Novel cysteine protease inhibitors and therapeutic application thereof

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula I

, where: m equals 0, 1 or 2, where if m=0, disappears such that an open ring or single bond forms, n equals 0, 1 or 2, wherein when n=0, disappears such that an open ring or single bond forms; m' and n' are independently equal to 0, 1 or 2; X denotes a carbon atom; Y denotes a carbon or sulphur atom; provided that m and n are not equal to 0 at the same time; denotes a single or double bond, if needed; --- absence of a bond or a single bond, if needed; R1 is selected from a group comprising CN, Hal, OAIk, OH, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, wherein Alk is optionally substituted with Hal or OAlk, where p=0 or 1; R3, R4, R5 and R6 are identical or different and are independently selected from a group comprising H, OAIk, Alk, Hal, OH; R2 is selected from a group comprising H and O, and p'=0 or 1; R7 is selected from a group comprising H, O, OH, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7, bonded with the same Y, together form lioksalan; wherein said Alk is optionally substituted with OAlk, -CO-(NR-Alk-CO)p'-OAlk, and p'=0 or 1; R and R', which are identical or different, are independently selected from a group comprising H, and Alk; or pharmaceutically acceptable salt or optical isomer or diastereomer thereof, except those compounds for which: R3, R4, R5, R6=H, R1=CN, denotes a single bond, and denotes -C(=N-(2,4,6-trimethylphenyl))-, -C(=N-(2,6- dimethylphenyl))-, -C(=N-(2,6-diethylphenyl))-, -C(=N(2-methylphenyl))-, -C(=N(2-ethylphenyl))-, -C(=N-(2-trifluoromethylphenyl))-, -C(=N-(2-isopropylphenyl))-, -C(=N-phenyl)-, -C(=N-(naphthyl)- or -C(=O)-, -CH2-, or R3, R5, R6=H, R4=OMe, R1=CN, denotes a single bond, and denotes -C(=O)-, or R3, R4, R5, R6=H, R1=NH2, denotes a single bond, and denotes -CH2- or -CH2-CH2-; or R3, R4, R5, R6=H, R,=NH2, denotes -CH2- or -CH2-CH2-, and denotes a single bond. The invention also relates to a cysteine protease based pharmaceutical composition based on compounds of formula I, use of the compound of formula I to prepare a drug for inhibiting cysteine protease, for treating and preventing cancer, as well as inflammatory diseases and others.

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

38 cl, 43 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where m is 0, 1 or 2, and when m=0 vanishesso that forms an open ring or a single bond;
n is 0, 1 or 2, and when n=0 vanishesso that forms an open ring or a single bond;
m' and n' are independently 0, 1 or 2;
X is a carbon atom;
Y represents a carbon atom or sulfur;
provided that m and n are not 0 at the same time;
means a single or double bond, as required;
means no communication or single bond, n is necessary;
R1selected from the group consisting of CN, Hal, OAlk, HE, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, and Alk optionally substituted by Hal or OAlk, with p=0 or 1;
R3, R4, R5, R6the same or different independently selected from the group consisting of N, OAlk, Alk, Hal, HE;
R2selected from the group consisting of N and O, and R'=0 or 1;
R7selected from the group consisting of N, O, HE, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7associated with the same Y, together with it form dioxolan; and this Alk optionally substituted OAlk, -CO-(NR-Alk-CO)p'-OAlk, and R'=0 or 1; R and R', identical or different, independently selected from the group consisting of H, Alk;
or its pharmaceutically acceptable salt or optical isomer, or diastereoisomer,
with the exception of those compounds in which:
R3, R4, R5, R6=N, R1=CN,means a single bond, andmeans-C(=N-(2,4,6-trimetilfenil))-, -C(=N-(2,6-dimetilfenil))-, -C(=N(2,6-diethylphenyl))-, -C(=N(2-were))-, -C(=N(2-ethylphenyl))-, -C(=N-(2-triptoreline))-, -C(=N-(2-isopropylphenyl))-, -C(=N-phenyl)-, -C(=N-(naphthyl)- or-C(=O)-, -CH2-or
R3, R5, R6=N, R4=OMe, R1=CN,means a single bond, andmeans-C(=O), or
R3, R4, R5, R6=N, R1=NH2,means a single bond, andmeans-CH2- or-CH2-CH2-; or
R3, R4, R5, R6=N, R1=NH2,means-CH2- or-CH2-CH2-andmeans a single bond.

2. The compound according to claim 1 with the additional exception of those compounds in which R3, R4, R5, R6=H, R1=CN,means a single bond, andmeans-C(=N-OH)-.

3. The compound according to claim 1 or 2, in which R1selected from the group consisting of CN, Hal, OAlk, HE, NRCN, C(CN)=C(OH)(OAlk), NRR', (Alk)p-C(O)NRR', piperidine, and Alk optionally substituted OAlk, and p=0 or 1;
R3, R4, R5, R6the same or different independently selected from the group consisting of N, OAlk, Alk, Hal;
means a single bond or Y represents a carbon atom or sulfur;
R2selected from the group consisting of N, O;
R7selected from the group consisting of N, O, HE, N-OH, N-OAlk, N-aryl, N-O-aryl, N-O-Alk-aryl, N-O-Alk-O-aryl, N-O-Alk-CO-(NR-Alk-CO)p'-OAlk, N-NR-CONRR', or 2 R7associated with the same Y, together with it form dioxolan, and R'=0 or 1;
R and R' are the same or different is independently selected from the group consisting of H, Alk.

4. The compound according to claim 1, in whichmeans a single bond, n=1, n'=1, a Y means the carbon atom.

5. The compound according to claim 1, in which R1selected from the group consisting of CN, Hal, OAlk, HE, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', C(O)NRR', piperidine, and Alk optionally substituted OAlk.

6. The compound according to claim 1, in which R3, R4, R5, R6the same or different independently selected from the group consisting of N, OAlk, Alk, Hal.

7. The compound according to claim 1, in which R7selected from the group consisting of O, N HE, N-OAlk, N-aryl, N-O-aryl, N-O-Alk-aryl.

8. The compound according to claim 1, in which R and R' are the same or different independently selected from the group consisting of H, Alk.

9. The compound according to claim 1, selected from the group including:
9-hydroxy-3-methoxy-N-indeno[1,2-b]pyrazin-2-carbonitril
3-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-dimethylamino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-(2-methoxy-ethoxy)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-amino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-(4,4-debtor-piperidine-1-yl)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
9-(1',3'-dioxolane-2'-yl)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9-(label is iamino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(aliakseyeu)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(benzylamino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 amoxiillin-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 phenoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-N-indeno[1,2-b]pyrazin-2,3-Dicarbonitrile
5,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
benzo[4,5]thieno[2,3-b]pyrazin-2,3-dicarbonitrile
5,10-dioxo-5,10-dihydro-benzo[g]cinoxacin-2,3-dicarbonitrile
9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-yl-cyanamide
3-(1-cyano-2-ethoxy-2-hydroxy-vinyl)-9-oxo-N-indeno[1,2-b]pyrazin-2-ka is bontril
3-ethylsulfanyl-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
7-chloro-9-methoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-(2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-yl)-ndimethylacetamide
9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-6-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dichloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-ethyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9 aliakseyeu-2-cyano-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-amoxiillin-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-(2-methoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-methoxyimino-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-acetoxysilane-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 redenominate)acetic acid tilby ether
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 redenominate)acetic is islote
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]-acetic acid ethyl ester
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]-acetic acid
7-chloro-3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
9-[(aminocarbonyl)hydrazono]-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile,
or their pharmaceutically acceptable salts, optical isomers or diastereomers,

10. The compound according to claim 1, selected from the group including:
9-hydroxy-3-methoxy-N-indeno[1,2-b]pyrazin-2-carbonitril
3-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-dimethylamino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-(2-methoxy-ethoxy)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-amino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-(4,4-debtor-piperidine-1-yl)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
9-(1',3 dioxolan-2'-yl)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9-(methoxyimino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(aliakseyeu)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(benzylamino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 amoxiillin-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 phenoxyimino-N-indeno[,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
benzo[4,5]thieno[2,3-b]pyrazin-2,3-dicarbonitrile
5,10-dioxo-5,10-dihydro-benzo[g]cinoxacin-2,3-dicarbonitrile
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-yl-cyanamide
3-(1-cyano-2-ethoxy-2-hydroxy-vinyl)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
3-ethylsulfanyl-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitril
7-chloro-9-methoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-(2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-yl)-ndimethylacetamide
9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-6-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dichloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-ethyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9 aliakseyeu-2-cyano-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-amoxiillin-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-(2-methoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-methoxyimino-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-acetoxysilane-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 redenominate)acetic acid ethyl ester
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 redenominate)acetic acid
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]acetic acid ethyl ester
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]-acetic acid
7-chloro-3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile 9-[(aminocarbonyl)hydras is but]-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile,
or their pharmaceutically acceptable salts, optical isomers or diastereomers.

11. The compound according to claim 1, selected from the group consisting of:
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9 methoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(benzylamino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 amoxiillin-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 phenoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide,
or their pharmaceutically acceptable salts, or optical isomers or diastereomers.

12. The pharmaceutical composition inhibiting cysteinate comprising the compound of the formula I

where m is 0, 1 or 2, and when m=0 vanishesso that forms an open ring or a single bond;
n is 0, 1 or 2, and when n=0 vanishesso that forms an open ring or a single bond;
m' and n' are independently 0, 1 or 2;
X oznachaet is a carbon atom;
Y represents a carbon atom or sulfur;
provided that m and n are not 0 at the same time;
means a single or double bond, as required;
means no communication or single bond, as required;
R1selected from the group consisting of CN, Hal, OAlk, HE, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, and Alk optionally substituted by Hal or OAlk, with p=0 or 1;
R3, R4, R5, R6the same or different independently selected from the group consisting of N, OAlk, Alk, Hal, HE;
R2selected from the group consisting of N and O, and R'=0 or 1;
R7selected from the group consisting of N, O, HE, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7associated with the same Y, together with it form dioxolan; and this Alk optionally substituted OAlk,-CO-(NR-Alk-CO)p'-OAlk, and R'=0 or 1;
R and R' are the same or different independently selected from the group consisting of H and Alk;
or its pharmaceutically acceptable salt or optical isomer, or a diastereoisomer.

13. The pharmaceutical composition according to item 12, in which the compound of formula I is determined according to any one of claims 1 to 9.

14. The pharmaceutical composition according to item 12 or 13, in which the compound of formula I selected from the group consisting of:
9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-hydro is C-3-methoxy-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-dimethylamino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-(2-methoxy-ethoxy)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-amino-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-(4,4-debtor-piperidine-1-yl)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
9-(1',3'-dioxolane-2'-yl)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(methoxyimino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-(aliakseyeu)-N-indeno[,1,2-b]pyrazin-2,3-dicarbonitrile
9-(benzylamino)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 amoxiillin-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 phenoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9-[phenylamino]-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-is metoxi-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
5,8-dimethoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-methoxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
benzo[4,5]thieno[2,3-b]pyrazin-2,3-dicarbonitrile
5,10-dioxo-5,10-dihydro-benzo[g]cinoxacin-2,3-dicarbonitrile
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-yl-cyanamide
3-(1-cyano-2-ethoxy-2-hydroxy-vinyl)-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
3-ethylsulfanyl-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
7-chloro-9-methoxyimino-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-chloro-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-(2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-yl)-ndimethylacetamide
9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-chloro-9-(2-phenoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
9 aliakseyeu-6-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
7-fluoro-8-methyl-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6,7-dindar-9-oxo-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
6-ethyl-9-Oxon-indeno[1,2-b]pyrazin-2,3-dicarbonitrile
2-cyano-9-[hydroxyimino]-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
9 aliakseyeu-2-cyano-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-amoxiillin-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-(2-methoxy-amoxiillin)-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-methoxyimino-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-acetoxysilane-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
2-cyano-9-oxo-N-indeno[1,2-b]pyrazin-3-carboxylic acid amide
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetic acid ethyl ester
(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 redenominate)acetic acid
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]-acetic acid ethyl ester
[2-(3-carbarnoyl-2-cyano-indeno[1,2-b]pyrazin-9 ylideneamino)-acetylamino]-acetic acid
7-chloro-3-hydroxy-9-oxo-N-indeno[1,2-b]pyrazin-2-carbonitrile
9-[(aminocarbonyl)hydrazono]-7-chloro-N-indeno[1,2-b]pyrazin-2,3-dicarbonitrile,
or their pharmaceutically acceptable salts, optical isomers or diastereomers.

15. The use of the compounds of formula I, as defined according to any one of p-14, to obtain the drug for inhibition of one or more cysteine proteases.

16. The application indicated in paragraph 15, in which the cysteine PR is easy belong to one or more groups: enzymes of the ubiquitin-dependent proteolysis; caspases, cathepsins; kalainov, as well as cysteine proteases of viruses, bacteria, fungi or parasitic organisms.

17. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of cancer and metastasis, neurodegenerative diseases such as Alzheimer's and Parkinson's disease, inflammatory diseases, cardiovascular diseases and/or infectivity and/or latency of viruses, in particular Herpes simplex virus-1 virus, Epstein-Barr or the SARS coronavirus.

18. The application 17, wherein the compound inhibits one or more enzymes of the ubiquitin-dependent proteolysis.

19. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of inflammatory diseases, neurodegenerative diseases, preferably of damage to nerve cells due to stroke); liver damage and liver failure due to acute or chronic infectious, ischemic or chemical liver damage; kidney damage and renal failure due to acute or chronic infectious, ischemic or chemical damage to the kidneys; heart damage and heart failure due to acute or chronicallyinfected, ischemic or chemical lesions of the heart, diabetes, caused by acute or chronic autoimmune, chemical, oxidative or metabolic lesions of the insulin β-cells of pancreatic islets.

20. The application of claim 19, wherein the compound inhibits one or more caspases.

21. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of cancer and metastasis; cardiovascular diseases; immunological disorders; diseases of the musculoskeletal system, osteoporosis and arthritis.

22. The application of item 21, wherein the compound inhibits one or more of cathepsins.

23. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of diseases associated with aging; late diabetes and cataracts.

24. The application of item 23, wherein the compound inhibits one or more kalainov.

25. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prophylaxis of viral infections and diseases.

26. Use A.25, in which viral infection and disease is selected from hepatitis a, hepatitis C, infection with SARS coronavirus, and caused by them is of Alemania, rhinoviral infections and diseases, adenoviral infections and diseases, polio.

27. Application on p. 25 or 26, wherein the compound inhibits one or more viral cysteine proteases.

28. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of bacterial infections and diseases.

29. Use p, in which bacterial infection and disease is selected from infections and diseases caused by Streptococcus, bacteria Clostridium sp. and staphylococci, gingivitis and periodontal diseases.

30. Use p or 29, wherein the compound inhibits one or more bacterial cysteine proteases.

31. Use p at which this compound inhibits one or more bacterial cysteine proteases selected from strathpine, clostridia, cysteine protease of Staphylococcus, gingipain.

32. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of fungal infections and diseases.

33. Use p at which this compound inhibits one or more fungal cysteine proteases.

34. The use of the compounds of formula I, as defined according to any one of p-14, to receive the of edicament for the treatment and/or prophylaxis of protozoal infections and diseases.

35. The application of clause 34, wherein the compound inhibits one or more cysteine proteases in parasitic protozoan organisms.

36. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of infestations and disease caused by tapeworms.

37. Use p at which this compound inhibits one or more cysteine proteases in parasitic flatworms.

38. The use of the compounds of formula I, as defined according to any one of p-14, for receiving medication for the treatment and/or prevention of infestations and diseases caused by round worms.

39. The application of § 38, wherein the compound inhibits one or more cysteine proteases in parasitic roundworms.

40. The application 17, wherein the drug is used in combination with one or more therapeutic interventions selected from cancer, neurological, thrombolytic, anti-oxidant, anti-infective, antihypertensive, diuretic, thrombolytic, immune, cardiovascular, anti-inflammatory, antiviral, antibacterial, antifungal, Antiprotozoal, antiparasitics events.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts exhibiting PI3 kinase inhibitor activity. In the formula (I), A represents a thiophen ring; n=1; R1 represents , where m=1; R30 represents H; R4 And R5 together with N atom whereto attached form a 5- or 6-members N-containing heterocyclic group which includes 0 or 1 additional heteroatom selected from N and O which is unsubstituted or substituted by one or more substitutes selected from C1-6alkyl, C1-6alkoxy, -N(R"')-alk-OR, -alk-OR, -O-alk-OR, -alk-C(O)NR2, -C(O)NR2, -alk-Het, -N(R)-Het, -O-Het, -N(R)-C(O)- alk-OR, -NR-S(O)2R, -N(R)-alk-S(O)2R, -N(R)-alk-OR, -alk-NR'R", -N(R"')-S(O)2R, S(O)2R"', -S(O)2-alk-ORf 5- or 6-members N-containing heterocyclic group, 5- or 6-members N-containing heteroaryl group which includes 0 or 1 additional heteroatom selected from N, O or S, oxo(=O), -SO2NR2, -SO2-alk-NR2 where alk means a C1-6alkylene chain; Het means a 5- or 6-members N-containing heteroaryl group or furan optionally substituted by C1-6alkyl; R means H or C1-6alkyl, or when 2 groups R are bound with N, they together with N atom form a saturated 5- or 6-members N-containing heterocyclic group; each R' and R" means independently H, C1-6alkyl or C1-6alkoxy; R'" represents C1-6alkyl, a 5- or 6-merous saturated N-containing heterocyclic group, or a 5- or 6-merous N-containing heteroaryl group; R2 means where R6 and R7 together with N atom whereto attached form a morpholine group; R3 represents an indazole group.

EFFECT: development of the effective method of preparing the compounds of formula (I), and their application for preparing a drug, a pharmaceutical composition, and a method of inhibition.

10 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the new fused pyrimidines of formula (I) and to their pharmaceutically acceptable salts exhibiting P13 kinase inhibitor properties; in formula (I), A represents a thiophen ring; n=1; R1 represents a group of formula , where m=1; R30 represents hydrogen; R4 and R5 together with N atom whereto attached form a 5- or 6-members saturated N-containing heterocyclic group which includes 1 additional heteroatom selected from N which is unsubstituted or substituted by C1-C3alkyl which can be substituted by OH; S(O)2C1-3alkyl; C(O)N(diC1-C3alkyl); N(CH3)2; CON(CH3)-CH2CH2OCH3; N(CH3)-CH2CH2OCH3; -C(O)morpholine or morpholine; R2 is selected from where R6 and R7 together with nitrogen atom whereto attached form a morpholine group which is unsubstituted; and R3 represents an indole group which is unsubstituted.

EFFECT: production of the compounds of formula (I), a pharmaceutical composition, their application for preparing a drug and a method of inhibition.

9 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to condensed heterocyclic derivative, represented by formula (I): where ring A represents 5-member monocyclic heteroaryl, containing 1 or 2 heteroatoms, selected from N or S; RA represents lower alkyl group, optionally substituted with hydroxyl group, COW1, COOW1 or CONW2W3, in which W1-W3 independently represent a hydrogen atom or lower alkyl group; m represents integer 0 or 2; ring B represents benzene ring or thiophene ring; RB represents halogen atom, cyano group, lower alkyl group or OW4, in which W4 represents a hydrogen atom or lower alkyl group; n represents integer 0-2; E1 represents an oxygen atom; E2 represents an oxygen atom; U represents a single bond or lower alkelene group; X represents group, represented by Y, -CO-Y, -SO2-Y, -S-L-Y, -O-L-Y, -CO-L-Y, -SO-L-Y, -SO2-L-Y, -S-Z or -O-Z, in which L represents a lower alkylene group optionally substituted with halogen or hydroxy group; Y represents group, represented by Z or -NW7W8, where W7 and W8 independently represent a hydrogen atom, lower alkyl group or Z on condition that W7 and W8 are not simultaneously hydrogen atoms, or W7 and W8 can bind together with adjacent nitrogen atom with formation of cyclic amino group; Z represents cycloalkyl group, optionally condensed with phenyl and optionally substituted with phenyl group, optionally substituted with halogen or alkoxy group; 6-8-member heterocycoalkyl group, which has 1 heteroatom, selected from nitrogen atom or oxygen atom, optionally condensed with phenyl and optionally substituted with phenyl; phenyl group optionally substituted with a substituent, selected from group, consisting of a halogen atom, cyano group, alkyl group, optionally substituted with halogen atom, hydroxy group or alkoxy group, alkoxy group, optionally substituted with halogen atom, hydroxy group, alkoxy group, alkoxy-carbonyl-oxy group or acyloxy group, alkylthio group, carboxy group and alkoxy-carbonyl group; pyridyl; or its pharmaceutically acceptable salt. Invention also relates to pharmaceutical composition possessing antagonistic activity with respect to gonatotropin-releasing hormone, based on the claimed compound.

EFFECT: obtained are novel compounds and based on them pharmaceutical composition, which can be applied in medicine for prevention or treatment of a disease depending on sex hormones, which is selected from group, consisting of benign prostatic hypertrophy, hysteromyoma, endometriosis, premature puberty, prostate cancer, ovarian cancer and breast cancer.

29 cl, 112 tbl, 428 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to application of thienopyridone derivatives of formula (I), in which B represents CH, represents , or , R represents H, R1 and R2, independently on each other, represent H, linear or branched (C1-C4)alkyl, (C1-C4)cycloalkyl, halogen or together form group -(CH2)n-, where n=1- 4, R3 and R4, independently on each other, represent H, R6 represents H, X represents -O-, or their pharmaceutically acceptable salts for preparation of pharmaceutical composition.

EFFECT: obtaining pharmaceutical composition, suitable for treatment of diabetes, metabolic syndrome and obesity.

8 cl, 1 tbl, 210 ex

Thienopyridines // 2415859

FIELD: chemistry.

SUBSTANCE: invention relates to pharmaceutically suitable salts which are given in claim 1. The invention also relates to medicinal agents based on the said compounds, which are HSP90 inhibitors.

EFFECT: novel compounds and medicinal agents based on said compounds are obtained, which can be used to treat diseases influenced by inhibition, regulation or modulation of HSP90.

3 cl, 1 tbl, 16 ex

FIELD: chemistry.

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

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

20 cl, 5 dwg, 193 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of tetrahydrobenzo[4,5]thiophene[2,3-d]pyrimidine derivatives, including groups of known compounds, having formula (I), for preparing a medicinal agent for treating and/or preventing diseases and disorders which require inhibition of the 17β-hydroxysteroid-dehydrogenase (17β-HSD) enzyme, more preferably which require inhbition of type 1 17β-HSD enzyme, type 2 17β-HSD enzyme or type 3 17β-HSD enzyme. In formula X denotes S or SO2, R1 and R2 are separately selected from a group which includes -C1-C12alkyl, where the alkyl can be straight, cyclic, branched or partially unsaturated, and can be optionally substituted with up to three substitutes, independently selected from a group consisting of hydroxyl, C1-C12alkoxy group, thiol, C1-C12alkylthio-, aryloxy group, -CO-aryl, -CO-OR, -O-COR, -O-CO-heteroaryl and a -N(R)2 group; where the said aryl group is phenyl or naphthyl and can be optionally substituted with up to 3 halogen atoms; where the said heteroaryl group is thienyl, furyl or pyridyl; -aryl and arylC1-C12alkyl, where the aryl is selected from a group consisting of phenyl, biphenyl, naphthyl, indanyl, indenyl and fluorenyl. Other values of substitutes are given in the formula of invention.

EFFECT: high efficiency of using novel compounds in therapy.

32 cl, 3 tbl, 7 dwg, 151 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compounds of formula where values of radicals are given in the formula of invention, and a pharmaceutically acceptable salt thereof. Said compounds have 17β-hydroxysteroid dehydrogenase enzyme (17β-HSD) inhibiting activity. The invention describes use of the formula (I) compound in treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, use of the formula (I) compound to prepare a medicinal agent for treating or preventing diseases or disorders which require inhibition of 17β- hydroxysteroid dehydrogenase enzyme, and a pharmaceutical composition based on the formula (I) compound.

EFFECT: derivatives are highly effective.

18 cl, 7 tbl

FIELD: chemistry.

SUBSTANCE: use of compounds of formula (I): where: X denotes >CR1R2 or, when R6 denotes H, X denotes >SO2; Y denotes >CR1R2; Z denotes >C=O, >CH2, single bond; R1 denotes H, R2 denotes H, -COOH, -OH; or R1 and R2 together denote =O, ethylenedioxy or hydroxyimino group; R3 denotes H, lower alkyl group; R4 denotes two H, =O, hydroxyimino group; R5 denotes H, lower alkyl group, halogen; R6 denotes H, lower alkoxy, COOH; R7 and R8 are identical or different from each other and each denotes H, lower alkyl, halogen; and pharmaceutically acceptable salts thereof and esters for preparing a medicinal agent.

EFFECT: agent having neuroprotective action against hypoxia.

2 tbl, 24 ex, 13 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) and formula (II), their tautomers and pharmaceutically acceptable salts. In formula (I) and in formula (II), X - S; R1 - H; R2 - NR5R6; R3 - 5-6-member heteroaryl with 1 heteroatom, selected from N and S, or phenyl, optionally substituted with one or two substituents, selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenalkyl and C1-C6-halogenalkoxy; R4 - H, C1-C6 alkyl, C1-C6 alkoxy or XR3, where X and R3 are determined above; R5 - H; R6 - H; L - N or CR7, where R7 - H; M - S. Invention also relates to pharmaceutical composition, containing as active component invention compound, to method of inhibiting activity of caseinkinase lε and to method of obtaining compounds of formula (I) or formula (II).

EFFECT: compounds of claimed invention possess properties of casein kinase lε inhibitors.

13 cl, 5 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: medicine; pharmacology.

SUBSTANCE: in formula (I) V represents -N (R1) (R2) or OR4; R4 represents H, C1-6alkyl, C1-6halogenalkyl or (C1-6alkylen)0-1R4' R4' represents C3-7cycloalkyl, phenyl, pyridyl, piperidinyl; and R4' is optionally substituted with 1 or 2 identical or different substitutes chosen from group consisting of C1-4alkyl, amino, C1-3alkylamino, C1-3dialkylamino, phenyl and benzyl; and each R1 and R2 independently represents L1, where L1 is chosen from group consisting from H, C1-6alkyl, C2-6alkenyl, C2-6alkinyl, - adamantyl, pyrrolidinyl, pyridyl, or R1 and R2 together with nitrogen atom to which attached, form X, where X represents pyrrolidinyl, piperazinyl, piperidinyl, morpholino; where X is optionally substituted with Y, where Y represents dioxolanyl, C1-9alkyl, phenyl, furanyl, pyrrolyl, pyridyl, pyrrolidinyl; and where X and Y are optionally split with Z, where Z represents -C1-3alkylen-, C1-3alkylen-. Other radical values are specified in formula of invention.

EFFECT: effective application for treatment of migraine and other headache mediated by action of CGRP-receptors.

34 cl, 11 dwg, 6 tbl, 201 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with the general formula (I) in the racemic, enantiomeric form or in any combination of these forms and in which: A represents -CH2-, -C(O)-, -C(O)-C(Ra)(Rb)-; X represents -CH-; Ra and Rb independently represent the hydrogen atom or a radical (C1-C6)alkyl; Rj represents the atom of hydrogen; a radical (C1-C8)alkyl, not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; (C2-C6)alkenyl; or a radical of the formula -(CH2)n-X1; R2 represents a radical (C1-C8)alkyl not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; (C2-C6)alkenyl; or a radical of the formula -(CH2)n-X1; each X1 independently represents (C1-C6)alkoxy, (C3-C7)cycloalkyl or heteroaryl, and radicals (C3-C7)cycloalkyl, aryl and heteroaryl are not necessarily replaced by one or more either identical or various assistants chosen from: -(CH2)n'-V1-Y1, halogen and; V1 represents -O-, -S- or a covalent bond; Y1 represents a radical (C1-C6)alkyl, not necessarily substituted hydroxyl or by one or more identical or different radicals of halogens; n represents an integer from 0 up to 6 and n ' - an integer from 0 up to 2 that if n is equal 0 then X1 does not represent a radical alkoxy); or R1 and R2 form together with the atom of nitrogen to which they are attached, heterobicycloalkyl or heterocycloalkyl, are not necessarily replaced by one or more either identical or various substitutes chosen from: hydroxy, (C1-C6)alkyl, not necessarily substituted by hydroxy, (C1-C6)alkoxycarbonyl, heterocycloalkyl and-C(O)NV1'Y1', in which V1' and Y1' independently represent the atom of hydrogen or (C1-C6)alkyl; or R1 and R2 together form a radical of the formula: R3 represents-Z3, -C(RZ3)(R'Z3)-Z3, -C(RZ3)(R'Z3)-(CH2)p-Z3 or -C(O)Z'3; RZ3 and R'Z3 independently represent atom of hydrogen or a radical (C1-C6)alkyl; Z3 represents Z3b, Z3c, Z3d or Z3e; Z3b represents (C1-C6)alkoxy, (C1-C6)alkythio, (C1-C6)alkylamino, or a radical di((C1-C6)alkyl) amino; Z3c represents aryl or a radical heteroaryl; Z3d represents C1-C6)alkoxycarbonyl, aminocarbonyl, (C1-C6)alkylaminocarbonyl, di((C1-C6)alkyl) aminocarbonyl, (C1-C6)alkyl-C(O)NH-, (C3-C7) cycloalkyl, heterocycloalkyl; and radicals (C3-C7) cycloalkyl and heterocycloalkyl are not necessarily replaced by one or more either identical or various substitutes chosen from: (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl and oxy, radicals aryl and heteroaryl are not necessarily replaced by one or more either identical or various substitutes chosen from: halogen, cyanogen, nitro, azide, oxy, (C1-C6)alkylcarbonyl-(C1-C6)alkenyl, (C1-C6)alkylaminocarbonyl-(C1-C6)alkenyl, -SO2-NR31R32, heterocycloalkyl, heteroaryl or -(CH2)P'-V3-Y3; R31 and R32 form together with atom of nitrogen to which they are attached, heterocycloalkyl, V3 represents -O-, -S-, -C(O)-, -C(O)-O-, -O-C(O)-, -SO2-, -SO2NH-, -NR'3-SO2-, -NR'3-, -NR'3-C(O)-, -C(O)-NR'3-, -NH-C(O)-NR'3- or covalent bonds; Y3 represents the atom of hydrogen; radical (C1-C6)alkyl, not necessarily replaced by one or more either identical or different radicals of halogens; radical aryl or a radical aryl-(C1-C6)alkyl; Z3e represents a radical of the formula

, Z'3 represents a radical aryl, not necessarily replaced by one or more oreither identical or various substitutes chosen from: halogen, nitro and -(CH2)P"-V'3-Y'3; V'3 represents -O-, -C(O)-, -C(O)-O, -C(O)-NR'3-,-NH-C(O)-NR'3- or covalent bonds; Y'3 represents the atom of hydrogen or a radical (C1-C6)alkyl, not necessarily replaced by one or more either identical or different radicals of halogens; R'3 represents the atom of hydrogen (C1-C6)alkyl or a radical (C1-C6)alkoxy; p represents an integer from 1 up to 4; p' and p" independently represent an integer from 0 up to 4; R4 represents a radical of the formula -(CH2)S-R'4; R'4 represents a radical guanidine; heterocycloalkyl containing, at least, one atom of nitrogen and not necessarily substituted (C1-C6)alkyl or aralkyl; heteroaryl containing, at least, one atom of nitrogen and not necessarily substituted (C1-C6)alkyl or a radical of the formula -NW4W'4; W4 represents an atom of hydrogen or (C1-C8) alkyl; W'4 represents a radical of the formula -(CH2)S-Z4; Z4 represents an atom of hydrogen (C1-C8) alkyl, (C3-C7)cycloalkyl, heteroaryl and aryl; s and s' independently represent an integer from 0 up to 6; and i) if R3 represents -C(O)-Z'3 and R4 represents a radical of the formula -(CH2)S-NW4W'4, and W4 and W'4 independently represent an atom of hydrogen or a radical C1-C6)alkyl, then -(CH2)s represents neither radical ethylene nor radical -(CH2)-CH((C1-C4)alkyl) and ii), if R3 represents -Z3c and Z3c represents phenyl or naphthyl, then phenyl and naphthyl are not substituted by cyanogen; also note that if R3 represents -Z3d, then Z3d, represents only one (C3-C7)cycloalkyl or heterocycloalkyl; or to their pharmaceutically acceptable salts. The invention also relates to the method of obtaining the compounds of the formula (I), to a pharmaceutical composition, and to the application of compounds of the formula (I) and (I ').

EFFECT: obtaining new biologically active compounds on their basis, possessing activity with respect to receptors MC4.

41 cl, 535 ex

The invention relates to a derivative phthalazine General formula (I) or their pharmaceutically acceptable salts, or hydrates, where R1and R2are the same or different from each other and each represents a halogen atom, a C1-C4alkyl group which may be substituted by a halogen atom, a hydroxyl group or a C1-C4alkoxygroup, which may be substituted by a halogen atom, or cyano; X represents a cyano, a halogen atom, hydroxyimino, optional O-substituted C1-C4alkyl group, or a heteroaryl group selected from thiazoline, thienyl, pyrazolidine, triazolinones and tetrazolyl groups that may be substituted WITH1-C4alkyl group; Y represents a cyclic amino group (i) - (v) described in paragraph 1 of the claims; (vi) etinilnoy or ethyl group substituted WITH1-C4alkyl group, which, in turn, replaced by a number of deputies referred to in paragraph 1 of the claims; (vii) optionally substituted phenyl group; (viii) pyridyloxy or thiazolidine group

The invention relates to new derivatives of 1-piperazine-1,2-dihydroindeno and their acid additive salts which are active in relation to dopamine receptors in the Central nervous system, in particular are potential antagonists of dopamine receptors D, medicinal products containing these derivatives as active ingredients, and to the use of these derivatives in the treatment of diseases of the Central nervous system

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds - arylamidrazone derivatives of formula ,

where R1 is a C2-C8 alkyl group or a C2-C8 alkoxy group, which can be substituted with a halogen or a C1-C8 alkoxy group; a 5-7-member aromatic heterocycle containing 1 or 2 oxygen, nitrogen or sulphur atoms, or phenyl, which can be substituted with a halogen, a C1-C8 alkyl group, a haloC1-C8alkyl group or a C1-C8alkoxy group; or NR4R5; R2 and R3 are identical or different, and each is a hydrogen atom, a halogen atom, a halogenC1-C8alkyl group, a C1-C8alkyl group, a C2-C6alkynyl group, a C1-C8alkoxy group, a cyano group, a C2-C6alkanoyl group or a C1-C8alkylsulphonyl group; A is a benzene, pyridine, quinoline or isoquinoline ring; D is a single bond or methylene; m assumes values from 1 to 3 and n assumes values from 1 to 5, having antagonistic effect on S1P3 receptors, as well as to medicinal agents and pharmaceutical compositions containing such compounds as an active ingredient.

EFFECT: improved properties.

13 cl, 161 ex, 19 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to stable solid medication, containing olmesartan medoxomil and amlodipine or its pharmaceutically acceptable salt. Said solid medication is, in fact, free of reducing sugars. Stable solid medication optionally can additionally contain hydrochlortiazide or its pharmacologically acceptable salt. Medicinal form is intended for treatment or prevention of diseases caused by hypertension.

EFFECT: solid medicinal form in accordance with invention has improved solubility properties in comparison with lactose-containing composition.

42 cl, 2 dwg, 4 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): or to their pharmaceutically acceptable derivatives selected from a group consisting of pharmaceutically acceptable salts and esters; in which: R1, R2, R3, R4, R5, R6, R7, R8a, R8b, R8c and R8d are such as presented in the patent claim 1. The invention also refers to compounds of formula (I), to a compounds selected from a group, to a pharmaceutical composition, to methods of treating, to a method of decreasing the plasma cholesterol level in a patient, to a method of modulating cholesterol metabolism, catabolism, synthesis, absorption, re-absorption, secretion or excretion in a mammal, to a method of modulating farnesoid X receptor activity, to a compound representing 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino [4,5-b]indole-5-isopropylcarboxamide, to a composition, to a method of reducing the risk of an onset or a recurrence, to a method of modulating triglyceride metabolism, catabolism, synthesis, absorption, re-absorption, secretions or excretion in a mammal, and also to a method of modulating bile acid metabolism, catabolism, synthesis, absorption, re-absorption, secretions or excretion in a mammal.

EFFECT: preparation of the new biologically active compounds showing possessing nuclear receptor activity.

73 cl, 76 ex, 3 dwg

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