Heterobicyclic sulphonamide derivatives for treating diabetes

FIELD: chemistry.

SUBSTANCE: described are heterobicyclic derivatives of formula (I)

, in which V denotes -C(R7)-; W denotes a single bond or -C(R8R9)-; X denotes O, S, SO, SO2 or N(R10); Y denotes -C(R11R12)-, -C(R11R12)C(R13R14)C(R11R12)C(R13R14)C(R15R16)-, -C(R11R12)C(R13R14)C(R15R16)C(R17R18)- or- C(R11)=C(R12)-; R1, R2, R3, R4 and R5 independently denote hydrogen, halogen, (lower)alkyl, fluoro(lower)alkyl, (lower)alkoxy group, fluoro(lower)alkoxy group, NH2-C(O); R6 denotes a phenyl, pyridyl, pyrazolyl or thiazolyl group, where the group is optionally substituted with 1-4 substitutes selected from a group consisting of halogen, cyano group, (lower)alkyl, (lower)alkoxy group, COOH, 1H-tetrazol-5-yl, 5-oxo-4H-[1,2,4]oxadiazol-3-yl, where (lower)alkyl is optionally substituted with COOH. A pharmaceutical composition is also described.

EFFECT: said compounds inhibit L-CPT1 and can be used as medicinal agents.

27 cl, 120 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I)

in which V represents-C(R7)-;
W represents a single bond or-C(R8R9)-;
X represents O, S, SO, SO2or N(R10);
Y represents-C(R11R12)-, -C(R11R12)C(R13R14)-C(R11R12)C(R13R14)C(R15R16)-, -C(R11R12)C(R13R14)C(R15R16)C(R17R18)- or-C(R11)=C(R12)-;
R1, R2, R3, R4and R5independently of one another represent hydrogen, halogen, (ness.)alkyl, fluorine(ness.)alkyl, (ness.)alkoxy is the SCP, fluorine(ness.)alkoxygroup, NH2-C(O);
R6represents phenyl, pyridyloxy, parasailing or thiazolidine group, the group optionally substituted by 1-4 substituents selected from the group consisting of halogen, ceanography, (ness.)of alkyl, (ness.)alkoxygroup, COOH, 1H-tetrazol-5-yl, 5-oxo-4H-[1,2,4]oxadiazol-3-yl, (ness.)alkyl optionally substituted by COOH;
R7represents hydrogen, halogen, (ness.)alkyl, (ness.)alkoxygroup, fluorine(ness.)alkyl, fluorine(ness.)alkoxygroup, the hydroxy-group or hydroxy(ness.)alkyl;
R8and R9represent hydrogen;
R10represents hydrogen;
R11, R12, R13, R14, R15, R16, R17and R18independently of one another represent hydrogen, phenyl group, COOH, C(O)O-(ness.)alkyl
and their pharmaceutically acceptable salts and esters.

2. Compounds according to claim 1, in which R11, R12, R13, R14, R15, R16, R17and R18independently from each other represent hydrogen or phenyl.

3. Compounds according to claim 1, in which W represents a single bond.

4. Compounds according to claim 1, in which X represents O, S, SO2or N(R10), and R10has the meanings given in claim 1.

5. Compounds according to claim 1, in which Y represents-C(R11, R 12)- or
-C(R11R12) (R13R14)-, and R11, R12, R13and R14have the meanings given in claim 1.

6. Compounds according to claim 1, in which R1, R2, R3, R4and R5independently of one another represent hydrogen, halogen or (ness.)alkoxygroup.

7. Compounds according to claim 1, in which R1represents (ness.)alkoxygroup.

8. Compounds according to claim 1, in which R1represents a methoxy group.

9. Compounds according to claim 1, in which R2, R3and R5represent hydrogen.

10. Compounds according to claim 1, in which R4represents a halogen.

11. Compounds according to claim 1, in which R4represents chlorine.

12. Compounds according to claim 1, in which R6represents a phenyl group, pyridyloxy, parasailing or thiazolidine the group with the specified group optionally substituted by 1-4 substituents selected from the group consisting of halogen, ceanography, (ness.)of alkyl, carboxy(ness.)of alkyl, (ness.)alkoxygroup, COOH, 1H-tetrazol-5-yl, 5-oxo-4H-[1,2,4]oxadiazol-3-yl.

13. Compounds according to claim 1, in which R6represents phenyl, pyridinyl, pyrazolidinone or thiazolidine group, this group optionally is substituted by 1-2 substituents selected from the group consisting of halogen, ceanography, (ness.)alkyl is, carboxy(ness.)of alkyl, (ness.)alkoxygroup, COOH, 1H-tetrazol-5-yl and 5-oxo-4H-[1,2,4]oxadiazol-3-yl.

14. Compounds according to claim 1, in which R6represents phenyl, pyridinyl or thiazolidine group, this group optionally is substituted by 1-2 substituents selected from the group consisting of halogen, (ness.)of alkyl, carboxy(ness.)the alkyl and COOH.

15. Compounds according to claim 1, in which R6is a 4-carboxyphenyl, 3-fluoro-4-carboxyphenyl, 3-chloro-4-carboxyphenyl, 2-carboxypropyl-5-yl, 4-carboxymethyl, 4-carboxymethylthio-2-yl or 2-carboxymethylthio-4-yl.

16. Compounds according to claim 1, in which R7represents hydrogen, halogen, (ness.)alkyl, (ness.)alkoxygroup or fluorine(ness.)alkoxygroup.

17. Compounds according to claim 1, in which R7represents a hydrogen or halogen.

18. Compounds according to claim 1, in which R7represents a hydrogen or fluorine.

19. Compounds according to claim 1, in which R11, R12, R13, R14, R15, R16, R17and R18independently from each other represent hydrogen or phenyl.

20. Compounds according to claim 1, in which R11, R12, R13, R14, R15, R16, R17and R18represent hydrogen.

21. Compounds according to claim 1, in which R11, R12, R13, R14, R15, R16, R17and R18 represent hydrogen, COOH or C(O)O-(ness.)alkyl.

22. Compounds according to claim 1, selected from the group consisting of 4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
2-Chloro-4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
5-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}pyridine-2-carboxylic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-methoxybenzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-methylbenzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-3-methylbenzoic acid,
2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazole-4-carboxylic acid,
[4-(1H-Tetrazol-5-yl)phenyl]amide 4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carboxylic acid,
[4-(5-Oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)phenyl]amide 4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carboxylic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,2,3,4-tetrahydroquinoxalin-6-ka is bonyl]amino}benzoic acid,
5-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]amino}pyridine-2-carboxylic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]amino}-2-fermenting acid,
4-{[4-(3-Permentantly)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(2,5-Differentiality)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(5-fluoro-2-methylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Deformationsvetsaren)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3,5-Dimethylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Chlorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
2-Fluoro-4-{[4-(3-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Chlorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
2-Fluoro-4-{[4-(3-permentantly)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(2,5-Differentiality)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting is islote,
2-Fluoro-4-{[4-(5-fluoro-2-methylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Deformationsvetsaren)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
4-{[4-(3,5-Dimethylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
4-{[4-(3-Carbamoylmethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
6-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}nicotinic acid,
2-Chloro-4-{[3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}-2-fermenting acid,
Phenylamide 3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carboxylic acid,
Pyridine-3-yl amide 3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carboxylic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2-phenyl-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[9-(5-Chloro-2-methoxybenzenesulfonyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-2-carbonyl]amino}benzoic acid,
2-Chloro-4-{[9-(5-chloro-2-methoxybenzenesulfonyl)-6,7,8,9-tetrahydro-oxa-9-athensallowed-2-carbonyl]amino}benzoic acid,
4-{[6-(5-Chloro-2-methoxybenzenesulfonyl)-3,4,5,6-tetrahydro-2H-benzo[b][1,4]oxathiin-8-carbonyl]amino}benzoic acid,
2-Chloro-4-{[6-(5-chloro-2-methoxybenzenesulfonyl)-3,4,5,6-tetrahydro-2H-benzo[b][1,4]oxathiin-8-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-trifluoromethyl-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-methoxy-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-methoxy-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-fluoro-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
2-Chloro-4-{[3-(5-chloro-2-methoxybenzenesulfonyl)-7-fluoro-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-fluoro-2,3-dihydroisoxazole-5-carbonyl]amino}-2-fermenting acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
2-Chloro-4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]the Mino}-2-fermenting acid,
4-{[7-Chloro-3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[8-Chloro-4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-methyl-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[4-(3-Chloro-2-methoxybenzenesulfonyl)-8-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
(4-forfinal)amide 3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carboxylic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[1-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydro-1H-4-oxa-1,5-diazonaphthalene-7-carbonyl]amino}benzoic acid,
Phenylamide 1-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydro-1H-4-oxa-1,5-diazonaphthalene-7-carboxylic acid,
Phenylamide 4-(5-chloro-2-methoxybenzenesulfonyl)-4H-benzo[1,4]oxazin-6-carboxylic acid,
(2-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}thiazol-4-yl)acetic acid,
(3-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}phenyl)acetic acid,
(4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}phenyl)acetic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]is casin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
(2-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-fluoro-2,3-dihydroisoxazole-5-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-fluoro-2,3-dihydroisoxazole-5-carbonyl]amino}phenyl)acetic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-Enzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}phenyl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
Phenylamide 4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carboxylic acid,
3-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[1-(5-Chloro-2-methoxybenzenesulfonyl)-1,4-dihydro-2H-benzo[d][l,3]oxazin-7-carbonyl]amino}benzoic acid,
(2-{[1-(5-Chloro-2-methoxybenzenesulfonyl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-7-carbonyl]amino}thiazol-4-yl)acetic sour the s and
(4-{[1-(5-Chloro-2-methoxybenzenesulfonyl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-7-carbonyl]amino}phenyl)acetic acid,
and their pharmaceutically acceptable salts and esters.

23. Compounds according to any one of claims 1 to 22, selected from the group consisting of
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-fermenting acid,
2-Chloro-4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
5-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}pyridine-2-carboxylic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]amino}benzoic acid,
2-Chloro-4-{[3-(5-chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}benzoic acid,
4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}-2-fermenting acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
2-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}thiazol-4-yl)acetic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid is,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}thiazol-4-yl)acetic acid and
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid
and their pharmaceutically acceptable salts and esters.

24. Compounds according to any one of claims 1 to 22, selected from the group consisting of
2-Chloro-5-{[4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-methyl-2,3-dihydroisoxazole-5-carbonyl]amino}phenyl)acetic acid,
(2-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-7-methyl-2,3-dihydroisoxazole-5-carbonyl]amino}thiazol-4-yl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazole-5-yl)acetic acid,
2-{[4-(5-Chloro-2-label benzazolyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazole-5-carboxylic acid,
(3-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
3-(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)propionic acid,
2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-5-methylthiazole-4-yl)acetic acid,
(3-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}pyrazole-1-yl)acetic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}-2-cyanobenzoic acid,
2-Fluoro-4-{[4-(2-methoxy-5-methylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}benzoic acid,
(2-{[4-(Toluene-3-sulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(2-{[4-(3-Chlorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(2-{[4-(3,5-Dimethylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid,
(3-{[3-(5-Chloro-2-methoxybenzenesulfonyl)-2,3-dihydroisoxazole-5-carbonyl]amino}pyrazole-1-yl)acetic acid,
4-{[4-(3-Chlorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Chlorobenzenesulfonyl)-1-oxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3-Chlorobenzo sulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3,5-Dimethylbenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3,5-Dimethylbenzenesulfonyl)-1-oxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(3,5-Dimethylbenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1-oxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1-oxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}phenyl)acetic acid,
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}phenyl)acetic acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}-2-fermenting acid,
4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}-2-fermenting acid,
2-Chloro-4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
2-Chloro-4-{[4-(5-chloro-2-methoxybenzenesulfonyl)-1,1-dioxo-1,2,3,4-tetrahydrobenzo[1,4]thiazin-6-carbonyl]amino}benzoic acid,
Ethyl ester of 4-(5-chloro-2-methoxybenzenesulfonyl)-6-phenylcarbamoyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
4-(5-Chloro-2-methoxybenzenesulfonyl)-6-phenylcarbamoyl-3,4-dihydro-2H-benzo[1,4]OK Azin-2-carboxylic acid,
Ethyl ester of 4-(5-chloro-2-methoxybenzenesulfonyl)-6-(2-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
4-(5-Chloro-2-methoxybenzenesulfonyl)-6-(2-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
Ethyl ester of 4-(5-chloro-2-methoxybenzenesulfonyl)-6-(3-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
4-(5-Chloro-2-methoxybenzenesulfonyl)-6-(3-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
Ethyl ester of 4-(5-chloro-2-methoxybenzenesulfonyl)-6-(4-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid and
4-(5-Chloro-2-methoxybenzenesulfonyl)-6-(4-tortenelmebol)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
and their pharmaceutically acceptable salts and esters.

25. Compounds according to any one of claims 1 to 22, selected from the group consisting of
(2-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}thiazol-4-yl)acetic acid and
(4-{[4-(5-Chloro-2-methoxybenzenesulfonyl)-8-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-carbonyl]amino}phenyl)acetic acid,
and their pharmaceutically acceptable salts and esters.

26. Pharmaceutical composition having inhibitory activity of L-CPT1 containing compound according to any one of claims 1 to 25 and pharmaceutically acceptable carriers and/or adjuvant prednaznachennaya for the treatment and/or prevention of diseases, selected from the group including hyperglycemia, impaired glucose tolerance, diabetes and associated pathologies, non-insulin-dependent diabetes mellitus, obesity, hypertension, syndrome of insulin resistance, metabolic syndrome, hyperlipidemia, hypercholesterinemia, fatty liver, atherosclerosis, coronary heart disease and renal failure.

27. Compounds according to any one of claims 1 to 25 for use as therapeutically active compounds for the treatment and/or prevention of diseases modulated by inhibitors SRT selected from the group including hyperglycemia, impaired glucose tolerance, diabetes and associated pathologies, non-insulin-dependent diabetes mellitus, obesity, hypertension, syndrome of insulin resistance, metabolic syndrome, hyperlipidemia, hypercholesterinemia, fatty liver, atherosclerosis, coronary heart disease and renal failure.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrazine-2-carboxamide derivatives of general

formula , where R1 denote a 5- or 6-member ring, having a formula given in claim 1, R2 denotes H or C1-C7-alkyl; R3 denotes phenyl, pyridinyl or pyrimidinyl, possibly substituted with the following substitutes: Cl, F or Br; R4 denotes H, CI, F, Br, CF3 or C1-C7-alkyl; R5 denotes C1-C7-alkyl; as well as pharmaceutically acceptable salts thereof. Disclosed compounds are metabotropic glutamate receptor (mGLUR 5) antagonists. The invention also pertains to a medicinal agent based on disclosed compounds.

EFFECT: improved method.

17 cl, 23 ex

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent having CXCR2 inhibiting properties. In formula I , X denotes -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- or -S-; R3, R4, R5 and R6 independently denote hydrogen, F, CI, Br, I; R7 denotes hydrogen; Y1, Y2, Y3 and Y4 independently denote -CR8- or nitrogen, provided that at least two of Y1, Y2, Y3 and Y4 denote -CR8-; where R8 denotes hydrogen, F, CI, Br, I; A denotes a cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; a bicyclic partially saturated 9-member cycloalkyl; a bicyclic partially saturated 9-10-member heterocycle in which two atoms in the ring are oxygen atoms; phenyl; naphthyl; a 5-6-member heteroaryl in which 1-3 atoms in the ring are oxygen, sulphur and nitrogen atoms; a 9-10-member bicyclic heteroaryl in which 1-3 atoms in the ring are nitrogen, oxygen and sulphur atoms; a 6-member heterocycle in which one atom in the ring is a nitrogen atom and which can be unsubstituted or substituted with alkyl having 1, 2, 3 or 4 carbon atoms, -C(O)CH3, -C(O)CH2CH3, -C(O)cyclopropyl, -C(O)CF3 and -C(O)OC(CH3)3; where phenyl, heterocyclic or heteroaryl radical is substituted with 1, 2 or 3 radicals selected from a group consisting of F, O, Br, I, OH, CN, NO2, SCF3, SF3, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; cycloalkyl having 3, 4, 5 or 6 carbon atoms; alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -NR9R10, C(O)R44, S(O)SR47, -(CH2)k-phenyl, 5-6-member heteroaryl, in which 1-3 atoms in the ring are nitrogen and sulphur atoms; where the phenyl radical may be substituted with F, CI, Br, I; R9 is an alkyl having 1, 2, 3 or 4 carbon atoms; R10 is an alkyl having 1, 2, 3 or 4 carbon atoms; R44 is an alkyl having 1, 2, 3 or 4 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms; R47 is an alkyl having 1, 2, 3 or 4 carbon atoms; k equals 0, 1, 2 or 3; s equals 1 or 2; B is -O-C(R11R12), -C≡C-, -CR52=CR53-, -C(R13R14)C(R15R16), -NR17-C(R18R19); R11, R12, R13, R14, R15, R16, R17, R18, R19, R52, R53 independently denote hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D is C(O)OH, C(O)NHR21 or C(=NR58)NHR22; R21 and R22 independently denote hydrogen, -SO2-alkyl having 1, 2, 3 or 4 carbon atoms, -SO2-phenyl; R58 is OH; R1 and R2 independently denote an alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where the alkyl radicals are unsubstituted or substituted with 1 radical selected from a group consisting of F, Cl, Br, I, phenyl substituted with OH; or R1 and R2, taken together with a carbon atom with which they are bonded form a 3-, 4-, 5- or 6-member carbocycle. The invention also relates to use of formula I compounds in preparing a medicinal agent which has CXCR2 inhibiting properties, to a medicinal agent which containing an effective amount of the disclosed compound and having CXCR2 inhibiting properties, as well as to use of formula II compounds (formula and values of radicals are given in the formula of invention) in preparing a medicinal agent having CXCR2 inhibiting properties.

EFFECT: high effectiveness of application.

10 cl, 384 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-(2-thiazolyl)amide of 2-(2-oxo-3-indolinylidene)hydrazine-4-oxo-4-phenyl-2-butenoic acid of formula: .

EFFECT: obtaining a compound having antibacterial and analgesic activity.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I): wherein dashed lines present single or double bonds, and the values of radicals R1, R2, R3, R4 are described in cl. 1 of the patent claim. Besides the invention refers to application and a based pharmaceutical composition for prevention and treatment of neurodegenerative diseases and other diseases wherein cell dystrophy and/or cell loss (apoptosis) caused by free radicals act the main part.

EFFECT: production of new compounds and the based pharmaceutical composition which can find application in medicine for prevention and treatment of neurodegenerative diseases.

6 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (III): , in which D is a benzene ring, 2-pyridone ring, pyridine ring, benzoxalone ring, benzoxadinone ring or benzimidazole ring; R1 denotes carboxy or hydroxy; R2 independently denotes a halogen atom; alkyl optionally substituted with a halogen atom, aryl or alkylamine; alkynyl, optionally substituted alkoxy; hydroxy; carboxy; alkoxy optionally substituted with phenyl, aromatic heterocyclic ring which denotes a 5-6-member aromatic monocyclic carbocyclic ring containing one or two heteroatoms, independently selected from oxygen and nitrogen atoms; alkylsulphonyl; aryloxy; amino optionally substituted with alkyl; acyl optionally substituted with alkyl or alkyloxy; alkyloxycarbonyl; alkanesulphonyl; arylsulphonyl or alkylcarbamoyl; carbamoyl optionally substituted with alkyl, phenyl, cycloalkyl, acetyl, alkanesulphonyl, heteroarylalkyl, cycloalkylalkyl, heteroaryl which denotes a 5-6-member aromatic monocyclic ring containing one or three heteroatoms independently selected from oxygen and nitrogen atoms, and which is optionally substituted with alkyl or cycloalkyl; acylcyano; nitro, aryl; heteroaryl which denotes a 5-6-member aromatic ring containing one or more heteroatoms independently selected from oxygen, sulphur and nitrogen atoms, and which is optionally substituted with alkyl; alkylsulphonyl; morpholinylsulphonyl; non-aromatic heterocyclic group which denotes a 5-6-member non-aromatic heterocyclic ring containing one or more nitrogen atoms and optionally an oxygen and/or sulphur atom; R3 denotes C1-C6alkyloxy, C1-C6alkylthio; R4 denotes a halogen atom or alkyloxy; R5 denotes alkyl; M denotes sulphonyl; L3 independently denotes alkylene optionally containing one oxygen or nitrogen atom, alkenylene, or -N(R7)-; R7 independently denotes a hydrogen atom, alkyl; Y denotes a single bond or CO; Z denotes CH or N; n equals 0 or 1; p equals 0, 1, or 2; q equals 0 or 1; provided that R1 does not denote carboxy when ring D is a benzene ring, -L3- denotes -(O-alkylene)- and the substitution position of L3 and Y is an ortho-position in ring D; to pharmaceutically acceptable salts thereof. The invention also relates to compounds of formula (IV), a pharmaceutical composition, a method of treating diseases associated with the DP receptor, use of compounds in any of the claims 1-17, as well as compounds of general formula (V).

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

30 cl, 8 ex, 62 tbl

FIELD: medicine.

SUBSTANCE: invention refers to derivatives of 2-pyridylmethylenecarboxamide of formula (I), where: -A represents a substituted or unsubstituted 5-member heterocyclyl group bound with carbonyl through carbon atom; -Z1 and Z2 which can be equal or different, represent hydrogen atom; C1-C5-alkyl; C5-alkoxycarbonyl; -Z3 represents substituted or unsubstituted C3-C7cycloalkyl; -Y represents C1-C5-halogenalkyl, containing to 5 halogen atoms which can be equal or different; X which can be equal or different, represents halogen atom, - n=0, 1, 2 or 3; and to their salts. Besides the invention describes a method of plant pathogenic fungi control with the use of such compounds.

EFFECT: there are prepared and described new derivatives of 2-pyridylmethylenecarboxamide which can be effective as fungicidal active agents.

8 cl, 96 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention refers to new compounds exhibiting antiproliferative activity of formula (1) where W means N or C-R2; X means -NH-; Y means CH; Z means halogen, -NO2, C2-C3alkynyl-, halogen-C1-C3alkyl- and -C(=O)-C1-C3alkyl, A means a group of formula (i), (ii) or (iii) Q1 means phenyl; B1, B2, B3 and B4 independently mean C-RgRh, N-Ri or O; R1 means hydrogen; R2 means a residue specified from the group including hydrogen, halogen and -OR4; Ra, Rb, Rc, Rd, Re and Rf independently mean hydrogen; Rg and Rh independently mean a residue specified from the group including hydrogen, =O, -OR4 and -NR4C(=O)R5; or mean optionally a residue monosubstituted or twice-substituted with equal or different substitutes and specified from the group including C1-C6alkyl and phenyl, the substitute/substitutes is/are specified from the group including R8/, -OR4, -C(=O)R4, -C(=O)OR4 and -C(=O)NR4R5 where R8/ and other values of radicals are specified in the patent claim, optionally in the form of their pharmacologically noncontaminating acid addition salts. The invention also concerns a pharmaceutical composition.

EFFECT: new compounds have effective biological properties.

8 cl, 6 dwg, 1086 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: in embodiments of the invention, specific compounds are used to prepare a medicinal agent for treating, relieving and preventing conditions associated with dysfunction of monoamine transmission. The compounds have general formula (1) , where: R1 and R2 are identical or different and denote hydrogen, alkyl, alkenyl, alkynyl, aryl, thio or alkylthio, or R1 and R2 may have extra substitutes which are selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkyloxy, morpholin-4-ylalkoxy, piperidin-1-ylalkyloxy, alkylamino, dialkylamino, arylamino.

EFFECT: more efficient use of compounds in preparing medicinal agents.

8 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel 5-6-member nitrogen-containing heterocyclic compounds, selected form derivatives of pyridine, pyrimidine, imidasoline, oxadiasoline, such as, for instance , which possess inhibiting activity with respect to aspartylprotease, such as "ВАСЕ-1".

EFFECT: obtaining pharmaceutical composition, method of aspartylprotease inhibition aimed at application of compounds for preparation of medication intended for treatment of state, mediated by aspartylprotease, such as "ВАСЕ-1".

4 cl, 1 tbl, 1832 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described a compound of formula [I]: where A cycle represents a benzene cycle optionally having substitute(s) different from R1, R1 represents a group of formula RaSO2NH-, RaSO2NH-CH2- or (Rb)(Rc)NSO2-, Ra represents C1-C6 alkyl group, C3-C10cycloalkyl group, an amino group, 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic heteroaryl group containing 1-2 heteroatoms, chosen from oxygen, sulphur and nitrogen atoms, Rb and Rc are identical or different, and each represents hydrogen atom, C1-C6alkyl group or C3-C10cycloalkyl group, one of R2 and R3 represents hydrogen atom, halogen atom or C1-C6alkyl group, and the other represents hydrogen atom, C1-C6alkyl group, C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the neighbouring carbon atom to form C3-C10cycloalkyl group, X represents oxygen atom, sulphur atom, or formula group of -NR4-; Y represents a group of formula -C(=O)-, -C(=S)- or CH(R5)-; Ar represents optionally substituted 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic group; Q represents a simple bond, C1-C6alkylene group or C2-C6alkenylene group, or its pharmaceutically acceptable salts There are described specific compounds of formula [I], and also intermediate compounds.

EFFECT: presented compounds exhibit affinity to mineralocorticoid receptor (MR) and are applicable for prevention or treatment of various diseases or diseased states associated with such receptor.

11 cl, 54 tbl, 410 ex

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