Isoindole compounds and use thereof as metabotropic glutamate receptor potentiation factors

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where
R1is a 3-7-membered carbocyclic ring which may be substituted by one or more A;
R2and R3independently selected from H;
R4and R6independently selected from the group consisting of H, hydroxy, F, Cl, Br, I, cyano, C1-6-alkyl, C1-6-alkylhalogenide, OC1-6of alkyl, OC1-6-alkylhalogenide,3-8-cycloalkyl,1-6-alkyl-C3-8-cycloalkyl, OS0-6-alkyl-C3-8-cycloalkyl and 5-7-membered ring that may contain one or more than one heteroatom of N, where R4and R6can be substituted by one or more A;
R5selected from the group consisting of H, F, Cl, Br, I, nitro, C1-6-alkyl, C1-6-alkylhalogenide, OC1-6-alkylhalogenide,2-6-alkenyl,2-6-quinil,3-8-cycloalkyl, C1-6-alkyl-C3-8-cycloalkyl, phenyl, C1-6-alkylphenyl, OC1-6-alkylphenyl, OC1-6alkylpyridine, C1-6-alkylchlorosilanes, Geterotsiklicheskie, OC1-6-alkylchlorosilanes, C(O)N (CO)R10C(O)OR10With0-6-NR10R11OS2-6-NR10R11(CO)NR 10R11and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more than one, and where any cyclic group may condense with a 5-7-membered ring that may contain one or more than one heteroatom N;
R7selected from the group consisting of H, F, Cl, Br, I, cyano, OC1-4-alkyl, C1-6-alkyl, C1-6-alkylhalogenide, OC1-6-alkylamino and C3-8-cycloalkyl;
R8and R9independently selected from the group consisting of N and C1-6-alkyl;
or, when n is greater than 1,
two or more than two of R8and/or R9on adjacent carbon atoms may be missing from education alkenylphenol or alkenylphenol group;
R10and R11independently selected from the group consisting of H, oxo, cyano, C1-6-alkyl, OC1-6of alkyl, C3-8-cycloalkyl,1-6-alkyl-C3-8-cycloalkyl, OS0-6-alkyl-C3-8-cycloalkyl, phenyl, C1-6-alkylphenyl,0-6-alkyl-geterotsiklicheskie, pyridyl and C1-6alkylpyridine where any cyclic group may condense with a 5-7-membered ring, and where any cyclic group possibly substituted by the Deputy selected from alkyl, halogeno and halogenoalkane;
And SEL the Academy of Sciences of the group, consisting of H, hydroxy, F, Cl, Br, I, cyano, C1-6-alkyl, C1-6-alkylhalogenide, OC1-6of alkyl, OC1-6-alkylhalogenide,3-8-cycloalkyl,1-6-alkyl-C3-8-cycloalkyl, OS0-6-alkyl-C3-8-cycloalkyl, phenyl, C1-6-alkylphenyl, OS0-6-alkylphenyl, C1-6-alkyl-pyridyl, C1-6-alkyl-geterotsiklicheskie, OS0-6-alkyl-pyridyl, (CO)R10With1-6-R10With1-6-alkyl(CO)R10With0-6-alkyls2R10With0-6-NR10R11With0-6-SR10and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N and O, where the specified 5-7-membered ring possibly substituted by one or more of R10and R11;
n is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8;
where specified heteroseksualci means a 5-7 membered saturated ring which may contain one or more than one heteroatom independently selected from the group consisting of N, O and S;
or its pharmaceutically acceptable salt, hydrate, MES, optical isomer, or combination thereof;
provided that the compound is not:
5-butyl-2-benzyl-2,3-dihydro-isoindole-1-he,
5-tert-butyl-2-benzyl-2,3-dihydro-isoindole-1-he,
5-phenyl-2-benzyl-2,3-dihydro-isoindole-1-he,
5-dimethylaminomethyl-2-Ben is Il-2,3-dihydro-isoindole-1-he,
6-butyl-2-benzyl-2,3-dihydro-isoindole-1-he,
6-tert-butyl-2-benzyl-2,3-dihydro-isoindole-1-he,
2-[2-(2-forfinal)ethyl]-2,3-dihydro-isoindole-1-he,
5-benzyloxy-6-methoxy-2-[2-(2-forfinal)ethyl]-2,3-dihydro-isoindole-1-he,
5-(4-chlorophenyl)-2-[2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-2,3-dihydro-isoindole-1-he,
2-(1-phenylethyl)-2,3-dihydro-isoindole-1-he,
2-(2-phenylethyl)-2,3-dihydro-isoindole-1-he,
2-benzyl-2,3-dihydro-isoindole-1-he,
2-(4-methoxy-benzyl)-2,3-dihydro-isoindole-1-he,
2-(2-aminomethyl-benzyl)-2,3-dihydro-isoindole-1-he,
2-(2-chloromethyl-benzyl)-2,3-dihydro-isoindole-1-he,
2-(2-methyl-benzyl)-2,3-dihydro-isoindole-1-he,
N-(3,4-dichlorobenzyl)phthalimide,
2-(2-brominated)-2,3-dihydro-isoindole-1-it.

2. The compound according to claim 1, where n represents 1, 2 or 3; each of R4, R6R and R9represents H; R1selected from the group consisting of phenyl and C3-7-cycloalkyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl; R7selected from the group consisting of H, Cl, Br, I, C1-6-alkyl and OS1-4-alkyl, and R5selected from the group consisting of C3-8-cycloalkyl,1-6-alkyl-C3-8-cycloalkyl, phenyl, C1-6-alkylphenyl, OC1-6-alkylphenyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more than one, and where any cyclic group may condense with a 5-7-membered ring that may contain one or more than one heteroatom n

3. The compound according to claim 1, where: n represents 1, 2 or 3; each of R4, R6, R8and R9represents H; R1selected from phenyl and C3-7-nikolkina, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl; R7selected from Cl, Br, I, and-och3and R5selected from C1-6-alkylphenyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more of A.

4. The compound according to claim 1, where n represents 1, 2 or 3; each of R4, R6, R8and R9represents H; R1represents phenyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl; R7selected from the group consisting of H, Cl, Br, I, C1-6-alkyl and OS1-4-alkyl, and R5is a 5-7-membered ring that may contain one or more than one heteroatom, ezavisimo selected from the group consisting of N, O and S, where 5-7-membered ring substituted by one or more than one And selected from the group consisting of C1-6-alkyl-heterocyclyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N and O.

5. The compound according to claim 1, where n is 1; each of R2, R3, R4, R6, R8and R9represents H; R1represents phenyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl; R7selected from Cl, Br, I, and-och3and R5selected from C1-6-alkylphenyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more of A.

6. The compound according to claim 1, where n represents 1, 2 or 3.

7. The connection according to claim 6, where n represents 1.

8. The connection according to claim 7, where each of R8and R9represents N.

9. The compound according to claim 1, where each of R4and R6represents N.

10. The compound according to claim 1, where R1selected from the group consisting of phenyl and C3-7-cycloalkyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, is r, I OC1-6-alkylhalogenide and OS0-6-alkylphenyl.

11. The connection of claim 10, where R1represents phenyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl.

12. The connection of claim 10, where R1represents a C3-7-cycloalkyl.

13. The connection section 12, where R1is cyclopropyl.

14. The connection indicated in paragraph 13, where n represents 1, 2 or 3.

15. The connection 14, where n represents 1.

16. The compound according to claim 1, where
R1represents phenyl, possibly substituted by one or more than one And selected from the group consisting of F, Cl, Br, I, OC1-6-alkylhalogenide and OS0-6-alkylphenyl; each of R2, R3, R4, R6, R8and R9represents H; and n represents 1.

17. The connection section 12, where R7selected from the group consisting of H, Cl, Br, I, C1-6-alkyl and OC1-4-alkyl.

18. The connection 17, where R7selected from the group consisting of H, Cl, Br, I, -CH3and-och3.

19. Connection p, where R7selected from CL, Br, I, and-och3.

20. The compound according to claim 1, where R5selected from the group consisting of C3-8-cycloalkyl, C1-6-alkyl-C3-8-cycloalkyl, phenyl, C1-6-alkylphenyl, OC1-6-alkylphenyl and 5-7-clenn the ring, which may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more than one, and where any cyclic group may condense with a 5-7-membered ring that may contain one or more than one heteroatom n

21. Connection claim 20, where R5selected from C1-6-alkylphenyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where R5may be substituted by one or more of A.

22. Connection item 21, where R5is a 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N, O and S, where 5-7-membered ring substituted by one or more than one And selected from the group consisting of C1-6-alkyl-heterocyclyl and 5-7-membered ring that may contain one or more than one heteroatom independently selected from the group consisting of N and O.

23. A compound selected from the presented in the following table:









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or its pharmaceutically acceptable salt, hydrate, MES, optical isomer, or combination thereof.

24. A compound selected from
7-chloro-5-(4-pyridin-4-yl-piperazine-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-{[(pyridine-3-ylmethyl)-amino]-methyl}-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-{[(pyridine-4-ylmethyl)-amino]-methyl}-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(benzylamino-methyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(phenethylamine-methyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-[(3-phenyl-propylamino)-methyl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(indan-2-illuminometer)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
1-{1-[7-methyl-1-oxo-2-(4-cryptomaterial)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperidine-4-yl}-1,3-dihydro-benzoimidazol-2-it;
7-methyl-5-[4-(3-phenylpropyl)-piperidine-1-ylmethyl]-2-(4-triptoreline-benzyl)-2,3-dihydroindol-1-it;
5-{4-[3-(4-imidazol-1-yl-phenyl)-propyl]-piperidine-1-ylmethyl}-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydroindol-1-it;
3-methyl-8-[1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-yl]-1-phenyl-1,3,8-triaza-Spiro[4.5]Decan-4-it;
5-[4-(3-phenyl-propyl)-piperidine-1-yl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-[4-(2-methoxy-ethyl)-piperazine-1-yl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-morpholine-4-yl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-[4-(2-oxo-2-pyrrolidin-1-yl-ethyl)-piperazine-1-yl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-iodine-2-(3-phenyl-propyl)-2,3-dihydro-isoindole-1-it;
2-[3-(3-fluoro-phenyl)-propyl]-7-iodine-2,3-dihydro-isoindole-1-it;
7-iodine-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-bromo-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-iodine-2-(4-methyl-benzyl)-2,3-dihydro-isoindole-1-it;
7-iodine-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-iodine-2-(1-methyl-3-phenyl-propyl)-2,3-dihydro-isoindole-1-it;
7-iodine-2-(4-ethyl-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-[1-(4-phenoxyphenyl)-ethyl]-2,3-dihydroindol-1-is on;
7-chloro-2-dibenzo[1,4]dioxin-2-ylmethyl-2,3-dihydro-isoindole-1-it;
7-iodine-2-(4-butyl-benzyl)-2,3-dihydro-isoindole-1-it;
2-(4-phenylsulfanyl-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(3-dimethylamino-prop-1-inyl)-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(3-dimethylamino-propyl)-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-phenoxy-benzyl)-5-(3-pyrrolidin-1-yl-propyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-[3-(4-methyl-piperazine-1-yl)-propyl]-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
tert-butyl ester 4-[2-(4-methylbenzyl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid;
5-bromo-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(hexahydropyrazino[1,2-a]pyrazin-2-yl)-7-methyl-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-pyridin-3-yl-2-(cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-pyridin-4-yl-2-(cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-(4-methylpiperazin-1-yl)-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-(4-methylpiperazin-1-yl)-2-(4-phenoxybenzyl)-2,3-dihydroindol-1-it;
5-bromo-7-methyl-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
5-bromo-7-methyl-2-(4-chloro-benzyl)-2,3-dihydro-isoindole-1-it;
5-(3-dimethylaminopropan-1-yl)-7-methyl-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
5-(hexahydropyrazino[1,2-a]Piras the h-2-yl)-7-methyl-2-(4-phenoxybenzyl)-2,3-dihydroindol-1-it;
2-(4-Chlorobenzyl)-5-(hexahydropyrazino[1,2-a]pyrazin-2-yl)-7-methyl-2,3-dihydroindol-1-it;
2-(4-Chlorobenzyl)-5-(3-dimethylaminopropan-1-yl)-7-methyl-2,3-dihydroindol-1-it;
7-methyl-5-(octahedral[1,2-a]pyrazin-2-yl)-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
2-(4-Chlorobenzyl)-7-methyl-5-pyridin-4-yl-2,3-dihydroindol-1-it;
2-(4-Chlorobenzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydroindol-1-it;
7-chloro-5-(3-dimethylamino-prop-1-inyl)-2-(4-triptoreline-benzyl)-2,3-dihydroindol-1-it;
5-(3-dimethylamino-prop-1-inyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1,2,3,6-pyridin-4-yl)-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
bromo-7-methoxy-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-(1-methyl-1,2,3,6-pyridin-4-yl)-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
7-methoxy-5-pyridin-4-yl-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
7-methoxy-5-pyridin-3-yl-2-(4-cryptomaterial)-2,3-dihydroindol-1-it;
tert-butyl ester 4-[7-methoxy-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid;
5-chloro-2-(4-triptoreline-benzyl)-7-trifluoromethyl-2,3-dihydro-isoindole-1-it;
5-bromo-7-chloro-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-pyridin-4-yl-2-(4-tripto the methoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-2-(4-phenoxy-benzyl)-5-pyridin-4-yl-2,3-dihydro-isoindole-1-it;
7-methyl-2-(4-phenoxy-benzyl)-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
5-(3-dimethylamino-pyrrolidin-1-yl)-7-methyl-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-[3-(4-methyl-piperazine-1-yl)-prop-1-inyl]-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-[3-(4-methyl-piperazine-1-yl)-propyl]-2,3-dihydro-isoindole-1-it;
7-chloro-5-pyridin-3-yl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(4-dimethylaminomethyl-phenyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-pyridin-4-yl-2,3-dihydro-isoindole-1-it;
7-chloro-5-(4-methyl-piperazine-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-Chlorobenzyl)-5-(4-methyl-piperazine-1-yl)-2,3-dihydroindol-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(3-dimethylamino-pyrrolidin-1-yl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(3-dimethylamino-pyrrolidin-1-yl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(4-pyridin-4-ylmethyl-piperazine-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(4-pyridin-4-ylmethyl-piperaz the n-1-carbonyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-[4-(2-pyridin-4-yl-ethyl)-piperazine-1-yl]-2-(4-cryptomaterial)-2,3-dihydro-isoindole-1-it;
5-chloro-2-(4-ethyl-benzyl)-7-trifluoromethyl-2,3-dihydro-isoindole-1-it;
7-methyl-5-[3-(4-methyl-piperazine-1-yl)-propyl]-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(4-pyridine-3-ylmethyl-piperazine-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydroindol-1-it;
5-[4-(3-dimethylamino-propyl)-piperazine-1-yl]-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-(4-chloro-benzyl)-7-methyl-5-(4-pyridin-4-ylmethyl-piperazine-1-yl)-2,3-dihydro-isoindole-1-it;
5-(3-dimethylaminomethyl-phenyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
6-chloro-3-oxo-2-(4-phenoxy-benzyl)-2,3-dihydro-1H-isoindole-4-carbonitrile;
7-methyl-5-[(1-phenyl-ethylamino)-methyl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(4-aminomethyl-phenyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(4-(morpholine-4-ylmethyl-phenyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(3-dimethylamino-pyrrolidin-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
(S)-5-(3-dimethylamino-pyrrolidin-1-yl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(3-dimethylamino-pyrrolidin-1-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(3-dimethylamino-pyrrolidin-1-yl)-2,3-dihydro-isoindole-1-it; 7-chloro-2-(4-chloro-benzyl)-5-(3-dimethylamino-pyrrolidin-1-yl)-2,3-dihydro-isoindole-1-it;
5-bromo-7-chloro-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(4-dimethylaminomethyl-phenyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(1-benzyl-1H-pyrazole-4-yl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(6-amino-pyridin-3-yl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-[4-(2-pyridin-2-yl-ethyl)-piperazine-1-yl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-[4-(2-pyridin-4-yl-ethyl)-piperazine-1-yl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-methyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
4-[7-chloro-2-(4-chloro-benzyl)-1-oxo-2,3-dihydro-1H-isoindole-5-yl]-pyridine-3-carbaldehyde;
7-methyl-5-(1-pyridine-4-ylmethyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-[3-(4-methyl-piperazine-1-yl)-prop-1-inyl]-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(1-pyridine-4-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-pyridine-3-ylmethyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(4-(morpholine-4-ylmethyl-phenyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(1H-imidazol-4-yl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-[pyridine-4-ylmethyl)-amino]-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-pyridine-4-ylmethyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(methyl-pyridine-3-ylmethyl-amino)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-isobutyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(methyl-pyridine-4-ylmethyl-amino)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-pyridine-4-ylmethyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-pyridin-2-ylmethyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-pyridine-3-ylmethyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-pyridine-4-ylmethyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
4-{4-[7-methyl-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperidine-1-ylmethyl}-benzonitrile;
5-(1-cyclopentyl-piperidine-4-ylmethyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(methyl-pyridine-3-ylmethyl-amino)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-(pyridine-3-ylamino)-2-(4-triptoreline ensil)-2,3-dihydro-isoindole-1-it;
5-(1-isopropyl-piperidine-4-ylmethyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(1-methyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(1-ethyl-piperidine-4-ylmethyl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(1-benzyl-pyrrolidin-3-ylamino)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-[1-(2-dimethylamino-ethyl)-1H-pyrazole-4-yl]-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-ethyl-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindole-1-it;
methyl ester 7-methyl-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid;
7-chloro-2-(4-chloro-benzyl)-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(1-pyridine-3-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydro-isoindole-1-it;
5-(3-dimethylaminomethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(3-morpholine-4-ylmethyl-[1,2,4]oxadiazol-5-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5-(3-diethylaminomethyl-[1,2,4]oxadiazol-5-yl)-7-methyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-5-(3-methylaminomethyl-[1,2,4]oxadiazol-5-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
5,7-dichloro-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-ethyl-2-(4-trifluoromethyl-benzyl)-2,-dihydro-isoindole-1-it;
7-methyl-5-(pyridine-2-ylethoxy)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-methyl-2-(4-methyl-benzyl)-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-benzyl-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-fluoro-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-methoxy-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-cyclopropylmethyl-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
4-[(7-methyl-1-oxo-5-pyridin-3-yl-1,3-dihydro-2H-isoindole-2-yl)methyl]benzonitrile;
7-chloro-5-ethyl-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-chloro-benzyl)-5-(1-pyridine-ylmethyl-piperidine-4-ylmethyl)-2,3-dihydro-isoindole-1-it;
7-chloro-2-(4-fluoro-benzyl)-5-(1-pyridine-ylmethyl-piperidine-4-ylmethyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(1-methyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
4-{4-[7-chloro-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperidine-1-ylmethyl}-benzonitrile;
7-chloro-2-cyclopropylmethyl-5-(1-pyridine-4-ylmethyl-piperidine-4-ylmethyl)-2,3-dihydro-isoindole-1-it;
4-[4-(7-chloro-2-cyclopropylmethyl-1-oxo-2,3-dihydro-1H-isoindole-5-ylmethyl)-piperidine-1-ylmethyl]-benzonitrile;
5-fluoro-7-iodine-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-(5-chloro-2-fluoro-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-dimethylamino-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-and indol-1-it;
2-(4-ethyl-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
7-chloro-2-(3-phenylprop-2-inyl)-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydroindol-1-it;
5-fluoro-7-chloro-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-{4-[7-methyl-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperazine-1-ylmethyl}-nicotinanilide;
6-{4-[7-methyl-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperazine-1-ylmethyl}-nicotinanilide;
7-iodine-5-methoxy-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
7-chloro-5-(4-pyridin-2-yl-piperazine-1-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-{4-[7-chloro-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperazine-1-ylmethyl}-nicotinanilide;
6-{4-[7-chloro-1-oxo-2-(4-triptoreline-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperazine-1-ylmethyl}-nicotinanilide;
7-chloro-5-methoxy-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
2-(3-fluoro-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(2-fluoro-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-deformedarse-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-isopropyl-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
4-{4-[7-chloro-2-(4-chloro-benzyl)-1-oxo-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperidine-1-ylmethyl}-benzonitrile;
4-{4-[7-chloro-1-oxo-2-(4-cryptonetx the-benzyl)-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperazine-1-methyl}-nicotinanilide;
7-chloro-2-(3-phenylpropyl)-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydroindol-1-it;
7-chloro-5-(pyridine-2-ylethoxy)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
4-{4-[7-chloro-2-(4-deformedarse-benzyl)-1-oxo-2,3-dihydro-1H-isoindole-5-ylmethyl]-piperidine-1-ylmethyl}-benzonitrile;
7-chloro-2-(4-deformedarse-benzyl)-5-(1-pyridine-ylmethyl-piperidine-4-ylmethyl-2,3-dihydro-isoindole-1-it;
2-(4-fluoro-3-methyl-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-(4-chloro-2-methyl-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
2-benzyl-5-bromo-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(4-ethyl-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(3-fluoro-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(2-fluoro-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(4-deformedarse-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(4-isopropyl-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it;
5-bromo-2-(4-fluoro-3-methyl-benzyl)-7-methyl-2,3-dihydro-isoindole-1-it
7-methyl-5-[3-(1-methyl-piperidine-4-yl)-propyl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it,
or their pharmaceutically acceptable salt, hydrate, MES, optical isomer, or combination thereof.

25. A compound selected from
7-methyl-5-pyridin-3-yl-2-(cryptomaterial)-2,3-dihydroindol-1-it;
7-methyl-5-(1-methyl-piperidine-4-ylmethyl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-is a;
7-methyl-5-(3-methylaminomethyl-[1,2,4]oxadiazol-5-yl)-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it;
4-[4-(7-chloro-2-cyclopropylmethyl-1-oxo-2,3-dihydro-1H-isoindole-5-ylmethyl)-piperidine-1-ylmethyl]-benzonitrile;
2-(4-dimethylamino-benzyl)-7-methyl-5-pyridin-3-yl-2,3-dihydro-isoindole-1-it;
7-chloro-2-(3-phenylpropyl)-5-(1-pyridin-2-ylmethyl-1H-pyrazole-4-yl)-2,3-dihydroindol-1-it
7-methyl-5-[3-(1-methyl-piperidine-4-yl)-propyl]-2-(4-triptoreline-benzyl)-2,3-dihydro-isoindole-1-it
or their pharmaceutically acceptable salt, hydrate, MES, optical isomer, or combination thereof.

26. Pharmaceutical composition having the ability to modulate metabotropic glutamate receptors (mGluR), comprising the compound according to any one of claims 1 to 25 and a pharmaceutically acceptable carrier or excipient.

27. The compound according to any one of claims 1 to 25 for use as a medicine.

28. The use of compounds according to any one of claims 1 to 25 in the manufacture of a medicine for therapy of neurological and psychiatric disorders associated with glutamate dysfunction.

29. Use p, where neurological and psychiatric disorders selected from cerebral disorders due to surgery coronary bypass surgery and grafting, stroke, cerebral ischemia, spinal cord injuries, head injuries, Perina what happens hypoxia, cardiac arrest, damage to the neurons when hypoglycemia, dementia, dementia with acquired immunodeficiency syndrome (AIDS), Alzheimer's disease, horii's chorea, amyotrophic lateral sclerosis, eye injuries, retinopathy, disorders, cognitive abilities, and idiopathic caused by drugs Parkinson's disease, muscular spasms and disorders associated with muscular spasticity including tremors, epilepsy, convulsions, cerebral disorders that are secondary to prolonged epileptic status, migraines, headaches, migraine, urinary incontinence, tolerance to the substance withdrawal syndrome substance, psychosis, schizophrenia, anxiety, generalized anxiety disorder, panic disorder, sociophobia, obsessive-compulsive disorder and post-traumatic stress disorder (PTSD), mood disorders, depression, mania, bipolar disorders, disorders of circadian rhythm disorders circadian rhythm of the body due to flight and time shift work, trigeminal neuralgia, hearing loss, tinnitus, macular degeneration in the eye, emesis, brain edema, pain, acute pain, chronic pain, severe pain, chronic intractable pain, neuropathic pain, pain, inflammation and post-traumatic pain, the days dyskinesia, sleep disorders, narcolepsy, attention deficit disorder/hyperactivity disorder and conduct disorder.

30. Method of modulating metabotropic glutamate receptors (mGluR), including the stage of introducing a therapeutically effective amount of a compound according to any one of claims 1 to 25 or a pharmaceutical composition according p.

31. The method of obtaining the compounds of formula Ic, including:
(a) the cyclization of the compounds of formula Ia:

in prisutstvie amine of formula R1(CR8R9)nNH2in the compound of formula Ib
and
(b) cross-combination of the compounds of formula Ib with a reagent containing R5with obtaining the compounds of formula IC
B
where variables are as defined according to claim 1.

32. The method of obtaining the compounds of formula If, including:
(a) the cyclization of the compounds of formula Ia

in the presence of propargylamine in the compound of formula Id
;
(b) the combination of the compounds of formula Id with a reagent containing R1with obtaining the compounds of formula Ie
;
(C) cross-combination of the compounds of formula Ie with a reagent containing R5with obtaining the compounds of formula If
,
where R1is particularly the phenyl group, and other variables are as defined according to claim 1.

33. The method of obtaining the compounds of formula Ih, including the interaction of isoindoline Ig

with an electrophile of the formula X(CR8R9)nR1obtaining the compounds of formula Ih
,
where R1is such as defined in claim 1, and X represents a leaving group.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 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: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of cis-2,4,5-triarylimidazoline of general formula I and pharmaceutically acceptable salts thereof, where X1 is selected from a group comprising lower alkoxy; X2 and X3 are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX4X5, -SO2NX4X5, -C(O)NX4X5, -C(O)X6, -SOX6, -SO2X6, -NC(O)-lower alkoxy, -C≡C-X7, provided that both X2 and X3 do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X2 or X3 denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X2 denotes -HX4X5, X3 does not denote hydrogen, X2 and X3 together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X4 and X5 are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO2-lower alkyl, -C(O)piperazinyl-3-one; X6 is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X7 is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y1 and Y2 are independently selected from a group comprising halogen; R is selected from a group comprising lower alkoxy, piperidinyl substituted with a five-member heterocyclic ring which contains one nitrogen heteroatom, piperidinyl substituted with a hydroxy, -CH2OH or -C(O)NH2, piperazinyl substituted with one or two R1 [1,4]diazepanyl, substituted R1, R1 can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R2, -C(O)R3, -SO2-lower alkyl, -SO2-five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R2 is selected from a group comprising -SO2-lower alkyl, hydroxy, lower alkoxy, -NH-SO2-lower alkyl, -cyano, -C(O)R4; R3 is selected from a group comprising a five-member heterocyclyl which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl, lower alkyl, lower alkenyl, lower alkyl substituted with a six-member heterocyclyl selected from piperidinyl, piperazinyl, 3-oxopiperazinyl, morpholinyl, C3-cycloalkyl; R4 is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR5R6; R5 and R6 are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C3-cycloalkyl. The invention also relates to a pharmaceutical composition based on the formula I compound, use of the formula I compound in preparing a medicinal agent and a method for synthesis of the formula I compound.

EFFECT: novel derivatives of cis-2,4,5-triarylimidazoline of general formula I are obtained, which can be used to treat diseases, based on reaction of the MDM2 protein with p53-like protein, particularly as anticancer agent.

54 cl, 412 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel derivatives of 1H-imidazole of formula I, in which R1 represents hydrogen, halogen atom, C1-3-alkyl group, and said C1-3-alkyl groupcan include 1-3 fluorine atoms or R1 represents cyclopropyl, piano, or methylsulfanyl group, R2 represents phenyl group, which can be substituted with 1 substituent Y, selected from methoxy, chlorine, fluorine, trifluoromethyl and cyano, or R2 represents pyridyl group, on condition that R2 is not 6-methyl-2-pyridyl group, or R2 represents fully saturated 6-7-member monocyclic, condensed bicyclic ring system or benzothiazolyl, benzodioxane or thiazole group, and said groups can be substituted by 1 fluorine atom, or R2 represents group of general formula CH2-R5, in which R5 represents phenyl group or fully saturated 7-member condensed bicyclic carbocyclic ring system, or R5 represents piperidine or tetrahydrofuran ring system, which can be substituted by methyl, or R2 represents methylsulfonylamino(C3)alkyl group, R3 represents hydrogen, halogen atom, C1-6-alkylsulfonyl, cyanogroup, or R3 represents C1-8-alkyl group, and said C1-8-alkyl group can be substituted by 1-3 fluorine atoms, or R3 represents phenyl group, which is substituted by substituent Y, where Y has value, specified above, or R3 represents furanyl group, R4 represents one of subgroups (i) or (ii), where R6 represents C4-8-branched or linear alkyl group or naphtyl group, R7 represents hydrogen atom, linear C1-6-alkyl group, R8 represents C2-6-alkyl group, substituted by 1-3 fluorine atoms, or R8 represents C3-8-cycloalkyl group, piperidine group, C3-8-cycloalkyl- C1-2-alkyl group, tetrahydrofuranyl- C1-2-alkyl group, C5-10-bicycloalkyl group, C5-10-bicycloalkyl-C1-2-alkyl group, C6-10-tricycloalkyl group, C6-10-tricycloalkyl-C1-2-alkyl group, and said groups can be substituted by 1-3 substituents, selected from methyl or hydroxyl, or R8 represents phenyl group, substituted by 1-2 substituents Y, specified above, or R8 represents naphtyl, 1,2,3,4-tetrahydronaphtyl or indanyl group, and said groups can be substituted by 1 substituent Y, or R8 represents phenyl- C1-3-alkyl group, diphenyl- C1-3-alkyl group, and said groups can be substituted ob their phenyl ring by 1 substituent Y, where Y has value specified above, or R8 represents benzyl group, substituted by 2 substituents Y, or R8 represents quinilinyl, pyridinyl, benzimidazole or naphtylmethyl group which can be substituted by substituent Y, where Y has value, specified above, or R8 represents asabicyclo[3,3,0]octanyl group, on condition that R8 is neither 6-methoxybenzothiazole-2-yl group, nor [3-chlor-5-(trifluoromethyl)pyrid-2-yl]methyl group, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, non-aromatic, monocyclic or bicyclic heterocyclic group, including only one nitrogen atom, having 7-10 ring atoms, which can be subslituted by 3 C1-3-alkyl groups, or R7 and R8 together with nitrogen atom, to which they are bound, form saturated, monocyclic heterocyclic group, optionally including another N atom, having 6 ring atoms, and said heterocyclic group is substituted by C1-3-alkyl groups, on condition that R7 and R8 together with nitrogen atom, to which they are bound, do not form trimethylsubstituted asabicyclo[3,3,0]octanyl group, as well as their stereoisomers and pharmacologically acceptable salts of said formula (I) compounds and their stereoisomers Invention also relates to intermediate compounds of formula XIV, pharmaceutical composition based on formula I compound, method of obtaining such pharmaceutical composition and application of formula T compound.

EFFECT: obtained are novel derivatives of IH-imidazole, which are modulators of cannabinoid CB2-receptors.

8 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel amide derivatives of general formula [1] in any of versions (A) or (B), or its pharmaceutically acceptable salt, which possess properties of tyrosinkinase BCR-ABL inhibitor. Amide derivative of general formula [1] represents compound: , where according to Version (A) R1 represents any of the following groups (1)-(3): (1) -) -CH2-R11 [R11 represents saturated 4-6 member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom, which is substituted by group selected from group, consisting of oxo, -CH2-R111 (R111 represents saturated 5-member nitrogen-containing heterocyclic group), saturated 5-member nitrogen-containing heterocyclic group, aminomethyl, monoalkylaminomethyl, dialkylaminomethyl and (5-methyl-2-oxo-1,3-Dioxol-4-yl)methyl, and in addition, can be substituted by 1 or 2 similar or different substituents, selected from group, consisting of (C1-C4)alkyl, (C1-C4 alkoxycarbonyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, amino, carbamoyl], (2) -O-R12 [R12 represents saturated 4-6-member nitrogen-containing heterocyclic group]; and (3) - CH=R13 [R13 represents saturated 4-6-member nitrogen-containing heterocyclic group, which can contain additional nitrogen atom, and which can be substituted by 1-3 similar or different substituents, selected from group, consisting of oxo, (C1-C4)alkyl]; R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy and carbamoyl; R3 represents hydrogen, halogen; Het1 represents any of groups with the following chemical formulae [4] and [6]: [4] [6] [19] [10] Het2 represents pyridyl or pyrimidinyl. According to Version (B) R1 represents -CH2-R14 [R14 represents saturated 4-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, which can be substituted by 1-3 similar groups, selected from (C1-C4)alkyl] R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy (C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C4)acyl, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, nitro, carbamoyl, mono(C1-C4)alkylcarbamoyl, di(C1-C4)alkylcarbamoyl or cyano; R3 represents hydrogen or halogen; Het1 represents any of groups with the following chemical formulas [9] and [10], Het2 represents pyridyl.

EFFECT: invention can be applied for treatment of chronic myeloleukosis, acute lymphoblastic leukosis and acute myeloblastic leukosis.

6 cl, 89 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to oxazole compound represented by formula (1) and its pharmaceutically acceptable salts. In formula (1) R1 represents phenyl group, which can contain one or two substituents, selected from the following groups (1-1)-(1-11): (1-1) hydroxy groups, (1-2) unsubstituted or halogen-substituted lower alkoxy groups, (1-3) lower alkenyloxy-groups, (1-4) lower alkinyloxy groups, (1-5) cycloC3-8alkyl (lower) alkoxy groups, (1-6) cycloC3-8alkyloxy groups, (1-7) cycloC3-8alkenyloxy groups, (1-8) dihydroindenyloxy groups, (1-9) hydroxyl-(lower)ankoxy groups, (1-10) oxiranyl(lower)alkoxy groups, and (1-11) phenyl(lower)-alkoxy groups; R2 represents phenyl group or heterocyclyl group, selected from pyridine, pyrasine, isoquinoline, pyrrolidine, piperazine, morpholine, each of which can contain one or two substituents, selected from the following groups (2-1)-(2-10):(2-1) hydroxy groups, (2-2) unsubstituted or halogen-substituted lower alkoxy groups, (2-3) unsubstituted or halogen-substituted lower alkyl groups, (2-4) lower alkenyloxy groups, (2-5) halogen atoms, (2-6) lower alkanoyl groups, (2-7) lower alkylthio groups, (2-8) lower alkylsulphonyl groups, (2-9) oxo groups and (2-10) groups lower alkoxy-lower alkoxy; and W represents bivalent group represented by formula (i) or (ii): formula (i) -Y -A -, formula (ii) -Y2-C(=O)-, where A1 represents lower alkenylene group or lower alkylene group, which can contain one substitutent, selected from group, consisting from hydroxy group and lower alkoxicarbonyl group, Y1 represents simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH- or -S(O)n-, where R3 and R4, each independently, represent a hydrogen atom or lower alkyl group, and m and n, each independently, represent integer, which has value 2, and Y represents pyperazine-diyl group, or bivalent group, represented by formula (iii) or (iv): formula (iii) -C (=O)-A2-N(R5)-, formula (iv) A3-N(R6)-, where A2 and A3, each independently, represent lower alkylene group, and R5 and R6, each independently, represent a hydrogen atom. Invention also relates to pharmaceutical composition, containing the invention compound as an active ingredient, to pharmaceutical composition for treatment or prevention of atopic dermatitis, which includes the invention compound, to application of the compound as medication, to application of the compound as phosphodiesterase 4 inhibitor and/or as inhibitor of production of tumour necrosis factor α and to method of treatment or prevention of diseases, mediated by phosphodiesterase 4 or mediated by tumour necrosis factor α, including introduction of efficient dose of the compound.

EFFECT: creation of pharmaceutical composition for treatment or prevention of diseases mediated by phosphodiesterase 4 or mediated by tumour necrosis factor, as well as for treatment or prevention of atopic dermatitis.

12 cl, 42 tbl, 486 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (3-trifluromethylphenyl)amide 6-(6-hydroxymethylpyrimidin-4-yloxy)naphthalene-1-carboxylic acid or tautomer or salt thereof. The invention also relates to a pharmaceutical composition which has protein kinase inhibiting activity, based on the said compound and use of the said compound to prepare pharmaceutical compositions for use in treating protein kinase dependent diseases, preferably proliferative diseases, particularly tumorous diseases.

EFFECT: improved properties of compounds.

6 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzo[d]isoxazol-3-ylamine compounds of formula I in free form or in form of salts with physiologically compatible acids, having antagonistic effect on KCNQ2/3 ion channel. In formula I , R1, R2, R3 and R4 independently denote H, F, CI, Br, I, -NR7R8, -OR9 or C1-C10alkyl, R5 denotes -C(=S)NR21R22 or (CHR6)n-R25, where n equals 1, 2 or 3, R6 denotes H or C1-C6 alkyl, R25 denotes aryl or heteroaryl, R7 and R8 independently denote H or C1-C10 alkyl, R9 denotes H, C1-C10alkyl or -(C1-C5alkylene)aryl, R21 denotes H, R22 denotes C1-C10alkyl, C2-C10alkenyl, C3-C8cycloalkyl, -(C1-C5alkylene)-C3-C8cycloalkyl, -(C1-C3alkylene)heterocycloalkyl, aryl, heteroaryl or -(C1-C5alkylene)aryl, wherein each of the heterocycloalkyl residues has 5-6 members, contains 1 or 2 heteroatoms in the ring, independently selected from oxygen and nitrogen, each of the aryl residues is phenyl, anthracenyl or naphthyl, each of the heteroaryl residues has 5 or 6 members and contains 1 or 2 heteroatoms in the ring, independently selected from oxygen, sulphur and nitrogen.

EFFECT: said compounds can be used to prepare a medicinal agent for curing pain, migraine, anxiety, uroclepsia or epilepsy.

17 cl, 203 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1, compounds of formula 5 and pharmaceutically acceptable salts thereof. In formulae 1 5 Y denotes -C(O)-, X denotes -N(R11)-, R1 denotes a residue of formula 1a or 1b - for formula 1 or residue of formulae 5a or 5b - for formula 5 1a 1b 5a 5b, R2 and R7 independently denote H, hydroxyl or (C1-C6)alkyl; R3 and R6 each independently denotes H, hydroxyl or (C1-C6)alkyl; R4 and R5 each independently denotes H or (C1-C6)alkyl; the rest of the radicals are described in the formula of invention. The invention also relates to separate compounds given in the formula of invention, a pharmaceutical composition having Bcl bound protein inhibiting properties, which contains a therapeutically effective amount of the disclosed compound, a method of treating a bc1 mediated disorder, involving introduction of a therapeutically effective amount of the disclosed compound and a method of treating a bc1 mediated disorder involving administration to a patient in need of treatment of an effective amount of camptothecin and therapeutically effective amount of the disclosed compound.

EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a heterocyclic compound or salt thereof, having formula (1): where R2 is hydrogen or a lower alkyl group; A is a lower alkylene group or a lower alkenylene group and R1 is a cyclo(C3-C8)alkyl group, an aromatic group or a heterocyclic group selected from a group consisting of groups (I)-(IV), defined in the formula of invention. The invention also relates to a pharmaceutical composition, having activity as a partial agonist of dopamine D2 receptors and/or a serotonin 5-HT2A receptor antagonist and/or an adrenalin α1 receptor antagonist and/or a serotonin absorption inhibitor and/or serotonin reuptake inhibitor based on said compounds, a method of preparing a pharmaceutical composition, use of said compounds as a partial agonist of dopamine D2 receptors and/or a serotonin 5-HT2A receptor antagonist and/or an adrenalin α1 receptor antagonist and/or a serotonin absorption inhibitor and/or serotonin reuptake inhibitor, as well as a method of producing formula I compounds.

EFFECT: novel compounds are obtained and described, which have a wide range of curative effect on mental disorders, including central nervous system disorders, without side effects and with high degree of safety.

22 cl, 3110 ex, 314 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclopenta[b]benzofuranyl derivatives of formula wherein substitutes R1, R2, R3, R4, R5, R6 and R7 and n are specified in the patent clam. These compounds exhibit properties of NF-kB-activity and/or AP-1 inhibitor/modulator. Also, the inventive subject matter are methods for preparing intermediate compounds thereof, a pharmaceutical composition containing them, administration thereof for prevention and/or treatment of inflammatory and autoimmune diseases, neurodegenerative diseases and hyperproliferative diseases caused by NF-kB- and/or AP-1-activity, and a method for prevention and/or treatment of said diseases.

EFFECT: preparation of new cyclopenta[b]benzofuranyl derivatives.

21 cl, 3 tbl, 151 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

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