Heteroarylalkylcarbamate derivatives, their obtaining and their application as enzyme faah inhibitors


FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , in which A is selected from one or several X and/or Y groups; X represents methylene group; Y represents C2-alkinylene group; n represent integer number from 1 to 5; R1 represents group R2, optionally substituted with one or several R3 and/or R4 groups; R2 represents group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphtyl, chinolinyl, isochinolinyl, dihydroisochinolinyl, 2-oxo-3,4-dihydrochinolinyl, indolyl, benzimidazolyl, pyrrolopyridinyl; R3 represents group selected from halogen atoms, groups C1-6-alkyl, C3-7-Cycloalkyl, C1-6-alkoxy, NR5R6 and phenyl; R4 represents group selected from groups: phenyl, naphtyl, pyridinyl; R4 group or groups can be substituted with one or several R3 groups, similar or different from each other; R5 and R6 independently on each other represent C1-6-alkyl group; R7 represents hydrogen atom or C1-6-alkyl group; R8 represents hydrogen atom or group C1-6-alkyl, C3-7-cycloalkyl, C3-7-Cycloalkyl- C1-3-alkylene; in form of base, acid-additive salt, hydrate or solvate. Invention also relates to methods of obtaining formula (I) compound by any of ii. 1-3, to compounds, determined by general formula (IV), (VII), to pharmaceutical composition, as well as to application of formula (I) compounds by any of ii. 1-3.

EFFECT: obtaining novel biologically active compounds possessing activity of enzyme FAAH inhibitors.

10 cl, 5 ex, 1 tbl

 

The object of the invention are derivatives of aryl - and heteroarylboronic, obtaining them and their use in therapy.

Already known derivatives phenylalkylamines and dioxane-2-allylcarbamate described respectively in documents FR2850377 A and WO2004/020430 A2, which are inhibitors of the enzyme FAAH (Fatty Acid Amido Hydrolase).

The need to identify and develop inhibitors of the enzyme FAAH always exists. Compounds according to the invention meet this goal.

Compounds according to the invention correspond to General formula (I):

in which

A is selected from one or more groups X, Y and/or Z;

X represents a methylene group, optionally substituted by one or two groups representing C1-6-alkyl, C3-7- cycloalkyl or C3-7-cycloalkyl-C1-3-alkylen;

Y denotes either C2-alkynylamino group, optionally substituted by one or two groups representing C1-6-alkyl, C3-7-cycloalkyl or

C3-7-cycloalkyl-C1-3-alkylene, or C2-alkynylamino group;

Z means a group of the formula:

m means an integer from 1 to 5;

p and q denote integers and are defined so that p+q is a number from 1 to 5;

n means an integer from 1 to 7;

R1means the group R2, optionally substituted ar is Oh or more groups R 3and/or R4;

R2means a group selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, teinila, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazoline, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthyl, chinoline, tetrahydroquinoline, izochinolina, tetrahydroisoquinoline, 2-oxo-3,4-dihydroquinoline,

1-oxo-3,4-dihydroisoquinoline, heatline, khinoksalinona, phthalazine, cinnoline, naphthyridine, benzofuranyl, dihydrobenzofuranyl, benzothiazyl, dihydrobenzofuranyl, indolyl, indolinyl, indazole, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazole, benzothiazole, benzisothiazole, benzotriazolyl, benzoxadiazole, benzothiadiazole, pyrrolopyridine, properidine, thienopyridine, imidazopyridine, oxazolopyridine, triazolopyridine, pyrazolopyrimidine, isoxazolidine, isothiazolinone;

R3means a group selected from halogen atoms of groups representing cyano-, nitro-, C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, hydroxyl, C1-6-thioalkyl,

C1-6-foralkyl, C1-6-feralcode, C1-6-vertially, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, COsub> 2R5, CONR5R6, SO2R5, SO2NR5R6, -O-(C1-3-alkylene)-Oh and phenyl, and phenyl group optionally substituted by one or more halogen atoms;

R4means a group selected from the group: phenyl, phenyloxy, benzyloxy, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl; and the group or groups R4can be substituted by one or more groups R3the same or different from each other;

R5and R6independently from each other mean a hydrogen atom or a C1-6is an alkyl group, or together with the atom or atoms to which they are linked, form a cycle selected from azetidine, pyrolidine, piperidino, morpholino, thiomorpholine, azepino or pieperazinove cycle, and this cycle is optionally substituted C1-6is an alkyl or benzyl group;

R7means a hydrogen atom or a C1-6is an alkyl group;

R8means a hydrogen atom or a group C1-6-alkyl,

C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkylen.

Thus, in the framework of the invention compounds of General formula (I) can contain multiple groups A, same or different from each other.

Of the compounds of General formula (I) first subgroup of compounds is formed by compounds in which:

And you are the wounds of one or more groups X and/or Y;

X represents a methylene group;

Y represents C2-alkynylamino group;

n means an integer from 1 to 5;

R1means the group R2, optionally substituted by one or more groups R3and/or R4;

R2means a group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, chinoline, izochinolina, dihydroisoquinoline, 2-oxo-3,4-dihydroquinoline, indolyl, benzimidazolyl, pyrrolopyridine;

R3means a group selected from halogen atoms, particularly chlorine atoms and fluorine, C1-6-alkyl groups, in particular methyl, C3-7-cycloalkyl, in particular cyclopropyl, C1-6-alkoxy, in particular methoxy, NR5R6and phenyl;

R4means a group selected from the group: phenyl, naphthyl, pyridinyl; and the group or groups R4can be substituted by one or more groups R3the same or different from each other;

R5and R6independently of one another denote C1-6-alkyl group, in particular methyl;

R7means a hydrogen atom or a C1-6is an alkyl group;

R8means a hydrogen atom or a group C1-6-alkyl, C3-7-cycloalkyl,

C3-7-cycloalkyl-C1-3-alkylen.

Of the compounds of the soup of the formula (I), a second subgroup of compounds is formed by compounds in which:

A, X, Y, Z, m, p, q, n, R1, R3, R4, R5, R6, R7, R8such as defined in the General formula (I) or in the first sub-group as defined above,

and R2means a group selected from pyridinyl, pyrimidinyl, oxazolyl, isoxazolyl, naphthyl, chinoline, izochinolina.

Of the compounds of General formula (I) third subgroup of compounds is formed by compounds in which:

A, X, Y, Z, m, p, q, n, R1, R2, R3, R4, R5, R6such as defined in the General formula (I) or subgroups, which are defined above;

R7means a hydrogen atom;

R8means a hydrogen atom or a C1-6-alkyl group, in particular methyl.

Of the compounds defined above subgroups include the following compounds:

- [2-(methylamino)-2-oxoethyl]-[(5-vinylpyridin-2-yl)methyl]carbamate,

- [2-(methylamino)-2-oxoethyl]-2-(5-vinylpyridin-2-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(6-vinylpyridin-3-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(2-phenylpyrimidine-5-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(5-phenylpyrimidine-2-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-[6-(4-chlorophenyl)pyrimidine-4-yl]ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-[6-(4-chlorophenyl)-2-(dimethylene is about)pyrimidine-4-yl]ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-(2-isoquinoline-7-retil)carbamate,

- [2-(methylamino)-2-oxoethyl]-2-(2-phenyl-1,3-oxazol-4-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-[5-(4-chlorophenyl)isoxazol-3-yl]ethylcarbamate,

- (2-amino-2-oxoethyl)-(3-pyridin-2-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-pyridin-3-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-pyridin-4-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-pyrimidine-5-ylpropyl)carbamate,

- [2-(methylamino)-2-oxoethyl]-3-[6-(4-chlorophenyl)pyrimidine-4-yl]propellernet,

- [2-(methylamino)-2-oxoethyl]-3-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]propellernet,

- [2-(methylamino)-2-oxoethyl]-3-[6-(4-chlorophenyl)-2-(dimethylamino)pyrimidine-4-yl]propellernet,

- (2-amino-2-oxoethyl)-(3-quinoline-2-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-quinoline-4-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-isoquinoline-1-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-isoquinoline-4-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-3-[5-(4-chlorophenyl)isoxazol-3-yl]propellernet,

- (2-amino-2-oxoethyl)-3-[3-(4-chlorophenyl)isoxazol-5-yl]propellernet,

- [2-(methylamino)-2-oxoethyl]-3-[3-(4-chlorophenyl)isoxazol-5-yl]propellernet,

- [2-(methylamino)-2-oxoethyl]-3-[3-(4-phenylphenyl)isoxazol-5-yl)propellernet,

- [2-(methylamino)-2-oxoethyl]-3-[3-(naphthalene-2-yl)isoxazol-5-yl]propellernet,

- (2-amino-2-oxoethyl)-(4-pyridine-2-libutil carb is Mat

- (2-amino-2-oxoethyl)-(4-pyridine-3-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-pyridin-4-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-pyrimidine-5-libutil)carbamate,

- [2-(methylamino)-2-oxoethyl]-4-[6-(4-chlorophenyl)pyrimidine-4-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[6-(4-chlorophenyl)-2-cyclopropylamino-4-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[6-(4-chlorophenyl)-2-(dimethylamino)pyrimidine-4-yl]BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-(4-(quinoline-2-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-quinoline-4-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-isoquinoline-1-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-isoquinoline-4-libutil)carbamate,

- [2-(methylamino)-2-oxoethyl]-4-[5-(4-chlorophenyl)isoxazol-3-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[3-(4-chlorophenyl)isoxazol-5-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[3-(4-phenylphenyl)isoxazol-5-yl]BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-[3-(naphthalene-2-yl)isoxazol-5-yl]BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-(5-pyridin-2-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-pyridin-4-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-pyrimidine-5-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-quinoline-2-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-quinoline-4-alpental)carbamate,

- (2-amino-2-octoate the)-(5-isoquinoline-1-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-isoquinoline-4-alpental)carbamate,

- (2-amino-2-oxoethyl)-(3-naphthalene-1-rprop-2-in-1-yl)carbamate,

- [2-(methylamino)-2-oxoethyl]-(3-naphthalene-1-rprop-2-in-1-yl)carbamate,

- (2-amino-2-oxoethyl)-(5-naphthalene-1-ipent-4-in-1-yl)carbamate,

- [2-(methylamino)-2-oxoethyl]-(5-naphthalene-1-ipent-4-in-1-yl)carbamate,

- [2-(methylamino)-2-oxoethyl]-[5-(4-fornatale-1-yl)Penta-4-in-1-yl]carbamate,

- [2-(methylamino)-2-oxoethyl]-[3-(pyridin-3-yl)-isoxazol-5-ylpropyl]carbamate,

- [2-(methylamino)-2-oxoethyl]-[3-(4-methoxynaphthalene-1-yl)-isoxazol-5-ylpropyl]carbamate.

Of the compounds of General formula (I) one subfamily of compounds is formed by compounds corresponding to General formula (I'):

in which

And selected from one or more groups X, Y and/or Z;

X represents a methylene group, optionally substituted by one or two groups of C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylen;

Y represents C2-alkynylamino group, optionally substituted by one or two groups representing C1-6-alkyl, C3-7-cycloalkyl or

C3-7-cycloalkyl-C1-3-alkylene, or C2-alkynylamino group;

Z means a group of the formula:

m means an integer from 1 to 5;

p and q denote integers, and defined the AK, that p+q is a number from 1 to 5;

n means an integer from 1 to 7;

R1means the group R2, optionally substituted by one or more groups R3and/or R4;

R2means a group selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, teinila, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazoline, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthyl, chinoline, tetrahydroquinoline, izochinolina, tetrahydroisoquinoline, 2-oxo-3,4-dihydroquinoline,

1-oxo-3,4-dihydroisoquinoline, heatline, khinoksalinona, phthalazine, cinnoline, naphthyridine, benzofuranyl, dihydrobenzofuranyl, benzothiazyl, dihydrobenzofuranyl, indolyl, indolinyl, indazole, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazole, benzothiazole, benzisothiazole, benzotriazolyl, benzoxadiazole, benzothiadiazole, pyrrolopyridine, properidine, thienopyridine, imidazopyridine, oxazolopyridine, triazolopyridine, pyrazolopyrimidine, isoxazolidine, isothiazolinone;

R3means a group selected from halogen atoms or groups: cyano-, nitro-, C1-6-alkyl, C1-6-alkoxy, hydroxyl, C1-6-thioalkyl, C1-6-foralkyl, C1-6-perlmx is, C1-6-vertially, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6,

SO2R5, SO2NR5R6, -O-(C1-3-alkylene)-O;

R4means a group selected from the group: phenyl, phenyloxy, benzyloxy, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl; and the group or groups R4can be substituted by one or more groups R3the same or different from each other;

R5and R6independently from each other mean a hydrogen atom or a C1-6-alkyl group or together with the atom or atoms to which they are linked, form a cycle selected from azetidine, pyrolidine, piperidino, morpholino, thiomorpholine, azepino or pieperazinove cycle, and this cycle is optionally substituted C1-6is an alkyl or benzyl group;

R7means a hydrogen atom or a C1-6is an alkyl group;

R8means a hydrogen atom or a group C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkylen.

Of the compounds of General formula (I') the first subgroup of compounds is formed by compounds in which:

And selected from one or more groups X and/or Y;

X represents a methylene group;

Y represents C2-quinil the new group;

n means an integer from 1 to 5;

R1means the group R2, optionally substituted by one or more phenyl groups, in particular phenyl;

R2means a group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, oxadiazolyl, naphthyl, chinoline, izochinolina, dihydroisoquinoline, 2-oxo-3,4-dihydroquinoline, indolyl, benzimidazolyl, pyrrolopyridine;

R7means a hydrogen atom or a C1-6is an alkyl group;

R8means a hydrogen atom or a group C1-6-alkyl,

C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkylen.

Of the compounds of General formula (I') the second subgroup of compounds is formed by compounds in which:

A, n and R1such as defined in the first subgroup, defined above;

R7means a hydrogen atom;

R8means a hydrogen atom or a C1-6-alkyl group, in particular methyl.

Of the compounds of General formula (I') include the following compounds:

- [2-(methylamino)-2-oxoethyl]-[(5-vinylpyridin-2-yl)methyl]carbamate,

- [2-(methylamino)-2-oxoethyl]-2-(5-vinylpyridin-2-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(6-vinylpyridin-3-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(6-phenylpyridazin-3-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(2-phenylpyrimidine-5-yl)these is a carbamate,

- [2-(methylamino)-2-oxoethyl]-2-(5-phenylpyrimidine-2-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-(2-isoquinoline-7-retil)carbamate,

- [2-(methylamino)-2-oxoethyl]-2-(4-phenyl-1H-imidazol-1-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(2-phenyl-1,3-oxazol-4-yl)ethylcarbamate,

- [2-(methylamino)-2-oxoethyl]-2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethylcarbamate,

- (2-amino-2-oxoethyl)-(3-pyridin-2-ylpropyl),

- (2-amino-2-oxoethyl)-(3-pyridin-3-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-pyridin-4-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-pyrimidine-5-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-quinoline-2-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-quinoline-4-ylpropyl)carbamate,

- (2-amino-2-oxoethyl)-(3-isoquinoline-1-ylpropyl)carbamate,

- [2-(methylamino)-2-oxoethyl]-(3-isoquinoline-4-ylpropyl)carbamate,

- [2-(methylamino)-2-oxoethyl]-3-(4-phenyl-1H-imidazol-1-yl)propellernet,

- [2-(methylamino)-2-oxoethyl]-3-(1H-benzimidazole-1-yl)propellernet,

- (2-amino-2-oxoethyl)-(4-pyridine-2-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-pyridine-3-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-pyridin-4-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-pyrimidine-5-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-(quinoline-2-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-quinoline-4-libutil)carbamate,

- (2-amino-2-oxoethyl)-(4-isoquinoline-1-libutil)carbamate,

- (2-amino-2-octoate the)-(4-isoquinoline-4-libutil)carbamate,

- [2-(methylamino)-2-oxoethyl]-4-(1H-benzimidazole-1-yl)BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-4-(1H-indol-1-yl)BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-(1H-indol-1-yl)BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-4-(1H-pyrrolo[2,3-b]pyridine-1-yl)BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-(1H-pyrrolo[2,3-b]pyridine-1-yl)BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-(3,4-dihydroisoquinoline-2(1H)-yl)BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-4-(2-oxo-3,4-dihydroquinoline-1-(2H)-yl)BUTYLCARBAMATE,

- [2-(methylamino)-2-oxoethyl]-4-(2-oxo-3,4-dihydroquinoline-1(2H)-yl)BUTYLCARBAMATE,

- (2-amino-2-oxoethyl)-(5-pyridin-2-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-pyridin-4-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-pyrimidine-5-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-quinoline-2-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-quinoline-4-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-isoquinoline-1-alpental)carbamate,

- (2-amino-2-oxoethyl)-(5-isoquinoline-4-alpental)carbamate,

- (2-amino-2-oxoethyl)-(3-naphthalene-1-rprop-2-in-1-yl)carbamate,

- [2-(methylamino)-2-oxoethyl]-(3-naphthalene-1-rprop-2-in-1-yl)carbamate,

- (2-amino-2-oxoethyl)-(5-naphthalene-1-ipent-4-in-1-yl)carbamate,

- [2-(methylamino)-2-oxoethyl]-(5-naphthalene-1-ipent-4-in-1-yl)carbamate.

Compounds of General formula (I) may contain one or more asymmetric carbons. They can exist in the form of Aisne is tomarow or diastereomers. These enantiomers or diastereoisomers, and also mixtures thereof, including racemic mixtures, form part of the invention.

The compounds of formula (I) may exist in the form of bases or acid additive salts. Such additive salts are part of the invention.

These salts are preferably derived from pharmaceutically acceptable acids, but the salts of other acids that are suitable, for example, for the purification or separation of compounds of formula (I), also form part of the invention.

Compounds of General formula (I) can be in the form of a hydrate or of a solvate, namely in the form of aggregates or other combination with one or more water molecules or with a solvent. Such hydrate and solvate are also part of the invention.

In the context of the invention means that:

- Ct-zwhere t and z can take values from 1 to 7, means a carbon chain which can have from t to z carbon atoms, for example C1-3means a carbon chain which can have from 1 to 3 carbon atoms;

- alkyl means saturated aliphatic group, linear or branched; for example, With1-6is an alkyl group means a carbon chain with 1-6 carbon atoms, linear or branched, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl;

- alkylen means divalent who assistnow alkyl group, linear or branched, for example With1-3-Allenova group means a divalent carbon chain of 1-3 carbon atoms, linear or branched, in particular methylene, ethylene, 1-mutilation, propylene;

- cycloalkyl means a cyclic alkyl group, for example, C3-7-cycloalkyl group means a cyclic carbon group having 3-7 carbon atoms, in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl;

- albaniles means a divalent unsaturated aliphatic group with 2 carbon atoms, in particular ethylene;

- C2-Akinyele means the group-C≡C-;

- alkoxy means an-O-alkyl group with a saturated aliphatic chain, linear or branched;

- thioalkyl means-S-alkyl group with a saturated aliphatic chain, linear or branched;

- foralkyl means an alkyl group in which one or more hydrogen atoms replaced by fluorine atom;

- feralcode means alkoxygroup, in which one or more hydrogen atoms replaced by fluorine atom;

- vertially means thioalkyl group in which one or more hydrogen atoms replaced by fluorine atom;

the halogen atom means fluorine, chlorine, bromine or iodine.

Compounds according to the invention can be obtained in different ways, proillyustriroval is generated by the following schema.

Scheme 1

The first method (scheme 1) obtain the compounds of General formula (I) is to be introduced into the reaction of the amine of General formula (II)in which R1A and n are such as defined in the General formula (I), with a carbonate of General formula (III)in which V denotes a hydrogen atom or a nitro-group, R7such as defined in the General formula (I), and R denotes a methyl or ethyl group. Then, the thus obtained urethane ester of General formula (IV) is converted into compound of General formula (I) by aminolysis an amine of General formula R8NH2where R8this is as defined in General formula (I). The reaction aminolysis can be carried out in a solvent such as methanol or ethanol, or a mixture of solvents, such as methanol and tetrahydrofuran.

Another method (scheme 2) obtain the compounds of General formula (I) consists in the introduction into the reaction of a derivative of General formula (V)in which R1, n and A are as defined in General formula (I), and W denotes hydroxyl, mesilate, tosylate group or a chlorine atom, bromine or iodine, with oxazolidinediones General structure (VI)in which R7this is as defined in General formula (I), to obtain the derivative of oxazolidinedione General structure (VII).

In the case when W stands for hydroxyl group, the reaction can be carried out, ledua conditions of Mitsunobu (Synthesis 1981, 1-28), for example, under the action of diethylazodicarboxylate or diisopropyl in the presence of triphenylphosphine. In the case where W stands for a chlorine atom, bromine or iodine or mesilate or tosylate group, the reaction can be carried out in the presence of a base, such as 1,1,3,3-tetramethylguanidine, hydride or sodium tert-piperonyl sodium in a solvent such as tetrahydrofuran, acetonitrile or dimethylformamide at a temperature of from 0 to 80°C. Then, the thus obtained derivative of oxazolidinedione General formula (VII) is converted into compound of General formula (I) by aminolysis an amine of General formula R8NH2where R8this is as defined in General formula (I).

Scheme 2

Compounds of General formula (I), (IV) and (VII)in which R1means a group of the type aryl-aryl, aryl-heteroaryl, heteroaryl-aryl or heteroaryl-heteroaryl, can also be obtained by reaction of the corresponding compounds of General formula (I), (IV) or (VII)in which R2substituted by chlorine atom, bromine, iodine or triflate group in the position in which shall be entered the group R4with a derivative of an aryl - or heteroarylboronic acid in the Suzuki reaction conditions (Chem. Rev. 1995, 95, 2457-2483) or a derivative of an aryl - or heteroaryl-trialkylamine under the reaction conditions Stille (Angew. Chem. Int. Ed. 1986, 25,504-524).

Carbon is you General formula (III) can be obtained by any method, described in the literature, for example, by reaction of an alcohol of General formula HOCHR5COOR, where R is a methyl or ethyl group, phenyl - or

4-nitrophenylphosphate, in the presence of a base such as triethylamine or diisopropylethylamine.

Compounds of General formula (II), (V) and (VI)and amines of General formula R8NH2when the retrieval method is not described, can be purchased or described in the literature, or can be obtained by other methods described in the literature or known to the expert.

Compounds of General formula (IV)in which n, A, R1and R7such as defined in the General formula (I), and R denotes a methyl or ethyl group, are novel and also form part of the invention except for the following connections:

- ethyl-2-[({[2-(5-hydroxy-1H-indol-3-yl)ethyl]amino}carbonyl)oxy]propanoate;

- ethyl-2-[({[2-[5-(phenylmethoxy)-1H-indol-3-yl]ethyl)amino}carbonyl)oxy]propanoate.

Compounds of General formula (IV) are useful as intermediates for the synthesis to obtain the compounds of General formula (I).

Compounds of General formula (VII)in which n, A, R1and R7such as defined in the General formula (I)are new and also form part of the invention except for the following connections:

iodide 2-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridine;

iodide 2-[2-(2,4-dioxo--oxazolidinyl)ethyl]-5-ethyl-1-methylpyridine;

iodide 4-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridine;

hydrochloride, 5-methyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;

hydrochloride, 5-methyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 3-(5-imidazo[1,2-a]pyridine-5-alpental)-2,4-oxazolidinedione;

- 3-[2-(5-methyl-4-thiazolyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(1H-pyrrol-2-yl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;

- 3-[3-(2-thienyl)propyl]-2,4-oxazolidinedione;

- 3-[4-(2-thienyl)butyl]-2,4-oxazolidinedione;

- 5-methyl-3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;

- 5-ethyl-3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(3-thienyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-methyl-2-thienyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-acetyl-2-thienyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-bromo-2-thienyl)ethyl]-2,4-oxazolidinedione;

- 5-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-2-thiophenecarboxaldehyde;

- 3-[3-[1-indolinyl)propyl]-2,4-oxazolidinedione;

- 3-[3-[1-indolinyl)propyl]-5-methyl-2,4-oxazolidinedione;

- 3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-5-methyl-2,4-oxazolidinedione;

- 5-ethyl-3-[2-(5-ethyl-2-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-5-isopropyl-2,4-oxazolidinedione;

- 3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 5-ethyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;

-5-ethyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;

-5-isopropyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 5-isopropyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;

- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-2,4-oxazolidinedione.

Compounds of General formula (VII) are useful as intermediates for the synthesis to obtain the compounds of General formula (I).

One subgroup of compounds of General formula (VII) to form compounds in which:

n, A, R1and R7such as defined in the General formula (I), provided that:

when R2mean group pyrrolyl, imidazo[1,2-a]pyridinyl or indolyl, R2substituted by one or more groups R3and/or R4;

when R2is peridiniales group, R2substituted by one or more groups R3and/or R4where R3is not the stands or ethyl;

when R2is teenlove group, R2substituted by one or more groups R3and/or R4where R3is not bromine, stands or a group CHO or

COCH3;

when R2is thiazolinones group substituted by a group R3, R3is not the stands.

In the following examples describe some of the compounds according to the invention. These examples are not limiting and only illustrate the present invention. Microanalysis, IR and NMR spectra and/or LC-MS (liquid chromatography in combination with mass-SP is ctroscopy) confirm the structure and purity of the compounds obtained.

PF (°C) mean melting temperature in degrees Celsius.

The numbers indicated in parentheses in the titles of the examples correspond to the numbers shown in the first column in the table below.

Example 1(compound No. 3)

[2-methylamino)-2-oxoethyl]2-(6-vinylpyridin-3-yl)ethylcarbamate

1.1. phenylmethyl-2-(6-vinylpyridin-3-yl)ethylcarbamate

To a solution of 4.5 g (25,60 mmol) phenylethylenediamine (Org. Proc. Res. & Develop.; 2002, 6, 74-77) in 25 ml of tetrahydrofuran, cooled to about -10°C, are added dropwise in an inert atmosphere a solution of 3.12 g (12,80 mmol)

9-borabicyclo[3.3.1]Manila (BBN) in 100 ml of tetrahydrofuran, maintaining the temperature of the reaction medium below -10°C. Continue to stir at -10°C for 1 hour, then at ambient temperature for 4 hours. Add 18 ml of an aqueous solution of sodium hydroxide (3n) and continue to mix for 1 hour. Then add 4.0 g (17,1 mmol) 5-bromo-2-phenylpyridine and 2.12 g (2.6 mmol) PdCl2(dppf).CH2Cl2(dppf: 1,1'-bis(diphenylphosphino)ferrocene). Continue to stir at ambient temperature for 18 hours.

The reaction mixture is cooled in a bath of ice water, then added dropwise 40 ml of a 2/1 mixture of buffer solution (pH 7) and 30%hydrogen peroxide. Left to mix with the ambient temperature of the tip is of 1 hour. Separate the aqueous phase is then extracted three times with dichloromethane. The organic phases are combined and washed successively with water and saturated aqueous sodium chloride. The organic phase is dried over sodium sulfate and the filtrate concentrated under reduced pressure. Obtained residue purified by chromatography on silica gel, elwira a 20/80 mixture of ethyl acetate and cyclohexane.

Obtain 2.9 g of product as a white solid substance.

PF (°C): 118°C

1.2. 2-(6-vinylpyridin-3-yl)ethanamine

To a solution of 1.8 g (5,42 mmol) phenylmethyl-2-(6-vinylpyridin-3-yl)ethylcarbamate obtained in stage 1.1, in 50 ml of dichloromethane, cooled to about 0°C, are added dropwise 9 ml of 33%Hydrobromic acid in acetic acid. Continue to stir at ambient temperature for 2 hours. Concentrate under reduced pressure, the residue is combined with dichloromethane and saturated aqueous sodium bicarbonate. Separate the aqueous phase and extracted twice its ethyl acetate. The combined organic phases are washed with saturated aqueous sodium chloride, dried over sodium sulfate and the filtrate concentrated under reduced pressure.

Get 0,86 g of the product in the form of oil used in the next stage.

1.3. ethyl-({[2-(6-vinylpyridin-3-yl)ethyl]amino}carbonyl)oxyacetic

Rest the R of 0.85 g (4,29 mmol) of 2-(6-vinylpyridin-3-yl)ethanamine, obtained in stage 1.2, and 1.25 g (5,58 mmol) of ethyl[(phenoxycarbonyl)oxy]acetate (J. Med. Chem., 1999, 42, 277-290) in 40 ml of toluene is heated to 60°C for 12 hours. Brought to ambient temperature, the insoluble fraction is separated by filtration and the filtrate concentrated under reduced pressure. Obtained residue purified by chromatography on silica gel, elwira a 30/70 mixture of ethyl acetate and cyclohexane.

Obtain 1.06 g of product in the form of oil.

1.4. [2-(methylamino)-2-oxoethyl]-2-(6-vinylpyridin-3-yl)ethylcarbamate

To a solution of 1.0 g (a 3.06 mmol) of ethyl({[2-(6-vinylpyridin-3-yl)ethyl]amino}carbonyl)oxoacetate obtained in stage 1.3, 6 ml of methanol, add 4.6 ml (9,17 mmol) of a solution of methylamine (2M) in tetrahydrofuran. Continue to stir at ambient temperature for 4 hours.

After concentration under reduced pressure, the obtained residue is purified by chromatography on silica gel, elwira a 95/5 mixture of dichloromethane and methanol. Get a solid white substance, which is crystallized in ethyl acetate.

Get 0,510 g of the product as white solid substance.

LC-MS: M+H=314

PF (°C): 130-132°C

1H-NMR (CDCl3) δ (ppm): 2,85 (d, 3H); 2.95 and (t, 2H); 3,55 (q, 2H); 4,60 (s, 2H); of 5.05 (Shir. s, 1H); 6,10 (Shir. s, 1H); to 7.50 (m, 3H); of 7.70 (m, 2H); 8.0 a (d, 2H); at 8.60 (s, 1H).

Example 2(compound No. 56)

[2-(methylamino)-2-oxoethyl]-4-(1H-indol-1-yl)BUTYLCARBAMATE

2.1. 1-(4-bromobutyl)-1H-indole

To a solution of 2 g (17,07 mmol) of 1H-indole, and 1.15 ml (51,22 mmol) of 1,4-dibromobutane in 80 ml of dimethylformamide, cooled in a bath of ice water, small portions added 0.96 g (17,07 mmol) of sodium hydroxide. Bath is removed and continue to stir at ambient temperature for 15 hours.

After concentration under reduced pressure, the residue is introduced into water and ethyl acetate. Separate the aqueous phase is twice extracted with her with ethyl acetate, the combined organic phases are washed with saturated aqueous sodium chloride, dried over sodium sulfate and the filtrate concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel, elwira a 1/99 mixture of ethyl acetate and cyclohexane.

Get 3 g of the product as a yellow oil.

2.2. 3-[4-(1H-indol-1-yl)butyl]-1,3-oxazolidin-2,4-dione

A solution of 3 g (11,90 mmol) 1-(4-bromobutyl)-1H-indole obtained in stage 2.1, to 2.41 g (23,80 mmol) of 1,3-oxazolidin-2,4-dione (J. Med. Chem., 1991, 34, 1538-1544) and is 2.74 g (23,80 mmol) 1,1,3,3-tetramethylguanidine in 30 ml of tetrahydrofuran is refluxed for 14 hours in an inert atmosphere.

Concentrate under reduced pressure. The residue is introduced into the ethyl acetate and water, separating the aqueous phase is twice extracted with her with ethyl acetate, the combined organic phases are washed on Ishenim aqueous solution of sodium chloride and dried over sodium sulfate. After evaporation of the solvent, the obtained residue is purified by chromatography on silica gel, elwira mixture 10/90, then 20/80 ethyl acetate and cyclohexane.

Receive 2 g of the product as white solid substance.

2.3. [2-(methylamino)-2-oxoethyl]-4-(1H-indol-1-yl)BUTYLCARBAMATE

Act as described in example 1 (stage 1.4). From 0,90 g (of 3.31 mmol) 3-[4-(1H-indol-1-yl)butyl]-1,3-oxazolidin-2,4-dione obtained in stage 2.2, and 5 ml Ltd (9.93 mmol) of a solution of methylamine (2M) in tetrahydrofuran after chromatography on silica gel with elution with a mixture 98/2 dichloromethane and methanol receive 0,70 g of the product in the form of a solid amorphous white substance.

LC-MS: M+H=304

PF (°C): 64-67°C

1H-NMR (CDCl3) δ (ppm): 1.50 in (m, 2H); 1,90 (m, 2H); 2,80 (d, 3H); 3,20 (q, 2H); 4,20(t, 2H); 4,55 (s, 2H); 5,95 (Sirs, 1H); 6,10 (Sirs, 1H); 6,50 (d, 1H); 7,20 (m, 3H); 7,40 (d, 1H); of 7.70 (d, 1H).

Example 3(compound 71)

[2-amino-2-oxoethyl]-(5-naphthalene-1-ipent-4-in-1-yl)carbamate

3.1. 5-naphthalene-1-ipent-4-in-1-ol

In an argon atmosphere to a suspension of 1.78 g (7 mmol) of 1-iodonaphthalene, to 1.48 ml (10.5 mmol) of triethylamine, of 0.066 g (0.35 mmol) of copper iodide and 0,147 g (0.21 mmol) of dichloride di(triphenylphosphine)palladium (Ph3P)2PdCl2in 4 ml of acetonitrile are added dropwise a solution of 0.59 g (7 mmol) of 4-pentyn-1-ol in 3 ml of acetonitrile . Stirred for 3 hours at ambient temperature, then add 4 g of the sid silicon and evaporated to dryness. The product was then purified by chromatography on silica gel, elwira mixture 80/20, then 60/40 cyclohexane and ethyl acetate to obtain 1.22 g of product as a yellow oil.

3.2. methanesulfonate 5-naphthalene-1-ipent-4-in-1-Il

To a solution of 1.2 g (5,71 mmol) 5-naphthalene-1-ipent-4-in-1-ol, obtained in stage 3.1, and 1.6 ml (11,4 mmol) of triethylamine in 12 ml of dichloromethane, cooled in an ice bath, is added dropwise a solution of 0.85 g (7,42 mmol) dimethanesulfonate in 5 ml of dichloromethane. Stirred for 1 hour at 0°C, then 2 hours at ambient temperature. Then add 25 ml of water and 75 ml of dichloromethane. The organic phase is decanted, washed with 25 ml of water, then with 25 ml of a saturated aqueous solution of sodium chloride. Dried over magnesium sulfate and evaporated to dryness to obtain 1.68 g of product as an orange oil, used directly in the next stage.

3.3. 3-(5-naphthalene-1-ipent-4-in-1-yl)-1,3-oxazolidin-2,4-dione.

Dissolve 1.64 g (5,70 mmol) methansulfonate 5-naphthalene-1-ipent-4-in-1-sludge obtained at the stage 3.2, and 0.72 g (7.1 mmol) of 1,3-oxazolidin-2,4-dione in 9 ml of tetrahydrofuran. Add 1.3 g to (11.4 mmol) of 1,1,3,3-tetramethylguanidine in solution in 3 ml of tetrahydrofuran. Refluxed over night. Add 25 ml of ethyl acetate and 6 g of silicon oxide. Is evaporated to dryness. The residue is purified by chromatography on silica gel, Elya is the ROI mixture 90/10, then 80/20 and 70/30 cyclohexane and ethyl acetate to obtain 1,33 g of the product as white solid substance.

PF (°C): 99-101°C

3.4. (2-amino-2-oxoethyl)-(5-naphthalene-1-ipent-4-in-1-yl)carbamate

Dissolve 0.75 g (2.56 mmol) of 3-(5-naphthalene-1-ipent-4-in-1-yl)-1,3-oxazolidin-2,4-dione obtained in stage 3.3, 18 ml of a 7M solution of ammonia (126 mmol) in methanol. Leave over night at ambient temperature. Then add 3 g of silica and evaporated to dryness. The residue is purified by chromatography on silica gel, elwira mixture 98/2, then 96/4 and 94/6 dichloromethane and methanol. Then recrystallized in a mixture of ethyl acetate and diisopropyl ether to obtain a 0.59 g of the product as white crystals.

LC-MS: M+H=311

PF (°C): 105-108°C

1H-NMR (CDCl3) δ (ppm): 8,33 (d, 1H); a 7.85 (m, 2H); 7,70-7,40 (m, 4H); 5,90 (SIRM, 1H); 5,50 (SIRM, 1H); 5,20 (SIRM, 1H); 4,55 (s, 2H); 3,50 (m, 2H); 2,70 (t, 2H); 1,95 (m, 2H).

Example 4(compound 29)

[2-(methylamino)-2-oxoethyl]-(3-[3-(4-chlorophenyl)isoxazol-5-yl]propyl)carbamate

4.1. 3-[3-(4-chlorophenyl)isoxazol-5-yl]propan-1-ol

To a solution of 1.18 ml (12.6 mmol) of Penta-4-in-1-ol and 2.0 g (10.5 mmol) of the chloride 4-chloro-N-hydroxybenzotriazole (J. Med. Chem. 1998, 41, 4556-4566) in 30 ml of dichloromethane, cooled in an ice bath, is added dropwise 1.6 ml (11.5 mmol) of triethylamine. Leave to interact on a night when the temperature environment is s. Add 50 ml of dichloromethane and 70 ml of water. The organic phase is separated and the aqueous phase is extracted with 2 times 50 ml of dichloromethane. Then the organic phase is washed 2 times with 70 ml of water, then 70 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel, elwira with a mixture of cyclohexane and ethyl acetate, to obtain 1.3 g (vs. 5.47 mmol) of product as a white solid substance.

PF (°C): 60-62°C

4.2. 3-{3-[3-(4-chlorophenyl)isoxazol-5-yl]propyl}-1,3-oxazolidin-2,4-dione

To a solution of 1.30 g (5,47 mmol) 3-[3-(4-chlorophenyl)isoxazol-5-yl]propan-1-ol, obtained in stage 4.1 and 0.9 ml (7,11 mmol) of triethylamine in 70 ml of dichloromethane, cooled in an ice bath, is added dropwise 0.5 ml (6.0 mmol) of methanesulfonamide. Then stirred for 2 hours at ambient temperature. Add 70 ml of water and separate the organic phase. The aqueous phase is extracted 2 times with 70 ml of dichloromethane. Then the organic phase was washed with 100 ml water and 100 ml saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated.

The residue is again dissolved in 60 ml of tetrahydrofuran and added 0.9 g (8.9 mmol) of 1,3-oxazolidin-2,4-dione and 1.1 ml (8,7 mmol) 1,1,3,3-tetramethylguanidine. Heated to 65°C over night. Introducing a mixture of 100 ml of water and 100 ml of ethyl acetate. The organic phase is separated and the aqueous phase was EXT Airout 2 times 80 ml of ethyl acetate. The organic phase was washed with 100 ml of water, then 100 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel, elwira mixture 90,5/0,5 dichloromethane and methanol, to obtain 1.0 g (3.1 mmol) of the product as white solid substance.

4.3. [2-(methylamino)-2-oxoethyl]-{3-[3-(4-chlorophenyl)isoxazol-5-yl]propyl}carbamate

Dissolve 0.6 g (of 1.87 mmol) 3-{3-[3-(4-chlorophenyl)isoxazol-5-yl]propyl}-1,3-oxazolidin-2,4-dione obtained in stage 4.2, in a mixture of 8 ml of tetrahydrofuran and 15 ml of methanol. Added to 2.8 ml of a 2M solution of methylamine (5.6 mmol) in tetrahydrofuran. Left to react overnight at ambient temperature, then evaporated. The residue is purified by chromatography on silica gel, elwira mixture 98/2 then 95/5 and 90/10 dichloromethane and methanol. Will recrystallized in a mixture of ethyl acetate and methanol, to obtain 0,49 g (1.4 mmol) of white crystals.

LC-MS: M+H=352

PF (°C): 158-160°C

1H-NMR (CDCl3) δ (ppm): of 7.75 (d, 2H); was 7.45 (d, 2H); 6,35 (s, 1H); 6,10 (Shir. s, 1H); 5,00 (Shir. s, 1H); 4,60 (s, 2H); to 3.35 (m, 2H); 2,85 (m+d, 5H); is 2.05 (m, 2H).

Example 5(compound 20)

[2-(methylamino)-2-oxoethyl]-(3-[6-(4-chlorophenyl)pyrimidine-4-yl]propyl)carbamate

5.1. 1-(4-chlorophenyl)-6-(tetrahydro-2H-Piran-2-yloxy)Gex-2-in-1-ol

To a solution 13,25 g (78,8 mmol) 2-(Penta-4-in-1 yloxy)tetrahydro-2H-Piran is 130 ml of anhydrous tetrahydrofuran, cooled to -78°C in an atmosphere of argon is added dropwise a 61.5 ml n-utility of 1.6 M (98,4 mmol) in hexane. Continue to mix for 1 hour at -78°C, then added dropwise a solution 12,18 g (86,6 mmol) 4-chlorobenzaldehyde in 40 ml of tetrahydrofuran. Continue to stir for 2 hours at -78°C, then the solution is again heated to 0°C and poured it onto 300 ml of a saturated aqueous solution of ammonium chloride. Extracted with 450 ml of ethyl acetate. The organic phase is washed with 50 ml of water, then 50 ml of a saturated aqueous solution of sodium chloride. Dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel, elwira mix 70/30 n-hexane and ethyl acetate to obtain 16,64 g (53,88 mmol) of the product as a colourless oil.

5.2. 1-(4-chlorophenyl)-6-(tetrahydro-2H-Piran-2-yloxy)Gex-2-in-1-he

To a suspension of 93 g (1.07 mol) of manganese dioxide in 500 ml of dichloromethane, cooled in an ice bath, is added dropwise a solution of 16,60 g (of 53.7 mmol) of 1-(4-chlorophenyl)-6-(tetrahydro-2H-Piran-2-yloxy)Gex-2-in-1-ol, obtained in stage 5.1. Continue to stir for 1.5 h, then filtered through celite and washed with dichloromethane. The filtrate is evaporated to obtain 16.3 g (53,1 mmol) of the product as yellowish oil.

5.3. 4-(4-chlorophenyl)-6-[3-(tetrahydro-2H-Piran-2-yloxy)propyl]pyrimidine

A mixture of 3.60 g (11,73 mmol) 1-(4-chlorophenyl)-6-(is etrahydro-2H-Piran-2-yloxy)Gex-2-in-1-it, obtained at the stage 5.2, of 9.45 g (117 mmol) of the hydrochloride of formamide and 25 g (234 mmol) of sodium carbonate in suspension in 108 ml of acetonitrile and 0.1 ml of water, stirred at 40°C for 5 hours. Then injected into 600 ml of water and 400 ml of a saturated aqueous solution of sodium carbonate. The organic phase is decanted, washed her 200 ml of water and 200 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel, elwira mix 70/30 n-hexane and ethyl acetate to obtain 3,22 g (9,67 mmol) of the product as yellowish oil.

5.4. 3-[6-(4-chlorophenyl)pyrimidine-4-yl]propan-1-ol

Dissolve 3,22 g (9,67 mmol) of 4-(4-chlorophenyl)-6-[3-(tetrahydro-2H-Piran-2-yloxy)propyl]pyrimidine obtained in stage 5.3, in 32 ml of methanol and add 16 ml of 4n hydrochloric acid in dioxane. Stirred for 1.5 hours at ambient temperature, then added in several portions to 150 ml Polynesians aqueous solution of sodium bicarbonate. Extracted with 350 ml of ethyl acetate. The organic phase is washed with 50 ml water and 50 ml saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to obtain 2,33 g (9,36 mmol) of product as a white solid substance.

PF (°C): 75-76°C

5.5. 3-{3-[6-(4-chlorophenyl)pyrimidine-4-yl]propyl}-1,3-oxazolidin-2,4-dione

To a solution of 0,111 g (0.44 mmol) of 3-[6-(4-chlorophenyl)pyrimid is n-4-yl]propan-1-ol, obtained at the stage 5.4, 0,077 g (0,76 mmol) of 1,3-oxazolidin-2,4-dione and 0,235 g (0.89 mmol) of triphenylphosphine in 4 ml of tetrahydrofuran, cooled in an ice bath, add 0.4 ml of 40%aqueous solution of diethylazodicarboxylate (0.9 mmol) in toluene. Then stirred overnight at ambient temperature. Introducing a mixture of ethyl acetate and water. The organic phase is washed with saturated aqueous sodium chloride, dried over sodium sulfate and evaporated. The residue is purified by chromatography on silica gel, elwira a 97/3 mixture of dichloromethane and methanol, to obtain 0,117 g (0.35 mmol) of the product in solid form.

5.6. [2-(methylamino)-2-oxoethyl]-{3-[6-(4-chlorophenyl)pyrimidine-4-yl]propyl}carbamate

Again dissolved 0,113 g (0.34 mmol) of 3-{3-[6-(4-chlorophenyl)pyrimidine-4-yl]propyl}-1,3-oxazolidin-2,4-dione obtained in stage 5.5, in a mixture of 4 ml of ethanol, 1 ml methanol and 1 ml of dichloromethane. Add 2 ml of a 8M solution of methylamine (16 mmol) in ethanol. Stirred for 2 hours at ambient temperature, then evaporated. The solid residue is introduced into diethyl ether, to get to 0.127 g (0.34 mmol) of the product as white solid substance.

LC-MS: M+H=363

PF (°C): 147-149°C

1H-NMR (CDCl3) δ (ppm): to 9.15 (s, 1H); with 8.05 (d, 2H); the 7.65 (s, 1H); at 7.55 (d, 2H); 6,15 (Sirs, 1H); 5,30 (Sirs, 1H); 4,55 (s, 2H); to 3.35 (m, 2H); 2,85 (m+d, 5H); 2,10 (m, 2H).

The following table shows the chemical structure of the ur and physical properties of some compounds according to the invention.

In the table below:

- all connections are in the form of a free base,

- I-propyl, n-butyl and t-butyl mean respectively isopropyl group, a group of linear butyl and tert-butyl.

nR1[A]nR7R8PF°C (M+H)
1.5-vinylpyridin-2-ylCH2HCH3136-138
2.5-vinylpyridin-2-yl(CH2)2HCH3(314)
3.6-vinylpyridin-3-yl(CH2)2HCH3130-132
4.6-phenylpyridazin-3-yl(CH2 2HCH3159-161
5.2-phenylpyrimidine-5-yl(CH2)2HCH3125-127
6.5-phenylpyrimidine-2-yl(CH2)2HCH3150-152
7.6-(4-Cl-phenyl)pyrimidine-4-yl(CH2)2HCH3139-141
8.6-(4-Cl-phenyl)-2-methylpyrimidin-4-yl(CH2)2HCH3140-142
9.6-(4-Cl-phenyl)-2-(dimethylamino)pyrimidine-4-yl(CH2)2HCH3131-133
10.izogi the Olin-7-yl (CH2)2HCH3134-136
11.4-phenylimidazol-1-yl(CH2)2HCH3111-113
12.2-phenyloxazol-4-yl(CH2)2HCH394-98
13.5-(4-Cl-phenyl)isoxazol-3-yl(CH2)2HCH3150-152
14.3-(4-Cl-phenyl)-1-methyl-1H-pyrazole-5-yl(CH2)2HCH3125-127
15.5-phenyl-1,2,4-oxadiazol-3-yl(CH2)2HCH3131-135
16. pyridine-2-yl(CH2)3HH114-115
17.pyridine-3-yl(CH2)3HH105-107
18.pyridine-4-yl(CH2)3HH161-162
19.pyrimidine-5-yl(CH2)3HH119-121
20.6-(4-Cl-phenyl)pyrimidine-4-yl(CH2)3HCH3147-149
21.6-(4-Cl-phenyl)-2-methylpyrimidin-4-yl(CH2)3HCH3(377)
22.6-(4-Cl-phenyl)-2-(dimethylamino)PI is kidin-4-yl (CH2)3HCH3150-152
23.the quinoline-2-yl(CH2)3HH117-119
24.the quinoline-4-yl(CH2)3HH150-152
25.isoquinoline-1-yl(CH2)3HH123-124
26.isoquinoline-4-yl(CH2)3HH154-156
27.5-(4-Cl-phenyl)isoxazol-3-yl(CH2)3HCH3138-140
28.3-(4-Cl-phenyl)isoxazol-5-yl(CH2 )3HH176-178
29.3-(4-Cl-phenyl)isoxazol-5-yl(CH2)3HCH3158-160
30.3-(4-phenylphenyl)-isoxazol-5-yl(CH2)3HCH3198-200
31.3-(naphthalene-2-yl)-isoxazol-5-yl(CH2)3HCH3143-145
32.3-(4-Cl-phenyl)-1-methyl-1H-pyrazole-5-yl(CH2)3HCH3(365)
33.4-phenylimidazol-1-yl(CH2)3HCH396-98
34.the benzimidazole--Il (CH2)3HCH3154-156
35.pyridine-2-yl(CH2)4HH141-143
36.pyridine-3-yl(CH2)4HH131-133
37.pyridine-4-yl(CH2)4HH124-126
38.pyrimidine-5-yl(CH2)4HH139-141
39.6-(4-Cl-phenyl)pyrimidine-4-yl(CH2)4HCH3101-103
40.6-(4-Cl-phenyl)-2-methylpyrimidin-4-yl(CH 2)4HCH3118-120
41.6-(4-Cl-phenyl)-2-cyclopropylamino-4-yl(CH2)4HCH3118-120
42.6-(4-Cl-phenyl)-2-(dimethylamino)pyrimidine-4-yl(CH2)4HCH3120-122
43.the quinoline-2-yl(CH2)4HH131-133
44.the quinoline-4-yl(CH2)4HH(302)
45.isoquinoline-1-yl(CH2)4HH119-121
46.isoquinoline-4-yl 2)4HH154-156
47.5-(4-Cl-phenyl)isoxazol-3-yl(CH2)4HCH3130-132
48.3-(4-Cl-phenyl)isoxazol-5-yl(CH2)4HCH3138-140
49.3-(4-phenylphenyl)isoxazol-5-yl(CH2)4HCH3193-195
50.3-(naphthalene-2-yl)isoxazol-5-yl(CH2)4HCH3158-160
51.3-(4-Cl-phenyl)-1-methyl-1H-pyrazole-5-yl(CH2)4HCH3144-146
52.4-Fe is eliminator-1-yl (CH2)4HH113-115
53.4-phenylimidazol-1-yl(CH2)4HCH3109-111
54.the benzimidazole-1-yl(CH2)4HCH3114-116
55.indol-1-yl(CH2)4HH100-102
56.indol-1-yl(CH2)4HCH364-67
57.pyrrolo[2,3-b]pyridine-1-yl(CH2)4HH102-104
58.pyrrolo[2,3-b]pyridine-1-yl 2)4HCH352-54
59.tetrahydroisoquinoline-2-yl(CH2)4HCH3(320)
60.2-oxo-3,4-dihydroquinoline-1(2H)-yl(CH2)4HH(320)
61.2-oxo-3,4-dihydroquinoline-1(2H)-yl(CH2)4HCH3(334)
62.pyridine-2-yl(CH2)5HH77-79
63.pyridine-4-yl(CH2)5HH155-157
64.pyrimidine-5-yl(CH2) HH115-117
65.the quinoline-2-yl(CH2)5HH(316)
66.the quinoline-4-yl(CH2)5HH115-117
67.isoquinoline-1-yl(CH2)5HH134-135
68.isoquinoline-4-yl(CH2)5HH(316)
69.naphthalene-1-ylC≡CCH2HH132-134
70.naphthalene-1-ylC≡CCH2HCH3 107-109
71.naphthalene-1-ylC≡C(CH2)3HH105-108
72.naphthalene-1-ylC≡C(CH2)3HCH373-76
73.4-F-naphthalene-1-ylC≡C(CH2)3HCH396-98
74.3-(pyridin-3-yl)isoxazol-5-yl(CH2)3HCH3133-135
75.3-(4-methoxynaphthalene-1-yl)isoxazol-5-yl(CH2)3HCH395-97

Compounds according to the invention were the subject of pharmacological tests to determine their inhibitory effect on the enzyme FAAH (hydrolase fatty acid amides).

In biruwa activity was confirmed in radioterminal test, based on measuring the product of hydrolysis (ethanolamine [1-3H]) of anandamide [ethanolamine 1-3H] by FAAH (Life Sciences (1995), 56, 1999-2005 and Journal of Pharmacology and Experimental Therapeutics (1997), 283, 729-734). So, the mouse brain (without cerebellum) was removed and kept at -80°C. Membrane homogenates were prepared immediately before the experiment by homogenization of tissue in Polytron'e in buffer Tris-HCl 10 mm (pH 8.0)containing 150 mm NaCl and 1 mm EDTA. Then the enzymatic reaction was performed in 70 μl of buffer containing bovine serum albumin without fatty acids (1 mg/ml). Consistently added test compounds in different concentrations of anandamide [ethanolamine 1-3H] (specific activity 15-20 CI/mmol)diluted to 10 μm cold anandamide membrane and the drug (400 mg frozen tissue on experience). After 15 minutes at 25°C. the enzymatic reaction was stopped by adding 140 μl of a mixture of chloroform/methanol (2:1). The mixture was stirred for 10 minutes, then centrifuged for 15 minutes at 3500 rpm/min an Aliquot (30 μl) of the aqueous phase containing ethanolamine [1-3H], calculated by the scintillation fluid.

Under these conditions, the most active compounds according to the invention have CI50(concentration inhibiting 50% of the enzymatic activity of the control FAAH is from 0.001 to 1 μm).

For example, the connection 68 table has CI50 0,267 um.

Thus, it is seen that the compounds according to the invention have inhibitory activity against the enzyme FAAH.

The activity in vivo of the compounds according to the invention was evaluated in the test for analgesia.

So, intraperitoneal (I.P. Pavlova.) introduction PBQ (phenylbenzophenone, 2 mg/kg in 0.9%sodium chloride solution containing 5% ethanol) male OF1 mice weighing 25-30 g causes spasms of the peritoneum on average 30 full or local reductions for the period from 5 to 15 minutes after injection. The test compounds were administered orally (p/o) or intraperitoneally (I.P. Pavlova.) suspension of Tween-80 concentration of 0.5% for 60 or 120 minutes prior to the introduction of PBQ. Under these conditions, the most potent compounds according to the invention at 35-70% reduce the number of spasms caused PBQ, in the dose range of 1 to 30 mg/kg

For example, the connection 48 table reduces spasms caused PBQ, 53% and 62% at p.o. a dose of 10 mg/kg, respectively, after 60 minutes and 120 minutes.

The enzyme FAAH (Chemistry and Physics of Lipids, (2000), 108, 107-121) catalyzes the hydrolysis of endogenous derivatives of amides and esters of various fatty acids, such as N-arachidonoylethanolamine (anandamide), N-palmitoylethanolamide, N-oleoylethanolamide, oleamide or 2-arachidonoylglycerol. In addition, these derivatives exhibit different pharmacological activity when interacting with cannabioids and vanilloid receptors.

Connect the means according to the invention block the path decomposition and increase tissue portion of these endogenous substances. They can be used for this purpose in the prevention and treatment of pathologies involving endogenous cannabinoid and/or any other substrate metabolized by the enzyme FAAH.

Can be called, for example, the following diseases and conditions:

pain, in particular acute or chronic pain of neurogenic type: migraine, neuropathic pain, including forms associated with the herpes virus and diabetes;

acute or chronic pain associated with inflammatory diseases: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vascularity, Crohn's disease, irritable bowel syndrome;

acute or chronic peripheral pain;

dizziness, vomiting, nausea, in particular resulting from chemotherapy;

eating disorders, particularly anorexia and cachexia of various nature;

neurological and psychiatric pathologies: tremor, dyskinesia, dystonia, spasticity, obsessive-compulsive disorder, Tourette's syndrome, all forms of depression and anxiety of any nature and origin, mood disorders, psychoses;

acute and chronic neurodegenerative diseases: Parkinson's disease, Alzheimer's disease, senile dementia, Huntington's chorea, lesions associated with cerebral ischemia and traumatic brain injury;

epilepsy;

bre is of sleep, including stopping of breathing during sleep;

cardiovascular disease, in particular hypertension, cardiac arrhythmia, arteriosclerosis, heart attacks, ischemia of the heart;

renal ischemia;

cancer: superficial skin tumors, papillomas and brain tumors, prostate tumors, brain tumors (glioblastomas, medulla-epithelioma, Protocol, neuroblastomas, tumors of embryonic origin, astrocytomas, astroblastoma, ependyma, oligodendrogliomas, plexus tumors in, neuroepithelioma, tumor epiphysis, ependymoblastomas, malignant meningiomas, sarcomatosis, malignant melanoma, sanomi);

disorders of the immune system, in particular autoimmune diseases: psoriasis, lupus erythematosus, diseases of the connective or connective tissue syndromes Segren, Ancylostoma spondylitis, undifferentiated spondylitis, Behcet's disease, autoimmune hemolytic anemia, multiple sclerosis, amyotrophic lateral sclerosis, amylose, rejection of transplants, disease, acting on plasmaatomic series;

allergic diseases: immediate or delayed hypersensitivity, allergic rhinitis or conjunctivitis, contact dermatitis;

infectious parasitic, viral or bacterial diseases: AIDS, meningitis; inflammatory diseases, in particular, is zabolevaniya joints: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vascularity, Crohn's disease, irritable bowel syndrome; osteoporosis; eye disease: ocular hypertension, glaucoma;

lung diseases: diseases of the respiratory tract, bronchial constriction, cough, asthma, chronic bronchitis, chronic airway obstruction, emphysema;

gastrointestinal diseases: irritable bowel syndrome, inflammatory intestinal disorders, ulcers, diarrhea;

urinary incontinence and bladder inflammation.

The use of the compounds of formula (I) in the form of a pharmaceutically acceptable base, salt, hydrate or MES for obtaining a medicinal product intended for the treatment of the above mentioned pathologies, is an integral part of the invention.

The object of the invention are also medications which contain a compound of the formula (I) or its salt, and pharmaceutically acceptable hydrate or MES the compounds of formula (I). These medicaments find their use in therapy, in particular in the treatment of the aforementioned disorders.

According to another of its aspects the present invention relates to pharmaceutical compositions containing as active ingredient at least one compound according to the invention. These pharmaceutical compositions contain an effective dose of a compound according to what obreteniyu or a pharmaceutically acceptable salt, the MES or hydrates of the compounds, and optionally one or more pharmaceutically acceptable excipients.

These excipients are chosen according to the pharmaceutical form and the desired method of administration, from the usual excipients which are specialist known.

In the pharmaceutical compositions according to the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal, rectal injection or injection through the lungs and eyes active ingredient the above-mentioned formula (I) or its possible salt, MES or hydrate can be administered to animals and humans for the prophylaxis or treatment of the above disorders or diseases in a single form receiving mixed with classical pharmaceutical excipients.

The appropriate common forms of introduction include forms for oral administration such as tablets, soft or hard gelatin capsules, powders, granules, chewing gum and oral solutions or suspensions, forms for sublingual, buccal, intratracheal, intraocular, intranasal, by inhalation, subcutaneous, intramuscular or intravenous forms of administration and rectal or vaginal forms of introduction. For topices is the first application of the compounds according to the invention can be used in creams, gels, lipsticks or lotions.

For example, a single form of the introduction of the compounds according to the invention in the form of tablets may contain the following components:

The connection according to the invention50.0 mg
Mannitol223,75 mg
Crosscarmellose sodium6.0 mg
Corn starch15,0 mg
The hypromellose2.25 mg
Magnesium stearate3.0 mg

These single forms can be dosed to allow a daily intake of 0.01 to 20 mg of active substance per kg of body weight, according to the galenical form.

May be special cases when suitable higher or lower dosages; these dosages are also not beyond the scope of the invention. According to usual practice, the dosage appropriate for each patient is determined by the physician in accordance with the method of administration, the weight and susceptibility of the specified patient.

The present invention according to another of its aspects relates also to a method of treatment of the above is use pathologies, which includes the patient an effective dose of the compounds according to the invention or one of its pharmaceutically acceptable salts, MES or hydrate specified connection.

1. The connection that meets the General formula (I)

in which a is selected from one or more groups X and/or Y;
X is methylene group;
Y means With2-alkynylamino group;
n means an integer from 1 to 5;
R1means the group R2, optionally substituted by one or more groups R3and/or R4;
R2means a group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, chinoline, izochinolina, dihydroisoquinoline, 2-oxo-3,4-dihydroquinoline, indolyl, benzimidazolyl, pyrrolopyridine;
R3means a group selected from halogen atoms, groups C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, NR5R6and phenyl;
R4means a group selected from the group: phenyl, naphthyl, pyridinyl;
moreover, the group or groups R4can be substituted by one or more groups R3the same or different from each other;
R5and R6independently of one another denote C1-6is an alkyl group;
R7means atom bodoro is a or C 1-6is an alkyl group;
R8means a hydrogen atom or a group1-6-alkyl, C3-7-cycloalkyl,3-7-cycloalkyl-C1-3-alkylen;
a base, an acid additive salt, hydrate or MES.

2. The compound of formula (I) according to claim 1, characterized in that:
R2means a group selected from pyridinyl, pyrimidinyl, oxazolyl, isoxazolyl, naphthyl, chinoline, izochinolina.

3. The compound of formula (I) according to claim 1, characterized in that:
R7means a hydrogen atom;
R8means a hydrogen atom or a C1-6is an alkyl group, a base, an acid additive salt, hydrate or MES.

4. The method of obtaining the compounds of formula (I) according to any one of claims 1 to 3, comprising a stage consisting in the conversion of the ether-carbamate of General formula (IV)

in which A, n, R1and R7such as defined in formula (I) according to claim 1, and R is a methyl or ethyl group,
by aminolysis an amine of General formula R8NH2in which R8this is as defined in formula (I) according to claim 1.

5. The method of obtaining the compounds of formula (I) according to any one of claims 1 to 3, including the state,

consisting in the transformation derived oxazolidinedione General formula (VII),
in which A, n, R1and R7such as defined in formula (I) according to claim 1,
p is for those of aminolysis an amine of General formula R 8NH2in which R8this is as defined in formula (I) according to claim 1.

6. The connection that meets the General formula (IV),

in which A, n, R1and R7such as defined in formula (I) according to claim 1, and R is a methyl or ethyl group, with the exception of the following compounds:
- ethyl-2-[({[2-(5-hydroxy-1H-indol-3-yl)ethyl]amino}carbonyl)oxy]propanoate;
- ethyl-2-[({[2-[5-(phenylmethoxy)-1H-indol-3-yl]ethyl}amino)carbonyl]oxy]propanoate.

7. The connection that meets the General formula (VII),

in which A, n, R1and R7such as defined in formula (I) according to claim 1, with the exception of the following compounds:
iodide 2-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridine;
iodide 2-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-5-ethyl-1-methylpyridine;
iodide 4-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridine;
hydrochloride, 5-methyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;
hydrochloride, 5-methyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 3-(5-imidazo[1,2-a]pyridine-5-alpental)-2,4-oxazolidinedione;
- 3-[2-(5-methyl-4-thiazolyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(1H-pyrrol-2-yl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;
- 3-[3-(2-thienyl)propyl]-2,4-oxazolidinedione;
- 3-[4-(2-thienyl)butyl]-2,4-oxazolidinedione;
- 5-methyl-3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;
- 5-ethyl-3-[2-(2-Tieni is)ethyl]-2,4-oxazolidinedione;
- 3-[2-(3-thienyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-methyl-2-thienyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-acetyl-2-thienyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-bromo-2-thienyl)ethyl]-2,4-oxazolidinedione;
- 5-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-2-thiophenecarboxaldehyde;
- 3-[3-[1-indolinyl)propyl]-2,4-oxazolidinedione;
- 3-[3-[1-indolinyl)propyl]-5-methyl-2,4-oxazolidinedione;
- 3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-5-methyl-2,4-oxazolidinedione;
- 5-ethyl-3-[2-(5-ethyl-2-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-5-isopropyl-2,4-oxazolidinedione;
- 3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 5-ethyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 5-ethyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 5-isopropyl-3-[2-(4-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 5-isopropyl-3-[2-(2-pyridinyl)ethyl]-2,4-oxazolidinedione;
- 3-[2-(5-ethyl-2-pyridinyl)ethyl]-2,4-oxazolidinedione.

8. Pharmaceutical composition having activity of inhibitors of enzymes FAAH containing at least one compound of formula (I) according to any one of claims 1 to 3, in the form of a pharmaceutically acceptable base, salt, hydrate or MES, and optionally one or more pharmaceutically acceptable excipients.

9. The use of the compounds of formula (I) according to any one of claims 1 to 3 in the form of a pharmaceutically acceptable base, salt, hydrate or MES for which Holocene medicines intended for the prevention or treatment of pathologies involving endogenous cannabinoid and/or any other substrate metabolized by the enzyme FAAH.

10. The use of the compounds of formula (I) according to any one of claims 1 to 3 in the form of a pharmaceutically acceptable base, salt, hydrate or MES for obtaining a medicinal product intended for the prevention or treatment of acute or chronic pain, dizziness, vomiting, nausea, eating disorders, neurological and psychiatric pathologies, acute or chronic neurodegenerative diseases, epilepsy, sleep disorders, cardiovascular disease, renal ischemia, cancers, disorders of the immune system, allergic diseases, infectious parasitic, viral or bacterial diseases, inflammatory diseases, osteoporosis, eye diseases, lung diseases, gastrointestinal diseases or urinary incontinence.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) to its salts, in which X is bivalent radical NR2, O; R1 is cyanogroup; n equals 1; R2 is: i) C1-10alkyl, substituted with aryl, where said aryl is substituted with radical -COOR4; or R2 is ii) C1-10alkyl, substituted with radical selected from -O-NR5a-C(=NR5b)-NR5cR5d, -NR7R8, radical

in which each Q1 independently is simple bond, -CH2-; each Q2 independently is O; each R4 independently is hydrogen; each R5a, R5b, R5c, R5d independently is hydrogen; R7 is C1-4alkyl; R8 is arylC1-4alkyl; R11 is aryl, C1-4alkylcarbonyl, C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, "Гет"2; each R12 independently is hydroxy, C1-4alkyl; R13a is C1-4alkyl; each R13b is C1-4alkyl; or R2 is iii) radical of formula:

-CpH2p-CH(OR14)-CqH2qR15 (b-3);

CH2-CH2-(O-CH2-CH2)m-OR14 (b-4);

CH2-CH2-(O-CH2-CH2)m-NRI7eR17b (b-5); where in radical (b-3) one of hydrogen atoms in -CpH2p- and one of hydrogen atoms in - CH(OR14)-CqH2q-, which are not part of R14, can be substituted with simple bond or C1-4alkandiyl group; p equals 1, 2 or 3; q equals 0, 1, 2 or 3; each m independently equals 1-10; each R independently is hydrogen, C1-4alkyl, C1-4alkylcarbonyl; R15 is substituent selected from group consisting of NR16aR16, pyrrolidine, pyperidinyl, homopyperidinyl, piperazinyl, , 4-(C1-4alkyl)-piperazinyl, 4-(C1-4alkylcarbonyl)-piperazinyl, 4-(C1-4alkyloxycarbonyl)-piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholinyl; R16a and R16b, independently on each other, are hydrogen, C1-6alkyl or C1-6alkyl, substituted with aryl; R17a and R17b, independently on each other, are hydrogen, C1-4alkyl; or R17a and R17b, together with nitrogen atom, to which they are bonded, form pyrrolidine, morpholinyl; each R18 independently is arylC1-4alkyl; R19 is hydrogen; R3 is nitrogroup; aryl is phenyl; "Гет"2 is piridyl. Invention also relates to pharmaceutical composition, to method of obtaining compound on any of ii 1-4, as well as to compounds of formula (IV-a), (IV-b),(V).

EFFECT: obtaining novel biologically active compounds possessing ability to inhibit HIV.

11 cl, 18 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining 5-bromo-7-azaindole obtaining, which includes: stage 1: reduction of 7-azaindole, receiving 7-azaindoline; stage 2: bromination of 7-azaindoline, receiving 5-bromo-7-azaindoline; stage 3: oxidation of 5-bromo-7-azaindoline receiving 5-bromo-7-azaindole.

EFFECT: elaboration of method of obtaining 5-bromo-7-azaindole.

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining 5-methoxy-7-azaindol, which includes mixing of 5-bromo-7-azaindole solution, copper (I) bromide and sodium methylate in mixture of "degassed" DMFA (dimethyl formamide) and methanol; mixing of obtained mixture at temperature of surrounding environment in nitrogen atmosphere; and then heating of mixture with reverse refrigerator.

EFFECT: elaboration of method of obtaining 5-methoxy-7-azaindole.

1 cl, 54 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: present invention is related to compounds of formula I , which are inhibitors of p38 kinase and may be used in medicine, where A represents N or N+O-; R1 represents phenyl or heterocyclyl; R2 represents heterocyclyl; R3 represents H, carbocyclic radical, aryl or heterocyclyl; R4 represents H, Ra, halogen, -ORa', -CN, -CONRa'Ra', -NRa'Ra', -NRa'CORa' or -NRa'CO2Ra; R5 may be connected to any of nitrogens of pyrazole ring of compound in formula I and represents H, alkyl, alkenyl, carbocyclic radical, aryl or heterocyclyl; Ra independently represents alkyl, carbocyclic radical, aryl or heterocyclyl; each Ra' independently represents H or Ra.

EFFECT: preparation of new biologically active compounds.

41 cl, 299 ex, 15 tbl

FIELD: chemistry.

SUBSTANCE: described are new derivatives of imidazo-pyridine with general formula I in racemic, enantiomeric form or in combination of these forms, and their pharmaceutically used salts. Radicals R1-R4 are described in the description.

EFFECT: these compounds have affinity to melanocortin receptor; possibility of using them in making medicinal agents for treating disorders, related to body weight, mental disorders, pain, sexual activity disorders.

21 cl, 5 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to practically pure polymorphic forms of A and B N-[({2-[4-(2-Ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridine-1-yl)phenyl] ethyl}-amino)carbonyl]-4-methylbenzolsulphone-amide, to pharmaceutical compositions containing specified polymorphic forms, and also to their application and application of pharmaceutical compositions containing them. Additionally, the invention concerns method of pain management, therapy of inflammation, osteoarthritis or rheumatoid arthritis, as involving introduction of saif polymorphic forms A and B.

EFFECT: new crystal forms of N-[({2-[4-(2-Ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridine-1-yl)phenyl] ethyl}-amino)carbonyl]-4-methylbenzolsulphone-amide are the most stable of the identified forms.

14 cl, 2 tbl, 12 ex, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of formula (I) or its pharmaceutically acceptable salt where radicals R1, R2, n1 and n2, Y and X are valued in the description, R3 stands for heterocyclic group of corollary formula (bb) (specified below). These compounds are phosphodiesterase (PDE) inhibitors, particularly PDE4 inhibitors. There is also disclosed production process of pharmaceutical compositions containing compound of formula or its pharmaceutically acceptable salt as an active component, and their application in manufacturing of a medicine for treatment and/or prevention of inflammatory and/or allergic disease in mammals, including humans, e.g. asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, allergic rhinitis, rheumatoid arthritis, disseminated sclerosis, Alzheimer's disease, depression or pain in mammals, including humans.

EFFECT: higher effectiveness of the composition and medication therapy.

20 cl, 686 ex

FIELD: chemistry.

SUBSTANCE: invention refers to N-substituted pyrazolo[3,4-b]pyridyl-3-sulphonylamides of formulas 1-3 , where 1 R=H; R1 =CH3; R2=H; R3= furfuryl, 2 R=CI; R1=CH3; R2= R3 = allyl, 3 R=H; R1 =H; R2=H; R3 = 2-chlorbenzyl.

EFFECT: production of new growth-regulating compounds to be used in agriculture as sunflower growth regulators in preplant seed treatment.

1 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to the compounds of the formula and their pharmaceutically acceptable salts used as inhibiting agent in the relation of fermentative beta-secretase and it also relates to pharmaceutical compositions based on the formula. In general formula one of RN and RN' represents hydrogen, and another represents - C(=O)-(CRR')0-6R100, or where R4 is chosen from the group including H; NH2; -NR50CO2R51; -(C1-C4)-alkyl-NR50CO2R51; where n7 is equal to 0, 1, 2 or 3; R50 represents H or C1-C6alkyl; R51 is chosen from the group including phenyl-(C1-C4)-alkyl and (C1-C6)-alkyl; X is chosen from the group including -(C1-C6)-alkylidenyl optionally substituted with 1, 2 or 3 metal groups; Z is chosen from the group including bond, SO2, SO and S; Y stands for (C1-C10)-alkyl; R1 represents -(C1-C6)-alkylphenyl where phenyl ring is optionally substituted by 1, 2, 3 or 4 halogen atoms; R and R' independently represent hydrogen or (C1-C6)-alkyl; R2 represents hydrogen; R3 represents hydrogen; Rc represents - (CR245R250)0-4-aryl; where aryl is optionally substituted by 1, 2 or 3 R200; R200 is chosen from the group including (C1-C6)-alkyl optionally substituted with 1, 2 or 3 groups R205; halogen; C=N; R205 stands for halogen; R245 and R250 in each case stands for H; either R245 or R250 are taken together with carbon atom whereto attached to form carbocycle from 3, 4, 5, 6 or 7 carbon atoms; R100 represents 5-6-merous heteroaryl with 1-2 heteroatoms chosen from nitrogen and sulphur, -phenyl-W-heteroaryl where heteroaryl is 5-6-merous ring containing 1-2 heteroatoms, chosen from nitrogen and oxygen and where cyclic parts of each group are optionally substituted by 1, 2 or 3 groups independently chosen among C1-C6alkyl, -(CH2)0-4-CO2-NR105R'105, -(CH2)0-4-SO2-NR105R'105, -(CH2)0-4-N(R150)-CO-R105, -(CH2)0-4-N(R150)-SO2-R105; W represents -(CH2)0-4; R105 and R'105 independently represent (C1-C6)-alkyl optionally substituted with -NH2 or halogen; R150 represents hydrogen.

EFFECT: compounds can be applied to prevent and treat diseases mediated by excess activity of beta-secretase such as Alzheimer's disease.

11 cl, 12 tbl, 3 dwg, 1729 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula (I): where R1 and R2 each independently represents a hydrogen atom, C1-8 alkyl or a halogen atom; R3 represents C1-8 alkyl, which can be substituted with 1-3 halogen atom(s) or phenyl; R4 represents a hydrogen atom or C1-8 alkyl; R5 and R6 each independently represents a hydrogen atom; X represents a sulphur atom or oxygen atom; ring A is 4-(trifluoromethyl)piperidin-1-yl, 2,2-difluoro-1,3- benzodioxol-5-yl or 3,4-dihydro-1H-isoquinolin-2-yl. The invention also relates to salts or solvates of this derivative, as well as medicinal preparation, pharmaceutical composition, method of preventing and/or treating diseases, caused by PPAR, and use of this derivative.

EFFECT: obtaining new biologically active compounds, which can be used for preventing and/or treating diseases caused by PPARδ.

8 cl, 39 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to a malononitrile compound with formula (I): where one of X1, X2, X3 and X4 stands for CR100, where R100 is a group with formula (II) each three of the other X1, X2, X3 and X4 is nitrogen or CR5, under the condition that, from one to three of X1, X2, X3 and X4 stands for nitrogen, Z is oxygen, sulphur or NR6. The malononitrile compound can be used a pesticide in agriculture.

EFFECT: obtaining a new pest control compound and its use as an active ingredient of a pesticide composition.

18 cl, 180 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula , in which R represents H, (C1-C12)-alkyl or (C1-C4)-alkyl-(C6-C12)-aryl. In the alkyl, one or more CH2-groups can be substituted with -O-. The invention also relates to the method of obtaining these compounds. The method involves reacting dimethylbenzoic acid ester with formula where R assumes values given above, with a chlorinating agent in an inert solvent or without a solvent at temperature above 40°C, and then cleaning, if necessary. Formula (I) compounds are essential intermediate products during synthesis of PPAR agonists with formula , in which R represents H, (C1-C12)-alkyl or (C1-C4)-alkyl-(C6-C12)-aryl. In the alkyl, one or more CH2-groups can be substituted with -O-; Y represents -(CH2)3-, 1,3-phenylene, 1,3-cyclohexanediyl; R' represents H, F, Br, CF3, (C1-C6)-alkyl, O-(C1-C6)-alkyl, phenyl; CF3; obtained from reaction of compounds with formula with formula (I) compounds in toluene, N-methylpyrrolidone or other aprotic solvents, in the presence of a suitable base, at temperature lying in the -78°C - +50°C interval, with subsequent extractive processing and, if necessary, crystallisation of the end product.

EFFECT: obtaining new compounds.

8 cl, 5 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry.

SUBSTANCE: invention concerns a compound of the formula (I) where A ring is (C3-C8)-cycloalkyl or (C3-C8)-cycloalkenyl where two carbon atoms in the cycloalkyl ring can be substituted by oxygen atoms; R1, R2 are H, F, Cl, Br, OH, CF3, OCF3, (C1-C6)-alkyl or O-(C1-C6)-alkyl independently from each other; R3 is H or (C1-C6)-alkyl; R4, R5 are H, (C1-C6)-alkyl independently from each other; X is (C1-C6)-alkyl where one carbon atom in the alkyl group can be substituted by oxygen atom; Y is (C1-C6)-alkyl where one carbon atom in the alkyl group can be substituted by oxygen atom; and its pharmaceutically acceptable salts. The invention also concerns such compounds as (+)-cis-2-(3-(2-(4-fluorphenyl)oxazole-4-ylmethoxy)cyclohexyloxymethyl)-6-methylbenzoic acid of the formula 6b , 2-{3-[2-(3-methoxyphenyl)-5-methyloxazole-4-ylmethoxy]cyclohexyl-oxymethyl}-6-methylbenzoic acid of the formula 53 and 2-methyl-6-[3-(5-methyl-2-n-tolyloxazole-4-ylmethoxy)cyclohexylomethyl]benzoic acid of the formula 70 , or their enantiomers. The invention also concerns pharmaceutical composition exhibiting PPARα agonist effect, including one or more compounds of the formula (I) as an active component together with a pharmaceutically acceptable carrier. The pharmaceutical composition is obtained by mixing of active compound of the formula (I) with a pharmaceutically acceptable carrier and rendering it a form viable for introduction.

EFFECT: obtaining of diarylcycloalkyl derivatives applicable as PPAR-activators.

9 cl, 2 tbl, 67 ex

FIELD: chemistry; oxa-and thiazole derivatives.

SUBSTANCE: oxa- and thiazole derivatives have general formula . Their stereoisomers and pharmaceutical salts have PPARα and PPARγ activity. The compounds can be used for treating diseases, eg. diabetes and anomaly of lipoproteins through PPARα and PPARγ activity. In the general formula, x has value of 1, 2, 3 or 4; m has value of 1 or 2; n has value of 1 or 2; Q represents C or N; A represents O or S; Z represents O or a bond; R1 represents H or C1-8alkyl; X represents CH; R2 represents H; R2a, R2b and R2c can be the same or different and they are chosen from H, alkoxy, halogen; R3 represents aryloxycarbonyl, alkyloxycarbonyl, alkyl(halogen)aryloxycarbonyl, cycloalkylaryloxycarbonyl, cycloalkyloxyaryloxycarbonyl, arylcarbonylamino, alkylsulphonyl, cycloheteroalkyloxycarbonyl, heteroarylalkenyl, alkoxyaryloxycarbonyl, arylalkyloxycarbonyl, alkylaryloxycarbonyl, halogenalkoxyaryloxycarbonyl, alkoxycarbonylaryloxycarbonyl, arylalkenyloxycarbonyl, aryloxyarylalkyloxycarbonyl, arylalkenylsulphonyl, heteroarylsulphonyl, arylsulphonyl, arylalkenylarylalkyl, arylalkoxycarbonyl-heteroarylalkyl, heteroaryloxyarylalkyl, where alkyl is in form of C1-8alkyl; Y represents CO2R4, where R4 represents H or C1-8alkyl; including all their stereoisomers and pharmaceutical salts, under the condition that, if A is O, then R3 is not aryloxycarbonyl or alkoxyaryloxycarbonyl.

EFFECT: the compounds can be used in curing such diseases as diabetes and lipoprotein anomalies.

10 cl, 30 dwg, 12 tbl, 584 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new displaced heterocyclic derivatives that can be used in treatment of diabetes and to reduce the content of cholesterol. In formula m is 1; n is 1; Q is C; A is -(CH2)x2-0-(CH2)x3-, where x2 varies from 1 to 3 and x3 is 0; B is a bond or it is (CH2)x4, where x4 varies from 1 to 2; X represents CH or N; X2, X3, X4, X5, X6 represent C, N, O; provided that one from X2 X3 X4 X5 and X6 represents N; and at least one of X2, X3, X4, X5, and X6 represents C; R1 represents H or C1-C6alkyl; R2 is H; R2a, R2b and R2c can be equal or different and selected from H, C1-C6alkyl, C1-C6alkoxy, halogen or thyano; R3 is selected from phenyloxycarbonile, C1-C6alkyloxycarbonile, phenylcarbinol, phenyl, alkoxy; Y represents CO2R4 (where R4 represents H or C1-C6alkyl); (CH2)m can be not necessarily displaced by 1 substitute.

EFFECT: produced are pharmaceutical composition for treatment of diabetes and to reduce the content of cholesterol.

13 cl, 2 tbl, 22 dwg, 88 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts and esters. In the general formula (I) X means oxygen (O) or sulfur (S) atom; R means hydrogen atom (H) or (C1-C6)-alkyl; R1 means H, -COOR, (C3-C8)-cycloalkyl or (C1-C6)-alkyl, (C2-C6)-alkenyl or (C1-C6)-alkoxyl and each of them can be unsubstituted or comprises substitutes; values of radicals R2, R3, R4, R5 and R6 are given in the invention claim. Also, invention relates to a pharmaceutical composition based on compounds of the general formula (I) and to intermediate compounds of the general formula (II) and the general formula (III) that are used for synthesis of derivatives of indane acetic acid. Proposed compounds effect on the blood glucose level and serum triglycerides level and can be used in treatment of such diseases as diabetes mellitus, obesity, hyperlipidemia and atherosclerosis.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 6 tbl, 6 sch, 251 ex

FIELD: organic chemistry, biochemistry, enzymes.

SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.

EFFECT: valuable medicinal and biochemical properties of compounds.

24 cl, 13 sch, 4 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: inventive subject matter is compouns and their pharmaceutically acceptable salts which can be applied in prevention and treatment of diseases caused by HCV infection. Structural formulae of the compounds are presented in the claim.

EFFECT: obtaining anti-HCV medicine including the claimed compound or its pharmaceutically acceptable salt as active component.

2 cl, 100 ex

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