RU2837548C1 - Novel pyrrolopyrimidine derivatives - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: group of inventions relates to a compound of formula C''

or pharmaceutically acceptable salts thereof, as well as a pharmaceutical composition, and a medicinal agent containing same, and use for preparing a medicinal agent for treating autoimmune diseases by inhibition of Janus kinase.

EFFECT: improved compared to (1-(2-hydroxy-ethanesulphonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile selectivity with respect to inhibition of JAK enzymes.

11 cl, 2 dwg, 3 tbl, 5 ex

Description

The invention relates to the field of chemical-pharmaceutical industry and medicine and represents new derivatives of pyrrolopyrimidines.

LEVEL OF TECHNOLOGY

Autoimmune diseases affect 8-10% of the world's population, often young people, children are susceptible to various disorders of the immune system. Autoimmune diseases are associated with a malfunction of the human immune system, which begins to perceive its own tissues as foreign and damage them. Disorders occur for various reasons, including to a large extent due to an unfavorable environment, aggressiveness of components included in food, air, water. Autoimmune diseases include: rheumatoid arthritis, systemic lupus erythematosus, scleroderma, multiple sclerosis, atopic dermatitis, alopecia, etc.

Rheumatoid arthritis is a chronic inflammatory disease associated primarily with joint damage, leading to irreversible changes expressed in the degradation of cartilage, bone tissue and, subsequently, weakening of muscles, ligaments and tendons. The development of the disease is based on autoimmune inflammation, characterized by an attack of the immune system on the cells of the body itself. In addition to joints, rheumatoid arthritis often affects internal organs - blood vessels, nervous system, kidneys, heart, lungs. Timely diagnosis and treatment can avoid irreversible consequences of complications. However, the treatment of rheumatoid arthritis requires a systematic approach based on a combination of supportive therapy (smoking cessation, balance of rest and exercise, therapeutic exercise, healthy sleep, diet, analgesics), drugs that inhibit the progression of the disease, if necessary, non-steroidal anti-inflammatory drugs.

The etiology of rheumatoid arthritis is complex due to its multifactorial nature [Skogoreva N.V., Makeeva A.V. Pathophysiological characteristics of rheumatoid arthritis: etiology, pathogenesis and principles of treatment. - 2015.]. The causes of the disease can be both genetic predisposition and the impact of the external environment, bad habits, infections, stress and excessive physical activity. At the moment, it is unknown how the infection leads to chronic joint inflammation. Perhaps rheumatoid arthritis develops as a result of long-term persistence of the pathogen in the joints or accumulation of its waste products in the synovial membrane. It is possible that when joint tissue is damaged by infection, new antigens appear, to which an immune response develops, that is, the process develops according to the type of autoimmune inflammation. In addition, rheumatoid arthritis may be based on molecular mimicry (similarity between foreign and self antigens), as a result of which, during the immune response to the pathogen's antigens, antibodies to the autoantigens of the joints are produced.

The treatment of rheumatoid arthritis is based on a combination of symptomatic and basic therapy. Basic therapy drugs have been used in rheumatology for over 30 years [Nasonov E.L. Use of tumor necrosis factor inhibitors in rheumatoid arthritis: the place of etanercept // Scientific and practical rheumatology. - 2008. - No. 5. - P. 1-20]. Basic therapy includes antitumor and cytostatic drugs: Methotrexate, Leflunomide, Sulfasalazine, Chrysanol, Tauredon, Plaquenil. Modern methods of basic treatment also involve the use of biological drugs, such as Infliximab, Rituximab, Abatacept, Anakinra. Symptomatic drugs include glucocorticoids and non-steroidal anti-inflammatory drugs aimed at reducing pain and increasing the degree of joint mobility. Among non-steroidal anti-inflammatory drugs, the following are distinguished: Celecoxib, Diclofenac, Lornoxicam, Movalis, Arcoxia, Nimesulide, Ibuprofen; among glucocorticoids, Dexamethasone, Triamcinolone, Prednisolone, Betamethasone.

Impact on the molecular mechanisms of autoimmune inflammation allows to fight symptoms of rheumatoid arthritis more effectively and to achieve stable remission with timely therapy. An example of a modern approach to therapy is the use of Baricitinib, which acts by inhibiting cytokine signaling pathways through reversible inhibition of enzymes known as Janus kinases (JAKs), specifically JAK1 and JAK2. JAK kinases are important growth factors and intercellular parts of cytokine signaling pathways. JAK kinases phosphorylate and activate signal transducers and activators of transcription (STATs), which move to the nucleus and induce transcription of effector genes [Leonard W. J., O'Shea J. J. Jaks and STATs: biological implications // Annual review of immunology. - 1998. - Vol. 16. - P. 293; McInnes I. B. et al. The JAK family belongs to the non-receptor cytoplasmic protein tyrosine kinases (PTKs), including four types: JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase 2) [McInnes I. B. et al. Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations // Arthritis Research & Therapy. - 2019. - Vol. 21. - No. 1. - P. 1-10]. JAK1 has attracted considerable attention since it was identified as a promising target for anti-rheumatoid arthritis drugs. In addition, other inflammations are closely associated with JAK/STAT signaling [Gao H. et al. Study on the binding mode of a pyrrolotriazine derivative with JAK2 by docking and MD simulation // Molecular Simulation. - 2019. - Vol. 45. - No. 3. - P. 230-238].

The efficacy of Baricitinib has been confirmed in mouse models of colorectal rheumatoid arthritis and other autoimmune diseases, such as atopic dermatitis and alopecia [Fridman J. S. et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050 // The Journal of Immunology. - 2010. - Vol. 184. - No. 9. - P. 5298-5307; Hoy S. M. Baricitinib: a review in moderate to severe atopic dermatitis // American journal of clinical dermatology. - 2022. - Vol. 23. - No. 3. - P. 409-420; Kwon O. et al. Efficacy and safety of baricitinib in patients with severe alopecia areata over 52 weeks of continuous therapy in two phase III trials (BRAVE-AA1 and BRAVE-AA2) // American Journal of Clinical Dermatology. - 2023. - T. 24. - No. 3. - P. 443-451].

In addition to its use in the treatment of autoimmune diseases, Baricitinib has other application profiles. Recently, Baricitinib became the first immunomodulatory drug for the treatment of COVID-19 to receive approval from the Food and Drug Administration [Rubin R. Baricitinib is first approved COVID-19 immunomodulatory treatment // JAMA. - 2022. - Vol. 327. - No. 23. - P. 2281-2281].

One of the main manifestations of a viral disease is a cytokine storm associated with an excessive inflammatory response. The inhibitory effect of Baricitinib on Janus kinases leads to a decrease in cytokine activity and, as a consequence, suppression of inflammatory processes [Roskoski Jr R. Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases // Pharmacological research. - 2016. - Vol. 111. - P. 784-803]. In addition, there is an assumption that Baricitinib can block the penetration of the SARS-CoV-2 virus into cells by inhibiting the AP2-associated kinase pathway, which is necessary for endocytosis of the virus into cells [Stebbing J. et al. Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients // EMBO molecular medicine. - 2020. - Vol. 12. - No. 8. - P. e12697]. Indeed, Baricitinib has gained particular prominence for its use in COVID therapy, including approval for use in combination with other active agents such as remdesivir. Numerous studies have shown that Baricitinib can reduce mortality and improve clinical outcomes in patients with severe viral diseases, particularly those caused by RNA viruses.

Along with high activity among the qualities of Baricitinib, negative manifestations are also noted in the form of side effects expressed in an increase in LDL (low density lipoprotein) (33.6%), upper respiratory tract infection (14.7%), nausea (2.8%), impaired fertility, manifestation of teratogenicity and embryolethality. There are also cases of anemia [Deprez V. et al. Therapeutic Maintenance of Baricitinib and Tofacitinib in Real Life // Journal of Clinical Medicine. - 2020. - Vol. 9. - No. 10. - P. 3319], palmar-plantar rash [Koumaki D. et al. Palmoplantar pustulosis-like eruption induced by baricitinib for the treatment of rheumatoid arthritis // European Journal of Case Reports in Internal Medicine. - 2020], psoriasis [Di Domizio J. et al. Baricitinib-induced paradoxical psoriasis // Journal of the European Academy of Dermatology and Venereology. - 2020. - Vol. 34. - No. 8. - P. e391-e393]. The prior art also reports the risk of thrombosis against the background of the use of JAK inhibitors, in particular Baricitinib [Faquetti M. L. et al. Identification of novel off targets of baricitinib and tofacitinib by machine learning with a focus on thrombosis and viral infection // Scientific reports. - 2022. - Vol. 12. - No. 1. - P. 1-11].

Also known from the prior art are attempts to create analogues of Baricitinib, possessing similar activity and a number of properties favorable in the field of pharmaceuticals. For example, such analogues are disclosed in patent RU 2601410, the compound of which was chosen by the Authors as the closest analogue of the present invention.

It is important to note that even modern drugs for the treatment of autoimmune diseases do not increase the life expectancy of patients and do not prevent their early disability. For example, despite the treatment, only 10% of patients have a benign course of rheumatoid arthritis with rare exacerbations, in 65-70% the disease is characterized by a slow but steady progression with frequent exacerbations and incomplete remissions, and the rest develop a "malignant" course with multiple joint lesions, resistance to drug therapy and severe, potentially fatal dysfunction of internal organs.

The development of modern accessible approaches to the treatment of autoimmune diseases, as well as the development of new means capable of slowing the progression of autoimmune diseases, is currently a pressing task with high social significance. At the same time, untimely diagnosis and incorrect treatment of autoimmune diseases fatally affect the health, duration and quality of life of patients up to complete loss of ability to work and irreversible disability.

The development of new molecules that are active in the treatment of autoimmune diseases and viral infections opens up opportunities to improve the profile of the physicochemical, technological and pharmacological characteristics of a pharmaceutical product. This expands the range of active agents that a drug development specialist has at his disposal when developing a new drug with improved characteristics. And the sustainable development of modern approaches to the synthesis of new active agents allows the introduction of ecological, resource-efficient, atom-economical innovative technologies into production, which contribute to economic development and minimize damage to the environment.

The discovery of the possibility of selective inhibition of cytokine signaling pathways using reversible inhibition of JAK enzymes has expanded the possibilities of therapy for autoimmune diseases and viral infections.

Thus, there is currently an urgent need to develop new active agents with improved profiles of physicochemical, technological and pharmacological properties for the treatment of autoimmune diseases and viral infections.

In connection with the Decree of the President of the Russian Federation of May 7, 2024 No. 309 "On the national development goals of the Russian Federation for the period up to 2030 and for the prospect of 2036" within the framework of the import substitution program "Pharma-2030", the authors of the present invention have made efforts aimed at strengthening technological sovereignty in the pharmaceutical industry, to create an innovative product based on new derivatives of pyrrolopyrimidines that exhibit high activity in the treatment of autoimmune diseases and viral infections.

The new pyrrolopyrimidine derivatives of the present invention, according to the Order of the Ministry of Health of Russia No. 514n "On approval of the criteria for classifying goods, works, services as innovative and high-tech products for the purposes of forming a plan for the procurement of such products", satisfy a set of criteria that classify the present inventions as innovative products. Thus, the said compounds differ significantly from the closest analogue and have improved properties, while the method for obtaining these compounds uses new technologies, intermediates and materials, therefore, the compounds and methods for their preparation according to the present invention meet the criteria of scientific and technical novelty.

Also, the present group of inventions is science-intensive, has an applied nature, has practical application, and in the future, using highly qualified intellectual work and the results of intellectual activity, will be actively implemented in the domestic chemical and pharmaceutical industry. At the same time, the price of new drugs according to the present invention with improved efficiency will be significantly lower than the price of analogues currently existing in the territory of the Russian Federation, which will allow achieving a positive economic effect of the sale of goods for the Russian Federation.

It should also be noted that, in accordance with the above-mentioned Order of the Ministry of Health of Russia No. 514n, the present group of inventions pertains to high-tech products, since it corresponds to the priority areas of development of science, technology and engineering in the Russian Federation, namely, biomedical and veterinary technologies (in accordance with the Decree of the President of the Russian Federation of July 7, 2011 No. 899 "On approval of priority areas of development of science, technology and engineering in the Russian Federation and the list of critical technologies of the Russian Federation"), is manufactured and performed by enterprises of knowledge-intensive sectors of the economy, namely, pharmaceutical and chemical; is manufactured and performed using the latest models of technological equipment, technological processes and technologies with the participation of highly qualified, specially trained personnel.

DISCLOSURE OF THE ESSENCE OF THE INVENTION

The objective of the present invention was to create new pyrrolopyrimidine derivatives that exhibit high activity against autoimmune diseases and viral infections.

The authors of the present invention have obtained and studied new pyrrolopyrimidine derivatives, in a particular case of the invention, compounds of formulas (A’’ - C’’) and their pharmaceutically acceptable salts, which have improved activity and selectivity in comparison with the analogue with respect to autoimmune diseases, in particular, with respect to the inhibition of JAK enzymes, as well as viral infections, while the authors of the invention have succeeded in achieving an improved safety profile, which is expressed, among other things, in a decrease in undesirable effects from taking the new pyrrolopyrimidine derivatives of the present invention, such as, among other things, impaired fertility, manifestation of teratogenicity and embryolethality. Studies of the properties of the new pyrrolopyrimidine derivatives within the framework of the present invention have made it possible to establish their improved physicochemical and technological properties.

New derivatives of pyrrolopyrimidine

Particular cases of new pyrrolopyrimidine derivatives, namely 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’), 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B’’), 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C’’).

The compounds of the present invention, including their salts, can be prepared according to the general synthesis scheme described below:

Scheme for the synthesis of pyrrolopyrimidine derivatives according to the present invention

The compounds of the present invention, including their salts, can be prepared according to the general synthesis scheme described below:

Scheme for the synthesis of pyrrolopyrimidine derivatives according to the present invention

The compounds of the present invention, including their salts, can be prepared according to the following synthesis scheme:

Scheme of synthesis of new derivatives of pyrrolopyrimidines A’’ - C’’

In the first stage, 4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine protected at the amino group of the pyrrole ring was obtained. (1a). For this, the calculated amount of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (I) protected at the amino group of the pyrrole ring, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and a base (preferably alkali or alkaline earth metal carbonates or phosphates, tertiary amines, in particular aliphatic ones, more preferably sodium carbonate) were loaded into a mixture of a water-miscible organic solvent (more preferably dioxane, acetone, acetonitrile) and purified water in a weight ratio of 1:10 to 10:1. The reaction vessel was evacuated and filled with an inert gas. Then a palladium catalyst (more preferably Pd(PPh₃)₄) and refluxed for 8-48 h (more preferably 16 h). The reaction mixture was diluted with a water-immiscible solvent (more preferably ethyl acetate) and purified water. The organic layer was separated, dried over sodium sulfate and concentrated on a rotary evaporator. An organic solvent (more preferably methyl tert-butyl ether (MTBE), diisopropyl ether, diethyl ether, tetrahydrofuran (THF), methyltetrahydrofuran, heptane, hexane) was added to the residue and kept at 2-10°C (more preferably at 4°C) for 2-24 h (more preferably overnight). Precipitate formation was observed. The resulting precipitate was filtered, washed with an organic solvent (preferably MTBE, diisopropyl ether, diethyl ether, THF, methyltetrahydrofuran, heptane, hexane) and dried.

In the second stage, the synthesis of the amino-protected pyrrole and pyrazole ring 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile (2a) was carried out. For this purpose, an organic solvent (more preferably acetonitrile, acetone, methanol, dimethylformamide) and a catalyst, for example, an organic base (preferably alkyl substituted guanidine, quaternary ammonium base), were added to the calculated amount of the amino-protected pyrrole ring 4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (1a) and the amino-protected pyrazole ring 2-(3-azetidinylidene)acetonitrile. The resulting mixture was stirred for 8-48 (preferably 16 h) at 10-50°C (preferably at room temperature). The reaction mixture was concentrated on a rotary evaporator. The residue was dissolved in a water-immiscible organic solvent (preferably ethyl acetate) and washed with purified water. The organic layer was separated, dried over sodium sulfate and concentrated on a rotary evaporator.

In the third step, the protective group of the pyrazole ring of the amino-protected pyrrole and pyrazole ring of 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile (2a) was removed according to methods known from the prior art [Wuts P. G. M., Greene T. W. Greene's protective groups in organic synthesis. - John Wiley & Sons, 2006.] to obtain the amino-protected pyrrole ring of 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile (3a).

At the fourth stage, products 4a’’, 5a’’, 6a’’ were synthesized. For this purpose, a base (preferably a tertiary amine, pyridine or quinoline derivatives, more preferably triethylamine) and a sulfochloride derivative or an activated thiocarboxylic acid derivative (more preferably 2-methoxyethane-1-sulfonyl chloride, 2-(methylthio)ethane-1-sulfonyl chloride, (methylthio)methanesulfonyl chloride, benzenemethanesulfonyl chloride) were added to a solution of the calculated amount of the pyrrole ring 3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile (3a) protected at the amino groups in an aprotic organic solvent (more preferably dichloromethane, tetrahydrofuran, acetone). The reaction mixture was stirred at 10-50°C (more preferably at room temperature) for 8-48 h (more preferably 16 h). Then it was diluted with purified water. The organic layer was separated, dried over sodium sulfate, concentrated on a rotary evaporator. The product was isolated by column chromatography on silica gel.

At the fifth stage, the synthesis of products A’’, B’’, C’’ was carried out. For this purpose, a reaction of removing the protective group of the pyrrole ring of compound 4a’’, 5a’’ or 6a’’ was carried out in accordance with methods known from the state of the art [Wuts P. G. M., Greene T. W. Greene's protective groups in organic synthesis. - John Wiley & Sons, 2006].

To obtain a salt of any of the compounds A’’, B’’, C’’, a calculated amount of acid in a protic organic solvent or water, or a mixture thereof, was added to a solution of a calculated amount of any of the compounds A’’, B’’, C’’ in a calculated amount of a protic organic solvent or water, or a mixture thereof. The reaction mixture was stirred at 5 - 70°C (more preferably at room temperature) for 1 - 24 h (more preferably for two hours). Upon completion of the reaction, the precipitate was filtered or the reaction mixture was evaporated, the residue was dried under reduced pressure (0.1 - 0.8 atm), at a temperature of 5 - 70°C (more preferably at room temperature).

The compounds of the invention, including their salts, can also be prepared according to the general synthesis scheme described below:

Scheme of synthesis of new derivatives of pyrrolopyrimidines A’’ - C’’.

In the first step, 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine was obtained (1). For this, the calculated amount of 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (I), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and a base (preferably alkali or alkaline earth metal carbonates or phosphates, tertiary amines, in particular aliphatic ones, more preferably sodium carbonate) were loaded into a mixture of a water-miscible organic solvent (more preferably dioxane, acetone, acetonitrile) and purified water in a weight ratio of 1:10 - 10:1. The reaction vessel was evacuated and filled with an inert gas. Then a palladium catalyst (more preferably Pd(PPh₃)₄) and refluxed for 8-48 h (more preferably 16 h). The reaction mixture was diluted with a water-immiscible solvent (more preferably ethyl acetate) and purified water. The organic layer was separated, dried over sodium sulfate and concentrated on a rotary evaporator. An organic solvent (more preferably methyl tert-butyl ether (MTBE), diisopropyl ether, diethyl ether, tetrahydrofuran (THF), methyltetrahydrofuran, heptane, hexane) was added to the residue and kept at 2-10 °C (more preferably at 4 °C) for 2-24 h (more preferably overnight). The formation of a precipitate was observed. The precipitate was filtered, washed with an organic solvent (more preferably MTBE,diisopropyl ether, diethyl ether, THF, methyltetrahydrofuran, heptane, hexane) and dried.

In the second stage, tert-butyl 3-(cyanomethyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (2) was synthesized. For this purpose, a polar organic solvent (more preferably acetonitrile, acetone, methanol, dimethylformamide) and a strong organic base (preferably alkyl substituted guanidine, quaternary ammonium base) were added to the calculated amount of 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1) and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate. The resulting mixture was stirred for 8-48 (preferably 16 h) at 10-50°C (preferably at room temperature). The reaction mixture was concentrated on a rotary evaporator. The residue was dissolved in a water-immiscible organic solvent (preferably ethyl acetate) and washed with purified water. The organic layer was separated, dried over sodium sulfate and concentrated on a rotary evaporator.

At the third stage, the synthesis of the salt 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile was carried out (3) For this purpose, a solution of an acid with a concentration of 0.5 - 30 wt. % was added to a solution of a calculated amount of tert-butyl 3-(cyanomethyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (2) in a calculated amount of an aprotic organic solvent (more preferably THF, ethyl acetate, acetonitrile). % (preferably hydrohalic acid, sulfuric acid derivatives, sulfuric acid, trifluoroacetic acid) in an aprotic organic solvent (more preferably dioxane, acetone, acetonitrile) in a molar ratio of compound 2 to acid of 1:1 - 1:100, and stirred for 8 - 48 (more preferably 16 h) at 10 - 50 °C (more preferably at room temperature). The reaction mass was concentrated on a rotary evaporator.

At the fourth stage, the synthesis of products 4’’, 5’’, 6’’ was carried out. For this purpose, a base (preferably a tertiary amine, pyridine or quinoline derivatives, more preferably triethylamine) and a sulfochloride derivative or an activated thiocarboxylic acid derivative (more preferably 2-methoxyethane-1-sulfonyl chloride, 2-(methylthio)ethane-1-sulfonyl chloride, (methylthio)methanesulfonyl chloride, benzenesulfonyl chloride) were added to a solution of a calculated amount of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile salt (3) in an aprotic organic solvent (more preferably dichloromethane, tetrahydrofuran, acetone). The reaction mixture was stirred at 10-50°C (more preferably at room temperature) for 8-48 h (more preferably 16 h). Then it was diluted with purified water. The organic layer was separated, dried over sodium sulfate, concentrated on a rotary evaporator. The product was isolated by column chromatography on silica gel.

At the fifth stage, products A'', B'', C'' were synthesized. For this purpose, trifluoroacetic acid was added to a solution of the calculated amount of one of 4'', 5'', 6'' in the calculated amount of an aprotic organic solvent (more preferably dichloromethane, tetrahydrofuran, acetonitrile). The reaction mixture was stirred at 5-50°C (more preferably at room temperature) for 0.5-5 h (more preferably 2 h), then concentrated on a rotary evaporator. The residue was dissolved in an aliphatic alcohol (more preferably methanol, ethanol, isopropanol, propanol). A solution of ammonia (3-25 wt %) in purified water was added, stirred at 5-50°C (more preferably at room temperature) for 8-48 h (more preferably 16 h). The resulting solution was concentrated on a rotary evaporator. The residue was diluted with purified water, acidified if necessary (preferably with potassium hydrogen sulfate (KHSO ₄ )) to 4-6 (pH = 4). Stirred at 5-50°C (more preferably at room temperature) for 6-24 h (more preferably overnight). Formation of a precipitate was observed. The precipitate was filtered, concentrated if necessary and chromatographed on silica gel, washed with purified water and/or diethyl ether and dried.

To obtain a salt of any of the compounds A’’, B’’, C’’, a calculated amount of acid, including hydrochloric acid, in a protic organic solvent or water was added to a solution of a calculated amount of any of the compounds A’’, B’’, C’’ in a calculated amount of a protic organic solvent or water. The reaction mass was stirred at 5 - 70 °C (more preferably at room temperature) for 1 - 24 h (more preferably for two hours). Upon completion of the reaction, the precipitate was filtered or the reaction mixture was evaporated, the residue was dried under reduced pressure (0.1 - 0.8 atm), at a temperature of 5 - 70 °C (more preferably at room temperature).

The following are the terms used in the description of the present invention. Unless otherwise specified, all technical and special terms used in the description have their generally accepted meaning in the art.

In the context of the present invention, the term “pharmaceutically acceptable excipient” characterizes substances of inorganic or organic origin used in the process of production, manufacture of medicinal products to impart to them the necessary physicochemical properties.

The term "pharmaceutical composition" in the context of the present invention means a substance comprising a therapeutically active agent and at least one of pharmaceutically acceptable and pharmacologically compatible excipients, such as, but not limited to, fillers, solubilizers, solvents, co-solvents, antioxidants, buffering agents, cryoprotectants, diluents, preservatives, stabilizers, humectants, emulsifiers, lubricants, sliding substances, suspending agents, thickeners, binding agents, sweeteners, flavors, effervescent agents, flavors, antibacterial agents, fungicides, prolonged delivery regulators, isotonic agents, pH regulating agents, the choice and ratio of which depends on the nature, purpose and dosage of the therapeutically active agent.

Non-limiting examples of suspending agents include ethoxylated isostearyl alcohol, polyoxyethylene, sorbitol and sorbitol ester, and mixtures of these substances. Stabilizers that can be used include, but are not limited to, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, colloidal silicon dioxide, polysorbate 80, sodium croscarmellose, and sodium lauryl sulfate.

The following may be used as antioxidants in the pharmaceutical composition: mannitol, ascorbic acid, tocopherol, β-carotene, lycopene.

The following may be used as fillers in the pharmaceutical composition, including starch, glucose, sucrose, lactose, magnesium oxide, sodium chloride, sodium hydrogen carbonate, kaolin, cellulose derivatives, calcium carbonate, dextrin, sorbitol, sodium croscarmellose, hydroxypropyl methylcellulose, magnesium stearate.

Protection of the pharmaceutical composition from the action of microorganisms can be ensured by means of various antibacterial and antifungal agents, such as, for example, sorbic acid, parabens (methylparaben, propylparaben, ethylparaben, butylparaben, isobutylparaben, isopropylparaben, benzylparaben, heptylparaben and mixtures thereof), chlorobutanol and similar compounds.

As isotonic agents, the pharmaceutical composition may include, but is not limited to, sugars, sodium chloride, sodium bicarbonate, etc. The prolonged action of the pharmaceutical composition may be provided, but is not limited to, by means of agents that slow down the absorption of the active agent (for example, hydrophilic and hydrophobic polymeric release retardants).

Non-limiting (illustrative) examples of suitable fillers include lactose, various types of starch, mannitol, microcrystalline cellulose, calcium carbonate and phosphate, etc.

Solvents and diluents that can be used include, but are not limited to, water, organic esters suitable for parenteral forms, ethanol, polyalcohols, and mixtures thereof. Examples of lubricants can include, but are not limited to, magnesium or calcium stearate, talc, sodium lauryl sulfate, sodium stearyl fumarate. Silicon dioxide, talc, kaolin, bentonites, etc. can act as lubricants. Various organic and inorganic acids or alkalis can be used to adjust pH, such as, but not limited to, hydrochloric acid, malic, ascorbic, citric, acetic, succinic, tartaric, fumaric, lactic, aspartic, glutaric, glutamic, sorbic acids, sodium hydroxide, etc. Examples of dispersing agents and spreading agents are starch, alginic acid and its salts, silicates.

The pharmaceutical composition can be administered to animals and humans orally, parenterally (intradermally, subcutaneously, intramuscularly, intravenously, intraarterially, into cavities), sublingually, locally, including but not limited to the above, ocular, nasal administration, etc., rectally in a standard form of administration, in the form of a mixture with traditional pharmaceutical carriers. Suitable standard forms of administration include (without limitation) oral forms: tablets, capsules, pellets, granules, powders, solutions, solutions for spraying in the oral and nasal cavity, syrups, suspensions, etc., oral: solutions, suspensions, emulsions, concentrates for the preparation of injection and infusion dosage forms, aerosols and powders for inhalation administration, pulmo powders (powders for spraying using an inhaler directly into the lungs), powders and lyophilisates for the preparation of injection and infusion dosage forms; rectal: suppositories, capsules, etc.; eye drops.

The term "pharmaceutically acceptable" in the context of the present invention means that the substance or composition to which the term applies must be chemically and/or toxicologically compatible with the other ingredients in the formulation and safe for the person being treated with the substance or composition.

"Pharmaceutically acceptable salt" in the context of the present invention means relatively safe and non-toxic organic and inorganic salts of the acids and bases claimed in the present invention.

The term "medicinal product" in the context of the present invention characterizes substances or their combinations that come into contact with the human or animal organism, penetrate into the organs, tissues of the human or animal organism, and are used for the prevention or treatment of diseases. Medicinal products include medicinal preparations in the form of finished dosage forms intended for administration into the animal or human organism by various methods, such as, but not limited to, orally, sublingually, locally, rectally, parenterally.

The term "pharmaceutical substance" or "substance" in the context of the present invention means a product of synthesis, which is any substance or mixture of substances of synthetic or other (biological, biochemical, mineral, plant, animal, microbial and other) origin, intended for the production of pharmaceutical compositions and medicinal products, which in the process of manufacturing a medicinal product (preparation) becomes an active ingredient of this medicinal product and determines its effectiveness. Such substances are intended to exhibit pharmacological activity or another direct effect in diagnosis, treatment, symptom relief, or disease prevention and symptom relief, or to affect the structure or function of the body.

The term “comprising”, “comprises” in the context of the present invention means that the said pharmaceutical substances, pharmaceutical compositions and medicinal products include the listed components, but do not exclude the inclusion of other components.

The term "effective amount" in the context of the present invention means an amount of a substance (as well as a combination of substances) that, when administered to a subject for the treatment or prevention of a disease, or at least one of the clinical symptoms of a disease or disorder, is sufficient for such treatment and/or prevention to have an effect on the disease, disorder or symptom. "Effective amount" is determined depending on the disease, disorder and/or symptoms of the disease or disorder, the severity of the disease, disorder and/or symptoms of the disease or disorder, the clinical picture and general health of the patient, as well as the age and/or weight of the subject who requires such treatment (prevention).

The term "dosage" as used herein characterizes the content of one or more active agents in quantitative terms per unit dose, or unit volume, or unit mass in accordance with the medicinal product, or for some types of medicinal products, the amount of active agent released from the medicinal product per unit time.

The term "powder" as used herein means a state of matter in which the solid substance or substances that comprise it are in a free dispersion system without a dispersion medium with a dispersion phase in the form of solid particles of various shapes.

The terms “approximately” and “about” used in the text mean approximately plus or minus ten percent of the specified value.

The term "impurities" in the context of the present invention is any component of a pharmaceutical substance that is not an active agent. The quality indicator of a pharmaceutical substance characterizes the content of impurities in the pharmaceutical substance that entered the substance during its synthesis, both production (technological impurities) and related impurities, as well as those formed during its degradation during storage, and is expressed as a percentage. The source of impurities may be reagents used in the synthesis of the starting materials, catalysts, process equipment, residues of filter materials, insufficiently purified starting materials used for the synthesis of pharmaceutical substances.

The term “physicochemical properties of substances” in the context of the present invention characterizes the density, shape, size and nature of the surface of particles, the specific surface of particles, the forces of adhesion (sticking together on the surface) and cohesion (sticking together of particles inside the body), surface activity, melting point, solubility, hygroscopicity, stability, reactivity of substances, etc.

Solubility in the context of the present invention characterizes the ability of a substance to form homogeneous systems with other substances - solutions in which the substance is in the form of individual atoms, ions, molecules or particles. Solubility is expressed by the concentration of the dissolved substance in its saturated solution either as a percentage or in weight or volume units related to g or cm³ (ml) of the solvent (e.g. g/100 g, or cm ³ /100 cm ³ , or g/ml).

The term "autoimmune diseases" in the context of the present invention characterizes a class of diseases in which the body's immune system mistakenly identifies its own cells, tissues or organs as foreign and attacks them, resulting in damage and destruction of normal tissues and the development of autoimmune inflammation. For example, autoimmune diseases include, but are not limited to, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes mellitus, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, psoriasis, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, scleroderma, vasculitis.

The term "immunomodulator" in the context of the present invention characterizes a group of biologically active substances that affect the immune system or participate in its functioning. The class of immunomodulators includes immunosuppressants (or immunosuppressants, substances that suppress the immune response) and immunostimulants (substances that enhance the immune response, activate immune cells, increase the production of antibodies, improve the body's ability to fight infections and diseases).

Stability is the ability of a medicinal product to maintain its properties and quality characteristics within specified limits during a specified shelf life and period of use, subject to established storage conditions. The stability of a medicinal product is a necessary condition for ensuring its therapeutic effect or the absence of new side effects.

Depending on the preserved properties and quality characteristics, the following types of drug stability are distinguished:

- chemical stability, in which the chemical integrity and activity of the active substance are maintained within the limits specified in the specification;

- physical stability, which preserves the original physical properties of the drug, including appearance, taste, homogeneity, solubility, suspendability, etc.;

- microbiological stability, which maintains the sterility or microbiological purity of the medicinal product in accordance with the specified requirements, or the effectiveness of the antimicrobial preservatives included in its composition within the specified limits;

- toxicological stability, in which there is no noticeable increase in the toxicity of the drug;

- therapeutic stability, in which the therapeutic effect of the drug remains unchanged.

The term “technological properties of substances” in the context of the present invention characterizes the bulk density, degree of compaction, flowability, moisture, fractional composition, dispersion, porosity, compressibility of substances, etc.

For the preparation of the novel pyrrolopyrimidine derivatives of the present invention, the following solvents, their deutero derivatives or mixtures thereof known in the art can be used: alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, isobutanol, tert-butanol, amyl alcohol and its isomers, cyclohexanol, benzyl alcohol, ethylene glycol, 1,2-propanediol, 1,3-propanediol, ketones such as acetone, butanone, methyl isobutyl ketone, 2-hexanone, cyclopentanone, cyclohexonone, ethers such as ethyl formate, methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, ethylene glycol diacetate, propylene glycol diacetate, Glycerol triacetate, diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, methyltetrahydrofuran, dioxane, anisole, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dimethoxyethane, diethoxymethane, diglyme, lactones such as butyrolactone, valerolactone, hydrocarbons such as n-pentane, n-hexane, n-heptane, n-octane, cyclohexane, methylcyclohexane, benzene, toluene, xylenes, cumene, tetralin, limonene, turpentine, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-dichloroethylene, trans-dichloroethylene, 1,1,2-trichloroethylene, 1,1,1-trichloroethane, 1-chlorobutane, chlorobenzene, dichlorobenzene, aprotic polar solvents such as acetonitrile, propionitrile, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, dimethylolethylene urea, dimethylolpropylene urea, dimethyl sulfoxide, sulfolane, nitromethane, difunctional solvents such as methoxyethanol, ethoxyethanol, 1-methoxypropan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, protic solvents such as water, acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, anhydrides such as acetic anhydride, ammonia, amines such as pyridine, thiethylamine, as well as supercritical fluids such as carbon dioxide, water, methane, ethane, propane, ethylene, propylene, methanol, ethanol, acetone, nitrogen oxides, sulfur oxide.

The term "alkyl" in the context of the present invention refers to a saturated hydrocarbon group with a straight or branched chain. Examples of alkyl groups include methyl, ethyl, propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, sec-butyl, tert-butyl), pentyl (e.g., n-pentyl, isopentyl, sec-pentyl, neopentyl), etc. The alkyl group can contain from 1 to about 20, from 2 to about 20, from 1 to about 10, from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 to about 3 carbon atoms.

The term "alkylene" in the context of the present invention refers to divalent saturated aliphatic radicals (e.g. ethylene), wherein the free valences are located at different carbon atoms.

The term "aliphatic" in the context of the present invention refers to hydrocarbons that do not contain rings.

The term "compound" in the context of the present invention includes all stereoisomers, geometric isomers, tautomeric forms, salts, hydrates, solvates, clathrates, anhydrides, unsolvated forms, isotopic forms. The compounds according to the invention, including their salts, can be prepared by known methods of organic synthesis and according to any of the many possible synthetic routes.

The term "tautomeric forms" in the context of the present invention means compounds formed as a result of the displacement of a double bond into the place of an adjacent single bond with the accompanying migration of a proton. Tautomeric forms include prototropic tautomers, which are isomeric states of protonation having the same empirical formula and overall charge.

The term "isotopic forms" in the context of the present invention means forms of compounds that include all possible isotopes of the atoms present in the compound or its precursor. Isotopes include atoms that have the same atomic number but different mass numbers.

The term "room temperature" in the context of the present invention means a temperature that approximately corresponds to the temperature in the room where the reaction or process is carried out, for example, a temperature of from about 20 to about 30°C.

The term "purified water" in the context of the present invention means an auxiliary substance or component for preparing medicinal products for use, for use in the synthesis process as a reagent or solvent, for cleaning containers, equipment, primary packaging materials. To obtain purified water, methods of ion exchange, reverse osmosis or two-stage reverse osmosis, ultrafiltration and/or electrodeionization, as well as distillation from water that meets the requirements for drinking water quality are used. Requirements for the quality of drinking water are established by SanPiN "Drinking water. Hygienic requirements for the quality of water in centralized drinking water supply systems. Quality control."

The term "organic solvent" in the context of the present invention means a substance of organic origin that has the ability to dissolve various compounds.

The term "polar organic solvent" in the context of the present invention means a class of organic solvents having the ability to dissolve polar compounds. Polar organic solvents include, but are not limited to, alcohols, in particular methanol, ethanol, propanol, isopropanol, butanol, ketones, in particular acetone, methyl ethyl ketone, acids, in particular formic acid, acetic acid, tetrahydrofuran, ethyl acetate, dimethylformamide, acetonitrile, dimethyl sulfoxide, nitromethane, acetonitrile, ethylene glycol, nitrobenzene, N-methylpyrrolidone.

The term "non-polar organic solvent" in the context of the present invention means a class of organic solvents that have the ability to dissolve non-polar compounds. Non-polar organic solvents include, but are not limited to, hexane, benzene, toluene, chloroform, dichloromethane, diethyl ether, diisopropyl ether, dibutyl ether, and dioxane.

The term "protic organic solvent" in the context of the present invention means a class of organic solvents containing a hydrogen atom capable of dissociation in the form of a proton. Protic organic solvents include, but are not limited to, alcohols, in particular methanol, ethanol, propanol, isopropanol, butanol, acids, in particular formic acid, acetic acid.

The term "aprotic organic solvent" in the context of the present invention means a class of organic solvents that do not contain a hydrogen atom capable of dissociating into a proton. Aprotic organic solvents include, but are not limited to, hexane, benzene, toluene, dioxane, chloroform, diethyl ether, dichloromethane, tetrahydrofuran, ethyl acetate, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide.

The term "water-miscible solvent" in the context of the present invention means a class of solvents that are miscible with water. Water-miscible solvents include, but are not limited to, tetrahydrofuran, methanol, isopropanol, ethanol, dioxane, dimethyl sulfoxide, dimethylformamide, acetonitrile, acetone.

The term "water-immiscible solvent" in the context of the present invention means a class of solvents that are not miscible with water. Water-miscible solvents include, but are not limited to, toluene, pentane, methyl ethyl ketone, methyl tert-butyl ether, isooctane, hexane, heptane, diethyl ether, ethyl acetate, dichloromethane, dichloroethane, cyclohexane, chloroform, carbon tetrachloride, butanol, benzene.

The term "base" in the context of the present invention means organic or inorganic compounds capable of accepting a proton. Organic bases include, but are not limited to, pyridine and its derivatives, in particular collidine, 2,6-lutidine, ammonium derivatives, in particular tributylamine, triethylamine, imidazole and its derivatives, benzimidazole and its derivatives, histidine, guanidine, in particular 1,1,3,3-tetramethylguanidine (TMG), phosphazenes, 1,5,7-triazabicyclo(4.4.0)dec-5-ene (TBD), 7-methyl-1,5,7-triazabicyclo(4.4.0)dec-5-ene (MTBD), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), quinuclidine, 2,2,6,6-tetramethylpiperidine (TMP), pempidine, 1,4-diazabicyclo[2.2.2]octane. Inorganic bases include, but are not limited to, ammonia or its solutions in water, soluble and slightly soluble in water alkali and alkaline earth metal hydroxides, amides, carbonates and hydrocarbonates. Strong inorganic bases include water-soluble alkali and alkaline earth metal hydroxides and amides. Weak inorganic bases include ammonium hydroxide, slightly soluble metal hydroxides, carbonates and hydrocarbonates.

The term "palladium catalyst" in the context of the present invention means compounds with catalytic activity containing palladium, or palladium. Palladium catalysts include, but are not limited to, tetrakis(triphenylphosphine)palladium, bis[1,2-bis(diphenylphosphino)ethane]palladium, dichlorobis(methyldiphenylphosphine)palladium, palladium on carbon, palladium (II) acetate (palladium acetate).

The term "hydrohalic acid" in the context of the present invention means an acid selected from hydrofluoric, hydrochloric, hydrobromic, hydroiodic.

Brief description of the drawings

The present invention is further illustrated by Fig. 1 and Fig. 2.

Fig. 1 shows the averaged severity of symptoms of arthritis induced by collagen antibodies across experimental groups.

Fig. 2 shows the average levels of cytokine activity in lung tissue and bronchoalveolar fluid across the experimental groups.

implementation of an invention

The stated problem is solved, and the stated technical result is achieved due to a compound selected from a group including compounds characterized by formula (I):

or its pharmaceutically acceptable salt,

where (X)’, (Y)’ independently of each other represent -CH or N;

a = 1, 2, 3, 4, 5;

b = 1, 2, 3, 4, 5;

(R ₁ )', R ₂ independently of each other represent a group A or B, where

A is branched or unbranched alkyl, cycloalkyl, alkenyl (an unsaturated hydrocarbon with a double bond), branched or unbranched hydrocarbon chain, branched or unbranched alkyloxy, branched or unbranched alkylthio, heterocycle or aryl;

B is hydroxy, mercapto, amino, halogen, azido, nitroso, nitro, nitrile, cyano, diazo, sulfo, COR ₃ , SO ₃ R ₃ , C(NR ₆ )NR ₄ R ₅ , OOR ₇ , NR ₄ R ₅ , NHNHR ₃ , NNR ₃ , (NO)NR ₃ , CH(NR ₃ )R ₃ , (SO)R ₃ , SO ₂ R ₃ , SO(NR ₄ )R ₃ ;

R ₃ is any of A, hydrogen, hydroxy, halogen, OM (where M = metal or ammonium cation), NR ₄ R ₅ ;

R ₄ , R ₅ independently of each other represent any of A;

R ₆ represents any of A;

R ₇ represents any of A or hydrogen;

wherein A may be substituted with one or more substituents selected from A or B.

The stated problem is solved, and the stated technical result is achieved due to a compound selected from a group including compounds characterized by formula (I)’ (the structure and radicals are indicated above), with the exception of:

if R ₂ is methyl substituted with cyano, (X)' is N, (Y)' is C, a = 1, b = 1, then (R ₁ )' does not represent C _1-6 alkyl, C _3-7 cycloalkyl, phenyl, 5- or 6-membered heteroaryl, indolyl, NQ ₂ Q ₃ or OQ ₄ , wherein said alkyl, cycloalkyl, phenyl or heteroaryl optionally contains 1, 2 or 3 substituents independently selected from F, CN and C _1-4 alkyl; Q ₂ and Q ₃ are independently selected from H, C _1-4 alkyl and phenyl and Q ₄ is C _1-6 alkyl, phenyl or benzyl;

if R ₂ is methyl substituted by cyano, (X)' and (Y)' represent a nitrogen atom; or (X)' represents a nitrogen atom and (Y)' represents methine; or (X)' represents methine and (Y)' represents a nitrogen atom (R ₁ )' does not represent SO ₂ (CH ₂ ) _n CH ₂ OH, SO ₂ (CH ₂ ) _n CH ₂ F, SO ₂ (CH ₂ ) _n CHF ₂ , SO ₂ (CH ₂ ) _n CF ₃ , SO ₂ (CH ₂ ) _n CO ₂ R ^1a , SO ₂ (CH ₂ ) _n CO ₂ H, CH ₂ CH ₂ SO ₂ CH ₃ , CH ₂ CH ₂ SO ₃ H, CH ₂ CH ₂ SO ₂ NH ₂ ; n=1 or 2; R ^1a is alkyl or cycloalkyl, preferably C ₁ -C ₃ alkyl;

if R ₂ is methyl substituted by cyano, (X)' and (Y)' are a nitrogen atom, or (X)' is methine and (Y)' is a nitrogen atom (R ₁ )' is not SO ₂ CH ₂ CH ₃ ,

if R ₂ is methyl substituted by cyano, (X)' is N, (Y)' is C, a = 1, b = 1, then (R ₁ )' does not represent a fragment of formula II:

if R ₂ is methyl substituted by cyano, (X)' is nitrogen N, (Y)' is carbon C, a = 1, b = 1, then (R ₁ )' does not represent a fragment of formula III:

1) T = H, L = CH ₃ , CH ₂ CH ₃ , Ph, CH(CH ₃ ) ₂ , CF ₃ , cyclopropyl;

2) T = CH ₃ , L = CH ₃ , CH ₂ CH ₃ , CH ₂ CH ₂ F, cyclopropyl;

3) T = CH(CH ₃ )Ph, L = CH ₃ ;

4) T = cyclopropyl, L = CH ₃ ;

5) T = CH(CH ₃ ) ₂ , L = CH ₃ ;

6) T = CH ₂ CH ₃ , L = cyclopropyl;

7) T = cyclopropyl, L = cyclopropyl, CH ₂ CH ₃ ;

8) T = CH ₂ CF ₃ , cyclopropyl.

The stated problem is solved, and the stated technical result is achieved due to a compound selected from a group including compounds characterized by formula IV’’:

Formula IV’’

or a pharmaceutically acceptable salt thereof, wherein X'' is a sulfonyl (-SO ₂ -) radical; Y'' is a C _1-6 -alkylene; Z'' is a C _1-6 -alkyloxy (-OC _1-6 -alkyl) or C _1-6 -alkylthio (-SC _1-6 -alkyl) radical.

One embodiment of the invention is to obtain a compound characterized by formula IV'', where Y'' is C _1-6 -alkylene, Z'' is C _1-6 -alkyloxy, and X'' is a sulfonyl (-SO ₂ -) radical or a pharmaceutically acceptable salt thereof.

One embodiment of the invention is to obtain a compound characterized by formula IV'', where Y'' is C _1-6 -alkylene, Z'' is C _1-6 -alkylthio, and X'' is a sulfonyl (-SO ₂ -) radical or a pharmaceutically acceptable salt thereof.

One embodiment of the invention is to obtain a compound characterized by formula IV'', where Y'' is C _1-6 -alkylene, Z'' is C _1-6 -alkyloxy, and X'' is a sulfonyl (-SO ₂ -) radical or a pharmaceutically acceptable salt thereof.

One embodiment of the invention is to obtain a compound characterized by formula IV'', where Y'' is C _1-6 -alkylene, Z'' is C _1-6 -alkylthio, and X'' is a sulfonyl (-SO ₂ -) radical or a pharmaceutically acceptable salt thereof.

The stated problem is solved and the claimed technical result is achieved due to 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula (A)’’

or a pharmaceutically acceptable salt thereof.

The stated problem is solved, and the claimed technical result is achieved due to the pharmaceutically acceptable salt of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by the formula Aa’’

The stated problem is solved and the claimed technical result is achieved due to 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by the formula B’’

or a pharmaceutically acceptable salt thereof.

The stated problem is solved, and the claimed technical result is achieved due to the pharmaceutically acceptable salt of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by the formula Bb’’

The stated problem is solved and the claimed technical result is achieved due to 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by the formula C’’

or a pharmaceutically acceptable salt thereof.

The stated problem is solved, and the claimed technical result is achieved due to the pharmaceutically acceptable salt of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by the formula Cc’’

In one embodiment of the present invention, X ₂ is an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the pharmaceutically acceptable salt of compound Aa’’ is a salt formed between compound A’’ and an inorganic acid.

In one embodiment of the present invention, the pharmaceutically acceptable salt of compound Bb’’ is a salt formed between compound B’’ and an inorganic acid.

In one embodiment of the present invention, the pharmaceutically acceptable salt of compound Cc’’ is a salt formed between compound C’’ and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound B’’ is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1, 2.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound B’’ is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1, 2.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1, 2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound B’’ is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the pharmaceutically acceptable salt of compound A'', B'' or C'' is a salt formed by compound A'', B'' or C'' and an organic acid.

More preferably, X ₂ is an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound B’’ is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid and the compound C’’ is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1 or 1:2, or if the organic acid is a dibasic acid, then z = 1, 2.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound B’’ is 1:1 or 1:2, or if the organic acid is a dibasic acid, then z = 1, 2.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1 or 1:2, or if the organic acid is a dibasic acid, then z = 1, 2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound A’’ is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound B’’ is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

One embodiment of the present invention is 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride.

One embodiment of the present invention is 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride.

One embodiment of the present invention is 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride.

The compound of formulae A'', B'', C'', or pharmaceutically acceptable salts thereof according to the present invention can be administered in the form of prodrugs. A prodrug can include a covalently linked carrier that releases the active parent drug when administered to a mammalian subject. Prodrugs can be prepared by modifying functional groups present in the compounds such that the modifications are cleaved, either during routine manipulation or in vivo , to the parent compounds. Prodrugs include, for example, compounds in which a hydroxyl or amino group is bonded to any group that, when administered to a subject, cleaves to form a free hydroxyl or amino group. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol functional groups in the compounds.

Typical prodrugs form an active metabolite by conversion of the prodrug by hydrolytic enzymes, hydrolysis of amides, lactams, peptides, carboxylic acid esters, epoxides, or cleavage of inorganic acid esters.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable excipient.

In some embodiments of the present invention, the pharmaceutical composition can be prepared using known conventional methods in the field of pharmacy.

One of the embodiments of the present invention is also a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 100.00 wt. % of the weight of the pharmaceutical composition.

One of the embodiments of the present invention is also a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.99 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 0.01 to 85.00 wt %, from 0.01 to 80.00 wt %, from 0.01 to 75.00 wt %, from 0.01 to 70.00 wt %, from 0.01 to 65.00 wt %, from 0.01 to 60.00 wt %, from 0.01 to 55.00 wt %, from 0.01 to 40.00 wt %, from 0.01 to 35.00 wt. %, from 0.01 to 30.00 wt. %, from 0.01 to 25.00 wt. %, from 0.01 to 20.00 wt. %, from 0.01 to 15.00 wt. %, from 0.01 to 10.00 wt. %, from 0.01 to 9.00 wt. %, from 0.01 to 8.00 wt. %, from 0.01 to 7.00 wt. %, from 0.01 to 6.00 wt. %, from 0.01 to 5.00 wt. %, from 0.01 to 4.00 wt. %, from 0.01 to 3.00 wt. %, from 0.01 to 2.00 wt. % or from 0.01 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 0.10 to 85.00 wt %, from 0.10 to 80.00 wt %, from 0.10 to 75.00 wt %, from 0.10 to 70.00 wt %, from 0.10 to 65.00 wt %, from 0.10 to 60.00 wt %, from 0.10 to 55.00 wt %, from 0.10 to 40.00 wt %, from 0.10 to 35.00 wt. %, from 0.10 to 30.00 wt. %, from 0.10 to 25.00 wt. %, from 0.10 to 20.00 wt. %, from 0.10 to 15.00 wt. %, from 0.10 to 10.00 wt. %, from 0.10 to 9.00 wt. %, from 0.10 to 8.00 wt. %, from 0.10 to 7.00 wt. %, from 0.10 to 6.00 wt. %, from 0.10 to 5.00 wt. %, from 0.10 to 4.00 wt. %, from 0.10 to 3.00 wt. %, from 0.10 to 2.00 wt. % or from 0.10 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 1.00 to 85.00 wt %, from 1.00 to 80.00 wt %, from 1.00 to 75.00 wt %, from 1.00 to 70.00 wt %, from 1.00 to 65.00 wt %, from 1.00 to 60.00 wt %, from 1.00 to 55.00 wt %, from 1.00 to 40.00 wt %, from 1.00 to 35.00 wt. %, from 1.00 to 30.00 wt. %, from 1.00 to 25.00 wt. %, from 1.00 to 20.00 wt. %, from 1.00 to 15.00 wt. %, from 1.00 to 10.00 wt. %, from 1.00 to 9.00 wt. %, from 1.00 to 8.00 wt. %, from 1.00 to 7.00 wt. %, from 1.00 to 6.00 wt. %, from 1.00 to 5.00 wt. %, from 1.00 to 4.00 wt. %, from 1.00 to 3.00 wt. %, or from 1.00 to 2.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 5.00 to 85.00 wt %, from 5.00 to 80.00 wt %, from 5.00 to 75.00 wt %, from 5.00 to 70.00 wt %, from 5.00 to 65.00 wt %, from 5.00 to 60.00 wt %, from 5.00 to 55.00 wt %, from 5.00 to 40.00 wt %, from 5.00 to 35.00 wt. %, from 5.00 to 30.00 wt. %, from 5.00 to 25.00 wt. %, from 5.00 to 20.00 wt. %, from 5.00 to 15.00 wt. %, from 5.00 to 10.00 wt. %, from 5.00 to 9.00 wt. %, from 5.00 to 8.00 wt. %, from 5.00 to 7.00 wt. % or from 5.00 to 6.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 10.00 to 85.00 wt %, from 10.00 to 80.00 wt %, from 10.00 to 75.00 wt %, from 10.00 to 70.00 wt %, from 10.00 to 65.00 wt %, from 10.00 to 60.00 wt %, from 10.00 to 55.00 wt %, from 10.00 to 40.00 wt %, from 10.00 to 35.00 wt. %, from 10.00 to 30.00 wt. %, from 10.00 to 25.00 wt. %, from 10.00 to 20.00 wt. % or from 10.00 to 15.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 15.00 to 85.00 wt %, from 15.00 to 80.00 wt %, from 15.00 to 75.00 wt %, from 15.00 to 70.00 wt %, from 15.00 to 65.00 wt %, from 15.00 to 60.00 wt %, from 15.00 to 55.00 wt %, from 15.00 to 40.00 wt %, from 15.00 to 35.00 wt. %, from 15.00 to 30.00 wt. %, from 15.00 to 25.00 wt. % or from 15.00 to 20.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. %, or from 0.50 to 1.00 wt. % of the weight of the pharmaceutical composition.

One embodiment of the present invention is the above-mentioned pharmaceutical composition, wherein at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, glidants, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.00 to 99.99 mass % of the mass of the pharmaceutical composition.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.01 to 99.99 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition of the present invention is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 wt. %, from 0.01 to 50.00 wt. %, or from 0.01 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 0.10 to 99.99 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 1.00 to 99.99 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 5.00 to 99.99 wt. %, from 5.00 to 95.00 wt. %, from 5.00 to 90.00 wt. %, from 5.00 to 85.00 wt. %, from 5.00 to 80.00 wt. %, from 5.00 to 75.00 wt. %, from 5.00 to 70.00 wt. %, from 5.00 to 65.00 wt. %, from 5.00 to 60.00 wt. %, from 5.00 to 55.00 wt. %, from 5.00 to 50.00 wt. %, from 5.00 to 45.00 wt. %, or from 5.00 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 10.00 to 99.99 wt. %, from 10.00 to 95.00 wt. %, from 10.00 to 90.00 wt. %, from 10.00 to 85.00 wt. %, from 10.00 to 80.00 wt. %, from 10.00 to 75.00 wt. %, from 10.00 to 70.00 wt. %, from 10.00 to 65.00 wt. %, from 10.00 to 60.00 wt. %, from 10.00 to 55.00 wt. %, from 10.00 to 50.00 wt. %, from 10.00 to 45.00 wt. % or from 10.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 15.00 to 99.99 wt. %, from 15.00 to 95.00 wt. %, from 15.00 to 90.00 wt. %, from 15.00 to 85.00 wt. %, from 15.00 to 80.00 wt. %, from 15.00 to 75.00 wt. %, from 15.00 to 70.00 wt. %, from 15.00 to 65.00 wt. %, from 15.00 to 60.00 wt. %, from 15.00 to 55.00 wt. %, from 15.00 to 50.00 wt. %, from 15.00 to 45.00 wt. % or from 15.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 20.00 to 99.99 wt. %, from 20.00 to 95.00 wt. %, from 20.00 to 90.00 wt. %, from 20.00 to 85.00 wt. %, from 20.00 to 80.00 wt. %, from 20.00 to 75.00 wt. %, from 20.00 to 70.00 wt. %, from 20.00 to 65.00 wt. %, from 20.00 to 60.00 wt. %, from 20.00 to 55.00 wt. %, from 20.00 to 50.00 wt. %, from 20.00 to 45.00 wt. % or from 20.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 25.00 to 99.99 wt. %, from 25.00 to 95.00 wt. %, from 25.00 to 90.00 wt. %, from 25.00 to 85.00 wt. %, from 25.00 to 80.00 wt. %, from 25.00 to 75.00 wt. %, from 25.00 to 70.00 wt. %, from 25.00 to 65.00 wt. %, from 25.00 to 60.00 wt. %, from 25.00 to 55.00 wt. %, from 25.00 to 50.00 wt. %, from 25.00 to 45.00 wt. % or from 25.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 30.00 to 99.99 wt. %, from 30.00 to 95.00 wt. %, from 30.00 to 90.00 wt. %, from 30.00 to 85.00 wt. %, from 30.00 to 80.00 wt. %, from 30.00 to 75.00 wt. %, from 30.00 to 70.00 wt. %, from 30.00 to 65.00 wt. %, from 30.00 to 60.00 wt. %, from 30.00 to 55.00 wt. %, from 30.00 to 50.00 wt. %, from 30.00 to 45.00 wt. % or from 30.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 35.00 to 99.99 wt. %, from 35.00 to 95.00 wt. %, from 35.00 to 90.00 wt. %, from 35.00 to 85.00 wt. %, from 35.00 to 80.00 wt. %, from 35.00 to 75.00 wt. %, from 35.00 to 70.00 wt. %, from 35.00 to 65.00 wt. %, from 35.00 to 60.00 wt. %, from 35.00 to 55.00 wt. %, from 35.00 to 50.00 wt. %, from 35.00 to 45.00 wt. % or from 35.00 to 40.00 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

In some embodiments of the present invention, the pharmaceutical composition can be prepared using known conventional methods in the field of pharmacy.

One of the embodiments of the present invention is also a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 100.00 wt. % of the weight of the pharmaceutical composition.

One of the embodiments of the present invention is also a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.99 wt. % of the weight of the pharmaceutical composition.

One embodiment of the present invention is a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 wt. %, from 0.01 to 50.00 wt. % or from 0.01 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 0.01 to 85.00 wt %, from 0.01 to 80.00 wt %, from 0.01 to 75.00 wt %, from 0.01 to 70.00 wt %, from 0.01 to 65.00 wt %, from 0.01 to 60.00 wt %, from 0.01 to 55.00 wt %, from 0.01 to 40.00 wt %, from 0.01 to 35.00 wt. %, from 0.01 to 30.00 wt. %, from 0.01 to 25.00 wt. %, from 0.01 to 20.00 wt. %, from 0.01 to 15.00 wt. %, from 0.01 to 10.00 wt. %, from 0.01 to 9.00 wt. %, from 0.01 to 8.00 wt. %, from 0.01 to 7.00 wt. %, from 0.01 to 6.00 wt. %, from 0.01 to 5.00 wt. %, from 0.01 to 4.00 wt. %, from 0.01 to 3.00 wt. %, from 0.01 to 2.00 wt. % or from 0.01 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.10 to 99.00 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 40.00 wt. %, from 0.10 to 35.00 wt. %, from 0.10 to 30.00 wt. %, from 0.10 to 25.00 wt. %, from 0.10 to 20.00 wt. %, from 0.10 to 15.00 wt. %, from 0.10 to 10.00 wt. %, from 0.10 to 9.00 wt. %, from 0.10 to 8.00 wt. %, from 0.10 to 7.00 wt. %, from 0.10 to 6.00 wt. %, from 0.10 to 5.00 wt. %, from 0.10 to 4.00 wt. %, from 0.10 to 3.00 wt. %, from 0.10 to 2.00 wt. % or from 0.10 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.50 to 99.00 wt. %, from 0.50 to 95.00 wt. %, from 0.50 to 90.00 wt. %, from 0.50 to 85.00 wt. %, from 0.50 to 80.00 wt. %, from 0.50 to 75.00 wt. %, from 0.50 to 70.00 wt. %, from 0.50 to 65.00 wt. %, from 0.50 to 60.00 wt. %, from 0.50 to 55.00 wt. %, from 0.50 to 50.00 wt. %, from 0.50 to 45.00 wt. % or from 0.50 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 1.00 to 99.00 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 40.00 wt. %, from 1.00 to 35.00 wt. %, from 1.00 to 30.00 wt. %, from 1.00 to 25.00 wt. %, from 1.00 to 20.00 wt. %, from 1.00 to 15.00 wt. %, from 1.00 to 10.00 wt. %, from 1.00 to 9.00 wt. %, from 1.00 to 8.00 wt. %, from 1.00 to 7.00 wt. %, from 1.00 to 6.00 wt. %, from 1.00 to 5.00 wt. %, from 1.00 to 4.00 wt. %, from 1.00 to 3.00 wt. % or from 1.00 to 2.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 5.00 to 85.00 wt %, from 5.00 to 80.00 wt %, from 5.00 to 75.00 wt %, from 5.00 to 70.00 wt %, from 5.00 to 65.00 wt %, from 5.00 to 60.00 wt %, from 5.00 to 55.00 wt %, from 5.00 to 40.00 wt %, from 5.00 to 35.00 wt. %, from 5.00 to 30.00 wt. %, from 5.00 to 25.00 wt. %, from 5.00 to 20.00 wt. %, from 5.00 to 15.00 wt. %, from 5.00 to 10.00 wt. %, from 5.00 to 9.00 wt. %, from 5.00 to 8.00 wt. %, from 5.00 to 7.00 wt. % or from 5.00 to 6.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 10.00 to 85.00 wt %, from 10.00 to 80.00 wt %, from 10.00 to 75.00 wt %, from 10.00 to 70.00 wt %, from 10.00 to 65.00 wt %, from 10.00 to 60.00 wt %, from 10.00 to 55.00 wt %, from 10.00 to 40.00 wt %, from 10.00 to 35.00 wt. %, from 10.00 to 30.00 wt. %, from 10.00 to 25.00 wt. %, from 10.00 to 20.00 wt. % or from 10.00 to 15.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 15.00 to 85.00 wt %, from 15.00 to 80.00 wt %, from 15.00 to 75.00 wt %, from 15.00 to 70.00 wt %, from 15.00 to 65.00 wt %, from 15.00 to 60.00 wt %, from 15.00 to 55.00 wt %, from 15.00 to 40.00 wt %, from 15.00 to 35.00 wt. %, from 15.00 to 30.00 wt. %, from 15.00 to 25.00 wt. % or from 15.00 to 20.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. %, or from 0.50 to 1.00 wt. % of the weight of the pharmaceutical composition.

One embodiment of the present invention is the above-mentioned pharmaceutical composition, wherein at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, glidants, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.00 to 99.99 mass % of the mass of the pharmaceutical composition.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.01 to 99.99 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition of the present invention is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 wt. %, from 0.01 to 50.00 wt. %, or from 0.01 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 0.10 to 99.99 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, in a therapeutically effective amount.

The stated problem is solved, and the claimed technical result is also achieved due to a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

In some embodiments of the present invention, the pharmaceutical composition can be prepared using known conventional methods in the field of pharmacy.

One of the embodiments of the present invention is also a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 100.00 wt. % of the weight of the pharmaceutical composition.

One of the embodiments of the present invention is also a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.99 wt. % of the weight of the pharmaceutical composition.

One embodiment of the present invention is a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 wt. %, from 0.01 to 50.00 wt. % or from 0.01 to 40.00 wt. %, from 0.01 to 35.00 wt. %, from 0.01 to 30.00 wt. %, from 0.01 to 25.00 wt. %, from 0.01 to 20.00 wt. %, from 0.01 to 15.00 wt. %, from 0.01 to 10.00 wt. %, from 0.01 to 9.00 wt. %, from 0.01 to 8.00 wt. %, from 0.01 to 7.00 wt. %, from 0.01 to 6.00 wt. %, from 0.01 to 5.00 wt. %, from 0.01 to 4.00 wt. %, from 0.01 to 3.00 wt. %, from 0.01 to 2.00 wt. % or from 0.01 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.10 to 99.00 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. %, from 0.10 to 35.00 wt. %, from 0.10 to 30.00 wt. %, from 0.10 to 25.00 wt. %, from 0.10 to 20.00 wt. %, from 0.10 to 15.00 wt. %, from 0.10 to 10.00 wt. %, from 0.10 to 9.00 wt. %, from 0.10 to 8.00 wt. %, from 0.10 to 7.00 wt. %, from 0.10 to 6.00 wt. %, from 0.10 to 5.00 wt. %, from 0.10 to 4.00 wt. %, from 0.10 to 3.00 wt. %, from 0.10 to 2.00 wt. % or from 0.10 to 1.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.50 to 99.00 wt. %, from 0.50 to 95.00 wt. %, from 0.50 to 90.00 wt. %, from 0.50 to 85.00 wt. %, from 0.50 to 80.00 wt. %, from 0.50 to 75.00 wt. %, from 0.50 to 70.00 wt. %, from 0.50 to 65.00 wt. %, from 0.50 to 60.00 wt. %, from 0.50 to 55.00 wt. %, from 0.50 to 50.00 wt. %, from 0.50 to 45.00 wt. % or from 0.50 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 1.00 to 99.00 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. % or from 1.00 to 40.00 wt. %, from 1.00 to 35.00 wt. %, from 1.00 to 30.00 wt. %, from 1.00 to 25.00 wt. %, from 1.00 to 20.00 wt. %, from 1.00 to 15.00 wt. %, from 1.00 to 10.00 wt. %, from 1.00 to 9.00 wt. %, from 1.00 to 8.00 wt. %, from 1.00 to 7.00 wt. %, from 1.00 to 6.00 wt. %, from 1.00 to 5.00 wt. %, from 1.00 to 4.00 wt. %, from 1.00 to 3.00 wt. % or from 1.00 to 2.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 5.00 to 85.00 wt %, from 5.00 to 80.00 wt %, from 5.00 to 75.00 wt %, from 5.00 to 70.00 wt %, from 5.00 to 65.00 wt %, from 5.00 to 60.00 wt %, from 5.00 to 55.00 wt %, from 5.00 to 40.00 wt %, from 5.00 to 35.00 wt. %, from 5.00 to 30.00 wt. %, from 5.00 to 25.00 wt. %, from 5.00 to 20.00 wt. %, from 5.00 to 15.00 wt. %, from 5.00 to 10.00 wt. %, from 5.00 to 9.00 wt. %, from 5.00 to 8.00 wt. %, from 5.00 to 7.00 wt. % or from 5.00 to 6.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 10.00 to 85.00 wt %, from 10.00 to 80.00 wt %, from 10.00 to 75.00 wt %, from 10.00 to 70.00 wt %, from 10.00 to 65.00 wt %, from 10.00 to 60.00 wt %, from 10.00 to 55.00 wt %, from 10.00 to 40.00 wt. %, from 10.00 to 35.00 wt. %, from 10.00 to 30.00 wt. %, from 10.00 to 25.00 wt. %, from 10.00 to 20.00 wt. % or from 10.00 to 15.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is from 15.00 to 85.00 wt %, from 15.00 to 80.00 wt %, from 15.00 to 75.00 wt %, from 15.00 to 70.00 wt %, from 15.00 to 65.00 wt %, from 15.00 to 60.00 wt %, from 15.00 to 55.00 wt %, from 15.00 to 40.00 wt. %, from 15.00 to 35.00 wt. %, from 15.00 to 30.00 wt. %, from 15.00 to 25.00 wt. % or from 15.00 to 20.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the pharmaceutical composition is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. % or from 0.50 to 1.00 mass % of the weight of the pharmaceutical composition.

One embodiment of the present invention is the above-mentioned pharmaceutical composition, wherein at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, glidants, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.00 to 99.99 mass % of the mass of the pharmaceutical composition.

One embodiment of the present invention is a pharmaceutical composition characterized in that it contains at least one pharmaceutically acceptable excipient in an amount of from 0.01 to 99.99 mass % of the mass of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition of the present invention is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 wt. %, from 0.01 to 50.00 wt. %, or from 0.01 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the above-mentioned pharmaceutical composition is from 0.10 to 99.99 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the pharmaceutical composition.

More preferably, the content of at least one pharmaceutically acceptable excipient in the pharmaceutical composition of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the pharmaceutical composition.

One embodiment of the present invention is the above-mentioned pharmaceutical composition comprising a compound of formula A’’ or a pharmaceutically acceptable salt thereof, or a compound of formula B’’ or a pharmaceutically acceptable salt thereof, or a compound of formula C’’ or a pharmaceutically acceptable salt thereof, characterized in that it exhibits therapeutic activity against autoimmune diseases selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia.

More preferably, a pharmaceutical composition comprising a compound of formula A’’ or a pharmaceutically acceptable salt thereof, or a compound of formula B’’ or a pharmaceutically acceptable salt thereof, or a compound of formula C’’ or a pharmaceutically acceptable salt thereof, is characterized in that it exhibits therapeutic activity against a disease according to the present invention selected from the group of JAK-mediated diseases or disorders.

More preferably, a pharmaceutical composition containing a compound of formula A’’ or a pharmaceutically acceptable salt thereof, or a compound of formula B’’ or a pharmaceutically acceptable salt thereof, or a compound of formula C’’ or a pharmaceutically acceptable salt thereof, is characterized in that it exhibits therapeutic activity against diseases selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, chronic polyarthritis, atopic dermatitis, juvenile idiopathic arthritis,

alopecia (focal alopecia, frontal fibrosing alopecia, alopecia areata, including severe or very severe forms), multiple sclerosis, disseminated sclerosis, amyotrophic lateral sclerosis, neurodegenerative Alzheimer's disease,

Type I diabetes, diabetic kidney disease, aggressive albuminuria reduction in biopsy-proven diabetic nephropathy, lupus, systemic lupus erythematosus, lupus nephritis, psoriasis,

inflammatory bowel disease, ulcerative colitis, Crohn's disease, severe pseudoparalytic myasthenia, immunoglobulin nephropathy, autoimmune thyroid disease, pemphigus vulgaris, bullous pemphigoid,

allergic reactions such as asthma, food allergies, atopic dermatitis and rhinitis,

viral diseases such as Epstein-Barr virus, hepatitis B, hepatitis C, human immunodeficiency virus, varicella-zoster virus and human papillomavirus, coronavirus, COVID-19,

skin rashes, skin irritations, skin sensitization (eg, contact dermatitis or allergic contact dermatitis), cutaneous lichen planus,

cancer including cancers that are characterized by the formation of solid tumors (e.g. prostate cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, Kaposi's sarcoma, Castleman disease, melanoma, etc.), blood cancers (e.g. lymphoma, leukemia such as acute lymphoblastic leukemia, acute myelogenous leukemia (AML), or multiple myeloma), and skin cancers such as cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma, typical cutaneous T-cell lymphomas include Sezary syndrome and mycosis fungoides, myeloproliferative disorders (MPDs) such as polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis with myeloid metaplasia (MMM), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), systemic mastocytosis (SM) associated with colitis cancer, colon cancer, colorectal cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), adenocarcinoma, small intestine cancer, rectal cancer, etc.,

Inflammatory diseases include inflammatory diseases of the eye (e.g., iritis, uveitis, scleritis, conjunctivitis, or related diseases), refractory non-infectious non-anterior uveitis, inflammatory diseases of the airways (e.g., upper respiratory tract including diseases of the nose and sinuses such as rhinitis or sinusitis, lower respiratory tract including bronchitis, chronic non-specific lung disease, etc.), inflammatory myopathy such as myocarditis and other inflammatory diseases, ischemia-reperfusion injury or diseases or conditions associated with an inflammatory ischemic event such as stroke or cardiac arrest, systemic inflammatory response syndrome, septic shock, large inflammatory hepatocellular adenomas,

anorexia, cachexia or fatigue caused by or associated with cancer,

pathological conditions associated with hypoxia or astrogliosis, such as diabetic retinopathy, cancer or neurodegeneration,

gout, prostate enlargement, dry eye syndrome and related disorders, IgG4-related disorders, idiopathic granulomatous mastitis, pyoderma gangrenosum, cutaneous dermatomyositis, idiopathic inflammatory myositis, chronic atypical neutrophilic dermatosis with lipodystrophy and fever (Nakayo-Nishimura syndrome), interferon gene stimulator-associated vasculopathy, Aicardi-Goutières syndrome, graft-versus-host disease including that following peripheral blood hematopoietic cell transplantation, neuromyelitis, immune thrombocytopenia, coronavirus pneumonia (COVID-19), symptoms associated with COVID-19 infection, hospital-acquired pneumonia in critically ill patients with a proinflammatory phenotype, lung injury after spontaneous subarachnoid hemorrhage, ocular mucous membrane pemphigoid, oral lichen planus, steroid-resistant/recurrent immune thrombocytopenia, pulmonary injury after intracerebral hemorrhage, moderate to severe traumatic intracerebral hemorrhage/contusion, recurrent giant cell arteritis, systemic sclerosis, therapy of non-segmental vitiligo, therapy of HIV symptoms, autoinflammatory syndrome, primary biliary cholangitis, recurrent or naive dermatomyositis, Sjogren's syndrome, inflammation and depression in people with HIV, APOL1-associated kidney disease, polymyalgia rheumatica, idiopathic inflammatory myopathy.

In some embodiments, one or more compounds of the present invention may be used in combination with other active agents.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing in an effective amount 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

One embodiment of the present invention is a medicinal product characterized in that at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, slip agents, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, characterized in that the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia.

More preferably, the disease of the present invention is selected from the group of JAK-mediated diseases or disorders.

In some embodiments, one or more compounds of the present invention may be used in combination with other active agents.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount of 0.50 to 100.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 100.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 95.00 mg, from 0.50 to 90.00 mg, from 0.50 to 85.00 mg, from 0.50 to 80.00 mg, from 0.50 to 75.00 mg, from 0.50 to 70.00 mg, from 0.50 to 65.00 mg, from 0.50 to 60.00 mg, from 0.50 to 55.00 mg, from 0.50 to 50.00 mg, 0.50 to 45.00 mg, 0.50 to 40.00 mg, 0.50 to 35.00 mg, 0.50 to 30.00 mg, 0.50 to 25.00 mg, 0.50 to 20.00 mg, 0.50 to 15.00 mg, 0.50 to 10.00 mg, 0.50 to 9.00 mg, 0.50 to 8.00 mg, 0.50 to 7.00 mg, 0.50 to 6.00 mg, 0.50 to 5.00 mg, 0.50 to 4.00 mg, 0.50 to 3.00 mg, 0.50 to 2.00 mg or 0.50 up to 1.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 10.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 9.50 mg, from 0.50 to 9.00 mg, from 0.50 to 8.50 mg, from 0.50 to 8.00 mg, from 0.50 to 7.50 mg, from 0.50 to 7.00 mg, from 0.50 to 6.50 mg, from 0.50 to 6.00 mg, from 0.50 to 5.50 mg, from 0.50 to 5.00 mg, from 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, or 0.50 to 2.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount from 1.00 to 5.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount from 2.00 to 4.00 mg.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.00 wt. % of the medicinal product weight.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.01 to 95.00 wt %, from 0.01 to 90.00 wt %, from 0.01 to 85.00 wt %, from 0.01 to 80.00 wt %, from 0.01 to 75.00 wt %, from 0.01 to 70.00 wt %, from 0.01 to 65.00 wt %, from 0.01 to 60.00 wt %, from 0.01 to 55.00 mass %, from 0.01 to 50.00 mass % or from 0.01 to 40.00 mass % of the mass of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.10 to 99.00 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 99.00 wt %, from 0.50 to 95.00 wt %, from 0.50 to 90.00 wt %, from 0.50 to 85.00 wt %, from 0.50 to 80.00 wt %, from 0.50 to 75.00 wt %, from 0.50 to 70.00 wt %, from 0.50 to 65.00 wt %, from 0.50 to 60.00 wt. %, from 0.50 to 55.00 wt. %, from 0.50 to 50.00 wt. %, from 0.50 to 45.00 wt. % or from 0.50 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 1.00 to 99.00 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. % or from 1.00 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. %, or from 0.50 to 1.00 wt. % of the mass of the drug.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in an amount of 1.00 to 99.99 wt. % of the medicinal product weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the drug of the present invention is from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the drug weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the mass of the drug.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the medicinal product.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the medicinal product.

In one embodiment of the present invention, an effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, is in the range of about 0.05 to 50.00 mg per day per patient in need of such treatment.

More preferably, the effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula A’’ or a pharmaceutically acceptable salt thereof according to the present invention is from 0.05 to 10.00 mg, from 0.05 to 9.00 mg, from 0.05 to 8.00 mg, from 0.05 to 7.00 mg, from 0.05 to 6.00 mg, from 0.05 to 5.00 mg, from 0.05 to 4.00 mg, from 0.05 to 3.50 mg, from 0.05 to 3.00 mg, from 0.05 to 2.50 mg, from 0.05 to 2.00 mg, 0.05 to 1.50 mg, 0.05 to 1.00 mg, 0.05 to 0.50 mg or 0.50 to 5.00 mg, 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, 0.50 to 2.00 mg or 1.00 to 5.00 mg, 1.00 to 4.50 mg, 1.00 to 4.00 mg, 1.00 to 3.50 mg, 1.00 to 3.00 mg, 1.00 to 2.50 mg, 1.00 to 2.00 mg or 2.00 to 5.00 mg or 1.00 to 4.00 mg per day.

If necessary, doses are usually divided into several smaller doses to be administered throughout the day.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing in an effective amount 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable excipient.

One embodiment of the present invention is a medicinal product characterized in that at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, slip agents, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a drug exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, characterized in that the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia. More preferably, the disease according to the present invention is selected from the group of JAK-mediated diseases or disorders.

In some embodiments, one or more compounds of the present invention may be used in combination with other active agents.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount of 0.50 to 100.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 100.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 95.00 mg, from 0.50 to 90.00 mg, from 0.50 to 85.00 mg, from 0.50 to 80.00 mg, from 0.50 to 75.00 mg, from 0.50 to 70.00 mg, from 0.50 to 65.00 mg, from 0.50 to 60.00 mg, from 0.50 to 55.00 mg, from 0.50 up to 50.00 mg, 0.50 to 45.00 mg, 0.50 to 40.00 mg, 0.50 to 35.00 mg, 0.50 to 30.00 mg, 0.50 to 25.00 mg, 0.50 to 20.00 mg, 0.50 to 15.00 mg, 0.50 to 10.00 mg, 0.50 to 9.00 mg, 0.50 to 8.00 mg, 0.50 to 7.00 mg, 0.50 to 6.00 mg, 0.50 to 5.00 mg, 0.50 to 4.00 mg, 0.50 to 3.00 mg, 0.50 to 2.00 mg or 0.50 to 1.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 10.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 9.50 mg, from 0.50 to 9.00 mg, from 0.50 to 8.50 mg, from 0.50 to 8.00 mg, from 0.50 to 7.50 mg, from 0.50 to 7.00 mg, from 0.50 to 6.50 mg, from 0.50 to 6.00 mg, from 0.50 to 5.50 mg, from 0.50 to 5.00 mg, from 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, or 0.50 to 2.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount from 1.00 to 5.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount from 2.00 to 4.00 mg.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof in an amount of 0.01 to 99.00 wt. % of the medicinal product weight.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.01 to 95.00 wt. %, from 0.01 to 90.00 wt. %, from 0.01 to 85.00 wt. %, from 0.01 to 80.00 wt. %, from 0.01 to 75.00 wt. %, from 0.01 to 70.00 wt. %, from 0.01 to 65.00 wt. %, from 0.01 to 60.00 wt. %, from 0.01 to 55.00 mass %, from 0.01 to 50.00 mass % or from 0.01 to 40.00 mass % of the mass of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.10 to 99.00 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 99.00 wt %, from 0.50 to 95.00 wt %, from 0.50 to 90.00 wt %, from 0.50 to 85.00 wt %, from 0.50 to 80.00 wt %, from 0.50 to 75.00 wt %, from 0.50 to 70.00 wt %, from 0.50 to 65.00 wt %, from 0.50 to 60.00 wt. %, from 0.50 to 55.00 wt. %, from 0.50 to 50.00 wt. %, from 0.50 to 45.00 wt. % or from 0.50 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 1.00 to 99.00 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. % or from 1.00 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. % or from 0.50 to 1.00 mass % of the mass of the medicinal product.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in an amount of 1.00 to 99.99 wt. % of the medicinal product weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the drug of the present invention is from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the drug weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the mass of the drug.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the medicinal product.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the medicinal product.

In one embodiment of the present invention, an effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, is in the range of about 0.05 to 50.00 mg per day per patient in need of such treatment.

More preferably, the effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula B’’ or a pharmaceutically acceptable salt thereof according to the present invention is from 0.05 to 10.00 mg, from 0.05 to 9.00 mg, from 0.05 to 8.00 mg, from 0.05 to 7.00 mg, from 0.05 to 6.00 mg, from 0.05 to 5.00 mg, from 0.05 to 4.00 mg, from 0.05 to 3.50 mg, from 0.05 to 3.00 mg, from 0.05 to 2.50 mg, from 0.05 to 2.00 mg, 0.05 to 1.50 mg, 0.05 to 1.00 mg, 0.05 to 0.50 mg or 0.50 to 5.00 mg, 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, 0.50 to 2.00 mg or 1.00 to 5.00 mg, 1.00 to 4.50 mg, 1.00 to 4.00 mg, 1.00 to 3.50 mg, 1.00 to 3.00 mg, 1.00 to 2.50 mg, 1.00 to 2.00 mg or 2.00 to 5.00 mg or 1.00 to 4.00 mg per day.

If necessary, doses are usually divided into several smaller doses to be administered throughout the day.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases, containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.

The stated problem is solved, and the claimed technical result is also achieved by means of a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing in an effective amount 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

One embodiment of the present invention is a medicinal product characterized in that at least one pharmaceutically acceptable excipient is selected from the group consisting of excipients, stabilizers, solubilizers, solvents, humectants, lubricants, slip agents, thickeners, sweeteners, flavors, aromas, fungicides, prolonged delivery regulators, co-solvents, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity or correcting substances.

One embodiment of the present invention is a drug exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, characterized in that the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia. More preferably, the disease according to the present invention is selected from the group of JAK-mediated diseases or disorders.

In some embodiments, one or more compounds of the present invention may be used in combination with other active agents.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of 0.50 to 100.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 100.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 95.00 mg, from 0.50 to 90.00 mg, from 0.50 to 85.00 mg, from 0.50 to 80.00 mg, from 0.50 to 75.00 mg, from 0.50 to 70.00 mg, from 0.50 to 65.00 mg, from 0.50 to 60.00 mg, from 0.50 to 55.00 mg, from 0.50 to 50.00 mg, 0.50 to 45.00 mg, 0.50 to 40.00 mg, 0.50 to 35.00 mg, 0.50 to 30.00 mg, 0.50 to 25.00 mg, 0.50 to 20.00 mg, 0.50 to 15.00 mg, 0.50 to 10.00 mg, 0.50 to 9.00 mg, 0.50 to 8.00 mg, 0.50 to 7.00 mg, 0.50 to 6.00 mg, 0.50 to 5.00 mg, 0.50 to 4.00 mg, 0.50 to 3.00 mg, 0.50 to 2.00 mg or from 0.50 to 1.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount from 0.50 to 10.00 mg.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 9.50 mg, from 0.50 to 9.00 mg, from 0.50 to 8.50 mg, from 0.50 to 8.00 mg, from 0.50 to 7.50 mg, from 0.50 to 7.00 mg, from 0.50 to 6.50 mg, from 0.50 to 6.00 mg, from 0.50 to 5.50 mg, from 0.50 to 5.00 mg, 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, or 0.50 to 2.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of 1.00 to 5.00 mg.

One embodiment of the present invention is a medicinal product containing a therapeutically effective amount of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of 2.00 to 4.00 mg.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof in an amount of from 0.01 to 99.00 wt. % of the medicinal product weight.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.01 to 95.00 wt %, from 0.01 to 90.00 wt %, from 0.01 to 85.00 wt %, from 0.01 to 80.00 wt %, from 0.01 to 75.00 wt %, from 0.01 to 70.00 wt %, from 0.01 to 65.00 wt %, from 0.01 to 60.00 wt %, from 0.01 to 55.00 mass %, from 0.01 to 50.00 mass % or from 0.01 to 40.00 mass % of the mass of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.10 to 99.00 wt. %, from 0.10 to 95.00 wt. %, from 0.10 to 90.00 wt. %, from 0.10 to 85.00 wt. %, from 0.10 to 80.00 wt. %, from 0.10 to 75.00 wt. %, from 0.10 to 70.00 wt. %, from 0.10 to 65.00 wt. %, from 0.10 to 60.00 wt. %, from 0.10 to 55.00 wt. %, from 0.10 to 50.00 wt. %, from 0.10 to 45.00 wt. %, or from 0.10 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 99.00 wt %, from 0.50 to 95.00 wt %, from 0.50 to 90.00 wt %, from 0.50 to 85.00 wt %, from 0.50 to 80.00 wt %, from 0.50 to 75.00 wt %, from 0.50 to 70.00 wt %, from 0.50 to 65.00 wt %, from 0.50 to 60.00 wt. %, from 0.50 to 55.00 wt. %, from 0.50 to 50.00 wt. %, from 0.50 to 45.00 wt. % or from 0.50 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 1.00 to 99.00 wt. %, from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. % or from 1.00 to 40.00 wt. % of the weight of the medicinal product.

More preferably, the content of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention in the drug is from 0.50 to 5.00 wt. %, from 0.50 to 4.50 wt. %, from 0.50 to 4.00 wt. %, from 0.50 to 3.50 wt. %, from 0.50 to 3.00 wt. %, from 0.50 to 2.50 wt. %, from 0.50 to 2.00 wt. %, from 0.50 to 1.50 wt. % or from 0.50 to 1.00 mass % of the mass of the medicinal product.

One embodiment of the present invention is a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient in an amount of 1.00 to 99.99 wt. % of the medicinal product weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the drug of the present invention is from 1.00 to 95.00 wt. %, from 1.00 to 90.00 wt. %, from 1.00 to 85.00 wt. %, from 1.00 to 80.00 wt. %, from 1.00 to 75.00 wt. %, from 1.00 to 70.00 wt. %, from 1.00 to 65.00 wt. %, from 1.00 to 60.00 wt. %, from 1.00 to 55.00 wt. %, from 1.00 to 50.00 wt. %, from 1.00 to 45.00 wt. %, or from 1.00 to 40.00 wt. % of the drug weight.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 1.00 to 99.90 wt.%, from 10.00 to 99.90 wt.%, from 20.00 to 99.90 wt.%, from 30.00 to 99.90 wt.%, from 40.00 to 99.90 wt.%, from 50.00 to 99.90 wt.%, from 60.00 to 99.90 wt.%, from 70.00 to 99.90 wt.%, from 80.00 to 99.90 wt.%, from 90.00 to 99.90 wt.%, from 95.00 to 99.90 wt.% or from 97.00 to 99.90 wt. % of the mass of the drug.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 10.00 to 99.50 wt. %, from 10.00 to 99.40 wt. %, from 10.00 to 99.30 wt. %, from 10.00 to 99.20 wt. %, from 10.00 to 99.10 wt. %, from 10.00 to 99.00 wt. %, from 10.00 to 98.90 wt. %, from 10.00 to 98.80 wt. %, from 10.00 to 98.70 wt. %, from 10.00 to 98.60 wt. %, from 10.00 to 98.50 wt. %, from 10.00 to 98.40 wt. %, from 10.00 to 98.30 wt. %, from 10.00 to 98.20 wt. %, from 10.00 to 98.10 wt. %, from 10.00 to 98.00 wt. % of the weight of the medicinal product.

More preferably, the content of at least one pharmaceutically acceptable excipient in the medicament of the present invention is from 90.00 to 99.90 wt. %, from 90.00 to 99.80 wt. %, from 90.00 to 99.70 wt. %, from 90.00 to 99.60 wt. %, from 90.00 to 99.50 wt. %, from 90.00 to 99.40 wt. %, from 90.00 to 99.30 wt. %, from 90.00 to 99.20 wt. %, from 90.00 to 99.10 wt. %, from 90.00 to 99.00 wt. %, from 90.00 to 98.90 wt. %, from 90.00 to 98.80 wt. %, from 90.00 to 98.70 wt. %, from 90.00 to 98.60 wt. %, from 90.00 to 98.50 wt. %, from 90.00 to 98.40 wt. %, from 90.00 to 98.30 wt. %, from 90.00 to 98.20 wt. %, from 90.00 to 98.10 wt. %, from 90.00 to 98.00 wt. %, from 95.00 to 99.90 wt. %, from 96.00 to 99.90 wt. %, from 97.00 to 99.90 wt. % or from 98.00 to 99.90 wt. % of the weight of the medicinal product.

In one embodiment of the present invention, an effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, is in the range of about 0.05 to 50.00 mg per day per patient in need of such treatment.

More preferably, the effective dosage of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile represented by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention is from 0.05 to 10.00 mg, from 0.05 to 9.00 mg, from 0.05 to 8.00 mg, from 0.05 to 7.00 mg, from 0.05 to 6.00 mg, from 0.05 to 5.00 mg, from 0.05 to 4.00 mg, from 0.05 to 3.50 mg, from 0.05 to 3.00 mg, from 0.05 to 2.50 mg, 0.05 to 2.00 mg, 0.05 to 1.50 mg, 0.05 to 1.00 mg, 0.05 to 0.50 mg or 0.50 to 5.00 mg, 0.50 to 4.50 mg, 0.50 to 4.00 mg, 0.50 to 3.50 mg, 0.50 to 3.00 mg, 0.50 to 2.50 mg, 0.50 to 2.00 mg or 1.00 to 5.00 mg, 1.00 to 4.50 mg, 1.00 to 4.00 mg, 1.00 to 3.50 mg, 1.00 to 3.00 mg, 1.00 to 2.50 mg, 1.00 up to 2.00 mg or from 2.00 to 5.00 mg or from 1.00 to 4.00 mg per day.

If necessary, doses are usually divided into several smaller doses to be administered throughout the day.

One embodiment of the present invention is a medicinal product containing compound A’’ or compound B’’ or compound C’’, or a pharmaceutically acceptable salt thereof, which is a solid medicinal product.

More preferably, the solid drug of the present invention is, but is not limited to, a tablet, capsule, pellet, dragee, granule, sachet, powder, lyophilisate.

More preferably, the solid preparation of the present invention is, but is not limited to, a dispersible tablet including an orodispersible tablet, a lyophilized tablet, a film-coated tablet, a buccal tablet, an effervescent tablet, a delayed/extended/modified release tablet.

One embodiment of the invention is a medicinal product that is a liquid medicinal product.

More preferably, the liquid drug of the present invention is, but is not limited to, a solution, a concentrate for preparing a solution, a syrup, a suspension.

One embodiment of the invention is a medicinal product that is a parenteral medicinal product.

Parenteral administration of drugs is a route of administration of drugs into the body that bypasses the gastrointestinal tract, as opposed to the oral route of administration of drugs. Parenteral drugs are sterile preparations intended for administration by injection, infusion, inhalation or implantation into the body of a human or animal. These include solutions, emulsions, suspensions, aerosols, powders and tablets for obtaining solutions and implantation, powders for inhalation, lyophilized preparations for obtaining dosage forms administered into the body parenterally (subcutaneously, intramuscularly, intravenously, intra-arterially, into various cavities).

Parenteral routes of administration include administration into tissues (intradermally, subcutaneously, intramuscularly, intraosseously), into vessels (intravenously, intraarterially, into lymphatic vessels), into cavities (into the pleural, abdominal, cardiac and joint cavities), into the subarachnoid space, as well as inhalation, intranasal and subconjunctival administration.

More preferably, the parenteral drug of the present invention is an infusion solution.

More preferably, the parenteral drug of the present invention is an injection solution.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for treating diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a medicament for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’ or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention, exhibiting properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, exhibiting the properties of a Janus kinase (JAK) inhibitor, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt, for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for the treatment of autoimmune diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for treating diseases by inhibiting Janus kinase.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for obtaining a medicinal product for the treatment of diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment of autoimmune diseases.

More preferably, the autoimmune disease of the present invention is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia.

More preferably, the disease of the present invention is selected from the group of JAK-mediated diseases or disorders.

More preferably, the disease is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, chronic polyarthritis, atopic dermatitis, juvenile idiopathic arthritis,

alopecia (focal alopecia, frontal fibrosing alopecia, alopecia areata, including severe or very severe forms), multiple sclerosis, disseminated sclerosis, amyotrophic lateral sclerosis, neurodegenerative Alzheimer's disease,

Type I diabetes, diabetic kidney disease, aggressive albuminuria reduction in biopsy-proven diabetic nephropathy, lupus, systemic lupus erythematosus, lupus nephritis, psoriasis,

inflammatory bowel disease, ulcerative colitis, Crohn's disease, severe pseudoparalytic myasthenia, immunoglobulin nephropathy, autoimmune thyroid disease, pemphigus vulgaris, bullous pemphigoid,

allergic reactions such as asthma, food allergies, atopic dermatitis and rhinitis,

viral diseases such as Epstein-Barr virus, hepatitis B, hepatitis C, human immunodeficiency virus, varicella-zoster virus and human papillomavirus, coronavirus, COVID-19,

skin rashes, skin irritations, skin sensitization (eg, contact dermatitis or allergic contact dermatitis), cutaneous lichen planus,

cancer including cancers that are characterized by the formation of solid tumors (e.g. prostate cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, Kaposi's sarcoma, Castleman disease, melanoma, etc.), blood cancers (e.g. lymphoma, leukemia such as acute lymphoblastic leukemia, acute myelogenous leukemia (AML), or multiple myeloma), and skin cancers such as cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma, typical cutaneous T-cell lymphomas include Sezary syndrome and mycosis fungoides, myeloproliferative disorders (MPDs) such as polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis with myeloid metaplasia (MMM), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), systemic mastocytosis (SM) associated with colitis cancer, colon cancer, colorectal cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), adenocarcinoma, small intestine cancer, rectal cancer, etc.,

Inflammatory diseases include inflammatory diseases of the eye (e.g., iritis, uveitis, scleritis, conjunctivitis, or related diseases), refractory non-infectious non-anterior uveitis, inflammatory diseases of the airways (e.g., upper respiratory tract including diseases of the nose and sinuses such as rhinitis or sinusitis, lower respiratory tract including bronchitis, chronic non-specific lung disease, etc.), inflammatory myopathy such as myocarditis and other inflammatory diseases, ischemia-reperfusion injury or diseases or conditions associated with an inflammatory ischemic event such as stroke or cardiac arrest, systemic inflammatory response syndrome, septic shock, large inflammatory hepatocellular adenomas,

anorexia, cachexia or fatigue caused by or associated with cancer,

pathological conditions associated with hypoxia or astrogliosis, such as diabetic retinopathy, cancer or neurodegeneration,

gout, prostate enlargement, dry eye syndrome and related disorders, IgG4-related disorders, idiopathic granulomatous mastitis, pyoderma gangrenosum, cutaneous dermatomyositis, idiopathic inflammatory myositis, chronic atypical neutrophilic dermatosis with lipodystrophy and fever (Nakayo-Nishimura syndrome), interferon gene stimulator-associated vasculopathy, Aicardi-Goutières syndrome, graft-versus-host disease including that following peripheral blood hematopoietic cell transplantation, neuromyelitis, immune thrombocytopenia, coronavirus pneumonia (COVID-19), symptoms associated with COVID-19 infection, hospital-acquired pneumonia in critically ill patients with a proinflammatory phenotype, lung injury after spontaneous subarachnoid hemorrhage, ocular mucous membrane pemphigoid, oral lichen planus, steroid-resistant/recurrent immune thrombocytopenia, pulmonary injury after intracerebral hemorrhage, moderate to severe traumatic intracerebral hemorrhage/contusion, recurrent giant cell arteritis, systemic sclerosis, therapy of non-segmental vitiligo, therapy of HIV symptoms, autoinflammatory syndrome, primary biliary cholangitis, recurrent or naive dermatomyositis, Sjogren's syndrome, inflammation and depression in people with HIV, APOL1-associated kidney disease, polymyalgia rheumatica, idiopathic inflammatory myopathy.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt for the treatment of diseases in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt to obtain a pharmaceutical composition or a medicinal product for the treatment of diseases in humans and animals.

The stated problem is solved, and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of diseases in humans and animals.

The stated problem is solved, and the claimed technical result is achieved by using a medicinal product containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of diseases in humans and animals.

The stated problem is solved, and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, to obtain a medicinal product for the treatment of diseases in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt for obtaining a pharmaceutical composition or a medicinal product for treating autoimmune diseases by inhibiting Janus kinase in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of autoimmune diseases by inhibiting Janus kinase in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a medicinal product containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of autoimmune diseases by inhibiting Janus kinase in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for obtaining a medicinal product for the treatment of autoimmune diseases by inhibiting Janus kinase in humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt for obtaining a pharmaceutical composition or a medicinal product for treating autoimmune diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of autoimmune diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a medicinal product containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of autoimmune diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for obtaining a medicinal product for the treatment of autoimmune diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt for obtaining a pharmaceutical composition or a medicinal product for treating diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a medicinal product containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for the treatment of diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a pharmaceutical composition containing a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt, for obtaining a medicinal product for treating diseases by inhibiting Janus kinase in mammals, including humans and animals.

The stated problem is solved and the claimed technical result is achieved by using a compound of formula A’’ or its pharmaceutically acceptable salt, or a compound of formula B’’ or its pharmaceutically acceptable salt, a compound of formula C’’ or its pharmaceutically acceptable salt for the treatment of diseases by inhibiting Janus kinase in mammals, including humans and animals.

More preferably, in the context of the present invention, the mammalian animals are domestic animals.

More preferably, within the framework of the present invention, domestic animals are, for example, but not limited to, sheep, goats, pigs, horses, camels, deer, rabbits, cats, dogs.

More preferably, the animal disease of the present invention is selected from the group consisting of rheumatoid arthritis, atopic dermatitis, focal alopecia, coronavirus infection, including covid-19, various types of cancer, asthma, pruritus, including that associated with allergic dermatitis, allergies, chronic respiratory diseases and other diseases in which immunosuppression and/or immunomodulation is desirable.

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula A’’, which includes removing the protective group R of the compound of formula 4a’’:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula A’’ or its pharmaceutically acceptable salt, which includes removing the protective group R of the compound of formula 4a’’ or its salt:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula A’’ or its pharmaceutically acceptable salt, which includes removing the protective group R of the compound of formula 4a’’:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula A’’ or its salt, which includes removing the protective group R of the compound of formula 4a’’ or its salt:

In one embodiment of the present invention, a salt, including a pharmaceutically acceptable salt, of compound A’’ is a salt formed by compound A’’ and an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound A'' is a salt formed between compound A'' and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound A’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound A’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound A is 1:1, 1:2, or 1:3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound A'' is a salt formed between compound A'' and an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound A’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound A’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound A’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the salt of compound 4a’’ is a salt formed between compound 4a’’ and an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 4a’’ is a salt formed between compound 4a’’ and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 4a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 4a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 4a’’ is 1:1, 1:2, or 1:3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound 4a’’ is a salt formed between compound 4a’’ and an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 4a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 4a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 4a’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the protecting group R is benzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl, tert-butoxycarbonyl, 1-adamantyloxycarbonyl, 2-adamantylcarbonyl, 2,4-dimethylpent-3-yloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl, vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N',N'-dimethylhydrazinyl, methoxymethyl, tert-butoxymethyl, benzyloxymethyl, 2-tetrahydropyranyl, N-pivaloyloxymethyl or 2-(trimethylsilyl)ethoxymethyl.

More preferably, the protecting group R is 2-(trimethylsilyl)ethoxycarbonyl.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt occurs in a mixture of an organic solvent and water or in a mixture of an organic solvent and an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the aprotic organic solvent within the framework of the present invention is selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-chlorobutane, chlorobenzene, dichlorobenzene, diethyl ether, diisopropyl ether, dibutyl ether, Methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dimethoxyethane, diethylene glycol dimethyl ether, diethoxymethane, dichloromethane, tetrahydrofuran, methyltetrahydrofuran, ethyl acetate, ethyl formate, methyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate, iso-butyl acetate, β-butyrolactone, γ-butyrolactone, γ-valerolactone, δ-valerolactone, ethylene glycol diacetate, propylene glycol diacetate, glycerol triacetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, 2-hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethyl acetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the protic organic solvent within the framework of the present invention is selected from the group including, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt is carried out by reacting the compound of formula 4a’’ or its salt with a fluorine-containing compound.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt is carried out by reacting the compound of formula 4a’’ or its salt with a fluorine-containing compound, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt is carried out by reacting the compound of formula 4a’’ or its salt with a fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt is carried out by reacting the compound of formula 4a’’ or its salt with an organic fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 4a’’ or its salt is carried out by reacting the compound of formula 4a’’ or its salt with an organic fluorine-containing acid, followed by treatment with an organic base.

More preferably, when removing the protective group R, the subsequent treatment is carried out with a base according to the present invention, which is an aqueous ammonia solution.

More preferably, when removing the protective group R, the subsequent treatment is carried out with a base according to the present invention, which is a solution of ammonia in alcohol.

More preferably, when removing the protective group R, the subsequent treatment is carried out with a base according to the present invention, which is a hydroxides or halides of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations, but not limited to, is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

More preferably, the base used in the present invention is, but is not limited to, imidazole, pyridine and its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, when removing the protective group R, the subsequent treatment is carried out with an organic base according to the present invention, which is an amine, including a primary amine.

More preferably, the primary amine of the present invention is, but is not limited to, a compound of the formula R ₂ 'NH ₂ , wherein R ₂ ' is C ₁ -C ₅ alkyl, aryl, alkylaryl, optionally substituted with C ₁ -C ₅ alkyl, halogen, alcohol, thiol, cyano, carboxyl, C ₁ -C ₅ alkyl or ester group.

More preferably, the primary amine of the present invention is, but is not limited to, a compound of the formula R ₂ 'N, wherein R ₂ ' is selected from the group consisting of methyl, ethyl, propyl, isopropyl or phenyl.

More preferably, the primary amine of the present invention is, but is not limited to, propylamine, butylamine or aniline.

More preferably, the organic base of the present invention is a secondary amine.

More preferably, the secondary amine of the present invention is, but is not limited to, a compound of formula R₂’R₃'NH, where R₂’, R₃’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or R₂' with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen.

More preferably, the secondary amine of the present invention is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'NH, wherein R ₂ ', R ₃ ' are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, phenyl or benzyl.

More preferably, the secondary amine of the present invention is, but is not limited to, diethylamine, diisopropylamine or diisobutylamine.

More preferably, the organic base of the present invention is a tertiary amine.

More preferably, the tertiary amine of the present invention is, but is not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or, when R₂' with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group.

More preferably, the tertiary amine of the present invention is, but is not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl or, when R₂' with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, where R₄' bonded to the nitrogen atom.

More preferably, the tertiary amine of the present invention is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'R ₄ 'N, wherein R ₂ ', R ₃ ', R ₄ ' are independently selected from the group consisting of methyl, ethyl, propyl or isopropyl.

More preferably, the tertiary amine of the present invention is, but is not limited to, N-methylformalin or triethylamine.

More preferably, the fluorine-containing compound of the present invention is selected from the group including, but not limited to, a fluorine-containing acid, tetrabutylammonium fluoride, lithium tetrafluoroborate, an alkali or alkaline earth metal fluoride, in particular cesium fluoride.

More preferably, the fluorine-containing acid of the present invention is hydrofluoric acid.

More preferably, the fluorine-containing acid of the present invention is an organic fluorine-containing acid.

More preferably, the organic fluorine-containing acid is selected from the group including, but not limited to, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, 2,4-difluorobenzoic acid, 2,6-difluorobenzoic acid, 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid, 4-fluorosalicylic acid and 5-fluorosalicylic acid.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a pharmaceutically acceptable salt thereof, characterized in that it further comprises reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a solvent.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a mixture of an organic solvent and water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-Chlorobutane, Chlorobenzene, Dichlorobenzene, Diethyl Ether, Diisopropyl Ether, Dibutyl Ether, Methyl tert-Butyl Ether, Ethyl tert-Butyl Ether, Cyclopentyl Methyl Ether, Dimethoxyethane, Diethylene Glycol Dimethyl Ether, Diethoxymethane, Dichloromethane, Tetrahydrofuran, Methyl Tetrahydrofuran, Ethyl Acetate, Ethyl Formate, Methyl Acetate, N-Propyl Acetate, Iso-Propyl Acetate, N-Butyl Acetate, Iso-Butyl Acetate, β-Butyrolactone, γ-Butyrolactone, γ-Valerolactone, δ-Valerolactone, Ethylene Glycol Diacetate, Propylene Glycol Diacetate, Glycerol Triacetate, Acetone, Methyl Ethyl Ketone, Methyl Isobutyl Ketone, 2-Hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethylacetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent selected from the group including, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is an aqueous solution of ammonia.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a solution of ammonia in alcohol.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a hydroxide or halide of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations, but not limited to, is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

One of the embodiments of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an organic base.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of, but not limited to, imidazole, pyridine or its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine, which have been characterized previously.

One embodiment of the present invention is a method for producing a compound of formula A'', characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a:

One embodiment of the present invention is a method for producing a compound of formula A'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a or a salt thereof:

One embodiment of the present invention is a method for producing a compound of formula A'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a':

where R and R ₁ are protecting groups, z = 1, 2 or 3.

One embodiment of the present invention is a method for producing a compound of formula A'' or a salt thereof, characterized in that X ₁ is an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

More preferably, X ₁ is an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

More preferably, X ₁ is an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the organic acid is a monobasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, to obtain a compound of formula A'', the removal of the protective group R ₁ from the compound of formula 2a to obtain a compound of formula 3a or a salt thereof occurs in an organic solvent.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in water or an ammonia solution.

In one embodiment of the present invention, the removal of the protective group R ₁ from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in a mixture of an organic solvent and water or an ammonia solution.

In one embodiment of the present invention, the removal of the protective group R ₁ from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in the aprotic organic solvent listed above.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in the protic organic solvent listed above.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride to produce a compound of formula 4a’’.

One embodiment of the present invention is a method for producing a compound of formula A’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride to produce a compound of formula 4a’’ or a salt thereof.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in an organic solvent.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in an organic solvent.

In one embodiment of the present invention, the reaction of the compound of formula 3a or its salt with 2-methoxyethane-1-sulfonyl chloride occurs in water or an ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in a mixture of an organic solvent and water or an ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in the aprotic organic solvent listed above.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-methoxyethane-1-sulfonyl chloride occurs in the protic organic solvent listed above.

The stated problem is solved, and the stated technical result is achieved by combining formula 4a’’:

where R is a protecting group.

The stated problem is solved, and the stated technical result is achieved by combining formula 4a’’:

or its salts, where R is a protecting group.

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula B’’, which includes removing the protective group R of the compound of formula 5a’’:

Within the framework of the present invention, the stated problem is solved and the claimed technical result is achieved by means of a method for obtaining a new compound of formula B’’ or its pharmaceutically acceptable salt, which includes removing the protective group R of the compound of formula 5a’’ or its salt:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula B’’ or its pharmaceutically acceptable salt, which includes removing the protective group R of the compound of formula 5a’’:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula B’’ or its salt,

which involves the removal of the protective group R of the compound of formula 5a’’ or its salt:

In one embodiment of the present invention, the salt, including a pharmaceutically acceptable salt, of compound B’’ is a salt formed by compound B’’ and an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound B’’ is a salt formed between compound B’’ and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound B’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid and compound B’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound B’’ is 1:1, 1:2, or 1:3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound B’’ is a salt formed between compound B’’ and an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid and compound B’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound B’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound B’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the salt of compound 5a’’ is a salt formed between compound 5a’’ and an acid.

More preferably, the acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 5a’’ is a salt formed between compound 5a’’ and an inorganic acid.

More preferably, the inorganic acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 5a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid for the above purposes is a dibasic acid, then the molar ratio of the salt-forming acid to compound 5a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid for the above purposes is a tribasic acid, then the molar ratio of the salt-forming acid to compound 5a’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic inorganic acid for the above purposes is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound 5a’’ is a salt formed between compound 5a’’ and an organic acid.

More preferably, the organic acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 5a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid for the above purposes is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 5a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 5a’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the protecting group R is benzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl, tert-butoxycarbonyl, 1-adamantyloxycarbonyl, 2-adamantylcarbonyl, 2,4-dimethylpent-3-yloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl, vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N',N'-dimethylhydrazinyl, methoxymethyl, tert-butoxymethyl, benzyloxymethyl, 2-tetrahydropyranyl, N-pivaloyloxymethyl or 2-(trimethylsilyl)ethoxymethyl.

More preferably, the protecting group R is 2-(trimethylsilyl)ethoxycarbonyl.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or a salt thereof occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or a salt thereof occurs in a mixture of an organic solvent and water or in a mixture of an organic solvent and an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the aprotic organic solvent within the framework of the present invention for the above purposes is selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-chlorobutane, chlorobenzene, dichlorobenzene, diethyl ether, diisopropyl ether, dibutyl ether, Methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dimethoxyethane, diethylene glycol dimethyl ether, diethoxymethane, dichloromethane, tetrahydrofuran, methyltetrahydrofuran, ethyl acetate, ethyl formate, methyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate, iso-butyl acetate, β-butyrolactone, γ-butyrolactone, γ-valerolactone, δ-valerolactone, ethylene glycol diacetate, propylene glycol diacetate, glycerol triacetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, 2-hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethyl acetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the protic organic solvent within the framework of the present invention for the above purposes is selected from the group comprising, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt is carried out by reacting the compound of formula 5a’’ with a fluorine-containing compound.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt is carried out by reacting the compound of formula 5a’’ or its salt with a fluorine-containing compound, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt is carried out by reacting the compound of formula 5a’’ or its salt with a fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt is carried out by reacting the compound of formula 5a’’ or its salt with an organic fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 5a’’ or its salt is carried out by reacting the compound of formula 5a’’ or its salt with an organic fluorine-containing acid, followed by treatment with an organic base.

More preferably, when removing the protective group R of compound 5a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is an aqueous ammonia solution.

More preferably, when removing the protective group R of compound 5a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is a solution of ammonia in alcohol.

More preferably, when removing the protective group R of compound 5a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is a hydroxides or halides of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations for the above purposes, but not limited to, is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

More preferably, as a base according to the present invention for the above purposes, there are used, but are not limited to, imidazole, pyridine and its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, when removing the protective group R of compound 5a’’ or its salt, the subsequent treatment is carried out with an organic base according to the present invention, which is an amine, including a primary amine.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'NH ₂ , wherein R ₂ ' is C ₁ -C ₅ alkyl, aryl, alkylaryl, optionally substituted with C ₁ -C ₅ alkyl, halogen, alcohol, thiol, cyano, carboxyl, C ₁ -C ₅ alkyl or ester group.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'N, wherein R ₂ ' is selected from the group consisting of methyl, ethyl, propyl, isopropyl or phenyl.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, propylamine, butylamine or aniline.

More preferably, the organic base of the present invention for the above purposes is a secondary amine.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, a compound of formula R₂’R₃'NH, where R₂’, R₃’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or R₂’ with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'NH, wherein R ₂ ', R ₃ ' are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, phenyl or benzyl.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, diethylamine, diisopropylamine or diisobutylamine.

More preferably, the organic base of the present invention for the above purposes is a tertiary amine.

More preferably, the tertiary amine of the present invention is, for the above purposes but not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or, when R₂' with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl or, when R₂' with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, where R₄' bonded to the nitrogen atom.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'R ₄ 'N, wherein R ₂ ', R ₃ ', R ₄ ' are independently selected from the group consisting of methyl, ethyl, propyl or isopropyl.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, N-methylformalin or triethylamine.

More preferably, the fluorine-containing compound of the present invention for the above purposes is selected from the group including, but not limited to, a fluorine-containing acid, tetrabutylammonium fluoride, lithium tetrafluoroborate, an alkali or alkaline earth metal fluoride, in particular cesium fluoride.

More preferably, the fluorine-containing acid of the present invention for the above purposes is hydrofluoric acid.

More preferably, the fluorine-containing acid of the present invention for the above purposes is an organic fluorine-containing acid.

More preferably, the organic fluorine-containing acid for the above purposes is selected from the group including, but not limited to, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, 2,4-difluorobenzoic acid, 2,6-difluorobenzoic acid, 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid, 4-fluorosalicylic acid and 5-fluorosalicylic acid.

One embodiment of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula B’’ or a pharmaceutically acceptable salt thereof, characterized in that it further comprises reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, including a pharmaceutically acceptable one, characterized in that it additionally includes reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an inorganic acid.

More preferably, the inorganic acid of the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, for the above purposes, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid for the above purposes is a dibasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, for the above purposes, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid for the above purposes is a tribasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention for the above purposes, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, for the above purposes, the salt of compound 1a is a salt formed between compound 1a and an organic acid.

More preferably, the organic acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

If the organic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, for the above purposes, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a solvent.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a mixture of an organic solvent and water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-Chlorobutane, Chlorobenzene, Dichlorobenzene, Diethyl Ether, Diisopropyl Ether, Dibutyl Ether, Methyl tert-Butyl Ether, Ethyl tert-Butyl Ether, Cyclopentyl Methyl Ether, Dimethoxyethane, Diethylene Glycol Dimethyl Ether, Diethoxymethane, Dichloromethane, Tetrahydrofuran, Methyl Tetrahydrofuran, Ethyl Acetate, Ethyl Formate, Methyl Acetate, N-Propyl Acetate, Iso-Propyl Acetate, N-Butyl Acetate, Iso-Butyl Acetate, β-Butyrolactone, γ-Butyrolactone, γ-Valerolactone, δ-Valerolactone, Ethylene Glycol Diacetate, Propylene Glycol Diacetate, Glycerol Triacetate, Acetone, Methyl Ethyl Ketone, Methyl Isobutyl Ketone, 2-Hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethylacetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent selected from the group including, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is an aqueous solution of ammonia.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a solution of ammonia in alcohol.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a hydroxide or halide of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations, without limitation, for the above purposes is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

One of the embodiments of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an organic base.

More preferably, the reaction of a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base selected from the group, but not limited to, imidazole, pyridine or its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

More preferably, in the context of the present invention, to obtain a compound of formula B’’, the reaction of a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine, which have been characterized previously.

One embodiment of the present invention is a method for producing a compound of formula B'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to obtain a compound of formula 3a:

One embodiment of the present invention is a method for producing a compound of formula B'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a or a salt thereof:

One embodiment of the present invention is a method for producing a compound of formula B'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a':

where R and R ₁ are protecting groups, z = 1, 2 or 3.

One embodiment of the present invention is a method for producing a compound of formula B'' or a salt thereof, characterized in that X ₁ is an acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

More preferably, X ₁ is an inorganic acid.

More preferably, the inorganic acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic inorganic acid for the above purposes is, but is not limited to, phosphoric acid.

More preferably, X ₁ is an organic acid.

More preferably, the organic acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic organic acid for the above purposes is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the organic acid is a monobasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in an organic or inorganic solvent, or a mixture thereof, as listed above.

One embodiment of the present invention is a process for producing a compound of formula B'' or a salt thereof, characterized in that R ₁ is benzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl, tert-butoxycarbonyl, 1-adamantyloxycarbonyl, 2-adamantylcarbonyl, 2,4-dimethylpent-3-yloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl, vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N',N'-dimethylhydrazinyl, methoxymethyl, tert-butoxymethyl, benzyloxymethyl, 2-tetrahydropyranyl, N-pivaloyloxymethyl or 2-(trimethylsilyl)ethoxymethyl.

One embodiment of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that it additionally includes reacting a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride to obtain the compound of formula 5a’’.

One embodiment of the present invention is a method for producing a compound of formula B’’ or a salt thereof, characterized in that it additionally includes reacting a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride to obtain a compound of formula 5a’’ or a salt thereof.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in an organic solvent.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in an organic solvent.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in a mixture of an organic solvent and water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in an aprotic organic solvent or its mixture with water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in the aprotic organic solvent listed earlier.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in a protic organic solvent or its mixture with water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with (methylthio)methanesulfonyl chloride occurs in the protic organic solvent listed earlier.

The stated problem is solved, and the stated technical result is achieved by combining formula 5a’’:

where R is a protecting group.

The stated problem is solved, and the stated technical result is achieved by combining formula 5a’’:

or its salts, where R is a protecting group.

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula C’’, which includes removing the protective group R of the compound of formula 6a’’:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula C’’ or its salt, including a pharmaceutical one, which includes removing the protective group R of the compound of formula 6a’’ or its salt:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula C’’ or its salt, which includes removing the protective group R of the compound of formula 6a’’:

Within the framework of the present invention, the stated problem is solved, and the claimed technical result is achieved by means of a method for obtaining a new compound of formula C’’ or its salt,

which involves the removal of the protective group R of the compound of formula 6a’’ or its salt:

In one embodiment of the present invention, the salt, including a pharmaceutically acceptable salt, of compound C’’ is a salt formed by compound C’’ and an acid.

More preferably, the acid of the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound C'' is a salt formed between compound C'' and an inorganic acid.

More preferably, the inorganic acid of the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, then the molar ratio of the salt-forming acid and the compound C’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, the molar ratio of the salt-forming acid to the compound C’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, the molar ratio of the salt-forming acid to the compound C’’ is 1:1, 1:2, or 1:3.

More preferably, in the context of the present invention, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound C'' is a salt formed between compound C'' and an organic acid.

More preferably, the organic acid of the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid and the compound C’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to the compound C’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to the compound C’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the salt of compound 6a’’ is a salt formed between compound 6a’’ and an acid.

More preferably, the acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

More preferably, the acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 6a’’ is a salt formed between compound 6a’’ and an inorganic acid.

More preferably, the inorganic acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 6a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid for the above purposes is a dibasic acid, then the molar ratio of the salt-forming acid to compound 6a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid for the above purposes is a tribasic acid, then the molar ratio of the salt-forming acid to compound 6a’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic inorganic acid for the above purposes is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, the salt of compound 6a’’ is a salt formed between compound 6a’’ and an organic acid.

More preferably, the organic acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 6a’’ is 1:1.

More preferably, within the framework of the present invention, the monobasic organic acid for the above purposes is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 6a’’ is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 6a’’ is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the protecting group R is benzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl, tert-butoxycarbonyl, 1-adamantyloxycarbonyl, 2-adamantylcarbonyl, 2,4-dimethylpent-3-yloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl, vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N',N'-dimethylhydrazinyl, methoxymethyl, tert-butoxymethyl, benzyloxymethyl, 2-tetrahydropyranyl, N-pivaloyloxymethyl or 2-(trimethylsilyl)ethoxymethyl.

More preferably, the protecting group R is 2-(trimethylsilyl)ethoxycarbonyl.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or a salt thereof occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or a salt thereof occurs in a mixture of an organic solvent and water or in a mixture of an organic solvent and an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the aprotic organic solvent within the framework of the present invention for the above purposes is selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-chlorobutane, chlorobenzene, dichlorobenzene, diethyl ether, diisopropyl ether, dibutyl ether, Methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dimethoxyethane, diethylene glycol dimethyl ether, diethoxymethane, dichloromethane, tetrahydrofuran, methyltetrahydrofuran, ethyl acetate, ethyl formate, methyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate, iso-butyl acetate, β-butyrolactone, γ-butyrolactone, γ-valerolactone, δ-valerolactone, ethylene glycol diacetate, propylene glycol diacetate, glycerol triacetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, 2-hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethyl acetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the protic organic solvent within the framework of the present invention for the above purposes is selected from the group comprising, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt is carried out by reacting the compound of formula 6a’’ with a fluorine-containing compound.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt is carried out by reacting the compound of formula 6a’’ or its salt with a fluorine-containing compound, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt is carried out by reacting the compound of formula 6a’’ or its salt with a fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt is carried out by reacting the compound of formula 6a’’ or its salt with an organic fluorine-containing acid, followed by treatment with a base.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the removal of the protective group R of the compound of formula 6a’’ or its salt is carried out by reacting the compound of formula 6a’’ or its salt with an organic fluorine-containing acid, followed by treatment with an organic base.

More preferably, when removing the protective group R of compound 6a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is an aqueous ammonia solution.

More preferably, when removing the protective group R of compound 6a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is a solution of ammonia in alcohol.

More preferably, when removing the protective group R of compound 6a’’ or its salt, the subsequent treatment is carried out with a base according to the present invention, which is a hydroxides or halides of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations for the above purposes, but not limited to, is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

More preferably, as a base according to the present invention for the above purposes, there are used, but are not limited to, imidazole, pyridine and its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, when removing the protective group R of compound 6a’’ or a salt thereof, the subsequent treatment is carried out with an organic base according to the present invention, which is an amine, including a primary amine.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'NH ₂ , wherein R ₂ ' is C ₁ -C ₅ alkyl, aryl, alkylaryl, optionally substituted with C ₁ -C ₅ alkyl, halogen, alcohol, thiol, cyano, carboxyl, C ₁ -C ₅ alkyl or ester group.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'N, wherein R ₂ ' is selected from the group consisting of methyl, ethyl, propyl, isopropyl or phenyl.

More preferably, the primary amine of the present invention for the above purposes is, but is not limited to, propylamine, butylamine or aniline.

More preferably, the organic base of the present invention for the above purposes is a secondary amine.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, a compound of formula R₂’R₃'NH, where R₂’, R₃’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or R₂’ with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'NH, wherein R ₂ ', R ₃ ' are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, phenyl or benzyl.

More preferably, the secondary amine of the present invention for the above purposes is, but is not limited to, diethylamine, diisopropylamine or diisobutylamine.

More preferably, the organic base of the present invention for the above purposes is a tertiary amine.

More preferably, the tertiary amine of the present invention is, for the above purposes but not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group, or, when R₂’ with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, aryl, alkylaryl, optionally substituted with C₁-C₅alkyl, halogen, alcohol, thiol, cyano, carboxyl, C₁-C₅-alkyl oxides, ester group.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, a compound of formula R₂’R₃’R₄’N, where R₂’, R₃’, R₄’ independently of each other represent C₁-C₅alkyl or, when R₂’ with R₃' together with the nitrogen atom form C₄-WITH₈cycloalkyl group or C₄-WITH₈a heterocyclic group where the heteroatom is oxygen, R₄' represents C₁-C₅alkyl, where R₄' bonded to the nitrogen atom.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, a compound of the formula R ₂ 'R ₃ 'R ₄ 'N, wherein R ₂ ', R ₃ ', R ₄ ' are independently selected from the group consisting of methyl, ethyl, propyl or isopropyl.

More preferably, the tertiary amine of the present invention for the above purposes is, but is not limited to, N-methylformalin or triethylamine.

More preferably, the fluorine-containing compound of the present invention for the above purposes is selected from the group including, but not limited to, a fluorine-containing acid, tetrabutylammonium fluoride, lithium tetrafluoroborate, an alkali or alkaline earth metal fluoride, in particular cesium fluoride.

More preferably, the fluorine-containing acid of the present invention for the above purposes is hydrofluoric acid.

More preferably, the fluorine-containing acid of the present invention for the above purposes is an organic fluorine-containing acid.

More preferably, the organic fluorine-containing acid for the above purposes is selected from the group including, but not limited to, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, 2,4-difluorobenzoic acid, 2,6-difluorobenzoic acid, 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid, 4-fluorosalicylic acid and 5-fluorosalicylic acid.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula C’’ or a pharmaceutically acceptable salt thereof, characterized in that it further comprises reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring to produce a compound of formula 2a.

where R and R ₁ are protecting groups.

One embodiment of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that it further comprises reacting a compound of formula 1a with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

where R and R ₁ are protecting groups.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, including a pharmaceutically acceptable one, characterized in that it additionally includes reacting a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring in the presence of a base to produce a compound of formula 2a.

,

where R and R ₁ are protecting groups.

In one embodiment of the present invention, a salt of compound 1a is used to obtain a compound of formula C’’ or a salt thereof, which is a salt formed between compound 1a and an acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

In one embodiment of the present invention, the salt of compound 1a is a salt formed between compound 1a and an inorganic acid.

More preferably, the inorganic acid of the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

If the inorganic acid is a monobasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, for the above purposes, the monobasic inorganic acid is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid for the above purposes is a dibasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, for the above purposes, the dibasic inorganic acid is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid for the above purposes is a tribasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention for the above purposes, the tribasic inorganic acid is, but is not limited to, phosphoric acid.

In one embodiment of the present invention, for the above purposes, the salt of compound 1a is a salt formed between compound 1a and an organic acid.

More preferably, the organic acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

If the organic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 1a is 1:1.

More preferably, within the framework of the present invention, for the above purposes, the monobasic organic acid is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1 or 1:2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, the molar ratio of the salt-forming acid to compound 1a is 1:1, 1:2, or 1:3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a solvent.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an organic solvent.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a mixture of an organic solvent and water or an ammonia solution.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in an aprotic organic solvent selected from the group including, but not limited to, pentane, hexane, heptane, octane, cyclohexane, methylcyclohexane, benzene, toluene, o-xylene, m-xylene, p-xylene, anisole, cumene, tetralin, limonene, turpentine, dioxane, chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene, cis-1,2-dichloroethene, trans-1,2-dichloroethene, trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1-Chlorobutane, Chlorobenzene, Dichlorobenzene, Diethyl Ether, Diisopropyl Ether, Dibutyl Ether, Methyl tert-Butyl Ether, Ethyl tert-Butyl Ether, Cyclopentyl Methyl Ether, Dimethoxyethane, Diethylene Glycol Dimethyl Ether, Diethoxymethane, Dichloromethane, Tetrahydrofuran, Methyl Tetrahydrofuran, Ethyl Acetate, Ethyl Formate, Methyl Acetate, N-Propyl Acetate, Iso-Propyl Acetate, N-Butyl Acetate, Iso-Butyl Acetate, β-Butyrolactone, γ-Butyrolactone, γ-Valerolactone, δ-Valerolactone, Ethylene Glycol Diacetate, Propylene Glycol Diacetate, Glycerol Triacetate, Acetone, Methyl Ethyl Ketone, Methyl Isobutyl Ketone, 2-Hexanone, cyclopentanone, cyclohexanone, dimethylformamide, dimethylacetamide, acetonitrile, propionitrile, dimethyl sulfoxide, N-methylpyrrolidone, acetic anhydride, tertiary amines such as triethylamine, sulfolane, pyridine and mixtures thereof.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent or a mixture thereof with water or an ammonia solution.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in a protic organic solvent selected from the group including, but not limited to, methanol, ethanol, n-propanol, iso-propanol, n-butanol, 2-butanol, iso-butanol, tert-butanol, 2-methyl-2-butanol, cyclohexanol, primary amines such as propylamine, secondary amines such as diisopropylamine, benzyl alcohol, phenol, 1,2-propanediol, 1,3-propanediol, methyloxyethanol, ethyloxyethanol, 1-methoxy-propan-2-ol, furfuryl alcohol, tetrahydrofurfuryl alcohol, ethyl lactate, formic acid acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and mixtures thereof.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is an aqueous solution of ammonia.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a solution of ammonia in alcohol.

More preferably, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base, which is a hydroxide or halide of quaternary ammonium cations.

More preferably, the hydroxide or halide of quaternary ammonium cations, without limitation, for the above purposes is selected from tetramethylammonium hydroxide, tetraethylammonium bromide, tetrapropylammonium chloride, tetrabutylammonium fluoride or benzalkonium chloride.

One of the embodiments of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an organic base.

More preferably, the reaction of a compound of formula 1a or a salt thereof with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a base selected from the group, but not limited to, imidazole, pyridine or its derivatives, in particular pyridine substituted with C ₁ -C ₅ alkyl, colidine, quinoline or quinoline substituted with C ₁ -C ₅ alkyl, benzimidazole, histidine, guanidine, phosphazene, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DBO), 4-(dimethylamino)pyridine, 2,2,6,6-tetramethylpiperidine or 2,6-lutidine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of an amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine.

More preferably, within the framework of the present invention, the reaction of the compound of formula 1a or its salt with 2-(3-azetidinylidene)acetonitrile protected at the amino group of the pyrazole ring occurs in the presence of a primary amine, a secondary amine or a tertiary amine, which have been characterized previously.

One embodiment of the present invention is a method for producing a compound of formula C'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to obtain a compound of formula 3a:

One embodiment of the present invention is a method for producing a compound of formula C'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to produce a compound of formula 3a or a salt thereof:

One embodiment of the present invention is a method for producing a compound of formula C'' or a salt thereof, characterized in that it further comprises removing the protective group R ₁ from the compound of formula 2a to obtain a compound of formula 3a':

, where R and R ₁ are protecting groups, z = 1, 2 or 3.

One embodiment of the present invention is a method for producing a compound of formula C'' or a salt thereof, characterized in that X ₁ is an acid.

More preferably, X ₁ according to the present invention for the above purposes is a monobasic, dibasic or tribasic acid.

More preferably, the acid of the present invention for the above purposes is a monobasic, dibasic or polybasic acid.

More preferably, X ₁ is an inorganic acid.

More preferably, the inorganic acid for the above purposes according to the present invention is a monobasic, dibasic or tribasic acid.

If the inorganic acid for the above purposes is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the inorganic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrochloric, hydrofluoric, hydrobromic, hydroiodic, nitric and nitrous acids.

If the inorganic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the inorganic acid is a dibasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic inorganic acid for the above purposes is selected from the group including, but not limited to, hydrogen sulfide, sulfurous, sulfuric and carbonic acids.

If the inorganic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the inorganic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic inorganic acid for the above purposes is, but is not limited to, phosphoric acid.

More preferably, X ₁ is an organic acid.

More preferably, the organic acid for the above purposes according to the present invention is a monobasic, dibasic or polybasic acid.

If the organic acid is a monobasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or, if the organic acid is a monobasic acid, then z = 1.

More preferably, within the framework of the present invention, the monobasic organic acid for the above purposes is selected from the group including, but not limited to, formic, acetic, monofluoroacetic, difluoroacetic, trifluoroacetic, propionic, butyric, isobutyric, valeric, caproic, enanthoic, p-toluic, anisic and phenylacetic acid.

If the organic acid is a dibasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1 or 1:2, or if the organic acid is a monobasic acid, then z = 1.2.

More preferably, within the framework of the present invention, the dibasic organic acid for the above purposes is selected from the group including, but not limited to, oxalic, malonic, succinic, dioxosuccinic, glutaric, α-hydroxyglutaric, 2-oxoglutaric, 3-oxoglutaric, adipic, pimelic, diaminopimelic, phthalic, isophthalic, teryphthalic, malic, suberic, azelaic, maleic, fumaric, tartaric, aspartic, glutamic, arabic and D-glucaric acid.

If the organic acid is a tribasic acid, then the molar ratio of the salt-forming acid to compound 3a is 1:1, 1:2, or 1:3, or if the organic acid is a tribasic acid, then z = 1, 2, 3.

More preferably, within the framework of the present invention, the tribasic organic acid for the above purposes is selected from the group including, but not limited to, citric, isocitric, aconitic, β-carboxyglutaric, 2-hydroxy-1,2,3-nonadecanetricarboxylic and benzene-1,3,5-tricarboxylic acid.

In one embodiment of the present invention, the removal of the R ₁ protecting group from the compound of formula 2a to obtain the compound of formula 3a or a salt thereof occurs in an organic or inorganic solvent, or a mixture thereof, as listed above.

One embodiment of the present invention is a method for producing a compound of formula C'' or a salt thereof, characterized in that R ₁ is benzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl, tert-butoxycarbonyl, 1-adamantyloxycarbonyl, 2-adamantylcarbonyl, 2,4-dimethylpent-3-yloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl, vinyl, 2-chloroethyl, 2-phenylsulfonylethyl, allyl, benzyl, 2-nitrobenzyl, 4-nitrobenzyl, diphenyl-4-pyridylmethyl, N',N'-dimethylhydrazinyl, methoxymethyl, tert-butoxymethyl, benzyloxymethyl, 2-tetrahydropyranyl, N-pivaloyloxymethyl or 2-(trimethylsilyl)ethoxymethyl.

One embodiment of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that it additionally includes reacting a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride to obtain a compound of formula 6a’’.

One embodiment of the present invention is a method for producing a compound of formula C’’ or a salt thereof, characterized in that it additionally includes reacting a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride to obtain a compound of formula 6a’’ or a salt thereof.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in an organic solvent.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in a mixture of an organic solvent and water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in an aprotic organic solvent or its mixture with water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in the aprotic organic solvent listed earlier.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in a protic organic solvent or its mixture with water or ammonia solution.

In one embodiment of the present invention, the reaction of a compound of formula 3a or a salt thereof with 2-(methylthio)ethane-1-sulfonyl chloride occurs in the protic organic solvent listed earlier.

The stated problem is solved, and the stated technical result is achieved by combining formula 6a’’:

where R is a protecting group.

The stated problem is solved, and the stated technical result is achieved by combining formula 6a’’:

or its salts, where R is a protecting group.

The stated problem is solved and the claimed technical result is achieved by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile or its pharmaceutically acceptable salt for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula A’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile or a pharmaceutically acceptable salt thereof for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula B’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile or a pharmaceutically acceptable salt thereof for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of the compound 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the production of a medicament for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof according to the present invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

due to the use of a medicinal product containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or its pharmaceutically acceptable salt, for the treatment and/or prevention of viral diseases.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases caused by RNA-containing viruses.

The task at hand is solved, and the stated technical result is achieved in

by using a pharmaceutical composition containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile, characterized by formula C’’, or a pharmaceutically acceptable salt thereof, for the production of a medicinal product for the treatment and/or prevention of viral diseases.

More preferably, the viral diseases for the treatment and/or prevention of which compound A’’ or its pharmaceutically acceptable salt, compound B’’ or its pharmaceutically acceptable salt, compound C’’ or its pharmaceutically acceptable salt, a pharmaceutical composition and/or a medicinal product containing said compounds according to the present invention are used, are viruses whose genome is encoded by a single-stranded sense (+)-strand and also an antisense (-)-strand of RNA and which use viral RNA-dependent RNA polymerase for their replication.

More preferably, the viral diseases of the present invention are caused by influenza viruses, coronaviruses, picornavirus, arenavirus, flavivirus, bunyavirus, filovirus, phlebovirus, hantavirus, enterovirus, togavirus, calicivirus, respiratory syncytial virus, parainfluenza virus, rhinovirus, metapneumovirus, rotavirus or noravirus.

More preferably, the virus of the present invention is a highly virulent or low virulent virus.

More preferably, the virus of the present invention is SARS-CoV, SARS-CoV-2, MERS-CoV or Influenza A, B, C.

More preferably, the influenza virus of the present invention is, but is not limited to, an influenza A virus, including strains A(H1N1), A(H1N1)pdm09, A(H1N2), A(H3N2), A(H2N2), A(H4N2), A(H7N2), swine flu type A, avian flu type A, including highly pathogenic strains (including H5N1 and H7N9).

The following are examples of the invention, which illustrate the invention, but do not cover all possible variants of its implementation and do not limit the invention.

A person skilled in the art will understand that other specific embodiments of the invention are also possible.

Examples

Example 1. Synthesis of new pyrrolopyrimidine derivatives

All reactions were carried out in solvents purified by standard methods. Laboratory equipment was used to carry out the reactions.

To weigh the components, electronic scales “VIBRA” were used (weighing limit 220 g, Min 0.01 g; e = 0.001 g; d = 0.0001 g).

The solutions were prepared in glass containers, flasks and glasses. Mixing and chemical reactions in small volumes were carried out on an LLG magnetic stirrer with adjustable rotation speed and heating of the working surface or a mechanical stirrer.

A RE100-Pro rotary evaporator with a VC100 vacuum controller and a C410 vacuum pump were used to distill off the solvents.

The samples were isolated using column chromatography.

To create a vacuum, we used a vacuum diaphragm pump MZ 2D NT (Vacuubrand), capacity 10 ^m3 /h, maximum residual pressure 50 mm Hg, electric motor power 370 W.

The pH of the solutions was measured using a Metler Toledo FiveEasy pH meter with a Mettler Toledo LE438 electrode.

LCMS analysis was performed using an LCMS system for the analysis of multicomponent organic mixtures: Shimadzu Analytical 10Avp HPLC, PE SCIEX API 165 mass spectrometer, Synergi 2um Hydro-RP 100A MercuryMS columns, 20x2.0 mm, Waters XBridge C18 3.5 um, 4.6x100 mm, Agilent eclipse XDB-C18 5 μm 150*4.3 mm.

NMR spectra were recorded at 25°C on Varian Mercury Plus instruments (400 MHz) using deuterodimethylsulfoxide (DMSO-d ₆ ), CDCl ₃ , D ₂ O at 50°C. The internal standard in the spectra corresponds to the residual signals of the solvents. The signals were assigned using the two-dimensional correlation spectroscopy methods COSY, HSQC.

Within the framework of the present invention, many new pyrrolopyrimidine derivatives were obtained and studied. The experimental results for the most promising compounds are shown below.

Step 1. Synthesis of 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1).

To a solution of 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1.00 g, 3.50 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (892.00 mg, 4.60 mmol) in a mixture of 10.00 mL dioxane and 5.00 mL purified water was added sodium carbonate (1.11 g, 10.50 mmol). The reaction vessel was evacuated and filled with argon. Then tetrakis(triphenylphosphine)palladium Pd(PPh ₃ ) ₄ (230.00 mg, 0.20 mmol) was added and the mixture was boiled for 16 h. The reaction mixture was diluted with ethyl acetate and purified water. The organic layer was separated, dried over sodium sulfate, and concentrated on a rotary evaporator. 20.00 ml of methyl tert-butyl ether (MTBE) were added to the residue, and the mixture was kept at 4°C overnight. Formation of a precipitate was observed. The formed precipitate was filtered, washed with MTBE, and dried. Yield: 563.00 mg (51%) of 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine ( 1 ).

LCMS [M+H ⁺ ]: 316.4.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.39 (s, 1H), 8.74 (d, J = 2.2 Hz, 1H), 7.73 (dd, J = 3.6, 2.3 Hz, 1H), 7.10 (dd, J = 3.6, 1.3 Hz, 1H), 5.62 (d, J = 1.8 Hz, 2H), 3.53 (t, J = 8.0 Hz, 2H), 0.83 (t, J = 7.8 Hz, 2H), -0.10 (s, J = 2.3 Hz, 9H).

Step 2. Synthesis of tert-butyl 3-(cyanomethyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (2).

To a solution of 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine ( 1 ) (1.00 g, 3.17 mmol) and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (616.00 mg, 3.17 mmol) in 22.00 mL of acetonitrile was added diazabicycloundecene (DBU) (47.50 μL, 0.32 mmol) and the mixture was stirred for 16 h at room temperature. The reaction mixture was concentrated on a rotary evaporator. The residue was dissolved in ethyl acetate and washed with purified water. The organic layer was separated, dried over sodium sulfate, and concentrated on a rotary evaporator. Tert-butyl 3-(cyanomethyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate ( 2 ) was obtained. Yield: 1.60 g, quantitative (about 100%).

LCMS [M+H ⁺ ]: 510.5.

^1H NMR (400 MHz, DMSO- _d6 ) δ 8.93 (s, 1H), 8.78 (s, 1H), 8.47 (s, 1H), 7.79 (d, J = 3.7 Hz, 1H), 7.20 (d, J = 3.7 Hz, 1H), 5.64 (s, 2H), 4.51 (d, J = 9.4 Hz, 2H), 4.22 (d, J = 9.5 Hz, 2H), 3.66 (s, 2H), 3.59 - 3.47 (m, 2H), 1.41 (s, 9H), 0.83 (t, J = 8.0 Hz, 2H), -0.10 (s, 9H).

Step 3. Synthesis of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile salt (3)

To a solution of tert-butyl 3-(cyanomethyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate ( 2 ) (4.80 g, 9.43 mmol) in 50.00 mL of tetrahydrofuran (THF) was added 50.00 mL of 3 M hydrochloric acid (HCl) in dioxane and the mixture was stirred for 16 h at room temperature. The reaction mixture was concentrated on a rotary evaporator. The hydrochloride salt of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile ( 3 ) was obtained. Yield: 4.20 g quantitative (about 100%).

LCMS [M+H ⁺ ]: 410.4.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 9.39 (s, 1H), 8.97 (d, J = 1.4 Hz, 1H), 8.81 (s, 1H), 8.06 (d, J = 3.7 Hz, 1H), 7.49 (d, J = 3.7 Hz, 1H), 5.71 (s, 2H), 4.81 - 4.63 (m, 2H), 4.47 - 4.30 (m, 2H), 3.64 - 3.35 (m, 3H), 0.92 - 0.77 (m, 2H), -0.09 (s, J = 1.2 Hz, 9H).

Next, product (3) was modified to obtain new pyrrolopyrimidine derivatives compounds A’’ - C’’ and their pharmaceutically acceptable salts.

1.1 Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile A’’

To a solution of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride salt (3) (2.00 g, 4.48 mmol) in 50.00 mL of dichloromethane were added triethylamine (2.49 mL, 18.00 mmol) and 2-methoxyethane-1-sulfonyl chloride (629.00 μL, 5.39 mmol). The reaction mixture was stirred at room temperature for 16 h. Then it was diluted with purified water. The organic layer was separated, dried over sodium sulfate, and concentrated on a rotary evaporator. The product was isolated by column chromatography on silica gel (eluent: hexane:ethyl acetate 1:1 - 2:3). 2-(1-((2-methoxyethyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (4’’) was obtained. Yield: 1.10 g, 46%.

LCMS [M+H ⁺ ]: 532.5.

^1H NMR (400 MHz, DMSO- _d6 ) δ 8.96 (s, 1H), 8.78 (s, 1H), 8.49 (s, 1H), 7.81 (d, J = 3.7 Hz, 1H), 7.19 (d, J = 3.7 Hz, 1H), 5.64 (s, 2H), 4.63 (d, J = 9.0 Hz, 2H), 4.25 (d, J = 9.0 Hz, 2H), 3.74 - 3.64 (m, 4H), 3.62 - 3.47 (m, 4H), 3.22 (s, 3H), 0.83 (t, J = 8.0 Hz, 2H), -0.10 (s, J = 1.0 Hz, 9H).

To a solution of 2-(1-((2-methoxyethyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (4'') (1.10 g, 2.07 mmol) in 70.00 mL of dichloromethane was added 35.00 mL of trifluoroacetic acid. The reaction mixture was stirred at room temperature for 2 h, then concentrated on a rotary evaporator. The residue was dissolved in 167.00 mL of methanol. A solution of 7.14 mL of ammonia in 14.30 mL of purified water was added, and the mixture was stirred at room temperature for 16 h. The resulting solution was concentrated on a rotary evaporator. The residue was diluted with purified water, potassium hydrogen sulfate (KHSO ₄ ) was added to pH = 4. The mixture was stirred at room temperature overnight. Formation of a precipitate was observed. The precipitate was filtered, washed with purified water, and dried. 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A'') was obtained. Yield: 497.00 mg, 60%.

LCMS [M+H ⁺ ]: 402.5.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.15 (s, 1H), 8.92 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 4.63 (d, J = 9.0 Hz, 2H), 4.25 (d, J = 9.0 Hz, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 3.22 (s, 3H).

1.2. Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile B''

To a solution of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride salt (3) (2.00 g, 4.48 mmol) in 50.00 mL of dichloromethane were added triethylamine (2.49 mL, 18.00 mmol) and (methylthio)methanesulfonyl chloride (868.00 mg, 5.39 mmol). The reaction mixture was stirred at room temperature for 16 h. Then it was diluted with purified water. The organic layer was separated, dried over sodium sulfate, and concentrated on a rotary evaporator. The product was isolated by column chromatography on silica gel (eluent: hexane:ethyl acetate 1:1 - 2:3). 2-(1-(((methylthio)methyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetoitrile (5’’) was obtained. Yield: 1.20 g, 49%.

LCMS [M+H ⁺ ]: 534.4.

^1H NMR (400 MHz, DMSO- _d6 ) δ 8.96 (s, 1H), 8.78 (s, 1H), 8.49 (s, 1H), 7.81 (d, J = 3.7 Hz, 1H), 7.19 (d, J = 3.7 Hz, 1H), 5.64 (s, 2H), 3.95 (s, 2H), 3.74 - 3.63 (m, 4H), 3.62 - 3.47 (m, 4H), 1.16 (s, 3H), 0.83 (t, J = 8.0 Hz, 2H), -0.10 (s, J = 1.0 Hz, 9H).

To a solution of 2-(1-(((methylthio)methyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetoitrile ( 5'' ) (1.20 g, 2.25 mmol) in 72.00 mL of dichloromethane was added 36.00 mL of trifluoroacetic acid. The reaction mixture was stirred at room temperature for 2 h, then concentrated on a rotary evaporator. The residue was dissolved in 167.00 mL of methanol. A solution of 7.14 mL of ammonia in 14.30 mL of purified water was added, and the mixture was stirred at room temperature for 16 h. The resulting solution was concentrated on a rotary evaporator. The residue was diluted with purified water, potassium hydrogen sulfate (KHSO ₄ ) was added to pH = 4. The mixture was stirred at room temperature overnight. Formation of a precipitate was observed. The precipitate was filtered, washed with purified water, and dried. 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B'') was obtained. Yield: 544.00 mg, 60%.

LCMS [M+H ⁺ ]: 404.5.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.15 (s, 1H), 8.92 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 3.95 (s, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 1.16 (s, 3H).

1.3. Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile C''

To a solution of 2-(3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride salt (3) (2.00 g, 4.49 mmol) in 50.00 mL of dichloromethane were added triethylamine (2.49 mL, 18.00 mmol) and 2-(methylthio)ethane-1-sulfonyl chloride (942.00 mg, 5.39 mmol). The reaction mixture was stirred at room temperature for 16 h. Then it was diluted with purified water. The organic layer was separated, dried over sodium sulfate, and concentrated on a rotary evaporator. The product was isolated by column chromatography on silica gel (eluent: hexane:ethyl acetate 1:1) to give 2-(1-((2-(methylthio)ethyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (6’’). Yield: 1.20 g, 50%.

LCMS [M+H ⁺ ]: 548.0.

^1H NMR (400 MHz, DMSO- _d6 ) δ 8.96 (s, 1H), 8.78 (s, 1H), 8.49 (s, 1H), 7.81 (d, J = 3.7 Hz, 1H), 7.19 (d, J = 3.7 Hz, 1H), 5.64 (s, 2H), 4.18 (d, J = 8.7 Hz, 2H), 3.86 (d, J = 8.7 Hz, 2H), 3.71 - 3.59 (m, 4H), 3.58 - 3.43 (m, 4H), 3.19 (s, 3H), 0.84 (t, J = 8.0 Hz, 2H), -0.10 (s, J = 1.0 Hz, 9H).

To a solution of 2-(1-((2-(methylthio)ethyl)sulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (6") (1.20 g, 2.19 mmol) in 72.00 mL of dichloromethane was added 36.00 mL of trifluoroacetic acid. The reaction mixture was stirred at room temperature for 2 h, then concentrated on a rotary evaporator. The residue was dissolved in 170.00 mL of methanol. A solution of 7.20 mL of ammonia in 14.80 mL of purified water was added, and the mixture was stirred at room temperature for 16 h. The resulting solution was concentrated on a rotary evaporator. The residue was diluted with purified water, potassium hydrogen sulfate (KHSO ₄ ) was added to pH = 4. The mixture was stirred at room temperature overnight. Formation of a precipitate was observed. The precipitate was filtered, washed with purified water, and dried. 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C'') was obtained. Yield: 593.00 mg, 65%.

LCMS [M+H ⁺ ]: 418.2.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.15 (s, 1H), 8.92 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 4.18 (d, J = 8.7 Hz, 2H), 3.86 (d, J = 8.7 Hz, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 2.12 (s, 3H).

1.4. Synthesis pharmaceutically acceptable salts of pyrrolopyrimidine derivatives of the present invention

1.4.1. Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D’’)

To a solution of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’) (1.00 g, 2.49 mmol) in 20.00 mL of methanol was added dropwise with stirring 3.00 mL of 1 M methanolic hydrochloric acid at room temperature. The reaction mixture was stirred for two hours. The formation of a precipitate was observed. The formed precipitate was filtered off and dried in air. 1.09 g of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D’’) was obtained. The reaction yield was quantitative (about 100%).

Elemental analysis of C ₁₇ H ₂₀ N ₇ O ₃ SCl: calculated C 46.63%, H 4.60%, N 22.39%, Cl 8.10%, O 10.96%, S 7.32%; found C 46.60%, H 4.58%, N 22.39%, Cl 8.14%, O 10.97%, S 7.35%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.21 (s, 1H), 8.94 (s, 1H), 8.70 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 4.63 (d, J = 9.0 Hz, 2H), 4.25 (d, J = 9.0 Hz, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 3.22 (s, 3H).

1.4.2. Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (E’’)

To a solution of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B’’) (1.00 g, 2.49 mmol) in 20.00 mL of methanol was added dropwise with stirring 3.00 mL of 1 M methanolic hydrochloric acid at room temperature. The reaction mixture was stirred for two hours. The formation of a precipitate was observed. The formed precipitate was filtered and dried in air. 1.09 g of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (E’’) was obtained. The reaction yield was quantitative (about 100%).

Elemental analysis of C ₁₆ H ₁₈ N ₇ O ₂ S ₂ Cl: calculated C 43.68%, H 4.12%, N 22.29%, Cl 8.06%, O 7.27%, S 14.57%; found C 43.66%, H 4.10%, N 22.27%, Cl 8.05%, O 7.25%, S 14.53%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.19 (s, 1H), 8.91 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 3.95 (s, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 1.16 (s, 3H).

1.4.3. Synthesis of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (F’’)

To a solution of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C’’) (1.00 g, 2.40 mmol) in 20.00 mL of methanol was added dropwise with stirring 3.00 mL of 1 M methanolic hydrochloric acid at room temperature. The reaction mixture was stirred for two hours. The formation of a precipitate was observed. The separated precipitate was filtered off and dried in air. 1.09 g of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (F’’) was obtained. The reaction yield was quantitative (about 100%).

Elemental analysis of C ₁₇ H ₂₀ N ₇ O ₂ S ₂ Cl: calculated C 44.98%, H 4.44%, N 21.60%, Cl 7.81%, O 7.05%, S 14.12%; found C 44.96%, H 4.45%, N 21.59%, Cl 7.84%, O 7.07%, S 14.15%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.21 (s, 1H), 8.90 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 7.66 - 7.58 (m, 1H), 7.08 (d, J = 1.9 Hz, 1H), 4.18 (d, J = 8.7 Hz, 2H), 3.86 (d, J = 8.7 Hz, 2H), 3.71 - 3.63 (m, 4H), 3.56 (t, J = 5.8 Hz, 2H), 2.12 (s, 3H).

Example 2. Obtaining dosage forms of new pyrrolopyrimidine derivatives

2.1 Film-coated tablets

To obtain a solid medicinal product in the form of a film-coated tablet containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’), the weighed components according to Table 1 are mixed in the following order: the substance 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’), mannitol, sodium croscarmellose and magnesium stearate are added to the calculated amount of microcrystalline cellulose, and mixed until smooth. The resulting mixture is subjected to wet granulation (granulation liquid - water 30-35% by weight of the dry components), the moistened mass is pressed through a sieve with a hole diameter of 2 mm (wet granulation), the resulting granules are dried in a drying cabinet at a temperature of 50-55 ° C, the dried granules are carefully rubbed through a sieve with a hole diameter of 1 mm. The resulting granulate is powdered with magnesium stearate. Tablet cores are obtained on the basis of the resulting granulate. The resulting tablet cores are film-coated.

Table 1. Composition of film-coated tablets containing 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’)

Components Quantity per 1 tablet, mg Quantity per 1 tablet, mg 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’) 2.0 mg 4.0 mg Microcrystalline cellulose 132.0 mg 132.0 mg Mannitol 52.0 mg 50.0 mg Croscarmellose sodium 12.0 mg 12.0 mg Magnesium stearate 2.0 mg 2.0 mg Film coating: Polyvinyl alcohol 2.46 mg 41% (from the weight of the film coating) 2.46 mg 41% (from the weight of the film coating) Macrogol 1.092 mg 18.2% (from the weight of the film coating) 1.092 mg 18.2% (from the weight of the film coating) Talc 0.966 mg 16.1% (from the weight of the film coating) 0.966 mg 16.1% (from the weight of the film coating) Titanium dioxide 1.416 mg 23.6% (from the weight of the film coating) 1.368 mg 23.6% (from the weight of the film coating)

Similarly, medicinal products of other new pyrrolopyrimidine derivatives, compounds (B’’) - (F’’), as well as their pharmaceutically acceptable salts, were obtained.

Example 3. Study of the therapeutic activity of new pyrrolopyrimidine derivatives in relation to autoimmune diseases

The therapeutic activity of the novel pyrrolopyrimidine derivatives of the present invention against recombinant Janus kinase proteins was determined using the LANCE Ultra kinase assay (PerkinElmer) in a 384-well plate format with a reaction volume of 10 μl. The obtained IC ₅₀ values (half-maximal inhibition concentrations) for the studied compounds were in the range of 4.0 - 5.5, 0.7 - 1.1, 85.0 - 117.0 nM for JAK1, JAK2 and JAK3, respectively.

The study of therapeutic activity against rheumatoid arthritis in a mouse antigen-induced arthritis model was conducted on 60 animals, randomly distributed into six groups of 10 animals in each group. The experiment involved female BALB/c mice aged 8-10 weeks, weighing 20.0±2.5 g. The mice had free access to water and food and were housed in a standard animal housing system in a vivarium.

Before the study, all animals were kept in quarantine for 14 days, after which time the individuals were weighed and examined to determine the absence of external damage, hair loss, or signs of intoxication. No deviations from the norm were found.

To induce the disease with arthritogenic antibodies, a cocktail of five monoclonal antibodies to type II collagen was used; the lipopolysaccharide from E. coli 0111:B4 supplied with the kit was used as an adjuvant. On the first day of the experiment, BALB/c mice were intraperitoneally injected with 1.5 mg of the five-clonal antibody cocktail in a volume of 200 μl. Three days later, the mice received 50 μg of lipopolysaccharide from E. coli 0111:B4 dissolved in 200 μl of sterile phosphate buffer as an adjuvant by intraperitoneal injection. Disease development was monitored for 10 days from the moment of administration of arthritogenic antibodies.

The severity of symptoms was assessed on a four-point scale: 0 - no redness and swelling of the distal parts of the limb, 1 - mild redness and/or swelling, 2 - moderate redness and/or swelling, 3 - severe redness and/or swelling, 4 - very severe redness and/or swelling.

Each limb was assigned a corresponding score, and the total value for all four limbs was determined as the severity of the disease in a given mouse.

The first group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’), the second group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B’’), the third group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C’’), The fourth group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D’’), the fifth group received (1-(2-hydroxyethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile according to the prototype, the sixth group received microcrystalline cellulose.

The compounds were administered orally through a tube in the form of a suspension once a day from the third day of the experiment at a dosage of 0.8 mg/kg of the mouse. The experiment was carried out for 13 days.

The mortality rate of animals in the control and experimental groups was also monitored during the studies. No fatal outcomes were recorded.

The results of the research are presented in Fig. 1.

Thus, the new pyrrolopyrimidine derivatives demonstrate statistically significant improved efficacy, expressed in a significant reduction in the severity of arthritis symptoms, normalization of joint structure and prevention of bone destruction compared to (1-(2-hydroxyethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile according to the prototype.

Also during the experiment, clinical symptoms associated with pain were recorded in the individuals. It is known from the state of the art that grip strength correlates with pain in patients with rheumatoid arthritis and reflects real-time changes in joint inflammation in mice with a rheumatoid arthritis model. Thus, the grip strength test was used to determine the pain symptoms of the individuals.

Grip strength was measured using a digital mouse grip strength meter. Each mouse was gently placed on a wire mesh connected to a force transducer. After the mouse had rested for 3 min, its tail was pulled and the grip strength was measured continuously until the mouse released the wire mesh. This was repeated five times for each mouse at intervals over 30 s. The reported grip strength is the average of the maximum recorded grip forces during the measurements (in grams).

The experimental results are presented in Table 2 below.

Table 2. Results of grip force measurement

Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Group 1 181 190 185 162 159 143 168 170 172 175 175 182 180 185 2 173 185 184 190 167 172 177 183 185 186 184 190 186 189 3 176 180 172 168 154 145 159 163 179 174 182 180 182 182 4 178 184 186 175 160 156 150 145 157 167 173 180 187 189 5 183 184 180 152 120 118 99 95 103 127 132 150 152 165 6 184 180 181 149 126 115 93 91 108 122 137 142 147 153

Before analyzing the activity of the new pyrrolopyrimidine derivatives claimed in the present invention, their toxicological properties were studied. The studies were conducted with oral administration of the compositions of the present invention on healthy adult rats (white Wistar rats weighing 180±5 g) that had undergone quarantine for 10-14 days. The animals had free access to water and food and were placed in a standard animal housing system in a vivarium. The experiments were conducted in accordance with established ethical standards. During the experiment, the general condition of the animals, their behavioral characteristics, intensity and nature of motor activity, presence and nature of seizures, coordination of movements, skeletal muscle tone, response to tactile, pain, sound and light stimuli, frequency and depth of respiratory movements, heart rate, condition of the fur and skin, color of the mucous membranes, pupil size, tail position, amount and consistency of feces, frequency of urination and color of urine, food and water consumption, changes in body weight and other indicators were recorded.

The dosages of new pyrrolopyrimidine derivatives according to the present invention up to 30 mg/kg/day per individual were studied with long-term administration (4 weeks) followed by observation (4 weeks). As a result of the studies, it was possible to establish the absence of visible manifestations of toxicological effects, intoxication and death of animals against the background of taking new pyrrolopyrimidine derivatives according to the present invention. Manifestations of dermatotoxicity were also not recorded.

Example 4. Study of the therapeutic antiviral activity of new pyrrolopyrimidine derivatives according to the present invention

The study of the therapeutic activity of the new pyrrolopyrimidine derivatives of the present invention against the influenza virus in a mouse model was conducted on 70 individuals randomly distributed into seven groups of 10 individuals in each group. The experiment involved female BALB/c mice aged 6-8 weeks, weighing 22.0±2.5 g. The mice had free access to water and food, and were placed in a standard animal housing system in a vivarium.

Before the study, all animals were kept in quarantine for 14 days, after which time the individuals were weighed and examined to determine the absence of external damage, hair loss, or signs of intoxication. No deviations from the norm were found.

Modeling of viral infection in mice was carried out by intranasal administration of a calculated number of viral units of the highly pathogenic influenza virus _H1N1 under anesthesia of individuals once at _a dose of 400 _TCID50 , diluted in PBS in a volume of 40 μl. During the experiment, the condition of the animals was recorded every day.

The first group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’), the second group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B’’), the third group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C’’), The fourth group received 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D’’), the fifth group received (1-(2-hydroxyethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile according to the prototype, the sixth group received microcrystalline cellulose, the seventh group was not infected and received microcrystalline cellulose.

The therapy was administered orally through a tube as a suspension twice daily starting on the third day of the experiment at a dosage of 20 mg/kg/day on a human basis. The experiment was carried out for 5 days.

At the end of the experiment, the animals were euthanized. The lung and tracheal tissues were removed and washed twice with 1 ml PBS containing 0.1% BSA. After centrifugation at 4°C, the lung tissues and bronchoalveolar fluid were collected and used for further cytokine analysis by enzyme immunoassay. The results of the studies are presented in Fig. 2.

Also during the experiment, viral load indicators were monitored, and after the individuals were killed, histopathological features of the tissues were recorded.

Based on the results of the experiment, it was possible to establish that the new pyrrolopyrimidine derivatives of the present invention reduce the level of viral hyperactivation of the immune system, reduce inflammatory processes and lung damage against the background of a viral disease, and also have a pronounced therapeutic activity in the treatment of viral diseases.

Example 5. Selectivity of new pyrrolopyrimidine derivatives towards JAK

Activity of the studied substances (2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A''), 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B''), 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C''), 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D''), (1-(2-hydroxy-ethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile (prototype) against recombinant Janus kinase proteins were determined using the LANCE Ultra kinase assay (PerkinElmer) in a 384-well plate format with a reaction volume of 10 μl. The reaction conditions were as recommended by the manufacturer, using 50 nM ULight-JAK-1 tyrosine kinase substrate, 2 nM labeled Europium anti-phospho antibodies, recombinant Janus kinase proteins, and test substances were added in the concentration range 0.1 nM to 100 µM in buffer (50 mM Tris-HCl, pH 8.0, 10 mM _MgCl2 , 0.5 mM TCEP, 0.01% Brij-35, 1 mM EGTA, and 0.05% BSA). IC50 values were obtained as the logarithm of the inhibitor concentration that achieved 50% kinase inhibition. Inhibitor selectivity was calculated for each inhibitor by dividing the IC50 for each JAK by the IC50 for the most potently inhibited JAK. Data shown are the average of three replicates and are representative of 2-4 separate experiments. One-way analysis of variance (ANOVA) with Dunnett's multiple comparison post hoc test was used to assess significant differences in kinase activity inhibition between JAK family members. Alternatively, analysis of variance was performed using the ANOVA test.

The results of the experiment are presented in Table 3.

Table 3. Determination of the selectivity of new compounds towards JAK

Inhibitor Selectivity JAK1 JAK2 JAK3 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile (A’’) 5 1 131 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(((methylthio)methyl)sulfonyl)azetidin-3-yl)acetonitrile (B’’) 6 1 124 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-(methylthio)ethyl)sulfonyl)azetidin-3-yl)acetonitrile (C’’) 5 1 128 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-((2-methoxyethyl)sulfonyl)azetidin-3-yl)acetonitrile hydrochloride (D’’) 5 1 131 (1-(2-hydroxyethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile (prototype) 3 1 100

Based on the results of the experiments, it was possible to record that the new pyrrolopyrimidine derivatives of the present invention exhibit the least pronounced activity with respect to JAK3. However, despite the reduced activity with respect to JAK3, the activity of the new pyrrolopyrimidine derivatives of the present invention with respect to JAK3 statistically significantly exceeds the similar activity of the prototype compound. The selectivity of the compounds of the present invention with respect to JAK2 is 5-6 times greater than the selectivity with respect to JAK1.

Thus, it can be concluded that the selectivity of the interaction with JAK of new pyrrolopyrimidine derivatives exceeds the selectivity of (1-(2-hydroxyethanesulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl)-acetonitrile according to the prototype.

Claims (13)

1. Compound of formula C'' or its pharmaceutically acceptable salts. 2. A pharmaceutical composition exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing a therapeutically effective amount of the compound of claim 1 and at least one pharmaceutically acceptable excipient. 3. The pharmaceutical composition according to claim 2, characterized in that the autoimmune disease is selected from the group including rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia. 4. The pharmaceutical composition according to claim 2, characterized in that at least one pharmaceutically acceptable excipient is selected from the group consisting of formulators, stabilizers, solubilizers, humectants, lubricants, glidants, thickeners, sweeteners, flavors, aromas, prolonged delivery regulators, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity and correcting substances. 5. A medicinal product exhibiting the properties of a Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases, containing an effective amount of a compound according to claim 1 and at least one pharmaceutically acceptable excipient. 6. The medicinal product according to claim 5, characterized in that at least one pharmaceutically acceptable excipient is selected from the group consisting of formulators, stabilizers, solubilizers, humectants, lubricants, slip agents, thickeners, sweeteners, flavorings, aromatizers, prolonged delivery regulators, diluents, fillers, emulsifiers, preservatives, antioxidants, buffering agents, cryoprotectants, pH-regulating agents, substances for maintaining isotonicity and correcting substances. 7. The medicinal product according to claim 5, characterized in that the autoimmune disease is selected from the group including rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia. 8. A medicinal product according to paragraph 5, characterized in that it is a solid medicinal product. 9. A medicinal product according to item 8, characterized in that it is a tablet or capsule. 10. Use of a compound according to claim 1 for obtaining a medicinal product according to claims 5-9 for treating autoimmune diseases by inhibiting Janus kinase. 11. The use according to claim 10, characterized in that the autoimmune disease is selected from the group including rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, atopic dermatitis, lupus and alopecia.