3-amino-6-(1-aminoethyl)tetrahydropyrane derivatives

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

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where R1represents a halogen or alkoxygroup;
U and W each represent N, V represents CH and R2represents H or F, or
U and V each represent CH, W pre is is a N and R 2represents H or F, or
U represents N, V represents CH, W represents CH or CRaand R2represents H or, when W represents CH, can represent F;
Rarepresents CH2HE or alkoxycarbonyl;
And represents the group CH=CH -, binuclear heterocyclic system D, a phenyl group which is mono-substituted in position 4
With1-4alkyl group, or phenyl group which is di-substituted in positions 3 and 4, where each of the two substituents independently from each other selected from the group including1-4alkyl and halogen;
Represents a mono - or di-substituted phenyl group, where
each Deputy is a halogen atom;
D is a group of

where Z represents CH or N, and
Q represents O or S;
or a salt of such compounds.

2. The compound of formula I according to claim 1, where, if U represents N and V represents CH, then W represents CRaand R2represents H;
or a salt of such compounds.

3. The compound of formula I according to claim 1, which is also a compound of the formula ICE

where R1represents a halogen or1-4alkoxygroup;
U and W each is th is a N, V represents CH and R2represents H or F, or
U and V each represent CH, W represents N and R2represents H or F, or
U represents N, V represents CH, W represents CH or CRaand R2represents H or, when W represents CH, can represent F;
Rarepresents CH2HE or C1-4alkoxycarbonyl;
And represents the group CH=CH -, binuclear heterocyclic system D, a phenyl group which is mono-substituted in position 4
C1-4alkyl group, or phenyl group which is disubstituted in positions 3 and 4, where each of the two substituents independently from each other selected from the group including1-4alkyl and halogen;
Represents a di-substituted phenyl group, in which each Deputy is a fluorine atom;
D is a group of
,
where Z represents CH or N, and
Q represents O or S;
or a salt of such compounds.

4. The compound of formula I according to claim 3, where, if U represents N and V represents CH, then W represents CRaand R2represents H;
or a salt of such compounds.

5. The compound of formula I according to claim 1, where R1represents a C1-4/sub> alkoxygroup;
or a salt of such compounds.

6. The compound of formula I according to claim 1, where a represents the group CH=CH -;
or a salt of such compounds.

7. The compound of formula I according to claim 1, where a represents a binuclear heterocyclic system D;
or a salt of such compounds.

8. The compound of formula I according to claim 1, where a represents a phenyl group which is mono-substituted in position 4 With1-4alkyl group, or phenyl group which is disubstituted in positions 3 and 4, where each of the two substituents independently from each other selected from the group including1-4alkyl and halogen;
or a salt of such compounds.

9. The compound of formula I according to claim 1, which is selected from the following compounds:
{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1R)-1-amino-2-(6-ftorhinolon-4-yl)ethyl]tetrahydropyran-3-yl}-[(E)-3-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-ftorhinolon-4-yl)ethyl]tetrahydropyran-3-yl}-[(E)-3-(2,5-differenl)allyl]amine;
6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4 is-pyrido[3,2-b][1,4]thiazin-3-one;
{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-l-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
methyl ester of 8-[(2R)-2-amino-2-{5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl]-2-methoxyaniline-5-carboxylic acid;
methyl ester of 8-[(2S)-2-amino-2-{5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl]-2-methoxyaniline-5-carboxylic acid;
8-((S)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl)-2-methoxyaniline-5-yl] methanol;
[8-((R)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl)-2-methoxyaniline-5-yl]methanol;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-the laminitis}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[l,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-(4-active compounds)amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-benzo[1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-(3-fluoro-4-methylbenzyl)amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-benzo[1,4]oxazin-3-one;
6-({(3S,6R)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}IU who yl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3S,6R)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3S,6R)-6-[(1R)-1-amino-2-(7-fluoro-2-methoxyquinoline-8-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(7-fluoro-2-methoxyquinoline-8-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(7-fluoro-2-methoxyquinoline-8-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(7-fluoro-2-methoxyquinoline-8-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-benzo[1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-benzo[1,4]oxazin-3-one;
or a salt of such compounds.

10. The connection according to claim 9, which is selected from the following compounds:
{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1R)-1-amino-2-(6-ftorhinolon-4-yl)ethyl]tetrahydropyran-3-yl}-[(E)-3-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-ftorhinolon-4-yl)ethyl]tetrahydropyran-3-yl}-[(E)-3-(2,5-differenl)allyl]amine;
6-({(3R,6S)-6-(1R)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
{(3R,6S)-6-[(1R)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-yl}-[3-(E)-(2,5-differenl)allyl]amine;
6-({(3S,6R)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
methyl ester of 8-[(2R)-2-amino-2-{5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl]-2-methoxyaniline-5-carboxylic acid;
methyl ester of 8-[(2S)-2-amino-2-{5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl]-2-methoxyaniline-5-carboxylic acid;
8-((S)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl)-2-methoxyaniline-5-yl]methanol;
[8-((R)-2-amino-2-{(2S,5R)-5-[(E)-3-(2,5-differenl)allylamino]tetrahydropyran-2-yl}ethyl)-2-methoxyaniline-5-yl]methanol;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamine is}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;
6-({(3R,6S)-6-[(1R)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-(4-active compounds)amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxyquinoline-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-benzo[1,4]oxazin-3-one;
6-({(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-({(3S,6R)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-yl}-(3-fluoro-4-methylbenzyl)amine;
{(3R,6S)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-silts what about the}methyl)-4H-benzo[1,4]oxazin-3-one;
6-({(3S,6R)-6-[(1R)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one and
6-({(3S,6R)-6-[(1S)-1-amino-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]tetrahydropyran-3-ylamino}methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one
or a salt of such compounds.

11. The compound of formula I according to one of claims 1 to 10 or its pharmaceutically acceptable salt as a medicine for the prevention or treatment of bacterial infections.

12. The use of the compounds of formula I according to one of claims 1 to 10 or its pharmaceutically acceptable salt to obtain drugs for prevention or treatment of bacterial infections.

13. The compound of formula I according to one of claims 1 to 10 or its pharmaceutically acceptable salt for the prevention or treatment of bacterial infections.



 

Same patents:

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: medicine, pharmaceutics.

SUBSTANCE: present invention refers to anhydrous crystalline vinflunine salts of general formula (I) prepared with 1 or 2 equivalents of a pharmaceutically acceptable inorganic or organic acid. . In formula (I) [The acid] represents hydrobromic, lactic or fumaric acid for a group of water-soluble crystalline salts, as well as para-toluenesulphonic, benzoic, mandelic and para-hydroxybenzoic acid for a group of relatively water-insoluble crystalline salts.

EFFECT: preparing the anhydrous crystalline vinflunine salts.

8 cl, 8 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel azaindole derivatives, having JAK-2 and JAK-3 kinase inhibiting activity, or pharmaceutically acceptable salts thereof. In formula (I): R3 denotes H; X1 denotes N or CR4; R2 denotes H, COOH, COOR' or CONHR'; R4 denotes H, F, R, OH, OR', COR', COOH, COOR', CONH2 or CN; or R2 and R4, taken together, form a benzene ring optionally substituted with 1-2 R10; R' denotes C1-3-alkyl or C1-3-alkenyl, each optionally substituted 1-2 R5; each R5 is independently selected from CN, unsubstituted C1-2alkyl, or two groups R5 together with a carbon atom with which they are bonded form a cyclopropyl ring; each R10 is independently selected from halogen, OCH3 or OH; R1 denotes or , R is H or denotes C1-2alkyl, optionally substituted with 1-3 R11; R6 denotes C1-4alkyl, optionally substituted with 1-5 R12; values of radicals R7 -R9, ring A, R11 -R14. The invention also relates to a pharmaceutical composition containing said compounds and a method of treating or reducing severity of a pathological condition such as allergy, asthma, amyotrophic lateral sclerosis, multiocular sclerosis, graft rejection, rheumatoid arthritis, solid malignant tumour, haematologic malignant disease, leukaemia, lymphoma and myeloproliferative disorders.

EFFECT: high efficiency of using the compounds.

41 cl, 6 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to substituted imidazopyridine derivatives of general formula (I) or enantiomers, diastereomers and tautomers and pharmaceutically acceptable salts thereof, in which A denotes -NH-, -CH2-, -CH2-CH2- or a bond; X denotes phenyl, phenyl condensed with a saturated heterocyclic 5- or 6-member ring, where the heterocyclic ring can contain one or two heteroatoms selected from O and N, and where the heterocyclic ring can further be substituted with an oxo group, a 6-member saturated heterocyclyl containing O as a heteroatom, a 5-6-member heteroaryl containing 1 or 2 heteroatoms selected from N, O and S, and where each phenyl and heteroaryl is possibly substituted with 1 to 2 R14 and/or 1 substitute R4b and/or 1 substitute R5; R1 and R2 are independently selected from the following groups: C1-6-alkyl and C1-6-alkylene-C3-7-cycloalkyl, and where each alkyl is possibly substituted with a OH group, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5-6-member ring which is possibly substituted with one substitute selected from C1-6-alkyl and O-C1-6-alkyl; R4b denotes C(O)NH2, C(O)OH, C(O)NH-C1-6-alkyl, C(O)N-(C1.6-alkyl)2, SO2-C1-6-alkyl, oxo group, and where the ring is at least partially saturated, NH2, NH-C1-6-alkyl, N-(C1-6-alkyl)2; R5 denotes a 6-member heteroaryl containing N as a heteroatom; R3 denotes -(CR8R9)n-T; R8 and R9 are independently selected from the following groups: H and C1-6-alkyl; n equals 1, 2, 3, 4, 5 or 6; T denotes or NR12R13; R10 denotes H, NH2, OH, C1-6-alkyl, possibly substituted with one OH, a halogen atom, NH(C1-6-alkyl) or N(C1-6-alkyl)2; q equals 1 or 2; Y denotes CH2, NR11 or O; R11 denotes H, or C1-6-alkyl; R12 and R13 are independently selected from the following groups: H, C1-6-alkyl, C1-6-alkynyl, (CH2)0-2-C3-7-cycloalkyl, and C1-6-alkylene-O- C1-6-alkyl, where C1-6-alkyl is possibly substituted with one halogen; R14 denotes a halogen atom, CN, C1-6-alkyl, possibly substituted with 1-3 substitutes selected from halogen atom, OH, O- C1-6-alkyl, O-C(O)C1-6-alkyl, O- C1-6-alkyl, possibly substituted with one substitute selected from OH, O- C1-6-alkyl, and O-C(O) C1-6-alkyl, or OH. The invention also relates to a pharmaceutical composition based on the compound of formula (I).

EFFECT: novel imidazopyridine derivatives are obtained, which can be used as melanocortin-4 receptor modulators.

17 cl, 8 tbl, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new compounds of formula , wherein A represents residues of formulae

, , , X represents O; X1-X4 represents N, CH, CR1 or C-, X9-X12 represents N, CH, CR4 or C-, X13-X16 represents N, CH, CR or C-, wherein C represents an attachment point of the group A to a residue of the structure of formula (I); R' represents H or alkyl; R represents alkoxy, or Het; R1 represents F, CI, Br, I, OH, CN, carboxy, CONR6R7, NR2COR8, NR2COOR8, alkoxy, fluorinated alkoxy, Ar, Het or OHet; or R1 represents one of the following formulas: wherein n is equal to 2 and m is equal to 3; R2 represents H, alkyl, fluorinated alkyl, cycloalkyl, Het or Het-NH-CO-; R4 represents F, Cl, Br, I, OH, alkoxy, cycloalkoxy, Het or OHet; or R4 represents one of the following formulae: , wherein n is equal to 2 and t is equal to 3; each R6 and R7 independently represents alkyl, or cycloalkyl, or R6 and R7 together represent alkylene group containing 5-6 carbon atoms which forms a cycle with N atoms; R8 represent alkyl, or cycloalkylalkyl; R9 represents alkyl; Ar represents aryl group; Het represents heterocyclic group which is completely saturated, particularly saturated or completely unsaturated containing 5 to 10 ring atoms in which at least 1 ring atom represents N, O or S atom which is unsubstituted or substituted once or several times by the substituted specified in cl. 1; and their pharmaceutically acceptable salts or solvates or N-oxides, or solvates of their pharmaceutically acceptable salts, or solvates of N-oxides of their pharmaceutically acceptable salts wherein said compound can be presented in the form of a polymorph, wherein if said compound shows chirality, it can be presented in the form of a mixture of enanthiomers or a mixture of diastereoisomers, or can be presented in the form of single enanthiomer or single diastereoisomer; and wherein at least one of the groups R, R1 or R4 represents Het or OHet, wherein the group Het is specified in each case in substituted or unsubstituted azabicyclooctyl, oxaazabicycloheptyl, diazabicycloheptyl, diazabicyclononyl, diazabicyclooctyl, pyrazolyl, dihydroimidazolyl, 1,4-diazepanyl, hezahydropyrrolopyrazinyl and octahydropyrrolopyridinyl. Also the invention refers to other compounds of formula (I), to specific compounds, to a pharmaceutical composition based on the compound of formula (I), to a method of selective activation/stimulation of α-7 nicotinic receptors, to application of the compound of formula (I) for making the drug.

EFFECT: there are produced new compounds showing effective biological properties.

53 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present application describes substituted bicyclic beta-lactams of formula I: which are class A and class C β-lactamase inhibitors wherein X, R1 and R2 are specified in the application, as well as a method for producing them. The compounds of formula I and their pharmaceutically acceptable salts are applicable for preparing a pharmaceutical composition and for producing a drug. The declared compounds are applicable for treating bacterial infections, optionally in a combination with a β-lactam antibiotic. Particularly, the compounds may be used with such β-lactam antibiotics, as e.g. imipenem, piperacillin or ceftazidime to control microorganisms resistant to β -lactam antibiotics due to the presence of β-lactamases.

EFFECT: preparing the composition for treating bacterial infections.

28 cl, 117 ex, 3 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

and ,

which can be used to inhibit lipid kinase, including PI3K, and treat lipid kinase-mediated disorders. Values of radicals are given in claim 1.

EFFECT: improved properties of the compound.

11 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 is selected from H, F, CI, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n equals 1-5; m equals 0 or 1; and Y is selected from CH2, NR3, (NR3R4)+X-, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X- is selected from pharmaceutically acceptable anions. The invention also relates to a method of producing said compound and to an antiviral pharmaceutical composition based on said compound of formula (I).

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used in medicine to treat a viral diseases such as herpes.

19 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: described is a compound of general formula: [1], where R1 denotes an optionally substituted C2-C12 alkyl, aryl or heterocyclic group which can be a mono- or bicyclic 5-11-member radical, where the heteroatoms can be nitrogen, oxygen or sulphur; X1 denotes C2-C4 an alkylene group; X2 denotes a bond; X3 denotes a group of general formula NR3 or CR4R5NR3 (where R3 denotes a hydrogen atom, optionally substituted lower alkyl group or imino-protective group) and R4 and R5 are identical or different, and each denotes a hydrogen atom or a lower alkyl group or bond; X4 denotes a lower alkylene or lower alkenylene or lower alkynylene group, which can be substituted with one or more oxo groups or a bond; X5 denotes a sulphur atom or bond; Y1 denotes an optionally substituted divalent 4-, 5- or 6-member alicyclic hydrocarbon residue or an optionally subsituted divalent 5- or 6-member alicyclic amine residue, where the heteroatoms can be nitrogen or oxygen; Z1, Z2, Z3, Z4, Z5 and Z6 are identical or different, and each denotes a nitrogen atom or a group of general formula CR7 (where R7 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted amino group, or an amino group substituted with one or more C1-6 alkyl groups, a lower alkyl group, a cycloalkyl, a lower alkoxy group or a monocyclic 5-member heterocyclic group which can be substituted with one or more halogen atoms, where the heteroatoms can be nitrogen, acid or sulphur or a group of general formula Q1CO2R10 (where R10 denotes a carboxyl-protective group and Q1 denotes a lower alkenylene group), provided that at least one of Z3, Z4, Z5 and Z6 denotes a nitrogen atom, or salt thereof. The invention also describes an antimicrobial agent based on said compound.

EFFECT: novel compounds which can be used as antimicrobial agents are obtained and described.

25 cl, 176 ex, 6 tbl

FIELD: medicine.

SUBSTANCE: invention refers to an agent for activation of lipoprotein lipase containing a benzene derivative of general formula (1) which is used for preventing and treating hyperlipidemia and obesity. The invention also refers to the benzene derivatives of general formula (1a).

EFFECT: composition improvement.

8 cl, 6 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: method is realised by mixing a compound of formula (B) with p-toluenesulphonic acid or a monohydrate of toluenesulphonic acid in less than 1 molar equivalent with respect to the compound of formula (B), in a solvent while heating. An additional amount of p-toluenesulphonic acid or monohydrate of p-toluenesulphonic acid is then added to the mixed solution while cooling in such an amount that their total molar equivalent with p-toluenesulphonic acid or monohydrate of p-toluenesulphonic acid at the mixing step is equal to 1 molar equivalent or more with respect to the compound of formula (B). At the last step, the obtained solution is crystallised to separate a compound of formula (A).

EFFECT: obtaining a compound of formula (A) with stable high output.

12 cl, 1 dwg, 3 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes the pyrrolo- and thiazolopyridinium compounds and their pharmaceutically acceptable salts covered by general structural formula I: wherein the values A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are those as presented in cl.1, and a pharmaceutical composition based on the given compound for inhibition of hypoxia-inducible factor (HIF) hydroxylase activity.

EFFECT: there are produced and described new compounds able to modulate hypoxia-inducible factor (HIF) stability and/or activity.

29 cl, 178 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I , and pharmaceutically acceptable salts thereof, where L denotes O, S, or CH2; Y denotes N or CH; Z denotes CR3; G denotes CH; R1 denotes a heteroaryl ring of formula , where D1 denotes S, O; D2 denotes N or CR12; D3 denotes CR12; R2 denotes (C6-C10)-aryl; 5-9-member mono- or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially saturated (C3-C7)-cycloalkyl; or a saturated 5-6-member heteocyclyl with 1 heteroatom selected from N, where said aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted with one or two groups independently selected from (C1-C6)-alkyl, F, Cl, Br, CF3, CN, NO2, OR6, C(-O)R6, C(=O)OR6, C(=O)NR6R7, saturated 6-member heterocyclyl with 2 heteroatoms independently selected from N or O, and S(O)2R6, and where said alkyl is optionally substituted with one -OR8 group; R3 denotes H; (C1-C6)-alkyl; (C2-C6)-alkenyl; Cl; Br; OR6; SR6; phenyl; or a 6-member heteroaryl with 1 heteroatom selected from N, where said alkyl and alkenyl are optionally substituted with one group selected from C(=O)OR8, -OR8, -NR8R9; or a saturated 6-member heterocyclyl with 1 heteroatom selected from N or O.

EFFECT: disclosed compounds are used in treating and preventing diseases mediated by insufficient level of glucokinase activity, such as sugar diabetes.

16 cl, 479 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side with considerable absorption in the region up to 410-420 nm, having general formulae (a)-(k) (structural formula and values of radicals are given in the description), composition which is stabilised with respect to UV radiation and containing novel UV-absorbers, and use of the novel compounds as UV light stabilisers for organic materials.

EFFECT: obtaining novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side.

13 cl, 23 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives, having HIV replication inhibiting properties, or pharmaceutically acceptable salts thereof. In formula (1): R1 denotes hydrogen; R2 and R3 independently denote hydrogen; R7 and R8 denote C1-6alkyl; R4 denotes cyano; R9 denotes C1-6alkyl optionally substituted with cyano, C2-6alkenyl substituted with cyano, C2-6alkynyl optionally substituted with cyano; R5 denotes C1-6alkyl optionally substituted with Ar or Het; C2-6alkenyl optionally substituted with Ar or Het; C2-6alkynyl optionally substituted with Ar or Het; C3-7cycloalkyl; Ar; Het; R6 denotes H, Het; Y denotes -OR11, -NR12R13; R11 denotes hydrogen or C1-6alkyl optionally substituted with hydroxy, C1-6alkoxy or pyridyl; R12 denotes hydrogen or C1-6alkyl; R13 denotes hydrogen or C1-6alkyl; or R12 and R13 together with a nitrogen atom, which is substituted by said two substitutes, form a morpholinyl; imidazolyl; X denotes -NR1-; Het denotes 5- or 6-member completely saturated ring, where one or two ring members are heteroatoms, each independently selected from nitrogen and sulphur, and where the rest of the ring members are carbon atoms; and where any member of the heterocycle with a nitrogen heteroatom can optionally be substituted with C1-6alkyl; where the 5- or 6-member ring can optionally be annelated with a benzene or thiophene ring; each aryl independently denotes phenyl or phenyl substituted with one substitute selected from C1-6alkoxy.

EFFECT: high efficiency of using said compounds.

7 cl, 4 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: there are described substituted imidazo[2,1-b]thiazoles of general formula the R1, R1, R3 R4, M1, M2 radical values are presented in the patent claim cl. 1, as well as methods for making them, drug preparations containing these compounds and application of these compounds for making the drug preparations.

EFFECT: higher efficacy.

23 cl, 3 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula

wherein: m, n, R0, R1, R2, R3 and R4 have the values presented in clause 1 of the patent claim provided the compound of formula (I) cannot represent N-methyl-1-(phenylsulphonyl)-1H-indole-4-methanamine.

EFFECT: compounds show 5-NT6 receptor antagonist activity that that allows them being used in the pharmaceutical composition.

19 cl, 3 tbl, 192 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel agents for controlling plant fungal diseases, specifically 3,7-dithia-1,5-diazabicyclo[3,3,0]octane as an agent against Bipolaris sorokiniana, Aspergillus fumigates, Aspergillus niger, synthesis of which takes place in a single step using readily available reactants in contrast to multi-step synthesis of existing agents used for controlling fungal diseases of plants and materials.

EFFECT: obtaining novel agents for controlling plant fungal diseases.

1 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel heteroaryl-substituted derivative of benzothiazole - 2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol where one or more atoms may be a detectable isotope, in form of a free base or pharmaceutically acceptable salt thereof, capable of binding with amyloid deposits, to pharmaceutical compositions based on the radioactive-labelled disclosed compound, to use of the detectable isotope-labelled disclosed compound for determining amyloid deposits, as well as use of the disclosed compound in producing a medicinal agent for preventing and/or treating Alzheimer's disease and familial Alzheimer's disease. The present invention also relates to a novel intermediate compound for producing the disclosed heteroaryl-substituted benzothiazole derivative

EFFECT: high efficiency of using the compounds during treatment.

15 cl, 1 tbl, 15 dwg, 82 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 2-substituted-2,3-dihydrooxazolo[3,2-a]pyrimidin-7-ones and 2-substituted-2,3,5,6-tetrahydrooxazolo[3,2-a]pyrimidin-7-ones of formula (I): where p, n, X, Y, R1, R2, R3, R4, R5, R6, R7 and R8 are described in the description. These compounds are modulators of metabotropic glutamate receptors (mGluR), particularly the mGluR2 receptor. Compounds in the present invention are therefore suitable for use as pharmaceutical agents, especially in treating and(or) preventing various disorders of the central nervous system (CNS), including, among others, acute and chronic neurodegenerative disorders, psychosis, convulsions, anxiety, depression, migraine, pain, sleep disorder and emesis.

EFFECT: improved method.

14 cl, 148 ex

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