Novel cysteine protease inhibitors, pharmaceutical compositions thereof and therapeutic application thereof

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

 

The text descriptions are given in facsimile form.

1. The compound of the formula:

in which
representsor
Ru, Rv, Rw is selected from the group consisting of halogen, NH2, Alk, AlkOAlk, aryl, Alk-phenyl, CF3With3-6cycloalkyl, -AlkOH, -CH2-(OS2H4)2-Och3,
each of R3, R4, R5, R6 represents the same or different groups which are independently selected from the group consisting of N, OAlk, Alk, Hal, HE F3;
Alk represents an aliphatic hydrocarbon group, simple or branched, having 1 to 20 carbon atoms, and
aryl represents an aromatic monocyclic or polycyclic hydrocarbon ring system of 6 to 14 carbon atoms.

2. The compound of formula (Ib) according to claim 1, in which
represents
and Ru are selected from Aryl, Alk, NH2Hal, Alk-phenyl, -AlkOH, -AlkOAlk,3-6cycloalkyl, -CF3, -CH2-(OC2H4)2-Och3.

3. The compound of formula (Ib) according to claim 1, in which R4=R5=H, and R3 and R6 are independently selected from the group consisting of H, Hal, Alk, OAlk, HE F3.

4. The compound according to claim 1, which is selected from the group consisting of:
1-Methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-is on
3-Methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
3-Amino-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Propyl-2,3,4,10,10a-pentasa-cyclopent[b]fluoren-9-it
3-Propyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Butyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Butyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Isobutyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Isobutyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Hydroxymethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Hydroxymethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Methoxymethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Methoxymethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Cyclopropyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Cyclopropyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Benzyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Benzyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Chloro-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
1-Bromo-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Bromo-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
6-Chloro-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
(7)-Chloro-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
7-Chloro-3-methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluo the EN-9-it
2-Methyl-2H-1,2,3,4,10-pentasa-cyclopent[b]fluoren-9-it
2-Benzyl-2H-1,2,3,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Isopropyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Isopropyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Trifluoromethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Trifluoromethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-[2-(2-Methoxy-ethoxy)-ethoxymethyl]-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-3-methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-6,7-dimethoxy-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-6,7-dimethoxy-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-1-propyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-3-propyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-5,8-dimethoxy-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-5,8-dimethoxy-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
6,7-Dihydroxy-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it.

5. A method of obtaining a connection to one of the preceding paragraphs, including the stage of interaction of the corresponding compounds of formulas (II) and (III):

in which R3, R4, R5, R6, T, U, V, W, X, Ru, Rv, Rw were defined as in any one of claims 1 to 4.

6. The method according to claim 5, in which R is an action carried out in an organic proton solvent in the presence of acid.

7. The pharmaceutical composition capable of inhibiting cysteinate comprising the compound of the formula

in which
representsor
Ru, Rv, Rw is selected from the group consisting of halogen, NH2, Alk, AlkOAlk, aryl, Alk-phenyl, CF3With3-6cycloalkyl, -AlkOH, -CH2-(OS2H4)2-Och3,
each of R3, R4, R5, R6 represents the same or different groups which are independently selected from the group consisting of N, OAlk, Alk, Hal, HE F3;
Alk represents an aliphatic hydrocarbon group, simple or branched, having 1 to 20 carbon atoms, and
aryl represents an aromatic monocyclic ring or polycyclic hydrocarbon ring system of 6 to 14 carbon atoms, and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, in which the compound of formula (Ib) as defined in any of claim 2 to 4.

9. The pharmaceutical composition according to claim 7, in which the specified compound of formula (Ib) selected from the group consisting of:
1-Methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Amino-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Amino-1,2,3 is,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Propyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Propyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Butyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Butyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Isobutyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Isobutyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Hydroxymethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Hydroxymethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Methoxymethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Methoxymethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Cyclopropyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Cyclopropyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Benzyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Benzyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Chloro-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
1-Bromo-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Bromo-1,2,3A,4,10A-pentasa-cyclopent[b]fluoren-9-it
6-Chloro-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
7-Chloro-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
7-Chloro-3-methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
2-Methyl-2H-1,2,3,4,10-pentasa-cyclopent[b]fluoren-9-it
2-Benzyl-2H-1,2,3,4,10-pentasa-cyclopent[b]luoren-9-it
1-Isopropyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Isopropyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Trifluoromethyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Trifluoromethyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-[2-(2-Methoxy-ethoxy)-ethoxymethyl]-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-3-methyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-6,7-dimethoxy-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-6,7-dimethoxy-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-1-propyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
6,7-Dimethoxy-3-propyl-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
1-Ethyl-5,8-dimethoxy-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it
3-Ethyl-5,8-dimethoxy-1,2,3A,4,10-pentasa-cyclopent[b]fluoren-9-it
6,7-Dihydroxy-1-methyl-2,3,4,10,10A-pentasa-cyclopent[b]fluoren-9-it.

10. The use of the compounds of formula (I), such as defined in any one of claims 1 to 4, to obtain drugs for inhibition of one or more cysteine proteases.

11. The use of claim 10, in which these cysteine proteases belong to one or several groups of enzymes deubiquitinase, caspases, cathepsins.

12. The use of claim 10, to obtain medicines for Leche is occurring and/or prevention of cancer and metastasis, neurodegenerative diseases, inflammatory disorders, cardiovascular diseases and/or viral and/or latent infections, where the specified compound inhibits one or more enzyme deubiquitinase.

13. The use of claim 10 for obtaining a medicinal product for the treatment and/or prevention of inflammatory disorders, neurodegenerative disorders, liver damage and liver failure resulting from acute or chronic infectious, ischemic or chemical liver damage, kidney damage and renal failure resulting from acute or chronic infectious, ischemic or chemical damage to the kidneys, heart failure and heart failure resulting from acute or chronic infectious, ischemic or chemical damage to the heart, diabetes, caused by acute or chronic autoimmune, chemical, oxidative or metabolic damage the insulin beta cells in the pancreatic Islands, where the specified compound inhibits one or more caspases.

14. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of cancer and metastasis, cardiovascular diseases, immunological disorders, diseases of the bones and the statutes, osteoporosis and arthritis, where the specified compound inhibits one or more of cathepsin(s).

15. The application 14, in which the disease of bones and joints is a osteoporosis or arthritis.

16. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of disorders occurring during aging, late diabetes and cataract, where the specified compound inhibits one or more kalainov.

17. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of viral infections and diseases, where the specified compound inhibits one or more viral cysteine proteases.

18. The application 17, wherein the specified viral infection and the disease is selected from hepatitis b And hepatitis C infections and diseases, activated by the SARS coronavirus, rhinoviral infections and diseases, adenoviral infections and diseases, polio.

19. The use of claim 10, for obtaining a medicinal product for treating and/or preventing bacterial infections and diseases, where the specified compound inhibits one or more cysteine proteases.

20. The application of claim 19, wherein the indicated bacterial infection or disease selected from streptococcal infections and diseases, infections and diseases caused by bacteria of the genus Clostridiumsp., staphylococcal infections and diseases, inflammatory diseases of the gums and periodontal diseases.

21. The application of claim 20, where the specified compound inhibits one or more bacterial cysteine proteases, which are selected from strathpine, clostridia, staphylococcal cysteine proteases, gingipain.

22. The use of claim 10, for obtaining a medicinal product for treating and/or preventing fungal infections and diseases, where the specified compound inhibits one or more fungal cysteine proteases.

23. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of protozoal parasitic infections and diseases, where the specified compound inhibits one or more cysteine proteases of parasitic protozoan organisms.

24. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of parasitic infections and diseases caused by tapeworms where specified compound inhibits one or more cysteine proteases of parasitic flatworms.

25. The use of claim 10, for obtaining a medicinal product for the treatment and/or prevention of parasitic infections and diseases caused by round worms, where the specified compound inhibits one or more cysteine is o proteases of parasitic roundworms.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione (glycoluril). The reaction takes place at 80°C for 60 minutes, where concentrated sulphuric acid is used in an aqueous medium and reagents are taken in the following molar ratios: glyoxal 2.0; urea 4.0; sulphuric acid 0.4; water 12, and the freshly prepared glyoxal solution is added while stirring for 20 minutes, after which the mixture is stirred for 40 more minutes.

EFFECT: novel method of producing glycoluril, which increases output of the end product and is simpler.

1 cl, 1 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 is selected from H, F, CI, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n equals 1-5; m equals 0 or 1; and Y is selected from CH2, NR3, (NR3R4)+X-, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X- is selected from pharmaceutically acceptable anions. The invention also relates to a method of producing said compound and to an antiviral pharmaceutical composition based on said compound of formula (I).

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19 cl, 2 tbl, 2 ex

FIELD: chemistry.

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6 cl, 32 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes a compound of general formula where A1 is selected from the following formula R1c denotes a hydrogen atom, a lower alkenyl group or a -Q3-A3(R1d)R1e group; A3 denotes a methane or lower alkyl group; Q3 denotes a single bond; R1d and R1e independently denote a hydrogen atom, hydroxyl group, lower alkyl group or hydroxyl-containing lower alkyl group, or together form a lower alkylene group in which one or two or more methylene groups constituting the lower alkylene group can be independently substituted with an oxygen atom; R1 denotes a lower alkenyl group or a lower alkynyl group; R2 denotes a phenyl, pyridyl or thienyl group, which can contain a -Q4-A4(R1g)R1h group; A4 denotes a nitrogen atom, a lower alkyl group optionally substituted with a hydroxy-lower alkyl group, or a methane group optionally substituted with a halogen atom, a hydroxyl group, a lower alkyl group or a hydroxy-lower alkyl group; Q denotes a single bond or a lower alkylene group in which one or two or more methylene groups constituting the lower alkylene group can be independently substituted with an oxygen atom; R1g and R1h independently denote a hydrogen atom, a lower alkyl group or a lower alkylsulphonyl group; R5 and R6 independently denote a hydrogen atom, a lower alkyl group or a hydroxyl-containing lower alkyl group, or a pharmaceutically acceptable salt thereof. The invention also describes a pharmaceutical composition based on compounds of formula I, having anti-cancer activity, an anticancer agent, a codrug, as well as an exposure sensitising agent containing the pharmaceutical composition.

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13 cl, 21 ex

FIELD: chemistry.

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EFFECT: said compounds are hepatitis C virus inhibitors and can be used in medicine.

3 cl, 6 ex

FIELD: chemistry.

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11 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula (I): or its pharmaceutically acceptable salt where Q is 2,6-pyrimidyl; where Q is optionally substituted by 1-5 substitutes JQ; Z is a link or NH; R1 is H; R2 is H; R3 is halogen or -(U)m-X where m is equal to 0; X is H or halogen; JQ is halogen, OCF3, -(Vn)-R", -(Vn)-CN or -(Vn)-(C1-4 halogenaliphatic group) where JQ is not H; V is C1-10aliphatic group where up to three methylene groups are substituted by GV where Gv is selected from -NH-, -NR-, -O-, -S-, -CO2-, -C(O)CO-, -C(O), -C(O)NH-, -C(O)NR-, -C(=N-CN)-, -NHCO-, -NRCO-, -NHSO2-, -NRSO2-, -NHC(O)NH-, -NRC(O)NH-, -NHC(O)NR-, -NRC(O)NR or -SO2-; and where V is optionally substituted by 1-6 substitutes JV; R" is H or an optionally substituted group selected from C1-6aliphatic group, C3-10cycloaliphatic group, C6-10aryl, 5-10-member heteroaryl or 5-10-member heterocyclyl; or two R" groups on the same substitute or various substitutes together with atom (s) whereto each group R" is attached, form optionally substituted 3-8-member heterocyclyl; where each optionally substituted R" group is independently and optionally substituted by 1-6 substitutes JR; R is an optionally substituted group selected from C1-6aliphatic group and C6-10aryl where each group R is independently and optionally substituted by 1-4 substitutes JR; each Jv and JR are independently selected from halogen, L, - (Ln)-R', - (Ln)-N(R')2, -(Ln)-OR', C1-4haloalkyl, -(Ln)-CN, - (Ln)-OH, -CO2R', -CO2H or -COR'; or two Jv, JR groups on the same substitute or various substitutes together with atom (s) whereto each group JV and JR is attached, form a 5-7-member saturated, unsaturated or partially saturated ring; R' is H or C1-6aliphatic group; L is C1-6aliphatic group where up to three methylene units are substituted by -C(O)-; each n is independently equal to 0 or 1. Besides, an invention refers to of a pharmaceutical composition for ROCK or JAK kinase inhibition on the basis of the given compounds, to a method of ROCK or JAK kinase activity inhibition, and also to application of the compounds of formula I, for preparing a drug where Q, Z, R1, R2 and R3 are those as described in cl. 1 of the patent claim, effective as protein kinase inhibitors, especially JAK and ROCK families kinase inhibitors.

EFFECT: there are prepared and described new compounds which can find the application in medicine.

42 cl, 6 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolopyrimidines of general formula (I) or pharmaceutically acceptable salts thereof, having JANUS: JAK2, JAK3 protein kinase, protein kinase A (PKA), serine/threonine protein kinase ROCK inhibiting properties. The compounds can be used to treat such diseases as allergy, asthma, atopic dermatitis and others. In structural formula (I): R1 denotes H; R2 denotes H; Z1 denotes C1-6aliphatic group or C5-7cycloaliphatic group, optionally substituted with 0-1 groups Jz; if the bond between Z1 and C is a double bond, then Z1 can also denote =O or =C(R)2; Z2 denotes H; or C1-10halogenalkyl, -(Vn)-CN, (Vn)-(heterocyclyl), where the heterocyclyl is a 6-member ring containing a nitrogen atom or two oxygen atoms as heteroatoms, -(Vn)-(phenyl) or -(Vn)-(C3-10cycloaliphatic group), optionally substituted with 0-1 groups Jz; or Z1 and Z2 together with the carbon atom with which they are bonded form a ring Q; Z3 denotes H or C1-6alkyl, optionally substituted with 0-1 groups Jz; or Z1, Z2 and Z3 together with the carbon atom with which they are bonded form a 6-8-member saturated bicyclic ring Q; where if the bond between Z1 and C is a triple bond, then Z2 and Z3 are absent; if the bond between Z1 and C is a double or triple bond, then Z3 is absent or Z2 and Z3 are absent; Q denotes a 3-8-member saturated or partially saturated monocyclic ring containing 0-2 heteroatoms selected from nitrogen, oxygen or sulphur, where said Q is optionally and independently condensed with Q1; where said Q is optionally substituted with 0-4 groups JQ, where said Q is optionally substituted with 0-4 groups JQ. Values of other radicals are given in the claim.

EFFECT: high efficiency of using the compositions.

35 cl, 5 dwg, 5 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel conformationally stable compounds of general formula (I), which imitate the secondary structure of reverse-configuration regions of biologically active peptides and proteins which are reverse-configuration mimetics. The compounds can be used to inhibit or treat disorders modulated by Wnt-signalling pathway, such as cancer, especially colorectal cancer. The invention also relates to a library containing the disclosed compound. In general formula (I), A denotes -(C=O)-, B denotes -(CHR4)-, D denotes -(C=O)-, E denotes -(ZR6)-, G denotes -(XR7)-, Z denotes CH, X denotes a nitrogen atom, W denotes -(C=O)NH-, R1 denotes benzyl; R2 denotes a heterocyclylC1-6alkyl group, including a 9-member condensed bicyclic ring having 2-3 heteroatoms selected from nitrogen, oxygen or sulphur atoms; a substituted hetercyclylC1-6alkyl group, including a 9-member condensed bicyclic ring having 2-3 heteroatoms selected from nitrogen, oxygen or sulphur atoms, an the ring has 1-3 substitutes independently selected from a group comprising halogen, piperidinyl, morpholinyl, C2-6alkenyl, phenyl, hydroxyphenyl, C1-6alkoxycarbonyl, dialkylamino, hydroxypiperidinyl, C1-6alkyl, hydroxyC1-6alkylpiperazinyl, amino, piperidinyl carbonyl; heterocyclyl-C1-6alkyl group having a 9-member condensed bicyclic ring which has one or two nitrogen atoms; and other values given in the claim. R4 denotes a substituted benzyl, having a substitute selected from disodium phosphate, monosodium phosphate, phosphate; R6 denotes hydrogen; R7 denotes: C1-6alkyl; C1-6alkynyl; C2-6alkenyl; substituted benzyl, having one or more substitutes independently selected from halogen and C1-6alkyl.

EFFECT: high efficiency of the compounds.

8 cl, 34 dwg, 19 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: described is a method of producing novel compounds of general formula , where NR1R2=NH2; NHAlk, where Alk=C1-C6, or cycloalkyl-C3-C6; NAlk2, where Alk=C1-C6, or cycloalkyl-C3-C6; N(CH2)n, where n=2, 3, 4, 5, 6; N(CH2CH2)2O; NHAr, where Ar=C6H5, C6H4R3, where R3=Alk(C1-C6), NO2, halide, which can be used as biologically active substances and intermediate products in synthesis of biologically active substances (anomalous nucleosides, nucleotides etc). Sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazin-7-ones are obtained via successive substitution of chlorine atoms in 2-NR1R2-4,6-dichloro-1,3,5-triazines with a hydroxy and azido group. The corresponding 2-NR1R2-4,6-dichloro-1,3,5-triazine reacts with aqueous sodium hydroxide solution followed by acidation and the obtained 4-NR1R2-6-chloro-(3H)-1,3,5-triazin-2-one is treated with sodium azide in an organic solvent such as acetone, acetonitrile, dimethylformamide or mixtures thereof.

EFFECT: obtaining sodium salts of 5-NR1R2-tetrazolo[1,5-a]-1,3,5-triazin-7-ones directly from 2-amino-4,6-dichloro-1,3,5-triazines without obtaining and use of bis- and mono-trinitromethyl-1,3,5-triazines.

1 cl, 2 tbl, 3 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

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to immunomodulatory interleukin-1 drugs. An interleukin composition contains interleukin-1, a cyclooxygenase inhibitor - diclofenac, taken in certain proportions.

EFFECT: compositions exhibit higher efficacy and have no side effects.

6 cl, 5 tbl, 6 ex

Amide derivatives // 2427575

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I), where m equals 1-2, and each R1 (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylthio, hydroxy-(2-6C)alkoxy, amino-(2- 6C)alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di[(1-6C)alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, halogen-(2-6C)alkylamino, amino-(2-6C)alkylamino, (1-6C)alkoxy-(2-6C)alkylamino, (1-6C)alkylamino-(2-6C)alkylamino, di-[(1-6C)alkyl]amino-(2-6C)alkylamino, heterocyclyl, heterocyclyl-(1-6C)alkyl, heterocyclyloxy, heterocyclyl-(1-6C)alkoxy and heterocyclylamino, where heterocyclyl is a 3-7-member monocyclic saturated ring containing one or two heteroatoms selected from nitrogen, oxygen and sulphur, wherein the heterocyclyl can have 1-2 substitutes defined in claim 1, and any of the substitutes R1 given above, which contains a CH3 group bonded to a carbon or nitrogen atom, can contain a substitute given in claim 1, R2 is a halogen, trifluoromethyl or (1-6C)alkyl; R3 is hydrogen, and R4 is hydroxy, (1-6C)alkyl or (1-6C)alkoxy; or pharmaceutically acceptable salts thereof. The invention also relates to methods for synthesis of said compounds, pharmaceutical compositions based on said compounds, and use of said compounds in treating diseases or medical conditions mediated by cytokines.

EFFECT: more effective use of the compounds.

13 cl, 8 tbl, 15 ex

Heterocompound // 2425832

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or pharmaceutically acceptable salt thereof, where symbols assume the following values; ring denotes

or , X denotes a single bond, -CH2-, -NR3-, -O-, -S-, R1 denotes a halogen; phenyl; pyridyl; (C3-C8)cycloalkyl; or (C1-C6) alkyl or (C2-C6) alkenyl, each of which can contain a halogen, -CONH2, phenyl or (C3-C8)cycloalkyl as a substitute, R2 denotes CN, -O-(C1-C6)alkyl, -C(=O)H, halogen; or (C1-C6)alkyl, which can be substituted with a halogen or -OH, R3 can form morpholino or 1-pyrrolidinyl together with R1 and nitrogen, and when X denotes a single bond, R1 and R2 can jointly form a 5-member ring and additionally contain -(C1-C6)alkyl as a substitute, R4 denotes the following ring: , , , , , , , , , , or , where any one of the bonds in the ring is linked to an oxazole ring, R5 denotes -H, (C1-C6)alkyl, which can be substituted by not less than one group selected from: -C(=O)NRXRY, -NHRX and -ORX- (C2-C6)alkenyl-; -C(=O)H; -C(=O)NRXRY, RX and RY can be identical or different and denote -H; or (C1-C6)alkyl. The invention also relates to a pharmaceutical composition based on said compounds, having SlP1 agonist activity.

EFFECT: compounds and compositions can be used in medicine for preventing and treating rejection during organ transplant, bone marrow or tissue transplant and autoimmune diseases.

16 cl, 84 tbl, 198 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, also aims at treating babies suffering intestinal colics. A mother and a breast-fed child are treated simultaneously. A cephalosporin antibiotic, an antistaphylococcal immunoglobulin, a staphylococcal bacteriophage, an antifungal agent, a phagocytosis activator are prescribed in the mother for 7-10 days. A staphylococcal bacteriophage, Hylak forte are prescribed to the baby. The second stage involves prescribing a bacterial preparation, an immunomodulator and a therapeutic staphylococcal anatoxin. The baby intakes Hylak forte and the bacterial preparation.

EFFECT: method allows relieving intestinal colics and preventing the development of complications.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to immunology and clinic laboratory diagnostics, and can be used to predict course of acute respiratory viral infections (ARVI) in children in the first days of disease and timely administration of immunomodulating medications. For this purpose by means of ELISA immunologic indices of spontaneous and induced interferon-γ in vitro (IFH-γ) are determined. Index of interferon-γ stimulation (IS IFH-γ) is calculated by division of index of induced level by index of spontaneous level of interferon-γ. Also carried out is calculation of lymphocyte activation index (LAI IFH-γ) per 1000 lymphocytes by division of index of induced interferon-γ by absolute number of patient's lymphocytes. Additionally in blood plasma determined is content of interleukin-10 (IL-10). If values of IS IFH-γ are higher than 3, LAI IFH-γ equals or is higher than 40, IL-10 is from 30 to 60 pg/ml favourable outcome of disease is predicted with therapeutic treatment which does not include immunomodulators. If IS IFH-γ is lower than 3, LAI IFH-γ is lower than 40, IL-10 is from 60 to 100 pg/ml, predicted are severe course of disease and development of complications, which requires urgent treatment by immunomodelling therapy. If IS IFH-γ is lower than 3, LAI IFH-γ is lower than 30, IL-10 is higher than 100 pg/ml, predicted are severe course of disease with development of bronchopulmonary complications and possible chronisation of pathologic process and recurrent ARVD, which requires additional introduction of immunomodelling medications.

EFFECT: increase of accuracy of early prediction of disease course severity and development of complications in children with ARVI, including those from 1 month old, which makes it possible to carry out necessary anti-viral and immunomodelling therapy, aimed at strengthening immunity cell responses, in due time.

3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the application of a biologically active peptide which represents the amino acid sequence SEQ ID No.1.

EFFECT: preparation of a drug for modulation of at least one of the following conditions: fatigue, liver glycogen level and blood lactic acid level.

30 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula or pharmaceutically acceptable salt thereof, synthesis methods thereof, pharmaceutical compositions containing said compounds, and use thereof to prepare a medicinal agent having mTOR kinase and/or PI3K kinase inhibiting action.

EFFECT: improved properties of the derivatives.

15 cl, 72 ex

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