MXPA06010235A - 3-‘4-heterocyclyl -1,2,3,-triazol-1-yl!-n-aryl-benzamides as inhibitors of the cytokines production for the treatment of chronic inflammatory diseases - Google Patents

Abstract

Disclosed compounds of formula (I), 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. Also disclosed are processes for preparing these compounds and pharmaceutical compositions comprising these compounds.

Description

3- [4-HETER0CICLIL-l, 2,3-TRIAZ0L-l-IL] -N-ARIL-BENZAMIDAS AS INHIBITORS OF THE PRODUCTION OF CYTOKINES FOR THE TREATMENT OF CHRONIC INFLAMMATORY DISEASES 1. TECHNICAL FIELD The present invention relates to compounds of the formula (I) The compounds of the invention inhibit the production of cytokines involved in inflammatory processes and are therefore useful for treating diseases and pathological conditions involving inflammation, such as a chronic inflammatory disease. The present invention also relates to processes for preparing these compounds and to pharmaceutical compositions comprising these compounds. 2. BACKGROUND INFORMATION Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are important biological entities, collectively called proinflammatory cytokines, which play a role in cytokine-mediated diseases. These, together with several 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 autoimmune diseases such as toxic shock syndrome, rheumatoid arthritis, osteoarthritis, diabetes and inflammatory bowel disease (Dinarello, CA, et al, 1984, Rev. Infect. Disease 6: 51). In these diseases, the chronic elevation of inflammation exacerbates or causes much of the observed pathophysiology. For example, rheumatoid synovial tissue becomes invaded by inflammatory cells that cause the destruction of cartilage and bone (Koch, AE, et al, 1995, J. Invest. Med. 43: 28-38). inflammatory changes mediated by cytokines may be involved in the pathogenesis of endothelial cells, including restenosis after percutaneous transluminal coronary angioplasty (PTCA) (Tashiro, H., et al, 2001 Mar, Coron Artery Dis 12 (2): 107 -13) An important and accepted therapeutic approach for the potential intervention of drugs in these diseases is the reduction of proinflammatory cytokines such as TNF (also called in its free form of secreted FNTa cells) and IL-lß.- Currently , there are a number of anti-cytokine therapies under clinical trials.The efficacy has been demonstrated with a monoclonal antibody directed against TNFa in a number of autoimmune diseases (Heath, P., "CDP571: An E ngineered 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, ECC, et al, 1997, British J. Rheum 35: 334-342 and Stack, WA, et al, 1997, Lancet 349: 521 -524). It is believed that the monoclonal antibody works by binding to both soluble TNFa and membrane-bound TNF. A soluble TNFa receptor that interacts with TNFa has been modified. The approach is similar to that previously described for monoclonal antibodies directed against TNFa; both agents bind to soluble TNF, thereby reducing their concentration. A version of this concept, 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 F? Ta receptor, Ro 45-2081, (Hoffman-LaRoche Inc.,? Utley,? J) has demonstrated efficacy in several animal models of allergic lung inflammation and acute lung damage. Ro 45-2081 is a recombinant chimeric molecule constructed from the soluble 55 kDa human FNT receptor condensed to the hinge region of the heavy chain IgGl gene and expressed in eukaryotic cells (Renzetti, et al, 1997, Inflamm Res.46: S143). IL-1 has been implicated as an immunological effector molecule in a large number of disease processes. The IL-1 receptor antagonist (IL-lra) had been examined in human clinical trials. The efficacy of the treatment of rheumatoid arthritis has been demonstrated (Antril, Amgen). In a phase III human clinical trial, IL-lra reduced the mortality rate in patients with septic shock syndrome (Dinarello, 1995, Nutrution 11, 492). Osteoarthritis is a disease of slow progression characterized by the destruction of articular cartilage. IL-1 is detected in synovial fluid and in the cartilage matrix of osteoarthritic joints. IL-1 antagonists have been shown to decrease 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 on the modulation of bone remodeling. Cytokines such as IL-1 and FNT are potent stimulators of NO production. NO is an important regulatory molecule in bones with effects on the osteoclast and osteoblast cell lineage (Evans, et al, 1996, J Bone Miner Res. 11, 300). The promotion of beta-cell destruction leading to insulin-dependent diabetes mellitus shows a dependence on IL-1. Some of this damage can be mediated through other effectors such as prostaglandins and thromboxanes. IL-1 can effect this process by controlling the level of both inducible nitric oxide synthetase and cyclooxygenase II expression (McDaniel et al, 1996, Proc Soc Exp Biol Med. 211, 24). Inhibitors of cytokine production are expected to block the expression of cyclooxygenase (COX-2) inductible. It has been shown that the expression of COX-2 is increased by cytokines and is believed to be the isoform of cyclooxygenase responsible for inflammation (MK O'Banion et al, Proc. Nati, Acad. Sci. US A, 1992, 89 , 4888.) Accordingly, cytokine inhibitors such as IL-1 would be expected to exhibit efficacy against those disorders currently treated with COX inhibitors, such as familial NSAIDs. These disorders include chronic and acute pain, as well as symptoms of inflammation and cardiovascular disease. The elevation of several cytokines during active inflammatory bowel disease (IBD) has been demonstrated. A mucosal imbalance of IL-1 and IL-lra-intestinal is present in patients with IBD. The insufficient production of endogenous IL-1ra can contribute to the pathogenesis of IBD (Cominelli, et al, 1996, Aliment Pharmacol Ther 10, 49). Alzheimer's 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 observed in Alzheimer's 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 the human immunodeficiency virus (HIV) has been identified. IL-lra demonstrated a clear relationship with acute inflammatory events as well as with different stages of disease in the pathophysiology of HIV infection (Kreuzer, et al, 1991, Clin Exp Immunol., 109, 54). IL-1 and TNF are both involved in periodontal disease. The destructive process associated with periodontal disease can be due to a deregulation of both IL-1 and TNF (Howells, 1995, Oral Dis. 1, 266). Proinflammatory cytokines such as FNTa and IL-lß are also important mediators of septic shock and associated cardiopulmonary dysfunction, acute dyspneic syndrome (ARDS) and multi-organ failure. In a study of patients who presented in a hospital with sepsis, a correlation was found between the levels of TNFα and IL-6, and the septic complications (Terregino et al, 2000, Ann. Emerg. Med., 35, 26 ). TNFa has also been implicated in muscle degradation and cachexia, associated with HIV infection (Lahdiverta et al, 1988, Amer. J. Med., 85, 289). Obesity is associated with an increasing incidence of infection, diabetes and cardiovascular disease. Abnormalities in TNFa expression have been observed for each of the aforementioned conditions (Loffreda, et al, 1998, FASEB J. 12, 57). It has been proposed that high levels of TNFa are implicated in other eating-related disorders, such as anorexia and bulimia nervosa. There are pathophysiological parallels between anorexia nervosa and cancer cachexia (Holden, et al, 1996, Med Hypotheses 47, 423). It was shown that an inhibitor of TNF production, HU-211, improves the outcome of closed brain trauma in an experimental model (Shohami, et al, 1997, J Neuro Immunol., 12, 169). It is known that atherosclerosis has an inflammatory component and it has been suggested that cytokines such as IL-1 and FNT promote the disease. In an animal model, an IL-1 receptor antagonist was shown to inhibit the formation of fatty streaks (Elhage et al, 1998, Circulation, 97, 242). TNFa levels rise in the airways of patients with chronic obstructive pulmonary disease and may contribute to the pathogenesis of the disease (M.A.

Higham et al, 2000, Eur. Respiratory J., 15, 281). Circulating TNFa may also contribute to the weight loss associated with this disease (N. Takabatake et al, 2000, Amer. J. Resp. &Crit. Care Med., 161 (4 Pt 1), 1179). It has also been found that elevated TNFa levels are associated with congestive heart failure and the level has been correlated with the severity of the disease (A.M. Feldman et al, 2000, Amer. College of Cardiology, 35, 537). In addition, TNFa has been implicated in reperfusion injury of the lung (Borjesson et al, 2000, Amer. J ". Physiol., 278, L3-12), kidney (Lemay et al, 2000, Transplantation, 69, 959). and the nervous system (Mitsui et al, 1999, Brain Res., 844, 192) .NTF is also a potent osteoclastogenic agent and is involved in bone resorption and diseases involving bone resorption (Abu-Amer et al. 2000, J. "Biol. Chem., 275, 27307). It has also been found to be highly expressed in chondrocytes from patients with traumatic arthritis (Melchiorri et al, 2000, Arthritis and Rheumatism, 41, 2165). It has also been found that TNFa plays a key role in the development of glomerulonephritis (Le Hir et al, 1998, Laboratory Investigation, 78, 1625). The abnormal expression of inducible nitric oxide synthetase (iNOS) has been associated with hypertension in spontaneously hypertensive rats (Chou et al, 1998, Hypertension, 31, 643). IL-1 has a role in the expression of iNOS • and, therefore, may also play a role in the pathogenesis of hypertension (Singh et al, 1996, Amer. J. Hypertension, 9, 867). It has also been shown that IL-1 induces uveitis in rats, which could be inhibited with IL-1 blockers. (Xuan et al, 1998, J. Ocular Pharmacol. And Ther., 14, 31). It has been shown that cytokines, including IL-1, FNT and GM-CSF, stimulate the proliferation of myelogenous leukemia blastocysts (Bruserud, 1996, Leukemia Res. 20, 65). IL-1 proved to be essential for the development of both irritant and allergic contact dermatitis. Epicutaneous sensitization can be prevented with the administration of an anti-IL-1 monoclonal antibody before the epicutaneous application of an allergen (Muller, et al, 1996, Am J Contact Dermat 7, 177). The data obtained from mice with inactivated IL-1 indicate the critical implication in fever of this cytokine (Kluger et al., 1998, Clin Exp Pharmacol Physiol. 25, 141). A variety of cytokines, including FNT, IL-1, IL-6 and IL-8, initiate the acute phase reaction that is stereotyped in fever, malaise, myalgia, headaches, cellular hypermetabolism and multiple endocrine and enzymatic responses (Beisel , 1995, Am J Clin Nutr., 62, 813). The production of these inflammatory cytokines rapidly follows a trauma or an invasion of the pathogenic organism. Other proinflammatory cytokines have been correlated with a variety of disease states. IL-8 correlates with the entry of neutrophils at sites of inflammation or damage. Blockade of antibodies against IL-8 has demonstrated a role of IL-8 in the neutrophil associated with tissue damage in acute inflammation (Harada et al, 1996, Molecular Medicine Today 2, 482). Therefore, an inhibitor of IL-8 production may be useful in the treatment of diseases predominantly mediated by neutrophils, such as stroke and myocardial infarction, alone or following thrombolytic therapy, thermal injury, adult acute dyspnoea syndrome (ARDS), multiorgan damage secondary to trauma, acute glomerulonephritis, dermatosis with inflammatory components, acute purulent meningitis or other central nervous system disorders, hemodialysis, leukapheresis, syndromes associated with granulocytic transfusion and necrotizing enterocolitis. The rhinovirus triggers the production of different inflammatory cytokines, predominantly IL-8, which causes symptomatic diseases such as acute rhinitis (Winther et al, 1998, Am J Rhinol 12, 17). Other diseases caused by IL-8 include reperfusion and myocardial ischemia, 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 of oncological diseases, including multiple myeloma and related plasma cell dyscrasias (Treon, et al, 1998, Current Opinion in Hematology 5: 42). It has also been shown to be an important mediator of inflammation within the central nervous system. High levels of IL-6 are observed in several neurological diseases, including the AIDS dementia complex, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, CNS trauma and viral and bacterial meningitis (Gruol, et al, 1991, Molecular Neurobiology 15: 307). IL-6 also plays a significant role in osteoporosis. In mouse models it has been shown to effect bone resorption and induce osteoclast activity (Ershler et al, 1997, Development and Comparative Immunol., 21: 487). There are marked cytokine differences, such as levels of IL-6, in vivo between osteoclasts of normal bone and bone of patients with Paget's disease (Mills, et al, 1991, Calcif Tissue Int. 61, 16). It has been shown that a number of cytokines are involved in cancer cachexia. The severity of the key parameters of cachexia can be reduced by treatment with anti-IL-6 antibodies or with IL-6 receptor antagonists (Strassmann, et al, 1995, Cytokins Mol Ther., 1, 107). Different contagious diseases, such as influenza, indicate that IL-6 and IFN alpha are key factors in both symptom formation and 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, et al, 1991, Protein Sci. 6, 929 ). Compounds that interfered with the production of cytokines, including IL-6 and FNT, were effective in blocking a passive cutaneous anaphylaxis in mice (Scholz et al, 1998, "Med.Chem., 41, 1050). is another proinflammatory cytokine with relevance for a number of therapeutic diseases, not only influences the proliferation and differentiation of hemocytes, 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 wound healing from burns, resolution of skin grafts, as well as cytostatic mucositis and radiotherapy-induced (Masucci, 1996, Medical Oncology 13: 149) . GM-CSF also seems to play a role in the replication of the human immunodeficiency virus (HIV) in the macrophage cell line with relevance to AIDS therapy (Crowe et al, 1997, Journal of Leukocyte Biology 62, 41). Bronchial asthma is characterized by an inflammatory process in the lungs. The involved cytokines include GM-CSF, among others (Lee, 1998, J R Coll Physicians' Lond 32, 56). Interferon? (IFN?) Has been implicated in a number of diseases. It has been associated with an increase in collagen deposition that is a central histopathological feature of graft-versus-host disease (Parkman, 1998, Curr Opin Hematol, 5, 22). After kidney transplantation, a patient was diagnosed with acute myelogenous leukemia. Retrospective analysis of peripheral blood cytokines revealed elevated levels of GM-CSF and IFNα. These elevated levels coincided with an increase in the peripheral blood leukocyte count (Burke, et 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 that produce IFN? (Ablumunits, et al, 1998, J Autoimmun., 11, 73). The IFN? together with TNF, IL-2 and IL-6 leads to the activation of most of the peripheral T cells before the development of lesions in the central nervous system for diseases such as multiple sclerosis (MS) and dementia complex of the AIDS (Martino et al, 1998, Ann Neurol, 43, 340). Atherosclerotic lesions cause 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 FNT, IL-1 and IFN ?. It is believed that these cytokines are involved in promoting apoptosis or programmed cell death of surrounding vascular smooth muscle cells, which causes atherosclerotic lesions (Geng, 1997, Heart Vessels Suppl 12, 16). Allergic subjects produce specific nRNA for IFN? following the Vespula poison test (Bonay, et al, 1991, Clin Exp Immunol., 109, 342). It has been shown that the expression of a number of cytokines, including IFNα, increases after a delayed-type hypersensitivity reaction, thus indicating a function for IFN? in atopic dermatitis (Szepietowski, et al, 1991, Br J Dermatol, 137, 195). Histopathological and immunohistological studies were carried out in cases of fatal cerebral malaria. Was the evidence of IFN? elevated among other cytokines, indicating a function in this disease (Udomsangpetch et al, 1997, Am J Trop Med Hyg. 57, 501). The importance of free radical species in the pathogenesis of different infectious diseases has been established. Nitric oxide synthesis is activated in response to infection with a certain virus via the induction of proinflammatory cytokines such as IFN? (Akaike, et al, 1998, Proc Soc Exp Biol Med. 217, 64). Patients chronically infected with the hepatitis B virus (HBV) can also develop cirrhosis and hepatocellular carcinoma. Viral gene expression and replication in transgenic mice with HBV 'can be suppressed by a post-transcriptional mechanism mediated by IFNα, TNF and IL-2 (Chisari, et al, 1995, Springer Semin Immunopathol 17, 261). The IFN? it can selectively inhibit bone resorption induced by cytokines. It seems to do this via the intermediation of nitric oxide (NO) which is an important regulatory molecule in bone remodeling. NO may be involved as a mediator of bone disease for diseases such as: rheumatoid arthritis, osteolysis associated with tumors and postmenopausal osteoporosis (Evans, et al, 1996, J Bone Miner Res. 11, 300). Studies with gene-deficient mice have shown that the IL-12-dependent production of IFN? it is critical in the control of early parasitic proliferation. Although this process is independent of nitric acid, the control of chronic infection seems to depend on NO (Alexander et al, 1997, Philos Trans R Soc Lond B Biol Sci 352, 1355). NO is an important vasodilator and there is convincing evidence of its role in cardiovascular shock (Kilbourn, et al, 1991, Dis Mon. 43, 277). Is the IFN required? for the progression of chronic intestinal inflammation in diseases such as Crohn's disease and inflammatory bowel disease (IBD) presumably through the intermediation of CD4 + lymphocytes, probably of the THl phenotype (Sartor 1996, Aliment Pharmacol Ther.10 Suppl 2, 43) . An elevated model of serum IgE is associated with different atopic diseases, such as' bronchial asthma and atopic dermatitis. The level of IFN? was negatively correlated with serum IgE, suggesting a function of IFN? in atopic patients (Teramoto et al, 1998, Clin Exp Allergy 28, 74). The international publication WO 01/01986 describes particular compounds that are supposed to have the ability to inhibit TNF-alpha. Certain compounds described in the international publication WO 01/01986 are indicated as being effective for treating the following diseases: dementia associated with HIV infection, glaucoma, optic neuropathy, optic neuritis, retinal ischemia, laser-induced optical damage, proliferative vitreoretinopathy induced by trauma or surgery, cerebral ischemia, hypoxia-ischemia, hypoglycaemia, domoic acid poisoning, anoxia, carbon monoxide or manganese poisoning or cyanide, Huntington's disease, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis and other demyelinating diseases , amyotrophic lateral sclerosis, cranial and spinal cord trauma, seizures, olivopontocerebellar atrophy, neuropathic pain syndromes, diabetic neuropathy, HIV-related neuropathy, MERRF and MELAS syndromes, Leber's disease, Wernicke encephalopathy, Rett syndrome, homocysteinuria, hyperprolinem ia, hyperhomocysteinemia, non-ketotic hyperglycemia, hydroxybutyric aminoaciduria, sulfite-oxidase deficiency, combined system disease, lead encephalopathy, Tourett syndrome, hepatic encephalopathy, drug addiction, drug tolerance, drug dependence, depression, anxiety and schizophrenia. International publication WO 02/32862 discloses that inhibitors of proinflammatory cytokines, including TNFa, are purportedly useful for treating acute and chronic inflammation in the lung, caused by inhalation of smoke, such as cigarette smoke. Antagonists of TNF seem to be also useful for the treatment of endometriosis, see international publication EP 1022027 Al. Infliximab, in clinical trials for RA, has also indicated to be useful for treating various inflammatory diseases, including Behcet's disease, uveitis and ankylosing spondylitis. Pancreatitis may also be regulated by the production of an inflammatory mediator, see J Surg Res May 15, 2000 90 (2) 95-101; Shock Sep. 1998 10 (3): 160-75. The p38MAP kinase pathway plays a role in the inflammation caused by B. burgdorferi and may be useful in the treatment of inflammation induced by the agent of Lyme disease. Anguita, J. et. al, The Journal of I munology, 2002, 168: 6352-6357. Compounds that modulate the release of one or more of the aforementioned inflammatory cytokines may be useful in the treatment of diseases associated with the release of these cytokines. For example, international publication WO 98/52558 describes heteroaryl urea compounds which are indicated as being useful in the treatment of cytokine mediated diseases. The international publication WO 99/23091 describes another class of urea compounds that are useful as anti-inflammatory agents. The international publication WO 99/32463 relates to aryl ureas and their use for treating diseases mediated by cytokines and by the proteolytic enzyme. International publication WO 00/41698 discloses aryl ureas which are said to be useful for treating diseases of p38 MAP kinase. The compounds active against p38 MAP kinase may also be useful for treating different types of cancers, as described in the international publication WO 03/068223. U.S. Patent No. 5,162,360 discloses N-substituted substituted aryl-N '-heterocycle compounds which are disclosed as being useful for treating hypercholesterolemia and atherosclerosis. The di-substituted heteroaryl and aryl compounds are also described in US Patent Nos. 6,080,763; 6,319,921; 6,297,381 and 6,358,945. It is assumed that the compounds of the patents possess anti-cytokine activity and are therefore useful for treating diseases associated with inflammation. The above-mentioned work supports the principle that the inhibition of cytokine production will be beneficial in the treatment of cytokine-mediated diseases. Therefore, there is a need for small molecule inhibitors to treat these diseases with optimized efficacy, pharmacokinetic and safety profiles.

THE INVENTION The aforementioned work supports the principle that the inhibition of cytokine production with small molecule compounds will be beneficial in the treatment of different disease states. It is therefore an object of the invention to provide compounds of the formula (I) It is another object of the invention to provide methods for treating diseases mediated by cytokines and pathological conditions involving inflammation, such as chronic inflammatory disease, using the novel compounds of the invention. It is even another object of the invention to provide pharmaceutical compositions and methods for preparing the aforementioned new compounds.

DETAILED DESCRIPTION OF THE INVENTION In the broadest generic modality, compounds of the formula (I) are provided wherein: Ar1 is selected from (i), (ii) and (iii) below: i) a carbocycle substituted with R1, R2 and Rx, (ii) in which one of E or F is nitrogen and the other is carbon, R1 is covalently linked to either E or F, and when the nitrogen is N-Rx, the double bond between E and F is not present; (iii) wherein c is a benzo ring fused to ring d which is a 5-70 membered heterocyclic ring optionally substituted with an oxo group (= 0) and one to two R groups, each independently being H or alkyl Cl -3; R1 is selected from hydrogen, N02, -N (RC) 2, JC (0) -N (RC) -, JS (0) mN (Rc) -, alkyl Cx-6 S (0) m- or R1 is selected between alkyl Cl-6, cycloalkyl C3-7, Cl-5 alkoxy or C3-7 cycloalkoxy, alkyl-thiol Cl-5 or cycloalkyl thiol C3-7, acyl Cl-5, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, alkenyl C2-5, alkynyl C2-5, heterocycle, heterocycloalkyl Cl-6, heteroaryl, heteroarylalkyl Cl-6 and nitrile; each of those already mentioned, when possible, is optionally partially or totally halogenated or optionally also substituted with alkylsulfonylamino, aminocarboxyl, alkoxy, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile; R 2 is selected from: hydrogen, halogen, nitrile, alkyl Cl-5 S (0) m-, aryl S (0) m, J-0-C (0) -0-, N (RC) 2-C (O ) - (CH2) a-, acetyl Cl-6, aroyl, alkoxycarbonyl Cl-6, alkyl Cl-6, cycloalkyl C3-7, alkoxy Cl-6, cycloalkoxy C3-5, alkyl Cl-5 alkoxy Cl-5, hydroxy , Cl-5 hydroxyalkyl and amino optionally mono or disubstituted with Cl-5 alkyl, aryl or arylalkyl Cl-5; each of those already mentioned, when possible, is optionally partially or fully halogenated or optionally also substituted with Cl-3 alkyl, alkylsulfonylamino, alkoxy, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile; each Rx is selected from C1-6 alkyl or C3-7 cycloalkyl, each being optionally substituted with Cl-3 and optionally partially or fully halogenated alkyl, Cl-4 acyl, aroyl, Cl-4 alkoxy, Cl-5 S alkyl ( 0) m-, each may optionally be partially or totally halogenated, halogen, alkoxycarbonyl Cl-6, carbocyclosulfonyl; each Rc is independently hydrogen or Cl-5 alkyl; xX A D, A and B in * of the formula (I) are each independently selected from N or CH, in which the hydrogen atom is optionally replaced with Rs; Het is a heteroaryl or heterocyclic ring, in which Het is optionally substituted with one to three R5; is 0, 1 or 2 J is selected from alkyl Cl-10 and cycloalkyl C3-7, each optionally substituted with Rb; R 3, R 4, R 6, R 7 and R 8 are each independently selected from hydrogen, halogen, Cl-5 alkyl, Cl-5 alkoxy, Cl-5 Cl-5 alkoxy alkyl, hydroxy, Cl-5 hydroxyalkyl or mono- or di-amino. substituted with Cl-5 alkyl, aryl or arylalkyl Cl-5; R5 is: Ra, -0-Ra, -S (0) m-Ra, -N (Ra) 2, -C (0) -Ra, -NH (CR7R8) nR, N (Ra) 2- (CH2)? - 2 -, - (CR7R8) n-Ra, -O (CR7R8) n-Ra, -C (O) -O (CR7R8) n-Ra, -C (O) (CR7R8) n-Ra-C (0) C (0) Ra, -C (0) C (0) Ra, -C (0) C (0) ORa, -C (0) NHRa O -C (0) NH (CR7R8) n-, each optionally substituted with Cl-3 alkyl, halogen or hydroxy, in which n is 1-5 or R5 is aryl, heteroaryl or heterocyclyl, each optionally substituted with Ra; Ra and Rb are each independently selected from hydrogen, Cl-6 alkyl, Cl-5 hydroxyalkyl, C2-5 alkenyl, C2-5 alkynyl, carbocycle, carbocycloalkyl CO-2, aryl, heterocycle, heteroaryl, Cl-5 alkoxy, alkylthio Cl-5, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5, diarylamino, acyl Cl-5, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, where each of the mentioned are optionally partially or fully halogenated, or Ra and Rb are selected from alkylsulfonylamino Cl-5, hydroxy, oxo, halogen, -CF3, -CH2-CF3 / nitro and nitrile, wherein each carbocycle, heterocycle or heteroaryl for Ra and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy; and X is O or S or its pharmaceutically acceptable salts, acids, esters or isomers. In another embodiment, compounds of the formula (I) are provided, as described above and in which $? -1 of the formula (I) is selected from: Het is J is selected from alkyl Cl-10, aryl and C3-7 cycloalkyl, each optionally substituted with Rb; R2 is independently selected from hydrogen, JOC (O) -O-, Cl-6 alkoxy, Cl-6 alkyl, Cl-6 acetyl, aroyl, halogen, methoxycarbonyl, phenylsulfonyl, Cl-5S (0) alkyl and C3- cycloalkyl 7 optionally substituted with Cl-3 alkyl, wherein each R2 'when possible, may optionally be partially or fully halogenated; R1 is selected from H, Cl-6 alkyl, Cl-5 S (0) m alkyl, JS (0) mN (Rc) -, Cl-5 alkoxy, Cloth 5-alkylthiol, NH2-C (0) - (CH2 ) n-, (RC) 2N alkyl Cl-6, acyl Cl-5 NH-, -NH2, -N02, heteroaryl selected from pyrazole, triazole, imidazole and tetrazole, and nitrile; ring d is a 5-6 membered heterocyclic ring, so that rings c and d are condensed to form the following: wherein each R is independently H or Cl-3 alkyl; R3 and R4 are independently selected from hydrogen, Cl-3 alkoxy, Cl-3 alkyl and halogen; n is 1-4; Ra and Rb are each independently selected from hydrogen, Cl-6 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-8 cycloalkyl, alkyl CO-2, aryl, Cl-5 alkoxy, Cl-5 alkylthio, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, acyl Cl-5, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, arylalkylamino Cl-5, alkylsulfonylamino Cl-5, hydroxy, halogen, -CF3, -CH2 -CF3 nitro, nitrile, or Ra and Rb are selected from; heterocycle selected from pyrrolidinyl, pyrrolinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, dioxalanyl, piperidinyl, piperazinyl, homopiperazinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxanyl , piperidinonyl, tetrahydropyrimidonyl, aziridinyl, pentamethylene sulfide, pentamethylene sulphoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide and tetramethylene sulfone and heteroaryl is selected from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl , pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyranyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, quinolinyl, quinazolinyl, naphthyridinyl, indazolyl, triazolyl, pyrazolo [3,4-b] pyrimidinyl, purinyl, pyrrolo [2, 3- 'b] pyridinyl, pyrazolo [3,4-b] iridinyl, tubocidinyl, oxazo [4, 5-b] pyridinyl and imidazo [4, 5-b] pyridinyl; wherein each aryl, heterocycle or heteroaryl for Ra and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy; and X is O. Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and wherein Ar1 is selected from (i) and (ii); R5 is: a) Ra, -0-Ra, -S (0) m-Ra, -N (Ra) 2, N (Ra) 2- (CH2) x.2-, -NH (CR7R8) nR, - (CR7R8) n-Ra or -O (CR7R8) "-Ra; OR R5 is: b) -C (0) -Ra, -C (0) -0 (CR7R8) n-Ra, -C (O) (CR7R8) n-Ra C (0) NHRa, -C (0) NH (CR7R8) n-, -C (0) C (0) Ra or -C (O) C (O) ORa; each of the aforementioned R5 is optionally substituted with Cl-3 alkyl, halogen or hydroxyl, and in which n is 1-3. Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and in which Ar1 is: or Ar1 is cyclobutyl, phenyl, naphthyl, tetrahydronaphthyl, indanyl and indenyl, each substituted with a group R1, Rx and R2; R1 is nitrile, N02, NH2, acyl Cl-3 NH-, J-S (0) m-N (Rc) - wherein J is alkyl Cl-10 or R1 is Rc R 2 is independently selected from C 1-6 alkyl, C 1-6 alkyl (0) m-, C 1-6 alkoxy and C 3-6 cycloalkyl optionally substituted with C 1-3 alkyl, each of which may be optionally partially or fully halogenated; R3 and R4 are each independently selected from hydrogen, Cl-3 alkyl, fluoro and chloro; R6 is selected from hydrogen and amino; n is 1-2; R and Rb are each independently selected from hydrogen, Cl-6 alkyl, C3-7 cycloalkyl, CO-2 alkyl, aryl, Cl-5 alkoxy, amino, Cl-5 alkylamino, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5. , acyl Cl-3, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, sulfonylamino Cl-5, hydroxy, halogen, -CF3, -CH2-CF3 nitro, nitrile; or Ra is selected from pyrrolidinyl, pyrrolinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulphone, piperidinyl, piperazinyl, -homopiperazinyl, piperidinonyl, tetrahydropyrimidonyl, aziridinyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl; wherein each aryl, heterocycle or heteroaryl for Ra and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy. Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and in which is: J-S (0) 2-NH-, wherein J is alkyl Cl-5, or R1 is nitrile, N02, NH2 or acyl Cl-3 NH-; wherein R x = R 2 each independently selected from alkyl Cl-5, alkyl Cl-5 S (0) m-, alkoxy Cl-4 and C3-5 cycloalkyl optionally substituted with Cl-2 alkyl, each of which may optionally be partially or fully halogenated; R8 is hydrogen, methyl, ethyl, CH20H and CH2OCH3. Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and in which R is selected from hydrogen, Cl-6 alkyl, C 3-6 cycloalkyl C 0-2 alkyl, phenyl, Cl-alkoxy 5, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5, acyl Cl-3, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, hydroxy, halogen, -CF3, -CH2 -CF3; or R is selected from morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulphone, piperazinyl, hsmopiperazinyl, pyrrolidinyl, piperidinyl, piperidinonyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl, wherein each phenyl, heterocycle or heteroaryl for R is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy. Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and in which Ra is selected from hydrogen, Cl-6 alkyl, C 3-6 cycloalkyl, phenyl, Cl-5 alkoxy, alkoxycarbonyl Cl -5, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5, acyloxy Cl-5, acylamino Cl-5, hydroxy, halogen, -CF3 / -CH2-CF3; or Ra is selected from morpholinyl, piperidinylpiperazinyl, or opiperazinyl, pyrrolidinyl and pyridinyl, wherein each phenyl, heterocycle or heteroaryl for Ra is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy.

Even in another embodiment, compounds of the formula (I) are provided, as described immediately above and in which of the formula (I) is selected from: R5 is: Cl-5 alkyl, C3-6 cycloalkyl, N (Ra) 2 (CH2) x.2-, halogen, Cl-3 alkoxy, hydroxy, -N (Ra) 2, -CF3, -CH2-CF3, aryl, -S (0) mR, -NH (CR7R8) n-Ra or - (CR7R8) nN (Ra) 2 each optionally substituted with Cl-3 alkyl, halogen or hydroxy, or R5 is -C (0) Ra , -C (0) C (0) Ra, -C (0) NHRa. Ra is selected from hydrogen, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, pyridinyl, mono or dialkylamino C? -S, arylamino, C3-6 cycloalkyl, Cl-5 alkyl and Cl-3 alkoxy, wherein each phenyl or heterocycle for R it is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxyl. The following are preferred modes of Het combined with VN-Ae '' ^ in ^ - s that Arl 'X' R3 R4 ^ e ^ -a formula (I) are as defined in any of the first seven modes already provided herein and in which : The following are representative compounds of the invention that can be made according to the general schemes and working examples set forth below: Table I Structure Name Benzyl ester of acid [2- (4- { 1- [5- ... JO (5-fer-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] -y ..? X * "1 H-1, 2,3-triazoI-4-yl.} -2-phenyl-2H-pyrazol-3-yl) -ethyl] -carbamic 3- [4- (1-Benzyl -2-ethyl-1 H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -? / - (5-y-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-benzamide 3- [4- (1-cyclopropyl-5-ethyl-1 H -pyrazol-4-yl) -1,2,3-triazol-1-yl] - / V- [3-methanesulfonylamino-2] -methoxy-5- (1-meth yl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (1-lsopropyl-5-methyl-1 H -pyrazole-4-yl) -1, 2,3-triazol-1-yl] -? / - [3-methanesulfonylamino-2-methoxy-5- (1-meth ylc-chloropyl) -phenyl] -4-methyl-benzamide Structure Name 3- [4- (1 -fer-Butyl-5-methyl-1 H -pyrazol-4-yl) -1,2,3-triazol-1-yl] - / V- [3-methansulfonic-2-methoxy-5] - (1-methyl-cyclopropyl) -phenyl] -4-methylene-benzamide 3- [4- (2-Acetyl-3-methyl-3 - / - imidazol-4-yl) -1,2,3- triazol-1-yl] -? / - (5-ene-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3 - [4- (2-Benzylsulfonyl-3-methyl-3H-imidazol-4-yl) -1, 2,3-triazoH -yl] -? / - (5-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (2-Benzoyl-3-methyl- 3H-imidazol-4-yl) -1, 2,3-triazo-yl] -? / - (5-fer-butyl-OH? X- "3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-benzamide 3- [4- (2-Benzoyl-3-methyl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -? / - [3-methanesulfonylamino-2 -methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Structure Name 3- [4- (2-Benzyl-3-methyl-3H-imidazole-4-yl) -1, 2 , 3-triazol-1-yl] -? / - (5-fer-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (2-Benzyloxymethyl- 3-methyl-3H-imidazol-4-yl) - [1,2,3] triazol-1 -yl] -? / - (5-fer-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide 3- [4- (2-Cyclobutyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -? / - [3-methanesulfonylamino-2-methoxy-5 - (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 15 3- [4- (2-Cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2,3-triazole-1 -iI] -? / - [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 20 3- [4- (2-Cyclopropyl-3-methyl -3H- imidazol-4-yl) -1, 2,3-triazol-1-yl] -? / - [5- (2-hydroxy-1,1-dimethyl-ethyl) -3-methanesulfonylamino-2 -methoxy-phenyl] -4-methyl-benzamide Structure Name 3- [4- (2-lsopropyl-3-methyl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl ] -? / - [3- methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-fer-Butyl-3-methyl-3H- Midazol-4-yl) -1, 2) 3-triazol-1-yl] -? / - [3-methansulfonic acid-2-methoxy-5- (1-methyl-cyclopropy) -phenyl] -4- methyl-benzamide 3- [4- (3-Benzyl-2-eti! -3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -? / - (5-yer-but) l-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyI-benzamide 3- [4- (3-fer-Butyl-2-cyclopropyl-3tf - imidazol-4-yl) -1, 2,3-triazol-1-yl] -? - (5- yer-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [ 4- (3-fer-ButyI-2-methyl-3H-imidazol-4-yl) -1, 2,3-triazoH -yl] - / V- [3-methanesulfonylamino-2-methoxy-5- (1 - methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Structure Name 3- [4- (3-fe / -Butyl-3H-imidazol-4-yl) -1,2,3-triazoM -yl] - ? / - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-yer-Butyl-3H-imidazole-4-yl) - 1, 2,3-triazol-1-yl] -? / - [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- ( 5-Ethyl-1-phenyl-1 H -pyrazol-4-yl) -1,2,3-triazol-1-yl] -? / - [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (5-Ethyl-1-phenyl-1W-pyrazol-4-yl) -imidazol-1 -yl] -? / - (2-methoxy) 5- trifluoromethyl-phenyl) -4-methyl-benzamide 3- [4- (5-Ethyl-1-phenyl-1 H -pyrazol-4-yl) -imidazol-1-yl] -? / - (3-methanesulfonylamino -2-methoxy-5- trifluoromethyl-phenyl) -4-methyl-benzamide Structure Name 3- [4- (5-Eti l-1-phenyl-1H-pyrazol-4-yl) - midazol-1-yl] -? / - [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methy1-benzamide 3- [4- (5-Ethyl-1-phenyl-1 H -pyrazol-4-yl) -imidazol-1-yl] -? / - [3- 10-methanesulfonylamino-2-methoxy- 5- (1-methyl-cyclopropyl) -phenyl] -4-hethyl-benzamide 3- [4- (6-Amino-pyridin-3-yl) -1, 2,3-triazol-1-yl] -? - (5-ene-butyl-3- 15-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [1- (1-Benzyl-piperidin-4-yl) -5-methy1-1 H-pyrrazol-4-yl] -1,2,3-triazol-1-yl} - / V- (5-fer-butyl-3- 20 -methansulfonyl-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (1-Benzyloxy-cyclopropyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -? / - (5-Fer-butyl-3-25-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide Structure Name 3-. { 4- [2- (2-Benzyloxy-1, 1-dimethyl-ethyl) -3-methyl-3-tf-imidazol-4-yl] -1,2,3-triazol-1-yl} -? / - (5-Fer-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -1- 'T or methyl-1 H -amidazol-4-yl] -1, 2,3-triazole-iVcC "* 1-yl} -? / - (5-Ier-butyI-3-methanesulfonylamino-2-methoxy-phenyI) -4-methyl-benzamide 3-. {4- [2- (4-Benzyl-piperazin-1-yl) -3- methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl.} -? / - (5-fer-butyl-3-methanesulfonylamino-2-methoxy-phenyl) ) - 4-methyl-benzamide 3- { 4- [2- (Hydroxy-phenyl-methyl] -3-methyl-3H-imidazol-4-yl] -1, 2,3-triazole- 1-yl.) -? / - [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3-. {4- [5- (2- Amino-ethyl) -1-phenyl-1H-pyrazol-4-yl] -1, 2,3-triazol-1-yl.} - - / - (5-fer-butyl-3-methanesulfonylamino-2-methoxy phenyl) -4-methyl-benzamide Structure Name 4- (4- {4- {5- (5-Fer-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2- methyl-phenyl] -1 H-1, 2,3-triazol-4-yl.} - 2-cyclopropyl-2H-pyrazol-3-yl) -piperidine-1-carboxylic acid? / - (5-fer-Butyl) -2-methansulfinyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-2-methanesulfinyl-phenyl) -3- [4- (5-ethyl-1-phenyl-1H-pyrazole -4-yl) - midazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-2-methanesulfinyl-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1, 2,3-triazole-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide,? ? / - (5-Fer-Butyl-2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1 H -pyrazol-4-yl) -> x 'imidazol-1-yl] -4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-2-methyl-pyridin-3-yl) -3- [4- (5-ethyl-1-phenyl-1 H-pyrazole-4- il) -imidazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-2-methyl-pyridin-3-yl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazole-1-yl} 4-methy1-benzamide? / - (5-fer-ButyI-3 { [(2-d.methylamino-ethyl) -methyl-amino] -methyl} -2-methoxy - phenyl) -4-methyl-3- (4-pyridin-3-yl-1, 2,3-triazol-1-yl) -benzamide? / - (5-fer-Butyl-3-cyano-2 -methoxyphenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-Fer-Butyl-3-cyano-2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -imidazol-1-yl ] -4-methyl-benzamide? / - (5-fer-Butyl-3-cyano-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazole-1-yl} - 4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- (4-furan-3-yl-1, 2,3-triazole-1 - il) -4-methyl-benzamide yy *,? / - (5-tert-Butyl-3-methanesulfonylamino- and 2-methoxy-phenyl) -3- (4-pyridin-3-yl-1,2,3-triazole-1) -yl) -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3,4-dimethyl-5- (4-pyridin-3-yl-1, 2,3-tr Azol-1-yl) -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - ((S) -2,2-dimethyl-1, 3- dioxolan-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - (1-cyclopropyl-5-methyl-1H-pyrazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino - 2-methoxy-phenyl) -3- [4- (1-cyclohexyl-5-methyl-1 H -pyrazol-4-yl) -1, 2,3-triazoM-yl] -4-methyl-benzamide Structure Name ? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-cyclohexyl-5-ethyl-1H-pyrazole-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-isopropyl-5-methyl-1 / - / - pyrazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonamino) - 2-methoxy-phenyl) -3- [4- (1-fer-butyl-5-methyl-1H-pyrazol-4-yl) -1, 2,3-triazol-1-yl] -4-met L-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-cyclopropyl-5-isopropyl-1H-pyrazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-cyclopropyl-5-ethyl) -1 H-pyrazol-4-yl) -1, 2,3-triazoM-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-isopropyl-5-methyl-1H-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide Structure Name? / - (5-fer-Butyl-3-methanesulfonylamino- and Ñ. 2-methoxy-phenyl) -3- [4- (2-cyclobutyl-3-fs .. methyl-SH-imidazoM-i-I ^. S-triazol-1-yl] -4-methyl-benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-dimethylammono-3-methyl-3H-imidazol-4-yl) - [1,2,3] triazol-1 -yl] -4-methyl-benzamide? / - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-diethyl-3-t-imidazo-4 -iI) -1, 2,3-triazol-1 -yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 ~ (2 , 3-dihydro-imidazo [2,1- £ >] thiazol-5-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-tert-Butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-cyclopropyl-2-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-isopropyl-2-methyl-3H-imidazol-4-yl) -1, 2, 3-triazole-1H] -4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-1-isopropyl -1-pyrazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-met ansulfonylamino-2-methoxy-phenyI) -3- [4- (5-cyclopropyl-1-isopropyl-1 H -pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl- Benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-isopropyl-1-phenyl-1H-pyrazol-4-yl) -1,2,3 -triazol-1-yl] -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-cyclopropyl-1-phenyl-1H- p -razol-4-yl) -1,2,3-triazoI-1-yl] -4-methyl-benzamide? / - (5-fer-ButyI-3-methanesulfonicinamino-2-methoxy-phenyl) - 3- [4- (5-ethyl-1-phenyl-1 H -pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -3-. { 4- [2- (2,2-dimethyl-propionyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino- and 2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-Vtf? 2,2-dimethyl-propyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} 4-methyl-benzamide? / - (5-Ier-ButyI-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-Hydroxy-1-methyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazoI-1-yl} -4-methyl-benzamide? - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2-hydroxy-1,1-dimethyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1, 2,3-triazoM-yl} -4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-cyclopropyl) -3-methyl-3 / - imidazol-4-yl] -1, 2,3-triazol-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-ethyl) -3-methyl-3H-imidazoI-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (cyclopropyl-hydroxy-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -3-. { 4- [5- (2-dimethylamino-ethyl) -1-phenyl-1 H -pyrazol-4-yl] -1,3,3-triazoI-1-yl} -4-methyl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (2- ° ../ P dimethylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (4-methy1-pyridin-3-yl) -1, 2,3-triazol-1-yl] -benzamide? / - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methy- 2-phenylsulfanyl-3-imidazol-4-yl) -10 1, 2,3-triazol-1-yl] -benzamide? / - (5-fer-Butyl-3-methanesulfonicinamino-2-methoxy-phenyl) - 4-Methyl-3- [4- (5-methyl-1-phenyI-1A7-pyrazol-4-yl) -imidazol-1-yl] -benzamide 15? / - (5-fer-Butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5-methyl-1- (1-methyl-piperidin-4-yl) -1H-pyrazol-4-yl] -1, 2,3-triazol-1-yl} -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [2-methyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-pyridin-2-yl-1) H-pyrazol-4-yl) -1, 2,3-triazol-1-yl] -benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- 3- [4- (2-morpholin-4-yl-thiazol-5-yl) -1,2,3-triazol-1-yl] -benzamide} / - (5-fer-Butyl-3-methanesulfonylamino - 2-methoxy-phenyl) -4-methylene-3-. { 4- [6- (2-methylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -benzamide / V- (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-morpholin-4-yl-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3 / -imidazol-4-yl) - p -razol-1-yl] -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyI-3- [4- (3-methyl-2-pyridin-4 -yl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl-benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- 3- [4- (5-methyl-1-piperidin-4-yl-1 / -pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide Structure Name? / - ( 5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-3- (4-pyridin-4-yl- [1, 2,3] triazol-1-yl) - benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-2-yl- [1,2,3] triazol-1-yl) -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5,6,7,8-tetrahydro-imidazo [1,2] -a] pyridn-3-yl) -1,2,3-triazol-1-yl] -benzamide? / - (5-fer-Butyl-3-methanesulfonylamine-2-methoxy-phenyl) 4-methyl-3- [4- (3-methyl-2-phenyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide A / - (5-fer Butyl-3-metansul phylamino- 2-methoxy-phenyl) -4-methyl-3-. { 4- [5- (2-morpholin-4-yl-ethyl) -1-phenyl-1 H-pyrazol-4-yl-1, 2,3-triazol-1-yl} -benzamide? / - (5-Fer-Butyl-3-methanesulfonyl-2-methoxy-phenyl) -4-methyl-3- [4- (1-phenyl-5-trifluoromethanes L-1 H -pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide Structure Name? / - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-3- [4- (1-methyl-2-pperazin-1-yl-1 H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-piperazin-1-yl-3/7-imidazole- 4-yl) -10 1, 2,3-triazol-1-yl] -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro-5H-pyrrolo [1, 2- a] imidazol-3-yl-5-cyclohexane)] - 15 [1,2,3] triazol-1-yl] -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide ? / - (5-fer-Butyl-3-methanesulfonicinamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-morpholin-4-yl-3H-methyldazole-4 -yl) - 1, 2,3-triazol-1-yl] -benzamide Structure Name? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro-5H-pyrroIo [1, 2- a] imidazol-3-iI-5- (2'-methyl-cycloproane))] - [1,2,3] triazol-1-yl3-benzamide / V- (5-fer-Butyl-3-methanesulfonyl) Non-2-methoxy-phenyl) -4-methyl-3- [4- (3-methy1-2-methylsulfanyl-3 / - / - imidazol-4-yl) -1,2,3-triazoM - il] -benzamide? / - (5-fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-etiI) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide? / - (5-Fer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (2-methyl-propane-2-suyphonyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} - benzamide? / - (5-fer-Butyl-3-methanesulfonyl-amino-2-methyl-phenyI) -3- [4- (2-cyclopropyl-3-methyl-3H-methyldazole-4-yl) -1.2 , 3-triazol-1-yl] -4-methyl-benzamide Structure Name / V- [5- (2-Hydroxy-1,1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide or their pharmaceutically acceptable salts, acids, esters or isomers. In all the compounds already described in the present application, in the case that the nomenclature is in conflict with the structure, it is to be understood that the compound is defined by the structure. Of particular importance, according to the invention, are the compounds of the formula (I) for use as pharmaceutical compositions with anti-cytokine activity. The invention further relates to the use of a compound of the formula (I) for preparing a pharmaceutical composition for the treatment and / or prevention of a disease or condition or cancer pathology mediated by cytokines. The invention further relates to pharmaceutical preparations containing, as active substance, one or more compounds of the formula (I) or one of its pharmaceutically acceptable derivatives, optionally combined with conventional excipients and / or vehicles.

The invention includes the use of any of the compounds already described, which contain one or more asymmetric carbon atoms which may occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. Said isomeric forms of these compounds are expressly included in the present invention. Each stereogenic carbon can be in the R or S configuration, or in a combination of configurations. It is to be understood that 'Isomer' includes any compound, as described above, as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereoisomers. Said isomeric forms of these compounds are expressly included in the present invention. Some of the compounds of the formula (I) may exist in more than one tautomeric form. The invention includes methods that use all those tautomers. The invention includes the use of any of the compounds already described which contain one or more isotopically-labeled forms. An isotopically-labeled form of an active agent of a combination of the present invention is identical to said active agent but due to the fact that one or more atoms of said active agent have been replaced with an atom or atoms having an atomic mass or a mass number different from the atomic mass or mass number of said atom that is usually found in nature. Examples of commercially readily available isotopes that can be incorporated into an active agent of a combination of the present invention according to established methods include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, for example, 2H, 3H, 13C, 14C, 15N, 180, 170, 31P, 32P, 3BS, 18F and 36C1, respectively. An active agent of a combination of the present invention, a prodrug thereof or a pharmaceutically acceptable salt of any of them containing one or more of the aforementioned isotopes and / or other isotopes of other atoms is contemplated within the scope of the present invention. invention. All terms as used in this specification, unless otherwise indicated, have their ordinary meaning as known in the art. For example, "Cl-4 alkoxy" is a Cl-4 alkyl with terminal oxygen, such as methoxy, ethoxy, propoxy, butoxy. All alkyl, alkenyl and alkynyl groups are to be understood as branched or unbranched, if structurally possible, unless otherwise indicated. Other more specific definitions are the following: The carbocycles include hydrocarbon rings containing between three and twelve carbon atoms. These carbocycles can be aromatic or non-aromatic ring systems. Systems with a non-aromatic ring can be mono- or poly-unsaturated. Preferred carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptanyl, cycloheptenyl, phenyl, indanyl, indenyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl, naphthyl, decahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl. Certain terms for cycloalkyl, such as cyclobutanyl and cyclobutyl, must be used interchangeably. The term "heterocycle" refers to a non-aromatic, 4-8 membered (but preferably 5 or 6 membered) monocyclic or non-aromatic 8-11 membered bicyclic heterocycle which may be saturated or unsaturated. Each heterocycle consists of carbon atoms and one or more, preferably between 1 and 4 heteroatoms selected from nitrogen, oxygen and sulfur. The heterocycle can be linked by any atom of the cycle, which results in the creation of a stable structure. Unless otherwise indicated, heterocycles include, but are not limited to, for example pyrrolidinyl, pyrrolinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, dioxalanyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3 dioxolanone, 1,3-dioxanone, 1,4-dioxanyl, piperidinonyl, tetrahydropyrimidonyl, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide and tetramethylene sulfone. It is to be understood that the term "heteroaryl" means a 5-8 membered aromatic monocyclic or 8-11 membered bicyclic ring containing 1-4 heteroatoms such as N, O and S. Unless otherwise indicated, said "heteroaryls" include aziridinyl, thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyranyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, quinolinyl, quinazolinyl, naphthyridinyl, indazolyl, triazolyl, pyrazolo [3,4-b] pyrimidinyl, purinyl, pyrrolo [2,3-b] iridinyl, pyrazolo [3, -b] pyridinyl, tuberzidinyl, oxazo [4,5-b] pyridinyl and imidazo [4, 5-b] pyridinyl. The term "heteroatom", as used herein, means atoms other than carbon atoms such as 0, N, S and P. In all carbon chains or alkyl groups, one or more atoms may optionally be replaced of carbon with heteroatoms: O, S or N, it is to be understood that if N is not substituted, then it is NH, it is also to be understood that the heteroatoms may replace either terminal carbon atoms or internal carbon atoms. within a branched or unbranched carbon chain. Said groups can be substituted, as described hereinabove, with group such as oxo to result in definitions such as, but not limited to: alkoxycarbonyl, acyl, amido and thioxo. The term "aryl", as used herein, means aromatic carbocycle or heteroaryl, as defined herein. Each aryl or heteroaryl, unless otherwise specified, includes its partially or fully hydrogenated derivative. For example, quinolinyl can include decahydroquinolinyl and tetrahydroquinolinyl, naphthyl can include its hydrogenated derivatives, such as tetrahydranaphthyl. Other partially or fully hydrogenated derivatives of the aryl and heteroaryl compounds described herein will be obvious to one of ordinary skill in the art. When used here, "nitrogen" and "sulfur" include any oxidized form of nitrogen and sulfur and the quaternized form of any basic nitrogen. For example, for a radical -S-alkyl Cl-6, unless otherwise specified, it is to be understood that this includes -S (O) -alkyl Cl-6 and -S (0) 2-Cl-alkyl 6, likewise, -S-Ra can be represented as phenyl-S (0) m- when Ra is phenyl and wherein m is 0, 1 or 2. The term "halogen", as used in the present specification, means bromine, chlorine, fluorine or iodine, preferably fluorine. The definitions "partially or totally halogenated"; partially or fully fluorinated; "substituted with one or more halogen atoms", includes, for example, mono, di or trihalo derivatives on one or more carbon atoms. For alkyl, a non-limiting example would be -CH2CHF2, -CF3 / etc. The compounds of the invention are only those contemplated as 'chemically stable', as will be appreciated by persons skilled in the art. For example, a compound that would have a 'free valency' or a 'carbanion' are not compounds contemplated by the methods of the invention described herein. The invention includes pharmaceutically acceptable derivatives of the compounds of the formula (I). A "pharmaceutically acceptable derivative" refers to any pharmaceutically acceptable salt or ester, or any other compound which, upon administration to a patient, is capable of (directly or indirectly) providing a compound useful for the invention or one of its metabolites pharmacologically active or pharmacologically active residues. It is to be understood that a pharmacologically active metabolite means any compound of the invention capable of being metabolized enzymatically or chemically. This includes, for example, hydroxylated or oxidized derivative compounds of the formula (I). Pharmaceutically acceptable salts include those derived from pharmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acids include hydrochloric, hydrobromic, sulfuric, nitric, perchloric, fumaric, maleic, phosphoric, glycolic, lactic, salicylic, succinic, toluene-p-sulfuric, tartaric, acetic, citric, methanesulfonic, formic, benzoic, malonic acids. , naphthalene-2-sulfuric and benzenesulfonic. Other acids, such as oxalic acid, while not pharmaceutically acceptable per se, may be employed in the preparation of salts useful as intermediates for obtaining the compounds and their pharmaceutically acceptable acid addition salts. Salts derived from appropriate bases include alkali metal (e.g., sodium), alkaline earth metal (e.g., magnesium), ammonium, and N- (Cl-C4) alkyl 4+ salts. Furthermore, within the scope of the invention is the use of prodrugs of the compounds of the formula (I). Prodrugs include those compounds which, upon simple chemical transformation, are modified to produce the compounds of the invention. Simple chemical transformations include hydrolysis, oxidation. and reduction. Specifically, when a prodrug is administered to a patient, the prodrug can be transformed to a compound described hereinabove, thus imparting the desired pharmacological effect.

GENERAL SYNTHESIS METHODS The invention additionally provides methods for making the compounds of the formula (I). The compounds of the invention can be prepared by the general methods and examples presented below, and methods known to those of ordinary skill in the art. In the following schemes, unless otherwise specified, Ar1, R1 -R6 and X in the formulas set forth below will have the meanings defined for these groups in the definition of the formula (I) of the invention described above. The intermediates used in the syntheses below are commercially available or readily prepared by methods known to those skilled in the art. More reference can be made in this regard with respect to US Patent No. 6,358,945, US Applications No. 09 / 714,539, 09 / 834,797, 10 / 120,028, 10 / 143,322 and 10 / 147,675, US Provisional Applications No. 60 / 567,693, 60 / 526,569, 60 / 570,284. Each of the aforementioned is incorporated in its entirety. The progress of the reaction can be monitored by conventional methods, such as thin layer chromatography (TLC). Intermediates and products can be purified by methods known in the art, including column chromatography, HPLC or recrystallization. In the following analysis, Q represents the ring between the phenyl ring and het of formula I, as shown below: (1) The compounds of the formula (I) having Q = a triazole (A t = B = N, D = CH) can be prepared as illustrated in Scheme I. An azide II intermediate is reacted with a heteroarylacetylene III intermediate in a suitable solvent such as EtOH, optionally in the presence of a copper salt such as CuSO4 with an appropriate reducing agent such as sodium ascorbate (Rostovtsev, VV et al. Chem., Int. Ed. Engl. 2002, 41, 2596) and optionally heating simultaneously to provide the thiazole intermediate IV. Coupling of the IV carboxylic acid with the desired aniline ArxNH2 using standard coupling conditions known in the art provides the compound of the formula (I) or a precursor which can also be modified by methods known in the art to provide the desired compound of the formula (I). The heteroarylacetylene III intermediate can be prepared by the reaction of intermediate V, wherein X is I, Br, Cl or -OS02CF3, with trimethylsilylacetylene VI, in the presence of a suitable catalyst such as (Ph3P) PdCl2, a copper salt such as Cul and a suitable base such as Et 3 N, with subsequent reaction with tetrabutylammonium bromide to remove the trimethylsilyl group. Alternatively, a heteroaraldehyde VII can be reacted with dimethyl 2-oxo-1-diazopropylphosphinate in the presence of a suitable base such as K 2 CO 3 to provide the desired intermediate III.

Scheme I vp The sequence of the reactions can be reversed, as illustrated in Scheme II. Using this procedure, the amide coupling step is carried out first with intermediate II to provide intermediate VIII. This is followed by a reaction with the heteroarylacetylene III intermediate to provide the desired compound of the formula (I).

Scheme II I The heteroarylaldehydes VII shown in Scheme I are commercially available or can be easily prepared from commercially available intermediates by methods known in the art. For example, as illustrated in Scheme III, heteroarylaldehydes can be prepared by direct reduction of the corresponding ester IX, for example by reaction with diisobutylaluminum hydride. Alternatively, ester IX can be reduced to an alcohol X by treatment with a suitable reducing agent such as lithium-butyl hydride. The alcohol can then be oxidized to aldehyde VII by treatment with a suitable oxidizing agent, such as Mn02. Start XI esters can be marketed, prepared from commercially available carboxylic acids or prepared by methods known in the art. In addition, many heteroarylaldehydes can be prepared by direct formylation of a heteroaryl moiety. For example, the treatment of an optionally substituted heteroaryl portion XI with a suitable base such as n-BuLi, in a suitable solvent such as THF, preferably while cooling to about -78 ° C, with subsequent treatment with a formylating agent. , such as dimethylformamide (XII), provides a heteroarylaldehyde VII. Scheme III HCL ^ Het X RO ^ ^ Het H T t O Y He O IX VII The compounds of the formula (I) having Q = imidazole (B = N; A = D = CH) can be prepared as described in Scheme IV. The aniline intermediate XIII is reacted with a heteroaryl ketone XIV, wherein Y is a leaving group such as Cl, Br or I, to provide the substituted aniline XV. The reaction of XV with a thiocyanate salt, such as potassium thiocyanate, provides the intermediate of 2-mercaptoimidazole XVI. Treatment of XVI with NaN02 in HN03 provides the imidazole intermediate XVII. Intermediate XVII can then be hydrolyzed and coupled with the desired aniline intermediate, as described above to provide the desired compound of formula (I). Scheme IV Another method that can be used to obtain the compounds of the formula (I) is illustrated in Scheme V. The halogenated intermediate XVIII, wherein hal = Br, I or Cl, can be linked with a derivatized heteroaryl portion (M -Het), using reactions known in the art. For example, if M is a trialkyltin moiety, a Stille coupling can be carried out (see, for example, JK Stille, Angew, Chem. Int. Ed. Engl., 1986, 25, 508) for a review, see V. Fariña et al, Org. Reac, 1991, 50, 1). Alternatively, if M is a boric acid group, a Suzuki cross-coupling reaction can be carried out (see, for example, J. Hassan et al, Chem Rev., 2002, 102, 1359 and N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457) to obtain the desired compound. In Scheme V, a more specific example for the synthesis of a compound of the formula (I) having Q = pyrazole is illustrated (X = Y = N; W = Z = C). Using this method, the phenylhydrazine intermediate XIX is treated with malondialdehyde (bismethylacetal) in the presence of an acid such as HCl to provide the pyrazole XX. Halogenation, for example by treatment of XX with bromine, provides XXI (Hal = Br). The treatment of XXI with the trialkylstannaylheteroaryl intermediate, for example, a tributylstannaylheteroaryl XXII, in the presence of a palladium catalyst such as Pd (PPh3) 4, in a suitable solvent such as dioxane, while heating to about 100 ° C, provides the coupled intermediate XXIII. Hydrolysis of the ester in intermediate XXIII and coupling of the resulting carboxylic acid with an aniline intermediate, as described above in Schemes I and IV, provides the desired compound of the formula (I). Scheme V XVlll XIX XX XXI XXIII EXAMPLES OF SYNTHESIS Abbreviations Boc-tert-butyloxycarbonyl I? -CPBA M-chloro-peroxybenzoic acid CDl Carbonyldiimidazole DIBAL-H-diisobutyl-aluminum hydride DIPEA N / N-Diisopropylethylamine DMAP 4-Dimethylaminopyridine DMF Dimethylformamide HATU O- (7-azabenzotriazol-1-yl) - N , N, N ', N' -tetramethyluronium hexafluorophosphate HOBt 1-Hydroxybenzotriazole LHMDS Lithium hexamethyldisilazide MTBE methyl tertiary butyl ether NMP N-methyl-2-pyrrolidinone PS Polystyrene TBAF Tetrabutylammonium fluoride TBD 1, 5, 7-Triazabicyclo [4.4. 0] dec-5- ene THF Tetrahydrofuran TMEDA Tetramethylethylenediamine TMS Trimethylsilyl Example 1: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-chloro-pyridin-3-yl) - [1,2,3] triazole-1 -yl] -4-methyl-benzamide A 2-chloro-5-iodopyridine (Aldrich; 2. 44 g, .2 mmol), (PPh3) 2PdCl2 (360 mg, 0.51 mmol) and Cul (97 mg, 0. 51 mmol) under? 2 were added 35 mL of Et3? and 1.00 g (10.2 mmol) of Me3SiCCH. The pale green / brown suspension was stirred for six days under N2. The mixture was concentrated and the resulting suspension was stirred with 50 ml of hot hexanes, and the orange solution was separated from the insoluble material. The remainder of the residue was washed three more times with hot hexanes and the combined washings were concentrated and chromatographed. After careful concentration, 1.4 g of 2-chloro-5-trimethylsilanylethynyl-pyridine was obtained as a beige solid. A 1 M solution of TBAF in THF (12 ml) was added to 500 mg (2.38 mmol) of 2-chloro-5-trimethylsilanylethynyl-pyridine and the black solution was stirred overnight. The mixture was concentrated, the resulting residue was stirred in 50 ml of Et20 for 1 h and the liquid was decanted from the solids. This washing procedure was repeated twice and the combined washings were concentrated and chromatographed to provide 240 mg of 2-chloro-5-ethynylpyridine as a colorless solid.

To a suspension of 308 mg (1.75 mmol) of 3-azido-4-methyl benzoic acid (US 04/102492) and 240 mg (1.75 mmol) of 2-chloro-5-ethynylpyridine in 1 ml of water and 2 ml of EtOH was added 243 μL (1.75 mmol) of Et3N. To this solution was added 1.75 ml of aqueous IMM sodium ascorbate followed by 1.75 ml of 0.1 M aqueous solution of CuS04 and the resulting yellow suspension was stirred for two days. A 1 M solution of acetic acid in water (1.75 ml) was added along with an additional 2 ml of water. The suspension was stirred for 1 h, then filtered, washed with water (2x2 ml) and hexanes (2x10 ml) and dried under suction to provide 470 mg of 3- [4- (6-chloro-pyridin-3) acid. -yl) -1,2,3-triazol-1-yl] -4-methyl-benzoic acid. 3- [4- (6-Chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl-benzoic acid (470 mg, 1.49 mmol), N- (3 -amino-5-er-buty1-2-methoxy-phenyl) -methane-sulfonamide (WO 02/083628) (488 mg, 1.79 mmol) and 0.87 ml (5.0 mmol) of DIPEA in 15 ml of DMF. Then 1.14 g (2.99 mmol) of HATU and 403 mg (2.99 mmol) of HOBt were added and the dark brown solution was stirred overnight at room temperature. The mixture was then partitioned between EtOAc and water. The layers were separated and the organic portion was washed with water (2x50 ml), brine (50 ml), dried (MgSO 4), filtered and concentrated. Chromatography gave 375 mg (0.66 mmol, 44%) of the title compound with 95% purity. ESI MS m / z 569 [C 27 H 29 ClN 6 4 S + H] +.

Example 2: N- (5-fcer-Butyl-2-methyl-pyridin-3-yl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] - [1, 2, 3] triazol-1-yl} -4-methyl-benzamide A solution of 500 mg (2.09 mmol) of 2-chloro-5-iodo pyridine in 1.64 g (23.1 mmol) of aminomethylcyclopropane was heated to 100 ° C in a sealed tube for 48 hours. The mixture was then concentrated, dissolved in EtOAc, washed with water and brine, dried with MgSO 4, filtered and concentrated. Recrystallization from hexanes afforded 440 mg (1.61 mmol, 77%) of cyclopropylmethyl- (5-iodo-pyridin-2-yl) -amine. ESI MS m / z 275 [C9HX1IN2 + H] +.

To 1.14 g (4.16 mmol) of cyclopropylmethyl- (5-iodo-pyridin-2-yl) -amine, 150 mg (0.21.mmol) of (PPh3) 2PdCl2 and 40 mg (0.21 mmol) of Cul under N2 was added 11 mL of Et3N and 0.59 mL (8.3 mmol) of Me3SiCCH. The pale green / yellow suspension was stirred overnight, concentrated and then partitioned between EtOAc and water. The organic portion was washed with water, brine, dried (Na2SO4), filtered, concentrated and chromatographed (0-30% EtOAc in hexanes), which produced a reddish brown solid. The residue was stirred with 10 ml of refluxing hexanes. The mixture was filtered and the solids were washed twice with 5 ml of hot hexanes. The filtrate and washings were combined and concentrated to provide 855 mg of cyclopropylmethyl- (5-trimethylsilanylethynyl-pyridin-2-yl) -amine as a fluffy yellow solid. To a solution at 0 ° C of 855 mg (3.50 mmol) of cyclopropylmethyl- (5-trimethylsilanylethynyl-pyridin-2-yl) -amine in 7 ml of THF, 7.0 ml (7.0 mmol) of TBAF-I was slowly added in THF The mixture was stirred for 2 hours, then poured into water and extracted with Et20. The Et20 was washed with brine. The washings were extracted once with Et20 and the combined extracts were diluted with 10 ml of CH2C12 and allowed to stand for 10 min. The solution was then decanted from the water that had been separated and dried with Na 2 SO 4, filtered, concentrated and chromatographed (1-20% EtOAc in hexanes) to provide 467 mg of 2- (cyclopropylmethyl) amino-5-ethynylpyridine.

HO VN3 3-Azido-4-methylbenzoic acid (497 mg, 2.81 mmol) was suspended in 6.5 mL of EtOH. To this mixture was added 4N NaOH until the mixture became homogeneous, followed by 2- (cyclopropylmethyl) amino-5-ethynyl pyridine (460 mg, 2.61 mmol) and 529 mg (2.67 mmol) of sodium ascorbate in 0.7 ml of Water. The mixture was stirred rapidly while 2.67 ml of a 0.1 M CuS04 solution was added. A yellow precipitate formed and the mixture was stirred rapidly for 14 hours. The mixture was poured into water and acidified carefully with HOAc. The resulting precipitate was filtered and washed with water. A fine yellow powder was isolated. This material was triturated in 1 mL of MeOH and 5 mL of NH 4 OH was added. The resulting green mixture was stirred for 10 min, then HOAc was carefully added until a white precipitate formed (pH 8-9). The precipitate was filtered and washed with 1% HOAc in water, then with water and hexanes to provide 607 mg (1.74 mmol, 65%) of 3- acid. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzoic '.

Example 2 was prepared by attaching 3- acid. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} 4-methyl-benzoic with 5-er-butyl-2-methyl-pyridin-3-ylamine (See US Provisional Application 60 / 567,693) in the same manner as Example 1. ESI MS m / z 496 [C29H33N70 + H] +.

Example 3: N- (5-fcer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-2-yl- [1,2,3] triazol-1-yl) ) -benzamide 4-Methyl-3- (4-pyridin-2-yl- [1, 2,3] triazol-1-yl) -benzoic acid was prepared from 3-azido-4-methyl benzoic acid and 2-ethynylpyridine ( Aldrich) in the same manner as 3- [4- (6-chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl-benzoic acid (Example 1).

Example 3 was prepared by linking 4-methyl-3- (4-pyridin-2-yl- [1,2,3] triazol-1-yl) -benzoic acid with N- (3-amino-5-tert-butyl) -2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. ESI MS m / z 533 [C27H3o? 604S + H] +.

Example 4: N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide Example 4 was prepared by attaching 3- acid. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methoxy-benzoic with 3-amino-5-er-butyl-2-methyl-benzonitrile (See US Provisional Application 60 / 567,693) in the same manner as Example 1. ESI MS m / z 536 [C3? H33N70 + H] +.

Example 5: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-fluoro-3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) ) -benzamide 4-Fluoro-3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) -benzoic acid was prepared from 3-azido-4-fluorobenzoic acid (US 04 / 102492) and 3-ethynylpyridine (Aldrich) in the same manner as 3- [4- (6-chloro-pyridin-3-yl) -1, 2, 3-triazol-1-yl] -4-methyl- benzoic (Example 1) Example 5 was prepared by linking 4-fluoro-3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) -benzoic acid with N- (3-amino-5-tert-butyl) -2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. ESI MS / z 539 [C26H27F? 604S + H] +.

Example 6: N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3-. { 4- [6- (cyclopropyl ethyl-amino) -pyridin-3-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide Example 6 was prepared by attaching 3- acid. { 4- [6 ~ (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzoic with 5-er-butyl-2-methanesulfinyl-phenylamine (see US Provisional Application 60 / 526,569) in the same manner as Example 1. ESI MS m / z 543 [C30H34? 6O2S + H] +. Example 7: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-methyl-pyridin-3-yl) [1,2,3] triazol-1-yl] -benzamide In a flask under N2, 87 mg (0.23 mmol) of (CH3CN) 2PdCl2 and 36 mg (0.19 mmol) of Cul were added, followed by 5 ml of dioxane, 131 mg (0.454 mmol) of t-BuP-HBF4, 649 mg (3.77 mmol) of 2-methyl-5-bromopyridine (Fluka), 1.3 ml (9.4 mmol) of Me3SiCCH and finally 0.64 ml (4.5 mmol) of i-Pr2NH. The mixture was stirred for one hour, it was filtered through celite and washed with EtOAc. The filtrate was washed with water and brine, and the washings were extracted once with EtOAc. The combined extracts were dried with Na 2 SO 4, filtered, concentrated and chromatographed (0-2% MeOH in CH 2 C 12) to provide 646 mg of 2-methyl-5-trimethylsilanylethynyl-pyridine. A mixture of 654 mg (3.45 mmol) of 2-methyl-5-trimethylsilanylethynyl-pyridine and 8 ml of 1 M TBAF in THF was stirred for 2 hours. The mixture was concentrated and chromatographed (10-50% EtOAc in hexanes) to provide 301 mg of 2-methyl-5-ethynylpyridine. 4-Methyl-3- [4- (6-methyl-pyridin-3-yl) - [1, 2, 3] triazol-1-yl] -benzoic acid was prepared from 3-azido-4-methylbenzoic acid and 2-methyl-5-ethynyl-pyridine in the same way as 3- [4- (6-chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl -benzoic acid (Example 1).

Example 7 was prepared by linking 4-methyl-3- [4- (6-methyl-pyridin-3-yl) - [1, 2,3] triazol-1-yl] -benzoic acid with N- (3-amino) -5- er-butyl-2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. ESI MS m / z 547 [C28H32? 604S + H] +.

Example 8: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3,4-dimethyl-5- (4-pyridin-3-yl- [1,2,3] triazole-1 -il) -benzamide A suspension of 100 mg (0.52 mmol) of 3-azido-4,5-dimethylbenzoic acid (US 04/102492), 54 mg (0.52 mmol) of 3-ethynyl-pyridine and 200 μL of EtOH up to 120 ° was heated. C in a sealed tube for 12 hours. The mixture was cooled and diluted with 500 μL of EtOH. The mixture was filtered and the solids were washed with EtOH (3x0.5 ml). The solids were dried to provide 50 mg of 3,4-dimethyl-5- (4-pyridin-3-yl- [1, 2,3] triazol-1-yl) -benzoic acid.

Example 8 was prepared by linking 3, 4-dimethyl-5- (4-pyridin-3-yl- [1, 2,3] triazol-1-yl) -benzoic acid with N- (3-amino-5-ter) -butyl-2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. ESI MS m / z 549 [C28H32? 604S + H] +.

Example 9: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (2-ethyl-pyridin-3-yl) - [1,2, 3] triazol-1-yl] -benzamide To an ice cooled suspension of 3-hydroxy-2-methylpyridine (2.0 g, 18.3 mmol) and N-phenyltriflimide (6.55 g; 18. 3 mmol) in 50 ml of CH2C12 was added dropwise 2.70 ml (19.4 mmol) of Et3 ?. The resulting suspension was stirred for 1 h at 0 ° C and for an additional 2 hours at room temperature. The mixture was then washed twice with 20 ml of 1M NaOH, once with partially saturated KC03 and once with brine. The extract was dried with Na 2 SO 4, filtered and concentrated to provide trifluoro-methanesulfonic acid 2-methyl-pyridin-3-yl ester as a pale brown oil. ESI MS m / z 242 [C7H6F3N03S + H] +. 2-Methyl-3-ethynyl-pyridine was prepared from 2-methyl-pyridin-3-yl ester of trifluoromethanesulfonic acid in the same manner as 2-chloro-5-ethynyl-pyridine (Example 1). 4-Methyl-3- [4- (2-methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzoic acid (5: 3 mixture with 4-methyl- 3- [5- (2-methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzoic acid) from 3-azido-4-methyl benzoic acid and 2-methyl- 3-ethynyl-pyridine in the same manner as 3, 4-dimethyl-5- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) -benzoic acid (Example 8).

Example 9 was prepared by attaching 4-methyl-3- [4- (2-methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzoic acid (5: 3 mixture with acid 4-methyl-3- [5- (2-methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzoic acid) with N- (3-amino-5-er-butyl) -2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. Preparative HPLC was used to separate N- (5- tert -butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- 3- [4- (2-Methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzamide of N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy) phenyl) -4-methyl-3- [5- (2-methyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzamide. ESI MS m / z 549 [C28H32? S04S + H] +.

Example 10: N- (5-tert-Butyl-3. {[[(2-dimethylamino-ethyl) methyl-amino] -methyl} -2-methoxy-phenyl) -4-methyl-3- (4 -pyridin-3-yl- [1,2,3] triazol-1-yl) -benzamide 4-Methyl-3- (4-pyridin-3-yl- [1, 2,3] triazol-1-yl) -benzoic acid was prepared from 3-azido-4-methylbenzoic acid and 3-ethynylpyridine (Aldrich ) in the same manner as 3- [4- (6-chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl-benzoic acid (Example 1).

Example 10 was prepared by attaching 4-methyl-3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) -benzoic acid with N- (3-amino-5-tert-butyl) -2-methoxy-benzyl) -N, N ', N' -trimethyl-ethane-1,2-diamine (see US Provisional Application 60 / 526,569) in the same manner as Example 1. ESI MS m / z 554 [C32H41? 702-H] ".

Example 11: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -4-chloro-3- (4-pyridin-3-yl- [1, 2, 3] triazol-1-yl ) -benzamide 4-Chloro-3- (4-pyridin-3-yl- [1, 2,3] triazol-1-yl) -benzoic acid was prepared from 3-azido-4-chloro-benzoic acid (US 04/102492 ) and 3-ethynyl pyridine (Aldrich) in the same way as 3- [4- (6-chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl- benzoic (Example 1).

Example 11 was prepared by linking 4-chloro-3- (4-pyridin-3-yl- [1, 2, 3] triazol-1-yl) -benzoic acid with N- (3-amino-5-tert-butyl) -2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. ESI MS m / z 555 [C2SH27C1? S0S + H] +.

Example 12: N- [3-Methanesulfonylamino-2-methoxy-5- (1-ethyl-cyclopropyl) -phenyl] -3- [4- (5-methoxy-pyridin-3-yl) - [1,2,3 ] triazol-1-yl] -4-methyl-benzamide -Ethynyl-3-methoxy pyridine was prepared from 5-bromo-3-methoxy pyridine (Frontier) in the same manner as 2-chloro-5-ethynyl-pyridine (Example 1). 3- [4- (5-Methoxy-pyridin-3-yl) '- [1,2] triazol-1-yl] -methyl-benzoic acid was prepared from 3-azido-4-methyl benzoic acid and 5-ethynyl-3-methoxypyridine in the same way as 3- [4- (6-chloro-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl- benzoic (Example 1).

Example 12 was prepared by attaching 3- [4- (5-methoxy-pyridin-3-yl) - [1,2,3] triazo.l-1-yl] -4-methyl-benzoic acid with N- [3 -amino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -methanesulfonamide (US 04/102492) in the same manner as Example 1. ESI MS m / z 563 [C28H30? sO5S + H] + .

Example 13: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-morpholin-4-ylmethyl-pyridin-3-yl) - [1 , 2,3] triazol-1-yl] -benzamide 4- (5-Ethynyl-pyridin-2-ylmethyl) -morpholine was prepared from 4- (5-bromo-pyridin-2-ylmethyl) -morpholine (US 6,358,945) in the same manner as 2-methyl-5- ethynylpyridine (Example 7).

A suspension of 87.5 mg (0.494 mmol) of 3-azido-4-methyl-benzoic acid and 100 mg (0.494 mmol) of 4- (5-ethynyl-pyridin-2-ylmethyl) -morpholine was suspended in 200 μL of EtOH and was heated to 140 ° C for 1 h in a microwave reactor. After cooling, the mixture was concentrated to provide 150 mg of 4-methyl-3- [4- (6-morpholin-4-ylmethyl-pyridin-3-yl) -1,2,3-triazole-1-yl. ] -benzoic acid and its triazole isomer 4-methyl-3- [5- (6-morpholin-4-ylmethyl-pyridin-3-yl) -1,2,3-triazol-1-yl] -benzoic acid in one 2: 1 ratio Example 13 was prepared by linking 4-methyl-3- [4- (6-morpholin-4-ylmethyl-pyridin-3-yl) - [1,2,3] triazol-1-yl] -benzoic acid (2: 1 with 4-methyl-3- [5- (6-morpholin-4-ylmethyl-pyridin-3-yl) -1,2, 3-triazol-1-yl] -benzoic acid) with N- (3-amino) -5- te -butyl-2-methoxy-phenyl) -methane-sulfonamide in the same manner as Example 1. Chromatography separated the isomers of triazole. ESI MS m / z 635 [C 32 H 39 N 7 O S + H] +.

Example 14: N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) ) -benzamide 4-Methyl-3- (4-pyridin-3-yl-1,2,3-triazol-1-yl) -benzoic acid (76.3 mg, 0.272 mmol) was suspended in 5 mL of CH2C12 and 1 mL of THF and 0.04 ml (0.4 mmol) of oxalyl chloride. Then a drop of DMF was added to the stirred suspension and the mixture was stirred for 2 hours. The resulting cloudy solution was concentrated to dryness and suspended in CH2C12. N- (3-Amino-5-er-butyl-2-methoxy-phenyl) -methane-sulfonamide (81 mg, 0.30 mmol) was added, then 0.06 ml (0.5 mmol) of 2,6-lutidine and the resulting solution it stirred throughout the night. The mixture was then washed with? AHS04IM,? AHC03 saturated and brine. The organic portion was dried with α2S04, filtered and concentrated. Chromatography (0-6.5% MeOH in CH2C12), with careful selection of pure pure fractions, yielded 80 mg (0.15 mmol, 55%) of Example 14. ESI MS m / z 535 [C27H30N6O4S + H] +.

Example 15: 3 - [4- (6-amino-pyridin-3-yl) [1, 2, 3] triazol-1-yl] -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide A 2-amino-4-bromopyridine (Aldrich, 500 mg, 2.89 mmol), (PhCN) 2PdCl2 (66 mg, 0.17 mmol), (t-Bu) 3P «BF4 (101 mg, 0. 345 mmol) and Cul (28 mg, 0.15 mmol) under N2, were added ml of dioxane, 1.02 ml (7.03 mmol) of Me3SiCCH and 0.49 ml (3.5 mmol) of i-Pr2NH. The mixture was heated to 80 ° C under an N2 atmosphere overnight. The mixture was then diluted with EtOAc and filtered through Celite. The filtrate was washed with NHC1 and brine. The organic phase was dried with Na 2 SO, filtered and concentrated. The reddish brown residue was crystallized from hexanes to provide 2-amino-4- (trimethylsilyl) ethynylpyridine (157 mg, 1.88 mmol, 65%). ESI MS m / z 191 [C 10 H 4 N 2 Si + H] +. The above-mentioned trimethylsilylalkyne (340 mg, 1.79 mmol) was dissolved in 3.6 ml of cold THF and 3.6 ml of 1.0 M TBAF in THF was slowly added to the stirring mixture. After 2 hours, the mixture was concentrated and partitioned between Et20 and water. The ether layer was washed with brine and the washings were extracted once with Et20. The extracts were combined, dried with MgSO 4, filtered and concentrated to provide 191 mg of 2-amino-5-ethynylpyridine (1.61 mmol, 91%). 3-Azido-4-methyl benzoic acid (240 mg, 1.24 mmol) was suspended in 3 mL of CH2C12 and 3 mL of THF. Oxalyl chloride (0.14 ml, 1.5 mmol) was added, followed by 1 drop of 10% DMF in THF. The mixture was stirred for 1 h and then concentrated. The residue was redissolved in dry CH2C12 (5 mL) and 391 mg (1.27 mmol) of N- (3-amino-5-er-butyl-2-methoxy-phenyl) -methane-sulfonamide was added followed by 0.4 mL (2.5 mL). mmol) of DIPEA. The mixture became homogeneous and stirred for 4 hours and then washed with aHSA4, MM and ?Ha03 saturated. The washings were extracted once with CH2C12 and the extracts were combined, dried with? A2S04, filtered and concentrated to provide 516 mg (93%) of 3-azido-N- (5-er-butyl-3-methanesulfonylamino -2-methoxy-phenyl) -4-methyl-benzamide as a tan powder.

To a stirring suspension of 310 mg (0.719 mmol) of 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in 2 ml of EtOH and 2 ml 4M NaOH was added dropwise until the mixture became homogeneous. A solution of 142 mg (0.719 mmol) of sodium ascorbate in 0.5 ml of water was added, followed by 100 mg (0.719 mmol) 2-amino-4-ethynylpyridine in 1 ml of EtOH. Finally, 0.72 ml of 0.1 M CuSO 4 was added and the resulting mixture was stirred vigorously for 14 hours. The mixture was then diluted with 40 ml of water and HOAc was added until a precipitate formed and the pH was about 6. The precipitate was filtered and washed with water and hexanes. The solids were chromatographed (0-5% MeOH / 0.5% NH 4 OH in CH 2 C 12) to provide 321 mg (0.584 mmol, 81%) of the title compound. ESI MS m / z 548 [C27H31N704S-H] ".

Example 16: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- (4-pyridin-3-yl- [1,2,3] triazol-1-yl) -benzamide 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -benzamide was prepared from 3-azido benzoic acid and N- (3-amino-5-er-butyl-2) -methoxy-phenyl) -methane-sulfonamide in the same manner as 3-azido-N- (5-er-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15). 3-Azido benzoic acid was prepared from 3-amino benzoic acid in the same manner as 3-azido-4-methylbenzoic acid.

Example 16 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -benzamide and 3-ethynylpyridine in the same manner as Example 15. ESI MS m / z Sil [C26H28? 604S + H] +.

Example 17: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -4-methyl-3- (4-pyridin-4-yl- [1,2,3] triazol-1-yl) ) -benzamide Example 17 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 4-ethynylpyridine hydrochloride (Aldrich) in the same way than Example 15. ESI MS m / z 535 [C27H30? 6O4S + H] +.

Example 18: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -benzamide Example 18 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 5-ethynyl-1-methyl-1H-imidazole ( Aldrich) in the same manner as Example 15. ESI MS m / z 538 [C26H3 ?? 704S + H] +.

Example 19: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-methylamino-pyridin-3-yl) - [1,2,3 ] triazol-1-yl] -benzamide To a solution of 2-methylaminopyridine (Aldrich, 1.00 g, 9.25 mmol) in 10 ml of 1: 1 HOAc and water was added 2.35 g (9.25 mmol) of I2. The resulting brown solution was heated to 80 ° C for 3 hours. After cooling to room temperature, the mixture was neutralized with saturated aHC03 and extracted with Et20. The extract was washed with water and brine, dried with MgSO 4, filtered and concentrated to give 540 mg of (5-iodo-pyridin-2-yl) -methyl-amine. (5-Ethynyl-pyridin-2-yl) -methyl-amine was prepared from (5-iodo-pyridin-2-yl) -methyl-amine in the same manner as 2-chloro-5-ethynyl-pyridine ( Example 1) .

Example 19 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methylbenzamide and (5-ethynyl-pyridin-2-yl) -methyl- amine in the same manner as Example 15. ESI MS m / z 564 [C28H33? 704S + H] +.

Example 20: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (4-methyl-pyridin-3-yl) - [1,2,3 ] triazol-1-yl] -benzamide 3-Ethynyl-4-methyl-pyridine was prepared from 3-bromo-4-methyl-pyridine in the same manner as 2-amino-3-ethynyl pyridine (Example 15).

Example 20 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-f-enyl) -4-methyl-benzamide and 3-ethynyl-4-methyl-pyridine in in the same way as Example 15. ESI MS m / z 549 [C28H32? e04S + H] +.

Example 21: N- (5-fcer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-f luoro-4-methyl-5- (4-pyridin-3-yl- [1, 2, 3] triazol-1-yl) -benzamide 3-Azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -5-fluoro-4-methyl-benzamide was prepared from 3-azido-5-fluoro-4-methylbenzoic acid (US 04/102492) and N- (3-amino-5-er-butyl-2-methoxy-phenyl) -methane-sulfonamide in the same manner as 3-azido-N- (5-er-butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15).

Example 21 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -5-fluoro-4-methyl-benzamide and 3-ethynyl-pyridine therein as in Example 15. ESI MS m / z 553 [C27H29F? 604S + H] +.

Example 22: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-methoxy-pyridin-3-yl) - [1,2,3] triazole-1 -yl] -4-methyl-benzamide -Ethynyl-2-methoxypyridine was prepared from 5-bromo-2-methoxy-pyridine (Aldrich) in the same manner as 2-chloro-5-ethynyl-pyridine (Example 1).

Example 22 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 5-ethynyl-2-methoxy-pyridine therein as in Example 15. ESI MS m / z 565 [C28H32? 605S + H] +.

Example 23: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-methoxy-pyridin-3-yl) -1,2,3-triazole-1- il] 4-methyl-benzamide -Ethynyl-3-methoxypyridine was prepared from 5-bromo-3-methoxy-pyridine (Frontier) in the same manner as 2-chloro-5-ethynyl-pyridine (Example 1).

Example 23 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 5-ethynyl-3-methoxy-pyridine () in in the same manner as Example 15. ESI MS m / z 565 [C28H32? 605S + H] +.

Example 24: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-dimethylamino-pyridin-3-yl) - [1,2,3] riazole-1 -yl] -4-methyl-benzamide To a solution of 2-amino-5-iodopyridine (1.00 g; 4. 55 mmol) in 10 ml of DMF was added 545 mg of 60% NaH (13.6 mmol) and 0.85 ml of iodomethane (13.6 mmol). The mixture was stirred for 14 hours and the mixture was neutralized with HOAc IM. The mixture was extracted with Et20, the extract was washed with water and brine, dried with MgSO4, filtered and concentrated. Chromatography (0-25% EtOAc in hexanes) afforded 700 mg (2.82 mmol) of (5-iodo-pyridin-2-yl) -dimethyl-amine. (5-Ethynyl-pyridin-2-yl) -dimethylamine was prepared from (5-iodo-pyridin-2-yl) -dimethyl-amine in the same manner as 2-chloro-5-ethynyl-pyridine ( Example 1) .

Example 24 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and (5-ethynyl-pyridin-2-yl) - dimethylamine in the same manner as Example 15. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 25: N- (5-tert-Butyl-3-methansul-onylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-methylsulfanyl-3H-imidazol-4-yl ) - [1,2,3] triazol-1-yl] -benzamide To a mixture of 2.65 g (11.4 mmol) of 1,2-dimethyl-isothiourea hydroiodide and 1.00 g (10.4 mmol) of 2-bromo-3-isopropoxy-propenal was added 8 ml of MeCN, 1.58 g (11.4 mmol). ) from K2C03 (Shilcrat, SC et al J. Org. Chem., 1997, 62, 8449-8454). The mixture was stirred at 35 ° C under N2 for 16 hours, water (20 ml) was added and the mixture was extracted with CH2C12 (200 ml). The extract was dried over MgSO4, filtered, concentrated and chromatographed (0 to 100% EtOAc in hexanes) to provide 1.09 g of 3-methyl-2-methylsulfanyl-3H-imidazole-4-carbaldehyde and 284 mg of l- methyl-2-methylsulfanyl-lH-imidazole-4-carbaldehyde.

To a mixture of 850 mg (5.44 mmol) of 3-methyl-2-methylsulfanyl-3-yl-imidazole-4-carbaldehyde and 1.34 g (7.00 mmol) of dimethyl-2-oxo-l-diazopropylphosphinate in 15 ml of MeOH was added 1.52 g (11.0 mmol) of K2C03. The mixture was stirred at room temperature for 28 hours. The mixture was diluted with saturated K2CO3 (10 mL) and extracted with CH2C12 (3 x 75 mL). The combined extracts were dried over MgSO4, concentrated and chromatographed (0 to 100% EtOAc in hexanes) to yield 5-ethynyl-1-methyl-2-methylsulfanyl-1H-imidazole (600 mg, 72%) as a liquid colorless.

Example 25 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 5-ethynyl-1-methyl-2-methylsulfanyl- li? -imidazole in the same manner as Example 15. ESI MS m / z 584 [C27H33? 704S + H] +.

Example 26: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-cyclopropylamino-pyridin-3-yl) - [1,2,3] triazole-1 -yl] -4-methyl-benzamide Cyclopropyl- (5-ethynyl-pyridin-2-yl) -amine was prepared from cyclopropyl- (5-iodo-pyridin-2-yl) -amine in the same manner as 2-chloro-5-ethynyl-pyridine ( Example 1) . Cyclopropyl- (5-iodo-pyridin-2-yl) -amine was prepared from 2-chloro-5-iodo-pyridine and cyclopropylamine in the same way as cyclopropylmethyl- (5-iodo-pyridin-2-yl) - amine (Example 2).

Example 26 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and cyclopropyl- (5-ethynyl-pyridin-2-yl) ) -amine in the same manner as Example 15. ESI MS m / z 590 [C30H35? 7O4S + H] +.

Example 27: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-1-methyl-ethyl) -3-methyl-3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide Ethyl chloroformate was added dropwise (1.19 ml, 12.4 mmol) in MeC? (5 ml) at 1.00 g (6.21 mmol) of 5-bromo-1-methyl-1H-imidazole (Aldrich) in 30 ml of MeC? low? 2 The mixture was stirred and allowed to warm to RT overnight. The mixture was concentrated and the residue was treated with 2M? -aOH. (100 ml) and extracted with CH2C12 (3 x 100 ml). The combined extracts were washed with brine, dried with MgSO 4, filtered, concentrated and chromatographed (0-50% EtOAc in hexanes) to yield 5-bromo-1-methyl-1H-imidazole-2-ethyl ester. -carboxylic like a yellow oil (800 mg). To a solution of 800 mg (3.43 mmol) of 5-bromo-l-methyl-lH-imidazole-2-carboxylic acid ethyl ester in Et3N (10 ml) and THF (10 ml) was added 33 mg (0.17 mmol). ) of Cul and 120 mg (0.10 mmol) of Pd (PPh3) 4. Then trimethylsilylacetylene (0.48 ml, 3.4 mmol) was added and the reaction was heated to 70 ° C under N2. After 12 hours, the mixture was cooled and filtered through a pad of celite, and then concentrated and chromatographed (0-50% EtOAc in hexanes) to produce the ethyl ester of l-methyl-5-trimethylsilanylethynyl-1H-imidazole-2-carboxylic acid as a brown oil (205 mg). A solution of 0.67 ml of 3M MeMgBr in ether (2.0 mmol) was added to a stirring solution at 0 ° C of 200 mg of l-methyl-5-trimethylsilanylethylinyl-2-methyl-2-carboxylic acid ethyl ester (0.80 mg). mmol) in 5 ml of THF for 15 min. The mixture was allowed to warm to RT and stirred overnight. Water (20 ml) was added and the mixture was extracted with EtOAc (3 x 100 ml). The combined extracts were washed with brine and dried with MgSO4.were filtered, concentrated and chromatographed (10-00O-EtOAc in hexanes) to yield 2- (1-methyl-5-trimethylsilanylethynyl-1H-imidazol-2-yl) -propan-2-ol as an oil. yellow (110 mg). A 2- (1-Methyl-5-trimethylsilanylethynyl-1H-imidazol-2-yl) -propan-2-ol (lOOmg, 0.42 mmol) in 5 mL of THF was added 1M TBAF in THF (1.3 mL, 1.3 mmol ). The reaction was stirred at RT overnight and then diluted with 50 mL of water and extracted with EtOAc (3 x 50 mL). The combined extracts were washed with brine and dried with MgSO 4, filtered and concentrated to provide 58 mg of 2- (5-ethynyl-1-methyl-1-yl-imidazol-2-yl) -propan-2-ol.

Example 27 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 2- (5-ethynyl-1-methyl-1H) -imidazol-2-yl) -propan-2-ol in the same manner as Example 15. ESI MS m / z 596 [C29H37? 705S + H] +.

Example 28: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide Example 28 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and cyclopropylmethyl- (5-trimethyl-silanyl-ethynyl-pyridine) -2-yl) -amine in the same manner as Example 15. ESI MS m / z 604 [C31H37? 704S + H] +.

Example 29: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-morpholin-4-yl-3-yl-imidazole-4 -yl) - [1,2,3] triazol-1-yl] -benzamide 4- (1-Methyl-lH-imidazol-2-yl) -morpholine (? Agarajan, K. et al. Indian J. Chem. Sect. B, 21, 10, 1982, 949-952) was dissolved (1.02 g, 6.08 mmol) in 35 ml of 1,4-dioxane under a? 2 atmosphere. The mixture was heated to 60 ° C and a solution of 0.34 ml (6.4 mmol) of Br2 in 10 ml of dichloroethane was slowly added. The mixture was heated for 1 h, then cooled. The mixture was concentrated and the residue was divided between 6.5 ml of? AOH 1? and 25 mL of EtOAc. The? AOH solution was extracted twice more with EtOAc and the extracts were washed with? AHC03 and brine, dried with? A2S04, filtered, concentrated and chromatographed (0-4% MeOH (0.5%? H4OH) in CH2C12) to provide 464 mg of 4- (5-bromo-1-methyl-1H-imidazol-2-yl) -morpholine. 4- (5-Ethynyl-1-methyl-1-yl-imidazol-2-yl) -morpholine was prepared from 4- (5-bromo-1-methyl-1H-imidazol-2-yl) -morpholine in the same 2-chloro-5-ethynyl-pyridine (Example 1).

Example 29 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 4- (5-ethynyl-1-methyl-1H -imidazol-2-yl) -morpholine in the same manner as Example 15. ESI MS m / z 623 [C30H38? 8O5S + H] +.

Example 30: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2,2-dimethyl-propionyl) -3-methyl-3Ji-imidazol-4-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide The preparation of 1- (5-ethynyl-l-methyl-lJi-imidazol-2-yl) -2, 2-dimethyl-propan-1-one was made from 5-bromo-l-methyl imidazole and pivaloyl in the same manner as l-methyl-5-ethynyl-1H-imidazole-2-carboxylic acid ethyl ester (Example 27).

Example 30 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 1- (5-ethynyl-1-methyl-1H -imidazol-2-yl) -2, 2-dimethyl-propan-1-one in the same manner as Example 15. ESI MS m / z 622 [C31H39? 705S + H] +.

Example 30: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-fcer-butylsulfanyl-3-methyl-3-yf-imidazol-4-yl) - [1 , 2,3] triazol-1-yl] -4-methyl-benzamide A 1.6 M solution of n-BuLi in hexanes was added (16.2 ml, 25.9 mmol), over a period of 5 minutes, at 2.06 g (25.9 mmol) of 1-methyl-lH-imidazole in 100 ml of THF at -78 ° C.

After stirring for 30 minutes, 5.00 ml was added (25.9 mmol) of t-butyldisulfide and the reaction was warmed to RT and stirred for 30 min. The solution was cooled to -78 ° C and an additional 16.2 ml (25.9 mmol) of n-BuLi was added over 5 minutes. The mixture was stirred until cooled for 1 h, at which time 6.57g (25.9 mmol) of I2 was added. The mixture was warmed to RT and stirred for 15 minutes. Saturated NaHS03 (20 mL) was added and the mixture was extracted with ether (4 x 100 ml). The extracts were combined and dried over MgSO4, filtered, concentrated and chromatographed (0 to 40% EtOAc in hexanes) to yield 2-er-butylsulfanyl-5-iodo-1-methyl-1H-imidazole as a tan-colored semi-solid (421 mg). 2- er-Butylsulfanyl-5-iodo-1-methyl-1H-imidazole was prepared from 2-er-butylsulfanyl-5-iodo-1-methyl-1H-imidazole in the same manner as 2-chloro-5 -etinyl-pyridine (Example 1).

Example 30 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 2-er-butylsulfanyl-5-ethynyl-1- methyl-lH-imidazole in the same manner as Example 15. ESI MS m / z 626 [C30H39N7O4S2 + H] +.

Example 32: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4 - [6- (Cyclopropylmethyl-amino) -5-methoxy-pyridin-3-yl] - [1, 2, 3] triazole-1-yl} -4-methyl-benzamide A mixture of 2.00 g (13.9 mmol) of 2-chloro-3-methoxypyridine (Lancaster) in 13.3 ml of aminomethylcyclopropane at 125 ° C was heated in a sealed tube for 4 days. The mixture was then cooled to room temperature and partitioned between Et20 and water. The aqueous layer was washed with Et20 and the combined extracts were washed with brine, dried with MgSO4, filtered and concentrated. The residue was passed through a plug of silica gel with CH2C12 to provide 1.25 g (7.01 mmol, 50%) of 2-cyclopropylmethylamino-3-methoxypyridine. To a mixture of 2-cyclopropyl-methylamino-3-methoxypyridine (430 mg, 2.41 mmol) in 7.5 ml of 2: 1 HOAc and water was added 612 mg (2.41 mmol) of I2. The mixture was heated to 100 ° C for 4 hours and an additional 320 mg of I2 was added. The mixture was heated for 2 hours, then cooled to room temperature and stirred for 12 hours. Saturated aHC03 (20 ml) and water (20 ml) were added and the suspension was extracted with EtOAc. The extract was then washed with 10% Na2S203, water and brine and dried with MgSO4, filtered and concentrated. The pure fractions of the chromatography (1-4% MeOH in CH2C12) were concentrated to give 145 mg of 2-cyclopropylmethylamino-3-methoxy-5-iodopyridine.

To a mixture of 2-cyclopropylmethylamino-3-methoxy-5-iodopyridine (145 mg, 0.477 mmol), (Ph3P) 2PdCl2 (17 mg, 0.024 mmol) and Cul (5 mg, 0.02 mmol) under N2 were added 2 ml from Et3N and 75 μL of Me3SiCCH (0.525 mmol). The resulting green suspension was stirred for 30 min at 50 ° C. The mixture was cooled to room temperature and partitioned between EtOAc and water. The organic extract was washed with water, washed with brine and dried with MgSO 4, filtered and concentrated. Chromatography (0-1% MeOH in CH2C12) gave 130 mg of 2-cyclopropanomethylamino-3-methoxy-5- (trimethylsilyl) ethynylpyridine contaminated with a small amount of Ph3P.

Example 32 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 2-cyclopropanomethylamino-3-methoxy-5- (trimethylsilyl ) ethynylpyridine in the same manner as Example 15. ESI MS m / z 634 [C 32 H 39 N 705 S + H] +. Example 33: 3-. { 4- [2- (Hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (5-Ethyl-1-methyl-1H-imidazol-2-yl) -phenyl-methanone was prepared from 5-bromo-1-methyl imidazole and benzoyl chloride in the same manner as the ethyl ester of methyl-5-ethynyl-lH-imidazole-2-carboxylic acid (Example 27).

A solution of 200 mg (0.951 mmol) of (5-ethynyl-l-methyl-lH-imidazol-2-yl) -phenyl-methanone in 1 ml of MeOH was added dropwise to a solution at 0 ° C of 54 ° C. mg (1.43 mmol) of? aBH4 in 5 ml of MeOH. After stirring for 2 hours, 10 ml of water was added and the mixture was extracted with CH2C12 (3 x 50 ml). The combined extracts were washed with brine, dried with MgSO4, filtered, concentrated and chromatographed (0-80% EtOAc in hexanes) to yield (5-ethynyl-1-methyl-1H-imidazol-2-yl) - phenyl-methanol as a white solid (75 mg). 3-Azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide acid was prepared from 3-azido-4-methylbenzoic acid and N- [3-amino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -methanesulfonamide in the same manner as 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15).

Example 33 was prepared from 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide and 5-ethynyl-1-methyl- 1H-imidazol-2-yl) -phenyl-methanol in the same manner as Example 15. ESI MS m / z 642 [C33H35? 705S + H] +.

Example 34: 3- [4- (2-Benzoyl-3-methyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 34 was prepared from (5-ethynyl-l-methyl-lH-imidazol-2-yl) -phenyl-methanone (Example 33) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 15. ESI MS m / z 640 [C33H33? 705S + H] +.

Example 35: 3- [4- (2-Benzoyl-3-methyl-3ff-imidazol-4-yl) - [1,2, 3] triazol-1-yl] -N- (5-tert-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide Example 35 was prepared from (5-ethynyl-l-methyl-lH-imidazol-2-yl) -phenyl-methanone (Example 33) and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino -2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 15. ESI MS m / z 642 [C33H35? 705S + H] +.

Example 36: 3- [4- (2-Benzylsulfonyl-3-methyl-3JT-imidazol-4-yl) - [1,2, 3] triazol-1-yl] -N- (5-tert-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 1-Methylimidazole (4.0 mL, 50.3 mmol) was dissolved in dry THF (250 mL) under an N2 atmosphere. The solution was cooled to -78 ° C and n-BuLi (2.5 M in hexanes, 20.1 ml, 50.3 mmol) was slowly added. After 15 min phenyl disulfide (11.0 g, 50.3 mmol) was added and the reaction was warmed to room temperature and stirred for 30 min. The reaction was then cooled to -78 ° C and a second portion of n-BuLi (20.1 ml, 50.3 mmol) was added. After 30 min, iodine (13.4 g, 50.3 mmol) was added. The reaction was warmed to room temperature and Et20 (400 mL) and 1 M sodium bisulfite (250 mL) were added. The layers were separated and the organic layer was washed with brine, dried over MgSO4 and filtered. The solution was concentrated and hexanes were added to the resulting precipitate. The precipitate was collected by vacuum filtration, washed with hexanes and dried under vacuum to provide 5-iodo-l-methyl-2-phenylsulfanyl-1H-imidazole (4.0 g, 25%) as a white solid: ESI MS m / z 317 [C10H9IN2S + H] +. 5-Iodo-1-methyl-2-phenylsulfanyl-1-yl-imidazole (2.0 g, 6.3 mmol) was dissolved in CH2C12 (50 mL). M-CPBA (2.8 g, 12.6 mmol) was added and the reaction was stirred for 1 hour, at which time a white precipitate formed. An additional portion of m-CPBA (1.0 g) was added and the reaction was stirred for 1 h. Saturated NaHCO3 was added and the layers were separated. The aqueous layer was extracted with CH2C1 and the combined extracts were washed with saturated NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in MeOH (60 ml) with a small amount of CH2C12. The mixture was boiled to homogenous, allowed to cool to room temperature and then cooled on ice. The resulting needles were collected by vacuum filtration, washed with MeOH and hexanes and then dried in vacuo to give benzenesulfonyl-5-iodo-1-methyl-1-t-imidazole (1.23 g, 56%) as a white solid. 2-Benzenesulfonyl-5-ethynyl-1-methyl-1H-imidazole was prepared from 2-benzenesulfonyl-5-iodo-1-methyl-1H-imidazole in the same manner as 2-chloro-5-ethynyl pyridine ( Example 1) .

Example 36 was prepared from 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide and 2-benzenesulfonyl-5-ethynyl-methyl- 1H-imidazole in the same manner as Example 15. ESI MS m / z 678 [C32H35N7OeS + H] +.

Example 37: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4 - [6 - (2-dimethylamino-ethylamino) -pyridin-3-yl] - [1, 2, 3] triazol-1-yl} -4-methyl-benzamide To a suspension of Example 1 (100 mg, 0.176 mmol), Pd2dba3 (13 mg, 0.014 mmol) and t-BuOK (68 mg, 0.70 mmol) in 1.5 mL of toluene, stirring under? 2 / N, N was added. dimethylaminoethylamine (31 mg, 0.35 mmol) and 2, 8, 9-triisobutyl-2,5,8,9-tetraaza-l-phosphabicyclo [3.3.3] undecane (9.0 mg, 0.026 mmol). The resulting suspension was heated to 100 ° C for 14 hours. The reaction was then cooled to room temperature and partitioned between EtOAc and water. The layers were separated, washing the organic portion twice with water and once with brine. The solution was dried with MgSO 4, filtered and concentrated. The pure fractions were isolated from the chromatography (2-7% MeOH (0.5%? H40H in CH2C12), combined and concentrated to provide 10 mg of Example 37. ESI MS m / z 621 [C31H40? 8O4S + H ] +.

Example 38: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3fT-imidazol-4-yl) -pyrazol- 1- il] -benzamide Butyl lithium (3.75 ml, 9.40 mmol) and TMEDA (2.24 ml, 14.85 mmol) were stirred at -20 ° C in hexanes (7 ml) in an ethanol / dry ice / water bath for 30 minutes. 1-Methylimidazole (0.5 mL, 6.27 mmol) was added and the mixture was stirred at room temperature for 1 h. After cooling to -20 ° C, Bu3SnCl (1.70 ml, 15.67 mmol) was added dropwise. The reaction was stirred for 15 minutes at -20 ° C, then at room temperature overnight before cooling rapidly with 1: 1 EtOAc / water (20 ml). The layers were separated and the aqueous layer was extracted with EtOAc (3x). The combined organics were washed with water, dried over Na 2 SO 4, concentrated and chromatographed (4:96 MeOH / EtOAc) to yield 1-methyl-5-tributylstannayl-1H-imidazole (0.486 g). A solution of 3-hydrazino-4-methyl benzoic acid was heated to reflux (See US Provisional Application 60 / 570,284) (1.0 g, 4.93 mmol), malonaldehyde (bismethylacetate) (0.82 mL, 4.93 mmol) and concentrated HCl (1 ml) in EtOH (20 ml) for 4 hours. After cooling to room temperature, the reaction was poured into ice water, neutralized with 2N NaOH and extracted with CH2C12 (3x). The organic layers were dried over Na 2 SO 4, filtered and concentrated to yield 4-methyl-3-pyrazol-1-yl-benzoic acid ethyl ester (536 mg, 47%) as a yellow oil. A solution of pyrazole (536 mg, 2.33 mmol) and bromine (0.167 mL, 3.26 mmol) in CHC13 (15 mL) was refluxed for 4.5 hours, then cooled and concentrated. Chromatography (1: 1 EtOAc / hexanes) afforded 3- (4-bromo-pyrazol-1-yl) -4-methyl-benzoic acid ethyl ester (0.739 g, 99%). Bromopyrazole (366 mg, 1.18 mmol) was dissolved in dioxane (2 ml) and washed abundantly with N2. L-Methyl-5-tributylstannayl-lH-imidazole (366 mg, 0.986 mmol) was added to the reaction flask in dioxane (0.5 mL), then the flask was purged with N2. After adding Pd (PPh3) (85 mg, 0.074 mmol), the reaction was heated to 100 ° C in a sealed tube. The reaction mixture was stirred with a 10% KF solution for 30 min, then diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3x). The layers were combined, dried over Na2SO4 and concentrated. The resulting residue was purified by chromatography on silica gel (5% MeOH / CH2Cl2) to yield the ethyl ester of 4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) -pyrazol- 1-yl] -benzoic acid (81 mg, 22%).

A solution of N- (3-amino-5-er-butyl-2-methoxy-phenyl) -methane-sulfonamide (81 mg, 0.261 mmol) in THF (4 mL) was stirred in a bath cooled to -78 ° C. and n-BuLi (0.22 ml, 0.548 mmol) was slowly added. The cold bath was removed and the reaction allowed to stir for 30 min. Then LHMDS (0.261 mmol) was added slowly. The suspension was transferred dropwise to a stirred solution of 4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) -pyrazol-1-yl] -benzoic acid ethyl ester compound. (81 mg, 0.261 mmol) in THF at 0 ° C. After 30 min cold MeOH was added and the mixture was partitioned between? Saturated HC1 and EtOAc, then extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over? A2S04, filtered, concentrated and chromatographed (1% MeOH (with 5%? H4OH) / CH2C12 to 5% MeOH (with 5%? H4OH) / CH2C12) to produce N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) -pyrazol-1-yl] ] -benzamide (47 mg, 33%) as an orange foam: ESI MS m / z = 537 [C27H32? 604S + H] +.

Example 39: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3- (4-furan-3-yl- [1,2,3] triazol-1-yl) -4- metil-benz mida To a solution of 96 mg (0.20 mmol) of furan-3-carbaldehyde (Aldrich) and dimethyl 2-oxo-l-diazopropilfosfinato (46 mg; 0.24 mmol) in 1.5 ml of MeOH was added 55.6 mg (0.402 mmol) of K2C03 The mixture was stirred for 4 hours and then 58 mg (0.134 mmol) of 3-azido-N- (5-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide was added followed by an additional 1 ml. of MeOH and 27 mg of sodium ascorbate in 0.2 ml of water. The mixture was stirred vigorously and 0.13 ml (0.013 mmol) of 0.1 M CuS04 was added. The top space was purged with? 2 and the vessel was sealed for 20 hours. The mixture was then partitioned between EtOAc and ÍM HCl, and the extract was washed with saturated αHC03 and brine. The extract was then dried with α2S04, filtered, concentrated and chromatographed (10-50% EtOAc in hexanes) to give 57 mg (0.11 mmol; 81%) of Example 39. ES MS m / z 524 [C2SH29? 505S + H] +.

Example 40: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (tetrahydro-furan-3-yl) - [1,2,3] triazole -1-yl] -benzamide Example 40 was prepared from tetrahydro-furan-3-carbaldehyde (Aldrich) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same as Example 39. ESI MS m / z 528 [C26H33N50sS + H] +. Example 41: N- (5-tert-Butyl-3-methansulonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyrimidin-5-yl- [1,2,3] triazole-1 -il) -benzamide Example 41 was prepared from pyrimidine-3-carbaldehyde (Matrix) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same way than Example 39. ESI MS m / z 536 [C26H29? 704S + H] +.

Example 42: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-thiazol-5-yl- [1,2,3] triazole-1-xl ) -benzamide Example 42 was prepared from thiazole-5-carbaldehyde (Matrix) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same way than Example 39. ESI MS m / z 541 [C25H28? 604S2 + H] +.

Example 43: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1, 5-dimethyl-lJ? -pyrazol-4-yl) - [1,2, 3] triazol-1-yl] -4-methyl-benzamide Example 43 was prepared from 1,5-dimethyl-1H-pyrazole-4-carbaldehyde (Matrix) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 methyl-benzamide in the same manner as Example 39. ESI MS m / z 552 [C27H33? 704S + H] +.

Example 44: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- ((S) -2,2-dimethyl- [1,3] dioxolan-4-yl) - [1,2,3] triazol-1-yl] -4-methyl-benzamide Example 44 was prepared from (S) -2, 2-dimethyl- [1,3] dioxolane-4-carbaldehyde (Matrix) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2 -methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 558 [C27H35? 506S + H] +.

Example 45: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-cyclopropyl-2-methyl-3-ylamino-4-yl) [1,2, 3] triazol-1-yl] -4-methyl-benzamide Ethyl acetimidate hydrochloride (5.0 g, 40 mmol) and cyclopropylamine (2.3 ml, 40 ml) were dissolved in 45 ml of EtOH and heated to 85 ° C in a sealed pressure vessel overnight. The mixture was cooled and concentrated to provide N-cilcopropyl acetamidine hydrochloride as a viscous oil. N-cyclopropyl-acetamidine hydrochloride (1.00 g, 7.43 mmol) and 2-bromo-3-isopropoxy-propene (Shilcrat, SC et al., J. "Org. Chem., 1997, 62, 8449-8454) were dissolved ( 1.45 g, 7.50 mmol) in 13 ml of CHC13 and 1.6 ml of water, then K2C03 (1.5 g, 11 mmol) was added and the mixture was stirred overnight.The reaction was partitioned between CH2C12 (60 ml) and water ( 30 ml) The layers were separated and the aqueous portion was extracted with CH2C12 (40 ml) The combined organic layers were washed with brine (30 ml), dried (MgSO4), filtered, concentrated and chromatographed to give 400 mg of 3-cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde.

Example 45 was prepared from 3-cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-fce.r-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 46: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide In 50 ml of Et20, 1.70 g (20.0 mmol) of cyclopropylcarboxamide and 2.9 g (20 mmol) of trimethyloxonium tetrafluoroborate were stirred for 16 hours. The resulting suspension was cooled to 0 ° C and the ether was decanted. The solids were washed with 20 ml of cold Et20 and the residue was dried under a current of 22. Then 10 ml of EtOH was added, followed by 2.5 ml of a 33% solution of Me? H2 in EtOH. The reaction vessel was sealed and heated to 80 ° C overnight. The mixture was cooled and concentrated to provide 3.7 g of N-methyl-cyclopropanecarboxamidine tetrafluoroborate as a gummy solid. To a solution of 2.32 g (12.5 mmol) of N-methyl-cyclopropanecarboxamidine tetrafluoroborate in 4 ml of MeC? 2.41 g (12.5 mmol) of 2-bromo-3-isopropoxy-propenal, 5.1 g (37 mmol) of K2C03 and 0.17 g were added. (0.62 mmol) of 18-crown-6. The mixture was stirred at RT overnight and then concentrated and redissolved in EtOAc. Water was added to dissolve the salts, the layers were separated and the aqueous phase was extracted twice with EtOAc. The combined extracts were washed with a small amount of water and brine, dried over Na 2 SO 4, filtered, concentrated and chromatographed (35-85% EtOAc in hexanes) to provide 646 mg of 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde as a pale yellow oil.

Example 46 was prepared from 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 47: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-1-methyl-1H-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide N-methyl-cyclopropanecarboxamidine tetrafluoroborate (0.19 g, 1.0 mmol) and 2-bromo-3-isopropoxy-propene (Shilcrat, SC et al., "Org. Chem., 1997, 62, 8449-8454) were dissolved (0.19 g, 1.0 mmol) in 1.3 ml of CHC13 and 0.16 ml of water, then K2C03 (0.45 g, 3.3 mmol) was added and the mixture was stirred overnight.The reaction was partitioned between CH2C12 and water. the aqueous portion was extracted with CH2C12.The combined organic layers were washed with brine, dried (MgSO4), filtered, concentrated and chromatographed to give 0.15 g of a 1: 1 mixture of 2-cyclopropyl-1-methyl. -lJi-imidazol-4 -carbaldehyde and 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde.

Example 47 was prepared from 2-cyclopropyl-1-methyl-1H-imidazole-4-carbaldehyde (as a 1: 1 mixture with 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde) and 3 - azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. Chromatography left the separation of Example 47 of Example 46. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 48: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5,6,7,8-tetrahydro-imidazo [1,2-a] ] pyridin-3-yl) - [1,2,3] riazol-1-yl] -benzamide Jo , 6, 7, 8-tetrahydro-imidazo [1,2-a] pyridine-3 -carbaldehyde (2: 1 with 5, 6, 7, 8-Tetrahydro-imidazo [1,2-a] pyridine- was prepared 2-carbaldehyde) from piperidin-2-ylidenamine hydrochloride (Aldrich) and 2-bromo-3-isopropoxy-propenal in the same manner as cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde (Example 45) .

Example 48 was prepared from 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridine-3-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2) -methoxy-phenyl) -methyl-benzamide in the same manner as Example 39. ESI MS m / z 578 [C 29 H 35? 704 S + H] +.

Example 49: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-cyclopropyl-1-isopropyl-1-t-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide 3-Cyclopropyl-3-oxo-propionic acid methyl ester (1.25 g, 8.79 mmol) was dissolved in 6.25 ml of CHC13 and 1.17 ml (8.79 mmol) was added. ) of dimethylformamide dimethylacetal. The mixture was heated to 60 ° C in a sealed container overnight. The mixture was then cooled and concentrated to provide 1.67 g of 2-cyclopropanecarbonyl-3-dimethylamino-acrylic acid methyl ester. In 10 ml of EtOH, 544 mg (2.76 mmol) of 2-cyclopropanecarbonyl-3-dimethylamino-acrylic acid methyl ester, 305 mg (2.76 mmol) of isopropylhydrazine hydrochloride and 226 (2.76 mmol) of sodium acetate were combined. The mixture was heated to 60 ° C for 12 hours. The mixture was then partitioned between water and EtOAc and the extract was washed with brine. The washings were extracted twice more with EtOAc and the extracts were combined, dried with Na2SO4, filtered and concentrated to provide 442 mg of an 85:15 mixture of methyl 5-cyclopropyl-1-isopropyl-1H-methyl ester. pyrazole-4-carboxylic acid and 5-cyclopropyl-1-isopropyl-1-pyrazol-3-carbaldehyde. To an ice-cooled solution of 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carboxylic acid methyl ester (442 mg, 2.12 mmol) in THF was slowly added 8.48 ml of DIBAL-H ÍM in CH2C12. After 2 hours, 1 ml of EtOAc was added, followed by saturated aqueous Na 2 SO 4 with very rapid stirring. After stirring for 10 min, the resulting suspension was diluted with EtOAc until free stirring and MgSO4 was added. The resulting suspension was stirred an additional 30 min and then filtered through celite. The filter cake was washed with EtOAc and the combined filtrate was concentrated to provide 337 mg of 5-cyclopropyl-1-isopropyl-1H-pyrazol-4-yl) -methanol. To a solution of 337 mg (1.87 mmol) of 5-cyclopropyl-1-isopropyl-1-pyrazol-4-yl) -methanol was added 813 mg (9.35 mmol) of activated MnO2. The suspension was stirred overnight and then filtered through celite (rinsed with CH2C12) and the filtrate was concentrated to provide an ivory colored solid. The solid was washed with hexanes to provide 170 mg of 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde.

Example 49 was prepared from 5-cyclopropyl-1-isopropyl-1-pyrazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-benzamide in the same manner as Example 39. ESI MS m / z 606 [C31H39? 704S + H] +.

Example 50: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-methyl-lJ-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide L-cyclopropyl-5-methyl-lH-pyrazole-4-carbaldehyde was prepared with ethyl acetoacetate and cyclopropylhydrazine oxalate (Gever, G. and Hayes, K. J., Org. Chem, 1949, 14, 813-818) in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).

Example 50 was prepared from l-cyclopropyl-5-methyl-lyr-pyrazole-4 -carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 578 [C 29 H 35? 70 S + H] +.

Example 51: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-diethyl-3J? -imidazol-4-yl) - [1, 2, 3] triazol-1-yl] -4-methyl-benzamide »'And J? - + HA yAx? - To 2-ethyl-5-formylimidazole (200 mg, 1611 mmol) in 2 ml of DMF was added 0.132 ml (1.65 mmol) of EtI and 224 mg (1.62 mmol) of K2C03 The mixture was stirred for 12 hours and then poured into water and extracted twice with EtOAc. The organic extracts were washed with brine, dried over Na 2 SO 4, filtered and concentrated. Chromatography (0.5-2.0% MeOH in CH2C12) gave 46 mg (0.30 mmol, 19%) of 1,2-diethyl-5-formyl-1H-imidazole and 106 mg (0.69 mmol, 43%) of 1.2- diethyl-4-formyl-1-JT-imidazole.

Example 51 was prepared from 1,2-diethyl-5-formyl-1H-imidazole and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37? 704S + H] +.

Example 52: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1, 2-diethyl-1H-imidazol-4-yl) -1,2,3- triazol-1-yl] -4-methyl-benzamide Example 52 was prepared from 1,2-diethyl-4-formyl-1H-imidazole (Example 51) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37? 704S + H] +.

Example 53: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (2-isopropyl-3-methyl-3J? -imidazol-4-yl) - [1, 2,3] triazol-1-yl] -4-methyl-benzamide 2-Isopropyl-3-methyl-3-pyridazole-4-carbaldehyde was prepared from isobutyramide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 53 was prepared from 2-isopropyl-3-methyl-3i-imidazole-4-carbaldehydes and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37? 704S + H] +.

Example 54: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3 - [4 - (3-isopropyl-2-methyl-3H-imidazol-4-yl) - [1, 2 , 3] triazol-1-yl] -4-methyl-benzamide 3-isopropyl-2-methyl-3-yl-imidazole-4-carbaldehyde was prepared from ethyl acetimidate hydrochloride and isopropylamine in the same manner as 3 - Cyclopropyl-2-methyl-3H-imidazole-4 -carbaldehyde (Example 45).

Example 54 was prepared from 3-isopropyl-2-methyl-3ff-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37? 704S + H] +.

Example 55: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-isopropyl-5-methyl-lH-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide L-isopropyl-5-methyl-lH-pyrazole-4-carbaldehyde was prepared with methyl acetoacetate and isopropylhydrazine hydrochloride in the same manner as 5-cyclopropyl-l-isopropyl-lH-pyrazole-4-carbaldehyde (Example 49) .

Example 55 was prepared from l-isopropyl-5-methyl-lJ-pyrazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37? 704S + H] +.

Example 56: 3- [4- (3-tert-Butyl-3H-imidazol-4-yl) - [1, 2, 3] triazol-1-yl] -N- (5-tert-but-il-3 - methansulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-tert-Butyl-3H-imidazole-4-carbaldehyde was prepared from ethyl formimidate hydrochloride (Aldrich) and terbutylamine in the same manner as 3-cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde ( Example 45).

Example 56 was prepared from 3-er-butyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -methyl-benzamide in the same manner as Example 39. ESI MS m / z 580 [C29H37N704S + H] +.

Example 57: 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -3-methyl-3H-imidazol-4-yl] - [1, 2, 3] triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide Example 58: 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -1-methyl-1H-imidazol-4-yl] - [1,2,3] riazol-1-yl} -N- (5-tert-butyl-3-ethanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide To 15 ml of MeCN was added 880 mg (4.99 mmol) of N-benzyl-piperazine and 1.16 g (5.00 mmol) of 1,2-dimethyl-isothiourea hydroiodide. The mixture was heated to reflux overnight. Then, 970 mg (5.02 mmol) of 2-bromo-3-isopropoxy-propenal and 2.07 g (15.0 mmol) of K2C03 and 250 mg of 18-crown-6, and the mixture was heated to reflux overnight. The mixture was cooled, concentrated and dissolved in EtOAc with a small amount of water to dissolve salts. The aqueous phase was extracted twice with EtOAc and the combined organic extracts were washed with water and brine, dried over MgSO4, concentrated and chromatographed to give 250 mg of 2- (4-benzyl-piperazin-1-yl) -3-methyl-3H-imidazole-4-carbaldehyde and '2- (4-benzyl-piperazine-1) il) -1-methyl-lN-imidazol-4 -carbaldehyde as a 1: 1 mixture of isomers.

Example 57 and Example 58 were prepared from a mixture of 2- (4-benzyl-piperazin-1-yl) -3-methyl-3H-imidazole-4-carbaldehyde and 2- (4-benzyl-piperazine- 1-methyl) -1H-imidazole-4-carbaldehyde in the same manner as Example 39. The isomers were separated by chromatography (4% EtOH in CH2C12 with 0.5% NH4OH). Example 57: ESI MS m / z 712. [C37H4SN904S + H] +. Example 58: ESI MS m / z 712 [C37H4SN904S + H] +.

Example 59: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-dimethylamino-3-methyl-3i2'-imidazol-4-yl) - [1, 2,3] triazol-1-yl] -4-methyl-benzamide Example 60: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-dimethylamino-l-methyl-lT-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide. 2-Dimethylamino-3-methyl-3H-imidazole-4-carbaldehyde and 2-dimethylamino-1-methyl-1H-imidazole-4-carbaldehyde were prepared from of 1, 2-dimethyl-isothiourea hydroiodide and dimethylamine in the same manner as 2- (4-benzyl-piperazin-1-yl) -3-methyl-3H-imidazole-4-carbaldehyde and 2- (4-benzyl) piperazin-1-yl) -l-methyl-1H-imidazole-4-carbaldehyde (Example 57 and Example 58).

Example 59 and Example 60 were prepared from a mixture of 2-dimethylamino-3-methyl-3-yl-imidazole-4-carbaldehyde and 2-dimethylamino-1-methyl-1H-imidazole-4-carbaldehyde therein as in Example 39. The isomers were separated by chromatography (4% EtOH in CH2C12 with 0.5% NH40H). Example 59: ESI MS m / z 581 [C28H36N804S + H] +. Example 60: ESI MS m / z 581 [C28H36N804S + H] +. Example 61: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-dihydro-imidazo [2, 1-b] thiazol-5-yl) - [1,2,3] triazol-1-yl] -4-methyl-benzamide 2,3-Dihydro-imidazo [2, lb] thiazole-5-carbaldehyde was prepared from 4,5-dihydro-thiazol-2-ylamine and 2-bromo-3-isopropoxy-propenal in the same way as cyclopropyl -2-methyl-3H-imidazole-4-carbaldehyde (Example 45).

Example 61 was prepared from 2,3-dihydro-imidazo [2, lb] thiazole-5-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 582 [C27H31? 70S2 + H] +.

Example 62: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclobutyl-3-methyl-3J? -imidazol-4-yl) -1.2 , 3-triazol-l-yl] -4-methyl-benzamide 2-Cyclobutyl-3-methyl-3J? -imidazole-4-carbaldehyde can be prepared from cyclobutane carboxamide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) .

Example 62 can be prepared from 2-cyclobutyl-3-methyl-3-yl-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methylbenzamide in the same manner as Example 39 Example 63: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] - [1, 2, 3] triazol-1-yl} -benzamide 3-Methyl-2- (1-methyl-cyclopropyl) -3H-imidazole-4-carbaldehyde was prepared from 1-methyl-cyclopropylcarboxamide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4. -carbaldehyde (Example 46).

Example 63 was prepared from 3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy) phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 64: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-ethyl-lH-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide 0 0 Y? /, Y, l \ l J, ^ 0A A \ Y or o > -H L-cyclopropyl-5-ethyl-lH-pyrazole-4-carbaldehyde was prepared with ethyl 3-oxopentanoate and cyclopropylhydrazine oxalate (Gever, G. and Hayes, K. J. Org. Chem, 1949, 14, 813-818) in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).

Example 64 was prepared from l-cyclopropyl-5-ethyl-lT-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methylbenzamide in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 65: N- (5-fcer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5,5-dimethyl-6,7-dihydro-5H-pyrrolo [1, 2-a] ] imidazol-3-yl) - [1,2,3] riazol-1-yl] -4-methyl-benzamide ,5-Dimethyl-6,7-dihydro-5N-pyrrolo [1,2-a] imidazole-3-carbaldehyde was prepared from 5,5-dimethyl-pyrrolidin-2-ylidenamine (Buckley, et al. Chem. Soc. 1947, 1507.) and 2-bromo-3-isopropoxy-propenal in the same way as cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde (Example 45).

Example 65 was prepared from 5,5-dimethyl-6,7-dihydro-5H-pyrrolo [1,2-a] imidazole-3-carbaldehyde and 3-azido-N- (5-er-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 66: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenxl) -3- [4- (7,7-dimethyl-6,7-dihydro-5H-pyrrolo [1,2-a ] imidazol-3-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide 7,7-Dimethyl-6,7-dihydro-5H-pyrrolo [1,2-a] imidazole-3-carbaldehyde can be prepared from 3,3-dimethyl-pyrrolidin-2-one (Reddy, PA et al. J ". Med. Chem. 1996, 1898.) and 2-bromo-3-isopropoxy-propenal in the same manner as cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde (Example 45) Example 66 can be prepared from 7,7-dimethyl-6,7-dihydro-5-pyrrolo [1,2-a] imidazole-3-carbaldehyde and 3-azido-N- (5-er-butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39.

Example 67: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-tert-butyl-3-methyl-3H-imidazol-4-yl) - [1 , 2,3] triazol-1-yl] -4-methyl-benzamide 2- er-Butyl-3-methyl-3H-imidazole-4-carbaldehyde was prepared from trimethyl acetamide in the same manner as 2-cyclopropyl-3-methyl-3-fluoro-4-carbaldehyde (Example 46).

Example 67 was prepared from 2-er-butyl-3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 594 [C30H39? 7O4S + H] +.

Example 68: N- (5- er-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3- [4- (3-tert-butyl-2-methyl-3-pyridin-4-yl) - [1 , 2,3] riazol-1-yl] -4-methyl-benzamide Cf t < 3-Butyl-2-methyl-3i-imidazole-4-carbaldehyde was prepared from ethyl acetimidate hydrochloride and tert-butylamine in the same manner as 3-cyclopropyl-2-methyl-3-imidazole- 4 -carbaldehyde (Example 45).

Example 68 was prepared from 3-er-butyl-2-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 594 [C30H39? 7O4S + H] +.

Example 69: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-fcer-butyl-5-methyl-lff-pyrazol-4-yl) - [1 , 2,3] triazol-1-yl] -4-methyl-benzamide 1- er-Butyl-5-methyl-1H-pyrazole-4-carbaldehyde was prepared with ethyl acetoacetate and tert-butylhydrazine hydrochloride in the same manner as 5-cyclopropyl-1-isopropyl-1-pyrazole-4-carbaldehyde (Example 49).

Example 69 was prepared from 1-er-butyl-5-methyl-lff-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 594 [C30H39? 704S + H] +.

Example 70: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-isopropyl-lH-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide -Ethyl-l-isopropyl-lH-pyrazole-4-carbaldehyde was prepared with ethyl ethyl 3-oxopentanoate and isopropylhydrazine hydrochloride in the same manner as 5-cyclopropyl-l-isopropyl-lH-pyrazole-4-carbaldehyde ( Example 49).

Example 70 was prepared from 5-ethyl-l-isopropyl-lH-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 594 [C30H39? 7O4S + H] +.

Example 71: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-trif luoromethyl-pyridin-3-yl) - [1/2, 3] triazol-1-yl] -benzamide Example 71 was prepared from 6-trifluoromethyl-pyridine-3-carbaldehyde (Matrix) and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 603 [C28H29F3? 604S + H] +.

Example 72: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro-5-pyrrolo [1,2-a] ] imidazol-3-yl-5- (2'-methyl-cycloproane))] - [1,2,3] triazol-1-yl] -benzamide Spiro [6,7-dihydro-5-pyrrolo [1,2-a] imidazol-5- (2'-methyl-cyclopropane)] -3-carboxaldehyde was prepared from l-methyl-4-aza-spiro [ 2.4] heptan-5-one (Bertus, P .; Szymoniak, J. SYNLETT, 2, 2003, 265-267) and 2-bromo-3-isopropoxy-propenal, in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 72 was prepared from spiro [6,7-dihydro-5H-pyrrolo [1,2-a] imidazol-5- (2'-methyl-cyclopropane)] -3-carboxaldehyde and 3-azido-N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 604 [C3? H37? 704S + H] +.

Example 73: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-cyclopropyl-2-isopropyl-3H-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide 3-Cyclopropyl-2-isopropyl-3J? -imidazole-4-carbaldehyde was prepared from isobutyramide and cyclopropylamine in the same way < than 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 73 was prepared from 3-cyclopropyl-2-isopropyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methylbenzamide in the same manner as Example 39. ESI MS m / z 606 [C31H39? 704S + H] +.

Example 74: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (2-cyclopropyl-3-isopropyl-3i? -imidazol-4-yl) - [1, 2,3] triazsl-1-yl] -4-methyl-benzamide 2-Cyclopropyl-3-isopropyl-3H-imidazole-4-carbaldehyde was prepared from cyclopropane carboxamide and isopropylamine in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 74 was prepared from 2-cyclopropyl-3-isopropyl-3-fJ-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) ) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 606 [C3? H39? 704S + H] +.

Example 75: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-isopropyl-lH-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide L-cyclopropyl-5-isopropyl-1H-pyrazole-4-carbaldehyde was prepared from ethyl -methyl-3-oxopentanoate and cyclopropylhydrazine hydrochloride in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole- 4 -carbaldehyde (Example 49).

The benzamide of Example 75 was prepared from 1-cyclopropyl-5-isopropyl-1-pyrazol-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy- f-enyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 606 [C31H39? 704S + H] +.

Example 76: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1,5-diisopropyl-lff-pyrazol-4-yl) - [1, 2, 3 ] triazol-1-yl] -4-methyl-benzamide 1, 5-Diisoopropyl-1H-pyrazole-4-carbaldehyde was prepared from ethyl 4-methyl-3-oxopentanoate and isopropylhydrazine hydrochloride in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4- carbaldehyde (Example 49).

Example 76 was prepared from 1,5-diisoopropyl-liT-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- benzamide in the same manner as Example 39. ESI MS m / z 608 [C31H4 ?? 704S + H] +.

Example 77: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -4-methyl-3- [4- (5-methyl-l-phenyl-li? -pyrazol-4-yl) - [1,2,3] triazol-1-yl] -benzamide Example 77 was prepared from 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (Maybridge) and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 614 [C32H35? 704S + H] +.

Example 78: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -benzamide 3-Methyl-2-phenyl-3Ji-imidazole-4-carbaldehyde was prepared from benzene carboxamide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) Example 78 was prepared from 3-methyl-2-phenyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methane-sulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 614 [C32H35? 704S + H] +.

Example 79: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-pyridin-4-yl-3-yl-imidazole-4 -yl) - [1,2,3] triazol-1-yl] -benzamide 3-Methyl-2-pyridin-4-yl-3H-imidazole-4-carbaldehyde was prepared from pyridine-4-carboxamide in the same manner as 2-cyclopro-yl-3-methyl-3H-imidazole-4 -carbaldehyde (Example 46).

Example 79 was prepared from 3-methyl-2-pyridin-4-yl-3-yl-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) ) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 615 [C31H34? 804S + H] +.

Example 80: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-l-pyridin-2-yl-lH-pyrazole-4 -yl) - [1,2,3] triazol-1-yl] -benzamide -Methyl-l-pyridin-2-yl-lH-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and 2-pyridylhydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4. -carbaldehyde (Example 49).

Example 80 was prepared from 5-methyl-l-pyridin-2-yl-lH-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methano-sulfonylamino-2-methoxy) phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 615 [C31H34N804S + H] +.

Example 81: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [2-methyl-3- (2,2,2-trifluoro-ethyl) -3ff-imidazol-4-yl] - [1,2,3] triazole-1-yl} -benzamide 2-Methyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazole-4-carbaldehyde was prepared from ethyl acetimidate hydrochloride and 2,2,2-trifluoroethylamine in the same manner as -cyclopropyl-2-methyl-3i? -imidazole-4-carbaldehyde (Example 45).

Example 81 was prepared from 2-methyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino -2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 620 [C28H32F3? 704S + H] +.

Example 82: 3- [4- (3-tert-Butyl-2-cyclopropyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- (5-fcer-butyl) -3-methanesulfonylamino-2-methoxy-phenyl) -4-ethyl-benzamide 3- f-Butyl-2-cyclopropyl-3-yl-imidazole-4-carbaldehyde was prepared from cyclopropylcarboxamide and terbutylamine in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) .

The benzamide of Example 82 was prepared from 3-tert-butyl-2-cyclopropyl-3-yl-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 620 [C32H41? 704S + H] +.

Example 83: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3- [4- (l-cyclohexyl-5-methyl-lH-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide L-cyclohexyl-5-methyl-1-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and cyclohexylhydrazine (TCI) in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde ( Example 49).

Example 83 was prepared from l-cyclohexyl-5-methyl-1-pyrazol-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 620 [C 32 H 4 ??? 704S + H] +. Example 84: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (2-morpholin-4-yl-thiazol-5-yl) - [1 , 2,3] triazol-1-yl] -benzamide Example 84 was prepared from 2-morpholin-4-yl-thiazole-5-carbaldehyde (Bionet) and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 626 [C29H35? 705S2 + H] +.

Example 85: N- (5- er-Bethyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-ethyl-2-phenyl-3H-imidazol-4-yl ) [1,2,3] triazol-1-yl] -benzamide 3-Ethyl-2-phenyl-3H-imidazole-4-carbaldehyde was prepared from benzene and ethylamine carboxamide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) .

Example 85 was prepared from 3-ethyl-2-phenyl-3i-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methane-sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 628 [C33H37? 704S + H] +.

Example 86: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1-J-pyrazol-4-yl) - [1, 2,3] triazol-1-yl] -4-methyl-benzamide , A 67 -Ethyl-l-phenyl-lH-pyrazole-4-carbaldehyde was prepared from ethyl 3-oxo-pentanoate and phenylhydrazine therein. 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).

Example 86 was prepared from 5-ethyl-1-phenyl-1H-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 628 [C33H37? 704S + H] + Example 87: 3- [4- (2-Benzyl-3-methyl-3J? -imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- (5- er-butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 2-Benzyl-3-methyl-3H-imidazole-4-carbaldehyde was prepared from 2-phenyl-acetamide in the same manner as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) .

Example 87 was prepared from 2-benzyl-3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfosyl-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 628 [C33H37? 704S + H] +.

Example 88: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-pyridin-2-yl-12T-pyrazol-4-yl ) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide -Ethyl-l-pyridin-2-yl-lH-pyrazole-4-carbaldehyde was prepared from ethyl 3-oxo-pentanoate and 2-pyridylhydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H -pyrazol-4-carbaldehyde (Example 49).

Example 88 was prepared from 5-ethyl-l-pyridin-2-yl-lH-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methane-sulfonylamino-2-methoxy) phenyl) -4-methyl-1-benzamide in the same manner as Example 39. ESI MS m / z 629 [C32H3e? 804S + H] +.

Example 89: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-3- [4- [spiro (6, -dihydro-5-pyrrolo [1,2-a] imidazol-3-yl-5-cyclohexane)] - [1,2,3] triazol-1-yl] -benzamide Spiro [6,7-dihydro-5Ji-pyrrolo [1,2-a] imidazole-5-cyclohexane] -3-carbaldehyde was prepared from 1-aza-spiro [.5] dec-2-ylidenamine (Buckley, et al., J. Chem. Soc. 1947, 1507.) and 2-bromo-3-isopropoxy-propenal in the same manner as cyclopropyl-2-methyl-3H-imidazole-4-carbaldehyde (Example 45).

Example 89 was prepared from spiro [6,7-dihydro-5H-pyrrolo [1,2-a] imidazole-5-cydohexane] -3-carbaldehyde and 3-azido-N- (5-er-butyl- 3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS / z 592 [C30H37? 7O4S + H] +.

Example 90: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-fluoro-phenyl) -5-methyl-li-pyrazol-4-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide Example 90 was prepared from 1- (4-fluorophenyl) -5-methyl-1H-pyrazole-4-carbaldehyde (Maybridge) and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 632 [C 32 H 34 F? 704 S + H] +.

Example 91: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclohexyl-5-ethyl-12? -pyrazol-4-yl) - [1, 2,3] triazol-1-yl] -4-methyl-benzamide L-cyclohexyl-5-ethyl-lH-pyrazole-4-carbaldehyde was prepared from ethyl 3-oxo-pentanoate and cyclohexylhydrazine (TCI) in the same manner as 5-cyclopropyl-l-isopropyl-1-pyrazole- 4-carbaldehyde (Example 49).

Example 91 was prepared from l-cyclohexyl-5-ethyl-lN-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 634 [C33H43? 704S + H] +.

Example 92: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5-methyl-l- (l-methyl-piperidin-4-yl) -lff-pyrazol-4-yl] - [1, 2, 3] riazol-1-yl} -benzamide ae submitted a solution of 11.2 g (99.0 mmol) of l-methyl-piperid-4-one and 13.0 g (100 mmol) of Boc-hydrazine in 150 ml of hexanes for 30 minutes. The hot solution was dried over MgSO4, filtered and allowed to cool. The resulting crystals were isolated and recrystallized from Et20 to provide 7.2 g of N '- (1-methyl-piperidin-4-ylidene) -hydrazinecarboxylic acid tert-butyl ester as a white solid. Im BoM solution in THF (30 ml) was added to 2.80 g (12.3 mmol) solids of N '- (1-methyl-piperidin-4-ylidene) -hydrazinecarboxylic acid tert -butyl ester. The mixture was stirred under N2 for 16 hours, after which 40 ml of 6M HCl was carefully added. The mixture was heated to 60 ° C for 30 min. The mixture was concentrated in vacuo at room temperature for 2 days. Petroleum ether (200 ml) and NaOH powder (5 g) were added, and the mixture was stirred manually for 30 min. The mixture was dried with MgSO 4, filtered and carefully concentrated to yield 1.3 g of (l-methyl-piperidin-4-yl) -hydrazine.

-Methyl-1- (1-methyl-piperidin-4-yl) -1H-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and (1-methyl-piperidin-4-yl) -hydrazine therein 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).

Example 92 was prepared from 5-methyl-1- (1-methyl-piperidin-4-yl) -IH-pyrazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino -2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 635 [C 32 H 42 N 804 S + H] +.

Example 93: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-cyclopropyl-1-phenyl-1-yl-pyrazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide -Cyclopropyl-1-phenyl-1H-pyrazole-4-carbaldehyde was prepared from methyl 3-cyclopropyl-3-oxo-propionate and phenylhydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H? pyrazole-4 -carbaldehyde (Example 49).

Example 93 was prepared from 5-cyclopropyl-1-phenyl-1-N-pyrazol-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methane-sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 640 [C3 H37? 70 S + H] +.

Example 94: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (l-cyclopropyl-5-pyridin-2-yl-li? -pyrazol-4-yl) - [1, 2, 3] triazol-1-yl] -4-methyl-benzamide A solution of isopropylmagnesium bromide (2M in Et20; 36.5 ml, 73.0 mmol) was added to 4.36 ml (36.6 mmol) of malonic acid monoethyl ester in 30 ml of THF under N2 at 0 ° C. The reaction was stirred at 0 ° C for 30 min, at room temperature for 30 min and then at 40 ° C for 30 min. The mixture was subsequently cooled to 0 ° C and a solution of imidazol-1-yl-pyridin-2-yl-methanone (prepared by stirring 3.00 g (24.3 mmol) of pyridine-2-carboxylic acid with 4.7 g (29 g) was slowly added (29 g. mmol) of CD1 in 30 ml of THF for 12 h). The reaction was allowed to warm to room temperature and was stirred for 12 hours. The mixture was then poured into ice-cold H3P0 1M (150 ml). Solid NaHCO3 was added to the mixture until the pH reached 7. The mixture was extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with NaHCO3 (100 mL) and brine, dried with MgSO4, filtered and concentrated to provide 2.5 g of ethyl 3-oxo-3-pyridin-2-yl-propionate as an oil.

L-cyclopropyl-5-pyridin-2-yl-lH-pyrazole-4-carbaldehyde was prepared from ethyl 3-oxo-3-pyridin-2-yl-propionate and cyclopropylhydrazine oxalate in the same way as -cyclopropyl-1-isopropyl-lH-pyrazole-4 -carbaldehyde (Example 49).

Example 94 was prepared from l-cyclopropyl-5-pyridin-2-yl-lH-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methano-sulfonylamino-2-methoxy phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 641 [C33H3e? 804S + H] +. Example 95: 3- [4- (3-Benzyl-2-ethyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- (5-tert-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) - -methyl-benzamide 3-Benzyl-2-ethyl-3H-imidazole-4-carbaldehyde and 1-benzyl-2-ethyl-1H-imidazole-4-carbaldehyde were prepared in the same manner as 1,2-diethyl-5-formylimidazole and 1, 2-diethyl-4-formylimidazole (Example 51).

Example 95 was prepared from 3-benzyl-2-ethyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same mode < than Example 39. ESI MS m / z 642 [C34H39? 704S + H] +.

Example 9.6: 3- [4- (l-Benzyl-2-ethyl-lH-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- (5-tert-butyl-3 -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide Example 96 was prepared from l-benzyl-2-ethyl-lff-imidazole-4-carbaldehyde (Example 95) and 3-azido-N- (5-erbutyl-3-methanesulfonylamino-2-methoxy-phenyl) ) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 642 [C34H39? 704S + H] +.

Example 97: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-isopropyl-1-phenyl-1H-pyrazol-4-yl) - [1,2, 3] triazol-1-yl] -4-methyl-benzamide -Isopropyl-1-phenyl-1H-pyrazole-4-carbaldehyde was prepared from ethyl 3-oxo-3-methyl-pentanoate and phenylhydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole -4-carbaldehyde (Example 49).

Example 97 was prepared from 5-isopropyl-1-phenyl-1H-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 642 [C34H39? 704S + H] +.

Example 98: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-methoxy-phenyl) -5-methyl-lH-pyrazol-4-yl] -l, 2,3-triazol-1-yl} -4-methyl-benzamide Example 98 was prepared from l- (4-methoxyphenyl) -5-methyl-lH-pyrazole-4-carbaldehyde (Maybridge) and 3-azido-N- (5-er-butyl-3-methano- sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 644 [C33H37? 705S + H] + Example 99: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2-cyclopropyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide 2-Cyclopropyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazole-4-carbaldehyde was prepared from cyclopropylcarboxamide and 2,2,2-trifluoroethylamine in the same manner as 2-cyclopropyl-3. -methyl-3H-imidazole-4-carbaldehyde (Example 46).

The Example 99 was prepared from 2-cyclopropyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-). methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 646 [C 30 H 34 F 3 N 7 O 4 S + H] +.

Example 100: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3 - [4 - (3-methyl-2-phenylsulf nyl-3H-imidazole -4-yl) - [1, 2, 3] triazol-1-yl] -benzamide 1-Methyl-2-thiophenyl-1H-imidazole (Ohta, S. et al., Bioorg, Med.Chem.Lett., 1992, 40, 2681-2685) (500 mg, 2.63 mmol) was dissolved in 5 ml of THF and it was cooled to -78 ° C, then n-BuLi (3.29 ml of a 1.6 M solution in hexanes, 5.26 mmol) was added dropwise. The solution was stirred at -78 ° C for 15 min and then a solution of DMF (1.02 ml, 13.1 mmol) in 2 ml of THF was added dropwise. After stirring for 10 min, the mixture was warmed to room temperature. After stirring for 1 h, the reaction was quenched with saturated aqueous? H4C1 and diluted with EtOAc (30 mL) and water (20 mL). The layers were separated and the organic portion was washed with water (20 ml), brine (20 ml), dried (MgSO 4), filtered, concentrated and chromatographed (0-5% MeOH in CH 2 C 12) to give 458 mg (2.10 mmol, 80%) of 1-methyl. -2-phenylsulfanyl-IJ-imidazole-4-carboxaldehyde.

Example 100 was prepared from l-methyl-2-phenylsulfanyl-lH-imidazole-4-carboxaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -methyl -benzamide in the same manner as Example 39. ESI MS m / z 646 [C32H3S? 704S2 + H] +.

Example 101: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -benzamide 3-Methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazole-carbaldehyde was prepared from 2-phenyl-isobutyramide in the same manner as 2-cyclopropyl-3-methyl-3-phenyl- imidazole-4-carbaldehyde (Example 46).

Example 101 was prepared from 3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methyl) -sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 656 [C 35 H 41? 704 S + H] +.

Example 102: 3- [4- (2-Benzyloxymethyl-3-methyl-3-yl-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- (5-tert-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 2-Benzyloxymethyl-3-methyl-3N-imidazole-4-carbaldehyde was prepared from 2-benzyloxy-acetamide in the same way as 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 102 was prepared from 2-benzyloxymethyl-3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-tert-butyl-3-methane-sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS / z 658 [C34H39? 705S + H] +.

Example 103: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (1-phenyl-5-trifluoromethyl-1H-pyrazol-4-yl) - [1,2,3] triazol-1-yl] -benzamide 1-Phenyl-5-trif luoromethyl-lN-pyrazole-4-carbaldehyde was prepared from the l-phenyl-5-trifluoromethyl-l-p-pyrazole-4-carboxylic acid ethyl ester (Maybridge) in the same way as the methyl ester. -cyclopropyl-l-isopropyl-lH-pyrazole-4-carbaldehyde (Example 49).

Example 103 was prepared from l-phenyl-5-trifluoromethyl-1-pyrazol-4-carbaldehyde and 3-azido-N- (5-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 668 [C 32 H 32 F 3? 704 S + H] +.

Example 104: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (l-fcer-butyl-piperidin-4-yl) -5-methyl-lH-pyrazol-4-yl] - [1,2,3] triazol-1-yl} -4-methyl-benzamide To 45.0 g (398 mmol) of l-methyl-piperid-4-one in 500 ml of acetone was added dropwise 60.0 g (423 mmol) of Mel for 1 h. The mixture was stirred for 3 hours, cooled to 0 ° C and filtered. The solids were washed with cold acetone and dried to provide 1,1-dimethyl-4-oxo-piperidinium iodide as a yellow solid (95.3 g). A suspension of 64.5 g (253 mmol) of iodide of 1 was stirred., l-dimethyl-4-oxo-piperidinium in 50 ml of water and 90 ml (860 mmol) of tert-butylamine for 15 min, at which time 1.0 ml of 40% Triton B in MeOH was added. The mixture was refluxed for 2 hours under N2 and then extracted with Et20 (4 x 100 ml). The aqueous phase was converted to a base with 20g of NaOH in 20 ml of water and then extracted further with Et20 (4 x 100 ml). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The residual oil was stirred with 1.5 1 of petroleum ether, which was decanted and concentrated. The residue was distilled under vacuum to provide 1.8 g of 1-erbutyl-piperid-4-one. To 1.8 g (11.6 mmol) of 1-er-butyl-piperid-4-one in 10 ml of hexanes was added Boc-hydrazine (1.59 g, 12.0 mmol) in 75 ml of hexanes. The mixture was refluxed for 30 minutes, dried hot with MgSO 4, still filtered hot and then concentrated to provide 3.0 g of N '- (1-er-Butyl-piperidin-4-ylidene) butyl ester. -hydrazinecarboxylic. An im-borane solution in THF (28.7 ml, 28.7 mmol) was added to the N '- (1-tert-Butyl-piperidin-4-ylidene) -hydrazinecarboxylic acid tert-butyl ester. The mixture was stirred for 16 hours and then 40 ml of 6M HCl HCl was added. The mixture was heated to 60 ° C for 30 min. The mixture was concentrated and 200 ml of petroleum ether were added, followed by? AOH powder (5 g). The suspension was manually stirred for 30 min and then the mixture was dried with MgSO 4, filtered and concentrated to yield 1.21 g of (1-er-butyl-piperidin-4-yl) -hydrazine (1.21 g). 1- (1-er-Butyl-piperidin-4-yl) -5-methyl-1H-pyrazole-4-carbalde was prepared from ethyl acetoacetate and (1-tert-butyl-piperidin-4-yl) - azine in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbalde (Example 49).

Example 104 was prepared from 1- (1-er-butyl-piperidin-4-yl) -5-methyl-li? -pyrazol-4-carbalde and 3-azido-N- (5- tert-butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 677 [C35H48? 804S + H] +.

Example 105: 3-. { 4- [2- (1-Benzyloxy-cyclopropyl) -3-methyl-3ff-imidazol-4-yl] - [1,2,3] triazol-1-yl} -N- (5-tert-butyl-3-ethanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide X .OBn H2? \ > 1-oxy-cyclopropanecarboxylic acid methyl ester (Acros, 1.00 g, 8.61 mmol) in 24 mL of THF was stirred with 516 mg (12.9 mmol) of α to H (60% in mineral oil) for 10 min. Then benzyl bromide (1.13 ml, 9.37 mmol) and Bu4I (0.32 g, 0.85 mmol) were added and the mixture was stirred overnight. The mixture was diluted with EtOAc and washed with saturated? H 4 Cl. The wash was extracted once with EtOAc and the combined extracts were washed with brine, dried over Na 2 SO 4, filtered, concentrated and chromatographed (0-50% EtOAc in hexanes) to provide 774 mg (3.75 mmol) of ester. 1-benzyloxy-cyclopropanecarboxylic acid methyl ester which was dissolved in 14 ml of 1: 1 EtOH / THF. Sodium oxide (IM, 5.63 ml) was added and the mixture was stirred for 4 hours. After concentrating, 5 ml of water was added and the solution was extracted once with Et20. The aqueous layer was then adjusted to a pH of 3 with HCl and the suspension was extracted twice with EtOAc. The extracts were washed with brine, dried with Na 2 SO 4, filtered and concentrated to give 723 mg of 1-benzyloxy-cyclopropanecarboxylic acid. To the previous acid (3.76 mmol) in 10 ml of CH2C12 was added 2.82 ml (5.64 mmol) of 2M oxalyl chloride in CH2C12 and a drop of DMF. After stirring for 15 min, the mixture was concentrated and redissolved in 4 ml of MTBE and 0.15 ml of CH2C12 and cooled to 0 ° C. Ammonium oxide (28% in water, 0.78 ml) was added and the mixture was stirred for 15 min, after which 1 ml of saturated NaHCO 3 was added. The mixture was extracted twice with EtOAc and the extracts were combined, washed with brine, dried with Na 2 SO 4, filtered and concentrated to give 550 mg of the amide of 1-benzyloxy-cyclopropanecarboxylic acid as a yellow oil. 2- (1-Benzyloxy-cyclopropyl) -3-methyl-3H-imidazole-4-carbalde was prepared from the amide of 1-benzyloxy-cyclopropanecarboxylic acid in the same manner as 2-cyclopropyl-3-methyl-3H -imidazole-4 -carbalde (Example 46).

Example 105 was prepared from 2- (1-benzyloxy-cyclopropyl) -3-methyl-3H-imidazole-4-carbalde and 3-azido-N- (5-tert-butyl-3-methane sulfonylamino- 2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 684 [C36H41? 705S + H] +.

Example 106: 3 -. { 4 - [2 - (2-Benzyloxy-1, 1-dimethyl-ethyl) -3-methyl-3H-imidazol-4-yl] - [1, 2, 3] triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-oxy-2,2-dimethyl-propionic acid methyl ester (3.00 g, 22.7 mmol) in 40 ml of THF at 0 ° C was treated with 1.0 g (25 mmol) of 60%? AH in mineral oil during 20 min. Benzyl bromide (2.97 ml, 25.0 mmol) was added dropwise over 10 minutes. The mixture was stirred overnight, 30 ml of water was added and the mixture was extracted with EtOAc (3 x 100 ml). The combined extracts were washed with brine, dried with MgSO4 / filtered and concentrated. The residue was dissolved in 40 ml of EtOH, 28 ml of 2M NaOH was added and the mixture was heated to 80 ° C for 12 hours. The mixture was cooled, neutralized with 2M HCl and extracted with EtOAc (3 x 100 mL). The combined extracts were washed with brine, dried with MgSO4, filtered, concentrated and chromatographed (10-100% EtOAc in hexanes) to give 2.4 g of 3-benzyloxy-2,2-dimethyl-propionic acid. To a 0 ° C solution of 2.4 g (11.4 mmol) of 3-benzyloxy-2,2-dimethyl-propionic acid and 1.65 ml (11.5 mmol) of Et 3 N in 80 ml of chloroform was added 1.04 ml (11.5 mmol). of ethyl chloroformate. After stirring for 15 min, NH3 gas was passed through the solution for 5 minutes. The resulting suspension was removed from the ice bath and allowed to stir overnight. The suspension was filtered and the filtrate was concentrated until practically dried. The resulting residue was crystallized from a mixture of benzene / hexanes (16 ml / 40 ml) to provide 2.3 g of 3-benzyloxy-2,2-dimethyl-propionamide. 2- (2-Benzyloxy-1, 1-dimethyl-ethyl) -3-methyl-3H-imidazole-4-carbaldehyde was prepared from 3-benzyloxy-2,2-dimethyl-propionamide in the same manner as -cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46).

Example 106 was prepared from 2- (2-benzyloxy-1,1-dimethyl-ethyl) -3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 700 [C37H45? 705S + H] +.

Example 107: 3-. { 4- [1- (1-Benzyl-piperidin-4-yl) -5-methyl-li-pyrazol-4-yl] - [1,2,3] triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 1- (1-Benzyl-piperidin-4-yl) -5-methyl-1H-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and (1-benzyl-piperidin-4-yl) -hydrazine therein Thus, 5-cyclopropyl-1-isopropyl-1-N-pyrazol-4-carbaldehyde (Example 49).

(L-Benzyl-piperidin-4-yl) -hydrazine was prepared from 1-benzyl-piperidin-4-one in the same manner as (1-methyl-piperidin-4-yl) -hydrazine (Example 92).

Example 107 was prepared from 1- (1-benzyl-piperidin-4-yl) -5-methyl-lH-pyrazole-4-carbaldehyde and 3-azido-N- (5-er-butyl-3-methanesulfonylamino -2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 711 [C38H46? 804S + H] +.

Example 108: 4- (4-. {L- [5- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] -1H- [4- (4. 1,2,3] triazol-4-yl.} -2-cyclopropyl-2H-pyrazol-3-yl) -piperidine-1-carboxylic acid N-Boc-4- (2-Ethoxycarbonyl-acetyl) -piperidine acid was prepared from N-Boc-piperidine-4-carboxylic acid in the same manner as ethyl 3-oxo-3-pyridin-2-yl-propionate (Example 94).

N-Boc-4 - (2-cyclopropyl-4-ethoxycarbonyl-2H-pyrazol-3-yl) -piperidine was prepared from N-Boc-4- (2-ethoxycarbonyl-acetyl) -piperidine and cyclopropylhydrazine oxalate in the same way as the ethyl ester of 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carboxylic acid (Example 49). A solution of 1.71 ml (3.42 mmol) of? AOH was added 2M at 0.540 g (1.49 mmol) N-Boc-4 - (2-cyclopropyl-4-ethoxycarbonyl-2H-pyrazol-3-yl) -piperidine in 15 ml of EtOH. After stirring at 60 ° C for 18 hours, the solution was concentrated and dissolved in 100 mL of EtOAc (100 mL) and 10 mL of 5% HCl (10 mL). The extract was washed with 50 ml of brine (50 ml), dried over MgSO, filtered, concentrated and chromatographed (0-100% EtOAc in hexanes) to yield 330 mg of N-Boc-4- (4- carboxy-2-cyclopropyl-2H-pyrazol-3-yl) -piperidine as a white powder. The above acid (300 mg, 0.894 mmol) was dissolved in ml of THF. To this solution was added 3.58 ml (3.58 mmol) of borane IN in THF. After stirring for 5 hours, the mixture was poured into 15 ml of 5% HCl. The solution was extracted with 200 mL of EtOAc and the extract was washed with saturated αHC03 and brine, dried over MgSO4, filtered, concentrated and chromatographed (10-100 EtOAc in hexanes) to yield 120 mg of N-Boc. -4- (2-cyclopropyl-4-hydroxymethyl-2H-pyrazol-3-yl) -piperidine. This alcohol (100 mg, 0.31 mmol) was stirred overnight in 10 ml of THF with 270 mg (3.1 mmol) of activated MnO2. The mixture was filtered and concentrated to provide 70 mg of N-Boc-4- (2-cyclopropyl-4-formyl-2H-pyrazol-3-yl) -piperidine.

Example 108 was prepared from N-Boc-4- (2-cyclopropyl-4-formyl-2H-pyrazol-3-yl) -piperidine and 3-azido-N- (5-er-butyl-3-methane) -sulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 141 [C38H50? 8OsS-lH] +.

Example 109: Benzyl Ester of [[2- (4-. {1-l- [5- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] - 1 H- [ 1, 2, 3] triazol-4-yl.} -2-phenyl-2H-pyrazol-3-yl) -ethyl] -carbamic Ethyl 5-benzyloxycarbonylamino-3-oxo-pentanoate was prepared from N-Cbz-β-alanine in the same manner as ethyl 3-oxo-3-pyridin-2-yl-propionate (Example 94). [2- (4-Formyl-2-phenyl-2H-pyrazol-3-yl) -ethyl] -carbamic acid benzyl ester was prepared from ethyl 5-benzyloxycarbonylamino-3-oxo-pentanoate in the same manner as N-Boc-4- (2-cyclopropyl-4-formyl-2N-pyrazol-3-yl) -piperidine (Example 108).

Example 109 was prepared from [2- (4-formyl-2-phenyl-2-pyr-3-yl) -ethyl] -carbamic acid benzyl ester and 3-azido-N- (5-tert-butyl) 3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 111 [C4? H44? 806S + H] +.

Example 110: N- (5-tert-Butyl-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) - [1,2,3] triazole -1-yl] -4-ethyl-benzamide AüC 3-azido-N- (5-er.-butyl-2-methoxy-phenyl) -4-methyl-benzamide was prepared from 3-azido-4- methylbenzoic (US 04/102492) and 5- er-butyl-2-methoxy-phenylamine in the same manner as 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- benzamide (Example 15).

Example 110 was prepared from 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) and 3-azido-N- (5-tert-butyl-2-methoxy-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 485 [C28H32? 602 + H] +.

Example 111: N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide 3-azido-N- (5-er-butyl-3-cyano-2-methoxy-phenyl) -4-methyl-benzamide was prepared from 3-azido-4-methyl benzoic acid (US 04/102492) and 3-amino-5- er-butyl-2-methoxy-benzonitrile in the same manner as 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15).

Example 111 was prepared from 2-cyclopropyl-3-methyl-3J? -imidazole-4-carbaldehyde (Example 46) and 3-azido-N- (5-tert-butyl-3-cyano-2-methoxy). phenyl) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 510 [C 29 H 31? 702 + H] +.

Example 112: N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) - [1, 2, 3] triazole -1-yl] -4-methyl-benzamide 3-azido-N- (5-er-butyl-2-methanesulfinyl-phenyl) -4-methyl-benzamide was prepared from 3-azido-4-methyl benzoic acid (US 04/102492) and 5- er- butyl-2-methanesulfinyl-phenylamine in the same manner as 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15).

Example 112 was prepared from 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) and 3-azido-N- (5-tert-butyl-2-methanesulfinyl-phenyl) -4- methyl-benzamide in the same manner as Example 39. ESI MS m / z 517 [C28H32? s02S + H] +.

Example 113: N- (5-tert-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imxdazol-4-yl) - [1,2 , 3] triazol-1-yl] -4-methyl-benzamide 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methyl-phenyl) -4-methyl-benzamide was prepared from 3-azido-4-methyl benzoic acid (US 04/102492) and N- (3-Amino-5-tert-butyl-2-methyl-phenyl) -methanesulfonamide in the same way < The 3-azido-N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide (Example 15).

Example 113 was prepared from 2-cyclopropyl-3-methyl-3H-imidazole-4-carbaldehyde (Example 46) and 3-azido-N- (5-tert-butyl-3-methanesulfonylamino-2-methyl-phenyl) ) -4-methyl-benzamide in the same manner as Example 39. ESI MS m / z 562 [C29H35? 703S + H] +.

Example 114: N- [3-Methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3- [4- (5-methyl-1-phenyl-1H-pyrazole-4 -yl) - [1,2,3] triazol-1-yl] -benzamide Example 114 was prepared from 5-methyl-l-phenyl-lH-pyrazole-4-carbaldehyde (Maybridge) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) ) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 612 [C32H33? 704S + H] +.

Example 115: 3- [4- (3-tert-Butyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5] - (1- ethyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 115 was prepared from 3-tert-butyl-3J? -imidazole-4-carbaldehyde (Example 56) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) ) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 116: 3- [4- (l-Isopropyl-5-methyl-lff-pyrazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 116 was prepared from l-isopropyl-5-methyl-lH-pyrazole-4-carbaldehyde (Example 55) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 578 [C 29 H 35? 704 S + H] +.

Example 117: 3- [4- (2-Isopropyl-3-methyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-ethanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 117 was prepared from 2-isopropyl-3-methyl-3J? -imidazole-4-carbaldehyde (Example 53) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl) -cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 578 [C29H35? 704S + H] +.

Example 118: 3- [4- (2-cyclopropyl-3-methyl-3J? -imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2 - methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 118 was prepared from 2-cyclopropyl-3-methyl-3i-imidazole-4-carbaldehyde (Example 46) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl) -cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 516 [C29H33? 704S + H] +.

Example 119: 3- [4- (2-Cyclobutyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamins-2-methoxy- 5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 119 can be prepared from 2-cyclobutyl-3-methyl-3H-imidazole-4-carbaldehyde and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) - phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39.

Example 120: N- [3-Methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -benzamide Example 120 was prepared from 3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazole-4-carbaldehyde (Example 63) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5 - (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same way as the Example 39. ESI MS m / z 590 [C30H35? 7O4S + H] +.

Example 121: 3- [4- (1-cyclopropyl-5-ethyl-1-pyrazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 121 was prepared from 1-cyclopropyl-5-ethyl-1H-pyrazole-4-carbaldehyde (Example 64) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4- methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 590 [C30H35? 7O4S + H] +.

Example 122: 3- [4- (l-tert-Butyl-5-methyl-lH-pyrazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2] -methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 122 was prepared from 1-er-butyl-5-methyl-1H-pyrazole-4-carbaldehyde (Example 69) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1- methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 123: 3- [4- (3-fcer-Butyl-2-methyl-3H-imidazol-4-yl) - [1,2, 3] triazol-1-yl] -N- [3-methanesulfonylamino-2] -methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 123 was prepared from 3-er-butyl-2-methyl-3H-imidazole-4-carbaldehyde (Example 68) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1- methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 124: 3- [4- (2-tert-Butyl-3-methyl-3J? -imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino- 2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 124 was prepared from 2-er-butyl-3-methyl-3J-imidazole-4-carbaldehyde (Example 67) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5 - (1- methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 592 [C30H37? 7O4S + H] +.

Example 125: 3- [4- (5-Ethyl-1-f-enyl-1-pyrazol-4-yl) [1, 2, 3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 305 SUMMARY Described compounds of the formula (I) are described that inhibit the production of cytokines involved in inflammatory processes and that, therefore, are useful to treat diseases and pathological conditions that involve inflammation, such as chronic inflammatory disease. Processes for preparing these compounds and pharmaceutical compositions comprising these compounds are also described.

Example 125 was prepared from 5-ethyl-1-phenyl-1H-pyrazole-4-carbaldehyde (Example 86) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 626 [C33H35? 704S + H] +.

Example 126: 3- [4- (3-Ethyl-2-phenyl-3H-imidazol-4-yl) - [1,2,3] triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy] -5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide Example 126 was prepared from 3-ethyl-2-phenyl-3H-imidazole-4-carbaldehyde (Example 85) and 3-azido-N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33) in the same manner as Example 39. ESI MS m / z 626 [C33H35? 704S + H] +.

Example 127: N- [3-Methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] - [1,2,3] triazol-1-yl} -benzamide Example 127 was prepared from 3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazole-4-carbaldehyde (Example 101) and 3-azido-N- [3-methanesulfonylamino-2 -methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide (Example 33). in the same way as Example 39. ESI MS m / z 655 [C35H39? 704S + H] +.

Example 128: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-hydroxymethyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide A mixture of 386 mg (0.587 mmol) of Example 102, 185 mg (2.94 mmol) of ammonium formate, 40 mg of Pd / C in 20 ml of MeOH (20 ml) was stirred with 0.1 ml (1.2 mmol) of acid Formic at RT for 12 hours. The mixture was filtered through celite and concentrated to provide 280 mg of Example 128. ESI MS m / z 568 [C27H33? 705S + H] +.

Example 129: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-formyl-3-methyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide Example 128 (400 mg, 0.705 mmol) was dissolved in THF (20 ml) and 308 mg of activated Mn02 was added. The reaction was stirred for 12 hours and then filtered through celite and concentrated. The residue was dissolved in EtOAc and washed with water and brine, dried with MgSO 4, filtered, concentrated and chromatographed (10-100% EtOAc in hexanes) to provide 200 mg of Example 129. ESI MS m / z 567 [C27H31? 705S + H] +.

Example 130: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide To a solution at 0 ° C of 45 mg (0.080 mmol) of the Example 129 in 10 ml of THF was slowly added 0.11 ml (0.32 mmol) of 3M MeMgBr in Et20. The mixture was allowed to warm to RT with stirring overnight. A solution of 10% HCl was added and the mixture was extracted with EtOAc (3 x 50 ml) and the combined organic extracts were washed with brine, dried with MgSO 4, concentrated and chromatographed (0-10% MeOH in CH 2 C 12 ) to provide Example 129 (45 mg). ESI MS m / z 582 [C28H35N705S] +.

Example 131: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (cyclopropyl-hydroxy-methyl) -3-methyl-SITimidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide To a 0 ° C solution of 50 mg (0.088 mmol) of Example In 129 ml of THF, 0.88 ml (0.44 mmol) of cyclopropylmagnesium bromide (0.5 M in THF) was added slowly. The mixture was allowed to warm to RT with stirring overnight. Water (50 ml) was added and the mixture was extracted with EtOAc (3 x 50 ml), the combined organic extracts were washed with brine, dried with MgSO 4, concentrated and chromatographed (0-10% MeOH in CH 2 C 12) to provide Example 131 (15 mg). ESI MS m / z 609 [C30H37? 7O5S + H] +.

Example 132: 3- [4- (2-Acetyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5-tert-butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide To 15 mg (0.026 mmol) of Example 130 in 5 ml of THF was added 7.6 mg (0.13 mmol) of activated MnO2. The reaction was stirred overnight, then filtered through celite and concentrated to provide 10 mg of Example 132. ESI MS m / z 580 [C28H33N705S + H] +.

Example 133: 3- [4- (2-cyclopropyl-3-methyl-3-yl-imidazol-4-yl) -1,2, 3-triazol-1-yl] -N- [5- (2-hydroxy-1 , 1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-benzamide A solution of TMSCHC? 2 (1.0 M) was added at 4.28 g (17.3 mmol) of (4-hydroxy-3,5-dinitrophenyl) -acetic acid in 63 ml of MeC? and 7 ml of MeOH. After 2 hours, it was added 0. 8 ml of acetic acid. After stirring for an additional 30 min, the solution was concentrated and partitioned between? Saturated HCO3 and EtOAc. The organic portion was washed with brine, dried with Na 2 SO 4, filtered and concentrated to give the methyl ester of (4-methoxy-3,5-dinitrophenyl) -acetic acid (3.22 g). Methyl iodide (3.36 ml, 54.0 mmol) was added to 3.65 g (13.5 mmol) of (4-methoxy-3,5-dinitrophenyl) -acetic acid in 40 ml of DMF at 0 ° C. Sodium hydride (60%, 1.62 g, 40.5 mmol) was carefully added in portions. The mixture was allowed to warm to RT, then diluted with water and extracted with EtOAc. The aqueous layer was extracted twice with EtOAc and the extracts were washed with water and brine. The extracts were combined, dried with Na 2 SO, filtered and concentrated to give a brown oil. Hexanes were added, swirled around the flask and decanted. This procedure was repeated twice and the resulting residue was dried in vacuo to provide 2.96 g of the 2- (4-methoxy-3,5-dinitrophenyl) -2-methylpropionic acid methyl ester. To a solution at 0 ° C of 1.30 g (4.35 mmol) of the 2- (4-methoxy-3,5-dinitrophenyl) -2-methyl-propionic acid methyl ester in 30 ml of THF was added dropwise. drop 17 ml (17 mmol) of DIBAL 1.0 M in CH2C12. After stirring for an additional 4 hours, 2 ml of MeOH was added slowly and then Na2SO4 saturated (2 ml). The resulting suspension was stirred rapidly for 20 min, then 40 ml EtOAc followed by MgSO4 was added. The resulting mixture was then stirred at RT for an additional 30 min. The mixture was filtered through celite and the filter cake was washed with EtOAc. The filtrate was concentrated to provide 580 mg of 2- (4-methoxy-3,5-dinitro-phenyl) -2-methyl-propan-1-ol. 2. (4-methoxy-3,5-dinitro-phenyl) -2-methyl-propan-1-ol was dissolved in 5 ml of CH2C12. Acetic anhydride was added followed by DMAP. The mixture was stirred overnight, then diluted in 15 mL of CH2C12 and washed with NaHCO4, saturated NaHC03 and brine. The CH2C12 solution was then dried with NaS04, filtered and concentrated to provide 2- (4-methoxy-3,5-dinitrophenyl) -2-methyl-propyl ester acetic acid (628 mg) as a brown oil. Acetic acid 2- (4-methoxy-3,5-dinitro-phenyl) -2-methyl-propylester (625 mg, 2.00 mmol) was dissolved in 10 ml of MeOH. Ethyl acetate (10 ml), ammonium formate (1.26 g, 20.0 mmol) and Pd / C (56 mg) were added and the mixture was heated to 40 ° C overnight. The mixture was then filtered through celite between saturated NaHCO 3 and EtOAc. The EtOAc extract was washed with brine. The washings were extracted once more with EtOAc. The extracts were combined, dried with Na 2 SO 4, filtered and concentrated to provide 500 mg of 2- (3,5-diamino-4-methoxy-phenyl) -2-methyl-propyl ester. To a solution of 500 mg (1.99 mmol) of acetic acid 2- (3,5-diamino-4-methoxy-phenyl) -2-methyl-propyl ester in 10 ml of MTBE was added 0.16 ml (2.0 mmol) of chloride of -methanesulfonyl and 0.35 ml (2.0 mmol) of DIPEA. The mixture was stirred overnight and then washed with saturated NH 4 Cl, saturated NaHCO 3 and brine. The ether layer was dried with Na2S0, filtered, concentrated and chromatographed (0-2.5% MeOH (0.05% NH4OH) in CH2C12) to provide 265 mg of 2- (3-amino-5-methanesulfonylamino-4-methoxy-phenyl) -2-methyl- propyl ester. Oxalyl chloride (0.11 mL, 1.3 mmol) was added to a stirring suspension of 148 mg (0.84 mmol) of 3-azido-4-methylbenzoic acid in 5 mL of 1: 1 CH2C12 / THF followed by 1 drop of DMF at 10% in THF. After stirring for 1 h, the now homogeneous mixture was concentrated to provide a dark oil. The acid chloride was dissolved in 5 ml of CH2C12 and 185 mg (0.56 mmol) of acetic acid 2- (3-amino-5-methanesulfonylamino-4-methoxy-phenyl) -2-methyl-propyl ester together with 0.2 ml (1.7 mmol) of 2,6-lutidine. The mixture was stirred overnight, then diluted with 10 mL of CH2C12 and washed with NaHCO4 (2x), saturated NaHC03 and brine. The organic portion was dried with Na 2 SO 4, filtered and concentrated to provide 2- [3- (3-azido-4-methyl-benzoylamino) -5-methanesulfonylamino-4-methoxy-phenyl] -2-methyl-propylester acetic acid. (238 mg).

To a stirring suspension of 49 mg (0.10 mmol) of acetic acid 2- [3- (3-azido-4-methyl-benzoylamino) -5-methanesulfonylamino-4-methoxy-phenyl] -2-methyl-propyl ester in 1 ml of EtOH 4N NaOH was added dropwise until the solids dissolved. 2-Cyclopropyl-5-ethynyl-1-methyl-1H-imidazole (125 mg, 0.855 mmol) was added followed by 20 mg (0.1 mmol) of sodium ascorbate in water. The mixture was stirred under N2 and CuSO 4 (0.1 M, 0.1 mL, 0.010 mmol) was added. The suspension was stirred overnight, then diluted with partially saturated NH 4 Cl and extracted with EtOAc. The extract was washed with brine and the washings were extracted once more with EtOAc. The extracts were combined, dried with Na 2 SO 4, filtered and concentrated. Chromatography (0-4% MeOH (0.5% NH0H) in CH2C12) gave the desired product with a light blue-green color. The product was then redissolved in EtOAc and washed again with NH 4 Cl with some drops of added NH 4 OH. The aqueous layer turned blue and the organic layer was washed once more with NH 4 Cl / NH 4 H and once with brine. The organic layer was then dried with Na 2 SO 4, filtered and concentrated to give Example 133 (83 mg). ESI MS m / z 594 [C 29 H 35 N 705 S + H] +.

Example 134: N- [5- (2-Hydroxy-1,1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide Example 134 was prepared in the same manner as 3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -N- [ 5- (2-hydroxy-l, 1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-f-enyl] -4-methyl-benzamide (Example 133) with 1.5 equivalents of 5-ethynyl-1- methyl-2- (1-methyl-cyclopropyl) -1H-imidazole. ESI MS m / z 608 [C30H37? 7O5S + H] +.

Example 135: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-piperidin-4-yl-li? -pyrazol- 4-yl) -1,2,3-triazol-1-yl] -benzamide Example 107 (210 mg, 0.30 mmol) and 10% Pd / C (65 mg) were stirred in 6 ml of MeOH with 1 g of ammonium formate for 8 hours. The mixture was then filtered through Celite and concentrated. The resulting residue was partitioned between water (5 ml) and EtOAc (100 ml). Brine (20 ml) and saturated aHC03 were added and the organic layer was separated and the aqueous layer was extracted with EtOAc (2 x 25 ml). The extracts were combined, washed with brine, dried over MgSO4 and concentrated to yield Example 135 (125 mg, 68%). ESI MS m / z 621 [C3? H40N8O4S + H] +.

Example 136: N- (5-fcer-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-piperazin-1-yl-3H-imidazole-4 -yl) -1, 2, 3-triazol-1-yl] -benzamide A mixture of Example 57 (100 mg, 0. 14 mmol) and 40 mg of Pd (OH) 2 in 10 ml of MeOH under an atmosphere of H2 for 72 hours. The mixture was filtered through Celite and concentrated to provide Example 136. MS m / z 622 [C30H39? 9O4S + H] +.

Example 137: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (1-methyl-2-piperazin-1-yl-1H-imidazole-4 -yl) - [1,2,3] triazol-1-yl] -benzamide Example 137 was prepared from Example 58 in the same manner as Example 136. ESI MS m / z 622 [C 30 H 39 N 9 O 4 S + H] +.

Example 138: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-f-enyl) -3-. { 4 - [2 - (1-hydroxy-cyclopropyl) -3-methyl-3ff-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide A solution of 190 mg (0.28 mmol) of Example 105 in 2 ml of EtOH was stirred over 30 mg of Pd / C under an atmosphere of H2 for 3.5 hours. Concentrated HCl (0.027 ml, 0.33 mmol) was added to the mixture, the temperature was warmed to 40 ° C and the mixture was stirred overnight. The mixture was cooled and filtered through celite. The filter cake was washed with CH2C12 and the combined filtrates were washed with saturated? HCO3 and brine. The organic extracts were dried with α2S04 / filtered and concentrated to provide Example 138 (130 mg). ESI MS m / z 594 [C29H35? 704S + H] +.

Example 139: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-ethyl-3H-imidazol-4-yl) - [1,2,3-hydrochloride ] triazol-1-yl] -4-methyl-benzamide Example 96 (120 mg, 0.187 mmol) was stirred with 15 mL of MeOH, 4 drops of concentrated HCl and 25 mg of Pd / C. The mixture was then stirred for 20 hours under an atmosphere of H2 at 50 ° C. The mixture was filtered through diatomaceous earth and concentrated. The residue was crystallized from MeOH / Et20 to provide 93 mg (0.16 mmol, 85%) of Example 138 as the hydrochloride salt. ESI MS m / z 552 [C 27 H 33 N 704 S + H] +.

Example 139: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-methanesulfonyl-3-methyl-3iT-imidazol-4-yl) -1,2, 3-triazol-l-yl] -4-methyl-benzamide To Example 25 (250 mg, 0.43 mmol) in 10 ml of MeOH (10 ml) was added 790 mg (2.6 mmol) of oxone in 10 ml of water. The mixture was stirred for 16 hours before being partitioned between CHC13 (10 mL) and water (10 mL) with 3 mL of NH4OH. The mixture was extracted with chloroform (3 x 60 ml), dried over MgSO 4, concentrated and chromatographed (25 to 100% EtOAc in hexanes) to give Example 139 (216 mg). ESI MS m / z 616 [C27H33N706S2 + H] +.

Example 140: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (2-methyl-propane-2-sulfonyl) -3H-imidazol-4-yl] -1, 2,3-triazol-1-yl} -benzamide Example 140 was prepared from Example 30 in the same manner as Example 139. ESI MS m / z 658 [C 30 H 39 N 7 O 6 S 2 + H] +.

Example 141: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-methanesulfinyl-3-methyl-3J? -imidazol-4-yl) -1, 2 , 3-triazol-l-yl] -4-methyl-benzamide To Example 25 (410 mg, 0.69 mmol) in 10 mL of MeOH (10 mL) was added 370 mg (1.2 mmol) of oxone in 10 mL of water. The mixture was stirred at 0 ° C for 22 hours before being partitioned between CHC13 (10 ml) and water (10 ml) with 3 ml NH4OH. The mixture was extracted with chloroform (3 x 60 ml), dried over MgSO 4, concentrated and chromatographed (85 to 100% EtOAc in hexanes) to give Example 141 (360 mg). ESI MS m / z 601 [C27H33N7OsS2 + H] +.

Example 142: N- (5-tert-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3-. { 4- [2- (hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide To a solution of 30 mg (0.047 mmol) of Example 35 in 2 ml of EtOH was added 7 mg (0.18 mmol) of NaBH 4. After stirring for 2 hours, 2 ml of water was added and the mixture was extracted with CH2C12 (3 x 20 ml). The combined organic extracts were washed with brine, dried with MgSO4 and concentrated to give 17 mg of Example 142. ESI MS m / z 645 [C33H37N705S + H] +.

Example 143: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-2, 2-dimethyl-propyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide Example 143 was prepared from Example 30 in the same manner as Example 142. ESI MS m / z 614. [C31H41N705S + H] +.

Example 144: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-piperidin-4-yl-lH-pyrazol-4-yl) - 1,2,3-triazol-1-yl] -4-methyl-benzamide To a solution of Example 108 (50 mg, 0.067 mmol) in 2 mL of MeOH was added 2M HCl (5 mL). The mixture was stirred for 12 hours. The solvent was removed in vacuo and the resulting residue was dissolved in CH2C12 (50 ml) and washed with saturated NaHCO3 (50 ml), brine (50 ml) and dried with MgSO4. The mixture was filtered, concentrated and chromatographed (10: 1 CH2Cl2: MeOH with 1% Et3N) to yield Example 144 (10 mg). MS m / z 647 [C33H42N804S + H] +.

Example 145: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2-hydroxy-1,1-dimethyl-ethyl) -3-methyl-3-J-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide Example 106 (250 mg, 0.36 mmol) and 50 mg of Pd / C (5%) were stirred in 10 ml of MeOH under an atmosphere of H2 for 12 hours. The mixture was filtered through a celite pad, concentrated and chromatographed (10-100% EtOAc in hexanes) to give Example 145 (15 mg). ESI MS m / z 610 [C 30 H 39 N 7 O 5 S + H] +.

Example 146: 3- { 4- [5- (2-Amino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide To a solution of 800 mg (1.03 mmol) of Example 109 in MeOH (40 ml) was added 3.6 g of? H4C02 and 150 mg of Pd / C The mixture was stirred at room temperature for 3 hours, filtered through celite and concentrated. The resulting residue was taken up in EtOAc (250 ml) and washed with a solution of water (10 ml) saturated NaHCO 3 (50 ml) and brine (20 ml). The organic layer was washed with brine (50 ml), dried over MgSO4 and concentrated to yield the 655 mg of Example 146 (1.01 mmol). MS m / z 643 [C33H38N804S + H] +.

Example 147: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [5- (2-dimethylamino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide Example 146 (250 mg, 0.389 mmol) was dissolved in 10 ml of MeOH. Formalin (0.6 ml of 37% aqueous formaldehyde) and 200 mg of Pd / C were added. The mixture was stirred under 1 atm of H2 for 48 hours, filtered through Celite, concentrated and purified by chromatography (0 to 10% MeOH in CH2C12, 0.5%? H4OH) to yield Example 147 (120 mg) . MS m / z 671 [C35H42? 804S + H] +.

Example 148: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5- (2-morpholin-4-yl-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -benzamide Example 146 (270 mg, 0.42 mmol) was dissolved in 8 ml of DMF followed by 0.25 ml (2.1 mmol) of 2,6-lutidine and 600 mg (2.3 mmol) of l-bromo-2- (2-bromo) ethoxy) -ethane. The mixture was stirred at 80 ° C for 12 hours, then dissolved in EtOAc (300 ml) and washed with saturated NaHCO 3, water and brine. The organic portion was dried over MgSO4, filtered, concentrated and chromatographed (0 to 10% MeOH in CH2C12; 0.5% NH4OH) to yield Example 148 (52 mg). MS m / z 713 [C37H44N805S + H] +.

Example 149: N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-phenyl-1H-pyrazol-4-yl) - imidazol-1-yl] -benzamide A solution of 2-bromo-1- (5-methyl-1-phenyl-1-pyrazol-4-yl) -ethanone (829 mg, 2.97 mmol) and 3-amino-4-methyl benzoic acid methyl ester was stirred. in 6 ml of EtOH at 75 ° C for 6 hours. The mixture was cooled and the resulting precipitate was filtered and washed with cold EtOH to provide 564 mg (1.55 mmol, 52%) of 4-methyl-3- [2- (5-methyl-1-phenyl-) methyl ester. lH-pyrazol-4-yl) -2-oxo-ethylamino] -benzoic acid as a white powder. A suspension of 380 mg (1.05 mmol) of methyl 4-methyl-3- [2- (5-methyl-1-phenyl-1, 5-pyrazol-4-yl) -2-oxo-ethylamino] -benzoic acid methyl ester and 203 mg (2.09 mmol) of KSCN in 4 ml of HOAc was stirred at 100 ° C for 4 hours, at which time a precipitate formed. The mixture was cooled to room temperature, filtered and washed with cold MeOH to provide 283 mg of 3- [2-mercapto-4- (5-methyl-1-phenyl-1-pyrazol-4-yl) methyl ester. ) -imidazol-1-yl] -4-methyl-benzoic acid (0.70 mmol, 67%). ESI MS m / z 405 [C 22 H 20 N 4 O 2 S + H] +. To 1 ml of 20% HN03 was added 28 mg of HN02. This mixture was then added to 3- [2-mercapto-4- (5-methyl-l-phenyl-lH-pyrazl-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid methyl ester ( 280 mg, 0.69 mmol) suspended in 5 ml of HOAc with rapid stirring in 15 min. After stirring for another 5 min, the solution was poured into ice-cooled water. The pH was adjusted to about 7 with NaHCO 3 and the mixture was extracted with EtOAc. The extract was washed once with brine, dried with Na 2 SO 4, filtered and concentrated. The resulting residue was chromatographed (5-60% EtOAc in hexanes) to provide 210 mg (0.56 mmol, 82%) of 4-methyl-3- [4- (5-methyl-1-phenyl-1H-methyl) methyl ester. pyrazol-4-yl) -imidazol-1-yl] -benzoic acid. ESI MS m / z 373 [C 22 H 20 N 4 O 2 + H] +. To 119 mg (0.32 mmol) of N- (3-amino-5-tert-butyl-2-methoxy-phenyl) -methane-sulfonamide in 4 ml of THF at -78 C was slowly added 0.42 ml of n-BuLi 1.6 M in hexanes (0.67 mmol). The cold bath was removed, the mixture was stirred for 30 min and 0.34 ml of LHMDS IN in THF (0.34 mmol) was added to the resulting purple solution. THF was added as necessary to facilitate agitation and the purple suspension was slowly transferred via syringe to a stirred solution of methyl 4-methyl-3- [4- (5-methyl-1-phenyl-1H-) methyl ester. pyrazol-4-yl) -imidazol-1-yl] -benzoic acid in 2 ml of THF at 0 ° C. After 20 min, cold MeOH was added and the solution was partitioned between? Partially saturated HC1 and EtOAc. The layer of EtOAc was then washed with brine. The washings were extracted once with EtOAc and the extracts were combined, dried with ? a2S04, filtered and concentrated. Chromatography (0-3.5% (MeOH with 5%? H40H) in CH2C12) gave Example 149. ESI MS m / z 613 [C33H36? 604S + H] +.

Example 150: N- (5- er-Butyl-3-methanesulfonylamino-2-ethoxy-phenyl) -3- [4- (l-isopropyl-5-methyl-lH-pyrazol-4-yl) r imidazole-1- il] -4-methyl-benzamide Example 150 was prepared from 2-tosyloxy-1- (5-methyl-1-isopropyl-1H-pyrazol-4-yl) -ethanone (Singh, SP et al, J. Indian Chem. Soc., 1997, 74, 940-942) in the same manner as Example 149. ESI MS m / z 579 [C30H38N6O4S + H] +.

Example 151: 3- [4- (5-Ethyl-l-phenyl-lff-pyrazol-4-yl) imidazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide To a solution at 0 ° C of 7.55 (37.7 mmol) of 5-ethyl-1-phenyl-1H-pyrazole-4-carbaldehyde (Example 86) in anhydrous TH'F (100 ml) under N2 was added, over 5 minutes, 15.7 (47.1 mmol) of MeMgBr 3.0 M in Et20. The mixture was warmed to room temperature and stirred for 16 hours, then 25 ml of 5% NH4C1 was added and the mixture was extracted with CH2C12 (70 ml) and the extract was washed with saturated NaCl (15 ml). The organic layer was separated, dried over MgSO4 and concentrated to yield 1- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -ethanol (7.91 g). ESI MS m / z 217 [C 13 H 16 N 20 + H] +. A solution of 7.9 g (36.5 mmol) of 1- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -ethanol in 100 ml of THF was stirred at RT in 24 g of activated MnO2 for 23 hours. The mixture was filtered through Celite and concentrated to yield 1- (5-ethyl-l-phenyl-lyr-pyrazol-4-yl) -ethanone (7.71 g). ESI MS m / z 215 [C? 3 H 14 N 20 + H] +. To a solution of 5.40 g (25.3 mmol) of 1- (5-ethyl-1-phenyl-1-pyrazol-4-yl) -ethanone in HOAc (30 ml) was added HBr in HOAc (30 ml). Bromine (1.42 mL, 27.7 mmol) was added dropwise and the mixture was stirred at RT for 45 minutes and poured into ice water (500 mL). The liquid was decanted and the remaining residue was washed with water, then dissolved in CH2C12 (500 ml) and washed with saturated NaHCO3, dried over MgSO4 and concentrated to yield 7.20 g of 2-bromo-1- (5- ethyl-l-phenyl-yl-pyrazol-4-yl) -ethanone. A solution of 7.20 g (24.6 mmol) of 2-bromo-1- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -ethanone and 8.52 g (51.6 mmol) of 3-methyl-3-methyl ester were heated. -amino-4-methylbenzoic acid in EtOH (30 ml) up to 75 ° C for 16 hours. The solution was cooled and allowed to stand at RT for 6 hours. The solids were extracted by. filtration and washed with cold EtOH to provide 3- [2- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -2-oxo-ethylamino] -4-methyl-benzoic acid methyl ester as a white powder (3.75g). ESI MS m / z 378 [C22H23N303 + H] +. A suspension of 3.75 g (9.94 mmol) of 3- [2- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -2-oxo-ethylamino] -4-methyl- methyl ester was stirred. benzoic acid and 2.9 g (30 mmol) of KSCN in 25 ml of HOAc at 100 ° C for 4 hours. The mixture was allowed to cool overnight before filtering and washing with cold MeOH. The solids were dried to provide 2.65 g of 3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -2-mercapto-imidazol-1-yl] -4-methyl acid methyl ester. -benzoic acid as an ivory solid. ESI MS m / z 419 [C23H22N402S + H] +. The above thioimidazole (2.65 g, 6.33 mmol) was suspended in 5 ml of HOAc and 0.63 ml of water and heated to 35 ° C. Hydrogen peroxide (2.36 g, 20.8 mmol) was added over 15 minutes. After heating at 40 ° C for 35 minutes, the mixture was cooled to 25 ° C and quenched with 10% Na 2 SO 3 (1 ml). After 15 min, concentrated NH40H (20 ml) was added and the resulting gummy orange solid was washed with water, then dissolved in EtOAc and washed with brine, dried over MgSO4, concentrated and chromatographed (10 to 80%). EtOAc in hexanes). The desired fractions were stirred in DCM with PS-TBD resin and carbon-dye, filtered through Celite and concentrated to yield 1.85 g of 3- [4- (5-ethyl-1-phenyl-1H) methyl ester. -pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid. ESI MS m / z 387 [C23H22N402 + H] +. To a solution of 70 mg (0.25 mmol) of N- [3-amino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -methanesulfonamide in 5 ml of low THF? 2 was added 1.04 ml of LHMDS (1.0 M). The mixture was stirred at RT for 15 minutes, at which time a solution of 3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid methyl ester ( 100 mg, 0.026 mmol) in 5 ml of THF (5 ml). After stirring for 45 minutes, 10 ml of saturated aHC03 was added. The mixture was extracted with CH2C12 (100 mL), dried with? A2S04, filtered, concentrated and chromatographed (30 to 100% EtOAc in hexanes) to yield Example 151 (69 mg). ESI MS m / z 625 [C34H36? 604S + H] +.

Example 152: N- (5-tert-Butyl-2-methyl-pyridin-3-yl) -3- [4- (5-ethyl-l-phenyl-lJ? -pyrazol-4-yl) -imidazole-1 -yl] -4-methyl-benzamide Example 152 was prepared from 5-tert-butyl-2-methyl-pyridin-3-alamine (see US Provisional Application 60 / 567,693) and 3- [4- (5-ethyl-1-ethyl) methyl ester. phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid (Example 151) in the same way as Example 151. ESI MS m / z 519 [C 32 H 34 N 60 + H] +.

Example 153: N- (5-tert-Butyl-2-methoxy-phenyl) -3- [4- (5-ethyl-l-phenyl-lff-pyrazol-4-yl) -imidazol-1-yl] -4 -methyl-benzamide Example 153 was prepared from 5-tert-butyl-2-methoxy-phenylamine and 3- [4- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -imidazole-1-methyl ester. -yl] -4-methyl-benzoic (Example 151) in the same way as Example 151. ESI MS m / z 534 [C33H35N502 + H] +.

Example 154: 3 - [4 - (5-Ethyl-l-l-pyrazol-4-yl) -imidazol-1-yl] -N- (2-methoxy-5-trif luoromethyl-f-enyl) -4 - methyl-benzamide Example 154 was prepared from 2-methoxy-5-trifluoromethyl-phenylamine and 3- [4- (5-ethyl-l-phenyl-lff-pyrazol-4-yl) -imidazol-1-yl methyl ester ] -4-methyl-benzoic acid (Example 151) in the same manner as Example 151. ESI MS m / z 546 [C3oH2eF3N502 + H] +.

Example 155: N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) 3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl ] -4-methyl-benzamide Example 155 was prepared from 3-amino-5-er-butyl-2-methoxy-benzonitrile and 3- [4- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) methyl ester -imidazol-1-yl] -4-methyl-benzoic acid (Example 151) in the same manner as Example 151. ESI MS m / z 559 [C34H34? 602 + H] +.

Example 156: N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] -4 -methyl-benzamide Example 156 was prepared from 5-er-butyl-2-methanesulfinyl-phenylamine and 3- [4- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -imidazole-1-methyl ester. -yl] -4-methyl-benzoic acid (Example 151) in the same manner as Example 151. ESI MS m / z 566 [C33H35N502S + H] +.

Example 157: N- (5-fcer-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazole-1- il] -4-methyl-benzamide Example 157 was prepared from N- (3-amino-5-tert-butyl-2-methyl-phenyl) -methanesulfonamide and 3- [4- (5-ethyl-1-phenyl-1H-) methyl ester pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid (Example 151) in the same way as Example 151. ESI MS m / z 611 [C34H38? 603S + H] +.

Example 158: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-phenyl-lff-pyrazol-4-yl) -imidazole-1- il] -4-methyl-benzamide Example 158 was prepared from N- (3-amino-5-tert-butyl-2-methoxy-phenyl) -methanesulfonamide and 3- [4- (5-ethyl-1-phenyl-1H-) methyl ester pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzoic acid (Example 151) in the same manner as Example 151. ESI MS m / z 611 [C34H38? 604S + H] +.

Example 159: 3- [4- (5-Ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] -N- (3-methanesulfonylamino-2-methoxy-5-trifluoromethyl-phenyl) -4-methyl-benzamide Example 159 was prepared from N- (3-amino-2-methoxy-5-trifluoromethyl-phenyl) -methanesulfonamide and 3- [4- (5-ethyl-1-phenyl-1-pyrazole-) methyl ester. 4-yl) -imidazol-1-yl] -4-methyl-benzoic acid (Example 151) in the same manner as Example 151. ESI MS m / z 639 [C31H29F3? ß04S + H] +.

Example 160: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-imidazol-1-yl) -benzamide? v '+ To a solution of 2-bromo-l-pyridin-3-yl-ethanone hydrobromide (Barlin, GB et al., Australian J. Chem, 1989, 1735) (500 mg, 1.78 mmol) in 2 ml of EtOH was added. 3-amino-4-methyl-benzoic acid methyl ester (Lancaster; 294 mg, 1.78 mmol) and NaHCO 3 (750 mg, 8.9 mmol), and the mixture was stirred for 2 hours. The mixture was then filtered and washed with MeOH, then the filtrate was concentrated to a small volume and dissolved in EtOAc. The EtOAc slurry was washed with water and brine, and the washings were extracted once more with EtOAc. The combined organic portions were dried with Na 2 SO 4, filtered, concentrated and chromatographed (0-5% MeOH in dichloromethane) to provide 84.5 mg of 4-methyl-3- (2-oxo-2-pyridine) methyl ester. 3-yl-ethylamino) -benzoic acid. A mixture of 4-methyl-3- (2-oxo-2-pyridin-3-yl-ethylamino) -benzoic acid methyl ester (84.5 mg) was heated; 0.297 mmol) and KSCN (58 mg, 0.59 mmol) in 1.5 mL of HOAc up to 100 ° C for 2 hours. The mixture was then poured into water and carefully brought to pH 8 with NaOH. The mixture was extracted immediately with EtOAc and the extract was washed with brine.

The washings were extracted once with EtOAc and the combined extracts were dried with Na 2 SO 4, filtered and concentrated to provide 3- (2-mercapto-4-pyridin-3-yl-imidazol-1-yl) - methyl ester - 4-methyl-benzoic acid (90 mg, 0.28 mmol, 93%). ESI MS m / z 326 [C 17 H 15 N 302 S + H] +. To a suspension of 85 mg (0.261 mmol) of 3- (2-mercapto-4-pyridin-3-yl-imidazol-1-yl) -4-methyl-benzoic acid methyl ester in 1.8 ml of water was added 0.68 ml of concentrated HN03 and 2 mg of NaN0. After 2 hours, the mixture was cooled to 0 ° C and 4N NaOH was added until a pH of about 10 was reached. The mixture was stirred for 30 min, then HOAc was added until the pH reached about 6. The resulting precipitate was filtered, washed with water and dried to provide 16 mg (0.057 mmol, 22%) of acid-methyl-3- (4-pyridin-3-yl-imidazol-1-yl) -benzoic acid. 4-Methyl-3- (4-pyridin-3-yl-imidazol-1-yl) -benzoic acid (15 mg, 0.054 mmol), N- (3-amino-5-butyl-2-methoxy) were dissolved. phenyl) -methane-sulfonamide (29 mg, 0.11) and HATU (49 mg, 0.11 mmol) in 1 ml of DMF, and the mixture was cooled to 0 ° C. Then diisopropylethylamine (19 μL, 0.11 mmol) was added, the cold bath was removed and the mixture was stirred overnight. The mixture was then poured into water and extracted with EtOAc. The organic portion was washed with NaHCO 3 and brine, and the washings were extracted once with EtOAc. The extracts were combined, dried with Na 2 SO 4, filtered and concentrated. Chromatography (0-6.5% MeOH / 0.5% NH4OH in CH2C12) afforded 23 mg (0.043 mmol, 80%) of Example 160. ESI MS m / z 534 [C28H31Ns04S + H] +.

Example 161: N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-morpholin-4-yl-ethyl) -pyridin-3-yl] -1,2, 3-triazol-1-yl} -benzamide Example 1 (500 mg, 0.88 mmol), Ph3As (27 mg, 0.088 mmol) and CsF (295 mg, 1.93 mmol) were combined in NMP (2.5 ml) and degassed by the freeze-thaw method. 2,6-Di-butyl-4-methylphenol (few crystals), Pd2 (dba) 3 (20 mg, 0.022 mmol) and tributylvinyl tin (310 μL, 1.06 mmol) were added and the reaction was heated to 70 ° C during the night. Additional Ph3As (27 mg, 0.088 mmol) and Pd2 (dba) 3 (20 mg, 0.022 mmol) were added and the reaction was heated at 70 ° C overnight. Water and EtOAc were added and the layers separated. The organic layer was dried over sodium sulfate, filtered and evaporated. The product, N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-vinyl-pyridin-3-yl) -1,2, 3- triazol-1-yl] -benzamide was used without purification in the next step. ESI MS m / z 561 [C29H32? 604S + H] +. The impure vinylpyridine (300 mg) above was dissolved in EtOH (5 ml). Morpholine (120 microL) and HOAc (3 drops) were added and the mixture was heated in a sealed tube at 50 ° C overnight. The reaction was evaporated and chromatographed (3% ammonium hydroxide, 10% MeOH, 20% chloroform, 67% EtOAc) and the product containing the fractions was evaporated. The residue was further purified by semi-preparative HPLC to provide Example 161 (21 mg). ESI MS m / z 648 [C33H41? 705S + H] +.

Example 162: N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-methylamino-ethyl) "- pyridin-3-yl] - [1,2,3] triazol-1-yl}. -benzamide Example 162 was prepared from N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-vinyl-pyridin-3-yl) -1 , 2, 3-triazol-1-yl] -benzamide (Example 151) and methylamine in the same manner as Example 151. ESI MS m / z 592 [C 30 H 37 N 7 O 4 S + H] +.

Example 163: N- (5-tert-Butyl-3-m.etansu.lf onylamino-2-methoxy-phenyl) -3-. { 4- [6- (2-dimethylamino-ethyl) -pyridin-3-yl] - [1,2,3] triazole-1-yl} -4-methyl-benzamide Example 163 was prepared from N- (5- tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-vinyl-pyridin-3-yl) -1 , 2, 3-triazol-1-yl] -benzamide (Example 151) and dimethylamine in the same manner as Example 151. ESI MS m / z 606 [C31H39? 704S + H] +.

METHODS OF USE In accordance with the invention, new methods are provided for using the compounds of the formula (I). The compounds described herein effectively block the production of inflammatory cytokines from cells. Inhibition of cytokine production is an attractive means to prevent and treat a variety of cytokine-mediated diseases or conditions associated with excessive production of cytokines, for example, diseases and pathological conditions involving inflammation. Therefore, the compounds are useful for the treatment of the diseases and conditions described in the Background section, including the following conditions and diseases: osteoarthritis, atherosclerosis, contact dermatitis, bone resorption diseases, injury by, asthma, multiple sclerosis , Guillain-Barre syndrome, Crohn's disease, ulcerative colitis, psoriasis, graft-versus-host disease, systemic lupus erythematosus and insulin-dependent diabetes mellitus, rheumatoid arthritis, toxic shock syndrome, Alzheimer's disease, diabetes, inflammatory bowel diseases, pain acute and chronic symptoms as well as symptoms of inflammation and cardiovascular disease, strokes, myocardial infarction, alone or after thrombolytic therapy, thermal injury, acute adult respiratory syndrome (ARDS), multiple organ damage secondary to trauma, acute glomerulonephritis, dermatosis with Acute inflammatory components, meningitis p acute urinary tract or other disorders of the central nervous system, syndromes associated with hemodialysis, leukapheresis, syndromes associated with the transfusion of granulocytes and necrotizing gout, complications that include restenosis after percutaneous transluminal coronary angioplasty, traumatic arthritis, sepsis, chronic obstructive pulmonary disease and insufficiency congestive heart The compounds of the invention may also be useful for anticoagulant or fibrinolytic therapy (and diseases or conditions related to such therapy), such as described in provisional application No. 60 / 403,422. The compounds of the invention are also inhibitors of p38 MAP kinase. The activity can be demonstrated using methods known in the art. See, for example, Branger et al, (2002) J "Immunol. 168: 4070-4077 As described in the Background of the Invention, the compounds of the invention will therefore be useful for treating, in addition to diseases Inflammatory, oncological diseases These diseases include, but are not limited to, solid tumors, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, Parathyroid glands and their distant metastases These disorders also include lymphomas, sarcomas and leukemias Examples of breast cancer include, but are not limited to, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ and lobular carcinoma in situ. Examples of cancers of the respiratory tract include, but are not limited to, small and small cell lung carcinoma, as well as bronchial adenoma. l and mesothelioma and pleuropulmonary biastoma. Examples of brain cancers include, but are not limited to, brainstem, optic and hypothalamic glioma, cerebellar and cerebral astrocytoma, medulloblastoma, ependymoma, as well as pituitary, neuroectodermal and pineal tumors. Examples of tumors of the peripheral nervous system include, but are not limited to, neuroblastoma, ganglioneuroblastoma, and peripheral nerve sheath tumors. Examples of endocrine and exocrine system tumors include, but are not limited to, thyroid carcinoma, adrenocortical carcinoma, pheochromocytoma, and carcinoid tumors. Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer. Tumors of female reproductive organs include, although not limited to, endometrial, cervical, ovarian, vaginal and vulvar cancer, as well as sarcoma of the uterus. Digestive tract tumors include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small bowel, and salivary gland cancers.

Tumors of the urinary tract include, but are not limited to, cancers of the bladder, penis, kidney, renal pelvis, ureter, and urethra. Ocular cancers include, but are not limited to, intraocular melanoma and retinoblastoma. Examples of liver cancer include, but are not limited to, hepatocellular carcinoma (hepatic cell carcinomas with or without a fibrolamellar variant), hepatoblastoma, cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma. Skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer and non-melanoma skin cancer. Cancers of the neck and head include, but are not limited to, laryngeal / hypopharyngeal / nasopharyngeal / oropharyngeal cancer and oral or labial cancer. Lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, cutaneous T-cell lymphoma, and lymphoma of the central nervous system. Sarcomas include, but are not limited to, soft tissue sarcoma, osteosarcoma, Ewings' sarcoma, malignant fibrous histiocytoma, lymphosarcoma, angiosarcoma, and rhabdomyosarcoma. Leukemias include, but are not limited to, acute myeloma leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. Plasma cell dyscrasias include, but are not limited to, multiple myeloma and Waldenstrom's macroglobulinemia. These disorders have been characterized in humans, but they also exist with a similar etiology in other mammals and can be treated with the pharmaceutical compositions of the present invention. For therapeutic use, the compounds may be administered in any conventional dosage form, in any conventional manner. Administration routes include, but are not limited to, intravenous, intramuscular, subcutaneous, intrasynovial, infusion, sublingual, transdermal, oral, topical, or inhalation. The preferred modes of administration are oral and intravenous. The compounds can be administered alone or in combination with adjuvants that improve the stability of the inhibitors, facilitate the administration of pharmaceutical compositions containing them in certain embodiments, provide increased solution or dispersion, increase the inhibitory activity, provide adjuvant therapy and the like, including other active ingredients. Advantageously, said combination therapies use lower doses of conventional therapeutic agents, thus avoiding possible toxicity and adverse side effects incurred when those agents are used as monotherapies. The compounds described above can be physically combined with conventional therapeutic agents or other adjuvants in a single pharmaceutical composition. In this regard, reference may be made to Cappola et al: US patent application No. 09 / 902,822, PCT / US 01/21860 and United States patent application No. 10 / 214,782, each incorporated herein by reference in its whole. Advantageously, the compounds can then be administered together in a single dosage form. In some embodiments, the pharmaceutical compositions comprising said combinations of compounds contain at least about 5%, but more preferably at least about 20%, of a compound of the formula (I) (w / w) or one of their combinations . The optimum percentage (w / w) of a compound of the invention may vary and is within the purview of those skilled in the art. Alternatively, the compounds can be administered separately (either serially or in parallel). The separate doses allow greater flexibility in the dosage regimen. As previously mentioned, the dosage forms of the compounds described herein include pharmaceutically acceptable carriers and adjuvants known to those of ordinary skill in the art. These vehicles and adjuvants include, for example, ion exchangers, alumina, aluminum stearate, lecithin, whey proteins, buffering substances, water, salts or electrolytes and cellulose-based substances. Preferred dosage forms include tablets, capsules, caplets, liquids, solutions, suspensions, emulsions, lozenges, syrups, reconstitutable powders, granules, suppositories and transdermal patches. Methods for preparing such dosage forms are known (see, for example, H.C. Ansel and N.G. Popovish, Pharmaceutical Dosage Forms and Drug Delivery Systems, 5th ed., Lea and Febiger (1990)). Levels and dose adjustments are recognized in the art and can be selected by those of ordinary skill in the art from the available methods and techniques suitable for a particular patient. In some embodiments, the dose levels are in the range of approximately 1-1000 mg / dose for a 70 kg patient. While a daily dose may be sufficient, up to 5 daily doses may be given. For oral doses, up to 2000 mg / day may be required. In this regard, reference can also be made to US provisional application No. 60 / 339,249. As the person skilled in the art will appreciate, lower or higher doses may be required, depending on the particular factors, for example, the specific dosage and treatment regimens will depend on factors such as the general health profile of the patient, the severity and the course of the patient's disorder or disposition, and the criteria of the treating physician.

BIOLOGICAL TESTS Inhibition of TNF production in THP cells The inhibition of cytokine production can be observed by measuring the inhibition of TNFa in THP cells stimulated by lipolisaccharides (for example, see W. Prichett et al., 1995, J. Inflammation, 45, 97). All cells and reagents were diluted in RPMl 1640 with phenol red and L-glutamine, enriched with additional L-glutamine (total: 4 mM), penicillin and streptomycin (50 units / ml each) and fetal bovine serum (FBS, 3 %) (GIBCO, all final conc.) The test was carried out under sterile conditions; only the test compound was not sterile. Initial stocks were prepared in DMSO followed by dilution in RPMl 1640 2 times higher than the final test concentration. Confluent THP.l cells (2xlOe cells / ml, final conc, American Type Culture Company, Rockville, MD) were added to polypropylene culture plates with 96 round bottom wells (Costar 3790, sterile) containing 125 μl of the compound of 'test (concentrated 2 times) or DMSO vehicle (controls, targets). The concentration of DMSO did not exceed 0.2% final. The cell mixture was preincubated for 30 min, 37 ° C, 5% C02 before stimulation with lipolisaccharide (LPS, 1 μg / ml final, Follow L-2630, serotype E. coli 0111.B4, stored as 1 mg / ml of stock in distilled H20 analyzed for endotoxin at -80 ° C). Whites (not stimulated) received H20 vehicle; the final incubation volume was 250 μl. Incubation overnight (18-24 hours) proceeded as previously described. The assay ended by centrifuging the plates for 5 min, at room temperature, 1600 rpm (400 x g); the supernatants were transferred to clean 96-well plates and stored at -80 ° C until the human FNTa was analyzed by a commercially available ELISA kit (Biosource # KHC3015, Camarillo, CA). Data were analyzed by non-linear regression (Hill's equation) to generate a dose-response curve, using the SAS software system (SAS institute, Inc., Cary, NC). The IC50 value calculated is the concentration of the test compound that caused a 50% decrease in the maximum production of TNFa. Preferred compounds have an IC50 < 1 uM in this essay.

Inhibition of other cytokines By similar methods, using monocytic peripheral blood cells, appropriate stimuli and commercially available ELISA kits (or other detection method, such as radioimmunoassay), for a particular cytokine, inhibition of IL-lbeta can be demonstrated, - GM-CSF, IL-6 and IL-8 for the preferred compounds (for example, see JC Lee et al, 1988, Int. J. I munopharmacol., 10, 835). All references described in this application, including patents, patent publications and literature citations, are hereby incorporated by reference in their entirety.

Claims (20)

1. CLAIMS 1. Compound of the formula (I)
2. (I); characterized in that: Ar1 is selected from (i), (ii) and (iii) continuation: (i) a carbocycle substituted with R1, R2 and Rx, (ii) in which one of E or F is nitrogen and the other is carbon, R1 is covalently bound either to E or F and, when nitrogen is N-R1, the double bond between E and F is not present; (iii) wherein c is a benzo ring fused to ring d which is a 5-7 membered heterocyclic ring optionally substituted with an oxo group (= 0) and one to two R groups, each independently being H or allyl Cl -3; R1 is selected from hydrogen, N02, -N (RC) 2, JC (O) -N (RC) -, JS (0) mN (Rc) -, alkyl Cl-6 S (0) m-, or R1 is select between "Cl-6 alkoyl, C3-7 cycloalkyl, Cl-5 alkoxy or C3-7 cycloalkoxy, Cloth 5-alkylthiol or C3-7 cycloalkyl thiol, Cl-5 acyl, Cl-5 alkoxycarbonyl, Cl-5 acyloxy, Cl-acylamino -5, C2-5 alkenyl, C2-5 alkynyl, heterocycle, heterocycloalkyl Cl-6, heteroaryl, heteroarylalkyl Cl-6 and nitrile, each of the aforementioned, when possible, is optionally partially or fully halogenated or optionally substituted in addition with alkylsulfonylamino, aminocarboxyl, alkoxy, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile, R2 is selected from: hydrogen, halogen, nitrile, alkyl Cl-5 S (0) m-, aryl S (0) m , J-0-C (0) -0-, N (R °) 2-C (0) - (CH2) n-, acetyl Ci-6, aroyl, alkoxycarbonyl Cl-6, alkyl Cl-6, cycloalkyl C3 -7, Cl-6 alkoxy, C3-5 cycloalkoxy, Cl-5 alkoxy Cl-5 alkyl, hydroxy, Cl-5 hydroxyalkyl and optional amino mono- or di-substituted with Cl-5 alkyl, aryl or arylalkyl Cl-5; each of those already mentioned, when possible, is optionally partially or fully halogenated or optionally also substituted with Cl-3 alkyl, alkylsulfonylamino, alkoxy, amino, alkylamino, dialkylamino, hydroxyl, oxo, nitro or nitrile; each Rx is selected from C1-6 alkyl or C3-7 cycloalkyl, each being optionally substituted with Cl-3 and optionally partially or fully halogenated alkyl, Cl-4 acyl, aroyl, Cl-4 alkoxy, Cl-5 S alkyl ( 0) m-, wherein each may optionally be partially or totally halogenated, 'halogen, alkoxycarbonyl Cl-6, carbocyclosulfonyl'; each Rc is independently hydrogen or Cl-5 alkyl; of the formula (I) are each independently selected from N or CH, in which the hydrogen atom is optionally replaced with R6; Het is a heteroaryl or heterocyclic ring, in which Het is optionally substituted with one to three R5; m is 0, 1 or 2; J is selected from alkyl Cl-10 and cycloalkyl C3-7, each optionally substituted with Rb; R3, R4, R6, R7 and R8 are each independently selected from hydrogen, halogen, Cl-5 alkyl, Cl-5 alkoxy, Cl-5 Cl-5 alkoxy alkyl, hydroxy, Cl-5 hydroxyalkyl or optionally mono or di -substituted with Cl-5 alkyl, aryl or arylalkyl Cl-5; R5 is: Ra, -0-Ra, -S (0) m-Ra, -N (Ra) 2, -C (0) -Ra, -NH (CR7R8) n-Ra, N (Ra) 2- ( CH2) x2- (CR7R8) n-Ra, -0 (CR7R8) n-Ra, -C (O) -0 (CR7R8) n-Ra, -C (O) (CR7R8) n-Ra, -C (0) C (0) Ra, -C (0) C (0) ORa, -C (0) NHRa or -C (0) NH (CR7R8) n-, each optionally substituted with Cl-3 alkyl, halogen or hydroxy, wherein n is 1-5; or R5 is aryl, heteroaryl or heterocyclyl, each optionally substituted with R; Ra and Rb are each independently selected from hydrogen, Cl-6 alkyl, Cl-5 hydroxyalkyl, 0.1-5 alkenyl, C2-5 alkynyl, carbocycle, carbocycloalkyl CO-2, aryl, heterocycle, heteroaryl, Cl-5 alkoxy, alkylthio Cl-5, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5, diarylamino, acyl Cl-5, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, each of the already mentioned is optionally partially or totally halogenated, or Ra and Rb are selected from alkylsulfonylamino Cl-5, hydroxy, oxo, halogen, CF3, -CH2-CF3, nitro and nitrile, in each carbocycle, heterocycle or heteroaryl for Ra and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy; and X is O or S or its pharmaceutically acceptable salts. 2. Compound according to claim 1, of the formula (I) is selected from:
3. Het is J is selected from alkyl Cl-10, aryl and C3-7 cycloalkyl, each optionally substituted with Rb; R2 is independently selected from hydrogen, J-0-C (0) -0-, Cl-6 alkoxy, Cl-6 alkyl, Cl-6 acetyl, aroyl, halogen, methoxycarbonyl, phenylsulfonyl, Cl-5 S alkyl (0) m- and C3-7 cycloalkyl optionally substituted with Cl-3 alkyl, wherein each R2, where possible, may optionally be partially or fully halogenated; R1 is selected from H, alkyl Cl-6, alkyl Cl-5 S (0) m-, JS (0) mN (Rc) -, alkoxy Cl-5, alkyl thiol Cl-5, NH2-C (O) - ( CH2) n-, (RC) 2N alkyl Cl-6, acyl Cl-5 NH-, -NH2, -N02, heteroaryl selected from pyrazole, triazole, imidazole and tetrazole, and nitrile; ring d is a 5-6 membered heterocyclic ring, so that rings c and d are condensed to form the following: wherein each R. is independently H or Cl-3 alkyl;
4. R3 and R4 are each independently selected from hydrogen, Cl-3 alkoxy, Cl-3 alkyl and halogen; n is 1-4; Ra and Rb are each independently selected from hydrogen, Cl-6 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-8 cycloalkyl, alkyl CO-2, aryl, Cl-5 alkoxy, Cl-5 alkylthio, amino, alkylamino Cl-5, dialkylamino Cl-5, arylamino, acyl Cl-5, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, arylalkylamino Cl-5, alkylsulfonylamino Cl-5, hydroxy, halogen, -CF3, -CH2 -CF3 nitro, nitrile, or Ra and Rb are selected from; heterocycle selected from pyrrolidinyl, pyrrolinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, dioxalanyl, piperidinyl, piperazinyl, homopiperazinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxanyl , piperidinonyl, tetrahydropyrimidonyl, aziridinyl, pentamethylene sulfide, pentamethylene sulphoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide and tetramethylene sulfone and heteroaryl is selected from thienyl, furanyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl , pyrazolyl, pyrrolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyranyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, quinolinyl, quinazolinyl, naphthyridinyl, indazolyl, triazolyl, pyrazolo [3,4-b] pyrimidinyl, purinyl, pyrrolo [2, 3-b] pyridinyl, pyrazolo [3, 4-b] pyridinyl , tubercidinyl, oxazo [4,5-b] pyridinyl and imidazo [4, 5-b] pyridinyl; in the examples, each aryl, heterocycle or heteroaryl for Ra and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy; and X is O. 3. Compound according to claim 2 and wherein Ar1 is selected from (i) and (ii); R5 is: a) Ra, -0-Ra, -S (0) m-Ra, -N (Ra) 2, N (Ra) 2- (CH2) X-2-, -NH (CR7R8) n-Ra , - (CR7R8) n-Ra or -0 (CR7R8) n-Ra; or R5 is: b) -C (0) -Ra, -C (O) -O (CR7R8) n-Ra, -C (0) (CR7R8) n-Ra, -C (0) NHRa, -C ( O) NH (CR7R8) n-, -C (0) C (0) R or -C (O) C (O) 0Ra; each of the aforementioned R5 is optionally substituted with Cl-3 alkyl, halogen or hydroxyl, and wherein n is 1-3. 4. Compound according to claim 3, wherein Ar1 is: or Ar1 is cyclobutyl, phenyl, naphthyl, tetrahydronaphthyl, indanyl or indenyl, each substituted with a group R1, Rx and R2; R1 is nitrile, N02, NH2, acyl Cl-3 NH-, J-S (0) m-N (Rc) -, wherein J is Cl-10 alkyl, or R1 is
5. - ^; R 2 is independently selected from C 1-6 alkyl, C 1-6 alkyl (0) m-, C 1-6 alkoxy and C 3-6 cycloalkyl optionally substituted with C 1-3 alkyl, each of which may be optionally partially or fully halogenated; R3 and R4 are each independently selected from hydrogen, Cl-3 alkyl, fluoro and chloro; R6 is selected from hydrogen and amino; n is 1-2; Ra and Rb are each independently selected from hydrogen, Cl-6 alkyl, C3-7 cycloalkyl, CO-2 alkyl, aryl, Cl-5 alkoxy, amino, Cl-5 alkylamino, dialkylamino Cl-5, arylamino, arylalkylamino Cl-5. , acyl Cl-3, alkoxycarbonyl Cl-5, acyloxy Cl-5, acylamino Cl-5, sulfonylamino Cl-5, hydroxy, halogen, -CF3, -CH2-CF3 nitro, nitrile; or Ra is selected from pyrrolidinyl, pyrrolinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulphone, piperidinyl, piperazinyl, homopiperazinyl, piperidinonyl, tetrahydropyrimidonyl, aziridinyl, isoxazolyl, oxazolyl, thiazolyl, thiadiazolyl, tetrazolyl, pyrazolyl, pyrrolyl, imidazolyl, pyridinyl. , pyrimidinyl, pyrazinyl and pyridazinyl; wherein each aryl, heterocycle or heteroaryl for R and Rb is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy. 5. Compound according to claim 4 and characterized in that
6. J-S (0) 2-NH-, wherein J is alkyl Cl-5, or R1 is nitrile, N02, NH2 or acyl Cl-3 NH-; wherein Rx = R2 each independently selected from alkyl Cl-5, alejuyl Cl-5 S (0) m-, alkoxy Cl-4 and cycloalkyl C3-5 optionally substituted with alkyl Cl-2, each of which can be optionally partially or totally halogenated; R8 is hydrogen, methyl, ethyl, CH20H and CH20CH3. 6. Compound according to claim 5 and characterized in that Ra is selected from hydrogen, Cl-6 alkyl, C3-6 cycloalkyl, CO-2 alkyl, phenyl, Cl-5 alkoxy, amino, Cl-5 alkylamino, dialkylamino Cl-5. arylamino, aralkylamino Cl-5 acyl Cl-3, Cl-5 alkoxycarbonyl, Cl-5 acyloxy, acylamino Cl-5, hydroxy, halogen, -CF3, -CH2-CF3; or Ra is chosen from morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, sulfone thiomorpholinyl, piperazinyl, homopiperazinyl, pyrrolidinyl, piperidinyl, piperidinonyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl, wherein ejue each phenyl, heterocycle or heteroaryl for Ra is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy. 7. Compound according to claim 6 and characterized in that R is selected from hydrogen, alkyl
7. Cl-6, C3-6 cycloalkyl, phenyl, Cl-5 alkoxycarbonyl Cl-5, amino, Cl-5, 5-Cl dialkylamino, arylamino, arylalkylamino Cl-5 acyloxy Cl-5 acylamino Cl-5, hydroxy, halogen, -CF3, -CH2-CF3; or Ra is chosen from morpholinyl, piperidinilpiperazinilo, homopiperazinyl, pyrrolidinyl and pyridinyl wherein each phenyl, heterocycle or heteroaryl for R is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxy.
8. 8. Compound according to claim 7 and characterized in that & t • X-B of the formula (I) is selected from: Het is Ar is R5 is: Cl-5 alkyl, C3-6 cycloalkyl, N (Ra) 2 (CH2) X-2-, halogen, Cl-3 alkoxy, hydroxy, -N (Ra) 2, -CF3, -CH2-CF3, aryl, -S (0) m-Ra, -NH (CR7R8) "- Ra or - (CR7R8) nN (R) 2 each optionally substituted with Cl-3 alkyl, halogen or hydroxy, or R5 is -C (0) Ra, -C (0) C (0) Ra , -C (0) NHRa; Ra is selected from hydrogen, morpholinyl, piperidinyl, pipera2Ínilo, pyrrolidinyl, pyridinyl, mono- or dialkylamino Cx_5, arylamino, C3-6 cycloalkyl, Cl-5 alkyl and Cl-3 alkoxy, wherein each phenyl or heterocycle for Ra is optionally substituted with amino, Cl-3 alkyl, halogen or hydroxyl.
9. 9. Compound according to any of claims 1-8 and characterized in that
10. 10. Compound selected from Benzyl [2- (4- { L- [5- (5- tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] -1H-1, 2, 3-triazol-4-yl.} -2-phenyl-2'-pyrazol-3-yl) -ethyl] -carbamic 3- [4- (l-Benzyl-2-ethyl-lH-imidazole-4- il) -1,2,3-triazol-1-yl] -N- (5-er-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (1 -Cyclopropyl-5-ethyl-lH-pyrazol-4-yl) -.1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) phenyl] -4-methyl-benzamide 3- [4- (1-Isopropyl-5-methyl-lH-pyrazol-4-yl) -1,2,3-triazol-1-yl] -N- [3- methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (l-tert-Butyl-5-methyl-lH-pyrazol-4-yl) -1 , 2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-Acetyl -3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl -benzamide 3- [4- (2-Benzenesulfonyl-3 ~ methyl-3i? -imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (2-Benzoyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5-er-butyl-3-methanesulfonylamino-2) -methoxyphenyl) -4-methyl-benzamide 3- [4- (2-Benzoyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3- methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-Benzyl-3-methyl-3.fi-imidazol-4-yl) -1, 2,3-tria2ol-l-yl] -N- (5-er-butyl-3-methanesulfonylamino-2-methoxyphenyl) -4-methyl-benzamide 3- [4- (2-Benzyloxymethyl-3-methyl-3H -imidazol-4-yl) - [1,2, 3] triazol-1-yl] -N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [ 4- (2-Cyclobutyl-3-methyl-3H-imidazol-4-yl) -1,2,3-tria2? II-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl) -cyclopropyl) -phenyl] - -methyl-benzamide 3- [4- (2-Cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [ 3-methanesulfonylamins-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-Cyclopropyl-3-methyl-3H-imidazol-4-yl) -1 , 2,3-triazol-1-yl] -N- [5- (2-hydroxy-l, 1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-benzamide 3- [ 4- (2-Isopropyl-3-methyl-3-fimidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1 -methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-tert-Butyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl ] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) il) -phenyl] -4-methyl-benzamide 3- [4- (3-Benzyl-2-ethyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- ( 5- er-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-er-Butyl-2-cyclopropyl-3-fimidazol-4-yl) - 1,2,3-triazol-1-yl] -N- (5-er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-tert-Butyl -2-methyl-3H-imidazol-4-yl) -1,2,3-tria2? Ll-il] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (3-tert-Butyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5-tert-butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-tert-Butyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -N - [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (5-Ethyl-l-phenyl-lH-pyrazol-4-yl) -1, 2, 3-tria2? L-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide. 3- [4- (5-Ethyl-1-phenyl-1H-pyrazol-4-yl) -imido-2-yl] -N- (2-methoxy-5-trifluoromethyl-phenyl) -4-methyl-benzamide 3 - [4- (5-Ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] • N- (3-methanesulfonylamino-2-methoxy-5-trifluoromethyl-phenyl) -4-methyl -benzamide 3- [4- (5-Ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] • N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (5-Ethyl-1-phenyl-1-pyrazol-4-yl) ) -imidazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (6-Amino-pyridine- 3-yl) -1, 2, 3-triazol-l-yl] -N- (5- tert -butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [1- (1-Benzyl-piperidin-4-yl) -5-methyl-1-phi-pyrazol-4-yl] -1,2,3-triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (1-Benzyloxy-cyclopropyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (2-Benzyloxy-1, 1-dimethyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -1-methyl-1-yl-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- tert -butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (Hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3-. { 4- [5- (2-Amino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -N- (5-tert-butyl-3-methansulfonylamino-2-methoxy-phenyl) -methyl-benzamide 4- (4-. {1 - [5- (5-tert -butyl) -butyl ester -butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] -1H-1, 2, 3-triazol-4-yl.} -2-cyclopropyl-2H-pyrazol-3-yl) -piperidine-1-carboxylic acid N- (5- tert-Butyl-2-methanesulfinyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3-yl-2-yl-4-yl) -1, 2 , 3-tria2? Ll-yl] -4-methyl-ben2amide N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3- [4- (5-ethyl-l-phenyl-l-pyrazol-4 -yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3 -triazol-l-yl] - -methyl-benzamide N- (5-tert-Butyl-2-methoxy-phenyl) -3- [4- (5-ethyl-l-phenyl-l-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-2-methyl-pyridin-3-yl) -3- [4- (5-ethyl-l- phenyl-lH-pyrazole -4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-2-methyl-pyridin-3-yl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} 4-methyl-benzamide N- (5- tert -Butyl-3- {[[(2-dimethylamino-ethyl) -methylamino] -methyl} -2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-l, 2,3-triazol-1-yl) -benzamide N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) -3- [4- (2 -cyclopropyl-3-methyl-3-fimidazol-4-yl) -1,2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-cyano-2 -methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl- 3-cyano-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- (4-furan-3-yl-1,2,3-triazol-1-yl) - 4-Methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- (4-pyridin-3-yl-1,2,3-triazol-1-yl) -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3,4-dimethyl-5- (-pyridin-3-yl-1,2,3-triazol-1-yl) -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- ((S) -2,2-dimethyl-1,3-dioxolan-4-yl) -1, 2 , 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-methyl-lü -pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - (1-cyclohexyl-5-methyl-1H-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -3- [4- (l-cyclohexyl-5-ethyl-l-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - (l-isopropyl-5-methyl-lü-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-er-butyl-5 -methyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] - -methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (l-cyclopropyl-5-isopropyl-li-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-ethyl-lH-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl- Benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-isopropyl-5-methyl-lH-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-pyridin-2-yl-1-pyrazole-4-) il) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl ~ 5-piperidin-4-yl-lH-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2) -methoxy-phenyl) -3- [4- (1, 5-dimethyl-l-pyrazole -4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- ( 1,2-diethyl-l-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy- phenyl) -3- [4- (1, 5-diisopropyl-1H-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl) -3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-ethyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-isopropyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazole- l -yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-tert-butyl-3-methyl-3H-imidazole- 4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2 -cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy) phenyl) -3- [4- (2-cyclopropyl-1-methyl-lH-imidazol-4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-isopropyl-3H- imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-dimethylamino-l-methyl-lH-imidazol-4-yl) -1,2, 3-triazol-l-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2) -methoxy-phenyl) -3- [4- (2-methanesulfonyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- ( 5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-methanesulfinyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazole-1- il] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-tert-butylsulfanyl-3-methyl-3H-imidazole-4- il) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-hydroxymethyl) -3-methyl-3ii-imidazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) ) -3- [4- (2-formyl-3-me til-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (2-Cyclobutyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3) -metanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-dimethylamino-3-methyl-3-yl-imidazol-4-yl) - [1,2,3] triazol-1-yl] -4-methyl -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-diethyl-3H-imidazol-4-yl) -1,2,3-triazole -1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-dihydro-imidazo [2, lb] thiazole] -5-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- ( 3-cyclopropyl-2-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2- methoxy-phenyl) -3- [4- (3-isopropyl-2-methyl-1-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5 -ter-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- ( 3-cyclopropyl-2-isopropyl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-tert-butyl-2 -methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 3- [4- (3-ethyl-2-phenyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-methoxy-pyridin-3-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5 - er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1-pyrazol-4-yl) -1, 2, 3-triazol-1-yl ] -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-pyridin-2-yl-lH-pyrazole-4 -yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5- ethyl-l-isopropyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy- phenyl) - 3- [4- (5-cyclopropyl-1-isopropyl-1-pyrazol-4-yl) -1, 2, 3-triazo l-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-isopropyl-1-phenyl-1-pyrazole- 4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5 -cyclopropyl-l-phenyl-l, -pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy) -phenyl) -3- [4- (5-ethyl-l-phenyl-lff-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5,5-dimethyl-6,7-dihydro-5H-pyrrolo [1,2- a] imidazol-3-yl) - [1,2,3 ] triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-chloro-pyridin-3-yl) - 1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-methoxy-pyridine- 3-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6 -dimethylamino-pyridin-3-yl) -1,2, 3-triazol-l-yl] - -methyl-be Nzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-cyclopropylamino-pyridin-3-yl) -1,2,3-triazole-1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (7,7-dimethyl-6,7-dihydro-5H-pyrrolo [1] 2-a] imidazol-3-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 -. { 4- [1- (4-methoxy-phenyl) -5-methyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-fluoro-phenyl) -5-methyl-lH-pyrazol-4-yl] -1, 2,3-triazol-1-yl} -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (l-tert-Butyl-piperidin-4-yl) -5-methyl-li? -pyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2-cyclopropyl-3- (2,2,2-trifluoro-ethyl) -3-ylamino-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (hydroxy-phenyl-methyl) -3-methyl-3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2 ~ (2, 2-dimethyl-propionyl) -3-methyl-3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} - Methyl-benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-2, 2-dimethyl-propyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-1-methyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2-hydroxy-1, 1-dimethyl-ethyl) -3-methyl-3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-cyclopropyl) -3-methyl-3-fluoro-4-yl] -1,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-ethyl) -3-methyl-3H-imidazol-4-yl] -1, 2,3-triazol-l-il} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (cyclopropyl-hydroxy-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [5- (2-dimethylamino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (2-dimethylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (2-dimethylamino-ethylamino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -5-methoxy-pyridin-3-yl] -1,2,3-triazol-1-yl} 4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-fluoro-4-methyl-5 ~ (4-pyridin-3-yl-1, 2, 3 -triazol-l-yl) -benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-chloro-3- (4-pyridin-3-yl-2, 3-yl) triazol-l-yl) -benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-fluoro-3- (4-pyridin-3-yl-l, 2,3-triazole -l-yl) -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3-yl-imidazol-4-yl) - 1, 2, 3-triazol-l-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-1) , 2,3-triazol-1-yl) -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-methyl-pyridine-3 -yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6- morpholin-4-ylmethyl-pyridin-3-yl) -1, 2, 3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl -3- [4- (2-methyl-pyridin-3-yl) -1, 2, 3-triazole-l -yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-imidazol-1-yl) -2-benzamide N - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-methylamino-pyridin-3-yl) -1,2,3-triazole-1- il] -benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-thiazol-5-yl-l, 2,3-triazol-1-yl) ) -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyrimidin-5-yl-l, 2,3-triazol-1-yl) -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-trifluoromethyl-pyridin-3-yl) -1, 2,3-triazole -l-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (tetrahydro-furan-3-yl) -1, 2, 3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-phenyl-1H- pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (4-methyl-pyridin-3-yl) -1, 2, 3-triazole-l- il] -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenylsulfanyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-l phenyl-lff-pyrazol-4-yl) -imidazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5-methyl-l- (l-methyl-piperidin-4-yl) -l-pyrazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [2-methyl-3- (2, 2, 2-trifluoro-ethyl) -3F-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-l-pyridin-2-yl-lH-pyrazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (2-morpholine 4-yl-thiazol-5-yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl- 3-. { 4- [6- (2-methylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-morpholin-4-yl-ethyl) -pyridin-3-yl] -1, 2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) -pyrazol-1-yl ] -benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-pyridin-4-yl-3-yl-imidazole-4 -yl) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5- methyl-l-piperidin-4-yl-li-pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy- phenyl) -4-methyl-3- (4-pyridin-4-yl- [1,2,3] triazol-1-yl) -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy- phenyl) -4-methyl-3- (4-pyridin-2-yl- [1,2,3] tria-zol-1-yl) -benzamide N- (5- er ~ Butyl-3-methanesulfonylamino-2- methoxy-phenyl) -4-methyl-3- [4- (5,6,7,8-tetrahydro-imidazo [1,2- a] pyridin-3-yl) -1,2,3-triazole-1- il] -benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-m) ethoxy-phenyl) -4-methyl-3-. { 4- [5- (2-morpholin-4-yl-ethyl) -1-phenyl-l-pyrazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (l-phenyl-5-trifluoromethyl-l-pyrazol-4-yl) -1 , 2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (l-methyl-2-piperazine -l-yl-lH-imidazol-4-yl) -1, 2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4- methyl-3- [4- (3-methyl-2-piperazin-1-yl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5- ter- Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro-5H-pyrrolo [1, 2-a] imidazol-3-yl-5-cyclohexane )] - [1, 2, 3] triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-morpholin-4-yl-3H-imidazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6 , 7-dihydro-5Ji-pyrrolo [1, 2-a] imidazol-3-yl-5- (2'-methyl-cycloproane))] - [1, 2, 3] triazol-1-yl] -benzamide N - (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-methylsulfanyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] -l, 2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (2-methyl-propane-2-sulfonyl) -3JI-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2, 3 -triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (5-ethyl-1-phenyl-1-J? pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- [3-methanesulfonylamino-2-methoxy-5- (l-methyl-cyclopropyl) -phenyl] -3- [4- (5 -methoxy-pyridin-3-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl) ] -4-Methyl-3- [4- (5-methyl-1-phenyl-1H-pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- [3-methanesulfonylamino- 2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) ~ 3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide and N- [5- (2-Hydroxy-1,1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide or its pharmaceutically acceptable salts.
11. 11. Compound according to claim 10, characterized in that the compound is selected from 3- [4- (6-Amino-pyridin-3-yl) -1,2,3-triazol-1-yl] -N- ( 5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide N- (5-er-Butyl-2-methanesulfinyl-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1, 2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-2-methyl-pyridin-3-yl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} 4-methyl-benzamide N- (5-tert-Butyl-3. {[[(2-dimethylamino-ethyl) -methylamino] -methyl} -2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-l, 2,3-triazol-1-yl) -benzamide N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- (4-pyridin-3-yl-1,2,3-triazol-1-yl) - N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3,4-dimethyl-5- (4-pyridin-3-yl-1,2,3-triazol-1-yl) benzamide -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-methoxy-pyridin-3-yl) -1,2, 3-tria2? ll-il ] -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-chloro-pyridin-3-yl) -1,2, 3- triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-methoxy-pyridin-3-yl) -1 , 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6-dimethylamino-pyridine-3 -yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (6- cyclopropylamino-pyridin-3-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (2-dimethylamino-ethylamino) -pyridin-3-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (cyclopropylmethyl-amino) -5-methoxy-pyridin-3-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [6- (2-dimethylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -4-Methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-fluoro-4-methyl-5- (4-pyridin-3-yl-l, 2, 3 -triazol-l-yl) -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-chloro-3- (4-pyridin-3-yl-1, 2, 3- triazol-1-yl) -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-fluoro-3- (4-pyridin-3-yl-l, 2,3-triazole -1-yl) -benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-1,2,3-triazole- 1-yl) -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-methyl-pyridin-3-yl) -1, 2 , 3-triazol-l-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-morpholin-4-ylmethyl-pyridine -3-yl) -1, 2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- ( 2-methyl-pyridin-3-yl) -1, 2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3 - [4- (6-methylamino-pyridin-3-yl) -1, 2, 3-triazole-1- il] -benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyrimidin-5-yl-l, 2,3-triazol-1-yl) ) -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (6-trifluoromethyl-pyridin-3-yl) -1, 2, 3 triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (4-methyl-pyridin-3-yl) -1 , 2, 3-triazol-l-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-methylamino-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [6- (2-morpholin-4-yl-ethyl) -pyridin-3-yl] -1,2,3-triazol-1-yl} -benzamide and N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -3- [4- (5-methoxy-pyridin-3-yl) -1, 2, 3- triazol-1-yl] -4-methyl-benzamide. Compound according to claim 10, characterized in that the compound is selected from: 3- [4- (2-Benzoyl-3-methyl-3-yl-imidazol-4-yl) -1,2,3-tria2? Ll -yl] -N- (5- er-butyl-3-methansulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (2-Benzoyl-3-methyl-3-imidazole -4 ~ il) -1, 2,3- tria2? Ll-il] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-Cyclopropyl -3-methyl-3Ji-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2-Cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [5- (2- hydroxy-l, 1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4-methyl-benzamide 3- [4- (2-isopropyl-3-methyl-3-yl-imidazol-4-yl) - 1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (2- tert-Butyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) phenyl] -4-methyl-benzamide 3- [4- (3-Benzyl-2-ethyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5- er-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-Ethyl-2-phenyl-3H-imidazol-4-yl) -1, 2, 3 -triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclop ropil) -phenyl] -4-methyl-benzamide 3- [4- (3-tert-Butyl-2-cyclopropyl-3-fidane-4-yl) -1,2,3-triazol-1-yl] -N- (5- tert -butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (3-tert-Butyl-2-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3 - [4- (3 - er-Butyl-3-yl-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -N- (5-tert-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4 -methyl-benzamide 3- [4- (3-er-Butyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5 - (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3-. { 4- [2- (2-Benzyloxy-1, 1-dimethyl-ethyl) -3-methyl-3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (4-Benzyl-piperazin-1-yl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [2- (Hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 3- [4- (1,5-diisopropyl-lH-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-isopropyl-3-methyl-3H-imida-zol-4-yl) -1,2,3-triazol-1-yl] -4-methyl -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-tert-butyl-3-methyl-3H-imidazol-4-yl) -1, 2 , 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3 -imidazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - (2-Cyclopropyl-3-isopropyl-3-yl-imidazol-4-yl) -1,2,3-tria2? -l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -3- [4- (2-methanesulfonyl-3-methyl-3-yl-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5- er-Butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -3- [4- (2-methansulfinyl-3-methyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-diethyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl ] -4-Methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-cyclopropyl-2-methyl-3H-imida-2-l-4-yl ) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3- isopropyl-2-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy- phenyl) -3- [4- (3-cyclopropyl-2-isopropyl-3-fimidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5 - tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-tert-butyl-2-methyl-3H-imidazol-4-yl) -1,2,3-triazole-1 -yl] -4-methyl-benzaraide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-ethyl-2-phenyl-3H-imidazol-4-yl) ) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamin o-2-methoxy-phenyl) -3- [4- (7, 7-dimethyl-6,7-dihydro-5H-pyrrolo [1,2-a] imidazol-3-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5 - er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2-cyclopropyl-3- (2,2,2-trifluoro-ethyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2, 2-dimethyl-propionyl) -3-methyl-3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-2,2-dimethyl-propyl) -3-methyl-3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-1-methyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2-hydroxy-1, 1-dimethyl-ethyl) -3-methyl-3-fimidazol-4-yl] 1,2,3-triazol-1-yl} -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3H-imidazol-4-yl) -1 , 2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenylsulfanil -3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- . { 4- [2-methyl-3- (2, 2, 2-trifluoro-ethyl) ~ 3.fi-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-pyridin-4-yl-3H-imidazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5,6 , 7, 8-tetrahydro-imidazo [1,2-a] pyridin-3-yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2 -methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenyl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -benzamide N- ( 5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-piperazin-1-yl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro- 5H-pyrrolo [1, 2-a] imidazol-3-yl-5-cyclohexane)] - [1,2,3] triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3-ylamino-4-yl] -1,2, 3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-morpholin-4-yl-3H-imidazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6 , 7-dihydro-5-yl-pyrrolo [1,2- a] imidazol-3-yl-5- (2'-methyl-cycloproane))] - [1,2,3] triazol-1-yl] -benzamide N - (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-methylsulfanyl-3-ylamino-4-yl) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3ii ~ imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- [5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl] -3- [4- (2-tert-butylsulfanyl-3-methyl-3H-imidazol-4-yl] -1, 2 , 3-triazol-1-yl.} -4-methyl-benzamide N- [5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [3-methyl-2- (2-methyl-propane-2-sulfonyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -benzamide 3-. { 4- [2- (1-Benzyloxy-cyclopropyl) -3-methyl-3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -N- (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide N- [5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-cyclopropyl) -3-methyl-3-yl-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-Methyl-benzamide 3- [4- (2-benzyl-3-methyl-3J? -imidazol-4-yl) -1,2,3-triazol-1-yl] -? - (5-ter- butyl-3-methanesulfonylamino-methoxy-nyl) -4-methyl-benzamide N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-1-phenyl-ethyl) -3H-imidazol-4-yl] -1, 2, 3-triazol-1-yl} -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-hydroxymethyl) -3-methyl-3H-imidazol-4-yl] -1, 2, 3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2, 3 -triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5,5-dimethyl-6,7-dihydro) -5H-pyrrolo [1,2-a] imidazol-3-yl] - [1,2,3] -triazol-l-yl.} -4-methyl-benzamide N- (5-tert-Butyl-3) -cyano-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl- ben2amide N- (5-tert-Butyl-2-methanesulfinyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3-yl-imidazol-4-yl) -1,2,3-triazole-1- il] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- [5- (2-hydroxy-1,1-dimethyl-ethyl) -3-methanesulfonylamino-2-methoxy-phenyl] -4 -methyl-3- { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl] -1,2,3-triazol-1-yl}. -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- { 4- [2- (cyclopropyl-hydroxy-m) ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-Methyl-benzamide 3- [4- (2-acetyl-3-methyl-3-yl-imidazol-4-yl) -1,2,3-triazol-1-yl] -? - (5-tert-butyl- 3-methanesulfonylamino-2-methoxyphenyl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-formyl-3-methyl-3. fi-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide and N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-dihydro-imidazo [2, 1-b] thiazol-5-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide, 13. Compound in accordance with claim 10, characterized in that the compound is selected from: [2- (4-. {l- [5- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-benzyl ester] -methyl-phenyl] -1H-1,2,3-triazol-4-yl.} -2-phenyl-2H-pyrazol-3-yl) -ethyl] -carbamic 3- [4- (1-Cyclopropyl- 5-ethyl-lJFí-pyrazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] - 4-Methyl-benzamide 3- [4- (1-Isopropyl-5-methyl-l-pyrazol-4-yl) -1,2,3-triazol-1-yl] -N- [3-met] ansulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (l-tert-Butyl-5-methyl-lH-pyrazol-4-yl) -1 , 2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (5-Ethyl -l-phenyl-lH-pyrazol-4-yl) -1, 2, 3 ~ triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3-. { 4- [1- (1-Benzyl-piperidin-4-yl) -5-methyl-1-pyrazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- tert -butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3-. { 4- [5- (2-Amino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 4- (4-. {1 - [5- (5- tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl) -2-methyl-phenyl] -lH-l, 2,3-triazol-4-yl.} -2-cyclopropyl-2J? -pyrazol-3- il) -piperidine-1-carboxylic acid N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclohexyl-5-methyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclohexyl-5 -ethyl-l-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] • 4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 3- [4- (l-isopropyl-5-methyl-lH-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl-benzamide N- (5- tert -Butyl- 3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-isopropyl-5-methyl-lH-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-methyl-1-yl-pyrazol-4-yl) -1,2, 3 -triazol-l-il] -4-methyl-b N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-tert-butyl-5-methyl-lH-pyrazol-4-yl) -1-enzyme, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-isopropyl -líí-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-ethyl-l-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-pyridin-2-yl-lH-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4 -methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-piperidin-4-yl-lH-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1,5-dimethyl -lH-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-pheny1) -3- [4- (5-ethyl-l-phenyl-lH-pyrazol-4-yl) -1,2,3-triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-) methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-pyridin-2-yl-lH -pyrazol-4-yl) -1,2, 3-tria2? ll-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4 - (5-Ethyl-l-isopropyl-1H-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino- 2-methoxy-phenyl) -3- [4- (5-cyclopropyl-l-isopropyl-lH-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-isopropyl-l-phenyl-l-pyrazol-4-yl) -1,2,3-triazole-1 -yl] - 4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-cyclopropyl-1-phenyl-1H-pyrazol-4-yl ) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N ~ (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-fluoro-phenyl) -5-methyl-1-ylpyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-methoxy-phenyl) -5-methyl-lJ-pyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (l-tert-Butyl-piperidin-4-yl) -5-methyl-lH-pyrazol-4-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide N- (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [5- (2-dimethylamino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-phenyl-1H-pyrazole-4- il) -1, 2, 3-triazol-l-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5-methyl-1- (1-methyl-piperidin-4-yl) -l-pyrazol-4-yl] -1,2,3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-l-pyridin-2-yl-lH-pyrazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl ~ 3H-imidazol-4-yl) -pyrazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3 - [4- (5-methyl-1-piperidin-4-yl-l-pyrazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5- (2-morpholin-4-yl-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2, 3-triazol-1-yl} -benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (1-phenyl-5-trifluoromethyl-lH-pyrazol-4-yl) -1 , 2,3-triazol-1-yl] -benzamide and N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3- [4- (5- methyl-l-phenyl-l-pyrazol-4-yl) -1,2, 3-triazol-l-yl] -benzamide. 14. Compound according to claim 10, characterized in that the compound is selected from:? - (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-thiazole-5) -yl-1,2,3-triazol-1-yl) -benzamide and? - (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (2- morpholin-4-yl-thiazol-5-yl) -1,2,3-triazol-1-yl] -benzamide. 15. Compound according to claim 10, characterized in that the compound is selected from 3- [4- (2-Benzyl-3-methyl-3-imidazol-4-yl) -1,2,3-triazole- 1-yl] -N- (5- er-butyl-3-methanesulfonylamino-2-methoxyphenyl) -4-methyl-benzamide ^ 3- [4- (2-er-Butyl-3-methyl-3H-imidazole-4 -yl) -1,2,3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4 - (3-Ethyl-2-phenyl-3-yl-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (3-methanesulfonylamino-2-methoxy-5- (1-methyl- cyclopropyl) -phenyl] -4-methyl-benzamide 3- [4- (3-er-Butyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -N- (5- tert-butyl-3-methanesulfonyl-amino-2-methoxy-phenyl) -4-methyl-benzamido 3- [4- (3-tert-Butyl-3H-imidazol-4-yl) -1, 2, 3 -triazol-l-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3-. {4- [2- (Hydroxy) phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl}. -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl) -cyclopropyl) phenyl] -4-methyl-benzamide N ~ (5- tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1,5-diisopropyl-lH-pyrazol-4-yl) - 1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-isopropyl-3- methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (2-tert-Butyl-3-methyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl) -3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-methyl-3H-imidazol-4-yl) -1, 2, 3-triazol-1-yl] -4- methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-cyclopropyl-3-isopropyl-3-fimidazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2-methanesulfonyl-3-methyl- 3.fi-imidazol-4-yl) -1,2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (2-methansulfinyl-3-methyl-3-yl-imidazole-4 -yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2- er-Butylsulfanyl-3-methyl-3H-imidazol-4-yl) -1, 2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2- methoxy-phenyl) -3- [4- (2-hydroxymethyl-3-methyl-3-fimidazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (2,3-diethyl-3H-imidazol-4-yl) -1,2,3-triazole-1-yl ] -4-Methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-isopropyl-2-methyl-3H-imidazol-4-yl) - 1, 2, 3-triazol-1-yl] - - methyl - benzamide N - (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (3-ethyl-2-phenyl) -3H-imidazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (7,7-dimethyl-6,7-dihydro-5H-pyrrolo [1,2- a] imidazol-3-yl) -1,2,3-triazol-1-yl] -4-methyl- N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- benzamide. { 4- [2- (hydroxy-phenyl-methyl) -3-methyl-3H-imidazol-4-yl] -1, 2,3-triazol-l-il} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-2,2-dimethyl-propyl) -3-methyl-3-fimidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-1-methyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (2-hydroxy-1, 1-dimethyl-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-cyclopropyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (1-hydroxy-ethyl) -3-methyl-3H-imidazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [2- (cyclopropyl-hydroxy-methyl) -3-methyl-3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -4-methyl-benzamide N ~ (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenylsulfanyl-3H-imidazole-4- il) -1,2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [2-methyl-3- (2, 2, 2 ~ trifluoro-ethyl) -3H-imidazol-4-yl] -1,2, 3-triazol-1-yl} -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-3-fimidazol-4-yl) -pyrazol-1 -yl] -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (l-methyl-2-pyridin-4-yl-l.fi-imidazole-4-) il) -1,2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5,6 , 7, 8-tetrahydro-imidazo [1,2-a] pyridin-3-yl) -1, 2,3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2 -methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-phenyl-3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- ( 5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- [spiro (6,7-dihydro-5-pyrrolo [1,2-a] imidazol-3-yl] -5- (2'-methyl-cycloproane))] - [1,2,3] triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4 -methyl-3- [4- (3-methyl-2- (1-methyl-cyclopropyl) -3H-imidazol-4-yl) -1,2,3-triazol-1-yl] -benzamide N- (5 - tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-morpholin-4-yl-3H-imidazol-4-yl) -1.2 , 3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 4-methyl l-3- [4- [spiro (6,7-dihydro-5H-pyrrolo [1,2-a] imidazol-3-yl-5-cydohexane]] - [1,2,3] triazol-1-yl ] -benzamide N- (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (3-methyl-2-methylsulfanyl-3-fimidazol-4-yl) - 1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [3-methyl-2- (2-methyl-propane-2-sulfonyl) -3H-imida-2-l-4-yl] -1,2,3-triazol-1-yl} -benzamide and N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3-. { 4- [3-methyl-2- (1-methyl-cyclopropyl) -3-ylamino-4-yl] -1,2, 3-triazol-1-yl} -benzamide. 16. Compound according to claim 10, characterized in that the compound is selected from 3 ~ [4- (l-Cyclopropyl-5-ethyl-1H-pyrazol-4-yl) -1,2,3-triazole-1- il] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide 3 ~ [4- (5-Ethyl-1-phenyl-1H-pyrazole- 4-yl) -1, 2, 3-triazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-benzamide N- ( 5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclohexyl-5-methyl-1-yl-pyrazol-4-yl) -1,2,3-triazole-1- il] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 ~ [4- (l-cyclohexyl-5-ethyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-isopropyl-5 -methyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) - 3- [4- (1-cyclopropyl-5-methyl-1-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-ter) -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-tert-butyl-5-methyl-lH-pyrazol-4-yl) -1, 2, 3-triazol-1-yl ] -4-Methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-cyclopropyl-5-isopropyl-1-pyrazol-4-yl) - 1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (1-cyclopropyl-5- ethyl-l-pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3 - [4- (1, 5-dimethyl-1-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino -2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1H-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N - (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-l-pyridin-2-yl-l-pyrazol-4-yl) -1, 2, 3-triazol-1-yl] -4-methyl-benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-1-isopropyl-1H- pyrazol-4-yl) -1, 2, 3-triazol-l-yl] -4-methyl-benzamide N- (5- ter-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-isopropyl-l-phenyl-lH-pyrazol-4-yl) -1,2,3-triazol-1-yl] -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [1- (4-fluorophenyl) -5-methyl-1-ylpyrazol-4-yl] -1,2,3-triazol-1-yl} -4-methyl-benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3-. { 4- [- (2-dimethylamino-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-tria2? -l-il} -4-methyl-benzamide N ~ (5- er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-phenyl-1H-pyrazole-4- il) -1, 2, 3-triazol-1-yl] -benzamide N- (5-er-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5-methyl-l- (l-methyl-piperidin-4-yl) -lH-pyrazol-4-yl] -1,2, 3-triazol-1-yl} -benzamide N- (5- tert -Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-l-pyridin-2-yl-lH-pyrazole-4- il) -1,2,3-triazol-1-yl] -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3-. { 4- [5- (2-morpholin-4-yl-ethyl) -1-phenyl-lH-pyrazol-4-yl] -1,2,3-triazol-1-yl} -benzamide and N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -4-methyl-3- [4- (5-methyl-l-phenyl-l-pyrazol-4 -yl) -1, 2,3-triazol-1-yl] -benzamide. 17. Compound according to claim 10, characterized in that the compound is selected from: 3- [4- (2-Benzylsulfonyl-3-methyl-3H-imidazol-4-yl) -1,2, 3-triazole-1 -yl] -N- (5- er-butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-benzamide 3- [4- (5-Ethyl-1-phenyl-1H-pyrazol-4-yl ) -imidazol-1-yl] -N- (2-methoxy-5-trifluoromethyl-phenyl) -4-methyl-benzamide 3- [4- (5-Ethyl-l-phenyl-lH-pyrazol-4-yl) -imidazol-1-yl] -N- (3-methanesulfonylamino-2-methoxy-5-trifluoromethyl-phenyl) -4-methyl-benzamide 3- [4- (5-Ethyl-l-phenyl-lH-pyrazole-4 -yl) -imidazol-1-yl] -N- [3-methanesulfonylamino-2-methoxy-5- (1-methyl-cyclopropyl) -phenyl] -methyl-benzamide N- (5-er-Butyl-2- methansulfinyl-phenyl) -3- [4- (5-ethyl-l-phenyl-l-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-2) -methoxy-phenyl) -3- [4- (5-ethyl-l-phenyl-1-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl- 2-methyl-pyridin-3-yl) -3- [4- (5-ethyl-l-phenyl-l-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-cyano-2-methoxy-phenyl) -3- [4- (5-ethyl-l-phenyl-L-pyrazol-4-yl) -imidazol-1-yl] -4- methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (l-isopropyl-5-methyl-l-pyrazol-4-yl) -imidazole-1- il] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -3- [4- (5-ethyl-1-phenyl-1-pyrazol-4-yl) -imidazol-1-yl] -4-methyl-benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- (4-pyridin-3-yl-imidazole- 1-yl) -benzamide N- (5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenyl) -4-methyl-3- [4- (5-methyl-1-phenyl-1-pyrazol-4 -yl) -imidazol-1-yl] -benzamide and N- (5-tert-Butyl-3-methanesulfonylamino-2-methyl-phenyl) -3- [4- (5-ethyl-l-phenyl-lf-pyrazole -4-yl) -imidazol-1-yl] -4-methyl-benzamide. 18. Pharmaceutical composition characterized in that it contains a pharmaceutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable vehicles and / or adjuvants. 19. Use of a compound according to claim 1 for preparing a medicament for treating an oncological disease. 20. Use of a compound according to claim 1 for preparing a medicament for treating a disease or condition selected from osteoarthritis, atherosclerosis, contact dermatitis, bone resorption diseases, reperfusion injury, asthma, multiple sclerosis, Guillain-Barre syndrome, Crohn's disease, ulcerative colitis, psoriasis, graft-versus-host disease, systemic lupus erythematosus, insulin-dependent diabetes mellitus, rheumatoid arthritis, toxic shock syndrome, Alzheimer's disease, diabetes, inflammatory bowel diseases, acute and chronic pain, strokes, infarction - of myocardium, alone or after thrombolytic therapy, thermal injury, adult acute-dyspeptic syndrome (ARDS), multiple organ damage secondary to trauma, acute glomerulonephritis, dermatosis with acute inflammatory components, acute purulent meningitis, syndromes associated with hemodialysis, leucoferisis , syndromes associated with large transfusion ulcers, necrotizing crust, restenosis after percutaneous transluminal coronary angioplasty, traumatic arthritis, sepsis, chronic obstructive pulmonary disease and congestive heart failure.