[3-AMINO-4-(5-METHYL-2-FURYL)-5,6,7,8-TETRAHYDROTHIENO[2,3-b]QUINOLIN-2-yl](PHENYL)METHANONE, EXHIBITING IMMUNOTROPIC PROPERTIES

Abstract

FIELD: medical and pharmaceutical chemistry; pharmacology.SUBSTANCE: use of [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone of formula (I) as an immunotropic agent.EFFECT: compound of formula (I) has a pronounced immunotropic effect, exceeding the effect of comparison medicinal products.1 cl, 1 tbl, 2 ex(I)

Description

[0001] The invention relates to the field of medical and pharmaceutical chemistry, pharmacology, namely to the use of an organic compound, [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone of formula (I), as an immunotropic agent that can be used in medicine and veterinary science.

[0002]

[0003] (I)

[0004] The human immune system is the organs whose function is to maintain the genetic individuality of the organism and protect it from external influences and internal pathological changes in cells [Yaglova N.V., Obernikhin S.S. Morphofunctional changes in the thymus in the offspring of mice during puberty and in adults after a single immunostimulating effect on the mother's body in the early stages of pregnancy / / Immunology. 2013; 34 (1): 15-19]. The organs of hematopoiesis and immunopoiesis include the red bone marrow, thymus, spleen, lymph nodes, palatine tonsils and Peyer's patches of the intestine [Yarilin A.A. Age-related changes in the thymus and T-lymphocytes / / Immunology. 2003; 24 (2): 117-117].

[0005] The thymus is the central organ of lymphocytopoiesis and immunogenesis, functioning after birth and undergoing gradual involution in humans after 20 years of age. Considering the role of this organ in immunity, it is worth noting its most important function – the differentiation of T-lymphocytes. In addition, the thymus produces hormones such as thymosin, thymulin, thymopoietin, and insulin-like growth factor 1 [Yarilin A.A. Age-related changes in the thymus and T-lymphocytes / / Immunology. 2003; 24(2): 117-117].

[0006] The spleen is a unique lymphoid organ with a complex histological organization, playing a key role in immune processes. In addition to participating in antigen-dependent differentiation of lymphocytes, the spleen performs such functions as the production of antibodies to substances that suppress erythropoiesis in the red bone marrow, the elimination from the bloodstream and subsequent destruction of old and damaged red blood cells and platelets, blood deposition and platelet accumulation [Vladimirskaya E.B. Normal hematopoiesis and its regulation / / Clinical oncohematology. 2015; 8 (2): 109-119].

[0007] The spleen is highly sensitive to various toxic effects. Thus, the combined action of selenium and ethyl carbamate causes a decrease in the area of ​​white pulp by 35-40% and an increase in the connective tissue component of the spleen [Samakina E.S., Struchko G.Yu., Merkulova L.M. et al. Evaluation of the structure of the rat spleen under the isolated and combined action of selenium and ethyl carbamate / / Acta Medica Eurasica. 2024; No. 4: 64-75]. These changes are accompanied by structural and functional disorders of lymphoid follicles and a decrease in immunological activity, which is especially pronounced when exposed to tobacco smoke, which leads to atrophy of lymphoid tissue by 60-65%. Similar structural changes can be observed in toxic hepatitis, accompanied by infiltration of immunocompetent cells with disruption of normal structural-functional relationships [Khasanov B.B., Zokirova N.B., Tukhtaev K.R.The influence of toxic maternal hepatitis on the structural and functional relationships of immunocompetent cells of the mammary gland of lactating rats and the small intestine of rat pups during the period of lactation / / Pediatrics. 2021; No. 4: 225-229].

[0008] The immunosuppressive effect on the body is associated with a significant decrease in the area of ​​the white pulp of the spleen, which can reach 50-55%, and a decrease in the number of lymphocytes [Vasiliev Yu.G., Vasiliev R.O., Berestov D.S. Morphology of the spleen of mice in control and during immunosuppression / / Technological trends in the sustainable functioning and development of the agro-industrial complex: materials of the International scientific and practical conference dedicated to the year of science and technology in Russia, Izhevsk, February 24-26, 2021. 2021: 91-95]. Also, damaging factors lead to morphofunctional changes in the spleen at the organ, tissue, cellular and molecular levels [Alekseeva N.T., Kvaratskhelia A.G., Sokolov D.A. et al. Functional morphology of immune structures of the spleen under the influence of damaging factors / / Journal of Anatomy and Histopathology. 2021; 10(3): 91-97].The reaction of immune structures consists of a redistribution of the ratio of lymphocyte-macrophage elements of the organ parenchyma and a change in the structure of microvessels in response to the influence of the factor.

[0009] Thus, the spleen, being a peripheral organ of the immune system, plays an important role in the regulation of both innate and adaptive immunity, since it contains about 25% of all circulating lymphocytes [Vasiliev Yu.G., Vasiliev R.O., Berestov D.S. Morphology of the spleen of mice in control and during immunosuppression / / Technological trends in the sustainable functioning and development of the agro-industrial complex: Proceedings of the International Scientific and Practical Conference dedicated to the Year of Science and Technology in Russia, Izhevsk, February 24-26, 2021. 2021: 91-95]. Damage to this organ as a result of exogenous exposure to various factors is associated with structural and functional disorders of the spleen.

[0010] Currently existing immunotropic drugs represent a large group of medicinal products of plant, bacterial, chemical origin, and also including hormones, cytokines and mediators that affect various parts of the immune system, the production of cytokines and antibodies [Kosimov Z.O., Khalilov A.N. Immunotropic drugs / / Economy and Society. 2022; No. 12 (103) -1: 662-665; Markova T.P. Immunotropic drugs and adaptogens / / Russian Medical Journal. 2019; No. 8 (I): 60-64]. This group of drugs is widely used in clinical practice in the complex pharmacocorrection of immunodeficiency states, acute and chronic infections, enhancing the effect of basic therapy.

[0011] There are several levels of action of immunotropic drugs: influence on the proliferation and differentiation of progenitor cells; influence on the movement of cells from primary lymphoid organs to secondary ones, from lymphoid organs to the bloodstream, from the bloodstream to tissues; participation in the process of presentation and recognition of antigens; influence on the functional activity of immunocompetent cells, on the production and secretion of cytokines, expression of their receptors [Okovity S.V. Clinical pharmacology of immunosuppressants / / Reviews of clinical pharmacology and drug therapy. 2003; 2(2): 2-34].

[0012] Speaking about the classification of immunotropic agents, it should be noted that it is multi-stage, which is associated with the complex organization of the immune system, which works in interaction with T-, B-cells, natural killers, macrophages and mediators (interferons, interleukins) [Markova T.P. Immunotropic drugs: pros and cons / / Remedium. Journal of the Russian drug market and medical equipment. 2004; No. 11: 45-49]. Consequently, immunotropic drugs have enormous potential in their mechanism of action and many opportunities to influence various parts of the immune system.

[0013] Immunosuppressants represent a large group of drugs that affect the immune system. These include glucocorticoids, which have pronounced anti-inflammatory activity and immunosuppressive properties. They can influence apoptosis in immune cells, alter their proliferation and differentiation, and affect the levels of cytokines and other regulatory factors. The use of glucocorticoids (GCs) is associated with transient lymphopenia affecting all T-lymphocyte subsets. Glucocorticoids can inhibit T-cell activation by reducing the production of proinflammatory cytokines. GCs reduce the rate of macrophage differentiation and impair their function, inhibit neutrophil adhesion to the endothelium, and suppress leukocyte migration to the site of inflammation. In addition, GCs reduce the number of eosinophils and basophils circulating in the blood [Dzherieva I.S., Volkova N.I., Davidenko I.Yu. et al.Glucocorticoid therapy – a risk factor for cardiovascular diseases / / Medical Bulletin of the South of Russia. 2022; 13(3): 93-106; Bogacheva N.V., Tuneva N.A., Smirnov A.A. et al. Development of a biological model of immunosuppression using dexamethasone / / Vyatka Medical Bulletin. 2018; 4(60): URL: https: / / cyberleninka.ru / article / n / razrabotka-biologicheskoy-modeli-immunosupressii-pri-pomoschi-deksametazona].

[0014] Thus, there is a wide range of pharmacological drugs with varying effects on multiple components of the immune system. However, the process of developing new agents that affect immunity continues.

[0015] Metabolic disorders, which include dyslipidemia, type 2 diabetes mellitus, overweight, obesity, arterial hypertension, and non-alcoholic fatty liver disease, are reaching the scale of a non-infectious pandemic in the modern world. A certain paradox should be noted: in patients with obesity and metabolic disorders, the immune response is activated, leading to the formation of chronic systemic inflammation, while at the same time, protection against infectious diseases, neoplastic processes, and the development of allergies, neurodegenerative, and autoimmune processes is reduced [Migacheva N.B., Skvortsova O.V., Kaganova T.I., Ginzburg A.S. / / Effective pharmacotherapy. 2023; 19(28): 30-36]. In the process of formation of metabolic disorders, there is a change in the quantitative characteristics of immunocompetent cells and the cytokine profile of the blood [Litvinova L.S., Kiriyenkova E.V., Aksenova N.N. et al.Features of cellular immunity and cytokine repertoire in patients with metabolic syndrome / / Bulletin of Siberian Medicine. 2012; 11(3): 53-57].

[0016] Currently, doctors have a wide range of medications that affect the functioning of the immune system. However, the search for new agents that have immunotropic activity while simultaneously having a positive effect on carbohydrate and lipid metabolism with hepatoprotective effects remains relevant.

[0017] New heterocyclic compounds from a series of cyanothioacetamide derivatives are of scientific interest in the direction of influencing the immune system. There are publications according to which a number of cyanothioacetamide derivatives are characterized by pronounced antiviral properties [Osolodkin DI, Kozlovskaya LI, Dueva EV et al. Inhibitors of Tick-Borne Flavivirus Reproduction from Structure-Based Virtual Screening / / ACS Medicinal Chemistry Letters.2013; 4(9): 869-874]. Derivatives of tetrahydropyridones and hexahydroquinolines, derivatives of cyanothioacetamide, exhibit a certain anti-inflammatory, analgesic activity [Bibik E.Yu., Yaroshevskaya O.G., Devdera A.V. et al. Search for agents with anti-inflammatory activity among tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivatives / / Chemical and Pharmaceutical Journal. 2017; 51(8): 16-19], exhibit antidepressant and analeptic properties [Bibik E.Yu., Saphonova AA, Yeryomin AV et al.Study of analeptic activity of tetrahydropyrido [2,1-b] [1,3,5] tiadiazine derivatives / / Research Result: Pharmacology and Clinical Pharmacology. 2017; 3(4): 20-25]. There are also publications describing the hepatoprotective, hypoglycemic and lipid-lowering effects of new cyanothioacetamide derivatives [Ketova E.S., Bibik E.Yu., Batishcheva G.A., Krivokolisko S.G. Comprehensive assessment of the hepatoprotective activity of new alpha-cyanothioacetamide derivatives / / Far Eastern Medical Journal. 2024; No. 1: 22-27; Tilchenko D.A., Bibik E.Yu., Frolov K.A. et al. Comparative characteristics of the effect of a new pyridine derivative on the course of diabetes mellitus in four experimental models / / International Research Journal. 2022; No. 9 (123): URL: https: / / research-journal.org / archive / 9-123-2022-september / 10.23670 / IRJ.2022.123.16; Tilchenko D.A., Bibik E.Yu., Ketova E.S. et al.Effect of new partially hydrogenated pyridines, cyanothioacetamide derivatives, on liver morphological indices in rats with dexamethasone-induced diabetes mellitus / / Journal of Siberian Medical Science. 2023: 7(1): 118-131; Effect of new alpha-cyanothioacetamide derivatives on biochemical indices in modeling metabolic disorders / / Bulletin of the Smolensk State Medical Academy. 2023; 22(2): 20-27; Comparative assessment of the effect of hypoglycemic agents and new cyanothioacetamide derivatives on liver blood markers / / New horizons: collection of materials and reports of the X scientific and practical. conf. with international. participation, Bryansk, Apr 14. 2023 / Bryansk State Technical University; edited by O.M. Golembiovskaya. – Bryansk, 2023: 485-489; Ketova E.S., Myazina A.V., Batishcheva G.A., et al.The relationship between biochemical and morphological parameters of the liver in an experiment with alimentary obesity and dexamethasone load against the background of pharmacocorrection with alpha-cyanothioacetamide derivatives / / Actual problems and prospects of pharmaceutical science and practice: proc. III int. scientific-practical. conf., Kemerovo, May 26, 2023 / Kemerovo State Medical University; editors: V.V. Bolshakov, E.M. Maltseva. – Kemerovo, 2023: 110-114; Ketova E.S., Batishcheva G.A., Bibik E.Yu., Krivokolisko S.G. Evaluation of hypoglycemic activity of new alpha-cyanothioacetamide derivatives / / Mechnikov Readings-2023: proc. 96th All-Russian scientific-practical. conf. student scientific society with international participation, St. Petersburg, April 26-27, 2023 / North-Western State Medical University named after I.I. Mechnikov; edited by N.V. Bakulina, S.V. Tikhonov. – St. Petersburg, 2023: 665-666].

[0018] The problem to be solved by the invention is to establish immunotropic activity among new derivatives of cyanothioacetamide.

[0019] The problem is solved by using [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone (I) (IUPAC name – [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone) as an immunotropic agent, which has a pronounced stimulating effect on the organs of the immune system – the thymus and spleen when modeling metabolic disorders using various methods: with intraperitoneal course administration of dexamethasone and with a combination of long-term high-fat and high-carbohydrate loads and subsequent administration of dexamethasone in comparison with drugs of the group of hypoglycemic agents biguanides (metformin), lipid-lowering agents statins (atorvastatin), immunostimulants (imunofan).

[0020] Compound (I) was obtained at the Khimex Research Laboratory of the Volodymyr Dahl Luhansk State University using the method described for similar compounds [Krivokolisko D.S., Dotsenko V.V., Bibik E.Yu. et al. Novel 4-(2-furyl)-1,4-dihydronicotinonitriles and 1,4,5,6-tetrahydronicotinonitriles: synthesis, structure, and analgesic activity / / Russian Journal of General Chemistry, 2021; 91(9): 1359-1374].

[0021] The closest in structure to the proposed compound are numerous derivatives of thieno[2,3-b]pyridine with a wide spectrum of biological action [Litvinov V.P., Dotsenko V.V., Krivokolisko S.G. Chemistry of thienopyridines and related systems / / Moscow: Nauka. 2006. 407 p. ISBN 5-02-033674-2].

[0022] It was established for the first time that the biologically active substance – [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methasone (I), exhibits immunotropic activity in an experiment on laboratory animals (mature male Wistar rats) when modeling metabolic disorders using intraperitoneal course administration of dexamethasone and with a combination of long-term high-fat and high-carbohydrate loads and subsequent administration of dexamethasone in comparison with drugs of the group of hypoglycemic agents biguanides (metformin), lipid-lowering agents statins (atorvastatin), immunostimulants (imunofan), surpassing the reference samples.

[0023] Pharmacological properties of the claimed compound.

[0024] Example 1.

[0025] Our preliminary virtual bioscreening and predictive analysis according to [Yang J., Kwon S., Bae Park SH et al. Galaxy Sagittarius: Structure- and Similarity-Based Prediction of Protein Targets for Druglike Compounds / / Journal of Chemical Information and Modeling. 2020; 60: 3246-3254; Gfeller D., Grosdidier A., ​​Wirth M. et al. SwissTargetPrediction: a web server for target prediction of bioactive small molecules / / Nucleic Acids Research. 2014; 42 (1): 32-39; Gfeller D., Michielin O., Zoete V. Shaping the interaction landscape of bioactive molecules / / Bioinformatics. 2013; 29: 3073-3079] showed that the mechanism of action of [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methasone (I) is associated with the fact that its molecules with a high degree of probability act on and have tropism for: nuclear gamma receptors activated by peroxisome proliferator-activated receptor-γ (PPAR-γ), Janus kinase (JAK), retinoid orphan receptor gamma (RORγ).In addition, the compound has affinity for: androstane receptors, G-protein-coupled receptors GPR40, hepatocyte nuclear factor 4α, prostanoid receptors of the EP1, EP2 and EP4 types, cannabinoid receptors CB type 1, arachidonate-5-lipoxygenase and, as a result, is potentially capable of possessing hepatoprotective properties, while exhibiting hypoglycemic, hypolipidemic and anti-inflammatory activity [Ketova E.S., Myazina A.V. Study of biochemical and morphometric parameters of the liver after alimentary and steroid load against the background of pharmacological correction with new derivatives of alpha-cyanothioacetamide / / Proceedings of the 71st All-Russian Scientific Conference of Young Scientists and Students with International Participation, Makhachkala, June 2, 2023 / Dagestan State Medical University; under the general. ed. M.N. Medzhidova. - Makhachkala, 2023: 444-447; Bibik E.Yu., Krivokolisko D.S., Batishcheva G.A. and others.Study of new 1,4-dihydropyridine derivatives as potential agents with anti-inflammatory activity: a randomized controlled trial / / Kuban Scientific Medical Bulletin. 2022; 29(1): 77-95; Ketova E.S., Batishcheva G.A., Bibik E.Yu. et al. The influence of new alpha-cyanothioacetamide derivatives on biochemical parameters in modeling metabolic disorders / / Bulletin of the Smolensk State Medical Academy. 2023; 22(2): 20-27; Tilchenko D.A., Bibik E.Yu., Frolov K.A. et al. Comparative characteristics of the influence of a new pyridine derivative on the course of diabetes mellitus in four experimental models / / International Research Journal. 2022; No. 9 (123): URL: https: / / research-journal.org / archive / 9-123-2022-september / 10.23670 / IRJ.2022.123.16; Ketova E.S., Batishcheva G.A., Bibik E.Yu. et al.Original derivatives of alpha-cyanothioacetamide as potential agents with lipid-lowering activity / / Current issues in medical science: collection of the 77th All-Russian scientific and practical conference of students and young scientists with international participation, dedicated to the 100th anniversary of the birth of prof. Nikolai Petrovich Pamputis, Yaroslavl, April 24-28, 2023 / Yaroslavl State Medical University; editor-in-chief I.N. Staroverov. - Yaroslavl, 2023: 298-299 (Current issues in medical science; No. 1)].

[0026] Example 2.

[0027] The experimental study was performed on 56 sexually mature male Wistar rats received from the bio-nursery of the limited liability company "SMK STEZAR" in Vladimir, at the Research Institute of Experimental Biology and Medicine of the Federal State Budgetary Educational Institution of Higher Education "Voronezh State Medical University named after N.N. Burdenko" of the Ministry of Health of the Russian Federation, in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and the rules for working with animals based on the provisions of the Helsinki Declaration and the recommendations contained in EU Directive 86 / 609 / ECC and the Council of Europe Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes, as well as in accordance with the rules of good laboratory practice for preclinical studies in the Russian Federation (Article 11 of Federal Law No. 61-FZ of 12.04.2010 "On the circulation of medicines"), with the order of the Ministry of Health of the Russian Federation dated April 1, 2016 No. 199n (On approval of the Rules of Good Laboratory Practice) and GOST 33044-2014 "Principles of Good Laboratory Practice", approved by Order of the Federal Agency for Technical Regulation and Metrology No. 1700-st dated November 20, 2014.

[0028] The design of the experiment was reviewed and approved at a meeting of the Ethics Committee of the Federal State Budgetary Educational Institution of Higher Education “Voronezh State Medical University named after N.N. Burdenko” of the Ministry of Health of the Russian Federation, protocol No. 5 dated October 18, 2022.

[0029] Group assignment was randomized using the "envelope method." Animals were divided into 7 groups of 8 animals each:

[0030] Intact group – rats received a standard daily diet and water freely available [GOST No. 33216-2014 “Guidelines for the maintenance and care of laboratory animals. Rules for the maintenance and care of laboratory rodents and rabbits”].

[0031] Control group No. 1 – rats were given intraperitoneal administration of dexamethasone at a rate of 0.125 mg / kg body weight per day for 13 days.

[0032] Control Group 2 – Rats in this group received an excess amount of palm oil in addition to their daily diet at a rate of 30 g / kg of body weight for 8 weeks, and their drinking water was replaced with a 20% fructose solution to induce a complex of disturbances. The animals in this group were then administered dexamethasone intraperitoneally at a rate of 0.125 mg / kg of body weight per day for 13 days.

[0033] Experimental group No. 1 – rats were modeled for disorders by intraperitoneal administration of dexamethasone (at the rate of 0.125 mg / kg of body weight per day for 13 days), then pharmacocorrection was carried out for 14 days using intragastric administration of a new derivative of cyanothioacetamide with the code AZ-023 at a dosage of 1.5 mg / kg.

[0034] Experimental group No. 2 – animals were modeled for disorders using a high-fat and high-carbohydrate diet (for 8 weeks, in addition to the diet, excess palm oil at the rate of 30 g / kg of body weight of rats + drinking water was replaced with a 20% fructose solution), as well as subsequent intraperitoneal administration of dexamethasone (at the rate of 0.125 mg / kg of weight per day for 13 days), then as a pharmacocorrection, a new compound from among the derivatives of cyanothioacetamide with the code AZ-023 was used intragastrically for 14 days at a dosage of 1.5 mg / kg.

[0035] Comparison group No. 1 – rats were modeled for disorders by intraperitoneal administration of dexamethasone (at the rate of 0.125 mg / kg body weight per day for 13 days), then pharmacocorrection was carried out for 14 days using intragastric administration of metformin (300 mg / kg body weight) and atorvastatin (200 mcg / kg body weight).

[0036] Comparison group No. 2 – the animals were modeled metabolic disorders using a high-fat and high-carbohydrate diet (for 8 weeks, in addition to the diet, excess palm oil at the rate of 30 g / kg of body weight of rats + drinking water was replaced with a 20% fructose solution), as well as subsequent intraperitoneal administration of dexamethasone (at the rate of 0.125 mg / kg of weight per day for 13 days), then as a pharmacocorrection, metformin (300 mg / kg of body weight) and atorvastatin (200 mcg / kg of body weight) were used intragastrically for 14 days, imunofan injections were administered intramuscularly once a day at the rate of 0.7 mcg / kg in saline according to the scheme: on the 1st, 3rd, 5th, 7th, 9th day.

[0037] The animals were kept in identical conditions and received food and water freely.

[0038] The experimental animals were weighed weekly to determine their average weight in the respective group.

[0039] Animals from control groups #1 and #2 were withdrawn from the experiment upon completion of the impairment modeling. All animals from the experimental and comparison groups were withdrawn from the experiment upon completion of pharmacotherapy with new cyanothioacetamide derivatives and existing medications, respectively.

[0040] Rats were euthanized by administering an overdose of isoflurane inhalation anesthesia using a veterinary anesthesia station equipped with a TES-3 vaporizer. Thymus and spleen samples were collected for organometry, determination of absolute organ weight, and calculation of their relative weight.

[0041] The immunotropic effect of the studied compound was assessed by the degree of increase in the absolute and relative weight of the thymus and spleen after pharmacological correction of the simulated disorders.

[0042] The obtained data were tested for normal distribution using the Shapiro-Wilk test. Because some data did not meet the criteria for normal distribution, the significance of differences between the compared variants was assessed using the Kruskal-Wallis test with multiple comparisons using the Mann-Whitney method. The statistical significance level was set at p < 0.05.

[0043] The immunotropic activity of [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone was compared with that of the reference drugs metformin, atorvastatin, and imunofan.

[0044] The results of the study of the absolute and relative weight of the thymus and spleen of experimental animals of the experimental groups are presented in Table 1.

[0045] Table 1. Results of the average values ​​of the absolute and relative mass of the thymus and spleen of experimental animals at the end of the modeling of all stages of the experiment and pharmacocorrection of disorders.

[0046] Group Weight of rats, g Thymus (absolute mass, g) Thymus (relative mass, %) Spleen (absolute weight, g) Spleen (relative mass, %) Intact group 464±12 0,47±0,08 0,10±0,004 0,98±0,11 0,20±0,008 Control group No. 1 418±12* 0,48±0,05 0,11±0,009 0,62±0,07* 0,15±0,005* Control group No. 2 434±13* 0,42±0,07 0,10±0,004 0,58±0,19* 0,13±0,004* Experimental group No. 1 395±11* 0,75±0,19* 0,19±0,006* 1,67±0,57* 0,40±0,006* Experimental group No. 2 440±11 0,89±0,37* 0,20±0,008* 1,73±0,55* 0,39±0,007* Comparison group No. 1 456±13 0,48±0,01 0,10±0,003 0,84±0,11 0,18±0,004* Comparison group No. 2 469±13 0,62±0,06* 0,13±0,004* 1,32±0,40 0,28±0,006*

[0047] Note: * – p<0.05 compared to the group of intact animals; ± – standard deviation of the thymus and spleen weight of animals within the group

[0048] Evaluating the data presented in Table 1, it can be concluded that the course of dexamethasone in animals of control group No. 1 did not lead to a significant change in the thymus weight relative to intact rats, but was associated with a decrease in the absolute (by 37% compared to intact rats) and relative (by 25% compared to intact rats) spleen weight. Sequential alimentary and glucocorticoid loading in animals of control group No. 2 led to a decrease in the absolute thymus weight by 11% compared to intact rats, and was also associated with a decrease in the absolute spleen weight by 41% and a 35% relative spleen weight compared to intact animals.

[0049] The use of a new cyanothioacetamide derivative in animals from experimental group #1, which were modeled for disorders by administering dexamethasone for 13 days, resulted in an increase in absolute and relative thymus weight. The absolute thymus weight in these animals increased by 56%, and the relative weight by 73%, compared to animals from control group #1. Spleen weight also showed a tendency to increase. Thus, the absolute spleen weight increased by 169%, and the relative weight by 167%, compared to animals from control group #1.

[0050] Intragastric administration of the studied compound to rats of experimental group No. 2 after sequential alimentary (high-fat and high-carbohydrate) and dexamethasone loads was associated with an increase in the absolute thymus weight by 112% and the relative thymus weight by 100% compared to similar indicators in animals of control group No. 2. The spleen weight in rats of experimental group No. 2 increased under the influence of the studied compound: the absolute spleen weight increased by 198%, the relative weight by 200% compared to similar indicators in animals of control group No. 2.

[0051] The use of metformin and atorvastatin in rats of comparison group No. 1 after modeling a course of dexamethasone load did not lead to a significant change in the weight of the thymus and spleen in comparison with similar indicators of animals of control group No. 1.

[0052] The use of metformin, atorvastatin and imunofan in rats of comparison group No. 2 after alimentary (high-fat and high-carbohydrate) and dexamethasone loads was associated with an increase in the absolute weight of the thymus by 48%, the relative weight of the thymus by 30%, the absolute weight of the spleen by 128% and the relative weight of the spleen by 115% compared with similar indicators of animals of control group No. 2.

[0053] Thus, according to the data in Table 1, the immunotropic activity of [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone is clearly demonstrated, consisting in an increase in the absolute and relative weights of the immune system organs - the thymus and spleen - under the influence of the studied compound compared to the values ​​​​of the control groups. Moreover, it should be noted that the increase in the weight of the thymus and spleen under the influence of the cyanothioacetamide derivative exceeds the similar activity of imunofan from the group of immunostimulants.

[0054] No adverse events were recorded during experimental studies.

[0055] The above statistical processing data, results and conclusions,

[0056] The described facts and observations clearly demonstrate the ability of [3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinolin-2-yl](phenyl)methanone (I) to exhibit pronounced immunotropic activity in vivo when modeling disorders using dexamethasone and alimentary loads. It should be noted that the studied compound is superior to the comparison drugs (metformin, atorvastatin, imunofan) in terms of the degree of expression of immunotropic properties.

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