Amidomethyl substituted derivatives of 1-(carboxyalkyl)cyclopentylcarbonylaminobenzazepin-n-acetic acid, method and intermediate material for obtaining them and medicinal agents containing these compounds

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula I, in which R1 represents hydrogen or a group, which forms a biologically labile ester, R2 represents hydrogen, C1-C4-alkyl or C1-C4-hydroxyalkyl, and R3 represents C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkyl; C1-C4-hydroxyalkyl, which is optionally substituted with a second hydroxy group and all hydroxy groups of which are optionally esterified with C2-C4-alkanoyl or amino-acid residue; (C0-C4-alkyl)2amino-C1-C6-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen; naphthyl-C1-C4-alkyl; C3-C6-oxoalkyl; phenylcarbonylmethyl, the phenyl group of which is optionally substituted 1-2 times with C1-C4-alkyl, C1-C4-alkoxy group and/or halogen, or 2-oxoazepanyl, or R2 and R3 together represent C4-C7-alkylene, methylene groups of which are optionally substituted 1-2 times with carbonyl, nitrogen, oxygen and/or sulphur and/or optionally substituted once with a hydroxy group, which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; C1-C4-alkyl; C1-C4-hydroxyalkyl, the hydroxy group of which is optionally esterified with C2-C4-alkanoyl or amino-acid residue; phenyl or benzyl, and R4 represents hydrogen or a group, which forms a biologically labile ester, where R1 and R4 groups are independently chosen from C1-C4-alkyl; C1-C4-alkoxy-C1-C4-alkoxy-C1-C4-alkyl; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di-(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4-alkyl, optionally substituted 1 or 2 times in the phenyl ring with halogen, C1-C4-alkyl or C1-C4-alkoxy group or C1-C4-alkylene chain, bonded with two neighbouring carbon atoms; dioxolanylmethyl, optionally substituted in the dioxolane ring with C1-C4-alkyl; C1-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted in the oxy-C1-C4-alkyl group with C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alkyl esters; 1-[[(C4-C7 cycloalkyloxy)carbonyl]oxy]C1-C4-alkyl esters, 2-oxo-1,3-dioxolan-4-yl-C1-C4-alkyl esters, which optionally contain a double bond in the dioxolane ring; 2-oxo-1,3-dioxolan-4-ylmethyl; and to physiologically compatible salts of acids with formula I and/or to physiologically compatible acid-additive salts of formula I compounds. The invention also relates to a pharmaceutical composition, to use of formula I compounds in paragraph 1, to a method of obtaining formula I compounds, as well as to compounds with general formula II.

EFFECT: obtaining new biologically active compounds, with inhibitory activity towards neutral endopeptidase, endothelin converting enzyme and soluble human endopeptidase.

20 cl, 80 ex, 9 tbl

 

The text descriptions are presented in facsimile form.

1. Compounds of General formula I, in which

R1denotes hydrogen or a group forming a biologically labile ester,
R2denotes hydrogen, C1-C4-alkyl or C1-C4-hydroxyalkyl, and R3represents C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-hydroxyalkyl, which is optionally substituted second hydroxy-group, and all of the hydroxy-group which is not necessarily tarifitsirovana C2-C4-alkanoyl or amino acid residue; (C0 4-alkyl)2amino-C1-C6-alkyl, C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times C1-C4-alkyl, C1-C4-alkoxygroup and/or halogen; naphthyl-C1-C4-alkyl, C3-C6-oxoalkyl; phenylcarbonylamino, phenyl group which is optionally substituted 1-2 times C1-C4-alkyl, C1-C4-alkoxygroup and/or halogen, or 2-oxoazetidin, or
R2and R3together denote C4-C7-alkylen, a methylene group which is optionally 1-2 times replaced by carbonyl, nitrogen, oxygen and/or sulfur and/or which is optionally substituted 1 time hydroxy-group, which does not necessarily etherification C2-C4-alkanoyl or amino acid residue; C1-C4-alkyl, C1-C4-hydroxyalkyl, the hydroxy-group which is not necessarily etherification C2-C4-alkanoyl or amino acid residue; phenyl or benzyl, and R4denotes hydrogen or a group forming a biologically labile ester,
where the group R1and R4independently from each other selected from C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkoxy-C1-C4and the Qila; C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4the alkyl, optional 1 or 2 times substituted in the phenyl ring by halogen, C1-C4-alkyl or C1-C4-alkoxygroup or C1-C4-alkalinous circuit associated with two adjacent carbon atoms; DIOXOLANYL, optionally substituted in the dioxolane ring C1-C4-alkyl, C2-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted with hydroxy-C1-C4is an alkyl group, a C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alilovic ester; 1-[[(C4-C7-cycloalkane)carbonyl]oxy]C1-C4-alkalemia esters, 2-oxo-1,3-dioxolane-4-yl-C1-C4alilovic esters, which are optionally contain a double bond in the dioxolane ring; 2-oxo-1,3-dioxolane-4-ylmethyl;
and the physiologically compatible salts of acids of formula I and/or physiologically compatible acid additive salts of compounds of formula I.

2. The compounds of formula I according to claim 1, in which
R1denotes hydrogen or a group forming a biologically labile ester,
R2denotes hydrogen, C1-C4 -alkyl or C1-C4-hydroxyalkyl, and
R3represents C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-hydroxyalkyl, which is optionally substituted second hydroxy-group, and the hydroxy-group of which is optionally substituted C2-C4-alkanoyl; C1-C4-alkylamino-C1-C4-alkyl, C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times C1-C4-alkyl, C1-C4-alkoxygroup and/or halogen; naphthyl-C1-C4-alkyl, C3-C6-oxoalkyl; phenylcarbonylamino, phenyl group which is optionally substituted 1-2 times C1-C4-alkyl, C1-C4-alkoxygroup and/or halogen, or 2-oxoazetidin, or
R2and R3together denote C4-C7-alkylen, a methylene group which is optionally 1-2 times replaced by carbonyl, nitrogen, oxygen and/or sulphur and which is optionally substituted 1 time C1-C4-alkyl, C1-C4-hydroxyalkyl, the hydroxy-group of which is optionally substituted C2-C4-alkanoyl; oxygen; phenyl or benzyl, and
R4denotes hydrogen or a group forming biologically labile complex e is Il,
and the physiologically compatible salts of acids of formula I and/or physiologically compatible acid additive salts of the compounds of formula I.

3. The compounds of formula I according to claim 1, in which R1denotes hydrogen, ethyl, methoxyethoxymethyl, (RS)-1-[[(isopropyl)carbonyl]oxy]ethyl (RS)-1-[[(ethyl)carbonyl]oxy]-2-methylpropyl, (RS)-1-[[(diclohexal)carbonyl]oxy]ethyl, 5-methyl-2-oxo-1,3-dioxolan-4-yl-methyl, 2-oxo-1,3-dioxolane-4-yl-methyl or (RS)-1-[[(ethoxy)carbonyl]oxy]ethyl.

4. The compounds of formula I according to claim 1, in which R2denotes hydrogen, methyl, ethyl, 2-hydroxyethyl or 3-hydroxypropyl.

5. The compounds of formula I according to claim 1, in which R3means isopropyl; methoxyethyl; 2-hydroxyethyl or 3-hydroxypropyl, each of the hydroxy-group optional etherification C2-C4-alkanoyl or amino acid residue; 3 atomic charges is n-propyl; cyclopropylmethyl; 2-methoxybenzyl, 4-methoxybenzyl, 4-methoxyphenylacetyl, 2,4-dimethoxybenzyl; 1-naphthylmethyl; 3-oxo-1,1-dimethylbutyl; phenyl-2-oxoethyl, 2-(4-methoxyphenyl)-2-oxoethyl, 3-(2-oxoazetidin), dimethylamino-n-propyl, (methyl)aminoethyl, amino-n-propyl, amino-n-butyl or amino-n-pentyl.

6. The compounds of formula I according to claim 1, in which R2and R3together represent morpholine; piperidine; 4-ketopyperidines; 4-hydroxypiperidine, optionally esterified C2-C4-alkanoyl is or amino acid residue of the hydroxy-group; piperazine or pyrrolidine.

7. The compounds of formula I according to claim 1, in which R4denotes hydrogen, C1-C4-alkyl, p-methoxybenzyl, N,N-di(C0-C4-alkyl)amino-C1-C6-alkyl, (RS)-1-[[(isopropyl)carbonyl]oxy]ethyl (RS)-1-[[(ethyl)carbonyl]oxy]-2-methylpropyl, (RS)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl, 5-methyl-2-oxo-1,3-dioxolan-4-yl-methyl, 2-oxo-1,3-dioxolane-4-yl-methyl or (RS)-1-[[(ethoxy)the carbonyl]oxy]ethyl.

8. The compounds of formula I according to claim 1, which is selected from the group including
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[isopropyl(methyl)amino]-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-(dimethylamino)-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl)-4-(diethylamino)-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[(2-hydroxyethyl)(methyl)amino]-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[(3-hydroxypropyl)(methyl)amino]-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)Cyclops is ntil]methyl}-4-(4-hydroxypiperidine-1-yl)-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxo-4-[4-(L-Wallace)piperidine-1-yl]butane acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-morpholine-4-yl-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxo-4-(4-oxopiperidin-1-yl)butane acid;
4-[bis(2-hydroxyethyl)amino]-2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-{ethyl[3-(ethylamino)propyl]amino}-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[[2-(dimethylamino)ethyl](methyl)amino]-4-oxobutanoic acid;
4-[(3-aminopropyl)(ethyl)amino]-2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-{methyl[2-(methylamino)ethyl]amino}-4-oxobutanoic acid;
4-[(4-aminobutyl)(methyl)amino]-2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]aminocarbonyl)cyclopentyl]methyl}-4-oxobutanoic acid;
4-[(4-aminobutyl)(ethyl)amino]-2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxobutanoic acid;
2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-{methyl[3-(methylamino)propyl]amino}-4-oxobutanoic acid and
4-[(5-aminopentyl)(methyl)amino]-2-{[1-({[1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-oxobutanoic acid,
together with their biologically labile esters and physiologically compatible salts of acids of these compounds of the formula I and/or physiologically compatible acid additive salts of these compounds of formula I.

9. The compounds of formula I according to one of the preceding paragraphs, in which the chiral carbon atom containing amide side chain in position 3 benzazepine frame is in the configuration of the "S".

10. Pharmaceutical composition having inhibitory activity against neutral endopeptidase (NEP), endothelin-converting enzyme (EKF) and soluble endopeptidase person (frequency-adjustable electric drive)containing a pharmacologically effective amount of the compounds of formula I according to claim 1 and a conventional pharmaceutical excipients and/or inert fillers.

11. The use of compounds of the formula I according to claim 1 to obtain a Lek is stannah funds intended for prevention and/or treatment of cardiovascular disorders or diseases.

12. The application of claim 11, in which cardiovascular disorder or disease selected from the group including congestive heart failure; hypertension, including secondary forms of hypertension, such as essential hypertension, renal hypertension and/or pulmonary hypertension.

13. Application connection double action, capable of inhibiting neutral endopeptidase and soluble endopeptidase person, for preparing a medicinal product intended for the prevention or treatment of sexual dysfunction, where the connection is double-acting, capable of inhibiting neutral endopeptidase and soluble endopeptidase man is a compound of formula I according to claim 1.

14. Use item 13, in which sexual dysfunction is selected from the group including female sexual dysfunction and male sexual dysfunction.

15. Use item 13, in which sexual dysfunction is a male sexual dysfunction.

16. Use item 13, in which dysfunction is selected from the group including erectile dysfunction, ejaculation disorder and disorders of desire.

17. The application of article 16, in which dysfunction is erectile dysfunction.

18. The use of compounds of formulas is I according to claim 1 to obtain drugs, intended for prevention and/or treatment of pathological conditions associated with apoptosis, which are neurodegenerative diseases selected from the group including ischemic stroke, cerebral ischemia and traumatic brain injury.

19. Method of producing compounds of the formula I

in which R1denotes hydrogen or a group forming a biologically labile ester,
R2denotes hydrogen, C1-C4-alkyl or C1-C4-hydroxyalkyl, and
R3represents C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-hydroxyalkyl, which is optionally substituted second hydroxy-group, and all of the hydroxy-group which is not necessarily tarifitsirovana C2-C4-alkanoyl or amino acid residue; (C0-C4-alkyl)2amino-C1-C6-alkyl, C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; phenyl-C1-C4-alkyl, the phenyl group of which is optionally substituted 1-2 times C1-C4-alkyl, C1-C4-alkoxygroup and/or halogen; naphthyl-C1-C4-alkyl, C3-C6-oxoalkyl; phenylcarbonylamino, phenyl group which is optionally substituted 1-2 times C1 -C4-alkyl, C1-C4-alkoxygroup and/or halogen, or 2-oxoazetidin, or
R2and R3together denote C4-C7-alkylen, a methylene group which is optionally 1-2 times replaced by carbonyl, nitrogen, oxygen and/or sulfur and/or which is optionally substituted 1 time hydroxy-group, which does not necessarily etherification C2-C4-alkanoyl or amino acid residue; C1-C4-alkyl, C1-C4-hydroxyalkyl, the hydroxy-group which is not necessarily etherification C2-C4-alkanoyl or amino acid residue; phenyl or benzyl, and
R4denotes hydrogen or a group forming a biologically labile ester,
where the group R1and R4independently from each other selected from C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkoxy-C1-C4-alkyl, C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4the alkyl, optional 1 or 2 times substituted in the phenyl ring by halogen, C1-C4-alkyl or C1-C4-alkoxygroup or C1-C4-alkalinous circuit associated with two adjacent carbon atoms; DIOXOLANYL, long is correctly substituted in the dioxolane ring C 1-C4-alkyl, C2-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted with hydroxy-C1-C4is an alkyl group, a C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alilovic ester; 1-[[(C4-C7-cycloalkane)carbonyl]oxy]C1-C4-alkalemia esters, 2-oxo-1,3-dioxolane-4-yl-C1-C4alilovic esters, which are optionally contain a double bond in the dioxolane ring; 2-oxo-1,3-dioxolane-4-ylmethyl;
as well as physiologically compatible salts of acids of formula I and/or physiologically compatible acid additive salts of compounds of the formula I, characterized in that the compound of General formula II

in which R101and R401independently from each other, represent a protective group of the acid, is introduced into reaction with the compound of General formula III

in which R2and R3have the above values,
in which R2and/or R3contain free hydroxy-group, if necessary, they enter into reaction with the compound of General formula IV

in which X denotes useplease group, or derivative of an amino acid containing a suitable protective group,
in which R101and/or R not indicate the necessary groups, forming a biologically labile ester, and/or in which R2and/or R3represent protective groups contained in any amino acid residue, consistently otscheplaut from the obtained compounds simultaneously or separately in any desired sequence and optionally the formed acid group in each case converted into biologically labile ester groups, and optionally the resulting acid of the formula I is converted into their physiologically compatible salts, or salts of acids of the formula I is converted into the free acids and/or bases of the formula I is converted into their acid additive salt, or an acid additive salt is transformed into free base of formula I.

20. Compounds of General formula II

in which R101denotes a protective group of the acid, and
R401denotes a protective group of the acid,
where the group R101and R401independently from each other selected from C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkoxy-C1-C4-alkyl, C3-C7-cycloalkyl; C3-C7-cycloalkyl-C1-C4-alkyl; N,N-di(C0-C4-alkyl)amino-C1-C6-alkyl; phenyl or phenyl-C1-C4the alkyl, optional 1 or 2 the Aza substituted in the phenyl ring by halogen, C1-C4-alkyl or C1-C4-alkoxygroup, or C1-C4-alkalinous circuit associated with two adjacent carbon atoms; DIOXOLANYL, optionally substituted in the dioxolane ring C1-C4-alkyl, C1-C6-alkanoyloxy-C1-C4-alkyl, optionally substituted with hydroxy-C1-C4is an alkyl group, a C1-C4-alkyl; 1-[[(C1-C4-alkyl)carbonyl]oxy]C1-C4-alilovic ester; 1-[[(C4-C7-cycloalkane)carbonyl]oxy]C1-C4-alkalemia esters, 2-oxo-1,3-dioxolane-4-yl-C1-C4alilovic esters, which are optionally contain a double bond in the dioxolane ring; and 2-oxo-1,3-dioxolane-4-ylmethyl.



 

Same patents:

FIELD: medicine.

SUBSTANCE: there are described new diazabicyclic aryl derivatives of general formula (I), where A', A", L and B, n possess the values as specified in the description which are cholinergic ligands to nicotinic acetylcholine receptors, as well as a based pharmaceutical composition. Owing to their pharmacological profile, the compound according to the invention, can be effective in treating such various diseases or disorders, as those associated with the cholinergic system of central nervous system (CNS), peripheral nervous system (PNS), as those associated with plain muscle contraction, endocrine diseases or disorders, neurodegenerative diseases or disorders, diseases or disorders involving inflammation, pain and abstinence symptoms caused by termination of abusing the chemical substances.

EFFECT: effective with regard to various diseases.

16 cl, 3 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: new derivative of diaminopyrroloquinazolines of formula (I) and their pharmaceutically acceptable salts possess properties of proteintyrosine posphatase PTP1 inhibitors which can be used for treating the diseases mediated by action of the latter, particularly for decreasing glucose content in blood. In formula (I) , A stands for 6-membered aromatic ring, or 5- or 6-membered aromatic ring which contains 1 or 2 heteroatoms chosen from S, N and O; R1 is specified from the group including the following radicals: C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl), benzyloxyC1-6alkyl and phenyl-(C1-6alkoxy)C1-6alkyl; R2 is specified from the group including the following radicals: hydrogen, C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl) and phenyl-(C1-6alkoxy)C1-6alkyl; R3 represents hydrogen or methyl; Ra is specified from the group including the following radicals: hydrogen, C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl(C1-6alkyl), benzyloxyC1-6alkyl or ; R10 represents hydrogen or ; x and y separately stand for integers 0 to 4; Rb and Rc are separately specified from the group including the following radicals: hydrogen, C1-6alkyl, perfluorochemical C1-6alkyl, substituted C1-6alkyl, C1-6alkoxy, phenoxy, halogen, (unsubstituted C1-6alkyl)-(substituted phenyl)-(C1-6alkyl), phenyl-(C1-6alkoxy) or ; R11 represents hydrogen, phenyl or unsubstituted C1-6alkyl; p stands for integer 0 to 1; Rd represents hydrogen, substituted C1-6alkyl or perfluorochemical C1-6alkyl; Re represents hydrogen, halogen, substituted C1-6alkyl and perfluorochemical C1-6alkyl; Rf represents hydrogen or C1-6alkyl; the substitutes found in alkyl groups are independently specified from the following groups: hydroxy, C1-6alkoxy, C1-6alkanoyl; and the substitutes found in substituted phenyl as Rb and Rc, are independently specified from the following groups: C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, hydroxyl, hydroxylC1-6alkoxy, halogen, perfluorC1-6alkyl and C1-6alkanoyl.

EFFECT: improved properties of the derivatives.

29 cl, 2 dwg, 48 ex

FIELD: medicine.

SUBSTANCE: invention covers new pyrrolopyrimidine and pyrrolotriazine derivatives substituted with carbamoyl group of formula [I], characterised as a CRF (corticotrophin release factor) receptor antagonist. The compounds can be effective as a therapeutic or preventive agent for such diseases, as depression, anxiety, Alzheimer's disease, Parkinson's disease, etc. in formula [I]: E means N or CR10; R1 means -OR4, -S(O)1R4 or-NR4R5; R2 means hydrogen, C1-6alkyl; R3 means hydrogen; R4 and R5 are identical or different, and independently mean hydrogen, C1-9alkyl, di(C3-7cycloalkyl)-C1-6alkyl, C1-6alkoxy-C1-6alkyl, di(C1-6alkoxy)-C1-6alkyl, hydroxy-C1-6alkyl, cyano-C1-6alkyl, carbamoyl-C1-6alkyl or di(C1-6alkyl)amino-C2-6alkyl, or R4 and R5 together form (CH2)m-A-(CH2)n where A means CHR9; R9 means hydrogen, hydroxy-C1-6alkyl, or cyano-C1-6alkyl; R10 means hydrogen; I means an integer 0, 1 and 2; m means an integer 1, 2, 3 and 4; n means an integer 0, 1, 2 and 3; Ar means phenyl, and specified phenyl is substituted by one or more substitutes being identical or different, and chosen from the group consisting of halogen, C1-6alkyl, trifluoromethyl; their individual isomers or pharmaceutically acceptable salts.

EFFECT: extended application.

9 cl, 2 dwg, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for phenyl; G stands for C1-C7-alkylene; Q stands for -NH-; and X stands for C1-C7- alkylene, or to its salts. In addition, the invention concerns a pharmaceutical composition, to application of compound of formula I as defined in claims 1-5 item, as well as the method for making the compound of formula I.

EFFECT: production of the new biologically active compounds inhibiting protein tyrosine kinase.

8 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention discloses new trisulphonated tribenzo-mononaphto-porphyrazines, methods for preparing and applying thereof as photosensitising compounds to treat various diseases with using photodynamic therapy. These water-soluble amphiphilic porphyrazines are substituted by various alkyl, aminoalkyl groups with or without carboxyl group.

EFFECT: higher clinical effectiveness.

26 cl, 12 ex, 10 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to new pyridine derivatives or to their pharmaceutically acceptable salts of general formula 1: wherein R1, R2, R3, R4, R5, R6 and R7 are independently chosen from the group including hydrogen atom, halogen, amino, C1-C6lower alkyl, C2-C6lower alkenyl, C1-C6lower alkoxy, C1-C10alkylamino, C4-C9cycloalkylamino, C4-C9heterocycloalkylamino, C1-C10aralkylamino, arylamino, acylamino, saturated heterocyclyl, acyloxy, aryl, heteroaryl, C1-C10aralkyl, aryloxy; X represents oxygen or sulphur atom; Y represents oxygen atom or N-R8, wherein R8 is chosen from the group including hydrogen atom; aforesaid aryl group is chosen from phenyl, naphthyl and condensed phenyl group; aforesaid heteroaryl and saturated heterocyclic groups represent pentagonal or hexagonal heterocyclic ring containing 1 to 2 heteroatoms chosen from oxygen, nitrogen and sulphur atom; or condensed heterocyclic ring; and aforesaid aryl and heteroaryl groups are those that 1 to 4 assistants chosen from group including halogen, C1-C6lower alkyl, C1-C6lower alkoxy are substituted. And specified compounds or their pharmaceutically acceptable salt of formula 1 are not compounds as follows 6-methyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 5-vinyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 6-methyl-8-furan-2-yl-3,4- dihydropyrano[3,4-c]pyridin-1-one, 3-tert-butyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-8-one and dimethyl ether (3S)-6,8-dimethyl-1-oxo-1,2,3,4-tetrahydro-[2,7]naphthyridine-3,5-dicarboxylic acids.

EFFECT: compounds possess inhibitory action with respect to formation of cytokines involved in inflammatory reactions, can be used as a therapeutic agent for treatment of inflammatory diseases, immune diseases, chronic inflammations; it provides antiinflammatory and analgesic action.

21 cl, 7 tbl, 144 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: described is novel application of 2-methylthio-5-methyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-on. Substance possesses anti-viral activity with respect to flue A (H5N1) virus, West Nile virus and other viral infections. Wide-spectrum anti-viral activity is discovered for the first time.

EFFECT: obtaining anti-viral substance with wide spectrum of action.

1 cl, 8 tbl, 4 ex

FIELD: printing industry.

SUBSTANCE: invention relates to ink for jet printing containing at least one dye-stuff, besides: dye-stuff is a compound represented by the following formula (I), or its salt; dye-stuff content (wt %) is 3.0 wt % or more to the total weight of ink for jet printing; in distributing molecules aggregates in ink for jet printing with dye-stuff concentration determined as 3.0 wt %, according to scatter range, measured using method of small-angle x-ray scattering, scatter distance value (d75 complying with the fact that 75% of distributing is 3.0 wt %) is 6.50 nm or more and 7.10 nm or less: common formula (I) , where M means alkali metal or ammonium; I means from 0 to 1, m means from 1 to 2, and n means from 2 to 3 under condition that l+m+n=3 and position of substituent replacing is position 4 and 4.

EFFECT: obtaining ink for jet printing.

3 cl, 1 ex, 9 tbl, 9 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel derivatives of 2,6-dihydro-7H- pyrazolo[3,4-d]pyradazin-7-one, 1,4-dihydropyrazolo[3,4-b]thiazin-5(6H)-one; N-acylated 4-imidazo[1,2-a]pyridin-2-yl- and 4-imidazo[1,2-a]pyrimidin-2-yl- anilines; amides of [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]pyperidin-4-carboxylic acid; amides of 2-(4-carbamoylpyperidin-1-yl)isonicotinic acid; amides of N-sulfonyl-1,2,3,4-tetrahydrochinolin-6-carboxylic acid; as well as to N-acylated 3-azolyl derivatives of 2-amino-4,5,6,7-tetrahydtithieno[2,3-c]pyridine possessing properties of Hh-signal cascade inhibitors.

EFFECT: compounds can be applied for use in pharmaceutical compositions and medications for treating diseases induced by abberant activity of Hedgehog (Hh) signal system, in particular, oncological diseases, for instance, for pancreatic carcinoma treatment.

23 cl, 13 dwg, 11 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: described are derivatives of 1,3,4-oxadiazol-2-on of formula (I) , where ARYL represents phenyl; Z represents -O(CH2)n- and n represents independent integer number from 1 to 5; X represents S; R1 represents C1-6alkyl; R2 represents phenyl, substituted with C1-6perfluoralkyl; or its pharmaceutically acceptable salt; based on it pharmaceutical composition; and method of disease treatment, where disease can be modulated by activity of PPAR-delta binding.

EFFECT: obtaining compounds which possess agonistic or antagonistic activity.

7 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: or its pharmacologically acceptable salts, where n equals 1, 2 or 3; and values of R1, R2, R3, R4, R3', R10, R11 are given in i.1 of formula.

EFFECT: compounds I have ability to inhibit release and/or synthesis of β-amyloid peptide, which allows to apply them in pharmaceutical composition.

25 cl, 3 dwg, 5 ex

Cynnamide compound // 2361872

FIELD: chemistry.

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

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new coumarin derivatives and their carboxamides, with general formula (I) , where R3 is chosen from a group consisting of H, carboxyl, alkyloxycarbonyl, 5'-(phenyloxadiazol-2')-yl, 5'-(pyridyl-4"-oxadiazol-2')-yl, , CONHR9, where R9 is chosen from a group consisting of fatty acids C2-C8, benzoxamido, isonicotinamido, unsubstituted, or mono-, or polysubstituted phenyl, in which the substitute can be hydroxy, C1-C8-alkoxy, CF3, carboxyl, alkyloxycarbonyl, OCH2CO2H, NO2, halogen, SO3H, SO2NHR11, where R11 is chosen from a group consisting of hydrogen, amidino, 2"-thizolyl, 3"-(511-methylisooxazolyl), 2"-pyrimidinyl, 2"-(4",6"-dimethylpyrimidinyl), 4"-(5",6"-dimethoxypyrimidinyl); R4 is chosen from a group consisting of hydrogen, CONHR10, where R10 is chosen from a group consisting of C2-C8 fatty acids, unsubstituted phenyl; R5 is chosen from a group consisting of H, C1-C4 alkyl; R6 is chosen from a group consisting of H, C1-C12-alkyl, halogen, NO2, CONHR13, where R13 is substituted phenyl; R7 is chosen from a group consisting of H, hydroxyl, C1-C4alkyl or alkoxyl, carboxyalkyleneoxyl, OCH2CONHR14, where R14 is chosen from a group consisting of unsubstituted, mono-, or polysubstituted phenyl, in which the substitute can be hydroxyl, OCH3, CF3, CO2H, CO2C2H5, NO2; R8 is chosen from a group consisting of H, C1-C4-alkyl or alkoxyl, NO2; under the condition that, when R3, R5 and R6 are H, and R7 is OH, R4 and R7 are not groups, chosen from H, C1-C6-alkyl or C1-C6-alkoxy. The invention also relates to pharmaceutical compositions based on formula I compounds and their use as medicinal preparations for protecting kidneys, for curing hypertonia, cardio-cerebrovascular diseases, non-achrestic diabetes, tumours, precancerous diseases and oedema.

EFFECT: enhanced effectiveness of the composition and treatment method.

17 cl, 6 tbl, 51 ex

FIELD: chemistry; medicine.

SUBSTANCE: invention relates to 3-phenylpropionic acid derivatives of formula (I) as ligand of peroxisome proliferator-activated gamma-receptor (PPARγ), to their pharmaceutically acceptable salts, as well as to their application, treatment method and based on them pharmaceutical composition. Compounds can be applied for treatment and prevention of diseases mediated by peroxisome proliferator-activated gamma-receptor (PPARγ), for instance type 2 diabetes, insulin-resistance, metabolic syndrome, complications resulting from or connected with diabetes, cardio-vascular dysfunctions, atherosclerosis, obesity, cognition disturbances and lipid metabolism derangements. In general formula (I): W represents COOH or -COO-C1 - C4-alkyl group; Y represents NH; Z represents S or O; X represents O; R1 - R8 each independently represents hydrogen atom or halogen atom; A represents mono-, bi- or tri-cyclic 5-13-member heteroaryl with 1 or 2 heteroatoms selected from N, S or O, aryl, selected from phenyl and naphtyl, or -N(C1-C4-alkyl)-CO-C3-C7-cycloalkyl, where heteroaryl is optionally substituted with 1-3 substituents, independently selected from group, consisting of C1-C4-alkyl, CN, phenyl halogen and phenyl, optionally substituted with 1-3 substituents, independently selected from C1-C4alkoxy, halogen and ethylenedioxy-group; and n represents integer number from 0 to 3 including; and their pharmaceutically acceptable salts.

EFFECT: increased efficiency of composition and treatment method.

20 cl, 14 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 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 refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.

EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.

29 cl, 746 ex, 6 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention covers new compounds of formula (I) where: one of groups R6, R7 and R8 meets formula (II) and groups X, Y1-Y4, R1-R14 and n possess the values specified in the patent claim, and also their pharmaceutically acceptable salts. Compounds I show activating effect with respect to PPARδ and/or PPARαreceptors.

EFFECT: applicability of compounds for treatment and prevention of the diseases modulated by PPARδ and PPARα agonists.

22 cl, 8 dwg, 1 tbl, 21 ex

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