1a, 5a-tetrahydro-s-thiacyclopropa[a]pentalenes: tricyclic derivatives of thiophene as s1p1/edg1 receptor agonists

FIELD: chemistry.

SUBSTANCE: described are novel thiophene derivatives of formula (1) and pharmaceutically acceptable salts thereof, where A is -CH2CH2-, -NH-CH2-, -CH2-O or -CH2NH-, R1 is hydrogen or alkyl, when X is C-R4, R1 additionally represents halogen, and when A is -CH2-CH2- or -CH2NH, R1 additionally represents alkoxy, R2 is hydrogen, alkoxy, fluoralkoxy, hydroxyalkoxy, hydroxyalkyl, di-(hydroxy)alkoxy, pyridinyl-3-methoxy, pyridinyl-4-methoxy, R3 is hydrogen, alkyl, trifluoromethyl, and when X is C-R4, R3 additionally represents halogen, and when A is -CH2-CH2-, R3 additionally represents alkoxy, X is N or C-R4, R4 is hydrogen, alkyl, alkoxy or halogen, R5 is methyl or ethyl. Also described are isomers of the said compounds, an initial compound for synthesis of formula (1) compound, which has agonistic effect on S1P1/EDG1 receptors, as well as a pharmaceutical composition based on formula (1) compound and use of formula (1) compound.

EFFECT: obtaining a pharmaceutical composition for preventing or treating diseases or disorders associated with activated immune system.

19 cl, 2 tbl, 167 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from the group which consists of teofanov formula (I)

where a represents a-CH2CH2-, -NH-CH2-, -CH2-O - or-CH2NH-;
R1represents hydrogen or alkyl, and when X represents C-R4, R1additionally represents a halogen, and in the case where a represents a-CH2-CH2- or-CH2NH-, R1additional means alkoxy;
R2represents hydrogen, alkoxy, feralcode, hydroxyalkoxy, hydroxyalkyl, di-(hydroxy)alkoxy, pyridine-3-ylethoxy or pyridine-4-ylethoxy;
R3represents hydrogen, alkyl, or trifluoromethyl and in the case when X represents C-R4, R3additionally represents a halogen, and in the case where a represents a-CH2-CH2- or-CH2NH-, R3additionally represents alkoxy;
X represents N or C-R4;
R4represents hydrogen, alkyl, alkoxy, or halogen; R5represents methyl or ethyl;
and its pharmaceutically acceptable salts, and the terms "alkyl", "alkoxy" and "hydroxyalkoxy" have the following meant is I:
the term "alkyl", alone or in combination with other groups, means a group with a saturated, linear or branched chain, containing from one to seven carbon atoms;
the term "alkoxy" means the group R-O in which R represents an alkyl group;
the term "hydroxyalkoxy" means a linear or branched alkoxygroup containing the hydroxy-group, and this group has at least two carbon atoms between the hydroxy-group and oxygen of alkoxygroup.

2. The compound according to claim 1, where
A represents a-CH2CH2- or-NH-CH2-;
R1represents hydrogen or alkyl, and when X represents C-R4, R1additionally signifies halogen;
R3represents hydrogen, alkyl, or trifluoromethyl and in the case when X represents C-R4, R3additionally signifies halogen; R5represents methyl.

3. The compound according to claim 1 or 2, where a represents-NH-CH2-.

4. The compound according to claim 1 or 2, where a represents a-CH2CH2-.

5. The compound according to claim 1 or 2, where a represents a-CH2NH-.

6. The compound according to any one of claims 1 or 2, where X represents N.

7. The compound according to any one of claims 1 or 2, where X represents C-R4.

8. The compound according to any one of claims 1 or 2, where Predstavljaet a C-R 4and R4represents a methoxy group, and R1represents hydrogen.

9. The compound according to any one of claims 1 or 2, where X represents C-R4and R4represents a methoxy group, and R1and R3both represent hydrogen.

10. The compound according to any one of claims 1 or 2, where R2is a group of hydroxyalkoxy, hydroxyalkyl, di-(hydroxy)alkoxy.

11. The compound according to any one of claims 1 or 2, where X represents C-R4and R4represents hydrogen, R1and R3both represent a methyl group, and R2is a group of hydroxyalkoxy, hydroxyalkyl, di-(hydroxy)alkoxy.

12. The compound of formula (II)

according to any one of claims 1 or 2.

13. The compound of formula (III)

according to any one of claims 1 or 2.

14. The compound according to claim 1, selected from the group consisting of the following compounds:
2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2,4-dimethoxybenzamide(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4 ethoxy-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-is etrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((S)-2,3-dihydroxypropane)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((S)-2,3-dihydroxypropane)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((S)-2,3-dihydroxypropane)-3-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)-3-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((S)-2,3-dihydroxypropane)-3-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)-3-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((S)-2,3-dihydroxypropane)-2-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)-2-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid is you,
4-((S)-2,3-dihydroxypropane)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R)-2,3-dihydroxypropane)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)-3-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)-3-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)-2-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-hydroxyethoxy)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)-3-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1 is,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)-3-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)-2-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-((R/S)-2-hydroxypropoxy)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)-3-methylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)-3-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)-2-Chlorobenzilate(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxypropoxy)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-floratone)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-floratone)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-t is trihydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-chloro-4-(2-floratone)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(2-floratone)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-forproperty)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-methoxy-4-propoxybenzene(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-methoxy-4-isopropoxyaniline(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4 isobutoxy-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(6-hydroxyhexyloxy)-2-methoxybenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
4-(3-hydroxy-2-hydroxymethylpropane)for 3,5-dimethylbenzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-methoxy-4-(pyridine-3-ylethoxy)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
2-methoxy-4-(pyridine-4-ylethoxy)benzylamine(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-carboxylic acid,
(pyridine-2-ylmethyl)amide(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop is ASO[and]pentalen-4-carboxylic acid,
3-(2-methoxyphenyl)-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)-2-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(2-hydroxyethoxy)-2-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((R)-2,3-dihydroxypropane)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(2-hydroxyethoxy)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(2-(R/S)-hydroxypropoxy)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(2-(2-floratone)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-it, and
3-[4-(3-hydroxypropoxy)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-it.

15. The compound according to claim 1, selected from the group consisting of the following compounds:
3-[4-(3-hydroxy-2-hydroxymethylpropane)for 3,5-dimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(S)-2,3-dihydroxypropane)-3-ethyl-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((R)-2,3-dihydroxypropane)-3-ethyl-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-ethyl-4-(2-hydroxyethoxy)-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)for 3,5-diethylphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-((S)-2,3-dihydroxypropane)-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-((R)-2,3-dihydroxypropane)-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-(2-hydroxyethoxy)-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-(2-hydroxypropoxy)-5-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-((S)-2,3-dihydroxypropane)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[2-chloro-4-((S)-2,3-dihydroxypropane)phenyl]-1-(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[2-chloro-4-((R)-2,3-dihydroxypropane)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[2-chloro-4-(2-hydroxyethoxy)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[2-chloro-4-(3-hydroxypropoxy)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[2-chloro-4-(2-hydroxypropoxy)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)-3-were]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)-2,3,5-trimetilfenil]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3,5-dichloro-4-((S)-2,3-dihydroxypropane)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3,5-dichloro-4-((R)-2,3-dihydroxypropane)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3,5-dichloro-4-(2-hydroxypropoxy)phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-((S)-2,3-dihydroxypropane)-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-((R)-2,3-dihydroxypropane)-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-chloro-4-(2-hydroxyethoxy)-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)-3-fluoro-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-dimetil-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((R)-2,3-dihydroxypropane)-3-fluoro-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[3-fluoro-4-(2-hydroxyethoxy)-5-methoxyphenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-(3-hydroxypropyl)phenyl]-1-(1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((S)-2,3-dihydroxypropane)for 3,5-dimetilfenil]-1-((1aR,5aS)-2-ethyl-1,1-dimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
3-[4-((R)-2,3-dihydroxypropane)for 3,5-dimetilfenil]-1-((1aR,5aS)-2-ethyl-1,1-dimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)propan-1-he,
1-((1aR,5aS)-2-ethyl-1,1-dimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)-3-[4-(3-hydroxypropoxy)for 3,5-dimetilfenil]-propane-1-he,
1-((1aR,5aS)-2-ethyl-1,1-dimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)-3-[4-(2-hydroxypropoxy)for 3,5-dimetilfenil]-propane-1-he,
2-(2-methoxyphenylazo)-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)Etalon,
2-(3,5-dimethylphenylimino)-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)Etalon and
2-[4-(2-hydroxyethyl)phenylamino]-1-((1aS,5aR)-1,1,2-trimethyl-1,1A,5,5A-tetrahydro-3-talkloop[and]pentalen-4-yl)Etalon.

16. A compound selected from the group which consists of teofanov formula (IV)

where R5/sup> is as defined for formula (I) in claim 1;
R6represents a hydroxy group, alkoxy or methyl;
the term "alkoxy" means the group R-O in which R represents an alkyl group, and the term "alkyl" means a group with a saturated, linear or branched chain, containing from one to seven carbon atoms.

17. Pharmaceutical composition comprising a compound according to any one of claims 1 to 15, having agonistic activity against receptors S1P1/EDG1, and a pharmaceutically acceptable carrier, intended for the prevention or treatment of diseases or disorders associated with an activated immune system.

18. The compound according to any one of claims 1 to 15, having agonistic activity against receptors S1P1/EDG1, or the composition according to 17 for the prevention or treatment of diseases or disorders associated with an activated immune system.

19. The use of compounds according to any one of claims 1 to 15 for obtaining a pharmaceutical composition for the prevention or treatment of diseases, disorders or disorders associated with an activated immune system.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described is a compound selected from a group consisting of formula II formula III and formula IV , or its salt or ester, where G1 is selected from a group which includes - (CR1R2)n-, n equals 0 or 1; R1 and R2 are independently selected from a group which includes hydrogen; X1, X2 and X3 are independently selected from a group consisting of hydrogen, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, G2 is a heterocycloalkyl linker optionally substituted with X4 and X5, where the heterocycloalkyl linker is selected from a group consisting of piperazinyl, 3,6-dihydro-2N-pyridinyl, [1,4]diazepanyl, 3,9-diazabicyclo[3,3,1]nonyl; X4 and X5 are independently selected from a group consisting of hydrogen and optionally substituted lower alkyl; CO2R; R is selected from a group consisting of optionally substituted lower alkyl and hydrogen; G3 is a bond; G4 is selected from a group consisting of hydrogen, aryl, selected from phenyl which is optionally substituted with a lower alkyl, halogen, lower haloalkyl or lower haloalkoxy; heteroaryl selected from pyridinyl which is optionally substituted with a halogen or lower haloalkyl; and optionally substituted cycloheteroalkyl selected from 1,3-benzodioxolyl. Described also are specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds are used as modulators of receptors activated by a peroxisomal proliferator.

5 cl, 2 tbl, 117 ex

FIELD: chemistry.

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

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

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds with general formula (I) and its isomers, where R1 is a hydrogen atom of an alkyl C1-4 group with a straight or branched chain, or a phenyl group, thienyl group or furyl group, optionally substituted with one or more alkyl C1-4 groups with a straight or branched chain, C1-4 alkoxy groups with a straight or branched chain, or halogen atoms; R2 is a hydrogen atom or an alkyl C1-4 group with a straight or branched chain, or a phenyl, benzyl, thienyl or furyl group, optionally substituted with a methylenedioxy group, or one or more alkyl C1-4 groups with a straight or branched chain, or C1-4 alkoxy-, hydroxyl-, trifluoromethyl- or cyano-group with a straight or branched chain, or halogen atoms, as well as to a method of producing said compound. The invention also relates to new intermediates with general formula (II) and their production.

EFFECT: radioligands A3 with antagonistic action are obtained and described, labeled with iodine isotopes with mass number 125, which have high specific activity.

16 cl, 3 ex, 2 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula compounds, as well as their pharmaceutically acceptable salts, a pharmaceutical composition based on them, with inhibitory activity towards phosphorylation of protein Tau, and to methods of producing said compounds. In formula (I), R5 is aryl, aryl(C1-C6)alkyl; R6 is halogen; R3 is (C1-C6)alkyl, possibly substituted with substitutes selected from halogen, OH, NH2, azetidine; or monocyclic aryl or heteroaryl, such as thiophene or pyridine, possibly substituted with substitutes selected from NO2, CN, (C1-C6)alkoxy, (C1-C6)alkyl; or CONR1R2, SO2Ra, C(=NH)R1b, COOR1c; R1, R2 independently represent a hydrogen atom, possibly substituted with one halogen atom, (C1-C6)alkyl, moncyclic aryl or monocyclic 5- or 6-member heteroaryl containing 1 or 2 heteroatoms, such as S, O, N, possibly substituted with one or more substitutes selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxyl, trifluoromethyl, N(CH3)2; or R1 and R2 can form a 5- or 6-member ring which optionally contains a heteroatom such as N; R1a is aryl, possibly substituted with (C1-C6)alkoxy; R1b is (C1-C6)alkyl, possibly substituted aryl or 6-member heteroaryl, containing 1 or 2 N atoms, where the substitute is (C1-C6)alkoxyl; R1c is (C1-C6)alkyl, (C2-C6)alkenyl; and their pharmaceutically acceptable salts.

EFFECT: aminoindazole derivatives as kinase inhibitor.

8 cl, 44 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel sulphonamide derivatives of general formula (I) , where R1 is phenyl, thiophenyl or furanyl, unsubstituted or substituted with one or two substitutes selected from a group consisting of halogen, lower alkyl, lower alkyl substituted with halogen, -O-lower alkyl substituted with halogen, NO2 or CN; R2-R4 and R2'-R4' is hydrogen, lower alkyl, phenyl or lower alkyl substituted with halogen; R5 is phenyl, pyridinyl, benzo[1,3]dioxolyl or benzofuranyl, unsubstituted or substituted with 1-3 substitutes selected from a group consisting of halogen, lower alkyl, lower alkyloxy, CN, nitro, amino, hydroxy, lower alkyl substituted with hydroxy, lower alkyl substituted with halogen, or substituted with -C(O)-NR"2, -(CR2)m-C(O)-R', -(CH2)m-heteroaryl, unsubstituted or monosubstituted -(CH2)m-lower alkoxy, lower alkyl, -(CH2)m-O-benzene or CH2OH, -O-C(O)-lower alkyl, -O-C(O)-NR2, -O-(CH2)m-C(O)OH, -O-lower alkynyl, -O-lower alkyl, substituted with halogen, -O-(CH2)m-heterocyclyl, -O-(CH2)m-phenyl, unsubstituted or monosubstituted hydroxy, -O-(CH2)m-heteroaryl, unsubstituted or monosubstituted with lower alkyl, -(CH2)m-NH-C(O)R', -(CH2)m-NH-S(O)2-R', -S(O)2-lower alkyl, -S(O)2-heterocyclyl, -S(O)2NH-cycloalkyl, or is C3-6cycloalkyl; R' is hydrogen, lower alkyl, lower alkynyloxy, hydroxy, C3-6cycloalkyl, heterocyclyl, which is unsubstituted or substituted with one or two substitutes selected from COOH, -C(O)O-lower alkyl, halogen or lower alkyl, or is phenyl, benzyl, heteroaryl, -(CH2)m-lower alkoxy or -(CHR)m-C(O)O-lower alkyl; R" is hydrogen, C3-6cycloalkyl, which is unsubstituted or substituted with one or two substitutes selected from halogen, or is lower alkyl, lower alkyl substituted with halogen, lower alkyl substituted with hydroxy, -(CH2)m-heterocyclyl, -NR2, heteroaryl, benzyl or -(CHR)m-C(O)O-lower alkyl; R is hydrogen or lower alkyl; X is -CHR-; m equals 0, 1, 2 or 3; and its pharmaceutically acceptable salts of an acid compound, optically pure enantiomers, racemates or diastereomeric mixtures. The invention also relates to medicine containing a formula I compound.

EFFECT: obtaining novel compounds which inhibit γ-secretase.

16 cl, 230 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I) , where

R1 -C1-8alkyl; R2 - pyridynyl, unnecessarily substituted with C1-8alkyl, quinolyl or isoquinolyl; R3 - hydrogen or C1-8alkylcarbonyl; R4 means group of formula G-L1-(CRR')n-, in which n is integer number from 0 to 3; R and R' are independently selected from group that includes atoms of hydrogen and lower alkyl groups; L1 means connection group, selected from group, which includes direct connection, groups -O-, -CO-, -NR"-, -O(CO)O-, -O-(CO)-, -(CO)O- and -NR"-(CO)-, where R" is lower alkyl; G is selected from group, including atoms of hydrogen, C1-8alkyl, C2-8alkenyl, C3-7dicloalkyl, phenylC1-8alkyl, pyridinyl, thiophenyl or residue of indan, and also phenyl, unnecessarily substituted with atom of halogen, C1-8alkoxy, cyano- or C1-8alkyl, which, in its turn, unnecessarily contains one or more atoms of halogen. Specified compounds are active and selective inhibitors of phosphodiesterase 4 (FDE4), therefore, they are applicable for treatment, prevention or suppression of pathological conditions, diseases or disorders, for which it is known that their behavior is relieved by inhibition of FDE4, such as asthma, chronic obstructive lung disease, rheumatoid arthritis, atopic dermatitis, psoriasis or syndrome of sore large gut. Invention is related also to pharmaceutical compositions on the basis of mentioned compounds, application of compounds, method for treatment of subject, when efficient amount of specified compounds is introduced to them. Besides invention is related to combined product for treatment or prevention of pathological condition or disease, behavior of which is relieved by inhibition of phosphodiesterase 4, including specified compound and another compound, selected from the group that includes (a) steroids, (b) immunosuppressive agents, (c) blockers of T-cells receptors, (d) anti-inflammatory medicinal agents, (e) β2-adrenergic agonists and (f) antagonists of muscarine receptors M3, for single-time, separate or serial use.

EFFECT: improved efficiency of compounds use.

11 cl, 2 tbl, 77 ex

FIELD: medicine.

SUBSTANCE: invention is related to new compounds of common formula IC1: , where A represents cyano; B represents hydrogen; R1, R2, R3 and R4 independently represent hydrogen; alkyl; halogen or nitro; R5 and R6 independently represent hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; heteroaryl; heteroarylalkyl; alkenyl; carboxyalkyl; cyanoalkyl; diphenylalkyl; aryl, arylalkoxyaryl, arylalkyl, arylalkylaryl, arylcarbonylaryl or aryloxyaryl, or R5 and R6, together with atom of nitrogen, to which they are connected, create heterocyclic ring system; or to salts of such compound; at the same time "heteroaryl" used separately or in combination, is related to mono-, bi- or tricyclic aromatic ring system, which contains up to 14 atoms included in ring, in which at least one ring contains at least one heteroatom, independently chosen from nitrogen, oxygen or sulfur, besides specified heteroaryl group may be unsubstituted or substituted with one to three substituents, independently selected from alkyl and alkoxy; "diphenylalkyl" is related to alkyl group, where each of two atoms of hydrogen is substituted with unsubstituted phenyl group; "aryl" is related to carbocyclic group, selected from group, which consists of phenyl, biphenyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, antryl, phenantryl, fluorenyl, indanyl, 2,3-dihydrobenzo[1,4]dioxynyl and benzo[1,3]dioxolyl group, besides specified aryl group may be unnecessarily substituted with functional groups in number from one to three, which are separately and independently selected from alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, cyano, halogen, halogenlkoxy, halogenalkyl and nitro groups, where in certain specific cases, if aryl group represents condensed system from several rings, in which not all the rings are aromatic, one of carbon atoms of which is not included into aromatic ring may be in oxidised condition, and according fragment of ring -CH2- will be substituted by fragment-C(O); "arylalkoxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkoxygroup, where aryl group is unsubstituted; "arylalkyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via alkyl group, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "aryloxy", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via oxygen bridge, where aryl group may be unsubstituted or substituted with 1-3 substituents, independently selected from group, which consists of halogen; "arylcarbonyl", used separately or in combination, is related to aryl group, which is connected to initial molecular fragment via carbonyl group, where aryl group is unsubstituted; "heterocyclic ring system", used separately or in combination, is related to monocyclic, bicyclic or polycyclic ring system, which contains up to 15 atoms included into ring, at least one of which represents heteroatom, independently selected from nitrogen, oxygen or sulfur, besides specified ring system may be saturated, partially unsaturated, unsaturated or aromatic, where specified heterocyclic fragment may be unnecessarily substituted with one or more substituents, every of which separately and independently is selected from group made of halogen and halogenalkyl, excluding the following compounds: {3-[(E)-2-cyano-2-(4-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-m-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(3-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-phenylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-benzylcarbamoyl-2-cyanovinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-o-tolylcarbamoylvinyl)indole-1-yl]acetic acid; [3-((E)-2-cyano-2-t-tolylcarbamoylvinyl)indole-1-yl]acetic acid; (3-[(E)-2-(4-bromophenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-ethylphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2~cyano-2-(4- ethoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; [3-((E)-2-cyano-2-isopropylcarbamoylvinyl)indole-1-yl]acetic acid; {3-[(E)-2-cyano-2-(3-etoxyphenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-[[2-(1H-indole-3-yl)ethyl]amino]-3-oxo-1-propenyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-chlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-3-(4-methyl-piperidine-1-yl)-3-oxopropenyl]indole-1-yl}acetic acid; {3-[(E)-2-(3-chloro-4-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(3-phenylpropylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2,3-dichlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-(5-chloro-2-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxybenzylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; and {3-[(E)-2-cyano-3-oxo-3-(4-phenyl-piperazine-1-yl)propenyl]indole-1-yl}acetic acid. Invention is also related to pharmaceutical composition, and also to application of compounds of clause 1.

EFFECT: production of biologically active compounds, which have activity of antagonist coupled with G-protein of chemoattractant receptor of molecules homologue released by Th2-cells.

11 cl, 156 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: medicine.

SUBSTANCE: invention covers compound of formula (IA) or to its pharmaceutically acceptable salts wherein R1 represents group R5S(O)2O where R5 represents C1-6alkyl group optionally substituted with one or more fluoro; Ra represents halogeno, and m is equal to 0, 1 or 2; R2a represents chloro; R2b represents chloro; R2c represents H or halogeno; R3 represents group CONHNR7R8 wherein NR7R8 represents piperidino or morpholino, or R3 represents group CONHR8 wherein R8 represents C5-7cycloalkyl group optionally substituted with C1-6alkoxycarbonyl group, or R8 represents pyridyl optionally substituted with one C1-5alkyl group where said alkyl is optionally substituted with one or more fluoro; and R4 represents H, C1-3alkyl group or halogeno. The compounds of formula (IA) are modulators of CB1 receptors and can find application in manufacturing of a medicinal agent with modulating activity in relation to CB1-receptor which can be used in treatment of obesity, psychiatric and neurologic disturbances.

EFFECT: higher clinical effectiveness.

5 cl, 21 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2-alkyl-5,6,7,8,9,10-hexahydro-4H-cyclonone[b]thiophenes of general formula : (1), where R=n-C5H11, n-C7H15, n-C9H19, characterised by that the mixture of cyclonone-1,2-diene and alka-1,2-diene (octa-1,2-diene, deca-1,2-diene, dodeca-1,2-diene) is reacted with ethylmagnesium bromide (EtMgBr/ether) in the presence of Mg (powder) and titanocene dichloride (Cp2TiCl2) catalyst, taken in molar ratio cyclonone-1,2-diene : alka-1,2-diene : EtMgBr : Mg : Cp2TiCl2= 10:10:(22-26):20:(1.0-1.4), preferably 10:10:24:20:1.2, in an argon atomosphere at room temperature (20-22°C) and atmospheric pressure for 6-8 hours and diethyl ether, with subsequent addition of an amount of elementary sulphur S8 which is equimolar to EtMgBr, benzene as a solvent and heating the reaction mass for 6 hours at temperature of approximately 40°C, then after evaporation of light solvents, the reaction mass is kept for 1 hour at temperature of approximately 140°C.

EFFECT: compounds can be used in the food industry as components of flavour boosters, biologically active compounds, dyes, oil additives and hydraulic liquids.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,2,3,4,5,6,7,9,10,11,12,13,14,15-tetradecahydrodicyclonone[b,d]thiophene of general formula : characterised by that, cyclonone-1,2-diene is reacted with ethylmagnesium bromide (EtMgBr/ether) in the presence of Mg (powder) and titanocene dichloride (Cp2TiCl2) catalyst taken in molar ratio cyclonone-1,2-diene : EtMgBr : Mg : Cp2TiCl2 = 20:(22-26):20:(1.0-1.4), preferably 20:24:20:1.2, in an argon atmosphere at room temperature (20-22°C) and atmospheric pressure for 6-8 hours in diethyl ether, with subsequent addition of an amount of elementary sulphur S8 which is equimolar to EtMgBr, benzene as a solvent and heating the reaction mass for 5 hours at temperature of approximately 40°C, then after evaporation of light solvents, the reaction mass is kept for 1 hour at temperature of approximately 140°C.

EFFECT: compounds can be used in fine organic synthesis and in production of biologically active heterocyclic compounds.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, and specifically to method for synthesis of 1,2,3,4,5,6,10,11,12,13,14,15,15a,15b-tetradecahydrodicyclonona[b,d]thiophene of general formula (1): , characterised by that, cyclonona1,2-diene is reacted with ethyl aluminium dichloride (EtAlCl2) in the presence of Mg (powder) and zirconocene dichloride catalyst (Cp2ZrCl2), taken in molar ratio cyclonona-1,2-diene : EtAlCl2 : Mg : Cp2ZrCl2 = 20 : (11-13) : 20 : (1.0-1.4), preferably 20:12:20:1.2, in an argon atmosphere at room temperature (20-22°C) and atmospheric pressure for 6-8 hours in tetrahydrofuran, with subsequent addition of elemental sulphur S8 in an amount equimolar to EtAlCl2, as well as benzene as solvent and heating the reaction mass for 6 hours at temperature of approximately 80°C.

EFFECT: design of a method for synthesis of 1,2,3,4,5,6,10,11,12,13,14,15,15a,15b- tetradecahydrodicyclonona[b,d]thiophene, which can be used in fine organic synthesis, as well as obtaining biologically active heterocyclic compounds.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: method of obtaining 6-thiaspiro[3,4]octane can be used in fine organic synthesis, in production of oil additives and biologically active substances. The method involves reacting methylenecyclobutane with triethylaluminium (AlEt3) in the presence of a catalyst in an argon atmosphere at room temperature and atmospheric pressure in hexane for 4 hours with subsequent addition to the reaction mass at temperature -40°C of thionyl chloride, taken in equimolar amount with respect to AIEt3 and stirring at that temperature for 6-8 hours.

EFFECT: output of the desired product after hydrolysis of the reaction mass is 53-74%.

1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 2,5-dialkyl-3,4-fullero[60]tetrahydrothiophenes of formula (I) . Essence of method lies in interaction of fullerene C60 with dialkylsulfide in presence of catalyst Cp2TiCl2 in toluol medium at temperature 140-160°C during 5-7 hours. Target product output is 47-70%.

EFFECT: obtaining compounds, which can be used as complex-forming agents, sorbents, biologically active compounds, as well as in creation of novel materials with set electronic, magnetic and optical properties.

1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 3,4-fullero(60)tetrahydrothiophen-1-on of formula (I) . Essence of method lies in interaction of fullerene C60 with dimethylsulfoxide in presence of catalyst Cp2ZrCl2 in toluol medium at temperature ˜20 °C during 66-78 hours. Target product output is 56-79%.

EFFECT: obtaining compound, which can be used as complex-forming agent, sorbent, biologically active compound, as well as in creation of novel materials with set electronic, magnetic and optical properties.

1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 2,5-diphenyl-3,4-fullero[60]tetrahydrothiophen-1-on of general formula (I) . Essence of method lies in interaction of fullerene C60 with dibenzylsulfoxide in presence of catalyst Cp2HfCl2 in toluol medium at temperature 140-160°C during 5-7 hours. Target product output is 43-68%.

EFFECT: obtaining compounds, which can be used as complex-forming agents, sorbents, biologically active compounds, as well as in creation of novel materials with set electronic, magnetic and optical properties.

1 tbl, 9 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 2,5-diphenyl-3,4-fullero[60]tetrahydrothiophen of formula (I) . Essence of method lies in interaction of fullerene C60 with dibenzylsulfide in presence of catalyst hafnocene dichloride Cp2HfCl2 in toluol medium at temperature 140-160°C during 4-8 hours. Target product output is 42-64%.

EFFECT: obtaining compound, which can be used as complex-forming agent, sorbent, biologically active compound, as well as in creation of novel materials with set electronic, magnetic and optical properties.

9 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 3,4-fullero(60)tetrahydrothiophene of formula (I) . Essence of method lies in interaction of fullerene C60 with dimethylsulfide in presence of catalyst Cp2TiCl2 in toluol medium at temperature ˜20°C during 66-78 hours. Target product output is 59-82%.

EFFECT: obtaining compound, which can be used as complex-forming agent, sorbent, biologically active compound, as well as in creation of novel materials with set electronic, magnetic and optical properties.

1 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to field of organic chemistry, namely to method of obtaining 2,5-dialkyl-3,4-fullero[60]tetrahydrothiophen-1-ons of general formula (I) . Essence of method lies in interaction of fullereneC60 with dialkylsufoxides in presence of catalyst Cp2ZrCl2 in toluol medium at temperature 140-160°C during 5-7 hours. Target product output is 40-65%.

EFFECT: obtaining compounds, which can be used as complex-forming agents, sorbents, biologically active compounds, as well as in creation of novel materials with set electronic, magnetic and optical properties.

1 tbl, 11 ex

Immunostimulants // 2385732

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, specifically to an agent of immunostimulating activity. The immunostimulant which represents a liquid nettle extract is prepared by repercolation under certain conditions.

EFFECT: immunostimulant exhibits effective immunostimulating properties that is expressed in intensified immune response, cell immune response and nonspecific resistance of an organism.

3 tbl, 3 ex

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