Antiviral agent for preventing and treating tick-borne encephalitis

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, particularly to application of an antiviral agent - 2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7-one dehydrate sodium salt (hereinafter - the Agent) for preventing and treating viral diseases caused by a tick-borne encephalitis virus. Also, there is described method for preventing and treating conditions caused by the tick-borne encephalitis virus in humans and animals involving introduction of the Agent presented above to humans and animals.

EFFECT: extended range of the drug preparations possessing a wide spectrum of action and used for treating and preventing tick-borne encephalitis.

20 cl, 2 ex, 1 tbl

 

The invention relates to medicine and pharmacy, in particular for the treatment and prevention of viral diseases, mainly caused by the tick-borne encephalitis virus.

In recent years in Russia and abroad are conducted intensive research on the development of chemotherapeutic agents for the treatment and prevention of viral infections. Special attention is paid to infections that occur with lesions of the Central nervous system (rabies, tick-borne encephalitis and other), which causes an acute disease with high mortality and severe post-infectious complications (see, for example, Ipparently, Omotowa, Gagalov and other Antiviral substances. - Riga, 1982. - P.7-8; Pierson, Ipparently. Questions Virology. - 1983. No. 4. - 74-78).

The incidence of people with tick-borne encephalitis is very topical at the present time for many areas of the Russian Federation. Currently available vaccines are not effective enough. Tick-borne encephalitis in epidemiological significance, severity of infection and mortality occupies a significant place among the natural focal viral infections (see, for example, DLO, Smolenko, Sahidic. Arboviruses and arboviral infections. - M., 1989. - 336 S.; Npisaa, Ikhsanov, ISA and other Antiviral substances in experimental therapy in the originate infections. - Minsk, 1986. - C-85; Abhorrence, ISA. Antiviral substances in experimental therapy of viral infections. - Minsk, 1986. - P.85-89). Currently, there are units effective and approved for use low molecular weight anti-viral compounds. Abroad for treatment and prevention of viral infections using such compounds as acyclovire, rib, amantadine, azithomycin and others, in our country, have found wide application rimantadine, ribamidil, exolon, methisazone, magasin, Poludan etc. These drugs are most often used in the treatment of mumps in children, influenzal pneumonia, genital herpes, shingles (see, for example, Higareda, Tuvalu, Wmerican. Questions Virology. - M - 1993. No. 1. - P.18-21; F.I.Hayden, R.I.Douglas, R.Simons. Antimicrob Agents chemother. - 1980. - Vol.18 - P.536-541).

One of the promising antiviral drug compounds for the treatment of tick-borne encephalitis is the sodium salt of 2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazine-7-she dehydrate (next Tool).

To date, the strategy of selection of efficient non-specific medical remedies for a number of viral infections described in the Guidelines for the preclinical evaluation of drugs (see Manual on experimental (preclinical) study of new pharmacological substances. ), The Ministry of health, 2005).

The technical result, which is aimed by the invention, is to expand the range of drugs with a broad spectrum of activity and intended for the treatment and prevention of tick-borne encephalitis virus.

This technical result is achieved by the fact that according to the invention for the treatment and prevention of tick-borne encephalitis used anti-inflammatory and antiviral drug.

While the disease or condition is a tick-borne encephalitis, caused by the tick-borne encephalitis virus, the drug is intended for system introduction using a metered quantity of a medicinal product, for example 30-100 mg/kg for the treatment and prevention of diseases.

The drug is made in the form of a solution, tablets or capsules and is intended for administration to humans, domestic and farm animals orally or by injection.

Technical solutions, which coincides with the set of essential features of the claimed invention, is not revealed, which allows to make a conclusion on the compliance of the claimed invention to such a condition of patentability as "novelty".

Declare the essential features that determine the receipt of the indicated technical result, avn is m not follow from the prior art, that allows to make a conclusion on the compliance of the claimed invention to such a condition of patentability as "inventive step".

The condition of patentability "industrial applicability" is confirmed by examples of specific performance.

Study of antiviral activity Means were carried out in experiments on cell cultures and in experimental infection of mice tick-borne encephalitis.

Statistical processing of the obtained results was performed by standard methods (see Gracin. Biometrics. - M - 1990).

Example 1.

To study the antiviral activity Funds in the cell culture spew used 24-hole tablets using methods JRC and belascoaran by the following schema.

Scheme 1. 1.1. The monolayer of cells in flasks T-25 were infected with tick-borne encephalitis virus with a multiplicity of 0.01 PFU/cells

1.2. After adsorption of the virus within 60 min monolayer cells were thoroughly washed with Hanks solution and pour 6 ml of the medium support Vehicle at a concentration of 0.5 μg/ml

1.3. Daily sampling for further research.

1.4. Scan sampling method belascoaran.

Scheme 2. 2.1. 20 mice weighing 18-20 g were injected intraperitoneally at 12 mg per 1 animal.

2.2. After 18 hours the mice were taken totally blood and received the serum by conventional methods is the IR.

2.3. Serum iactiveaware at 56°C for 30 minutes

2.4. The virus was titrated by ten-fold dilutions from 10-1up to 10-9and added into 24-well plates (1 breeding in 4 wells). The virus was adsorbing within 60 minutes

2.5. After adsorption contributed agar floor, while the serum of fetuses of cows was replaced with serum of mice containing the Tool.

2.6. Accounting experiment was carried out for 4-5 hours.

In our experiments we worked 2 experiments with a constant dose Funds 0.5 μg/ml (which is 1/16 of the dose acute toxicity in cell culture). For experimental infections were prepared by 10-fold dilution of the virus on support environment (working environment 199 + 2% serum fruits cows). When identifying antiviral activity Funds method JRS using a dose of 0.5 μg/ml and 1 μg/ml cytopathic effect occurred simultaneously for 4-7 days depending on the dose of virus in the experience and in control. Further study of the antiviral activity Means were carried out by the method of belascoaran.

2-3-day cell culture spew grown in 24-hole tablets, infected 10-multiple dilutions of the virus. After adsorption of the virus within 60 minutes in the tablets were made and 1 ml agar coating with 1 μg/ml in final volume. For 4-5 hours monolayer cells were fixed, and then stained with crystal the ical purple and count the plaques. In experiments using the scheme No. 1 marked decrease in the reproduction of the virus in 10 times.

In the experiments, the set of scheme 2, noted a decrease in the reproduction of the virus in 100 times. For the production of these experiments the serum from mice were obtained and used in the day of production experience. When conducting experiments using serum stored at -70°C, reduce the reproduction of the virus is not marked.

Thus, when introducing Means at a dose of 0.5 μg/ml and 1 μg/ml in an environment of support and agar surface, as well as when using the serum of mice containing the Tool, marked decrease in the reproduction of the virus from 10 to 100 times.

Example 2.

To study the antiviral activity Funds in the model of experimental infection of mice tick-borne encephalitis used white mice weighing 18-20, Animals were infected intraperitoneally 0.5 ml of tenfold dilutions of the virus - 4 animals per dilution. The tool was administered at various times at 3 and 12 mg per 1 animal. The titer of the virus was calculated by the method of reed and turns into a hissing drone.

This work has adopted the following schemes Means of laboratory animals.

Scheme 1. 1.1. The virus was injected intraperitoneally in 0.5 ml two groups of animals.

1.2. After 6 days, the experimental group of animals were administered the Vehicle 12 mg per 1 animal.

1.3. After 24 h the same group of animals, e.g. the or 3 mg to 1 animal before the end of the clinical manifestations of infection in the control group of animals.

Scheme 2. 2.1. The tool was administered for 6 days before the introduction of the virus in a dose of 12 mg per 1 animal every 24 hours

2.2. On the seventh day simultaneously administered 12 mg Tools and 0.5 ml of the virus in the working dose of one animal.

Scheme 3. 3.1. Means at a dose of 3 mg per 1 animal was administered the day before the introduction of the virus.

3.2. After 2 h after infection has introduced the Tool in a dose of 3 mg

3.3. In further conducted daily injection Means at a dose of 3 mg until the end of the clinical manifestations in the control group.

Scheme 4. 4.1. 12 mg per 1 animal was injected on the day of introduction of the virus.

4.2. Every 24 h was administered 3 mg Money before the end of the clinical manifestations of infection in the control group of animals.

For all groups of animals were monitored for 30 days. Account of experiments were carried out daily for clinical signs and mortality.

Evaluation of the antiviral effect Means were carried out by three parameters: the manifestation of clinical signs of infection, the survival rate of animals and increase life expectancy.

The main results are presented in the table. From the data obtained it follows that the Tool has antiviral activity. Intraperitoneal injection of Funds creates some protection of animals against experimental infection. Antiviral activity was noted on the test of survival of the animal, as well as the increase in average life expectancy (ALE) from 17 to 25 days. Reducing the dose of administered Funds up to 3 mg per 1 animal (that was 1/32 dose-dependent acute toxicity) caused the animals from experimental infection up to 70%.

Results of a study of the effectiveness of extra-preventive action of the Tools on white mice infected with tick-borne encephalitis virus, are presented in table 1.

Table 1
The effectiveness of extra-preventive action of the Tools on white mice infected with tick-borne encephalitis virus
The group of animalsThe method of introduction of the virusDose Means, route of administrationThe number of injections of the virusThe number of injections FundsALEThe death of animals in %
acute controlp/0.5 ml-1-16,6765
scheme 1 p/0.5 ml12 mg/kg and 3 mg/kg/br 0.5 ml1816,650
scheme 2p/0.5 ml12 mg/kg/br 0.5 ml1425,030
scheme 3p/0.5 ml3 mg/kg/br 0.5 ml1616,6760
scheme 4p/0.5 ml12 mg/kg and 3 mg/kg/br 0.5 ml11220,030
Note: p/ - subcutaneous;/br - intraperitoneally

Thus, the introduction of Tools for prophylactic prevention of infection were protected from death to 70% of the animals. The average life expectancy of lethally infected animals as a result of Funds increased by 8.3 days.

The invention contributes to expanding the range of drugs, with a wide range of actions and intended for the treatment and prevention of tick-borne encephalitis virus.

1. The use of antiviral agents - sodium salt of 2-methylthio-6-nitro-1,2,4-triazolo[5,1-C]-1,2,4-triazine-7-it dihydrate (next Tool) for the prevention and treatment of viral diseases caused by tick-borne encephalitis virus.

2. The use according to claim 1, wherein the disease or condition is a tick-borne encephalitis.

3. The use according to claim 1, characterized in that the medicinal product is intended for system administration.

4. The use according to claim 1, characterized in that use metered quantity of the drug.

5. The use according to claim 1, characterized in that the specified Tool is intended for administration to humans, domestic and farm animals.

6. The use according to claim 1, wherein the drug is administered orally.

7. The use according to claim 1, wherein the drug is administered by injection.

8. The use according to claim 6, characterized in that for the treatment and prevention of diseases of the number of drugs in each dosed amount of 30-100 mg/kg

9. The use according to claim 1, characterized in that the drugs are made in the form of tablets.

10. The use according to claim 1, otlichayas the same time, what drug is made in the form of capsules.

11. The use according to claim 1, characterized in that the drugs are made in the form of injectable form.

12. The way to prevent and treat conditions caused by tick-borne encephalitis virus, human or animal, characterized in that it comprises the administration to a human or animal suffering from a disease or condition, medications (sodium salts of 2-methylthio-6-nitro-1,2,4-triazolo[5,1-C]-1,2,4-triazine-7-it dihydrate.

13. The method according to item 12, wherein the medical treatment and disease prevention.

14. The method according to item 12, wherein the disease is a tick-borne encephalitis.

15. The method according to item 12, characterized in that the introduction of the drugs carry a metered amount.

16. The method according to item 12, wherein the drug is administered orally.

17. The method according to item 12, characterized in that for the treatment and prevention of diseases of the number of drugs in each dosed amount of 30-100 mg/kg

18. The method according to clause 16, the drug is made in the form of tablets or capsules.

19. The method according to item 12, wherein the drug is administered by injection.

20. The method according to item 12, wherein the drug is made in the form in which actionnow form.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolo-[1,2-a]benzimidazole derivatives of formula I , where NR2 assumes morpholino or diethylamino values, and Ar is 4-methoxyphenyl or 4-chlorophenyl, having antioxidant and antiradical properties.

EFFECT: obtaining novel sulphates possessing useful biological properties.

2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

FIELD: chemistry.

SUBSTANCE: present invention refers to the field of organic chemistry, notably to derivatives of dihydroimidazole with the general formula (I) and to its pharmaceutically acceptable salts where X1 and X2 denote halogen; R1 and R2 are chosen from the group including -H, -CH3, -CH2CH3 on the condition that both R1 and R2 do not denote hydrogen; R3 denotes -H or -C(=O)-R7; and if R6 denotes hydrogen, then R4 denotes -OCH3, -OCH2CH3 or -OCH(CH3)2; R5 denotes -H, - halogen, -CF3, -OCH3, -C(CH3)2, - cyclopropyl, - cyano group, -C(CH3)3, -C(CH3)2OR (where R denotes -H), -C(CH3)2CH-OR (where R denotes -CH3), -C(CH3)2CN, -C(CH3)2COR (where R denotes -CH3), -SR (where R denotes -CH2CH3) or -SO2R (where R denotes -CH3, -CH2CH3, 1-pyrrolidine, -NH-tert-butyl); and if R6 does not denote hydrogen, then R4 denotes -OCH2CH3; R5 denotes hydrogen, -Cl, -OCH3, tert butyl; R6 denotes -Cl, cyclopropyl, -SO2R (where R denotes -CH3, 1-pyrrolidine, -NH-tert-butyl or -N(CH3)2); and R7 is chosen from the group including i) -CH3, -CH(CH3)2, -CH2CH(CH3)2, cyclopropyl, cyclobutyl, -CH2CH2Ph, 2-furanyl, phenyl or phenyl substituted with chlorine, -OCH3 or cyano group, ii) 1-piperidinyl, iii) -NRc2 (where Rc denotes -CH2CH2OH, -CH2CH2OCH3 or -CH2CH(OH)CH2OH, iv) substituted piperazidine with the formula where R is chosen from the group including a) hydrogen, c) -CH(CH3)2, k) -CH2CH2Rd (where Rd denotes -OH, -OCH3, -CF3, -SO2CH3, -NH2, -NHCOCH3, -NHSO2CH3, 4-morfolinil, 2-izotiazolidinil-1, 1-dioxide), l) -CH2CH2CH2Re (where Re denotes -OCH3, -SO2CH3, -SO2CH2CH3, -CN), m) -CH2-CO-Rh (where Rh denotes -NH2, 1-pyrrolidinyl, 4-morfolinil), n) -SO2Ri (where Ri denotes -CH3, -CH2CH3), o) -CORj (where Rj denotes -CH3, 2-tetrahydrofuranyl, -NH2, -N(CH3)2), p) 4-tetrahydro-2H-thiopiranyl-1,1-dioxide, q) 4-piperidinyl-1-acetyl, r) 4-piperidinyl-1-dimethylcarboxamide, and s) 3-tetrahydrothiophenyl-1,1-dioxide; v) substituted oxopiperazine with the formula where R denotes -H; and vi) substituted piperidine with the formula where R denotes -CONH2, -OH, -CH2OH, -CH2CH2OH, 1-pyrrolidinyl, 1-piperidinyl, 1-(4-methylpiperazinyl) or 4-morfolinil. Moreover, the invention refers to the pharmaceutical composition based on the compound with the formula (I), to application of the formula (I) compound for production of a drug, to the production process of the formula (I) compound.

EFFECT: new derivatives of dihydroimidazole that may be used as anticancer drugs.

40 cl, 204 ex

FIELD: pharmachology.

SUBSTANCE: invention describes new compounds with general formula (I-c) Where R1 is a radical (d-1) or (d-2) (radical values are given in the invention formula) and pharmaceutical composition containing them. The described compounds are the hepatitis C inhibitors and can be used in medicine.

EFFECT: enhanced hepatitis C inhibition.

5 cl, 1 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds selected from a group consisting of compounds of formula: and or to their pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition, as well as to using at least one compound under cl.1 and/or its pharmaceutically acceptable salts.

EFFECT: preparing new biologically active compounds which exhibit the properties of cycline-dependent kinase inhibitors.

11 cl, 86 tbl

Kinase inhibitors // 2440352

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula : a pharmaceutically acceptable salt or solvate thereof, having Syk kinase inhibiting properties. The invention also relates to a pharmaceutical composition containing said compound, methods of treating diseases whose development is aided by c-kit receptor activity, such as arthritis, rheumatoid arthritis, tumours, mantle cell lymphoma, as well as a method of inhibiting angiogenesis.

EFFECT: improved method.

13 cl, 4 tbl, 10 dwg

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: 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).

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used in medicine to treat a viral diseases such as herpes.

19 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel macrocyclic compounds of formulae pharmaceutically acceptable salts or stereoisomers thereof, where R1 = -OR5, -NH-SO2R6; R2 = hydrogen; R3 = C1-6-alkyl; R4 = isoquinolinyl, possibly substituted; n equals 4 or 5; R5 = hydrogen; R6 = C3-7-cycloalkyl, and a pharmaceutical composition containing said compounds.

EFFECT: novel compounds have hepatitis C virus replication inhibitory action and can be used in medicine.

6 cl, 32 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or tautomer thereof

or enantiomer or physiologically acceptable salt, where R1 is o-bromo, R2 is n-fluoro, R3 is C1-C4 alkyl, R6 is thiazolyl-2-yl, X is methylene and Z is morpholinyl. The invention also relates to methods of producing (versions) compounds of formula (I) and (Ia). The compound of formula (I) or (Ia) is used to prepare a pharmaceutical composition for treating or preventing HBV infections and HBV-induced diseases such as hepatitis B.

EFFECT: bromophenyl substituted thiazolyl dihydropyrimidines for HBV infection control.

20 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to an immunodepressant based on a heterocyclic compound of formula

or to its pharmaceutically acceptable salt where X represents a nitrogen atom or CH, both or one of R1 or R2 represents a hydrogen atom, hydroxyl, a halogen atom, an amino group, C1-C6 alkoxy or C1-C6 alkyl: R3 represents a hydrogen atom, difluoromethyl, an amino group, methyl or hydroxymethyl; R4 or R5 represents a hydrogen atom or C1-C6 alkyl; R6 represents morpholino (optionally substituted by one or two C1-C6 alkyl groups), pyrrolidinyl (optionally substituted by hydroxy C1-C6 alkyl), piperidine (which is optionally substituted by an oxygen atom, hydroxyl, formyl or C1-C6 alkyl), piperazinyl (optionally substituted by one or two oxygen atoms, where a nitrogen atom in position 4 is optionally substituted by a substitute selected from a groups consisting of formyl, C1-C6 hydroxyalkyl, C1-C6 alkoxycarbonyl, C1-C6 oxoalkyl, furoyl, benzoyl, methoxybenzoyl, benzylcarbonyl, dimethylcarbamoyl, diethylcarbamoyl, morpholinocarbonyl and methoxyacetyl) or 1,4-diazepano (optionally substituted by one oxygen atom where a nitrogen atom in position 4 is optionally substituted by a substitute selected from a group consisting of formyl, C1-C6 oxoalkyl). Also, the invention refers to a heterocyclic compound of general formula

and to an anticancer drug based on the compound of formula (II).

EFFECT: there are produced new immunodepressant based on the compound of formula (I) and compound of formula (II) which can be used as anticancer drugs.

12 cl, 8 tbl, 60 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology and can be used for treating chronic infectious prostatitis. That is ensured by prescribing antibiotics to be responded: fluoroquinolones, or tetracycline, or macrolides. The dietary supplement Rekicene-RD is prescribed 1-2 tablespoons 3 times a day during meal for 8 weeks.

EFFECT: method provides prevention of relapses, as well as improvement of a remote therapeutic effect.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula:

in which: X represents one of the following groups: - a phenyl group optionally substituted by one or more groups, optionally selected from one of the following atoms and groups: halogen, (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkoxy, NRaRb, R1 represents hydrogen atom, halogen, (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkoxy, amino, the group NRcRd; with the alkyl and alkoxy groups being optionally substituted by one or more halogens, hydroxy, amino or (C1-C6)alkoxy, R2 represents one of the following groups: -hydrogen atom, - (C1-C6)alkyl group optionally substituted by one or more groups optionally substituted by hydroxy, halogen, amino, the group NRaRb, the phenyl group, the - (C1-C3)alkoxygroup optionally substituted by one or more groups independently selected from hydroxy, halogen, amino, the group NRaRb, - (C3-C7)cycloalkyl((C1-C6)alkyl, - (C3-C7)cycloalkyl(C1-C6)alkoxy, -(C2-C6)alkenyl, - (C2-C6)alkinyl, - the group -CO-R5,- the group -CO-NR6R7,- the group -CO-O-R8,- the group -NR9-CO-R10,- the group -NR11R12,- halogen atom,- the cyanogroup,- the phenyl group optionally substituted by one or more groups optionally selected from the following atoms and groups: halogen, (C1-C6)alkoxy, NRaRb, -CO-R5, -CO-NR6R7, -CO-O-R8, (C3-C7)cycloalkyl(C1-C6)alkyl, (C3-C7)cycloalkyl(C1-C6)alkoxy, (C1-C6)alkyl group optionally substituted by one or more hydroxy groups or NRaRb R3 represents hydrogen atom, (C1-C6)alkyl, (C1-C6)alkoxy or halogen atom, R4 represents hydrogen atom, (C1-C4)alkyl, (C1-C4)alkoxy or fluorine atom, R5 represents hydrogen atom, the phenyl group or (C1-C6)alkyl, R6 and R7, the same or different represents hydrogen atom or (C1-C6)alkyl, or together with nitrogen atom forms a 4-7-member cycle optionally containing the other heteroatom selected from N, O or S,R8 represents (C1-C6)alkyl, R9 and R10, the same or different, represent hydrogen atom or (C1-C6)alkyl, R11 and R12, the same or different, represent (C1-C6)alkyl, or together with nitrogen atom form a 4-7-member cycle optionally containing the other heteroatom selected from N, O or S, Ra and Rb independently represent hydrogen atom, (C1-C6)alkyl or together with nitrogen atom form a 4-7-member cycle, Rc represent hydrogen atom, and Rd represents (C1-C6)alkyl and at least one of the substitutes R1, R2, R3 and R4 are different from hydrogen; and when R3 means methyl, X is unsubstituted; when R1 means methyl, X is unsubstituted; when R2 means chlorine, X is other than parafluorophenyl; in the form of a base or an acid addition salt. The invention also refers to the compounds selected from the group, to a drug, to a pharmaceutical composition, as well as to application of the compounds of formula (I) by any of cl. 1-4.

EFFECT: preparing new biologically active compounds for treating or preventing the diseases associated with nuclear receptor NOT.

13 cl, 18 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat such diseases as hypertension, congestive heart failure, cardiac hypertrophy and others. In formula I R1 denotes a) cyclohexyl or trifluoromethyl; or b) phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 2-imidazolyl, 2-thiazolyl, 2-benzothienyl, 4-benzofuryl, 4-benzothienyl, 7-benzofuryl, 2,3-dihydro-7-benzofuryl, 7-benzothienyl, 1,3-benzodioxol-4-yl, 7-indazolyl, or 8-quinolinyl, optionally substituted with 1-3 substitutes, and X and Y each denotes a single bond; R2 denotes methyl, ethyl, propyl, butyl, pentyl, hexyl, 5-pentenyloxy, 3,33-trifluoropropyl, 4,4-difluoropentyl, 3-(cyclopropyl)propyl, 4-(cyclopropyl)butyl, 3-hydroxypropyl, 4-hydroxybutyl, 4-hydroxypentyl, 4-hydroxyhexyl, 5-hydroxyhexyl, 2-hydroxyethoxy etc, given in the claim; R3 denotes H, F, OH, methoxy, ethoxy, 3-hydroxypropoxy, acetylamino, propionylamino, (2-methylpropionyl)amino, or butanoylamino; A denotes 2,4-disubstituted morpholine with R1XCR2R3Y, bonded on the second position and Q bonded on the fourth position, 1,3-disubstituted piperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-dibustituted-3-methylpiperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-disubstituted benzene or 1,3-disubstituted cyclohexane; Q denotes Q1, Q2, Q4, Q5, Q9, or Q10 given in the claim, to which A and N are bonded on cut-off bonds, R4 denotes H or methyl.

EFFECT: obtaining novel compounds having aspartic protease inhibitor properties, particularly renin inhibitor.

10 cl, 1 tbl, 166 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described compounds of formula

as well as their pharmaceutically acceptable salts where the substitutes are those as described in the patent claim. The compounds of formula (I) are 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme inhibitors.

EFFECT: making the compounds effective for treating and preventing the diseases, such as insulin-independent diabetes and metabolic syndrome, particularly obesity, eating disorders or dislipidemia.

15 cl, 1 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: present invention is related to new quinolone derivatives of general formula (I) where R1: C3-6cycloalkyl or lower alkylene C3-6cycloalkyl, R2: -H or halogen, R3: -H, halogen, -OR0 or -O-(lower alkylene)-phenyl, R0: are the same or different from each other, and each represents -H or lower alkyl, R4: lower alkyl, halogen(lower alkyl), lower alkyleneC3-6cycloalkyl, C3-7cycloalkyl or a heterocyclic group, where cycloalkyl and the heterocyclic group specified in R4 can be respectively substituted, R5: -NO2, -CN, -L-Ra, -C(O)R0, -O-Rb, -N(R6)2, lower alkylene-N(R6)(Rc), -N(R6)C(O)-Rd, lower alkylene-N(R6)C(O)-Rd, lower alkylene-N(R0)C(O)O-(lower alkyl), -N(R0)C(O)N(R0)-Re, lower alkylene-N(R0)C(O)N(R0)-Re, -N(R0)S(O)2N(R0)C(O)-Rd, -CH=NOH, C3-6cycloalkyl, (2,4-dioxo-1,3-thiazolidin-5-yliden)methyl or (4-oxo-2-tioxo-1,3-thiazolidin-5-yliden)methyl where cycloalkyl specified in R5 can be respectively substituted, R6: H, lower alkyl, lower alkylene-CO2R0 or lower alkylene-P(O)((OPp)2, where lower alkylene specified in R6 can be substituted, L: lower alkylene or lower alkenylene which can be respectively substituted, Ra: -OR0, -O-(lower alkylene)-phenyl, -O-(lower alkylene)-CO2R0, -CO2R0, -C(O)NHOH, -C(O)N(R6)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-phenyl, -C(O)N(R0)-S(O)2-(heterocyclic group), -NH2OH, -OC(O)R0, -OC(O)-(halogen(lower alkyl)), -P(O)(ORp)2, phenyl or the heterocyclic group where phenyl or the heterocyclic group specified in Ra can be substituted, Rp: R0, lower alkylene-OC(O)-(lower alkyl), lower alkylene-OC(O)-C3-6cycloalkyl, lower alkylene-OC(O)O-(lower alkyl), Rb: H, lower alkylene-Rba or lower alkenylene-Rba where lower alkylene or lower alkenylene specified in Rb can be substituted, Rba: -OR0, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-[phenyl, -C(NH2)-NOH, -C(NH2)=NO-C(O)-(lower alkylene)-C(O)R0, -CO2-(lower alkylene)-phenyl, -P(O)(ORp)2, -C(O)R0, -C(O)-phenyl, C3-6cycloalkyl, phenyl or the heterocyclic group where phenyl and the heterocyclic group specified in Rba can be substituted, Rc: H, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-P(O)((OPp)2, phenyl where lower alkylene and phenyl are specified in Rd can be substituted, Rd: C1-7-alkyl, lower alkenyl, halogen(lower alkyl), lower alkylene-Rda, lower alkylenylene-Rda, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where lower alkylene, cycloalkyl, phenyl, naphthyl and the heterocyclic group specified in Rd can be substituted, Rda: -CN, -OR0, -O-(lower alkylene)-CO2R0, -O-naphthyl, -CO2R0, -CO2-(lower alkylene)-N(R0)2, -P(O)(ORp)2, -N(R6)2, -C(O)N(R0)-phenyl, -C(O)N(R0)-(lower alkylene which can be used by -CO2R0)-phenyl, -N(R0)C(O)-phenyl, -N(R0)C(O)-OR0, -N(R0)C(O)-O-(lower alkylene)-phenyl, -N(R0)S(O)2-phenyl, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where phenyl, naphthyl and heterocyclic group specified in Ra can be substituted, Re: lower alkylene-CO2R0, phenyl, -S(O)2-phenyl or -S(O)2-(heterocyclic group), where phenyl and the heterocyclic group specified in Re can be substituted, X: CH, A: C(R7), R7: -H, or R4 and R7 together can form lower alkylene, where the substituted groups have the substituted specified in cl.1, and provided 7-(cyclohexylamino)-1-ethyl-6-fluor-4-oxo-1,4-dohydroquinoline-3-carbonitryl is excluded. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I) and application of formula (I) for preparing a thrombocyte aggregation inhibitor or a P2Y12 inhibitor.

EFFECT: there are produced new quinol-4-one derivatives showing effective biological properties.

11 cl, 83 tbl, 71 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gastroenterology, physiotherapy, rexlexotherapy. Method includes carrying out drug therapy. Additionally, taking into account degree of expression of anxiety-depressive disorders by Hamilton scale data, antidepressant asaphen is introduced. In case of clinically expressed disorders asaphen is introduced in dose 75 mg per day, in case of subclinically expressed affective disorders - in dose 50 mg per day. Intake of asaphen is realised during 30 days. Taking into account individual peculiarities of vegetative balance state magnetic laser puncture is performed. For this purpose used is wavelength 1.3 mcm, modulated mode, frequency 2.4 Hz, magnetic-acupuncture nozzle 50 mT. Impact is carried out during 10-30 s per one biologically active point. In case of sympathicotonia point Gl 4 is sedated and points E 25, E 36, MC 6 are toned up. In case of vagotonia point Gl 4 is toned up and points E 25, E 36, MC 6 are sedated. Course includes 10-12 procedures.

EFFECT: method increases patients' life quality, reduces treatment terms, increases remission duration, reducing number of recurrences due to correction of state of day chronobiorhythms, psychoemotional sphere and vegetative balance.

2 ex, 2 tbl

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: 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

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

Up!