Indazolone derivatives as 11b-hsd1 inhibitors

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I) and pharmaceutically acceptable salts, where R1-R7 mean the same as provided in the invention description and claim. Compounds of the formula (I) are specific inhibitors of 11b-HSD1. They can be applied in treatment and/or prevention of diseases caused by dysfunctions related to 11b-HSD1 enzyme, particularly in treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, especially diabetes type "П". Additionally subject matter includes pharmaceutical composition for treatment and/or prevention of the said diseases.

EFFECT: improved efficiency of derivatives.

21 cl, 1 tbl, 146 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I):

where R1represents hydrogen or lower alkyl;
R2represents phenyl, phenyl-lower alkyl, pyridyl, pyridyl-lower alkyl, C3-C6-cycloalkyl,3-C6-cycloalkyl-lower alkyl, fluoro-lower alkyl or lower alkyl, where the phenyl optionally substituted by one or two halogen atoms, and lower alkyl optionally substituted by one Deputy, selected from the group consisting of HE, CN, lower alkoxy, and C(O)NR8NR9;
R3represents hydrogen;
R4represents hydrogen or halogen;
R5depict is to place a hydrogen or halogen;
R6represents hydrogen or lower alkyl;
R7represents lower alkyl, phenyl or naphthyl, where phenyl optionally substituted with one to three substituents, independently selected from lower alkyl, fluoro-lower alkyl, lower alkoxy, fluoro-lower alkoxy, dioxo-lower alkylene, halogen, cyano, phenoxy and 5-methyl-[1,3,4]-oxadiazol-2-yl, and lower alkyl optionally substituted with halogen or3-C6-cycloalkyl;
R8and R9independently from each other selected from the group consisting of hydrogen and lower alkyl;
and their pharmaceutically acceptable salts.

2. Compounds according to claim 1, where R1represents hydrogen.

3. Compounds according to claims 1 and 2, where R2represents phenyl-lower alkyl or pyridyl-lower alkyl, where the phenyl optionally substituted by one or two halogen atoms.

4. Compounds according to claims 1 and 2, where R2represents benzyl or pyridinylmethyl, where benzyl optionally may be substituted by 1 or 2 halogen atoms.

5. Compounds according to claims 1 and 2, where R2represents benzyl, 4-tormentil, 4-Chlorobenzyl, 3,4-diferensial or pyridine-2-ylmethyl.

6. Compounds according to claims 1 and 2, where R2represents phenyl.

7. Compounds according to claims 1 and 2, where R4represents hydrogen, fluorine or chlorine.

8. Compounds according to claims 1 and 2, where R5the present is the focus of a hydrogen.

9. Compounds according to claims 1 and 2, where R6represents hydrogen.

10. Compounds according to claims 1 and 2, where R7represents lower alkyl or phenyl, where phenyl optionally substituted with one to three substituents, independently selected from lower alkyl, fluoro-lower alkyl, lower alkoxy, fluoro-lower alkoxy, dioxo-lower alkylene, halogen, cyano, phenoxy and 5-methyl-[1,3,4]-oxadiazol-2-yl.

11. Compounds according to claims 1 and 2, where R7represents phenyl, substituted with 1-2 substituents selected from the group consisting of lower-alkyl, fluoro-lower-alkyl, halogen and cyano.

12. Compounds according to claims 1 and 2, where R7represents a 3-chloro-2-were, 2,3-dichlorophenyl, 3-chloro-4-forfinal, 3-trifluoromethyl-4-forfinal, 3-cyanophenyl, 2.5-differenl, 3-chloro-2-forfinal, 5-chloro-2-forfinal or 2-chlorophenyl.

13. Compounds according to claims 1 and 2, where R7is a fluoro-lower alkyl or lower alkyl substituted by cyclopropyl.

14. Compounds according to item 13, where R7is cyclopropylmethyl.

15. Compounds according to claims 1 and 2, selected from the group consisting of the following compounds:
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-methylbenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-4-forbindelsesfaneblad,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
N-(1-is ensil-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-dichlorobenzenesulfonate,
(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide naphthalene-2-sulfonic acid,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-4-methylbenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-methoxybenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-dichloro-6-methylbenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-triftoratsetilatsetonom,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-diftorbenzofenonom,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-propylbenzenesulfonyl,
(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide 2,3-dihydrobenzo[1,4]dioxin-6-sulfonic acid,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-chloro-2,5-dimethylbenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-chloro-3-triftoratsetilatsetonom,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-fluoro-3-triftoratsetilatsetonom,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-chloro-5-triftoratsetilatsetonom,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-phenoxybenzenesulfonyl,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-(5-methyl-[1,3,4]oxadiazol-2-yl)benzosulfimide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chlorobenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-methoxybenzenesulfonamide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-deformator benzosulfimide,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl) - for 3,5-bistrifluormethylbenzene,
(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide propane-2-sulfonic acid,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-N-dimethylbenzenesulfonamide,
N-(3-oxo-1-propyl-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
2,3-dichloro-N-(3-oxo-1-propyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
3-chloro-4-fluoro-N-(3-oxo-1-propyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
3-chloro-2-methyl-N-(3-oxo-1-phenethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
3-chloro-4-methyl-N-(3-oxo-1-phenethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
4-chloro-2,5-dimethyl-N-(3-oxo-1-phenethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
N-(3-oxo-1-phenethyl-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
N-(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
3-chloro-N-(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-methylbenzenesulfonamide,
3-chloro-N-(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-methylbenzenesulfonamide,
3-cyano-(1-isobutyl-3-oxo-2,3-dihydroindol-5-yl)benzosulfimide,
3 deformedarse-(1-isobutyl-3-oxo-2,3-dihydroindol-5-yl)benzosulfimide,
4-cyano-(1-isobutyl-3-oxo-2,3-dihydroindol-5-yl)benzosulfimide,
4-fluoro-N-(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
-chloro-4-fluoro-1N-(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
2,4-dichloro-(1-isobutyl-3-oxo-2,3-dihydroindol-5-yl)-5-methylbenzenesulfonamide,
3-chloro-N-(1-ethyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-methylbenzenesulfonamide,
3-chloro-(1-cyclopropylmethyl-3-oxo-2,3-dihydroindol-5-yl)-2-methylbenzenesulfonamide,
3-chloro-(1-cyclopropylmethyl-3-oxo-2,3-dihydroindol-5-yl)-4-forbindelsesfaneblad,
(1-cyclopropylmethyl-3-oxo-2,3-dihydroindol-5-yl)-4-fluoro-3-triftoratsetilatsetonom,
3-chloro-(1-cyclopropylmethyl-3-oxo-2,3-dihydroindol-5-yl)benzosulfimide,
2,4-dichloro-(1-cyclopropylmethyl-3-oxo-2,3-dihydroindol-5-yl)-5-methylbenzenesulfonamide,
3-chloro-[1-(2-methoxyethyl)-3-oxo-2,3-dihydroindol-5-yl]-2-methylbenzenesulfonamide,
4-fluoro-[1-(2-methoxyethyl)-3-oxo-2,3-dihydroindol-5-yl]-3-triftoratsetilatsetonom,
3-chloro-4-fluoro-[1-(2-methoxyethyl)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
2,4-dichloro-[1-(2-methoxyethyl)-3-oxo-2,3-dihydroindol-5-yl]-6-methylbenzenesulfonamide,
3-chloro-2-methyl-N-[3-oxo-1-(2,2,2-triptorelin)-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
4-fluoro-[3-oxo-1-(2,2,2-triptorelin)-2,3-dihydroindol-5-yl]-3-triftoratsetilatsetonom,
4-fluoro-N-(3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
2,4-dichloro-6-methyl-N-(3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
3-chloro-2-methyl-N-(3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H and dasol-5-yl)benzosulfimide,
4-fluoro-N-[1-(2-hydroxy-2-methylpropyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-3-triftoratsetilatsetonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-4-forbindelsesfaneblad,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-fluoro-3-triftoratsetilatsetonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-methylbenzenesulfonamide,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,3-dichlorobenzenesulfonate,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-cyanobenzenesulfonyl,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chlorobenzenesulfonamide,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-chloro-3-triftoratsetilatsetonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-deformationsanalyse,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-triftoratsetilatsetonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftormetilfullerenov,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,5-diftorbenzofenonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-dichlorobenzenesulfonate,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftoratsetilatsetonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-5-chloro-2-Forbes sulfonamid,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-chlorobenzenesulfonamide,
(1-benzyl-4-chloro-3-oxo-2,3-dihydroindol-5-yl)-3-chloro-2-methylbenzenesulfonamide,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-4-fluoro-3-triftoratsetilatsetonom,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,3-dichlorobenzenesulfonate,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-dichlorobenzenesulfonate,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-5-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-triftormetilfullerenov,
3-chloro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3 deformedarse-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
4-fluoro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-3-triftoratsetilatsetonom,
[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide 2,3-dihydrobenzo[1,4]dioxin-6-sulfonic acid,
2,4-dichloro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-6-methylbenzenesulfonamide,
5-chloro-2,4-debtor-N-[1(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
4-chloro-2,5-debtor-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3-chloro-[1-(4-terbisil)-3-oxo-2,3-dihydroindol-5-yl]-2-methyl shall enthaltene,
3-cyano-[1-(4-terbisil)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide naphthalene-1-sulfonic acid,
3-chloro-4-fluoro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3-chloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-2-methylbenzenesulfonamide,
3-chloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-4-forbindelsesfaneblad,
[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-4-fluoro-3-triftoratsetilatsetonom,
3-chloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-3-triftormetilfullerenov,
2,4-dichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-5-methylbenzenesulfonamide,
3,4-dichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
4,5-dichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-2-forbindelsesfaneblad,
2,4,5-trichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
2,3-dichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
2,4-dichloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-6-methylbenzenesulfonamide,
3-chloro-N-[1-(2,4-diferensial)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-forbindelsesfaneblad,
N-[1-(2,4-diferensial)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-cryptomaterial UNAMID,
3-chloro-N-[1-(2,4-diferensial)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-methylbenzenesulfonamide,
N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-triftoratsetilatsetonom,
3-chloro-N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-methylbenzenesulfonamide,
2,3-dichloro-N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide naphthalene-1-sulfonic acid,
3-chloro-N-[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-methylbenzenesulfonamide,
[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide naphthalene-1-sulfonic acid,
2,3-dichloro-N-[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
N-[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-triftoratsetilatsetonom,
N-[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-3-deformationsanalyse,
N-[1-(2-chloro-4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-3-triftormetilfullerenov,
3-chloro-N-[1-(2-cyanoethyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-methylbenzenesulfonamide,
N-[1-(2-cyanoethyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-triftoratsetilatsetonom,
2,4-dichloro-N-[1-(2-cyanoethyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-6-methylbenzenesulfonamide,
3-chloro-N-[1-(2-cyanoethyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-forbindelsesfaneblad,
N-[6-chloro-1(2-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-triftoratsetilatsetonom,
5-chloro-N-[6-chloro-1-(2-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-forbindelsesfaneblad,
2,3-dichloro-N-[6-chloro-1-(2-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3-chloro-N-(6-chloro-3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)-2-methylbenzenesulfonamide,
N-(6-chloro-3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)-4-fluoro-3-triftoratsetilatsetonom,
2-[5-(3-chloro-2-methylbenzenesulfonamide)-3-oxo-2,3-dihydroindol-1-yl]methylacetamide,
2,4-dichloro-[1-(3,4-diferensial)-2-methyl-3-oxo-2,3-dihydroindol-5-yl]-6-methylbenzenesulfonamide and
3-chloro-[1-(3,4-diferensial)-2-methyl-3-oxo-2,3-dihydroindol-5-yl]-2-methylbenzenesulfonamide,
and their pharmaceutically acceptable salts.

16. Compounds according to claims 1 and 2, selected from the group consisting of the following compounds:
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-methylbenzenesulfonamide,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,5-diftorbenzofenonom,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2-chlorobenzenesulfonamide,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,3-dichlorobenzenesulfonate,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-5-chloro-2-forbindelsesfaneblad,
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-chloro-2-methylbenzenesulfonamide,
3-cyano-[1-(4-terbisil)-3-oxo-2,3-dihydroindol-5-yl]benzosulfimide,
2,3-dichloro-N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3-chloro-N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-2-methylbenzenesulfonamide,
4-fluoro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-3-triftoratsetilatsetonom,
3-chloro-4-fluoro-N-[1-(4-terbisil)-3-oxo-2,3-dihydro-1H-indazol-5-yl]benzosulfimide,
3-chloro-[1-(3,4-diferensial)-3-oxo-2,3-dihydroindol-5-yl]-2-methylbenzenesulfonamide,
N-[1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]-4-fluoro-3-triftoratsetilatsetonom and
3-chloro-2-methyl-N-(3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
and their pharmaceutically acceptable salts.

17. Compounds according to claims 1 and 2, selected from the group consisting of the following compounds:
2,3-dichloro-N-(6-chloro-3-oxo-1-pyridin-2-ylmethyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-2,4-diftorbenzofenonom,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)-3-cyanobenzenesulfonyl,
(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide propane-2-sulfonic acid,
3-cyano-N-(3-oxo-1-phenyl-2,3-dihydro-1H-indazol-5-yl)benzosulfimide,
(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide 22,2-cryptgethashparam acid,
(1-benzyl-6-chloro-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide propane-2-sulfonic acid,
[6-chloro-1-(4-Chlorobenzyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide propane-2-sulfonic acid,
N-(1-benzyl-6-fluoro-3-oxo-2,3-dihydro-1H-indazol-5-yl)triftormetilfullerenov,
(1-isobutyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)amide propane-2-sulfonic acid,
[1-(3,4-diferensial)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide propane-2-sulfonic acid,
[1-(2-methoxyethyl)-3-oxo-2,3-dihydro-1H-indazol-5-yl]amide propane-2-sulfonic acid and
N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-cyclopropanesulfonyl,
and their pharmaceutically acceptable salts.

18. The compound according to claims 1 and 2, which is N-(1-benzyl-3-oxo-2,3-dihydro-1H-indazol-5-yl)-cyclopropanesulfonyl and its pharmaceutically acceptable salts.

19. The pharmaceutical composition intended for the treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, particularly type II diabetes, comprising a compound according to any one of claims 1 and 2, and a pharmaceutically acceptable carrier and/or adjuvant.

20. Compounds according to claim 1 or 2 for use as therapeutic active substances for the treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, particularly type II diabetes.

21. Compounds according to claim 1 or 2 for use as therapeutic active substances for the treatment and/or prevention of diseases which are caused by disorders associated with enzyme beta-hydroxysteroiddehydrogenase 1.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new imidazole derivatives of general formula I , where R1 is C1-C10alkyl or C3-C10cycloalkyl, each possibly and independently substituted with 1 substitute selected from C3-C10cycloalkyl or aryl or a heteroaryl group, possibly substituted with one or two halogens; aryl or heteroaryl; R2 is C1-C10alkoxy or C1-C10thioalkyl; R3 is C1-C10alkoxy, possibly substituted with one C1-C10alkoxy or nitrile, where the said alkoxy group can be cyclic or can contain one O heteroatom; R4 is C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or C3-C10cycloalkyl, each possibly and independently substituted with 1 or 2 substitutes selected from C1-C10alkoxy, C3-C10cycloalkyl, carboxylic ester, or with one or two aryl or heteroaryl groups, possibly substituted with one substitute selected from C1-C10alkyl, C3-C10cycloalkyl, nitro or halogen; aryl or heteroaryl, each possibly and independently substituted with 1-3 substitutes selected from C1-C10alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl group, possibly substituted with one halogen; where up to three hydrogen atoms of the alkyl group can be substituted with fluorine atoms; where the said cycloalkyl can independently have one or two carbon atoms substituted with O or N; where the said aryl denotes an aromatic ring having 6 to 10 carbon atoms, including mono- and bicyclic compounds; and where the said heteroaryl denotes an aromatic ring having 3 to 10 carbon atoms, including mono- and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulphur atoms; except compounds given in paragraph 1. The invention also pertains to use of the said compounds for making a medicinal agent, a treatment and prevention method, a compound of formula II (values of radicals are given in the formula of invention).

EFFECT: new imidazole derivatives having positive allosteric modulator effect on GABAB receptor are obtained.

30 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of a 5-hydroxy-4-thiomethylpyrazole compound, where a pyrazole compound of general formula is reacted with a sulphur compound of general formula X-S(O)n-R (2) in the presence of a base and formaldehyde to form a 5-hydroxy-4-thiomethyl compound of general formula , where radicals and symbols in the said formulae are defined in the formula of invention.

EFFECT: easier synthesis of the desired 5-hydroxy-4-thiomethylpyrazole compound with high output in mild conditions in a single step without using special equipment, expensive catalyst or a transition metal etc, where the process can be carried out virtually without formation of hazardous wastes from a catalyst etc; owing to this, the method is environmentally safe and can be used in industry.

6 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where R is hydrogen or (lower)alkyl; R1 is a (lower)alkyl or (C3-C7)cycloalkyl; X is nitrogen while Y is carbon or Y is nitrogen while X is carbon; m equals 0 or 1; Z is C(O) or SO2; R2 is selected from a group consisting of (lower)alkyl, (C3-C7)cycloalkyl or (C3-C7)cycloalkyl substituted with (lower)alkyl, (lower)phenylalkyl, where the phenyl ring is not substituted or is mono- or disubstituted with (lower)alkoxy or halide, pyridyl which is mono- or disubstituted with a halide, and NR3R4 or when Z is C(O), R2 can also be a (lower)alkoxy; R3 is hydrogen or (lower)alkyl; R4 is selected from a group consisting of (lower)alkyl, (lower)alkoxyalkyl, (C3-C7)cycloalkyl, unsubstituted phenyl or phenyl which is mono-substituted with (lower)alkoxy, or (lower)phenylalkyl, where phenyl is not substituted or is mono- or disubstituted with a halide; or R3 and R4 together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-member heterocyclic ring which optionally contains an additional heteroatom selected from oxygen, the said heterocyclic ring is unsubstituted or substituted with one or two groups independently selected from (lower)alkyl, halide and alkyl halide, or is condensed with a phenyl or cyclohexyl ring, and to their pharmaceutically acceptable salts, as well as to pharmaceutical compositions containing these compounds.

EFFECT: obtaining novel compounds and pharmaceutical compositions based on the said compounds, which are suitable for treating and/or preventing diseases which are associated with modulation of H3 receptors.

25 cl, 2 tbl, 93 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 4-phenylpyrimidine-2-carbonitrile of formula

(values of R, R1, R2 are given in the formula of invention) or their pharmaceutically acceptable salts which have inhibition properties towards catepsin K and catepsin S. The invention also relates to use of derivatives of formula I for treating catepsin K and catepsin S related disorders, as well as to a pharmaceutical composition containing the said derivative.

EFFECT: improved properties of derivatives.

9 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: in novel compounds of the formula (I) R is radical selected out of i) , ii) , iii) , iv) , where R7 is halogen, cyano, C1-4alkyl, C1-4alkoxy; p is integer within 0 to 3; R1 is hydrogen, C2-4alkenyl or C1-4alkyl; R2 is hydrogen or C1-4alkyl; R3 and R4 are independently hydrogen or C1-4alkyl; R5 is: phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; naphthyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen; benzofurane substituted with 1-3 groups selected independently out of C1-4alkyl or halogen; R6 is hydrogen or (CH2)qR8; R8 is hydrogen; m is zero or 1; n is 1; q is an integer within 1 to 4; r is 1 or 2; provided that if R5 is phenyl substituted with 1-3 groups selected independently out of trifluoromethyl, C1-4alkyl, cyano or halogen, then R is not radical i) ; and pharmaceutically acceptable salts or solvates thereof. The invention also refers to method (A) of compound obtainment, to compound application, to pharmaceutical composition, as well as to mammal treatment method.

EFFECT: obtainment of novel bioactive compounds with tachykinin receptor antagonist activity.

16 cl, 116 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I

where A, B and D each denotes N or CR5, where one of A, B and D denotes N, R1 denotes OR6, R2 denotes halogen, C1-C4alkyl, halogen(C1-C4)alkyl or OR7, R3 denotes a heteroarylalkyl group in which the heteroaryl fragment contains 5-6 atoms in the ring, at least one of which is an N atom, and the alkyl fragment with a branched or straight chain contains 1-5 carbon atoms, R4 denotes C3-C10cyclalkyl, C6-C14aryl, unsubstituted or substituted with one or more substitutes selected from a group comprising halogen, alkoxy, terazol-5-yl, 2-(heterocyclyl)tetrazol-5-yl or a carboxy group; heteroaryl containing 5-6 atoms in the ring; heterocyclic group saturated or partially saturated, containing 5-6 atoms in the ring, at least one of which is an N atom, unsubstituted or substituted with one or more substitutes selected from a group comprising alkoxy, alkoxyalkoxy, oxo, alkoxycarbonyl, alkylsulfanyl, alkylsufonyl or phenylsulfonyl; R5 denotes H; R6 denotes H or C1-C4alkyl with a branched or straight chain, unsubstituted or substituted with one or more halogens, R7 denotes H or C1-C12alkyl with a branched or straight chain, unsubstituted or substituted with one or more substitutes selected from a group which includes halogen; C3-C10cyclalkyl; saturated heterocyclic group containing 5-6 atoms in the ring, at least one of which is an O atom, or a heterocylcylalkyl group in which the heterocyclic fragment is saturated, partially saturated or unsaturated and contains 5-10 atoms in the ring, at least one of which is an O atom; or to a pharmaceutically acceptable salt thereof, as well as to a pharmaceutical composition for inhibiting PDE4 enzyme activity and to use of the said compound to prepare a medicinal agent.

EFFECT: novel compounds which can be used in medicine are obtained and described.

65 cl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

Triazole derivative // 2383536

FIELD: chemistry.

SUBSTANCE: described are novel triazole derivatives with general formula where values of radicals are given in the formula of invention, a pharmaceutical composition containing said derivatives, and a method of treating autoimmune diseases. Compounds with general formula (1) and their pharmaceutically acceptable salts have inhibition effect on S1P and its Edg-1 receptor (S1P1).

EFFECT: possibility of use as a pharmaceutical product.

43 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention proposes 5-member heterocyclic inhibitors of kinase p38, including kinase p38α and kinase p38β, based on pyrazoles and imidazoles, with the general formula given below , in which ring B is phenyl, and C is a pyrazole or imidazole ring, and the rest of the symbols assume values given in paragraph 1 of the formula of invention.

EFFECT: there are described pharmaceutical compositions containing said compounds, as well as methods of using the compounds and compositions, including a method of treating, preventing or suppressing one or more symptoms of diseases and conditions mediated by kinase p38 which include, but not limited to, inflammatory diseases and conditions.

31 cl, 6 tbl, 175 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

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