Pyrazine derivatives, useful as adenosine receptor antagonists

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where a represents a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-membered cyclic system containing at least one heteroaromatic cycle and containing at least one heteroatom selected from O, S and N; optionally substituted by one or more substituents independently selected from the group consisting of halogen atoms, C1-4of alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-4of alkyl, C1-4alkoxy and hydroxy-group;
Represents a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-membered heteroaromatic cycle that contains at least one heteroatom selected from S and N; optionally substituted by one or more substituents independently selected from the group consisting of halogen atoms, C1-4of alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-4Alki is a, aryl and C1-4alkylthio;
and either
a) R1represents a group of the formula:

where L represents a linking group selected from the group consisting of a direct link, -(CO)-, -(CO)NR'- and-SO2-;
R' and R" are independently selected from hydrogen atoms;
n has a value from 0 to 1; and
G is selected from the group consisting of a hydrogen atom and C1-4of alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-membered heteroaromatic cycle containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic group, where the heterocyclic group denotes a non-aromatic saturated 6-membered carbocyclic ring in which one or two carbon atoms replaced by a heteroatom N; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted by one or more substituents from halogen atoms;
and R2represents a group selected from hydrogen atoms, halogen atoms and C1-4of alkyl, C2-5the quinil,1-4alkoxy, -NH2and ceanography, where alkyl and alkyline groups can be unsubstituted or substituted with one aryl group;
or
b) R2, R1and the group-NH-, which is attached with R1form a group selected the group of formula (IIA) and (IIb):

where Raselected from a hydrogen atom or a group selected from C1-4of alkyl, C3-8cycloalkyl, aryl, aryl-C1-4of alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-membered heteroaromatic cycle containing at least one heteroatom selected from O and N; saturated heterocyclic ring, where the heterocyclic group denotes a non-aromatic saturated 6-membered carbocyclic ring in which one carbon atom replaced by a heteroatom selected from O and N; and (C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted by one or more groups selected from halogen atoms, ceanography, triptoreline and carbamoyl;
Rbdenotes hydrogen;
and its pharmaceutically acceptable salts and N-oxides;
provided that the compound is not selected from
N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-Alperin-2-yl]benzamide,
N-[3-etoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-Alperin-2-yl]benzamide, and
N-[3-etoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-Alperin-2-yl]formamide.

2. The compound according to claim 1, where a represents an optionally substituted monocyclic five - or six-membered heterocyclic ring or an optionally substituted phenyl ring.

3. Connect the s according to claim 1, where a represents an optionally substituted pyridine, oxazolo, furan, pyrazole nucleus, pyrazinone or phenyl group.

4. The compound according to claim 1, where a represents an optionally substituted pyridine, oxazolo, furan or pyrazol group.

5. The compound according to claim 4, where the group a represents a pyridine ring, unsubstituted or substituted by alkoxygroup or halogen atoms.

6. The compound according to claim 1, where the group a represents a pyridine ring, unsubstituted or substituted by one or two halogen atoms.

7. The connection according to claim 6, where the group a represents a pyridine ring, unsubstituted or substituted by one halogen atom.

8. The compound according to claim 1, where In represents an optionally substituted monocyclic, five - or six-membered heterocyclic ring containing one or two nitrogen atom.

9. The connection of claim 8, where In represents an optionally substituted pyridine or pyrimidine group.

10. The compound according to claim 1, where the group is a pyridine ring, unsubstituted or substituted by one or two halogen atoms.

11. The connection of claim 10, where the group is a pyridine ring, unsubstituted or substituted by one halogen atom.

12. The compound according to claim 1, where R1represents a group of formula is:

where L represents a direct bond or a group -(CO)-,
R' and R" are independently selected from hydrogen atoms;
n is 0-1; and
G is selected from the group consisting of a hydrogen atom, a C1-4alkyl, C3-8cycloalkyl, aryl or heteroaryl groups, where C1-4alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted by one or more substituents selected from halogen atoms.

13. The connection section 12, where G is selected from the group consisting of a hydrogen atom, a C1-4alkyl, C3-8cycloalkyl, aryl or heteroaryl group, where the aryl or heteroaryl groups are unsubstituted or substituted by one or more substituents selected from halogen atoms.

14. The connection section 12, where R1represents a group of the formula:

where L represents a group -(CO)-,
R' and R" are independently selected from hydrogen atoms;
n is 0-1; and
G is selected from the group consisting of a hydrogen atom and C3-8cycloalkyl groups, optionally substituted by one or more substituents selected from halogen atoms.

15. The connection 14, where G is selected from the group consisting of a hydrogen atom and C3-8cycloalkyl group.

16. Link is on 14 where:
G represents a C3-5cycloalkyl group, optionally substituted by one or more substituents selected from halogen atoms, and n has a value of 0-1.

17. The compound according to claim 1, where R2represents a hydrogen atom.

18. The compound according to any one of claims 1 to 11, where R2, R1and the group-NH-, which is attached with R1form the group of formula (IIA) or (IIb):

where Raselected from C3-8cycloalkyl, saturated heterocyclic ring, aryl and heteroaryl; where the aryl or heteroaryl groups are unsubstituted or substituted by one or more halogen atoms; and
Rbrepresents a hydrogen atom.

19. Connection p, where R2, R1and the group-NH-, which is attached with R1form a residue of formula (IIb):

where Raselected from C3-8cycloalkyl, saturated heterocyclic ring, aryl and heteroaryl; where the aryl or heteroaryl groups are unsubstituted or substituted by one or more halogen atoms.

20. The compound according to claim 1, which is selected from the following compounds:
6-(3-forfinal)-5-pyridin-4-Alperin-2-amine,
5-(3-chloropyridin-4-yl)-6-(3-forfinal)pyrazin-2-amine,
6-(3-forfinal)-5-(forbidin-4-yl)pyrazin-2-amine,
6-(3-forfinal)-5-(1,3-thiazol-5-yl)pyrazin-2-amine,
6-(2-furyl)-5-pyridin-4-Alperin-2-amine,
6-(2-furyl)-5-[2-(methylthio)pyrimidine-4-yl]pyrazin-2-amine,
5-pyridin-4-yl-6-(2-thienyl)pyrazin-2-amine,
6-(2-furyl)-5-pyrimidine-4-Alperin-2-amine,
6-(2-furyl)-5-(2-methylpyrimidin-4-yl)pyrazin-2-amine,
5-(2-cyclopropylamino-4-yl)-6-(2-furyl)pyrazin-2-amine,
6-(2-furyl)-5-(2-phenylpyrimidine-4-yl)pyrazin-2-amine,
6-pyridin-2-yl-5-pyridin-4-Alperin-2-amine,
6-pyridin-3-yl-5-pyridin-4-Alperin-2-amine,
5,6-piperidin-4-Alperin-2-amine,
N-[6-(5-methyl-2-furyl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
6-(2-forfinal)-5-pyridin-4-Alperin-2-amine,
N-[6-(3-herperidin-4-yl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(3-chloropyridin-4-yl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(1,3-oxazol-5-yl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(1,3-oxazol-2-yl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-chloropyridin-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-chloropyridin-4-yl)-6-pyridin-2-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-chloropyridin-4-yl)-6-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-chloropyridin-4-yl)-6-pyridin-3-Alperin-2-yl]-2,2-dimethylpropanamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-4-Alperin-2-yl]t is chloroanthracene,
6-(3-forfinal)-N-pyridin-3-yl-5-pyridin-4-Alperin-2-amine,
N-[6-(3-forfinal)-5-pyridin-4-Alperin-2-yl]pyrimidine-5-amine,
N-[6-(3-forfinal)-5-pyridin-4-Alperin-2-yl]acetamide", she
N-[6-(2-forfinal)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
6-(2-furyl)-N-pyridin-3-yl-5-pyridin-4-Alperin-2-amine,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]pyrimidine-5-amine,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]acetamide", she
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]propanamide,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]cyclobutanecarboxylic,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]cyclopentanecarboxylic,
N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]-2-methylpropanamide,
2-cyclopentyl-N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]acetamide", she
4-fluoro-N-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]benzamide,
N-cyclopentyl-N'-[6-(2-furyl)-5-pyridin-4-Alperin-2-yl]urea,
N-{6-(2-furyl)-5-[2-(methylthio)pyrimidine-4-yl]pyrazin-2-yl}acetamide", she
N-{6-(2-furyl)-5-[2-(methylthio)pyrimidine-4-yl]pyrazin-2-yl}cyclopropanecarboxamide,
N-[5-pyridin-4-yl-6-(2-thienyl)pyrazin-2-yl]acetamide", she
N-[6-(2-furyl)-5-pyrimidine-4-Alperin-2-yl]acetamide", she
N-[6-(2-furyl)-5-pyrimidine-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(2-furyl)-5-(2-methylpyrimidin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(2-cyclopropylamino-4-yl)-6-(2-furyl)pyrazin-2-yl]cyclopropanecarboxylic the ID,
N-[6-(2-furyl)-5-(2-phenylpyrimidine-4-yl)pyrazin-2-yl]acetamide", she
N-[6-(2-furyl)-5-(2-phenylpyrimidine-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-(6-pyridin-2-yl-5-pyridin-4-Alperin-2-yl)acetamide", she
N-(6-pyridin-2-yl-5-pyridin-4-Alperin-2-yl)cyclopropanecarboxamide,
N-cyclopentyl-N'-(6-pyridin-2-yl-5-pyridin-4-Alperin-2-yl)urea,
N-(4-forfinal)-N'-(6-pyridin-2-yl-5-pyridin-4-Alperin-2-yl)urea,
N-(6-pyridin-3-yl-3-pyridin-4-Alperin-2-yl)cyclopropanecarboxamide,
N-(6-pyridin-3-yl-5-pyridin-4-Alperin-2-yl)cyclobutanecarboxylic,
N-cyclopentyl-N'-(6-pyridin-3-yl-5-pyridin-4-Alperin-2-yl)urea,
N-(4-forfinal)-N'-(6-pyridin-3-yl-5-pyridin-4-Alperin-2-yl)urea,
6-pyridin-3-yl-5-pyridin-4-yl-N-1,3-thiazol-2-Alperin-2-amine,
N-(5,6-piperidin-4-Alperin-2-yl)cyclopropanecarboxamide,
3-bromo-6-(3-forfinal)-5-pyridin-4-Alperin-2-amine,
3-bromo-6-(2-furyl)-5-pyridin-4-Alperin-2-amine,
3-bromo-6-pyridin-3-yl-5-pyridin-4-Alperin-2-amine,
3-amino-5-(2-furyl)-6-pyridin-4-Alperin-2-carbonitril,
3-ethinyl-6-(2-furyl)-5-pyridin-4-Alperin-2-amine,
6-(2-furyl)-3-(phenylethynyl)-5-pyridin-4-Alperin-2-amine,
6-(2-furyl)-3-methoxy-5-pyridine-4-Alperin-2-amine,
3-ethyl-6-(2-furyl)-5-pyridin-4-Alperin-2-amine,
N-[3-cyano-6-(2-furyl)-5-pyridin-4-Alperin-2-yl]acetamide", she
N-[6-(2-furyl)-3-methoxy-5-pyridine-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[3-ethyl-6-(2-furyl)-5-pyridin-4-yl is irisin-2-yl]acetamide", she
5-phenyl-6-pyridin-4-Alperin-2,3-diamine,
5-(3-forfinal)-6-pyridin-4-Alperin-2,3-diamine,
3-amino-5-(3-forfinal)-6-pyridin-4-Alperin-2-ol,
6-(3-forfinal)-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
6-(3-forfinal)-2-methyl-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
5-(3-forfinal)-6-pyridin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-it,
6-(3-forfinal)-5-pyridin-4-yl-2-(trifluoromethyl)-1H-imidazo[4,5-b] pyrazin,
5-(4-forfinal)-6-pyridin-4-Alperin-2,3-diamine,
5-(3-were)-6-pyridin-4-Alperin-2,3-diamine,
5-(2-forfinal)-6-[2-(methylthio)pyrimidine-4-yl]pyrazin-2,3-diamine,
6-(2-forfinal)-5-[2-(methylthio)pyrimidine-4-yl]-1H-imidazo[4,5-b]pyrazin,
5-(3-chlorophenyl)-6-[2-(methylthio)pyrimidine-4-yl]pyrazin-2,3-diamine,
6-(3-chlorophenyl)-5-[2-(methylthio)pyrimidine-4-yl]-1H-imidazo[4,5-b]pyrazin,
5-(3-forfinal)-6-[2-(methylthio)pyrimidine-4-yl]pyrazin-2,3-diamine,
6-(3-forfinal)-5-[2-(methylthio)pyrimidine-4-yl]-1H-imidazo[4,5-b]pyrazin,
5-(2-furyl)-6-pyridin-4-Alperin-2,3-diamine,
3-amino-5-(2-furyl)-6-pyridin-4-Alperin-2-ol,
6-(2-furyl)-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
2-cyclopentyl-6-(2-furyl)-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
2,6-di-2-furyl-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
6-(2-furyl)-2-pyridin-3-yl-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
6-(2-furyl)-2,5-piperidin-4-yl-1H-imidazo[4,5-b]pyrazin,
6-(2-furyl)-2-pyridin-2-yl-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
6-(2-furyl)-2-pyrazin-2-yl-5-pyridin-4-what-1H-imidazo[4,5-b]pyrazin,
5-(5-methyl-2-furyl)-6-pyridin-4-Alperin-2,3-diamine,
5-(1-benzofuran-2-yl)-6-pyridin-4-Alperin-2,3-diamine,
5-pyridin-3-yl-6-pyridin-4-Alperin-2,3-diamine,
5-pyridin-3-yl-6-pyridin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-it,
2-(4-forfinal)-6-pyridin-3-yl-5-pyridin-4-yl-1H-imidazo[4,5-b]pyrazin,
5-(2-furyl)-6-pyrimidine-4-Alperin-2,3-diamine,
3-amino-5-(2-furyl)-6-pyrimidine-4-Alperin-2-ol,
6-(2-furyl)-5-pyrimidine-4-yl-1H-imidazo[4,5-b]pyrazin,
5-(2-furyl)-6-pyrimidine-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-it,
6-(2-furyl)-2-pyridin-3-yl-5-pyrimidine-4-yl-1H-imidazo[4,5-b]pyrazin,
5-(2-furyl)-6-[2-(methylthio)pyrimidine-4-yl]pyrazin-2,3-diamine,
3-amino-5-(2-furyl)-6-[2-(methylthio)pyrimidine-4-yl]pyrazin-2-ol,
6-(2-furyl)-5-[2-(methylthio)pyrimidine-4-yl]-1H-imidazo[4,5-b]pyrazin,
5-(3-methyl-2-furyl)-6-pyrimidine-4-Alperin-2,3-diamine,
5-[2-(methylthio)pyrimidine-4-yl]-6-(2-thienyl)pyrazin-2,3-diamine,
5-[2-(methylthio)pyrimidine-4-yl]-6-(2-thienyl)-1H-imidazo[4,5-b]pyrazin,
3-(2-furyl)-2-pyridin-4-yl-5H-pyrrolo[2,3-b]pyrazin,
3-(2-furyl)-6-phenyl-2-pyridin-4-yl-5H-pyrrolo[2,3-b]pyrazin,
6-cyclohexyl-3-(2-furyl)-2-pyridin-4-yl-5H-pyrrolo[2,3-b]pyrazin,
5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-amine,
5-(3,5-differencein-4-yl)-6-pyridin-3-Alperin-2-amine,
N-[6-(6-hydroxypyridine-3-yl)-5-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
1-cyclopropyl-3-(6-(pyridin-2-yl)-5-(pyridin-4-yl)pyrazin-2-yl)urea,
N-[5-3-herperidin-4-yl)-6-(6-methoxypyridine-3-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5,6-bis(3-herperidin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-quinoline-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-(5-methoxypyridine-3-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-(6-hydroxypyridine-3-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-(1-oxidability-3-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-pyrimidine-5-Alperin-2-yl]cyclopropanecarboxamide,
N-[3-(3-herperidin-4-yl)-2,2'-piperazin-6-yl]cyclopropanecarboxamide,
N-[5-(3-fluoro-1-oxidability-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-(5-herperidin-2-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[6-(2-forfinal)-5-(3-herperidin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[6-(2,4-differenl)-5-(3-herperidin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-(1,3-oxazol-2-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]propanamide,
2-cyclopentyl-N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]acetamide", she
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopentanecarboxylic,
3,3,3-Cryptor-N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]propanamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]cyclobutanecarboxylic,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-ilpi Azin-2-yl]acetamide", she
2-cyclopropyl-N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]acetamide", she
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]-2-morpholine-4-ylacetamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]-2-methylpropanamide,
N-[5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2-yl]methanesulfonamide,
N-[5-(3,5-differencein-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3,5-differencein-4-yl)-6-pyridin-4-Alperin-2-yl]cyclopropanecarboxamide,
N-[5-(3,5-differencein-4-yl)-6-(1-oxidability-3-yl)pyrazin-2-yl]cyclopropanecarboxamide,
N-[5-(3,5-debtor-1-oxidability-4-yl)-6-pyridin-3-Alperin-2-yl]cyclopropanecarboxamide,
N-[6-(3,5-differencein-2-yl)-5-(3-herperidin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide,
6-(4-forfinal)-2-(3-herperidin-4-yl)-3-pyridin-3-yl-5H-pyrrolo[2,3-b]pyrazin,
2-(3-herperidin-4-yl)-6-pyridin-2-yl-3-pyridin-3-yl-5H-pyrrolo[2,3-b]pyrazin,
2-(3-herperidin-4-yl)-3,6-piperidin-3-yl-5H-pyrrolo[2,3-b]pyrazin,
4-[2-(3-herperidin-4-yl)-3-pyridin-3-yl-5H-pyrrolo[2,3-b]pyrazin-6-yl]benzonitrile,
4-[2-(3-herperidin-4-yl)-3-pyridin-3-yl-5H-pyrrolo[2,3-b]pyrazin-6-yl]benzamide,
2-(3-herperidin-4-yl)-3-pyridin-3-yl-5H-pyrrolo[2,3-b]pyrazin,
5-(3-herperidin-4-yl)-6-pyridin-3-Alperin-2,3-diamine,
2-(4-forfinal)-5-(3-herperidin-4-yl)-6-pyridin-3-yl-1H-imidazo[4,5-b]pyrazin,
5-(3-herperidin-4-yl)-6-pyridin-3-yl-2-[4-(triptoreline)phenyl]-1H-imidazo[4,5-b]pyrazin,
2-[1-(chlorphenyl)ethyl]-5-(3-herperidin-4-yl)-6-pyridin-3-yl-1H-imidazo[4,5-b]pyrazin,
5-(3-herperidin-4-yl)-2-(methylthio)-6-pyridin-3-yl-1H-imidazo[4,5-b]pyrazin,
5-(3-herperidin-4-yl)-2-morpholine-4-yl-6-pyridin-3-yl-1H-imidazo[4,5-b]pyrazin,
5-(3-herperidin-4-yl)-6-pyridin-3-yl-N-(2,2,2-Cryptor-1-methylethyl)pyrazin-2-amine,
5-(3-herperidin-4-yl)-6-pyridin-3-yl-N-(2,2,2-triptorelin)pyrazin-2-amine.

21. The compound according to claim 1 for use for the treatment of a pathological condition or disease that is alleviated by antagonism of the adenosine receptor And2B.

22. Pharmaceutical composition having antagonistic activity against adenosine receptor And2Bcontaining the compound according to any one of claims 1 to 20, together with a pharmaceutically acceptable diluent or carrier.

23. The use of compounds according to any one of claims 1 to 20 for the manufacture of a medicinal product for the treatment of a pathological condition or disease that is alleviated by antagonism of the adenosine receptor And2B.

24. The application of item 23, where the pathological condition or disease is a asthma, bronchoconstriction, allergic diseases, hypertension, atherosclerosis, reperfusion injury, myocardial ischemia, retinopathy, inflammation, disorders of the gastrointestinal tract, disorders of cell proliferation, diabetes and/or autoimmune diseases.

25. The method of treatment of a subject suffering is his pathological condition or disease, which is alleviated by antagonism of the adenosine receptor And2Bthat includes the introduction of a specified subject an effective amount of a compound according to any one of claims 1 to 20.

26. The method according A.25, where the pathological condition or disease is a asthma, bronchoconstriction, allergic diseases, hypertension, atherosclerosis, reperfusion injury, myocardial ischemia, retinopathy, inflammation, disorders of the gastrointestinal tract, disorders of cell proliferation, diabetes and/or autoimmune diseases.

27. Combination product containing:
(i) the compound according to any one of claims 1 to 20; and
(ii) another compound selected from (1) antagonists of muscarinic M3 receptors, (2) β2-agonists, (3) PDE4 inhibitors, (4) corticosteroids, (5) antagonists of leukotriene D4, (6) inhibitors of egfr-kinase, (7) inhibitors R kinase, (8) agonists of the receptor NK1, (9) CRTh2 antagonists, (10) inhibitors of syk kinase, (11) CCR3 antagonists and (12) antagonists of VLA-4.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to oxazolidinone derivatives of formula (I) or pharmaceutically acceptable salts thereof, synthesis method thereof and pharmaceutical compositions containing said derivatives which are used as an antibiotic. Oxazolidinone derivatives, where R1 and R1' independently denote hydrogen or fluorine; R2 denotes -OR7, fluorine, monophosphate or metal phosphate; and R7 denotes hydrogen, C1-3alkyl or an acylated amino acid group, where the amino acid is alanine, glycine, proline, proline, isoleucine, leucine, phenylalanine, β-alanine or valine; R3 denotes hydrogen, a C1-4alkyl group which is unsubstituted or substituted cyano, , -(CH2)m-OR7 (m equals 0, 1, 2, 3, 4) or a ketone group. Oxazolidinone derivatives of formula (I) have antibacterial activity against different human and animal pathogens.

EFFECT: oxazolidinone derivatives, having inhibiting activity towards a wide range of bacteria and having low toxicity.

27 cl, 4 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

, where R1 is selected from a group comprising hydrogen, lower alkyl, lower hydroxyl, lower alkoxyalkyl, lower halogenalkyl, lower cyanoalkyl; unsubstituted or substituted phenyl; lower phenylalkyl, where the phenyl ring can be unsubstituted or substituted; and heteroaryl, selected from pyridyl and pyrimidinyl; R2 denotes hydrogen or halogen; G denotes a group selected from

, where m equals, 0, 1; R3 is selected from lower alkyl, cycloalkyl and lower cycloalkylalkyl; n equals 0, 1; R4 denotes lower alkyl, as well as pharmaceutical compositions.

EFFECT: said compounds are used to treat or prevent diseases associated with histaminase receptor modulation.

19 cl, 1 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel pyrazole derivatives of formula (I) or pharmaceutically acceptable salts thereof, having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths accompanied by high level of Trk, to a method of producing said derivatives, use thereof to prepare a medicinal agent, pharmaceutical compositions based on said derivatives, a method of inhibiting Trk activity and a method of obtaining antiproliferative action. where A denotes a single bond or C1-2alkylene; where the said C1-2alkylene can be optionally substituted with one R22; ring C is a phenyl or a 5-6-member heterocyclic ring with 1-2 heteroatoms selected from N or S. Values of R1-R7, R22 and n are given in the formula of invention.

EFFECT: obtaining pharmaceutically acceptable salts having tyrosine kinase Trk inhibiting properties and used for treating or preventing malignant growths.

20 cl, 5 dwg, 193 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of cis-2,4,5-triarylimidazoline of general formula I and pharmaceutically acceptable salts thereof, where X1 is selected from a group comprising lower alkoxy; X2 and X3 are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX4X5, -SO2NX4X5, -C(O)NX4X5, -C(O)X6, -SOX6, -SO2X6, -NC(O)-lower alkoxy, -C≡C-X7, provided that both X2 and X3 do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X2 or X3 denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X2 denotes -HX4X5, X3 does not denote hydrogen, X2 and X3 together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X4 and X5 are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO2-lower alkyl, -C(O)piperazinyl-3-one; X6 is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X7 is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y1 and Y2 are independently selected from a group comprising halogen; R is selected from a group comprising lower alkoxy, piperidinyl substituted with a five-member heterocyclic ring which contains one nitrogen heteroatom, piperidinyl substituted with a hydroxy, -CH2OH or -C(O)NH2, piperazinyl substituted with one or two R1 [1,4]diazepanyl, substituted R1, R1 can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R2, -C(O)R3, -SO2-lower alkyl, -SO2-five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R2 is selected from a group comprising -SO2-lower alkyl, hydroxy, lower alkoxy, -NH-SO2-lower alkyl, -cyano, -C(O)R4; R3 is selected from a group comprising a five-member heterocyclyl which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl, lower alkyl, lower alkenyl, lower alkyl substituted with a six-member heterocyclyl selected from piperidinyl, piperazinyl, 3-oxopiperazinyl, morpholinyl, C3-cycloalkyl; R4 is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR5R6; R5 and R6 are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C3-cycloalkyl. The invention also relates to a pharmaceutical composition based on the formula I compound, use of the formula I compound in preparing a medicinal agent and a method for synthesis of the formula I compound.

EFFECT: novel derivatives of cis-2,4,5-triarylimidazoline of general formula I are obtained, which can be used to treat diseases, based on reaction of the MDM2 protein with p53-like protein, particularly as anticancer agent.

54 cl, 412 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel derivatives of 1H-imidazole of formula I, in which R1 represents hydrogen, halogen atom, C1-3-alkyl group, and said C1-3-alkyl groupcan include 1-3 fluorine atoms or R1 represents cyclopropyl, piano, or methylsulfanyl group, R2 represents phenyl group, which can be substituted with 1 substituent Y, selected from methoxy, chlorine, fluorine, trifluoromethyl and cyano, or R2 represents pyridyl group, on condition that R2 is not 6-methyl-2-pyridyl group, or R2 represents fully saturated 6-7-member monocyclic, condensed bicyclic ring system or benzothiazolyl, benzodioxane or thiazole group, and said groups can be substituted by 1 fluorine atom, or R2 represents group of general formula CH2-R5, in which R5 represents phenyl group or fully saturated 7-member condensed bicyclic carbocyclic ring system, or R5 represents piperidine or tetrahydrofuran ring system, which can be substituted by methyl, or R2 represents methylsulfonylamino(C3)alkyl group, R3 represents hydrogen, halogen atom, C1-6-alkylsulfonyl, cyanogroup, or R3 represents C1-8-alkyl group, and said C1-8-alkyl group can be substituted by 1-3 fluorine atoms, or R3 represents phenyl group, which is substituted by substituent Y, where Y has value, specified above, or R3 represents furanyl group, R4 represents one of subgroups (i) or (ii), where R6 represents C4-8-branched or linear alkyl group or naphtyl group, R7 represents hydrogen atom, linear C1-6-alkyl group, R8 represents C2-6-alkyl group, substituted by 1-3 fluorine atoms, or R8 represents C3-8-cycloalkyl group, piperidine group, C3-8-cycloalkyl- C1-2-alkyl group, tetrahydrofuranyl- C1-2-alkyl group, C5-10-bicycloalkyl group, C5-10-bicycloalkyl-C1-2-alkyl group, C6-10-tricycloalkyl group, C6-10-tricycloalkyl-C1-2-alkyl group, and said groups can be substituted by 1-3 substituents, selected from methyl or hydroxyl, or R8 represents phenyl group, substituted by 1-2 substituents Y, specified above, or R8 represents naphtyl, 1,2,3,4-tetrahydronaphtyl or indanyl group, and said groups can be substituted by 1 substituent Y, or R8 represents phenyl- C1-3-alkyl group, diphenyl- C1-3-alkyl group, and said groups can be substituted ob their phenyl ring by 1 substituent Y, where Y has value specified above, or R8 represents benzyl group, substituted by 2 substituents Y, or R8 represents quinilinyl, pyridinyl, benzimidazole or naphtylmethyl group which can be substituted by substituent Y, where Y has value, specified above, or R8 represents asabicyclo[3,3,0]octanyl group, on condition that R8 is neither 6-methoxybenzothiazole-2-yl group, nor [3-chlor-5-(trifluoromethyl)pyrid-2-yl]methyl group, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, non-aromatic, monocyclic or bicyclic heterocyclic group, including only one nitrogen atom, having 7-10 ring atoms, which can be subslituted by 3 C1-3-alkyl groups, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, monocyclic heterocyclic group, optionally including another N atom, having 6 ring atoms, and said heterocyclic group is substituted by C1-3-alkyl groups, on condition that R7 and R8 together with nitrogen atom, to which they are bound, do not form trimethylsubstituted asabicyclo[3,3,0]octanyl group, as well as their stereoisomers and pharmacologically acceptable salts of said formula (I) compounds and their stereoisomers Invention also relates to intermediate compounds of formula XIV, pharmaceutical composition based on formula I compound, method of obtaining such pharmaceutical composition and application of formula T compound.

EFFECT: obtained are novel derivatives of IH-imidazole, which are modulators of cannabinoid CB2-receptors.

8 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel amide derivatives of general formula [1] in any of versions (A) or (B), or its pharmaceutically acceptable salt, which possess properties of tyrosinkinase BCR-ABL inhibitor. Amide derivative of general formula [1] represents compound: , where according to Version (A) R1 represents any of the following groups (1)-(3): (1) -) -CH2-R11 [R11 represents saturated 4-6 member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom, which is substituted by group selected from group, consisting of oxo, -CH2-R111 (R111 represents saturated 5-member nitrogen-containing heterocyclic group), saturated 5-member nitrogen-containing heterocyclic group, aminomethyl, monoalkylaminomethyl, dialkylaminomethyl and (5-methyl-2-oxo-1,3-Dioxol-4-yl)methyl, and in addition, can be substituted by 1 or 2 similar or different substituents, selected from group, consisting of (C1-C4)alkyl, (C1-C4 alkoxycarbonyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, amino, carbamoyl], (2) -O-R12 [R12 represents saturated 4-6-member nitrogen-containing heterocyclic group]; and (3) - CH=R13 [R13 represents saturated 4-6-member nitrogen-containing heterocyclic group, which can contain additional nitrogen atom, and which can be substituted by 1-3 similar or different substituents, selected from group, consisting of oxo, (C1-C4)alkyl]; R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy and carbamoyl; R3 represents hydrogen, halogen; Het1 represents any of groups with the following chemical formulae [4] and [6]: [4] [6] [19] [10] Het2 represents pyridyl or pyrimidinyl. According to Version (B) R1 represents -CH2-R14 [R14 represents saturated 4-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, which can be substituted by 1-3 similar groups, selected from (C1-C4)alkyl] R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy (C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C4)acyl, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, nitro, carbamoyl, mono(C1-C4)alkylcarbamoyl, di(C1-C4)alkylcarbamoyl or cyano; R3 represents hydrogen or halogen; Het1 represents any of groups with the following chemical formulas [9] and [10], Het2 represents pyridyl.

EFFECT: invention can be applied for treatment of chronic myeloleukosis, acute lymphoblastic leukosis and acute myeloblastic leukosis.

6 cl, 89 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel anhydrous tetomilast type A crystalline form, having powder X-ray diffraction spectrum essentially the same as the powder X-ray diffraction spectrum having characteristic peaks at 2θ = 10.5°, 13.1°, 18.4°, 21.9° and 25.8°, pharmaceutical compositions based thereon and synthesis methods thereof.

EFFECT: considerable advantages in terms of industrial production owing to significantly better filterability.

8 cl, 14 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

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