Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, method of production and application thereof

FIELD: chemistry.

SUBSTANCE: invention refers to of serotonin receptor 5-NT6 antagonists, simultaneously regulating calcium ions homeostasis in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of general formula I, its pharmaceutically acceptable salt and/or hydrate. In general formula I where: R1 is amides substitute selected from optionally substituted C1-C5 alkyl; R2i represents one or number of identical or various substitutes selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar represents halogen unsubstituted or substituted C1-C6 alkyl, C1-C6 alkoxy, phenyl substituted with amides or trifluoromethyl or optionally substituted aromatic hexamerous heterocycle containing 1-2 nitrogen atoms per one cycle, W represents ethyl group-CH2CH2 - vinyl group or ethynyl group. Invention also concerns new compounds selected from group of compounds of formula 1, methods of production thereof, pharmaceutical compositions and methods of their use.

EFFECT: production of composition that simultaneously regulates calcium ions homeostasis in cells.

34 cl, 7 dwg, 4 tbl, 9 ex

 

The text descriptions are given in facsimile form.

1. Antagonist of 5-HT6serotonin receptors, simultaneously regulating the homeostasis of calcium ions in the cells that represent substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1, its pharmaceutically acceptable salt and/or hydrate:

where R1is a Deputy amino group selected from optional for EDINOGO C 1-C5of alkyl;

R2irepresents one or more identical or different substituents selected from hydrogen, halogen, C1-C3of alkyl, CF3, OCF3;

Ar represents an unsubstituted or substituted with halogen, C1-C6the alkyl, C1-C6alkoxy, substituted amino group, or a trifluoromethyl phenyl or possibly substituted aromatic 6-membered heterocycle containing 1-2 nitrogen atom in the cycle;

W represents an ethyl group,- CH2CH2-, vinyl group or etinilnoy group.

2. Antagonist according to claim 1, which represents a substituted 5-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.1

where R1and R2i have the above meaning; R3represents the group CH=CH-Ar, in which Ar has the abovementioned meaning.

3. Antagonist according to claim 2, represents a substituted CIS-5-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.1.1, 1.1.2 or substituted TRANS-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.1.3, 1.1.4

where R2represents H, F, CH3, CF3, OCF3; Ar presented yet an optionally substituted phenyl or optionally substituted pyridyl.

4. Antagonist according to claim 2, representing CIS-2-methyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(1), TRANS-2-methyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(2), TRANS-2-methyl-5-[2-(pyridin-4-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(3), CIS-2-methyl-5-[2-(pyridin-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(4), TRANS-2-methyl-5-[2-(pyridin-2-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(5), CIS-2-tert-butyl-5-[2-(pyridine-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(6), CIS-2-methyl-5-(2-phenylphenyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(1), TRANS-2-methyl-5-(2-phenylphenyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(1), TRANS-2-methyl-5-[2-(pyridin-4-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(2), CIS-2-methyl-5-[2-(pyridin-3-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(2), TRANS-2-methyl-5-[2-(pyridin-2-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(3), CIS-2,8-dimethyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(3), TRANS-2,8-dimethyl-5-[2-phenylphenyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(4), CIS-2,8-dimethyl-5-[2-(pyridine-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(4), TRANS-2,8-dimethyl-5-[2-(pyridin-4-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(5), CIS-2-benzyl-8-methyl-5-[2-(pyridin-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(5), TRANS-2-methyl-5-[2-(4-forfinal)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(6), the IP-2-methyl-5-[2-(3-forfinal)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(6), TRANS-2,8-dimethyl-5-[2-(4-trifluoromethyl-phenyl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(7), CIS-2,8-dimethyl-5-[2-(3-triptoreline)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(7), TRANS-2-methyl-5-[2-(4-triptoreline)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(8), CIS-2-methyl-5-[2-(4-methoxyphenyl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(8), CIS-2-methyl-5-[2-(4-dimethylaminophenyl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(9) or TRANS-2,8-dimethyl-5-[2-(4-forfinal)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(9)corresponding to the following formula or its pharmaceutically acceptable salt:

5. Antagonist according to claim 1, which represents a substituted 5-ethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.2

where R1, R2iand Ar have the abovementioned meaning.

6. Antagonist according to claim 5, represents a substituted 5-ethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.2.1 and 1.2.2

where R2represents H, F, CH3, CF3, OCF3; Ar has the above meaning.

7. Antagonist according to claim 5, which represents a 2-methyl-5-(2-phenylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(1), 2-methyl-5-[2-(pyridin-4-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(2), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(3), 2-methyl-5-[2-(pyridin-2-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(4), 2-tert-butyl-5-[2-(pyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(5), 2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2(6), 2,8-dimethyl-5-(2-phenylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(1), 2,8-dimethyl-5-[2-(pyridin-4-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(2), 2,8-dimethyl-5-[2-(pyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(3), 2,8-dimethyl-5-[2-(pyridin-2-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(4), 2,8-dimethyl-5-[2-(6-meth is pyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(5), 2,8-dimethyl-5-[2-(pyrazin-2-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(6), 2-methyl-5-(2-phenylethyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(7), 2-methyl-5-[2-(pyridin-4-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(8), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(9), 2-methyl-5-[2-(pyridin-2-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(10), 2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(11), 2-methyl-5-(2-phenylethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(12), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(13), 2-methyl-5-(2-phenyl-ethyl)-6-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.2(1), 2-methyl-5-(2-phenyl-ethyl)-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.2(2) or 2-methyl-5-[2-(pyridin-3-yl)ethyl]-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.2(3) corresponding to the following formula or its pharmaceutically acceptable salt:

8. Antagonist according to claim 1, which represents a substituted 5-ethinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.3

where R1, R2iand Ar have the abovementioned meaning.

9. The antagonist of claim 8, represents a substituted 5-ethinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1.3.1 and 1.3.2

where R2represents H, F, CH3, CF3, OCF3; Ar has the above meaning.

10. The antagonist of claim 8 or 9, which represents a 2-methyl-5-phenylethynyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(1), 2-methyl-5-(pyridine-2-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(2), 2-methyl-5-(pyridine-3-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(3), 2-methyl-5-(pyridine-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(4), 2-methyl-5-(pyrimidine-5-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(5), 2-methyl-5-phenylethynyl-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(1), 2-methyl-5-(Piri is in 2-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro 1H-pyrido[4,3-b]indoles of General formula 1.3.1(2), 2-methyl-5-(pyridine-3-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(3), 2-methyl-5-(pyridine-4-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(4), 2-methyl-5-(pyridine-3-ylethynyl)-6-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.2(1), 2,8-dimethyl-5-phenylethynyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(5), 2,8-dimethyl-5-(pyridine-2-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(6), 2,8-dimethyl-5-(pyridine-3-ilagan)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(7), 2,8-dimethyl-5-(pyridine-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(8), 2-methyl-5-(pyridine-3-ylethynyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(9), 2-methyl-5-(4-methoxyphenylacetyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(10), 2-methyl-5-(4-perforating)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(11), 2-methyl-5-(3-perforating)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(12), 2-methyl-5-(4-cryptomaterial)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(13), 2-methyl-5-(pyridine-3-ylethynyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(14), 2,8-dimethyl-5-(4-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(15), 2,8-dimethyl-5-(3-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(16), 2,8-dimethyl-5-(4-cryptomaterial)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(17), 2,8-dimethyl-5-(3-cryptomaterial)-2,3,4,5-tetrahydro-1H-pyrido-[4,3-b]indole 1.3.1(18), 2,8-dimethyl-5-(2-cryptomaterial)2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(19), 2,8-dimethyl-5-(2-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(20), 2,8-dimethyl-5-(4-methoxyphenylacetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(21), 2,8-dimethyl-5-(4-dimethylaminophenyl-ethinyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(22), 2,8-dimethyl-5-(3-methoxyphenylacetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(23) or 2,8-dimethyl-5-(2-methoxyphenylacetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(24) corresponding to the following formula or its pharmaceutically acceptable salt:

11. Pharmaceutical composition, which is an antagonist of serotonin 5-HT6receptors and simultaneously regulating the homeostasis of calcium ions in cells, for various dosage forms containing as active principle antagonist according to any one of claims 1 to 10 in an effective amount.

12. A method of obtaining a pharmaceutical composition according to claim 11 mixing an effective amount of the active agent, which represents an antagonist of serotonin 5-HT6receptors selected from at least one substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of General formula 1, or its pharmaceutically acceptable salt and/or hydrate according to any one of claims 1 to 10 with inert fillers and/or solvents.

13. The drug is in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing for the prevention and treatment of cognitive disorders and neurodegenerative diseases, pathogenesis of which is associated with serotonin 5-HT6receptors and excessive intracellular CA ion content+2including the antagonist according to any one of claims 1 to 10 or the pharmaceutical composition according to claim 11 in an effective amount, except drug, including active Nacha what about General formula

where R1represents CH3C2H5, PhCH2; R2represents failure 6-CH3-3-Py-(CH2)2-;

R3represents H, CH3, Br.

14. The drug is in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, for the prevention and treatment of Alzheimer's disease Hungtington, including the antagonist of serotonin 5-HT6receptor according to any one of claims 1 to 10 or the pharmaceutical composition according to claim 11 in an effective amount, excluding the active principle of General formula A.

15. The drug is indicated in paragraph 13, including as an antagonist of serotonin 5-HT6receptors 2,8-dimethyl-5-[2-phenylethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(1).

16. The drug is in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing for the prevention and treatment of mental disorders and schizophrenia, comprising the antagonist of serotonin 5-HT6receptor according to any one of claims 1 to 10 or the pharmaceutical composition according to claim 11 in an effective amount, excluding drug for the treatment of schizophrenia, including the active principle of General formula A.

17. Drug in clause 16, including as an antagonist of serotonin 5-HT6is eception 2,8-dimethyl-5-[2-phenylethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(1).

18. Drug in clause 16, including as an antagonist of serotonin 5-HT6receptors 2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole of formula 1.2.1(5).

19. The drug according to any one of p-18 to improve mental abilities.

20. The method of prevention and treatment of various diseases, pathogenesis of which is associated with serotonin 5-HT6receptors and excessive intracellular CA ion content+2in animals and humans, which consists in the administration of a medicinal product according to any one of PP-19 in an effective amount.

21. Substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1, and their pharmaceutically acceptable salts and/or hydrates:

where R1is a Deputy amino group selected from optionally substituted C1-C5of alkyl,

R2irepresents one or more identical or different substituents selected from hydrogen, halogen, C1-C3of alkyl, CF3, OCF3;

Ar represents an unsubstituted or substituted with halogen, C1-C6the alkyl, C1-C6alkoxy, substituted amino group, or a trifluoromethyl phenyl or possibly substituted aromatic 6-membered heterocycle, provided the 1-2 nitrogen atom in the cycle;

W represents an ethyl group,- CH2CH2-, vinyl group or etinilnoy group, except 2-methyl-5-phenethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-methyl-5-[2-(pyridin-2-yl)ethyl)]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-methyl-5-[2-(pyridin-4-yl)ethyl)]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,8-dimethyl-5-[2-(pyridin-4-yl)ethyl)]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-methyl-8-trifluoromethyl-5-[2-(pyridin-4-yl)ethyl)]-2,3,4,5-Tetra-hydro-1H-pyrido[4,3-b]indole, 2-methyl-8-carboxy-5-[2-(pyridin-4-yl)ethyl)]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-methyl-8-ethoxycarbonyl-5-[2-(pyridin-4-yl)ethyl)]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-C1-C5alkyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, 2-C1-C5alkyl-8-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, 2-benzyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-benzyl-8-chloro-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-benzyl-8-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 7-methyl-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 7-chloro-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 7-trifluoromethyl-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]in the ol, 8-bromo-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 8-chloro-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 8-trifluoromethyl-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,6-dimethyl-8-chloro-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,7,8-trimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 7,8-dichloro-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,8-dimethyl-7-chloro-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,7-dimethyl-8-chloro-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2,8,9-trimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole, 2-methyl-8-chloro-5-[2-(pyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and 2-methyl-5-[2-(2-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole,

or their pharmaceutically acceptable salts.

22. Compounds according to item 21, which represents a substituted 5-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.1

where R1and R2ihave the above meaning; R3represents the group CH=CH-Ar, in which Ar has the abovementioned meaning.

23. Compounds according to article 22, which represents a substituted CIS-5-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles the General formula 1.1.1, 1.1.2 and substituted TRANS-5-vinyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.1.3, 1.1.4

where R2represents H, F, CH3, CF3;

Ar has the abovementioned meaning.

24. Compounds according to item 23, which represents a CIS-2-methyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(1), TRANS-2-methyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(2), TRANS-2-methyl-5-[2-(pyridin-4-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(3), CIS-2-methyl-5-[2-(pyridin-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(4), TRANS-2-methyl-5-[2-(pyridin-2-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(5), CIS-2-tert.-butyl-5-[2-(pyridin-3-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1(6), CIS-2-methyl-5-(2-phenylphenyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(1), TRANS-2-methyl-5-(2-phenylphenyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(1), TRANS-2-methyl-5-[2-(pyridin-4-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(2), CIS-2-methyl-5-[2-(pyridin-3-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(2), TRANS-2-methyl-5-[2-(pyridin-2-yl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(3), CIS-2,8-dimethyl-5-(2-phenylphenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(3), TRANS-2,8-dimethyl-5-[2-phenylphenyl]-2,3,4,5-tetrahydro-1H-pyrido[43-b]indole 1.1.3(4), CIS-2,8-dimethyl-5-[2-(pyridin-3-yl)vinyl]-2.3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(4), TRANS-2,8-dimethyl-5-[2-(pyridin-4-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(5), CIS-2-benzyl-8-methyl-5-[2-(pyridin-2-yl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(5), TRANS-2-methyl-5-[2-(4-forfinal)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(6), CIS-2-methyl-5-[2-(3-forfinal)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(6), TRANS-2,8-dimethyl-5-[2-(4-triptoreline)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(7), CIS-2,8-dimethyl-5-[2-(3-triptoreline)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(7), TRANS-2-methyl-5-[2-(4-triptoreline)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(8), CIS-2-methyl-5-[2-(4-methoxyphenyl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.1(8), CIS-2-methyl-5-[2-(4-dimethylaminophenyl)vinyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido|4,3-b]indole 1.1.1(9), TRANS-2,8-dimethyl-5-[2-(4-forfinal)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.1.3(9),

or their pharmaceutically acceptable salts.

25. Compounds according to item 21, which represents a substituted 5-ethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.2

where R1, R2iand Ar have the abovementioned meaning.

26. Connection A.25 that represents a substituted 5-ethyl-2,3,4,5 tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.2.1 and 1.2.2

where R2represents H, F, CH3, CF3, OCF3;

Ar has the abovementioned meaning.

27. Connection p representing substituted 2,8-dimethyl-5-(2-phenylethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(1), 2,8-dimethyl-5-[2-(pyridin-2-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(4), 2,8-dimethyl-5-[2-(pyrazin-2-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(6), 2-methyl-5-(2-phenylethyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(7), 2-methyl-5-[2-(pyridin-4-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(8), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(9), 2-methyl-5-[2-(pyridin-2-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(10), 2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-8-fluoro-2,3,4,5-tetrahydro-1H-Piri-up[4,3-b]indole 1.2.1(11), 2-methyl-5-(2-phenylethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(12), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.1(13), 2-methyl-5-(2-phenylethyl)-6-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.2.2(1), 2-methyl-5-(2-phenylethyl)-6-trifluoromethyl-2,3,4,5-etrahydro-1H-pyrido[4,3-b]indole 1.2.2(2), 2-methyl-5-[2-(pyridin-3-yl)ethyl]-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indole 1.2.2(3),

or their pharmaceutically acceptable salts.

28. Compounds according to item 21, which represents a substituted 5-Atini the -2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.3

where R1, R2iand Ar have the abovementioned meaning.

29. Connection p that represents a substituted 5-ethinyl-2,3,4,5-tetrahydro-1H-pyrido[|4,3-b]indoles of General formula 1.3.1 and 1.3.2

where R2represents H, F, CH3, CF3, R1;

Ar has the abovementioned meaning.

30. Join on clause 29, which represents a 2-methyl-5-phenylethynyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(1), 2-methyl-5-(pyridine-2-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(2), 2-methyl-5-(pyridine-3-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(3), 2-methyl-5-(pyridine-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(4), 2-methyl-5-(pyrimidine-5-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3(5), 2-methyl-5-phenylethynyl-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(1), 2-methyl-5-(pyridine-2-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.3.1(2), 2-methyl-5-(pyridine-3-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(3), 2-methyl-5-(pyridine-4-ylethynyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(4),2-methyl-5-(pyridine-3-ylethynyl)-6-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.2(1), 2,8-dimethyl-5-phenylethynyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(5), 2,8-dimethyl-5-(pyridine-2-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.(6), 2,8-dimethyl-5-(pyridine-3-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(7), 2,8-dimethyl-5-(pyridine-4-ylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(8), 2-methyl-5-(pyridine-3-ylethynyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(9), 2-methyl-5-(4-methoxyphenylacetyl)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(10), 2-methyl-5-(4-perforating)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(11), 2-methyl-5-(3-perforating)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(12), 2-methyl-5-(4-cryptomaterial)-8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(13), 2-methyl-5-(pyridine-3-ylethynyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(14), 2,8-dimethyl-5-(4-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(15), 2,8-dimethyl-5-(3-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(16), 2,8-dimethyl-5-(4-cryptomaterial)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(17), 2,8-dimethyl-5-(3-cryptomaterial)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(18), 2,8-dimethyl-5-(2-cryptomaterial)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(19), 2,8-dimethyl-5-(2-perforating)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(20), 2,8-dimethyl-5-(4-methoxyphenylacetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(21), 2,8-dimethyl-5-(4-dimethylaminophenyl-ethinyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(22), 2,8-dimethyl-5-(3-methoxy-phenylethynyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(23), 2,8-dimethyl-5-(2-m is toxigenicity)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 1.3.1(24),

or their pharmaceutically acceptable salts.

31. The method of obtaining substituted 5-[2-phenyl(or heterocyclyl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles according to any one of p-24 interaction 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 2 with the corresponding acetylene General formula 3

where R1, R2iand Ar have the abovementioned meaning.

32. The method of obtaining substituted 5-[2-phenyl(or heterocyclyl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles according to any one of p, 25-27 the hydrogenation of substituted 5-[2-phenyl(or heterocyclyl)vinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 1.1.

33. The method of obtaining substituted 5-[2-phenyl(or heterocyclyl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles according to any one of p, 25-27 interaction 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General formula 2 with substituted afilename General formula 4

where Ar represents optionally substituted phenyl or optionally substituted aromatic 6-membered heterocycle containing 1-2 nitrogen atom in the cycle.

34. The way to obtain 5-[2-phenyl(or heterocyclyl)acetylenyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles according to any one of p, 28-30, which consists in the interaction 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of General the formula 2 with halogenation General formula 5

where Hal denotes Cl, Br or I;

Ar represents optionally substituted phenyl or optionally substituted aromatic 6-membered heterocycle containing 1-2 nitrogen atom in the cycle.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention concerns new piperidinyl compounds of the formula (I) and (II) which are selectively binding integrine receptors, pharmaceutical compositions and application of the compositions for obtaining medication with antagonistic effect on integrine receptors, where W, R2, Z and q are described in the claim.

EFFECT: pharmaceutical composition for obtaining medication with antagonistic effect on integrine receptors.

33 cl, 1 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the method of production of analogues of natural alkaloids of harman series (eleagnine) having potential biological activity, namely, to the method of 1-substituted -4phenyl-2,3,4,9-terahydro-1H-beta-carboline of general formula where one of R1 and R2 denotes hydrogen atom, and the other represents alkyl with 1 or 2 hydrogen atoms or aryl, hetaryl, or R1 and R2 together with carbon atom to which they are banded derive optionally substituted indol-3-on. The method is cyclisation of aldehydes by substituted tryptamine with acids, at the same time beta-phenyltryptamine is used as substituted tryptamine, aliphatic or aromatic aldehydes or optionally substituted isatins are used as aldehydes, mineral salts or Lewis catalysts are used as acids.

EFFECT: production of analogues of natural alkaloids of harman series (eleagnine) having potential biological activity.

1 cl, 4 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new tricyclic derivatives of the formula (I) and their pharmaceutically acceptable salts, where: 1 to 3 of A1, A2, A3 and A4 are nitrogen atoms, while the rest are -CH- groups; G1 is a group selected out of -CH2-O-, -CH2-CH2-, - CH=CH-; -N(C1-C4alkyl)-CH2; G2 is a group selected out of -O-CH2-, -CH=CH-, -CH2- CH2-; R4 can be identical or different and are selected out of a group including hydrogen or halogen atoms; p are independently equal to 0, 1 or 2; Y is and optionally substituted residuum selected out of the group of alkyl, cycloalkyl, alkylaryl, alkylcycloalkylalkyl; Z is a tetrazolyl, -COOR5, -CONR5R5, NHSO2R5 or -CONHSO2R5 group, where R5 is hydrogen or optionally substituted alkyl or aryl. The invention also concerns a method of obtaining the claimed compounds.

EFFECT: possible application in treatment and prophylactics of inflammation and allergy diseases.

20 cl, 2 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I and their pharmaceutically acceptable salts as factor Xa inhibitors, medicine based on them, as well as a method of their obtaining and application. In the general formula I R0 is monocyclical or bicyclical 6-9-membered heterocyclyl selected out of the group of benzothiophenyl, pyridyl or monocyclical 5-membered heterocyclyl containing 1, 2 heteroatoms selected out of nitrogen or oxygen, where the mentioned heterocyclyl is monosubstituted by R8 and additionally substituted by monocyclical 5-membered heterocyclyl containing 1 heteroatom of sulfur, where heterocyclyl is monosubstituted by R8; R8 is a halogen or substructure , which is 6-membered partially unsaturated or aromatic cyclical group in the formula I, containing 1 nitrogen heteroatom, and which is substituted by 1 R23 group or oxogroup under a condition that the mentioned cyclical group is not a phenyl residuum; Q is a direct link, -(C0-C2)-alkylene-C(O)-NR10-, -(C1-C6)-alkylene; -R1 is a hydrogen atom; R2 is a direct link, V is a 6-membered cyclical residuum with 1 heteroatom selected out of nitrogen, where the mentioned cyclical residuum is unsubstituted, bicyclical 12-membered heterocyclyl with 1-2 heteroatom selected out of nitrogen, where the mentioned cyclical residuum is unsubstituted; G is a direct link; M a hydrogen atom, -(C1-C8)-alkyl where alkyl is unsubstituted; R3 is a hydrogen atom; R23 is a hydrogen atom, -(C0-C4)-alkylene -O-R19 (where R19 is a) hydrogen atom, b) -(C1-C4)-alkyl where alkyl is unsubstituted or monosubstituted by R13), -(C0-C4)-alkylene-C(O)-R11, -(C0-C4)-alkylene-C(O)-O-R11; R11 and R12 can both or individually be hydrogen atom, -(C1-C6)-alkyl: -O-R17 or R13 is -C(O)-O-R10; R10 and R20 are hydrogen atoms or -(C1-C6)-alkyl independently from each other, R17 is -(C1-C6)-alkyl; and its pharmaceutically acceptable salts.

EFFECT: possible application in effecting blood coagulation, inflammation reaction or fibrinolysis, or in treatment and prophylactics of diseases caused by Xa factor, eg cardiovascular disorders, thromboembolic diseases or restenosis.

11 cl, 1 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new enantiomers of (+)-and(-)-trans-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido[4,3-b]indol and method of its obtaining. Being optical antipodes for each other, enantiomers exhibit different biological activity and can be applied as an active component in pharmaceutical compositions of nootropic and sedative action for treatment of different individual status of patients.

EFFECT: obtaining of the claimed compound.

1 ex, 5 tbl, 5 cl

FIELD: chemistry.

SUBSTANCE: invention concerns pyrido[2,3-b]pyrazine derivatives of the general formula I where R1 and R2 are hydrogen, unsubstituted C1-C8 alkyl or substituted with hydroxy-, alkoxy-, nitro- or CO2-alkyl, aryl, heteroaryl selected out of the group of pyrinidile or benzodioxalyl, independently from each other; R4 is hydrogen, R3 is a NR9R10 group where R9 is hydrogen and R10 is a -C(Y)NR11R12 group where Y is O or S and R11 is hydrogen, R12 is an alkyl, alkenyl, alkinyl, cycloalkyl, aryl, possibly substituted by a haloid nitro-, trifluormethyl, alkyl, substituted aryl or heterocyclyl selected out of the group of furanyl or morpholinyl, alkyl or their salts endurable physiologically, their solvates, hydrates and polymorphous forms, where the mentioned compounds can be in the forms of theirs racemates, pure enantiomers and/or diastereomers, or anatiomer and/or diastereomer mixes, or tautomers. The invention also describes a medicine based on the compounds, a method of the medicine obtaining, and application of the medicine in treatment of diseases or abnormalities caused by misdirected cellular signal transduction processes.

EFFECT: possible application in cancer treatment.

12 cl, 2 tbl, 38 ex

FIELD: chemistry.

SUBSTANCE: invention concerns a new 1-(3,4-diethoxyphenyl)-2,3,5,6-tetrahydro-(3,4-diethoxybenzo)[g]quinoxalino[2,3-b]indolisine hudrochloride of the formula: which exhibits direct anticoagulation effect and credibly prolongs coagulation time for nitrate blood and coagulability change rate in the concentration of 1 mg/ml at 36.5%. LD50 for intraperitoneal introduction to white mice comprised 355.0 (310.0÷410.0) mg/kg. T"пл" 160-161°C (isopropanol).

EFFECT: obtaining of the claimed compound.

1 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns malonamide derivatives of the formulae (IA) or (IB) , and pharmaceutically acceptable acid additive salts of them, where R1, R1',(R2)1,2,3, R3, R4, R14, L, and are such as described in this invention. Also the invention concerns a medicine with inhibition effect on γ-secretase, which can be applied in treatment of Alzheimer's disease.

EFFECT: obtaining new malonamide derivatives with beneficial biological properties.

17 cl, 188 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to compounds with general formulae (I) and (II) and their pharmaceutical salts, their use as inhibitors of HIV-integrase and to pharmaceutical salts based on them. In formula (I) , R1 represents H or NR2R5; R2 represents CH3; R5 represents 1) C(O)CH2SO2CH3, 2) C(O)C(O)N(CH3)2, 3) SO2N(CH3)2 or 4) SO2R20 where R20 represents , , or ; or alternatively, R2 and R5 together with a nitrogen atom, to which they are bonded, form or , R3 represents hydrogen; R4 represents 1) n-fluorobenzyl, 2) 4-fluro-3-methylbenzyl, 3) 3-chlorobenzyl or 4) 3-chloro-4-methylbenzyl; R12 and R14 both represent H, except that, when R5 represents C(O)C(O)N(CH3)2 and R4 represents n-fluorobenzyl, and n equals 1, then R12 and R14 both represent H, or both represent CH3; and n is an integer, equal to 0, 1 or 2.

EFFECT: compounds can be used for treating HIV-infection.

12 cl, 5 dwg, 1 tbl, 8 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to application as ligands of 5-NT6 receptor azaheterocyclic compositions of general formula 1 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates , where R2 and R3 independently represent substitute of amides chosen from hydrogen; substituted carbonyl; substituted aminocarbonyl; substituted aminothiocarbonyl; substituted sulphonyl; C1-C5-alkyl, optionally substituted with C6-C10-aryl, optionally substituted with heterocyclil, C6-C10-arylaminocarbonyl, C6-C10- arylaminothiocarbonyl, C5-C10-azaheteroaryl, optionally substituted with carboxyl, nitrile group; optionally substituted with aryl; R1k are 1 to 3 independent substitutes to cyclic system chosen from hydrogen, optionally substituted C1-C5-alkyl, C1-C5-alkyloxy, C1-C5-alkenyl, C1-C5- alkenyl, halogen, trifluoromathyl, nitrile, carboxyl, optionally substituted heterocyclil, substituted sulphonyl, optionally substituted carboxyl; dashed line with accompanying continuous line () corresponds to single or double bond; n=1.2 or 3. Invention also concerns a pharmaceutical formulation, production method and tabletted, capsulated or injection medical product in pharmaceutically acceptable package.

EFFECT: agent has improved efficiency.

17 cl, 8 tbl, 5 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: device includes core containing at least one pharmaceutically active agent. Core is made from elastomeric composition selected from the group consisting of poly(dimethylsiloxane), siloxane-based elastomer including 3,3,3-trifluoropropyl groups attached to Si atom of siloxane units, siloxane-based elastomer, which includes poly(alkyleneoxide) groups, and their mixtures. The said core is encased by membrane. Membrane is made from the same elastomeric composition as core. Pharmaceutically active agent is selected from the group, which includes anti-allergic agents, anti-infection agents, anti-asthmatic agents, anti-inflammatory agents, anti-virus agents, anti-bacterial agents, anti-histamine means, anti-fungal agents, anesthetics, opioids, vasorelaxants, muscarinic agents, sympathomimetics, corticosteroids and their mixtures. Delivering device, according to invention, for nasal or otological application ensures preliminary set, constant rates of release of one or more pharmaceutically active agents.

EFFECT: device is safe and does not cause discomfort to patients.

8 cl, 6 dwg, 1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: eczema is suggested to be treated using atypical neuroleptic eglonyl (i.e. sulpiride) and antidepressant - selective inhibitor of serotonin re-uptake trittico (i.e. trazodone).

EFFECT: essentially increased remission for longer than a year and elimination of treatment complications.

5 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new derivatives of 1- and 7-[ω-(benzhydryl-4-piperazinyl-1)alkyl]-3-alkyloxantines of the general formulae I and II, including their pharmaceutically acceptable salts and/or salt hydrates, the derivatives showing antihistaminic and antiallergenic effect. In the general formulae I and II : R = H, Me, CH2Ph; R1 = Me, "н" - C4H9; n = 0-3; X = H, OH, OCOCH2CH2COOH; Y = Y1 = H, Cl, F; on the condition that R and R1 are not both methyl. Compounds of the invention feature high antihistaminic and antiallergenic activity. E.g., 7-[4-(benzhydryl-4-piperazinyl-1)butyl]-3-methyloxantine dihydrochloride surpasses most efficient antihistaminic and antiallergenic medications, such as cetirizine, loratadine and azelastine, in activity and lasting effect.

EFFECT: obtaining a compound with high antihistaminic and antiallergenic activity.

2 cl, 3 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new tricyclic derivatives of the formula (I) and their pharmaceutically acceptable salts, where: 1 to 3 of A1, A2, A3 and A4 are nitrogen atoms, while the rest are -CH- groups; G1 is a group selected out of -CH2-O-, -CH2-CH2-, - CH=CH-; -N(C1-C4alkyl)-CH2; G2 is a group selected out of -O-CH2-, -CH=CH-, -CH2- CH2-; R4 can be identical or different and are selected out of a group including hydrogen or halogen atoms; p are independently equal to 0, 1 or 2; Y is and optionally substituted residuum selected out of the group of alkyl, cycloalkyl, alkylaryl, alkylcycloalkylalkyl; Z is a tetrazolyl, -COOR5, -CONR5R5, NHSO2R5 or -CONHSO2R5 group, where R5 is hydrogen or optionally substituted alkyl or aryl. The invention also concerns a method of obtaining the claimed compounds.

EFFECT: possible application in treatment and prophylactics of inflammation and allergy diseases.

20 cl, 2 tbl, 46 ex

FIELD: medicine.

SUBSTANCE: present invention refers to medicine and concerns microparticles containing sphere mainly consisting of cross-linked agarose carbohydrate and allergen covalently bonded with sphere, applied for immune system disturbance treatment. Used allergen is produced of plant pollen, specifically of timothy grass pollen. Application of specified microparticles provides effective treatment for patients suffering from allergy, as well as reduces by-effects of parenteral introduction.

EFFECT: development of effective method of allergy treatment and prevention.

9 cl, 4 dwg, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to derivatives of phtalazine with general formula (I) , in which R represents a methyl or difluromethyl group; R1 represents phenyl or oxazolyl or thiophenyl, chemically bonded to a phtalazine ring through a carbon-carbon bond. Both phenyl and the above mentioned heterocycle are substituted with a carboxylic group, and optionally with a second functional group, chosen from methoxy-, nitro-, N-acetylamino-, N-metanesulphonylamino- group. The invention also relates to pharmaceutical salts of such derivatives. The given compounds with general formula (I) are inhibitors of phosphodiesterase.

EFFECT: objective of the invention is also the method of obtaining compounds with general formula (I) and pharmaceutical compositions for treating allergies and antiphlogistic diseases based on the given compounds.

9 cl, 9 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: description is given of a derivative of carboxylic acid with general formula , where R1 represents a hydrogen atom, C1-4alkyl, benzyl, E represents C(=O)-, -SO2- or -CH2-;R2 represents a halogen atom, C1-6 alkyl, C1-6 alkoxy, hydroxyl, C1-4 alkyl, substituted -OR8 , R3 represents a halogen atom, C1-6 alkyl, C1-6 alkoxy; R4 represents a hydrogen atom, C1-6alkyl; R5 represents C1-6 alkyl, C1-10 alkoxy, R8 represents C1-4 alkyl, phenyl; represents a benzol ring; G represents (1) C1-6 alkylene; represents dihydrobenzoxazine; m and n represent 0 or an integer from 1 to 4; I represents 0 or an integer from 1 to 8, where, when m is more or equal to 2, R2 is the same or different; when n is more or equal to 2, R3 is the same of different; when i is more or equal to 2, R5 is the same of different, or its pharmaceutical salt. Since the compound with formula (I), is linked to the DP receptor and has antagonistic effect to the DP receptor.

EFFECT: it is useful for preventing and/or curing such diseases as allergic rhinitis, allergic conjunctivitis, bronchial asthma, malt cell disease, migraine, contact dermatitis, stroke, ulcerative colitis, thrombocyte aggregration or sleep disorder.

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compounds with general formula (I) or its pharmaceutically acceptable salts; and including its any stereoisomer forms;X and Y are independently N or CR1; Z represents S, O, NR1 or CR12;every R1-R6 represent independently H or not influencing substitute, which is alkyl (C1-10), allkenyl (C2-10), alkynil (C2-10), aryl ("C'5-12), arylalkyl, arylalkenyl or arylalkynil, each of which can not obligatorily contain one or more heteroatoms selected from O, S and N and each of which can be substituted further one; or not obligatorily substituted forms of acyl, arylacyl, alkyl,alkenyl alkynyl or arylsulphonyl or their forms which contain heteroatoms in alkyl,alkynyl or aryl fragments or representing OR, SR, NR2, COOR, CONR2, where R is N or alkyl alkenyl, alkynyl, or aryl not obligatorily substituted, as defined above, when C is a substituted atom not influencing substitute can be a halohen, OOCR, NROCR, where R is H or its substitute shown above, or can equal 0; nl is equal to 0-4; n2 is equal to 0-1, where * means that CR5=CR5 can be substituted by C=C; n3 is equal to 0-4;where nl+n2+n3 exceeds or equals 2; b is equal to 0-2; where the following combinations of R-groups can be associated with cycle formation, which can saturated or unsaturated R2-R2, one R2+R3, R3+ one R4, R4+R4, one R5 + the other R5, one R5 + one R6 and R6+R6; where cycle can not be aromatic, when the cycle formation components are represented by two R5; and where, when n2 is unity 1, neither of n1 nor n3 can be equal to 0, the invention also relates to pharmaceutical composition, based on these compounds, possessing a modulating ability relative to CXCR4- and/or CCRS-receptor; to modulation method CXCR4- and/or CCRS-receptor; to method of treatment of a statec described by unusual activity CXCR4- and/or CCR5-receptor and application of the described compounds for production of pharmaceutical.

EFFECT: new compounds feature useful biological properties.

36 cl, 171 ex

Antiallergic agent // 2324491

FIELD: medicine; pharmacology.

SUBSTANCE: antiallergic agent is produced by toluene extraction of the birch bark and contains the active components such as betulin, lupeol and O-caffeate taken in particular quantities.

EFFECT: agent is efficient against allergy and doesn't reveal side effects.

11 tbl, 9 ex

Indanol derivatives // 2323937

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): (where R1 and R2 may be identical or different, and each is a 1,3-substituted aryl with substituents from group α; R3 stands for any of the following groups: -CO-R4, -CO-O-R4, -CO-NH-R4, -CO-CH2-N(Ra)Rb, -(CH2)m-CO-R5, -(CH2)m-R5, -CO-NH-CO-N(Ra)Rb, -CO-NH-SO2-N(Ra)Rb, -CO-NH-CO-(CH2)m-N(Ra)Rb, or -CO-NH2; R4 stands for a lower alkyl, cycloalkyl, cycloalkyl substituted with 1-3 substituent from group α, lower alkenyl, lower alkynyl, halogen-substituted lower alkyl, hydroxyl-substituted lower alkyl, lower alkoxyalkyl, lower aliphatic acyloxyalkyl or lower alkoxycarbonylalkyl; R5 stands for hydroxyl, -OR4 or -N(Ra)Rb; Rа and Rb may be identical or different, each of them stands for hydrogen, hydroxyl, lower alkoxy group, hydroxyl-substituted lower alkoxyl, hydroxyl-substituted lower alkoxyalkyl, lower alkoxy lower alkoxyalkyl, cyano lower alkyl, cyano lower alkoxyalkyl, carboxy lower alkyl, carboxy lower alkoxyalkyl, aliphatic lower alkoxycarbonyl lower alkoxyalkyl, carbamoyl lower alkyl group, carbamoyl lower alkoxyalkyl, lower aliphatic acylamino lower alkyl, lower aliphatic acylamino lower alkoxyalkyl, lower alkylsulphonylamino lower alkyl, lower alkylsulphanylamino lower alkoxyalkyl, (N-hydroxy-N-methylcarbamoyl) lower alkyl, (N-hydroxy-N-methylcarbamoyl) lower alkoxyalkyl, (N-lower alkoxy-N-methylcarbamoyl) lower alkyl, (N-lower alkoxy-14-methylcarbamoyl) lower alkoxyalkyl or R4, or both, including associated nitrogen, stand for nitrogen-containing heterocyclic group or nitrogen-containing 1-3 substituted heterocyclic group with substituents from group α; m is an integer from 1 to 6; А stands for carbonyl; В stands for straight bond; D stands for oxygen atom; Е stands for С14 alkylene; n is an integer from 1 to 3; and α group is a group of substituents, which consist of halogen atoms, lower alkyls, hydroxy lower alkyls, halogen lower alkyls, carboxy lower alkyls, lower alkoxyls, hydroxy lower alkoxyls, hydroxy lower alkoxyalkyls, lower alkoxycarbonyls, carboxyls, hydroxyls, lower aliphatic acyls, lower aliphatic acylamines, (N-hydroxy-N-methylcarbamoyl) lower alkyls, (N-lower alkoxy-N-methylcarbamoyl) lower alkyls, hydroxy lower aliphatic acylamines, amines, carbamoyls and cyano groups), or pharmacologically suitable salt thereof. Invention also relates to pharmaceutical composition and method for disease prevention and treatment.

EFFECT: preparation of novel biologically active compounds.

18 cl, 117 ex

FIELD: chemistry.

SUBSTANCE: invention refers to veterinary science, in particular to products intended to increase capacity for survival and yield of poultry. For this purpose common composition 1,3-di(3-piperidine-2-hydroxypropyl)-6-methyluracil of formula: is used. Composition is characterised by natural resistance, antioxidant activity, activates nonspecific factors of immune system, as well as possesses medicinal properties to provide detoxification of nitrates and nitrites. Composition has the appearance of white powder, is highly soluble in water and can be added in specified doses to chickenfeed.

EFFECT: production of composition providing increase of capacity for survival and yield of poultry.

6 tbl, 5 ex

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