ZA200107446B - Compounds useful as anti-inflammatory agents. - Google Patents

Description

Compounds Useful as Anti-inflammatory Agents

APPLICATION DATA

This application claims benefit to US provisional applications: 60/124.148 filed March 12, 1999 and 60/165.867 filed November 16. 1999.

TECHNICAL FIELD OF THE INVENTION

This invention relates to novel compounds which inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease.

This invention also relates to processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

BACKGROUND OF THE INVENTION

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are important biological entities collectively referred to as proinflammatory cytokines. These, along with several other related molecules, mediate the inflammatory response associated with the immunological recognition of infectious agents. The inflammatory response plays an important role in limiting and controlling pathogenic infections.

Elevated levels of proinflammatory cytokines are also associated with a number of diseases of autoimmunity such as toxic shock syndrome, rheumatoid arthritis, osteoarthritis, diabetes and inflammatory bowel disease (Dinarello, C.A., et al., 1984,

Rev. Infect. Disease 6:51). In these diseases, chronic elevation of inflammation exacerbates or causes much of the pathophysiology observed. For example, rheumatoid synovial tissue becomes invaded with inflammatory cells that result in destruction to cartilage and bone (Koch. A.E., er al., 1995, J. Invest. Med. 43: 28-38). An important and accepted therapeutic approach for potential drug intervention in these diseases is the reduction of proinflammatory cytokines such as TNF (also referred to in its secreted cell-

free form as TNFa) and IL-1. A number of anti-cytokine therapies are currently in clinical trials. Efficacy has been demonstrated with a monoclonal antibody directed against TNFa in a number of autoimmune diseases (Heath. P., “CDP571: An Engineered

Human IgG4 Anti-TNFa Antibody” IBC Meeting on Cytokine Antagonists,

Philadelphia, PA. April 24-5, 1997). These include the treatment of rheumatoid arthritis,

Crohn’s disease and ulcerative colitis (Rankin, E.C.C.. er al., 1997, British J. Rheum. 33: 334-342 and Stack. W.A,, er al., 1997. Lancet 349: 521-524). The monoclonal antibody is thought to function by binding to both soluble TNFa and to membrane bound TNF. ic A soluble TNFa receptor has been engineered that interacts with TNFa. The approach is similar to that described above for the monoclonal antibodies directed against TNFa; both agents bind to soluble TNFa. thus reducing its concentration. One version of this construct, called Enbrel (Immunex, Seattle, WA) recently demonstrated efficacy in a

Phase III clinical trial for the treatment of rheumatoid arthritis (Brower et al., 1997,

Nature Biotechnology 15: 1240). Another version of the TNFa receptor, Ro 45-2081 (Hoffman-LaRoche Inc., Nutley, NJ) has demonstrated efficacy in various animal models of allergic lung inflammation and acute lung injury. Ro 45-2081 is a recombinant chimeric molecule constructed from the soluble 55 kDa human TNF receptor fused to the hinge region of the heavy chain IgG1 gene and expressed in eukaryotic cells (Renzetti, er al, 1997, Inflamm. Res. 46: S143).

IL-1 has been implicated as an immunological effector molecule in a large number of disease processes. IL-1 receptor antagonist (IL-1ra) had been examined in human clinical trials. Efficacy has been demonstrated for the treatment of rheumatoid arthritis (Antril, Amgen). In a phase III human clinical trial IL-1ra reduced the mortality rate in patients with septic shock syndrome (Dinarello, 1995, Nutrution 11,492). Osteoarthritis is a slow progressive disease characterized by destruction of the articular cartilage. IL-1 1s detected in synovial fluid and in the cartilage matrix of osteoarthritic joints.

Antagonists of IL-1 have been shown to diminish the degradation of cartilage matrix components in a variety of experimental models of arthritis (Chevalier, 1997, Biomed

Pharmacother. 51, 58). Nitric oxide (NO) is a mediator of cardiovascular homeostasis,

neurotransmission and immune function: recently it has been shown to have important effects in the modulation of bone remodeling. Cytokines such as IL-1 and TNF are potent stimulators of NO production. NO is an important regulatory molecule in bone with effects on cells of the osteoblast and osteoclast lineage (Evans, er al.. 1996, J Bone

Miner Res. 11,300). The promotion of beta-cell destruction leading to insulin dependent diabetes mellitus shows dependence on IL-1. Some of this damage may be mediated through other effectors such as prostaglandins and thromboxanes. IL-1 can effect this process by controlling the level of both cyclooxygenase II and inducible nitric oxide synthetase expression (McDaniel et al., 1996, Proc Soc Exp Biol Med. 211, 24).

Inhibitors of cytokine production are expected to block inducible cyclooxygenase (COX- 2) expression. COX-2 expression has been shown to be increased by cytokines and it is believed to be the isoform of cyclooxygenase responsible for inflammation (M.K.

O’Banion ef al., Proc. Natl. Acad. Sci.U.S.A4, 1992. 89, 4888.) Accordingly, inhibitors of cytokines such as IL-1 would be expected to exhibit efficacy against those disorders currently treated with COX inhibitors such as the familiar NSAIDs. These disorders include acute and chronic pain as well as symptoms of inflammation and cardiovascular disease.

Elevation of several cytokines have been demonstrated during active inflammatory bowel disease (IBD). A mucosal imbalance of intestinal IL-1 and IL-1ra is present in patients with IBD. Insufficient production of endogenous IL-1ra may contribute to the pathogenesis of IBD (Cominelli, ef al., 1996, Aliment Pharmacol Ther. 10, 49).

Alzheimer disease is characterized by the presence of beta-amyloid protein deposits, neurofibrillary tangles and cholinergic dysfunction throughout the hippocampal region.

The structural and metabolic damage found in Alzheimer disease is possibly due to a sustained elevation of IL-1 (Holden, et al, 1995, Med Hypotheses, 45. 559). A role for

IL-1 in the pathogenesis of human immunodeficiency virus (HIV) has been identified.

IL-1ra showed a clear relationship to acute inflammatory events as well as to the different disease stages in the pathophysiology of HIV infection (Kreuzer, et al., 1997, Clin Exp

Immunol. 109, 54). IL-1 and TNF are both involved in periodontal disease. The destructive process associated with periodontal disease may be due to a disregulation of both IL-1 and TNF (Howells, 1995, Oral Dis. 1, 266).

Proinflammatory cytokines such as TNFa and IL-1 are also important mediators of septic shock and associated cardiopulmonary dysfunction. acute respiratory distress syndrome (ARDS) and multiple organ failure. TNFa has also been implicated in cachexia and muscle degradation, associated with HIV infection (Lahdiverta er al., 1988,

Amer. J. Med., 85,289). Obesity is associated with an increase incidence of infection, diabetes and cardiovascular disease. Abnormalities in TNFa expression have been noted for each of the above conditions (Loffreda. er al., 1998, FASEB J 12, 57). It has been proposed that elevated levels of TNFa are involved in other eating related disorders such as anorexia and bulimia nervosa. Pathophysiological parallels are drawn between anorexia nervosa and cancer cachexia (Holden, er al., 1996, Med Hypotheses 47,423).

An inhibitor of TNFa production, HU-211, was shown to improve the outcome of closed brain injury in an experimental model (Shohami, et al., 1997, J Neuroimmunol. 72, 169).

Atherosclerosis is known to have an inflammatory component and cytokines such as IL-1 and TNF have been suggested to promote the disease. In an animal model an IL-1 receptor antagonist was shown to inhibit fatty streak formation (Elhage er al., 1998,

Circulation, 97, 242).

The abnormal expression of inducible nitric oxide synthetase (iNOS) has been associated with hypertension in the spontaneously hypertensive rat (Chou er al., 1998, Hypertension, 31, 643). IL-1 has a role in the expression of iNOS and therefore may also have a role in the pathogenesis of hypertension (Singh ef al., 1996, Amer. J. Hypertension, 9, 867).

IL-1 has also been shown to induce uveitis in rats which could be inhibited with IL-1 blockers. (Xuan et al., 1998, J. Ocular Pharmacol. and Ther., 14, 31). Cytokines including IL-1, TNF and GM-CSF have been shown to stimulate proliferation of acute myelogenous leukemia blasts (Bruserud, 1996, Leukemia Res. 20, 65). IL-1 was shown to be essential for the development of both irritant and allergic contact dermatitis,

Epicutaneous sensitization can be prevented by the administration of an anti- IL-1 monoclonal antibody before epicutaneous application of an allergen (Muller, er al.. 1996.

Am J Contact Dermat. 7. 177). Data obtained from IL-1 knock out mice indicates the critical involvement in fever for this cytokine (Kluger er al.. 1998. Clin Exp Pharmacol

Physiol. 25, 141). A variety of cytokines including TNF, IL-1. IL-6 and IL-8 initiate the acute-phase reaction which is stereotyped in fever, malaise. myalgia. headaches. cellular hypermetabolism and multiple endocrine and enzyme responses (Beisel, 1995, 4m J Clin

Nutr. 62. 813). The production of these inflammatory cytokines rapidly follows trauma or pathogenic organism invasion.

Other proinflammatory cytokines have been correlated with a variety of disease states.

IL-8 correlates with influx of neutrophils into sites of inflammation or injury. Blocking antibodies against IL-8 have demonstrated a role for IL-8 in the neutrophil associated tissue injury in acute inflammation (Harada er al., 1996, Molecular Medicine Today 2, 482). Therefore, an inhibitor of IL-8 production may be useful in the treatment of diseases mediated predominantly by neutrophils such as stroke and myocardial infarction, alone or following thrombolytic therapy, thermal injury, adult respiratory distress syndrome (ARDS), multiple organ injury secondary to trauma, acute glomerulonephritis, dermatoses with acute inflammatory components, acute purulent meningitis or other central nervous system disorders, hemodialysis, leukopherisis, granulocyte transfusion associated syndromes, and necrotizing enterocolitis.

Rhinovirus triggers the production of various proinflammatory cytokines, predominantly

IL-8, which results in symptomatic illnesses such as acute rhinitis (Winther et al., 1998,

Am J Rhinol. 12, 17).

Other diseases that are effected by IL-8 include myocardial ischemia and reperfusion, inflammatory bowel disease and many others.

The proinflammatory cytokine IL-6 has been implicated with the acute phase response.

IL-6 is a growth factor in a number in oncological diseases including multiple myeloma and related plasma cell dyscrasias (Treon. er al., 1998, Current Opinion in Hematology 3: 42). It has also been shown to be an important mediator of inflammation within the central nervous system. Elevated levels of IL-6 are found in several neurological disorders including AIDS dementia complex. Alzheimer’s disease. multiple sclerosis, systemic lupus erythematosus, CNS trauma and viral and bacterial meningitis (Gruol., ef al., 1997, Molecular Neurobiology 15: 307). IL-6 also plays a significant role in osteoporosis. In murine models it has been shown to effect bone resorption and to induce osteoclast activity (Ershler er al.. 1997. Development and Comparative Immunol. 21 487). Marked cytokine differences, such as IL-6 levels, exist in vivo between osteoclasts of normal bone and bone from patients with Paget’s disease (Mills, ef al., 1997, Calcif

Tissue Int. 61, 16). A number of cytokines have been shown to be involved in cancer cachexia. The severity of key parameters of cachexia can be reduced by treatment with anti IL-6 antibodies or with IL-6 receptor antagonists (Strassmann, er al, 1995, Cytokins

Mol Ther. 1, 107). Several infectious diseases, such as influenza, indicate IL-6 and [FN alpha as key factors in both symptom formation and in host defense (Hayden, et al, 1998, J Clin Invest. 101, 643). Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis,

Castleman’s disease, psoriasis and post-menopausal osteoporosis (Simpson, er al., 1997,

Protein Sci. 6,929). Compounds that interfered with the production of cytokines including IL-6. and TNF were effective in blocking a passive cutaneous anaphylaxis in mice (Scholz et al., 1998, J. Med. Chem., 41, 1050).

GM-CSF is another proinflammatory cytokine with relevance to a number of therapeutic diseases. It influences not only proliferation and differentiation of stem cells but also regulates several other cells involved in acute and chronic inflammation. Treatment with

GM-CSF has been attempted in a number of disease states including burn-wound healing, skin-graft resolution as well as cytostatic and radiotherapy induced mucositis (Masucci, 1996, Medical Oncology 13: 149). GM-CSF also appears to play a role in the replication of human immunodeficiency virus (HIV) in cells of macrophage lineage with relevance to AIDS therapy (Crowe et ai., 1997, Journal of Leukocyte Biology 62, 41). Bronchial asthma is characterised by an inflammatory process in lungs. Involved cytokines include

GM-CSF amongst others (Lee, 1998, J R Coll Physicians Lond 32, 56). :

Interferon y (IFN y) has been implicated in a number of diseases. It has been associated with increased collagen deposition that is a central histopathological feature of graft- versus-host disease (Parkman. 1998, Curr Opin Hematol. 5, 22). Following kidney transplantation, a patient was diagnosed with acute myelogenous leukemia.

Retrospective analysis of peripheral blood cytokines revealed elevated levels of GM-CSF and IFN y. These elevated levels coincided with a rise in peripheral blood white cell count (Burke, er al., 1995, Leuk Lymphoma. 19.173). The development of insulin- dependent diabetes (Type 1) can be correlated with the accumulation in pancreatic islet cells of T-cells producing IFN y (Ablumunits, el al., 1998, J Autoimmun. 11, 73). IFNy along with TNF, IL-2 and IL-6 lead to the activation of most peripheral T-cells prior to the development of lesions in the central nervous system for diseases such as multiple sclerosis (MS) and AIDS dementia complex (Martino ef al., 1998, Ann Neurol. 43, 340).

Atherosclerotic lesions result in arterial disease that can lead to cardiac and cerebral infarction. Many activated immune cells are present in these lesions, mainly T-cells and macrophages. These cells produce large amounts of proinflammatory cytokines such as

TNF, IL-1 and IFN vy. These cytokines are thought to be involved in promoting apoptosis or programmed cell death of the surrounding vascular smooth muscle cells resulting in the atherosclerotic lesions (Geng, 1997, Heart Vessels Suppl 12, 76). Allergic subjects produce mRNA specific for IFN y following challenge with Vespula venom (Bonay, es al, 1997, Clin Exp Immunol. 109, 342). The expression of a number of cytokines, including IFN y has been shown to increase following a delayed type hypersensitivity reaction thus indicating a role for IFN y in atopic dermatitis (Szepietowski, ef al., 1997,

Br J Dermatol. 137, 195). Histopathologic and immunohistologic studies were performed in cases of fatal cerebral malaria. Evidence for elevated IFN y amongst other cytokines was observed indicating a role in this disease (Udomsangpetch er al., 1997, Am

J Trop Med Hyg. 57, 501). The importance of free radical species in the pathogenesis of various infectious diseases has been established. The nitric oxide synthesis pathway is activated in response to infection with certain viruses via the induction of proinflammatory cytokines such as IFN y (Akaike, et al., 1998, Proc Soc Exp Biol Med 217,64). Patients, chronically infected with hepatitis B virus (HBV) can develop cirrhosis and hepatocellular carcinoma. Viral gene expression and replication in HBV transgenic mice can be suppressed by a post-transcriptional mechanism mediated by IFN ¥, TNF and IL-2 (Chisari. ef al.. 1995. Springer Semin Immunopathol. 17. 261). IFNy can selectively inhibit cytokine induced bone resorption. It appears to do this via the intermediacy of nitric oxide (NO) which is an important regulatory molecule in bone remodeling. NO may be involved as a mediator of bone disease for such diseases as: the rheumatoid arthritis, tumor associated osteolysis and postmenopausal osteoporosis (Evans, ef al., 1996, J Bone Miner Res. 11, 300). Studies with gene deficient mice have demonstrated that the IL-12 dependent production of IFN y is critical in the control of early parasitic growth. Although this process is independent of nitric oxide the control of chronic infection does appear to be NO dependent (Alexander er al, 1997. Philos Trans

R Soc Lond B Biol Sci 352, 1355). NO is an important vasodilator and convincing evidence exists for its role in cardiovascular shock (Kilbourn, ef al, 1997, Dis Mon. 43, 277). IFNy is required for progression of chronic intestinal inflammation in such diseases as Crohn’s disease and inflammatory bowel disease (IBD) presumably through the intermediacy of CD4+ lymphocytes probably of the TH] phenotype (Sartor 1996,

Aliment Pharmacol Ther. 10 Suppl 2, 43). An elevated level of serum IgE is associated with various atopic diseases such as bronchial asthma and atopic dermatitis. The level of

IFN y was negatively correlated with serum IgE suggesting a role for IFN y in atopic patients (Teramoto et al., 1998, Clin Exp Allergy 28, 74).

Compounds which modulate release of one or more of the aforementioned inflammatory cytokines can be useful in treating diseases associated with release of these cytokines. For example, WO 98/52558 discloses heteroaryl urea compounds which are indicated to be useful in treating cytokine mediated diseases. WO 99/23091 discloses another class of urea compounds which are useful as anti-inflammatory agents.

U.S. Pat. No. 5,162,360 discloses N-substituted aryl-N’-heterocyclic substituted urea compounds which are described as being useful for treating hypercholesterolemia and atheroclerosis.

The work cited above supports the principle that inhibition of cytokine production will be beneficial in the treatment of various disease states. Some protein therapeutics are in late development or have been approved for use in particular diseases. Protein therapeutics are costly to produce and have bioavailability and stability problems. Therefore a need exists for new small molecule inhibitors of cytokine production with optimized efficacy. pharmacokinetic and safety profiles.

BRIEF SUMMARYOF THE INVENTION

In view of the work cited above there is a clear need for compounds that inhibit cytokine production in order to treat various disease states.

It is therefore an object of the invention to provide novel compounds which inhibit the release of inflammatory cytokines such as interleukin-1 and tumor necrosis factor.

It is a further object of the invention to provide methods for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease, using the novel compounds of the invention. Itis yet a further object of the invention to provide processes of preparation of the above- mentioned novel compounds.

DETAILED DESCRIPTION OF THE INVENTION

In one generic aspect of the invention, there is provided compounds of the formula(l):

0

Ars. J AATX—Y—2Z oy

H H

(D wherein:

Ar is selected from the group consisting of: pyrrole, pyrrolidine, pyrazole, imidazole. oxazole, thiazole, furan and thiophene; wherein Ar; may be substituted by one or more R,, R» or Rj;

Arn is: phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl or indole each being optionally substituted with zero to three R> groups;

Xis: a) a Cs.g cycloalkyl or cycloalkenyl optionally substituted with 0-2 oxo groups or 0-3 C4 branched or unbranched alkyl, C,.4 alkoxy or C, alkylamino chains; b) phenyl, furan, thiophene, pyrrole. imidazolyl, pyridine, pyrimidine, pyridinone, dihydropyridinone, maleimide, dihydromaleimide, piperdine, piperazine or pyrazine each being optionally independently substituted with 0-3 C, branched or unbranched alkyl,

Cialkoxy, hydroxy, nitrile, mono- or di-(C;.3 alkyl)amino, C,.¢ alkyl-S(O)m, or halogen;

Y is: a bond or a C, saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH, S(O), S(O), or S and wherein Y is optionally independently substituted with 0-2 oxo groups and one or more C4 branched or unbranched alkyl which may be substituted by one or more halogen atoms;

Z is: a) phenyl, pyridine. pyrimidine. pyridazine, imidazole, furan, thiophene. pyran, which are optionally substituted with one to three groups consisting of halogen, C, alkyl,

Ci. alkoxy, hydroxy, mono- or di-(C,.; alkyl)amino, C,. alkyl-S(O), , COOH and phenylamino wherein the phenyl ring is optionally substituted with one to two groups consisting of halogen, C,.¢ alkyl and C,. alkoxy; b) tetrahydropyran. tetrahydrofuran. 1,3-dioxolanone, 1,3-dioxanone, 1.4-dioxane, morpholine, thiomorpholine. thiomorpholine sulfoxide, piperidine, piperidinone, piperazine, tetrahydropyrimidone, cyclohexanone, cyclohexanol, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide or tetramethylene sulfone which are optionally substituted with one to three groups consisting of nitrile, C,.¢ alkyl, C,. alkoxy. hydroxy, mono- or di-(C;.3 alkyl)amino-C,.; alkyl, phenylamino-C, 3 alkyl and C,_; alkoxy-C,.3 alkyl; c) Ci. alkoxy, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to groups selected from the group consisting of C3 alkyl, C,.s alkoxyalkyl, pyridinyl-C,; alkyl, imidazolyl-C,.; alkyl, tetrahydrofuranyl-C.; alkyl, phenylamino, wherein the phenyl ring is optionally substituted with one to two halogen, C;.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, C,.¢ alkyl-S(O),,. and phenyl-

S(O)m, wherein the phenyl ring is optionally substituted with one to two halogen, C,¢ ] alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino; ’

Ris: : (a) Cs.j0 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with one to three phenyl, naphthyl or heterocyclic groups selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl. isoxazoly! and isothiazolyl; each such phenyl. naphthyl or heterocycle selected from the group hereinabove described in this paragraph. and being substituted with 0 to 5 groups selected from the group consisting of halogen, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated. Cs.g cycloalkyl. Cs cycloalkenyl, hydroxy. nitrile, Ci; alkyloxy which is optionally partially or fully halogenated. NH,C(O) and di(C,.3)alkylaminocarbonyl, (b) Cs. cycloalkyl selected from the group consisting of cyclopropyl, cyvclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl. bicyclopentanyl, bicyclohexanyl and bicycloheptany! each being optionally be partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S, CHOH, >C=0, >C=S and NH; (¢) Cs.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,_s branched or unbranched alkyl, phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each such phenyl, naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from the group consisting of halogen, C). branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, hydroxy, nitrile, Cy; alkoxy which is optionally partially or fully halogenated,

NH,C(O) and mono- or di(C,.3)alkylaminocarbonyl; (d) a Cs cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C3 alkyl groups; (e) nitrile; or (f) C14 branched or unbranched alkoxycarbonyl, C,¢ branched or unbranched alkylaminocarbonyl, C,.c branched or unbranched alkylcarbonylamino-C,.;-alkyl;

Ro 1s: a C4 branched or unbranched alkyl optionally partially or fully halogenated. acetyl, aroyl, C, branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl;

Rj is: a) phenyl, naphthyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl. benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl, wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of phenyl, naphthyl, heterocycle selected from the group hereinabove described in this paragraph, C,_¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, phenyl C,.; alkyl, naphthyl C,.s alkyl, halogen, hydroxy, nitrile, C,.3 alkyloxy which may optionally be partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(O), a mono- or di<(C;. 3)alkyl aminocarbonyl, C,.s alkyl-C(O)-C 4 alkyl, amino-C,.s alkyl, mono- or di-(C,. 3)alkylamino-C, 5 alkyl, amino-S(O),, di-(C;.3)alkylamino-S(O),, R4-C.s alkyl, Rs -

Cis alkoxy, R¢ —C(0O)-C,.s alkyl and R; -C,.s alkyl(Rg)N, carboxy-mono- or di-(C,_s)- alkyl-amino; b) afused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl. tetrahydronaphthyl, benzocycloheptanyl and i3 benzocycloheptenyl. or a fused heterocyclyl selected from the group consisting of cyclopentenopyridine. cyclohexanopyridine. cyclopentanopyrimidine, cyclohexanopyrimidine. cyclopentanopyrazine. cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine. cyclopentanoquinoline. cyclohexanoquinoline, cyclopentanoisoquinoline. cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole. cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from the group consisting of pheny!, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl. pyrrolyl. imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, and isothiazolyl, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.; alkoxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(0O), a mono- or di-(C,.3)alkyl aminocarbonyl, C4 alkyl-OC(O), Cs alkyl-C(0)-C,.4 branched or unbranched alkyl, an amino-C,.s alkyl, mono- or di-(C.3)alkylamino-C, 5 alkyl, Rg -Cj.s alkyl, Ry¢-C.s alkoxy, R;; —C(O)-C,.s alkyl, and R;>-C,.salkyl(R;3)N; c) cycloalkyl selected from the group consisting of cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptyl, wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three

Ci.3 alkyl groups; d) Cs. cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,_; alkyl groups;

e) acetyl. aroyl. alkoxycarbonylalkyl or phenylsulfonyl; or f) Ci. branched or unbranched alkyl optionally partially or fully halogenated; or R; and R3 taken together may optionally form a fused phenyl or pyridiny! ring; each Rg and R;; is independently selected from the group consisting of: hydrogen and C4 branched or unbranched alkyl optionally be partially or fully halogenated; each Rs, Rs, Re. Ry, Ro, Rig, Rij and Ry 1s independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; mis0,1o0r2;

WisOorS and pharmaceutically acceptable derivatives thereof.

In one embodiment of the invention there are compounds of the formula(l) as provided above and wherein:

Ar; is naphthyl, tetrahydronaphthyl, indanyl or indenyl and

Wis O.

In another embodiment of the invention, there are the compounds of the formula (I) as provided immediately above and wherein:

Ar 1s selected from thiophene and pyrazole; i5

X is Cs.y cycloalkyl or Cs.scycloalkenyl optionally substituted with 0-2 oxo groups or 0-3 C4 branched or unbranched alkyl. C, alkoxy or C, alkylamino: or X is phenyl, pyridine, tetrahydropyridine, pyrimidine. furan or thiophene each being optionally independently substituted with 0-3 C4 branched or unbranched alkyl. C,_alkoxy. hydroxy. nitrile, mono- or di-(C,.; alkyl)amino, C,.¢ alkyl-S(O), or halogen;

R, is C)4alkyl branched or unbranched. cyclopropyl or cyclohexyl optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups;

R; is C4alkyl branched or unbranched, phenyl, pyrimidinyl, pyrazolyl or pyridinyl each being optionally substituted as described hereinabove in the broadest generic aspect, alkoxycarbonylalkyl or cyclopropyl or cyclopentyl optionally substituted as described hereinabove in the broadest generic aspect.

In yet another embodiment of the invention are the compounds of the formula(l) as provided immediately above and wherein:

Ar) is pyrazole;

X is cyclopentenyl, cyclohexeny! or cycloheptenyl, optionally substituted with an oxo group or 0-3 C,4 branched or unbranched alkyl, C,_4alkoxy or C).salkylamino; or X is phenyl, pyridine, furan or thiophene each being optionally independently substituted with 0-3 C,4 branched or unbranched alkyl. C,4alkoxy, hydroxy, nitrile, mono- or di- (C3 alkyl)amino, C,.¢ alkyl-S(O)n, or halogen.

In yet still another embodiment of the invention there the compounds of the formula(l) as provided immediately above and wherein:

Y is -CH2-, -CH2CH2-, -CH2NH-, -CH2CH2NH- or a bond; and

Zis phenyl, imidazole, furan, piperazine, tetrahydropyran, morpholine, thiomorpholine, thiomorpholine sulfoxide, piperidine, pyridine. secondary or tertiary amine wherein the amino nitrogen is covalently bonded to groups selected from the group consisting of C;.3 alkyl and C,.; alkoxyalkyl. phenylamino wherein the phenyl ring is optionally substituted with one to two halogen. C,¢ alkoxy. hydroxy or mono- or di-(C,.; alkyl)amino. Cj. alkyl-S(O),, and phenyl-S(O)n, wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino.

In yet a further embodiment of the invention there are the compounds of the formula(l) as provided immediately above and wherein:

Ar) is 5-tert-butyl-pyrazol-3-yl: wherein the pyrazole ring may be substituted by

Rs;

R; is C;4alkyl branched or unbranched, phenyl, pyrimidinyl, pyrazolyl, pyridinyl each being optionally substituted as described hereinabove in the broadest generic aspect, alkoxycarbonylalkyl or cyclopropyl or cyclopentyl optionally substituted as described hereinabove in the broadest generic aspect.

In astill yet further embodiment of the invention there are the compounds of the formula(l) as provided immediately above and wherein X is pyridinyl.

In yet another further embodiment of the invention there are the compounds of the formula(l) as provided immediately above and wherein the pyridinyl is attached to Ar, via the 3-pyridiny! position.

The following are representative compounds of formula(l) of the invention: 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(morpholin-4-yl)phenyl)naphthalen- 1 - yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(morpholin-4-yl- methyl)phenyl)naphthalen-1-yljurea; 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-(2-(morpholin-4- yl)ethyl)phenyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-dimethylaminophenyl)naphthalen-1 - yl]urea; .

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-( 5-(morpholin-4-yl)phenyl)naphthalen-1- yl]urea; 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(morpholin-4-yl-

methyl)phenyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yDnaphthalen-1-yljurea;

1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(5-morpholin-4-ylmethyl-pyridin-2- ylnaphthalen-1-yl]urea;

1 -[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-y1]-3-(4-(5-morpholin-4-ylmethyl-fur-2- yl)naphthalen-1-yljurea;

i5 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)naphthalen-1-yl}jurea; 1-[5-tert-butyl-2-methyl-2H-pyrazol-3-yl]-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-

yl)naphthalen-1-yl)urea; 1-[5-terz-butyl-2-phenyl-2H-pyrazol-3-yl}-3-[4-(4-piperdin- 1-ylmethyl- phenyl)naphthalen-1-yljurea;

1-[5-tert-butyl-2-phenyl-2H-pyrazol-3-yl]-3-[4-(4-(4-methylpiperazin-1- yl)methylphenyl)naphthalen-1-yl)urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3,4-di(morpholin-4-yl- methyl)phenyl)naphthalen-1-yljurea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-pyridin-4-ylmethyl- pyridin-3-yl)naphthalen-1-yl]jurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(1-0xo-

thiomorpholin-4-ylmethyl)pyridin-3-yl)naphthalen-1-yl]urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(1-oxo-thiomorpholin-4- ylmethyl)pyridin-3-yl)naphthalen-1-yl]urea;

40 1-[5-fert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-tetrahydropyran-4- ylmethyl-pyridin-3-yl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(1-oxo- tetrahydrothiophen-3-ylmethyl)pyridin-3-yl)naphthalen-1-yljurea;

45

1-[3-tert-butyl-2-(6-methyl-pvridin-3-y1)-2H-pyrazol-3-yl]-3-[4-(6-(imidazol- 1- ylmethyl)pyridin-3-yl)naphthalen-1-yljurea: 1-[2-(3-dimethylaminomethylphenyl)-5-(1-methyl-cyclohexyl)-2H-pyrazol-3-yl]-3-[4-(6- morpholin-4-ylmethyl-pyridin-3-yl)naphthalen-1-yl]urea; 1-[2-(5-(1-methyl-cyclohexyl)-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6- morpholin-4-ylmethyl-pyridin-3-yl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylmethyl-pyrimidin-§- yl)naphthalen-1-yl]urea; 1-[5-tert-buty}-2-(6-methyl-pyridin-3-y})-2H-pyrazol-3-y1}-3-[4-(3-methoxy-5-(2- morpholin-4-yl-ethoxy)phenyl)naphthalen-1-yljurea, 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(2-morpholin-4-yl- ethoxy)phenyl)naphthalen-1-yl)urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-3- (dimethylamino)phenyi)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-3- (methylsulfonyl)phenyl)naphthalen-1-yl]urea;

S-tert-butyl-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)naphthalen-1- ylJureido}thiophene-2-carboxylic acid methyl ester; 5-tert-butyl-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)naphthalen-1- yljureido} thiophene-2-carboxylic acid methylamide; 5-tert-butyl-1-methyl-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)naphthalen-1- yljureido}-1H-pyrrole-2-carboxylic acid methyl ester; 5-tert-butyl-1-methyl-3- {3-{4-(6-morpholin-4-ylmethyl-pyridin-3-y})naphthalen-1- yllureido}-1H-pyrrole-2-carboxylic acid methylamide; 2-acetylamino N-(5-tert-butyl-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)naphthalen- 1-yljureido}thiophen-2-ylmethyl)acetamide; 40 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-morpholin-4-yl-cyclohex-1- enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(3-morpholin-4-yl-cylohept-1- enyl)naphthalen-1-yljurea; 45

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-(3-(2-morpholin-4-vI- ethylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-morpholin-4-yl-cyclohept-1-

enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(pyvridin-4-yl- methylamino)cyclohex-1-enyl)naphthalen-1-yljurea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-(3- (dimethylaminoethylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(pyridin-3-yl- methylamino)cyclohex-1-enyl)naphthalen-1-yljurea;

” 1-[S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(phenyl- methylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[S-tert-butyi-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-

phenylethylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(furan-2-yl- methylamino)cyclohex-1-enyl)naphthalen-1-yljurea;

1-[5-tert-butyl-2-(6~methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(2-pyridin-2-yl- ethylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4~(3-(2-piperdin-1-yl- ethylamino)cyclohex-1-enyl)naphthalen-1-ylJurea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-imidazol-4-yl- ethylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(pyridin-2-yl-

methylamino)cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-(4- methoxyphenyl)ethylamino)cyclohex-1-enyl)naphthalen-1-yljurea;

40 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-morpholin-4-ylmethyl-3-oxo- cyclohex-1-enyl)naphthalen-1-yljurea; 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-(1 -oxo-tetrahydrothiophen-3- ylmethyl)-3-oxo-cyclohex-1-enyl)naphthalen-1-yljurea;

45

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(1-oxo-thiomorpholin-4-yimethyl)-3- oxo-cyclohex-1-enyl)naphthalen-1-yljurea: 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-methylpiperazin-1-ylmethyl)-3-o0xo- cyclohex-1-enyl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4- {6-0x0-1-(tetrahydro- pyran-4-ylmethyl)-1,2.3.6-tetrahydro-pyridin-4-yl}naphthalen- 1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(2-0x0-1-pyridin-4- ylmethyl-piperdin-4-yl)naphthalen-1-yl]urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-0x0-1-pyridin-4-yl-1.2 3 6-tetrahydro- pyridin-4-yl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-(6-0x0- 1-pyridin-4-yl- 1,2,3,6-tetrahydro-pyridin-4-yl)naphthalen-1-yljurea; 5-tert-butyl-3-{3-[4-(6-oxo0-1-pyridin-4-yl-1,2.3.6-tetrahydro-pyridin-4-yl)naphthalen-1- ylJureido}thiophene-2-carboxylic acid methyl ester; 5-tert-butyl-1-methyl-3-{3-[4-(6-0x0-1-pyridin-4-yl-1,2,3,6~tetrahydro-pyridin-4- yl)naphthalen-1-yljureido} pyrrole-2-carboxylic acid methyl ester; 5-tert-butyl-1-methyl-3-{3-[4-(6-0x0-1-pyridin-4-yl-1,2 3 6-tetrahydro-pyridin-4- yDnaphthalen-1-yljureido} pyrrole-2-carboxylic acid methyl amide; 5-tert-butyl-3-{3-[4-(3-morpholin-4-yl-cyclohex-1-enyl)naphthalen-1- yljureido}thiophene-2-carboxylic acid methyl ester; 5-tert-butyl-1-methyl-3-{3-[4-(3-morpholin-4-yl-cyclohex-1-enyl)naphthalen-1- yllureido}pyrrole-2-carboxylic acid methyl ester; and

S-tert-butyl-1-methyl-3-{3-[4-(3-morpholin-4-yl-cyclohex-1-enyl)naphthalen-1- yljureido}pyrrole-2-carboxylic acid methyl amide and the pharmaceutically acceptable derivatives thereof. 40 In another embodiment of the invention there are provided the following compounds of formula(I): 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4~(morpholin-4-yl- methyl)phenyl)naphthalen-1-yl]urea; 45

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(2-(morpholin-4- yl)ethyl)phenyl)naphthalen-1-yl}urea: 1-[5 -tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(3-(morpholin-4-yl- methyl)phenyl)naphthalen-1-yljurea; 1 -[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-(6-morpholin-4-ylmethyl-pyridin-3- yl)naphthalen-1-yljurea; 1 -[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(5-morpholin-4-yImethyl-pyridin-2- yl)naphthalen-1-yljurea; 1-[5-terr-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(S-morpholin-4-yImethyl-fur-2- yl)naphthalen-1-yljurea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3 -yl}-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)naphthalen-1-yl]urea; 1 -[5-fert-butyl-2-methyl-2H-pyrazol-3-yl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yDnaphthalen-1-ylJurea and the pharmaceutically acceptable derivatives thereof.

In another generic aspect of the invention. there are provided compounds of the formula (1a):

Ww

Ars. J AATX—Y—Z y

H H

(Ia) wherein:

Ar is: pyrrole, pyrrolidine, pyrazole, imidazole. oxazole, thiazole, furan and thiophene;

wherein Ar, is optionally substituted by one or more R;. Ror Rj:

Ar, IS: phenyl, naphthyl, quinoline. isoquinoline. tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline. benzimidazole. benzofuran. indany!. indeny! and indole each being optionally substituted with zero to three R; groups;

Xs: a Cs.3 cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, C, alkoxy or C,4 alkylamino chains each being branched or unbranched; is phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, tetrahydropyridinyl, pyrimidinyl, pyridinonyl, dihydropyridinonyl. maleimidyl, dihydromaleimidy], piperdinyl, benzimidazole, 3H-imidazo[4,5-b]pyridine, piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C4 alkyl,

Ci4alkoxy, hydroxy, nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di-(C;.; alkylamino)carbonyl, NH,C(O), C, alkyl-S(O)m, or halogen;

Y is: a bond or a C4 saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more C atoms are optionally replaced by O,

N, or S(O)m and wherein Y is optionally independently substituted with one to two oxo groups, nitrile, phenyl, hydroxy or one or more C,4 alkyl optionally substituted by one or more halogen atoms;

Zis:

aryl. indanyl. heteroaryl selected from benzimidazolyl. pyridinyl. pyrimidinyl. pyridazinyl. pyrazinyl. imidazolyl, pyrazolyl. triazolyl. tetrazolyl. furanyl. thienyl and pyranyl, heterocycle selected from piperazinyl. tetrahydropyrimidonyl. cyclohexanonyl, cyclohexanolyl. 2-oxa- or 2-thia-5-aza-bicyclo[2.2.1]heptanyl. pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetramethylene sulfidyl, tetramethylene sulfoxidyl or tetramethylene sulfonyl. tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, 1.3-dioxanonyl, 1.4-dioxanyl, morpholino, thiomorpholino, thiomorpholino sulfoxidyl. thiomorpholino sulfonyl, piperidinyl, piperidinonyl, pyrrolidinyl and dioxolanyl, each of the aforementioned Z are optionally substituted with one to three halogen, C,.¢ alkyl, Ci. alkoxy. C,.3 alkoxy-C,.3 alkyl. C,. alkoxycarbonyl, aroyl, heteroaroyl, heterocycleC,_;acyl wherein the heteroaryl and heterocycle are as defined hereinabove in this paragraph, C,.;acyl, oxo, hydroxy, pyridinyl-C,_; alkyl, imidazolyl-C,.; alkyl, tetrahydrofuranyl-C, ; alkyl, nitrile-C_; alkyl, nitrile. carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C;. alkoxy, hydroxy or mono- or di-(C,3 alkyl)amino, amino-S(O)m, Ci. alkyl-S(O)r, or phenyl-S(O), wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy, hydroxy, halogen or mono- or di-(C,.; alkyl)amino; or Z is optionally substituted with one to three amino, aminocarbonyl or amino-C;.; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC;. salkyl, Cy.alkyl, arylCo.3alkyl, Cy.s alkoxyC,.s alkyl, C,.s alkoxy, aroyl, C,.;acyl, C,. 3alkyl-S(O)m- or arylCy.3alkyl-S(O)n- each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C,.¢ alkyl, C,¢ alkoxy, hydroxy or mono- or di-(C,.3 alkyl)amino; or Zis optionally substituted with one to three aryl, heterocycle or heteroaryl as - hereinabove described in this paragraph each in turn is optionally substituted by halogen,

Cy alkyl or C4 alkoxy; or Z is hydroxy. hydroxyC;.salkyl, halogen. nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C,.galkyl, aminoC,.¢alkyl, arylCo. salkyl, Cys alkoxyC,.; alkyl, C).s alkoxy, aroyl, Ci.zacyl, C).3alkyl-S(O)m- , arylCy.zalkyl-

S(O)m- - nitrileC alkyl or C_;alkoxyC,.3alkyl. each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen. C, alkyl.

C1. alkoxy. hydroxy or mono- or di-(C,.; alkyl)amino. C,, alkoxyheteroarylCy.;alkyl, heteroarylCo.;alkyl or heterocycyleCo.alkyl wherein the heteroaryl and heterocycle is hereinabove described in this paragraph, or Z is C,.ealkyl branched or unbranched, C,¢alkoxy. C;.;acylamino. nitrileC, 4alkyl, C6 alkyl-S(O)m. and phenyl-S(O),.. wherein the pheny! ring is optionally substituted with one to two halogen, C,.; alkoxy. hydroxy or mono- or di-(C,.; alkyl)amino:

Riis: a) C).jo branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three phenyl, naphthyl or heterocyclic groups selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl; each such phenyl, naphthyl or heterocycle, selected from the group hereinabove described, being substituted with 0 to 5 groups selected from the group consisting of halogen, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, C;_g cycloalkyl, Cs.g cycloalkenyl, hydroxy, nitrile, C,.; alkyloxy which is optionally partially or fully halogenated, NH,C(O) and di(C,.3)alkylaminocarbonyl: b) Cs. cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptyl, each optionally partially or fully halogenated and optionally substituted with one to three

Cis alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group . consisting of O, S, CHOH, >C=0, >C=S and NH; ¢) Cs. branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,.; branched or unbranched alkyl, phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each such phenyl,

naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from the group consisting of halogen. C,_, branched or unbranched alkyl which is optionally partially or fully halogenated. cyclopropyl. cyclobutyl. cyclopentanyl. cyclohexanyl. cycloheptanyl. bicyclopentanyl. bicyclohexanyl. bicycloheptanyl. hydroxy, nitrile, C3 alkoxy which is optionally partially or fully halogenated, NH,C(O) and mono- or di(C;. 3)alkylaminocarbony!: d) a Cs cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl. cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C;.; alkyl groups; e) nitrile; or f) Ci. branched or unbranched alkoxycarbonyl. C.¢ branched or unbranched alkylaminocarbonyl, C;.¢ branched or unbranched alkylcarbonylamino-C,_;-alkyl;

Rj is: a C).¢ branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile, or R; is acetyl, aroyl, Cy branched or unbranched alkoxy optionally partially or fully halogenated, halogen. methoxycarbonyl or phenylsuifonyl;

Rj is: a) phenyl, naphthyl or heterocyclic group selected from the group consisting of 25s pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl. isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl, wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a phenyl, naphthyl, heterocycle selected from the group hereinabove described in this paragraph. C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl. cyclobutyl, cyclopentyl. cyclohexyl, cycloheptyl. bicyclopentyl, bicyclohexyl. bicycloheptyl, phenyl C,.s alkyl, naphthyl C,_s alkyl. halogen, hydroxy. oxo. nitrile, C;_; alkoxy optionally partially or fully halogenated, C,.3 alkoxyCj.salkyl, C;.athioalkyl, C,.sthioalky!C, salkyl, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph, nitro. amino, mono- or di-(C,_;)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(O), a mono- or di-(C.3)alkyl aminocarbonyl, C,s alkyl-C(O)-C, alkyl. amino-C.s alkyl, mono- or di-(C;. 3)alkylamino-C,.s alkyl, amino-S(0),, di-(C,.3)alkylamino-S(O),, Ry -C,.s alkyl, Rs -C).s alkoxy, R¢—C(0O)-C,s alkyl and R;-C,.; alkyl(Rg)N, carboxy-mono- or di-(C}.5 )-alkyl- amino; b) a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heterocyclyl! selected from the group consisting of cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from the group consisting of phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl. imidazolyl, pyrazolyl. thienyl, furyl, isoxazolyl, and isothiazolyl,

Ci branched or unbranched alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.3 alkoxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described, nitro, amino, mono- or di-(C)_3)alkylamino, phenylamino,

naphthylamino. heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described. NH,C(0), a mono- or di-(C 1-3)alkyl aminocarbonyl. C, alkyl-OC(O), C,.s alkyl-C(0O)-C,_ branched or unbranched alkyl, an amino-C,.s alkyl, mono- or di-(C,.;)alkylamino-C,.s alkyl, Rg-C_s alkyl. Ryo -Cj.s alkoxy, Ry; -C(0)-C,. alkyl and Ry; -C,.salkyl(R3)N;

C) cycloalkyl selected from the group consisting of cyclopropyl, cyvclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptyl, wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three C3; alkyl groups; d) Cs. cycloalkenyl selected from the group consisting of cyclopentenyl. cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,.; alkyl groups; e) acetyl, aroyl, C,.salkoxycarbonylC, alkyl or phenylsulfonyl; or f) Ci. branched or unbranched alky! optionally partially or fully halogenated; orR, and R; taken together optionally form a fused phenyl or pyridinyl ring; each Rg and R;3 is independently selected from the group consisting of: hydrogen and C,4 branched or unbranched alkyl optionally partially or fully halogenated; each Ry, Rs, Rg, Rs, Ro, Ryo Rj and Ry; is independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; mis 0,1 or 2;

WisOorS;

wherein X is directly attached to one or two -Y-Z. and pharmaceutically acceptable derivatives thereof.

In one embodiment of the invention there are compounds of the formula(la) as provided above and wherein:

Ar, is naphthyl, tetrahydronaphthyl. indanyl or indenyl and

Wis O.

In another embodiment of the invention are compounds of the formula (Ia) as provided immediately above and wherein:

Ar, is thiophene or pyrazole each substituted independently by one to three R;, R; or Rj;

X is: a Cs. cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C,4 alkyl, C4 alkoxy or C4 alkylamino chains each being branched or unbranched; phenyl, indanyl, furanyl, thienyl, imidazolyl, pyridinyl, pyrazinyl, tetrahydrapyridinyl, pyrimidinyl, pyridinonyl, piperdinyl, benzimidazole or piperazinyl; each being optionally independently substituted with one to three C,4 alkyl, C,.alkoxy, hydroxy. nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di-(C,.; alkylamino)carbonyl, NH,C(0O), C, alkyl-S(O)m or halogen;

Y is:

a bond or a C, saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated. wherein one or more C atoms are optionally replaced by O or N, and wherein Y is optionally independently substituted with one to two oxo groups. nitrile, phenyl, hydroxy or one or more C,. alkyl optionally substituted by one or more halogen atoms;

Zis: phenyl, heteroaryl selected from pyridinyl, imidazolyl, furanyl and thienyl, heterocycle selected from piperazinyl, 2-0xa-5-aza-bicyclof2.2.1}heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetrahydrofuranyl. morpholino, ‘thiomorpholino and piperidinyl, each of the aforementioned Z are optionally substituted with one to three halogen, C,. alkyl, C,.¢ alkoxy, C,.; alkoxy-C,.3 alkyl, C,.s alkoxycarbonyl, aroyl, morpholinocarbonyl, C;acyl, oxo, hydroxy, pyridinyl-C,.3 alkyl, imidazolyl-C,.3 alkyl, tetrahydrofuranyl-C,_; alkyl, nitrile-C,.3 alkyl, nitrile, carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C).¢ alkoxy, hydroxy or mono- or di-(C,.3 alkyl)amino, amino-S(O)n, Ci.s alkyl-S(O)m or phenyl-S(O), wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy, hydroxy, halogen or mono- or di-(C;3 alkyl)amino; or Z is optionally substituted with one to three amino, aminocarbonyl or amino-C,.; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC,. alkyl, Cy_salkyl, arylCy.jalkyl, C,.s alkoxyC,.; alkyl, C,.s alkoxy, aroyl, C,.sacyl, C;. 3alkyl-S(O)n- or arylCy.3alkyl-S(O)m- each of the aforementioned alkyl and aryl attached to the amino group are optionally substituted with one to two halogen, C;.¢ alkyl or Cy. alkoxy; or Z is optionally substituted with one to three aryl. heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen,

Ci alkyl or C, alkoxy;

or Z is hydroxy. hydroxyCj.;alkyl. halogen. nitrile. amino wherein the N atom is optionally independently mono- or di-substituted by aroyl, C,_3acyl, C,_¢alkyl. C;.s alkoxyC,.; alkyl, pyridinylC,_;alkyl, tetrahydrafuranylC,.;alkyl. nitrileC;4alkyl or phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C, alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino. or Z is Cy.¢alkyl branched or unbranched, C;_¢alkoxy or nitrileC; yalkyl;

R, is:

C4 branched or unbranched alkyl optionally partially or fully halogenated; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl optionally partially or fully halogenated and optionally substituted with one to three C,.3alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S and NH;

Cs.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,_s branched or unbranched alkyl; cyclopentenyl and cyclohexenyl optionally substituted with one to three C,.; alkyl groups;

R, 1s: aC; branched or unbranched alkyl optionally partially or fully halogenated and : optionally substituted with nitrile;

R; is: phenyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and pyrazolyl, wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a phenyl. heterocycle selected from the group hereinabove described in this paragraph.

Ci. branched or unbranched alkyl! which is optionally partially or fully halogenated. cyclopropyl, cyclobutyl. cyclopentyl. cyclohexyl. cycloheptyl. bicyclopentyl, bicyclohexyl. bicycloheptyl, phenyl C,.; alkyl, naphthyl C,_s alkyl. halogen, hydroxy, oxo, nitrile, C,._; alkoxy optionally be partially or fully halogenated, C,_; alkoxyC,.salkyl,

Ci.sthioalkyl, C).sthioalkylC,.salkyl. phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.;)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(O), a mono- or di-(C,.3)alkyl aminocarbonyl, C,.s alkyl-C(O)-C, alkyl, amino-C,_; alkyl, mono- or di-(C,. 3)alkylamino-C,.s alkyl, amino-S(0),, di-(C,.3)alkylamino-S(O),, Ry -Cy.s alkyl, Rs -Cy_s alkoxy, R¢—C(0)-C, 5 alkyl and R; -C, 5 alkyl(Rg)N, carboxy-mono- or di-(C,.s )-alkyl- amino; a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl; wherein the fused aryl is substituted with 0 to 3 groups independently selected from the group consisting of phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, and isothiazolyl, Ci. branched or unbranched alky! which is optionally partially or fully halogenated, halogen, nitrile, C,.; alkoxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C,.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this - paragraph, NH,C(O), a mono- or di-(C,.;)alkyl aminocarbonyl, C,4 alkyl-OC(O), C,.s alkyl-C(O)-C; 4 branched or unbranched alkyl, an amino-C,.5 alkyl, mono- or di-(C,. s)alkylamino-C,s alkyl, Ry-C).s alkyl, Rjo-C,s alkoxy, R); —-C(0)-C,.s alkyl and R,;-C,. salkyl(Ri3)N;

cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl. cyclopentyl. cyclohexyl. cycloheptyl. wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three C3 alkyl groups;

C.ealkoxycarbonylC, alkyl; or R; and R; taken together optionally form a fused phenyl or pyridinyl ring; each Rg and Ry; is independently selected from the group consisting of: hydrogen and C,.; branched or unbranched alkyl optionally partially or fully halogenated; and each Ry, Rs, Rg, Ry, Rg, Rig. Ry) and R3 is independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; wherein X is directly attached to one -Y-Z.

In yet still another embodiment of the invention there are the compounds of the formula(la) as provided immediately above and wherein:

Ar) is pyrazole;

X is: cyclopentenyl. cyclohexenyl, cycloheptenyl, optionally substituted with an oxo group or one to three C, alkyl, C,4 alkoxy or Cy alkylamino chains each being branched or unbranched;

phenyl. furanyl. thienyl. pyridinyl. pyraziny! piperidinyl or pyrimidiny1 each being optionally independently substituted with one to three C,., alkyl, Cy.,alkoxy. hydroxy or halogen,

Zis: phenyl, heteroaryl selected from pyridinyl. imidazolyl and furanyl, heterocycle selected from 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholino, thiomorpholino, thiomorpholino sulfoxide and piperidinyl. each of the aforementioned Z are optionally substituted with one to three halogen, C;.¢ alkyl, Ci.¢ alkoxy, Cy; alkoxy-C, ; alkyl, C,.¢ alkoxycarbonyl, aroyl, morpholinocarbonyl, C;_jacyl, oxo, hydroxy, pyridinyl-C;_; alkyl, imidazolyl-C, ; alkyl, tetrahydrofuranyl-C, ; alkyl, nitrile-C,.3 alkyl. nitrile, carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, Cy. alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, amino-S(O)m, C,.¢ alkyl-S(O)m, or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen, C, alkoxy, hydroxy, halogen or mono- or di-(C,.3 alkyl)amino; or Z is optionally substituted with one to three amino, aminocarbony! or amino-C,.; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC,. salkyl, C;salkyl, arylCy.zalkyl, Cs alkoxyC,_salkyl, C,.s alkoxy, aroyl, C;sacyl, C;. 3alkyl-S(O)m-, pyridinylCy.zalkyl, tetrahydrafuranylCy alkyl, or arylCy.3alkyl-S(O)m- each of the aforementioned alkyl and ary! attached to the amino group is optionally substituted with one to two halogen, C,. alkyl or C,.¢ alkoxy; or Z is hydroxy, hydroxyC,.;alkyl, halogen. nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C, alkyl, pyridinylCy.alkyl, tetrahydrafuranylCo.jalkyl, C,.s alkoxyC.; alkyl, C,.sacyl. nitrileC)_salkyl or phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy. hydroxy or mono- or di-(C,.3 alkyl)amino, or Z is Cy_salkyl branched or unbranched. C,.¢alkoxy or nitrileC,_alkyl;

R; is:

C,.4 branched or unbranched alkyl optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl. cyclohexanyl and cycloheptanyl optionally partially or fully halogenated and optionally substituted with one to three C3 alky! groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S and NH;

C;.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,.; branched or unbranched alkyl; cyclopentenyl and cyclohexenyl optionally substituted with one to three C,.; alkyl groups;

R, is: a Cy. branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile;

Rs; is: phenyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyridazinyl and pyrazolyl. wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a phenyl, heterocycle selected from the group hereinabove described in this paragraph, C, branched or unbranched alkyl which is optionally partially or fully halogenated, phenyl

Ci-s alkyl, halogen, hydroxy, oxo, nitrile, C,.3 alkoxy optionally partially or fully halogenated, C).3thioalkyl, C;.sthioalkylC,.salkyl, amino, mono- or di-(C;.3)alkylamino,

NH,C(O) or a mono- or di-(C;.3)alkyl aminocarbonyl,

C,salkoxycarbonylC).¢alkyl; or R; is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups or Ry and R, taken together optionally form a fused pheny! or pyridinyl ring.

In yet a further embodiment of the invention there are the compounds of the formula(la) as provided immediately above and wherein:

Y is -CH,-, -O-(CH2)o-3-, -CH2CH,-, -CH,NH-. -CH,CH,-NH-, NH-CH,CH,-, -CH,-NH-CHz-, -NH-, -NH-C(O)-, -C(0O)-, -CH(OH)-, -CH(CH,CH3;)- or a bond; i5

X is: cyclohexenyl optionally substituted with an oxo group or one to three C).4 alkyl, C4 alkoxy or C4 alkylamino chains each being branched or unbranched; phenyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidiny! each being optionally independently substituted with one to three C,.; alkyl. C;. alkoxy. hydroxy or halogen;

Zis: phenyl, heteroaryl selected from pyridinyl, imidazolyl and furanyl, heterocycle selected from 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholino, thiomorpholino, thiomorpholino sulfoxide and piperidinyl, each of the aforementioned Z are optionally substituted with one to three halogen, C;.¢ alkyl, C, alkoxy, C,.; alkoxy-C,.; alkyl, C,.¢ alkoxycarbonyl, aroyl, morpholinocarbonyl, C,acyl, oxo, hydroxy, pyridinyl-C,.3 alkyl, imidazolyl-C)3 alkyl,

tetrahydrofuranyl-C,.; alkyl. nitrile-C,_; alkyl. nitrile. carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy, hydroxy or mono- or di-(Cy; alkyl)amino. amino-S(O)m, C1. alkyl-S(O)y,. or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy. hydroxy. halogen or mono- or di-(C,.3 alkyl)amino; or Z is optionally substituted with one to three amino or aminocarbonyl wherein the N atom is optionally independently mono- or di-substituted by aminoC, alkyl, C,.zalkyl, arylCo.zalkyl, C;.s alkoxyC,.; alkyl, C,.s alkoxy, aroyl, C.;acyl, C;.;alkyl-S(O),n- or arylCo.3alkyl-S(O)m- each of the aforementioned alkyl and ary! attached to the amino group is optionally substituted with one to two halogen, C,. alkyl or C,.¢ alkoxy; or Z is hydroxy, hydroxyC,.;alkyl, halogen. nitrile. amino wherein the N atom is optionally independently mono- or di-substituted by C,.;alkyl, pyridinylC,.,alkyl, tetrahydrafuranylC,.,alkyl, C,.3 alkoxyC,.; alkyl, C.;acyl, nitrileC,4alkyl, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, or Z is Cy¢alkyl branched or unbranched, C;.salkoxy or nitrileC,_salkyl;

R, is:

Ci branched or unbranched alkyl optionally partially or fully halogenated;

Ry is: aC; branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile;

Rj; is: phenyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl. and pyrazolyl, wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of C).; branched or unbranched alkyl which is optionally partially or fully halogenated. C;.; alkoxy which optionally partially or fully halogenated, C,.;thioalkyl. C).;thioalkylC.salkyl, amino or

NH,C(O);

Ci-salkoxycarbonyl; or Rs is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C;_; alkyl! groups.

In a yet still further embodiment of the invention there are the compounds of the formula(la) as provided immediately above and wherein:

Ar is 5-tert-butyl-pyrazol-3-yl; wherein the pyrazole ring is substituted independently by one to two R; or Rj;

X is: cyclohexenyl; phenyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidiny! each being optionally independently substituted with C,_;alkoxy or hydroxy; :

Zis: phenyl, heteroaryl selected from pyridinyl and furanyl, heterocycle selected from 2-oxa- 5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, tetrahydrofuranyl, piperazinyl, morpholino, thiomorpholino and piperidinyl, each of the aforementioned Z are optionally substituted with one to three Ci. alkyl, Cy; alkoxy, oxo, hydroxy or NH,C(O)-;

or Z is hydroxyC,.;alkyl. amino wherein the N atom is optionally independently mono- or di-substituted by pyridinylmethyl. tetrahydrafuranylmethyl. C,_; alkoxyC,.3 alkyl. C;.3acyl or nitrileC,4alkyl, or Z is nitrileC, 4alkyl:

Rj is: phenyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, and pyrazolyl, wherein such phenyl or heterocyclic group is optionally substituted with one to two groups selected from the group consisting of C., alkyl which is optionally partially or fully halogenated, C|. alkoxy which optionally partially or fully halogenated, C.,thioalkyl, C,.;thioalkylC).3alkyl. amino or NH,C(O);

C,.3alkoxycarbonyl; or Rj is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,.3 alkyl groups.

In an even further embodiment of the invention there are the compounds of the formula(la) as provided immediately above and wherein X is pyridinyl.

In a yet still even further embodiment of the invention there are compounds of the formula(la) as provided immediately above and wherein the pyridinyl is attached to Ar, via the 3-pyridinyl position.

The following are representative compounds of formula(la) of the invention: 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-morpholin-4-yl-methyiphenyl)- naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[3-(4-morpholin-4-yl-methylphenyl)- naphthalen-1-yl]-urea;

5s 1- [5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(5-morpholin-4-yl-methylfuran-2-y1)- naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-(morpholin-4-yI- methyl)cyclohexenyl)-naphthalen-1-yl]-urea;

1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(4-morpholin-4-yl)ethylphenyl)- naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-dimethylaminomethylpheny!)-

naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(5 -(morpholin-4-yl-methyl)pyridin-2-yl)- naphthalen-1-yl]-urea;

1-5 -tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3 -yl)- naphthalen-1-yl}-urea; 1-{5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea;

1 -[5-tert-butyl-2-methyl-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3-yl)- naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-(morpholin-4-

yl)ethylamino)cyclohexenyl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3,4-(morpholin-4-yl-methyl)phenyl)- naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(4-methylpiperzin- -yl-methyl)phenyl)- naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(piperdin-1 -yl-methyl)phenyl)- naphthalen-1-yl)-urea;

40 1-[5-tert-butyl-2-(6-methyl-pyridin-3 -yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-(pyridin-2- yDethylamino)cyclohexenyl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(2-(pyridin-4-

45 yl)ethylaminomethyl)phenyl)naphthalen-1-ylj-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-{4-(4-(pyridin-3-yl- methylaminomethyl)phenyl)naphthalen-1-yl]}-urea: 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(3,4-

dimethoxyphenylmethyl)-3-hydroxyphenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2 -p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-0x0-1,6-dihydro-pyridin-3- yl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(morpholin-4-yl-

methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(morpholin-4-yl- methyl)imidazol-1-yl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(morpholin-4-yl-methyl)imidazol-1- yDnaphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-y1)-2H-pyrazol-3-yl]-3-[4-(4-(furan-3-yl-methyl)-3-

hydroxyphenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazo}-3-yl}-3-{4-(6-(4- hydroxybutylamino)pyridin-3-yl)-naphthalen-1-yl]-urea;

l-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-(4-(pyridin-3-yl-methyl)- 3-hydroxyphenyl)naphthalen- 1-yl]-urea; 1-[5-tert-butyl-2-(4-methyi-3-carbamylphenyl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yl]}-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(imidazol-2-yl- methyl)-3-hydroxyphenyl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(3-hydroxymorpholin-

4-yl-methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-y1)-2H-pyrazol-3-yl}-3-[4-(4-(N-2-methoxyethy-N- methylaminomethyl)phenyl)naphthalen-1-yl}-urea;

40 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]}-3-[4-(4-(4-hydroxymorpholin- 4-yl-methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(morpholin-4-yl- methyl)cyclohexenyl)-naphthalen-1-yl]-urea;

45 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[{4-(4-(tetrahydrofuran-3-yl-

methyl)-3-hydroxyphenyl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-y1)-2H-pyrazol-3-y1]-3-[4-(4-(N.N-di-(2- methoxyethyl)aminomethyl)phenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-y1]-3-[4-(6-(3- cyanopropoxy)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-morpho} in-4-yl-

methyl-piperdinyl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(N.N-di-(2- cyanoethyl)aminomethyl)phenyl)naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4~(1-morpholin-4-yl-indan-5-yl)- naphthalen-1-yl)-urea: 1-[5-tert-butyl-2-(6-methyl-pyridin-3 -yD)-2H-pyrazol-3-yl}-3-[4-(4-(furan-2-yl-methyl)-3- hydroxyphenyl)naphthalen-1-yl]-urea,

1-[S-tert-butyl-2-(6-methyl-pyridin-3 -yl)-2H-pyrazol-3 -yl]-3-[4-(4-(thiomorpholin-4-yl- methyl)phenyl)naphthalen-1-yl1]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]}-3-[4-(4-(3-

carboxamidomorpholin-4-yl-methyl)phenyl)naphthalen-1 -yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(2-methyl-3-oxo- piperzin-1-yl-methyl)phenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl}-3-{4-(6-(morpholin-4-yl- methyl)pyndin-3-yl)naphthalen-1-yl]}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(4- hydroxybutyloxy)pyridin-3-y1)-naphthalen- 1-yl]-urea;

1-[3-tert-butyl-1'H-[1,4']bipyrazol-5-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3- yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(furan-2-yl-methyl)-3-

40 methoxyphenyl)naphthalen-1-ylj-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(5-(morpholin- 4carbonyl)pyrazin-2-yl)naphthalen-1-yl]-urea;

45 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydrothiopyran- 4-yl-amino)pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazol-3-yl}-3-{4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea:

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(2.6- dimethylmorpholin-4-yl-methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methoxypyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(2-aminoypyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-y!- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-oxo0-1,6-dihydropyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-

4-yl-methyl)pyridin-3-yl)-naphthalen-1-yi]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl-4- carbonyl)pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[5S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(2-oxa-5-aza- bicyclo[2.2.1]hept-5-yl-methyl)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(3-carbamylphenyl)naphthalen-1-yl}- urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N- (pyridin-3-yl-methyl)aminomethyl)phenyl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-

(pyridin-2-yl-methyl)aminomethy!)phenyl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N- (tetrahydrofuran-2-yl-methyl)aminomethyl)phenyl)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl- methyl)-4-methoxypyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(1 -morpholin-4-y]- propyl)pyridin-3-yl)-naphthalen-1-yl]-urea;

40 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-{4-(6-(N-(3- methoxypropyl)amino)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(N-(3-

45 methoxypropyl)-N-methylamino)pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[3-tert-butyl-1'-methyl-1"H-[1.4']bipyrazol-5-yl}-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-benzyl-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3-yl)- naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-N-di-(2- cyanoethyl)aminomethyl)phenyl)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(4-carbamylphenyl)naphthalen-1-yl}- urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(1 -oxo0- tetrahydrothiopyran-4yl-amino)pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydropyran-dyl- amino)pyridin-3-yi)-naphthalen-1-yl}-urea; 1-{3-tert-butyl-1'-(3-cyanopropyl)-1'H-[1.4']bipyrazol-5 -yl]-3-[{4-(6-(morpholin-4-yl-

methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yi]-3-[4-(3 -methanesulfinylphenyl)naphthalen-1- yl]-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-methanesulfonylphenyl)naphthalen-1- yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(3-sulfonamidophenyl)naphthalen-1-yl]- urea; .

1-[5S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl1}-3-[4-(3-(morpholin-4- yl)carbonylphenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(5-(tetrahydrothiopyran-

4yl-amino)pyrazin-2-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6- (methylcarbonylamino)pyridin-3-yl)-naphthalen-1-yl]-urea;

40 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-4-carbonyl)phenyl)- naphthalen-1-yl}-urea; 1-[3-tert-butyl-1'-(3-methylsulfanylpropyl)-1'H-[1,4']bipyrazol-5-y1}-3-[4-(6-(morpholin- 4-yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

45 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(5-(morpholin-4-yi-carbonyl)pyridin-3-

yl)-naphthalen-1-yl]}-urea: 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(5-(morpholin-4-y|- methyl)pyrazin-2-vl)-naphthalen-1-yl]-urea;

bh) 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-aminopyridin-3- yl)naphthalen-1-ylj-urca; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(1 -methylpiperdin-4-

yl-amino)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(2-methyl-3-oxo- piperzin-1-yl-methyl)pyridin-3-yl)naphthalen- 1-yl}-urea;

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl- carbonyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-y1)-2H-pyrazol-3-yl}-3-[4~(6-(N ,N-di-(2- methoxyethyl)aminomethyl)pyridin-3-yl)naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl1]-3-[4-(6-(1 -oxo- thiomorpholin-4-yl-methyl)pyridin-3-yl)naphthalen- 1-yl]-urea; 1-{5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydropyran-4-

yl-amino)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl}-3-[4-(5-(morpholin-4-yl- methyl)pyrazin-2-yl)naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(2-methyl-3-oxo-piperzin-1-yl- methyl)pyridin-3-yl)naphthalen-1-yl}-urea;

1-[5-tert-buty]-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(pyridin-3-yl-oxy)pyridin-3- yDnaphthalen-1-yl]-urea 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(pyridin-3-yl-amino)pyridin-3- yl)naphthalen-1-yl]-urea;

40 1-[5-tert-butyl-2-(2-methoxypyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-y]- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(5-carbamylpyridin-3-yl)naphthalen-1-

45 yl}-urea;

1-[5-tert-butyl-2-(2-aminopyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-y|- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[S-tert-butyl-2-(2-methylpyrimidin-53-yl)-2H-pyrazol-3-yl]-3-[4-(4-(morpholin-4-y1-

methyl)phenyl)naphthalen-1-yl}-urea; 1-[3-tert-butyl-1"-methyl-1'H-[1.4']bipyrazol-5-yl}-3-[4-(6-(morpholin-4-yi- methyl)phenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(2-cyclopropylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(pyridin-3-yl-amino)pyrimidin-5- ylnaphthalen-1-yl]-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-yl- amino)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(thiomorpholin-4-yl-methyl)pyridin-3-

yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(3-benzyl-3H-imidazo[4,5-b]pyridin-6- yl)naphthalen-1-yl}-urea;

1-[5-tert-butyl-2~(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(pyridin-3-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl-carbonyl)pyrimidin-S- yDnaphthalen-1-yl]-urea;

1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl-methyl)pyrimidin-5- yDnaphthalen-1-yl}-urea; 1-{5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(3-amino-4-carbamylphenyl)naphthalen-

1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(1-oxo-thiomorpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

40 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(pyridin-3-yl-methyl)pyridin-3- yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(hydroxy-pyridin-3-yl-methyl)pyridin- 3-yDnaphthalen-1-yl]-urea;

45 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl-

methyl)pyrimidin-3-yl)naphthalen-1-yl}-urea; and the pharmaceutically acceptable derivatives thereof.

In another embodiment of the invention there are provided the following compounds of the formula(la): 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(5-(morpholin-4-yl-methyl)pyridin-2-yl)- naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3-yl)- naphthalen-1-yl]j-urea; 1-[S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(2-(pyridin-2- yl)ethylamino)cyclohexenyl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(pyridin-3-yl- methylaminomethyl)phenyl)naphthalen-1-ylj-urea; : 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(morpholin-4-yl- methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(4- hydroxybutylamino)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(4-methyl-3-carbamylphenyl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-(4-(4-(3-hydroxypiperidin- 1-yl-methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(4-hydroxymorpholin- 4-yl-methyl)phenyl)naphthalen-1-yl]-urea; 40 1-[5-tert-butyl-2-(6-methyl-pyrnidin-3-yl)-2H-pyrazol-3-yl}-3-[4-(3-(morpholin-4-yl- methyl)cyclohexenyl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(tetrahydrofuran-3-yl- 45 methyl)-3-hydroxyphenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl1}-3-[4-(4-(N .N-di-(2-

methoxyethyl)aminomethyl)phenyl)naphthalen-1-yl]-urea: 1-[S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-y1}-3-[4-(6-(3- cyanopropoxy)pyridin-3-yl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-{4-(4-morpholin-4-yl- methyl-piperdinyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N,N-di-(2-

cyanoethyl)aminomethyl)phenyl)naphthalen-1-yl)-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(furan-2-yl-methyl)-3- hydroxyphenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(thiomorpholin-4-y!- methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]}-3-[4-(4-(3- carboxamidopiperidin-1-yl-methyl)phenyl)naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(2-methyl-3-oxo- piperzin-1-yl-methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl}-3-(4-(6-(morpholin-4-yl-

methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]}-3-[4-(6-(4- hydroxybutyloxy)pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[3-tert-butyl-1'H-[1,4']bipyrazol-5-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3- yDnaphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydrothiopyran- 4-yl-amino)pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl1)-2H-pyrazol-3-y1]-3-[4-(6-(2,6-

40 dimethylmorpholin-4-yl-methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methoxypyridin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea;

45 1-[5-tert-butyl-2-(2-aminoypyridin-5-y1)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl1}-3-[4-(6-(morpholin-4-yl-4- carbonyl)pyridin-3-yi)-naphthalen-1-yl}-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(2-0xa-5-aza- bicyclo[2.2.1]hept-5-yl-methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N- (pyridin-3-yl-methyl)aminomethyl)phenyl)-naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N-

(tetrahydrofuran-2-yl-methyl)aminomethyl)phenyl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-

methyl)-4-methoxypyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-( 1 -morpholin-4-yl- propyl)pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[3-tert-butyl-1'-methyl-1'H-[1,4']bipyrazol-5-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-{4-(6-(1-ox0- tetrahydrothiopyran-4yl-amino)pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-y1}-3-[4-(6-(tetrahydropyran-4yl- amino)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(5-(tetrahydrothiopyran-

4yl-amino)pyrazin-2-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6- (methylcarbonylamino)pyridin-3-yl)-naphthalen-1-ylj-urea;

1-[3-tert-butyl-1'-(3-methylsulfanylpropyl)-1'H-[1.4']bipyrazol-5-yl]-3-[4-(6-(morpholin- 4-yl-methyl)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(1-0x0- thiomorpholin-4-yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

40 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydropyran-4- yl-amino)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-

45 yl-methyl)pyridin-3-yl)naphthalen-1-yl}-urea;

1-[5-tert-butyi-2-(2-aminopyrimidin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-y- methyl)pyridin-3-yl)naphthalen-1-yl]-urea: 1-[3-tert-butyl-1'-methyl-1'H-[1,4']bipyrazol-5-y1}-3-[4-(6-(morpholin-4-yl- methyl)phenyl)naphthalen-1-yl]-urea: 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(1-oxo-tetrahydrothiopyran-4-yl- amino)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-(thiomorpholin-4-yl-methyl)pyridin-3- yl)naphthalen-1-yl]j-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(2-(morpholin-4-yl-carbonyl)pyrimidin-5- ylnaphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl-methyl)pyrimidin-5- yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(1-oxo-thiomorpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(2-methylpyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl- methyl)pyrimidin-5-yl)naphthalen-1-yl]-urea and the pharmaceutically acceptable derivatives thereof.

In yet another generic aspect of the invention, there are provided compounds of the formula (1):

J

G- Ar—X—Y—Z ry

H H ty 40 wherein:

Gis: an aromatic Ce. ¢ carbocycle or a nonaromatic Cs. carbocycle saturated or unsaturated: a 6-10 membered heteroaryl containing 1 or more heteroatoms chosen from O, N and S: a 5-8 membered monocyclic heterocycle containing one or more heteroatoms chosen from O, N and S; or an 8-11 membered bicyclic heterocycle. containing one or more heteroatoms chosen from

O.NandS§S; wherein G is substituted by one or more R;, R> or Rj:

Aris: phenyl, naphthyl, quinolinyl, isoquinolinyl, tetrahydronaphthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzimidazolyl, benzofuranyl, dihydrobenzofuranyl, indolinyl, benzothienyl, dihydrobenzothienyl, indanyl. indenyl or indolyl each being optionally substituted by one or more Ry or Rs;

X is: a Cs.g cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, C4 alkoxy or C4 alkylamino chains; phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl. imidazolyl, pyridinyl, pyrimidinyl, pyridinonyl, dihydropyridinonyl, maleimidyl, dihydromaleimidyl, piperdinyl, benzimidazole, 3H-imidazo[4,5-b]pyridine. piperazinyl, pyridazinyl or pyrazinyl,;

Y is:

a bond or a C,. saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated. wherein one or more methylene groups are optionally replaced by O. N. or S(O)m and wherein Y is optionally independently substituted with one to two oxo groups. phenyl or one or more C,_, alkyl optionally substituted by one or more halogen atoms;

Lis: phenyl, pyridinyl. pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl. thienyl, pyranyl each being optionally substituted with one to three halogen, Cy. alkyl. C, alkoxy, hydroxy. amino. mono- or di-(C, ; alkyl)amino, C,¢ alkyl-S(O)m, CN. CONH,, COOH or phenylamino wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkyl or C.¢ alkoxy; tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3-dioxanonyl, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfoxidyl, thiomorpholino sulfonyl, piperidinyl, piperidinonyl, piperazinyl, tetrahydropyrimidonyl, cyclohexanonyl, cyclohexanolyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl. pentamethylene sulfonyl, tetramethylene sulfide, tetramethylene sulfoxidyl or tetramethylene sulfonyl each being optionally substituted with one to three nitrile, C4 alkyl, C,.¢ alkoxy, hydroxy, amino, mono- or di-(C,.; alkyl)amino-C,_; alkyl, CONH,, phenylamino-C,_; alkyl or C,_; alkoxy-C,_; alkyl; halogen, Cy alkyl, nitrile, amino, hydroxy, C,.¢ alkoxy, NH,C(O). mono- or di(C,.zalkyl) aminocarbonyl. mono- or di(C,.¢alkyl)amino, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to C,.; alkyl or C,_s alkoxyalkyl, pyridinyl-C;.3 alkyl. imidazolyl-C,_; alkyl, tetrahydrofuranyl-C,.; alkyl, nitrile-C, 3 alkyl, carboxamide-C, 3 alkyl, phenyl, wherein the phenyl ring is optionally substituted with one to two halogen,

C4 alkoxy, hydroxy or mono- or di-(C).; alkyl)amino, C, alkyl-S(O)p, or phenyl-

S(O)m. wherein the phenyl ring is optionally substituted with one to two halogen, C.¢ alkoxy, hydroxy. halogen or mono- or di-(C,.; alkyl)amino:

Ci. alkyl-S(O)m, and phenyl-S(O)n,. wherein the phenyl ring is optionally substituted with one to two halogen. C;¢ alkoxy. hydroxy or mono- or di-(C,.; alkyl)amino; each R| 1s independently:

Ci.10 alky! optionally be partially or fully halogenated. and optionally substituted with one to three Cs. cycloalkanyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazoly! or isothiazolyl; each of the aforementioned being optionally substituted with one to five groups selected from halogen, Cy. alkyl which is optionally partially or fully halogenated, Cs.s cycloalkanyl, Cs.g cycloalkenyl, hydroxy, nitrile, C,_; alkoxy which is optionally partially or fully halogenated or NH,C(O), mono- or di(C,.3alkyl)amino, and mono- or di(C;.3alkyl)aminocarbonyl; cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, or cycloheptyloxy each being optionally partially or fully halogenated and optionally substituted with one to three C,.3alkyl groups optionally partially or fully halogenated. CN, hydroxyC;.;alkyl or aryl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O)m, CHOH, >C=0, >C=S or NH; phenyloxy or benzyloxy each being optionally partially or fully halogenated and optionally substituted with one to three C;.3 alkyl groups optionally partially or fully halogenated, CN, hydroxyC,.;alkyl} or aryl; or an analog of such cycloaryl group wherein one to two ring methyne groups are independently replaced by N; cyclopropanyl, cyclobutanyl, cyclopentanyl. cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C3 alkyl groups optionally partially or fully halogenated, CN. hydroxyC,.;alkyl or aryl: or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O)n. CHOH. >C=0.>C=S or NH;

Cs.j0 branched or unbranced alkenyl each being optionally partially or fully halogenated, and optionally be substituted with one to three C\.s branched or unbranched alkyl, phenyl. naphthyl, pyridinyl. pyrimidinyl. pyrazinyl. pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl. isoxazolyl or isothiazolyl, each of the aforementioned being substituted with zero to five halogen, C;.¢ alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl. bicyclopentanyl. bicyclohexanyl and bicycloheptanyl, hydroxy, nitrile, C,.3 alkyloxy which is optionally partially or fully halogenated. NH,C(O). mono- or di(C,. salkyl)aminocarbonyl; the Cj.o branched or unbranced alkenyl being optionally interrupted by one or more heteroatoms chosen from O, N and S(O); cyclopentenyl. cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C;_zalkyl groups; nitrile, halogen; methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl; silyl containing three C,.4 alkyl groups optionally partially or fully halogenated; : :

Cs. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH or

S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrrolidinyl, pyrrolyl, one or more C,.4 alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidinyl, piperazinyl. imidazolyl, phenyl, pyridinyl, tetrazolyl, or mono- or di(C).;alkyl)amino optionally substituted by one or more halogen atoms: each Ro. R.. and Rs 1S aC), branched or unbranched alkyl optionally partially or fully halogenated. acetyl, aroyl, C4 branched or unbranched alkoxy. each being optionally partially or fully halogenated. halogen, nitrile. methoxycarbonyl. Cy.3 alkyl-S(O), optionally partially or fully halogenated. or phenylsulfonyl;

C,. alkoxy, hydroxy, amino, or mono- or di-(C, alkyl)amino, nitrile, halogen;

ORg; nitro; or mono- or di-(C;4 alkyl)amino-S(O); optionally partially or fully halogenated, or

H;NSO;3; each Rj; is independently: phenyl, naphthyl, morpholinyl, pyridinyl. pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl. imidazolyl, pyrazolyl, thiazolyl, oxazoyl, triazolyl, tetrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl. quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl. phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, each of the aforementioned is optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl as hereinabove described in this paragraph, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated. cyclopropanyl, cyclobutanyl. cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C,.s alkyl, naphthyl C,.s alkyl, halogen, hydroxy, oxo, nitrile, C,.3 alkyloxy optionally partially or fully halogenated,

phenyloxy, naphthyloxy. heteroaryloxy or heterocyclicoxy wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, nitro. amino. mono- or di-(C).;alkyl)amino. phenylamino, naphthylamino. heteroaryl or heterocyclic amino : wherein the heteroaryl heterocyclic moiety is as hereinabove described in this paragraph,

NH;C(O), a mono- or di-(C,.;alkyl) aminocarbonyl, C,.s alkyl-C(O)-C, alkyl, amino-C,. 5 alkyl, mono- or di-(C,.;alkyl)amino-C,.s alkyl. amino-S(0),, di-(C,.;alkyl)amino-S(0O),.

R7-C,.s alkyl, Rg-C;.5 alkoxy. Ro-C(O)-C,.5 alkyl, R;o-C.5 alkyl(R;;)N. carboxy-mono- or di-(C,.salkyl)-amino: a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthy!, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl. cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl, cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl, cyclohexanoquinolinyl, cyclopentanoisoquinolinyl, cyclohexanoisoquinolinyl, cyclopentanoindolyl. cyclohexanoindolyl, cyclopentanobenzimidazolyl, cyclohexanobenzimidazolyl. cyclopentanobenzoxazolyl, cyclohexanobenzoxazoly!l, cyclopentanoimidazolyl, cyclohexanoimidazolyl, cyclopentanothienyl and cyclohexanothienyl; wherein the fused aryl or fused heteroaryl ring is independently substituted with zero to three phenyl, naphthyl. pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl. thienyl, furyl, isoxazolyl, isothiazolyl. C.¢ alkyl which is optionally partially or fully halogenated, halogen, nitrile, C)_; alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.3alkyl)amino, phenylamino, naphthylamino, heteroary] or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, NH;C(O), mono- or di-(C;. salkyl)aminocarbonyl, C,. alkyl-OC(O), C,.s alkyl-C(O)-C,.4 alkyl. amino-C,_s alkyl. mono- or di-(C).3)alkylamino-C,.s alkyl, R}2-C;.s alkyl, Ry3-C,_s alkoxy, Rj4-C(0)-C;.s alkyl or Ry5-Cy.s alkyl(R6)N;

cyclopropanyl. cyclobutanyl. cyclopentanyl. cyclohexanyl. cycloheptanyl. bicyclopentanyl. bicyclohexanyl or bicycloheptanyl. each being optionally partially or fully halogenated and optionally substituted with one to three C;.3 alkyl groups. or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O. S. CHOH, >C=0. >C=S or NH; cyclopentenyl, cyclohexenyl. cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C).3 alkyl groups,

Ci-4 alkyl-phenyl-C(O)-C,4 alkyl-, C,.4 alkyl-C(O)-C 4 alkyl- or C4 alkyl-phenyl-

S(O)m-C.4 alkyl-;

C,. alkyl or C,.¢ branched or unbranched alkoxy each of which is optionally partially or fully halogenated or optionally substituted with R;;

OR 5 or Cy alkyl optionally substituted with OR 3; amino or mono- or di-(C,.salkyl)amino optionally substituted with Rg;

R20C(O)N(R21)-, R220- or R23R24NC(0)-; Ry6(CH2)mC(OIN(R2))- or

RasC(O)NCH2)mN(R21)-;

C;.¢alkenyl substituted by R23R24NC(O)-;

Cs.¢ alkynyl branched or unbranched carbon chain, optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH,

S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl. morpholinyl, piperidinyl, piperazinyl, imidazoly], phenyl, pyridinyl, tetrazoly! one or more C4 alkyl optionally substituted by one or more halogen atoms. nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl,

pyridinyl, tetrazolyl. or mono- or di(C, alkyl)amino optionally substituted by one or more halogen atoms: or aroyl;

Rg is a:

C4 alkyl optionally partially or fully halogenated and optionally substituted with Ry; each Rs, Rg, Ro. Rig, Ri2, Ris. Ria, Ris, Riz, Ryo, Ras and Ry is independently: nitrile, phenyl. morpholino, piperidinyl, piperazinyl, imidazolyl, pyridinyl, tetrazolyl, amino or mono- or di-(C, _4alkyl)amino optionally partially or fully halogenated; each Rj) and Ry; is independently: hydrogen or C,.4 alkyl optionally partially or fully halogenated;

Rs is independently: hydrogen or a C,4 alkyl optionally independently substituted with oxo or Rs;

Ryo is independently:

Ci.10 alkyl optionally partially or fully halogenated, phenyl, or pyridinyl,

Rj; is independently: hydrogen or C,.; alkyl optionally partially or fully halogenated; each Ry, Ry; and Ry, is independently: hydrogen, C,.¢ alkyl optionally partially or fully halogenated, said C).¢ alkyl is optionally interrupted by one or more O, N or S. said C,.¢ alkyl also being independently optionally substituted by mono- or di-(C,.;alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono- or di~(C4alkyhamino each of which is optionally partially or fully halogenated and optionally substituted with mono- or di-(C,_3alkyl)amino;

or Ry»; and Ray taken together optionally form a heterocyclic or heteroaryl ring; m=0.1 or 2;

WisOorSand pharmaceutically acceptable derivatives thereof.

In another embodiment of the invention there is provided compounds of the formula(ll) as described immmediately above. and wherein

Gis: phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl, benzocycloheptenyl, indanyl, indenyl; pyridinyl, pyridonyl, quinolinyl, dihydroquinolinyl, tetrahydroquinoyl, isoquinolinyl, tetrahydroisoquinoyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl. benzpyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, benzooxazolonyl. benzo[1,4Joxazin-3-onyl, benzodioxolyl, benzo[1,3}dioxol-2-onyl, benzofuran-3-onyl. tetrahydrobenzopyranyl, indolyl, indolinyl, indolonyl, indolinonyl, phthalimidyl; oxetanyl, pyrrolidinyl, tetrahydrofuranyl. tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, dioxanyl. tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl, thiazolinyl, imidazolinyl, tertrahydropyridinyl, homopiperidinyl, pyrrolinyl, tetrahydropyrimidinyl, decahydroquinolinyl, decahydroisoquinolinyl, thiomorpholinyl, thiazolidinyl, dihydrooxazinyl, dihydropyranyl, oxocanyl, heptacanyl, thioxanyl or dithianyl; wherein G is substituted by one or more R,, R; or Rs;

In another embodiment of the invention there is provided compounds of the formula(Il) as described immediately above. and wherein

Gis phenyl. pyridinyl. pyridonyl. naphthyl. quinolinyl, isoquinolinyl, pyrazinyl, benzimidazolyl, benzoxazolyl. benzofuranyl. benzothiophenyl, benzpyrazolyl, dihydrobenzofuranyl. dihydrobenzothiophenyl. indanyl, indenyl. indolyl. indolinyl. indolonyl or indolinonyl, wherein G is substituted by one or more R;, Ra or Rj:

Aris: naphthyl, quinolinyl. isoquinolinyl. tetrahydronaphthyl. tetrahydroquinolinyl. tetrahydroisoquinolinyl. indanyl. indenyl or indolyl each being optionally substituted by one or more Ry or Rs groups;

X is: ~ phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl. imidazolyl, pyridinyl, pyrimidinyl, pyndinonyl, dihydropyridinonyl. maleimidyl. dihydromaleimidyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl

Y is: a bond or a Cy saturated or unsaturated carbon chain wherein one of the carbon atoms is optionally replaced by O, N, or S(O), and wherein Y is optionally independently substituted with one to two oxo groups, phenyl or one or more C,_; alkyl optionally substituted by one or more halogen atoms;

Zis:

phenyl. pyridinyl. pyrimidinyl. pyridazinyl. pyrazinyl. imidazolyl. furanyl. thienyl. dihydrothiazolyl. dihydrothiazolyl sulfoxidyl. pyranyl. pyrrolidiny] which are optionally substituted with one to three nitrile. C;.3 alkyl. C;_; alkoxy. amino. mono- or di-(C.; alkyl)amino, CONH: or OH; tetrahydropyranyl, tetrahydrofuranyl, 1.3-dioxolanonyl. 1.3-dioxanonyl. 1,4-dioxanyl, morpholinyl, thiomorpholinyl. thiomorpholino sulfoxidyl, piperidinyl. piperidinonyl. piperazinyl, tetrahydropyrimidonyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl. pentamethylene sulfonyl, tetramethylene sulfidyl, tetramethylene suifoxidy!l or tetramethylene sulfonyl which are optionally substituted with one to three nitrile, C;.3 alkyl, C,.; alkoxy, amino, mono- or di-(C,.; alkyl)amino. CONH,, or OH; nitrile, C, alkyl-S(O)n. halogen. hydroxy. C, alkoxy. amino, mono- or di-(C,.¢ alkyl)amino, mono- or di-(C,.; alkyl)aminocarbonyl or NH,C(O); each R, is independently:

Cs. alkyl optionally partially or fully halogenated, and optionally substituted with one to three Ci.¢cycloalkyl, phenyl, thienyl, furyl. isoxazolyl or isothiazolyl; each of the aforementioned being optionally substituted with one to three groups selected from halogen, C;_; alkyl which is optionally partially or fully halogenated, hydroxy, nitrile or

C,.salkoxy which is optionally partially or fully halogenated; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups optionally partially or fully halogenated,

CN, hydroxyC,.salky! or phenyl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S, CHOH, >C=0, >C=S or

NH; or silyl containing three C,4 alkyl groups optionally partially or fully halogenated,

R> is independently: halogen. C,.; alkoxy, C;.; alkyl-S(O)n, optionally partially or fully halogenated. phenylsulfony! or nitrile;

Rj; is independently: phenyl, morpholino, pyridinyl, pyrimidinyl, pyrazinyl. pyrrolyl, pyrrolylidinyl, imidazolyl, pyrazolyl, each being optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl as hereinabove described in this paragraph, C, alkyl which is optionally partially or fully halogenated. cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl. bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C,.; alkyl, naphthyl C,_s alkyl. halogen, oxo, hydroxy, nitrile, C,_; alkyloxy optionally partially or fully halogenated. phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.;alkyl)amino, phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, NH,C(O), a mono- or di-(C;. salkyl)aminocarbonyl, C,.s alkyl-C(O)-C,4 alkyl, mono- or di-(C;.3alkyl)amino, mono- or di-(Cy.3)alkylamino-C,.s alkyl, mono- or di-(C,salkyl)amino-S(O),, R7-C,.s alkyl, Rg-C).s alkoxy, Ro-C(0)-C;.5 alkyl, R1o-Cy.s alkyl(R};)N, carboxy-mono- or di-(C,.5)-alky!}- amino; :

Ci; alkyl or C4 alkoxy each being optionally partially or fully halogenated or optionally substituted with R;7;

OR; or C4 alkyl optionally substituted with OR 3; amino or mono- or di- (C,-5 alkyl)amino optionally substituted with Rg;

R20C(O)N(R2))-. R220- : R23R24NC(O)-; R26CH,C(OIN(Ry))- or R2C(O)CHaN(R2:)-:

Cs,.ialkenyl substituted by R3R23;NC(O)-: or

Cs. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated and optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl. morpholinyl, piperidinyl. piperazinyl, imidazolyl. phenyl, pyridinyl, tetrazolyl or one or more C;_4 alkyl optionally substituted by one or more halogen atoms; and

Ry; and Ry, taken together optionally form imidazolyl. piperidinyl, morpholinyl, piperazinyl or a pyridinyl ring.

In yet another embodiment of the invention there is provided compounds of the formula(ll) as described immediately above. and wherein:

G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl. isoquinolinyl, pyrazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indolyl, indolinyl, indolonyl or indolinonyl. wherein G is substituted by one or more R,, R; or R3;

Ar is naphthyl;

Xis phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl each being optionally independently substituted with one to three C,_4 alkyl, C,. salkoxy, hydroxy, nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di~(C alkylamino)carbonyl, NH,C(0), C,.¢ alkyl-S(O),, or halogen;

Y is: a bond or a C4 saturated carbon chain wherein one of the carbon atoms is optionally replaced by

O.N or S and wherein Y is optionally independently substituted with an oxo group:

Zis: phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl. dihydrothiazolyl, dihydrothiazolyl sulfoxide, pyranyl or pyrrolidinyl which are optionally substituted with one to two C.; alkyl or C,_; alkoxy; tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfoxidyl, piperidinyl, piperidinonyl, piperazinyl or tetrahydropyrimidonyl which are optionally substituted with one to two C,.; alkyl or C,.; alkoxy; or

C,.; alkoxy; is each R; is independently:

C;.s alkyl optionally partially or fully halogenated, and optionally substituted with phenyl substituted with zero to three halogen, C,.; alkyl which is optionally partially or fully halogenated, hydroxy, nitrile or C;.3alkoxy which is optionally partially or fully halogenated; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,.3 alkyl groups optionally partially or fully halogenated,

CN, hydroxyCi.3alkyl or phenyl; and an analog of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentany! or bicyclohexanyl wherein one ring methylene group is replaced by O; and silyl containing three C,., independently alkyl groups optionally partially or fully halogenated,

each Rj is independently: bromo. chloro. fluoro. methoxy. methylsulfony! or nitrile: each Rj is independently: phenyl, morpholino, pyridinyl, pyrimidinyl, pyrrolylidinyl. 2,5-pyrrolidin-dionyl, imidazolyl, pyrazolyl, each of the aforementioned is optionally substituted with one to three C,.; alky! which is optionally partially or fully halogenated. halogen, oxo, hydroxy, nitrile and C,.; alkyloxy optionally partially or fully halogenated;

C,.3 alkyl or C,.3 alkoxy each being optionally partially or fully halogenated or optionally substituted with R;+;

OR; or C3 alkyl optionally substituted with ORs; amino or mono- or di-(C;-3 alkyl)amino optionally substituted with Rs:

RyC(O)N(R23)-, R»O- ; R233R2aNC(0)-; R2sCHC(O)N(R2))- or Ry6C(O)CHN(R2)-;

C,4 alkenyl substituted by R;3R24NC(O)-; or

C,4 alkynyl substituted with pyrroldinyl or pyrrolyl; and

R,3 and Ry4 taken together optionally form morpholino.

In yet still another embodiment of the invention there is provided compounds of the formula(ll) as described immediately above, and wherein

G is phenyl. pyridinyl. pyridonyl. naphthyl. quinolinyl. isoquinolinyl. dihydrobenzofuranyl. indanyl. indolinyl. indolonyl. or indolinonyl. wherein G is substituted by one or more Rj, R; or Rj:

Ar is 1-naphthyl;

Xs: phenyl, imidazolyl, pyridinyl, pyrimidinyl. piperdinyl, piperazinyl, pyridazinyl or pyrazinyl;

Y is: a bond or -CH,-, -CH,CH,-, -C(0)-, -O-, -S-. -NH-CH,CH,CH,-, -N(CHj)-, or -NH-; each R, is independently:

Cs.s alkyl optionally partially or fully halogenated, and optionally substituted with phenyl; cyclopropyl, cyclopentanyl, cyclohexanyl and bicyclopentany] optionally substituted with one to three methyl! groups optionally partially or fully halogenated, CN, hydroxymethyl or phenyl; or 2-tetrahydrofuranyl substituted by methyl; or trimethyl silyl, each R; is independently:

phenyl. morpholinyl. pyridinyl. pyrimidinyl. pyrrolylidinyl. 2.5-pyrrolidin-dionyl. imidazolyl or pyrazolyl. wherein any of the aforementioned is optionally substituted with

Ci-2 alkyl which is optionally partially or fully halogenated;

Cis alkyl or Cy; alkoxy each being optionally partially or fully halogenated or optionally substituted with diethylamino;

ORs or C3 alkyl optionally substituted with OR 3: amino or mono- or di-(C,_; alkyl)amino optionally substituted with Rs:

CH3C(O)NH-, R2:0- ; R23R2aNC(0)-; R2sCH2C(O)N(R21)- or Ra6C(O)CHaN(R2)-;

Ca.alkenyl substituted by Ry3R4NC(O)-; or

C24 alkynyl substituted with pyrroldinyl or pyrrolyl;

R23 and Ry4 are H or Ry; and Ry4 taken together optionally form morpholino; and

Ry¢ is morpholino.

In another embodiment of the invention there is provided of the formula(ll) as described immediately above, and wherein

Gis phenyl, pyridinyl or naphthyl wherein G is substituted by one or more R;, R, or Rj;

X is: imidazolyl or pyridinyl;

Y is: -CH,., -NH-CH,CH:CHa- or -NH-;

Z is morpholino: each R) is independently: tert-butyl, sec-butyl. tert-amy! or phenyl;

R; is chloro; :

Rj is independently: methyl, methoxy, methoxymethyl, hydroxypropyl, acetamide, morpholino or morpholinocarbonyl.

In yet a further embodiment of the invention there is provided of the formula(ll) as described immediately above, and wherein X is pyridinyl.

In yet a further embodiment of the invention there is provided of the formula(ll) as described immediately above, and wherein the pyridinyl is attached to Ar via the 3- pyridinyl position.

The following are representative compounds of the formula(ll): 1-(3-Cyano-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl]-urea 1-(3-Fluoro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl]-urea 1-(4-Chloro-2-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(2-Chloro-5-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea

1-(3.4-Dimethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 1-(3-lodo-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-ylj-urea

1-{4-(6-Morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1-yl]-3-m-tolyl-urea 1-(4-Methylsulfanyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea

1-(3-Chloro-4-methyl-pheny1)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea 1-(4-Chloro-3-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-

yl}-urea 1-(2,5-Dichloro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}- urea

1-[4-(6-Morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1-yl]-3-naphthalen-2-yl-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]}-3-phenyl-urea 1-(3-Chloro-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea

1-(4-Chloro-3-trifluoromethyl-phenyl)- 3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-3-(2,4,6-trichloro-phenyl)-

urea 1-(2-Methyl-3-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea

1-(4-Methyl-2-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-urea 1-(2,3-Dichloro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea

40 1-(2-Methoxy-5-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl}-urea 1-(2-Chloro-6-methyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- | -

45 yl]-urea

1-(2.4-Dichloro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-y 1)-naphthalen-1-yl]- urea 1-(4-Methyl-3-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-

yl]-urea 1-(2.4-Dimethy!-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}- urea

1-(2,3-Dimethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 1-(4-Cyano-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl]-urea

1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-3-(3 ,4.5-trimethoxy- phenyl)-urea 1-Biphenyl-4-yl-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl]-urea

1-(2,5-Difluoro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-y1}- urea

1-(3-Chloro-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyi-pyridin-3-yl)-naphthalen- 1-yl}-urea

1-(2-Fluoro-3-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)- naphthalen-1-ylj-urea 1-(4-Benzyloxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-

urea 1-(2-Methylsulfanyl-phenyl)-3-[{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea

1-(2-Fluoro-6-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(4-Fluoro-3-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea

40 1-{4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-y1]-3-(2,4,5-trimethyl-pheny!)- urea 1-{4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-3-(4-trifluoromethyl- 45 phenyl)-urea

1-(3-Methylsulfanyl-phenyl)-3-{4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1- yl]-urea 1-(2-Methoxy-phenyl)-3-{4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1-ylj-urea

1-(2-Fluoro-5-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(4-Methoxy-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl]-urea 1-(2-Fluoro-5-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea 1-(4-Ethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 1-(2,5-Dimethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 1-(4,5-Dimethyl-2-nitro-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl]-urea 1-(5-Chloro-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-urea

1-(2-Isopropyl-6-methyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(2-Difluoromethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- l-ylJ-urea 1-(4-Isopropyl-phenyl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 1-(4-Methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 1-(3-Ethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 1-(2-Ethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea 40 1-(4-Butoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 4-{3-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1 -yl]-ureido} -benzoic acid ethyl ester 45

1-(4-Butyl-2-methyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-vi)-naphthalen-1- yli]-urea 1-(2,6-Dibromo-4-isopropyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(3-Methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -vl}-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl}-3-(4- trifluoromethylsulfanyl-phenyl)-urea 5-{3-[4-(6-Morpholin-4-ylmethy!-pyridin-3-yl)-naphthalen-1-yl}-ureido } -isophthalic acid dimethyl ester 1-(3-Cyclopentyloxy-4-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 3-{3-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-ureido} -benzoic acid ethyl ester 1-(5-tert-Butyl-2-hydroxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(2-Hydroxymethyl-4-phenyl-cyclohexyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(2-Methylsulfanyl-5-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-yImethyl-pyridin-3- yl)-naphthalen-1-yl]-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-3-(4-pentyloxy-biphenyl-3- yl)-urea 4-Methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-ureido)}- benzoic acid methyl ester 1-(2,5-Diethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl]- urea : 1-Benzothiazol-6-yl-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 40

N-(2,5-Diethoxy-4-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}- ureido}-phenyl)-benzamide 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-3-(3-phenoxy-phenyl)-urea 45

1-(5-Ethanesulfonyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethy1-pyridin-3-yl)- naphthalen-1-yl]-urea 4-Methoxy-3- {3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-ureido }-N- phenyl-benzamide 1-(2-Methyl-1.3-dioxo-2 3-dihydro- 1H-isoindol-5-yl)-3-[4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl}-urea 1-(2,3-Dimethyl-1H-indol-5-yl)-3-[4-(6-morpholin-4-ylmethy!-pyridin-3-yl)-naphthalen- 1-yl]-urea

N-Butyl-4-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}- ureido}-benzenesulfonamide 1-[3-(2-Methyl-[1,3]dioxolan-2-yl)-phenyl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(3-Methoxy-5-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(2,4-Dimethoxy-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 1-(2-Methyl-4-nitro-phenyl)-3-[4-(6-morpholin-4-yImethy!-pyridin-3-yl)-naphthalen-1- yl}-urea 1-(2-Methoxy-4-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea 1-(4-Chloro-2-nitro-phenyl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1- yl}-urea 1-(5-Chloro-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl]-urea 1-(3,5-Dimethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea 40 1-[4~(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-3-(4-trifluoromethoxy- phenyl)-urea 1-[4~(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-y1}-3-(3- trifluoromethylsulfanyl-phenyl)-urea 45 1-[4~(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-3-(2-phenoxy-phenyl)-urea

1-(2-Methoxy-5-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea

1-(5-Chloro-2.4-dimethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-y1)- naphthalen-1-yl]-urea

1-(2-tert-Butyl-5-methyl-pyridin-4-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(3-Methyl-naphthalen-2-yl)-3-{4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen- 1 -

ylj-urea 1-(3-tert-Butyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1 -yl]- urea

1-(4-Methyl-biphenyl-3-yi)-3 -[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-urea 1-(4-tert-Butyl-biphenyl-2-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea

1-(5-Chloro-2,4-dimethoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-y1)- naphthalen-1-yl}-urea 1-(5-Isopropyl-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-

naphthalen-1-yl]-urea 1-(5-sec-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea

1-(5-tert-Butyl-2-methoxy-3-propyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(5-tert-Butyl-2-methoxymethyl-phenyl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)- naphthalen-1-yl}-urea

40 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methyl-phenyl)-3-(4-{6-[(3-methoxy-propyl)-methyl-amino]-pyridin-3-

45 yl}-naphthalen-1-yl)-urea

1-(5-tert-Butyl-2-methyl-phenyl)-3-{4-(4-morpholin-4-ylmethyl-imidazol- 1 -yl)- naphthalen-1-yl]-urea 1-(5-tert-Butyl-2-methyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea 1-(5-tert-Butyl-2-methyl-phenyl)-3- {4-[6-(3-methoxy-propylamino)-pyridin-3-yl]- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methyl-pyridin-3-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-morpholin-4-yl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-(6-tert-Butyl-2-chloro-3-methyl-pyridin-4-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl]-3-(3-trifluoromethyl- ’ phenyl)-urea 1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-3-(4-trifluoromethoxy- phenyl)-urea 1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl]}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-(2-methyl-pyrimidin-5-yl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-(3-hydroxy-propyl)-phenyl]-3-[4-(6-morpholin-4-yimethyl-pyridin-3- yl)-naphthalen-1-yl]-urea 1-[5-tert-Butyl-2-(3-morpholin-4-yl-3-oxo-propyl)-phenyl]-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 40 I-[5-tert-Butyl-2-(morpholine-4-carbonyl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl]-urea

N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl)-ureido}-phenyl)-acetamide 45 and the pharmaceutically acceptable derivatives thereof.

In addtion to the abovementioned representative compounds the following prophetic compounds of the formula(ll) may be made by the general methods described hereinbelow: ] -[4-(6-{[Bis-(2-cyano-ethyl)-amino]-methyl}-pyridin-3-yl)-naphthalen-1-yl]-3-(5-tert- butyl-2-methoxy-phenyl)-urea

1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[4-(2-methyl-3-oxo-piperazin-1-ylmethyl)- phenyl]-naphthalen-1-yl}-urea 1-[4-(6-{[Bis-(2-methoxy-ethyl)-amino]-methyl}-pyridin-3-yl)-naphthalen-1 -yiJ-3-(3- tert-butyl-2-methoxy-phenyl)-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3- {4-[6-(2-methyl-3-oxo-piperazin-1 -ylmethyl)- pyridin-3-yl}-naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(1-0x0-1 14-thiomorpholin-4-ylmethyl)- pyridin-3-yl}-naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-thiomorpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea

1-(5-tert-Butyl-2-methyl-phenyl)-3-{4-[6-(1-0x0-114-thiomorpholin-4-ylmethyl)-pyridin- 3-yl}-naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methyl-phenyl)-3-{4-[6-(2-methyl-3-oxo-piperazin- 1 -ylmethy))- pyridin-3-yl}-naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3- {4-{4-(1-oxo0-1 I-thiomorpholin-4-ylmethyl)- phenyl]-naphthalen-1-yl}-urea 1-[4-(4-{[Bis-(2-cyano-ethyl)-amino}-methyl}-phenyl)-naphthalen-1 -y1]-3-(5-tert-butyl- . 2-methoxy-phenyl)-urea 1-(2-Methoxy-5-pentafluoroethyl-phenyl)-3-[4-(4-morpholin-4-ylmethyl-piperidin-1-yl)- naphthalen-1-yl]-urea 40 1-(2-Methoxy-5-trifluoromethyl-pyridin-3-yl)-3-{4-[2-(4-oxo-piperidin-1-vImethyl)- pyrimidin-5-yl}-naphthalen-1-yl}-urea 1-(2-Methoxy-5-trimethylsilanyl-phenyl)-3- {4-[4-(tetrahydro-pyran-4-ylamino)-phenyl]- naphthalen-1-yl}-urea

1-(3-Methoxy-naphthalen-2-y1)-3-[4-(4-morpholin-4-ylmethyl-piperidin-1-vl)- naphthalen-1-yl]-urea

1-(3-Methyl-naphthalen-2-yl)-3-[4-(4-morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl}- urea 1-(3-tert-Butyl-5-methanesulfinyl-phenyl)-3-{4-[6-(1-methyl-piperidin-4-ylmethyl)-

pyridin-3-yl]-naphthalen-1-yl}-urea 1-(3-tert-Butyl-phenyl)-3-{4-(3-pyridin-3-yl-propoxy)-naphthalen-1-yl]-urea 1-(3-tert-Butyl-phenyl)-3-[4-(4-morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl]-urea

1-(4-Methoxy-biphenyl-3-yl)-3-{4-[4-(tetrahydro-pyran-4-ylmethyl)-imidazol-1-yl]- naphthalen-1-yl}-urea 1-(4-Methyl-biphenyl-3-yl)-3-{4-[4-(2-pyridin-4-yl-ethyl)-piperazin-1-yl]-naphthalen-1-

yl}-urea 1-(4-tert-Butyl-biphenyl-2-yl)-3-[4-(pyridin-4-yImethoxy)-naphthalen-1-yl]}-urea 1-(4-tert-Butyl-biphenyl-2-yl)-3-{4-[2-(1-ox0-114-thiomorpholin-4-ylmethyl)-3H-

imidazol-4-yl]-naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-hydroxy-phenyl)-3-[4-(5-morpholin-4-ylmethyl-pyrazin-2-yl)- naphthalen-1-yl}-urea

1-(5-tert-Butyl-2-methoxy-3-propyl-phenyl)-3-{4-[4-(pyrrolidine-1-carbonyl)-phenyl]- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(2-morpholin-4-ylmethyl-pyrimidin-5-yl)- naphthalen-1-yl}-urea

1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(4-thiomorpholin-4-ylmethyl-phenyl)- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-phenyl)-naphthalen-1-

40 ylJ-urea : 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[4-(tetrahydro-pyran-4-ylamino)-phenyl]- naphthalen-1-yl}-urea

45 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-{6-(4-methyl-piperazin-1-ylmethy})-pyridin-3- yl]-naphthalen-1-yl}-urea

1-(5-tert-Butyl-2-methoxy-pyridin-3-yl)-3-{4-[6-(4-0x0-piperidin-1-ylmethyl)-pyridin-3- yl]-naphthalen-1-yl}-urea

1-(5-tert-Butyl-2-methyl-benzooxazol-7-yl)-3-[4-(6-pyridin-4-yimethyl-pyridin-3-y1)- naphthalen-1-yl]-urea 1-(5-tert-Butyl-2-methyl-pheny!)-3-{4-(4-morpholin-4-yImethyl-phenyl)-naphthalen-1- yl]-urea

1-(5-tert-Butyl-2-phenoxy-phenyl)-3-{4-[6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yli]- naphthalen-1-yl}-urea 1-(5-tert-Butyl-2-pyrrolidin-1-yl-phenyl)-3-[4-(4-methoxy-6-morpholin-4-ylmethyl-

pyridin-3-yl)-naphthalen-1-yl]-urea 1-(5-tert-Butyl-2-pyrrolidin-1-yl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-vl}-urea

1-(5-tert-Butyl-3-cyano-2-methoxy-phenyl)-3-{4-[2-(2,6-dimethyl-morpholin-4- ylmethyl)-pyrimidin-5-yl]-naphthalen-1-yl}-urea 1-(5-tert-Butyl-4'-dimethylamino-biphenyl-3-yl)-3-[4-(2-morpholin-4-ylmethyl- pyrimidin-5-yl)-naphthalen-1-ylj-urea

1-(6-Methoxy-3,3-dimethyl-indan-5-yl)-3- {4-[4-(morpholine-4-carbonyl)-phenyl]- naphthalen-1-yl}-urea 1-(6-tert-Butyl-2-chloro-3-methyl-pyridin-4-yl)-3-[4-(6-thiomorpholin-4-yimethyl-

pyridin-3-yl)-naphthalen-1-yl]-urea 1-(6-tert-Butyl-benzo[1,3}dioxol-4-yl)-3-{4-[6-(morpholin-4-ylamino)-pyridin-3-yl}- naphthalen-1-yl}-urea

1-(7-Methoxy-1.4,4-trimethyl-1,2,3.4-tetrahydro-quinolin-6-yl)-3-{4-[6-(tetrahydro- pyran-4-yloxy)-pyridin-3-yl]-naphthalen-1-yl}-urea 1-(7-tert-Butyl-2,4-dimethyl-benzooxazol-5-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea

40 1-[2-Methoxy-5-(1-methyl-1-phenyl-ethyl)-phenyl]-3-{4-[6-(2-pyridin-4-yl-ethyl)- pyridazin-3-ylj-naphthalen-1-yl}-urea 1-[2-Methoxy-5-(1-methyl-cyclohexyl)-phenyl]-3-{4-[4-(1-methyl-piperidin-4-

45 ylsulfanyl)-phenyl]-naphthalen-1-yl}-urea

1-[2-Methoxy-5-(1-methyl-cyclopropyl)-phenyl}-3-[4-(2-morpholin-4-ylmethyl- pyrimidin-5-yl)-naphthalen-1-yl}-urea 1-[2-Methoxy-5-(2-methyl-tetrahydro-furan-2-yl)-phenyl}-3-[4-(5-morpholin-4-vimethyl-

pyridin-2-yl)-naphthalen-1-yl}-urea 1-[2-Methoxy-5-(3-trifluoromethyl-bicyclof1.1.1]pent-1-yl)-phenyl]-3-[4-(4-morpholin- 4.ylmethyl-phenyl)-naphthalen-1-yl}-urea

1-[3-tert-Butyl-5-(1-methyl-1H-imidazol-4-yl)-phenyl]-3-[(4-(5-morpholin-4-ylmethy!- pyridin-2-yl)-naphthalen-1-yl}-urea 1-[3-tert-Butyl-5-(2-pyrrolidin-1-yl-ethyl)-phenyl]-3-{4-[6-(1 -methyl-piperidin-4-yloxy)- pyridin-3-yl]-naphthalen-1-yl}-urea

1-[3-tert-Butyl-5-(3-pyrrolidin-1-yl-prop-1-ynyl)-phenyl]-3-[4-(6-morpholin-4-yimethyl- pyridin-3-yl)-naphthalen-1-yl}-urea 1-[4-(6-Imidazol-1-ylmethyl-pyridin-3-yl)-naphthalen-1 -yl}-3-[2-methoxy-5-(1-phenyl-

cyclopropyl)-phenyl}-urea 1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl]-3-[4-(4-thiomorpholin-4-ylmethyl- phenyl)-naphthalen-1-yl]-urea

1-{5-(1-Cyano-cyclopropyl)-2-methoxy-phenyl]-3-{4-(2-morpholin-4-ylmethyl- pyrimidin-5-yl)-naphthalen-1-yl}-urea 1-{5-(1-Hydroxymethyl-cyclopropyl)-2-methoxy-phenyl]-3-[4-(4-morpholin-4-ylmethyl- phenyl)-naphthalen-1-yl]-urea

1-[S-tert-Butyl-1-(2-diethylamino-ethyl)-2-oxo-1.2-dihydro-pyridin-3-yl]-3-{4-[6-(1- methyl-piperidin-4-yloxy)-pyridin-3-ylj-naphthalen-1-yl }-urea 1-{5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl]-3-[4-(2-morpholin-4-yli-ethoxy)-naphthalen-

1-ylJ-urea 1-[5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl]-3-{4-[4-(4-methyl-piperazine- 1 -carbonyl)- phenyl}-naphthalen-1-yl}-urea

40 1-[5-tert-Butyl-2-(2,5-dioxo-pyrrolidin-1-yl)-phenyl}-3-{4-[6-(1 H-imidazol-2-ylmethyl)- pyridin-3-yi]-naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-(2-methyl-pyrimidin-3-yl)-phenyl]-3-[4-(5-pyridin-4-ylmethyl-pyridin- 2-yl)-naphthalen-1-ylj-urea

45

1-[5-tert-Butyl-2-(2-morpholin-4-yl-2-oxo-ethoxy)-phenyl}-3- {4-[6-(2-pyridin-4-yI- ethyl)-pyridazin-3-yl]-naphthalen-1-v1}-urea 1-[5-tert-Butyl-2-(2-morpholin-4-yl-2-oxo-ethylamino)-phenyl]-3- {4-[4-(1-methyI- piperidin-4-ylamino)-piperidin-1-yl]-naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-(6-methyl-pyridin-3-y1)-phenyl]-3-{4-[5-(2-pyrrolidin-1 -yl-ethyl)- pyridin-2-yl]-naphthalen-1-yl}-urea 1-[5-tert-Butyl-2-methoxy-3-(3-morpholin-4-yl-3-oxo-propenyl)-phenyl}-3-[4-(6- pyrrolidin-1-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea 1-[S-tert-Butyl-3-(2-diethylamino-ethoxy)-2-methoxy-phenyl}-3- {4-[4-(tetrahydro-pyran- 4-yloxy)-phenyl]}-naphthalen-1-yl}-urea

IS

1-[5-tert-Butyl-3-(2-pyrrolidin-1-yl-ethyl)-benzofuran-7-yl}-3-[4-(4-morpholin-4- ylmethyl-phenyl)-naphthalen-1-yl}-urea 1-[6-tert-Butyl-4-(2-dimethylamino-ethyl)-3-ox0-3.4-dihydro-2H-benzo[ 1 ,4Joxazin-8- yl}-3-{4-[6-(thiomorpholin-4-ylamino)-pyridin-3-yl]-naphthalen-1-y1}-urea 1-{5-tert-Butyl-2-methoxy-3-[2-(1-methyl-piperidin-4-yloxy)-ethyl)-phenyl }-3-[4-(4- morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl]-urea 2-(4-tert-Butyl-2-{3-[4-(5-pyrrolidin-1-ylmethyl-pyridin-2-yl)-naphthalen-1-yl]-ureido } - phenoxy)-N-methyl-acetamide 2-[4-tert-Butyl-2-(3-{4-[6-(2,6-dimethyl-morpholin-4-ylmethyl)-pyridin-3-yl]- naphthalen-1-yl}-ureido)-phenoxy]-acetamide 3-(5-tert-Butyl-2-methoxy-3- {3-[4-(6-pyrrolidin-1-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-ureido}-phenyl)-acrylamide 3-{3-tert-Butyl-5-[3-(4-{4-[2-(1-0x0- 1 14-thiazolidin-3-yl)-ethy!]-phenyl } -naphthalen-1- yl)-ureido}-pheny!}-N.N-dimethyl-propionamide 3-{4-[3-(5-tert-Butyl-2-methoxy-phenyl)-ureido}-naphthalen-1-yl}-benzamide 4-tert-Butyl-2-{3-[4-(2-chloro-4-morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl]- 40 ureido}-benzamide

N-(4-tert-Butyl-2-{3-[4-(6-0x0-1.6-dihydro-pyridin-3-yl)-naphthalen- 1-yl}-ureido} - phenyl)-2-morpholin-4-yl-acetamide 45 N-[3-tert-Butyl-5-(3-{4-[5-(tetrahydro-pyran-4-ylamino)-pyridin-2-yl]}-naphthalen-1-y!} - ureido)-phenyl]-2-morpholin-4-yl-acetamide

N-{4-tert-Butyl-2-(3-{4-[4-(1-methyl-piperidin-4-vioxy )-phenyl}-naphthalien-1-yl}- ureido)-phenyl]j-acetamide and the pharmaceutically acceptable derivatives thereof.

In yet another embodiment of the invention. there is provided the following compounds of the formula(ll): 1-(2-tert-Butyl-5-methyl-pyridin-4-yl)-3 -[4~( 6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

IS

1-(3-Methyl-naphthalen-2-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-urea; 1-(3-tert-Butyl-phenyl)-3-[4-(4-morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl]-urea; 1-(3-tert-Butyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea; 1-(4-Methyl-biphenyl-3-y1)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- ylj-urea; 1-(4-tert-Butyl-biphenyl-2-yl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1- yl]-urea; 1-(5-Chloro-2.4-dimethoxy-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]}-urea; 1-(5-Isopropyl-2-methyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-y})- naphthalen-1-yl]-urea; 1-(5-sec-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-3-propyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- 40 naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxymethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 45 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(2-morpholin-4-ylmethyl-pyrimidin-5-yl)- naphthalen-1-yl]-urea;

1-(5-tert-Butyl-2-m ethoxy-phenyl)-3-[4-(4-thiomorpholin-4-ylmethyl-phenyl)- naphthalen-1-yl]-urea:

1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea:

1 -(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-phenyl)-naphthalen-1 - yl]-urea;

1-(5-tert-Butyl-2-methoxy-phenyl)-3-{ 4-[4-(tetrahydro-pyran-4-ylamino)-phenyl}- naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(4-methyl-piperazin-1 -ylmethy!)-pyridin-3-

yl}-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methyl-phenyl)-3-(4- {6-{(3-methoxy-propy!l)-methyl-amino}-pyridin-3- yl}-naphthalen-1-yl)-urea:

1 -(5-tert-Butyl-2-methyl-phenyl)-3-[4-(4-morpholin-4-ylmethyl-imidazol-1 -yh)- naphthalen-1-yl]-urea;

1-5 -tert-Butyl-2-methyl-phenyl)-3-[4-(4-morpholin-4-ylmethyl-phenyl)-naphthalen- I- ylj-urea;

1-(5-tert-Butyl-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]}-urea; 1-(5-tert-Butyl-2-methyl-pheny1)-3-{4-[6-(3-methoxy-propylamino)-pyridin-3-y1]-

naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methyl-pyridin-3-yl)-3-[4-( 6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea;

1-(5-tert-Butyl-2-morpholin-4-yl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea; 1-(6-tert-Butyl-2-chloro-3-methyl-pyridin-4-yl)-3-[{4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea;

40 1-(6-tert-Butyl-2-chloro-3-methyl-pyridin-4-y1)-3-[4-(6-thiomorpholin-4-ylmethyI- pyndin-3-yl)-naphthalen-1-yl}-urea; 1-[2-Methoxy-5-(1 -methyl-cyclopropyl)-phenyl}-3-[4-(2-morpholin-4-ylmethyl-

45 pynmidin-5-yl)-naphthalen-1-yl]-urea;

1-[4-(6-Morpholin-4-ylmethyi-pyridin-3-yl)-naphthalen-1-y1}-3-(3-trifluoromethyl- phenyl)-urea: 1-[4-(6-Morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1-yi]-3-(4-trifluoromethoxy-

phenyl)-urea: 1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl}-3-{4-(4-thiomorpholin-4-ylmethyl- phenyl)-naphthalen-1-vl}-urea;

1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl]-3-[4-(6-morpholin-4-yimethyl-pyridin-3-

yl)-naphthalen-1-yl}-urea; 1-[5-(1-Cyano-cyclopropy!)-2-methoxy-phenyl}-3-[{4-(2-morpholin-4-yimethyl- pyrimidin-5-yi)-naphthalen-1-yl}-urea,

1-[5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl]}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-[S-tert-Butyl-2-(2-methyl-pyrimidin-5-yl)-phenyl]-3-[{4-(5-pyridin-4-ylmethyl-pyridin-

2-yl)-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(2-methyl-pyrimidin-5-yl)-phenyl}-3-{4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl]-urea;

1-[5-tert-Butyl-2-(3-hydroxy-propyl)-phenyl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(3-morpholin-4-yl-3-oxo-propyl)-phenyl]-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[5-tert-Butyl-2-(morpholine-4-carbonyl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl}-urea;

2-[4-tert-Butyl-2-(3-{4-[6-(2,6-dimethyl-morpholin-4-ylmethyl)-pyridin-3-yl]-

naphthalen-1-yl}-ureido)-phenoxy]-acetamide; 3-{4-[3-(5-tert-Butyl-2-methoxy-phenyl)-ureido}-naphthalen-1-yl}-benzamide; 4-tert-Butyl-2-{3-[4-(2-chloro-4-morpholin-4-ylmethyl-phenyl)-naphthalen-1-yl}-

40 ureido}-benzamide; and the pharmaceutically acceptable derivatives thereof.

45

In yet a further another embodiment of the invention there is provided the following compounds of the formula(Il): 1-(2-tert-Butyl-5-methyl-pyridin-4-yl)-3-{4-(6-morpholin-4-yimethy!-pyridin-3-y!)- naphthalen-1-yl]-urea: 1-(3-tert-Butyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-v1]- urea;

1-(4-Methyl-biphenyl-3-yl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl]-urea; 1-(4-tert-Butyl-biphenyl-2-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1 -

yl}-urea; 1-(5-Isopropyl-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea;

1-(5-sec-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-ylj-urea; 1-(5-tert-Butyl-2-methoxymethyl-phenyl)-3-(4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-ylj-urea; 1-(5-tert-Butyl-2-methyl-phenyl)-3-(4-{6-[(3-methoxy-propyl)-methyl-amino]-pyridin-3-

yl}-naphthalen-1-yl)-urea; 1-(5-tert-Butyl-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

1-(5-tert-Butyl-2-methyl-pyridin-3-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl]-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yD-naphthalen-1-yl}-urea;

40 1-[5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(2-methyl-pyrimidin-5-yl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl- 45 pyridin-3-yl)-naphthalen-1-yl}-urea;

1-[3-tert-Butyl-2-(3-hydroxy-propyl)-phenyl]}-3-{4-(6-morpholin-4-vimethyl-pyridin-3- yl)-naphthalen-1-yl]}-urea: 1-[5-tert-Butyl-2-(morpholine-4-carbonyl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl- pyrdin-3-yl)-naphthalen-1-yi]-urea;

N-(5-tert-Butyl-2-methoxy-3- { 3-[4-(6-morpholin-4-yImethyl-pyridin-3-yl)-naphthalen-1- yl}-ureido}-phenyli)-acetamide i0 and the pharmaceutically acceptable derivatives thereof.

In yet still another generic aspect of the invention, there is provided compounds of the formula(111):

Ww 6. JM _a—x-y—z

Ey

H

(II) wherein:

E is carbon or a heteroatom group chosen from -O-, -NH- and -S-; "Gis: an aromatic Ce.10 carbocycle or a nonaromatic Cj.jgcarbocycle saturated or unsaturated; a 6-14 membered monocyclic, bicyclic or tricyclic heteroaryl containing 1 or more heteroatoms chosen from O, N and S:

a 6-8 membered monocyclic heterocycle containing one or more heteroatoms chosen from O. Nand S: or an 8-11 membered bicyclic heterocycle. containing one or more heteroatoms chosen from O. N and S; wherein G is optionally substituted by one or more R;, R; or Rj;

Ar is: : phenyl. naphthyl, quinolinyl, isoquinolinyl. tetrahydronaphthyl. tetrahydroquinolinyl, tetrahydroisoquinolinyl. benzimidazolyl. benzofuranyl. dihydrobenzofuranyl, indolinyl, benzothienyl, dihydrobenzothienyl, indany!, indeny! or indolyl each being optionally substituted by one or more Ry or Rs;

X is: a Cs.g cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, C4 alkoxy or C;.4 alkylamino chains each being branched or unbranched; aryl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinony], dihydropyridinonyl, maleimidyl. dihydromaleimidyl, piperdinyl, benzimidazole, 3H- imidazo[4,5-b]pyridine, piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C4 alkyl, C.4alkoxy, hydroxy, nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di-(C,.; alkylamino)carbonyl, NH,C(O), Cy alkyl-S(O)m or halogen;

Y is: abond ora C, saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more C atoms are optionally replaced by O,

N. or S(O). and wherein Y is optionally independently substituted with one to two oxo groups. nitrile, phenyl or one or more C, alkyl optionally substituted by one or more halogen atoms;

Zis: aryl. heteroaryl selected from pyridinyl. piperazinyl, pyrimidinyl, pyridazinyl. pyrazinyl. imidazolyl, pyrazolyl. triazolyl. tetrazolyl. furanyl. thienyl and pyranyl. heterocycle selected from tetrahydropyrimidonyl. cyclohexanonyl, cyclohexanolyl. 2-oxa- or 2-thia-

S-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetramethylene sulfidyl. tetramethylene sulfoxidyl or tetramethylene sulfonyl, tetrahydropyranyl. tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3- dioxanonyl, 1,4-dioxanyl, morpholino. thiomorpholino, thiomorpholino sulfoxidyl, thiomorpholino sulfonyl, piperidinyl, piperidinonyl, pyrrolidinyl and dioxolanyl, : each of the aforementioned Z are optionally substituted with one to three halogen, C,.¢ alkyl, C,.¢ alkoxy, C,; alkoxy-C,.; alkyl. C,.¢ alkoxycarbonyl, aroyl, C,.;acyl, oxo, hydroxy, pyridinyl-C,_; alkyl, imidazolyl-C,.; alkyl, tetrahydrofuranyl-C, ; alkyl, nitrile-

C,-; alkyl, nitrile, carboxy, pheny! wherein the phenyl ring is optionally substituted with one to two halogen, C,, alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, C, alkyl-

S(O)m, or phenyl-S(O), wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy, halogen or mono- or di-(C,.; alkyl)amino; or Z is optionally substituted with one to three amino or amino-C,.3 alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC,_salkyl, C,.alkyl, arylCq.zalkyl, C;.salkoxyC, 3 alkyl, C,.s alkoxy, aroyl, C,.;acyl, C;_3alkyl-S(O)n- or arylCy.3alkyl-S(O)m- each of the aforementioned alkyl and ary} attached to the amino group is optionally substituted with one to two halogen, C, alkyl or C,.¢ alkoxy; or Z is optionally substituted with one to three aryl, heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen,

Ci alkyl or C4 alkoxy;

or Z is hydroxy. halogen. nitrile. amino wherein the N atom is optionally independently mono- or di-substituted by Cyjacyl. Cy.ealkyl or Cy_zalkoxyCialkyl. Cy alkyl branched or unbranched. C).salkoxy, C).;acylamino. nitrileC) alkyl. C4 alky}-S(O),. and phenyl-

S(O)m. wherein the phenyl ring is optionally substituted with one to two halogen. C alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino; each R, is independently:

C.10 alkyl branched or unbranched optionally partially or fully halogenated, wherein one or more C atoms are optionally independently replaced by O, N or S(O),,, and wherein said Cy.j¢ alkyl is optionally substituted with one to three Cs.io cycloalkyl, hydroxy. oxo. phenyl, naphthyl, pyridinyl, pyrimidinyl. pyrazinyl. pyridazinyl, pyrrolyl, pyrrolidiny]. imidazolyl, pyrazolyl. thienyl, furyl, dioxolanyl, isoxazoly} or isothiazolyl; each of the aforementioned being optionally substituted with one to five groups selected from halogen, C,.¢ alkyl which is optionally partially or fully halogenated. C34 cycloalkanyl,

Cs.g cycloalkenyl. hydroxy, nitrile, C,.3 alkoxy which is optionally partially or fully halogenated or NH;C(O), mono- or di(C,_jalkyl)amino, and mono- or di(C, salkyl)aminocarbonyl, orR;is cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, or cycloheptyloxy each being optionally partially or fully halogenated and optionally substituted with one to three

Ci; alkyl groups optionally partially or fully halogenated, nitrile, hydroxyC,.salkyl or aryl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O), CHOH, >C=0, >C=S or NH; : phenyloxy or benzyloxy each being optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups optionally partially or fully halogenated, nitrile, hydroxyC,.;alky! or aryl; or an analog of such cycloaryl group wherein one to two ring methyne groups are independently replaced by N;

cyclopropyl. cyclobutyl. cyclopentyl. cyclohexyl. cycloheptyl. bicyclopentanyl. bicyclohexanyl or bicycloheptanyl. each being optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl optionally partially or fully halogenated. nitrile, hydroxyC,.;alky!l or aryl: or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O).

CHOH, >C=0, >C=S or NH;

C;.10 branched or unbranced alkenyl each being optionally partially or fully halogenated, and optionally substituted with one to three C,.s branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl. pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazoly! or isothiazolyl. each of the aforementioned being substituted with one to five halogen, Cy. alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, hydroxy, nitrile, C,.; alkyloxy which is optionally partially or fully halogenated, NH,C(O), mono- or di(C;. salkyl)aminocarbonyl; the Cj. 0 branched or unbranced alkeny! being optionally interrupted by one or more heteroatoms chosen from O, N and S(O); cyclopentenyl, cyclohexenyl, cyclohexadienyl. cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,.; alkyl groups; 0X0, nitrile, halogen; silyl containing three C,4 alkyl groups optionally partially or fully halogenated; or

Ci. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH or

S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, hydroxy, pyrroldinyl, pyrrolyl, tetrahydropyranyl, one or more C, 4 alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidinyl,

piperazinyl. imidazolyl. phenyl. pyridinyl. tetrazolyl. or mono- or di(C,_jalky!)amino optionally substituted by one or more halogen atoms: each R,. Ry. and Rs 1s a C |. branched or unbranched alkyl optionally partially or fully halogenated, C, ¢acyl, aroyl, C;.y branched or unbranched alkoxy. each being optionally partially or fully halogenated. halogen, methoxycarbonyl, C;_; alkyl-S(O),, optionally partially or fully halogenated, or phenyl-S(O)m;

ORg. C6 alkoxy. hydroxy. nitrile. nitro. halogen; or amino-S(O)n,- wherein the N atom is optionally independently mono- or di-substituted by Ci.salkyl or arylCyp.3alkyl. or amino wherein the N atom is optionally independently mono- or di-substituted by C,_;alkyl. arylCo.;alkyl, C,.¢acyl, C,.calkyl-S(O),- or arylC. 3alkyl-S(O)m-, each of the aforementioned alkyl and ary! in this subparagraph are optionally partially or fully halogenated and optionally substituted with one to two Cg alkyl or C,¢ alkoxy; each R; is independently: phenyl. naphthyl, morpholino, pyridinyl, pyrimidinyl. pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazoyl, [1,3,4]oxadiazol, triazolyl, tetrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl. benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl. purinyl or indazolyl, each of the aforementioned is optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl as hereinabove described in this paragraph, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl. bicyclopentanyl, bicyclohexanyl. bicycloheptanyl, phenyl C,.s alkyl,

naphthyl C.s alkyl. halogen. hydroxy. oxo. nitrile.

C,.; alkoxy optionally partially or fully halogenated, phenyloxy. naphthyloxy. heteroaryloxy or heterocyclicoxy wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph. nitro. amino. mono- or di-(C,.zalky)lamino. phenylamino. naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl heterocyclic moiety is as hereinabove described in this paragraph.

NH2C(O). a mono- or di-(C,.;alkyl) aminocarbonyl, C,.s alkyl-C(O)-C, alkyl. amino-Ci.s alkyl. mono- or di-(C,.salkyl)amino, mono- or di-(C,. salkyl)amino-C,.5 alkyl, amino-S(O),. di-(C,.;alkyl)amino-S(O),, R;-C,.z alkyl, Rg-C.s alkoxy, Ro-C(0)-C.5 alkyl, Ri¢-C}-s alkyl(R;,)N. carboxy-mono- or di-(C,_salkyl)-amino;

a fused aryl selected from benzocyclobutanyl. indanyl. indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl. or a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl, cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl,

cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl, cyclohexanoquinolinyl, cyclopentanoisoquinolinyl, cyclohexanoisoquinolinyl, cyclopentanoindolyl, cyclohexanoindolyl, cyclopentanobenzimidazolyl, cyclohexanobenzimidazolyl, cyclopentanobenzoxazolyl, cyclohexanobenzoxazolyl, cyclopentanoimidazolyl, cyclohexanoimidazolyl, cyclopentanothienyl and cyclohexanothienyl; wherein the fused aryl or fused heteroaryl ring is independently substituted with zero to three phenyl, naphthyl, pyridinyl, pyrimidinyl. pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl. thienyl, furyl, isoxazolyl, isothiazolyl, C).¢ alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.; alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C,.3alkyl)amino, phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, NH,C(O), mono- or di-(C). salkyl)aminocarbonyl, C4 alkyl-OC(O), Cs alkyl-C(O)-C,4 alkyl, amino-C,.; alkyl,

mono- or di-(C,.3)alkylamino-C,_s alkyl, Ry,-C).s alkyl, Ry3-C,_s alkoxy, R;4-C(0)-C,.s alkyl or Ry5-Cj.s alkyl(Ry6)N;

cyclopropanyl. cyclobutanyl. cyclopentanyl, cyclohexanyl, cycloheptanyl. bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, each being optionally be partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups. or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S. CHOH, >C=0, >C=S or NH; cyclopentenyl, cyclohexenyl, cyclohexadienyl. cycloheptenyl, cycloheptadienyl, bicyclohexeny! or bicycloheptenyl. each optionally substituted with one to three C,_; alkyl groups;

C14 alkyl-phenyl-C(O)-C,4 alkyl-, Cy, alkyl-C(O)-C,., alkyl- or C4 alkyl-phenyl-

S(O)n-Ci.4 alkyl-;

Ci alkyl or Cy. branched or unbranched alkoxy each of which is optionally partially or fully halogenated or optionally substituted with R;7;

OR; or C4 alkyl optionally substituted with OR sg; amino or mono- or di-(C;_salkyl)amino optionally substituted with Ro;

R20C(O)N(R21)-, R2:0- or Ry3R24NC(O)-; Ry6(CH2)mC(O)N(R21)-, Ry3R24NC(0)-C. salkoxy or R26C(O)(CH2)mN(R21)-; Cyealkenyl substituted by Ry;3R24NC(0)-;

Ca. alkynyl branched or unbranched carbon chain, optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH,

S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl one or more C,_, alkyl optionally substituted by one or more halogen atoms. nitrile. morpholino, piperidinyl. piperazinyl. imidazolyl. phenyl. pyridinyl. tetrazolyl. or mono- or di(C,4 alkyl)amino optionally substituted by one or more halogen atoms:

Cy.eacyl or aroyl;

Re 1s a:

C4 alkyl optionally partially or fully halogenated and optionally substituted with Rye; each R5. Rg, Ro. Rio, Ri2. Ris. Rs. Rus. R72, Ryo, Ri; and Ryg 1s independently: nitrile, phenyl. morpholino, piperidinyl, piperazinyl. imidazolyl, pyridinyl, tetrazolyl. amino or mono- or di-(C,4alkyl)amino optionally partially or fully halogenated; each Rj; and Ry, is independently: hydrogen or C4 alkyl optionally partially or fully halogenated;

Ryg is independently: hydrogen or a C4 alkyl optionally independently substituted with oxo or Rs;

Rao is independently:

Ci.10 alkyl optionally partially or fully halogenated, phenyl, or pyridinyl;

Ry is independently: hydrogen or C;.; alkyl optionally partially or fully halogenated, each Ry;, Ry; and Ry, is independently: hydrogen, C,.¢ alkyl optionally partially or fully halogenated. said C,.¢ alkyl is optionally interrupted by one or more O, N or S, said C,.¢ alkyl also being independently optionally substituted by mono- or di-(C,_;alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono-

or di-(Cy.salkyl)amino each of which is optionally partially or fully halogenated and optionally substituted with mono- or di~(C,.;alkyl)amino; or Rz3 and Ry, taken together optionally form a heterocyclic or heteroaryl ring; m=0,10r2;

Wis O or S and pharmaceutically acceptable derivatives thereof.

In another embodiment of the invention there is provided compounds of the formula(ll]) as described above and wherein:

Eis -CH;-, -NH- or -O-;

Wis O; and :

Gis: phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthy], : benzocycloheptanyl, benzocycloheptenyl, indanyl, indenyl, pyridinyl, pyridonyl, quinolinyl, dihydroquinolinyl, tetrahydroquinoyl, isoquinolinyl, tetrahydroisoquinoyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzthiazolyl, benzooxazolyl, benzofuranyl, benzothiophenyl, benzpyrazolyl, dihydrobenzofuranyl, dibenzofuranyl, dihydrobenzothiophenyl, benzooxazolonyl, benzo[1,4)oxazin-3-onyl, benzodioxolyl, benzo[1,3)dioxol-2-onyl, benzofuran-3-onyl, tetrahydrobenzopyranyl, indolyl, 2,3-dihydro-1H-indolyl, indolinyl, indolonyl, indolinonyl, phthalimidyl, chromoyl, oxetanyl, pyrrolidinyl. tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholino. tetrahydropyranyl, dioxanyl. tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl. 3.4-dihvdro-2H-benzo[1.4]Joxazinyl. thiazolinyl. imidazolinyl, tertrahydropyridinyl. homopiperidinyl. pyrrolinyl. tetrahydropyrimidinyl. decahydroquinolinyl. decahydroisoquinolinyl, thiomorpholino. thiazolidinyl. dihydrooxazinyl. dihydropyranyl. oxocanyl. heptacanyl. thioxanyl or dithianyl; wherein G is optionally substituted by one or more Ry, R; or Rj.

In yet another embodiment there are provided compounds of the formula(IIl) as described immediately above and wherein:

E is -NH-;

G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl. isoquinolinyl, pyrazinyl, benzimidazolyl, benzooxazolyl, benzooxazolonyl. benzofuranyl, benzothiophenyl, benzpyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, 3.4-dihydro-2H- benzo[1,4Joxazinyl, indanyl, indenyl, indolyl, indolinyl, indolonyl, 2.3-dihydro-1H- indolyl or indolinonyl, wherein G is optionally substituted by one or more R), R; or R;;

Aris: naphthyl, quinolinyl. isoquinolinyl, tetrahydronaphthyl, tetrahydroquinolinyl. tetrahydroisoquinolinyl. indanyl, indenyl or indolyl each being optionally substituted by one or more Rs or Rs groups;

Xis: phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridinonyl, dihydropyridinonyl, maleimidyl, dihydromaleimidyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C4 alkyl, C;.4alkoxy, hydroxy, nitrile, amino, mono- or di-(C_;

alkyl)amino. mono- or di-(C).; alkylamino)carbonyl. NH>C(O). C,.¢ alkv}-S(O),, or halogen;

Y is: s abondor a C, saturated or unsaturated carbon chain wherein one or more of the C atoms is optionally replaced by O, N. or S(O)n and wherein Y is optionally independently substituted with one to two oxo groups. nitrile. phenyl or one or more C,.4 alkyl optionally substituted by one or more halogen atoms;

Zis: phenyl, heteroaryl selected from pyridinyl, piperazinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl. furanyl, thienyl and pyranyl, heterocycle selected from 2-oxa-5- aza-bicyclo[2.2.1]heptanyl, tetrahydropyrimidonyl, pentamethylene sulfidyl. pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetramethylene sulfidyl. tetramethylene sulfoxidyl tetramethylene sulfonyl, tetrahydropyranyl. tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3-dioxanonyl, 1.4-dioxanyl, morpholino, thiomorpholino, thiomorpholino sulfoxidyl, piperidinyl, piperidinonyl, dihydrothiazolyl, dihydrothiazoly! sulfoxidyl, pyrrolidiny! and dioxolanyl which are optionally substituted with one to three nitrile, C, 3 alkyl, C,.; alkoxy, amino, mono- or di-(C,.; alkyl)amino. CONH; or OH; or Z is optionally substituted by phenyl. heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen, C;.; alkyl or

C3 alkoxy; : or Z is nitrile, nitrileC,.; alkyl, Cy. alkyl-S(O),,, halogen, hydroxy, C,.; alkyl, C,.3 acylamino, C,.; alkoxy, amino, mono- or di-(C,.; alkyl)aminocarbony|1. or amino mono or di-substituted by aminoC,.¢ alkyl or C,.;alkoxyC;.;alkyl; each R) is independently:

Claims (1)

1. What is Claimed is:

   1. A compound of the formula(l): X Ar;—X—Y—Z An N 2 H H (D wherein: Ar, is selected from the group consisting of: pyrrole, pyrrolidine, pyrazole, imidazole, oxazole, thiazole, furan and thiophene; wherein Ar; may be substituted by one or more R,, R; or Rj; Ar; is: phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl or indole each being optionally substituted with zero to three R; groups; Xs: a Cs.g cycloalkyl or cycloalkenyl optionally substituted with 0-2 oxo groups or 0-3 C4 branched or unbranched alkyl, C,, alkoxy or C4 alkylamino chains; phenyl, furan, thiophene, pyrrole, imidazolyl, pyridine, pyrimidine, pyridinone, dihydropyridinone, maleimide, dihydromaleimide, piperdine, piperazine or pyrazine each being optionally independently substituted with 0-3 C4 branched or unbranched alkyl, Ci4alkoxy, hydroxy, nitrile, mono- or di-(C,.; alkyl)amino, C,. alkyl-S(O)n, or halogen;

   Y is:

   a bond or a C4 saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O.

   NH, S(O). S(O); or S and wherein Y is optionally independently substituted with 0-2 oxo groups and one or more Cj4 branched or unbranched alkyl which may be substituted by one or more halogen atoms; Z is:

   phenyl, pyridine, pyrimidine, pyridazine, imidazole, furan, thiophene, pyran, which are optionally substituted with one to three groups consisting of halogen, C, alkyl, Cy alkoxy, hydroxy. mono- or di-(C;.3 alkyl)amino.

   Cj. alkyl-S(O)., , COOH and phenylamino wherein the phenyl ring is optionally substituted with one to two groups consisting of halogen, C,¢ alkyl and C,.¢ alkoxy; tetrahydropyran, tetrahydrofuran, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine sulfoxide, piperidine, piperidinone, piperazine, tetrahydropyrimidone, cyclohexanone, cyclohexanol, pentamethylene sulfide,

   pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide or tetramethylene sulfone which are optionally substituted with one to three groups consisting of nitrile, C,.4 alkyl, C,. alkoxy, hydroxy, mono- or di~(C,. 3 alkyl)amino-C, ; alkyl, phenylamino-C,.3 alkyl and C,.3 alkoxy-C).3 alkyl;

   Ci alkoxy, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to groups selected from the group consisting of C,.; alkyl, C,.; alkoxyalkyl, pyridinyl-C,_3 alkyl, imidazolyl-C.3 alkyl. tetrahydrofuranyl-C,.; alkyl, phenylamino, wherein the phenyl ring is optionally substituted with one to two halogen, C,. alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, Cy. alky}-S(O)m, and phenyl-S(O),,, wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,_3 alkyl)amino;

   Ris:

   Cs.;0 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with one to three phenyl. naphthyl or heterocyclic groups selected from the group consisting of pyridinyl. pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl. thienyl, furyl. isoxazolyl and isothiazolyl; each such phenyl, naphthyl or heterocycle selected from the group hereinabove described in this paragraph, and being substituted with 0 to 5 groups selected from the group consisting of halogen,

   C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, Cs.g cycloalkyl, Cs.g cycloalkenyl, hydroxy. nitrile, C,.3 alkyloxy which is optionally partially or fully halogenated, NH>C(O) and di(C,.;)alkylaminocarbonyl;

   Cs.7 cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptany! each being optionally be partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S, CHOH, >C=0, >C=S and NH;

   Ci.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,.s branched or unbranched alkyl, phenyl, naphthyl! or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl. imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each such phenyl, naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from the group consisting of halogen, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptany], bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, hydroxy, nitrile, C,.3 alkoxy which is optionally partially or fully halogenated, NH,C(O) and mono- or di(C,. 3)alkylaminocarbonyl;

   a Cs. cycloalkenyl selected from the group consisting of cyclopentenyl. cyclohexenyl. cyclohexadienyl. cycloheptenyl, cycloheptadienyl. bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C 1-3 alkyl groups; nitrile; or

   C,.¢ branched or unbranched alkoxycarbonyl, C,_¢ branched or unbranched alkylaminocarbonyl, Cy.¢ branched or unbranched alkylcarbonylamino-C; ;-alkyl; R> IS: a C,.¢ branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, Cy. branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl; Rj; is: phenyl, naphthyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl. pyrrolyl, imidazolyl, pyrazolyl, thienyl, fury], tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl. purinyl and indazolyl, wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of phenyl, naphthyl, heterocycle selected from the group hereinabove described in this paragraph, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, phenyl C,_s alkyl, naphthyl C,.c alkyl, halogen, hydroxy, nitrile, C,.; alkyloxy which may optionally be partially or fully halogenated. phenyloxy. naphthyloxy. heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph. nitro. amino, mono- or di-(C,.3)alkylamino, phenylamino. naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph.

   NH,C(0O), a mono- or di-(C;.3)alkyl aminocarbonyl, C5 alkyl-C(O)-C, alkyl, amino-C;. 5 alkyl, mono- or di-(C.3)alkylamino-C,.s alkyl, amino-S(O),, di-(C;.3)alkylamino-S(O),, Rs -C).s alkyl, Rs -Ci.s alkoxy, R¢—C(0O)-C|.s alkyl and R; -C.s alkyl(Rg)N. carboxy- mono- or di-(C,.s)-alkyl-amino;

   a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl. benzocycloheptanyl and benzocycloheptenyl, or a fused heterocyclyl selected from the group consisting of cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine,

   cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from the group consisting of phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, and isothiazolyl, C,.s branched or unbranched alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.; alkoxy which is optionally partially or fully halogenated. phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C,.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph.

   NH,C(O), a mono- or di-(C,.3)alkyl aminocarbonyl, C4 alkyl-OC(O). C,.s alkyl-C(O)-C, 4 branched or unbranched alkyl, an amino-C,.s alkyl. mono- or di-(C,.3)alkylamino-C,.s alkyl. Ry-C.s alkyl, Ryo -C,.s alkoxy. R,, —C(0)-Ci.5 alkyl. and R2-C.salkyl(R3)N: cycloalkyl selected from the group consisting of cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl and bicycloheptyl, wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups;

   Cs. cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,_; alkyl groups; acetyl, aroyl, alkoxycarbonylalkyl or phenylsulfonyl; or

   C,.¢ branched or unbranched alkyl optionally partially or fully halogenated; or R| and R; taken together may optionally form a fused phenyl or pyridiny! ring; each Rg and R,; is independently selected from the group consisting of: hydrogen and C,.4 branched or unbranched alkyl optionally be partially or fully halogenated; each Rs, Rs, Rg, R7, Rg, Ryo. Rit and Ry; is independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; mis0,1or2; WisOorS and pharmaceutically acceptable derivatives thereof.

   2, The compound according to claim 1 wherein: Ar; is naphthyl. tetrahydronaphthyl. indanyl or indenyl and Wis O.

   3. The compound according to claim 1wherein: Ar, is selected from thiophene and pyrazole; X is Cs.7 cycloalkyl or Cs.scycloalkeny! optionally substituted with 0-2 oxo groups or 0-3 C,.4 branched or unbranched alkyl. C, alkoxy or Ci. alkylamino; or X is phenyl, pyridine, tetrahydropyridine, pyrimidine. furan or thiophene each being optionally independently substituted with 0-3 C,_ branched or unbranched alkyl, C; alkoxy, hydroxy, nitrile, mono- or di-(C,.3 alkyl)amino, C,.s alkyl-S(O)n, or halogen; R; is C;4alkyl branched or unbranched, cyclopropyl! or cyclohexy! optionally partially or fully halogenated and optionally substituted with one to three C_; alkyl groups; Rjis Ci4alkyl branched or unbranched optionally partially or fully halogenated; phenyl, pyrimidinyl, pyrazolyl or pyridiny! each being optionally substituted with one to five groups selected from the group consisting of phenyl, naphthyl, pyrimidinyl, pyrazolyl, pyridinyl, C,., branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl. cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, phenyl Cs alkyl, naphthyl C,.s alkyl, halogen, hydroxy, nitrile, C,.; alkoxy which may optionally be partially or fully halogenated, phenyloxy, naphthyloxy. heteraryloxy wherein the heterocyclic moiety is pyrimidinyl, pyrazolyl or pyridinyl. nitro. amino, mono- or di-(C,;)alkylamino,

   phenylamino, naphthylamino. heterocyclylamino wherein the heterocyclyl moiety is pyrimidinyl, pyrazolyl or pyridinyl. NH.C(O), a mono- or di-(C,.3)alkyl aminocarbonyl.

   Ci.5 alkyl-C(0)-C, 4 alkyl. amino-C,.s alkyl. mono- or di-(C,.;)alkylamino-C _s alkyl. amino-$(0)s, di-(C).3)alkylamino-5(0).. Ry -C.s alkyl, Rs -C).s alkoxy. Rg —C(O)-C.s alkyl and R7-C,.s alkyl(Rg)N, carboxy-mono- or di-(C,.s)-alkyl-amino; alkoxycarbonylalkyl: or cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups;

   4. The compound according to claim 3 wherein: Ar, is pyrazole; X is cyclopentenyl, cyclohexeny! or cycloheptenyl, optionally substituted with an oxo group or 0-3 C,.4 branched or unbranched alkyl, Cy4alkoxy or C,salkylamino; or X is phenyl, pyridine, furan or thiophene each being optionally independently substituted with 0-3 C4 branched or unbranched alkyl, C,4alkoxy, hydroxy, nitrile, mono- or di- (C13 alkyl)amino, C,.¢ alkyl-S(O)n or halogen.

   5. The compound according to claim 4 wherein: Y is -CH2-, -CH2CH2-, -CH2NH-, -CH2CH2NH- or a bond; and Zis phenyl. imidazole. furan, piperazine. tetrahydropyran. morpholine. thiomorpholine. thiomorpholine sulfoxide, piperidine. pyridine. secondary or tertiary amine wherein the amino nitrogen is covalently bonded to groups selected from the group consisting of C,.; alkyl and C,.s alkoxyalkyl, phenylamino wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,_; alkyl)amino, C;_ alkyl-S(O), and phenyl-S(O)n, wherein the phenyl ring is optionally substituted with one to two halogen. C,.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino.

   6. The compound according to claim 5 wherein: Ar, is 5-fert-butyl-pyrazol-3-yl: wherein the pyrazole ring may be substituted by Rs; } Rj is

   Cj.salkyl branched or unbranched optionally partially or fully halogenated; phenyl, pyrimidinyl, pyrazolyl or pyridinyl each being optionally substituted with one to five groups selected from the group consisting of phenyl, naphthyl, pyrimidinyl, pyrazolyl, pyridinyl, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, phenyl C,_s alkyl, naphthyl C,.s alkyl, halogen, hydroxy, nitrile, C,.3 alkoxy which may optionally be partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is pyridinyl, nitro, amino, mono- or di-(C.;)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is pyridinyl, NH,C(O), a mono- or di-(C;.3)alkyl aminocarbonyl, Cs alkyl-C(O)-C, 4 alkyl, amino-C,.; alkyl, mono- or di-

   (C.3)alkylamino-C,.s alkyl, amino-S(O}),, di-(C;.3)alkylamino-S(O);, R4 -C,.s alkyl, R; - Cs alkoxy, R¢—C(0)-C,.s alkyl and R;-C|.s alkyl(Rg)N, carboxy-mono- or di-(C.s)- alkyl-amino;

   alkoxycarbonylalkyl: or cyclopropyl! or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups.

   3

   7. The compound according to claim 6 wherein X is pyridinyl.

   8. The compound according to claim 7 wherein the pyridinyl is attached to Ar) via the 3-pyridinyl position.

   9. A compound of the formula (la): X Ars—X—Y—Z AN N Pall) H H (Ia)

   20 . wherein: Ar is: pyrrole, pyrrolidine, pyrazole, imidazole, oxazole, thiazole, furan and thiophene: wherein Ar, is optionally substituted by one or more R;, R; or Rj; An is:

   phenyl. naphthyl. quinoline. isoquinoline. tetrahydronaphthyl. tetrahydroquinoline. tetrahydroisoquinoline. benzimidazole. benzofuran. indanyl. indenyl and indole each being optionally substituted with zero to three Ra groups: X is: a Cs_g cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, C14 alkoxy or C, alkylamino chains each being branched or unbranched, phenyl, furanyl. thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, tetrahydropyridinyl, pyrimidinyl, pyridinonyl, dihydropyridinonyl. maleimidy!, dihydromaleimidyl, piperdinyl, benzimidazole, 3H-imidazo[4.5-b]pyridine, piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C,4 alkyl, C,4alkoxy, hydroxy, nitrile, amino, mono- or di-(C,_; alkyl)amino, mono- or di-(C.3 alkylamino)carbonyl, NH,C(O), Ci alkyl-S(O)m or halogen; Y is: a bond or a C, saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more C atoms are optionally replaced by O,

   N. or S(O)m and wherein Y is optionally independently substituted with one to two oxo groups, nitrile, phenyl, hydroxy or one or more C,. alkyl optionally substituted by one or more halogen atoms; Zis: aryl, indanyl, heteroaryl selected from benzimidazolyl, pyridinyl, pyrimidinyli, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl and pyranyl, heterocycle selected from piperazinyl, tetrahydropyrimidonyl, cyclohexanonyl, cyclohexanolyl, 2-oxa- or 2-thia-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetramethylene sulfidyl,

   tetramethylene sulfoxidyl or tetramethylene sulfonyl. tetrahydropyrany1. tetrahydrofuranyl. 1.3-dioxolanonyl. 1.3-dioxanonyl. 1.4-dioxanyl, morpholino. thiomorpholino. thiomorpholino sulfoxidyl. thiomorpholino sulfonyl. piperidinyl. piperidinonyl, pyrrolidinyl and dioxolanyl.

   each of the aforementioned Z are optionally substituted with one to three halogen, C. alkyl.

   Cy. alkoxy.

   Cy.; alkoxy-C,.3 alkyl.

   Ci. alkoxycarbonyl, aroyl. heteroaroyl, heterocycleC,.jacyl wherein the heteroaryl and heterocycle are as defined hereinabove in this paragraph, C).3acyl, oxo, hydroxy. pyridinyl-C,_; alky!, imidazoly!-C,.; alkyl. tetrahydrofuranyl-C, ; alkyl, nitrile-C,.; alkyl, nitrile, carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,_ alkoxy, hydroxy or mono- or di-(C,; alkyl)amino, amino-S(O)n.

   Ci.¢ alkyl-S(O),, or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy. halogen or mono- or di-(C,.3 alkyl)amino; or Z is optionally substituted with one to three amino. aminocarbonyl or amino-C).; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC;. ealkyl, Ciaalkyl, arylCo.alkyl, C,.s alkoxyC\.; alkyl, C;.s alkoxy, aroyl, C;.3acyl, C,. 3alkyl-S(O)m- or arylCo.3alkyl-S(O)m- each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C, alkyl, C).¢ alkoxy, hydroxy or mono- or di-(C,.3 alkyl)amino;

   or Z is optionally substituted with one to three aryl. heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen, Ci alkyl or C4 alkoxy; or Z is hydroxy, hydroxyC,.;alkyl, halogen, nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C.¢alkyl, aminoC,.salkyl, arylCq. salkyl, Cys alkoxyC,.; alkyl, C).s alkoxy, aroyl, C).3acyl, C,.3alkyl-S(O)n- , arylCoalkyl- S(O)m-, nitrileC,4alkyl or C,.3alkoxyC,.;alkyl, each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C4 alkyl, Ci alkoxy, hydroxy or mono- or di~(C,.; alkyl)amino, C., alkoxyheteroarylCo.alkyl,

   heteroarylCoalkyl or heterocycyleCy.;alkyl wherein the heteroaryl and heterocycle is hereinabove described in this paragraph,

   or Z is C.salkyl branched or unbranched. C.salkoxy. C,.;acylamino. nitrileC, alkyl. Ci.6 alkyl-S(O)m. and phenyl-S(O)m. wherein the phenyl ring is optionally substituted with one to two halogen. C,.¢ alkoxy, hydroxy or mono- or di-(C;.3 alkyl)amino; Ris:

   Ci.j0 branched or unbranched alkyl optionally partially or fully halogenated. and optionally substituted with one to three phenyl, naphthyl or heterocyclic groups selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl. thienyl, furyl. isoxazolyl and isothiazolyl; each such phenyl, naphthyl or heterocycle. selected from the group hereinabove described, being substituted with O to 5 groups selected from the group consisting of halogen, C,.s branched or unbranched alkyl which is optionally partially or fully halogenated, Cs.5 cycloalkyl, Cs.s cycloalkenyl, hydroxy, nitrile, Cy.3 alkyloxy which is optionally partially or fully halogenated, NH,C(O) and di(C,.3)alkylaminocarbonyl;

   Cs.7 cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl. bicyclopentyl, bicyclohexyl and bicycloheptyl, each optionally partially or fully halogenated and optionally substituted with one to three

   C,.3alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S, CHOH, >C=0, >C=S and NH;

   Cs.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,_s branched or unbranched alkyl. phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazoly), thienyl, fury], isoxazolyl and isothiazolyl, and each such phenyl, naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from the group consisting of halogen, Ci branched or unbranched alkyl! which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl,

   bicyclopentanyl. bicyclohexanyl. bicycloheptanyl, hydroxy. nitrile. C,.; alkoxy which is optionally partially or fully halogenated. NH.C(O) and mono- or di(C,. 3)alkylaminocarbonyl:

   aCs. cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl. bicyclohexenyl and bicycloheptenyl. wherein such cycloalkenyl group is optionally substituted with one to three C,_; alkyl groups: nitrile; or

   C.¢ branched or unbranched alkoxycarbonyl. C,.¢ branched or unbranched alkylaminocarbonyl, C,.¢ branched or unbranched alkylcarbonylamino-C,_3-alkyl; R; is:

   a C.¢ branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile, or R; is acetyl. aroyl, C4 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl; R; 1s: phenyl, naphthyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyi. indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl. purinyl and indazolyl, wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a phenyl, naphthyl, heterocycle selected from the group hereinabove described in this

   . | WO 00/55139 PCT/US00/03865 paragraph.

   C,.« branched or unbranched alkyl which is optionally partially or fully halogenated. cyclopropyl. cyclobutyl. cyclopentyl. cyclohexyl, cycloheptyl. bicyclopentyl. bicyclohexyl. bicycloheptyl, phenyl C,.s alkyl. naphthyl Cs alkyl, halogen. hydroxy. oxo. nitrile, C3 alkoxy optionally partially or fully halogenated, Ci;

   alkoxyC,.salkyl, C,sthioalkyl.

   C_sthioalkylC,.salkyl, phenyloxy. naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph, nitro. amino. mono- or di-(C,.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(O), a mono- or di-(C,.3)alkyl aminocarbonyl, C).s alkyl-C(0)-C, alkyl, amino-C,.s alkyl. mono- or di-(C;. 3)alkylamino-C,.s alkyl. amino-S(O)a,. di-(C,.;)alkylamino-S(O),. Ry -C;.s alkyl, Rs -Cy.s alkoxy.

   Re —C(0O)-C,.s alkyl and R7-C,.s alkyl(Rs)N, carboxy-mono- or di-(C,.s )-alkyl- amino;

   a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl. benzocycloheptanyl and benzocycloheptenyl, or a fused heterocyclyl selected from the group consisting of cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine,

   cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from the group consisting of phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl. and isothiazolyl, C;.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.; alkoxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy. heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described, nitro,

   amino. mono- or di-(C;.;)alkylamino. phenylamino. naphthylamino. heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described. NH,C(O). a mono- or di-(C,.3)alkyl aminocarbonyl, C, alkyl-OC(O), Cs alkyl-C(O)- C4 branched or unbranched alkyl. an amino-C,_s alkyl. mono- or di-(C,.3)alkylamino-C;. 3 alkyl. Rg -Ci.s alkyl. Ri0-Ci.s alkoxy. Ry —-C(0)-C.s alkyl and Ri2 Cis alkyl(R};3)N; cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl. cyclohexyl, cycloheptyl. bicyclopentyl. bicyclohexyl and bicycloheptyl. wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups;

   Cs.7 cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,.; alkyl groups; acetyl, aroyl, C)¢alkoxycarbonylC, ¢alkyl or phenylsulfonyl; or

   Ci. branched or unbranched alkyl optionally partially or fully halogenated; or R| and R; taken together optionally form a fused phenyl or pyridinyl ring; each Rg and R,3 is independently selected from the group consisting of: hydrogen and C,,, branched or unbranched alkyl optionally partially or fully halogenated; each Ry, Rs, Rg, Rs, Rg, Rig. Ry; and Rj; is independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; misO0,1or2;

   Wis O or S: wherein X is directly attached to one or two -Y-Z. and the pharmaceutically acceptable derivatives thereof .

   10. The compound according to claim 9 wherein: Ar, is naphthyl, tetrahydronaphthyl. indanyl or indenyl and Wis O.

   11. The compound according to claim 10 wherein: Ar; is thiophene or pyrazole each substituted independently by one to three R;, R» orRj; X is: a Cs.7 cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, C4 alkoxy or C,4 alkylamino chains each being branched or unbranched; phenyl, indanyl, furanyl. thienyl, imidazolyl, pyridinyl, pyrazinyl, tetrahydrapyridinyl, pyrimidinyl, pyridinonyl, piperdinyl, benzimidazole or piperazinyl; each being optionally independently substituted with one to three C,., alkyl, C,_alkoxy, hydroxy, nitrile, amino,

   mono- or di-(C,.; alkyl)amino. mono- or di-(C).3 alkylamino)carbonyl.

   NH,C(0). C,.¢ alkyl-S(O),, or halogen:

   Y is:

   a bond or a C4 saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more C atoms are optionally replaced by O or N, and wherein Y is optionally independently substituted with one to two oxo groups, nitrile, phenyl, hydroxy or one or more C.; alkyl optionally substituted by one or more halogen atoms;

   Z is: phenyl. heteroaryl selected from pyridinyl, imidazolyl, furanyl and thienyl, heterocycle selected from piperazinyl, 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetrahydrofuranyl, morpholino, thiomorpholino and piperidinyl, each of the aforementioned Z are optionally substituted with one to three halogen, C,.¢ alkyl, C,.¢ alkoxy, C,.; alkoxy-C,.; alkyl, C;.¢ alkoxycarbonyl, aroyl,

   morpholinocarbonyl, C_3acyl, oxo, hydroxy, pyridinyl-C,_ alkyl, imidazolyl-C,. alkyl, tetrahydrofuranyl-C,.; alkyl, nitrile-C,_; alkyl, nitrile, carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,.3 alkyl)amino, amino-S(O)m, C).¢ alkyl-S(O)y, or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy, halogen or mono- or di-(C,.3 alkyl)amino; or Z is optionally substituted with one to three amino, aminocarbony! or amino-C,.; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC;. salkyl, C;alkyl, arylCy.;alkyl, C,.5 alkoxyC,.; alkyl, C,.s alkoxy, aroyl, C,sacyl.

   C,. 3alkyl-S(O)n- or arylCy.;alkyl-S(O)n- each of the aforementioned alkyl and aryl attached to the amino group are optionally substituted with one to two halogen, C,.¢ alkyl or C,.¢ alkoxy;

   or Z is optionally substituted with one 10 three aryl, heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen.

   C,.6 alkyl or C4 alkoxy; s or Zis hydroxy. hydroxyC,.;alkyl. halogen. nitrile. amino wherein the N atom is optionally independently mono- or di-substituted by aroyl, C,.;acyl. Cisalkyl, Cys alkoxyC,_; alkyl. pyridinylC;.;alkyl. tetrahydrafuranylC,_;alkyl, nitrileC,_4alkyl or phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, or Z is C;.salkyl branched or unbranched. C,salkoxy or nitrileC, 4alkyl; R; 1S:

   C\.4 branched or unbranched alkyl optionally partially or fully halogenated; 1s cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S and NH;

   Cs.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,.s branched or unbranched alkyl; cyclopentenyl and cyclohexenyl optionally substituted with one to three C,_; alkyl groups; : : R, 1s: a C;. branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile; R; is:

   phenyl or heterocyclic group selected from the group consisting of pyridinyl. pyrimidinyl. pyrazinyl. pyridazinyl and pyrazolyl. wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting 5s of a phenyl. heterocycle selected from the group hereinabove described in this paragraph,

   C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl. cyclobutyl, cyclopentyl. cyclohexyl, cycloheptyl, bicvclopentyl, bicyclohexy). bicycloheptyl, phenyl C,.s alkyl, naphthyl C,_s alkyl. halogen, hydroxy, oxo, nitrile, C,_; alkoxy optionally be partially or fully halogenated. C, ; alkoxyC,.salkyl,

   C,.sthioalkyl, Cy.sthioalkylC,.salkyl, phenyloxy, naphthyloxy. heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described in this paragraph, nitro, amino. mono- or di-(C.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH,C(O), a mono- or di-(C,.3)alky) aminocarbonyl. Cys alkyl-C(O)-C,. alkyl, amino-C,.s alkyl, mono- or di-(C,. 3)alkylamino-C,.s alkyl, amino-S(O),, di-(C,.3)alkylamino-S(O),, R, -Cy.s alkyl, Rs ~Cy.s alkoxy, R¢—C(O)-C,.5 alkyl and R;-C,.s alkyl(Rg)N, carboxy-mono- or di-(C}.s )-alkyl- amino; a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl; wherein the fused aryl is substituted with 0 to 3 groups independently selected from the group consisting of phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, fury), isoxazolyl. and isothiazolyl, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, halogen, nitrile, C,.3 alkoxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.3)alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described in this paragraph, NH>C(O), a mono- or di-(C;.3)alkyl aminocarbonyl, C,., alkyl-OC(O), C,_s alkyl-C(0O)-C,4 branched or unbranched alkyl, an amino-C,.s alkyl. mono- or di-(C;,.

   s)alkylamino-C,.s alkyl. Ro-Cisalkyl. Ryo -C.s alkoxy. Ry; —C(0)-C, x alkyl and Ri: -C. s alkyl(R)3)N; cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl. cyclopentyl, cyclohexyl. cycloheptyl. wherein the cycloalkyl is optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups: C,salkoxycarbonylC; alkyl; or R; and R, taken together optionally form a fused phenyl or pyridiny! ring; each Rg and R); is independently selected from the group consisting of: hydrogen and C;_ branched or unbranched alkyl optionally partially or fully halogenated; and each Ry, Ri. Re, Ry, Ry, Rip. Ry) and Rj; is independently selected from the group consisting of morpholine, piperidine, piperazine, imidazole and tetrazole; wherein X is directly attached to one -Y-Z.

   12. The compound according to claim 11 wherein: Ar, is pyrazole; Xis: cyclopentenyl, cyclohexenyl, cycloheptenyl, optionally substituted with an oxo group or one to three C4 alkyl, C4 alkoxy or C4 alkylamino chains each being branched or unbranched;

   phenyl. furanyl. thienyl. pyridinyl. pyrazinyl piperidinyl or pyrimidinyl each being optionally independently substituted with one to three Cy; alkyl, C 1-2alkoxy, hydroxy or halogen;

   Zis: phenyl, heteroaryl selected from pyridinyl. imidazolyl and furanyl, heterocycle selected from 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholino, thiomorpholino. thiomorpholino sulfoxide and piperidinyl. each of the aforementioned Z are optionally substituted with one to three halogen, C,.¢ alkyl, C, alkoxy.

   C;.; alkoxy-C,.; alkyl, C,¢ alkoxycarbonyl, aroyl, morpholinocarbonyl.

   C;.3acyl, oxo, hydroxy, pyridinyl-C,.; alkyl, imidazotyl-C,_; alkyl,

   tetrahydrofuranyl-C,_; alkyl, nitrile-C, 3 alkyl, nitrile, carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C).¢ alkoxy, hydroxy or mono- or di~(C,.3 alkyl)amino, amino-S(O)m, C;.¢ alkyl-S(O)y,, or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen, C, 4 alkoxy, hydroxy. halogen or mono- or di-(C,.3 alkyl)amino;

   or Zis optionally substituted with one to three amino, aminocarbonyl or amino-C,_; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC;. ealkyl, Cj.zalkyl, arylCo.zalkyl, C,.s alkoxyC,.3 alkyl, C,.s alkoxy, aroyl, C_3acyl, C,. 3alkyl-S(O)m-, pyridinylCo.3alkyl, tetrahydrafuranylCo.;alkyl, or arylCo.;alkyl-S(O)m- each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C;.¢ alkyl or C alkoxy; or Z is hydroxy. hydroxyC,.;alkyl. halogen, nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C.alkyl, pyridinylCy.3alkyl, tetrahydrafuranylCo alkyl, C.s alkoxyC,.; alkyl, C;.3acyl, nitrileC;_4alkyl or phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino,

   or Z is C)-salkyl branched or unbranched. C,alkoxy or nitrileC, alkyl; Ris:

   Ci. branched or unbranched alky! optionally partially or fully halogenated; cyclopropyl, cyclobutyl. cyclopentanyl. cyclohexanyl and cycloheptanyl optionally partially or fully halogenated and optionally substituted with one to three C;.3 alkyl groups. or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from the group consisting of O, S and NH;

   Cs.10 branched alkenyl optionally partially or fully halogenated and optionally substituted with one to three C,.; branched or unbranched alkyl; cyclopentenyl and cyclohexenyl optionally substituted with one to three C,.3 alkyl groups; R, 1s: aC), branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile; Rj is: phenyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyridazinyl and pyrazolyl, wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a phenyl, heterocycle selected from the group hereinabove described in this paragraph, C,., branched or unbranched alkyl which is optionally partially or fully halogenated, phenyl

   C,.;alkyl, halogen, hydroxy. oxo, nitrile, Cy; alkoxy optionally partially or fully halogenated, C_sthioalkyl. C.;thioalkylC,.salkyl. amino. mono- or di-(C,.;)alkylamino. NH,C(O) or a mono- or di-(C,_3)alkyl aminocarbonyl.

   C,.salkoxycarbonylC, salkyl; or R; is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups or R, and R; taken together optionally form a fused pheny! or pyridinyl ring.

   13. The compound according to claim 12 wherein: Y is -CH,-, -O-(CH2)o.3-, -CH,CH;-, ~-CH,NH-, -CH,CH,-NH-, NH-CH,CH,-, 15s -CH;-NH-CH:-, -NH-, -NH-C(O)-, -C(0O)-, -CH(OH)-, -CH(CH,CH3)- or a bond; Xis: cyclohexeny! optionally substituted with an oxo group or one to three C;4 alkyl, C;.4 alkoxy or C4 alkylamino chains each being branched or unbranched; phenyl, pyridinyl, pyrazinyl, piperidinyl or pyrimidinyl each being optionally independently substituted with one to three C,.; alkyl, Cyalkoxy, hydroxy or halogen; Zis: : phenyl, heteroaryl selected from pyridinyl, imidazoly! and furanyl, heterocycle selected from 2-oxa-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholino, thiomorpholino, thiomorpholino sulfoxide and piperidinyl,

   each of the aforementioned Z are optionally substituted with one to three halogen.

   C6 alkyl, Cs alkoxy.

   C3 alkoxy-C.; alkyl.

   C,. alkoxycarbonyl. aroyl. morpholinocarbonyl.

   C,.acyl. oxo, hydroxy, pyridiny}-C,.; alkyl, imidazolyl-C,.; alkyl. tetrahydrofuranyl-C,_; alkyl. nitrile-C,; alkyl. nitrile. carboxy, phenyl wherein the phenyl ring is optionally substituted with one to two halogen.

   C, alkoxy. hydroxy or mono- or di-(C,.; alkyl)amino. amino-S(O)m, C16 alkyl-S(O). or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen.

   C, alkoxy, hydroxy. halogen or mono- or di-(C,.; alkyl)amino; or Z is optionally substituted with one to three amino or aminocarbony! wherein the N atom is optionally independently mono- or di-substituted by aminoC,_¢alkyl, C\.alkyl, arylCo.alkyl, C,.s alkoxyC,.3 alkyl, C,.s alkoxy. aroyl.

   C;;acyl, C;.;alkyl-S(O)n- or arylCy.salkyl-S(O)n- each of the aforementioned alkyl! and aryl attached to the amino group is optionally substituted with one to two halogen, C,¢ alkyl or C, 4 alkoxy;

   or Z is hydroxy, hydroxyC,.;alkyl, halogen, nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C,.salkyl, pyridinylC.,alkyl, tetrahydrafuranylC, alkyl, C;.; alkoxyC,.; alkyl, C,_sacyl, nitrileC,_salkyl, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C,.¢ alkoxy, hydroxy or mono- or di-(C,_ alkyl)amino,

   or Z is Csalkyl branched or unbranched, C,.¢alkoxy or nitrileC; 4alkyl;

   Rj is: C4 branched or unbranched alky! optionally partially or fully halogenated,

   R; is: a C).3 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with nitrile;

   Rs is:

   phenyl or heterocyclic group selected from the group consisting of pyridinyl. pyrimidinyl, and pyrazolyl. wherein such phenyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of C;_; branched or unbranched alkyl which is optionally partially or fully halogenated, C,.; alkoxy which optionally partially or fully halogenated. C,.sthioalkyl. C,.;thioalkylC_salkyl. amino or NH,C(O);

   C,.;alkoxycarbonyl; or Rj is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups.

   14. The compound according to claim 13 wherein: Ary is 5-tert-butyl-pyrazol-3-yl; wherein the pyrazole ring is substituted independently by one to two R> or Rj; X is: cyclohexenyl; phenyl, pyridinyl, pyraziny!, piperidinyl or pyrimidinyl each being optionally independently substituted with Cj.alkoxy or hydroxy; Zis: phenyl. heteroaryl selected from pyridiny! and furanyl, heterocycle selected from 2-oxa- 5-aza-bicyclo[2.2.1]heptanyl. pentamethylene sulfidyl, pentamethylene sulfoxidyl, tetrahydrofuranyl, piperazinyl. morpholino, thiomorpholino and piperidinyl,

   each of the aforementioned Z are optionally substituted with one to three C;_; alkyl. C;.; alkoxy. oxo . hydroxy or NH.C(O)-; or Z is hydroxyC;.;alkyl. amino wherein the N atom is optionally independently mono- or di-substituted by pyridinylmethyl. tetrahydrafuranylmethyl, C,; alkoxyC,.3 alkyl, C,.;acy! or nitrileC, 4alkyl, or Z 1s nitrileC, alkyl: R; is: phenyl or heterocyclic group selected from the group consisting of pyridinyl. pyrimidinyl. and pyrazolyl. wherein such phenyl or heterocyclic group is optionally substituted with one to two groups selected from the group consisting of C,.; alkyl which is optionally partially or fully halogenated, C;., alkoxy which optionally partially or fully halogenated, C.pthioalkyl, Ci.»thioalkylC, alkyl, amino or NH,C(O); C,-;alkoxycarbonyl; or Rj is cyclopropyl or cyclopentyl each optionally partially or fully halogenated and optionally substituted with one to three C,.3 alkyl groups.

   15. The compound according to claim 14 wherein X is pyridinyl. :

   16. The compound according to claim 15 wherein the pyridinyl is attached to Ar, via the 3-pyridinyl position.

   17. A compound of the formula (11):

   J Go Ar—X—Y—Z N NT H H uy wherein: Gis: an aromatic Cq.jo carbocycle or a nonaromatic Cs. ocarbocycle saturated or unsaturated; a 6-10 membered heteroaryl containing 1 or more heteroatoms chosen from O.

   N and S; a 5-8 membered monocyclic heterocycle containing one or more heteroatoms chosen fromO,NandS; or an 8-11 membered bicyclic heterocycle, containing one or more heteroatoms chosen from O,NandS; wherein G is substituted by one or more Ry, R; or R3;

   Aris: phenyl, naphthyl, quinolinyl. isoquinolinyl, tetrahydronaphthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzimidazolyl, benzofuranyl, dihydrobenzofuranyl, indolinyl,

   benzothienyl. dihydrobenzothienyl. indanyl. indeny! or indolyl each being optionally substituted by one or more Ry or R::

   Xs: aCsg cycloalkyl or cycloalkenyl optionally substituted with one to two oxo groups or one to three C4 alkyl, Cy alkoxy or C4 alkylamino chains; phenyl, furanyl. thienyl, pyrrolyl, pyrazolyl. imidazolyl, pyridinyl. pyrimidinyl. pyridinonyl. dihydropyridinonyl. maleimidyl. dihydromaleimidyl, piperdinyl, benzimidazole. 3H-imidazo[4,5-b]pyridine, piperazinyl, pyridazinyl or pyrazinyl; Y is:

   a bond or a C,_; saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, N, or S(O)m and wherein Y is optionally independently substituted with one to two oxo groups, phenyl! or one or more C,_; alkyl optionally substituted by one or more halogen atoms; Zis: phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl, pyranyl. each being optionally substituted with one to three halogen, C,.¢ alkyl, C,.¢ alkoxy. hydroxy, amino, mono- or di-(C,_; alkyl)amino, C, alkyl-S(O)m.

   CN, CONH;, COOH or phenylamino wherein the phenyl ring is optionally substituted with one to two halogen.

   C,.4 alkyl or C4 alkoxy; tetrahydropyranyl. tetrahydrofuranyl. 1.3-dioxolanonyl, 1.3-dioxanonyl, 1,4-dioxanyl, morpholinyl. thiomorpholinyl, thiomorpholino sulfoxidyl, thiomorpholino sulfonyl,

   piperidinyl. piperidinonyl. piperazinyl. tetrahydropyrimidonyl, cyclohexanonyl. cyclohexanolyl. pentamethylene sulfidyl. pentamethylene sulfoxidyl. pentamethylene sulfonyl. tetramethylene sulfide. tetramethylene sulfoxidyl or tetramethylene sulfonyl each being optionally substituted with one to three nitrile, C,.¢ alkyl. C alkoxy, hydroxy. amino, mono- or di-(C.; alkyl)amino-C,_; alkyl, CONH,. phenylamino-C,_; alkyl or C,.3 alkoxy-C, 3 alkyl; halogen, C,.4 alkyl. nitrile. amino, hydroxy, C,.¢ alkoxy, NH,C(O), mono- or di(C, alkyl) aminocarbonyl, mono- or di(C-;alkyl)amino, secondary or tertiary amine wherein the amino nitrogen is covalently bonded to C,.; alkyl or Cs alkoxyalkyl. pyridinyl-C.; alkyl, imidazolyl-C,.; alkyl. tetrahydrofuranyl-C, 5 alkyl, nitrile-C,_; alkyl. carboxamide-C,_; alkyl, phenyl, wherein the phenyl ring is optionally substituted with one to two halogen.

   Ci.¢ alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino, C,.¢ alkyl-S(O)m. or phenyl- S(O)m. wherein the phenyl ring is optionally substituted with one to two halogen, C, alkoxy, hydroxy, halogen or mono- or di-(C,; alkyl)amino;

   Ci.¢ alkyl-S(O)m, and phenyl-S(O),. wherein the phenyl ring is optionally substituted with one to two halogen, C,_¢ alkoxy, hydroxy or mono- or di-(C).3 alkyl)amino; each R, is independently: Ci-10 alkyl optionally be partially or fully halogenated, and optionally substituted with one to three Cs.jgcycloalkanyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl; each of the aforementioned being optionally substituted with one to five groups selected from halogen, Ci. alkyl which is optionally partially or fully halogenated, C;_g cycloalkanyl, Cs.g cycloalkenyl, hydroxy, nitrile, C,.; alkoxy which is optionally partially or fully halogenated or NH,C(O), mono- or di(C,.salkyl)amino, and mono- or di(C,.;alkyl)aminocarbonyl;

   cyclopropyloxy. cyclobutyloxy. cyclopentyloxy. cyclohexyloxy. or cycloheptyloxy each being optionally partially or fully halogenated and optionally substituted with one to three

   C,.; alkyl groups optionally partially or fully halogenated. CN. hydroxyC,.;alkyl or aryl: or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O. S(O)m. CHOH. >C=0, >C=S or NH; phenyloxy or benzyloxy each being optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups optionally partially or fully halogenated, CN, hydroxyC,.salkyl or aryl: or an analog of such cycloaryl group wherein one to two ring methyne groups are independently replaced by N; cyclopropanyl, cyclobutanyl. cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl optionally partially or fully halogenated, CN, hydroxyC,.;alkyl or aryl; or an analog of such cycloalkyl! group wherein one to three ring methylene groups are independently replaced by O, S(O)m, CHOH, >C=0. >C=S or NH;

   Cs.10 branched or unbranced alkenyl each being optionally partially or fully halogenated, and optionally substituted with one to three C,_s branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazotyl. thienyl, furyl, isoxazoly! or isothiazolyl. each of the aforementioned being substituted with one to five halogen, C,.¢ alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, hydroxy, nitrile, C;.; alkyloxy which is optionally partially or fully halogenated, NH,C(O), mono- or di(C,. salkyl)aminocarbonyl; the Cj_;o branched or unbranced alkenyl being optionally interrupted by one or more heteroatoms chosen from O, N and S(O);

   cyclopentenyl. cyclohexenyl. cyclohexadienyl. cycloheptenyl. cycloheptadienyl, bicyclohexenyl or bicycloheptenyl. wherein such cycloalkenyl! group is optionally substituted with one to three C.: alkyl groups: nitrile, halogen; methoxycarbonyl. ethoxycarbonyl and propoxycarbonyl, silyl containing three C,. alkyl groups optionally partially or fully halogenated:

   Cs. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O. NH or S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl. one or more C,.4 alkyl optionally substituted by one or more halogen atoms, nitrile. morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or mono- or di(C,.alkyl)amino optionally substituted by one or more halogen atoms; each Ry, Ry, and Rs is a C6 branched or unbranched alkyl optionally partially or fully halogenated. acetyl, aroyl, C,4 branched or unbranched alkoxy, each being optionally partially or fully halogenated, halogen, methoxycarbonyl. C,.; alkyl-S(O),, optionally partially or fully halogenated, or phenylsulfonyl; ’

   Ci.¢ alkoxy, hydroxy, amino, or mono- or di-(C,.4 alkyl)amino, nitrile, halogen; OR; oo nitro; or mono- or di-(C,4 alkyl)amino-S(0), optionally partially or fully halogenated. or H;NSO;:

   each Rj; is independently:

   phenyl, naphthyl. morpholinyl. pyridinyl. pyrimidinyl. pyrazinyl. pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl. oxazoyl. triazolyl, tetrazolyl. thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl. quinolinyl, isoquinolinyl, indolyl,

   benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl. benzpyrazolyl, benzothiofuranyl. cinnolinyl, pterindinyl. phthalazinyl. naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, each of the aforementioned is optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl] as hereinabove described in this paragraph, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl. cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C,.; alkyl, naphthyl C;.5 alkyl, halogen, hydroxy, oxo, nitrile, C,.3 alkyloxy optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C;.salky)lamino, phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl heterocyclic moiety is as hereinabove described in this paragraph, NH,C(0), a mono- or di-(C,.3alkyl) aminocarbonyl, C).s alkyl-C(O)-C,4 alkyl, amino-C,. 5 alkyl, mono- or di-(C;.3alkyl)amino-C,.; alkyl, amino-S(O), di-(C;_3alkyl)amino-S(0O),, R;-C,.s alkyl, R3-Cy.s alkoxy, Ro-C(0O)-C,.s alkyl, Ro-C,.5 alkyl(R;,)N, carboxy-mono- or di-(C,.salkyl)-amino;

   a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl,

   cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl, cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl,

   cyclohexanoquinolinyl. cyclopentanoisoquinolinyl. cyclohexanoisoquinolinyl. cyclopentanoindolyl. cyclohexanoindolyl. cyclopentanobenzimidazolyl. cyclohexanobenzimidazolyl. cyclopentanobenzoxazolyl, cyclohexanobenzoxazolyl, cyclopentanoimidazolyl. cyclohexanoimidazolyl. cyclopentanothienyl and cyclohexanothienyl: wherein the fused aryl or fused heteroaryl ring is independently substituted with zero to three phenyl. naphthyl. pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl. imidazolyl, pyrazolyl. thienyl, furyl. isoxazolyl. isothiazolyl, C; alkyl which is optionally partially or fully halogenated, halogen, nitrile. C.; alkyloxy which is optionally partially or fully halogenated. phenyloxy, naphthyloxy. heteroaryloxy or heterocyclicoxy wherein the heteroary! or heterocyclic moiety is as hereinabove described in this paragraph, nitro. amino. mono- or di-(C,.;alkyl)amino, phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety 1s as hereinabove described in this paragraph, NH,C(O), mono- or di~(C;. salkylaminocarbonyl, C)4 alkyl-OC(O). C,.5 alkyl-C(0)-C 4 alkyl, amino-C,.; alkyl,

   i5. mono- or di-(C.3)alkylamino-Cy.s alkyl. R;>-C.s alkyl, R}3-C}.s alkoxy, R,4-C(0)-Cy.s alkyl or R}5-C 5 alkyl(R6)N; cyclopropanyl, cyclobutanyl, cyclopentanyl. cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycioheptanyl, each being optionally be partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S, CHOH. >C=0. >C=S or NH; cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C,.; alkyl groups;

   Cy. alkyl-phenyl-C(0)-C,; alkyl-, C4 alkyl-C(0)-C, 4 alkyl- or C4 alkyl-phenyl- S(O)m-Ci4 alkyl-;

   C,.¢ alkyl or C,., branched or unbranched alkoxy each of which is optionally partially or fully halogenated or optionally substituted with Rs; OR; or C alkyl optionally substituted with OR g; amino or mono- or di-(C;.salkyl)amino optionally substituted with Rg; R20C(O)N(Rz)-, Ry;0- or R5R24NC(O)-: Rag(CH2)mC(O)N(R2))- or R26C(O)CH2)mN(R21)-; C,alkenyl substituted by R23R2sNC(O)-;

   C,. alkynyl branched or unbranched carbon chain, optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH, S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl, morpholinyl, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazoly! one or more C4 alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino. piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or mono- or di(C, 4 alkyl)amino which may be substituted by one or more halogen atoms; or aroyl; Rsis a: Ci alkyl optionally partially or fully halogenated and optionally substituted with Ry; each Ry, Rg, Ro, Rio, Ria, Ris. Rs. Ris, Ri7, Ris, Ras and Ry is independently: nitrile, phenyl, morpholino, piperidinyl, piperazinyl, imidazolyl, pyridinyl, tetrazolyl, amino or mono- or di-(C,4alkyl)amino optionally partially or fully halogenated;

   each R;) and Rs is independently: hydrogen or C, alkyl optionally partially or fully halogenated: Rig is independently: hydrogen or a C, alkyl optionally independently substituted with oxo or Ras; Rag is independently:

   Ci.10 alkyl optionally partially or fully halogenated. phenyl, or pyridinyl; Ry; is independently: hydrogen or C,.; alkyl optionally partially or fully halogenated; each Ras. Ra; and Ras is independently: hydrogen, C,.¢ alkyl optionally partially or fully halogenated, said C,.¢ alkyl is optionally interrupted by one or more O, N or S, said C, alkyl also being independently optionally substituted by mono- or di-(C,.3alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono- or di-(C;_salkyl)amino each of which is optionally partially or fully halogenated and optionally substituted with mono- or di-(C,_;alkyl)amino; or Ry; and Ry4 taken together optionally form a heterocyclic or heteroaryl ring; m=0,1or2; Wis O or S and pharmaceutically acceptable derivatives thereof.

   18. The compound according to claim 17 wherein: Gis: phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl,

   benzocycloheptanyl. benzocycloheptenyl. indanyl. indenyl; pyridinyl, pyridonyl. quinolinyl. dihydroquinolinyl. tetrahydroquinoyl. isoquinolinyl. tetrahydroisoquinoyl, pyridazinyl. pyrimidinyl. pyrazinyl, benzimidazolyl. benzthiazolyl, benzoxazolyl, benzofuranyl. benzothiophenyl. benzpyrazolyl, dihydrobenzofuranyl. dihydrobenzothiophenyl, benzooxazolonyl. benzo[ 1.4]Joxazin-3-onyl. benzodioxolyl. benzo[1,3]dioxol-2-onyl, benzofuran-3-onyl. tetrahydrobenzopyranyl. indolyl, indolinyl, indolonyl, indolinonyl, phthalimidyl. chromoyl; oxetanyl, pyrrolidinyl, tetrahydrofuranyl. tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl. dioxanyl. tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl, thiazolinyl. imidazolinyl. tertrahydropyridinyl. homopiperidinyl, pyrrolinyl, tetrahydropyrimidinyl, decahydroquinolinyl, decahydroisoquinolinyl, thiomorpholinyl, thiazolidinyl, dihydrooxazinyl., dihydropyranyl, oxocanyl, heptacanyl, thioxanyl or dithianyl; 1s wherein G is substituted by one or more R;. R; or Rj.

   19. The compound according to claim 18 wherein Gis phenyl, pyridinyl, pyridonyl, naphthyl. quinolinyl. isoquinolinyl, pyrazinyl, benzimidazolyl. benzoxazolyl, benzofuranyl. benzothiophenyl, benzpyrazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indanyl, indenyl, indolyl, indolinyl, indolonyl or indolinonyl, wherein G is substituted by one or more R;, R; or Rj; Aris: naphthyl, quinolinyl, isoquinolinyl, tetrahydronaphthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indanyl, indenyl or indolyl each being optionally substituted by one or more R, or Rs groups; X is:

   phenyl. furanyl. thienyl, pyrrolyl, pyrazolyl. imidazolyl. pyridinyl. pyrimidinyl. pyridinonyl, dihydropyridinonyl. maleimidyl, dihydromaleimidy!, piperdinyl. piperazinyl, pyridazinyl or pyrazinyl:

   Y is: a bond or a C\.4 saturated or unsaturated carbon chain wherein one of the carbon atoms is optionally replaced by O, N, or S(O), and wherein Y is optionally independently substituted with one to two oxo groups. phenyl or one or more C,_ alkyl optionally substituted by one or more halogen atoms; Zis:

   phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl. imidazolyl, furanyl, thienyl, dihydrothiazolyl, dihydrothiazolyl sulfoxidyl, pyranyl, pyrrolidinyl which are optionally substituted with one to three nitrile, C,_; alkyl, C,.; alkoxy, amino, mono- or di-(C,3 alkyl)amino, CONH; or OH; : 20 tetrahydropyranyl, tetrahydrofuranyl. 1,3-dioxolanonyl, 1,3-dioxanonyl, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfoxidyl, piperidinyl. piperidinonyl, piperazinyl, tetrahydropyrimidonyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetramethylene sulfidyl, tetramethylene sulfoxidyl or tetramethylene sulfonyl which are optionally substituted with one to three nitrile, C3 alkyl, C,.; alkoxy, amino, mono- or di-(C,_; alkyl)amino, CONHj,, or OH; nitrile, C, atkyl-S(O),, halogen, hydroxy, C4 alkoxy, amino, mono- or di-(C;. alkyl)amino, mono- or di-(C;.; alkyl)aminocarbonyl, or NH,C(O);

   each R, is independently:

   C;.¢ alkyl optionally partially or fully halogenated. and optionally substituted with one to three C;.¢cycloalkyl. phenyl. thienyl, furyl. isoxazolyl or isothiazolyl; each of the aforementioned being optionally substituted with one to three groups selected from halogen, C,.; alkyl which is optionally partially or fully halogenated. hydroxy, nitrile or

   C,.;alkoxy which is optionally partially or fully halogenated; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,.3 alkyl groups optionally partially or fully halogenated,

   CN. hydroxyCj.;alkyl or phenyl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O. S, CHOH, >C=0, >C=S or NH; or silyl containing three C,.4 alkyl groups optionally partially or fully halogenated; R; is independently: halogen, C;.; alkoxy, C.; alkyl-S(O), optionally partially or fully halogenated, phenylsulfonyl or nitrile; Rj is independently: phenyl, morpholino, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrrolylidinyl, imidazolyl, pyrazolyl, each being optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl as hereinabove described in this paragraph, C,.s alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C,_s alkyl. naphthyl C,.s alkyl, halogen, oxo, hydroxy, nitrile, C,_; alkyloxy optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph. nitro. amino. mono- or di-(C,.zalkyl)amino. phenylamino. naphthylamino. heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph. NH,C(O). a mono- or di-(C,. salkyl)aminocarbonyl. C,.s alkyl-C(O)-C,4 alkyl. mono- or di-(C,.;alkyl)amino. mono- or di-(Cj.a)alkylamino-C,.s alkyl, mono- or di-(C,.3alkyl)amino-S(O),. R;-C,.s alkyl, Rg-C).s alkoxy, Rg-C(0O)-C\.5 alkyl, R1o-C\.5 alky}(R11)N, carboxy-mono- or di-(C).s)-alkyl- amino;

   C,.; alkyl or C4 alkoxy each being optionally partially or fully halogenated or optionally substituted with Ry7; ORs or C4 alkyl optionally substituted with ORs; amino or mono- or di- (C;-s alkyl)amino optionally substituted with Rg; Is R20C(O)N(R21)-, R220- ; R23R24NC(O)-; RpsCH,C(O)N(R2))- or Rz6C(O)CH,N(R2))-; C,4alkenyl substituted by R23R4NC(O)-; or

   C,.4 alkynyl! branched or unbranched carbon chain optionally partially or fully halogenated and optionally independently substituted with one to two oxo groups, " pyrroldinyl, pyrrolyl, morpholinyl, piperidinyl, piperazinyl. imidazolyl, phenyl, pyridinyl, tetrazolyl or one or more C,4 alkyl optionally substituted by one or more halogen atoms; and Ras and Raq taken together optionally form imidazolyl, piperidinyl, morpholinyl, piperazinyl or a pyridinyl ring. :

   20. The compound according to claim 19 wherein:

   G is phenyl. pyridinyl. pyridonyl. naphthyl. quinolinyl. isoquinolinyl. pyrazinyl. benzothiophenyl. dihydrobenzofuranyl. dihvdrobenzothiophenyl. indanyl. indolyl. indolinyl. indolonyl or indolinonyl. wherein G is substituted by one or more Ry. R; or Rs: S Ar is naphthyl; X is phenyl. imidazolyl. pyridinyl, pyrimidinyl. piperdinyl. piperazinyl, pyridaziny! or pyrazinyl each being optionally independently substituted with one to three C4 alkyl, Ci. salkoxy. hydroxy, nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di-(C,.3 alkylamino)carbonyl. NH,C(O), Ci. alkyl-S(O)m or halogen; Y is: a bond or aC, saturated carbon chain wherein one of the carbon atoms is optionally replaced by O, N or S and wherein Y is optionally independently substituted with an oxo group; Zis: phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, dihydrothiazolyl, dihydrothiazolyl sulfoxide, pyranyl or pyrrolidinyl which are optionally substituted with one to two C,.» alkyl or C,.; alkoxy; tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfoxidyl, piperidinyl, piperidinonyl, piperaziny} or tetrahydropyrimidonyl which are optionally substituted with one to two C,.; alkyl or C,.; alkoxy; or

   C,.; alkoxy; each R, is independently:

   Cs.s alkyl optionally partially or fully halogenated. and optionally substituted with phenyl substituted with zero to three halogen. C,_; alkyl which is optionally partially or fully halogenated. hydroxy. nitrile or C,_;alkoxy which is optionally partially or fully halogenated; cyclopropyl. cyclobutyl. cyclopentanyl. cyclohexanyl, bicyclopentanyl or bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,_; alkyl groups optionally partially or fully halogenated, CN, hydroxyC,_alky! or phenyl; and an analog of cyclopropyl. cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentany! or bicyclohexany! wherein one ring methylene group is replaced by O; and silyl containing three C,.; independently alkyl groups optionally partially or fully halogenated; each R; is independently: bromo, chloro, fluoro, methoxy, methylsulfony! or nitrile; each Rj is independently: phenyl. morpholino, pyridinyl, pyrimidinyl, pyrrolylidinyl, 2,5-pyrrolidin-dionyl, imidazolyl, pyrazolyl. each of the aforementioned is optionally substituted with one to three C,.; alkyl which is optionally partially or fully halogenated, halogen, oxo, hydroxy, nitrile and C3 alkyloxy optionally partially or fully halogenated; :

   Ci. alkyl or C,.3 alkoxy optionally partially or fully halogenated or optionally substituted with Ry7; ORjg or C,.; alkyl optionally substituted with OR i; amino or mono- or di-(C;-3 alkyl)amino optionally substituted with Ro;

   R20C(O)N(R3))-. R220- : Ry;:R1NC(0O)-: Ra26CH2C(O)N(R4)- or R24C(O)CHaN(R2))-: C,_ alkenyl substituted by R33R24NC(O)-: or Cy4 alkynyl substituted with pyrroldinyl or pyrrolyl; and R»; and Ry, taken together optionally form morpholino.

   21. The compound according to claim 20 wherein G is phenyl, pvridinyl, pyridonyl, naphthyl. quinolinyl, isoquinolinyl. dihydrobenzofuranyl, indanyl, indolinyl. indolonyl, or indolinony! . wherein G is substituted by one or more R;, R; or Rs; Ar is 1-naphthyl; X is: phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl; Y is: a bond or -CH;-, -CH,CH>-, -C(0)-, -O-, -S-, -NH-CH,CH,CH,- . -N(CH3)-, or -NH-; each R, is independently: Css alkyl optionally partially or fully halogenated, and optionally substituted with phenyl;

   cyclopropyl. cyclopentanyl. cyclohexanyl and bicyclopentanyl optionally substituted with one to three methyl groups optionally partially or fully halogenated. CN. hydroxymethyl or phenyl: or 2-tetrahvdrofurany! substituted by methyl; or trimethyl silyl: 3 each Rj; is independently: phenyl. morpholinyl, pyridinyl, pyrimidinyl. pyrrolylidinyl, 2,5-pyrrolidin-dionyl, imidazolyl or pyrazolyl, wherein any of the aforementioned is optionally substituted with

   C;. alkyl which is optionally partially or fully halogenated; Ci; alkyl or C,.; alkoxy each being optionally partially or fully halogenated or optionally substituted with diethylamino; ORyz or Cy; alkyl optionally substituted with ORs; amino or mono- or di-(C,.; alkyl)amino optionally substituted with Rg; CH;C(O)NH-. R20- ; R23R24NC(0)-; R26CH2C(O)N(R3))- or RyC(O)CHN(Ry))-;

   ~Cy.4alkenyl substituted by R23R24NC(O)-; or

   C,.4 alkynyl substituted with pyrroldinyl or pyrrolyl; Ryzand Ry are H or Ry; and Raq taken together optionally form morpholino; and R26 1s morpholino.

   22. The compound according to claim 21 wherein Gis phenyl. pyridinyl or naphthyl wherein G is substituted by one or more R,. R> or Rj; X is: imidazolyl or pyridinyl: Y is: -CH,.. -NH-CH,CH,CH,- or -NH-; Z is morpholino; each R, is independently: tert-butyl, sec-butyl. tert-amyl or phenyl; R; is chloro; Rs is independently: methyl, methoxy. methoxymethyl, hydroxypropyl. acetamide. morpholino or morpholinocarbonyl.

   23. The compound according to claim 22 wherein X is pyridinyl.

   24. The compound according to claim 23 wherein the pyridinyl is attached to Ar via the 3-pyridinyl position.

   25. A compound of the formula (III):

   w o. M_ _Ar—x—v—z =o H (Ii) wherein: E is carbon or a heteroatom group chosen from -O-. -NH- and -S-: Gis: to an aromatic Ce. carbocycle or a nonaromatic Cj.jocarbocycle saturated or unsaturated; a 6-14 membered monocyclic. bicyclic or tricyclic heteroaryl containing 1 or more heteroatoms chosen from O, N and S; a 6-8 membered monocyclic heterocycle containing one or more heteroatoms chosen from O,N and S; or : an 8-11 membered bicyclic heterocycle. containing one or more heteroatoms chosen from O, N and S;

   20 . wherein G is optionally substituted by one or more Ry, Ry or Rj; Ar is: phenyl, naphthyl, quinolinyl, isoquinolinyl. tetrahydronaphthyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, benzimidazolyl, benzofuranyl, dihydrobenzofurany!, indolinyl, benzothienyl, dihydrobenzothienyl, indanyl. indenyl or indolyl each being optionally substituted by one or more Ry or Rs; Xis:

   a Cs.g cycloalkyl] or cycloalkenyl optionally substituted with one 10 two oxo groups or one to three C4 alkyl.

   C4 alkoxy or Ci alkylamino chains each being branched or unbranched:

   aryl, furanyl. thienyl. pyrrolyl. pyrazolyl. imidazolyl. pyridinyl, pyrimidinyl. pyridinonyl. dihydropyridinonyl. maleimidyl, dihydromaleimidyl, piperdinyl, benzimidazole. 3H- imidazo[4.5-b]pyridine. piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C;_4alkyl, C,4alkoxy. hvdroxy. nitrile, amino, mono- or di-(C,.; alkyl)amino, mono- or di-(C,_; alkylamino)carbonyl.

   NH,C(O), Cy.¢ alkyl-S(O)n, or halogen; Y is: a bond or a C,, saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more C atoms are optionally replaced by O, N, or S(O) and wherein Y is optionally independently substituted with one to two oxo groups, nitrile. phenyl! or one or more C,_; alky! optionally substituted by one or more halogen atoms;

   Z is: aryl, heteroaryl selected from pyridinyl, piperazinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl. triazolyl, tetrazolyl, furanyl, thienyl and pyranyl, heterocycle selected from tetrahydropyrimidonyl, cyclohexanonyl, cyclohexanolyl, 2-oxa- or 2-thia-

   S5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl. tetramethylene sulfidyl, tetramethylene sulfoxidyl or tetramethylene sulfonyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3- dioxanonyl, 1.4-dioxanyl, morpholino, thiomorpholino, thiomorpholino sulfoxidyl, thiomorpholino sulfonyl, piperidinyl, piperidinony), pyrrolidinyl and dioxolanyl,

   each of the aforementioned Z are optionally substituted with one to three halogen, C, alkyl, C,.¢ alkoxy.

   C,_; alkoxy-C,.3 alkyl, C,.¢ alkoxycarbonyl, aroyl, C,.;acyl, oxo,

   hydroxy, pyridinyl-C,_; alkyl. imidazolyl-C.; alkyl. tetrahydrofuranyl-C,; alkyl. nitrile-

   Cj.3 alkyl. nitrile. carboxy. phenyl wherein the phenyl ring is optionally substituted with one to two halogen. Cy. alkoxy, hydroxy or mono- or di-(C,.; alkyl)amino. Cc alkyl- S(O), or phenyl-S(O),, wherein the phenyl ring is optionally substituted with one to two halogen. Cy. alkoxy. hydroxy. halogen or mono- or di-(C,_; alkyl)amino; or Z is optionally substituted with one to three amino or amino-C,.; alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC).salkyl. C, alkyl. arylCo.alkyl, Cis alkoxyCi; alkyl, C,_salkoxy. aroyl, Cj3acyl, C.3alkyl-S(O)y- or arylCo.3alkyl-S(O)n- each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C, alkyl or C,. alkoxy; or Z is optionally substituted with one to three aryl. heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen, Cis alkyl or C4 alkoxy; or Zis hydroxy. halogen, nitrile, amino wherein the N atom is optionally independently mono- or di-substituted by C,.3acyl, C.¢alkyl or C;_zalkoxyC,_;alkyl, C,salkyl branched or unbranched, C;.salkoxy, C3acylamino, nitrileC; alkyl, C.¢ alkyl-S(O)y,, and phenyl- S(O)m, wherein the phenyl ring is optionally substituted with one to two halogen, C, alkoxy, hydroxy or mono- or di-(C,.3 alkvl)amino; each R, is independently: Ci-10 alkyl branched or unbranched optionally partially or fully halogenated, wherein one or more C atoms are optionally independently replaced by O, N or S(O). and wherein said Cy.)p alkyl is optionally substituted with one to three Cs.) cycloalkyl, hydroxy, oxo, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidiny!, imidazolyl, pyrazolyl, thienyl, furyl, dioxolanyl, isoxazolyl or isothiazolyl; each of the aforementioned being optionally substituted with one to five groups selected from halogen, C,_ alkyl which is optionally partially or fully halogenated, C;_3 cycloalkanyl, Css cycloalkenyl, hydroxy. nitrile, C,.; alkoxy which is optionally partially or fully halogenated or NH>C(O). mono- or di(C,.:alkyl)amino. and mono- or di(C,.salkyl)aminocarbonyl: or R; is cyclopropyloxy. cyclobutyloxy. cyclopentyloxy. cyclohexyloxy, or cycloheptyloxy each being optionally partially or fully halogenated and optionally substituted with one to three

   C,.3 alkyl groups optionally partially or fully halogenated. nitrile, hydroxyC,.;alkyl or aryl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O)m. CHOH. >C=0, >C=S or NH; phenyloxy or benzyloxy each being optionally partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups optionally partially or fully halogenated, nitrile. hydroxyC,.;alkyl or aryl; or an analog of such cycloary! group wherein one to two ring methyne groups are independently replaced by N; cyclopropyl, cyclobutyl. cyclopentyl. cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C,3 alkyl! optionally partially or fully halogenated, nitrile, hydroxyC,.jalkyl or aryl; or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S(O), CHOH, >C=0, >C=S or NH;

   Cj.10 branched or unbranced alkenyl each being optionally partially or fully halogenated, and optionally substituted with one to three C,_s branched or unbranched alkyl, phenyl. naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl, each of the aforementioned being substituted with one to five halogen, C6 alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl. bicyclohexany! and bicycloheptanyl, hydroxy, nitrile, C3 alkyloxy which is optionally partially or fully halogenated, NH,C(O), mono- or di(C,.

   salkyl)aminocarbonyl: the Cs.io branched or unbranced alkenyl! being optionally interrupted by one or more heteroatoms chosen from O. N and S(O), cyclopentenyl, cyclohexenyl. cyclohexadienyl. cycloheptenyl, cycloheptadieny]. bicyclohexenyl or bicycloheptenyl, wherein such cycloalkenyl group is optionally substituted with one to three C,.; alkyl groups; oxo, nitrile, halogen; silyl containing three C4 alkyl groups optionally partially or fully halogenated: or

   Cs. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH or S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups. hydroxy, pyrroldinyl, pyrrolyl, tetrahydropyranyl, one or more C, alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or mono- or di(C;.3alkvi)amino optionally substituted by one or more halogen atoms; each Ry. Ry, and Rs is a Cy. branched or unbranched alkyl optionally partially or fully halogenated. C,_gacvl, aroyl, C,.4 branched or unbranched alkoxy, each being optionally partially or fully halogenated. halogen, methoxycarbonyl, C.3 alkyl-S(O)r, optionally partially or fully halogenated, or phenyl-S(O)pm; : ORs, C,.6 alkoxy, hydroxy, nitrile, nitro, halogen; or amino-S(0),- wherein the N atom is optionally independently mono- or di-substituted by Ciealkyl or arylCy.zalkyl, or amino wherein the N atom is optionally independently mono- or di-substituted by C, alkyl, arylCq.;alkyl, C,.¢acyl, Cy.¢alkyl-S(O)n- or arylCy.

   3alkyl-S(O)n-. each of the aforementioned alkyl and aryl in this subparagraph are optionally partially or fully halogenated and optionally substituted with one to two C4 alkyl or C,.¢ alkoxy:

   each R; is independently: phenyl, naphthyl, morpholino, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyi, pyrrolidinyl, imidazolyl. pyrazolyl. thiazolyl. oxazoyl, [1,3,4]oxadiazol. triazolyl,

   tetrazolyl, thienyl, furyl. tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl. indolyl. benzimidazolyl. benzofuranyl. benzoxazolyl, benzisoxazolyl. benzpyrazolyl, benzothiofuranyl. cinnolinyl. pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, each of the aforementioned is optionally substituted with one to three phenyl, naphthyl, heterocycle or heteroaryl as hereinabove described in this paragraph, C,.¢ branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C,_; alkyl, naphthyl C,.s alkyl, halogen, hydroxy, oxo. nitrile, C,.; alkoxy optionally partially or fully halogenated, phenyloxy. naphthyloxy. heteroaryloxy or heterocyclicoxy wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C,_zalky)lamino, phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl heterocyclic moiety is as hereinabove described in this paragraph.

   NH,C(O), a mono- or di-(C,;_salkyl) aminocarbonyl, C,_s alkyl-C(O)-C, alkyl, amino-C,_s alkyl. mono- or di-(C,.salkyl)amino. mono- or di-(C,.

   salkyl)amino-C,.s alkyl. amino-S(O),, di-(C;.;alkyl)amino-S(O),, R7-C,.; alkyl, Rg-C;.s alkoxy, Re-C(O)-C, 5 alkyl, Rjo-C.s alkyl(Ry})N, carboxy-mono- or di-(C;.salkyl)-amino; a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidiny], cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl,

   cyclopentanopyridazinyl. cyclohexanopyridazinyl. cyclopentanoquinolinyl. cyclohexanoquinolinyl. cyclopentanoisoquinolinyl. cyclohexanoisoquinolinyl, cyclopentanoindolyl. cyclohexanoindolyl. cyclopentanobenzimidazolyi. cyclohexanobenzimidazolyl. cyclopentanobenzoxazolyl. cyclohexanobenzoxazolyl.

   cyclopentanoimidazolyl. cyclohexanoimidazolyl. cyclopentanothienyl and cyclohexanothienyl: wherein the fused aryl or fused heteroaryl ring is independently substituted with zero to three phenyl. naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl. imidazolyl, pyrazolyl. thienyl, furyl. isoxazolyl, isothiazolyl, C, alkyl which is optionally partially or fully halogenated. halogen, nitrile, C,.3 alkyloxy which is optionally partially or fully halogenated, phenyloxy. naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph. nitro. amino. mono- or di-(C).3alkyl)amino, phenylamino. naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, NH,C(Q), mono- or di-(C,.

   1s salkyhaminocarbonyl, C,4 alkyl-OC(O). C,.s alkyl-C(0)-C 4 alkyl, amino-C,.s alkyl, mono- or di-(Cy.3)alkylamino-C,s alkyl, Rj-C).s alkyl, Ri3-C).s alkoxy, R;4-C(O)-C,.5 alkyl or R|5-C.s alkyl(R,6)N; cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl,

   bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, each being optionally be partially or fully halogenated and optionally substituted with one to three C,.; alkyl groups. or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S, CHOH, >C=0, >C=S or NH;

   cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C,.; alkyl groups;

   Ci4 alkyl-phenyl-C(O)-C, alkyl-, C4 alkyl-C(0)-C, 4 alkyl- or C4 alkyl-phenyl-

   S(O)u-Ci4 alkyl-;

   C).6 alkyl or C,_ branched or unbranched alkoxy each of which is optionally partially or fully halogenated or optionally substituted with Rs; OR 3 or Cy. alkyl optionally substituted with ORs; 3 amino or mono- or di-(C,.salkyl)amino optionally substituted with Rg; R2oC(O)N(R2))-, R220- or R23R2aNC(O0)-: R26(CH)mC(OIN(R21)-, R23R2aNC(O)-C;. salkoxy or RasC(O)(CHa)mN(R21)-:

   Cs.salkenyl substituted by Ry3R24NC(O)-;

   C,.¢ alkynyl branched or unbranched carbon chain, optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH, S(O)m and wherein said alkynyl group is optionally independently substituted with one to two oxo groups, pyrroldinyl, pyrrolyl, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl one or more C4 alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or mono- or di(C4 alkyl)amino optionally substituted by one or more halogen atoms;

   C,.-¢acyl or aroyl; Rgis a: :

   C).a alkyl optionally partially or fully halogenated and optionally substituted with Ry; each Ry, Rg, Ro, Rig, Riz, Riz. Ris, Ris, Ry, Ris, R25 and Rye is independently: nitrile, phenyl, morpholino. piperidinyl, piperazinyl, imidazolyl, pyridinyl, tetrazolyl, amino or mono- or di-(C;salkyl)amino optionally partially or fully halogenated;

   each Ry; and Ry is independently: hydrogen or C,_, alkyl optionally partially or fully halogenated; Ris is independently: hydrogen or a C4 alkyl optionally independently substituted with oxo or Ras; R20 1s independently:

   Ci.10 alkyl optionally partially or fully halogenated. phenyl, or pyridinyl; Ry) is independently: hydrogen or C,_; alkyl optionally partially or fully halogenated; each Rj;, R); and Ras is independently: hydrogen, C; alkyl optionally partially or fully halogenated, said C4 alkyl is optionally interrupted by one or more O, N or S, said C,.¢ alkyl also being independently optionally substituted by mono- or di-(C.;alkyl)aminocarbonyl, phenyl, pyridinyl, amino or mono- or di-(Cy4alkyl)amino each of which is optionally partially or fully halogenated and optionally substituted with mono- or di-(C,.;alkyl)amino; or Rz3 and Ry4 taken together optionally form a heterocyclic or heteroaryl ring; m=0,1or2; Wis OorS and pharmaceutically acceptable derivatives thereof.

   26. The compound according to claim 25 wherein: Eis -CH;-, -NH- or -O-;

   W is O and Gis: phenyl. naphthyl. benzocyclobutany!. dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl, benzocycloheptenyl. indanyl, indenyl; pyridinyl, pyridony!, quinolinyl, dihydroquinolinyl, tetrahydroquinoyl. isoquinolinyl, tetrahydroisoquinoyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzthiazolyl, benzooxazolyl, benzofuranyl, benzothiophenyl, benzpyrazolyl, dihydrobenzofuranyl, dibenzofurany!, dihydrobenzothiophenyl, benzooxazolonyl, benzo[1,4]oxazin-3-onyl, benzodioxolyl, benzo{1,3]dioxol-2-onyl, benzofuran-3-onyl, tetrahydrobenzopyranyl, indolyl, 2.3-dihydro-1H-indolyl, indolinyl. indolonyl, indolinonyl, phthalimidyl; oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, morpholino, tetrahydropyranyl, dioxanyl, tetramethylene sulfonyl, tetramethylene sulfoxidyl, oxazolinyl, 3,4-dihydro-2H-benzo{1,4Joxazinyl, thiazolinyl. imidazolinyl, tertrahydropyridinyl, homopiperidinyl, pyrrolinyl, tetrahydropyrimidinyl, decahydroquinolinyl, decahydroisoquinolinyl, thiomorpholino, thiazolidinyl, dihydrooxazinyl, dihydropyranyl, oxocanyl, heptacanyl, thioxanyl or dithianyl; wherein G is optionally substituted by one or more Ri, R; or Rs.

   27. The compound according to claim 26 wherein Eis -NH-; G is phenyl, pyridinyl, pyridonyl, naphthyl, quinolinyl. isoquinolinyl, pyraziny], benzimidazolyl, benzooxazolyl. benzooxazolonyl, benzofuranyl, benzothiophenyl, benzpyrazolyl. dihydrobenzofuranyl. dihydrobenzothiophenyl, 3,4-dihydro-2H-

   benzo[1.4Joxazinyl. indanyl. indenyl. indolyl. indolinyl. indolonyl. 2.3-dihydro-1H- indotyl or indolinonyl. wherein G is optionally substituted by one or more R,. R, or Rj:

   Ar is:

   naphthyl. quinolinyl, isoquinolinyl, tetrahydronaphthyl. tetrahydroquinolinyl, tetrahydroisoquinolinyl. indanyl. indenyl or indolyl each being optionally substituted by one or more Ry or Rs groups:

   X is: phenyl, furanyl. thienyl, pyrrolyl, pyrazolyl. imidazolyl, pyridiny], pyrimidinyl, pyridinonyl, dihydropyridinony!, maleimidyl, dihydromaleimidyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl; each being optionally independently substituted with one to three C,4 alkyl, C,4alkoxy, hydroxy. nitrile, amino, mono- or di~(C;.3 alkyl)amino, mono- or di-(C,.3 alkylamino)carbonyl, NH,C(O), C,.¢ alkyl-S(O)r, or halogen;

   Y is: ‘a bond or a C4 saturated or unsaturated carbon chain wherein one or more of the C atoms is optionally replaced by O, N, or S(O) and wherein Y is optionally independently substituted with one to two oxo groups, nitrile, phenyl or one or more C4 alkyl optionally substituted by one or more halogen atoms;

   Zis:

   phenyl, heteroaryl selected from pyridinyl, piperazinyl, pyrimidinyl, pyridazinyl,

   pyrazinyl, imidazolyl. furanyl, thienyl and pyranyl, heterocycle selected from 2-oxa-5-

   aza-bicyclo[2.2.1]heptanyl. tetrahydropyrimidonyl. pentamethylene sulfidyi. pentamethviene sulfoxidyl. pentamethylene sulfonyl. tetramethylene sulfidyl. tetramethylene sulfoxidy! tetramethylene sulfonyl. tetrahydropyranyl. tetrahydrofurany!.

   1.3-dioxolanonyl, 1.3-dioxanonyl. 1.4-dioxanyl. morpholino. thiomorpholino. thiomorpholino sulfoxidyl. piperidinyl. piperidinonyl. dihydrothiazolyl. dihydrothiazolyl sulfoxidyl, pyrrolidinyl and dioxolanyl which are optionally substituted with one to three nitrile, C, 5 alkyl, C,.3 alkoxy. amino. mono- or di-(C,.; alkyl)amino. CONH; or OH; or Z is optionally substituted by phenyl. heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen, C3 alkyl or C3 alkoxy: or Z is nitrile, nitrileC,.3 alkyl. Cy alkyl-S(O)m. halogen, hydroxy. C,.; alkyl, C,.; acylamino, C4 alkoxy, amino. mono- or di-(C,.3 alkyl)aminocarbonyl. or amino mono or di-substituted by aminoC, alkyl or C;_;alkoxyC,_;alkyl; each R, is independently:

   Ci. alkyl branched or unbranched optionally partially or fully halogenated. wherein one or more C atoms are optionally independently replaced by O, N or S(O), and wherein said C, alkyl is optionally substituted with one to three C;.scycloalkyl, oxo, phenyl, dioxolanyl, pyrrolidinyl, furyl, isoxazolyl or isothiazolyl: each of the aforementioned being optionally substituted with one to three groups selected from halogen, C.; alkyl which is optionally partially or fully halogenated, hydroxy, nitrile and C,.;alkoxy which is optionally partially or fully halogenated; : cyclopropyl, cyclobutyl, cyclopentanyl. cyclohexanyl, bicyclopentanyl! or bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C;_; alkyl groups optionally partially or fully halogenated, nitrile, hydroxyC,_salkyl or phenyl: or an analog of such cycloalkyl group wherein one to three ring methylene groups are independently replaced by O, S, CHOH, >C=0, >C=S or NH;

   0X0;

   Cj. alkynyl branched or unbranched carbon chain optionally partially or fully 5s halogenated. wherein one or more methylene groups are optionally replaced by O. NH or S(O)m and wherein said alkynyl group is optionally independently substituted with one to two 0x0 groups. hydroxy, pyrroldinyl. pyrrolyl. tetrahydropyranyl, C,.; alkyl optionally substituted by one or more halogen atoms. nitrile. morpholino, piperidinyl, piperaziny!. imidazolyl, phenyl, pyridinyl. tetrazolyl. or mono- or di(C,.3alkyl)amino optionally substituted by one or more halogen atoms; or silyl containing three C)4 alkyl groups optionally partially or fully halogenated; R; is independently: a C,_s branched or unbranched alky! optionally partially or fully halogenated, acetyl. aroyl, C,.4 branched or unbranched alkoxy, each being optionally partially or fully halogenated, halogen, methoxycarbonyl, C,. alkyl-S(O), optionally partially or fully halogenated, or phenyl-S(O)m;

   C,.3 alkoxy, hydroxy, nitrile, nitro, halogen; or amino-S(O),,- wherein the N atom is optionally independently mono- or di-substituted by C,.alkyl or arylCy alkyl, or amino wherein the N atom is optionally independently mono- or di-substituted by C,.zalkyl. arylCo_alkyl, C.sacyl, C,4alkyl-S(O)n- or arylC. 3alkyl-S(O)n-, each of the aforementioned alkyl and aryl in this subparagraph are optionally partially or fully halogenated and optionally substituted with one to two C;3 alkyl or C, ; alkoxy;

   R; is independently: phenyl. morpholino. pyridinyl. pyrimidinyl, pyrazinyl. pyrrolyl. pyrrolidinyl. imidazolyl.

   [l.3.4]oxadiazol, pyrazolyl. cach is optionally substituted with one to three phenyl, naphthyl. heterocycle or heteroaryl as hereinabove described in this paragraph. C; alkyl which is optionally partially or fully halogenated, cyclopropanyl, cyclobutanyl. cyclopentanyl. cyclohexanyl, cycloheptanyl. bicyclopentanyl, bicyclohexanyl. bicycloheptanyl, phenyl Cys alkyl. naphthyl Cys alkyl. halogen, oxo, hydroxy. nitrile, C3 alkoxy optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy or heterocyclicoxy wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph. nitro, amino. mono- or di-(C,3alkyl)amino. phenylamino, naphthylamino, heteroaryl or heterocyclic amino wherein the heteroaryl or heterocyclic moiety is as hereinabove described in this paragraph, NH,C(O), a mono- or di~(C,. salkyl)aminocarbonyl, C,.5 alkyl-C(O)-C, alkyl, mono- or di-(C;.3alkyi)amino, mono- or di-(C,.3)alkylamino-C,_s alkyl, mono- or di-(C,_alkyl)amino-S(O),, R;-C,.s alkyl, Rg-C.s alkoxy, Ro-C(0O)-C,.s alkyl, Rj¢-C).s alkyl(R{()N, carboxy-mono- or di-(C,.s)-alkyl- amino; Ci alkyl or C4 alkoxy each being optionally partially or fully halogenated or optionally substituted with Ry; ORs or Cy.6 alkyl optionally substituted with OR 3; amino or mono- or di- (C,-; alkyl)amino optionally substituted with Ro; : R20C(O)N(R21)-, R220- ; R233R2aNC(O)-; Ra6CH2C(O)N(R21)-, R23R24NC(O)-C). alkoxy or R;C(O)CH2N(Ry))-;

   Cy.salkenyl substituted by R23R4NC(O)-; or

   Cs. alkynyl branched or unbranched carbon chain optionally partially or fully halogenated wherein one of the methylene groups is optionally replaced by O. and optionally independently substituted with one to two oxo groups, pyrroldinyl. pyrrolyl. morpholino, piperidinyl, piperazinyl. imidazolyl. phenyl. pyridinyl, tetrazolyl or one or more C4 alkyl optionally substituted by one or more halogen atoms:

   Ci.zacyl; and Ry; and Ry, taken together optionally form imidazolyl. piperidinyl. morpholino, piperazinyl or a pyridinyl ring.

   28. The compound according to claim 27 wherein: Gis phenyl, pyridinyl, pyridonyl, naphthyl. quinolinyl, isoquinolinyl, pyrazinyl, 3.4-dihydro- 2H-benzo[1,4]oxazinyl, benzothiophenyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, benzooxazolyl, indanyl, indolyl. indolinyl. indolonyl or indolinony!, wherein G is -optionally substituted by one or more R;. R; or Rs; Ar is naphthyl; X is phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperdinyl, piperazinyl, pyridazinyl or pyrazinyl each being optionally independently substituted with one to three C)4alkyl, C). aalkoxy, hydroxy, nitrile, amino, mono- or di~(C;.3 alky})amino, mono- or di-(C;.3 alkylamino)carbonyl, NH,C(O), C\.¢ alkyl-S(O) or halogen; Y is: abondor a C,, saturated carbon chain wherein one or more of the C atoms is optionally replaced by O. N or S and wherein Y is optionally independently substituted with nitrile or oxo: Zis: phenyl. pyridinyl. pyrimidinyl, pyridazinyl. pyrazinyl. imidazolyl, dihydrothiazolyl. dihydrothiazoly] sulfoxide, pyranyl, pyrrolidinyl. phenylpiperazinyl. tetrahydropyranyl. tetrahydrofuranyl. dioxolanyl, 2-oxa-3-aza-bicyclo[2.2.1]heptanyl. morpholino, thiomorpholino, thiomorpholino sulfoxidyl. piperidinyl, piperidinonyl, piperazinyl or tetrahydropyrimidonyl each of which are optionally substituted with one to two C,. alkyl or C.» alkoxy; or Z is hydroxy, C, ; alkyl, C, ; alkoxy. C,, acylamino, C, ; alkylsulfonyl, nitrile C,, alkyl or amino mono or di-substituted by C, ; alkoxyC, ; alkyl; each R; 1s independently:

   C.s alkyl branched or unbranched optionally partially or fully halogenated, wherein one or more C atoms are optionally independently replaced by O, N or S(O)m, and wherein said C,.s alkyl is optionally substituted with oxo. dioxolanyl, pyrrolidinyl, furyl or phenyl each optionally substituted with one to three halogen, C,.3 alkyl which is optionally partially or fully halogenated. hydroxy, nitrile and C,.3alkoxy which is optionally partially or fully halogenated; cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or : bicyclohexanyl, each being optionally partially or fully halogenated and optionally substituted with one to three C3 alkyl] groups optionally partially or fully halogenated, nitrile, hydroxyC,.;alkyl or phenyl; and an analog of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, bicyclopentanyl or bicyclohexanyl wherein one ring methylene group is replaced by O;

   0X0;

   C,. alkynyl optionally partially or fully halogenated wherein one or more methylene groups are optionally replaced by O. and optionally independently substituted with one to two oxo groups, hydroxy. pyrroldinyl. pyrrolyl. tetrahydropyranyl. C,_ alkyl optionally substituted by one or more halogen atoms. nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl. tetrazolyl. or mono- or di(C,.;alkyl)amino optionally substituted by one or more halogen atoms; or : silyl containing three C,.; alkyl groups optionally partially or fully halogenated, each Ris independently: a C4 alkyl optionally partially or fully halogenated, C,4 alkoxy optionally partially or fully halogenated, bromo, chloro, fluoro. methoxycarbonyl, methyl-S(O)m, ethyl-S(O)m each optionally partially or fully halogenated or phenyl-S(O),,; or R, is mono- or di-C, ;acylamino, amino-S(O),, or S(O), amino wherein the N atom is mono- or di-substituted by C, alkyl or phenyl, nitrile, nitro or amino; each R; is independently: phenyl, morpholino, pyridinyl, pyrimidinyl, pyrrolidinyl, 2,5-pyrrolidin-dionyl, imidazolyl, [1,3,4Joxadiazol, pyrazolyl. each of the aforementioned is optionally substituted with one to three C).; alkyl which is optionally partially or fully halogenated, halogen, oxo, hydroxy, nitrile and C,.; alkoxy optionally partially or fully halogenated; Cy alkyl or Cy 3 alkoxy optionally partially or fully halogenated or optionally substituted withR;y;

   OR 3 or C.; alkyl] optionally substituted with OR 5: amino or mono- or di-(C;-3 alkyl)amino optionally substituted with Ry; R20C(OIN(R;1)-. R220- ; R233R2uNC(O)-: Ra¢CHaC(O)N(R2:)-. NH>C(O)methoxy or R,6C(O)YCH:N(Ray )-: Cas alkenyl substituted by R;R24NC(O)-: or

   C,.4 alkynyl substituted with pyrroldinyl or pyrrolyl:

   Ci.zacyl and Rs; and Ry, taken together optionally form morpholino.

   29. The compound according to claim 28 wherein G is phenyl, pyridinyl, pyridonyl, 2-naphthyl. quinolinyl, isoquinolinyl, dihydrobenzofuranyl, indanyl, 5-indolyl, 3-0xo0-3.4-dihydro-2H-benzo[1,4]oxazin-8-yl, benzooxalolyl, 2,3-dihydrobenzooxazol-7-yl, 2-oxo0-2,3-dihydro-1H-indol-5-yl, indolinyl, indolonyl, or indolinonyl . wherein G is optionally substituted by one or more R;, R; or Rs; Ar is 1-naphthyl; Xis: phenyl, imidazolyl, pyridinyl, pyrimidinyl, piperdinyl, piperazinyl, pyridaziny! or pyrazinyl; Y is:

   a bond or -CH,-, -CH;CH;-. -C(O)-. -O-. -S-, -NH-CH,CH,CH;- . -N(CHj)-. CH, (CN)CH,-NH-CH, or -NH-; Zis morpholino. dioxolanyl. tetrahydrofuranyl. pyridinyl, 2-oxa-5-aza- bicyclo[2.2.1]heptanyl. C,_;alkoxyphenylpiperazinyl, hydroxy. C\.;alkyl, N,N-diC,.;alkoxyC,.;alkylamino, C,.;acylamino. C, salkylsulfony! or nitrileC,_alkyl; each R; is independently:

   Ci.s alkyl optionally partially or fully halogenated wherein one or more C atoms are optionally independently replaced by O or N, and wherein said Cs alkyl is optionally substituted with oxo, dioxolanyl, pyrrolidinyl, furyl or phenyl optionally substituted by

   C,.;alkoxy; cyclopropyl. cyclopentanyl, cyclohexanyl and bicyclopentanyl optionally substituted with one to three methyl groups optionally partially or fully halogenated, nitrile, hydroxymethyl or phenyl; or 2-tetrahydrofuranyl substituted by methyl; or trimethyl silyl; propynyl substituted hydroxy or tetrahydropyran-2-yloxy; Ry is is mono- or di-C,.;acylamino, amino-S(O),, or S(O), amino wherein the N atom is mono- or di-substituted by C,_salky! or phenyl. bromo, chloro. fluoro, nitrile, nitro, amino, methylsulfonyl optionally partially or fully halogenated or phenylsulfonyl; each Rj; is independently:

   phenyl. morpholino. pyridinyl. pyrimidinyl. pyrrolidinyl. 2.5-pyrrolidin-dionyl. imidazolyl. [1.3.4]oxadiazol or pyrazolyl. each is optionally substituted with C,.; alky] which is optionally partially or fully halogenated:

   Ci. alkyl or C,.; alkoxy each being optionally partially or fully halogenated or optionally substituted with diethylamino; OR z or C,.; alkyl optionally substituted with OR: amino or mono- or di-(C,.; alkyl)amino optionally substituted with Ro; CH; C(O)NH-, R2;0- ; R23R24NC(0)-; R26CH2C(O)N(Ra2))-. NH,C(O)methoxy or R26C(O)CH N(R21)-; i5 Cyaalkenyl substituted by R23R24NC(O)-; or

   Ca. alkynyl substituted with pyrroldinyl or pyrrolyl;

   C,.2acyl; and R33 and Ry4 are H or Ry; and Raq taken together optionally form morpholino; and Rj¢ is morpholino.

   30. The compound according to claim 29 wherein Gis phenyl, pyridinyl, 5-indolyl, 3-ox0-3.4-dihydro-2H-benzo(1,4]}oxazin-8-yl, benzooxalolyl, 2,3-dihydrobenzooxazol-7-yl, 2-0x0-2,3-dihydro-1H-indo}-5-yl or 2- naphthyl wherein G is optionally substituted by one or more R;, R; or Ry;

   X is: imidazolyl, pyridinyl. pyrimidinyl or pyraziny!; Y is: a bond. CH»(CN)CH;-NH-CHa. -CH--. -NH-CH>CH>CH,- or -NH-: Z is morpholin-4yl. dioxolan-2yl. tetrahydrofuranyl, pyridinyl. 2-oxa-5-aza- bicyclo[2.2.1]hept-5yl. methoxyphenyipiperazinyl. hydroxy. methyl. N.N- dimethoxyethylamino. acetylamino. methylsulfonyl or cyanoethyl, each R, is independently: tert-butyl, sec-butyl, tert-amyl, phenyl. terrahydropyran-2-yloxypropynyl, hydroxypropynyl, trihalomethyl, 2,2-diethylpropionyl or cyclohexanyl; R; is chloro, nitro, amino, nitrile. methylsulfonylamino, diacetylamino, phenylsulfonylamino, N,N-di(methylsulfonyl)amino. methylsulfonyl or trihalomethylsulfonyl; R; is independently: methyl, C,_; alkoxy, methoxymethyl., hydroxypropyl, dimethylamino. C,.qalkylamino. NH,C(O)methoxy, acetyl, pyrrolidinyl, imidazolyl, pyrazolyl, morpholino or morpholinocarbonyl. :

   31. The compound according to claim 30 wherein X is pyridinyl.

   32. The compound according to claim 31 wherein the pyridinyl is attached to Ar via the 3-pyridinyl position.

   33. A compound selected from: 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl1}-3-[4-(4-(morpholin-4-yI- methyl)phenyl)naphthalen-1-vljurea:

   1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-y1]-3-[4-(4-(2-(morpholin-4-

   ylethyl)phenyl)naphthalen-1-yljurea: 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl1]-3-{4-(3-(morpholin-4-yl-

   methyl)phenyl)naphthalen-1-yl]urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yhnaphthalen-1-yl]urea;

   1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(5-morpholin-4-ylmethyl-pyridin-2- yl)naphthalen-1-yl}urea; 1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(5-morpholin-4-ylmethyl-fur-2- yDnaphthalen-1-yljurea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)naphthalen-1-yljurea; 1-[S-tert-butyl-2-methyl-2H-pyrazol-3-yl}-3-[4-(6-morpholin-4-yimethyl-pyridin-3-

   yl)naphthalen-1-yljurea 1-[5-tert-butyi-2-p-tolyl-2H-pyrazol-3-yl]}-3-[4-(5-(morpholin-4-yl-methyl)pyridin-2-yl)- naphthalen-1-yl]-urea;

   1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3-yl)- naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(2-(pyridin-2- yl)ethylamino)cyclohexenyl)-naphthalen-1-yl}-urea;

   1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(4-(pyridin-3-yl- methylaminomethyl)phenyl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(morpholin-4-y|-

   40 methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(4- hydroxybutylamino)pyridin-3-yl)-naphthalen-1-yl}-urea;

   45 1-[5-tert-butyl-2-(4-methyl-3-carbamylphenyl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-y1}-3-[4-(4-(3 -hydroxypiperidin- 1-yl-methyl)phenyl)naphthalen-1-yl}-urea:

   1-[5-tert-butyl-2-( 6-methyl-pyridin-3-y1)-2H-pyrazol-3-yl]-3-[4-(4-(4-hydroxymorpholin- 4-yl-methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-( 6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(3-(morpholin-4-yl- methyl)cyclohexenyl)-naphthalen- 1-yl}-urea;

   1-[S-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(tetrahydrofuran-3-yl- methyl)-3-hydroxyphenyl)naphthalen-1 -yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N.N-di-(2-

   methoxyethyl)aminomethyl)phenyl)naphthalen-1-yl}-urea: 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(3- cyanopropoxy)pyridin-3-yl)naphthalen-1-vl}-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-y!]-3-[4-(4-morpholin-4-yl- methyl-piperdinyl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(N,N-di-(2- cyanoethyl)aminomethyl)phenyli)naphthalen-1-ylj-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(furan-2-yl-methyl)-3- hydroxyphenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(thiomorpholin-4-y}-

   methyl)phenyl)naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(3- carboxamidopiperidin-1-yl-methyl)phenyl)naphthalen-1-yl]-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(2-methyl-3-0xo0- piperzin-1-yl-methyl)phenyl)naphthalen-1-yl}-urea; 1-{S-tert-butyl-2-(2-methylpyrimidin-S-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

   40 1-{5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(4- hydroxybutyloxy)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[3-tert-butyl-1'H-[1,4']bipyrazol-5-yl]-3-[4-(6-(morpholin-4-yl-methyl)pyridin-3-

   45 yDnaphthalen-1-ylj-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-y1)-2H-pyrazol-3-yl}-3-[4-(6-(tetrahydrothiopyran- 4-yl-amino)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(2-cyanoethyl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-vl-

   methyl)pyridin-3-yl)-naphthalen-1-yl]-urea: 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(2.6- dimethylmorpholin-4-yl-methyl)pyridin-3-v1)-naphthalen-1-yl]-urea:

   1-[5-tert-butyl-2-(2-methoxypyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea: 1-[S-tert-butyl-2-(2-aminoypyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)-naphthalen-1-yl]-urea:

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(6-(morpholin-4-yl-4- carbonyl)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl1]-3-[4-(6-(2-0xa-5-aza-

   bicyclo[2.2.1]hept-5-yl-methyl)pyridin-3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(4-(N-(2-cyanoethyl)-N- (pyridin-3-yl-methyl)aminomethyl)phenyl)-naphthalen- 1-yl]-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl}-3-[4-(4-(N-(2-cyanoethyl)-N- (tetrahydrofuran-2-yl-methyl)aminomethy!)phenyl)-naphthalen-1-yl]-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-{4-(6-(morpholin-4-yl- methyl)-4-methoxypyridin-3-yl)-naphthalen-1-yl}-urea;

   1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]}-3-[4-(6-(1-morpholin-4-yl- propyl)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[3-tert-butyl-1'-methyl-1'H-[1,4']bipyrazol-5-yl}-3-[4-(6-(morpholin-4-yl-

   methyl)pyridin-3-yl)naphthalen-1-yl}-urea; 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(1-0xo0- : } tetrahydrothiopyran-4yl-amino)pyridin-3-yl)-naphthalen-1-yl}-urea;

   40 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(tetrahydropyran-4yl- amino)pyridin-3-yl)-naphthalen-1-yl}-urea; 1-{5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl1}-3-[4-(5-(tetrahydrothiopyran- 4yl-amino)pyrazin-2-yl)-naphthalen-1-yl}-urea;

   45 1-[5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-

   (methylcarbonylamino)pyridin-3-yl)-naphthalen-1-ylj-urea: 1-[3-tert-butyl-1'-(3-methylsulfanylpropyl)-1'H-[1 4]bipyrazol-5-y1}-3-[4-(6-(morpholin- 4-yl-methyl)pyridin-3-yl)naphthalen- 1 -¥1}-urea:

   1-[5-tert-butyl-2-(2-methylpyrimidin-35-yl)-2H-pyrazol-3-y1}-3-[4-(6-(1 -oxo- thiomorpholin-4-yl-methyl)pyridin-3-yl)naphthalen-1-yl]-urea;

   1 -[5-tert-butyl-2-(2-methylpyrimidin-3-y1)-2H-pyrazol-3-yl}-3-[4-(6-(tetrahydropyran-4-

   yl-amino)pyridin-3-yl)naphthalen-1-vi}-urea;

   ] -[5-tert-butyl-2-(2-methylthiopyrimidin-5-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4- yl-methyl)pyridin-3-yl)naphthalen-1-yvi]-urea;

   1-[5-tert-butyl-2-(2-aminopyrimidin-3-yl)-2H-pyrazol-3-yl]-3-[4-(6-(morpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl]-urea; 1-[3-tert-butyl-1'-methyl-1'H-[1,4'Ibipyrazol-5-yl]-3-[4-(6-(morpholin-4-yl- methyl)phenyl)naphthalen-1-yl}-urea:

   1-[S-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(1 -oxo-tetrahydrothiopyran-4-yl- amino)pyridin-3-yl)naphthalen-1-ylj-urea;

   I -[5-tert-butyl-2-p-tolyl-2H-pyrazol-3 -y1]-3-[4-(6-(thiomorpholin-4-yl-methyl)pyridin-3-

   ylnaphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(2~(morpholin-4-yl-carbonyl)pyrimidin-3- ylnaphthalen-1-yl}-urea;

   I-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl}-3-[4-(2-(morpholin-4-yl-methyl)pyrimidin-5- yhnaphthalen-1-yl}-urea; 1-[5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl]-3-[4-(6-(1-ox0-thiomorpholin-4-yl- methyl)pyridin-3-yl)naphthalen-1-yl}-urea;

   1-[5-tert-butyl-2-(2-methylpyrimidin-3-yl)-2H-pyrazol-3-yl]-3-[4-(2-(morpholin-4-yl- methyl)pyrimidin-5-yl)naphthalen-1-vi]-urea; : 1-(2-tert-Butyl-5-methyl-pyridin-4-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-

   40 naphthalen-1-yl]-urea; 1-(3-tert-Butyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]- urea;

   45 1-(4-Methyl-biphenyl-3-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-urea;

   1-(4-tert-Butyl-biphenyl-2-y1)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)-naphthalen-1- yl}-urea:

   1-(5-1sopropyl-2-methyl-phenyl)-3-{4-(6-morpholin-4-yImethyl-pyridin-3-yl)-

   naphthalen-1-ylj-urea: 1-(5-sec-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pvridin-3-yl)- naphthalen-1-yl]-urea;

   1-(5-tert-Butyl-2-methoxymethyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]j-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-yImethyl-pyridin-3-yl)-

   naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-methyl-phenyl)-3-(4- { 6-[(3-methoxy-propyl)-methyl-amino}-pyridin-3- yl}-naphthalen-1-yl)-urea;

   1-(5-tert-Butyl-2-methyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methy!-pyridin-3-yl)-3-{4-(6-morpholin-4-yimethyl-pyridin-3-yl)- naphthalen-1-yl]-urea;

   1-[5-(1,1-Dimethyl-propyl)-2-methoxy-phenyl}-3-{4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yij-urea; 1-[5-tert-Butyl-2-(1H-pyrazol-4-yl)-phenyl]-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-

   naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(2-methyl-pyrimidin-5-yl)-phenyl}-3-[4-(6-morpholin-4-ylmethyi- pyridin-3-yl)-naphthalen-1-yl]-urea;

   1-[5-tert-Butyl-2-(3-hydroxy-propyl)-phenyl}-3-[4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(morpholine-4-carbonyl)-phenyl]-3-[4-(6-morpholin-4-ylmethyi- pyridin-3-yl)-naphthalen- 1-yl}-urea;

   40 N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-ureido}-phenyl)-acetamide; 1-(3-Methyl-naphthalen-2-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1 -

   45 yl}-urea;

   N-(5-tert-Butyl-2-methoxy-3-{ 3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- }- vl]-ureido} -phenyl)-acetamide; 1-[5-tert-Butyl-3-(2.3-dihydroxy-propy1)-2-hydroxy-phenyl}-3-[4-(6-morpholin-4-

   ylmethyl-pyridin-3-vl)-naphthalen-1-yl]-urea; 1-(2.3-Dimethyl-1H-indol-5-y1)-3-[4~( 6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1-yl]-urea;

   I-{5-tert-Butyl-2-methyl-3-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl}-phenyl }-3-[4-(6- morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea;

   1 -(2-Methoxy-5-trifluoromethyl-phenyl)-3-{4-(6-morpholin-4-ylmethyi-pyridin-3-yl)- naphthalen-1-yl]-urea;

   1S 1 -[5-(2.2-Dimethyl-propionyl)-2-methyl-phenyl]-3-[4-(6-morpholin-4-yimethyl-pyridin- 3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-Butyl-3-(3-hydroxy-prop-1 -ynyl)-2-methyl-phenyl]-3-[{4-(6-morpholin-4-

   ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(3-hydroxy-prop-1-ynyl)-phenyl}-3-{4-(6-morpholin-4-ylmethyl- pyridin-3-yl)-naphthalen-1-yl]-urea;

   1-[5-tert-Butyl-3-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-2-methoxy-phenyl]-3-[4-(6- morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1 -yl]-urea; 1-[5-tert-Butyl-3-(2,3-dihydroxy-propyl)-2-methoxy-phenyl]-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea;

   1-(5-tert-Butoxy-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea; 1-[5-(1-Cyano-cyclopropyl)-2-methoxy-phenyl]-3-{4-(6-morpholin-4-ylmethyl-pyridin-

   3-yl)-naphthalen-1-yl]-urea; 1-[5-tert-Butyl-3-(2-diethylamino-ethyl)-2-methoxy-pheny!]-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)-naphthalen-1-yl]-urea;

   40 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-[1,3]dioxolan-2-yl-pyridin-3-yl)-naphthalen- 1-yl]-urea; 1-(5-tert-Butyl-2-pyrrolidin-1-yl-pheny!)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea; 45 1-(5-tert-Butyl-2-dimethylamino-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-y})-

   naphthalen-1-y1]-urea: 1-(5-tert-Butyl-2-propoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

   1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-hydroxymethyl-pyridin-3-yl)-naphthalen-1-

   yl}-urea: 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2,6-dimethyl-morpholin-4-ylmethyl)-

   pyridin-3-yl]-naphthalen-1-yl}-urea; 1-(5-Cyclohexyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea;

   1 -(2,4-Dimethoxy-5-trifluoromethyl-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-methoxy-3-nitro-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yi]-urea;

   1-(3-Amino-5-tert-butyl-2-methoxy-phenyl)-3-[4-(6-methy!-pyridin-3-yl)-naphthalen-1- ylj-urea; N-Acetyl-N-(5-tert-butyl-2-methoxy-3-{3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-

   naphthalen-1-yl}-ureido}-phenyl)-acetamide; 1-(6-tert-Butyl-4-methyl-3-oxo0-3.4-dihydro-2H-benzo(1 ,4Joxazin-8-yl)-3-[4-(6- morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-urea;

   1-(5-tert-Butyl-2-ethoxy-phenyl)-3-{4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-isopropoxy-phenyl)-3-[4-(6-morpholin-4-yimethyl-pyridin-3-yl)- naphthaien-1-yl}-urea;

   1-(5-tert-Butyl-2-imidazol-1-yl-phenyl)-3-{4-(6-morpholin-4-yImethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

   1-(5-tert-Butyl-3-ethylamino-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-

   40 3-yl)-naphthalen-1-yl}-urea; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen- 1 -

   yl]-ureido}-phenyl)-bis(methanesulfon)amide;

   45 1-[5-tert-Butyl-2-(1-methyl-1H-pyrazol-4-yl)-phenyl}-3-[{4-(6-morpholin-4-ylmethyl-

   pyridin-3-yl)-naphthalen-1-yl}-urea;

   1-(2-Methanesulfinyl-5-triflucromethyl-phenyl)-3-[{4-(6-morpholin-4-yImethyl-pyridin-3- yl)-naphthalen-1-yl]-urea:

   1-[4-(6-{[Bis-(2-methoxy-ethyl)-amino]-methyl}-pyridin-3-yl)-naphthalen-1-y1}-3-(3- tert-butyl-2-methoxy-phenyl)-urea: N-[1-(5-{4-[3-(5-tert-Butyl-2-methoxy-phenyl)-ureido]-naphthalen-1-y1}-pyridin-2- ylmethy!)-pyrrolidin-3-yl]-acetamide:

   1-(1-Acetyl-3.3-dimethyl-2.3-dihydro-1H-indol-5-yl)-3-[4-(6-morpholin-4-ylmethy!- pyridin-3-yl)-naphthalen-1-yl]-urea; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-

   yl]-ureido}-phenyl)-propionamide; 1-(5-tert-Butyl-2-methyl-benzooxazol-7-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea;

   1-[4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-y1]-3-(3- trifluoromethanesulfonyl-phenyl)-urea; N-(5-tert-Butyl-2-methoxy-3-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-ureido }-phenyl)-isobutyramide;

   2-(4-tert-Butyl-2-{3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl}-ureido} - phenoxy)-acetamide; 1-(5-tert-Butyl-2-o0x0-2,3-dihydro-benzooxazol-7-yl)-3-[4-(6-morpholin-4-ylmethyl-

   pyridin-3-yl)-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-3-cyano-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]j-urea;

   1-(5-tert-Butyl-benzooxazol-7-yl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]}-urea;

   N-(5-tert-Butyl-2-methoxy-3- {3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- ylj-ureido}-phenyl)-benzenesulfonamide; 40 Ethanesulfonic acid (5-tert-butyl-2-methoxy-3-{3-{4-(6-morpholin-4-ylmethyl-pyridin-3- yl)-naphthalen-1-yl}-ureido}-phenyl)-amide; 1-(5-tert-Butyl-2-methoxy-pheny!)-3-[4-(2-morpholin-4-yimethyl-pyrimidin-5-yl)-

   45 naphthalen-1-yl}-urea;

   1-(5-tert-Butyl-2-methylsulfanyl-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-y1)- naphthalen-1-yl]-urea: 1-(5-tert-Butyl-2-methoxy-pyridin-3-y1)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl}-urea:

   2.2.2-Trifluoro-ethanesulfonic acid (3-tert-butyl-2-methoxy-3- {3-[4-(6-morpholin-4- vlmethyl-pyridin-3-yl)-naphthalen-]-y1j-ureido}-phenyl)-amide: N-(5-{4-[3-(5-tert-Butyl-2-methyl-phenyl)-ureido}-naphthalen-1-yl}-pyrazin-2-yl)- methanesulfonamide; 1-[4-(6-{[Bis-(2-cyano-ethyl)-amino}-methyl } -pyridin-3-yl)-naphthalen-1-yl]-3-(5-tert- butyl-2-methoxy-phenyl)-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(4-methyl-piperazin-1-yimethyl)-pyridin-3- yl}-naphthalen-1-yl}-urea: 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-thiomorpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yli]-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2,6-dimethyl-piperidin-1-ylmethyl)-pyridin- 3-ylj-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(1-oxo-tetrahydro-thiopyran-4-ylamino)- pyridin-3-yl}-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(tetrahydro-pyran-4-ylamino)-pyridin-3-yl]- naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6-{[(2-cyano-ethyl)-(tetrahydro-furan-2- ylmethyl)-amino]-methyl}-pyridin-3-yl)-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2-methoxymethyl-morpholin-4-ylmethyl)- pyridin-3-yl]-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2-methyl-3-oxo-piperazin-1-ylmethyl)- pyridin-3-yl}-naphthalen-1-yl}-urea; 40 1-(5-{4-[3-(5-tert-Butyl-2-methoxy-phenyl)-ureido]-naphthalen-1-yl}-pyridin-2- ylmethyl)-piperidine-3-carboxylic acid amide; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(1-0xo0-114-thiomorpholin-4-ylmethyl)- pyridin-3-yl}-naphthalen-1-yl}-urea; 45 1-(3,3-Dimethyl-2-ox0-2.3-dihydro-1H-indol-5-yl})-3-[4-(6-morpholin-4-ylmethyl-

   wooeo/s5139 PCT/US00/03865 ’ pyridin-3-yl)-naphthalen-1 -ylj-urea: 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(3-oxo-piperazin-1 -ylmethyl)-pyridin-3-yl})- naphthalen-1-yl}-urea:

   1-(5-tert-Butyl-2-methoxy-phenyl)-3-(4- {6-((tetrahydro-furan-3-ylamino)-methyl]- pyridin-3-yl}-naphthalen-1-yl)-urea: 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(6- { [(2-cyano-ethyl)-pyridin-3-ylmethyl-amino)-

   methyl }-pyridin-3-yl)-naphthalen-1-yl}-urea: 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2-0xa-5-aza-bicyclo[2.2.1 Jhept-5-ylmethyl)- pyridin-3-yl]-naphthalen-1-yl}-urea;,

   1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(2.6-dimethyl-morpholin-4-ylmethyl)- pyridin-3-yl}-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-(4- { 6-[4-(3-methoxy-phenyl)-piperazin-1- ylmethyl}-pyridin-3-yl}-naphthalen- 1 -yl)-urea;

   1-(5-tert-Butyl-2-methoxy-phenyl)-3- {4-[6-(morpholine-4-carbonyl)-pyridin-3-yl}- naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-[4-(5-morpholin-4-ylmethyl-pyrazin-2-yl)-

   naphthalen-1-yl]-urea; 1-(6-tert-Butyl-3-0x0-3,4-dihydro-2H-benzo[ 1.4 )oxazin-8-yl)-3-[4-(6-morpholin-4- ylmethyl-pyridin-3-yl)-naphthalen-1-yl]j-urea;

   1-(3-Amino-5-tert-butyl-2-methoxy-phenyl)-3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)- naphthalen-1-yl]-urea; N-(5-{4-[3-(5-tert-Butyl-2-methoxy-phenyl)-ureido}-naphthalen-1-yl}-pyridin-2-y1)- acetamide;

   N-(5-tert-Butyl-2-methoxy-3- { 3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1- yl}-ureido}-phenyl)-N-methyl-acetamide; : N-(5-tert-Butyl-2-methoxy-3- {3-[4-(6-morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-

   40 yl}-ureido}-phenyl)-2,2,2-trifluoro-acetamide; 1-(5-tert-Butyl-2-methoxy-phenyl)-3-{4-[6-(pyridin-3-yloxy)-pyridin-3-yl]-naphthalen-1- yl}-urea;

   45 [4-(6-Morpholin-4-ylmethyl-pyridin-3-yl)-naphthalen-1-yl]}-carbamic acid 3-tert-butyl- phenyl ester;

   HF WO 00/25130 PCT/US00/03865. N -(5-ter-Butyl-2-methoxy-3 -{3-[4-(6-morpholin-4-yimethyl-pyridin-3 -yl}-naphthalen-1- yl}-ureido }-phenyl)-meathanesulfonamide and the pharmaceutically acceptable derivaiivas thereof,

   34. A pharmaceutical composidon comprising a pharmaceutically effective amount of a compound according 10 claims 1,9. 17 or 25.

   35. The use of a compound according to any one of claims 1, 9, 17 or 25 in the treatment of a disease mediated by cytokines.

   306. The use according to claim 33 wherein the cytokine-mediated disease is selected from rheumatoid arthritis, osteoarthritis, Crohn’s disease, ulcerative colitis, multiple sclerosis, Guillain-Barre syndrome, psoriasis, graft versus heart disease, systemic lupus erythematosus, diabetes, toxic shock syndrome, osteoporosis, Alzheimer’s disease, acute and chronic pain, contact dermatitis and atherosclerosis.

   37. The use of a compound according to any one of claims 1, 9, 17 or 25 in the treatment of a neutrophil-mediated disease selected from stroke, myocardial infarction, thermal injury, adult respiratory distress syndrome (ARDS), multiple organ injury secondary to trauma, acute glomerulonephritis, dermatoses with acute inflammatory components, acute purulent meningitis, hemodialysis, leukopherisis, glanulocyte transfusion associated syndromes and necrotizing entrerocolitis. AMENDED SHEETteoo

   38. A method of making a compound of the formula(l) according to claim 1, comprising: a) reacting an arylamine with phenyl chloroformate in a suitable halogenated solvent with a suitable base at 0 — 85°C for about 2 — 24 hours: 0 Ar CICOPh ar Jpn 2 Ho b) isolating and subsequently reacting the product of step a) with an arylamine shown below in a non-protic anhydrous solvent at 0 — 110°C for about 2 — 24 hours, to produce a compound of the formula (I): o w Z-Y-X-Ar,-NH —X—Y — Ar, AL Ph 2 Arn I A X—Y—2 "NN" "0 — . H H H (Ds wherein Wis O and Ar, Ar, X, Y and Z are as defined in claim 1.

   39. A method of making a compound of the formula(la) according to claim 9, comprising: a) reacting an arylamine with phenyl chloroformate in a suitable halogenated solvent with a suitable base at 0 — 85°C for about 2 — 24 hours: Ar, ICO,Ph Ar. JL _.Ph SNH, ——— NO H :

   C. id b) isolating and subsequently reacting the product of step a) with an arylamine shown below in a non-protic anhydrous solvent at 0 — 110°C for about 2 — 24 hours. to produce a compound of the formula (Ia): i x Z-Y-X-AryNH, Ars=X—Y—Z Ar~_ Pddab Ar, ~ No o-Fh ! N N H H H (la); wherein W is O and Ar, Arn. X,Y and Z are as defined in claim 9.

   40. A method of making a compound of the formula(II) according to claim 17, comprising: a) reacting an arylamine with phenyl chloroformate in a suitable halogenated solvent with a suitable base at 0 — 85°C for about 2 ~ 24 hours: 0) Go CICO,Ph G. J Ph NH, ———— N Oo H 5 b) isolating and subsequently reacting the product of step a) with an arylamine shown below in a non-protic anhydrous solvent at 0 — 110°C for about 2 — 24 hours, to produce a compound of the formula (II): _ i A Z-Y-X-Ar-NH, Ar—X—Y—7Z Go oT Gy oP NE H H H (I); wherein Wis O and G, Ar, X, Y and Z are as defined in claim 17.

   41. A method of making a compound of the formula(IIl) according to claim 25, comprising: 3 a) reacting an arylamine with phenyl! chloroformate in a suitable halogenated solvent with a suitable base at 0 — 85°C for about 2 — 24 hours: CICO 7 Go 2Ph G6. J ..Ph NH, —— NO H 3 b) isolating and subsequently reacting the product of step a) with an arylamine shown below in a non-protic anhydrous solvent at 0 —- 110°C for about 2 — 24 hours, to produce a compound of the formula (III): i x Z-Y-X-Ar-NH, Ar—X—Y—2 G< Geog i al

   ) . H H 13 AD; wherein Eis N-H, Wis O and G, Ar, X, Y and Z are as defined in claim 235.

   42. A compound of the formula according to any one of claims 1, 9, 17 or 33, i substantially as herein described and exemplified.

   43. A pharmaceutical composition according to claim 34, substantially as herein described and exemplified.

   44. The use according to claim 35 or claim 37, substantially as herein described and exemplified.

   45. A method according to any one of claims 38 to 41, substantially as herein described and exemplified. : 280 k AMENDED SHEET