Compounds, pharmaceutical compositions containing thereof and method for treatment of cytokine-mediated disease

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel aromatic compounds that can be used in treatment of diseases or pathological states accompanying by inflammation, for example, chronic inflammation diseases. Invention describes compound of the formula (II): wherein G means phenyl, pyridinyl, pyrazolyl and wherein G is substituted with one or some groups R1, R2 or R3; Ar means naphthyl; X means (C5-C8)-cycloalkyl or cycloalkenyl optionally substituted with 1-2 oxo-groups, phenyl, furanyl, pyridinyl or pyrazolyl; Y means a bond or saturated either unsaturated branched or unbranched (C1-C4)-carbon chain wherein one or some methylene groups are optionally and independently substituted with oxygen (O) or nitrogen (N) atoms; Y is optionally substituted with oxo-group; Z means phenyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, morpholinyl, thiomorpholinyl, piperidinyl, piperidinonyl, piperazinyl, pentamethylenesulfoxidyl wherein each of them is optionally substituted with 1-3 (C1-C6)-alkyls or group -CONH2, (C1-C6)-alkyl, nitrile, hydroxy-group, (C1-C6)-alkoxy-group, secondary or tertiary amine wherein amine nitrogen is bound covalently with (C1-C3)-alkyl or (C1-C5)-alkoxyalkyl, tetrahydrofuranyl-(C1-C3)-alkyl, nitrile-(C1-C3)-alkyl, carboxamide-(C1-C3)-alkyl; R1 means independently in each case (C1-C10)-alkyl which is optionally partially or completely halogenated and optionally substituted with 1-3 hydroxy-groups, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl wherein each of them is optionally substituted with 1-3 groups -CN, halogen atom, (C3-C6)-alkynyl branched or unbranched carbon chain and one or some methylene groups is optionally replaced for atom O and indicated alkynyl group is optionally substituted with one or some (C1-C4)-alkyl groups; R2 means branched or unbranched (C1-C6)-alkyl that is optionally partially or completely halogenated, branched or unbranched (C1-C4)-alkoxy-group that in each case is optionally partially or completely halogenated, halogen atom, (C1-C6)-alkoxy-group, hydroxy-group, mono- or di-(C1-C4)-alkyl-amino-group, group -OR6, nitro-group or group mono- or di-(C1-C4)-alkyl-amino-S(O)2 that is optionally partially or completely halogenated, or group -H2NSO2; R3 in each case means independently phenyl, pyridinyl, pyrimidyl, pyrrolidinyl, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, (C1-C4)-alkynyl group or branched or unbranched (C1-C6)-alkoxy-group wherein each of them is optionally partially halogenated, -OR18 or (C1-C6)-alkyl optionally substituted with group -OR18, amino-group or mono- either di-(C1-C5)-alkyl-amino-group, (C2-C6)-alkynyl branched or unbranched carbon chain wherein one or some methylene groups are optionally replaced for atom O, and indicated alkynyl group is optionally substituted with one or some (C1-C4)-alkyl groups; R6 means (C1-C4)-alkyl that is optionally partially or completely halogenated; in each case R18 means independently hydrogen atom, (C1-C4)-alkyl; W means atom O, and its pharmaceutically acceptable derivatives. Also, invention describes a pharmaceutical composition containing these compounds and a method for treatment of disease mediated by cytokines and based on indicated compounds. Invention provides synthesis of novel compounds possessing valuable biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of treatment.

12 cl, 1 tbl, 38 ex

 

Information about the date of the application

This application claims the priority of provisional patent applications U.S. 60/124148 of 12 March 1999 and 60/165867 dated November 16, 1999

The technical field of the invention

The present invention relates to new compounds that inhibit production of cytokines involved in inflammatory processes and can therefore be used for treating diseases and pathological conditions involving inflammation such as chronic inflammatory diseases. The present invention relates also to methods of producing such compounds and to pharmaceutical compositions containing these compounds.

Background of invention

The tumor necrosis factor (TNF) and interleukin-1 (IL-1) are important biological factors, generally called proinflammatory cytokines. Along with some other related molecules they mediate the inflammatory response associated with immunological detection of infectious agents. The inflammatory response plays an important role in limiting the development of pathogenic infections and control.

Elevated levels of proinflammatory cytokines are also associated with many autoimmune diseases, such as toxic shock syndrome, rheumatoid arthritis, osteoarthritis, diabetes, and inflammatory diseases the intestine (..Dinarello and others, Rev. Infect. Disease 6: 51, 1984). In these diseases chronic amplification of the inflammatory response exacerbates or causes many of the observed pathological manifestations. So, for example, rheumatism in synovial tissue infiltrating inflammatory cells, leading to destruction of cartilage and bone (..Koch etc., J. Invest. Med. 43: 28-38, 1995). In these diseases is important and recognized therapeutic approach based on the possible use of drugs is to reduce the levels of proinflammatory cytokines, such as TNF (isolated from cells form also called TNFα) and IL-1β. Currently undergoing clinical trials a large number of therapeutic agents for the treatment mediated by cytokines diseases. For numerous autoimmune diseases was confirmed the efficacy of monoclonal antibodies to TNFα (.Heath, "CDP571: An Engineered Human IgG4 Anti-TNFα Antibody", proceedings of the IBC conference Meeting on Cytokine Antagonists, Philadelphia, Pennsylvania, April 24-25, 1997). Such applications include the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis (E.C.C.Rankin and others, British J. Rheum. 35: 334-342, 1997; W.A.Stack and others, Lancet 349: 521-524, 1997). It is assumed that the monoclonal antibody carries out its function by binding to both soluble TNFαand associated with the membrane TNF.

Was scons wirawan the soluble receptor of TNFα that interacts with TNFα. This approach is similar to the approach described above for monoclonal antibodies to TNFα; both agents are associated with soluble TNFα, thereby reducing its concentration. One embodiment of this design, called Enbrel, Immunex, Seattle, PCs Washington, recently in phase III clinical trials was shown to be effective in the treatment of rheumatoid arthritis (Brower and others, Nature Biotechnology 15: 1240, 1997). For another variant of the receptor TNFα, Ro 45-2081 (company Hoffman-LaRoche Inc., Natli, PCs, new Jersey, was demonstrated the effectiveness of its application in various models with animals allergic lung inflammation and acute lung damage. Ro 45-2081 is a recombinant chimeric molecule constructed by merging soluble human TNF receptor having a molecular weight of 55 kDa gene hinge region of the heavy chain IgG1, which is expressed in eukaryotic cells (Renzetti and others, Inflamm. Res. 46: str, 1997).

IL-1 as immunological effector molecules involved in the development of numerous diseases. Receptor antagonist IL-1 (IL-1ra) has been studied in clinical trials in humans. Was demonstrated its effectiveness in the treatment of rheumatoid arthritis (Antrim, Amgen). In phase III clinical test the project on the people of IL-1ra reduced the mortality rate of patients suffering from the syndrome of septic shock (Dinarello, Nutrution 11, 492, 1995). Osteoarthritis is subprocessors disease characterized by destruction of the joint cartilage. IL-1 was detected in the synovial fluid and cartilage matrix of joints affected by osteoarthritis. In various experimental models of arthritis, it was found that antagonists of IL-1 can reduce the decomposition of the components of cartilage matrix (Chevalier, Biomed Pharmacother., 51, 58, 1997). Recently it was found that nitric oxide, which is a mediator of cardiovascular homeostasis, neural transmission and immune function, plays an important role in the modulation of bone repair. Strong stimulators of the production of NO are cytokines, such as IL-1 and TNF. NO is a molecule with an important regulatory function in the bone, which affects the cells lining of osteoblasts and osteoclasts (Evans and others, J. Bone Miner Res. 11, 300, 1996). Increased destruction of beta cells, leading to the development of insulin-dependent diabetes, is dependent on IL-1. Some of these lesions may be mediated by other effectors, such as prostaglandins and thromboxanes. IL-1 can influence this process by controlling the expression level as cyclooxygenase II and inducible synthetase of nitric oxide (McDaniel and others, Proc. Soc. Exp. Biol. Med., 11, 24, 1996). It is expected that inhibitors of the production of cytokines inhibit the expression of inducible cyclooxygenase (SOH-2). It is established that the expression of MOR-2 increases under the action of cytokines, and it is assumed that it represents the isoforms of cyclooxygenase, which causes inflammation (M.K.O'Banion and others, Proc. Natl. Acad. Sci. U.S.A, 89, 4888, 1992). Therefore, one should expect that inhibitors of cytokines, such as IL-1, must have effectiveness against violations that are currently treated using inhibitors SOH, such as conventional non-steroidal anti-inflammatory drugs (NCPLS). Such disorders include acute and chronic pain and inflammatory symptoms and cardiovascular diseases.

It was found that the level of certain cytokines is increased in inflammatory bowel disease (IBD). In patients suffering from inflammatory bowel diseases, there is an imbalance of IL-1 and IL-1ra in the intestinal mucosa. Insufficient production of endogenous IL-1ra may affect the pathogenesis of IBD (Cominelli and others, aliment oil displayed pure. Pharmacol. Ther. 10, 49, 1996). Alzheimer's disease is distinguished by the presence of deposits of beta-amyloid protein, the presence of neurofibrillary plexus and cholinergic dysfunction in the hippocampus. Structural and metabolic disorder that is found in Alzheimer's disease, in the o f due to the constant high level of IL-1 (Holden and others, Med. Hypotheses, 45, 559, 1995). It is established that IL-1 plays a role in the pathogenesis caused by the human immunodeficiency virus (HIV). Establish clear communication of IL-1ra with acute inflammation, as well as various stages of the disease with the pathophysiology of HIV infections (Kreuzer and others, Clin. Exp. Immunol., 109, 54, 1997). IL-1 and TNF are involved in the disease of the periodontium. The process of destruction associated with periodontal disease may be caused by dysregulation of both IL-1 and TNF (Howells, Oral Dis. 1, 266, 1995).

Proinflammatory cytokines, such as TNFα and IL-1βare also important mediators of septic shock and associated cardiopulmonary dysfunction, acute respiratory distress syndrome in adults (rdsw) and multiple organ failure. TNFα also involved in cachexia and degradation of muscle tissue associated with HIV infection (Lahdiverta and others, Amer. J. Med., 85, 289, 1988). Obesity is accompanied by increased likelihood of infection, diabetes, and cardiovascular disease. It is established that for each of the above States, there are anomalies in the expression levels of TNFα (Loffreda and others, FASEB J. 12, 57, 1998). It is assumed that elevated levels of TNFα present and other disorders associated with eating, such as anorexia nervosa and bulimia. Found patapis the ideological Parallels between anorexia nervosa and cancer cachexia (Holden and others, Med. Hypotheses 47, 423, 1996). Using an experimental model, it was found that the inhibitor of the production of TNFα HU-211 improves rehabilitation after closed head injury (Shohami, etc., J. Neuroimmunol. 72, 169, 1997). It is known that atherosclerosis is an inflammatory component, and it is assumed that such cytokines as IL-1 and TNF stimulate the development of the disease. On models with animals it was found that the receptor antagonist IL-1 inhibits the formation of fat (Elhage and others, Circulation, 97, 242, 1998).

Abnormal expression of inducible synthetase of nitric oxide (iNOS) was accompanied by the development of hypertension in rats with spontaneous hypertension (Chou and others, Hypertension, 31, 643, 1998). IL-1 affects the expression of iNOS and therefore may also participate in the pathogenesis of hypertension (Singh and others, Amer. J. Hypertension, 9, 867, 1996).

It is established that IL-1 induces the development of uveitis in rats, which is amenable to inhibition by using antagonists of IL-1 (Xuan and others, J. Ocular Pharmacol. and Ther., 14, 31, 1998). Demonstrated that cytokines, including IL-1, TNF and GM-CSF stimulate the proliferation of blast cells of acute myelogenous leukemia (Bruserud, Leukemia Res. 20, 65, 1996). It is established that IL-1 is important for the development of inflammatory and allergic contact dermatitis. Sensitization of the surface of the skin can be prevented by introducing a monoclone the high antibodies to IL-1 before application of the allergen on the skin (Muller and others, Am. J. Contact. Dermat. 7, 177, 1996). The results obtained in experiments on mice, which was absent in IL-1 suggests that this cytokine is critical in the development of fever (Kluger and others, Clin. Exp. Pharmacol. Physiol., 25, 141, 1998). Various cytokines, including TNF, IL-1, IL-6 and IL-8, initiate the acute phase reaction, which is usually characteristic of fever, malaise, myalgia, headaches, cellular hypermetabolism and numerous endocrine and enzymatic responses (Beisel, Am. J. Clin. Nutr. 62, 813, 1995). After injury or infection by pathogenic organisms quickly begins production of these inflammatory cytokines.

Other proinflammatory cytokines are associated with a variety of painful conditions. The level of IL-8 correlated with the influx of neutrophils to sites of inflammation or damage. Using blocking antibodies to IL-8 was found that IL-8 plays a role in mediated neutrophil tissue damage in acute inflammation (Harada and others, Molecular Medicine Today 2, 482, 1996). Thus, the inhibitor of the production of IL-8 may be used to treat diseases that predominantly mediated by neutrophils, such as stroke and myocardial infarction, caused by thrombolytic therapy or independently of it, heat damage, respiratory distress syndrome of adults (rdsw), multiple organ damage in achiev is Tate injury, acute glomerulonephritis, dermatoses, including components of acute inflammation, acute purulent meningitis or other Central nervous system damage, hemodialysis, lamfers, syndromes associated with transfusion of granulocytes, and necrotizing enterocolitis.

Rhinovirus triggers the production of various proinflammatory cytokines, mainly IL-8, which leads to symptomatic disease, such as acute rhinitis (Winther and others, Am. J. Rhinol. 12, 17, 1998).

Other diseases, in the development with the participation of IL-8, include ischemia of the heart muscle and reperfusion, inflammatory bowel disease and many other diseases.

The proinflammatory cytokine IL-6 is involved in acute phase reactions. IL-6 is a growth factor for many cancer diseases, including multiple myeloma and related dyscrasia plasma cell (Treon and other, Current Opinion in Hematology 5: 42, 1998). It is established that he is an important mediator of inflammation in the Central nervous system. Elevated levels of IL-6 detected in some neurological disorders, including complex, dementia associated with AIDS, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, CNS injury and viral and bacterial meningitis (Gruol and other, Molecular Neurobiology 15: 307, 1997). IL-6 also plays an important role in osteoporosis. When modeling in mice was fitted is but he mediates bone resorption and induces the activity of osteoclasts (Ershler and others, Development and Comparative Immunol. 21: 487, 1997). Pronounced differences in the levels of cytokines, such as levels of IL-6 detected in vivo between osteoclasts healthy bones and bones of patients suffering from disease Tuck (Mills and others, Calcif Tissue Int. 61, 16, 1997). It is established that many cytokines are involved in the development of cancer cachexia. The severity of the core symptoms of cachexia can be reduced by treatment with antibodies to IL-6 or antagonists of the receptor for IL-6 (Strassmann and others, Cytokins Mol. Ther. 1, 107, 1995). In some infectious diseases such as influenza, IL-6 and IFNα are the main factors for the formation of symptoms, and to protect the host (Hayden and others, J. Clin. Invest. 101, 643, 1998). Overexpression of IL-6 mediates the pathology of many diseases, including multiple myeloma, rheumatoid arthritis, disease Castleman, psoriasis and postmenopausal osteoporosis (Simpson and others, Protein Sci. 6, 929, 1997). Compounds that affect the production of cytokines, including IL-6 and TNF, was effective in blocking the passive cutaneous anaphylaxis in mice (Scholz and others, J. Med. Chem., 41, 1050, 1998).

GM-CSF is another proinflammatory cytokine, is associated with numerous therapeutic diseases. It affects not only the proliferation and differentiation of stem cells, n and also regulates some other cells, involved in acute and chronic inflammation. Attempts were made to treatment with GM-CSF of many painful conditions, including the healing of wounds caused by burns, resorption of the graft skin, and mucositis induced cytotoxic agents and radiotherapy (Masucci, Medical Oncology 13: 149, 1996). GM-CSF, probably also plays a role in replication of human immunodeficiency virus (HIV) in the cells lining macrophages in the treatment of AIDS (Crowe and others, Journal of Leukocyte Biology 62, 41, 1997). Bronchial asthma is characterized by presence of inflammatory process in the lungs. Participating in this cytokines include, inter alia, GM-CSF (Lee, J. R. Coil. Physicians Lond., 32, 56, 1998).

It is established that interferon γ (IFN-γ) participates in the development of many diseases. It is associated with increased deposition of collagen, which is the main histopathological feature of the disease graft-versus-host (Parkman, Curr. Opin. Hematol., 5, 22, 1998). One of the patients after kidney transplantation was diagnosed with acute myelogenous leukemia. Retrospective analysis of cytokines in peripheral blood showed elevated levels of GM-CSF and IFN-γ. These elevated levels correlate with the increase in the number of leukocytes in peripheral blood (Burke and others, Leuk. Lymphoma. 19, 173, 1995). The development of insulin-dependent diabetes (type 1) may correlate with nakopleniem cells pankreaticheskogo islet T cells, which produce IFN-α (Ablumunits etc., J. Autoimmun., 11, 73, 1998). IFN-γ along with TNF, IL-2 and IL-6 leads to the activation of the majority of peripheral T-cells before the development of lesions in the Central nervous system in such diseases as multiple sclerosis (PC) and the complex of dementia, AIDS-related (Martino et al., 1998, Ann Neurol. 43, 340). Atherosclerotic damage cause arterial disease, which can lead to heart attack and brain. In areas such damage, there are many activated immune cells, mainly T cells and macrophages. These cells produce large amounts of proinflammatory cytokines, such as TNF, IL-1 and IFN-γ. It is assumed that these cytokines are involved in the stimulation of apoptosis (i.e. programmed cell death) of the neighboring cells of smooth muscles of blood vessels, which leads to atherosclerotic damage (Geng, Heart Vessels Suppl., 12, 76, 1997). In humans, suffering from allergies, once infected by the venom of the wasp (p. hot) is produced by mRNA-specific IFN-γ (Bonay and others, Clin. Exp. Immunol., 109, 342, 1997). It was found that after the hypersensitive reaction of the delayed type increases the expression of many cytokines, including IFN-y, which indicates the role of IFN-γ in the development of atopic dermatitis (Szepietowski, etc., Br. J. Dermatol. 137, 195, 1997). For cases of fatal cerebral who enoy malaria were conducted histopathological and immunohistopathological research. Was revealed elevated levels of IFN-α compared with other cytokines, suggesting its role in the development of this disease (Udomsangpetch, and others, Am. J. Trop. Med. Hyg. 57, 501, 1997). It was established that different free radicals are involved in the pathogenesis of various infectious diseases. In response to infection by certain viruses is the activation pathway of nitric oxide in the induction of proinflammatory cytokines, such as IFN-α (Akaike, etc, Proc. Soc. Exp. Biol. Med. 217, 64, 1998). In patients who are chronic carriers of hepatitis b virus (HBV), can develop cirrhosis and carcinoma of the liver cells. Expression of virus gene and its replication in transgenic mice infected with HBV can be suppressed by using posttranscriptional mechanism, mediated IFN-α, TNF and IL-2 (Chisari and others, Springer Semin. Immunopathol. 17, 261, 1995). IFN-γ can selectively inhibit induced cytokine bone resorption. This process takes place, probably with the participation of nitric oxide (NO), which is an important regulatory agent influencing the restoration of the bone. NO may be involved as a mediator of bone disease for diseases such as rheumatoid arthritis associated with tumor osteolysis and postmenopausal osteoporosis (Evans and others, J. Bone Miner Res. 11, 300, 1996). Studies conducted on mice with deficiency of the gene, prodemos who has demonstrated, that is dependent on IL-12 production of IFN plays a crucial role in combating the growth of parasites in the initial stage. Although this process is not dependent on nitric oxide, the effectiveness of the fight against chronic infection depends, apparently, from NO (Alexander and others, Philos. Trans. R. Soc. Lond. C. Biol. Sci. 352, 1355, 1997). NO is an important vasodilator agent, while there is evidence that it plays a role in the development of cardiovascular shock (Kilbourn and others, Dis. Mon. 43, 277, 1997) INFγ participates in the development of chronic inflammation of the intestine in such diseases as Crohn's disease and inflammatory bowel disease (IBD), mainly due to the presence of CD4+-lymphocytes, which, as I believe, to TN-phenotype (Sartor, aliment oil displayed pure Pharmacol. Ther. 10, Annex 2, 43, 1996). Elevated levels of serum IgE are associated with different atopic diseases, such as bronchial asthma and atopic dermatitis. The level of IFN-γ negatively correlated with levels of IgE in serum, indicating a role of IFN-γ in the development of atopic diseases in patients (Teramoto and others, Clin. Exp. Allergy 28, 74, 1998).

Compounds that have the ability to modulate one or more of the above inflammatory cytokines, can be used for the treatment of diseases mediated by the release of these cytokines. For example, in WO 98/52558 described derivatives of heteroaryl the guilt, which can primatice to ensure mediated by cytokines diseases. In WO 99/23091 describes another class of derivatives of urea, which can be used as anti-inflammatory agents.

In the patent US 5162360 described (N-substituted aryl)-N'-heterocyclization derivatives of urea, which can be used for the treatment of hypercholesteremia and atherosclerosis.

The above quoted publication suggests that the inhibition of the production of cytokines may be important under different conditions. Some of therapeutic agent on the basis of protein are under development or approved for use in certain cases. Therapeutic agent-based protein are expensive, and they are characterized by certain problems related to bioavailability and stability. There is therefore a need to develop new inhibitors of cytokines with low molecular weight, with an excellent efficacy, pharmacokinetic properties and safety profiles.

BRIEF description of the INVENTION

With the above publications in the field of technology there is a need for compounds that inhibit the production of cytokines for the treatment of various painful conditions.

So about the time, the present invention was based on the task to obtain new compounds that inhibit the release of inflammatory cytokines, such as interleukin 1 and tumor necrosis factor.

Another object of the invention is to develop a method of treatment of inflammatory diseases and pathological conditions, such as chronic inflammatory diseases, using the new compounds according to the invention.

The objective of the invention is a further development of the method of obtaining the above-mentioned novel compounds.

DETAILED description of the INVENTION

In accordance with the first object, the invention provides compounds of formula (I):

in which

Ar1selected from the group comprising pyrrole, pyrrolidine, pyrazole, imidazole, oxazole, thiazole, furan and thiophene, while Ar1may be substituted by one or more groups R1, R2or R3,

Ar2means phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl or indole, each of which is optionally substituted by 0 to 3 groups of R2,

X means

a)5-C8cycloalkyl or cycloalkenyl, optionally substituted 0-2-oxopropyl or 0-3 branched or unbranched1 4alkyl, C1-C4alkoxy-or1-C4alcaligenaceae, or

b) phenyl, furan, thiophene, pyrrole, imidazole, pyridine, pyrimidine, pyridine, dihydropyridine, maleimide, digitaleye, piperidine, piperazine or pyrazin, each of which independently of each other optionally substituted by 0-3 substituents selected from the group comprising a branched or non-branched C1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, mono - or di(C1-C3alkyl)amino group, a group With1-C6alkyl-S(O)mor halogen,

Y represents a bond or a saturated or unsaturated branched or unbranched1-C4the carbon chain which is optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH, S(O), S(O)2or S, and Y is optionally independently substituted by 0-2 of exography and one or more branched or unbranched1-C4alkyl groups which may be substituted by one or more halogen atoms,

Z means

a) phenyl, pyridine, pyrimidine, pyridazine, imidazole, furan, thiophene, Piran, which optionally is substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, the hydroxy-group, mono - or di(C1-C3alkyl)amino group, group C1-C6alkyl-S(O)mgroup COOH and phenylaminopropyl, with the phenyl ring optionally substituted with 1-2 substituents selected from halogen, C1-C6the alkyl and C1-C6alkoxygroup,

b) tetrahydropyran, tetrahydrofuran, 1,3-dioxolane, 1,3-dioxane, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine, piperidine, piperidine, piperazine, tetrahydropyrimidine, cyclohexanone, cyclohexanol, pentamethylene, pentamethyldisiloxane, pentamethylbenzene, tetramethylbenzene, tetramethyleneglutaric or tetramethylsilane, are not substituted by 1-3 substituents selected from nitrile,1-C6of alkyl, C1-C6alkoxygroup, hydroxy-group, mono - or di(C1-C3alkyl)amino-C1-C3of alkyl, phenylamino-C1-C3the alkyl and C1-C3alkoxy-C1-C3the alkyl, or

in)1-C6alkoxygroup, secondary or tertiary amine, where the amine nitrogen is covalently bonded to groups selected from a range, including C1-C3alkyl, C1-C5alkoxyalkyl, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, phenylaminopropyl, where phenyl is also optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups, the group With1-C6alkyl-S(O)mand the group phenyl-S(O)min which the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups,

R1means

a) branched or unbranched3-C10alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 phenyl, raftiline or heterocyclic groups selected from a range, including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, each such phenyl, naphthyl or heterocycle selected from those described above in this paragraph number, substituted 0-5 substituents selected from the group comprising halogen, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov,3-C8cycloalkyl,5-C8cycloalkenyl, the hydroxy-group, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannami, the group of NH2C(O) and di(C1-C3)alkylaminocarbonyl,

b)3-C7qi is loukil, selected from the group comprising cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, bicyclopentyl, bicyclohexyl and bicycloheptane, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 C1-C3alkyl groups, or similar cycloalkyl group, in which 1-3 ring methylene groups are replaced by groups independently of one another selected from the series comprising O, S, SEN, >C=O, >C=S and NH,

C) branched C3-C10alkenyl, which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from branched or unbranched1-C5of alkyl, phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group independently selected from a range including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, and each of the aforesaid phenyl, naftalina or heterocyclic group substituted by 0-5 substituents selected from the group comprising halogen, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, bicyclepart the Nile, bicyclohexyl, bicycloheptane, the hydroxy-group, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, the group of NH2C(O) and mono - or di(C1-C3)alkylaminocarbonyl,

g)5-C7cycloalkenyl selected from the group comprising cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl and bicycloheptene, with each such cycloalkenyl group optionally substituted With 1-31-C3alkyl groups,

d) nitrile or

e) branched or unbranched1-C6alkoxycarbonyl, branched or unbranched1-C6alkylaminocarbonyl, branched or unbranched1-C6alkylcarboxylic-C1-C3alkyl,

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, acetyl, aroyl, branched or unbranched1-C4alkoxygroup, which is optionally partially or fully galogenirovannami, halogen, methoxycarbonyl or phenylsulfonyl,

R3means

a) phenyl, naftalina or heterocyclic group selected from a range, including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imides is poured, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolin, chinoline, ethenolysis, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazole, respiratory, benzothiophene, cinnoline, pteridine, phthalazine, naftemporiki, honokalani, hintline, purines and indazoles, such phenyl, naftalina or heterocyclic group optionally substituted by 1-5 substituents selected from the group comprising phenyl, naphthyl, heterocycle selected from those described above in this paragraph several, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptene, phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, halogen, hydroxy-group, nitrile, C1-C3alkyloxy, which optionally may be partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heteroepitaxy, where the heterocyclic fragment selected from those described above in this paragraph number, the nitro-group, amino group, mono - or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation where heterocyclyl fragment selected from those described above in this paragraph number, gr is the foam NH 2C(O), mono - or di(C1-C3)alkylaminocarbonyl, C1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl group, amino-S(O)2the group di(C1-C3alkylamino-S(O)2, R4-C1-C5alkyl, R5-C1-C5alkoxygroup, R6-C(O)-C1-C5the alkyl group of R7-C1-C5the alkyl (R8)N, carboxy-mono - or di-C1-C5alkylamino,

b) condensed aryl selected from the group comprising benzocyclobutene, indanyl, indenyl, dihydronaphtho, tetrahydronaphthyl, benzocycloheptene and benzocycloheptene, or condensed heterocyclyl selected from the group comprising cyclopentenopyridine, cyclopentenopyridine, cyclopentenopyridine, cyclohexanediamine, cyclopentenopyridine, cyclohexanediamine, cyclopentenopyridine, cyclopentenopyridine, cyclopentanediol, cyclohexanediol, cyclopentanethiol, cyclohexanethiol, Cyclopentanone, cyclohexanone, cyclopentanemethanol, cyclohexanedimethanol, cyclopentanemethanol, cyclohexanemethanol, cyclopentanemethanol, cyclohexanedimethanol, cyclopentanethiol and cyclohexanethiol, these condensed aryl recondensation heterocyclyl ring is substituted by 0 to 3 substituents, selected from the group comprising phenyl, naphthyl and heterocyclyl selected from the group including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, geterotsiklicheskikh in which heterocyclyl fragment selected from those described above in this paragraph group, a nitrogroup, amino group, mono - or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation in which heterocyclyl fragment selected from those described above in this paragraph group, the group of NH2C(O), mono - or di(C1-C3)alkylaminocarbonyl, group1-C4alkyl-OC(O)branched or unbranched1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl, R9-C1-C5alkyl, R10-C1-C5alkoxygroup, R11-C(O)-C1-C5the alkyl group and R12-C1-C5Alki(R13)N,

C) cycloalkyl, selected isgroup, including cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptene, this cycloalkyl optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups,

g) C5-C7cycloalkenyl selected from the group comprising cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl and bicycloheptene, this cycloalkenyl group optionally substituted With 1-31-C3alkyl groups,

e) acetyl, aroyl, alkoxycarbonyl or phenylsulfonyl or

e) branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, or

R1and R2together can optionally form a condensed phenyl or pyridinoline ring,

R8and R13each independently from each other selected from the group comprising hydrogen and branched or unbranched1-C4alkyl which is optionally partially or fully galogenidov,

R4, R5, R6, R7, R9, R10, R11and R12each independently from each other selected from the group comprising morpholine, piperidine, piperazine, imidazole and tetrazole,

m means 0, 1 or 2,

W stands for O or S

and their pharmaceutically acceptable derivatives.

According to one embodiments of the invention preferred compounds of formula (I)in which Ar2means naphthyl, tetrahydronaphthyl, indanyl or indenyl, and W means Acting

In another embodiment of the invention among directly above preferred those compounds of formula (I)in which Ar1selected from thiophene and pyrazole,

X means5-C7cycloalkyl or5-C7cycloalkenyl, optionally substituted 0-2-oxopropyl or 0-3 branched or unbranched1-C4alkyl groups With1-C4alkoxygroup or1-C4alkylaminocarbonyl, or X is phenyl, pyridine, tetrahydropyridine, pyrimidine, furan or thiophene, each of which independently of each other optionally substituted by 0-3 substituents selected from the group comprising branched or unbranched1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, mono - or di(C1-C3alkyl) amino group, a group With1-C6alkyl-S(O)mand halogen,

R1means a branched or unbranched1-C4alkyl, cyclopropyl or cyclohexyl, which are optionally partially or fully galogenirovannyie and optional Zam is disposed 1-3 1-C3alkyl groups,

R3means a branched or unbranched1-C4alkyl, phenyl, pyrimidinyl, pyrazolyl or pyridinyl, each of which is optionally substituted as specified in the description of the first object of the invention, alkoxycarbonylmethyl or cyclopropyl or cyclopentyl, each of which is optionally partially or fully galogenidov and optionally substituted as indicated in the description of the first object of the invention.

According to another variant embodiment of the invention among directly above preferred those compounds of formula (I), in which

Ar1means pyrazole and

X means cyclopentenyl, cyclohexenyl or cycloheptenyl, optionally substituted oxopropoxy or 0-3 substituents selected from the group comprising branched or unbranched1-C4alkyl, C1-C4alkoxygroup and C1-C4alkylamino, or X is phenyl, pyridine, furan or thiophene, each of which independently of each other optionally substituted by 0-3 substituents selected from the group comprising branched or unbranched1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, mono - or di(C1-C3alkyl) amino group, a group With1-C6alkyl-SO) mand halogen.

According to the following variant of the invention, among directly above preferred those compounds of formula (I), in which

Y represents-CH2-,-CH2CH2-,-CH2NH-,-CH2CH2NH - or a bond, and

Z signifies phenyl, imidazole, furan, a piperazine, tetrahydropyran, morpholine, thiomorpholine, thiomorpholine, piperidine, pyridine, secondary or tertiary amine, where the amine nitrogen is covalently bonded to groups selected from the series, including1-C3alkyl and C1-C5alkoxyalkyl, or means further phenylaminopropyl, in which the phenyl ring is optionally substituted with 1-2 substituents selected from halogen, C1-C6alkoxygroup, hydroxy-group and mono - or di(C1-C3alkyl) amino group, a group With1-C6alkyl-S(O)mand the group phenyl-S(O)min which the phenyl ring is optionally substituted with 1-2 substituents selected from halogen, C1-C6alkoxygroup, hydroxy-group and mono - or di(C1-C3alkyl) amino group.

In accordance with another embodiment of the invention among directly above preferred those compounds of formula (I), in which

Ar1mean 5-tert-butylphenol-3-yl, where the pyrazol ring may be substituted by a group R while

R3means a branched or unbranched1-C4alkyl, phenyl, pyrimidinyl, pyrazolyl or pyridinyl, each of which is optionally substituted as specified in the description of the first object of the invention, alkoxycarbonylmethyl or cyclopropyl or cyclopentyl, each of which is optionally substituted as specified in the description of the first object of the invention.

In another embodiment of the invention among directly above preferred those compounds of formula (I)in which X is pyridinyl.

According to the following variant of the invention, among directly above preferred those compounds of formula (I), in which the pyridinyl is attached to Ar1in the 3rd position pyridinyl.

As examples of compounds of formula (I) according to the invention include the following:

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-yl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(2-(morpholine-4-yl)ethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-dimethylaminophenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-yl)phenyl)naphthalene-1-yl]urea,

p> 1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletiler-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(b-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-methyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-phenyl-2H-pyrazole-3-yl]-3-[4-(4-piperidine-1-ylmethylene)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-phenyl-2H-pyrazole-3-yl]-3-[4-(4-(4-methylpiperazin-1-yl)were)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3,4-di(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-pyridin-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(b-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-tetrahydropyran-4-iletileri-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-externalization-3-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(imidazol-1-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[2-(3-dimethylaminomethylphenol)-5-(1-methylcyclohexyl)-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[2-(5-(1-methylcyclohexyl)-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-methoxy-5-(2-morpholine-4-ylethoxy)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-morpholine-4-ylethoxy)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-3-(dimethylamino)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-3-(methylsulphonyl)phenyl)naphthalene-1-yl]urea,

methyl ester 5-tert-butyl-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}thiophene-2-carboxylic acid,

methylamide 5-tert-butyl-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]thiophene-2-carboxylic acid,

methyl ester 5-tert-butyl-1-methyl-3-[3-[4-(6-morpholine-4-ylmethylene the Jn-3-yl)naphthalene-1-yl]ureido}-1H-pyrrole-2-carboxylic acid,

methylamide 5-tert-butyl-1-methyl-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}-1H-pyrrole-2-carboxylic acid,

2-acetylamino-N-(5-tert-butyl-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]thiophene-2-ylmethyl)ndimethylacetamide,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-morpholine-4-icicles-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-morpholine-4-illlogic-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(2-morpholine-4-ylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-morpholine-4-illlogic-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(pyridine-4-ylmethylamino)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(dimethylaminomethylene)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(pyridine-3-ylmethylamino)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(phenylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-phenylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(furan-2-ylmethylamino)qi is logex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-pyridin-2-ylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-piperidine-1-ylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-imidazol-4-ylethylamine)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(pyridine-2-ylmethylamino)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-(4-methoxyphenyl)ethylamino)cyclohex-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl-3-oxocyclohexa-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(1-externalization-3-ylmethyl)-3-oxocyclohexa-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(1-Osotimehin-4-ylmethyl)-3-oxocyclohexa-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-methylpiperazin-1-ylmethyl)-3-oxocyclohexa-1-enyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-{6-oxo-1-(tetrahydropyran-4-ylmethyl)-1,2,3,6-tetrahydropyridine-4-yl}naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(2-oxo-1-pyridin-4-iletilerini--yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-oxo-1-pyridin-4-yl-1,2,3,6-tetrahydropyridine-4-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-oxo-1-pyridin-4-yl-1,2,3,6-tetrahydropyridine-4-yl)naphthalene-1-yl]urea,

methyl ester 5-tert-butyl-3-{3-[4-(6-oxo-1-pyridin-4-yl-1,2,3,6-tetrahydropyridine-4-yl)naphthalene-1-yl]ureido}thiophene-2-carboxylic acid,

methyl ester 5-tert-butyl-1-methyl-3-[3-[4-(6-oxo-1-pyridin-4-yl-1,2,3,6-tetrahydropyridine-4-yl) naphthalene-1-yl]ureido}pyrrole-2-carboxylic acid,

methylamide 5-tert-butyl-1-methyl-3-{3-[4-(6-oxo-1-pyridin-4-yl-1,2,3,6-tetrahydropyridine-4-yl)naphthalene-1-yl]ureido}pyrrole-2-carboxylic acid,

methyl ester 5-tert-butyl-3-{3-[4-(3-morpholine-4-icicles-1-enyl)naphthalene-1-yl]ureido}thiophene-2-carboxylic acid,

methyl ester 5-tert-butyl-1-methyl-3-{3-[4-(3-morpholine-4-icicles-1-enyl)naphthalene-1-yl]ureido}pyrrole-2-carboxylic acid and

methylamide 5-tert-butyl-1-methyl-3-[3-[4-(3-morpholine-4-icicles-1-enyl)naphthalene-1-yl]ureido}pyrrole-2-carboxylic acid,

and their pharmaceutically acceptable derivatives.

According to another variant embodiment of the invention provides the following compounds of formula (I):

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3[4-(4-(2-(morpholine-4-yl)ethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletiler-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-methyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

and their pharmaceutically acceptable derivatives.

The second object of the invention are the compounds of formula (Ia):

in which

Ar1means pyrrole, pyrrolidine, pyrazole, imidazole, oxazole, thiazole, furan and thiophene, while Ar1optionally substituted by one or more groups R1, R2or R3,

Ar2means phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl and indole, each of which is optionally substituted by 0 to 3 groups of R2,

X means

- C5-C8cycloalkyl or cycloalkenyl, optionally substituted by 1-2 exography or 1-3 1-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or unbranched,

- phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, tetrahydropyridine, pyrimidinyl, pyridinyl, dihydropyridines, maleimides, dihydropyrimidin, piperidinyl, benzimidazole, 3H-imidazo[4,5-b]pyridine, piperazinil, pyridazinyl or pyrazinyl, each of which is independently optionally substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl)amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y represents a bond or a saturated or unsaturated branched or unbranched1-C4the carbon chain which is optionally partially or fully galogenirovannami, one or more C atoms are optionally replaced by O, N or S(O)ma Y in each case independently optionally substituted by 1-2 exography, nitrile, phenyl, hydroxypropoxy or one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms,

Z means

aryl, and the Daniel, heteroaryl selected from benzimidazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, tanila and pyranyl, the heterocycle selected from a piperazinil, tetrahydropyrimidine, cyclohexanone, cyclohexanol, 2-oxa - or 2-thia-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetraethyleneglycol, tetramethyldisiloxane or tetramethylsilane, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, morpholinopropan, thiomorpholine, Tomorrowland, Tomorrowland, piperidinyl, piperidinyl, pyrrolidinyl and DIOXOLANYL,

each of the above values Z groups are optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, C1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, heteroaryl, heterocyclic1-C3acyl, where heteroaryl and heterocycle are specified above in this paragraph value1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, n is home to the thrill-C 1-C3alkyl, nitrile, carboxylate, phenyl, and phenyl ring optionally substituted with 1-2 substituents selected from the group comprising halogen, C1-C6alkoxygroup, the hydroxy-group and mono - or di(C1-C3alkyl)amino group, the amino group-S(O)mgroup1-C6alkyl-S(O)mand the group phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups, or Z is optionally substituted by 1-3 substituents selected from the group comprising amino, aminocarbonyl and amino-C1-C3alkyl, where N is the atom independently optionally mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-C3alkyl-S(O)mor group arils0-C3alkyl-S(O)m-while each of the above Akilov and arrow attached to the amino group, optionally substituted by 1-2 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, the hydroxy-group and mono - or di(C1-C3alkyl) amino is the Rupp, or Z is optionally substituted by 1-3 substituents selected from the group comprising aryl, heterocycle or heteroaryl, as defined above in this paragraph, that each of the mentioned substituents, in turn, optionally substituted with halogen, C1-C6the alkyl or C1-C6alkoxygroup,

or Z means a hydroxy-group, hydroxys1-C3alkyl, halogen, nitrile, amino group, where N is the atom independently optionally mono - or Disaese1-C6the alkyl, amino1-C6the alkyl, aryls0-C3the alkyl, C1-C5Alcock-ICI1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-C3alkyl-S(O)m-, group arils0-C3alkyl-S(O)m-NITRILES1-C4the alkyl or C1-C3alkoxyl1-C3the alkyl, where each of the above Akilov and arrow attached to the amino group, optionally substituted by 1-2 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, the hydroxy-group and mono - or di(C1-C3alkyl) amino group, With1-C6alkoxyglycerols0-C3the alkyl, heteroaryl0-C3the alkyl or heterocycle0-C3the alkyl, where heteroaryl, heterotic who have above in this paragraph the values or Z means a branched or unbranched1-C6alkyl, C1-C6alkoxygroup,1-C3allmenalp, NITRILES1-C4alkyl, C1-C6alkyl-S(O)mand phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups,

R1means

a) branched or unbranched1-C10alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising phenyl, naphthyl and heterocyclic groups selected from a range, including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, while each of the aforesaid phenyl, naftalina or heterocyclic groups selected from the above range, substituted 0-5 substituents selected from the group comprising halogen, branched or unbranched C1-C6alkyl which is optionally partially or fully galogenidov,3-C8cycloalkyl,5-C8cycloalkenyl, the hydroxy-group, nitrile, C1-C3alkyloxy, which is optionally partially or fully galore arowana, the group of NH2C(O) and di(C1-3)alkylaminocarbonyl,

b)3-C7cycloalkyl selected from the group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptene, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 C1-C3alkyl groups, or similar cycloalkyl group, in which 1-3 ring methylene groups are replaced by groups independently of one another selected from the series comprising O, S, SEN, >C=O, >C=S and NH,

C) branched C3-C10alkenyl, which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising branched or unbranched1-C5alkyl, phenyl, naphthyl and heterocyclic group, where each of heterocyclics group independently selected from a range including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, and each such phenyl, naftalina or heterocyclic group substituted by 0-5 substituents selected from the group comprising halogen, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, the CEC shall propel, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, bicyclopentyl, bicyclohexyl, bicycloheptane, the hydroxy-group, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, the group of NH2C(O) and mono - or di(C1-C3)alkylaminocarbonyl,

g)5-C7cycloalkenyl selected from the group comprising cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl and bicycloheptene, with each such cycloalkenyl group optionally substituted by 1-3 C1-C3alkyl groups,

d) nitrile or

e) branched or unbranched1-C6alkoxycarbonyl, branched or unbranched1-C6alkylaminocarbonyl, branched or unbranched1-C6alkylcarboxylic-C1-C3alkyl,

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov and optionally substituted by nitrile,

or R2means acetyl, aroyl, branched or unbranched1-C4alkoxygroup, which is optionally partially or fully galogenirovannami, halogen, methoxycarbonyl or phenylsulfonyl,

R3means

a) phenyl, Naftoli heterocyclic group, selected from a range including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolin, chinoline, ethenolysis, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazole, respiratory, benzothiophene, cinnoline, pteridine, phthalazine, naftemporiki, honokalani, hintline, purines and indazoles, such phenyl, naftalina or heterocyclic group optionally substituted by 1-5 substituents selected from the group comprising phenyl, naphthyl, heterocycle selected from those described above in this paragraph several, branched or unbranched With1-C6alkyl which is optionally partially or fully galogenidov, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptene, phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, halogen, hydroxy-group, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C3alkoxyl1-C5alkyl, C1-C3thioalkyl,1-C3thioalkyl1-C5alkyl, fenoxaprop, naphthyloxy, heterokaryosis, in which the heterocyclic fragment selected from those described above in this is the paragraph number, the nitro-group, amino group, mono - or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation in which heterocyclyl fragment selected from those described above in this paragraph number, group NH2C(O), mono - or di(C1-C3)alkylaminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl group, amino-S(O)2the group di(C1-C3)alkylamino-S(O)2, R4-C1-C5alkyl, R5-C1-C5alkoxygroup, R6-C(O)-C1-C5the alkyl group of R7-C1-C5the alkyl(R8)N and carboxy-mono - or di(C1-C5)alkylamino,

b) condensed aryl selected from the group comprising benzocyclobutene, indanyl, indenyl, dihydronaphtho, tetrahydronaphthyl, benzocycloheptene and benzocycloheptene, or condensed heterocyclyl selected from the group comprising cyclopentenopyridine, cyclopentenopyridine, philopotamidae, cyclohexanediamine, cyclopentenopyridine, cyclohexanediamine, cyclopentenopyridine, cyclopentenopyridine, cyclopentanediol, cyclohexanediol, cyclopentanethiol, cyclohexanethiol, Cyclopentanone, cyclohexanone, the Cyclops is monobenzylether, cyclohexanedimethanol, cyclopentanemethanol, cyclohexanemethanol, cyclopentanemethanol, cyclohexanedimethanol, cyclopentanethiol and cyclohexanethiol, these condensed aryl or condensed heterocyclyl ring is substituted by 0 to 3 substituents, independently from each other selected from the group comprising phenyl, naphthyl and heterocyclyl selected from the group including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, geterotsiklicheskikh in which heterocyclyl fragment selected from the above range, the nitro-group, amino group, mono - or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation in which heterocyclyl fragment selected from the above range, the group of NH2C(O), mono - or di(C1-C3)alkylaminocarbonyl, group1-C4alkyl-OC(O)branched or unbranched1-C5alkyl-C(O)-C1-C4alkyl, amino-C1/sub> -C5alkyl, mono-or di(C1-C3)alkylamino-C1-C5alkyl, R9-C1-5alkyl, R10-C1-C5alkoxygroup, R11-C(O)-C1-C5the alkyl group and R12-C1-C5the alkyl(R13)N,

C) cycloalkyl selected from the group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptene, this cycloalkyl optionally partially or fully galogenidov and optionally substituted by 1-3 C1-C3alkyl groups,

g)5-C7cycloalkenyl selected from the group comprising cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl and bicycloheptene, this cycloalkenyl group optionally substituted by 1-3 C1-C3alkyl groups,

e) acetyl, aroyl,1-C6alkoxycarbonyl1-C6alkyl or phenylsulfonyl or

e) branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, or

R1and R2together optionally form a condensed phenyl or pyridinoline ring,

R8and R13each independently from each other selected from the group comprising hydrogen and branched or HEPA is extensive With 1-C4alkyl which is optionally partially or fully galogenidov,

R4, R5, R6, R7, R9, R10, R11and R12each independently from each other selected from the group comprising morpholine, piperidine, piperazine, imidazole and tetrazole,

m means 0, 1 or 2,

W stands for O or S,

thus X is directly attached to one or two groups-Y-Z,

and their pharmaceutically acceptable derivatives.

According to one embodiments of the invention preferred compounds of formula (Ia)in which Ar2means naphthyl, tetrahydronaphthyl, indanyl or indenyl, and W means Acting

In another embodiment of the invention among directly above preferred those compounds of formula (Ia), in which

Ar1means thiophene or pyrazole, each of which is independently from each other substituted by 1 to 3 groups of R1, R2or R3,

X means

- C5-C7cycloalkyl or cycloalkenyl, optionally substituted by 1-2 exography or 1-31-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or unbranched,

- phenyl, indanyl, furanyl, thienyl, imidazolyl, pyridinyl, pyrazinyl, tetrahydropyridine, pyrimidinyl, pyridinyl, Pipa is idini, the benzimidazole or piperazinil, each of which independently of each other optionally substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl)amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y represents a bond or a saturated or unsaturated branched or unbranched1-C4-carbon chain, which optionally partially or fully galogenirovannami, one or more C atoms are optionally replaced by O or N, and Y in each case independently optionally substituted by 1-2 exography, nitrile, phenyl, hydroxy-group or one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms,

Z means

- phenyl, heteroaryl selected from pyridinyl, imidazolyl, furanyl and tanila, the heterocycle selected from a piperazinil, 2-oxa-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetrahydrofuranyl, morpholinopropan, thiomorpholine and piperidinyl, each of the above values Z groups are optionally substituted by 1-3 C is Mascitelli, selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup,1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, morpholinoethyl,1-C6acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, nitrile, carboxylate, phenyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or if (C1-C3alkyl) amino groups, the amino group-S(O)mgroup1-C6alkyl-S(O)mand the group phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups,

or Z is optionally substituted by 1-3 substituents selected from the group comprising amino, aminocarbonyl and amino-C1-C3alkyl, where N is the atom in each case independently optionally mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group 1-C3alkyl-S(O)mor group arils0-C3alkyl-S(O)m-while each of these Akilov and arrow attached to the amino group, optionally substituted by 1-2 substituents selected from the group comprising halogen, C1-C6alkyl and C1-C6alkoxygroup, or Z is optionally substituted 1-3 aryl, heterocyclic or heteroaryl groups, as indicated above in this paragraph, each of which, in turn, optionally substituted with halogen, C1-C6the alkyl or C1-C6alkoxygroup,

or Z means a hydroxy-group, hydroxys1-C3alkyl, halogen, nitrile, amino group, where the N-atom in each case independently optionally mono - or Disaese Arola,1-C3the acyl, C1-C6the alkyl, C1-C5alkoxyl1-C3the alkyl, pyridinyl1-C6the alkyl, tetrahydrofuranyl1-C3the alkyl, nitrile1-C4the alkyl or phenyl, with phenyl ring optionally substituted with 1-2 substituents selected from the group comprising halogen, C1-C6alkoxygroup, the hydroxy-group and mono - or di(C1-C6alkyl)amino group, or Z means a branched or unbranched1-C6alkyl, C1-C6alkoxygroup or NITRILES1-C 6alkyl,

R1means

branched or unbranched optionally partially or fully halogenated1-C4alkyl,

- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl that are not necessarily fully or partially galogenirovannyie and optionally substituted With 1-31-C3alkyl groups, or similar such cycloalkyl group, in which 1-3 ring methylene groups are replaced by groups independently from each other selected from O, S and NH,

- extensive With3-C10alkenyl, which is optionally partially or fully galogenidov and optionally substituted by 1-3 branched or unbranched1-C5alkyl groups,

- cyclopentenyl and cyclohexenyl, optionally substituted With 1-31-C6alkyl groups,

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov and optionally substituted by nitrile,

R3means

- penello or heterocyclic group selected from a range, including pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and pyrazolyl, such phenyl or heterocyclic group is optionally substituted by 1-5 substituents selected from the group comprising phenyl, heterocycle, in which the last of the above in this paragraph number, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptene, phenyl-C1-C6alkyl, naphthyl-C1-C5alkyl, halogen, hydroxy-group, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C6alkoxyl1-C5alkyl, C1-C3thioalkyl,1-C3thioalkyl1-C5alkyl, fenoxaprop, naphthyloxy, heterokaryosis, in which the heterocyclic fragment selected from those described above in this paragraph number, the nitro-group, amino group, mono - or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation in which heterocyclyl fragment selected from those described above in this paragraph number, group NH2C(O), mono - or di(C1-C3)alkylaminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl group, amino-S(O)2the group di(C1-C3)alkylamino-S(Oh)2, R4-C1-C5alkyl, R6-C1-C5alkoxygroup, R6-C(O)-C 1-C5the alkyl group of R7-C1-C5the alkyl(R8)N and carboxy-mono - or di(C1-C5)-alkylamino,

- condensed aryl selected from the group comprising benzocyclobutene, indanyl, indenyl, with such a condensed aryl substituted by 0-3 substituents, independently from each other selected from the group comprising phenyl, naphthyl and heterocyclyl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, teinila, furil, isoxazolyl and isothiazoline, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, geterotsiklicheskikh in which heterocyclyl fragment selected from those described above in this paragraph group, a nitrogroup, amino group, mono-or di(C1-C3)alkylamino, phenylaminopropyl, naphtylamine, heterocyclisation in which heterocyclyl fragment selected from those described above in this paragraph group, the group of NH2C(O)and mono - or di(C1-C3)alkylaminocarbonyl, group1-C4alkyl-OC(O)branched or unbranched1-C5alkyl-C(O)-C1 -C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl, R9-C1-C5alkyl, R10-C1-C5alkoxygroup, R11-C(O)-C1-C5the alkyl group and R12-C1-C5the alkyl(R13)N,

- cycloalkyl selected from the group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, this cycloalkyl optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups,

- C1-C6alkoxycarbonyl1-C6alkyl, or

R1and R2together optionally form a condensed phenyl or pyridinoline ring,

R8and R13each independently from each other selected from the group comprising hydrogen and branched or unbranched1-C4alkyl which is optionally partially or fully galogenidov, and

R4, R5, R6, R7, R9, R10, R11and R12each independently from each other selected from the group comprising morpholine, piperidine, piperazine, imidazole and tetrazole,

thus X is directly attached to one group-Y-Z.

In the following embodiment of the invention among directly above preferred those compounds is of formula (Ia), in which

Ar1means pyrazole,

X means

- cyclopentenyl, cyclohexenyl, cycloheptenyl, optionally substituted oxopropoxy or 1-31-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or unbranched,

- phenyl, furanyl, thienyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidinyl, each of which is independently optionally substituted by 1-3 substituents selected from the group comprising From1-C2alkyl, C1-C2alkoxygroup, the hydroxy-group and halogen,

Z means

phenyl, heteroaryl selected from pyridinyl, imidazolyl and furanyl, heterocycle selected from 2-oxa-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetrahydrofur wounded, tetrahydropyranyl, piperazinil, morpholinopropan, thiomorpholine, Tomorrowland and piperidinyl,

each of the above values Z groups are optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup,1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, morpholinoethyl,1-C3acyl, oxoprop, the hydroxy-group, original-C 1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, nitrile, carboxylate, phenyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups, the amino group-S(O)mgroup1-C6alkyl-S(O)mand the group phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C6alkyl) amino groups, or Z is optionally substituted by 1 to 3 amino groups, aminocarbonyl groups or amino-C1-C6alkyl groups, where N is the atom optionally in each case independently mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-C3alkyl-S(O)m-, pyridinyl0-C3the alkyl, tetrahydrofuranyl0-C3the alkyl or the group arils0-C3alkyl-S(O)m-while each of the above Akilov and arrow, prisoedinennykh to the amino group, optionally substituted by 1-2 atoms of Galaga is a, With1-C6alkyl groups or With1-C6alkoxygroup,

or Z means a hydroxy-group, hydroxys1-C3alkyl, halogen, nitrile, amino group, where N is the atom optionally in each case independently mono - or Disaese1-C6the alkyl, pyridinyl0-C3the alkyl, tetrahydrofuranyl0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C3the acyl, nitrile1-C4the alkyl or phenyl, with phenyl ring optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups, or Z means a branched or unbranched1-C6alkyl, C1-C6alkoxygroup or NITRILES1-C4alkyl,

R1means

branched or unbranched1-C4alkyl which is optionally partially or fully galogenidov,

- cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl and cycloheptenyl that are not necessarily fully or partially galogenirovannyie and optionally substituted With 1-31-C3alkyl groups, or similar such cycloalkyl group, in which 1-3 ring methylene groups are replaced by groups independently selected from O, S and NH,

- razvetvlenno is th 3-C10alkenyl, which is optionally partially or fully galogenidov and optionally substituted by 1-3 branched or unbranched1-C3alkyl groups,

- cyclopentenyl and cyclohexenyl, optionally substituted With 1-31-C3alkyl groups,

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov and optionally substituted by nitrile,

R3means

is phenyl or heterocyclic group selected from a range, including pyridinyl, pyrimidinyl, pyridazinyl and pyrazolyl, such phenyl or heterocyclic group is optionally substituted by 1-5 substituents selected from the series comprising phenyl, heterocycle, selected from those described above in this paragraph group, a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, phenyl-C1-C5alkyl, halogen, hydroxy-group, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C3thioalkyl,1-C3thioalkyl1-C5alkyl, amino group, mono - or di(C1-C3)alkylamino, the group of NH2C(O) or mono - or di(C1-C3)Ala is a melamine-carbonyl,

- C1-C6alkoxycarbonyl1-C6alkyl,

or R3means cyclopropyl or cyclopentyl, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups, or

R1and R2together optionally form a condensed phenyl or pyridinoline ring.

According to the following variant of the invention, among directly above preferred those compounds of formula (Ia), in which

Y represents-CH2-, -O-(CH2)0-3-, -CH2CH2-, -CH2NH-, -CH2CH2-NH-, NH-CH2CH2-, -CH2-NH-CH2-, -NH-,-NH-C(O)-, -C(O)-, -CH(OH)-, -CH2(CH2CH3)- or a bond,

X means

- cyclohexenyl, optionally substituted oxopropoxy or 1-31-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or unbranched,

is phenyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidinyl, each of which is optionally independently substituted by 1-3 substituents selected from the group comprising From1-C2alkyl, C1-C2alkoxygroup, the hydroxy-group and halogen,

Z means

- phenyl, heteroaryl selected from pyridinyl, imidazolyl and furanyl, gets recycl, selected from 2-oxa-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetrahydrofuranyl, tetrahydropyranyl, piperazinil, morpholinopropan, thiomorpholine, Tomorrowland and piperidinyl,

each of the above values Z groups are optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup,1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, morpholinoethyl,1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazo-Lil-C1-C3alkyl, tetrahydrofur wounded-C1-C3alkyl, nitrile-C1-C3alkyl, nitrile, carboxylate, phenyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, the amino group-S(O)mgroup1-C6alkyl-S(O)mand the group phenyl-S(O)m, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, or Z is optionally substituted by 1 to 3 amino groups or aminocarbonyl and groups where N is the atom optionally in each case independently mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-C3alkyl-S(O)mor group arils0-C3alkyl-S(O)m-while each of the above Akilov and arrow attached to the amino group, optionally substituted by 1-2 halogen atoms, With1-C6alkyl groups or With1-C6alkoxygroup, or Z means a hydroxy-group, hydroxys1-C3alkyl, halogen, nitrile, amino group, where N is the atom optionally in each case independently mono - or Disaese1-C3the alkyl, pyridinyl1-C2the alkyl, tetrahydrofuranyl1-C2the alkyl, C1-C3alkoxyl1-C3the alkyl, C1-C3the acyl, nitrile1-C4the alkyl, phenyl, with phenyl ring optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, or Z means a branched or unbranched1-C6alkyl, C1-C6alkoxygroup or NITRILES1-C4alkyl,

R1 means a branched or unbranched1-C4alkyl which is optionally partially or fully galogenidov,

R2means a branched or unbranched1-C3alkyl which is optionally partially or fully galogenidov and optionally substituted by nitrile,

R3means

is phenyl or heterocyclic group selected from a range, including pyridinyl, pyrimidinyl and pyrazolyl, such phenyl or heterocyclic group is optionally substituted by 1-5 substituents selected from a range, including branched or unbranched1-C3alkyl which is optionally partially or fully galogenidov,1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C3thioalkyl,1-C3thioalkyl1-C5alkyl, amino group or the group NH2C(O),

- C1-C3alkoxycarbonyl,

or R3means cyclopropyl or cyclopentyl, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups.

In accordance with another embodiment of the invention among directly above preferred those compounds of formula (Ia), in which

Ar1about the mean 5-tert-butylphenol-3-yl, where pyrazol ring in each case independently substituted with 1-2 groups R2or R3,

X means

- cyclohexenyl,

is phenyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidinyl, each of which is optionally independently substituted With1-C2alkoxygroup or hydroxy-group,

Z means

phenyl, heteroaryl selected from pyridinyl and furanyl, heterocycle selected from 2-oxa-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, tetrahydrofuranyl, piperazinil, morpholinopropan, thiomorpholine and piperidinyl, each of the above values Z groups are optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl, C1-C3alkoxygroup, oxoprop, the hydroxy-group and the group of NH2C(O)-, or Z signifies hydroxy-C1-C3alkyl, amino group, where N is the atom optionally in each case independently mono - or Disaese pyridinylmethyl, tetrahydrofuranyl,1-C3alkoxy-C1-C3the alkyl, C1-C3the acyl or nitrile-C1-C4the alkyl, or Z means NITRILES1-C4alkyl,

R3means

is phenyl or heterocyclic group selected from a range, including pyridinyl, pyrimidinyl and pyrazolyl, this phenyl and the heterocyclic group optionally substituted with 1-2 substituents, selected from the group comprising From1-C2alkyl which is optionally partially or fully galogenidov,1-C2alkoxygroup, which is optionally partially or fully galogenirovannami,1-C2thioalkyl,1-C2thioalkyl-C1-C3alkyl, amino group and the group of NH2C(O),

- C1-C3alkoxycarbonyl,

or R3means cyclopropyl or cyclopentyl, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups.

In another embodiment of the invention among directly above preferred those compounds of formula (Ia)in which X is pyridinyl.

According to the following variant of the invention, among directly above preferred those compounds of formula (Ia), in which the pyridinyl is attached to Ar1in the 3rd position pyridinyl.

As examples of compounds of formula (Ia) according to the invention include the following:

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[3-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-ilmatieteen-2-yl)naphthalene-1-yl]urea,

1-[Tret-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(4-(morpholine-4-yl)ethylphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-dimethylamino-were)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-ylmethyl)pyridine-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-methyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-(morpholine-4-yl)ethylamino)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3,4-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-methylpiperazin-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(piperidine-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-(pyridin-2-yl)ethylamino)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(2-(pyridin-4-yl)ethylaminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(pyridine-3-ylmethylamino)FeNi is)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3,4-dimethoxyphenethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-oxo-1,6-dihydropyridines-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)imidazol-1-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)imidazol-1-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(furan-3-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxyethylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(pyridine-3-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(4-methyl-3-carbamylethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(imidazol-2-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-hydroxymorphinan-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-2-methoxyethyl-N-methylamine is methyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(4-hydroxyprolin-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(tetrahydrofuran-3-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di-(2-methoxyethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(3-cyanopropyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-iletilmedigini)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di(2-cyanoethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(1-morpholine-4-Ilinden-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(furan-2-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(thiomorpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-carboxamidotryptamine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(2-methyl-3-oxop perazin-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxybutyrate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(furan-2-ylmethyl)-3-methoxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-carbonyl)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methoxypyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-oxo-1,6-dihydropyridines-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morphol is n-4-yl-4-carbonyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(3-carbamylethyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(pyridine-3-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(pyridine-2-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(tetrahydrofuran-2-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)-4-methoxypyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-morpholine-4-ylpropyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(N-(3-methoxypropyl)amino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(N-(3-methoxypropyl)-N-methylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-benzyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-b is Teal-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-N-di(2-cyanoethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(4-carbamylethyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-(3-cyanopropyl)-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-methanesulfonyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-methanesulfonyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-sulfonatophenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-yl)carbonitril)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(5-(tetrahydrothiopyran-4-ylamino)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(methylcarbonate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-yl-4-carbonyl)phenyl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-(3-methylsulfinylpropyl)-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]3-[4-(5-(morpholine-4-yl-carbonyl)pyridin-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-ylmethyl)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-aminopyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-methylpiperidin-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-yl-carbonyl)pyridin-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(N,N-di(2-methoxyethyl)aminomethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-ylmethyl)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-is oil-2H-pyrazole-3-yl]-3-[4-(6-(pyridine-3-yloxy)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(pyridine-3-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methoxypyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-carbanilide-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyrimidine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-cyclopropylamino-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(pyridine-3-ylamino)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-oxitetraciclina-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(thiomorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-benzyl-3H-imidazo[4,5-b]pyridine-6-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(pyridine-3-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-feast of the evils-3-yl]-3-[4-(2-(morpholine-4-ylcarbonyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-amino-4-carbamylethyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(pyridine-3-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(hydroximino-Dean-3-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-betsiamites-5-yl)-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

and their pharmaceutically acceptable derivatives.

According to another variant embodiment of the invention provides the following compounds of formula (Ia):

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-ylmethyl)pyridine-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-(pyridin-2-yl)ethylamino)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(pyridine-3-ylmethylamino)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-ylmethyl)phenyl)nafta is Jn-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxyethylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(4-methyl-3-carbamylethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-hydroxypiperidine-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(4-hydroxyprolin-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(tetrahydrofuran-3-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di(2-methoxyethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(3-cyanopropyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-iletilmedigini)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di(2-cyanoethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(furan-2-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-feast of the evils-3-yl]-3-[4-(4-(thiomorpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-carboxamidotryptamine-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(2-methyl-3-oxopiperidin-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxybutyrate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methoxypyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyridin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-yl-4-carbonyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]3-[4-(6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(pyridine-3-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(tetrahydrofuran-2-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4(6 - (morpholine-4-ylmethyl)-4-methoxypyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-morpholine-4-ylpropyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(5-(tetrahydrothiopyran-4-ylamino)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(methylcarbonate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-(3-methylsulfinylpropyl)-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)Piri is INF-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyrimidine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-14-(6-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-14-(6-(1-oxo-tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(thiomorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-yl-carbonyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea

and their pharmaceutically acceptable derivatives.

In accordance with a third object of the invention it has further compounds of formula (II):

in which

G oz is ACHAT

aromatic With6-C10carbocycle or saturated or unsaturated non-aromatic3-C10carbocycle,

- 6-10-membered heteroaryl containing one or more heteroatoms selected from O, N and S,

- 5-8-membered monocyclic heterocycle containing one or more heteroatoms selected from O, N and S, or

- 8-11-membered ring of the bicyclic heterocycle containing one or more heteroatoms selected from O, N and S, with G replaced by one or more groups R1, R2or R3,

Ar denotes phenyl, naphthyl, chinoline, ethenolysis, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, dihydrobenzofuran, indolinyl, benzothiazyl, dihydrobenzofuranyl, indanyl, indenyl or indolyl, each of which is optionally substituted by one or more groups R4or R5,

X means

- C5-C8cycloalkyl or cycloalkenyl, optionally substituted by 1-2 exography or 1-31-C4alkyl, C1-C4alkoxy-or1-C4alcaligenaceae,

- phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinyl, dihydropyridines, maleimides, dihydropyrimidin, piperidinyl, benzimidazole, 3H-imidazo[4,5-b]pyridine, piperazinil, pyridazinyl or pyrazinyl,

Y represents a bond or a saturated or unsaturated branched or unbranched1-C4-carbon chain, which optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, N or S(O)ma Y is optionally independently substituted with 1-2 exography, phenyl or one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms,

Z means

is phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl, pyranyl, each of which is optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, the hydroxy-group, amino group, mono - or di (C1-C3alkyl) amino group, a group With1-C6alkyl-S(O)mthe group CN, CONH group2group COOH and phenylaminopropyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkyl groups or With1-C6alkoxygroup,

- tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, morpholine, thiomorpholine, Tomorrowland, Tomorrowland, piperidinyl, piperidinyl, piperazinil, those who rapidreader, cyclohexanone, cyclohexanol, pentamethylanisole, pentamethyldisiloxane, pentamethylbenzonitrile, tetramethylbenzene, tetramethyldisiloxane or tetramethylsilane, each of which is optionally substituted by 1-3 substituents selected from the group comprising nitrile,1-C6alkyl, C1-C6alkoxygroup, the hydroxy-group, amino group, mono - or di(C1-C3alkyl)amino-C1-C3alkyl, CONH group2phenylamino-C1-C3alkyl and C1-C3alkoxy-C1-C3alkyl,

- halogen, C1-C4alkyl, nitrile, amino group, a hydroxy-group, With1-C6alkoxygroup, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl, mono - or di(C1-C3alkyl) amino group, secondary or tertiary amine, with an amine nitrogen is covalently bonded with1-C3the alkyl or C1-C5alkoxyalkyl, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, carboxamide-C1-C3alkyl, phenyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, the group With1-C6alkyl-S(O)mthe group or phenyl-S(O) mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups,

- C1-C6alkyl-S(O)mand phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups,

R1in each case, independently means

- C1-C10alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From3-C10cycloalkenyl, the hydroxy-group, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, with each of the above substituents optionally is substituted by 1-5 substituents selected from halogen, C1-C6of alkyl, which is optionally partially or fully galogenidov,3-C8cycloalkenyl,5-C8cycloalkenyl, hydroxy-group, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, group NH2C(O), mono - or di(C1-C3alkyl)amino and mono - or di (C1-C3alkyl) amine is carbonyl,

- cyclopropylamino, cyclobutylamine, cyclopentylamine, cyclohexyloxy or cyclohexyloxy, each of which is optionally partially or fully galogenirovannami and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, the group CN, hydroxys1-C3alkyl and aryl, or similar such Pelourinho group, in which 1-3 ring methylene groups are independently replaced by O, S(O)m, CHOH, >C=O, >C=S or NH,

- fenoxaprop or benzyloxy, each of which is optionally partially or fully galogenirovannami and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, the group CN, hydroxys1-C3alkyl and aryl, or similar such cycloartenol group, in which 1-2 ring methylene groups are independently replaced by N,

- cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl or bicycloheptane, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl, which optionally is actiono or fully galogenidov, the group CN, hydroxys1-C3alkyl and aryl, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S(O)m, CHOH, >C=O, >C=S or NH,

branched or unbranched3-C10alkenyl, which in each case optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising branched or unbranched1-C5alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, each of these substituents is substituted by 1-5 substituents selected from the group comprising halogen, C1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl and bicycloheptane, the hydroxy-group, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannyie, the group of NH2C(O) and mono - or di(C1-alkyls3aminocarbonyl, such branched or unbranched3-C10alkenyl optionally interrupted by one or more heteroatoms selected from O, N and S(O)m,

- cyclopentenyl, C is clohexane, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl or bicycloheptene, this cycloalkenyl group optionally substituted With 1-31-C3alkyl groups,

- nitrile, halogen,

- methoxycarbonyl, etoxycarbonyl and propoxycarbonyl,

- silyl containing three1-C4alkyl groups which are optionally partially or fully galogenirovannyie,

- C3-C6alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH or S(O)mand Alchemilla group optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(C1-C3alkyl)amino group, optionally substituted by one or more halogen atoms,

R2, R4and R5every means

branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, acetyl, aroyl, except the run or unbranched 1-C4alkoxygroup, which in each case optionally partially or fully galogenirovannami, halogen, methoxycarbonyl, group1-C3alkyl-S(O)mwhich is optionally partially or fully galogenirovannami, or phenylsulfonyl,

- C1-C6alkoxygroup, the hydroxy-group, amino group, mono - or di(C1-C4alkyl) amino group, nitrile or halogen,

group OR6,

the nitrogroup or

group, mono - or di(C1-C4alkyl)amino-S(O)2which is optionally partially or fully galogenirovannami, or group H2NSO2,

R3in each case, independently means

is phenyl, naphthyl, morpholinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolin, chinoline, ethenolysis, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazole, respiratory, benzothiophene, cinnoline, pteridine, phthalazine, naftemporiki, honokalani, hintline, purines or indazole, with each of the above radicals optionally substituted by 1-3 substituents selected from the group comprising phenyl, naphthyl, heterocycle or heteroaryl that described above in this paragraph, again in twinny or unbranched 1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl, bicycloheptane, phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, halogen, hydroxy-group, oxoprop, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heterokaryosis and heteroepitaxy, where the heterocyclic or heteroaryl fragment described above in this paragraph, nitro-group, amino group, mono - or di(C1-C3alkyl)amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling, where the heteroaryl or heterocyclic fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3alkyl)amino-C1-C5alkyl group, amino-S(O)2the group di(C1-C3alkyl)amino-S(O)2, R7-C1-C5alkyl, R8-C1-C5alkoxygroup, R9-C(O)-C1-C5the alkyl group of R10-C1-C5the alkyl(R11)N and carboxy-mono - or di(C1-C5 alkyl)amino group,

- condensed aryl selected from benzocyclobutene, indanyl, indenyl, dihydrosafrole, tetrahydronaphthyl, benzocycloheptene and benzocycloheptene, or condensed heteroaryl selected from cyclopentenopyridine, cyclopentenopyridine, cyclopentenopyridine, cyclohexanedimethanol, cyclopentenopyridine, cyclohexanedimethanol, cyclopentenopyridine, cyclopentenopyridine, cyclopentadecanolide, cyclohexanediamine, cyclopentanethiol, cyclohexanemethylamine, cyclopentanediol, cyclohexanediol, cyclopentanecarbonitrile, cyclohexylbenzothiazole, cyclopentanecarbonitrile, cyclohexylbenzothiazole, cyclopentanemethanol, cyclohexanedimethanol, cyclopentadienyl and cyclohexadienyl, with a condensed aryl or condensed heteroaryl ring is independently substituted by 0-3 substituents selected from the group comprising phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, isothiazolin,1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannami, phenyloxy the PU, naphthyloxy, heterokaryosis or heterocyclics, where the heteroaryl or heterocyclic fragment described above in this paragraph, nitro-group, amino group, mono - or di(C1-C3alkyl)amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling, where the heteroaryl or heterocyclic fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl, group1-C4alkyl-OC(O)1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl, R12-C1-C5alkyl, R13-C1-C5alkoxygroup, R14-C(O)-C1-C5the alkyl group and R15-C1-alkyls5R16)N,

- cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl or bicycloheptane, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S, CHOH, >C=O, >C=S or NH,

- cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicycles enyl or bicycloheptene, each of which is optionally substituted With 1-31-C3alkyl groups,

- C1-C4alkylphenyl-C(O)-C1-C4alkyl, C1-C4alkyl-C(O)-C1-C4alkyl or C1-C4alkylphenyl-S(Oh)m-C1-C4alkyl-,

- C1-C6alkyl group or a branched or unbranched1-C6alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C6alkyl, optionally substituted by a group OR18,

the amino group or mono - or di (C1-C5alkyl) amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R26(CH2)mC(O)N(R21)- or R26C(O)(CH2)mN(R21)-,

- C2-C6alkenyl substituted by a group R23R24NC(O)-,

- C2-C6alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH, S(O)mand Alchemilla group optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, morpholinium, piperidinium, piperazinil is m, imidazolyl, phenyl, pyridinyl, tetrazolyl, one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(C1-C4alkyl) amino group which may be substituted by one or more halogen atoms, or

- aroyl,

R6means1-C4alkyl which is optionally partially or fully galogenidov and optionally substituted by a group R26,

R7, R8, R9, R10, R12, R13, R14, R15, R17, R19, R25and R26each independently of one another denotes nitrile, phenyl, morpholinopropan, piperidinyl, piperazinil, imidazolyl, pyridinyl, tetrazolyl, amino or mono - or di(C1-C4alkyl) amino group which is optionally partially or fully galogenirovannami,

R11and R16each independently of one another denotes hydrogen or C1-C4alkyl which is optionally partially or fully galogenidov,

R18in each case independently denotes hydrogen or C1-C4alkyl, which is optionally independently substituted by oxopropoxy or group R25,

R20in each case the e means independently With 1-C10alkyl which is optionally partially or fully galogenidov, phenyl or pyridinyl,

R21in each case independently denotes hydrogen or C1-C3alkyl which is optionally partially or fully galogenidov,

R22, R23and R24each independently of one another denotes hydrogen, C1-C6alkyl which is optionally partially or fully galogenidov, and specified With1-C6alkyl optionally interrupted by one or more atoms O, N or S, and independently optionally substituted mono - or di(C1-C3alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono - or di(C1-C4alkyl) amino group, each of these substituents optionally partially or fully galogenidov and optionally substituted mono - or di(C1-C3alkyl) amino group, or

R23and R24together optionally form a heterocyclic or heteroaryl ring,

m means 0, 1 or 2 and

W stands for O or S,

and their pharmaceutically acceptable derivatives.

According to one embodiments of the invention among directly above preferred those compounds of formula (II), in which

G means

is phenyl, naphthyl, benzocyclobutene, dihydronaphtho, t is traditonally, benzocycloheptene, benzocycloheptene, indanyl, indenyl,

- pyridinyl, pyridinyl, chinoline, dihydroquinoline, tetrahydropyranyl, ethenolysis, tetrahydrothieno, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophene, respiratory, dihydrobenzofuranyl, dihydrobenzofuranyl, benzoxazolyl, benzo[1,4]oxazin-3-IMT, benzodioxolyl, benzo[1,3]dioxol-2-IMT, benzofuran-3-IMT, tetrahydropyranyl, indolyl, indolinyl, indolyl, indolinyl, phthalimide, bromoil,

- oxetanyl, pyrrolidinyl, tetrahydrofur wounded, tetrahydrothiophene, piperidine, piperazinil, morpholinyl, tetrahydropyranyl, dioxane, tetramethylsilane, tetramethyldisiloxane, oxazolines, thiazolines, imidazolines, tetrahydropyridine, homopiperazine, pyrrolidyl, tetrahydropyrimidines, decahydroquinoline, decahydroquinoline, thiomorpholine, thiazolidine, dihydroxyphenyl, dihydropyran, axokine, heptenyl, dioxane or ditional,

thus G is substituted by one or more groups R1, R2or R3.

In another embodiment of the invention among directly above preferred those compounds of formula (II), in which

G means phenyl, pyridinyl, pyridinyl, naphthyl, chinoline, ethenolysis, pyrazinyl, Ben is imidazolyl, benzoxazolyl, benzofuranyl, benzothiophene, respiratory, dihydrobenzofuranyl, dihydrobenzofuranyl, indanyl, indenyl, indolyl, indolinyl, indolyl or indolinyl, while G is substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl, chinoline, ethenolysis, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, indanyl, indenyl or indolyl, each of which is optionally substituted by one or more groups R4or R5,

X is phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinyl, dihydropyridines, maleimides, dihydropyrimidin, piperidinyl, piperazinil, pyridazinyl or pyrazinyl,

Y represents a bond or a saturated or unsaturated With1-C4-carbon chain, where one of the carbon atoms is optionally replaced by O, N or S(O)ma Y is optionally independently substituted with 1-2 exography, phenyl or one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms,

Z means

is phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, furanyl, thienyl, dihydrothiazolo, dihydrodesoxymorphine, pyranyl, pyrrolidinyl, are not substituted by 1-3 substituents selected from the group VK is causa nitrile, With1-C3alkyl, C1-C3alkoxygroup, amino group, mono - or di(C1-C3alkyl)amino group, a CONH group2and HE,

- tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, morpholine, thiomorpholine, Tomorrowland, piperidinyl, piperidinyl, piperazinil, tetrahydropyrimidines, pentamethylanisole, pentamethyldisiloxane, pentamethylbenzonitrile, tetraethyleneglycol, tetramethyldisiloxane or tetramethylsilane, are not substituted by 1-3 substituents selected from the group comprising nitrile,1-C3alkyl, C1-C3alkoxygroup, amino group, mono - or di(C1-C3alkyl) amino group, a CONH group2and HE,

- nitrile,1-C6alkyl-S(O)m, a halogen, a hydroxy-group, With1-C4alkoxy group, amino group, mono - or di(C1-C6alkyl) amino group, mono - or di(C1-C3alkyl)aminocarbonyl or the group NH2C(O),

R1in each case, independently means

- C1-C6alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From3-C6cycloalkyl, phenyl, thienyl, furyl, isoxazolyl and isothiazolin, where each sukasana substituents optionally is substituted by 1-3 substituents, selected from halogen, C1-C4of alkyl, which is optionally partially or fully galogenidov, hydroxy-group, nitrile and C1-C3alkoxygroup, whose optionally partially or fully galogenirovannami,

- cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, the group CN, hydroxys1-C3alkyl and phenyl, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S, CHOH, >C=O, >C=S or NH, or

- silyl containing three1-C4alkyl groups which are optionally partially or fully galogenirovannyie,

R2in each case independently denotes halogen, C1-C3alkoxygroup, group1-C3alkyl-S(O)mwhich is optionally partially or fully galogenirovannami, phenylsulfonyl or nitrile,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, each of which is optionally substituted 1-3 mandated what teli, selected from the group comprising phenyl, naphthyl, heterocycle or heteroaryl that described above in this paragraph With1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl, bicycloheptane, phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, halogen, exography, the hydroxy-group, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heterokaryosis or heterocyclics, where the heteroaryl or heterocyclic fragment described above in this paragraph, nitro-group, amino group, mono - or di(C1-C3alkyl) amino group, phenylaminopropyl, naphtylamine, heteroaryl-nogroup or heterocycling, where the heteroaryl or heterocyclic fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, mono - or di(C1-C3alkyl)amino group, mono - or di(C1-C3)alkylamino-C1-C5alkyl group mono - or di(C1-C3alkyl)amino-S(O)2, R7-C1-C5alkyl, R8-C1-C5ALCO is the system of groups, R9-C(O)-C1-C5lccl, the group R10-C1-C5the alkyl(R11)N and carboxy-mono - or di(C1-C5)-alkyl-amino group,

- C1-C3alkyl group or a C1-C4alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C6alkyl, optionally substituted by a group OR18,

the amino group or mono-or di(C1-C5alkyl) amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R2BCH2C(O)N(R21)- or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-, or

- C2-C4alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami and optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, morpholinium, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or one or more1-C4alkyl groups which are optionally substituted by one or more halogen atoms, and

R23and R24together optionally form imidazolidine, piperidinyl is, morpholinyl, piperazinilnom or pyridinoline ring.

According to another variant embodiment of the invention among directly above preferred those compounds of formula (II), in which

G means phenyl, pyridinyl, pyridinyl, naphthyl, chinoline, ethenolysis, pyrazinyl, benzothiophene, dihydrobenzofuranyl, dihydrobenzofuranyl, indanyl, indolyl, indolinyl, indolyl or indolinyl, while G is substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl,

X is phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperidinyl, piperazinil, pyridazinyl or pyrazinyl, each of which is optionally independently substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl) amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y represents a bond or saturated With1-C4the carbon chain, with one of the carbon atoms is optionally replaced by O, N or S, and Y is optionally independently substituted by exography,

Z means

is phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, dihydrothiazolo, dihydrothiazolo sulfoxide, pyranyl or pyrrolidinyl, which is optional substituted With 1-21-C2alkyl groups or With1-C2alkoxygroup,

- tetrahydropyranyl, morpholinyl, thiomorpholine, tomorro-lignosulfonate, piperidinyl, piperidinyl, piperazinil or tetrahydropyrimidines, which is optional substituted With 1-21-C2alkyl groups or With1-C2alkoxygroup, or

- C1-C3alkoxygroup,

R1in each case, independently means

- C1-C5alkyl which is optionally partially or fully galogenidov and optionally substituted phenyl, substituted by 0-3 substituents selected from the group comprising halogen, C1-C3alkyl which is optionally partially or fully galogenidov, the hydroxy-group, nitrile and C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,

- cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, the group CN, hydroxys1-C3alkyl and phenyl, or similar cyclopropyl, cyclobe the sludge, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl, where one ring methylene group is replaced by O or

- silyl containing three independent1-C2alkyl groups which are optionally partially or fully galogenirovannyie,

R2in each case independently denotes bromine, chlorine, fluorine, methoxy group, methylsulphonyl or nitrile,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrrolidinyl, 2,5-pyrrolidinedione, imidazolyl, pyrazolyl, where each of these radicals optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, halogen, oxoprop, the hydroxy-group, nitrile and C1-C3alkyloxy, which is optionally partially or fully galogenirovannami,

- C1-C3alkyl group or a C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C3alkyl group optionally substituted by a group OR18,

the amino group or mono - or di(C1-C3alkyl) amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R26CH2C(O)N(R21)- or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-, or

- C2-C4quinil, replaced by pyrrolidinium or pyrrolidon, and

R23and R24together optionally form morpholinopropan.

According to the following variant of the invention, among directly above preferred those compounds of formula (II), in which

G means phenyl, pyridinyl, pyridinyl, naphthyl, chinoline, ethenolysis, dihydrobenzofuranyl, indanyl, indolinyl, indolyl or indolinyl, while G is substituted by one or more groups R1, R2or R3,

Ar is 1-naphthyl, X is phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperidinyl, piperazinil, pyridazinyl or pyrazinyl, Y represents a bond or-CH2-, -CH2CH2-, -C(O)-, -O-, -S-, -NH-CH2CH2CH2-, -N(CH3)- or-NH-,

R1in each case, independently means

- C3-C5alkyl which is optionally partially or fully galogenidov and optionally substituted phenyl,

- cyclopropyl, cyclopentyl, cyclohexenyl or bicyclopentyl, optionally substituted by 1-3 substituents selected from the group comprising methyl, which is optionally partially and fully galogenidov, the group CN, hydroxymethyl and phenyl, or 2-tetrahydrofuranyl, replaced by stands, or

- trimethylsilyl,

R3in each case, independently means

- phenyl, morpholinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, 2,5-pyrrolidinedione, imidazolyl or pyrazolyl, where each of these radicals optionally substituted C1-C2the alkyl, which is optionally partially or fully galogenidov,

- C1-C3alkyl group or a C1-C3alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted diethylaminopropyl,

- OR18or1-C3alkyl, optionally substituted by a group OR18,

the amino group or mono - or di(C1-C3alkyl)amino group, optionally substituted by a group R19,

- CH3C(O)NH-, R22O-, R23R24NC(O)-, R26CH2C(O)N(R21)- or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-, or

- C2-C4quinil, replaced by pyrrolidinium or pyrrolidon,

R23and R24mean N or R23and R24together optionally form morpholinopropan and

R26means morpholinopropan.

In another embodiment of the invention among directly the above preferred those compounds of formula (II), in which

G means phenyl, pyridinyl or naphthyl, with G replaced by one or more groups R1, R2or R3,

X means imidazolyl or pyridinyl,

Y represents-CH2-, -NH-CH2CH2- or-NH-,

Z means morpholinopropan,

R1in each case independently denotes tert-butyl, sec-butyl, treamill or phenyl,

R2means chlorine and

R3in each case independently denotes methyl, methoxy group, methoxymethyl, hydroxypropyl, ndimethylacetamide, morpholinopropan or morpholinoethyl.

In the following embodiment of the invention among directly above preferred those compounds of formula (II)in which X is pyridinyl.

In accordance with another embodiment of the invention among directly above preferred those compounds of formula (II), in which the pyridinyl is attached to Ar in the 3rd position pyridinyl.

As examples of compounds of the formula (II) according to the invention include the following:

1-(3-cyanophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-forfinal)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-chloro-2-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-chloro-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)n is Talin-1-yl]urea,

1-(3,4-dimetilfenil)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-itfeel)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-m-tolylacetic,

1-(4-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-chloro-4-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-chloro-3-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,5-dichlorophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-naphthalene-2-Ilocano,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-phenylacetone,

1-(3-chlorophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-chloro-3-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(2,4,6-trichlorophenyl)urea,

1-(2-methyl-3-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methyl-2-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dichlorophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxy-5-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-chloro-6-were)-3-[4-(6-morpho is in 4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,4-dichlorophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methyl-3-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,4-dimetilfenil)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dimetilfenil)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-cyanophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3,4,5-trimethoxyphenyl)urea,

1-biphenyl-4-yl-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,5-differenl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-chloro-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-fluoro-3-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-benzyloxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-fluoro-6-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-fluoro-3-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(2,4,5-trimetilfenil)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-triptorelin the l)urea,

1-(3-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-fluoro-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methoxy-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-fluoro-5-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-ethoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,5-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4,5-dimethyl-2-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-chloro-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-isopropyl-6-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-deformational)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-isopropylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-ethylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-ethoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-butoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]machev is well,

ethyl ester of 4-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-ureido}benzoic acid,

1-(4-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,6-dibromo-4-isopropylphenyl)-3-[4-(6-morpholine-4-ylmethylene-DIN-3-yl)naphthalene-1-yl]urea,

1-(3-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-triftormetilfullerenov)urea,

dimethyl 5-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}isophthalic acid,

1-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

ethyl ester of 3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzoic acid,

1-(5-tert-butyl-2-hydroxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-hydroxymethyl-4-phenylcyclohexyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methylsulfanyl-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-pentyloxide-3-yl)urea,

methyl ester of 4-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzoic acid,

1-(2,5-dioxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1 benzothiazol the-6-yl-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(2,5-diethoxy-4-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)benzamide,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-phenoxyphenyl)urea,

1-(5-econsultancy-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

4-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}-N-phenylbenzene,

1-(2-methyl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dimethyl-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-butyl-4-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzosulfimide,

1-[3-(2-methyl-[1,3]dioxolane-2-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-methoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,4-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methyl-4-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxy-4-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-chloro-2-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-chloro-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3,5-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)Naftali is-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-trifloromethyl)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triftormetilfullerenov)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(2-phenoxy-phenyl)urea,

1-(2-methoxy-5-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-chloro-2,4-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3,5-bistrifluormethylbenzene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-tert-butyl-5-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-methylnaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methylbiphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-chloro-2,4-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-isopropyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-sec-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-propylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]machev is well,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-(4-[6-[(3-methoxypropyl)methylamino]pyridine-3-yl]naphthalene-1-yl)urea,

1-(5-tert-butyl-2-were)-3-[4-(4-(morpholine-4-iletisimimize-1-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-{4-[6-(3-methoxypropylamine)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylpyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-morpholine-4-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-2-chloro-3-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triptoreline)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-trifloromethyl)urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]machev is well,

1-[5-tert-butyl-2-(3-hydroxypropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-morpholine-4-yl-3-oxopropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(morpholine-4-carbonyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)ndimethylacetamide

and their pharmaceutically acceptable derivatives.

In addition to the above as examples of compounds of the following common methods of synthesis can be obtained the following compounds of the formula (II):

1-[4-(6-{[bis(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[4-(2-methyl-3-oxopiperidin-1-ylmethyl)phenyl]naphthalene-1-yl}urea,

1-[4-(6-[[bis-(2-methoxyethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxo-[(4-thiomorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-[6-(1-oxo-1l4-thiomorpholine-4-ylmethyl)the feast of the DIN-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-were)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[4-(1-oxo-1l-thiomorpholine-4-ylmethyl)phenyl]naphthalene-1-yl}urea,

1-[4-(4-{[bis(2-cyanoethyl)amino]methyl}phenyl)naphthalene-1-yl]-3-(5-tertbutyl-2-methoxyphenyl)urea,

1-(2-methoxy-5-pentafluorophenyl)-3-[4-(4-(morpholine-4-iletilerini-1-yl)naphthalene-1-yl]urea,

1-(2-methoxy-5-triptorelin-3-yl)-3-{4-[2-(4-oxopiperidin-1-ylmethyl)pyrimidine-5-yl]naphthalene-1-yl}urea,

1-(2-methoxy-5-trimethylsilylethynyl)-3-{4-[4-(tetrahydropyran-4-ylamino)phenyl]naphthalene-1-yl}urea,

1-(3-methoxynaphthalene-2-yl)-3-[4-(4-(morpholine-4-iletilerini-1-yl)naphthalene-1-yl]urea,

1-(3-methylnaphthalene-2-yl)-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(3-tert-butyl-5-methanesulfonyl)-3-{4-[6-(1-methylpiperidin-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(3-tert-butylphenyl)-3-[4-(3-pyridin-3-ylpropionic)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(4-methoxybiphenyl-3-yl)-3-{4-[4-(tetrahydropyran-4-ylmethyl)imidazol-1-yl]naphthalene-1-yl}urea,

1-(4-methylbiphenyl-3-yl)-3-{4-[4-(2-pyridin-4-retil)piperazine-1-yl]naphthalene-1-yl}urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(pyridine-4-ylethoxy)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-{4-[2-(1-about the co-114-thiomorpholine-4-ylmethyl)-3H-imidazol-4-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-hydroxyphenyl)-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-propylphenyl)-3-{4-[4-(pyrrolidin-1-carbonyl)phenyl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(4-thiomorpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[4-(tetrahydropyran-4-ylamino)phenyl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxypyridine-3-yl)-3-[4-[6-(4-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methylbenzothiazole-7-yl)-3-[4-(6-pyridin-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-phenoxyphenyl)-3-{4-[6-(tetrahydropyran-4-yloxy)-pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-pyrrolidin-1-ylphenyl)-3-[4-(4-methoxy-6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-pyrrolidin-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-cyano-2-methoxyphenyl)-3-{4-[2-(2,6-dimethylocta-Lin-4-ylmethyl)PI is kidin-5-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-4'-dimethylaminophenyl-3-yl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-(6-methoxy-3,3-dietlinde-5-yl)-3-{4-[4-(morpholine-4-carbonyl)phenyl]naphthalene-1-yl}urea,

1-(6-tert-butyl-2-chloro-3-methylpyridin-4-yl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butylbenzo[1,3]dioxo]-4-yl)-3-[4-[6-(morpholine-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(7-methoxy-1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl)-3-[4-[6-(tetrahydropyran-4-yloxy)pyridine-3-yl]naphthalene-1-yl}urea,

1-(7-tert-butyl-2,4-dimethyl-benzoxazol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[2-methoxy-5-(1-methyl-1-phenylethyl)phenyl]-3-{4-[6-(2-pyridin-4-retil)pyridazin-3-yl]naphthalene-1-yl}urea,

1-[2-methoxy-5-(1-methylcyclohexyl)phenyl]-3-{4-[4-(1-methylpiperid-DIN-4-ylsulphonyl)phenyl]naphthalene-1-yl}urea,

1-[2-methoxy-5-(1-methylcyclopropyl)phenyl]-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-[2-methoxy-5-(2-methyl-tetrahydrofuran-2-yl)phenyl]-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[2-methoxy-5-(3-cryptometrics[1.1.1]Penta-1-yl)phenyl]-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[3-tert-butyl-5-(1-methyl-1H-imidazol-4-yl)phenyl]-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-5-(2-pyrrolidin-1-retil)phenyl]-3-{4-[6-(1-methylp is peridin-4-yloxy)pyridine-3-yl]naphthalene-1-yl}urea,

1-[3-tert-butyl-5-(3-pyrrolidin-1-rprop-1-inyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-imidazol-1-iletileri-3-yl)naphthalene-1-yl]-3-[2-methoxy-5-(1-vinylcyclopropyl)phenyl]urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(4-thiomorpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[5-(1-cyanocyclohexyl)-2-methoxyphenyl]-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-[5-(1-hydroxymethylglutaryl)-2-methoxyphenyl]-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[5-tert-butyl-1-(2-diethylaminoethyl)-2-oxo-1,2-dihydropyridines-3-yl]-3-{4-[6-(1-methylpiperidin-4-yloxy)pyridine-3-yl]naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(2-morpholine-4-ylethoxy)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-{4-[4-(4-methylpiperazin-1-carbonyl)phenyl]naphthalene-1-yl}urea,

1-[5-tert-butyl-2-(2,5-dioxopiperidin-1-yl)phenyl]-3-[4-[6-(1H-imidazol-2-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(5-pyridin-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-morpholine-4-yl-2-oksidoksi)phenyl]-3-[4-[6-(2-pyridin-4-retil)pyridazin-3-yl]naphthalene-1-yl}urea,

1-[5-tert-butyl-2-(2-morpholine-4-yl-2-oxoethylidene)phenyl]-3-{4-[4-(1-methylpiperidin-4-ylamino)piperidine-1-yl]naphthalene-1-yl}urea,

1-[5-tert-butyl-2-(6-metylene the Jn-3-yl)phenyl]-3-{4-[5-(2-pyrrolidin-1-retil)pyridine-2-yl]naphthalene-1-yl}urea,

1-[5-tert-butyl-2-methoxy-3-(3-morpholine-4-yl-3-oxopropyl)phenyl]-3-[4-(6-pyrrolidin-1-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2-diethylaminoethoxy)-2-methoxyphenyl]-3-[4-[4-(tetrahydropyran-4-yloxy)phenyl]naphthalene-1-yl}urea,

1-[5-tert-butyl-3-(2-pyrrolidin-1-retil)benzofuran-7-yl]-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[6-tert-butyl-4-(2-dimethylaminoethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-3-{4-[6-(thiomorpholine-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-{5-tert-butyl-2-methoxy-3-[2-(1-methylpiperidin-4-yloxy)ethyl]phenyl}-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

2-(4-tert-butyl-2-[3-[4-(5-pyrrolidin-1-iletileri-2-yl)naphthalene-1-yl]ureido}phenoxy)-N-methylacetamide,

2-[4-tert-butyl-2-(3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}ureido)phenoxy]ndimethylacetamide,

3-(5-tert-butyl-2-methoxy-3-[3-[4-(6-pyrrolidin-1-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acrylamide,

3-{3-tert-butyl-5-[3-(4-{4-[2-(1-oxo-1l4-thiazolidin-3-yl)ethyl]phenyl}naphthalene-1-yl)ureido]phenyl}-N,N-dimethylpropanamide,

3-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}benzamide,

4-tert-butyl-2-[3-[4-(2-chloro-4-morpholine-4-ylmethylene)naphthalene-1-yl]ureido}benzamide,

N-(4-tert-butyl-2-{3-[4-(6-oxo-1,6-dihydropyridines-3-yl)naphthalene-1-yl]ureido}phenyl)-2-morpholine-4-ylacetamide,

N-[3-tert-butyl-5-(3-{4-[5-(tetrahydrofur is n-4-ylamino)pyridine-2-yl]naphthalene-1-yl}ureido)phenyl]-2-morpholine-4-ylacetamide,

N-[4-tert-butyl-2-(3-{4-[4-(1-methylpiperidin-4-yloxy)phenyl]naphthalene-1-yl}ureido)phenyl]ndimethylacetamide

and their pharmaceutically acceptable derivatives.

According to another variant embodiment of the invention provides the following compounds of formula (II):

1-(2-tert-butyl-5-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-methylnaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methylbiphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-chloro-2,4-acid)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-isopropyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-sec-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-propylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]mo is evina,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(4-thiomorpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[4-(tetrahydropyran-4-ylamino)phenyl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-(4-{6-[(3-methoxypropyl)methylamino]pyridine-3-yl]-naphthalene-1-yl)urea,

1-(5-tert-butyl-2-were)-3-[4-(4-(morpholine-4-iletisimimize-1-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-(4-(morpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-{4-[6-(3-methoxypropylamine)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methylpyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-morpholine-4-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-2-chloro-3-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-2-chloro-3-methylpyridin-4-yl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[2-IU the hydroxy-5-(1-methylcyclopropyl)phenyl]-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triptoreline)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(4-trifloromethyl)urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(4-thiomorpholine-4-ylmethylene)naphthalene-1-yl]urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1-cyanocyclohexyl)-2-methoxyphenyl]-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(5-pyridin-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxypropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-morpholine-4-yl-3-oxopropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(morpholine-4-carbonyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

2-[4-tert-butyl-2-(3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl]ureido)phenoxy]ndimethylacetamide,

3-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}benzamide,

4-tert-butyl-2-[3-[4-(2-chloro-4-morpholine-4-ylmethylene)nafta is Jn-1-yl]ureido}benzamide

and their pharmaceutically acceptable derivatives.

In another embodiment of the invention it has further the following soedineniya formula (II):

1-(2-tert-butyl-5-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methylbiphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-isopropyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-sec-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-ylmethylene-DIN-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-(4-{6-[(3-methoxypropyl)methylamino]pyridine-3-yl]naphthalene-1-yl)urea,

1-(5-tert-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylpyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-ileti is pyridin-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxypropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(morpholine-4-carbonyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)ndimethylacetamide

and their pharmaceutically acceptable derivatives.

The fourth object of the invention are the compounds of formula (III):

in which

E. means carbon or containing a heteroatom group selected from-O-, -NH - and-S-,

G means

aromatic With6-C10carbocycle or saturated or unsaturated non-aromatic3-C10carbocycle,

- 6-14-membered monocyclic, bicyclic or tricyclic heteroaryl containing one or more heteroatoms selected from O, N and S,

- 6-8-membered monocyclic heterocycle containing one or more heteroatoms selected from O, N and S, or

- 8-11-membered ring of the bicyclic heterocycle containing one or more heteroatoms selected from O, N and S, while G is optionally substituted by one or more groups R1, R2or R3,

Ar denotes phenyl, naphthyl, chinoline, eskinol the sludge, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, dihydrobenzofuran, indolinyl, benzothiazyl, dihydrobenzofuranyl, indanyl, indenyl or indolyl, each of which is optionally substituted by one or more groups R4or R5,

X means

- C5-C8cycloalkyl or cycloalkenyl, optionally substituted by 1-2 exography or 1-31-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or unbranched,

- aryl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinyl, dihydropyridines, maleimides, dihydropyrimidin, piperidinyl, benzimidazole, 3H-imidazo[4,5-b]pyridine, piperazinil, pyridazinyl or pyrazinyl, each of which is optionally independently substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl)amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y represents a bond or a saturated or unsaturated branched or unbranched1-C4-carbon chain that n is necessarily partially or fully galogenirovannami, one or several C-atoms are optionally replaced by O, N or S(O)mand Y is optionally independently substituted with 1-2 exography, nitrile, phenyl or one or more1-C4alkyl groups which are optionally substituted by one or more halogen atoms,

Z means

aryl, heteroaryl selected from pyridinyl, piperazinil, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, tanila and pyranyl, a heterocycle selected from tetrahydropyrimidine, cyclohexanone, cyclohexanol, 2-oxa - or 2-thia-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetramethylene-fidela, tetramethyldisiloxane or tetramethylsilane, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxaspiro, morpholinopropan, thiomorpholine, dimorpholinyldiethyl, thiomorpholine, piperidine, piperidinyl, pyrrolidinyl and DIOXOLANYL,

each of the above values Z groups are optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup,1-C3alkoxy-C1-C3alkyl, C1-C6aldoxycarb the sludge, aroyl,1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-Salkil, nitrile-C1-C3alkyl, nitrile, carboxylate, phenyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, the group With1-C6alkyl-S(O)mand the group phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups,

or Z is optionally substituted by 1 to 3 amino groups or amino-C1-C3alkyl groups, with the N-atom is optionally independently mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-alkyl-C3(O)mor group arils0-C3alkyl-S(O)m-while each of these Akilov and arrow attached to the amino group, optionally substituted by 1-2 halogen atoms, With1-C6alkyl groups or With1-C6alkoxygroup, is whether Z is optionally substituted 1-3 aryl groups, heterocyclic or heteroaryl groups, which are described above in this paragraph, each of these groups, in turn, optionally substituted with halogen, C1-C6the alkyl or C1-C6alkoxygroup, or Z means a hydroxy-group, halogen, nitrile, amino group, where the N atom is optionally independently mono - or Disaese1-C3the acyl, C1-C6the alkyl or C1-C3alkoxyl1-C3the alkyl, branched or unbranched1-C6alkyl, C1-C6alkoxygroup,1-C3allmenalp, NITRILES1-C4alkyl group With1-C6alkyl-S(O)mthe group or phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, With1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups,

R1in each case, independently means

branched or unbranched1-C10alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O, N or S(O)mand specified With1-C10alkyl optionally substituted by 1-3 substituents selected from the group comprising From1-C10cycloalkyl, the hydroxy-group, oxoprop, phenyl naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thienyl, furyl, DIOXOLANYL, isoxazolyl and isothiazolin, each of these substituents optionally is substituted by 1-5 substituents selected from halogen, C1-C6of alkyl, which is optionally partially or fully galogenidov,3-C8cycloalkenyl,5-C8cycloalkenyl, hydroxy-group, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, group NH2C(O), mono - or di(C1-C3alkyl)amino and mono - or di(C1-C3alkyl)aminocarbonyl,

or R1means

- cyclopropylamino, cyclobutylamine, cyclopentylamine, cyclohexyloxy or cyclohexyloxy, each of which is optionally partially or fully galogenirovannami and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, nitrile, hydroxys1-C3alkyl and aryl, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S(O)m, CHOH, >C=O, >C=S or NH,

- fenoxaprop or benzyloxy, each of which is optionally frequent is a rule or fully galogenirovannami and optionally substituted by 1-3 substituents, selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, nitrile, hydroxys1-C3alkyl and aryl, or similar such cycloartenol group, in which 1-2 ring methylene groups are independently replaced by N,

- cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl or bicycloheptane, each of which is optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully galogenidov, nitrile, hydroxys1-C3alkyl and aryl, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S(O)mSNON, >C=O, >C=S or NH,

branched or unbranched3-C10alkenyl, which in each case optionally partially or fully galogenidov and optionally substituted by 1-3 substituents selected from the group comprising branched or unbranched1-C5alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolin, each of these substituents is substituted by 1-5 substituents, select the tion from the group including halogen, C1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl or bicycloheptane, the hydroxy-group, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenidov, the group of NH2C(O) and mono - or di(C1-C3alkyl)aminocarbonyl, with specified branched or unbranched1-C10alkenyl optionally interrupted by one or more heteroatoms selected from O, N and S(O)m,

- cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl or bicycloheptene, this cycloalkenyl group optionally substituted With 1-31-C3alkyl groups,

- oxoprop, nitrile, halogen,

- silyl containing three1-C4alkyl groups which are optionally partially or fully galogenirovannyie, or

- C3-C6alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH or S(O)mand Alchemilla group optionally independently substituted -2-oxopropyl, hydroxy-group, pyrrolidinyl, pirrallo, tetrahydropyranyl, one or more C1-C4alkyl groups, optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(alkyl) amino group, optionally substituted by one or more halogen atoms,

R2, R4and R5every means

branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov,1-C6acyl, aroyl, branched or unbranched1-C4alkoxygroup, which in each case optionally partially or fully galogenirovannami, halogen, methoxycarbonyl, group1-C3alkyl-S(O)mwhich is optionally partially or fully galogenirovannami, or group, phenyl-S(O)m,

- OR6With1-C6alkoxygroup, the hydroxy-group, a nitrile, a nitro-group, halogen or

group, amino-S(O)m-, where N is the atom is optionally independently mono - or Disaese1-C6the alkyl or arils1-C6the alkyl, or amino group, where the N atom is optionally independently mono - or Disaese1-C3the alkyl, aryls0-C3the alkyl, C1- 6the acyl group1-C6alkyl-S(O)mor group arils0-C3alkyl-S(O)m-while each of these in this paragraph Akilov and allow optionally partially or fully galogenidov and optionally substituted With 1-21-C6alkyl groups or With1-C6alkoxygroup,

R3in each case, independently means

is phenyl, naphthyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl,[1,3,4]oxadiazol, triazolyl, tetrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolin, chinoline, ethenolysis, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazole, respiratory, benzothiophene, cinnoline, pteridine, phthalazine, naftemporiki, honokalani, hintline, purines or indazole, with each of the above radicals optionally substituted by 1-3 substituents selected from the group comprising phenyl, naphthyl, a heterocycle or heteroaryl, which are described in this paragraph, branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl, bicycloheptane, phenyl-C1 -C5alkyl, naphthyl-C1-C5alkyl, halogen, hydroxy-group, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heterokaryosis or heterocyclics, where the heterocyclic or heteroaryl fragment described above in this paragraph, nitro-group, amino group, mono - or di(C1-C3alkyl) amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling, where the heterocyclic or heteroaryl fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C5alkyl)amino group, mono - or di(C1-C3alkyl)amino-C1-C5alkyl group, amino-S(O)2the group di(C1-C3alkyl)amino-S(O)2, R7-C1-C5alkyl, R8-C1-C5alkoxygroup, R9-C(O)-C1-C5the alkyl group of R10-C1-C5the alkyl(R11)N and carboxy-mono - or di (C1-C5alkyl)amino group,

- condensed aryl selected from benzocyclobutene, indanyl, indenyl, dihydrosafrole, tetrahydronaphthyl, benzocycloheptene benzocycloheptene, or condensed heteroaryl selected from cyclopentenopyridine, cyclopentenopyridine, cyclopentenopyridine, cyclohexanedimethanol, cyclopentenopyridine, cyclohexanedimethanol, cyclopentenopyridine, cyclopentenopyridine, cyclopentadecanolide, cyclohexanediamine, cyclopentanethiol, cyclohexanemethylamine, cyclopentanediol, cyclohexanediol, cyclopentanecarbonitrile, cyclohexylbenzothiazole, cyclopentanecarbonitrile, cyclohexylbenzothiazole, cyclopentanemethanol, cyclohexanedimethanol, cyclopentadienyl and cyclohexadienyl, but such a condensed aryl or condensed heteroaryl ring is independently substituted by 0-3 substituents selected from the group comprising phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, isothiazolin,1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkyloxy, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heterokaryosis or heterocyclics, where the heteroaryl or heterocyclic fragment described above in this paragraph, a nitrogroup, amino is the Rupp, mono - or di(C1-C3alkyl) amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling, where the heteroaryl or heterocyclic fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl, group1-C4alkyl-OC(O)1-C5alkyl-C(O)-C1-C4alkyl, amino-C1-C5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl, R12-C1-C5alkyl, R13-C1-C5alkoxygroup, R14-C(O)-C1-C5the alkyl group and R15-C1-alkyls5R16)N,

- cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, bicyclopentyl, bicyclohexyl or bicycloheptane, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S, CHOH, >C=O, >C=S or NH,

- cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl or bicycloheptene, each of which is optionally substituted With 1-31-C3alkyl groups,

- C1-C4alkylphenyl-C(O)-C1-C4alkyl,C 1-C4alkyl-C(O)-C1-C4alkyl or C1-C4alkylphenyl-S(O)m-C1-C4alkyl-,

- C1-C6alkyl group or a branched or unbranched1-C6alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C6alkyl, optionally substituted by a group OR18,

the amino group or mono - or di(C1-C5alkyl)amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O, R23R24NC(O)-, R26(CH2)mC(O)N(R21)-, R23R24NC(O)-C1-C3alkoxygroup or R26C(O)(CH2)mN(R21)-,

- C1-C6alkenyl substituted by a group R23R24NC(O)-,

- C2-C6alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH, S(O)mand Alchemilla group optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl, one or more1-C 4alkyl groups which are optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(C1-C4alkyl)amino group, optionally substituted by one or more halogen atoms,

- C1-C6acyl or aroyl,

R6means1-C4alkyl which is optionally partially or fully galogenidov and optionally substituted by a group R26,

R7, R8, R9, R10, R12, R13, R14, R15, R17, R19, R25and R26each independently of one another denotes nitrile, phenyl, morpholinopropan, piperidinyl, piperazinil, imidazolyl, pyridinyl, tetrazolyl, amino or mono - or di(C1-C4alkyl)amino group which is optionally partially or fully galogenirovannami,

R11and R16each independently of one another denotes hydrogen or C1-C4alkyl which is optionally partially or fully galogenidov,

R18in each case independently denotes hydrogen or C1-C4alkyl, which is optionally independently substituted by oxopropoxy or group R25,

R20in each case, independently means1-C10alkyl, which is first optionally partially or fully galogenidov, phenyl or pyridinyl,

R21in each case independently denotes hydrogen or C1-C3alkyl which is optionally partially or fully galogenidov,

R22, R23and R24each independently of one another denotes hydrogen, C1-C6alkyl which is optionally partially or fully galogenidov, when this is specified With the1-C6alkyl optionally interrupted by one or more atoms O, N or S, and independently optionally substituted mono - or di(C1-C3alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono - or di(C1-C4alkyl)amino group, and each of these radicals optionally partially or fully galogenidov and optionally substituted mono - or di(C1-C3alkyl)amino group, or

R23and R24together optionally form a heterocyclic or heteroaryl ring,

m means 0, 1 or 2 and

W stands for O or S,

and their pharmaceutically acceptable derivatives.

In another embodiment of the invention among the above preferred those compounds of formula (III), in which

E. means-CH2-, -NH - or-O-,

W means On and

G means

is phenyl, naphthyl, benzocyclobutene, dihydronaphtho, tetrahydronaphthyl, benzocycloheptene, benzocycloheptene, and the Daniel, indenyl,

- pyridinyl, pyridinyl, chinoline, dihydroquinoline, tetrahydropyranyl, ethenolysis, tetrahydrothieno, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophene, respiratory, dihydrobenzofuranyl, dibenzofurans, dihydrobenzofuranyl, benzoxazolyl, benzo[1,4]oxazin-3-IMT, benzodioxolyl, benzo[1,3]dioxol-2-IMT, benzofuran-3-IMT, tetrahydropyranyl, indolyl, 2,3-dihydro-1H-indolyl, indolinyl, indolyl, indolinyl, phthalimide,

- oxetanyl, pyrrolidinyl, tetrahydrofur wounded, tetrahydrothiophene, piperidine, piperazinil, morpholino, tetrahydropyranyl, dioxane, tetramethylsilane, tetramethyldisiloxane, oxazolines, 3,4-dihydro-2H-benzo[1,4]oxazinyl, thiazolyl, imidazolyl, tetrahydropyridine, homopiperazine, pyrrolidyl, tetrahydropyrimidines, decahydroquinoline, decahydroquinoline, thiomorpholine, thiazolidine, dihydroxyphenyl, dihydropyran, axokine, heptenyl, dioxane or ditional, while G is optionally substituted by one or more groups R1, R2or R3.

According to another variant embodiment of the invention among directly above preferred those compounds of formula (III), in which

E. means-NH-,

G means phenyl, pyridinyl, PI is idoneal, naphthyl, chinoline, ethenolysis, pyrazinyl, benzimidazolyl, benzoxazolyl, benzoxazolyl, benzofuranyl, benzothiophene, benzimidazolyl, dihydrobenzofuranyl, dihydrobenzofuranyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, indanyl, indenyl, indolyl, indolinyl, indolyl, 2,3-dihydro-1H-indolyl or indolinyl, while G is optionally substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl, chinoline, ethenolysis, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, indanyl, indenyl or indolyl, each of which is optionally substituted by one or more groups R4or R5,

X is phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinyl, dihydropyridines, maleimides, dihydropyrimidin, piperidinyl, piperazinil, pyridazinyl or pyrazinyl, each of which is optionally independently substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl) amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y represents a bond or a saturated or unsaturated With1-C4-carbon chain is, where one or more C atoms are optionally replaced by O, N or S(O)mand Y is optionally independently substituted with 1-2 exography, nitrile, phenyl or one or more1-C4alkyl groups, optionally substituted by one or more halogen atoms,

Z means

phenyl, heteroaryl selected from pyridinyl, piperazinil, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, furanyl, tanila and pyranyl, heterocycle selected from 2-oxa-5-azabicyclo[2.2.1]heptane, tetrahydropyrimidine, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetraethyleneglycol, tetramethyldisiloxane, tetramethylsilane, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, morpholinopropan, thiomorpholine, dimorpholinyldiethyl, piperidinyl, piperidinyl, dihydrothiazolo, degidratatia.lechenie, pyrrolidinyl and DIOXOLANYL, each of which is optionally substituted by 1-3 substituents selected from the group including nitrile,1-C3alkyl, C1-C3alkoxygroup, amino group, mono - or di(C1-C3alkyl)amino group, a CONH group2and HE,

or Z is optionally substituted phenyl, heterocycle or heteroaryl, as defined above in this paragraph,each of which, in turn, optionally substituted with halogen, C1-C3the alkyl or C1-C3alkoxygroup,

or Z denotes nitrile, nitrile1-C3alkyl group With1-C6alkyl-S(O)m, a halogen, a hydroxy-group, With1-C3alkyl, C1-C3allmenalp,1-C4alkoxygroup, amino group, mono - or di(C1-C3alkyl)aminocarbonyl or amino group, mono or disubstituted amino1-C6the alkyl or C1-C3al-Kocsis1-C3the alkyl,

R1in each case, independently means

branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O, N or S(O)mand specified With1-C6alkyl optionally substituted by 1-3 substituents selected from the group comprising From3-C6cycloalkyl, oxoprop, phenyl, DIOXOLANYL, pyrrolidinyl, furyl, isoxazolyl or isothiazole, each of which is optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C3alkyl which is optionally partially or fully galogenidov, the hydroxy-group, nitrile and C1-C3alkoxygroup, which is optionally partially or fully ha is egenirovan,

- cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups optionally partially or fully galogenirovannyie, nitrile, hydroxys1-C3the alkyl or phenyl, or similar such cycloalkyl group, in which 1-3 ring methylene groups are independently replaced by O, S, CHOH, >C=O, >C=S or NH,

- oxoprop,

- C3-C6alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, and one or more methylene groups are optionally replaced by O, NH or S(O)mand Alchemilla group optionally independently substituted with 1-2 exography, hydroxy-group, pyrrolidinyl, pirrallo, tetrahydropyranyl,1-C4the alkyl, which is optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(C1-C3alkyl)amino group which is optionally substituted by one or more halogen atoms, or

- silyl containing three1-C4alkyl groups, which are optional the tion partially or fully galogenirovannyie,

R2in each case, independently means

branched or unbranched1-C5alkyl which is optionally partially or fully galogenidov, acetyl, aroyl, branched or unbranched1-C4alkoxygroup, which in each case optionally partially or fully galogenirovannami, halogen, methoxycarbonyl, group1-C2alkyl-S(O)mwhich is optionally partially or fully galogenirovannami, or group, phenyl-S (O)m,

- C1-C3alkoxygroup, the hydroxy-group, a nitrile, a nitro-group, halogen or

group, amino-S(O)m-, where N is the atom is optionally independently mono - or Disaese1-C3the alkyl or arils0-C3the alkyl, or amino group, where the N atom is optionally independently mono - or Disaese1-C3the alkyl, aryls0-C3the alkyl, C1-C3the acyl group1-C4alkyl-S(O)mor group arils0-C3alkyl-S(O)m-while each of these in this paragraph Akilov and allow optionally partially or fully galogenidov and optionally substituted With 1-21-C3alkyl groups or With1-C3alkoxygroup,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pirate the sludge, pyrrolyl, pyrrolidinyl, imidazolyl,[1,3,4]oxadiazol, pyrazolyl, each of which is optionally substituted by 1-3 substituents selected from the group comprising phenyl, naphthyl, heterocycle or heteroaryl, as they are described above in this paragraph With1-C6alkyl which is optionally partially or fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, beclometason, bicyclohexyl, bicycloheptane, phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, halogen, oxoprop, the hydroxy-group, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, fenoxaprop, naphthyloxy, heterokaryosis or heterocyclics, where the heteroaryl or heterocyclic fragment described above in this paragraph, nitro-group, amino group, mono - or di(C1-C3alkyl) amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling, where the heteroaryl or heterocyclic fragment described above in this paragraph, the group of NH2C(O), mono - or di(C1-C3alkyl)aminocarbonyl,1-C5alkyl-C(O)-C1-C4alkyl, mono - or di(C1-C3alkyl) amino group, mono - or di(C1-C3)alkylamino-C1-C5alkyl, a group of MES is - or di(C 1-C3alkyl)amino-S(O)2, R7-C1-C5alkyl, R8-C1-C5alkoxygroup, R9-C(O)-C1-C5the alkyl group of R10-C1-C5the alkyl(R11)N and carboxy-mono - or di(C1-C5)-alkylamino,

- C1-C3alkyl group or a C1-C4alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C6alkyl, optionally substituted by a group OR18,

the amino group or mono - or di(C1-C5alkyl)amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R26CH2C(O)N(R21)-, R23R24NC(O)-C1-C2alkoxygroup or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-,

- C2-C4alkylamino branched or unbranched carbon chain optionally partially or fully galogenirovannami, while one of the methylene groups is optionally replaced by O, and optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl the m or one or more 1-C4alkyl groups, optionally substituted by one or more halogen atoms, or

- C1-C3acyl and

R23and R24together optionally form imidazolidine, piperidinyl, morpholino, piperazinilnom or pyridinoline ring.

According to the following variant of the invention, among directly above preferred those compounds of formula (III), in which

G means phenyl, pyridinyl, pyridinyl, naphthyl, chinoline, ethenolysis, pyrazinyl, 3,4-dihydro-2H-benzo[1,4]oxazinyl, benzothiophene, dihydrobenzofuranyl, dihydrobenzofuranyl, benzoxazolyl, indanyl, indolyl, indolinyl, indolyl or indolinyl, while G is optionally substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl,

X is phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperidinyl, piperazinil, pyridazinyl or pyrazinyl, each of which is optionally independently substituted by 1-3 substituents selected from the group comprising From1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, amino, mono - or di(C1-C3alkyl)amino group, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group1-C6alkyl-S(O)mand halogen,

Y means the link Il is rich With 1-C4-carbon chain, where one or more C atoms are optionally replaced by O, N or S, and Y is optionally independently substituted by nitrile, or by exography,

Z signifies phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, dihydrothiazolo, dihydrotestosterone, pyranyl, pyrrolidinyl, phenylpiperazines, tetrahydropyranyl, tetrahydrofuranyl, DIOXOLANYL, 2-oxa-5-azabicyclo[2.2.1]heptenyl, morpholinopropan, thiomorpholine, Tomorrowland, piperidinyl, piperidinyl, piperazinil or tetrahydropyrimidines, each of which is optionally substituted With 1-21-C2alkyl groups or With1-C2alkoxygroup, or

Z means a hydroxy-group, With1-C3alkyl, C1-C3alkoxygroup,1-C3allmenalp,1-C3alkylsulfonyl, nitrile-C1-C3alkyl or amino group, mono - or disubstituted With1-C3alkoxyl1-C3the alkyl,

R1in each case, independently means

branched or unbranched1-C5alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O, N or S(O)mand specified With1-C5alkyl optionally substituted by exography, DIOXOLANYL is m, pyrrolidinium, fullam or phenyl, each of which is optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C3alkyl which is optionally partially or fully galogenidov, the hydroxy-group, nitrile and C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,

- cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl, each of which is optionally partially or fully galogenidov and optionally substituted With 1-31-C3alkyl groups optionally partially or fully galogenirovannyie, nitrile, hydroxys1-C3the alkyl or phenyl, or similar cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, bicyclopentyl or bicyclohexyl in which one ring methylene group is replaced by O,

- oxoprop,

- C2-C4quinil, which is optionally partially or fully galogenidov, and one or more methylene groups are optionally replaced by O, and optionally independently substituted with 1-2 exography, hydroxy-group, pyrrolidinyl, pirrallo, tetrahydropyranyl,1-C4the alkyl, which is optionally substituted by one or more halogen atoms, nitrile, morpholinopropan, Pipa is Iginla, the piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or mono - or di(C1-C3alkyl) amino group which is optionally substituted by one or more halogen atoms, or

- silyl containing three1-C2alkyl groups which are optionally partially or fully galogenirovannyie,

R2in each case, independently means1-C4alkyl which is optionally partially or fully galogenidov,1-C4alkoxygroup, which is optionally partially or fully galogenirovannami, bromine, chlorine, fluorine, methoxycarbonyl, group, methyl-S(O)mor ethyl-S(O)meach of which is optionally partially or fully galogenirovannami, or group, phenyl-S(O)m,

or R2means a mono - or dis1-C3allmenalp, group, amino-S(O)mor S(O)m-an amino group, where the N atom is mono - or Disaese1-C3the alkyl or phenyl, nitrile, nitro-group or amino group,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrrolidinyl, 2,5-pyrrolidinedione, imidazolyl,[1,3,4]oxadiazol, pyrazolyl, each of which is optionally substituted by 1-3 substituents selected from the group comprising From1-C3alkyl which is optionally partially or fully halogen is Rowan, halogen, oxoprop, the hydroxy-group, nitrile and C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,

- C1-C3alkyl group or a C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami or optionally substituted by a group R17,

- OR18or1-C3alkyl, optionally substituted by a group OR18,

the amino group or mono - or di(C1-C3alkyl)amino group, optionally substituted by a group R19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R26CH2C(O)N(R21)-, NH2C(O)methoxy group, or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-,

- C2-C4quinil, replaced by pyrrolidinium or pyrrolidon, or

- C1-C3acyl and

R23and R24together optionally form morpholinopropan.

In accordance with another embodiment of the invention among directly above preferred those compounds of formula (III), in which

G means phenyl, pyridinyl, pyridinyl, 2-naphthyl, chinoline, ethenolysis, dihydrobenzofuranyl, indanyl, 5-indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl, benzoxazolyl, 2,3-dihydroisoxazole-7-yl, 2-oxo-,3-dihydro-1H-indol-5-yl, indolinyl, indolyl or indolinyl, while G is optionally substituted by one or more groups R1, R2or R3,

Ar is 1-naphthyl,

X is phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperidinyl, piperazinil, pyridazinyl or pyrazinyl,

Y represents a bond or-CH2-, -CH2CH2-, -C(O)-, -O-, -S-, -NH-CH2CH2CH2-, -N(CH3)- ,- CH2(CN)CH2-NH-CH2or-NH-,

Z means morpholinopropan, DIOXOLANYL, tetrahydrofuranyl, pyridinyl, 2-oxa-5-azabicyclo[2.2.1]heptenyl,1-C3alkoxybenzenes, the hydroxy-group, With1-C3alkyl, N,N-dis1-C3alkoxy-C1-C3alkylamino,1-C3allmenalp,1-C3alkylsulfonyl or NITRILES1-C3alkyl,

R1in each case, independently means

- C1-C5alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O or N, as specified With the1-C5alkyl optionally substituted by exography, DIOXOLANYL, pyrrolidinyl, fullam or phenyl, optionally substituted C1-C3alkoxygroup,

- cyclopropyl, cyclopentyl, cyclohexenyl and bicyclopentyl, optionally substituted by 1-3 methyl groups, to the verge optionally partially or fully galogenirovannyie, nitrile, hydroxymethyl or phenyl, or 2-tetrahydrofuranyl, replaced by stands,

- trimethylsilyl or

- PROPYNYL substituted hydroxy-group or tetrahydropyran-2-lexigraphy,

R2means a mono - or dis1-C3allmenalp, group, amino-S(O)mor S(O)m-an amino group, where the N atom is mono - or Disaese1-C3the alkyl or phenyl, bromo, chloro, fluoro, nitrile, nitro-group, an amino group, a methylsulphonyl, which is optionally partially or fully galogenidov, or phenylsulfonyl,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrrolidinyl, 2,5-pyrrolidinedione, imidazolyl, [1,3,4]oxadiazol or pyrazolyl, each of which is optionally substituted C1-C2the alkyl, which is optionally partially or fully galogenidov,

- C1-C3alkyl group or a C1-C3alkoxygroup, each of which is optionally partially or fully galogenirovannami or optionally substituted diethylaminopropyl,

- OR18or1-C3alkyl, optionally substituted by a group OR18,

the amino group or mono - or di(C1-C3alkyl) amino group, optionally substituted by a group R19,

- CH3C(O)NH-, R22O-, R23R24NC(O)-, R26CH C(O)N(R21)-, NH2C(O)methoxy group, or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24NC(O)-,

- C2-C4quinil, replaced by pyrrolidinium or pyrrolidon, or

- C1-C2acyl and

R23and R24mean N or R23and R24together optionally form morpholinopropan and

R26means morpholinopropan.

In accordance with another embodiment of the invention among directly above preferred those compounds of formula (III), in which

G means phenyl, pyridinyl, 5-indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl, benzoxazolyl, 2,3-dihydroisoxazole-7-yl, 2-oxo-2,3-dihydro-1H-indol-5-yl or 2-naphthyl, with G optionally substituted by one or more groups R1, R2or R3,

X means imidazolyl, pyridinyl, pyrimidinyl or pyrazinyl,

Y represents a bond, CH2(CN)CH2-NH-CH2, -CH2-, -NH-CH2CH2CH2- or-NH-,

Z means morpholine-4-yl, dioxolane-2-yl, tetrahydrofuranyl, pyridinyl, 2-oxa-5-azabicyclo[2.2.1]hept-5-yl, methoxyphenylpiperazine, the hydroxy-group, methyl, N,N-dimethoxyaniline, acetylamino, methylsulphonyl or cyanoethyl,

R1in each case independently denotes tert-butyl, sec-butyl, tert-AMI is, phenyl, tetrahydropyran-2-aloxiprin, hydroxypropyl, trihalomethyl, 2,2-diethylpropion or cyclohexanyl,

R2means chlorine, a nitro-group, amino group, nitrile, methylsulfonylamino, deacetylating, phenylcarbonylamino, N,N-di(methylsulphonyl)amino group, a methylsulphonyl or trihalomethanes,

R3in each case independently denotes methyl,1-C3alkoxygroup, methoxymethyl, hydroxypropyl, dimethylaminopropyl,1-C4alkylamino, NH2C(O)methoxy group, acetyl, pyrrolidinyl, imidazolyl, pyrazolyl, morpholinopropan or morpholinoethyl.

In another embodiment of the invention among directly above preferred those compounds of formula (III)in which X is pyridinyl.

According to the following variant of the invention, among directly above preferred those compounds of formula (III), in which the pyridinyl is attached to Ar in the 3rd position pyridinyl.

As examples of compounds of the formula (III) according to the invention include the following:

1-(4-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-[4-(4-(morpholine-4-iletilerini-1-yl)naphthalene-1-yl]urea,

1-(6-chloro-4-triptorelin-2-yl)-3-[4-(6-morpholine-4-eletype the one-3-yl)naphthalene-1-yl]urea,

1-(4-deformational)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-methylnaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[2-methoxy-5-(1-methyl-1-phenylethyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

3-(5-[4-[3-(5-tert-butyl-2-were)ureido]naphthalene-1-yl}pyridine-2-ylamino)propyl ester(5-tert-butyl-2-were)carbamino acid,

1-(6-tert-butylbenzo[1,3]dioxol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

1,3-bis[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,2-dimethyl-[1,3]dioxolane-4-ylmethyl)-2-hydroxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-pyrrolidin-1 ylethoxy)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-hydroxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dimethyl-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(2-p-tolyloxy-5-triptoreline)urea,

1-[2-(2-methoxyphenoxy)-5-triptoreline]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-Maur the Olin-4-iletileri-3-yl)naphthalene-1-yl]-3-naphthalene-1-Ilocano,

1-[5-tert-butyl-2-methyl-3-[3-(tetrahydropyran-2-yloxy)prop-1-inyl]phenyl}-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-{5-tert-butyl-2-[3-(tetrahydropyran-2-yloxy)prop-1-inyl]phenyl}-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-hydroxymethyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxydibenzoyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,5-di-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[3-(4-bromo-1-methyl-1H-pyrazole-3-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(1-acetyl-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-oxazol-5-ylphenyl)urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-[1,3,4]oxadiazol-2-ylphenyl)urea,

1-(2-methoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

(4-tert-butyl-2-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)amide, furan-2-carboxylic acid,

1-(2-methoxy-4-phenyliminomethyl)-3-[4-(6-morpholine-4-ylmethylene-DIN-3-yl)naphthalene-1-yl]urea,

1-(5-methoxy-2-were)-3-[4(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-hydroxynaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N,N-diethyl-4-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzosulfimide,

1-(2,2-debtorrent[1,3]dioxo-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1,1-dimethylpropyl)-2-phenoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(2,2-dimethylpropyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

isopropyl ester of 2-chloro-5-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzoic acid,

1-(4-amino-3,5-dibromophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(3-hydroxyprop-1-inyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxyprop-1-inyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,2-dimethyl-[1,3]dioxolane-4-ylmethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butoxy-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1-cyanocyclohexyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,/p>

1-[5-tert-butyl-3-(2-diethylamino-ethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-[1,3]dioxolane-2-espiridion-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-pyrrolidin-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-dimethylaminophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-propoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-hydroxymethyluracil-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

2-(5-tert-butyl-2-methoxyphenyl)-N-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]acetamide", she

1-(2-methoxy-5-phenoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-cyclopentylacetyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(3-pyridin-3-iparralde-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-cyclohexyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-ylmethylene-DIN-3-yl)naphthalene-1-yl]urea,

1-(2,4-dimethoxy-5-triptoreline)-3-[4-(6-morpholine-4-ilma is espiridion-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-methylpyridin-3-yl)naphthalene-1-yl]urea,

N-acetyl-N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

1-(6-tert-butyl-4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[6-tert-butyl-4-(2-morpholine-4-retil)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-isopropoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-imidazol-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-4-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)methanesulfonamide,

1-(5-tert-butyl-3-ethylamino-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)bis(metasolv)amide,

1-[5-tert-butyl-2-(1-methyl-1H-pyrazole-4-yl)phenyl]3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methanesulfonyl-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-econsultancy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-{[bis(2-methoxyethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(3-dimethylaminopropan-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

N-[1-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)-pyrrolidin-3-yl]acetamide", she

1-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)propionamide,

1-(5-tert-butyl-2-methylbenzothiazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triftormetilfullerenov)urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)isobutyramide,

2-(4-tert-butyl-2-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenoxy)aptamil,

1-(5-tert-butyl-2-oxo-2,3-dihydroisoxazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-piano-2-methoxypyridine-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthas the Lin-1-yl]urea,

1-(6-tert-butyl-3-cyano-2-hydroxypyridine-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-cyano-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(1,3 .3m-trimethyl-2,3-dihydro-1H-indol-5-yl)urea,

1-(5-tert-butylbenzothiazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)benzosulfimide,

(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amelataltiedy acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(4-(morpholine-4-iletileri-DIN-1-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1-methyl-1H-pyrazole-4-yl)phenyl]-3-[4-(4-(morpholine-4-iletilerini-1-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxypyridine-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amide 2,2,2-cryptgethashparam acid,

N-(5-{4-[3-(5-tert-butyl-2-were)ureido]naphthalene-1-yl}pyrazin-2-yl)methane is sulfonamid,

1-[4-(6-{[bis(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(2,6-dimethylpiperidin-1-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxitetraciclina-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(tetrahydropyran-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-{[(2-pianeti)-(tetrahydrofuran-2-ylmethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methoxymethylethoxy-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(2-morpholine-4-ylethylamine)methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

amide 1-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)piperidine-3-carboxylic acid,

amide 1-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)piperidine-4-carboxylic acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-ox is-1l4-thiomorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

1-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-{4-[6-(4-acetylpiperidine-1-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}-3-(5-tert-butyl-2-methoxyphenyl)urea,

ethyl ester of 4-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)piperazine-1-carboxylic acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(2-pyridin-3-ylethylamine)methyl]pyridine-3-yl]naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(tetrahydrofuran-3-ylamino)methyl]pyridine-3-yl]naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-[[(2-pianeti)pyridine-3-ylmethylamino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(2-methylsulfonylamino)methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-[6-[(2-piperazine-1-ylethylamine)methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-(pyrimidine-2-reparation-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-6-(4-pyridine-2-reparation-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[4-(3-methoxyphenyl)-piperazine-1-ylmethyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(morpholine-4-carbonyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-thia-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-[4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl]pyridine-2-yl)acetamide", she

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)-N-methylacetamide,

N-(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)-2,2,2-triptorelin,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(pyridine-3-yloxy)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(pyridine-3-ylamino)pyridine-3-yl]naphthalene-1-yl]urea,

3-tert-BUTYLPEROXY ester[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]carbamino acid,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)methanesulfonamide

and their Pharma is efticiency acceptable derivatives.

According to another variant embodiment of the invention provides the following compounds of formula (III):

1-(3-methylnaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)acetamide", she

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-hydroxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dimethyl-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-{5-tert-butyl-2-methyl-3-[3-(tetrahydropyran-2-yloxy)prop-1-inyl]phenyl}-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(2,2-dimethylpropyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl) naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(3-hydroxyprop-1-inyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxyprop-1-inyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,2-dimethyl-[1,3]dioxolane-4-ylmethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butoxy-2-methoxyphenyl is)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1-cyanocyclohexyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2-diethylaminoethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-[1,3]dioxolane-2-espiridion-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-pyrrolidin-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-dimethylaminophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-propoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-hydroxymethyluracil-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-cyclohexyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,4-dimethoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-nitrophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-methylpyridin-3-yl)naphthalene-1-yl]urea,

N-acetyl-N-(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

1-(6-tert-butyl-4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxaze the-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-isopropoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-imidazol-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-ethylamino-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)bis(metasolv)amide,

1-[5-tert-butyl-2-(1-methyl-1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methanesulfonyl-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-{[bis-(2-methoxyethyl)amino]methyl]pyridine-3-yl) naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

N-[1-(5-[4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)pyrrolidin-3-yl]acetamide", she

1-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)propionamide,

1-(5-tert-butyl-2-methylbenzothiazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triftormetilfullerenov)urea,

N(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)isobutyramide,

2-(4-tert-butyl-2-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenoxy)ndimethylacetamide,

1-(5-tert-butyl-2-oxo-2,3-dihydroisoxazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-cyano-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butylbenzothiazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)benzosulfimide,

(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amelataltiedy acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxypyridine-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amide 2,2,2-cryptgethashparam acid,

N-(5-[4-[3-(5-tert-butyl-2-were)ureido]naphthalene-1-yl}pyrazin-2-yl)methanesulfonamide,

1-[4-(6-{[bis(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}Icewine,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylpiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxitetraciclina-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(tetrahydropyran-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-{[(2-cyanoethyl)-(tetrahydrofuran-2-ylmethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(2-methoxymethylethoxy-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

amide 1-(5-[4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)piperidine-3-carboxylic acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxo-4-thiomorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(tetrahydrofuran-3-ylamino)methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-{[(2-cyanoethyl)pyridine-3-ylmethylamino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[4-(3-methoxyphenyl)piperazine-1-ylmethyl]pyridine-3-yl}-naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(morpholine-4-carbonyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-[4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-yl)acetamide", she

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-N-methylacetamide,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-2,2,2-triptorelin,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(pyridine-3-yloxy)pyridine-3-yl]naphthalene-1-yl}urea,

3-tert-BUTYLPEROXY ester[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]carbamino acid,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)methanesulfonamide

p> and their pharmaceutically acceptable derivatives.

In addition to the above as examples of compounds of the following common methods of synthesis can be obtained the following compounds of the formula (III):

1-(5-tert-butyl-2-methylsulfinylphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-chloropyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylaminomethyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}-2-oxo-2H-pyridin-1-yl)methanesulfonamide,

amide 5-tert-butyl-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzoxazol-2-carboxylic acid,

2-(5-tert-butyl-7-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzoxazol-2-yl)acetamide", she

5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}benzamide

and their pharmaceutically acceptable derivatives.

Any of the compounds according to the invention, containing one or more asymmetric carbon atoms can exist as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. All such isomeric forms of these compounds are included in the scope of the present invention. Ka is every stereogenic carbon atom may be in the R - or S-configuration or combination of configurations.

Some of the compounds of formula (I), (Ia), (II) and (III) can exist in more than one tautomeric form. All such tautomers are included in the scope of the present invention.

All terms used in the present description, are, unless otherwise indicated, conventional in the field values. So, for example, "C1-C4alkoxygroup" is a1-C4alkyl with limit oxygen atom, in particular methoxy, ethoxy-, propoxy-, pentox and hexachrome. All alkyl, alkeline and alkyline group can have a branched or unbranched chain, if possible from the point of view of their structure and if not specified otherwise. The following are the definitions of the terms used in the present description.

The term "aroyl" in the context of the present description means "benzoyl" or "naftol".

The term "carbocycle" means an aliphatic hydrocarbon radical containing from three to twelve carbon atoms. Carbocycle include hydrocarbon rings containing from three to ten carbon atoms. This carbocycle can be either aromatic or non-aromatic ring system. Non-aromatic ring system may be mono - or polyunsaturated. As examples of preferred carbocycles can be called (but not limited to only what they are) cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptenyl, cycloheptenyl, phenyl, indanyl, indenyl, benzocyclobutene, dihydronaphtho, tetrahydronaphthyl, naphthyl, decahydronaphthalene, benzocycloheptene and benzocycloheptene. Some terms that relate to cycloalkyl, such as cyclobutyl and cyclobutyl, can be used interchangeably concepts.

The term "heterocycle" refers to a stable non-aromatic 4-to 8-membered (but preferably 5 - or 6-membered) monocyclic or non-aromatic 8-11 membered bicyclic heterocyclic radical, which may be saturated or unsaturated. Each heterocycle consists of carbon atoms and one or more, preferably 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. The heterocycle may be attached via any atom in the ring, which leads to the formation of a stable structure. Unless otherwise specified, examples of the heterocycles can be called (but not limited to) oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophene, piperidine, piperazinil, morpholinyl, tetrahydropyranyl, dioxane, tetramethylsilane, tetramethyldisiloxane, oxazolines, thiazolines, imidazolines, tetrahydropyridine, homopiperazine, pyrrolidyl, tetrahydropyrimidines, DECA is hydrogenolysis, decahydroquinoline, diazolidinyl, dihydroxyphenyl, dihydropyran, axokine, heptenyl, dioxane, ditional or 2-oxa - or 2-thia-5-azabicyclo[2.2.1]heptenyl.

The term "heteroaryl" means an aromatic 5-8 membered monocyclic or 8-11 membered bicyclic ring containing 1-4 heteroatoms such as N, O and S. Unless otherwise stated, such heteroaryl include pyridinyl, pyridinyl, chinoline, dihydroquinoline, tetrahydropyranyl, ethenolysis, tetrahydrothieno, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophene, respiratory, dihydrobenzofuranyl, dihydrobenzofuranyl, benzoxazolyl, benzo[1,4]oxazin-3-IMT, benzodioxolyl, benzo[1,3]dioxol-2-IMT, tetrahydropyranyl, indolyl indolinyl, indolyl, indolinyl, phthalimide.

The term "heteroatom" in the context of the present description refers to atoms other than carbon atom, such as O, N, S and R.

The term "aryl" in the context of the present description means an aromatic carbocycle or heteroaryl, which is defined above.

Terms that are analogous to the above-mentioned cyclic residues, such as aryloxy or heteroaryl mean aryl, heteroaryl, a heterocycle, as defined above, attached to their respective group.

In context, this is the first description of the concept of "nitrogen" and "sulfur" include any oxidized form of nitrogen and sulfur and quaternion the form of any of the nitrogenous base.

The term "halogen" in the context of the present description means bromine, chlorine, fluorine or iodine.

The compounds according to the invention include only those compounds that are considered to be "chemically stable" in that regard, as is customary in the art. For example, the compounds having floating valence" ("dangling valency"), or "carbanion" not subject to the compounds according to the invention.

In the scope of the invention also includes pharmaceutically acceptable derivatives of compounds of formula (I), (Ia), (II) and (III). The term "pharmaceutically acceptable derivative" refers to any pharmaceutically acceptable salt or pharmaceutically acceptable ether compounds according to the invention or any other compound which upon administration to the patient can turn (directly or indirectly) in connection according to the invention, in its farmacologicas active metabolite or farmacologicas active residue. Under "farmacologicas active metabolite" in this regard refers to any compound according to the invention, capable of metabolism, enzymatic or chemical means. Examples of such compounds are gidroksilirovanii or oxidized derivatives of compounds of formula (I), (Ia), (II) or (III).

Pharmaceutically acceptable salts of the compounds according to the invention include salts derived from pharmaceutically when mimih inorganic and organic acids and bases. As an example, the corresponding acid can be called hydrochloric, Hydrobromic, sulphuric, nitric, perchloro, fumaric, maleic, phosphoric, glycolic, lactic, salicylic, succinic, toluene-p-sulfuric, tartaric, acetic, citric, methansulfonate, formic, benzoic, malonic, naphthalene-2-sulfuric and benzosulfimide acid. In addition, can be used, and other acids, for example oxalic acid, which, while not in themselves pharmaceutically acceptable, but may nevertheless be used to obtain salts suitable for use as intermediates in obtaining the compounds according to the invention and their pharmaceutically acceptable acid additive salts. Salts derived from appropriate bases include alkali metal salts (for example sodium), salts of alkaline earth metals (e.g. magnesium), ammonium salts and N-(C1-C4alkyl)4+salt.

In addition, the compounds according to the invention include prodrugs of compounds of formula (I), (Ia), (II) and (III). Prodrugs are compounds that result from simple chemical transformations converted into compounds according to the invention. Such simple chemical transformations are hydrolysis, oxidation and reduction. Thus, in particular, when the introduction is AI prodrugs according to the invention the patient is a prodrug can turn into a connection according to the invention, showing thereby the target of pharmacological action.

Application methods

The invention provides methods of using compounds of formula (I), (Ia), (II) and (III). Compounds according to the invention effectively block the production of cells of inflammatory cytokines. Inhibition of the production of cytokines is a promising method for the prevention and treatment of various diseases associated with excess biogas produced cytokines, such as diseases and pathological conditions associated with inflammation. Thus, the compounds according to the invention can be used for the treatment of such conditions. These conditions include chronic inflammatory diseases, including (but not limited to, osteoarthritis, multiple sclerosis, Guillain-Barre syndrome, Crohn's disease, ulcerative colitis, psoriasis, the disease is graft versus host disease, systemic lupus erythematosus and insulin-dependent diabetes mellitus. Compounds according to the invention can also be used to treat other disorders that are associated with the activity of Pro-inflammatory cytokines present in elevated concentrations, such as responses to various infectious agents and numerous autoimmune diseases such as rheumatoid arthritis, toxic shock syndrome, diabetes, and inflammatory bowel disease, not related to arecoline above diseases, and which are described in the section "Background of invention".

In addition, since the compounds according to the invention are inhibitors of the production of cytokines, we should expect that they should block the expression of inducible cyclooxygenase (SOH-2). It is established that the expression of MOR-2 increases under the action of cytokines, and it is assumed that the cyclooxygenase represents the isoforms of cyclooxygenase, which is responsible for inflammation (MCO Banion and others, Proc. Natl. Acad. Sci. U.S.A., 89, 4888, 1992). Therefore, one should expect that the new compounds according to the invention should be effective against those diseases that are currently difficult to treat inhibitors SOH, such as conventional non-steroidal anti-inflammatory drugs (NCPLS). Such disorders include acute and chronic pain and inflammatory symptoms and cardiovascular diseases.

As mentioned in the section "Background of invention", IL-8 affects the influx of neutrophils to sites of inflammation or damage. Thus, in accordance with another object of the invention compounds according to the invention can be used to treat diseases that predominantly mediated by neutrophils, such as stroke and myocardial infarction, caused by thrombolytic therapy or independently of it, those who viewed the damage, respiratory distress syndrome of adults (rdsw), multiple organ damage as a result of trauma, acute glomerulonephritis, dermatoses, including components of acute inflammation, acute purulent meningitis or other Central nervous system damage, hemodialysis, lamfers, syndromes associated with transfusion of granulocytes, and necrotizing enterocolitis.

For therapeutic purposes, the compounds according to the invention can be introduced in any suitable dosage form in any conventional way. Such methods of introduction include, but is not limited to, intravenous, intramuscular, subcutaneous, intrasynovial, infusion, sublingual, intradermal, oral or introduction by inhalation. Preferred are oral and intravenous method of administration.

Compounds according to the invention can be entered individually or in combination with adjuvants that enhance stability of the inhibitors, facilitate the introduction thereof in the pharmaceutical compositions of certain types, provide a higher solubility or dispersibility, increase inhibitory activity, provide an opportunity adjunctive therapy, etc. as well as other active substances. When such combined therapy is preferable to use smaller doses of conventional therapeutic agents that provides in order to avoid possible toxic and harmful side effects, occurs when these agents are used for monotherapy. Compounds according to the invention can be combined in any physical way with conventional therapeutic means or other adjuvants in the same pharmaceutical composition. Preferably the connection should be entered together in a single standard dosage forms. In specific embodiments, the implementation of pharmaceutical compositions comprising such combinations of compounds contain at least about 5%, more preferably at least about 20% (wt.%), the compounds of formula (I), (Ia), (II) or (III) or combinations of these compounds. The optimal percentage (wt.%) compounds according to the invention may vary and should be determined by experts in this field. In another embodiment, compounds can be entered separately (either sequentially or in parallel). Separate introduction enables more flexible dosage regimen.

As indicated above, the dosage forms of the compounds of the present invention include pharmaceutically acceptable carriers and adjuvants known to specialists in this field. These carriers and adjuvants include, for example, ion exchange resins, alumina, aluminum stearate, lecithin, proteins from the serum, sautereau substances, water, salts or electroly the s and connections based on cellulose. For the preferred dosage forms include tablets, capsules, caplette, liquids, solutions, suspensions, emulsions, tablets, syrups, recovered powders, granules, suppositories, and transdermal patches. Methods of preparing such dosage forms are known (see, for example, ..Ansel and N.G.Popovish, Pharmaceutical Dosage Forms and Drug Delivery Systems, 5th ed., published by Lea and Febiger (1990)). The dose levels and requirements are well known in the field, and they can be matched to a particular patient based on the available methods and tools. In certain embodiments, the dose levels of approximately 1-1000 mg/dose for a patient weighing 70 kg While it may be sufficient to use one dose a day, however, is less than the allowable introduction to 5 doses per day. When ingested by may require doses up to 2000 mg/day. The person skilled in the art can determine which lower or higher doses may be required depending on specific factors. For example, specific doses and modes of introduction may depend on factors such as the General health of the patient, the severity and course of the disease in the patient or a predisposition thereto, and they shall be appointed by decision of the treating physician.

Below the invention is illustrated in the examples. These examples illustrate the preferred Varian is s implementation of the present invention and should not be construed as limiting in any way its volume.

Since, as indicated above, the following examples are illustrative, for specialists in this area it is obvious that, if necessary, specific reagents or conditions of reactions for the individual compounds can accordingly be modified. Original products are used in the following reactions, either available commercially or can be easily obtained by professionals in this area of the commercially available products.

GENERAL METHODS of SYNTHESIS

Compounds according to the invention can be obtained according to method a, B or C, as illustrated in scheme I, preferably by the method of C. Additionally, such methods are described, for example, in the application PCT/US 99/29165 and patent applications U.S. 60/124148 and 60/165867. Each of these claims in full included in the present description by reference.

Scheme I

The diagram above D is the radical Ar1(for compounds of formulas I and Ia) or G (for connection formulas II or III), D' is a group Ar2-X-Y-Z (or its predecessor) for compounds of formulas I and Ia or group Ar-X-Y-Z (or its predecessor) for compounds of formula II or III.

According to the method And the mixture of the amine of formula IV and the isocyanate of the formula V is dissolved in aprotonin anhydrous solvent such as THF, simple ether, toluene, dioxane Il is ethyl acetate. The preferred solvent is THF. The mixture is stirred at a temperature of from 0 to 45°C, preferably at 25°C for 2-24 h to remove volatile components. The result of purification of the residue by recrystallization from suitable for this purpose solvent, such as ethyl acetate/hexane, ethyl acetate/methanol, THF/petroleum ether, ethanol/water, or by chromatography on silica gel using, for example, hexanol and ethyl acetate as eluents, to give the product of formula I, Ia, II or III (E stands for NH).

According to method B amine of formula IV is dissolved in a halogenated solvent such as methylene chloride, chloroform or dichloroethane. The preferred solvent is methylene chloride. The mixture is diluted with aqueous alkali, such as sodium bicarbonate or potassium carbonate, cooled in an ice bath and add phosgene. The mixture is intensively stirred for 5-30 minutes, preferably within 10 minutes the Organic layer is dried with such an agent, as MgSO4or Na2SO4and remove volatile components to obtain the corresponding isocyanate D-N=C=O. Then, the isocyanate and the amine of the formula VI are mixed in aprotonin anhydrous solvent such as THF, simple ether, toluene, dioxane, methylene chloride or ethyl acetate. The preferred solvent is THF. The mixture is stirred while the temperature is from 0 to 45° C, preferably at 25°C for 2-24 h to remove volatile components. The result of purification of the residue by recrystallization or chromatography on silica gel, as indicated above, get the product of formula I, Ia, II or III (E stands for NH).

The required isocyanate can also be obtained from the carboxylic acid (D-CO2N interaction with CHLOROFORMATES, such as ethylchloride, in the presence of an acceptable base, such as triethylamine, in a suitable for this purpose, a solvent such as THF, at a temperature of approximately 0°C. the Obtained mixed anhydride is treated with an aqueous solution of sodium azide. When heated solution obtained acylated suitable for this purpose, a solvent such as toluene, at a temperature of about distillation, there is a rearrangement reaction of kurzius, leading to the in situ isocyanate D-N=C=O.

According to the method In the amine of formula IV is dissolved in an acceptable solvent such as a halogenated solvent such as methylene chloride, chloroform or dichloroethane. The preferred solvent is methylene chloride. You can add an appropriate base, such as triethylamine, and then phenylcarbamate. The mixture is stirred at a temperature of from 0 to 85°C, preferably at a temperature of distillation, for 2-24 h to remove volatile components to obtain the carbamate of formula VII. This carbamate and amine of the formula VI are mixed in aprotonin anhydrous solvent such as THF, simple ether, toluene, dioxane, methylene chloride or ethyl acetate. The preferred solvent is THF. The mixture is stirred at a temperature of from 0 to 110°C, preferably at a temperature of distillation, for 2-24 h to remove volatile components. After purification of the residue as described above, get the product of formula I, Ia, II or III (E stands for NH). This method can be done in reverse order, i.e. first, you can get the carbamate from D NH2and to put this carbamate interaction with amine D-NH2. In example 37 describes the synthesis of the compounds of formula III in which E denotes-O-, as in example 38 considered the synthesis of compounds of formula III in which E denotes-CH2-.

The method used to obtain the amines of formula IV, depends on the nature of the target group D. In General, the intermediates of formula IV can be obtained by methods known in this field. Some of these General methods illustrated in the following schemes. Connection D'-NCO or D'-NH2in scheme I are commercially available compounds or can be obtained by methods known in this field. If D' is a precursor group Ar2-X-Y-Z or Ar-X-Y-Z, then the target is the end product of formula I, Ia, II Il the III can be obtained by methods known in this field. Illustrative examples of such methods are presented in the following section, Examples of synthesis".

Aminopyrazole formula XV necessary to obtain compounds of the formula I or Ia can be obtained in accordance with scheme II. The hydrazine of formula X, which carries the substituent R3can be obtained by the method of G or D. According to method G arilbred formula VIII is dissolved in aprotonin inert solvent such as THF, 1,4-dioxane or diethyl ether, and cooled to a low temperature in an inert atmosphere. This preferred solution is the temperature of -77°C. then added dropwise a strong base dissolved in aprotonin inert solvent, such as hexane, THF or ether, supporting actionnow temperature below 0°C, preferably below -60°C. Preferred bases are alkyllithium reagents, most preferably second-utility. After addition of base, the reaction mixture is stirred for 30 to 90 minutes until until used original arilbred. Then add an excess of dialkyldithiocarbamate, maintaining the reaction temperature below 0°C, preferably below 60°C. as dialkyldithiocarbamate preferable to use di-tert-utilisationbased. The reaction mixture per mesilat at low temperature and after 0.5 and 2 h, warmed to room temperature. The reaction is stopped by addition of water and the product extracted with aprotonin solvent, such as ethyl acetate, diethyl ether or chloroform. The organic layers dried with such agents as MgSO4or Na2SO4and remove volatile components. The residue is dissolved in a protonic solvent, such as methanol or isopropanol, cooled, preferably to 0-5°C, and treated with acid. While it is preferable to use hydrochloric, Hydrobromic, sulfuric and triperoxonane acid. The most preferred hydrochloric acid in gaseous form. After adding an excess of the acid mixture is maintained at a temperature of distillation of the solvent until then, until you used up all the source material. After cooling, the obtained arylhydrazines salt of the formula X is filtered and dried.

Scheme II

According to method D. arylamine bearing the substituent R3(formula IX), is dissolved in a concentrated aqueous acid, such as hydrochloric, Hydrobromic or sulphuric acid, and cooled to a temperature of an ice bath. The most preferred carboxylic acids with concentratie from 3 BC to 8 BC, more preferably 6 N. Then added dropwise agent nitrosation in the water, maintaining a lower temperature. Preferred is tempera is ur 0-5° C. the Preferred reagent is sodium nitrite. The reaction mixture is stirred for 10-90 min and then add the reducing agent, maintaining a lower temperature. Preferable the temperature 0-5°C. as a reducing agent can be used such as zinc, iron, samarium iodide and chloride tin (II). The most preferred reducing agent is tin chloride (II), dissolved in aqueous hydrochloric acid with a concentration from 3 BC to 8 BC, more preferably 6 N. the Reaction mixture is stirred for 0.5-3 h and then the reaction stopped by the addition of alkali to bring the pH up to 12-14. You can use such alkaline reagents as sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide. The most preferred alkaline reagent is potassium hydroxide. The aqueous solution is extracted with aprotonin organic solvent, such as diethyl ether, chloroform, ethyl acetate and methylene chloride. The organic layers dried with such agents as MgSO4and Na2SO4and remove volatile components with getting arylhydrazines (formula X), which can be used in subsequent reactions without further purification.

β-Ketonitriles bearing the substituent R1(formula XIV)may be obtained in accordance with the method F or g According to the method of E. hydride m is metal, such as sodium hydride, potassium hydride or lithium hydride, is suspended in an anhydrous inert aprotonin a solvent such as diethyl ether, THF and dioxane, at a temperature in the range from 35 to 85°C. the Most preferred metal hydride is sodium hydride, and the most preferred solvent is THF at a temperature of 75°C. Then in anhydrous inetrnal aprotonin a solvent such as diethyl ether, THF or dioxane, dissolve alkilany ether, preferably methyl ester (formula XI), and acetonitrile and the resulting solution was added dropwise to the above suspension metal hydride. The preferred solvent is THF. The mixture is maintained at elevated temperature for 3-24 h, cooled to room temperature and diluted with aprotonin solvent and aqueous acid. Then the organic layer was washed with water and brine, dried with such agents as MgSO4and Na2SO4and remove volatile components with obtaining β-ketonitriles (formula XIV), which can be used further without additional purification.

In another embodiment according to the method W solution of a strong base, such as alkylate and metal amide, for example n-utility, second-utility, motility and diisopropylamide lithium, in an anhydrous inert aprotonin a solvent such the AK diethyl ether, THF and dioxane, cooled to a temperature below 0°C. the Preferred base is n-utility, the preferred solvent is THF, and the preferred temperature is the temperature at -77°C. Further added dropwise a solution of tsianuksusnogo acid (formula XII) in anhydrous inert aprotonin a solvent such as diethyl ether, THF and dioxane, preferably THF, maintaining the reaction temperature below 0°C, preferably at the level of -77°C. the Reaction mixture is stirred for 10-45 min, heating it to 0°C. a Solution of dianion tsianuksusnogo acid cooled to a temperature below -25°C, preferably up to -77°C. Next, add the acid chloride alkilani acid (formula XIII)dissolved in anhydrous inert aprotonin a solvent such as diethyl ether, THF and dioxane, preferably THF. The reaction mixture is heated for 10-30 min to 0°and the reaction stopped by addition of an aqueous acid. The product is extracted with an organic solvent, such as chloroform, ethyl acetate, simple ether and methylene chloride. The combined organic extracts are dried with the help of such agents, as MgSO4and Na2SO4and remove volatile components with obtaining β-ketonitriles (formula XIV), which can be used further without additional purification./p>

Target aminopyrazole (formula XV) can be obtained then in accordance with the method 3 or I. According to method 3 arylhydrazines formula X and β-ketonitriles formula XIV are mixed in an organic solvent, such as toluene, ethanol, isopropanol or tert-butanol. The preferred solvent is ethanol. Then add the acid, such as hydrochloric acid, p-toluensulfonate acid or sulfuric acid. The preferred acid is Cocentaina hydrochloric acid. Then the mixture for 10 to 24 h incubated with heating at a temperature of 50-100°C, preferably at 80°S, and then cooled to room temperature. The mixture is diluted with aprotonin organic solvent such as ethyl acetate, a simple ether, chloroform or methylene chloride, and washed with aqueous alkali, such as sodium bicarbonate and potassium carbonate. The organic layer is dried with such agents as MgSO4and Na2SO4and remove volatile components to obtain a residue, which is purified by recrystallization or chromatography on silica gel using hexanol and ethyl acetate as eluents. Next fraction with a high content of product are collected and removed volatile components to obtain the desired aminopyrazole (formula XV).

In another embodiment according to the method And arylhydrazines formula X and β-ketonitriles is ormula XIV mixed in an organic solvent, such as toluene, ethanol, isopropanol or tert-butanol. The preferred solvent is toluene. The mixture was kept at the temperature of distillation within 3-24 h with azeotropic removal of water and after the processing described above, receive aminopyrazole formula XV.

Other necessary aminoheterocycles that can be used in the synthesis of compounds of formula I or Ia can be obtained by methods known in this field and described in the literature. Refer to the following schemes III-XV examples are illustrative, and therefore that it is obvious for specialists in this field, the specific reagents and conditions for reaction may vary depending on the individual compounds. Intermediate products used in the reactions of the diagrams shown below are either commercially available or can be obtained in a simple way by specialists in this field from commercially available materials.

In scheme III, method K, illustrates the General process for the synthesis of the target aminothiophenes.

Scheme III

A mixture of 1-aryl-5-alkylborane-1,4-dione (XVI) and sulfatide agent, such as a reagent Lawesson (Lawesson) or the sulfide of phosphorus (V), preferably the reagent Lawesson, dissolved in aprotonin anhydrous solvent such as toluene, THF or dioxane. PR is pactically solvent is toluene. The mixture was incubated with heating at an elevated temperature, preferably at a temperature of distillation of the solvent, for 1 to 10 hours After removal of the volatile components, the residue is purified by chromatography on silica gel using hexanol and ethyl acetate as eluent. Fractions with a high content of product are collected and removed volatile components with obtaining substituted thiophene of formula XVII.

This substituted thiophene of the formula XVII are dissolved in a solvent such as acetic anhydride or acetic acid. The preferred solvent is acetic anhydride. The mixture is cooled to 0-30°C, preferably -10°C. Next, add a solution of concentrated nitric acid in a solvent such as acetic anhydride or acetic acid, preferably acetic anhydride, cooling the mixture to 0-30°C, preferably -10°C. the mixture is stirred for 10-120 min, poured onto ice and extracted with aprotonin solvent, such as diethyl ether, chloroform, ethyl acetate or methylene chloride. The organic extracts are washed with aqueous alkali, dried with such agents as MgSO4and Na2SO4and remove volatile components. The residue is purified by chromatography on silica gel using hexanol and ethyl acetate as eluents. Fractions with high content about the ukta collect and remove volatile components to obtain 2-aryl-5-alkyl-3-nitrothiophene. This 2-aryl-5-alkyl-3-nitrothiophene restore using metal, such as iron, tin or zinc, or by catalytic hydrogenation. It is preferable to restore to use iron in acetic acid and to carry out such restoration at a temperature in the range from 50 to 110°S, more preferably at 100°within 5-30 minutes After cooling to room temperature the reaction mixture is diluted with water, neutralized by alkali, such as sodium hydroxide, potassium hydroxide, potassium carbonate or sodium bicarbonate, and extracted with aprotonin solvent, such as diethyl ether, ethyl acetate or methylene chloride. The organic extracts are dried with the help of such agents, as MgSO4and Na2SO4and remove volatile components to obtain the desired aminothiophene formula XVIII.

Scheme IV illustrates the overall method of obtaining the required aminopurine, as described by Stevenson and others (J. Am. Chem. Soc., 1937, 59, 2525). Thus acelrolaclo (formula XIX) dissolved in aprotonin a solvent such as a simple ether or THF, and treated with a strong base, such as sodium, ethoxide sodium or sodium hydride, and the resulting anion is subjected to interaction with Bromeliaceae (formula XX) at low temperature, for example at 0°C. After stirring the reaction mixture until then, until the IPM is shabetta all the source material, it was poured into cold water and extracted with aprotonin solvent. Then the combined extracts dried with such agents as MgSO4or Na2SO4. The resulting diketonates (formula XXI) can be used further without additional purification or to purify by distillation or by chromatography on silica gel. Further diketonates in proton solvent such as ethanol, is heated in the presence of a mineral acid such as sulfuric or hydrochloric acid, for 5-10 h and extracted with aprotonin solvent. Then the combined extracts dried with such agents as MgSO4or Na2SO4. Received furan ester (formula XXII) can be used further without additional purification or to purify by distillation or by chromatography on silica gel. Further, this furan ester in proton solvent such as ethanol, is treated with hydrazinehydrate and the mixture was incubated with heating in 2-5 days. Then hydrazine produce by the method described above and treated with hot formic acid, after which the resulting forenames (formula XXIII) purified by distillation or chromatography on silica gel.

Scheme IV

Substituted 4-aminoanisole can be synthesized analogously to the method described by Lakhan and others (J. Het. Chem., 1988, 25, 1413) and pollastri the bath in scheme V. The mixture of arolina (formula XXIV), aldehyde (formula XXV) and anhydrous ammonium acetate in uksunay acid withstand heating at 100-110°C for 3-6 h, cooled to room temperature and then the reaction stopped by adding water. After extraction aprotonin solvent receive the product of formula XXVI, which can be used subsequently without further purification or clean by recrystallization or chromatography on silica gel.

Scheme V

Substituted 3-aminopyrazole (formula XXX) can be synthesized analogously to the method described by Aiello and others, J. Chem. Soc. Perkins Trans. I, 1981, 1. This method is illustrated in scheme VI. The mixture eraldivxetuna (formula XXVII) and amine (formula XXVIII) in acetic acid withstand heating at 100-110°C for 3-6 h and then processed in the usual way. The resulting product (formula XXIX) in acetic acid is treated with a nitration agent, such as nitric acid or potassium nitrate in concentrated sulfuric acid. The mixture is poured forth into cold water and extracted with aprotonin solvent. Then the combined extracts dried with such agents as MgSO4and Na2SO4. Obtained after removal of volatile components nitropyrrole can be used without further complement Inoi cleaning or clean by recrystallization or chromatography on silica gel. This nitropyrrole reduced to amine with iron in acetic acid or by catalytic hydrogenation using palladium on charcoal. The resulting aminopyrrolo (formula XXX) can be used further without additional purification or clean by recrystallization or chromatography on silica gel.

Scheme VI

Similarly a mixture of an amine of formula XXXI and 3-aryl-2,5-dioxolane (formula XXXII) in acetic acid withstand heating at 80-110°C for 2-24 hours Then the reaction mixture was diluted with water and extracted with an organic solvent. After that, the combined extracts dried with such agents as MgSO4or Na2SO4and then remove the volatile components. The resulting pyrrole is treated with a nitration agent, and then by the method described above to restore the compounds of formula XXXIII. The resulting product can be used subsequently without further purification or clean by recrystallization or chromatography on silica gel. This process is illustrated in scheme VII.

Scheme VII

Substituted 5-aminothiazole (formula XXXVII) can be obtained similarly to the method described by Gerwald and others, J. Prakt. Chem. 1973, 315, 539. As shown in scheme VIII, to the mixture of aminosilica forms the crystals XXXIV, aldehyde of formula XXXV and sulfur in anhydrous solvent such as ethanol or methanol, are added dropwise base, such as triethylamine. The mixture was incubated with heating at 50°C for 1-3 hours then the mixture is cooled and remove the excess sulfur. Next, to the mixture to neutralize it add acetic acid and collect the solid. The resulting Imin formula XXXVI is treated with acid, such as hydrochloric or toluensulfonate acid, water and an organic solvent. After consumption of starting material the reaction mixture is subjected to processing, receiving the product formula XXXVII, which can be used subsequently without further purification or clean by recrystallization or chromatography on silica gel.

Scheme VIII

Substituted 2-aminothiophene (formula XXXIX) can be synthesized analogously to the method described by Gewald and others (J. Prakt. Chem., 1973, 315, 539) and illustrated in scheme IX. The mixture of disubstituted thiophene-3-carboxylic acid (formula XXXVIII) in proton solvent such as acetic acid, is treated at a temperature of 0-50°With a nitration agent, such as nitric acid or potassium nitrate in concentrated sulfuric acid. After consumption of starting material the reaction mixture was poured onto ice and the product extracted with diproton the m solvent. The combined extracts are dried with the help of such agents, as MgSO4and Na2SO4and remove volatile components. The resulting nitrothiophen reduced to amine with iron in acetic acid or by catalytic hydrogenation using palladium on charcoal. The resulting aminothiophene can be used subsequently without further purification or clean by recrystallization or chromatography on silica gel.

Scheme IX

1,5-disubstituted 3-aminopyrazole (formula XLII) can be obtained in accordance with the scheme X is similar to the method described by Ege and others (J. Het. Chem., 1982, 19, 1267). To anhydrous tert-butanol add potassium and the mixture is cooled to 5°C. After that add the hydrazine of formula XL, then cyanocobalamin formula XLI. The mixture is within 3-10 h heated under reflux at a temperature of distillation. After that, the mixture is cooled to room temperature and poured onto a mixture of ice water. The resulting product is extracted with an organic solvent. The combined extracts are dried with the help of such agents, as MgSO4or Na2SO4and remove volatile components. The resulting product of formula XLII can be used further without additional purification or clean by recrystallization or by chromatography on si is imagele.

Scheme X

2-amino-3,5-disubstituted tifany can be synthesized according to scheme XI similarly to the method described by Knoll and others, J. Prakt. Chem., 1985, 327, 463. The mixture of substituted N-(3-aminothiazol)formamidine (formula XLIII) and substituted bromide (formula XLIV) in proton solvent such as methanol or ethanol, is heated, preferably maintained at a distillation temperature for 5-30 min and then cooled to a temperature below room temperature. The resulting tietenkin filtered and dried. Next, tietenkin formula XLV processing aqueous acid is transformed into typename (formula XLVI).

Scheme XI

1,4-disubstituted 2-aminopyrene (formula L) can be synthesized analogously to the method described by Brodrick and others (J. Chem. Soc. Perkin Trans. I, 1975, 1910) and illustrated in scheme XII. This potassium salt of FamilyTree formula XLVII in water is treated with the amine of formula XLVIII and acetic acid, and the mixture was incubated with heating at 50 to 90°C for 5-30 minutes After cooling, the resulting aminonitriles formula XLIX is collected by filtration and then stirred at room temperature in the presence of a base, such as ethanol atoxic potassium, 2-5 h to remove volatile components. The residue is diluted with water and extracted with an organic solvent. Joint the United extracts are dried with the help of such agents, as MgSO4and Na2SO4and remove volatile components. The resulting product (formula L) can be used further without additional purification or clean by recrystallization or chromatography on silica gel.

Scheme XII

1,2-disubstituted 4-aminoimidazole (formula LII) can be obtained by recovery of the corresponding nitro compounds (formula LI), for example with iron in acetic acid or by catalytic hydrogenation, using the method described by Al-Shaar and others (J. Chem. Soc. Perkin Trans. I, 1992, 2779) and illustrated in scheme XIII.

Scheme XIII

2,4-disubstituted 5-aminoindazole (formula LVII) can be obtained similarly to the method described in Poupaert and others (Synthesis, 1972, 622) and illustrated in scheme XIV. When this acid chloride of the acid of formula LIII is added to the cooled mixture of 2-aminonitriles formula LIV and bases, such as triethylamine, in aprotonin a solvent such as THF, benzene, toluene or ether. Preferable the temperature 0°C. the Mixture is stirred for 12-24 h and washed with water. After removal of the volatile components of the resulting product of formula LV is treated with ethyl mercaptan and dry hydrogen chloride in dry methylene chloride within 5-30 minutes of Solid hydrochloride 5-imino-1,3-oxazole (formula LVI) collect f is litraly, dissolved in dry pyridine and the solution is saturated with hydrogen sulfide for 4 h at 0°C. the Mixture is diluted with an organic solvent, washed with water and dried. After removal of volatile components receive 5-amino-1,3-oxazole (formula LVII), which can be used subsequently without further purification or clean by chromatography on silica gel.

Scheme XIV

1,4-disubstituted 2-aminopyrazole can be synthesized in accordance with scheme XV according to the method described in Lancini, etc., J. Het. Chem., 1966, 3, 152. To a mixture of substituted aminoketone (formula LVIII) and cyanamide in water and acetic acid is added aqueous sodium hydroxide until then, until the pH value reaches to 4.5. After that, the mixture was incubated with heating at 50 to 90°C for 1-5 h, cooled and alkalinized with ammonium hydroxide. The resulting product of formula LIX is collected by filtration and dried.

Scheme XV

Arylamine and heteroelement intermediate products of the formula IV (G-NH2for the synthesis of compounds of formulas II and III are either commercially available products or can be easily obtained by methods known in this field. For example, the necessary arylamine and heteroarenes can be obtained by nitration and recovery substituted aryl or heteroaryl the ring, as illustrated for the synthesis of some 5-membered heterocyclic amines (Ar1-NH2) in the above schemes. In another embodiment, substituted arrowy ether can be turned into arylamine, as illustrated for the substituted furan in the above scheme IV and described below in example 17. In the section "Examples of synthesis described the processes of production and other compounds G-NH2and Ar1-NH2.

Methods to obtain the intermediates of formulas V and VI (scheme I, D' means a group Ar-X-Y-Z or Ar2-X-Y-Z), described below.

Scheme XVI

According to method L (scheme XVI) bromelin formula LX, which is or may be commercially available product, or can be easily obtained by a person skilled in the art, is subjected to the interaction with cycloalkanones formula LXI in the presence of a catalyst based on a transition metal, for example, a catalyst based on palladium (II), such as chloride bis(triphenylphosphine)palladium(II), and in the presence of bis(triphenylphosphino) chelating agent, such as 1,2-bis(diphenylphosphino)ethane (DFFA), 1,1'-bis(diphenylphosphino)ferrocene (DFFF) or 1.3 bis(diphenylphosphino)propane (DFFP), preferably DFFF, and base, preferably sodium bicarbonate, in an acceptable solvent, preferably DMF, at a temperature of prima is but 150° With obtaining the compounds of formula LXII. This compound of formula LXII can then be used (in the form of compounds of formula (VI) in method B (scheme I) or turn into isocyanate of formula LXIII interaction with phosgene or an equivalent amount of phosgene in the presence of a base such as sodium bicarbonate, in an acceptable solvent such as dichloromethane, at a temperature of approximately 0°and to use (in the form of compounds of formula (V) in method A. the resulting product of formula LXIV can be further modified by methods known to experts in this field, to obtain the desired compounds of formula I, as described in the examples below synthesis.

According to the method M bromide of formula LXV is subjected to interaction in the presence of a strong base such as tert-utility, in an acceptable solvent such as THF, with the presence of TBT chloride at a temperature in the range of from about -50 to -100°C, preferably at about -78°With obtaining the compounds of formula LXVI. This compound of formula LXVI is subjected to further interaction with the compound of the formula LX in an acceptable solvent such as THF or 1,4-dioxane, in the presence of a catalyst based on a transition metal, preferably tetrakis(triphenylphosphine)palladium(0), at a temperature of from about 50 to 150°C, preferably at about 100°C, in a tightly ukuporenna the tube with obtaining the compounds of formula LXVII. Then this compound of formula LXVII can be used (in the form of compounds of formula (VI) in method B or C (scheme I) or converted into the corresponding isocyanate, as described for method L and use (in the form of compounds of formula (V) in method A.

In scheme XVII illustrates methods to attach Y and Z to X. According to method N if necessary, to obtain a product in which Y comprises the amino nitrogen attached to X, group X containing ketone, can be subjected to interaction with group Y-Z containing terminal primary or secondary amine, under conditions gidroaminirovaniya. For example, the ketone of formula LXIV combined with primary or secondary amine in an appropriate solvent such as THF. Then add the acid, such as acetic acid, and then acceptable reducing agent, preferably cyanoborohydride sodium or (triacetoxy) borohydride sodium, to obtain the desired product of formula LXVIII.

The example method illustrated On the process of obtaining a methylene group for Y, and primary or secondary amine to Z. the group X, the carrier aldehyde and halogen, preferably bromine (formula LXIX), can be subjected to interaction with primary or secondary amine under conditions gidroaminirovaniya as described for method N, to obtain the compounds of formula LXX. This intermediate product you can use is to use a similar method M

Scheme XVII

As in the above cases, additional intermediate products corresponding to formula V, VI and VII can be synthesized by methods similar to those described in the literature or known to specialists in this field. Some examples of such synthesis are given below in the section "Examples of synthesis".

EXAMPLES SYNTHESIS

Example 1

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-cyclohexene-3-yl)naphthalene-1-yl]urea

According to the above described method L in a tightly useprivatekey tube with a volume of 350 ml in an inert atmosphere placed 4-bromo-1-naphtylamine (LXXI) (1.97 g, 8.9 mmole, 1 EQ.), 2-cyclohexenone (1.65 g, 17.2 mmole, 1.9 equiv.) powder sodium bicarbonate (2.17 g of 25.8 mmole, 2.9 equiv.) 1,3-bis(diphenylphosphino)propane (177 mg, 0.43 mmole, of 0.05 equiv.) chloride bis(triphenylphosphine)palladium (II) (302 mg, 0.43 mmole, of 0.05 EQ.) and DMF (degassed, 100 ml). The mixture was incubated with heating at 150°within 8 hours After cooling back to ambient temperature the mixture is diluted with 100 ml EtOAc and filtered through diatomaceous earth. After this, the solution is transferred into a separating funnel and washed with water (100 ml) and saturated brine (100 ml). After drying over MgSO4volatile components are removed under vacuum. The product is then purified column chromatography with the use of the eat EtOAc (10 to 50%) in hexano as eluent to obtain 1.3 g of material, which is recrystallized from a hot mixture of EtOAc/hexane to obtain 800 mg of the compound of formula LXXII (3.4 mmole, yield 38%) as a dark brown solid.

The compound of formula LXXII (100 mg, at 0.42 mmole, 1 EQ.) dissolved in methylene chloride (20 ml) and add saturated aqueous sodium bicarbonate solution (20 ml). The mixture is intensively stirred at 0°C for 15 minutes Then shuffle off to the organic layer in one portion via syringe is added phosgene (about a 2.0 molar solution in toluene, 0.63 ml, of 1.26 mmole, 3.0 EQ.). Directly after mixing resume and continue at 0°C for 20 minutes and Then the layers are separated, then the aqueous phase is extracted with methylene chloride (1×25 ml). The combined organic phases are dried (Na2SO4), filtered and3/4the solvent is removed in vacuum. Directly after this, the solution of the isocyanate of formula LXXIII diluted with anhydrous THF (8 ml) and treated with a compound of formula LXXIV at room temperature (method A). Next, the mixture is left to mix overnight in nitrogen atmosphere, and then add Meon (2 ml) and the volatile components removed in vacuo. This way, get listed in the title compound 1 as an orange/red foamy substance (200 mg, 0,41 mmole, 74%). This product twice paracrystalline is up during the night from EtOAc to obtain 49 mg of yellow crystals (t PL168-170°).

Example 2

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-[3-(morpholine-4-yl) cyclohexan-1-yl]naphthalene-1-yl}urea

According to the above method, the product from example (1) (93 mg, 0,19 mmole, 1 EQ.) and morpholine (30 μl, 0.34 in mmole, 1.8 EQ.) dissolved in 1.0 ml anhydrous THF and treated with acetic acid (16 μl, of 0.28 mmole, 1.5 EQ.) and (triacetoxy)with sodium borohydride (80 mg, of 0.39 mmole, 2 EQ.). The reaction mixture was stirred at room temperature for 2 days, and then add 5%aqueous NaOH solution (3 ml) and then the reaction mixture was extracted with EtOAc (3×3 ml). The combined organic phases are washed once with water and then brine, dried (Na2SO4), filtered and the solvents removed in vacuo. After column chromatography using EtOAc/hexanol as eluent obtain 64 mg of a foamy substance, yellowish-brown (0,11 mmole, 60%). This product is re-chromatographic using 5%Meon in methylene chloride to obtain specified in the title compound 2 as a foamy substance light purple (50 mg).

Example 3

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-{4-[5-(morpholine-4-ylmethyl)FSD-2-yl]naphthalene-1-yl}urea

According to the above method On to a mixture of 5-bromo-2-fural is Devida (LXXV) (1,76 g) and research (1,00 ml) in 40 ml anhydrous THF at room temperature, add acetic acid (0,60 ml), and then triacetoxyborohydride sodium (3.28 g). The mixture is stirred at room temperature for 3 h and then poured into saturated sodium bicarbonate solution (100 ml). After intensive stirring for 5 min, the layers separated and the aqueous layer was extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography gain of 2.09 g (8,49 mmole, yield 84%) of compound LXXVI.

According to the above described method M connection LXXVI (0,678 g, was 2.76 mmole) dissolved in 10 ml of anhydrous THF in an atmosphere of inert gas and the solution cooled to-78°C. Then added dropwise tert-utility (4,0 ml of 1.7 molar solution in pentane) and the solution stirred at -78°C for 30 minutes then add the presence of TBT chloride (0,60 ml, to 0.72 g, 2.2 mmole) and the solution stirred for another 30 min at -78°C. add the buffer with pH 7 (feast upon. NaH2PO4/Na2HPO4) (10 ml) and the mixture is heated to room temperature. The layers are separated and the aqueous layer was extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography receive 0,526 g (1.15 mmole, yield 42%) of compound LXXVII.

This compound LXXVII (0,399 g, 0,874 mmole) and compound LXXI (0,200 g ,901 mmole) according to the above described method M is dissolved in 10 ml of anhydrous 1,4-dioxane in a tightly useprivatekey tube in an atmosphere of inert gas. The solution Tegaserod and rinsed with nitrogen (twice). Next add tetrakis(triphenylphosphine)palladium(0) (0,057 g 0,049 mmole), after which the solution Tegaserod and again rinsed with nitrogen (twice). The tube is hermetically sealed and heated to 100°within 24 hours After cooling to room temperature the mixture is diluted with EtOAc, add saturated aqueous potassium carbonate solution (10 ml) and the mixture stirred for 1 h at room temperature. The mixture is filtered through diatomaceous earth and the layers separated. The aqueous layer was extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography receive 0,314 g of yellow oil, which contains a compound LXXVIII along with bromide presence of TBT. This mixture is used in the next stage without additional purification.

Connection LXXVIII (0,283 g, 0,917 mmole) is subjected to interaction with phenylcarbamate LXXIV (0,395 g of 1.13 mmole) according to method C. the resulting product is distilled Express chromatography to obtain specified in the title compound 3 as a yellow solid (0,338 g, 0,600 mmole, yield 65%), which is optionally purified by recrystallization with getting 0,131 g specified in the title compound 3 (tPL144-146°).

Example 4

1-[5-tert-butyl-2-p-tolyl-2H-feast of the ol-3-yl]-3-{4-[6-(morpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea

Similar to the method described in R.J.Chambers and A.Marfat (Synthetic Communications, 1997, 27, 515), a mixture of 2,5-dibromopyridine (LXXIX) (9,90 g, 41,78 mmole), Pd(DFFF)Cl2(1.51 g, of 1.85 mmole), anhydrous Meon (40 ml), anhydrous DMF (40 ml) and anhydrous triethylamine (12 ml) for 10 min, rinsed in a Parr apparatus a stream of carbon monoxide and then stirred at a pressure of carbon monoxide 80 psi with 50°C for 4 h the Mixture was diluted with EtOAc (600 ml), washed with water (2×100 ml) and brine (1×100 ml), dried (sodium sulfate), filtered and evaporated to dryness. The residue is purified rapid chromatography on silica gel (40%EtOAc in hexano) to obtain the compound LXXX in the form of a light orange solid (3,733 g, 17,28 mmole, 41%).

To a solution of compound LXXX (165,9 mg, 0,7679 mmole) in anhydrous THF (10 ml) at-78°With added dropwise diisobutylaluminium from 1.0 molar solution in THF) (2.0 ml, 2.0 mmole). The mixture was stirred at -78°C for 2 h, after which add a saturated solution of potassium carbonate (0.6 ml), the mixture is heated to room temperature and stirred for 30 minutes Then add the sodium sulfate and the mixture is stirred for 10 minutes, the Solid is removed by filtration and the filtrate evaporated to dryness. The residue is purified rapid chromatography on silica gel (20%EtOAc in hexano) obtaining Aldagi is and LXXXI in the form of a white solid (80 mg, 0.43 mmole, 56%).

To a solution of compound LXXXI (367,7 mg, 2.0 mmole) in anhydrous 1,2-dichloroethane (10 ml) is added morpholine (of 0.20 ml, 0.20 g, 2.3 mmole)and then glacial acetic acid (0,12 ml of 0.13 g, 2.1 mmole) and triacetoxyborohydride sodium (625 mg, 2,95 mmole). The mixture is stirred at room temperature for 30 minutes Then add saturated sodium bicarbonate solution (10 ml) and the mixture is intensively stirred for 30 minutes, the Layers separated and the aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers washed with brine, dried (sodium sulfate), filtered and evaporated to dryness. After the rapid-chromatography (1%triethylamine in EtOAc) of the residue receive connection LXXXII in the form of a light yellow oil (460,8 mg, 1,79 mmole, 91%).

To a solution of tert-utility (1,42-molar solution in pentane) (2,80 ml, 3,98 mmole) in anhydrous THF (20 ml) at -78°With added dropwise a solution of compound LXXXII (460,8 mg, 1,792 mmole) in anhydrous THF (10 ml) and the mixture was stirred at -78°C for 10 minutes Then add the presence of TBT chloride (0,49 ml of 0.59 g, 1.8 mmole) and the mixture was stirred at -78°even for 15 minutes then add buffer with pH 7 (feast upon. Na2HPO4/NaH2PO4) (10 ml) and the mixture is heated to room temperature. The layers are separated and the aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers washed with brine, dried (Sul is at sodium), filtered and evaporated to dryness. After the rapid-chromatography (EtOAc) of the residue receive connection LXXXIII in the form of a colorless oil (548,8 mg, 1,17 mmole, 65%).

Degassed solution of compound LXXXIII (302 mg, 0,646 mmole), compound LXXI (177 mg, 0,797 mmole) and Pd(PPhg)4 (55 mg, 0.48 mmole) in anhydrous 1,4-dioxane (10 ml) is heated to 100°C in a hermetically sealed tube for 16 h Black precipitate is removed by filtration and the tube was washed with EtOAc. The combined filtrate is stirred with a solution of potassium fluoride (40%) (10 ml) for 30 minutes Then add water and brine, the layers separated and the aqueous layer was extracted with EtOAc (4×50 ml). The combined organic layers washed with brine, dried (sodium sulfate), filtered and evaporated to dryness. After rapid chromatography (5%Meon and 1%triethylamine in EtOAc) of the residue receive connection LXXXIV in the form of a light brown solid (157,6 mg of 0.49 mmole, 76%).

Connection LXXXIV and phenylcarbamate LXIV subjected to interaction in accordance with method C. After purification Express chromatography using 5%Meon and 1%triethylamine in EtOAc as eluent followed by recrystallization from EtOAc/hexanol get mentioned in the title compound 4 as a white solid (tPL169-170°).

Example 5

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-{4-[3-(morpholine-4-yl)phenyl]naphthalene-1-yl}the urine is in

3 bromaniline (3.0 ml, 4.7 g, 28 mmol), 2-bromatology ether (4,2 ml of 7.7 g, 33 mmole) and diisopropylethylamine (15 ml, 11 g, 86 mmol) was dissolved in anhydrous DMF (20 ml) in an atmosphere of inert gas and heated to 100°C for 6 hours After cooling to room temperature the mixture is poured into water (300 ml) and extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography obtain 2.9 g (12 mmol, yield 43%) of compound LXXXVI

Compound LXXXVI (1.73 g, 7,13 mmole) dissolved in anhydrous THF (30 ml) and cooled to -78°C. Then added dropwise tert-utility (10.0 ml of 1.7 molar solution in pentane) and the solution stirred at -78°C for 30 minutes then add the presence of TBT chloride (1.90 ml, 2.28 g, 7,00 mmol) and the solution stirred for 45 min at -78°C. Then add a buffer with a pH of 7 (feast upon. NaH2PO4/Na2HPO4) (10 ml) and the mixture is heated to room temperature. The layers are separated and the aqueous layer was extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography receive 2.28 g (are 5.36 mmole, yield 77%) of compound LXXXVII.

Compound LXXXVII (1,49 g, 3,51 mmole) and compound LXXI (0,69 is, 3.11 mmole) was dissolved in 20 ml of anhydrous 1,4-dioxane in a tightly useprivatekey tube in an atmosphere of inert gas. Then, the solution Tegaserod and rinsed with nitrogen (twice). After that add tetrakis(triphenylphosphine)palladium (0) (0.21 g, of 0.18 mmole) and the solution again Tegaserod and rinsed with nitrogen (twice). The tube is hermetically sealed and can withstand heating at 100°C for 17 hours After cooling to room temperature the mixture is diluted with EtOAc, add saturated aqueous potassium carbonate solution (10 ml) and the mixture stirred for 1 h at room temperature. After that, the mixture is filtered through diatomaceous earth and the layers separated. The aqueous layer was extracted with EtOAc. The combined organic layers washed with brine, dried (Na2SO4), filtered and evaporated to dryness. After purification of the residue Express chromatography receive 0,363 g (1,19 mmole, 38%) connection LXXXVIII.

Connection LXXXVIII (0,360 g of 1.18 mmole) in accordance with the method is subjected to interaction with phenylcarbamate LXIV (0,69 g, 1.97 mmole). The resulting product is distilled Express chromatography to obtain a colorless solid matter (0,433 g, 0.77 mmole, yield 66%), which is further purified by recrystallization from EtOAc/hexanol getting 0,344 g specified in the title compound 5 (tPL18 8-190°).

Table 1 presents other compounds according to the invention, the cat is who get methods similar to that described above.

Table 1
Approx. No.R1R3XaYbZintPLthat °
6tert-Bu4-MePhphenyl4-CH24-morpholinyl146-148
7tert-Bu4-MePhphenyl3-CH24-morpholinyl120-122
8tert-Bu4-MePhphenyllink4g-(4-morpholinyl)>230
9tert-Bu4-MePhphenyl4-CH24-morpholinyl183-186
10tert-Bu4-MePhphenyl4-CH2NMe2P.108-114
11tert-Bu4-MePh2-pyridyl5-CH24-morpholinylfoam
12tert-Bu4-MePh1-cycloheptenyl link3g-(4-morpholinyl)133-135
13tert-Bu6-Me-3-pyridyl3-pyridyl6-(CH2)4-morpholinyl162 to 165
14tert-BuMe3-pyridyl6-(CH2)4-morpholinylfoam
15tert-Bu6-Me-3-pyridyl1-cyclohexenyl3-[NH-(CH2)2]4-morpholinyl
Note:

andthe number refers to the position X, which is attached to naftalinovogo ring (Ar2)

bthe number refers to the position X, which is attached to the Yinthe number refers to the position Z, which is attached to Y (or X, if Y denotes a bond),

gthe number refers to the position X, which is attached to z

Example 16

1-[4-(6-{[bis-(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-were)urea

To a solution of 4-tert-butyltoluene (by 33.7 mmole) in acetonitrile (150 ml) at 0°With add tetrafluoroborate nitrile-ion (40.5 mmole). After soaking for 30 min at room temperature, the reaction mixture was diluted with water is th (50 ml) and extracted with EtOAc (3× 30 ml). The combined organic extracts washed with brine and dried (MgSO4). Obtained after removal of volatiles in vacuo the residue is purified Express chromatography using 10%methylene chloride/petroleum ether as eluent to obtain 4-tert-butyl-2-nitrotoluene.

4-tert-butyl-2-nitrotoluene (1.1 mmole) is dissolved in DMF (10 ml). Next add the catalyst (10%Pd/C, 5 mg), and then add di-tert-BUTYLCARBAMATE (1.4 mmole). This mixture is blown with argon, and then incubated in an atmosphere of H2(1 ATM) for 12 hours the Mixture is filtered through a bed of diatomaceous earth, the filtrate is diluted with water and extracted with EtOAc (3×10 ml). The combined organic extracts washed with brine and dried (MgSO4). After evaporation of volatile components to obtain 265 mg of N-BOC-5-tert-butyl-2-methylaniline in the form of a crystalline solid.

To a mixture of N-BOC-5-tert-butyl-2-methylaniline (0.8 mmole) and triethylamine (0,22 mole) in benzene (10 ml) at room temperature using a syringe add trichloride boron (0.4 mmole). The obtained heterogeneous mixture was stirred at 80°C for 30 minutes then remove the heat source and add aminonaphthalene LXXXIX (0.7 mmole). The reaction mixture was stirred at room temperature for 16 hours Then the reaction mixture was diluted with water (10 ml) and the extras is Giroud EtOAc (3× 10 ml). The combined organic extracts washed with brine and dried (MgSO4). Obtained after removal of volatiles in vacuo the residue is purified Express chromatography using 10%Meon/EtOAc as eluent to obtain 300 mg of the target urea XC.

This urea is placed in acidic conditions to remove the acetal, which manifests the presence of the aldehyde function. This aldehyde in 1,2-dichloroethane add 1.25 equivalents of bis (2-cyanoethyl) amine, and then add triacetoxyborohydride sodium (1.5 equivalent). After column chromatography (5%Meon/EtOAc) receive specified in the header of the connection 16.

Example 17

1-(6-tert-butyl-2-chloro-3-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea

To a stirred solution of N-BOC-1-amino-4-bromonaphthalene (15,5 mmole) in anhydrous THF (40 ml) at -78°add n-BuLi (47 mmol). The yellow-green solution was stirred at -78°C for 2 h, and then transferred into a solution of triethylborane (5,64 g, 54,2 mmole) in anhydrous THF (25 ml) at -42°C. the Reaction mixture is allowed to warm to room temperature during the night as heat baths. After stirring for 16 h add 5%aqueous HCl (25 ml) and the mixture is stirred for 15 minutes the Aqueous layer was saturated with Sodium chloride and the layers separated. the same phase is extracted with diethyl ether (3× 60 ml) and then the combined organic phases are extracted with a 0.5-molar solution of NaOH (6×30 ml). The combined alkaline extracts are acidified with 3M HCl (30 ml) to a pH of about 2 and the suspension is extracted with diethyl ether (3×100 ml). The combined ether extracts are dried (MgSO4), filtered and removed solvent to obtain Bronevoy acid XCI in the form of a beige solid (2.3 g), which is used further without additional purification.

5-bromo-2-(morpholine-4-ylmethyl)pyridine (0,70 mmole) and compound XCI (0,70 mmole) is dissolved in a biphasic mixture of dimethoxyethane (2 ml) and 2-molar aqueous Na2CO3(1 ml). The reaction mixture is rinsed with stream N for 15 min, add the Pd catalyst and the mixture was incubated with heating at 85°C for 16 hours then the reaction mixture is cooled to room temperature and partitioned between water (10 ml) and EtOAc (75 ml). The layers are separated and the organic phase washed with brine (20 ml), dried (MgSO4), filtered and removed solvent to obtain a brown solid. After column chromatography receive the product XCII in the form of a beige solid.

Connection XCII (0,50 mmole) dissolved in 2 ml of anhydrous dioxane and add HCl (2.5 mmole). The solution was stirred at room temperature for 16 hours Then to the resulting suspension add the diethyl ether (5 ml) and the mixture cooled to 0° C. After neutralization with aqueous NaOH and filtered receive 4-16-(morpholine-4-ylmethyl)pyridine-3-yl]-1-aminonaphthalene (XCIII) as light brown solid (100 mg).

A mixture of methyl ester 2-tert-butyl-6-chloro-5-methylpyridin-4-carboxylic acid (2,27 g, 9,39 mmole) and LiOH monohydrate (2,36 g, 56.3 mmole) in Meon (30 ml) and water (10 ml) was stirred at room temperature for 24 h Then the reaction mixture was concentrated and purified by chromatography on silica gel (eluent: 5%TFUK in dichloromethane) to give the corresponding carboxylic acid (1,41 g, 66.3 per cent).

To mix the solution obtained at the previous stage carboxylic acid (0.54 g, a 2.36 mmole) and triethylamine (0,66 ml, 4.75 mmole) in THF (6 ml) at -10°With added dropwise ethylchloride (0,34 ml, 3,51 mmole). The resulting mixture was stirred at 0°C for 1 h then add a solution of sodium azide (0.40 g, 6.0 mmol) in water (2 ml) and stirring is continued for another 1 h, the Mixture is extracted with toluene. The organic phase separated, dried with sodium sulfate and concentrate to a volume of 15 ml. of the Concentrate is heated under reflux for 2 h, which is accompanied by formation in situ isocyanate, and then add a solution of compound XCIII (0.39 g, of 1.23 mmole) in dichloromethane (5 ml). The reaction mixture was stirred at room themes is the temperature value during the night. After concentration and chromatography on silica gel (eluent: EtOAc) get mentioned in the title compound 17 (0,60 g, 89.9 percent).

Example 18

1-(5-tert-butyl-2-were)-3-(4-[6-[(3-methoxypropyl)methylamino]pyridine-3-yl)naphthalene-1-yl)urea

2.5-dibromopyridine (100 mg) is heated in a hermetically sealed tube to 115°in the presence of 3-methoxypropyl-1-methylamine (2 ml) for 48 h with connection XCIV. After the reaction combinations Suzuki (Suzuki) connection XCIV connection XCI and removal of the tert-BUTYLCARBAMATE (similar to that described in example 17 the process) and get targeted naphtylamine XCV.

5-tert-butyl-2-methylaniline (of 0.56 mmole) dissolved in dichloromethane (20 ml). Then add an equal volume of saturated aqueous sodium bicarbonate and two-phase solution is cooled to 0°C. during the addition of phosgene (1,93 M in toluene, at 0.80 ml) stirring is halted. Directly after mixing resume and continue for 15 min with the reaction mixture at 0°C. the Layers are separated, the organic phase is dried over solid magnesium sulfate and the solution is concentrated to approximately the volume of 5 ml Next add the necessary naphtylamine (XCVI, of 0.47 mmole) in 5 ml of dichloromethane. The reaction mixture was stirred at room temperature for 16 hours After a rapid-chromatography with the use of the cation 7%Meon/EtOAc as eluent and subsequent trituration with simple ether get mentioned in the title compound 18.

Example 19

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triptoreline)urea

Stir a solution of 3-triptorelin (4.7 mmole) in dry THF (30 ml) is treated at 0°phenylcarbamate (4.8 mmole). After 2 hours the reaction is stopped by addition of an aqueous saturated solution of sodium bicarbonate and extracted with EtOAc. The combined organic layers washed with aqueous saturated sodium bicarbonate solution and brine and dried over solid MgSO4. After concentrating receive carbamate XCVI (97%). After that, the mixture of compounds XCIII (example 17) (0,06 mmole) and the specified carbamate (0.05 mmole) is heated for 2 days in a tightly sealed tube. Then the reaction mixture is cooled to room temperature. Next add PS-trisamine (100 mg, firm Argonaut) and PS-isocyanate polymers (150 mg, firm Argonaut) and the reaction mixture is shaken for 3 days. After that the reaction mixture is filtered and concentrated to obtain specified in the connection header 19.

In examples 20-25 illustrates the synthesis of aryl - and heteroelement that can be used as an intermediate product IV in methods a-C (see section "General synthetic methods") to obtain compounds of the formula II or III.

Example 20

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]amine

Methyl-4-tert-butylphenoxyacetyl (20 mmol) dissolved in Meon (160 ml) and treated with water (40 ml) and LiOH monohydrate (30 mmol). Then the reaction mixture was allowed to mix at room temperature over night. Then under reduced pressure to remove volatile components, the resulting residue was diluted with water and neutralized to pH 4 with 1 N. sulfuric acid. The obtained solid is filtered off, washed with water and dried to obtain 4-tert-butylphenoxy acid in the form of not-quite-white solid (3.8 g, 99%).

Anhydrous DMF (139 mmol) cooled to 0°and treated With POCl3(79.6 mmole). After 5 min add 4-tert-butylphenoxy acid (to 19.9 mmole) and the reaction vessel placed in an oil bath with a temperature of 110°C. the Reaction mixture was stirred for 2 h, at the same time all solids dissolved. After cooling to room temperature the reaction mixture was poured into a mixed solution NaPF6(to 19.8 mmole) in water (200 ml). Upon completion of precipitation it is filtered off, washed with water and dried to obtain compound XCVII (7,8 g, 97%).

Connection XCVII (5 mmol) is dissolved in EtOH (50 ml) and the resulting suspension is treated with hydrazinehydrate (5 mmol). After that the reaction vessel placed in an oil bath with a temperature of 90°and the reaction mixture is stirred at reflux for 2 hours After cooling the reaction mixture to room temperature, the volatile components are removed under reduced pressure. The residue is dissolved in ice water, the solid is filtered off, washed with water and dried, obtaining 4-(4-tert-butylphenyl)pyrazole (973 mg, 97%).

This 4-(4-tert-butylphenyl)pyrazole (0.5 mmole) suspended in MeCN (2 ml), cooled to 0°With process and NO2BF4(0.6 mmole). The reaction mixture is allowed to slowly warm to room temperature and stirred at room temperature (RT) for 2 hours After termination of the reaction by addition of an aqueous NaHCO3volatile components are removed under reduced pressure. The residue is dissolved in water and extracted with CH2Cl2. The combined organic phases, dried over MgSO4and concentrated to a yellow oil, which chromatographic on silica gel (eluent: CH2Cl2/EtOAc in a ratio of 6:4)to give the 4-(4-tert-butyl-2-nitrophenyl) pyrazole as a yellow crystalline solid (71 mg, 58%).

4-(4-tert-butyl-2-nitrophenyl)pyrazole (a 0.27 mmole) is dissolved in EtOH (3 ml) and treated with 10%Pd/C (0.2 equiv. in terms of the weight of nitro compounds), and then NH4CO2H (2.7 mmole). After 30 min, the catalyst was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure. The residue is dissolved in water,the resulting solid is filtered off, washed with water and dried (54 mg, 93%), receiving specified in the header of the connection 20.

Example 21

3-amino-2-methoxy-5-tert-butylpyridinium

The ammonium hydroxide (25 ml, 11%) add ethylnitrosourea (3,3 ml, 4.0 g, and 29.7 mmole) and stirred over night as described in A.V.Amet and others, Russian Chemical Bulletin, 1996, 45(2), 393-398. Next, the reaction mixture is alkalinized 4h. hydrochloric acid, extracted with simple ether (3×25 ml)and then EtOAc (3×100 ml). The combined EtOAc extracts are dried (magnesium sulfate), filtered and evaporated to dryness to obtain nitroacetate in the form of a pale yellow solid (1.7 g, 16.3 mmole, 55%).

To 100 ml of cooled ice nitromethane in the atmosphere of nitrogen is added slowly trichloramine (45,5 g, 341 mmol). Then within hours added dropwise a solution of malononitrile (21,5 ml, and 22.6 g, 341 mmol) in 50 ml of nitromethane, keeping the temperature below 10°C. Then slowly for 2.5 h add a solution of tert-butyl chloride (88 ml of 74.9 g, 809 mmol) in 25 ml of nitromethane, keeping the temperature below 10°C. the Reaction mixture is closed and placed in the freezer for 60 hours thereafter, to the reaction mixture to suppress intense reaction dropwise in 4 hours to add saturated aqueous bicarbonate sodium (500 ml), keeping the temperature below 10°C. Then heterogeneous with whom ect is neutralized with solid sodium bicarbonate (50 g). The layers are separated and the aqueous layer was extracted with methylene chloride (3×250 ml). The combined organic extracts dried (magnesium sulfate) and concentrated in vacuo to obtain 42 g of a partially crystalline brown oil. The residue is distilled in vacuum at 100°C. the First fraction is collected, after which the capacitor begins the formation of solids. Then turn off the cooling water and the condenser is heated by using a heating gun to melt the solids. This fraction is collected up until the condenser by passing cooling water through it will not stop the formation of solid substances, which results in the target dinitrile in the form melting at a low temperature solid cream color (19 g, 155 mmol, 46%).

The solution of this dinitrile (961 mg, of 7.9 mmole) in anhydrous hexano (50 ml) is cooled in an atmosphere of nitrogen to -70° in a bath of dry ice/acetone. After this dropwise within 20 min add diisobutylaluminium (DIBAH) (17.5 ml, 1.0 M in cyclohexane). The mixture is stirred at -70°C for 45 min and then at room temperature for 5 hours, the Reaction mixture was cooled to 0°With, then slowly add 2-molar aqueous solution of hydrochloric acid (45 ml), keeping the temperature below 10°C. the Mixture is stirred at room the Oh temperature for 15 hours The layers are separated and the aqueous layer was extracted with simple ether (3×25 ml). The combined organic extracts dried (magnesium sulfate), filtered and evaporated to dryness to obtain the desired dialdehyde in the form of a viscous yellow oil (600 mg, and 4.68 mmole, 60%).

The solution of this aldehyde (271 mg, 2,11 mmole), nitroacetate (223 mg, and 2.14 mmole) and piperidine (20%in EtOH) (250 μl, of 0.51 mmole) in absolute EtOH (3 ml) incubated with heating at 65°C for 3 hours After cooling to room temperature the reaction mixture was concentrated in vacuo. The residue is purified rapid chromatography on silica gel (EtOAc) to give the target nitropyridine in the form of a yellow solid (280 mg, 1,43 mmole, 67%).

A mixture of nitropyridine (150 mg, from 0.76 mmole), pentachloride phosphorus (199 mg, 0.96 mmole) and phosphorus oxychloride (1 drop) was heated to a temperature distillation in a hermetically sealed tube. After 2 h of phosphorus oxychloride is removed in vacuo and the residue is stirred in ice-cold water (10 ml) for 18 hours then collect the desired product as a brown solid (95 mg, of 0.44 mmole, 58%).

To a solution of 2-chloro-3-nitro-5-tert-butylpyridinium (30 mg, of 0.14 mmole) in anhydrous Meon (1.5 ml) under nitrogen atmosphere add a solution of sodium methoxide (of 1.57 g of sodium in 40 ml of anhydrous Meon) (85 μl, of 0.14 mmole). The reaction mixture during the night heated in hermetically sealed in the cabin in an oil bath with a temperature of 80-90° C. thereafter, the volatile components are removed under vacuum, the residue is dissolved in EtOAc (15 ml), washed with water (10 ml) and brine (10 ml), dried (magnesium sulfate), filtered and evaporated to dryness. After rapid chromatography of the residue on silica gel (10%EtOAc in hexano) get the target 2-methoxy-3-nitro-5-tert-butylpyridinium in the form of a vitreous yellow solid (12 mg, 0,057 mmole, 41%).

To the suspension obtained at the previous stage intermediate product (12 mg, 0,057 mmole) and Pd/C (10%, 14 mg) in absolute EtOH (1 ml) is added ammonium formate (22 mg, 0.35 mmole) and the mixture is heated to 50°C for 1 h, After cooling, the reaction mixture is filtered through diatomaceous earth and washed with Meon. The filtrate is evaporated to dryness, obtaining mentioned in the title compound 21 as a brown solid (10 mg, by 0.055 mmole, 100%).

Example 22

N-acetyl-5-amino-3,3-dimethylindoline

The solution oxindole (5.0 g, 37.5 mmole) in acetic anhydride (7,1 ml, 75,1 mmole) and acetic acid (25 ml) is heated under reflux for 20 hours After cooling to room temperature the reaction mixture was diluted with water (200 ml). The obtained solid is filtered off, washed with water and dried to obtain N-acetylindole in the form of a white solid (5.2 g, 79%).

A mixture of this N-acetylindole (2.0 g, 11.4 mmole), iodine is ETANA (1,56 ml, 25,1 mmole) and potassium carbonate (3.1 g, of 22.8 mmole) in DMSO (20 ml) was stirred at room temperature for 20 hours then the reaction mixture is diluted with water. The obtained solid is filtered off, washed with water and dried to obtain N-acetylpenicillamine as an orange solid (1.9 g, 84%).

The solution of this N-acetylpenicillamine (500 mg, 2.5 mmole) in 3 N. sulfuric acid (7 ml) and THF (7 ml) is heated under reflux for 4 hours After cooling to room temperature the reaction mixture was diluted with simple ether. The ether layer is washed with water and brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The residue is purified rapid chromatography on silica gel (eluent: 30%EtOAc in hexano) to produce dimethoxyindole as a red solid (228 mg, 57%).

The solution of this dimethoxyindole (220 mg, 1.4 mmole) in toluene (5 ml) is treated with 65%solution of Red-Al in toluene (0,64 ml of 2.05 mmole) at 80°C. After stirring at 100°C for 4 h and the reaction stopped by adding 1 n sodium hydroxide solution. The organic layer was separated, washed with water and brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue is purified rapid chromatography on silica gel (eluent: 25%EtOAc in hexano) in obtaining dimethylindoline in the form of blue light is about oil (121 mg, 60%).

The solution of this dimethylindoline (65 mg, of 0.44 mmole) and triethylamine (0,12 ml, from 0.88 mmole) in dry dichloromethane (3 ml) is treated with acetylchloride (0.05 ml, of 0.66 mmole) at 0°C. the Mixture is allowed to warm to room temperature and stirred for 16 h Then the reaction stopped by the addition of water and the product extracted with simple ether. The organic layer was washed with water and brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue is purified rapid chromatography on silica gel (eluent: 30%EtOAc in hexano) to obtain N-acetylpiperidine in the form of a light yellow oil (68 mg, 82%).

The solution of this N-acetylpiperidine (65 mg, 0.34 in mmole) in acetic acid (2 ml) is treated with fuming nitric acid (24 μl, 0.57 mmole) at room temperature and the resulting mixture was stirred for 1 h then the reaction stopped by adding a saturated solution of sodium bicarbonate and the product extracted with EtOAc. The organic layer was washed with water and brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue is purified rapid chromatography on silica gel (eluent: 50%EtOAc in hexano) to obtain the desired nitrated indoline in the form of a light orange solid (66 mg, 67%).

A mixture of N-acetyl-3,3-dimethyl-5-nitroindoline (64 mg, of 0.27 mmole), ammonium formate (86 mg, of 1.36 mmole) and 10%palla the Oia coal (5 mg) in the Meon (5 ml) was stirred at room temperature for 2 hours The reaction mixture was filtered through a short plug of diatomaceous earth. Thereafter, the filtrate was concentrated in vacuo. The residue is purified rapid chromatography on silica gel (eluent: 50%EtOAc in hexano) obtaining specified in the title compound 22 as a white solid (48 mg, 87%).

Example 23

8-amino-6-tert-butyl-3-oxo-4-N-methylbenzamide

To a solution of 4-tert-butyl-2,6-dinitrophenol (3,15 g, 13,13 mmole) in 100 ml of acetonitrile, add ammonium formate (5.0 g, 78,8 mmole) and 10%palladium on coal (1.0 g). The mixture is heated under reflux for 20 min, then allowed to cool and filtered through diatomaceous earth. The residue was washed with EtOAc and the combined organic phases are evaporated in vacuum. The residue is dissolved in dichloromethane and filtered through korotkow plug of silica gel. After removal of solvent in vacuo get 2-amino-4-tert-butyl-6-NITROPHENOL in the form of a red solid (a 4.86 mmole, yield 37%).

To a solution of 2-amino-4-tert-butyl-6-NITROPHENOL (258 mg, of 1.23 mmole) and chloride of benzyltriethylammonium (BTEA) (280 mg, of 1.23 mmole) in 5 ml of chloroform, add finely ground NaHCO3(413 mg, to 4.92 mmole). The mixture is cooled to 0°and dropwise via syringe over 15 min add β-chlorocatechol (0,12 ml of 1.47 mmole) in 1.5 ml of chloroform. Upon completion EXT is the case, the mixture is left to mix at 0° C for 1 h the mixture is allowed to warm to ambient temperature and finally gently heated under reflux for 6 hours resulting crude orange mixture is allowed to cool, and then filtered through diatomaceous earth to separate a white precipitate, which is washed thoroughly with a large amount of chloroform. After removal of the solvent in vacuum, the oily residue is treated with water (40 ml) and stirred with a spatula, resulting in a yellow precipitate. This pure 6-tert-butyl-8-nitro-3-osobennosti filtered and dried first in a stream of air and then in vacuum (1.05 mmole, 85%).

To a solution of 6-tert-butyl-8-nitro-3-osobennostyu (51 mg, of 0.20 mmole) in 3.5 ml of DMF at 0°one portion add sodium hydride (10 mg, 60%dispersion in mineral oil, 0.24 mmole). After 20 min using a syringe add methyliodide (20 μl, 0.24 mmole). Mixture is allowed to slowly warm to ambient temperature overnight. To the crude mixture to terminate the reaction, add saturated aqueous solution of ammonium chloride and extracted with EtOAc (3×10 ml). The combined organic phases are washed with water and then brine, then dried over sodium sulfate. After filtration and removal of solvents in vacuo get 6-tert-butyl-8-nitro-3-oxo-4-N-methylbenzamide (100%).

This 6-tert-butyl-8-nitro-3-oxo-4-N-mate benzoxazin (53 mg, 0.2 mmole) was dissolved in 12.5 ml of acetonitrile. After that add cyclohexen (0,20 ml, 2.0 mmole) and 10%palladium on coal (75 mg). The mixture is heated under reflux for 1 h, then cooled to ambient temperature and filtered through diatomaceous earth. The residue was washed with EtOAc and the combined organic phases are evaporated in vacuum, obtaining mentioned in the title compound 23 (100%).

Example 24

7-amino-5-tert-butyl-3H-benzoxazol-2-he

To a solution of 2-amino-4-tert-butyl-6-NITROPHENOL (300 mg, 1,43 mmole) and pyridine (0,30 ml) in methylene chloride (30 ml) is added 4-nitrophenylphosphate (280 mg, of 1.39 mmole). The mixture is stirred for 24 hours the resulting solution was washed with aqueous sodium bicarbonate (2×20 ml), dried over solid magnesium sulfate and concentrated to obtain an orange solid. After column chromatography (silica gel, eluent: 40%EtOAc/petroleum ether) to obtain 5-tert-butyl-7-nitro-3H-benzoxazol-2-he (70%).

This 5-tert-butyl-7-nitro-3H-benzoxazol-2-he (200 mg, 0.9 mmole) was dissolved in EtOH (10 ml). After that add cyclohexane (4 ml) and 10%palladium on coal (50 mg). The mixture is heated under reflux for 3 h, and then cooled to ambient temperature and filtered through diatomaceous earth. After column chromatography (silica gel, eluent: 25%EtOc/petroleum ether) get mentioned in the title compound 24 (70%).

Example 25

7-amino-5-tert-butyl-2-methylbenzothiazol

2-amino-4-tert-butyl-6-NITROPHENOL are dissolved in triethylorthoformate (10 ml). The reaction mixture was stirred over night at 100°C. After evaporation of volatile components in vacuo get 5-tert-butyl-2-methyl-7-nitrobenzoxazole (110 mg).

This 5-tert-butyl-2-methyl-7-nitrobenzoxazole (100 mg, 0.4 mmole) is dissolved in EtOH (20 ml). After that add the catalyst (10%Pd/C (100 mg), and then ammonium formate (160 mg, 0.3 mmole). The obtained heterogeneous mixture was stirred at 100°C for 1 h After filtration and subsequent evaporation receive specified in the title compound 25 (85 mg).

In examples 26-29 considered a synthesis of the four heteroelement that can be used as an intermediate product IV in methods a-C (see section "General synthetic methods") to obtain compounds of the formula I or Ia.

Example 26

5-(5-amino-3-tert-butylphenol-1-yl)-2-methylbenzamide

3-iodine-4-methylphenylamine (10 g, 43 mmole) was dissolved in 6 BC HCl (40 ml) and cooled to 0°With intensive stirring during this process. Sodium nitrite (2.9 g, 1.03 EQ.) dissolved in water (5 ml) and this solution is added dropwise to the reaction mixture. After 30 minutes using a dropping funnel to add the chloride dihydrate tin(II) (22, g, 1 mol) in 6 BC HCl (100 ml) and the reaction suspension is stirred at 0°C for 3 hours After that, the pH value with 40%aqueous sodium hydroxide solution set 14 and the aqueous mixture extracted with EtOAc (6×50 ml), dried (MgSO4) and concentrated to obtain 3-iodine-4-methylphenylhydrazine (7 g, 57%). This material is used directly in subsequent reactions without further purification.

The solution of the above phenylhydrazine (5,08 g, 22 mmole) 4,4-dimethyl-3-oxopentanenitrile (a 3.06 g, 1.1 EQ.) in EtOH (100 ml)containing conc. HCl (3 ml), heated under reflux for 17 h, then cooled to room temperature. The pH value with 40%aqueous sodium hydroxide solution set at 14. The aqueous mixture is extracted with EtOAc (3×50 ml), dried (MgSO4) and concentrated to obtain 5-tert-butyl-2-(3-iodine-4-were)-2H-pyrazole-3-ylamine (6.3 g, 86%). This material is used directly in subsequent reactions without further purification.

5-tert-butyl-2-(3-iodine-4-were)-2H-pyrazole-3-ylamine (2 g, 5.6 mmole) combine with cyanide zinc (397 mg, 0.6 EQ.) and tetrakis(triphenylphosphine) palladium (0) (325 mg, 5 mol.%) in deoksigenirovanii dimethylformamide (10 ml). The obtained yellow suspension incubated with heating at 100°C for 4 h, cooled to room temperature, and then diluted with Russolo and 2 N. HCl. The aqueous mixture is extracted with EtOAc (6×10 ml), dried (MgSO4) and concentrate. The residue is purified Express chromatography, elwira a mixture of 20%EtOAc/petroleum ether, to obtain 1.3 g (91%) of the target nitrile.

This nitrile (150 mg, 0.6 mmole) in EtOH (5 ml) for 2 h, heated to 100°in the presence of 10 N. NaOH. After that the reaction mixture is cooled to room temperature, neutralized with 50%HCl, extracted with EtOAc (6×10 ml), dried (MgSO4) and concentrate to obtain specified in the title compound 26 (130 mg, 80%).

Example 27

5-amino-2-methoxypyridine (5.0 g, 40 mmol) dissolved in 6 BC HCl (10 ml) and cooled to 0°With intensive stirring during this process. Sodium nitrite (2.8 g, 41 mmol) dissolved in water (10 ml) and this solution is added to the reaction solution. After 30 minutes add the chloride dihydrate tin (II) (52 g, 230 mmol) in 6 BC HCl (20 ml) and the reaction suspension is stirred at 0°for 2.5 hours, the pH Value with 40%aqueous sodium hydroxide solution set at 13. Then add ethyl ether and the mixture extracted with EtOAc (4×70 ml), dried (MgSO4) and concentrated to obtain 5-hydrazino-2-methoxypyridine as an orange solid (5.1 g).

A solution of 5-hydrazino-2-methoxypyridine (2.5 g, 18 mmol) and 4,4-dimethyl-3-oxopentanenitrile (2.3 g, 1 mmol) in toluene (50 ml) is heated under reflux for 17 h in a flask, equipped with a trap Dean-stark, and then cooled to room temperature. Then the reaction mixture was concentrated and the residue purified column chromatography on silica gel, elwira a mixture of 30%EtOAc/petroleum ether, to obtain specified in the connection header 27 in the form of a yellowish-brown solid (3.5 g, 80%).

Example 28

5-amino-3-tert-butyl-1-(2-pyridone-5-yl)pyrazole

To the solution obtained in example 27 product (0.6 g, 2.4 mmole) in acetic acid (3 ml) is added 48%HBr in acetic acid (3 ml). The reaction mixture is heated to 120°C for 15 min, cooled to room temperature and then the pH value using a 10%aqueous solution of sodium hydroxide install 7.5. The aqueous mixture is extracted with EtOAc (4×15 ml), dried (MgSO4) and concentrate to obtain a yellowish brown solid. Specified in the title compound 28 (0,46 g, 82%) was obtained after recrystallization from a simple ether.

Example 29

5-amino-3-tert-butyl-1-(2-cyanoethyl)pyrazole

A solution of 2-cyanoethylidene (3.0 g, 35 mmol) and 4,4-dimethyl-3-oxopentanenitrile (4,2 g, 34 mmole) in toluene (50 ml) is heated under reflux for 17 h in a flask equipped with a trap Dean-stark, and then cooled down to room temperature is. The suspension is filtered and the filtrate concentrated. Column chromatography of the residue on silica gel with elution with a mixture of 50%EtOAc/petroleum ether get mentioned in the title compound 29 as a colourless solid (2.6 g, 40%).

Example 30

1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazole-3-yl]-3-{4-[6-(morpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea

Pinacolin (100 mmol) and diethyloxalate (120 mmol) dissolved in THF (200 ml), cooled to -78°and treat hexamethyldisilazide lithium (Li-HMDS, 120 mmol, 1-molar solution in THF). Then the ice bath removed and the reaction mixture allowed to warm to room temperature. After 2 h to remove volatile components and the crude residue is dissolved in ice SPLA (200 ml). Then add hydrazinoacetate (110 mmol), the reaction mixture was placed in an oil bath with a temperature of 90°C and stirred overnight. After that the SPLA is removed under reduced pressure and the crude residue is dissolved in aqueous NaHCO3getting a solution with a pH of 6. Next, the solid is filtered off, washed with water and dried to obtain the target pirazolonove ester (12.9 g, 66%).

KO-tert-Bu (67 mmol) was dissolved in DMSO (120 ml). Further, one portion of the type obtained in the previous phase phrasology ether (12 g, 61 mmol) and the reaction mixture is peremeshivayte within 15 minutes After that add tert-butylbromide (92 mmole) and the reaction mixture was stirred at room temperature for 45 minutes Then DMSO is removed under reduced pressure and the crude residue is diluted with ice water and extracted with CH2Cl2. The combined organic phases, dried over MgSO4and concentrate to obtain an isomeric mixture of pyrazoles as an orange oil (21 g). The target isomer is isolated in the form of an oil by chromatography on silica gel, elwira CH2Cl2(13.3 g, 70%).

Phrasology fluids (13.3 g, 43 mmole) was dissolved in pure TFOC (150 ml) and stirred at room temperature for 3 hours then remove the volatile components and the crude residue is diluted with ice water and extracted with CH2Cl2. The combined organic phases are washed with water, dried over MgSO4and concentrate to obtain the desired carboxylic acid as a thick oil which partially crystallizes (10.2 g, 94%).

Anhydrous DMF (282 mmole) is cooled to 0°and treated With POCl3(161 mmol). After 5 min add obtained at the previous stage pyrazol derivative of acetic acid (10.2 g, 40 mmol) and the suspension was placed in an oil bath with a temperature of 110°C. After that the reaction mixture is stirred for 2 hours at this dissolves all solid. After cooling to room so the temperature of the reaction mixture is poured into a mixed solution NaPF 6(80 mmol) in water (400 ml). Upon completion of precipitation it is filtered off, washed with water and dried, obtaining the target viramidine salt XCVIII (14.6 g, 78%).

This salt XCVIII (233 mg, 0.5 mmole) was dissolved in DMSO (10 ml) and treated with sulfate S-methylisothiazoline (0.25 mmole) and K2CO3(0.25 mmole). After that the reaction mixture is placed in an oil bath with a temperature of 90°C and stirred for 2 hours, After cooling the reaction mixture to room temperature to remove volatile components under reduced pressure. The residue is dissolved in ice-cold water and extracted with diethyl ether. The combined organic phases, dried over MgSO4and concentrated to obtain a brown resin. Target ethyl ester is purified by chromatography on silikagelevye column, elwira a mixture of CH2Cl2/EtOAc to 1:1 ratio, to obtain a yellow oil, which crystallized upon standing (157 mg, 98%).

Obtained in the previous phase of the ester (150 mg, of 0.47 mmole) is dissolved in Meon (4 ml) and water (1 ml), treated with LiOH monohydrate (0.7 mmole) and stirred at room temperature overnight. Then remove the volatile components and the residue diluted with water and neutralized to pH 4 with 1 N. sulfuric acid. The solid is filtered off, washed with water and dried (113 mg, 82%).

The obtained carboxylic acid (105 mg, 0.36 and IMO is I) is suspended in benzene (4 ml) and treated with triethylamine (0,61 mmole). The resulting solution is treated with diphenylphosphorylacetate (DFFA) (0.54 mmole) and allowed to mix at room temperature for 6 hours the Organic phase was washed with aqueous NaHCO3and water, dried over MgSO4and filtered. The resulting solution was treated with compound LXXXIV (example 4) (115 mg, of 0.36 mmole) and the reaction mixture is placed for 1 h in an oil bath with a temperature of 90°C. then remove the volatile components and the crude residue purified preparative thin-layer chromatography on two plates, elwira a mixture of CH2Cl2/MeOH in a ratio of 9:1, to obtain specified in the connection header 30 in the form of not-quite-white solid (61 mg, 28%).

Replacing the sulfate S-methylisothiazoline used in the reaction with the compound XCVIII, you can get other substituted pyrimidines corresponding to the formula XCVIV. So, for example, using hydrochloride ndimethylacetamide, you can get 2-methylpyrimidine similar connection XCVIV. The use of sulfate O-methylisothiazoline and guanidine carbonate allows to obtain 2-methoxypyridine and 2-aminopyrimidine counterparts. When replacing the sulfate S-methylisothiazoline the monohydrate of hydrazine or N-methylhydrazino can be obtained respectively pyrazole-4-ilen or 1-methylpyrazole-4-ilen ring instead of the substituted pyrimidine in connection XCVIV. Each and is similar analogues connection XCVIV can be used in the above-described methods for obtaining the appropriate analogues of compound 30.

In the examples 31-36 described the synthesis of substituted naphthylamines, which can be used as an intermediate product VI (D'-NH2), as described for methods B and C in the section "General synthetic methods", to obtain various compounds according to the invention.

Example 31

5-(4-aminonaphthalene-1-yl)-2-pyridin-3-ylmethylene

In a tube with a solution of 2.0 g of 1-amino-4-bromonaphthalene (9.0 mmol, 1 EQ.) in 70 ml of DMF added to 1.75 ml of 2-cyclohexen-1-it (18.0 mmol, 2.0 equiv.) 2.3 g of sodium bicarbonate (to 27.0 mmol, 3.0 EQ.) and 186 mg of 1,3-bis(diphenylphosphino)propane (DFFP, 0.45 mmole, of 0.05 EQ.). The mixture for 15 min bubbled with dry nitrogen gas, then add 316 mg chloride bis(triphenylphosphine)palladium (II) (0.45 mmole, of 0.05 EQ.) and the tube is hermetically sealed. The mixture was incubated with heating at 150°C for 8 h, and then cooled to ambient temperature, diluted with EtOAc (150 ml) and filtered through diatomaceous earth. The mixture was washed with water and then brine. The organic layer is dried (MgSO4), filtered and concentrated. Crude oil is purified column chromatography on SiO2using from 10 to 50% EtOAc in mixtures of hexanol as eluents, to obtain 2.0 g of thick liquid containing 3-(4-aminonaphthalene-1-yl)cyclohex-2 northward and DMF (respectively in a molar ratio of 1:2, with 5.22 mmole naphtylamine, the output 58 of theoretical).

To a solution of 4.0 g of 3-(4-aminonaphthalene-1-yl)cyclohex-2-Aenon mixed with DMF (1:2, of 10.4 mmole, 1 EQ.) in 50 ml of toluene type of 2.72 g of di-tert-butyl-dicarbonate (12.5 mmole, 1.2 EQ.) and 1.5 ml of triethylamine (10,4 mmole, 1 EQ.). The mixture was incubated with heating at 100°C overnight, then cooled to ambient temperature. Next, the reaction mixture was washed with 0.1%aqueous HCl (2×50 ml), water and brine, dried (MgSO4), filtered and concentrated. The crude product precipitated and washed with 10%EtOAc in hexane to obtain, after filtration of 2.5 g of the target tert-BUTYLCARBAMATE (7.4 mmole, 71% yield of theoretical).

To a solution of 186 mg obtained in the previous phase of tert-butylated-carbamate (0.55 mmole, 1 EQ.) in 1.6 ml of anhydrous tert-butanol add 52 μl pyridine-3-carboxaldehyde (0.55 mmole, 1 EQ.) and of 1.65 ml solution of tert-butoxide potassium (1.0 M, 1,32 mmole, 3 EQ.). This mixture is heated under reflux overnight and then cooled. Next add Meon (5 ml) and a solution of HCl in dioxane (4.0 M) until it's time until the pH value is set to approximately 1, after which the reaction mixture is stirred for 1.5 h at ambient temperature. Then to the mixture to terminate the reaction, add saturated aqueous solution of NaHCO3and extracted with EtOAc (2×50 ml). The aqueous layer was treated with 4 N. aqueous solution of NaOH until then, until the pH value of not mouth which becomes approximately 12, and then extracted twice more. The combined organic extracts washed with brine, dried (MgSO4), filtered and concentrated to obtain crude mixture of products containing naphtylamine as still protected carbamate. After that, the residue is dissolved in dichloromethane (3 ml), treated with 2 ml TFUK and left to mix on the weekend at ambient temperature. Then the reaction mixture is stopped and the mixture is neutralized with saturated aqueous NaHCO3, extracted with dichloromethane (3×50 ml), dried (MgSO4) and filtered. Further volatile components removed in vacuo and the crude product is purified column chromatography on SiO2using from 50 to 100% EtOAc in mixtures of hexanol as eluent, to obtain 35 mg specified in the title compound 31 (0,11 mmole, yield 20% of theoretical).

Example 32

5-(4-aminonaphthalene-1-yl)-2-(tetrahydrofuran-3-ylmethyl)phenol

To a solution of 3.16 g of tetrahydro-3-freeway acid (27 mmol, 1 EQ.) in 25 ml of anhydrous dichloromethane add a 7.85 g dicyclohexylcarbodiimide (DCC, 38 mmol, 1.4 EQ.) and of 4.54 ml of triethylamine (32,6 mmole, 1.2 EQ.). After that add the hydrochloride of N-methylethanolamine, and then 60 mg DMAP ((4-dimethylamino) pyridine). This is an exothermic reaction and therefore add another 25 ml of dichloromethane. A mixture of paramashiva the t at ambient temperature over night, and then filtered through diatomaceous earth and concentrated. The residue is treated with simple ether, a white solid is filtered off and discarded. From the mother liquor to remove solvent and the residue is purified column chromatography on SiO2using 15-25%EtOAc in hexano as mixtures eluents, to obtain the desired amide as a colorless oil (yield 55% of theoretical), which still contains 10% dicyclohexylamine. This product is used in subsequent reactions without further purification.

To a solution of 1.0 g of the above amide (6,28 mmole, 1 EQ.) in 60 ml of anhydrous THF at -78°With dropwise with a syringe type of 12.6 ml of a 1.0-molar solution DIBAH in toluene (12.6 mmole, 2.0 EQ.). After 30 minutes of stirring at -78°to the reaction mixture to terminate the reaction, add 50 ml of the Meon and 50 ml of water. The reaction mixture was transferred into a separating funnel and add 250 ml of a simple ester. After that add 1 N. aqueous solution of HCl until then, until you dissolve all solid. The layers are separated and the aqueous phase is additionally extracted twice with simple ether in portions of 100 ml the combined organic phases are washed with saturated aqueous NaHCO3and then brine, dried over Na2SO4filter and concentrate. The crude product is purified by chromatography on when likehere using 0-5%Meon in dichloromethane as mixtures eluents. In this way receive the target 3-tetrahydrofuranyl aldehyde in the form of easily escaping containing impurities colorless oil (200 mg).

To a solution of 200 mg of tert-butylnaphthalene (0,59 mmole, 1 EQ.) in 1.6 ml of anhydrous tert-butanol add 200 mg, obtained in the previous phase 3-tetrahydrofuroyl aldehyde (in excess) and of 1.78 ml solution of tert-butoxide potassium tert-butanol (1.0 M of 1.78 mmole, 3 EQ.). The mixture was incubated with heating at 40°C overnight, then cooled and stop the reaction by adding saturated aqueous solution of NH4Cl. The resulting product is extracted with a mixture of dichloromethane with methanol (3×100 ml). The combined extracts washed with brine, dried over MgSO4and concentrate. According to1H-NMR analysis consumes only 10% of Aenon. The residue (300 mg) was dissolved in 4.0 ml of dichloromethane and treated with 4 ml of a mixture of dichloromethane with TFUK in the ratio of 1:1. The reaction mixture was stirred for 1.5 h, then neutralized with a saturated aqueous solution of NaHCO3, alkalinized 4h. NaOH solution and extracted with dichloromethane/methanol (3×100 ml). The combined organic extracts washed with brine, dried (MgSO4), filtered and concentrated. The crude product is purified column chromatography on silica gel using 10 to 50% EtOAc in hexano as the mixture is th 3 pottow, obtaining specified in the connection header 32 (35 mg, of 0.11 mmole, yield 19% of theoretical).

Example 33

4-[5-(4-aminonaphthalene-1-yl)pyridine-2-yloxy]butyronitrile

To a solution of 2,5-dibromopyridine (500 mg, 2.1 mmole) and 3-cyano-1-propanol (270 mg, 3.1 mmole) in DMSO (2 ml) is added 1M hexamethyldisilazide sodium (Na-GMDS, 2.1 ml, 2.1 mmole). Then the reaction mixture was stirred at room temperature overnight. Next, to the reaction mixture was added EtOAc and the mixture washed with water (2×10 ml). EtOAc-fraction is dried over anhydrous sodium sulfate and evaporated on a rotary evaporator. The crude product is purified column rapid chromatography on silica gel using a mixture of 40%EtOAc/hexane, receiving 200 mg of 5-bromo-2-cyanopiperidine in the form of a pale yellow solid (39,3%).

To the obtained in the previous stage intermediate product (100 mg, 0.4 mmole) and CBZ-protected NativeWindow acid XCVIX (obtained according to the method of obtaining Boc-analog XCl in example 17) (200 mg, of 0.62 mmole) in DME (4 ml) is added 2-molar sodium carbonate solution (2 ml). The solution is blown with nitrogen for 10 minutes and then add tetranitroaniline palladium (20 mg). The reaction mixture was kept with heating at 90°C for 48 h, then cooled to room temperature. Next, to the reaction with whom thou add EtOAc and the mixture washed with water (2× 10 ml). EtOAc-fraction is dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified column rapid chromatography on silica gel, elwira a mixture of 40%EtOAc/hexane, to obtain 70 mg of the product (39%).

To the obtained in the previous phase of the reaction product combinations (70 mg, 0.16 mmole) in EtOH (5 ml) add cyclohexen (263 mg, 3.2 mmole) and 10%Pd/C (20 mg). The reaction mixture was kept with heating under nitrogen atmosphere overnight and cooled to room temperature. After that, the reaction mixture is filtered through diatomaceous earth, washed with Meon and concentrate. The crude product is purified column rapid chromatography on silica gel, elwira a mixture of 50%EtOAc/hexane, receiving 15 mg specified in the title compound 33 (31%).

Example 34

The dihydrochloride[5-(4-aminonaphthalene-1-yl)pyridin-2-yl]-(tetrahydro-thiopyran-4-yl)amine

It tetrahydro-1,4-thiopyrano (2.0 g, 17.2 mmole) and hydroxylamine hydrochloride (2.0 g, or 28.7 mmole) in EtOH (10 ml) add trihydrate sodium acetate (4.0 g, of 29.4 mmole) in 20 ml of water. The reaction mixture is heated under reflux for 3 h, cooled to room temperature and concentrated on a rotary evaporator to a volume of 15 ml, the Residue is cooled in an ice bath and filtered to obtain 2.0 g oximoula product as a white solid substances is and with t PL80-83° (88,7%).

In a dry flask containing THF (20 ml) and 1M alumoweld lithium (AGL) in diethyl ether (19 ml) at room temperature, add obtained in the previous phase of the oxime (500 mg, 3,82 mmole). The reaction mixture is heated under reflux for 3 h, cooled to room temperature and the reaction excess AGL stopped by adding a mixture of ice and water. After extraction with EtOAc and concentration obtain 340 mg (76%) target 4-aminotetrahydrofuran.

To the obtained in the previous phase amine (170 mg, 1.4 mmole) in dry pyridine (1 ml) was added 2,5-dibromopyridine (250 mg, 1.1 mmole), after which the reaction mixture was kept with heating at 110-120°C for 5 days. Then the reaction mixture is extracted with EtOAc, washed with water, dried over anhydrous sodium sulfate and concentrated to obtain crude product. This crude product is purified column rapid chromatography on silica gel using a mixture of 30%EtOAc/hexane as eluent, to obtain 100 mg of the pure product (33,3%).

To the obtained in the previous stage intermediate product (80 mg, 0,293 mmole) and RE-secure NativeWindow acid XCI (example 17) (140 mg, 0,488 mmole) in DME (4 ml) is added 2M sodium carbonate (2 ml) and chloride bis (triphenylphosphine) palladium (15 mg). The reaction mixture was kept with heating at 90°C in an atmosphere of AZ is that for 18 h and cooled to room temperature. After that the reaction mixture is extracted with EtOAc, washed with water, dried over anhydrous sodium sulfate and concentrated to obtain crude product. This crude product is purified column rapid chromatography on silica gel using a mixture of 30%EtOAc/hexane as eluent, to obtain 110 mg of the pure product HSH (86,0%)

To connect HSH (35 mg, 0.08 mmole) in dioxane (1 ml) is added a mixture of 4M HCl/dioxane (0.6 ml). Then the reaction mixture was stirred at room temperature for 48 hours After adding diethyl ether to give the product as hydrochloride, which is filtered to obtain 18 mg (55%) specified in the connection header 34.

Example 35

The dihydrochloride[5-(4-aminonaphthalene-1-yl)pyridin-2-yl]-(tetrahydro-Piran-4-yl)amine

To 2-amino-5-bromopyridine (250 mg, 1.44 mmole) and RE-secure NativeWindow acid XCl (example 17) (688 mg, 2.4 mmole) in 5 ml of DME added 2M sodium carbonate (2.5 ml) and chloride bis(triphenylphosphine)palladium (30 mg). The reaction mixture was kept with heating at 90°C in nitrogen atmosphere for 18 h and cooled to room temperature. Then the reaction mixture is extracted with EtOAc, washed with water, dried over anhydrous sodium sulfate and concentrated. The residue is purified column rapid chromatography on silica gel, elwira a mixture of 40%EtOAc/hexane is, to obtain 370 mg of the reaction product of a combination of HSH (76,4%).

This intermediate product (200 mg, 0,597 mmole) and tetrahydropyrane (120 mg, 1,19 mmole) in dichloroethane (5 ml) was added glacial acetic acid (0.2 ml, to 3.58 mmole) and triacetoxyborohydride sodium (380 mg, to 1.79 mmole). The reaction mixture was stirred at room temperature for 48 h, and then extracted with EtOAc, washed with water, dried over anhydrous sodium sulfate and concentrated. The residue is purified column rapid chromatography on silica gel, elwira a mixture of 50%EtOAc/hexane as eluent, to obtain 120 mg of the compound XCXI (48,0%).

Obtained in the previous phase connection XCXI dissolved in dichloromethane (3 ml) and treated triperoxonane acid (1 ml).

The reaction mixture was stirred for 3 h and concentrated. The residue is dissolved in EtOAc (20 ml), washed with sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated to obtain 90 mg specified in the title compound 35 (98,5%).

Example 36

[5-(4-aminonaphthalene-1-yl)pyridin-2-yl]-(1-methylpiperidin-4-yl)Amin

To a mixture of compound HSH (example 35) (110 mg, of 0.33 mmole) and 1-methyl-4-piperidone (80 mg, 0.7 mmole) in dichloroethane (6 ml) was added glacial acetic acid (120 mg, 2.0 mmole) and triacetoxyborohydride sodium (220 mg, of 1.03 mmole). The reaction mixture p is remediat at room temperature for 96 h, and then extracted with EtOAc, washed with water, dried over anhydrous sodium sulfate and concentrated. The residue is purified column rapid chromatography on silica gel using a mixture of 10% MeOH/CH2Cl2/0.1 tea (triethanolamine) as eluent, to obtain 60 mg of the pure product (42,0%).

Obtained at the previous stage, the product is dissolved in dichloromethane (3 ml) and treated triperoxonane acid (1 ml). The reaction mixture was stirred for 2.5 h and concentrated to obtain 94 mg specified in the title compound 36 (100%).

Example 37

In example 37 illustrates the synthesis of compounds of formula III in which E means Acting

3-tert-BUTYLPEROXY ester[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]carbamino acid

Connection LXXXIV (example 4) (100 mg, 0.31 in mmole) dissolved in dichloromethane (20 ml). Then add an equal volume of saturated aqueous sodium bicarbonate and two-phase solution is cooled to 0°C. Further added phosgene (1,93 M in toluene, and 0.40 ml) stirring to stop it. Immediately after stirring the reaction mixture resume and continue for 15 min at 0°C. After that, the layers separated, the organic phase is dried over solid magnesium sulfate and the solution concentrated to a volume of approximately 5 ml and Then add 3-tert-butyl the enol (100 mg, 0.67 mmole) in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 19 hours After the Express chromatography using EtOAc as eluent obtain 71 mg specified in the connection header 37.

Example 38

In example 38 illustrates the synthesis of compounds of formula III in which E denotes CH2.

2-(5-tert-butyl-2-methoxyphenyl)-N-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ndimethylacetamide

Connection LXXXIV (example 4) (100 mg, 0.4 mmole) and sodium salt of 5-tert-butyl-2-methoxyphenylacetic acid (154 mg, 0.4 mmole) dissolved in dichloromethane (15 ml). Next add the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (172 mg, 0.9 mmole) and the reaction mixture was stirred at ambient temperature for 16 hours After cleaning liquid chromatography high resolution (IHVR) receive 30 mg specified in the connection header 38.

Similar to the above methods also receive the following connections:

1-(2-tert-butyl-5-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were]-3-{4-[6-(morpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-and is methylpyridin-3-yl)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methylbiphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(6-morpholine-4-iletileri-Z-yl)naphthalene-1-yl]urea,

amid-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)piperidine-3-carboxylic acid,

1-(5-isopropyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-sec-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(tetrahydrofuran-3-ylamino)-methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[4-(3-methoxyphenyl)piperazine-1-ylmethyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-{[(2-cyanoethyl)-(tetrahydro-furan-2-ylmethyl)amino]methyl]pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-[[(2-cyanoethyl)pyridine-3-ylmethylamino]methyl]pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxo-[4-thiomorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(1-oxitetraciclina-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylpiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methoxymethylethoxy-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(2-thia-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-pyridine-2-reparation-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(morpholine-4-carbonyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(pyridine-3-yloxy)pyridine-3-yl]nafta is Jn-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(tetrahydropyran-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-were)-3-(4-[6-[(3-methoxypropyl)methylamino]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylpyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-[[bis(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxypropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(morpholine-4-carbonyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-yl)acetamide", she

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

N-(5-tert-butyl-2-methoxy-3-{3-[4-(morpholin-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-N-methylacetamide,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-2,2,2-triptorelin,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)methanesulfonamide.

Evaluation of the biological properties

Inhibition of production of TNF in THP-cells

Inhibition of production cytokinemia can be assessed by measuring the inhibition of TNFα in stimulated with lipopolysaccharides THP-cells (see, for example, W.Prichett etc., J. Inflammation, 45, 97, 1995). All cells and reagents were diluted in RPMI medium 1640 containing phenol red and L-glutamine with the addition of another portion of L-glutamine (total: 4 mm), penicillin and streptomycin (50 units/ml each) and fetal bovine serum (FBS, 3%) (company GIBCO, all concentrations are final concentrations). The analysis was carried out in sterile conditions; receiving the test compound was carried out under non-sterile conditions. The original Royal solutions were prepared in DMSO, and then diluted with RPMI medium 1640 to achieve concentrations greater than 2 times the final required for analysis of the concentration. Confluently THP.1 cells (final concentration 2×106cells/ml, American Type Culture Company, Rockville, PCs Maryland) were made in 96-well polypropylene round-bottom plates to cultivation (type Costar 3790; sterilin the e), containing 125 μl of the test compounds (2-fold concentration) or media representing DMSO (control net). The final concentration of DMSO did not exceed 0.2%. The mixture containing the cells were subjected to pre-incubation for 30 min at 37°C, 5% CO2before stimulation with lipopolysaccharide (LPS; final concentration 1 μg/ml; Siga L-2630, from serotype V E. coli; stored at -80°in the form of a stock solution with a concentration of 1 mg/ml in distilled H2About ongoing monitoring for the presence of endotoxin). In control samples (estimulando) was added to the media, representing the N2About; the final volume of incubation was 250 μl. Incubation overnight (18-24 h) was performed by the method described above. The process was stopped by centrifugation tablets at 1600 rpm (400xg for 5 min at room temperature; supernatant was transferred into a clean 96-well plates and stored at -80°through analysis in respect of the human TNFβ using a commercially available ELISA kit (type Biosource #KHC3015, Camarillo, PCs California). Data were analyzed by the method of nonlinear regression (using equations hill), receiving the dependence of the dose-response using mathematical software SAS Software System (SAS Institute, Inc., Kari, PCs North Carolina). R is shitennou value IC 50represents the concentration of test compound which causes a 50%increase decrease production of TNFα compared with the maximum value.

Using this method of analysis was the assessment of the preferred compounds, including compounds described in the examples of synthesis, and it was found that for them IC50is less than 10 microns.

Inhibition of other cytokines

Similar methods using cells of peripheral blood monocytes, appropriate incentives and commercially available ELISA kits (or other detection method such as radioimmunoassay analysis), fit for a particular cytokine, it can be demonstrated that inhibition of IL-1β, GM-CSF, IL-6 and IL-8 (see, for example, J.C. Lee, and others, Int. J. Immunopharmacol., 10, 835, 1988).

1. The compound of formula (II)

in which G denotes phenyl, pyridinyl, pyrazolyl,

thus G is substituted by one or more groups R1, R2or R3,

Ar means naphthyl;

X means C5-C8cycloalkyl or cycloalkenyl, optionally substituted by 1-2 exography, phenyl, furanyl, pyridinyl or pyrazinyl,

Y represents a bond or a saturated or unsaturated branched or unbranched C1-C4-carbon chain, while one or more methylene groups are optionally independently replaced by O or N, Y is optionally substituted by exography,

Z signifies phenyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, morpholinyl, thiomorpholine, piperidine, piperidinyl, piperazinil, pentamethyldisiloxane, each of which is optionally substituted 1-3 C1-C6alkilani or CONH group2C1-C6alkyl, nitrile, hydroxy-group, C1-C6alkoxygroup, secondary or tertiary amine, with an amine nitrogen is covalently bonded to the C1-C3the alkyl or C1-C5alkoxyalkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, carboxamide-C1-C3alkyl,

R1in each case, independently mean C1-C10alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 hydroxy groups, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, each of which is optionally substituted by 1-3 groups CN, halogen, C3-C6alkylamino branched or unbranched carbon chain, one or more methylene groups are optionally replaced by O, and the said Alchemilla group optionally substituted by one or more C1-C4alkyl groups,

R2means a branched or unbranched C1-C6 alkyl which is optionally partially or fully galogenidov, branched or non-branched C1-C4alkoxygroup, which in each case optionally partially or fully galogenirovannami, halogen, C1-C6alkoxygroup, the hydroxy-group, mono - or di(C1-C4alkyl)amino group, a group OR6the nitrogroup or

group mono - or di(C1-C4alkyl)amino-S(O)2which is optionally partially or fully galogenirovannami, or group H2NSO2,

R3in each case independently denotes phenyl, pyridinyl, pyrimidyl, pyrrolidinyl, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, C1-C6alkylamino group or a branched or non-branched C1-C6alkoxygroup, each of which is optionally partially galogenirovannami, OR18or C1-C6alkyl optionally substituted by a group OR18the amino group or mono - or di(C1-C5alkyl)amino group, a C2-C6alkylamino branched or unbranched carbon chain, one or more methylene groups are optionally replaced by O, and the said Alchemilla group optionally substituted by one or more C1-C4alkyl groups,

R6means C 1-C4alkyl which is optionally partially or fully galogenidov,

R18in each case independently denotes hydrogen, C1-C4alkyl,

W means that,

and its pharmaceutically acceptable derivatives.

2. The compound according to claim 1, in which G denotes phenyl, pyridinyl, while G is substituted by one or more groups R1, R2or R3.

3. The compound according to claim 2, in which G denotes phenyl, pyridinyl, while G is substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl,

X is phenyl, furanyl, pyridinyl or pyrazinyl,

Y represents a bond or a saturated or unsaturated branched or unbranched C1-C4-carbon chain, where one methylene group is optionally replaced by O or N, and Y is optionally independently substituted by exography, Z denotes phenyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, morpholinyl, thiomorpholine, piperidine, piperidinyl, piperazinil, pentamethyldisiloxane, nitrile, hydroxy-group, C1-C4alkoxygroup,

R1in each case, independently mean C3-C6alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 hydroxy groups, cyclopropyl, CYCLOBUTANE is, cyclopentenyl, each of which is substituted by 1-3 groups CN,

R2means halogen, C1-C6alkoxygroup, group C1-C3alkyl-S(O)2which is optionally partially or fully galogenirovannami or H2NSO2,

R3in each case independently denotes phenyl, pyridinyl, pyrimidinyl, pyrrolidinyl, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, C1-C6alkyl group or a C1-C6alkoxygroup, each of which is optionally partially galogenirovannami, OR18or C1-C6alkyl, optionally substituted by a group OR18the amino group or mono - or di(C1-C5alkyl)amino group, a C2-C4alkylamino branched or unbranched carbon chain, one or more methylene groups are optionally replaced by O, and the said Alchemilla group optionally substituted by one or more C1-C4alkyl groups.

4. The compound according to claim 3, in which G denotes phenyl, pyridinyl, while G is substituted by one or more groups R1, R2or R3,

Ar denotes naphthyl, X is phenyl, pyridinyl or pyrazinyl,

Y represents a bond or a saturated C1-C4-carbon chain, where one of the carbon atoms optional the o is replaced by O or N, and Y is optionally independently substituted by exography,

Z signifies phenyl, tetrahydropyranyl, morpholinyl, thiomorpholine, piperidine, piperidinyl, piperazinil, are not substituted by 1-2 C1-C2alkyl groups,

R1in each case, independently mean C3-C5alkyl which is optionally partially or fully galogenidov and optionally substituted by 1-3 hydroxy groups, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl,

R2in each case independently denotes bromine, chlorine, fluorine or methoxy group,

R3in each case independently denotes phenyl, pyridinyl, pyrimidyl, pyrrolidinyl, group OR18or C1-C3alkyl, optionally substituted by a group OR18the amino group or mono - or di(C1-C3alkyl)amino group.

5. The compound according to claim 4, in which

G means phenyl, pyridinyl, while G is substituted by one or more groups R1, R2or R3,

Ar is 1-naphthyl,

X is phenyl, pyridinyl or pyrazinyl,

Y represents a bond or-CH2-, -CH2CH2-, -C(O)-, -NH-CH2CH2CH2-, -N(CH3)- or-NH-,

R1in each case, independently mean C3-C5alkyl which is optionally partially or is fully galogenidov, cyclopropanol, cyclobutanol, Cyclopentanol, cyclohexanol, cycloheptanol, each of which is substituted by 1-3 substituents selected from the group comprising methyl, which is optionally substituted by 1-3 groups CN,

R3in each case independently denotes phenyl, pyridinyl, pyrimidinyl, pyrrolidinyl, C1-C6alkyl group, each of which is optionally partially or fully galogenirovannami, OR18or C1-C6alkyl, optionally substituted by a group OR18the amino group or mono - or di(C1-C3alkyl)amino group.

6. The compound according to claim 5, in which G denotes phenyl or pyridinyl, while G is substituted by one or more groups R1, R2or R3,

X is pyridinyl,

Y represents-CH2-, -NH-CH2CH2CH2- or-NH-,

Z means morpholinopropan,

R1in each case independently denotes tert-butyl, sec-butyl, tert-amyl or phenyl,

R2means chlorine and

R3in each case independently denotes methyl or methoxy group.

7. The connection according to claim 6, in which X is pyridinyl.

8. The connection according to claim 7, in which the pyridinyl is attached to Ar in the third position pyridinyl.

9. The compound of formula II according to claim 1, selected from the group including:

1-[5-tert-butyl-2-p-tolyl-2H-p is razol-3-yl]-3-[4-(4-(morpholine-4-yl-methyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(2-(morpholine-4-yl)ethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-yl-methyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-morpholine-4-iletiler-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-methyl-2H-pyrazole-3-yl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(5-(morpholine-4-ylmethyl)pyridine-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(2-(pyridin-2-yl)ethylamino)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(pyridine-3-ylmethylamino)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-yl-methyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-b is Teal-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxyethylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(4-methyl-3-carbamylethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-hydroxypiperidine-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(4-hydroxyprolin-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(3-(morpholine-4-ylmethyl)cyclohexenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(tetrahydrofuran-3-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di(2-methoxyethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(3-cyanopropyl)pyridine-3-yl)naphthalene-1-yl] urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(morpholine-4-iletilmedigini)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N,N-di(2-cyanoethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(furan-2-ylmethyl)-3-hydroxyphenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(thiomorpholine-4-ylmethyl)phenyl)nafta is Jn-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(3-carboxamidotryptamine-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(2-methyl-3-oxopiperidin-1-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(4-hydroxybutyrate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methoxypyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyridine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-yl-4-carbonyl)pyridine-3-yl)naphthalene-1-the l]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(pyridine-3-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-(tetrahydrofuran-2-ylmethyl)aminomethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)-4-methoxypyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-morpholine-4-ylpropyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(5-(tetrahydrothiopyran-4-ylamino)pyrazin-2-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-2H-pyrazole-3-yl]-3-[4-(6-(methylcarbonate)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-3-methylsulfinylpropyl)-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(tetrahydropyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-aminopyrimidine-5-yl)-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-1'-methyl-1 N-[1,4']beparasy-5-yl]-3-[4-(6-(morpholine-4-ylmethyl)phenyl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-ylamino)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(thiomorpholine-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylcarbonyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-3-yl]-3-[4-(6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazole-3-yl]-3-[4-(2-(morpholine-4-ylmethyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-(2-tert-is util-5-methylpyridin-4-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-tert-butylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-methylbiphenyl-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(4-tert-butylbiphenyl-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-isopropyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-sec-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-were)-3-(4-{6-[(3-methoxypropyl)methylamino]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-were)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylpyridin-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1,1-dimethylpropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxy who ropyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(morpholine-4-carbonyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

1-(3-methylnaphthalene-2-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)acetamide", she

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-hydroxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,3-dimethyl-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-{5-tert-butyl-2-methyl-3-[3-(tetrahydropyran-2-yloxy)prop-1-inyl]phenyl}-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(2,2-dimethylpropyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(3-hydroxyprop-1-inyl)-2-were]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(3-hydroxyprop-1-inyl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2,2-dimethyl-[1,3]dioxolane-4-ylmethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]mo is eve

1-[5-tert-butyl-3-(2,3-dihydroxypropyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butoxy-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-(1-cyanocyclohexyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-3-(2-diethylaminoethyl)-2-methoxyphenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-11,3]dioxolane-2-espiridion-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-pyrrolidin-1-yl-phenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-dimethylaminophenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-propoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-hydroxymethyluracil-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-cyclohexyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2,4-dimethoxy-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxy-3-nitrophenyl)-3-[4-(6-morpholine-4-eletype the one-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-methylpyridin-3-yl)naphthalene-1-yl]urea,

N-acetyl-N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)acetamide", she

1-(6-tert-butyl-4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxy-phenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-isopropoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-imidazol-1-ylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-ethylamino-2-methoxyphenyl)-3-14-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)bis(metasolv)amide,

1-[5-tert-butyl-2-(1-methyl-1H-pyrazole-4-yl)phenyl]-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(2-methanesulfonyl-5-triptoreline)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-{[bis(2-methoxyethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

N-[1-(5-[4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)pyrrolidin-3-yl]acetamide", she

1-(1-azeti the -3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)propionamide,

1-(5-tert-butyl-2-methyl-benzooxazol-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]-3-(3-triftormetilfullerenov)urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)isobutyramide,

2-(4-tert-butyl-2-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenoxy)ndimethylacetamide,

1-(5-tert-butyl-2-oxo-2,3-dihydroisoxazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-3-cyano-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butylbenzothiazole-7-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido]phenyl)benzosulfimide,

(5-tert-butyl-2-methoxy-3-[3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amide econsultancy acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(2-morpholine-4-iletilerimde-5-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methylsulfinylphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-IU is oxopyridine-3-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)amid,2,2-cryptgethashparam acid,

N-(5-[4-[3-(5-tert-butyl-2-were)ureido]naphthalene-1-yl}pyrazin-2-yl)methanesulfonamide,

1-[4-(6-{[bis(2-cyanoethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]-3-(5-tert-butyl-2-methoxyphenyl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(4-methylpiperazin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylpiperidin-1-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxitetraciclina-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(tetrahydropyran-4-ylamino)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-{[(2-cyanoethyl)-(tetrahydrofuran-2-ylmethyl)amino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methoxymethylethoxy-4-ylmethyl)-pyridine-3-yl]naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2-methyl-3-oxopiperidin-1-ylmethyl)-pyridine-3-yl]naphthalene-1-yl}urea,

amid-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-ylmethyl)PI is uridin-3-carboxylic acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[6-(1-Osotimehin-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(3-oxopiperidin-1-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[(tetrahydrofuran-3-ylamino)methyl]pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(6-[[(2-cyanoethyl)pyridine-3-ylmethylamino]methyl}pyridine-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-[6-(2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(2,6-dimethylmorpholine-4-ylmethyl)pyridine-3-yl]naphthalene-1-yl}urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-(4-{6-[4-(3-methoxyphenyl)piperazine-1-ylmethyl]-pyridine-3-yl}naphthalene-1-yl)urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(morpholine-4-carbonyl)pyridine-3-yl]naphthalene-1-yl} urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(5-morpholine-4-iletileri-2-yl)naphthalene-1-yl]urea,

1-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(3-amino-5-tert-butyl-2-methoxyphenyl)-3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

N-(5-{4-[3-(5-tert-butyl-2-methoxyphenyl)ureido]naphthalene-1-yl}pyridine-2-yl)acetamide", she

N-(5-tert-butyl-2-methyl-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-N-methylacetamide,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)-2,2,2-triptorelin,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(pyridine-3-yloxy)pyridine-3-yl]naphthalene-1-yl]urea,

3-tert-BUTYLPEROXY ester[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]carbamino acid,

N-(5-tert-butyl-2-methoxy-3-{3-[4-(6-morpholine-4-iletileri-3-yl)naphthalene-1-yl]ureido}phenyl)methanesulfonamide,

and their pharmaceutically acceptable derivatives.

10. The pharmaceutical composition inhibiting the production of cytokines containing a pharmaceutically effective amount of a compound according to claim 1.

11. A method of treating diseases mediated by cytokines, which consists in the introduction to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 1.

12. The method according to claim 11, where the specified mediated by cytokines disease is a disease from the group comprising rheumatoid arthritis, osteoarthritis, Crohn's disease, ulcerative colitis, multiple sclerosis, Guillain-Barre syndrome, psoriasis, graft versus host, si is dark red erythematosus, diabetes, toxic shock, osteoporosis, Alzheimer's disease, acute and chronic pain, contact dermatitis, and atherosclerosis.



 

Same patents:

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention describes compound of the formula (I): wherein B represents oxygen atom (O) or -NR1; J represents 5-membered heteroaromatic ring representing group of the formula (J-1): optionally substituted with 1-2 radicals R5 wherein Q represents -NR5; each X, Y and Z represents independently nitrogen atom (N), -CH or - CR5; B1 represents O; R2 represents hydrogen atom (H) or (C1-C6)-alkyl optionally substituted with one halogen atom, or (C2-C6)-alkynyl; or R1 and R2 taken in common form a binding chain consisting of 2-3 members and comprising at least one carbon atom, optionally comprising one carbon atom as -C(=O), optionally substituted with R3 wherein R3 represents (C1-C2)-alkyl; each R represents independently H, (C1-C6)-alkyl, halogen atom or -CN; each R5 represents independently (C1-C6)-halogenalkyl or halogen atom, or each ring is substituted with one R6; each R6 represents independently halogen atom; n represents a whole number 1 or 2. Also, invention describes a composition used for control of insects and comprising the biologically effective dose of compound of the formula (I) and at least one additional component chosen from group comprising surface-active substances, solid and liquid diluting agents, and methods for control of insects with using compositions based on compounds of the formula (I) and compounds of the formula (I). Proposed compounds of the formula (I) possess insecticide activity and can be used in agriculture.

EFFECT: valuable insecticide properties of compounds and compositions.

11 cl, 26 tbl, 4 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel oxazolidinones of the general formula (I): , their pharmaceutically acceptable salts, hydrates and salt hydrates that inhibit factor Xa selectively and possess anti-thrombosis effect. Also, invention relates to a method for synthesis of these compounds (variants) and using the known substituted oxazolidinones of the general formula (A): as agent inhibiting factor Xa selectively and possessing anti-thrombosis effect, and to a medicinal agent based on at least one compound of the formula (I) or at least one compound of the general formula (A). Values of substitutes R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are given in the invention claim.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and agent.

10 cl, 2 tbl, 252 ex

FIELD: chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (1): and their salts wherein values R1, k, Ar, n, j, Y, R and R2 are determined in the invention claim. Novel compounds are able to modulate activity of chemokine receptors. Also, invention relates to using indicated compounds for treatment of human immunodeficiency virus or feline immunodeficiency virus and to a pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 100 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds represented by the general formula (I): and their pharmaceutically acceptable salts and esters possessing agonistic activity with respect to peroxisome proliferator receptors PPARα and/or PPARγ, to a pharmaceutical composition based on thereof and their using for preparing medicines wherein R1 means thiophenyl or phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkoxy-group, (C1-C8)-alkyl and (C1-C8)-alkyl substituted with one-three halogen atoms; R2 means hydrogen atom or (C1-C8)-alkyl; R3 means phenoxy-, (C2-C8)-alkenyloxy- or (C1-C8)-alkoxy-group; R4 means hydrogen atom or (C1-C8)-alkyl wherein one of substitutes R5 and R6 means compound of the formula and another one means hydrogen atom and wherein the bond between carbon atoms Ca and Cb means a carbon-carbon simple or double bond; R7 means hydrogen atom or (C1-C8)-alkyl; R8 means hydrogen atom or (C1-C8)-alkyl being any of A and A1 means nitrogen atom and another means oxygen or sulfur atom; n means 1, 2 or 3.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

30 cl, 1 tbl, 14 sch, 86 ex

FIELD: organic chemistry, chemical technology, insecticides.

SUBSTANCE: invention relates to derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide represented by the general formula (I): wherein R represents (C1-C6)-alkyl group that can be substituted with one or some halogen atoms; R1 represents hydrogen atom, (C1-C6)-alkyl group that can be substituted with one or some substituted chosen from group of substitutes A, (C2-C6)-alkenyl group or acyl group; X represents group of the formula -C-R2 or nitrogen atom; each among R2 and R3 represents independently hydrogen atom, halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from group of substitutes A, (C3-C7)-cycloalkyl group, (C2-C6)-alkenyl group, (C3-C7)-cycloalkenyl group, formyl group, group of the formula: -CH=NOR4 (wherein R4 represents hydrogen atom or (C1-C6)-alkyl group, cyano-group, phenyl group that can be substituted with one or some substitutes chosen from group of substitutes B, 5- or 6-membered heterocyclic group (heterocycle comprising 1-2 heteroatoms that are similar and chosen from nitrogen atom), (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or phenoxy-group. The group of substitutes A represents group consisting of halogen atom, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group, cyano-group and phenyl group. The group of substitutes B represents group consisting of halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from above given group of substitutes A, (C1-C6)-alkoxy-group that can be substituted with one or some substitutes chosen from above given group of substitutes A, or its salt. Also, invention relates to insecticide comprising a derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide or its salt as an active component and a carrier optionally. Also, invention relates to a method for synthesis of derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide. Invention provides synthesis of derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide possessing the high insecticide activity.

EFFECT: improved method of synthesis, valuable properties of derivatives.

18 cl, 3 tbl, 91 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound represented by the structural formula: or its pharmaceutically acceptable salt wherein Z represents -(CH2)n-; double dotted line represents a double bond; n = 0-2; R1 and R2 are chosen independently from the group comprising hydrogen atom (H), alkyl with 1-6 carbon atoms; R3 means H, hydroxy-, alkoxy-group with 1-6 carbon atoms, -C(O)OR17 or alkyl with 1-6 carbon atoms; Het means monocyclic heteroaromatic group consisting of 6 atoms and comprising 5 carbon atoms and one heteroatom chosen from nitrogen atom (N) and wherein Het is bound through ring carbon atom and wherein Het-group has one substitute W chosen independently from the group comprising bromine atom (Br), heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N; heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N substituted with OH-substituted alkyl with 1-6 carbon atoms or =O; R21 -aryl-NH-; -C(=NOR17)R18; R21-aryl; R41-heteroaryl representing group consisting of 5-6 atoms comprising 3-5 carbon atoms and 1-4 heteroatoms chosen independently from the group: N, S and O; R8 and R10 are chosen independently from group comprising R1; R9 means H; R11 is chosen from group comprising R1 and -CH2OBn wherein Bn means benzyl; B means -(CH2)n4CR12=CR12a(CH2)n5; n4 and n5 mean independently 0; R12 and R12a are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; X means -O-; Y means =O; R15 is absent as far as double dotted line mean a simple bond; R16 means lower alkyl with 1-6 carbon atoms; R17 and R18 are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; R21 means 1-3 substituted chosen independently from group comprising hydrogen atom, -CN, -CF3, halogen atom, alkyl with 1-6 carbon atoms and so on; R22 is chosen independently from group comprising hydrogen atom; R24-alkyl with 1-10 carbon atoms; R25-aryl and so on; R23 is chosen independently from group comprising hydrogen atom, R24-alkyl with 1-10 carbon atoms, R25-aryl and -CH2OBn; R24 means 1-3 substitutes chosen independently from group comprising hydrogen atom, halogen atom, -OH, alkoxy-group with 1-6 carbon atoms; R25 means hydrogen atom; R41 means 1-4 substitutes chosen independently from group comprising hydrogen atom, alkyl with 1-6 carbon atoms and so on. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to receptors activated by protease and comprising the effective dose of derivative of nor-seco-chimbacine of the formula (I) and a pharmaceutically acceptable excipient. Also, invention relates to methods for inhibition of thrombin and cannabinoid receptors comprising administration in mammal derivative of nor-seco-chimbacine of the formula (I) in the effective dose as active substance. Invention provides derivatives of nor-seco-chimbacine as antagonists of thrombin receptors.

EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition.

8 cl, 1 tbl, 18 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of sulfonamide of the general formula (I): wherein A means a substitute chosen from 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms chosen from oxygen (O), nitrogen (N) or sulfur (S) optionally substituted with 1 or 2 halogen atoms, (C1-C4)-alkyl or phenyl radical, or 5- or 6-membered heteroaryl radical comprising 1 or 2 atoms of O, N or S; bicyclic heteroaromatic ring comprising from 1 to 3 heteroatoms chosen from O, N or S and optionally substituted with 1 or 2 halogen atoms or (C1-C4)-alkyl; R1 means hydrogen atom (H), (C1-C4)-alkyl, benzyl; n means 0, 1, 2, 3 or 4; R2 means -NRR5 or the group of the formula: wherein a dotted line means optional chemical bond; R, R4 and R5 mean independently H or (C1-C4)-alkyl; or one of its physiologically acceptable salts. Compounds of the formula (1) possess antagonistic activity with respect to serotonin HT6-receptors that allows their using in pharmaceutical composition and for preparing a medicament.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, anti-microbial preparations.

SUBSTANCE: invention relates to compounds useful as anti-microbial agents. Claimed compounds are effective against to certain human and animal pathogens, including Gram-positive aerobic bacteria such as multi-resistant staphylococcus, streptococcus and enterococcus, as well as anaerobic organisms such as species Bacterioides spp. and Clostridia spp., and acid resistant organisms such as Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium spp.

EFFECT: new anti-microbial agents.

2 ex, 5 tbl

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel oxazolidinones of the general formula (I): , their pharmaceutically acceptable salts, hydrates and salt hydrates that inhibit factor Xa selectively and possess anti-thrombosis effect. Also, invention relates to a method for synthesis of these compounds (variants) and using the known substituted oxazolidinones of the general formula (A): as agent inhibiting factor Xa selectively and possessing anti-thrombosis effect, and to a medicinal agent based on at least one compound of the formula (I) or at least one compound of the general formula (A). Values of substitutes R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are given in the invention claim.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and agent.

10 cl, 2 tbl, 252 ex

FIELD: organic chemistry, chemical technology, insecticides.

SUBSTANCE: invention relates to derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide represented by the general formula (I): wherein R represents (C1-C6)-alkyl group that can be substituted with one or some halogen atoms; R1 represents hydrogen atom, (C1-C6)-alkyl group that can be substituted with one or some substituted chosen from group of substitutes A, (C2-C6)-alkenyl group or acyl group; X represents group of the formula -C-R2 or nitrogen atom; each among R2 and R3 represents independently hydrogen atom, halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from group of substitutes A, (C3-C7)-cycloalkyl group, (C2-C6)-alkenyl group, (C3-C7)-cycloalkenyl group, formyl group, group of the formula: -CH=NOR4 (wherein R4 represents hydrogen atom or (C1-C6)-alkyl group, cyano-group, phenyl group that can be substituted with one or some substitutes chosen from group of substitutes B, 5- or 6-membered heterocyclic group (heterocycle comprising 1-2 heteroatoms that are similar and chosen from nitrogen atom), (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or phenoxy-group. The group of substitutes A represents group consisting of halogen atom, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group, cyano-group and phenyl group. The group of substitutes B represents group consisting of halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from above given group of substitutes A, (C1-C6)-alkoxy-group that can be substituted with one or some substitutes chosen from above given group of substitutes A, or its salt. Also, invention relates to insecticide comprising a derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide or its salt as an active component and a carrier optionally. Also, invention relates to a method for synthesis of derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide. Invention provides synthesis of derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide possessing the high insecticide activity.

EFFECT: improved method of synthesis, valuable properties of derivatives.

18 cl, 3 tbl, 91 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzimidazole of the general formula (I): wherein A represents -CH2- or -C(O)-; Y represents -S- or -NH-; R1 and R2 represent independently hydrogen atom, (C1-C8)-alkyl, (C5-C9)-bicycloalkyl optionally substituted with one or some similar or different (C1-C6)-alkyl radicals, or radical of the formula -(CH2)n-X wherein X represents amino-group, (C3-C7)-cycloalkyl and other values of radicals also given in the invention claim; R3 represents -(CH2)p-W-(CH2)p'-Z3 wherein W3 represents a covalent bond, -CH(O)- or -C(O)-; Z3 represents (C1-C6)-alkyl, aryl radical, heteroaryl and other values of radical also; V3 represents -O-, -S-, -C(O)-, -C(O)-O-, -SO2- or a covalent bond; Y3 represents (C1-C6)-alkyl radical optionally substituted with one or some halogen-radicals, amino-group, di-((C1-C6)-alkyl)-amino-group, phenylcarbonylmethyl, heterocycloalkyl or aryl radicals; p, p' and p'' represent independently a whole number from 0 to 4; R4 represents radical of the formula: -(CH2)s-R''4 wherein R''4 represents heterocycle comprising at least one nitrogen atom and optionally substituted with (C1-C6)-alkyl or aralkyl, and other values of radicals given in the invention claim also. Also, invention relates to a pharmaceutical composition showing antagonistic property with respect to GnRH and based on these compounds. Also, using above proposed compounds for preparing a medicament is considered. Invention provides synthesis of novel compounds, preparing pharmaceutical composition and medicament based on thereof in aims for treatment of such diseases as endometriosis, fibroma, polycystic ovary, breast, ovary and endometrium cancer, gonadotropic hypophysis desensitization in medicinal stimulation of ovary in fertility treatment in females.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

18 cl, 2 tbl, 538 ex

FIELD: organic chemistry, anti-microbial preparations.

SUBSTANCE: invention relates to compounds useful as anti-microbial agents. Claimed compounds are effective against to certain human and animal pathogens, including Gram-positive aerobic bacteria such as multi-resistant staphylococcus, streptococcus and enterococcus, as well as anaerobic organisms such as species Bacterioides spp. and Clostridia spp., and acid resistant organisms such as Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium spp.

EFFECT: new anti-microbial agents.

2 ex, 5 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted indoles or its pharmaceutically acceptable salts of the formula (I): , wherein R1 means hydrogen (H) atom, halogen atom, -CN, nitro-group, -SO2R4, -OH, -OR4, -SO2NR5R6, -CONR5R6, -COOH, -COOCH3, -NR5R6, phenyl, naphthyl or (C1-C6)-alkyl wherein the latter group is possibly substituted with one or more substitutes chosen independently from halogen atom, -OR8 and -NR5R6 wherein x = 2; R2 means (C1-C7)-alkyl; R3 means phenyl, naphthyl or heteroaryl and each of them is possibly substituted with one or more substitutes chosen independently from H, halogen atom, -CN, -OH, -SO2R4, -OR4, -SO2NR5R6, -CONR5R6, phenyl, naphthyl, (C1-C6)-alkyl wherein the latter group is possibly substituted with one or more substitutes chosen independently from halogen atoms, -OR8 and -NR5R6, -S(O)xR7 wherein x = 2; R4 means (C1-C6)-alkyl; R5 and R6 mean independently H, (C1-C6)-alkyl, or R5 and R6 in common with nitrogen atom to which they are bound can form 6-membered saturated heterocyclic ring comprising one atom chosen from -NR16; R7 means (C1-C6)-alkyl; R8 means H, (C1-C6)-alkyl; R16 means H, -COY-(C1-C4)-alkyl wherein Y means oxygen atom (O) and wherein alkyl group in the substitute group can be direct, branched or cyclic, and wherein heteroaryl means 5-6-membered heteroaromatic ring comprising from 1 to 3 heteroatoms chosen from nitrogen (N), oxygen (O) and sulfur (S) atoms, or means 6,6-condensed bicyclic aromatic ring system comprising one nitrogen atom. Compounds of the formula (I) can be used in production of a medicinal agent used in treatment of asthma and chronic obstructive disease.

EFFECT: valuable medicinal properties of compounds.

7 cl, 2 tbl, 59 ex

FIELD: chemistry of heterocyclic organic compounds, medicine.

SUBSTANCE: invention relates to a novel heterocyclic derivative of the formula (I'): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents-CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R5 represents (C2-C8)-alkenyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; R20 represents phenyl substituted with unsubstituted (C1-C6)-alkyl, (C1-C6)-alkyl substituted with fluorine atom, (C1-C4)-alkoxy-group, phenyl-(C1-C4)-alkoxy-group, hydroxyl group, halogen atom, nitro-group, unsubstituted amino-group or amino-group substituted with (C1-C4)-alkyl; n means a whole number from 1 to 4, or to its pharmaceutically acceptable salt. Also, invention relates to heterocyclic derivative of the formula (I): , wherein R1 represents hydrogen atom or (C1-C6)-alkyl; R2 represents -CO-C(R4)=C(R4)-R5 wherein R4 represents hydrogen atom; R represents (C4-C8)-alkyl or (C2-C8)-alkenyl or -CO-C≡C-R6 wherein R6 represents (C1-C8)-alkyl; R3 represents hydrogen atom or (C1-C4)-alkyl; X represents oxygen atom or sulfur atom; n means a whole number from 1 to 4, or its pharmaceutically acceptable salt. Compounds of the formulas (I') and (I) are effective as a hypoglycemic agent, hypolipidemic agent, agent improving resistance to insulin, therapeutic agent in treatment of diabetes mellitus, therapeutic agent in treatment of diabetes mellitus complications, agents enhancing tolerance to glucose, anti-arteriosclerotic agent, agents against obesity or agent for X syndrome.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 2 tbl, 56 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention relates to a compound of the general formula [I]: wherein R1 and R2 can be similar or different and each represents (C1-C10)-alkyl group; each among R3 and R4 represents hydrogen atom; R5 and R6 can be similar or different and each represents hydrogen atom or (C1-C10)-alkyl group; Y represents 5-6-membered aromatic heterocyclic group or condensed aromatic heterocyclic group comprising one or some heteroatoms chosen from nitrogen atom, oxygen atom and sulfur atom wherein heterocyclic group can be substituted with 0-6 of similar or different groups chosen from the following group of substitutes α, and so on; n means whole values from 0 to 2; [Group of substitutes α]: hydroxyl group, halogen atoms, (C1-C10)-alkyl groups, (C1-C10)-alkyl groups wherein each group is monosubstituted with group chosen from the following group of substitutes β, (C1-C4)-halogenalkyl groups, (C3-C8)-cycloalkyl groups, (C1-C10)-alkoxy-groups, (C1-C10)-alkoxy-groups wherein each group is monosubstituted with group chosen from the following group of substitutes and so on; [Group of substitutes β]: hydroxyl group, (C3-C8)-cycloalkyl groups that can be substituted with halogen atom or alkyl group, (C1-C10)-alkoxy-group, (C1-C10)-alkylthio-groups, (C1-C10)-alkylsulfonyl groups, (C1-C10)-alkoxycarbonyl groups, amino-group, carbamoyl group (wherein its nitrogen atom can be substituted with similar or different (C1-C10)-alkyl groups), (C1-C6)-acyl groups, (C1-C10)-alkoxyimino-groups, cyano-group, optionally substituted phenyl group; [Group of substitutes γ]: optionally substituted phenyl group, optionally substituted aromatic heterocyclic groups, cyano-group. Also, invention relates to herbicide comprising derivative of isoxazoline of the formula [I] as an active component or its pharmaceutically acceptable salt. Invention provides the development of isoxazoline derivative possessing the herbicide activity with respect to resistant weeds, selectivity for cultural crop and weed.

EFFECT: valuable herbicide properties of substances.

18 cl, 24 tbl, 106 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new benzofuran derivatives of formula 1 , wherein X represents group of formula -N= or -CH=; Y represents optionally substituted amino group, optionally substituted cycloalkyl group, or optionally substituted saturated heterocycle; A represents direct bond, carbon chain optionally containing double bond in molecular or in the end(s) thereof, or oxygen atom; R1 represents hydrogen, halogen, lower alkoxy, cyano, or amino optionally substituted with lower alkyl B represents optionally substituted benzene ring of formula ; and R2 represents hydrogen or lower alkyl; or pharmaceutically acceptable salt thereof. Invention also relates to pharmaceutical composition containing abovementioned compounds, uses thereof and method for thrombosis treatment.

EFFECT: new compounds for thrombosis treatment.

27 cl, 2 tbl, 429 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 2-phenylaminoimidazoline phenylketone that can be used as IP antagonists. Invention describes 2-phenylaminoimidazoline phenylketone of the general formula (I): wherein R1 mean optionally substituted aryl wherein R1 is optionally substituted with 1, 2 or 3 substitutes chosen independently from series including alkoxy-group, aryl aryloxy-, aralkyloxy-group, halogen atom, ethylenedioxy-group or optionally substituted heterocyclyl that means a monovalent saturated carbocyclic radical comprising from 3 to 7 atoms in cycle and comprising one or two heteroatoms chosen independently from nitrogen and oxygen atoms, and can be optionally substituted with one or more substitutes chosen independently from alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkyl sulfonyl, furanyloxy-group; R2 means hydrogen atom; A means -C(O)-(CH2)n- or -C(O)-CH2-O-; index n means a whole number from 2 to 6, or its pharmaceutically acceptable salt or solvate. Invention provides preparing novel compounds showing useful biological properties.

EFFECT: valuable properties of compounds.

16 cl, 1 tbl, 23 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel amino- and hydroxy-derivatives of phenyl-3-aminomethylquinolone-2 of the general formula (1):

wherein R1, R2, R3 and R4 are independently similar or different and R1 is chosen from hydrogen atom (H), Alk, OAlk; R2 is chosen from H, Alk, OAlk, -OCF3; R3 is chosen from H, Alk, OAlk, -SCH3; R4 is chosen from H. Alk, OAlk, or R2 and R3 are chosen from -(CH2)3, -OCH2O-, -OCH2CH2O-; R5 means H or Alk; R6, R7 and R9 mean H; R8 is chosen independently from the following substitutes:

wherein n = 1, 2, 3; Het represents furan; R represents hydrogen atom or alkyl. In case of hydroxy-derivatives at least one among R6, R7, R8 or R9 is -OH and other represent H. Also, invention relates to methods for synthesis of these compounds and to a pharmaceutical composition based on these compounds inhibiting activity of NO-synthase. Invention provides preparing novel compounds and pharmaceutical compositions based on thereof in aims for treatment of diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

32 cl, 1 tbl, 132 ex

.FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their physiologically acceptable salts also possessing properties for decrease the blood sugar content. In compound of the formula (I) A means phenyl wherein phenyl residue can be substituted up to three times with fluorine (F), chlorine (Cl) and bromine (Br) atoms; R1 and R2 mean hydrogen atom (H); R3, R4, R5 and R6 mean independently of one another H, F, Cl, Br, -NO2, -O-(C1-C6)-alkyl, (C1-C6)-alkyl, -COOH; R7 means H, (C1-C6)-alkyl wherein alkyl can be substituted up to three times with -OH, -CF3, -CN, COOH, -COO-(C1-C6)-alkyl, -CO-NH2, -NH2, -NH-(C1-C6)-alkyl, -N-[(C1-C6)-alkyl]2, -NHCO-(C1-C6)-alkyl, -NHCOO-(C1-C6)-alkyl or -NHCOO-(C1-C4)-alkylenephenyl; in (CH2)m m can mean 0-6 and aryl means phenyl, O-phenyl, CO-phenyl, benzo[1,3]dioxolyl, pyridyl, indolyl, piperidinyl, tetrahydronapthyl, 2,3-dihydrobenzo[1,4]dioxynyl, benzo[1,2,5]thiadiazolyl, pyrrolidinyl, morpholinyl wherein aryl residue can be substituted mono- or multiple with R9 wherein R9 means F, Cl, Br, -OH, -NO2, -CF3, -OCF3, (C1-C6)-alkyl, (C1-C6)-alkyl-OH, -O-(C1-C6)-alkyl, -COOH, -COO-(C1-C6)-alkyl. Also, invention relates to a pharmaceutical composition and a method for preparing a medicinal agent.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

7 cl, 2 sch, 1 tbl, 293 ex

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