WO2013147649A2 - Inhibitors of the pi3k/akt/ikk/nf-kb signalling pathway, pharmaceutically acceptable salts thereof and compositions containing said inhibitors for the prophylaxis and treatment of viral diseases - Google Patents

Abstract

The invention relates to inhibitors of the PI3K/AKT/IKK/NF-kB signalling pathway, to analogues thereof and to pharmaceutically acceptable salts thereof, and also to pharmaceutical compositions containing said inhibitors for the prophylaxis and treatment of viral diseases. The invention is linked to methods for the prophylaxis and treatment of viral diseases using inhibitors of the PI3K/AKT/IKK/NF-kB signalling pathway, to analogues thereof, and to pharmaceutically acceptable salts thereof, and also to pharmaceutical compositions containing said inhibitors for the treatment of viral diseases and for the production of drugs.

Description

 PI3K / AKT / IKK / NF-kV signaling pathway inhibitors, their pharmaceutically acceptable salts and compositions containing them for the prevention and treatment of viral diseases

Technical field

This invention relates to the field of prevention and treatment of viral diseases, namely, the use of PI3K / AKT / IKK / NF-kB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and treatment of viral diseases. State of the art

Sources available at the time of filing this application describe the use of PI3K / AKTAKK / NF-kB signaling pathway modulators for the treatment of various cancers, rheumatoid arthritis, inflammatory and immune diseases. For example, in US patent US6869956 (US2003022898) describes methods of treating inflammatory and immune diseases using signaling pathway inhibitors.

PI3K / AKTAKK / NF-kB - IkappaB kinase inhibitors (IKK).

Patent application US2011268722 (WO2011133879) describes combined antitumor preparations containing PI3K / AKT / IKX / NF-kB signaling pathway inhibitors. US20060025419 describes the use of PI3K / AKT / IKK / NF-kB signaling pathway inhibitors for the treatment of melanoma, and US20100249142 for the treatment of a number of oncological diseases. The use of PI3K / AKTAKK / NF-kB signaling pathway inhibitors for monitoring the effects of immunomodulators (US2011111417), local anesthesia (US2010159015), treatment of diseases of the nervous system (US2005075341), as immunomodulators (EP2010537), etc. is also described. For some signaling pathway inhibitors

P13K / AKTLKK / YB-kV published information on their use in the treatment of viral diseases, for example:

1.LU294002 Influenza (J Gen Virol. 2007 Mar; 88 (Pt 3): 942-50. Shin YK, Liu Q, Tikoo SK, Babiuk LA, Zhou Y. Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada). (Vaccine and Infectious Diseases Organization, University of Saskatchewan, Saskatoon, Canada)

2. Pyrrole Idin Dithiocarbamate (ROTS) / Influenza, (Journal of Antimicrobial Chemotherapy (2003) 52, 8-10 DOI: 10.1093 / jac / dkg282 Noboru Uchide and Kunio Ohyama Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan) (Noboru Uchide and Kunio Ohiyama, Department of Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Natural Sciences, 1432-1 Khorinouchi, Hachioji, Tokyo 192-0392, Japan)) 3. Curcumin / Flu (Food Chemistry (Food Chemistry, Volume 119, Issue 4, April 15, 2010, pp. 1346-1351) Volume 119, Issue 4, 15 April 2010, Pages 1346-1351 Da- Yuan Chena, Jui -Hung Shienb, Laurence Tileyc, Shyan-Song Chioua (Sheng-Yang Wang, Tien-Jye Chang, Ya-Jane Lee, Kun-Wei Chan, Wei-Li Hsu).

4. Aspirin / Influenza, (Cell Microbiol. (Cell Microbiology) 2007 Jul; 9 (7): 1683-94. Epub 2007 Feb 23. Mazur I, Wurzer WJ, Ehrhardt C, Pleschka S, Puthavathana P, Silberzahn T, Wolff T, Planz O, Ludwig S. (Institute of Molecular Virology, ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany). (Molecular Virology Institute, ZMBE, Wilhelm University of Westphalia, von- Esmarch Street 56, D-48149 Munster, Germany).)

Disclosure of invention

 Terms

IKK is understood to mean IkB kinase, an enzymatic complex that is involved in the cellular response to inflammation and is located in the PI3K / AKTAK 7NF-kB signaling cascade.

(1) Information disclosing the essence of the invention

The present invention relates to the use of PI3K / AKTAKK / NF-kB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and / or treatment of various viral diseases.

 1. In one embodiment, the present invention provides a PI3K / Akt / IKK / Nf-kB signaling pathway inhibitor, or a pharmaceutically acceptable salt thereof, for the prevention and / or treatment of at least one disease from Table 1.

2. In another embodiment, the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease from Table 1, comprising at least one PI3K7Ak ^ KK / Nf-kB signaling pathway inhibitor or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent. 3. In another embodiment, the present invention provides a dosage form for the prophylaxis and / or treatment of at least one disease from Table 1, comprising a PI3K / Akt / IK / Nf-kB signaling pathway inhibitor or a pharmaceutically acceptable salt thereof.

4. In another embodiment, the present invention provides an IKK inhibitor or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of at least one disease from Table 1.

5. In another embodiment, the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease from Table 1, comprising an IKK inhibitor or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, excipient or diluent. 6. In another embodiment, the present invention provides a dosage form for the prevention and / or treatment of at least one disease from table 1, containing an IKK inhibitor or a pharmaceutically acceptable salt thereof.

7. In another embodiment, the present invention provides at least one compound from Table 2, or a pharmaceutically acceptable salt thereof, for the prevention and / or treatment of at least one disease from Table 1.

8. In another embodiment, the present invention provides an analogue of at least one of the compounds from table 2 or its pharmaceutically acceptable salt, for the prevention and / or treatment of at least one disease from table 1. 9. In another embodiment, the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of at least one disease of Table 1, comprising at least one of the compounds of Table 2, or a pharmaceutically acceptable salt thereof, and at least one a pharmaceutically acceptable carrier, excipient or diluent. 10. In another embodiment, the present invention provides a dosage form comprising at least one of the compounds of Table 2 or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of at least one disease of Table 1.

11. In another embodiment, the present invention provides a medicament for the prevention and / or treatment of at least one of the diseases of Table 1, comprising in a therapeutically effective amount of at least one of the compounds of Table 2 or a pharmaceutically acceptable salt thereof.

12. In another embodiment, the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline

for the prevention and / or treatment of at least one disease from table 1.

13. In another embodiment, the present invention provides the use of at least one compound of Table 2 or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of viral diseases.

14. In another embodiment, the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline

or its pharmaceutically acceptable salt for the prevention and / or treatment of at least one of the diseases from table 1.

15. In another embodiment, the present invention provides a compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline

or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of type A influenza. 16. In another embodiment, the present invention provides a pharmaceutical composition for the prophylaxis and / or treatment of type A influenza, comprising 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline

or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, excipient or diluent.

16. In another embodiment, the present invention provides at least one compound from table 2 or its pharmaceutically acceptable salt used (used) for the prevention and / or treatment of at least one of the diseases from table 1. 17. In another embodiment, the present invention provides a method for the prevention and / or treatment of at least one disease from table 1 person and / or an animal by administering to such a person and / or animal in a therapeutically effective amount of at least one PI3K7AktAKK / Nf-kB inhibitor of the signaling pathway or a pharmaceutically acceptable salt thereof.

18. In another embodiment, the present invention provides a method of preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal a therapeutically effective amount of at least one IKK inhibitor or a pharmaceutically acceptable salt.

19. In another embodiment, the present invention provides a method for preventing and / or treating at least at least one disease from table 1 of a person and / or animal by administering to such a person and / or animal in a therapeutically effective amount of at least one compound from table 2 or a pharmaceutically acceptable salt thereof.

20. In another embodiment, the present invention provides a method for the prevention and / or treatment of influenza and / or SARS by administering to such a person and / or animal 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2- a] quinoxaline

or a pharmaceutically acceptable salt thereof in a therapeutically effective amount.

21. In another embodiment, the present invention provides a method for preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal a therapeutically effective amount of a pharmaceutical composition comprising at least one compound of Table 2 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent.

22. In another embodiment, the present invention provides a method for preventing and / or treating at least one disease from a human and / or animal table 1 by administering to such a person and / or animal in a therapeutically effective amount of a pharmaceutical composition comprising at least one PI3K / Akt / IKJ / Nf-kB inhibitor of the signaling pathway or its pharmacologically acceptable salt or one IKK inhibitor or its pharmaceutically acceptable salt or at least one compound from table 2 or its pharmaceutics Eski acceptable salt thereof, and at least one pharmaceutically acceptable carrier, excipient or diluent, and at least one other drug or an antiviral drug or compound from table 3. 23. In another embodiment, the present invention provides a pharmaceutical composition for preventing and / or treating at least one disease from a human and / or animal table 1, comprising at least one PI3K / Akt / IKK / Nf-kB signaling inhibitor the pathway or its pharmacologically acceptable salt or at least one IKK inhibitor or its pharmaceutically acceptable salt or at least one compound from table 2 or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable nose an agent, excipient or diluent, in combination with at least one other drug or antiviral drug or drug used to prevent and / or treat at least one disease indicated in table 1, for example, but not limited to at least one compound or the drug from table 3.

24. In another embodiment, the present invention provides at least one signaling pathway inhibitor PBK / Akt / IKK / Nf-kB, an IKK inhibitor or a compound of Table 2 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for prophylaxis and / or treating at least one disease indicated in table 1.

25. In another embodiment, the present invention provides at least one PI3K / Akt / IKK / Nf-kB signaling pathway inhibitor, an IKK inhibitor, or a compound of Table 2, or a pharmaceutically acceptable salt thereof, together with at least one other drug used for prophylaxis and / or treatment of at least one disease indicated in table 1, including at least one compound from table 3, for the manufacture of a combination drug for the prevention and / or treatment of at least one disease Table 1.

26. In another embodiment of the present invention, instead of a PI3B / Akt KK / Nf-kB signaling pathway inhibitor, an IKK inhibitor, or a compound of Table 2, a solvate or solvate of a salt thereof or a salt adduct thereof or a complex salt thereof thereof is used physiologically a functional derivative or its analogue or its stereoisomer or its prodrug.

27. In another embodiment of the present invention, instead of the compound or preparation of Table 3, the solvate or solvate of its salt or its salt adduct or its complex salt, its physiologically functional derivative, or its analog, or its stereoisomer or its prodrug, is used as the biologically active substance.

28. In another embodiment of the present invention, instead of the disease indicated in table 1, at least one other disease is associated with at least one virus indicated in table 1.

Many of the diseases listed in table 1 pose a serious danger and even lead to the death of the patient. Despite the fact that medical preparations have been developed for the treatment of some of the listed diseases, many of them are ineffective and have severe side effects. In addition, virus mutations lead to a decrease in the effectiveness of existing drugs. Subject to the foregoing, the discovery or development of new drugs against these diseases, new methods of using known substances for the treatment of patients and treatment methods are of great importance, both in social and commercial terms.

EFFECT: obtaining / invention of a new biologically active compound, including those indicated in table 2, which can be used to prevent and / or treat and / or alleviate the symptoms and consequences of at least one disease indicated in table 1 (compounds in regarding which previously there was no information about the possibility of its use in the treatment of the corresponding disease), new methods of treating such diseases, new pharmaceutical compositions and combinations for the treatment of these diseases knowledge, the new use of the above substances for the treatment of the above diseases, as well as for the production of medicines for the treatment of the above diseases. The compounds listed in table 1 and methods for their preparation are known in the art. Many of the molecules described in Table 2 are already manufactured commercially. Thus, the inventions described in this application have industrial applicability.

Examples of pharmaceutical compositions and dosage forms.

To use the present invention, it is possible to use any dosage forms, non-limiting examples of such dosage forms may be:

Dosage: capsules, tablets

 Not dosed: gel, ointment, syrup, extract, elixir, emulsion, medicinal pencil, decoctions, medicine

Mixed type: patch (can be either a dosage or non-dosage form)

 Dosage forms of the present invention can be of various state of aggregation

 Hard: tablets, powders, capsules, dragees, granules, caramel, medicinal pencil

 Soft: ointments, creams, pastes, gels, TTS, suppositories

 Liquid: solutions, tinctures, suspensions, emulsions, drops, syrups, medicines

 Gaseous: aerosols.

The present invention also relates to any pharmaceutically acceptable carrier that assists in the delivery to the body as an active substance. any of the substances described in this application, any of its forms or prodrugs.

 Any variant of the substance described in this application can be used in any acceptable dosage form. As an example of the compositions of the dosage forms, any examples of compositions and / or dosage forms commonly used for systemically used drugs can be given.

 For the purpose of making a variant of the pharmaceutical composition of the present invention, but not limited to these examples, an effective amount of a substance from the class described or covered by this application or its salt can be taken. Also, use is possible in a mixture (composition) with a pharmaceutically acceptable carrier (vehicle), where the carriers can be a wide variety of forms and substances depending on the composition that is intended to be administered to the patient. It is more convenient that these pharmaceutical compositions be in standardized doses, for example, for oral administration or parenteral administration.

So, in the preparation of solid and liquid dosage forms for oral administration, it is possible to use any of the drugs commonly used in the manufacture of this kind a substance or agent in various combinations, for example, water, glycols, oils, starch, solid carriers such as sugar, kaolin, diluents, lubricants, binders, disintegrating agents, disintegrating agents, alcohols, and the like. For parenteral compositions containing any of the substances described in this application, the carrier may be sterile water, saline, or other ingredients, for example, substances that improve solubility. In injection solutions, for example, the carrier may consist of physiological or saline solution, glucose solution, or a mixture of saline and glucose solution, buffer. In the case of the preparation of injectable suspensions, they may also be prepared in a representative or representatives of liquid carriers, dispersing agents and similar substances and compositions suitable for each specific case or series of cases.

 Also included in the present invention is a therapeutically active agent, as described herein or coated with it, in the form of a powder, which is intended to be converted shortly before administration into a liquid form.

The pharmaceutical composition may also contain various other ingredients known in the art, such as stabilizing agents, lubricant, buffer, emulsifier, viscosity and / or tackifier, any surfactant, preservative, antioxidant, colorant, other additives and the like. In the present invention, it is possible to contain an ester containing at least one of the substances listed above or covered by the present invention.

Alternatively, but not limited to, it is possible to create the pharmaceutical composition described above in the form of a dosage (unit dosage form).

 The dosage in the description is used as a physically separate part, used for a single application. Such a portion contains a certain amount of the active ingredient necessary to obtain a therapeutic effect together with an acceptable pharmaceutical carrier.

Examples of such dosages are tablets of various shapes and appearance, capsules, powder sachets, lozenges, plates, suppositories, suppositories, injection solutions and so on, as well as various combinations of the above, but not limited to. When creating a solid dosage form in the form of tablets of the claimed medicinal product, starch in an amount of 0.1 mg to 100 mg per tablet was used as a filler to give the best flowability and compressibility of the active substance. Potato and / or modified starch may be used.

 As lubricants and glidants, stearic acid, aerosil or collie don are used. These substances provide good flowability and uniform supply of tableted masses from the hopper into the matrix, and as a result gives higher accuracy and consistency in the dosage of the drug substance. Contribute to the easier ejection of tablets from the matrix, preventing the formation of scratches on their faces.

In order to impart acceptable organoleptic properties to the composition, lactose in an amount of up to 60 mg can be added.

The result is a mixture of substances having good technological properties in the process of granulation and tableting. The manufactured tablets have properties that meet the requirements of a pharmaceutical agent. They have a marketable appearance without chips and cracks, with the necessary strength and disintegration, and are stored for at least 2 years.

The new pharmaceutical formulation is in the form of a solid dosage form, preferably, but not necessarily, coated in the form of a tablet. The presence of the shell of the claimed composition gives, firstly, the stability of the composition during storage, and secondly, improves its appearance and organoleptic properties. Through the use of a composition consisting of at least a PI3 / Akt / IKK / Nf-kB signaling pathway or IKK inhibitor or compound indicated in table 2 and at least one other drug used for the prevention and / or treatment of at least one disease indicated in table 1, for example, the compound or preparation of table 3, a synergistic effect is achieved. Non-limiting examples of such a combination composition may include the following: a pharmaceutical composition comprising at least two formulations. For example, a pharmaceutical composition for treating influenza and / or acute respiratory viral infections caused by influenza virus, containing 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2- a] quinoxaline in an amount of 0.1 mg to 100 mg and oseltamivir in an amount of 0.1 mg to 100 mg. According to the invention, any or at least one compound from table 3 can be used in one composition with any or at least one compound from table 2, for the prevention and / or treatment of at least one disease indicated in table 1.

The effective dose for the active substances of this invention depends on the chosen route of administration, as well as on other factors, such as the age and weight of the patient, which are known to the attending physician. The dosage also depends on the disease to be prevented and / or treated. The daily dose for the prophylaxis and / or treatment of the diseases from Table 1 may range from 0.01 to 300 mg / kg of the weight of a patient who needs prophylaxis and / or treatment. The active compounds of this invention can be administered from one to three times per day (i.e., from one to three doses per day) at a dose of about 0.01 to about 100 mg / kg of patient weight, although depending on the weight and the patient’s condition, the nature and severity of the disease that the patient suffers from, and especially the route of administration, it will be necessary to adjust this dose. However, changes in dosage may occur depending on the characteristics of the patients to be treated and the individual response of the subject to the indicated drug, as well as the type of pharmaceutical composition selected, the period of use and the time interval during which such administration is carried out. For example, the oral administration of the compound from table 2 - 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2-a] quinoxaline 1, 2, 3 or 4 times a day at a dose in the range of 0.01 up to 100 mg / kg or from 0.1 to 10 mg / kg, from 1 mg / kg to 200 mg / kg, from 0.1 mg / kg to 1 mg / kg, from 50 mg / kg to 200 mg / kg , from 25 mg / kg to 100 mg / kg of patient weight, when taken for a period of up to 1 month, provides prophylaxis and / or treatment of influenza and other diseases from Table 1.

Other examples of doses for the compound 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2-a] quinoxaline prevention and / or treatment of influenza and other diseases from table 1 - from 0.1 to 10 mg / kg , from 1 mg / kg to 200 mg / kg, from 0.1 mg / kg to 1 mg / kg, from 50 mg / kg to 200 mg / kg, from 25 mg / kg to 100 mg / kg. For any embodiment and embodiment of the present invention, non-limiting examples of the PI3K / Akt / IKK / Nf-kB signaling pathway inhibitors and / or IKK inhibitors used therein may be the compounds (at least one compound) shown in Table 2.

For any embodiment and embodiment of the present invention, non-limiting examples of the drugs and compounds used therein used to prevent and / or treat at least one of the diseases from Table 1, the compounds of Table 3 can be used in combination with at least one the compound shown in table 2. Due to the combined use of at least one inhibitor of the PI3K / AktAKK / Nf-kB signaling pathway or inhibitor of IKK or the compound indicated in table 2 with at least one other they drug used for preventing and / or treating at least one disease indicated in Table 1 (e.g., at least one compound of Table 3), can be achieved by a synergistic therapeutic effect. Non-limiting an example of such joint use can be the simultaneous administration of at least two drugs, one from table 2, the other from table 3. For example, for the treatment of influenza and / or SARS caused by influenza A 4- (2'-aminoethyl) amino-1 virus , 8-dimethylimidazole [1,2-a] quinoxaline in doses from 0.01 mg / kg body weight to 100 mg / kg body weight is applied 1, 2, 3 or 4 times a day at the same time or at intervals of up to 24 hours with oseltamivir in doses from 0.01 mg / kg body weight to 100 mg / kg body weight) for a period of up to 1 month.

Other dosage options for oseltamivir when used together:

 Adults and children over 12 years of age are prescribed 75 mg 2 times a day by mouth for 5 days. Increasing the dose of more than 150 mg / day does not increase the effect. Children over 40 kg or older than 8 years who can swallow capsules can also receive treatment by taking 75 mg capsule 2 times a day, as an alternative to the recommended dose of Tamiflu suspension (see below). Children over 1 year of age are recommended a suspension for oral administration within 5 days:

children weighing less than 15 kg are prescribed 30 mg 2 times a day; children weighing 15-23 kg - 45 mg 2 times a day; children weighing 23-40 kg - 60 mg 2 times a day; children over 40 kg - 75 mg 2 times a day.

Another example: any compound from table 2 is used simultaneously with at least one compound or drug listed in table 3. These same drugs can be used in different sequences, including, for example, the drug from table 3 - from 1 minute to 2 weeks after taking the drug from table 2 and vice versa - the drug from table 2 during the same time intervals after taking the drug from table 3. It is assumed both single and repeated use of both drugs simultaneously or one after d another - during any of the indicated periods in a different sequence. One possible example of the regimen of administration: the drug from table 2 is administered orally or by injection in the dose range from 0.01 to 100 mg / kg 1.2 or 3 times a day on the day of infection and the drug from table 3 is orally in the range doses from 0.01 to 100 mg / kg 1, 2 or 3 times a day for 1-60 days after infection with the virus from table 1 or for 1 day to 2 weeks, or 2 days to 3 weeks. The best example of carrying out the invention

The present invention can be illustrated by the following examples. However, it should be understood that the invention is not limited to the specific details of these and other examples given in the text of this application.

Example 1. Biological activity in vitro. The use of compounds for the treatment of virus agents can be demonstrated by the activity of the compounds from the table

2 in the next experiment.

 For example, the compounds are taken:

 "58 IKK Inhibitor III, BMS-345541

Jfa52 IKK-2 Inhibitor IV, TPCA-1

 IKK Inhibitor VII

 J4O56 IKK-2 Inhibitor VIII

N ° 80 NF-KB Activation Inhibitor All compounds taken were dissolved in 100% DMSO, final concentration 4 mM. For experiments, concentrations of 10 and 1 μM were used, and the DMSO content was 0.25%. However, for compounds 60 (Ikk inhibitor VII) and 80 (NF-κΒ activation inhibitor), additional acidification of the pH was required by the addition of HCl to achieve final concentrations of 20 and 3 μM, respectively.

Cytopathic effect measurement

An influenza-induced cytopathic effect was examined on a culture of MDCK cells (Madin-Darby canine kidney) by infecting them with the influenza A virus subtype FM1. Cells were infected in the presence of 10 μg / ml trypsin in DMEM and test substances at a concentration of 10 and 1 μM (three repetitions for each concentration). Oseltamivir (Tamiflu) at a concentration of 100 μM was used as a control. To assess cytotoxicity, uninfected cells were incubated in the presence of the same concentrations of compounds. After a 5-day incubation period, the plates were processed to detect live cells (using the resazurin method). Virus inhibition and cytotoxicity (cell death caused by test compounds in the absence of viral infections) are expressed as a percentage. Cell morphology was monitored by visual inspection during the experiment.

JVo 58 58 52 52 60 60 56 56 80 80

C, μM 10 1 10 1 10 1 10 1 10 1

Inhibition of 100 27 37 13 10 0 44 3 50 40 virus,%

Standard 4 11 17 3 5 4 19 7 3 4 deviation

Toxicity,% 0 0 3 8 2 1 1 20 18 12 17

Example 2 In-vivo biological activity The effectiveness of PI3K / Akt / IKK / Nf-kB inhibitors of the signaling pathway, for example, but not limited to, compounds of Table 2 or IKK inhibitors for the purposes of the present invention can be confirmed by the example of a number of PI3K7Ak1 [KK / Nf-kB inhibitors the signaling pathway, which are inhibitors of IKK, in relation to the experimental form of influenza A in white mice intranasally infected with the influenza virus, strains A / Aichi / 2/68 (H3N2). The work can be used influenza virus, strain A / Aichi / 2/68 (H3N2), adapted to the lungs of white mice. For research, white mice weighing 10-12 g can be used.

Animals kept in a vivarium intended for uninfected animals at a temperature of (20.0 ± 2.0) ° C are observed for 3 days prior to use in work.

Animals are discarded for which the following symptoms are noted: depressed state, lethargy, poor mobility, lack of coordination of movements, symptoms of paralysis or paresis of limbs, absence of limbs or tail (or parts of these organs), convulsions, ruffled coat, dirty grayish coat, catarrhal phenomena, lack of appetite, excessive drinking or, conversely, rejection of water, bloody or yellowish masses at the root of the tail, diarrhea, flatulence, skin lesions

To identify the protective activity of the test compound in 2 doses, 20 animals are used. Additionally, 20 animals are included to control the toxicity of the compound at its maximum dose, 20 animals (herd control - saline solution) and 20 animals (infected untreated group). For control the antiviral activity is a group treated with Tamiflu - 20 animals.

 Thus, to conduct studies to evaluate the protective performance of 1 test compound in two doses, 120 mice (6 groups of 20 animals each) are required.

 The schedule of administration of the drug, oral, after 1 hour, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours, 144 hours.

 A virus-containing suspension is injected into both nostrils of white mice under light ether anesthesia in a volume of 50 μl. The infectious dose is 10 to 30 LD50 of the A / Aichi / 2/68 influenza virus (H3N2) for 20 mice in each group. Observation of animals is carried out within 14 days from the moment of infection, recording their death.

 Oseltamivir (brand name Tamiflu®), remantadine, arbidol and others can be used as comparison preparations. These samples exhibit protective activity in the described experiment.

 An example composition 3.1.

 Composition, mg per tablet:

Compound 58 of table 2 - 10

 Microcrystalline Cellulose 50

Potato or modified starch 10 Polyvinylpyrrolidone 10

Cellulose 10

Dibasic Calcium Phosphate 25

Magnesium Stearate 2

Hydroxypropyl methylcellulose 20

Examples of compositions 3.2.

 Composition, mg per tablet:

 Any substance from table 2 - 10

 Microcrystalline Cellulose 50

 Potato or modified starch 10

Polyvinylpyrrolidone 10

 Cellulose 10

 Dibasic Calcium Phosphate 25

 Magnesium Stearate 2

Hydroxypropyl methylcellulose 20.

Table 1.

Viruses and the diseases they cause The table contains the name of the viruses and a non-limiting list of examples of diseases associated with the corresponding virus.

Infectious Disease

 agent

 12

 Adenovirus is a type of acute respiratory viral infection (SARS), SARS associated with adenovirus or caused by adenovirus, adenovirus infection

 Bird Sarcoma Virus Bird Sarcoma Virus

 Koksaki virus aseptic meningitis, myocarditis, VZ (Koksaki virus pericarditis

 type VZ)

Enterovirus 71 HFMD Continuation of Table 1.

12

 Virus Diseases associated with the virus

Epstein - Epstein - Barr, for example, but not Barr, VEB limited to

 Chronic fatigue syndrome

 Infectious mononucleosis (multiglandular adenosis, glandular fever, Filatov’s disease), Lymphogranulomatosis (Hodgkin’s disease), Burkitt’s lymphoma (Central African lymphoma), Some of non-Hodgkin’s lymphomas, Nasopharyngeal carcinoma (nasopharyngeal cancer), General variability, Variable

 Alice's Syndrome in Wonderland

 Hepatitis, Herpes, Post-transplant lymphoproliferative disease,

 Herpetic tonsillitis (herpangina),

Multiple sclerosis,

Hairy Leukoplakia, Kikuchi Disease

Continuation of Table 1.

12

 Flaviviruses dengue fever, fever

 West Nile tick-borne

 encephalitis, Japanese encephalitis, yellow fever

 Hepatitis b virus hepatitis b

 Hepatitis C virus hepatitis C

 Cytomegalovirus cytomegaly

 HIV virus, AIDS

immunodeficiency

human HIV

 Human papillomavirus, human cervical cancer

 T virus - leukemia

cell leukemia

human type I

 Influenza A virus, acute respiratory viral (influenza virus serotype of infection (SARS), influenza, influenza A, type A influenza virus, diseases

subtype A) associated with influenza viruses

H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7 3, H5N2, H10N7 and others. Continuation of Table 1.

12

 Herpesvirus, Kaposi's sarcoma

associated with

Kaposi's sarcoma

 Myxoma virus myxomatosis

 Poliovirus polio

 Polyoma virus polyoma

 Respiratory acute respiratory syncytial virus viral infections (ARVI)

Rhinovirus (for example, but not acute respiratory confining to type viral infections (ARVI), 2.16.39) rhinovirus infections

 Rotavirus rotavirus infection

 (intestinal flu)

 Coronavirus Severe Acute Respiratory Syndrome

Sendai virus parainfluenza infection

SV40 polyoma virus

Chickenpox virus chickenpox, herpes zoster Continuation of Table 1.

12

 Adeno-associated diseases and conditions, the virus associated with or caused by the virus.

Other diseases associated with at least one virus indicated in this table are also considered indicated in this table.

Table 2.

Examples of compounds (molecules) - PI3KyAk ^ KIC / Nf-kB inhibitors of the signaling pathway and / or inhibitors

Femara (letrozole)

Fe ara (Letrozole) // ^

 Ν

 4 - [(4-cyanophenyl) - (l, 2,4-triazol-1-yl) methyl] benzonitrile

4 - [(4-cyanophenyl) - (1,2,4-triazol-1-yl1) methyl] benzonitrile

Temodal (Temozolomide)

Temodal (Temozolomide)

3 -methy 1-4-oxoimidazo [5, 1 - d] [l, 2,3,5] tetrazine-8- carboxamide

3-methyl-4-O oxoimidazo [5, 1 - d] [1,2,3,5] tetrazine-8-carboxamide

(2hydroxyacetyl)

 -10,13,16-trimethyl 1-

6,7,8,11,12,14,15,16-octahydrocyclopenta [a] fe

nantren-3-he

Taxotere (Docetaxel)

 Taxotere (Docetaxel)

N-debenzoyl-N-tert- butoxycarbonyl- 10- deacetyltaxol

M-debenzoyl 1-> 1-tert-

butoxycarbonyl-10-deacetyltaxol

Erucylphosphocholine

[(Z) -docos-13-enyl] 2-

(trimethylammonium) ethyl

phosphate

 R .

[(2) -docos-13-enyl] 2- o ^' o

(trimethylammonium) ethyl

phosphate

Glivec, Gleevec (Imatinib)

Glivec (Imatinib) methanesulfonic acid; 4 - [(4- methylpiperazin- 1 - yl) methyl] -N- [4-methyl-3-

[(4-pyridin-3- ylpyrimidin-2-yl) amino] phenyl] benzamide 6

4- [(4-methylpiperazin-1 - yl) methyl] -1 - [4-methyl-3-

[(4-pyridin-3-yl-pyrimidin-2-yl1) amino] phenyl] benzyl

d methanesulfonate

Nexavar (Sorafenib)

Nexavar (Sorafenib)

4- [4 - [[4-chloro-3-

(trifluoromethyl) phenyl] carb n amoylamino] phenoxy] -N- methylpyridine-2- carboxamide

4- [4 - [[4-chloro-3- (trifluoromethyl) phenyl] car bamoylamino] phenoxy] -M-methylpyridin-2-carboxamide

Sutent (Sunitinib)

Sutent (Sutenib)

N- [2- (diethylamino) ethyl] - 5 - [(Z) - (5-fluoro-2-oxo- 1 H-indol-3-ylidene)

methyl] -2,4-dimethyl-l H-

pyrrole-3-carboxamide;

(2S) -2- hydroxybutanedicarbonic acid - [2- (diethylamino) ethyl] - 5 - [(Ζ) - (5-φτορ-2-οκςο-1Η- indol-3-ylidene) methyl] - 2,4-dimethyl1 - 1 H-pyrrole-3-carboxamide (2S) -2-hydroxybutanedicarboxylic acid Phenylacetic acid

2-phenylacetic acid 2-phenylacetic acid

Triciribine phosphate

(6-Amino-4-methyl-8- (-D- ribofuranosy l) -4 #, 8 # - N— ('N OH pyrrolo [4,3,2- ife] pyrimido [4,5- cjpyridazine)

 (6-amino-4-methyl-8- (-0- but it is ribofuranosyl) -4H, 8H-pyrrolo [4,3,2-??] Pyrimido [4,5-c] pyrazine)

Declopramide

4-amino-3-chloro-N- [2-

(diethylamino) ethyl] benzam

ide

4-amino-3-chloro-1 - [2-

(diethylamino) ethyl] benzyl

d Dithiocarbamate carbamodithioate carbamodithioate s

Leucovorin

(2R) -2 - [[4 - [(2-amino-5- formyl-4-οχο- 1,6,7,8- tetrahydropteridin-6-yl) methylamino] benzoyl] am

ino] pentanedioic acid

2H) -2 - [[4 - [(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl) methylamino] benzoyl1] a

mino] pentadicarboxylic

acid

PP121 H l-Cyclopentyl-3- (lH-pyrrolo [2,3-b] pyridin-5-yl) - lH-pyrazolo [3,4-d] pyrimidin-4-amine

1-Cyclopentyl-3 - (1 H-pyrrolo [2,3-b] pyridin-5-yl1) - 1 H-pyrazolo [3,4-d] nHpHMHflHH-4-aMHH

SW30

2 - ((4-amino-3- (3-hydroxypropinyl) - 1 H-pyrazolo [3,4-d] pyrimidin- 1 - yl) methyl) -5-methyl-3-o- tolylquinazolin-4 (3H) -one

2 - ((4-amino-3- (3-hydroxypropinyl) - 1 H-pyrazolo [3,4-d] nHpHMHflHH-1-yl) methyl) -

5-methyl-3-o-tolylquinazolin-4 (3H) -one

1-Ethyl-2 - [(2-N-phenyl-N-methyl) aminostyryl)] - 3- phenyl-6- (benzothiazol-2-yl) benzimidazolium iodide

1-Ethyl-2 - [(2-M-phenyl- -

methyl1) aminostyril)] - 3- phenyl-6- (benzothiazol-2-yl) benzoimidazolium

iodide

Akt Inhibitor IX, API 59CJ-OMe

9-methoxy-2- chb methylellipticinium acetate

9-methoxy-2- methyllipticinium

acetate

Akt Inhibitor VI, Akt-in

H-Ala-Val-Thr-Asp-His-

Pro-Asp-Arg-Leu-Trp-Ala-

Trp-Glu-Lys-Phe-OH Akt Inhibitor VIII, Isozyme-Selective, Akti-1/2 l, 3-Dihydro-l- (l - ((4- (6-phenyl-lH-imidazo [4,5-g] quinoxalin-7-yl) phenyl ) methyl) -4- piperidinyl) -2H- benzimidazol-2-one,

1,3-dihydro-1- (1 - ((4- (6-phenyl- 1 H-imdazo [4,5 -] quinaxalin-7-yl) phenyl1) methyl1) -4-piperidine) -2H-benzimidazole- 2-he

Akt Inhibitor VII, TAT- Akt-in

H-Tyr-Gly-Arg-Lys-Lys-

Arg-Arg-Gln-Arg-Arg-Arg-

Ala-Val-Thr-Asp-His-Pro-

Asp-Arg-Leu-Trp-Ala-Trp-

Glu-Lys-Phe-OH

piperidinyl) methyl) phenyl) - 2-phenyl-7- quinolinecarboxamide, 3HC1,

Mixture of N- (2- (Diethylamino) ethyl) -2- (4- ((4- (2,3-dihydro-2-oxo-1 H-benzimidazole-1-yl) - 1-piperidinylmethyl) methyl) phenyl) -3-phenyl-6-quinolinecarboxamide and N- (2- (diethylamino) ethyl) -2- (4 - ((4- (2, 3-dihydro-2-oxo-1 H-benzimidazole-1-yl) - 1- piperidinylmethyl) methyl) phenyl) -3-phenyl-7-quinolinecarboxamide, ZNS1

Mixture of l - ((3- (4 - ((4- (2,3-

Dihydro-2-οχο-ΙΗ- benzimidazol- 1 -yl) - 1 - piperidinyl) methyl) phenyl) -

2-phenyl-6- quinoxalinyl) carbonyl) -4- methylpiperazine and l - ((2-

(4 - ((4- (2,3-Dihydro-2-oxo-

1H- benzimidazol- 1 -yl) - 1 - piperidinyl) methyl) phenyl) -

3-phenyl-6- quinoxalinyl) carbonyl) -4- methylpiperazine, 3HC1

 Mixture i - ((3- (4 - ((4- (2,3-

Dihydro-2-oxo-1 H-benzimidazole-1-yl) - 1 - piperidine) methyl) phenyl) -

2-phenyl-6-quinoxalinyl) carbonyl) -

4-methylpiperazine and 1 - ((3-

(4 - ((4- (2,3-dihydro-2-oxo-1 H-benzimidazol-1-yl) -1-piperidine) methyl) phenyl) -

2-phenyl-7-quinoxalinyl) carbonyl) -

4-methylpiperazine, ZNS1 PHT-427

4-Dodecyl-N- (1,3,4-thiadiazol-2-yl) benzenesulfonamide,

4-Dodecyl-G \ G- (1,3,4-thiadiazole-2-y1) beolsulfamide

Akt Inhibitor XV, Isozy m e-Selective

5-Hydroxy-3-phenyl-2- (4- ((4- (5-pyridin-2-yl-lH-

1, 2,4-triazol-3-yl) piperdin- 1 -yl) methyl) phenyl) - 1, 6- naphthyridine

5-Hydroxy-3-phenyl-2- (4- compositions may be as follows:

pharmaceutical

a composition comprising at least two drugs. For example, pharmaceutical

composition for treatment influenza and / or SARS caused by influenza virus containing 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1, 2-a] quinoxaline weighing from 0.1 mg to 100 mg and oseltamivir weighing from 0.1 mg up to 100 mg, any compound from table 2 applies

at the same time ((4- (5-pyridin-2-yl-1H-1,2,4-triazol-3-yl) piperidin-1 - yl1) methyl) phenyl) - 1,6-naphthyridine

NF-kB Activation Inhibitor IV

(E) -2-Fluoro-4'- methoxystilbene

(Ε) -2-Φτορ-4'- methoxystilbene

Hexahydro-10-methoxy-9-methyl-1 1 (-methylamino) -

9,13-epoxy-1 #, 9 # - diindolo [1,2, 3 ^ b: 3 ', 2', -

1sh] pyrrolo [3,4-j] [1, 7] benzodiazonin-1 -o

Quercetin he

2- (3,4-dihydroxyphenyl) - Af ^0H

3,5,7-trihydroxy-4 # - chromen-4-one

2- (3, 4-dihydroxyphenyl1) - OH O

3,5,7-Trigger Droxy-4 # - chrome-4-one

Myricetin

3,5,7-Trihydroxy-2- (3,4,5-trihydroxyphenyl) - 4- chromenone

 3,5,7-trihydroxy-2-

(3, 4, 5 -trihydroxyphenyl) -

4-chromenone

BMS-066

2 -methoxy-N - ((6- (1 -methyl-

4- (methylamino) - 1, 6-dihydroimiazo [4,5-d] pyrrolo [2,3-b] pyridin-7-yl) pyridin-2-

yl) methyl) acetamide

2-MeTOKCH-N - ((6- (1-methyl-

4- (methylamino) -1,6-d igidroimidazo [4,5-d] nHpHflo [2,3-b] nnpHflHH-7-yl) pyridin-2-yl1) methyl) acetamide

PHA 408

8- (5-chloro-2- (4-CI 0 N - methy lpiperazin- 1 - yl) isonicotinamido) - 1 - (4-fluorophenyl) -4,5-dihydro- 1 H-benzo [g] indazole-3 - carboxamide N

8- (5-chloro-2- (4-methylpiperazin-1 - yl) isonicotinamide) - 1 - (4-fluorophenyl) -4,5- dihydroSh- benzo [§] indazole e-3 - carboxamide

72 DLBS 1425 Cancer Biol Ther. 2010 Oct

 15; 10 (8): 814-23. Epub 2010 Oct extract of Phaleria 15.

 macrocarpa Induction of cellular apoptosis in human breast cancer by Phaleria DLBS 1425, a Phaleria macrocarpa macrocarpa compound extract, via down-regulation of PI3-kinase / AKT pathway.

 Tandrasasmita OM, Lee JS, Baek SH, Tjandrawinata RR.

73 GDC0941

2- (lH-indazol-4-yl) -6- (4- methanesulfonylpiperazin- 1 - ylmethyl) -4-morpholin-4- ylthieno (3,2-d) pyrimidine

2- (1 H-indazol-4-yl) -6- (4-

 methanesulfonylgasherazi

n-1-methylmethyl) -4-morpholin-4-ylthieno (3,2-d) nnpHMHflHH

87 CHEMBL1762790 but

5- (l- (4-amino-6-methyl- 1,3,5 -triazin-2-y 1) - 1 H- benzo [d] imidazol-2- HN ylamino) benzene- 1, 3-diol

5- (1- (4-amino-6-methyl- H ₂ N

 1,3,5-triazin-2-y1) -1H-benzoVDi and idazol-2-ylamino) benzene-1, 3-diol

88 CHEMBL1082621 1

N- (2-

(dimethylamino) ethyl) -4- (3-

(2 - ((7-fluoro-5-methoxy-2-

(1, 3,5-trimethyl- 1 H-pyrazol- ^ΗΝ γ °

4-yl) -lH-indol-3- yl) methylene) -3-oxo-2,3- dihydrobenzofuran-5- yl) ureido) -N- methylbenzamide

> 2-dimethylamino) ethyl) - F 4- (3- (2 - ((7-fluoro-5-methoxy-2- (1,3,5-trimethyl-1 H-pyrazolo-4- sludge) - 1 H-indo l-3 - for 1) methylene) -3-oxo-2,3-dihydrobenzofuran-5-yl) ureido) -g> G-methylbenzamide

CHEMBL211113 0

5 - [5 - (2-chloropheny l) furan- el

2-ylmethylene] thiazolidine- 2,4-dione

5 - [5 - (2-chlorophenyl) furan-2-ylmethylmethylene] thiosolid

en-2,4-dion

CHEMBL538346

3 - (4-morpholin-4-yl-pyrido [3 ', 2 ^* : 4,5] furo [3,2-d] pyrimidin-2-yl) -phenol

hydrochloride

3 - (4-morpholino-4-yl-pyrido [3 ', 2': 4,5] furo [3,

2 ^] pyrimidin-2-yl) phenol

hydrochloride

1, 3,5-triazin-2-yl) - 1 H- benzo [!] Imidazol-2-ylamino) phenol

CHEMBL1213118

3- (2-amino-l, 3-benzothiazol-6-yl) - 1 - {[2- (4-methylpiperazin-1 - at l) quinolin-3-l] methy 1} - lH-pyrazolo [3 , 4- d] pyrimidin-4-amine

3- (2-amino-1,3-benzothiazol-6-yl) - 1 - {[2-

(4-methylpiperazin-1 - yl) quinolin-3-yl] methyl} - 1H-pyrazolo [3,4-d] pyrimidin-4-amine

CHEMBL1669605

8 - [(5-Chloro-2- {4 - [(l- {2- [(2-hydroxyethyl) amino] -2- oxoethyl} - lH-pyrazol-4-yl) methyl] piperazin- 1 - yl} isonicotinoyl) amino] - 1 - (4-fluoropheny l) -4, 5 - dihydro-lH-

43

 87

CHEMBL1760154

1 - (4- (1 - (4-amino-6-methyl-l, 3,5-triazin-2-yl) -lH- benzo [d] imidazol-2-y lamino) pheny l) -3 - methylurea

1 - (4- (1 - (4-amino-6-methyl- 1,3,5-triazin-2-yl) - 1 H-benzo ^] imidazol-2-y1atto) phenyl) -3-methylurea

CHEMBL490428

6,6-dimethyl-2- (6- (6- methy lpyridazin-3 - ylamino) -2H- benzo [b] [l, 4] oxazin-4 (3H) - yl) -6,7-dihydrothiazolo [5 , 4- c] pyridin-4 (5H) -one

6,6-dimethyl-2- (6- (6-methylpyridazin-3 - ylamino) -2H-benzo [b] [1, 4] oxazin- 4 (ZN) -yl) -6,7-dihydrothiazole o [5, 4-s] pyridin-4 (5H) -one

CHEMBL1213117

N- (6- (4-amino-l - ((2- (4-methy lpiperazin- 1 - yl) quinolin-3-yl) methyl) - lH-pyrazolo [3,4-d] pyrimidin-3-yl ) benzo [d] thiazol-2- yl) acetamide

N- (6- (4-aMHH0-l - ((2- (4-methylpiperazin-1 - yl) quinolin-3-yl) methyl) -

1 Niprazolo [3,4-d] nHpMHflHH-3-yl) benzo [^] thiazol-2-yl) asetamide

109 CHEMBL1257653 1

 0- = S = 0

 6- (lH-indazol-4-yl) -l- methyl-4- (4-

(methylsulfonyl) phenoxy) - lH-pyrazolo [3,4-b] pyridine

6- (1H-indazol-4-yl) -1 - methyl-4- (4-

(methylsulfonyl) phenoxy

 ) -1H-pyrazolo [3,4-Hb] pyridine

BY CHEMBL1083192

5- (6 - ((4-

(Methylsulfonyl) piperazin-

1- yl) methyl) -4- morpholinothieno [3,2-d] pyrimidin-2-yl) pyrimidin-

2- amine

5- (6 - ((4-

(methanesulfonyl) piperaz

in- 1 -yl) methyl) -4- morpholinotieno [3, 2 -

morpholin-4-ylthieno [3, 2-y] pyrimidin-2-yl) pyridin-2-amine

113 CHEMBL1091978

5- (7-methyl-6 - ((4- (methylsulfonyl) piperazin-

1- yl) methyl) -4- morpholinothieno [3,2-

 d] pyrimidin-2-yl) pyrimidin-

2- amine

5- (7-methyl-6 - ((4- (methylsulfonyl) piperaz

 in- 1-yl) methyl) -4-morpholinothieno [3, 2-d] nnpHMHflHH-2-yl) pyrimidin-2-amine

114 CHEMBL1672328

N-6- (6-methoxypyridin-3-yl) -2-morpholino-4,5'- bipyrimidine-2 ', 6-diamine N N N 1

M-6- (6-methoxypyridin-3-yl) -2-morpholino-4, 5-

CHEMBL496332

2- (6- (l- (2-hydroxy-3- methoxypropy 1) - 1 H-pyrazol-4-yl) -2H- benzo [b] [l, 4] oxazin-4 (3H) - yl) - 6,6-dimethyl-6,7-dihydrothiazolo [5,4-c] pyridin-4 (5H) -one

2- (6- (l - (2-hydroxy-3 - methoxypropyl) -

1 Npyrazol-4-yl) -2H-benzo [b] [1, 4] oxazin-

4 (ZN) -yl) -6,6-dimethyl-6,7-dihydrothiazolo [5,4-s] pyrimidin-4 (5H) -one

CHEMBL1290744

3 - (6- (6-methoxypyridin-3 - ylamino) -2- morpholinopyrimidin-4-yl) phenol

3 - (6- (6-methoxypyridin-3 - ylamino) -2-

morpholinopyrimidin-4-yl) phenol

CHEMBL1289975

3- (6- (lH-indazol-5-ylamino) -2- morpholinopyrimidin-4-yl) phenol

3 - (6- (1 H-indazol-5-ylamino) -2-OH morpholinopyrimidin-4-yl) phenol

BY

 CHEMBL208977

5- (5'-nitro [2,2 '] bifuranyl-5- ylmethylene) thiazolidine-

2,4-dione

5- (5'-nitro [2,2] bifuryl-

5-ylmethylene) thiazolidin-2

 4-dione

CHEMBL208698

 ABOUT

5- [5-phenyl) fiiran-2-ylmethylene] thiazolidine-2,

 4- dione

5- [5-phenyl) furan-2-ylmethylene] thiazolidin-2,

4-dion

PX-13-170H

(lE, 4S, 4aR, 5R, 6aS, 7S, 9aR)

-5- (Acetyloxy) -l - [[[3-

(dimethylamino) propyl] met hylamino] methylene] -

4a, 5,6,6a, 7,8,9,9a- octahydro-7, 11-dihydroxy-

4- (methoxymethyl) -4a, 6a- dimethylcyclopenta [5,6] nap htho [l, 2-c] pyran-

2.10 (lH, 4H) -dione

 (lE, 4S, 4aR, 5R, 6aS, 7S, 9aR)

-5- (Acetyl) -1 - [[[3-

(dimethylamino) propyl] methylamino] methylene] -

4a, 5,6,6a, 7,8,9,9a- octahydro-7, 11- dihydroxy-4-

(methoxymethyl) -4a, 6-dimethylcyclopenta [5,6] on fluoro [1,2-c] pyran-

2.10 (1H, 4H) -dione PX-866

(lE, 4S, 4aR, 5R, 6aS, 9aR) - 5- _? 0 (Acetyloxy) -l - [(di-2- propen-1- ylamino) methylene] - ϊ I g

4,4a, 5,6,6a, 8,9,9a- octahydro- 11 -hydroxy-4- one

(methoxymethyl) -4a, 6a- dimethylcyclopenta [5,6] nap)

htho [l, 2-c] pyran- ί

 2.7.10 (lH) -trione

(lE, 4S, 4aR, 5R, 6aS, 9aR) - 5-

(Acetyloxy) -1 - [(di-2-propenylamino) methylene] -

4,4a, 5,6,6a, 8,9,9a- octahydro-1 1-hydroxy-4-

(methoxymethyl) -4a, 6-dimethylcyclopenta [5,6] per

phtho [1,2-s] pyran-

2.7.10 (1H) -trione

PX-866-170H

(lE, 4S, 4aR, 5R, 6aS, 7S, 9aR)

- 5- (Acetyloxy) -l - [(di-2- propen-1- ylamino) methylene] -

4a, 5,6,6a, 7,8,9,9a- octahydro-7, 11-dihydroxy-

4- (methoxymethyl) -4a, 6a- dimethylcyclopenta [5,6] nap htho [l, 2-c] pyran-

2.10 (lH, 4H) -dione

 (lE, 4S, 4aR, 5R, 6aS, 7S, 9aR)

- 5 - (Acetyl oxy) - 1 - [(di-2 - propenylamino) methylene] - 4,4a, 5,6,6a, 8,9,9-octahydro-7, 11-dihydroxy-4- (methoxymethyl) -4- (methoxymethyl) -4a, 6-dimethylcyclopenta [5,6] on fluoro [1,2-s] pyran- 2,10 (1H, 4H) -dione

CHEMBL1669608

8 - [(5-Chloro-2- {4 - [(l-methyl- 1 H-pyrazol-4-yl) methyl] piperazin-1 - yl} isonicotinoyl) amino] - 1 - (4-fluorophenyl) -4 5- dihydro-lH- benzo [g] indazole-3-

carboxamide

8 - [(5-Chloro-2- {4 - [(1-methyl-1H-pyrazol-4-yl) methyl] piperazin-1 - yl} isonicotinoyl) aMHHo] - 1 - (4-fluorophenyl) -4, 5- dihydro-1H- benzo [] indazole-3 - carboxylic acid amide

fluorophenyl1) -4,5-dihydro-1H-benzo ^] indazole-3-carboxylic acid amide

CHEMBL1669599

8 - {[2- (4 - {[l- (2-Amino-2-oxoethyl) - 1 H-pyrazol-4-yl] methyl} piperazin-l -yl) -5-chloroisonicotinoyljamino} - 1 - (4 -fluorophenyl) -4,5- dihydro-lH- benzo [g] indazole-3- carboxamide

8 - {[2- (4 - {[1- (2-Amino-2-

oxoethyl) - 1 H-pyrazol-4-yl] methyl} piperazin-1 - yl) -5-chloroisonicotinoyl] amino} - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo [] indazole-3 - carboxamide CHEMBL1669565

Ethyl [4 - ({4- [4 - ({[3-

(aminocarbonyl) - 1 - (4- fluoropheny l) -4, 5 -dihy dro-

1 H-benzo [g] indazol-8-yl] amino} carbonyl) -5-chloropyridin-2-yl] piperazin-l -yl} methyl) -

1 H-pyrazol- 1 -yl] acetate

Ethyl [4 - ({4- [4 - ({[3-

(aminocarbonyl) - 1 - (4- fluoropheny l) -4, 5 - digi dro -

1H-benzo ^] indazol-8-yl] amino} carbonyl) -5-chloropyridin-2-yl] piperazin-1 - yl} methyl) - 1 H-pyrazol-1 - yl] acetate

160 I CHEMBL1669596

Methyl [4 - ({4- [4 - ({[3- (aminocarbonyl) - 1 - (4- fluorophenyl) -4,5-dihydro-lH-benzo [g] indazol-8-yljamino} carbonyl) -5 - chloropyridin-2-yljpiperazin-1-yl} methyl) - 1 H-pyrazol-1-yl] acetate Methyl [4 - ({4- [4 - ({[3- (aminocarbonyl)) - 1 - (4-fluoropheny l) -4, 5-dihydro-1H-benzo ^] indazol-8-yl] amino} carbonyl) -5-chloropyridin-2-yl] piperazin-1 - yl} methyl) - 1 H-pyrazol-1 - yl ]acetate

(aminocarbonyl) - 1 - (4-

Aiogorpepu1) -4,5-dihydro-

1H-benzo [] indazol-8-yl] amino} carbonyl) -5-chloropyridin-2-yl] piperazin-1-yl} methyl) - 1 H-pyrazol-1 - yl] acetate

CHEMBL1669603

8 - [(5-Sygo-2- {4 - [(1- {2-

[(2-methoxyethyl) amino] -2- oxoethyl} - lH-pyrazol-4- yl) methyl] piperazin- 1 - yl} isonicotinoyl) amino] -l-

(4-fluorophenyl) -4,5- dihydro-lH- benzo [g] indazole-3 - carboxamide

8 - [(5-Chloro-2- {4 - [(1- {2 - [(2-methoxyethyl) amino] -2-oxoethyl} - 1 H-pyrazol-4-yl) methyl] piperazin-1 - yl } isonicotinoyl) amino] - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo [g] indazole e-3 - carboxamide

CHEMBL1669600

8 - ({5-SYHO-2- [4 - ({1- [2-

(methylamino) -2-oxoethyl] - lH-pyrazol-4- y 1} methy l) piperazin- 1 - yl] isonicotinoyl} amino) - 1 -

(4-fluorophenyl) -4,5- dihydro-lH- benzo [g] indazole-3 - carboxamide

8 - [(5-Chloro-2- {4 - [(1- {2 - [(2-

methyl) amino] -2-oxoethyl} - 1 H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] -1- (4-fluorophenyl) -4,5-dihydro-Ш-benzo [ §] indazole-3- carboxamide 165 CHEMBL592893

8 - {[5-Chloro-2- (4- methylpiperazin- 1 - in l) isonicotinoyl] -amino} - 1 -

(4-fluorophenyl) -4,5- H

dihydro-lH- benzo [g] indazole-3-

carboxamide

8- (5-chloro-2- (4-methylpiperazin-1 - yl) isonicotinoyl) - 1 - (3—

 fluorophenyl) -4,5-dihydro-lH-6eH3o [g] indazole-3-carboxamide

166 CHEMBL1669571

8 - ({5-CYO-2- [4- (1H-pyrazol-4- in lmethy l) piperazin-1 - yljisonicotinoyl} amino) - 1 - (4-fluoropheny l) -4, 5 - dihydro-lH- benzo [g] indazole-3 - carboxamide nn

H

8- (5-chloro-2 - [(4- (1H-pyrazol-4-ylmethylpiperazin-1 - yl] isonicotinoyl) - 1 - (3 - fluorophenyl) -4,5-dihydro-lH-6eH3o [g] indazole -3- carboxamide

CHEMBL601079

8 - ({5-C ogo-2- [4- (2- methoxyethyl) piperazin- 1 - yljisonicotinoyl} amino) - 1 -

(4-fluoro-phenyl) -4,5- dihydro-ΙΗ- benzo [g] indazole-3 - carboxamide

8 - ({5-Chloro-2- [4- (2-methoxyethyl) piperazin-1 - yl] isonicotinoyl} amino) - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo (] indazole- 3- carboxamide 168 I CHEMBL1669601

8 - ({5-Chloro-2- [4 - ({l- [2- (isopropylamino) -2- oxoethyl] - 1 H-pyrazol-4-yl} methyl) piperazin- 1 - yl] isonicotinoyl} amino) - 1 - (4-fluoropheny l) -4,5 - dihydro-lH- benzo [g] indazole-3- carboxamide

8 - [(5-Chloro-2- {4 - [(1- {2 - [(2-isopropyl) amino] -2-oxoethyl} - 1 H-pyrazol-4-yl) methyl] piperazin-1 - yl } isonicotinoyl) amino] - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo [g] indazole-3-carboxamide

169 CHEMBL1669560

8- (5-chloro-2- (4-methylpiperazin- 1 - in l) isonicotinamido) - 1 - (4-chloro-3-hydroxyphenyl) -

4,5-dihydro-lH- benzo [g] indazole-3- carboxamide

8- (5-chloro-2- (4-methylpiperazin-1 - yl) isonicotinoyl) - 1 - (4-chloro-3-hydroxyphenyl) - 4,5-dihydro-1H-benzo [§] indazole-3-carboxy d

170 CHEMBL1669595

8 - {[5-Sygo-2- (4 - {[1- (3-hydroxypropy 1) - 1 H-pyrazol- 4-at l] methy 1} piperazin-1 - at l) isonicotinoyl] amino} - 1 - (4-fluorophenyl) -4,5- dihydro-III- benzo [g] indazole-3- carboxamide

8 - {[5-Chloro-2- (4 - {[1- (3-hydroxypropyl) - 1 H-pyrazol-4-yl] methyl} piperazin-1-yl) isonicotinoyl] amino} - 1 - (4- fluorophenyl) -4,5-dihydro-Ш- benzo [§] indazole-3 - carboxamide

CHEMBL1669602

8 - ({5-sygo-2- [4 - ({1- [2- (dimethylamino) -2- oxoethyl] - 1 H-pyrazol-4- at 1} methy l) piperazin- 1 - at 1] isonicotinoy 1} amino) - 1 - (4-fluorophenyl) -4,5- dihydro-lH- benzo [g] indazole-3- carboxamide

8 - [(5-Chloro-2- {4 - [(1- {2- [dimethylamino] -2-oxoethyl} - 1 H-pyrazol-4-yl) methyl] piperazin-1 - yl} isonicotinoyl) amino]

GSK690693

4- (2- (4-Amino- 1,2,5- oxadiazol-3-yl) -l-ethyl-7-

{[((3S) -3- piperidinylmethyljoxy} - 1 H- imidazo [4,5-c] pyridin-4-yl) - 2-methyl-3-butyn-2-ol

4- (2- (4-amino-1,2,5-oxadiazol-3-yl) - 1-ethyl-7- {[(3S) -3-piperidinylmethyl] oxy} - 1H-imidazo [4,5- c] pyridin-4-yl) -2-methyl-3-butyn-2-ol

187 Palomid 529 (P529)

8- (l-Hydroxyethyl) -2- methoxy-3- (4- methoxybenzy loxy) benzo [c]

 cumarine-6-one

8- (l-hydroxyethyl) -2- methoxy-3- (4- methoxybenzyloxy [s] mind

 rin-6-he

188 AZD6482 O

2 - [[(lR) -l- [7-methyl-2- (4-morpholinyl) -4-oxo-4H- pyrido [1, 2-a] pyrimidin-9-yl] ethyl] amino] benzoic acid X ^t

2 - [[(t) -1- [7-methyl-2- (4-morpholinyl) -4-oxo-4H-pyrido [1,2-a] pyrimidi1

 9- yl] ethyl] amino] benzoic

acid

Continuation of Table 2.

Name and Developer

SB-2312

 S * BIO Pte Ltd

Multiplex PI3K inhibitors PROGENICS

 Progenies Pharmaceuticals Inc mTOR / PI3K Dual Inhibitors SBIO

 S * BIO Pte Ltd

Lor220

 Lorus Therapeutics Inc KAR1141

 Karus Therapeutics Ltd

Isoform Selective PI3Kalpha and PI3Kbeta inhibitors SANOFI AVENTIS

Sanofi (formerly Sanofi-aventis)

Irreversible PI3K inhibitor PATHWAY

Pathway Therapeutics Ltd.

 GSK615

 Glaxo SmithKline pic

 GSK1059615

 GlaxoSmithKline pic

 Gdg0349

 Genentech, Inc.

 CUDC907

 Curis inc

 CU906

 Curis inc

 INK-1117

 Intellikine

 PWT33597

 Pathway Therapeutics Ltd.

RG7603 F. Hoffmann-La Roche Ltd

PI3K Inhibitors LICR

 Ludwig Institute for Cancer Research Ltd

PI3K Inhibitor F. HOFFMANN-LA ROCHE

 F. Hoffmann-La Roche Ltd

PI3K Inhibitor BAYER SCHERING

 Bayer HealthCare Pharmaceuticals (formerly Bayer Schering Pharma AG)

XL499

 Exelixis inc

X339

 Xcovery

Wx037

 WILEX AG

SAR245409

Sanofi (formerly Sanofi-aventis)

INK128

 Intellikine

 BYL719

 Novartis AG

 Ckd712

 Chong Kun Dang Pharmaceutical Corp (CKD Pharm)

AQX1125

 Aquinox Pharmaceuticals Inc

RG7321

 F. Hoffmann-La Roche Ltd

 RG7422

 F. Hoffmann-La Roche Ltd

 PF04691502

 Pfizer inc

 AEZS126

 Albany Molecular Research Inc

 AEZS132

Albany Molecular Research Inc BAY806946

 Bayer ag

CHR4432

 Chroma Therapeiiti.ee Ltd GDCO0941

F. Hoffmann-La Roche Ltd

RU2013 / 000243

149

Table 3.

Examples of drugs and drug candidates for the prevention and / or treatment of diseases,

 associated with the corresponding viruses.

Infectious- Disease Compound or drug agent,

 used for the prevention and / or treatment of the corresponding disease

Adenovirus acute bacterial species

 respiratory nn3aT (IRS 19);

 viral infection colostrum, lysozyme

(ARVI), ARVI (recombinant, associated with human)

 adenovirus or (IgaZym);

 called ribavirin

 adenovirus, (Ribavirin BEND A); adenovirus acetylcysteine

 infection (acetylcysteine

 BRAINFARMA);

clarithromycin 3

150

 (Synclar);

 pseudoephedrine hydrochloride,

 tryptolidine

 hydrochloride

 (Actifed) and others.

Sarcoma virus Bird sarcoma Bleomycin sulfate birds (Bleozen) and others.

Coxsackie Aseptic Virus

VZ (menengitis virus, myocarditis, (Picovir) and others.

Coxsackie type pericarditis

OT)

Enterovirus HFMD Ribavirin and

71 others.

Disease Virus, Valomacyclovir

 Epstein — associated with (EPB348, MIV606) Barr, EBV Epstein virus — and others.

 Barr for example but not

 limited to

 Chronic syndrome

 fatigue

 Infectious

 mononucleosis

 (multiglandular

glandular adenosis fever, Filatov’s disease),

Lymphogranulomatosis (Hodgkin's disease), Burkitt's lymphoma (Central African lymphoma), Some of

non-Hodgkin lymphomas,

 Nasopharyngeal carcinoma

 (nasopharyngeal

cancer)

Total variable immune

failure,

Stevens Syndrome—

Johnson

 Alice's Syndrome in Wonderland

 Hepatitis,

 Herpes,

Post-transplant lymphoproliferative disease, Herpetic tonsillitis (herpangina), 3

152

 Multiple sclerosis,

 Hairy

 leukoplakia,

 Kikuchi disease

Dengue flaviviruses, R04588161 - Western fever drug

 Nile, tick-borne encephalitis developed, Japanese by F.

 Encephalitis, Yellow Hoffmann-La Roche Fever Ltd, ST148 H ST610 - Preparations

 developed by SIGA,

Humabs BioMed SA, drugs

 HMB 1513,

 HMB 1514,

 HMB1522,

 developed by Humabs

BioMed SA),

 Dengue vaccine

 ARBOVAXT and others.

Hepatitis B virus hepatitis B Entecavir (Teviral);

In lamivudine (2 eih);

interferon alfa (person)

 (Veldona); hepatitis A

In antigens

 (recombinant)

Amvax B);

 adefovir (Biofovir), tilorone and

 Tilorone-based drugs

 (Tiloron,

 Lavomax and

Amiksin) and others

Hepatitis B virus hepatitis C ribavirin (Viranis,

With Ribavirin

 AUROBINDO); interferon alpha

2a (elnfoStat), tiloron and

 Tilorone-based drugs

 (Tiloron,

 Lavomax and

Amiksin), telaprevir (Incivek), Victrelis, and others.

Cytomegal cytomegaly, Ganciclovir cytomegalovirus virus (Ganciclovir APP infection PHARMA);

 valaciclovir hydrochloride

(Zelitrex), tilorone and tilorone-based drugs

 (Tiloron,

Lavomax and

Amiksin) and others.

HIV virus, AIDS Ritonavir (Norvir); efavirenz immunodeficiency (human Adco-a, Efavirenz);

 HIV lamivudine (Adco-

Lamivudine);

 zidovudine (Adco-

Zidovudine);

 nevirapine (Adco-

Nevirapine);

 stavudine (Stavudac) and others.

Human papilloma - human papilloma, interferon alpha T RU2013 / 000243

155

human cervical cancer 2b

 (recombinant, human)

 (Anterferon); capsid protein

 human papillomavirus type 11 L1 (recombinant); capsid protein

 human papillomavirus type 16 L1 (recombinant); capsid protein

 human papillomavirus type 18 L1 (recombinant); capsid protein

 human papillomavirus type 6 L1 (recombinant) (Gardasil) and others.

Leukemia virus cytarabine

 T-cell (Cytarabine APP Leukemia PHARMA),

human type I mercaptopurine

 (Mercapthol),

enocytabine (Sunrabin),

 daunorubicin hydrochloride

 (Cerubidine) and others.

Influenza A virus acute respiratory acute respiratory viral infections and / or influenza

(influenza virus viral infections and / or influenza type A serotype A, (ARVI), influenza, flu (for example, but not influenza type A virus, diseases limited to subtype A) associated with zanamivir

 H1N1 influenza viruses, (zanamivir),

 H2N2, H3N2, H5N1, Oseltamivir

H7N7, H1N2, H9N2, (oseltamivir),

H7N2, H7N3, H5N2, Oseltamivir

H10N7 and others. phosphate (oseltamivir phosphate),

 Amantadine

 (amantadine),

Rimantadine

(rimantadine), methylphenylthiomethyldimethylaminomethylhydroxybromindole carboxylic acid ethyl ester (INN:

 umifenovirum for example

 Arbidol)

 Pentanedioic acid imidazolylethanamide (e.g.

Ingavirin)

 Triazavirin,

Ribavirin, EV-077

(company drug

Evolva Holding SA), Tilloron and

 Tilorone-based drugs

 (Tiloron,

 Lavomax and

Amiksin), peramivir,

 taribavirin, T-705,

Fludase, and others

Herpesvirus, Kaposi's sarcoma Interferon alpha-associated

bath with (recombinant) sarcoma (Interferon ACHE),

Kaposi paclitaxel (Panataxel) and others.

Myxoma virus myxomatosis Attenuated strain of MICS-98 rabbit myxoma virus and others.

Poliovirus polio poliovirus type 1

 (live, attenuated), poliovirus type 2 (live,

 attenuated) poliovirus type 3 (live,

 attenuated) (Biopolio);

 poliovirus type 1 (inactivated), poliovirus type 2 (inactivated), poliovirus type 3 (inactivated) (Poliorix) and others.

Polyoma virus polyoma Human immunoglobulins and others.

Respiratory acute respiratory palivizumab syncytial viral infection (Synagis), ribavirin virus

 (ARVI) (Virazole) and others.

Acute respiratory rhinovirus Ambroxol;

(for example, but viral infections of amoxicillin; not (SARS), thymomodulin and others limited to rhinovirus.

type 2.16.39) infection

Rotavirus rotavirus infection human rotavirus

 (intestinal flu) serotype G1 genotype

 P8 (live, attenuated) (Rotarix); rotavirus (live) (RotaTeq) and others.

Severe acute coronavirus Inhibitors of small respiratory interfering RNA syndrome SILENCE and others. Sendai virus parainfluenza vaccine PIV1

 ASTRAZENECA infection and others.

SV40 virus polyoma Docetaxel,

carboplatin, azathioprine, paclitaxel, bleomycin sulfate and others.

Chickenpox virus, smallpox, Acyclovir smallpox herpes zoster (Acyclovir-Acre);

 amantadine hydrochloride

 (Symmetrel);

 famciclovir

(Famvir);

 valaciclovir hydrochloride

 (Zelitrex) and others

Adeno-associator of the disease and condition, Drugs, ovanny virus associated with used for the virus or prophylaxis and / or treatment thereof diseases and conditions associated with or caused by the virus

Other drugs and compounds used or developed for the prevention and / or treatment of least

 one of

 diseases listed in this table or

 associated with viruses

 listed in this table are also considered indicated in this table

Industrial applicability The invention is applicable in the field of prevention and treatment of viral diseases, namely, in the use of PBK / AKT / IKK / NF-KB signaling pathway inhibitors, their pharmaceutically acceptable salts, and pharmaceutical compositions and dosage forms containing them for the prevention and treatment of viral diseases .

Claims

CLAIM

1. The use of at least one RVK / AKTLKK / NF-kB signaling pathway inhibitor for the preparation of a prophylaxis and treatment for viral diseases.

2. An application in which at least one RVK / AKTLKK / NF-kB signaling pathway inhibitor is selected from the group consisting of Erlotinib, carboplatin, GSK 1120212 (trametinib), Letrozole, Temozolomide, 4-1 - (6-chloro- 2-methoxyacridin-9-yl) - 1-N, 1-Ν-diethylrentan-1, 4-diamine,

Bortezomib, 1,1-dimethylpiperidinium-4-yl) octadecyl phosphate (D 21266), Dexamethasone, Docetaxel, [(g) -docos-13-enyl] 2- (trimethylammonium) ethyl phosphate, Paclitaxel, Imatinib, Sorafenib, Sutenib, 2-phenylacetic acid

(2K) -2 - [[4 - [(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl) methylamino] benzoyl] amino] pentadicarboxylic acid, Nicotinic acid, pyridin-3 - carboxylic acid, 5-quinoxalin-6-ylmethylenediazolidin-2,4-dione, (5- (4-Fluoro-2-hydroxyphenyl1) furan-2-ylmethylene) thiazolidine-2,4-dione, 5- ( 2,2-difluorobenzo [1,3] dioxol-5-ylmethylene) thiazolidin-2,4-dione, 3- (4-Morpholinothieno [3,2- (1] pyrimidin-2-yl) phenol, 2HC1, N- (2,3- Dihydro-7,8-dimethoxyimidazo [1, 2-c] quinazolin-5-yl) -3-pyridinecarboxamide, 2 - ((4-amino-3- (3-fluoro-4-hydroxyphenyl) - 1H-pyrazolo [3 , 4- <1] pyrimidin-1-yl) methyl) -5-methyl-3-o-tolylquinazolin-4 (3Н) -one, 5- (Benzo [1,3] dioxol1-5-ylmethylene) thiazolidene-2 , 4-dione, - ((1E) - (6-Bromimidazo [1,2-a] pyridin-3-yl) methylene) - '-methyl-M "- (2-methyl-5-nitrobenzene) sulfohydrazide, HC1 , (±) -7-Methyl-2- (morpholin-4-yl1) -9- (1-phenyl aminoethyl1) pyri to [1,2-a] pyrimidin-4-one, 2- (6-

Aminopurin-9-ylmethyl1) -5-methyl-3-o-tolyl-3H-quinazolin-4-one, 17P-Hydroxyvortmannin, 1-Cyclopentyl-3- (1H-pyrrolo [2,3-b] pyridin-5- il1) -1H-pyrazolo [3,4-1] pyrimidin-4-amine, 2 - ((4-amino-3 - (3-hydroxypropinyl) - 1 H-pyrazole o [3, 4-py] pyrimine din- 1 - yl) methyl) -5-methyl-3-o-tolylquinazolin-4 (3Н) -one, a mixture of 6Н-indeno [1,2-e] tetrazolo [1,5-b] [1,2,4] triazin-6-one and 10H-indeno [1, 2-n] tetrazolo [1, 5-b] [1, 2,4] triazin-10-one,

a, a, Dimethyl-4- (2-methyl-8- (2- (3-pyridin1) ethynyl) -1H-imidazo [4, 5-c] quinolin-1-yl) benzoacetonitrile, 1 L6-Hydroxymethyl 1- chiro-inositol-2- (K) -2-0-methyl-3-0-octadecyl-sn-glycerocarbon, 1 - ((1-O-octadecyl-2-Ο-methylglycero) phospho) -3-deoxy-myo -inositol, 1 - ((1 -O- octadecylglycero) phospho) -3-deoxy-myo-inositol, 1-Ethyl-2 - [(2-H-phenyl-K-methyl) aminostyril]] - 3-phenyl-6- (benzothiazol-2-yl) benzimidazolium iodide , 9-Methoxy-2-methyllipticinium acetate, H-Ala-Val-Thr-Asp-His-Pro-Asp-Arg-Leu-Trp-Ala-Trp-Glu-Lys-Phe-OH, 1,3-Dihydro 1- (1 - ((4- (6-phenyl-1H-imidazo [4,5-] quinoxalin-7-yl) phenyl) methyl) -4-piperidine) -2H-benzimidazol-2-one, H-Tyr -Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Ala-Val-Thr-Asp-His-Pro-Asp-Arg-Leu-Trp-Ala-Trp-Glu-Lys-Phe -OH, 10- (4 '- (K-diethylamino) butyl) -2-chlorophenoxazine, HC1, 3-Formylchromone thiosemicarbazone, complex with CuCl ₂ , Mixture - (2- (Diethylamino) ethyl) -2- (4- ( (4- (2,3-dihydro-2-oxo-1H-benzimidazole-1-yl) - 1-piperium dinylmethyl) methyl) phenyl) -3 - phenyl-6-quinolinecarboxamide and 1 - (2-diethylamino) ethyl) -2- (4- ((4- (2,3-dihydro-2-oxo-1 H-benzimidazole- 1-yl) - 1 - piperidinylmethyl) methyl) phenyl) -3-phenyl-7-quinolinecarboxamide, HCH1, Mixture 1 - ((3- (4 - ((4- (2,3-Dihydro-2-oxo-1 N-benzimidazole-1-yl) - 1-piperidine) methyl) phenyl) -2-phenyl-6-quinoxalinyl) carbonyl) -4-methylpiperazine and 1 - ((3- (4- ((4- (2,3 -Dihydro-2-oxo-1 H-benzimidazole-1-yl) -1-piperidine) methyl) phenyl) -2-phenyl-7-quinoxalinyl) carbonyl) -4-methylpiperazine, ZNS1, 4-Dodecyl- - (1 , 3,4-thiadiazole-2-y1) bezolsulfamide, (E) -2-Fluoro-4'-methoxystilbene, [5- (p- Fluorophenyl) -2-ureido] thiophene-3-carboxamide, 5- (thien-3-yl 1) thiophene-3-amino-2-carboxamide, Ν- (3, 5-Bis-trifluoromethylphenyl) -5-chloro-2 -hydroxybenzamide, (5-Phenyl-2-ureido) thiophene-3-carboxamide, 2-amino-6- (2- (cyclopropylmethoxy) -6-hydroxyphenyl) -4- (4-piperidinyl) -3-iridinecarbonitrile, 5- (5,6-Dimethoxybenzimidazole-1-yl) -3- (2-methanesulfonylbenzyloxy) thiophene-2-carbonitrile, 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1,2-a] quinoxaline, 7 - Methoxy-5,11,12-trihydroxycoumestane, [4- (4-Benzo [b] thiophen-2-yl-pyrimidin-2-yl1) phenyl] - (4-pyrrolidine - 1-yl-piperidin-1 - yl) methanone , M- (6-Chloro-9H-P-carbolin-8-yl ) nicotinamide, 1-amino-2-urea-4- (4-chlorophenyl) -6- (4-aminosulfanylphenyl) benzene, 17- Acetoxydzholkinolide (17-AJB), M- (6- (6-chloro-5- ( 4-fluorophenylsulfonamide) pyridin-3-yl) benzo (<1) thiazol-2-yl) acetamide, 7-methoxy-4- (4-nitrophenylthio) furo [2,3-b] quinoline, 3- [4- ( 4-morpholino) pyrido [3 ', 2': 4,5] furo [3,2- (1] pyrimidin-2-yl] phenol,

Hexahydro-10-methoxy-9-methyl-11 (-methyl amino) -9, 13-epoxy-1H, 9H-diindolo [l, 2,3-gh: 3 ', 2M * -lm] nHppono [3,4 -j] [1,7] benzodiazonin-1-ο, quercetin, myricetin, 2-ΜετοκοΗ-Ν - ((6- (1-methyl-4- (methylamino) -1,6-dihydroimidazo [4,5- ( 1] pyrido [2,3-b] pyridin-7-yl) pyridin-2-yl1) methyl) acetamide, 8- (5-chloro-2- (4- methylpiperazin-1-yl) isonicotinamide) - 1 - (4-fluorophenyl) -4,5-dihydro1H-benzo [] indazole-3-carboxamide, Phaleria macrocarpa extract, 2- (1 H-indazol-4-yl) -6 - (4-methanesulfonylpiperazin-1-methylmethyl) -4-morpholin-4-ylthieno (3,2- (1) pyrimidine, 1 - (4 - ((2- (2-aminopyrimidin-5-yl) -7-methyl -4-morpholinothieno (3,2-y) pyrimidin-6-yl) methyl) piperazin-1-yl) -2-hydroxypropanone-1,2,4-difluoro-K- (2- (methoxy) -5- ( 4- (4-pyrazinyl) -6-quinolinyl) -3-pyridinyl) benzenesulfonamide, 2-Methyl-2- [4- (3-methyl-2-oxo-8-quinolin-3-yl-2, 3-dihydroimidazo [4, 5-c] quinolin-1-yl) phenyl] propionitrile, 1- [4- (3-Ethyl-7-morpholin-4-yl-3H- [1,2,3] triazolo [4,5- c1] feast midin-5-yl) phenyl] -3- [4- (4-methylpiperazin-1-carbonyl1) phenyl] urea, ZSTK474, SF 1126, 6-amino-4- (4-phenoxyphenylethylamino) quinoline, 3-Chloro-4 - nitro - (5-nitro-2-thiazolyl) benzamide, 4-Methyl- ¹ - (3-phenylpropyl) benzene-1,2-diamine, 5-Hydroxy- (2,6-diisopropylphenyl) - -isoindole-1 , 3-dione, 6,6-Dimethyl-2- (phenylimino) -6,7-dihydro-5H-benzo [1,3] oxathiol-4-one, 1- (3,5-di-tert-butyl- 4-hydroxyphenyl) -2- (2- (3-hydroxypropylamino) - 5,6-dimethyl-1H-benzo [(1] imidazol-1-yl) ethanone, 2-AMHHO-N- {4- [5- ( 2-phenanthranyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] phenyl} acetamide, 5- (1- (4-amino-6-methyl-1,3,5-triazin-2-yl) - 1H-benzo [(1] imidazol-2-yl but) benzene-1,3-diol, N- (2- dimethylamino) ethyl) -4- (3 - (2 - ((7-fluoro-5-methoxy-2- (1,3,5-trimethyl-1 H-pyrazolo-4-yl) - 1 H-indole-3 -yl) methylene) -3-oxo-2,3-dihydrobenzofuran-5-yl) ureido) -methylbenzamide, 5- [5- (2-chlorophenyl) furan-2-ylmethylmethylene] thiosolidide-2,4-dione, 3- (4-morpholino-4-ylpyrido [3 ', 2': 4,5] furo [3,2-y] pyrmidin-2-yl) phenol hydrochloride, - [4 - [[4- (Dimethiamino) - 1- pyreridinyl] carbonyl] phenyl] -M '- [4- [4,6-di (4-morpholinyl) -1,3,5-triazin-2-yl] phenyl] urea, 5- [6- (4 - methanesulfonylpiperazin-1-methylmethyl) -4-morpholin-4-ylthieno [3,2- (1] pyrimidin-2-yl] -4-methylpyrimidin-2-ylamine, 1- [4- (3-Ethyl-7- morpholin-4-yl-ZN- [1,2,3] triazolo [4,5- <1] pyrimidin-5- l) phenyl] -3- {4 - [(4-methylpiperazin-1-yl) carbonyl] phenyl} urea, 3 - (1 - (4-amino-6-methyl-1, 3,5-triazin-2- il) -1H-benzo [] midazol-2-ylamino) phenol, 3- (2-amino-1, 3-benzothiazol-6-yl) - 1 - {[2- (4-methylpiperazin-1 - yl) quinoline -3-yl] methyl} - 1 H-pyrazolo [3,4-c1] pyrimidin-4-amine, 8 - [(5-Chloro-2- {4 - [(1- {2 - [(2-hydroxyethyl ) amino] -2-oxoethyl} -1H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] - 1 - (4-φτo phenyl) -4,5-dihydro-lH-benzo [g ] indazol-3-carbocamide, 3- [6- (4-Methanesulfonylpiperazin-1-ylmethyl) -4-morpholin-4-ylthieno [3,2-c!] pyrimidin-2-yl] phenol, 2- (2- (2-aminopyrimidin-5-yl) -4-morpholinothieno [3,2-y] pyrimidin-6-yl) p Opan-2-ol, 17- Hydroxycormormannine analogue, 6- (4-Methanesulfonyl-piperazin-l-ylmethyl) -4-morpholin-4-yl-2-pyridin-3-ylthieno [3,2-s1] pyrimidine, (3- (6 - ((4 - (methylsulfonyl) piperazin-1-yl) methyl) -4-morpholinothieno [3,2-c1] pyrimidin-2-yl) phenyl) methanol, 2- (2-hydroxyethylamino) -6- (3-chloroanilino) - 9 -isopropylpurine hydrochloride, 2-Morpholino-8-phenylchromen-4-one, 1 - (4- (1 - (4-amino-6-methyl-1, 3, 5-triazin-2-yl) - 1 N-benzo [g] imidazole -2-ylamino) phenyl) -3-methylurea, 6,6-dimethyl-2- (6- (6-methylpyridazin-3-ylamino) -2H-benzo [b] [1, 4] oxazin- 4 (3N) -yl) -6,7-dihydrothiazolo [5,4-c] pyridin-4 (5H) -one, N- (6- (4-amino-1 - ((2- (4-methylpiperazine- 1-yl) x inolin-3-yl) methyl) - 1H pyrazolo [3,4- (1] pyrimidin-3-yl) benzo [(1] thiazol-2-yl) asetamide, 1- (4- (4- (3-oxa) -8-azabicyclo [3.2.1] octan-8-yl) -6-morpholino-1,3,5-triazin-2-yl) phenyl) -3- (pyrimidin-4-yl) urea, 2- (2 - (2-amino-4-methyl-pyrimidin-5-yl) -4-morpholinothieno [3,2- (1] pyrimidin-6-yl) propan-2-ol, 6- (1H-indazol-4-yl ) -1-methyl-4- (4- (methylsulfonyl) phenoxy) -1H-pyrazolo [3,4-b] pyridine, 5- (6- ((4- (methanesulfonyl) piperazin-1-yl) methyl) - 4- morpholinothieno [3,2-y] pyrimidin-2-yl) pyrimidin-2-amine, 2- (difluoromethyl) -1- (4,6-dimorpholin-4-yl-1,3,5-triazin-2 -yl) -1H-benzimidazole, 5- (6 - {[4- (methanesulfonyl) piperazin-1 - yl] methyl} -4-morpho yn-4-yl-thieno [3,2-a] pyrimidin-2- il) pyridin-2-amine, 5- (7-methyl-6 - ((4- (methylsulfonyl) piperazin-1-yl) methyl) -4-morpholinothieno [3,2-] pyrimidin-2-yl) pyrimidin- 2-amine, M-6- (6-methoxypyridin-3-yl) -2- morpholino-4, 5-bipyrimidin-2 ', 6-diamine, 3- (4-morpholino-6- (pyridin-2-yl ) pyrimidin-2-yl) phenol, 6- (1H-indol-4-yl) pteridine-2,4-diamine, 5- (7- (methylsulfonyl) -2-morpholino-6,7-dihydro-5H-pyrrolo [2,3-th] pyrimidin-4-yl) -pyrimidin-2-amine, 1-methyl-3- [4-morpholin-4-yl-1 - (1-pyridin-3-yl methyl-piperidin -4 -yl) -1H-pyrazolo [3,4-c1] pyrimidin-6-yl] urea, 2- (6- (1H-pyrazolo-4-yl) -2,3-dihydrobenzo [b] [1, 4] oxazin-4-yl) - 6,6-dimethyl-6,7-dihydrothiazolo [5,4-s] pyr midin-4 (5H) -one, 4- {6-chlorimidazo [1,2-a] pyridin-3-yl} -2 - [(2-methyl-5-nitrobenzene) sulfonyl] -1,3-thiazole, 3- (4-morpholino-6- (pyridin-4-yl) pyrimidin-2-yl) phenol, 3- (2,4-diaminopteridin-6-yl) phenol, 2 - ((4-amino-3- ( 3-fluoro-5-hydroxyphenyl) -1H-pyrazolo [3,4- <1] pyrimidin-1-yl) methyl) -5-methyl-3-o-tolylquinazolin-4 (3Н) -one, 2- [4 -Fluoro-3- (3-fluoro-5-hydroxyphenyl) indazol-1-ylmethyl] -5-methyl-3-o-tolyl-3H-quinazolin-4-one, 2- (6- (1 - (2- hydroxy-3-methoxypropyl) -1Npyrazol-4-yl) -2H-benzo [b] [1,4] oxazin-4 (3N) -yl) -6,6-dimethyl-6,7-dihydrothiazolo [5,4 -c] pyrimidine -4 (5H) -one, 3- (6- (6-methoxypyridin-3-ylamino) -2-morpholinopyrimidin-4- il) phenol, 3 - (6- (1 H-indazol-5-ylamino) -2-morpholinopyrimidin-4-yl) phenol, 2- (6- (1 H-pyrazol-4-yl) -2.3- dihydrobenzo [b] [1, 4] oxazin-4-yl) -5, 5-dimethyl-5,6-dihydrobenzo [c!] thiazol-7 (4H) -one, 5,5-dimethyl-2- (6 - (6-methylpyridin-3-yl) -2,3-dihydrobenzo] [1,4] oxazin-4-yl) -5,6-dihydrobenzo [o!] Thiazol-7 (4H) -one, 3 - [ 5 - (2, 4-dioxothiazolidin-5 - ylidenemethyl) furan-2-yl] -4-hydroxybenzoic acid, 5- [5- (3-hydroxyphenyl) furan-2-ylmethylene] thiazolidine-2,4-dione, 5 - [5- (3-methoxyphenyl) furan-2-ylmethylene] thiazolidin-2,4-dione, 5- [5- (2-bromo-4-nitrophenyl) furan-2-ylmethylene] thiazolidin-2,4-dione , 5- [5- (4-hydroxyphenyl) furan-2-ylmet ylene] thiazolidin-2,4-dione, 5- [5- (2,4-difluorophenyl) furan-2-yl1-methylene] thiazolidin-2,4-dione, 3 - [5 - (2, 4-dioxothiazolidine-5- or denmethyl) furan-2-yl] -4-hydroxybenzoic acid, 5- [5- (3-hydroxyphenyl) furan-2-ylmethylene] thiazolidin-2, 4-dione, 1-Ethylamino-3- (3- (p - tolylamino) -3,4-dihydropyrido [2,3-b] pyrazin-6-yl) urea, 3- [5- (2,4-dioxothiazolidin-5-ylidenomethyl) furan-2-yl] benzoic acid methyl ester 5- (5-benzo [1,3] dioxol-5-yl-furan-2-ylidenomethyl) thiazolidin-2, 4-dione, 3- (5 - ((4-oxo-2-thioxothiazolidin-5-ylidene ) methyl) furan-2-yl) benzoic acid, 5- (5'-nitro [2,2] bifuryl-5-ylmethylene) thia zolidin-2, 4-dione, 5- [5-phenyl) furan-2-ylmethylene] thiazolidin-2, 4-dione, 4- (4- Chlorophenyl) -4- [4- (1H-pyrazol-4-yl) phenyl] piperidine, 2- [6-amino-9H-purin-9-yl) methyl] -5-methyl-3- (2-methyl) - 4 (3N) quinazolinone, PKI-179, 1-cyclopentyl-3- (1H-pyrrolo [2,3-b] pyridin-5-yl) -1H-pyrazolo [3,4-c1] pyrimidin-4-amino , PX-13-170H, (lE, 4S, 4aR, 5R, 6aS, 9aR) - 5 - (Acetyl oxy) -1- [(di-2-propenylamino) methylene] -4,4a, 5,6,6a 8,9,9a-octahydro-11-hydroxy-4- (methoxymethyl) -4a, 6a-dimethylcyclopenta [5,6] naphtho [1,2-c] pyran-2,7,10 (1H) -trion, PX-866-170H, 3- [2,4-diamino-6- (3-hydroxyphenyl) pteridin-7-yl] phenol, 1- (4 - {[3-Carbamoyl-1- (4-fluorophenyl) -4 , 5-dihydro-1H-benzo ^] indazol-8-yl] carbamoyl} -5-clopyridin-2-yl) -4 - [(1-methyl-1 H-pyrazol-4-yl) methyl] pipe razin-2-carboxylic acid, 1-Indan-5-yl-4-ureido-1H-pyrazole-3-carboxamide, piperidine-3-carboxylic acid (4-carbamoyl-5-ureidothothiophen-2-yl) amide, 8- [(5-Chloro-2- {4- [(1-methyl-1 H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) aMHHo] - 1 - (4-fluorophenyl) -4.5 -dihydro-1 H-benzo [] indazole-3-carboxylic acid amide, 8- (5-chloro-2- (4-hydroxypiperidin-1-yl) dihydro-lH-benzo [g] indazole-3-carboxylic acid amide, 8- (5-chloro-2- (2-methoxyethylamino) isonicotinoylamido) -1- (4-fluorophenyl1) -4,5-dihydro-1H-benzo ^] indazole-3-carboxylic acid amide, 8 - {[2- (4 - {[1- (2-amino-2-oxoethyl) -1H-pyrazo -4- yl] methyl} piperazin-1-yl) -5-chloroisonicotinoyl] amino} -1- (4-fluorophenyl) -4,5-dihydro-1H-benzo ^] indazole-3-carboxamide, Ethyl [4- ({4 - [4- ({[3- (aminocarbonyl) - 1 - (4-fluorophenyl) -4,5-dihydro-1 H-benzo [g] indazol-8-yl] amino} carbonyl) -5 - chloropyridine - 2 -yl] piperazin-1-yl} methyl) - 1 H-pyrazol-1-yl] acetate, Methyl [4 - ({4- [4 - ({[[3- (aminocarbonyl) -1- (4-trifluorophenyl) -4, 5-dihydro-1 H-benzo [g] indazol-8-yl]

amino} carbonyl) -5-chloropyridin-2-yl] piperazin-1-yl} methyl) - 1 H-pyrazol-1-yl] acetate, 8- (5-chloro-2- (4-methylpiperazin-1-yl) ) isonicotinoyl) -1- (3-hydroxyphenyl) -4, 5-dihydro-1 H-benzo [g] indazole-3-carboxamide, 2-methoxyethyl- [4 - ({4- [4 - ({[3- (aminocarbonyl) - 1 - (4-yiogorpepu1) -4,5-dihydro-1 H-benzo ^] indazol-8-yl] amino} carbonyl) -5-chloropyridin-2-yl] piperazin-1-yl} methyl ) - 1 H-pyrazole-1-yl] acetate, 8 - [(5-Chloro-2- {4 - [(1- {2 - [(2-methoxyethyl) amino] -2-oxoethyl} -1H-pyrazole -4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo ^] indazole-3-carboxamide, 8- [(5-Chlorine -2- {4 - [(1- {2 - [(2-met il) amino] -2-oxoethyl} -1H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] -1- (4-fluorophenyl) -4,5-dihydro-1H-benzo ^] indazole-3-carboxamide, 8- (5-chloro-2- (4-methylpiperazin-1-yl) isonicotinoyl) - 1 - (3 - fluorophenyl) -4, 5 - dihydro-1 N-benzo [g] in dazole -3-carboxamide, 8 - (5-Chl op-2- [(4- (1 H-pyrazol-4-ylmethylpiperazin-1-yl]

isonicotinoyl) - 1 - (3-fluorophenyl) -4,5-dihydro-1 H-6eH3o [g] indazole-3-carboxamide, 8 - ({5-Chloro-2- [4- (2-methoxyethyl) piperazine- 1-yl] isonicotinoyl} amino) - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo ^] indazole-3-carboxamide, 8 - [(5-Chloro-2- {4- [(1 - {2 - [(2-isopropyl) amino] -2-oxoethyl} - 1H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] - 1 - (4-fluorophenyl) -4.5 dihydro-1H-benzo | ] indazole-3-carboxamide, 8- (5-chloro-2- (4-methylpiperazin-1-yl) isonicotinoyl) - 1 - (4-chloro-3-hydroxyphenyl) -4,5-dihydro-lH-benzo [ g] indazole-3-carboxamide, 8 - {[5-Chloro-2- (4 - {[1- (3-hydroxypropyl) -1H-pyrazol-4-yl] methyl} piperazine-1-yl) isonicotinoyl] amino } - 1 - (4-fluorophenyl) -4,5-dihydro-1H-benzo [§] indazole-3-carboxamide, 8 - [(5-Chloro-2- {4 - [(1- {2- [dimethylamino ] -2-oxoethyl} -1H-pyrazol-4-yl) methyl] piperazin-1-yl} isonicotinoyl) amino] -1- (4-fluorophenyl) -4,5-dihydro-1H-benzo [] indazole-3 -carboxamide, 8- {[5-Chloro-2- (4- {[1 - (2- {[2- (methylthio) ethyl] amino} -2-oxoethyl) - 1 H-pyrazol-4-yl] methyl } piperazine-1-l) isonicotine oyl] amino} -1- (4-fluorophenyl) -4,5-dihydro-1H-benzo ^] indazole-3-carboxamide, N- [3- (2, 1, 3-Benzothiazol-5-ylamino) -2 -quinoxalyl] -4-methyl benzosulfamide, NVP-BKM120, GSK690693, 4- (2- (4-amino-1,2,5-oxadiazol-3-yl) -1-ethyl-7 - {[(38) - 3-piperidinylmethyl] oxy} - 1 H-dazo [4, 5-c] pyridin-4-yl) -2-methyl-3-butyn-2-ol, ^ - {4- [3- (3,5-Dimethoxyphenylamine) - quinoxaline-2-yl1sulfamoyl] phenyl} -3-methoxy-4-methylbenzamide, NVP-BGT-226, PF-4691502, 8- [4- (1-aminocyclobutyl) phenyl] -9-phenyl- 1,2,4 -triazolo [3,4 -!] [1,6] naphthyridin-3 (2H) -one dihydrochloride, (8) -2- (4-chlorophenyl) -1- (4 - ((5K, 7K) -7- hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta [<h] pyrimidin-4-yl) piperazin-1-yl) -3- (isopropylamino) propan-1one, BAY80-6946, 5-fluoro-3 -phenyl-2- [(S) - 1 - (9H-purin-6-ylamino) -propyl] -ZH-quinazolin-4-one, trans-4- [4-amino-5 - (7-methoxy-1 N-indol-2-yl) imidazo [5, 1 - g [1, 2,4] triazin-7-yl] cyclohexane-carboxylic acid, AZD8055, CCT128930, 8- (1-Hydroxyethyl) -2-methoxy-3- (4-methoxybenzyloxy [c] coumarin-6-one, AZD6482, M- {5- [4-Chloro-3- (2-hydroxyethanesulfonylamino amino) phenyl] -4-methylthiazol-2-yl} acetamide, 2- (4-aminopyrazolo [3,4-c1] pyrimidin-1-yl methyl) -5-methyl-3-о-tolyl-3Н-quinazolin-4- he, (28) -S- [2- (tert-butyl) - 4'-methyl [4,5'-bitiazole] -2'-yl] -1,2-pyrrolidinedicarboxamide, 5- [5- (4- Fluorophenyl) furan-2-ylmethylene] thiazolidin-2,4-dione, 5- (7- (methylsulfonyl) -2-morpholino-6,7-dihydro-5H-pyrrolo [2,3- c!] Pyrimidin-4- il) pyrimidin-2-amine.

3. The use according to claim 1 or claim 2, wherein the PI3K / AKT IKK / NF-kB signaling pathway inhibitor is a compound selected from the group consisting of [5- (p-Fluorophenyl) -2-ureido] thiophen-3 -carboxamide, 2-amino-6- (2- (cyclopropylmethoxy) -6-hydroxyphenyl) -4- (4-piperidinyl) -3-pyridinecarbonitrile, 4- (2'-aminoethyl) amino-1,8-dimethylimidazole [1 , 2-a] quinoxaline, [4- (4-Benzo [b] thiophen-2-ylpyrimidin-2-yl) phenyl] - (4-pyrrolidin-1-ylpiperidin-1 - yl) methanone, [4- (4 -Benzo [b] thiophen-2-yl-pyrimidin-2-yl1) phenyl] - (4-pyrrolidin-1-ylpiperidin-1-yl) methanone.

4. The use of claim 3, wherein the PDK / AKT / IK TNF-kB signaling pathway inhibitor is 4- (2'-aminoethyl) amino-1, 8-dimethylimidazole [1, 2-a] quinoxaline.

5. The use according to claim 1 or claim 2, wherein the PI3K / AKT / IKK / NF-kB signaling pathway inhibitor is administered in combination with an antiviral drug.

6. The use according to claim 5, in which the antiviral drug is oseltamivir.

7. The use of claim 6, wherein the PDKJAKTAKK / NF-kB signaling pathway inhibitor is 4- (2'-aminoethyl) amino-1, 8-dimethylimidazole [1, 2-a] quinoxaline.

8. The use of claim 1 or claim 2, wherein the viral infection is influenza A or adenovirus infection.

9. A pharmaceutical composition for the prevention and treatment of viral infections in the form of a solid dosage form for oral administration, containing an effective amount of a PBK / AKT IKK / NF-kB signaling pathway inhibitor according to claim 1 or claim 2, as an active component and a carrier comprising microcrystalline cellulose, potato or modified starch, polyvinylpyrrolidone, methyl cellulose, dibasic calcium phosphate, magnesium stearate, hydroxypropyl methyl cellulose.

10. The drug according to claim 9, which is a tablet.