Pyrrolopyrazine kinase inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to use of novel pyrrolopyrazine derivatives of formula , where variables Q and R are as defined in the claim, which inhibit JAK and SYK.

EFFECT: high effectiveness when treating autoimmune and inflammatory diseases.

11 cl, 59 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I:

where R is an R1or R2;
R1represents a C1-C6-alkyl, lower alkoxygroup, C3-C8-cycloalkyl or C3-C8-cycloalkyl-C1-C10-alkyl, optionally substituted by one or more R1a;
R1ais an R1bor R1c;
R1brepresents a hydroxy-group;
R1crepresents a C1-C6-alkyl;
R2represents N(R2a)2;
each R2aindependently represents H or R2b;
each R2bindependently represents a C1-C6-alkyl, phenyl, heteroaryl, C3-C8-cycloalkyl, heteroseksualci or heteroseksualci-C1-C10-alkylene, optionally substituted by one or the multiple R 2c;
R2cis an R2dor R2e;
R2drepresents halogen, oxoprop or hydroxy-group;
R2erepresents N(R2g)2-C(=O)(R2g), -C(=O)O(R2g), -C(=O)N(R2g)2, -N(R2g)C(=O)(R2g), -S(=O)2(R2g), -S(O)2N(R2g)2C1-C6-alkyl, C1-C6-alkoxygroup, C1-C6-halogenated, phenyl, heteroaryl, heterokaryosis,3-C8-cycloalkyl or heteroseksualci, optionally substituted by one or more R2f;
each R2findependently represents H, halogen, C1-C6-alkyl, C1-C6-alkoxygroup, C1-C6-halogenated;
each R2gindependently represents H, C1-C6-alkyl, C1-C6-alkoxygroup, C1-C6-halogenated or phenyl;
Q2represents a C3-C8-cycloalkyl,5-C7-cycloalkenyl, heteroseksualci or heteroaryl, optionally substituted by one or more Q2a;
Q2ais a Q2bor Q2c;
Q2brepresents halogen, oxoprop, the hydroxy-group, -CN, -SCH3, -S(O)2CH3or-S(=O)CH3;
Q2cis a Q2dor Q2e;
or two Q2atogether form the BIC is Klionsky ring system, optionally substituted by one or more Q2bor Q2c;
Q2drepresents-O(Q2e), -S(=O)2(Q2e), -C(=O)N(Q2e)2, -S(O)2(Q2e), -C(=Q)(Q2e), -C(=O)O(Q2e), -N(Q2e)2; -N(Q2e)C(=O)(Q2e), -N(Q2e)C(=O)(Q2eor-N(Q2e)C(O)N(Q2e)2;
each Q2eindependently represents H or Q2e;
each Q2e'independently represents a C1-C6-alkyl, phenyl, benzyl, C1-C6-halogenated,3-C8-cycloalkyl,5-C7-cycloalkenyl, heteroseksualci or heteroaryl, optionally substituted by one or more Q2f;
Q2fis a Q2gor Q2h;
Q2grepresents a halogen, a hydroxy-group, cyano, oxoprop or-C(=O)(Q2h);
Q2hrepresents a C1-C6-alkyl, C1-C6-halogenated, C1-C6-alkoxygroup, amino group, phenyl, benzyl, C3-C8-cycloalkyl, heteroseksualci or heteroaryl, optionally substituted by one or more Q2i;
Q2irepresents a halogen, a hydroxy-group, cyano, C1-C6-alkyl, C1-C6-halogenated or C1-C6-alkoxygroup;
where the term "heteroaryl" as here used, means the mod is acyclically or bicyclic radical, containing from 5 to 18 atoms in the cycle containing at least one aromatic ring containing 4 to 8 atoms in the ring including one or more heteroatoms N, O or S and the remaining atoms in the ring are carbon atoms, provided that interconnection point or heteroaryl radical is an aromatic ring;
the term "heteroseksualci", "heterocyclyl" or "heterocycle" as used here, denotes a monovalent saturated cyclic radical, consisting of 1-2 rings or 3 rings containing from 3 to 8 atoms in the ring including one or more ring carbon atoms and one or more ring carbon atoms and one or more ring heteroatoms (chosen from N, O or S(O)0-2), where the point of connection can be either through a carbon atom or through a heteroatom;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R is an R1.

3. The compound according to claim 2, where R1represents a C1-C6-alkyl.

4. The compound according to claim 1, where R is an R2and R2represents NH(R2a).

5. The compound according to claim 1, where Q2is heteroseksualci, optionally substituted by one or more Q2a.

6. The compound according to claim 1, where Q2is heteroaryl, optionally substituted ar is them or more Q 2a.

7. The connection according to claim 6, where Q2represents pyridine.

8. The connection according to claim 6, where Q2ais a Q2cand Q2cis heteroseksualci, optionally substituted by one or more Q2d.

9. The compound according to claim 1, where Q2represents a C3-C8-cycloalkyl.

10. The compound according to claim 1, selected from the group including:
1-[2-(1-benzazolyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-[2-(1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
isopropylated 2-cyclohex-1-enyl-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid;
isopropylated 2-cyclohexyl-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid;
1-{2-[2-(4-acetylpiperidine-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(5-methoxypyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
tert-butyl ether [1-(7-isopropylcarbamate-5H-pyrrolo[2,3-b]pyrazin-2-yl)piperidine-3-yl]methylcarbamate acid;
isopropylated 2-(3-methylaminopropyl-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid; compound with triperoxonane acid;
2,2-dimethyl-1-(2-pyrrolidin-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
1-[7-(2,2-dimethylpropyl)-2'-pyrrolidin-1-yl-5H-[2,5']bi[pyrrolo[2,3-b]pyrazinyl]-7'-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(2-pyrrolidin-1-espiridion-4-yl)-spiralo[2,3-b] pyrazin-7-yl]propane-1-he;
1-[2-(1-cyclopentyl-1H-[1,2,3]triazole-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-{2-[2-(3-dimethylaminopropan-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(2-thiomorpholine-4-espiridion-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-{2-[2-(2-methylpyrrolidine-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
1-[2-(1,3-dihydroindol-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-[2-(2,3-dihydroindol-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-3,4-dihydro-2H-isoquinoline-1-he;
1-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-3,4-dihydro-1H-quinoline-2-he;
2-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-2,3-dihydroindol-1-he;
1-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]piperidine-2-he;
1-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]pyrrolidin-2-he;
1-[2-(1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(6-pyrrolidin-1-espiridion-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(4-pyrrolidin-1-espiridion-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-(2-pyridin-2-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
tert-butyl ether [1-(7-isopropylcarbamate the-5H-pyrrolo[2,3-b]pyrazin-2-yl)piperidine-3-yl]methylcarbamate acid;
isopropylated 2-(3-methylaminopropyl-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid; compound with triperoxonane acid;
(tetrahydropyran-4-yl)amide 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-3-carboxylic acid;
cyclopentolate 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
(tetrahydropyran-4-yl)amide 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
1-(2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
5-[7-(2,2-dimethylpropionic)-5H-pyrrolo [2,3-b]pyrazin-2-yl]thiophene-3-carboxylic acid;
(2-dimethylaminoethyl)amide 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-3-carboxylic acid;
1-{2-[2-(3-methoxyphenyl)cyclopent-1-enyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
ethyl ester of 6-{2-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]cyclopent-1-enyl}pyridine-2-carboxylic acid;
2,2-dimethyl-1-[2-(2-vinylcyclopentane-1-enyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
ethyl ester 5-{2-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]cyclopent-1-enyl}-1H-indole-2-carboxylic acid;
cyanomethylation 4-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
(1-methylcyclohexyl)-{2-[5-(morpholine-4-carbonyl)thiophene-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}meanon;
1-(2-furan-3-yl-5H-Pierre is lo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
(1-ethylpropyl)amide 4-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(4-hydroxy-4-methylpiperidin-1-carbonyl)thiophene-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
2,2-dimethyl-1-[2-(2-pyrrolidin-1-espiridion-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-{2-[2-(3-dimethylaminopropan-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(2-thiomorpholine-4-espiridion-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-{2-[2-(2-methylpyrrolidine-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
1-{2-[2-(3-hydroxypyrrolidine-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[2-(3,3-debtorprovidian-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(2-azepin-1-espiridion-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-{2-[2-((S)-3-ftorpirimidinu-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[2-((R)-3-ftorpirimidinu-1-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[2-(1,1-dioxo-1λ6-thiomorpholine-4-yl)pyridine-4-yl]-5H-pyrrolo[3,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(2-chloropyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-{2-[2-(1-oxo-1λ4 -thiomorpholine-4-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
1-[2-(2-cyclopent-1-Anileridine-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
(1-methylcyclohexyl)-[2-(2-pyrrolidin-1-espiridion-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]metano;
1-[2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
(1-ethylpropyl)amide 5-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(3,3-diversecity-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
{2-[5-(4-hydroxypiperidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
(1-methylcyclohexyl)-{2-[2-(1-oxo-1λ4-thiomorpholine-4-yl)-pyridin-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}meanon;
{2-[5-(azetidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
{2-[5-(3-hydroxyazetidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
1-{2-[2-((1S,5R,6R)-6-hydroxymethyl-3-azabicyclo[3.1.0]Gex-3-yl)pyridine-4-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
(1-methylcyclohexyl)-{2-[5-(morpholine-4-carbonyl)thiophene-2-yl]-5H-pyrrolo [2,3-b] pyrazin-7-yl}meanon;
diethylamid 5-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
cyclopentylamine 5-[7-(1-methylcyclohexanol the Nile)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(4-hydroxy-4-methylpiperidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
bis-(2-hydroxyethyl)amide 5-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
(2-hydroxyethyl)methylamide 5-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(3-hydroxypyrrolidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
cyanomethylation 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
bis-(2-hydroxyethyl)amide 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
1-{2-[5-(4-hydroxy-4-methylpiperidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[5-(azetidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-{2-[5-(pyrrolidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
2,2-dimethyl-1-{2-[5-(piperidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
3-dimethylamino-1-{5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carbonyl}azetidin-3-carbonitrile;
1-{2-[5-(4-hydroxypiperidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[4-(azetidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-{2-[4-(pyrrolidin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
2,2-dimethyl-1-{2-[4-(piperidine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
(1-methylcyclohexyl)-{2-[5-(4-methylpiperazin-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}meanon;
{2-[5-(4-dimethylaminopyridine-1-carbonyl)thiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
1-(2-cyclopent-1-enyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-(2-pyrrolidin-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
1-[7-(2,2-dimethylpropyl)-2'-pyrrolidin-1-yl-5H-[2,5']bi[pyrrolo[2,3-b]pyrazinyl]-7'-yl]-2,2-DIMETHYLPROPANE-1-he;
N-{1-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]pyrrolidin-3-yl}ndimethylacetamide;
2,2-dimethyl-1-[2-(2-methylpyrrolidine-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-[2-(4-acetylpiperidine-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-(2-morpholine-4-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
1-[2-(5-Florinda-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-[2-(5-methoxyindol-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-(2-indol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
1-(2-indazol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
1-[2-(3,4-dihydro-1H-isoquinoline-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(1,3,4,9-tetrahydro-β-carbolin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2-{1-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]p the Razin-2-yl]-1H-indol-3-yl}ndimethylacetamide;
2,2-dimethyl-1-[2-(1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(3-phenylpyrrolidine-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-(2-imidazol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(2-Mei-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(2-methyl-4,5-dihydroimidazole-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-[2-(2-ethylimidazole-1-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-(2-thiophene-2-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dimethyl-1-[2-(1H-pyrrol-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-(2-thiophene-3-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dimethyl-1-(2-oxazol-5-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dimethyl-1-[2-(1H-pyrazole-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
tert-butyl ester 4-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]pyrazole-1-carboxylic acid;
2,2-dimethyl-1-(2-pyrazole-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dimethyl-1-[2-(2H-pyrazole-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-(2-pyrrol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dimethyl-1-[2-(1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-(2-thiazol-5-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
3-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-1H-indol-5-carbonitrile;
1-[2-(5-fluoro-1H-shall ndol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
[2-(1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methylcyclohexyl)methanon;
1-{2-[1-(2-hydroxy-1-hydroxymethylene)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-(2-benzo[b]thiophene-2-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(5-phenylthiophene-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(1-methyl-1H-indol-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-[2-(1H-indol-2-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-[2-(1H-indol-3-yl)-5-methyl-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(5-phenyl-1H-pyrrol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-{2-[1-(2-hydroxyethyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(6-fluoro-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-{2-[1-(2-methanesulfonyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-[2-(5-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-[2-(1-ethyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(5-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-(2-{1-[2-(4-methylpiperazin-1-yl)ethyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
2,2-dime the Il-1-{2-[1-(2-morpholine-4-retil)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}propane-1-he;
1-{2-[1-(3-hydroxy-2-hydroxymethylpropane)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
1-{2-[1-(3-hydroxy-2-hydroxymethylpropane)-1H-pyrrolo[2,3-b]pyridine-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(6-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
1-[2-(6-methoxy-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-{2-[1-(2-amino-ethyl)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(6-morpholine-4-espiridion-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
(1-methylcyclohexyl)-[2-(6-morpholine-4-espiridion-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]metano;
1-[2-(1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
1-(2-imidazo[1,2-a]pyridine-3-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
2,2-dimethyl-1-[2-(1H-pyrrolo[2,3-b]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(1H-pyrrolo[3,2-C]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(1H-pyrrolo[2,3-C]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-[2-(1-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]propane-1-he;
2,2-dimethyl-1-{2-[1-(2-oxo-2-piperazine-1-retil)-1H-indol-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-ID}propane-1-he;
1-(2-{1-[2-(4-aminopiperidin-1-yl)-2-oxoethyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-DIMETHYLPROPANE-1-he;
(1-methylcyclohexyl)-[2-(1-methyl-1H-what irolo[2,3-b]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]metano;
2,2-dimethyl-1-(2-{1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indol-3-yl}-5H-pyrrolo[2,3-b]pyrazin-7-yl)propane-1-he;
(1-methylcyclopentene)-[2-(1-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]metano;
1-[2-(5-methoxypyridine-3-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-DIMETHYLPROPANE-1-he;
(1-ethylpropyl)amide 4-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(4-hydroxy-4-methylpiperidin-1-carbonyl)thiophene-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
(2-hydroxyethyl)methylamide 5-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
((S)-2-hydroxy-1,2-dimethylpropyl)amide 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid;
4-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
(2-amino-2-methylpropyl)amide 4-[7-(1-methylcyclohexanecarboxylic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]thiophene-2-carboxylic acid;
{2-[5-(4-dimethylaminopyridine-1-carbonyl)thiophene-3-yl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-(1-methylcyclohexyl)methanon;
(3-hydroxy-2,2-dimethylpropyl)amide 2-cyclopropyl-5H-pyrrolo[2,3-6]pyrazin-7-carboxylic acid;
tert-butylamide 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid;
tert-butyl ester 2-[7-(2,2-dimethylpropionic)-5H-pyrrolo[2,3-b]pyrazin-2-yl]pyrrole-1-carboxylic acid
(3-hydroxy-2,2-dimethylpropyl)amide 2-thiophen-yl-5H-pyrrolo[2,3-b]pyrazin-7-carboxylic acid.

11. The use of compounds according to any one of claims 1 to 10 for preparing a medicinal product intended for the treatment of inflammatory disorders or autoimmune disorders.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to dihydrothienopyrimidinesulphoxides of formula 1, and pharmaceutically acceptable salts thereof , where X denotes SO, R1 denotes H, R2 denotes H or a residue selected from C1-C10alkyl, which is optionally substituted with one or more residues selected from OR2.1, where R2.1 denotes H or C1-C6alkyl, R2.2 and R2.3 independently denote H or C1-C6alkyl, where Het is a 6-member monocyclic, saturated heterocycle containing 1 heteroatom selected from N or O, and where the hetaryl is a 5-11-member mono- or bicyclic, optionally anellated heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, S or O, and where the cycloalkyl can be saturated, or R2 denotes a monocyclic C3-cycloalkyl, which is optionally substituted with a residue selected from a branched or linear C1-C6alkanol, C1-C3alkylene-OR2.1, or R2 denotes phenyl which is optionally substituted with a halogen, or R2 denotes a residue selected from Het and hetaryl, each optionally substituted with one or more residues selected from halogen, OH, oxo group and OR2.1, C1-C6alkyl, and where R3 denotes a bicyclic 9-11-member unsaturated or partially saturated heterocycle which is optionally substituted with one or more residues selected from a group comprising F, O, Br, CF3, CN, OH, methyl, ethyl, propyl, isopropyl, -O-methyl, -O-ethyl, phenyl, NR2.2R2.3, where the phenyl is optionally substituted with F, Cl or Br. The invention also relates to pharmaceutical compositions based on said compounds, having phosphodiesterase 4 (PDE4) inhibiting activity.

EFFECT: obtaining novel compounds and pharmaceutical compositions based thereon, which can be used in medicine to treat respiratory or gastrointestinal complaints or diseases, inflammatory diseases of joints, skin or eyes, diseases of the peripheral or central nervous system or cancers.

20 cl, 1 tbl, 156 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound, namely 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluor-1,5-naphthyridin-2(1H)-one monohydrate which possess strong antibacterial activity. This compound is highly safe and applicable in the production of pharmaceutical preparations as a parent drug. What is furthermore described is a method for preparing 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluor-1,5-naphthyridin-2(1H)-one monohydrate of formula 19 and methods for preparing intermediate compounds.

EFFECT: preparing the compounds possessing strong antibacterial activity.

8 cl, 1 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline compounds of formula (I) and physiologically acceptable acid addition salts and N oxides thereof, wherein R denotes a polycyclic group of formula (R) wherein * indicates the quinolinyl radical binding site; A denotes (CH2)a, where a equals 0, 1, 2 or 3; B denotes (CH2)b, where b equals 0, 1, 2 or 3; X' denotes (CH2)x where x equals 0, 1, 2 or 3; Y denotes (CH2)y where y equals 0, 1, 2 or 3; provided that a+b=1, 2, 3 or 4, x+y=1, 2, 3 or 4, and a+b+x+y=3, 4, 5, 6 or 7; Q denotes N; R1 denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, phenoxycarbonyl or benzyloxycarbonyl, where phenyl rings in last two said groups are unsubstituted or carry 1, 2 or 3 substitutes selected from halogen, C1-C4-alkyl or C1-C4-halogenalkyl; R2 denotes hydrogen; R3 denotes hydrogen; p=0, 1 or 2; R4, if present, denotes C1-C4-alkyl and is bonded with X and/or Y, if p=2, two radicals R4, which are bonded with adjacent carbon atoms of X or Y, together can also denote a straight C2-C5-alkylene; q=0; n=0; m=0; X denotes S(O)2; which is located in position 3 of quinoline; Ar denotes a radical Ar1, wherein Ar1 is a phenyl, wherein the phenyl can be unsubstituted or can carry 1 substitute Rx wherein Rx denotes halogen, CN, C1-C6-alkyl, C1-C6-halogenalkyl, C1-C6-alkoxy, C1-C6-halogenalkoxy, C1-C6-alkylthio, C1-C6-halogenalkylthio, NRx1 Rx2, wherein Rx1 and Rx2 independently denote hydrogen, C1-C6-alkyl, or Rx1 and Rx2 together with a nitrogen atom form an N-bonded 5-, 6- or 7-member saturated heteromonocyclic ring or an N-boned 7-, 8-, 9- or 10-member saturated heterobicyclic ring, which are unsubstituted or carry 1, 2, 3 or 4 radicals selected from C1-C4-alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treatment using the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel quinoline derivatives are obtained, which respond to modulation of the serotonin 5-HT6 receptor.

23 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where: A is CA1; E is CE1; W is (CH2)n; Y is (CH2)P; n and p are independently equal to 0 or 1; R1 is a phenyl which is substituted with a phenyl {which is optionally substituted with a halogen, hydroxy, CH(O), CO2H, C1-4alkyl, C1-4alkyl-(N(C1-4alkyl)2), C1-4alkyl(NH2), C1-4alkyl(NH(C1-4alkyl)), C1-4hydroxyalkyl, CF3, C1-4alkylthio, C1-4alkyl(heterocyclyl) or C1-4alkylNHC(O)O(C1-4alkyl)} or a heterocyclyl; and the heterocyclyl is optionally substituted with C1-6alkyl; R2 is NHC(O)R3; and R3 is C1-4alkyl {substituted with NR7R8 or a heterocyclyl}, C3-7cycloalkyl (optionally substituted with a NR43R44 group) or a heteroaryl; where R7, R8, R43 and R44 are as defined in claim 1; wherein the heteroaryl is optionally substituted with a halogen, C1-4alkyl, CF3, C1-4alkoxy, OCF3, heterocyclyl or an amino(C1-4alkyl) group; R7 and R8 are independently C1-6alkyl; A1, E1 and G1 are independently hydrogen or halogen; unless otherwise stated, the heterocyclyl is optionally substituted with C1-6alkyl; R25 is C1-6alkyl; R50 is hydrogen or C1-6alkyl (optionally substituted with a NR51R52 group); R30, R36, R40, R42 or R44 is independently hydrogen, C1-6alkyl(optionally substituted with hydroxy, C1-6alkoxy, C1-6alkylthio, C3-7cycloalkyl (which is optionally substituted with hydroxy) or NR45R46), C3-7cycloalkyl (optionally substituted with a hydroxy(C1-6alkyl) group) or a heterocyclyl (optionally substituted with C1-6alkyl); R29, R35, R39, R41, R43, R45, R46 and R51 are independently hydrogen or C1-6alkyl; where the heterocyclyl is a non-aromatic 5- or 6-member ring containing one or two heteroatoms selected from a group comprising nitrogen and oxygen; and where the aryl is phenyl or naphthyl; and where the heteroaryl is an aromatic 5- or 6-member ring, optionally condensed with another ring (which can be carbocyclic and aromatic or non-aromatic), having one or two heteroatoms selected from a group comprising nitrogen, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a PDE4-mediated disease state.

10 cl, 81 dwg, 15 tbl, 375 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel imidazopyridin-2-one derivatives of general formula or pharmacologically acceptable salts thereof, where (R1)n-A is a 1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3,4-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, 3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group or 3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl group, B is a 3-6-member saturated or partially saturated monocyclic hydrocarbon group and can contain 1 or 2 oxygen atoms, a nitrogen atom and/or sulphonyl groups as ring components, B can have as substitutes identical or different R2 in amount of m, R2 is a substitute represented at a carbon atom or a nitrogen atom forming B, R2 is a substitute selected from a group consisting of a hydroxy group, a halogen atom, a cyano group, an oxo group, a C1-4alkyl group (where the C1-4 alkyl group can be substituted with 1 C1-4 alkoxy group) and a C1-4 alkoxy group, when R2 is a substitute represented at a carbon atom forming B, and R2 is a substitute selected from a group consisting of a C1-4 alkyl group and a C1-4 alkylcarbonyl group, when R2 is a substitute represented at a nitrogen atom forming B, m is any integer from 0 to 2, Q is a bond or a C1-4 alkylene group, R3 and R4 are identical or different and each denotes a hydrogen atom or a halogen atom, and R5 and R6 are identical or different and each denotes a hydrogen atom, a halogen atom or a C1-4 alkyl group. The invention also relates to specific compounds of formula (I), pharmacologically acceptable salts of compounds of formula (I), a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel imidazopyridin-2-one derivatives, having mTOR inhibiting action, are obtained.

21 cl, 161 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrole nitrogen-containing heterocyclic derivatives of formula (I) or their pharmaceutically acceptable salts:

,

wherein: X means C, N; each R1,R2 means H; R3 means C1-10alkyl; R4 means -[CH2CH(OH)]rCH2NR9R10, -(CH2)nNR9R10; provided X means N, R5 is absent, each R6, R7, R8 means H, halogen; provided X means C, each R5, R6, R7, R8 means H, halogen, hydroxyC1-10alkyl, C1-10alkyl, phenyl, 6-member heteroaryl with one N, -OH, -OR9, -NR9R10, -(CH2)nCONR9R10, -NR9COR10, -SO2R9 and -NHCO2R10, wherein said phenyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, C1-10alkoxyl, halogen; each R9, R10 means H, C1-10alkyl wherein C1-10alkyl is unsubstituted or additionally substituted by one or more group C1-10alkyl, phenyl, halogenophenyl, -OH, C1-10alkoxy, OH- C1-10alkyl; or R9 and R10 together with an attached atom form a 5-6-member heteroring which may contain one O; n is equal to 2- 6; z is equal to 1-2; r is equal to 1-6;.

EFFECT: compounds may be used as protein kinase inhibitors.

14 cl, 2 tbl, 67 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of antibiotics, which represent compounds of formula (I) and their pharmaceutically acceptable salts, where U, V, W, X, R1, R2, R3, R4, R5, R6, A, B, D, E, G, m and n are determined in description. Invention also relates to pharmaceutical composition, containing said compounds and their application for obtaining medication for prevention or treatment of bacterial infections.

EFFECT: obtaining useful antimicrobial agents, efficient against various pathogens of people and animals.

23 cl, 1 tbl, 186 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing N-[5-(3-dimethylamino-acryloyl)-2-fluorophenyl]-N-methylacetamide of formula (I). The method is realised by reacting N-(5-acetyl-2-fluorophenyl)-N-methylacetamide of formula (VI) with excess N,N-dimethylformamide dimethylacetal (NNDMF-DMA) in the presence of a nonpolar solvent at temperature of 70-90°C. The invention discloses a method of producing a N-{2-fluoro-5-[3-(thiophene)-2-carbonyl-pyrazolo[1,5-a]pyrimidin-7-yl]phenyl}-N-methylacetamide compound of formula (II), which involves methylation of N-(5-acetyl-2-fluorophenyl)-acetamide at temperature of 15-50°C, reacting the obtained compound of formula (VI) with NNDMF-DMA, and reacting the obtained compound of formula (I) with (5-amino-1H-pyrazol-4-yl)thiophen-2-yl-methanone in glacial acetic acid at temperature of 60-90°C in the presence of an aliphatic alcohol. The invention also relates to an intermediate compound of formula (VI).

EFFECT: improved method of producing a compound which is an intermediate compound in synthesis of compounds with affinity for the GABAA receptor.

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel imidazopyridine or imidazopyrimidine derivatives of formula (I) and to pharmaceutically acceptable salts and esters thereof, where A is N or C(R6); R1 is hydrogen, lower alkyl; R2 is halogen, C(O)NR7R8 or C(O)OR9; R3 is hydrogen, NR10R11; R4 is hydrogen, lower alkyl; R5 is phenyl or thiazolyl or pyridine, which can be substituted with one substitute independently selected from a group consisting of halogen; R6 is hydrogen, halogen, CN, C3-C6cycloalkyl; R7 and R8 are independently selected from a group consisting of hydrogen, lower alkyl, lower alkoxy-lower alkyl, fluoro-lower alkyl, C3-C6cycloalkyl, N(H,lower alkyl)-lower alkyl, hydroxy- lower alkyl, hydroxy-lower alkoxy- lower alkyl, N(lower alkyl2)C(O)- lower alkyl, lower alkoxy, hydroxy-lower alkyl-oxetanyl- lower alkyl, oxo-tetrahydrofuranyl, tetrahydrofuranyl-lower alkyl, hydroxy-fluoro-lower alkyl, tetrahydrofuranyl, phenyl and thiazolyl or pyridine, or R7 and R8 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of pyrrolidinyl, azetidinyl, morpholinyl, 5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazinyl, 3,4-dihydro- 1H-pyrrolo[1,2-a]pyrazinyl, 2-oxa-6-aza-spiro[3.3]heptyl, 5,6-dihydro- 8H-imidazo[1,2-a]pyrazinyl, [1,4]oxazepanyl, piperazinyl, thiomorpholinyl and 2-oxa-5-aza-bicyclo[2.2.1]heptyl, where the heterocyclyl is optionally substituted with 1 or 2 substitutes independently selected from a group consisting of halogen, lower alkyl, lower alkyl-C(O), lower alkoxy-lower alkyl, oxo, hydroxy, hydroxy-lower alkyl, N(lower alkyl2); R9 is lower alkyl; R10 and R11 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of piperidinyl, morpholinyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel imidazopyridine or imidazopyrimidine derivatives which are PDE10A inhibitors.

24 cl, 94 ex

FIELD: chemistry.

SUBSTANCE: described are novel triazolopyridazines of general formula , stereoisomeric or tautomeric forms thereof and physiologically acceptable salts thereof, where Q1 denotes H, -C1-6alkyl, optionally substituted with fluorine, or -C3-6cycloalkyl; Q2 and Q3 independently denote H, -C1-6alkyl; R1-R3 independently denote H, -C1-6 alkyl, -C3-6cycloalkyl, -O-C3-6cycloalkyl, -O-C1-8alkyl, a heterocyclic residue etc; R4-R8 independently denote H, -C1-6 alkyl, -OH, -O-C1-8 alkyl, halogen, SF5 etc, a method for production thereof and use as medicinal agents.

EFFECT: compounds have antithrombotic activity and particularly inhibit the protease-activated receptor.

6 cl, 2 tbl, 242 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formulas

and or pharmaceutically acceptable salts thereof, wherein the values R1-R13, Ra, Rb, Rc, Rd, Rf, Rq, n are presented in the patent claim possessing the properties of protein p53 activator.

EFFECT: compounds may be used in treating cancer and diseases caused by a fungal, bacterial or parasitic infection, eg malaria.

16 cl, 38 dwg, 12 tbl, 16 ex

Solid forms // 2496780

FIELD: chemistry; pharmaceutics.

SUBSTANCE: invention relates to crystalline forms of 4-[9-(tetrahydrofuran-3-yl)-8-(2,4,6-trifluorophenylamino)-9H-purin-2-ylamino]cyclohexan-1-ol of formula , which have kinase inhibiting properties and can be used to treat or prevent: (a) cancer; (b) an inflammatory condition or (c) an immunologic condition. The invention particularly relates to a crystalline form A, having an X-ray powder diffraction pattern with peaks at about 12.4, 16.0 and 18.5°2θ and further has peaks at about 17.7, 23.2 and 24.1°2θ; a hydrate crystalline form A, having an X-ray powder diffraction pattern with peaks at about 6.5, 13.0 and 23.0°2θ and further has peaks at about 13.4, 20.1 and 23.8°2θ; a crystalline form of a hydrochloride salt A, having an X-ray powder diffraction pattern with peaks at about 17.3, 18.7 and 22.4°2θ, and contains about two mole equivalents of chloride ions.

EFFECT: invention relates to methods of producing a crystalline form A, a pharmaceutical composition containing said crystalline forms and a treatment method.

15 cl, 16 dwg, 9 ex

FIELD: medicine.

SUBSTANCE: present invention describes compounds of formula I: wherein: X1 and X2 independently represent CH or N; R1 represents fluorine or hydrogen; R2 represents hydrogen, halogen; Ar represents phenyl substituted by 1-3 groups optionally substituted in each specific case in a group consisting of hydrogen, halogen, cyano group; R3 is independently specified in each specific case in a group consisting of: (i) CH2OH; (ii) CH2O-C(=O)(CH2)nCO2R4, wherein n has a value of 2 to 5; (iii) CH2O-C(=O)CH2OCH2CO2R4; (iv) CH2OCOR5; (v) CH2OC(=O)CHR6NH2; (vi) C(=O)R5, and (vii) CH2OP(=O)(OH)2; R4 represents hydrogen or C1-10 alkyl; R5 represents hydrogen or C1-10 alkyl, C1-3 dialkylamino-C1-10 alkyl, C1-6 alkoxy or pyridinyl, R6 represents C1-6 alkyl or a side chain of a natural amino acid; or a pharmaceutically acceptable salt thereof. Besides, the invention describes a pharmaceutical composition having HTVRT inhibitory activity and containing a compound according to cl.1.

EFFECT: there are prepared and described new compounds inhibiting HIV-1 reverse transcriptase and effective for preventing and treating HIV-1 infections and treating AIDS or ARC.

13 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new triazolium salts of general formula (I) stereo- and tautomer forms and physiologically acceptable salts thereof, wherein X- C-R1 or N, R1-hydrogen, C1-6alkyl or halogen; A- is an anion of a pharmacologically acceptable organic or inorganic acid; Q1 is hydrogn, -C1-6alkyl optionally substituted, -C3-6cycloalkyl, -C(O)-O-R11 or - C(O)-R11; R11 -C1-6alkyl; Q2 and Q3 are hydrogen; R2- R9 independently mean hydrogen, -C1-6alkyl optionally substituted, -O-(C1-8)alkyl optionally substituted, etc., and using the above compounds as a drug preparation.

EFFECT: compounds possess antithrombotic activity, particularly, they inhibit the protease-activated receptor 1 (PAR1), and may be used in treating the diseases such as myocardial infarction, angina, stroke, and others.

4 cl, 2 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: described is a sodium salt of 2-methyl-6-fluoro-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7(4H)-one , having antiviral activity with respect to influenza virus A(H1N1).

EFFECT: improved properties of the compound.

1 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes pyrrolo[2,3-d]pyrimidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof, where R1 is C1-4 alkyl, optionally substituted with a hydroxy group, as well as a crystalline form A of a salt of N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl} methane sulphonamide with maleic acid. Disclosed also is a method of producing a salt of N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl} methane sulphonamide with maleic acid.

EFFECT: improved properties of the composition, having inhibiting activity on Janus kinase and a method of treating allergic reactions, allergic dermatitis, atopic dermatitis, eczema or itching in mammals.

17 cl, 7 ex, 4 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of general formula (I), or pharmaceutically acceptable salts thereof, where X1 denotes N, N-R3, C-R3 or O; X2 denotes N, CH or C-CH3; X3 denotes N or C, where X1, X2 and X3 all do not simultaneously denote N; X4, X5 each independently denotes C or N; X6 denotes N or C-R1 ; where at least two and not more than four of X1, X2, X3, X4, X5 and X6 denotes N; and where the bonds between X1 and X2, X2 and X3, X3 and X4, X4 and X5, X5 and X1, as well as X5 and X6 can each independently be single or double, or , can form an aromatic ring, under the condition that a chemically stable structure is formed; R denotes -(cyclohexyl)R2; R1 denotes a halide, nitro group, -CN, -CH2CN, -OH, -NH2, -COOH or -Y1R4; Y1 denotes -O-, -SO2, -NHSO2-, -C(O)O- or a bond; R4 denotes (C1-C6)alkyl, phenyl or benzyl, each of which is substituted with 0-3 times with a hydroxy group or a halogen; n equals 0, 1 or 2; R3 denotes H or (C1-C6)alkyl; R2 denotes H, -OH, =O or -Y2-Y3-Y4-R5, where Y2 denotes -C(O)-, -C(O)NRa-, -NH- or a bond; Y3 denotes (C1-C6)alkylene or a bond; Y4 denotes -NRa-, -S-, -SO2-, -NRaC(O)-, -NHSO2- or a bond; R5 denotes (C1-C6)alkyl, (C3-C10)cycloalkyl, a 5-6-member heterocyclyl containing 1-2 heteroatoms selected from N and O, where R5 is optionally substituted with -OH or -NHRa; where each Ra independently denotes hydrogen or (C1-C6)alkyl; Z denotes hydrogen. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: obtaining novel pyrimidine derivatives which are useful for therapeutic or preventive treatment of a c-Jun N-terminal kinase-mediated disorder.

14 cl, 3 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to 7-benzoyl-8-hydroxy-6-phenyl-9-(3-phenyl-2-quinoxalinyl)-10H-pyrido[1,2-a]quinoxalin-10-one of formula (1)

EFFECT: obtaining a novel compound which can be used in medicine as a drug having analgesic activity.

3 ex, 1 tbl

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