced every second day, 8-10 times.

EFFECT: method provides recovered patency of the lachrymal ducts and prevented recurrent postoperative stenosis following dacryorhinocystostomy, including due to mechanical dilatation of the duct by means of the gel the physical characteristics of which differ from those of tears.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a multidose ophthalmic composition containing prostaglandin as a therapeutic ingredient, mannitol or sorbitol 0.15-0.5 wt/vol %, propylene glycol or glycerol 0.2-1.8, borate 0.25-0.5 wt/vol %, an antimicrobial preserving agent 0.0003-0.003 wt/vol % representing a polymer quaternary ammonium compound and water. Said composition has pH 6.4-7.2 and is benzalconium chloride free. Besides, the invention refers to the use of said ophthalmic composition for preparing a drug for treating glaucoma, eye infections, allergies and inflammations.

EFFECT: preparing the ophthalmic composition which exhibits improved antimicrobial preserving activity and improved buffer properties.

16 cl, 8 tbl, 21 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely ophthalmology, and may be used for treating, stabilising and/or preventing macular degeneration. The therapy involves introduction of a therapeutically effective amount of the C5 agent in a combination with a VEGF agent in an individual in need thereof. The C5 agent is bound with C5 complement and has the sequence SEQ ID N0:4 or SEQ ID N0:67.

EFFECT: invention provides an additive or synergetic effect ensured by the combination that leads to improved visual acuity especially in the patients suffering wet age-related macular degeneration (AMD) as compared with the VEGF monotherapy.

67 dwg, 8 ex

Up!