Pyridin-4-yl derivatives as immunomodulatory agents

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyridine derivatives of formula

wherein A, R1, R2, R3, R4, R5 and R6 are presented in the description, preparing and using them as pharmaceutically active compounds as immunomodulatory agents.

EFFECT: preparing the pharmaceutical composition showing agonist activity with respect to S1P1/EDG1 receptor and using it for prevention and treatment diseases or disorders associated with activated immune system.

20 cl, 244 ex, 2 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where And is a
,,,
, or
where the asterisks indicate the bond through which the connection to the pyridine group of formula (I);
R1represents a C1-4alkyl or chlorine;
R2represents a C1-5alkyl, C1-4alkoxygroup or C3-6cycloalkyl;
R3represents hydrogen, C1-4alkyl or C1-4alkoxygroup;
R4represents hydrogen, C1-4alkyl, C1-4alkoxygroup or halogen;
R5represents-CH2-(CH2)n-CONR51R52, 1-(3-carboxyethylidene)-2-acetyl, 1-(2-carboxypropyl)-2-acetyl, 1-(3-carboxypropyl)-2-acetyl, hydroxy-group, hydroxys2-5alkoxygroup, di-(hydraxis1-4alkyl)C1-4alkoxygroup, 2,3-dihydroxypropyl, -OCH2-(CH2)m-NR51R52, -OCH2-CH(OH)-CH2-NR51R52or-OCH2-CH(OH)-CH2-NHCOR54;
R51represents hydrogen, C1-3alkyl, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylene or 2-carboxyethyl;
R52represents hydrogen, methyl or ethyl;
R54represents hydroxymethyl;
m represents the integer 1;
n represents 0 or 1; and
R6represents hydrogen, C1-4alkyl or halogen;
and salt of such compounds.

2. With the Association according to claim 1, where And is a
,,,
or
where the asterisks indicate the bond through which the connection to the pyridine group of formula (I); and salt of such compounds.

3. The compound according to claim 1, where a is a

where the asterisks indicate the bond through which the connection to the pyridine group of formula (I); and salt of such compounds.

4. The connection according to one of claims 1 to 3, where R1represents a C1-4alkyl; and the salts of such compounds.

5. The connection according to one of claims 1 to 3, where R1represents methyl or ethyl; and the salt of such compounds.

6. The connection according to one of claims 1 to 3, where R1represents methyl; and the salts of such compounds.

7. The connection according to one of claims 1 to 3, where R2represents a C1-3alkyl, C1-3alkoxygroup or cyclopentyl; and the salt of such compounds.

8. The connection according to one of claims 1 to 3, where R2represents a C2-5alkyl; and the salts of such compounds.

9. The connection according to one of claims 1 to 3, where R2represents ethyl, n-propyl, isopropyl, isobutyl or 3-pentyl; and the salt of such compounds.

10. The connection according to one of claims 1 to 3, where at least one of the Rsup> 3, R4and R6represents a group other than hydrogen; and the salts of such compounds.

11. The connection according to one of claims 1 to 3, where R3represents hydrogen; and the salts of such compounds.

12. The connection according to one of claims 1 to 3, where R3represents hydrogen; and R4represents a C1-4alkyl or C1-4alkoxygroup; and R6represents a C1-4alkyl or halogen; and salts of such compounds.

13. The connection according to one of claims 1 to 3, where R3represents hydrogen; and R4represents a C1-3alkyl or a methoxy group; and R6represents methyl, ethyl or chlorine; and a salt of such compounds.

14. The connection according to one of claims 1 to 3, where R5represents-CH2-(CH2)n-CONR51R52the hydroxy-group, hydroxys2-5alkoxygroup, di-(hydraxis1-4alkyl)-C1-4alkoxygroup, 2,3-dihydroxypropyl, -OCH2-(CH2)m-NR51R52, -OCH2-CH(OH)-CH2-NR51R52or-OCH2-CH(OH)-CH2-NHCOR54; and the salt of such compounds.

15. The connection according to one of claims 1 to 3, where R5represents-CH2-(CH2)n-CONR51R52hydraxis2-5alkoxygroup, di-(hydraxis1-4alkyl)-C1-4alkoxygroup, 2,3-dihydroxypropyl, -OCH2-(CH2) m-NR51R52, -OCH2-CH(OH)-CH2-NR51R52or-OCH2-CH(OH)-CH2-NHCOR54; and the salt of such compounds.

16. The connection according to one of claims 1 to 3, where R5is a 3-hydroxy-2-hydroxymethylpropane, 2,3-dihydroxypropyl or-OCH2-CH(OH)-CH2-NHCOR54; and the salt of such compounds.

17. The compound according to claim 1, selected from the group including:
N-(3-{4-[5-(2-Chloro-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
3-{4-[5-(2-Chloro-6-isobutylpyrazine-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
N-(3-{4-[5-(2-Chloro-6-isobutylpyrazine-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
3-{4-[5-(2-Isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
2-Hydroxy-N-(2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propyl)ndimethylacetamide;
3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-METHYLPHENOL;
(R)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
(S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadi the ol-3-yl]-6-methylphenoxy}propane-1,2-diol;
2-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylpenicillin}propane-1,3-diol;
2-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}ethanol;
3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propan-1-ol;
N-(3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
3-{4-[5-(2,6-Diisobutylene-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
3-{4-[5-(2-Chloro-6-isopropoxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
N-(3-{4-[5-(2-Chloro-6-isopropoxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
3-{4-[5-(2-Ethoxy-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
3-{4-[5-(2-Isopropoxy-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
2-Hydroxy-N-(2-hydroxy-3-{4-[5-(2-isopropoxy-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propyl)ndimethylacetamide;
4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenol;
(R)-3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
(R)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
(S)-3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-dio is;
(S)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
(S)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}propane-1,2-diol;
N-(3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-(3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methyl-6-propylenoxide}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methyl-6-propylenoxide}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Chloro-4-[5-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-(3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methoxy-6-methylphenoxy}-2-hydroxypropy is)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-4-[3-(2-ethyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{4-[5-(2-Ethyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenol;
2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenol;
(R)-3-{2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
(S)-3-{2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
(R)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
(S)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
(R)-3-{2-Chloro-6-methoxy-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
(S)-3-{2-Chloro-6-methoxy-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
N-(3-{2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine the-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Chloro-6-methoxy-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2,6-Dimethyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,3,4]oxadiazol-2-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((R)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,3,4]oxadiazol-2-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-6-methyl-4-[5-(2-methyl-6-propylpyridine-4-yl)-[1,3,4]oxadiazol-2-yl]phenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
2-{2-Ethyl-4-[5-(2-isopropyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}ethanol;
(S)-3-{2-Ethyl-4-[5-(2-isopropyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
N-(3-{2-Ethyl-4-[5-(2-isopropyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
2-Hydroxy-N-((S)-2-hydroxy-3-{4-[5-(2-isopropyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methyl-6-propylenoxide}propyl)ndimethylacetamide;
N-((S)-3-{2-Ethyl-4-[5-(2-isopropyl-6-methylpyridin-4-yl)-[1,3,4]thiadiazole-2-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}propane-1,2-diol;
3-{2-Bromo-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]phenoxy}propane-1,2-diol;
1-{2-Chloro-4-[5-(2-isobutyl-6-METI the pyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-3-(2-hydroxyethylamino)propan-2-ol;
2-Hydroxy-N-(2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-3-methylphenoxy}propyl)ndimethylacetamide;
N-(3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-(3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenol;
(S)-3-{4-[5-(2-Isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methyl-6-propylenoxide}propane-1,2-diol;
2-Hydroxy-N-(2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-3-methoxyphenoxy}propyl)ndimethylacetamide;
2-Hydroxy-N-((S)-2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methyl-6-propylenoxide}propyl)ndimethylacetamide;
2-Hydroxy-N-(2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-methoxy-6-methylphenoxy}propyl)ndimethylacetamide;
N-((R)-3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
(R)-3-{2-Ethyl-4-[3-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-6-methylphenoxy}propane-1,2-diol;
(S)-3-{2-Ethyl-4-[3-(2-isobutyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-6-methylphenoxy}propane-1,2-diol;
2-is hydroxy-N-((R)-2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethylphenoxy}propyl)ndimethylacetamide;
2-Hydroxy-N-((S)-2-hydroxy-3-{4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethylphenoxy}propyl)ndimethylacetamide;
N-((R)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Chloro-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-6-methoxyphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)-[1,3,4]thiadiazole-2-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
2-Ethyl-4-{5-[2-(1-ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-METHYLPHENOL;
(R)-3-(2-Ethyl-4-{5-[2-(1-ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methylphenoxy)propane-1,2-diol;
(S)-3-(2-Ethyl-4-{5-[2-(1-ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methylphenoxy)propane-1,2-diol;
(R)-3-(4-{5-[2-(1-Ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2-methyl-6-propylenoxide)propane-1,2-diol;
(S)-3-(4-{5-[2-(1-Ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2-methyl-6-propylenoxide)propane-1,2-diol;
N-[(R)-3-(2-Ethyl-4-{5-[2-(1-ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methylphenoxy)-2-hydroxypropyl]-2-hydroxyacetate;
N-[(S)-3-(2-Ethyl-4-{5-[2-(1-ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methylphenoxy)-2-hydroxypropyl]-2-hidroxi Itemid;
N-[(R)-3-(4-{5-[2-(1-Ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2-methyl-6-propylenoxide)-2-hydroxypropyl]-2-hydroxyacetate;
N-[(S)-3-(4-{5-[2-(1-Ethylpropyl)-6-methylpyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2-methyl-6-propylenoxide)-2-hydroxypropyl]-2-hydroxyacetate;
3-{4-[5-(2,6-Diethylpyrazine-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propane-1,2-diol;
3-{4-[5-(2,6-Diethylpyrazine-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}propane-1,2-diol;
N-((S)-3-{4-[5-(2,6-Diethylpyrazine-4-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-(3-{4-[5-(2-Ethoxy-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
(R)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methoxypyridine-4-yl)-[1,2,4] oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
(S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methoxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}propane-1,2-diol;
N-((R)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methoxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methoxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
(R)-3-{4-[5-(2-Cyclopentyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}propane-1,2-diol;
(S)-3-{4-[5-(2-Cyclopentyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}propane-1,2-diol;
N-((R)-3-{4-[5-(2-Cyclopentyl-6-methylpyridin-4-the l)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido;
N-((S)-3-{4-[5-(2-Cyclopentyl-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamido; and
(S)-3-{2-Ethyl-4-[5-(2-isobutyl-6-methylpyridin-4-yl)oxazol-2-yl]-6-methylphenoxy}propane-1,2-diol;
and salt of such compounds.

18. Pharmaceutical composition having agonistic activity against receptor S1P1/EDG1, including a connection according to one of claims 1 to 17 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

19. The connection according to one of claims 1 to 3 and 17, or its pharmaceutically acceptable salt intended for use as drugs having agonistic activity against receptor S1P1/EDG1.

20. The use of compounds according to one of claims 1 to 17 or its pharmaceutically acceptable salt to obtain a pharmaceutical composition having agonistic activity against receptor S1P1/EDG1, for the prevention or treatment of diseases or disorders associated with an activated immune system.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to heterocyclic compounds of formula ,

wherein X2 represents residue C-Z-R2 or C-R3, wherein Z represents NH or S; R1 is selected from structures , and R2 and R3 have the values specified in cl.1 of the patent claim, or to their pharmaceutically acceptable salts. The invention also refers to a pharmaceutical composition, a series of specific compounds, application of the declared compounds and to an intermediate compound for preparing the compounds of formula (I).

EFFECT: compounds under the invention have affinity to muscarine receptors and can be used in treating, relieving and preventing diseases and conditions mediated by muscarine receptors.

13 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I

,

where A represents S or Se; B represents H or ; R1 represents aryl selected from the following structures:

R2 represents H or ; R3 represents H or C1-C8 alkyl; R4 and R5 independently represent H or C1-C8 alkyl; R6 represents H, C1-C8 alkyl, C2-C7 alkenyl, alkaline metal or alkaline earth metal; R11 and R12 independently represent H, C1-C8 alkyl or halogen; R21 represent H, halogen or C1-C7 alkyl; m and n independently represent integers having values 1-4; p represents an integer having a value of 1-5; q represents an integer having a value of 1-4; r represents an integer having a value of 1-3; s represents an integer having a value of 1-5; as an activator of peroxisome proliferator-activated receptor (PPAR) and its hydrate, solvate, stereoisomer and pharmaceutically acceptable salt, and to a pharmaceutical composition.

EFFECT: preparing an agent for muscle strengthening, an agent for memory improvement, a therapeutic agent for dementia and Parkinson's disease.

15 cl, 8 tbl, 348 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new thiophene derivatives of formula (I) where A is represented by *-CO-CH2CH2-, *-CO-CH=CH, where the asterisks indicate the link through which the formula (I) thiophene group is bound; R1 is represented by C2-5alkyl; R2 is represented by hydrogen, methyl or ethyl; R3 is represented by hydrogen; R4 is represented by C1-4alkyl; R5 is represented by a hydroxy group, 2,3-di-hydroxypropoxygroup or -OCH2-CH(OH)-CH2-NHCOR52; R52 is represented by hydroxymethyl, and R6 is represented by C1-4alkyl; and to its salt. The invention also refers to the pharmaceutical composition that is agonistic in relation to S1P1/EDG1 receptor on the basis of the mentioned compounds.

EFFECT: new compounds and a composition based on them that may find their application in medicine as immunomodulating agents.

17 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to new compounds of formula I-9 where q is represented by 1; R11 is represented by C3-8-alkyl; C3-8-cycloalkyl or C3-8-cycloalkyl-C1-3-alkyl; A is represented by phenyl substituted by one or more substituting groups independently chosen from R12; and R12 is represented by -(CH2)-NR13R14; R13 is represented by C1-6-alkylcarbanil; and R14 is represented by hydrogen; and to the pharmaceutically acceptable salts of such compounds and to the pharmaceutical compositions based on such compounds. It has been revealed that the compounds of formula I-9 are histamine NZ-receptor antagonists and thus that they can be used in treatment of diseases connected with expression of such receptors.

EFFECT: compounds of formula I-9 can be used in treatment of diseases connected with expression of histamine NZ-receptors.

6 cl, 216 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): where R1 and R2 represent hydrogen and a group which is hydrolysed in a physiological environment, optionally substituted lower alkanoyl or aroyl; X represents a methylene group; Y represents oxygen atom; n represents the number 0, 1, 2 or 3 and m represents the number 0 or 1; R3 represents a group of pyridine N-oxide according to formula A, B or C which is attached as shown by an unmarked linking: where R4, R5, R6 and R7 independently represent aryl, heterocycle, hydrogen, C1-C6-alkyl, C1-C6-alkylthio, C6-C12-aryloxy or C6-C12-arylthio group, C1-C6-alkylsulphonyl or C6-C12-arylsulphonyl, halogen, C1-C6-haloalkyl, trifluoromethyl, or heteroaryl group; or where two or more residues R4, R5, R6 and R7 taken together represent an aromatic ring, and where P represents a central part, preferentially chosen from regioisomers 1,3,4-oxadiazol-2,5-diyl, 1,2,4-oxadiazol-3,5-diyl, 4-methyl-4H-1,2,4-triazol-3,5-diyl, 1,3,5-triazine-2,4-diyl, 1,2,4-triazine-3,5-diyl, 2H-tetrazol-2,5-diyl, 1,2,3-thiadiazol-4,5-diyl, 1-alkyl-3-(alkoxycarbonyl)-1R-pyrrol-2,5-diyl, where alkyl is presented by methyl, thiazol-2,4-diyl, 1H-pyrazol-1,5-diyl, pyrimidine-2,4-diyl, oxazol-2,4-diyl, carbonyl, 1H-imidazol-1,5-diyl, isoxazol-3,5-diyl, furan-2,4-diyl, benzole-1,3-diyl and (Z)-1-cyanoethene-1,2-diyl, and where the regioisomers of the central part include both regioisomers produced by exchanging the nitrocatechol fragment and the -(X)n-(Y)m-R3 fragment. Also, the invention refers to a method for making a compound of formula I, as well as to a method for treating an individual suffering central and peripheral nervous system disorders, to a pharmaceutical composition based on the compounds of formula I, and also to their application for preparing the drug and as COMT inhibitor.

EFFECT: there are produced and described new compounds which show a potentially effective pharmaceutical properties in treating a number of central and peripheral nervous system disorders.

25 cl, 64 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I) where A denotes *-CO-CN=CH-, *-CO-CH2CH2-, or where the sign * indicates the thiophene bonding site in formula (I), R1 denotes hydrogen or methyl, R2 denotes n-propyl or isobutyl, R3 denotes hydrogen, methyl, ethyl, n-propyl, isopropyl or isobutyl, R4 denotes hydrogen or methoxy, R5 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy or hydrogen, R6 denotes -(CH2)k-(CHR65)p-CHR66-CONR61R62 hydroxy, hydroxy(C2-C4)alkoxy, di(hydroxy(C1-C4)alkyl)(C1-C4)alkoxy, 2,3-dihydroxypropoxy, -OCH2-(CH2)m-NHCOR64, -OCH2-CH(OH)-CH2-NR61R62, -OCH2- CH(OH)-CH2-NHCOR64 or -OCH2-CH(OH)-CH2-NHSO2R63, R61 denotes hydrogen, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylethyl, carboxymethyl or C1-C4alkylcarboxymethyl, R62 denotes hydrogen, R63 denotes methyl or ethyl, R64 denotes hydroxymethyl, methyl aminomethyl or 2-methyl aminoethyl, R65 denotes hydrogen, R66 denotes hydrogen, m equals 1 or 2, k equals 0, p equals 1, R67 denotes hydrogen, C1-C4alkyl or halogen, and to a salt thereof. The invention also relates to a pharmaceutical composition for preventing or treating diseases or disorders associated with an activated immune system based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as immunodepressants.

31 cl, 2 tbl, 114 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 1H-quinazoline-2,4-diones of formula and to their pharmaceutically acceptable salts where R1 and R2 have the values specified in cl. 1 of the patent claim. The specified compounds exhibit antagonistic activity with respect to the AMPA receptor.

EFFECT: reception of a pharmaceutical composition for preparing a preparation used for treating a condition mediated by the AMPA receptor and first of all for treating epilepsy or schizophrenia.

8 cl, 81 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula (I) and to its pharmaceutically acceptable acid-additive salts. The compounds under the present invention are active to bind cannabinoid (CB) receptor. In general formula (I) , X stands for -S-, -S(=O)-, -S(=O)2-, -S(=O)2N(H)-, -P(=O)(OCH3)-, -P(=O)(OH)-, -N(H)-, -N(CH3)-, -N(H)C(=O)N(H)-, -C(=O)-, -C(=O)O-, -N(H)C(=O)-, -C(H)(OH)-, -C(H)=N-, -C(H)=C(H)-, -CH2N(H)-or -C(=NH)-; R1 stands for phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indolyl, quinolinyl, 1,2,3,4-tetrahydroquinolinyl, isoquinolinyl, benzimidazolyl, 2-oxo-1,3-dihydrobenzimidazolyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl or indanyl which can be optionally substituted; R2 stands for hydrogen, -OR4 or -N(R5)R6; R3 stands for hydrogen; cyano; oxadiazolyl, piperazinyl or tetrazolyl optionally substituted with methyl; -C(=O)R7, -OR8 or N(R9)R10. Besides, the invention concerns method of producing compound of formula I and to pharmaceutical composition active to bind cannabinoid (CB) receptor, containing compound of formula I as an active component.

EFFECT: higher efficiency of compounds.

5 cl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel α-(N-sulfonamido)acetamides of the formula (I) or their optical isomers wherein values R1, R, R2 and R3 are given in the invention claim. Proposed compounds are inhibitors of production of β-amyloid peptide and can be used for inhibition of production of β-amyloid peptide. Also, invention relates to pharmaceutical composition based on these compounds and to a method for inhibition of production of β-amyloid peptide.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

22 cl, 23 sch, 4 tbl, 501 ex

The invention relates to new derivatives of pianolasociety, pharmaceutical compositions containing these derivatives, their use for the treatment of hypertension or asthma in mammals, including humans, and method for producing the above compounds and compositions

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the use of a metal of group 4 or 5 of the periodic system specified in titanium, zirconium, hafnium, niobium and tantalum, or its oxide for preparing a drug used for treating or preventing a disease characterised by undesired expression and/or release of interferon-γ inducible protein of weight 10 kDa, IP-10 in a subject. The invention also refers to a method of treating or preventing the disease characterised by undesired expression and/or release of interferon-γ inducible protein of weight 10 kDa, IP-10, which implies the extraction of a biological fluid in a subject suffering said disease, the ex vivo contact of the biological fluid and the metal specified in titanium, zirconium, hafnium, niobium and tantalum, or its oxide, the fluid return after the contact with the metal to the subject stated above. The invention also provides the use of the method stated above or its oxide for the in vitro removal of interferon-γ inducible protein of weight 10 kDa, and a method for removing said protein. The invention also refers to a device for biological fluid purification which comprises a purification chamber with a fluid inlet and outlet and containing metal particles specified in titanium, zirconium, hafnium, niobium and tantalum, or its oxide, used for biological fluid purification, and a filter coupled with the fluid inlet and outlet to prevent said particles from escaping from the purification chamber.

EFFECT: invention provides the selective decrease of expression and release of chemokine, namely interferon-γ inducible protein of weight 10 kDa, IP-10.

25 cl, 6 tbl, 16 dwg

FIELD: medicine.

SUBSTANCE: The invention relates to pharmacology, in particular, to medication for preventing or treating herpes labialis or herpes genitalis. The homeopathic medication or biologically active additive with anti-viral effect or preventing or treating herpes labialis or herpes genitalis contains: Nisylen, Cepa, Euphrasia, Belladonna and Mericulis Solubilis, furthermore, the components are present with a certain dilution and amount. The combination of the said components is used for production of homeopathic medication or biologically active additive with anti-viral effect or preventing or treating herpes labialis or herpes genitalis.

EFFECT: production of medication which effectively treats herpes labialis or herpes genitalis.

14 cl, 1 ex

FIELD: medicine.

SUBSTANCE: invention is referred to the field of medicine, namely to dermatovenerology and immunology and can be used for treatment of patients with sexually transmitted urogenital infections caused by chlamydiae and/or micoplasma. It includes the infusion of antibiotics of macrolides group or immunotropic drug that is selected individually, for which purpose the sensitivity of patient to immunotropic drugs is determined. That is done by in vitro definition of interferons in the samples of peripheral blood and urogenital scrapings before and after addition of each studies drug. As the result the immunotropic drug selected for treatment is the one that induces the increase of interferon activity in studied material by no less than 4 U/ml compared to the baseline level in the samples of peripheral blood and urogenital scrapings.

EFFECT: method provides for etiologic recovery, prevention of disease relapses, particularly due to effective interferons production on systemic and local level.

1 dwg, 4 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compounds of general formula in which is or (values of radicals are given in the claim), a method of producing said compounds, a pharmaceutical composition containing said compounds and therapeutic application thereof.

EFFECT: compounds are cysteine protease inhibitors and can be used in medicine.

25 cl, 1 tbl, 41 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly immunology, namely immunocorrection drugs, and can be used as an inducer of a granulocyte-macrophage colony-forming factor in cells of a mononuclear phagocyte system in vitro and for efferent therapy in pathological conditions accompanied by decrease in cell-mediated immunity. The drug represents oxidised dextrane of average molecular weight 35 - 65 kDa. The drug can be presented in the form of a solution or a nanoliposomal emulsion of the concentration of oxidised dextrane 1-5 wt %. The drug is applied by introduction in a cell culture of the mononuclear phagocyte system in an amount containing oxidised dextrane 125-250 mcg per culture medium 1 ml.

EFFECT: drug under the invention exhibits high biocompatibility.

8 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, and concerns an immunomodulatory drug preparation showing antiviral properties. Substance of the invention consists in the fact that the offered drug preparation contains sodium nucleinate 2 to 50 mg/ml, sodium chloride 3 to 10 mg/ml and apyrogenic water with pH making within 6.0 to 7.5.

EFFECT: preparation has a direct antiviral effect, suppresses reproductive ability of viruses.

2 cl, 3 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, namely to allergology, and can be used for prevention of development of respiratory allergies in a subject. That is ensured by introduction of an effective amount of Lactobacillus rhamnosus GG (LGG) either in a pregnant mother's body, and/or postnatal in a feeding mother's body, or in a subject directly.

EFFECT: introduction of LGG allows preventing an early allergic sensitisation and the following development of respiratory allergies due to higher production of serum antibodies IgA in a subject, and also prevention of allergic inflammation in lungs and respiratory ways.

12 cl, 13 ex, 9 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to optimised fused protein for blocking BLyS or APRIL, which contains extracellular region of N-end of truncated TACI (transmembrane activator and CAML-partner) and Fc sequence IgG. TACI segment of fused protein contains sequence of amino-end region of extracellular region, starting with 13-th amino acid residue, complete sequence of stem area from TACI and is obtained from native sequence of TACI between 12-th and 120-th amino acids. Segment Fc of immunoglobulin IgG of fused protein contains hinge region, CH2 region and CH3 region, TACI segment and Fc segment are fused either directly or through linker sequence. In addition, claimed is DNA sequence which codes fused protein, expression vector, host-cell, pharmaceutical composition, containing fused protein, and application of fused protein for blocking BLyS or APRIL. Obtained fused protein does not degrade in process of expression, possesses high biological activity and high level of expression.

EFFECT: fused protein in accordance with claimed invention can be used in treatment of diseases, associated with abnormal immunologic functions and in treatment of diseases caused by abnormal proliferation of B-lymphocytes.

10 cl, 6 dwg, 8 ex

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