Compounds suitable as anti-inflammatory agents

 

(57) Abstract:

The invention relates to new compounds of the formula (I)

in which Ar1means pyrazole which may be substituted by one or more groups R1, R2or R3; Ar2means naphthyl, tetrahydronaphthyl, each of which is optionally substituted by 0-1 groups R2; X means5-C8cycloalkenyl, phenyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, furan, pyridinoyl, pyrazolyl, pyridinyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, piperidinyl; Y represents a bond or a saturated branched or unbranched1-C4the carbon chain, with one methylene group is optionally replaced with NH, or and Y is optionally independently substituted by oxopropoxy; Z means morpholine, group, pyridinyl, furanyl, tetrahydrofuranyl, thiomorpholine, pentamethylbenzene, pentamethylbenzene, secondary or tertiary amine, the nitrogen atom of the amino group covalently linked to the following groups selected from a range that includes the C1-C3alkyl and C1-C5alkoxyalkyl; R1means31-C6alkyl which is optionally partially or fully galogenidov, halogen; R3means phenyl, pyrimidinyl, pyrazolyl, which is substituted by one branched or unbranched1-C6the alkyl, and pyridinyl, optionally substituted C1-C3alkoxygroup or amino group, W denotes O and its pharmaceutically acceptable salts. Compound 1 inhibited the production of cytokines, which allows their use in pharmaceutical compositions for treating diseases mediated by cytokines. 4 N. and 6 C.p. f-crystals, 1 table.

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 Lakin-1 (IL-1) are important biological factors, in General 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 bowel disease (C. A. 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 (A. E. Koch and others, 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 referred to as TNF) and IL-1. Currently undergoing clinical trials large calennig autoimmune diseases was confirmed the efficacy of monoclonal antibodies to TNF (R. Heath, "CDP571: An Engineered Human IgG4 Anti-TNF Antibody", proceedings of the IBC conference Meeting on Cytokine Antagonists, Philadelphia, pieces 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, etc., Lancet 349: 521-524, 1997). It is assumed that the monoclonal antibody carries out its function by binding to both soluble TNF and associated with membrane TNF.

Was designed the soluble receptor of TNF, which interacts with TNF. This approach is similar to the approach described above for monoclonal antibodies to TNF; both agents are associated with soluble TNF, 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 TNF receptor, 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 recombi what about the molecular mass of 55 kDa, with the genome of the hinge region of the heavy chain IgG1, which is expressed in eukaryotic cells (Renzetti and others, Inflamm. Res. 46: page 143, 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 trials in humans IL-1ra reduced the mortality rate of patients suffering from the syndrome of septic shock (Dinarello, Nutrution 11, 492, 1995). Osteoarthritis is a weakly progressive disease characterized by the 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 Acosta, 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., 211, 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 assume 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 sinusoida 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 is probably 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 TNF and IL-1 are important mediators of septic shock and associated cardiopulmonary dysfunction, acute respiratory distress syndrome in adults (rdsw) is th 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 TNF (Loffreda and others, FASEB J. 12, 57, 1998). It is assumed that elevated levels of TNF are also present in other disorders associated with eating, such as anorexia nervosa and bulimia. Found pathophysiological 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 TNF 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 has vli).

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 the introduction of monoclonal antibodies to IL-1 before application of the allergen on the skin (Muller and others, Am. J. Contact. Dermal. 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 qi 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 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.

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.

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, but 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 involved in the party for 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-. 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) can be correlated with the accumulation in the cells pankreaticheskogo islet T cells that produce IFN- (Ablumunits etc., J. Autoimmun., 11, 73, 1998). IFN - 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 if the programming 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- (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-, which indicates the role of IFN - in the development of atopic dermatitis (Szepietowski, etc., Br. J. Dermatol. 137, 195, 1997). For cases of fatal cerebral malaria were conducted histopathological and immunohistopathological research. Was revealed elevated levels of IFN - 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- (Akaike, etc, Proc. Soc. Exp. Biol. Med. 217, 64, 1998). In patients who are chronic carriers of hepatitis b virus (HBV), m is infected with HBV, can be suppressed by using posttranscriptional mechanism, mediated IFN-, TNF and IL-2 (Chisari and others, Springer Semin. Immunopathol. 17, 261, 1995). IFN - may be 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 demonstrated that dependent 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). IFN - participates in the development of chronic inflammation of the intestine in such diseases as Crohn's disease and vospalitelnost, 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 - negatively correlated with levels of IgE in serum, indicating a role of IFN - 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 derivative heteroarylboronic that can be used for the treatment 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 walking cases. Therapeutic agent-based protein are expensive, and it has certain problems associated with 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.

Thus, 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 new SOEDINENIYa the 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-C4alkyl, C1-C4alkoxy or C1-C4alkylaminocarbonyl 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 branched or unbranched1-C4alkyl, C1-C4alkoxygroup, the hydroxy-group, nitrile, mono - or di(C1-C3alkyl)amino group, gnuu 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, a group WITH1-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, pentamethylenetetrazol, which optionally is substituted by 1-3 substituents selected from nitrile, C1-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 the phenyl ring is optionally substituted by 1-2 halogen atoms, C1-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 neonaticides 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 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 galogenirovannami, the group of NH4C(O) and di(C1-C3)alkylaminocarbonyl,

b)3-C7cycloalkyl 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, CHOH, >C=O, &g 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, 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-C3alkoxycarbonyl, branched or unbranched1-C6alkylaminocarbonyl, branched or unbranched1-C6alkylcarboxylic-C1-C3alkyl,

R2means a branched or unbranched C1-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, 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, votary 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, 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-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) 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 or condensed heterocyclyl ring substituted by 0-3 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 non-branched C1-C6alkyl which is optionally partially or fully galogenidov, halogen, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami, venrooy above in this paragraph group, 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 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-C5the alkyl(R13)N,

C) cycloalkyl selected from the group comprising cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptene, this cycloalkyl optionally partially or fully galogenidov and optionally substituted WITH 1-31-C3alkyl groups,

g)5-C7cycloalkenyl selected from the group comprising cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl and bicycloheptene, this cycloalkylcarbonyl 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 a branched or non-branched C1-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 is a group or 0-3 branched or non-branched C1-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 optionally substituted WITH 1-31-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 purwahono the 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 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)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 with rupalee 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 R3while

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, alkoxycarbonyl-alkyl 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 LASS="ptx2">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,

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]mochiv-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-pyridine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-(6-methylpyridin-3-yl)-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-(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-3-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-metalcloak)-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-iletileri-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 who-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-mirasol-3-yl]-3-[4-(3-(furan-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-pyridine-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-thylamino)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-4-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-feast is 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-Mohn-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 1-31-C4alkyl, C1-C4alkoxy - or1-C4alcaligenaceae, each of which is branched or ner is inil, 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) and 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, N or S(O)mand 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, indanyl, heteroaryl selected from benzimidazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolidinone, 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 values, C1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, nitrile, carboxylate, phenyl, and phenyl ring optionally substituted by 1-2 zamestitel1-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, C1-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 group,

or Z is optionally substituted by 1-3 substituents selected from the group comprising aryl, heterocycle 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-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola, C1-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 and heterocycle are above in this paragraph, values, or Z means a branched or unbranched1-C6alkyl, WITH6alkyl-S(O)mand phenyl-S(O)mwhere the phenyl ring is optionally substituted by 1-2 halogen atoms, C1-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 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(C1-3)alkylaminocarbonyl,1-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 a branched or non-branched C1-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, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohe the UB>3alkoxygroup, which is optionally partially or fully galogenirovannami, the group of NH2C(O) and mono - or di(C1-C3)alkylaminocarbonyl,

g) C5-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) the, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furret, 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, hydroxypropy, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C3alkoxyl1-C5alkyl, C1-C3thioalkyl,1-C3thioalkyl1-C5alkyl, fenoxaprop, naphthyloxy, heterokaryosis in which heterocycl>-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, cyclopentenopyridine, cyclohexanediamine, cyclopentenopyridine, cyclohexanediamine, cyclopentenopyridine, cyclopentenopyridine, cyclopentanediol, cyclohexanediol, cyclopentanethiol, imidazole, 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 who 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,

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 WITH 1-31-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,

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 Kotor is inil, pyrazinyl, tetrahydropyridine, pyrimidinyl, pyridinyl, piperidinyl, benzimidazole or piperazinil, each of which independently of each other 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)aminogroup, mono - or di(C1-C3alkylamino)the carbonyl group of NH2C(O), group C1-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, pentamethylene,

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, morpholinoethyl,1-C3acyl, 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 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-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 UB>1-C5alkoxyl1-C3the alkyl, C1-C5alkoxygroup, Arola,1-C3the acyl group1-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 is 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, neediness1-C3the alkyl, tetrahydrofuranyl1-C3the alkyl, nitrile1-C4the alkyl or phenyl, with phenyl ring optionally substituted with 1-2 substituents selected by the SUB>alkyl)amino group,

or Z means a branched or unbranched C1-C6alkyl, C1-C6alkoxygroup or NITRILES1-C4alkyl,

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 by 1-3 C1-C3alkalyne 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 non-branched C1-C5alkyl groups,

- cyclopentenyl and cyclohexenyl, optionally substituted by 1-3 C1-C3alkyl groups,

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov and optionally substituted nitrilosides 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, 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, oxoprop, nitrile, C1-C3alkoxygroup, which is optionally partially or fully galogenirovannami,1-C3alkoxo-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), a mono - or d is 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, 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,

- 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(With 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(O0)1-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,

R4, R5, R6, R7, R9

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

In the following embodiment of the invention among directly above preferred those compounds 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, tetrahydrofuranyl, tetrahydropyranyl, piperazinil, morpholinopropan, thiomorpholine, Tomorrowland and p is -3 substituents, selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxygroup, C1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, morpholinoethyl,1-C3acyl, 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, C1-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, C1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups, or Z is optionally substituted by 1 to 3 amino groups, aminocarbonyl groups or amino-C1-C3alkyl groups, where N is the atom optionally in each case independently mono - or Disaese aminos1-C6the alkyl, C1-C3the alkyl, aryls0-C3the alkyl, C1-C5alkoxyl-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 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-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, C1-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 unbranched11-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,

- extensive WITH3-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, razvetvlenno the 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)alkylaminocarbonyl,

- 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, long 4alcaligenaceae, 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, heterocycle selected from 2-oxa-5-azabicyclo[2.2.1]heptane, pentamethylbenzonitrile, pentamethyldisiloxane, pentamethylbenzonitrile, tetrahydrofuranyl, tetrahydrofuranyl, 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, C1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl, morpholinoethyl, C1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, NITR the AMI halogen, 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-C3alkyl) amino groups, or Z is optionally substituted by 1 to 3 amino groups or aminocarbonyl 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 arils1-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 disame the Ohm, WITH1-C3alkoxyl1-C3the alkyl, C1-C3the acyl, nitrile1-C4the alkyl, phenyl, with phenyl ring optionally substituted by 1-2 halogen atoms, C1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl) amino groups, or Z means a branched or unbranched C1-C6alkyl, C1-C6alkoxygroup or NITRILES1-C4alkyl,

R1means 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-C3al the SUB>-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

Ar1mean 5-tert-butylphenol-3-yl, where the 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 C1-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 g is/SUB>-C3alkoxygroup, oxoprop, the hydroxy-group and the group of NH2C(O)-,

or Z is 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, such phenyl or heterocyclic group is optionally substituted with 1-2 substituents selected from the group comprising C1-C2alkyl which is optionally partially or fully galogenidov,1-C2alkoxygroup, which is optionally partially or fully galogenirovannami,1-C2thioalkyl, C1-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 neoba the plants directly among the 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 perivela.

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-mirasol-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-[5-tert-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-dimethylaminomethylphenol)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 the et-butyl-2-methyl-2H-pyrazole-3-yl]-3-[4-(6-(morpholine-4-ylmethyl)nereden-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-(pyridine-2-yl)ethylamino)cyclohexenyl)naphthalene-1-yl]urea,

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

1-[5-tert-butyl-2-(-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-(morpholin-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-mirasol-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-methylaminomethyl)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-HYDR shall Sitel)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-machineryin-3-yl)-2H-pyrazole-3-yl]-3-[4-(4-morpholine-4-iletilerini-1)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-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-is util-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-(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-p-tolyl-2H-pyrazole-3-yl]-3-[4-(4-(3-carbamylethyl)naphthalene-1-yl]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-metaperiodic-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-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-(4-(4-caramelfairy-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-(morpholin-[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 is lexi)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-of gasoline�]-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-(2-(morpholine-4-ylcarbonyl)pyrimidine-5-yl)naphthalene-1-yl]urea,

1-[5-tert-butyl-2-n-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-(hydroxypyridine-3-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, as well as 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-met-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)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-(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 who 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-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]aftalion-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-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-methyl is et-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'H-[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-yl-carbonyl)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):

where G means

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,

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

Ar denotes phenyl, naphthyl, chinoline, ethenolysis, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, dihydrobenzofuran, indolinyl, benzo is ascoltami 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, librarymanager, mono - or di(C1-C3alkyl)amino group, a group WITH1-C6alkyl-S(O)mthe group CN, CONH group2the COOH group and phenylaminopropyl, where the phenyl ring is optionally substituted by 1-2 halogen atoms, WITH1-C4alkyl groups or WITH1-C6alkoxygroup,

- tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, morpholine, thiomorpholine, Tomorrowland, Tomorrowland, piperidinyl, piperidinyl, piperazinil, tetrahydropyrimidines, 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, C1-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,an 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 and irinel, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, Tinel, 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)aminocarbonyl,

- 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 C1-C3alkyl which is optionally partially 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,

- fenoxaprop or benzyloxy what estately, 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 is optionally partially 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)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, 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 galogenirovannami, 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, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadiene, bicyclohexyl or bicycloheptene, this cycloalkenyl group optionally substituted by 1-3 C1-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, which neobyazatelnoe on, 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

- a branched or non-branched C1-C6alkyl which is optionally partially or fully galogenidov, acetyl, aroyl, branched or unbranched1-C4alkoxygroup, which in each case optionally partially or fully galogenirovannami, halogen, methoxycarbonyl, group C1-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

2NSO2,

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, described above 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-C3alkyloxy, which is optionally partially or fully halogenide the th or heteroaryl fragment described above in this paragraph, the 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, C1-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-C5alkyl) 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, silentninja, 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, 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)amino the>WITH5alkyl, mono - or di(C1-C3)alkylamino-C1-C5alkyl, R12-C1-C5alkyl, R13-C1-C5alkoxygroup, R14C(O)-C1-C5the alkyl group and R15-C1-alkyls5(R16)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 1-3 C1-C3alkyl groups,

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

- C1-C6alkyl group or a branched or unbranched1-C6alkoxygroup, each cor CLASS="ptx2">- 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 R23R24N(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, imidazolyl, phenyl, pyridinyl, tetrazolyl, 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(C1-C4alkyl)amino group, which may be the B>-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 mean C1-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, RIn partially or fully galogenidov, with the specified1-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, tetrahydronaphthyl, benzocycloheptene, benzocycloheptene, indanyl, indenyl,

- pyridinyl, pyridinyl, chinoline, dihydroquinoline, tetrahydropyranyl, ethenolysis, tetrahydrothieno, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, the phenyl, 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, tetrahydrofuranyl, 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, benzimidazolyl, benzoxazolyl, benzofuranyl, benzothiophene, respiratory, dihydrobenzofuranyl, dihydrobenzofuranyl, indanyl, indenyl, indolyl, indolinyl, indolyl or indolinyl, with G replaced odonel, 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 comprising nitrile,1-C3alkyl, C1-C3alkoxygroup, amino group, mono - or di(C1-C3alkyl)amino group, a CONH group2and grainy, 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-C4alkoxygroup, 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

- C3-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 of these substituents optionally is substituted by 1-3 substituents selected from halogen, C1-C3of alkyl, which NPY, 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 C1-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, SEN, >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 by 1-3 substituents selected from g is UB>1-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, 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 group mono - or di(C1-C3alkyl)amino-S(O)2, R7-C1-C5alkyl, R8-C1-C5alkoxy 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,

- OR18or C1-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)- 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 neoblasts>

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-C4-carbon chain, where one of the carbon atoms is optionally replaced by O, N or S, and Y is optionally independently substituted by exography,

Z means

- generanl or pyrrolidinyl, which optionally substituted WITH 1-21-C2alkyl groups or WITH1-C2alkoxygroup,

- tetrahydropyranyl, morpholinyl, thiomorpholine, Tomorrowland, 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

- C3-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 C1-C3alkyl, which is optionally frequent is cyclobutyl, 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,

- OR18or C1-C3alkyl group optionally substituted by a group OR19,

- R20C(O)N(R21)-, R22O-, R23R24NC(O)-, R26CH2C(O)N(R21)-, 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 halogenerator, optionally substituted by 1-3 substituents selected from the group comprising methyl, which is optionally partially or 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,

- OR18or C1-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 R23R23and R24mean N or R23and R24together optionally form morpholinopropan and

R26means morpholinopropan.

In another embodiment of the invention among directly 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-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, 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 fanini 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)naphthalene-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-tolyl-urea,

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]macevich">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-morpholine-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)nafta is P>

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-triptoreline)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-(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]urea,

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

ethyl ester 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-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 the Dol-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)naphthalene-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)navino,

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]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-met the 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]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-iletilerini-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-114-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-114-thiomorpholine-4-ylmethyl)pyridine-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}MoA

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

1-[2-methoxy-5-(1-methylcyclohexyl)phenyl]-3-{4-[4-(1-methylpiperidin-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) is-yl)naphthalene-1-yl]urea,

1-[3-tert-butyl-5-(2-pyrrolidin-1-retil)phenyl]-3-{4-[6-(1-methylpiperidin-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-pyridine-4-iletileri)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-methylpyridin-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) shall methylpropionamide,

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-(tetrahydropyran-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)Naftan,

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]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-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-[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-methoxy-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-iletilerini-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)naphthalene-1-yl]ureido}benzamide

and their pharmaceutically acceptable derivatives.

In another embodiment, the invention provides the following compounds of the 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 the Lin-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-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">The fourth object of the invention are the compounds of formula (III)

in which E denotes carbon or containing a heteroatom group selected from-O-,

-NH - and-S-,

G means

aromatic WITH6-C10carbocycle or saturated or unsaturated non-aromatic C3-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,

thus G is optionally substituted 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 OI or 1-31-C4alkyl, C1-C4alkoxy or C1-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 unbranched C1-C4-carbon chain, which optionally partially or fully galogenirovannami, with one or several C-atoms are optionally replaced by O, N or S(O)ma Y is optionally independently substituted with 1-2 exography, nitrile, phenyl or one or more C1-C4alkyl groups, which neoba selected from pyridinyl, the 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, tetraethyleneglycol, tetramethyldisiloxane or tetramethylsilane, tetrahydropyranyl, tetrahydrofuranyl, 1,3-DIOXOLANYL, 1,3-dioxanone, 1,4-dioxane, 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, C1-C3alkoxy-C1-C3alkyl, C1-C6alkoxycarbonyl, aroyl,1-C3acyl, oxoprop, the hydroxy-group, pyridinyl-C1-C3alkyl, imidazolyl-C1-C3alkyl, tetrahydrofuranyl-C1-C3alkyl, nitrile-C1-C3alkyl, nitrile, carboxypropyl, phenoxypropane 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, C1-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, C1-C3the acyl group1-alkyl-C3(OH)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 C1-C6alkoxygroup, or 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 IDA N atom is optionally independently mono - or Disaese1-C3the acyl, C1-C6the alkyl or C1-C3alkoxyl1-C3the alkyl, branched or unbranched1-C3alkyl, 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, C1-C6alkoxygroup, hydroxy groups or mono - or di(C1-C3alkyl)amino groups,

R1in each case, independently means

branched or non-branched C1-C10alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O, N or S(O)ma specified WITH1-C10alkyl optionally substituted by 1-3 substituents selected from the group comprising FROM3-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 mandated anirban, C3-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 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, hydroc uppy 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)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, tigroup, 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 unbranched3-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 cycloalkane group optionally substituted by 1-3 C1-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 with 1-2 exography, hydroxy-group, pyrrolidinyl, pirrallo, tetrahydropyranyl, one or more C1-With1-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, C1-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,

- OR6C1-C6alkoxygroup, the hydroxy-group, a nitrile, a nitro-group, halogen or

group, amino-S(O)mwhere N is the atom is optionally independently mono - or Disaese C1-C6the alkyl or arils0-C3the alkyl, or amino group, where the N atom is optionally independently mono - or Disaese1-C3the alkyl, aryls0-C3the alkyl, C1-C6the acyl group1-C6alkyl-S(O)mor group is the super partially or fully galogenidov and optionally substituted WITH 1-21-C6alkyl groups or C1-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 non-branched C1-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,oxygraph 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 and benzocycloheptene, or condensed heteroaryl selected from cyclopentenopyridine, cyclopentenopyridine, cyclopentenopyridine, cyclohexylidene, cyclopentenopyridine, 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, nitro-group, amino group, mono - or di(C1-C3alkyl)amino group, phenylaminopropyl, naphtylamine, geteroarilsulfoksidu or heterocycling,and(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 by 1-3 C1-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 1-3 C1-C3alkyl groups,

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

the system of groups, 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)-,

- C2-C6alkenyl substituted by a group R23R24N(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-C4alkyl groups which are optionally substituted by one or more of the m, tetrazolium 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 optionally partially or polnostyu>1-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, Il,

- 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, tetrahydrofuranyl, 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 wachet phenyl, pyridinyl, pyridinyl, 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 NH21-C4-carbon chain, 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-C3Alki heteroaryl, as defined above in this paragraph, each of which is 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, C1-C3alkyl, C1-C3allmenalp,1-C4alkoxygroup, amino group, mono - or di(C1-C3alkyl)aminocarbonyl or amino group, mono or disubstituted amino1-C6the alkyl or C1-C3alkoxyl1-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)ma 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, CSUB>1-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 C1-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 more halogen atoms, or

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

R2in each case, independently means

- a branched or non-branched C1-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 Disaese C1-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 alkylamine groups or WITH1-C3alkoxygroup,

R3in each case, independently means

- phenyl, morpholinopropan, pyridinyl, pyrimidinyl, pyrazinyl, 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, bicyclopentyl, bicyclohexyl, bicycloheptane, phenyl-C1-C5alkyl, naftilos1-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 to enter the l-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-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,

- OR18or C1-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)-, R26CH2(O)N(R21)-, R23R24NC(O)-C1-C2alkoxygroup or R26C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24N(O)-,

- C2-C4alkylamino branched or unbranched operneonesern replaced by Oh, and optionally independently substituted with 1-2 exography, pyrrolidinium, pirrallo, morpholinopropan, piperidinium, piperazinil, imidazolyl, phenyl, pyridinyl, tetrazolyl or one or more1-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 SUB>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 saturated WITH1-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 1-2C1-C2alkyl groups or C1-C2alkoxygroup, or

Z means a hydroxy-group, C1-C3alkyl, C1-C3alkoxygroup,1-C3allmenalp,1-C3alkylsulfonyl, nitrile-C1-C3alkyl or amino group, mono - or disubstituted WITH1- a branched or non-branched C1-C5alkyl which is optionally partially or fully galogenidov, with one or more C atoms are optionally independently replaced by O, N or S(O)ma specified WITH1-C5alkyl optionally substituted by exography, DIOXOLANYL, pyrrolidinyl, 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 by 1-3 C1-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,

- oxagrelate 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, 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 three C1-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 Disaese C1-C3the alkyl SS="ptx2">- 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 galogenidov, 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,

- OR18or C1-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 R25C(O)CH2N(R21)-,

- C2-C4alkenyl substituted by a group R23R24N(O)-,

- C2-C1quinil, replaced by pyrrolidinium or pyrrolidon, or

- Cx2">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-2,3-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, C1-C3alkoxybenzenes, the hydroxy-group, WITH1-C3alkyl, N,N-dis1-C3alkoxy-C1-C3alkylamino, C1-C3allmenalp,1-C3alkylsulfonyl or NITRILES1-C3alkbottle partially or fully galogenidov, one or more C atoms are optionally independently replaced by O or N, and the specified C1-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, which are 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 Disaese C1-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, CTU 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)-, 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]oxa is consequently replaced 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-amyl, 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, C1-C3alkoxygroup, methoxymethyl, hydroxypropyl, dimethylaminopropyl,1-C4alkylamino, NH2C(O)methoxy group, acetyl, pyrrolidinyl, imidazolyl, pyrazolyl, morpholinopropan or morpholinoethyl.

In another Varian), 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-iletileri-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-{iridin-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-morpholine-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)Naftali>

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]oxidiazol-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-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-methoxy-2-were)-3-[4-(6-morpholine-4-iletilerini-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]mine,

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,

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-cawino,

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-pyridine-3-iparralde-1-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-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-3-[4-(6-Mar-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-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)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-(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)amide econsultancy acid,

1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(4-morpholine-4-iletilerini-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-treas 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-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}MOC is about 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-oxo-114-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 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-pyridine-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-cyanoethyl)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[Holin-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,

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 pharmaceutically 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 is methylpyridin-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,

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]mo is tx2">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]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,

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-azole-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-Tr is ethoxy-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-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)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}macewen>

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-114-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-iletilerini-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-dioxyphenyl)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

and their pharmaceutically acceptable derivatives.

In addition to the above as examples of compounds described by either the 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-7-{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. Each stereogenic carbon atom may be in the R - or S-configuration or combination of configurations.

Some of the compounds of formula (I), (Ia), (asego of the 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) cyclopropyl, cyclobutyl, cyclopentylmethyl, 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, decahydroquinoline, decahydro is 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 the context of the present description Ponary.

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 formulas is installed from pharmaceutically acceptable 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-C4alkalyne)+4salt.

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 PII 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 excessive production of 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 relating to the 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 (M. K. O'Banion and others, the OEWG. 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 oposredovanie from it, thermal 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 administration methods.

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 descripitions funds to avoid potential toxic and harmful side effects that occur in the case when such 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 about aritin, proteins from serum, sautereau substances, water, salts or electrolytes 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, N. With. 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 valid the introduction of up 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, seriesnot the doctor.

Below the invention is illustrated in the examples. These examples illustrate preferred embodiments 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/US99/29165 and patent applications U.S. 60/124148 and 60/165867. Each of these claims in full included in the present description by reference.

The diagram above D is the radical Ar1(for compounds of formulas I and Ia) or G (for compounds of formula II is PU 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 or 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 is nom 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 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 about 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. Preferred Rustem 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 a 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 common methods proillyustrirovannymi or can be obtained by the 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 or 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, maintaining the reaction 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 slashed is the temperature below 0°C preferably below -60°C. as dialkyldithiocarbamate preferable to use di-tert-utilisationbased. The reaction mixture is stirred 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.

According to method D. arylamine bearing the substituent R3(formula IX), is dissolved in a concentrated aqueous acid, such as hydrochloric, is entrusted hydrochloric acid with concentratie 3 N. up to 8 N., more preferably 6 N. Then added dropwise agent nitrosation in the water, maintaining a lower temperature. Preferred is a temperature of 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 Na2SO4her reactions without additional purification.

-Ketonitriles bearing the substituent R1(formula XIV) may be obtained in accordance with the method F or g According to method E. the metal hydride 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 of the 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 from the receiving-ketonitriles (formula XIV), which can be used further without additional the foreign metal, for example, n-utility, second-utility, motility and diisopropylamide lithium, in an anhydrous inert aprotonin a solvent such as 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. the Solution 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°C 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 UB> and remove volatile components from the receiving-ketonitriles (formula XIV), which can be used further without additional purification.

Target aminopyrazole (formula XV) can be obtained then in accordance with method C or I. According to method C arylhydrazines formula X-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 to 100°C, preferably at 80°C, 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 Na4SO4and remove volatile components to obtain a residue, which is purified by recrystallization or chromatography on silica gel using hexie components to obtain the desired aminopyrazole (formula XV).

In another embodiment according to the method And arylhydrazines formula X-ketonitriles formula XIV are 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, illustrates the General process for the synthesis of the target aminothiophenes.

A mixture of 1-aryl-5-al is respectfully reagent of Lawesson, dissolve in aprotonin anhydrous solvent such as toluene, THF or dioxane. The preferred 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 to 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 to 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 water school is purified by chromatography on silica gel using hexanol and ethyl acetate as eluents. Fractions with a high content of product are collected and removed 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°C., more preferably at 100°C for 5-30 min 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 national XX) at low temperature, for example at 0°C. After stirring the reaction mixture until then, until you used up all the source material, it was poured into cold water and extracted with aprotonin solvent. Then the combined extracts dried with such agents as MgS4or 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) acidtreated similarly to the method described by Lakhan and others (J. Het. Chem., 1988, 25, 1413) and illustrated in scheme V. the mixture of arolina (formula XXIV), aldehyde (formula XXV) and anhydrous ammonium acetate in acetic acid withstand heating at 100-110°C for 3-6 h, cooled to room temperature and then the reaction stopped by the addition of 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.

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 are dried with the help of these to use in further without additional purification 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.

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.

Substituted 5-aminothiazole (formula XXXVII) can be obtained similarly to the method described by Gerwald and others, J. Prakl. Chem. 1973, 315, 539.

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 ek 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.

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. then 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 AI XI is similar 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 temperature of distillation, 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).

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. The combined extracts are dried with the help of such agents, as MgSO4and Na2

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.

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. Preferred at temperatures of 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) is collected by filtration, 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 the additional cleaning or clean by chromatography on silica gel.

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.

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 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 describes the 1-NH2.

Methods to obtain the intermediates of formulas V and VI (scheme I, D' means the group Ar-X-Y-Z or Ar2-X-Y-Z), described below.

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 about 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 rectitude 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 following examples of 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°C, to obtain 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 closed 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 Provillus the CT, 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 can then be used similarly to M.

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 SP is

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°C for 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 using 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.

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

La, 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 tOAc/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-furaldehyde (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 I (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. 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 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, 0,901 mmole) according to the above described method M radagaisus 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°C for 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 (t)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 pounds per square inch at 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 warialda 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 the buffer with a pH of 7 (feast upon. Na2HPO4/NaH2PO4) (10 ml) and the mixture is heated to room temperature. Slo (sodium sulfate), 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 LXXXITI (302 mg, 0,646 mmole), compound LXXI (177 mg, 0,797 mmole) and Pd(PPh3)4(55 mg, 0.48 mmole) in anhydrous 1,4-dioxane (10 ml) is heated to 100°C in 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 tOAc/hexanol get mentioned in the title compound 4 as white is(morpholine-4-yl)phenyl]naphthalene-1-yl}urea

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 the I) 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 t 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 tOAc/hexanol getting 0,344 g specified in the title compound 5 (tPL188-190°C).

The table shows other connections izobreteniya-(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 (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 (3×10ml). 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 Treaty 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 extracted with 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/tO 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% MeOH/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°C. add n-BuLi (47 mmol). The yellow-green solution was stirred at -78°C for 2 h, and then per the I 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 aqueous 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 a stream of N2within 15 minutes, 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 tO (75 ml). The layers are separated and the organic phase washed with brine (20 ml), dried (MgSO4), filtered and removed solvent is CSO solids.

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 diethyl ether (5 ml) and the mixture cooled to 0°C. After neutralization with aqueous NaOH and filtration obtain 4-[6-(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°C is 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 tolt heated under reflux for 2 h, that 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 temperature overnight. 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°C 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 reactionat approximately to a 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 using 7% Meon/tO 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°With 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 in the soedineniya 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°C and treated l3(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 komatshini sedimentation 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°C and the reaction mixture was 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°C and treated with 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/EtO is ejogo substances (71 mg, 58%).

4-(4-tert-butyl-2-nitrophenyl)pyrazole (a 0.27 mmole) is dissolved in t (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, etc., Russian Chemical Bulletin, 1996, 45(2), 393-398. Next, the reaction mixture is alkalinized 4 N. hydrochloric acid, extracted with simple ether (3×25 ml) and then EtOAc (3×100 ml). United tO extracts 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 races is for 2.5 hours, 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 sodium bicarbonate (500 ml), keeping the temperature below 10°C. Then, the heterogeneous mixture 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%).

Solution this is Cetona. 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°C., then slowly add 2-molar aqueous solution of hydrochloric acid (45 ml), keeping the temperature below 10°C. the Mixture is stirred at room temperature for 15 hours, the Layers 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) and n is uuma and the residue is stirred in ice-cold water (10 ml) for 18h. After that, 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 is heated in a hermetically sealed tube 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%(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), iodomethane (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 in VI the ml) is treated with 65% solution of Red-Al in toluene (of 0.64 ml, is 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) obtaining dimethylindoline as a pale blue 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 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% palladium on 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 the Les 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°C and added dropwise via syringe over 15 min add-chlorocatechol (0,12 ml of 1.47 mmole) in 1.5 ml of chloroform. Upon completion of the addition, the mixture is left to be mixed 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°C in one portion add sodium hydride (10 mg, 60% dispersion in mineral oil, 0.24 mmole). the second temperature during the night. 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-methylbenzamide (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 t is 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% tO/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 a sub is SS="ptx2">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) (22,8 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 (MgSO4and Kon is 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 brine 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% tO/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°C. 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°C, intensive mixing 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) 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, 18 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% Nug 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 the same is lisali of 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 to room temperature. 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°C and treated with 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 temperator in water Panso3getting 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 stirred for 15 minutes then 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 is up to 0°C 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 temperature the reaction mixture was poured into a mixed solution NaPF6(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 in the ratio is ditusa stage ester (150 mg, to 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, of 0.36 mmole) 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. After that remove 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, MD 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 of such counterparts 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 barbola, 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, exit 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).

3and extracted with EtOAc (2×50 ml). The aqueous layer was treated with 4 N. aqueous solution of NaOH until it's time until the pH value is set about 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 SiOthe unity 31 (0,11 mmole, a yield of 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. The mixture is stirred at ambient temperature overnight, 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 the solvent, and the residue is purified column chromatography on SiO2using 15-25% EtOAc in hexano as mixtures allentow, 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-minute stirring at -78°C 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 silica gel 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).

1H-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 4 N. 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 mixtures eluents, 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 (2x10 ml). tO-fraction is dried over anhydrous sodium sulfate and evaporated on a rotary evaporator. The crude product is distilled to-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 the Re-analogue of XCI 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 mixture was added EtOAc and the mixture washed with water (2×10 ml). tO-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% tO/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 Express chromatography HP CLASS="ptx2">Example 34

The dihydrochloride [5-(4-aminonaphthalene-1-yl)pyridin-2-yl]-(tetrahydrothiopyran-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 in the form of a white solid with tPL80-83°C (88.7 per cent).

In a dry flask containing THF (20 ml) and 1 M 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 videochat 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 a nitrogen atmosphere 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.

/P>

To 2-amino-5-bromopyridine (250 mg, 1.44 mmole) and RE-secure NativeWindow acid XCI (example 17) (688 mg, 2.4 mmole) in 5 ml of DME is added 2 M sodium carbonate (2.5 ml) and chloride bis(triphenylphosphine)palladium (30 mg). The reaction mixture was kept with heating at 90°C. in a 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, 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% tO/hexane as eluent, to obtain 120 mg of the compound XCXI (48,0%).

Obtained in the previous phase connection XCXI RA is amerivault 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 was stirred 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% Meon/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 the form-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-butylphenol (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-dimethyl who for 16 PM 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-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,

amide 1-(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-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)-(tetrahydrofuran-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-(6-thiomorpholine-4-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-methoxyphenyl)-3-{4-[6-(1-oxo-14-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-Jn-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]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-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-mate the ro-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-(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,

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

Assess the production of cytokines can be assessed by measuring inhibition in TNF stimulated with lipopolysaccharides TNR-cells (see, for example, W. Prichett, etc., J. Inflammation, 45, 97, 1995). All cells and reagents were diluted environment RPMT 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 the analysis of concentration.

Confluently TNR.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; sterile) 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; end concentrate 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 kept at -80°C until analyzed in relation to human TNF 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). The calculated value IC50represents the concentration of test compound which causes a 50% increase decrease production of TNF 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 m the current monocytes peripheral blood, 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-1, 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 (I)

in which Ar1means pyrazole which may be substituted by one or more groups R1, R2or R3;

AG2means naphthyl, tetrahydronaphthyl, each of which is optionally substituted by 0-1 groups R2;

X means5-C8cycloalkenyl, phenyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, furanyl, pyridinyl, pyrazolyl, pyridinyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, piperidinyl;

Y represents a bond or a saturated branched or unbranched1-C4the carbon chain, with one methylene group is optionally replaced by NH or Y is optionally independently substituted by oxopropoxy;

Z means morpholino group, pyridinyl, furanyl, tetrahydrofuranyl, myomorpha is covalently linked to the following groups, selected from a range that includes WITH1-C3alkyl and C1-C5alkoxyalkyl;

R1means3-C10alkyl which is optionally partially or fully galogenidov;

R2means a branched or unbranched1-C6alkyl which is optionally partially or fully galogenidov, halogen;

R3means phenyl, pyrimidinyl, pyrazolyl, which is substituted by one branched or unbranched1-C6the alkyl, and pyridinyl, optionally substituted C1-C3alkoxygroup or amino group;

W means that,

and its pharmaceutically acceptable salts.

2. Connection on p. 1, in which Y represents-CH2-, -CH2CH2-, -CH2NH-, -CH2CH2NH - or a bond, and Z means morpholine, pyridinyl, furanyl, tetrahydrofuranyl, thiomorpholine, pentamethylbenzene, pentamethylbenzene, secondary or tertiary amine, the nitrogen atom of the amino group covalently linked to the following groups selected from a range that includes WITH1-C3alkyl and C1-C5alkoxyalkyl.

3. Connection on p. 2, in which Ar1mean 5-tert-butylphenol-3-and pyrazolyl, which is substituted by one branched or unbranched1-C6the alkyl, and pyridinyl, optionally substituted C1-C3alkoxygroup or amino group.

4. Connection on p. 3, wherein X is pyridinyl.

5. Connection on p. 4, in which the pyridinyl is attached to AG1in the 3rd position pyridinyl.

6. The compound of formula (I) under item 1, selected from the group including

1-[5-tert-butyl-2-p-tolyl-2H-pyrazole-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-(is Holin-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-(pyridine-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-yl-methyl)phenyl)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-(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-(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)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-(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)-2 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-(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-(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-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-iletileri-3-yl)naphthalene-1-yl]urea,

1-(5-tert-butyl-2-ethoxymethylene)-3-[4-(6-morpholine-4-ilma is-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-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)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-hydroxy the Lin-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)-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]dicotyledon-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]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 is espiridion-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-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)sobouti CLASS="ptx2">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-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,

LASS="ptx2">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-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]cash}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 the>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 salts.

7. Pharmaceutical composition for treating diseases mediated by cytokines and neutrophils containing a pharmaceutically effective amount of the compounds under item 1.

8. 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 the compounds under item 1.

9. The method according to p. 8, 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 disease, systemic lupus erythematosus, diabetes, toxic shock, osteoporosis, Alzheimer's disease, acute and chronic pain, contact dermatitis, and atherosclerosis.

10. The method of treatment mediated by neutrophils disease selected from the group including a shot, the e as a result of injury, acute glomerulonephritis, dermatitis, accompanied by acute inflammation, acute purulent meningitis, hemodialysis, lamfers (leukopheresis) associated with the transfusion of granulocytes syndromes, and necrotizing enterocolitis, which consists in the introduction to a patient in need of such treatment, a therapeutically effective amount of the compounds under item 1.

Priority items:

12.03.1999 on PP.1-13;

16.11.1999 on PP.1-13.



 

Same patents:

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to new N-heterocyclic derivatives of the formula (I):

where: A means-OR1-C(O)N(R1R2or-N(R1R21; each X, Y and Z independently represents N or C(R19); each U represents N or C(R5), provided that U is N only when X represents N, and Z and Y denote CR19; each W represents N or CH; V denotes: (1) N(R4); (2) C(R4)H; or (3) the groupdirectly related to the group -(C(R14R20)n-A,denotes a 5-6-membered N-heterocyclyl, optionally containing 6-membered ring additional heteroatom selected from oxygen, sulfur and NR6where R6denotes hydrogen, optionally substituted phenyl, 6-membered heterocyclyl containing 1-2 nitrogen atom, optionally substituted 5-membered heterocyclyl containing 1-2 nitrogen atom, aminosulfonyl, monoalkylammonium, dialkylaminoalkyl,1-6alkoxycarbonyl, acetyl, etc

The invention relates to chemistry and medicine, in particular relates to new chemical compounds - derivatives of 3,4-bis(furazan-3-yl)furoxan General formula I:

where R = R1= HE, NH2N3lowest alkoxy or a group of the General formula NR2R3where R2= R3= N or R2and R3together with the nitrogen atom form piperidinyl cycle, or R = NH2and R1- (lower alkanoyl)amino group, provided that R and R1not represent methoxy, possessing pharmacological activity

The invention relates to organic chemistry and pharmacology, and relates new connection - 1-(1,1-dissociator-3)-2-morpholinobenzenediazonium hydrochloride, increasing resistance to acute hypoxia with hypercapnia

The invention relates to new compounds of the formula (I) and their pharmaceutically acceptable salts and esters possessing inhibitory ability against endothelioma receptors, the Compounds can be used to treat diseases associated with abnormal vascular tone and endothelial dysfunction

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to organic chemistry and can find application in medicine

The invention relates to pharmaceutically acceptable salts of the compounds of formula (I) or solvate specified salts in which the compound of formula (I) is in the form of (R)-enantiomer, (S)-enantiomer or the racemate

The invention relates to imidazole derivative of the formula (I), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to a method for producing compounds of formula I:

where R is tert-butoxycarbonyl, benzoyl or the remainder of the straight or branched aliphatic acid, R1means phenyl or a straight or branched alkyl or alkenyl and R2means hydrogen or acetyl, which comprises: (a) simultaneous protection of the hydroxyl groups in positions 7 and 10 10-deacetylbaccatin III trichloroethylene derivatives with obtaining the compounds of formula III:

b) subsequent etherification of the hydroxyl group of the compounds of formula III in position 13 interaction with the compound of the formula VII:

where R is tert-butoxycarbonyl, benzoyl or the remainder of the straight or branched aliphatic acid and R1means phenyl or a straight or branched alkyl or alkenyl, obtaining the compounds of formula IV:

(C) removing trichloroethylene protective groups of the compounds of formula IV with connection inflectional acetylation of the hydroxyl group in position 10 of the compounds of formula V to obtain the compounds of formula VI:

e) acid hydrolysis oxazolidinone ring compounds of the formula VI to obtain the compounds of formula I

The invention relates to imidazole derivative of formula (1), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to omega-Amida N-arylsulfonamides formula I

and/or stereoisomeric forms of the compounds I and/or physiologically acceptable salts of the compounds I where R1means phenyl, phenyl, substituted once with halogen, the rest of the heterocycle of the following groups: morpholine, pyrrolidine; R2means N; R3means -(C1-C4)-alkyl-C(O)-N(R6)-R7where R6and R7together with the nitrogen to which they are bound, form a residue of formula IIa, IIe

moreover, in formula IIa, IIe q indicates an integer of zero or 1, Z denotes the carbon atom or a covalent bond, and R8means a hydrogen atom or halogen, or R3means -(C1-C4)-alkyl-C(O)-Y, where Y means the remainder of the formula IIC or IId

moreover, in formulas IIc and IId, R8means H or halogen, R9means H, or R3means -(C1-C4)-alkyl-C(O)-N(R9)-(CH2)about-N(R4)-R5and R9has the above values, means the integer 2 and R is substituted by-O-, And means covalent bond, B means -(CH2)m- where m is zero, X is-CH=CH-

The invention relates to new derivatives of 1,3-diaryl-2-pyridin-2-yl-3-(pyridine-2-ylamino)propanol of the formula (I)

where Z denotes-NH-(C1-C16-alkyl)-(C=O)-; -(C=O)-(C1-C16-alkyl)-(C=O)-;

-(C=O)-phenyl-(C=O)-; AND1AND2AND3AND4denote independently of each amino-acid residue, E represents-SO2-R4and-CO-R4; R1- phenyl, thiazolyl, oxazolyl, thienyl, thiophenyl and others, R2- N., HE, CH2HE, OMe; R3Is h, F, methyl, OMe; R4denotes -(C5-C16-alkyl), -(C0-C16-alkylen)-R5, -(C=O)-(C0-C16-alkylen)-R5, -(C=O)-(C0-C16-alkylene)-NH-R5and others, R5denotes-COO-R6, -(C=O)-R6-(C1-C6-alkylen)-R7, phenyl, naphthyl and others, R6denotes H, -(C1-C6) alkyl; R7denotes H, -(C1-C7-cycloalkyl, phenyl, naphthyl and others, l, q, m, n, o, p denote 0 or 1, and l+q+m+n+o+p is greater than or equal to 1, and their pharmaceutically acceptable salts
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