5-substituted indazole as kinase inhibitors


FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

 

The scope of the invention

The present invention relates to 5-substituted indazol - containing compounds, methods of producing such compounds, compositions containing such compounds that are useful for inhibiting kinases such as glikogensintetazy-kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNKl, aurora, pim 1 and nek 2.

Background of the invention

Protein kinases are a class of enzymes that catalyze the transfer of a phosphate group from ATP to the tyrosine, serine, threonine, or his-tag residues located on the protein substrate. It is obvious that protein kinases play a role in normal cell growth. Many proteins, receptors, growth factors contain intracellular domains, which function as protein kinases, and it is through this function they perform signal transmission. The interaction of growth factors with their receptors is a necessary event in the normal regulation of cell growth and protein phosphorylation of the substrate is often associated with modulation of cell growth.

It is well known that abnormal phosphorylation of the protein can be directly associated with certain painful conditions or may be a factor contributing to the development of such diseases. As a result, protein kinases are the two who are targets, are sent to new pharmaceutical research (Cohen, P. Nature Reviews Drug Discovery, 1:309-315, 2002). Various inhibitors of protein kinases have clinical application for the treatment of a wide range of different diseases, such as cancer, chronic inflammatory diseases, diabetes and stroke.

Protein kinases represent a large and diverse family of enzymes that catalyze the phosphorylation of proteins and play a key role in cellular signaling. Protein kinases can be positive or negative regulatory action, depending on their target proteins. Protein kinases are involved in specific signaling pathways that regulate cellular functions, such as, but not limited to, metabolism, development, cell cycle, cell adhesion, function of blood vessels, apoptosis and angiogenesis. As a result, the disturbance of cellular signaling activity is associated with many diseases, the most characteristic of which include cancer and diabetes. Regulation of signal transduction by cytokines and communication of signaling molecules with the proto-oncogenes and tumor-suppressor genes have been sufficiently documented. Similarly, the link between diabetes, viral infections and associated conditions are also attributed to the regulation of protein kinases.

Because protein is Inez regulate almost every cellular process, including metabolism, cell proliferation, cell differentiation and cell survival, they are attractive targets for therapeutic intervention in various painful conditions. For example, control of the cell cycle and angiogenesis, where protein kinases play an important role, are the cellular processes associated with various painful conditions, such as, but not limited to, cancer, inflammatory diseases, abnormal angiogenesis and related diseases, atherosclerosis, macular degeneration, diabetes, obesity and pain.

Elucidation of the intricate pathways of protein kinases and the complexity of the relationships and interactions between different protein kinases and kinase pathways emphasizes the importance of developing pharmaceutical products that may act as modulators, regulators or inhibitors of protein kinases, with a favorable effect on various kinases or different kinase pathway.

Therefore, it is assumed that due to the complexity of intracellular signaling cascades proteinkinase ways, means, which influence on different paths at the same time, may be necessary for significant clinical activity. Although it is believed that a single tool that provides the combined effects, is attractive, there is the duty to regulate the need to identify and use tools who are aiming for the right combination and the various ways that are clinically effective in the circumstances of a particular disease.

Glikogensintetazy-kinase-3 (GSK-3) is a serine/threonine kinase encoded by two isoforms, GSK-3α and GSK-3β, with a molecular mass of 51 and 47 kDa, respectively. They have a 97% sequence similarity in their kinase catalytic domains. GSK-3α isoform has an elongated glycine-rich N-terminal tail. Was identified minor variant splicing GSK-3β (expressed at the level of ~15% of the total) with the insertion of 13 amino acids in the kinase domain. This option had a lower activity against tau. GSK-3 has been preserved in many forms in the process of evolution, and is still present in all mammals with high homology in the kinase domain. Both isoforms are expressed in many mammalian tissues, including the brain. Pharmacological inhibitors of GSK-3 can not selectively inhibit one of the isoforms.

GSK-3β plays an important role in the control of metabolism, differentiation, and survival. It was originally identified as an enzyme capable of fosforilirovanii and, consequently, to inhibit glikogensintetazy. Subsequently, it was found that GSK-3β is identical to the tau protein kinase 1 (TPK1), the enzyme that phosphorylates au protein epitopes, which, as it was discovered, also hyperphosphorylated in Alzheimer's disease and some Touratech.

Interestingly, phosphorylation of GSK-3β protein kinase B (AKT) leads to loss of kinase activity, and an assumption was made that this inhibition may mediate some of the effects of neurotrophic factors. Moreover, phosphorylation of β-catenin (a protein involved in cell survival), implemented by GSK-3β, leading to its destruction-dependent obyedinionnaya proteasomal way.

Therefore, it was found that the inhibition of GSK-3β activity can lead to neurotrophic activity. There is evidence that lithium, non-competitive inhibitor of GSK-3β increases neuritogenic in some models and may also enhance the survival of nerve cells through the induction of survival factors such as Bcl-2, and inhibition of the expression of proapoptotic factors, such as P53 and Bax.

Further studies showed that β-amyloid increases the activity of GSK-3β and phosphorylation of protein tau. Moreover, this hyperphosphorylation and neurotoxic effects of β-amyloid blocked by lithium chloride and antisense mRNA GSK-3β. Taken together, these observations suggest that GSK-3β may be a link between the two major pathological processes in Alzheimer's disease: abnormal, processi the g APP (amyloid protein precursor) and hyperphosphorylated protein tau.

These experimental observations suggest that GSK-3β may find application in the prevention and treatment of neuropathologically consequences and a lack of cognitive abilities and attention associated with Alzheimer's disease, and other acute and chronic neurodegenerative diseases. They include, but are not limited to: Parkinson's disease, chaupati (e.g., fronto-temporo-parietal dementia, corticobasal degeneration, a disease of the Peak, progressive supranuclear palsy) and other dementia including vascular dementia; acute stroke and others traumatic lesions; cerebrovascular disorders (e.g., age-related macular degeneration); brain and spinal cord; peripheral neuropathy; retinopathy and glaucoma.

GSK-3β may also find use for the treatment of other diseases, such as insulin-independent diabetes, and obesity; manic depressive illness; schizophrenia; alopecia; inflammation; cancer, such as breast cancer, non-small cell carcinoma of the lung, thyroid cancer, T or B-cell leukemia and several virus-induced tumors.

Rho kinase (ROCK), the first Rho effectors, which have been described, are serine/threonine kinases that play important roles in fundamental cellular processes is igrali, cell proliferation and cell survival. Abnormal activation of the Rho/ROCK path observed in various disorders. Examples of painful conditions where the compounds of the present invention have potentially beneficial therapeutic effects due to their anti-vasospastic activity include cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, spasm of cerebral vessels after subarachnoid hemorrhage, pulmonary hypertension, and atherosclerosis. The property of muscle relaxation is also useful for the treatment of asthma, male erectile dysfunctions, female sexual dysfunctions syndrome hyperreactive bladder. Damage to the brain and spinal cord in an adult vertebrate animal activates ROCK, by inhibiting this growth and spread of neuritis. Inhibition of ROCK leads to the induction of growth of new axons, the distribution of axons through the lesion in the Central nervous system, rapid regeneration and enhanced functional recovery after acute neural lesions in mammals (spinal cord injury, traumatic brain injury). Also, it was confirmed that the inhibition of Rho/ROCK the way it is effective is diversified in other animal models of neurodegeneration, for example, shock, inflammatory and demyelinating diseases, Alzheimer's disease, and for treatment of pain. Inhibitors of Rho/ROCK path and therefore have the potential to prevent neurodegeneration and stimulation of neuroregenerative in various neurological disorders, including spinal cord injury, Alzheimer's disease, stroke, multiple sclerosis, amyotrophic lateral sclerosis, as well as for the treatment of pain. It was shown that ROCK inhibitors have anti-inflammatory properties. Thus, the compounds of the present invention can be used to treat neuropeptidergic diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis and inflammatory pain, as well as other inflammatory diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, common lupus and inflammatory bowel disease. Because the ROCK inhibitors reduce cell proliferation and cell migration, they could be useful for the treatment of cancer and tumor metastasis. Moreover, if the evidence suggesting that the ROCK inhibitors inhibit cytoskeletal rearrangeable in viral invasion, thus, they also have p the potential therapeutic value for use as antiviral and antibacterial agents. The ROCK inhibitors are also useful for treatment of insulin resistance and diabetes. In addition, it was shown that ROCK inhibitors reduce the progression of cystic fibrosis (Abstract S02.3, 8th World Congress on Inflammation, Copenhagen, Denmark, June 16-20, 2007).

In addition, it was shown that Rho-associated twisted into a spiral-form helix protein kinase (ROCK)-1 and -2 enhances the phosphorylation of the light chain of myosin (MLC) by inhibiting MLC phosphatase, and MLC phosphorylation. This leads to the regulation of contraction of actin-myosin. Recent reports have shown that inhibition of ROCK leads to the interruption of the inflammatory cell chemotaxis and inhibition of contraction of smooth muscles in models of lung inflammation associated with asthma. Therefore, inhibitors of Rho/ROCK pathway should be useful for the treatment of asthma.

The Janus kinase (JAK) are an important family of intracellular tyrosine kinases (PTK) with 4 members present in mammals, JAK1, JAK2, JAK3 and TYK2, as well as homologues of chicken, fish, and Drosophila. JAK play a critical role in several important intracellular signaling pathways, including the main way of JAK/STAT, Central to the mediation of signal transmission cytokines. It is this Central role in the signaling of cytokines supports the view that specific inhibitors of JAK can find a wide those who piticescu use in situations where the activity of cytokines leads to disease. Important examples include autoimmune diseases such as rheumatoid arthritis and psoriasis, myeloproliferative syndromes, such as, leukemia, lymphoma and cardiovascular diseases.

JAK2, a member of the family of Janus kinases (JAK) tyrosine proteinkinase (PTK)is an important intracellular mediator of signal transmission cytokines. Mutation of the JAK2 gene are associated with hematological cancer and aberrant JAK activity is also associated with various immune diseases, including rheumatoid arthritis.

Kinase Aurora are a multigene family of mitotic serine-treoninove kinases, which act as a new class of oncogenes. These kinases include as members of aurora-A, aurora-B and aurora-B. They hyperactivity and/or over-expressed in several solid tumors, including, but not limited to, breast cancer, ovarian, prostate, pancreas and colorectal cancer. In particular, aurora-A is centrosomal kinase, and its localization is dependent on the cell cycle and plays an important role in the development of cell cycle and cell proliferation. Aurora-A is located in the area 20ql3 chromosome, which is often amplificates in some different types of malignant tumors, such as colorectal RA is, breast cancer and bladder. Inhibition of aurora kinase activity can help in reducing cell proliferation, tumor growth and potentially oncogenesis.

Therefore, there remains a need to develop methods that include the use of drugs based on the same active substance, capable of aiming to act on a few specific types of kinases or kinase pathways. In particular, such methods affect the desired combination of multiple targets with achievement thus clinical efficacy.

Brief description of the invention

The main variant embodiment, the present invention provides compounds of formula (I)

or their pharmaceutically acceptable salts, where

A represents

R1represents hydrogen, alkyl, aryl, heterocycle, heteroaryl, RaRbN-, RcRdN-C(O)- or RcRdN-S(O)2-;

R2represents hydrogen, alkoxycarbonyl, alkyl, alkylaryl, arylcarbamoyl, heterocyclicamines or ReRfN-alkyl-C(O)-;

R3represents alkyl, alkoxy, aryl, cyano, cycloalkyl, halogen, halogenated, heteroaryl, nitro, or RgRhN;

R4represents the t of an alkyl, alkoxyalkyl, aryl, cycloalkyl, heteroaryl, heterocycle, heterocyclyl, RjRkN or RjRkN-alkyl-;

R5represents alkyl, aryl or heteroaryl;

R6represents alkyl, alkoxyalkyl, RjRkN-alkyl-, aryl, cycloalkyl or heteroaryl;

R7represents alkyl, aryl or heteroaryl;

Raand Rb, each independently, represent hydrogen, alkyl, arylalkyl, cycloalkyl, cycloalkenyl, heteroallyl, R4-C(O)- or R5-S(O)2-;

Rcand Rd, each independently, represent hydrogen, alkyl or heteroaryl;

Reand Rf, each independently, represent hydrogen, alkyl, arylalkyl, heteroallyl, R6-C(O)- or R7-S(O)2-;

Rgand Rh, each independently, represent hydrogen, alkyl or alkylaryl;

Rjand Rk, each independently, represent hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl or heterocycle;

Ri, Rii, Riii, Riv, Rv, Rvi, Rvii, Rviii, Rix, Rx, Rxi, Rxii, Rxiii, Rxiv, Rxv, Rxvi, Rxvii, Rxviii, Rxix, Rxx, Rxxi, Rxxiiand Rxxiii, each independently, represent alkyl, alkoxy, alkoxyalkyl, alkoxyaryl the Nile, alkoxycarbonyl, aryl, arylalkyl, aryl(hydroxy)alkyl, aryloxyalkyl, arylcarbamoyl, alltoall, carboxy, carboxylic, cianelli, cycloalkyl, cycloalkenyl, cycloalkylcarbonyl, halogen, heteroaryl, heteroaromatic, heterocycle, heterocyclyl, heterocyclicamines, hydroxyalkyl, trialkylsilyl, H2NC(O)-alkyl, ZaZbN-, ZaZbThe N, ZcZdNC(O) -, or ZcZdNS(O)2-, where RXiV, Rxv, RXViand RXViican attend any of the open valences in the compounds (xiv), (xv), (xvi) or (xvii);

Zaand Zb, each independently, represent hydrogen, alkyl, alkoxycarbonyl, aryl, arylalkyl, cycloalkyl, H2NC(O)-, H2The NC(O)-, H2NC(O)-alkyl, NC(O)- or NC(O)-alkyl-;

Zcand Zd, each independently, represent hydrogen, alkyl, alkoxyalkyl, aryl, arylalkyl, aryl(hydroxy)alkyl, cycloalkyl, cycloalkenyl, heteroallyl, heterocycle, heterocyclyl, hydroxyalkyl, H2NC(O)-alkyl-, NC(O)-alkyl-, N-alkyl - or CHZeZf;

Zerepresents aryl or heteroaryl;

Zfis heteroallyl, heterocyclyl or Z1Z2N-alkyl-;

m is 0, 1 or 2;

a has a value of 0 or 1;

b is 0, 1 or 2;

c has the value 0, 1, 2, or 3; and

d is 0, 1, 2, 3, or 4.

It also provides pharmaceutically acceptable compositions comprising a therapeutically effective amount of the compounds of formula (I) in combination with a pharmaceutically acceptable carrier.

The aim of the present invention is to provide compounds that are useful for the prevention or treatment of diseases caused by abnormal activity of protein kinases. In addition, the invention also provides pharmaceutically effective compositions of the compounds of the present invention, which are useful for the prevention or treatment of such diseases.

The present invention also relates to pharmaceutical compositions that include at least one 5-substituted indazol compound of formula (I), which can exist in the form of its pharmaceutically acceptable salts or prodrugs, in the presence or in the absence of pharmaceutically acceptable carriers, pills, adjuvants or other auxiliary substances.

Compounds of the present invention have ingibiruemoi activity against GSK-3, ROCK-1, ROCK-2, JAK2, as well as other kinases and are useful for the inhibition of such kinases. Some compounds of the present invention are selective for one or more kinases and can be floor the EIT for the selective inhibition of such kinases. Therefore, the compounds of the present invention are useful as active ingredient to obtain a composition which provides a prophylactic and/or therapeutic treatment of diseases caused by abnormal activity of GSK-3, and more specifically, neurodegenerative diseases such as Alzheimer's disease. In addition, the compounds of the present invention are also useful as active ingredient to obtain a composition for prophylactic and/or therapeutic treatment of neurodegenerative diseases such as Parkinson's disease, chaupati (e.g., fronto-temporo-parietal dementia, corticobasal degeneration, a disease of the Peak, progressive supranuclear palsy) and other dementia including vascular dementia; acute stroke and others traumatic lesions; cerebrovascular disorders (e.g., age-related macular degeneration); brain and spinal cord; peripheral neuropathy; retinopathy and glaucoma; and other diseases such as insulin-independent diabetes (such as type II diabetes) and obesity; manic depressive illness; schizophrenia; alopecia; cancers, such as breast cancer, non-small cell carcinoma of the lung, thyroid cancer, T or B-cell leukemia and n is the virus-induced tumors.

Detailed description of the invention

Compounds of the present invention have the formula (I)described above. More specifically, the compounds of formula (I) can include, but are not limited to, compounds where A is a (ii), (iii), (iv), (vii), (x), (xiv), (xv), (xvi), (xvii), (xviii), (xix), (xx), (xxi), (xxii) or (xxiii).

In another variant embodiment of the present invention discloses a compound of formula (I), where A is a (ii)

R1represents hydrogen, aryl, heteroaryl, heterocycle, RaRbN or RcRdN-C(O)-; R2represents hydrogen, alkoxycarbonyl, heterocyclicamines, alkylsulphonyl or ReRfN-alkyl-C(O)-; R4represents alkyl, alkoxyalkyl, aryl, cycloalkyl, heterocycle, heterocyclyl, RjRkN or RjRkN-alkyl-; R5represents alkyl, aryl or heteroaryl; Raand Rb, each independently, represent hydrogen, arylalkyl, cycloalkenyl, R4-C(O)- or R5-S(O)2-; Rcand Rd, each independently, represent hydrogen or heteroaryl, Reand Rf, each independently, represent hydrogen or alkyl, Rjand Rk, each independently, represent hydrogen, alkyl, aryl, cycloalkyl or heterocycle; Riirepresents alkyl, alkoxyalkyl, alkoxycarbonyl, aryl, arylalkyl, aryl(hydroxy)alkyl, aryloxyalkyl, arylcarbamoyl, alkoxycarbonylmethyl, alltoall, carboxy, carboxylic, cycloalkyl, cycloalkenyl, cycloalkylcarbonyl, halogen, heteroaryl, heteroaromatic, heterocycle, heterocyclyl, heterocyclicamines, hydroxyalkyl, trialkylsilyl, ZaZbN-, ZaZbThe N - or ZcZdNC(O)-; Zaand Zb, each independently, represent hydrogen, alkyl or H2The NC(O)-; Zcand Zd, each independently, represent hydrogen, alkyl, alkoxyalkyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heteroallyl, heterocyclyl, hydroxyalkyl or N-alkyl-; m is 0; and b is 0, 1 or 2.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (iii)

R1represents hydrogen or RaRbN-; R2represents hydrogen; R4is an RjRkN-alkyl-; Raand Rb, each independently, represent hydrogen or R4-C(O)-; Rjand Rkeach represent alkyl; Riiiis alkoxycarbonyl, alkyl, arylalkyl, cianelli, heterocyclyl or H2NC(O)-alkyl-; c is meant the e 0, 1 or 2; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (iv)

R1represents hydrogen or R3RbN-; R2represents hydrogen; R3and Rbeach represent hydrogen; RiVrepresents aryl, arylalkyl, heterocycle, heterocyclyl, ZaZbThe N or ZcZdNS(O)2-; Zaand Zb, each independently, represent hydrogen or alkyl; Zcand Zdeach represent alkyl; c is 0, 1 or 2; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (vii)

R1represents hydrogen, alkyl, or RaRbN; R2represents hydrogen; Raand Rbeach represent hydrogen; RViirepresents alkyl, alkoxycarbonyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heterocyclicamines, hydroxyalkyl or ZcZdNC(O)-; Zcand Zd, each independently, represent hydrogen, alkyl, alkoxyalkyl, aryl, arylalkyl, aryl(hydroxy)alkyl, cycloalkyl, cycloalkenyl, heteroallyl, heterocycle, heteros KelKel, hydroxyalkyl or CHZeZf, Zerepresents aryl or heteroaryl, Zfis heteroallyl, heterocyclyl or Z1Z2N-alkyl-; b is 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (x),

R1represents hydrogen; R2represents hydrogen; Rxrepresents alkyl, aryl, or ZaZbN-; Zaand Zb, each independently, represent hydrogen, alkyl, aryl or arylalkyl; b has a value of 1 or 2; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xiv),

R1represents hydrogen; R2represents hydrogen; RXiVis a ZaZbN-; Zaand Zb, each independently, represent hydrogen or cycloalkyl; c is 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xv),

(xv)

R1represents hydrogen or R3RbN-; R2represents hydrogen; Rsub> 3and Rbeach represent hydrogen; Rxvis a ZaZbN-; Zaand Zb, each independently, represent hydrogen, alkoxycarbonyl, aryl, arylalkyl or cycloalkyl; d is 0 or 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xvi)

R1represents hydrogen; R2represents hydrogen; RXViis a ZaZbN-; Zaand Zb, each independently, represent hydrogen or cycloalkyl; d is 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xvii)

R1represents hydrogen; R2represents hydrogen; RXViirepresents aryl or ZaZbN-; Zaand Zb, each independently, represent hydrogen, alkyl, alkoxycarbonyl, aryl, arylalkyl, cycloalkyl or H2NC(O)-alkyl-; d is 0 or 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xviii)

R1 is an RaRbN-; R2represents hydrogen; Raand Rbeach represent hydrogen; c is 0; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xix)

R1is an RaRbN-; R2represents hydrogen; Raand Rbeach independently represent hydrogen; c is 0; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xx)

R1is an RaRbN-; R2represents hydrogen; R4is an RjRkN-alkyl-; Raand Rbeach represent hydrogen or R4-C(O)-; Rjand Rkindependently represent alkyl; Rxxis a ZaZbN - or heterocycle; Zaand Zbindependently represent hydrogen or alkyl; c is 0 or 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xxi)

R1is an Ra bN-; R2represents hydrogen; Raand Rbeach represent hydrogen; RXXirepresents alkoxy; d is 1; and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xxii)

R1is an RaRbN-; R2represents hydrogen; R4is an RjRkN-alkyl-; Raand Rb, each independently, represent hydrogen or R4-C(O)-; Rjand Rkeach represent alkyl; c is 0 and m is 0.

In another variant embodiment of the present invention, is disclosed a compound of formula (I), where A is a (xxiii)

R1is an RaRbN-; R2represents hydrogen; Raand Rbeach represent hydrogen; c is 0; and m is 0.

Specific variants of the embodiment under consideration as part of the present invention include, but are not limited to, compounds of formula (I), for example:

5-(1-benzyl-1H-1,2,3-triazole-5-yl)-1H-indazol connection with 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazole;

5-(1H-1,2,3-triazole-5-yl)-1H-indazol;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-Inda is ol;

5-[1-(2-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(4-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3-methoxybenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(4-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(4-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2-bromobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(4-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

2-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;

3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;

4-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;

5-{1-[2-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{1-[3-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{1-[3-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{1-[4-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-[1-(4-tert-butylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

methyl 3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl} benzoate;

methyl 4-{[4-(1H-indazol-5-yl)-1H-1,2,triazol-1-yl]methyl}benzoate;

5-[1-(2,4-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2,3-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2,4-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(2,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-(3,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-{1-[2,4-bis(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

N-cyclohexyl-6-(1H-indazol-5-yl)imidazo[2,1-b][1,3]thiazole-5-amine;

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrazin-3-amine;

5-[1-benzyl-4-(4-forfinal)-1H-indazol-5-yl]-1H-indazol;

N-{3-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-indazol-1-yl]propyl}-N,N-dimethylamine;

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;

5-[4-(4-forfinal)-1-(1-phenylethyl)-1H-indazol-5-yl]-1H-indazol;

2-(1H-indazol-5-yl)-N-isopropylimidazole[1,2-a]pyrimidine-3-amine;

4-(1H-indazol-5-yl)-N-phenyl-1,3-thiazol-2-amine;

5-(2-methyl-1,3-thiazol-4-yl)-1H-indazol;

N-ethyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;

N-benzyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;

4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;

4-(1H-indazol-5-yl)-N-(2-phenylethyl)-1,3-thiazol-2-amine;

N-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;

N-butyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;

N-(4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;

2-(1H-indazol-5-yl)-N-(4-shall ethoxyphenyl)imidazo[1,2-a]pyrimidine-3-amine;

2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine;

methyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-yl]glycinate;

N-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;

N-(4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;

2-(1H-indazol-5-yl)-N-(4-methoxyphenyl)imidazo[1,2-a]pyridine-3-amine;

tert-butyl 4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-indazol-1-yl}piperidine-1-carboxylate;

3,5-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-phenyl-1H-indazol;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(1-methylpiperidin-4-yl)carbonyl]-1H-indazol-3-amine;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-methoxyacetate;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

Ν-[5-(1-benzyl-lΗ-1,2,3-triazole-4-yl)-lΗ-indazol-3-yl]butanamide;

5-[4-(4-forfinal)-1-piperidine-4-yl-1H-indazol-5-yl]-1H-indazol;

5-{4-(4-forfinal)-1-[2-(1-methylpyrrolidine-2-yl)ethyl]-1H-indazol-5-yl}-1H-indazol;

5-{4-(4-forfinal)-1-[3-(4-methylpiperazin-1-yl)propyl]-1H-indazol-5-yl}-1H-indazol;

ethyl 5-(1H-indazol-5-yl)isoxazol-3-carboxylate;

5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide;

5-(3-benzisoxazol-5-yl)-1H-indazol;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide;

5-(3-propylenoxide-5-yl)-1H-indazol;

N-benzyl-4-(1H-indazol-5-yl)-5-phenyl-1,3-thiazol-2-amine;

4-(1H-shall indazol-5-yl)-N,5-diphenyl-1,3-thiazole-2-amine;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol;

5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol;

2-(1H-indazol-5-yl)-3-phenylimidazo[1,2-a]pyrimidine;

5-[1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[3-(piperidine-1-ylcarbonyl)isoxazol-5-yl]-1H-indazol;

5-(1H-indazol-5-yl)-N-phenylisoxazol-3-carboxamide;

N-cyclohexyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-[3-(piperidine-1-ylmethyl)isoxazol-5-yl]-1H-indazol;

[5-(1H-indazol-5-yl)isoxazol-3-yl]methanol;

5-(1H-indazol-5-yl)-N-(2-methoxyethyl)isoxazol-3-carboxamide;

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol;

5-(4-benzyl-1H-1,2,3-triazole-1-yl)-1H-indazol;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol-3-amine;

5-(3-isobutylthiazole-5-yl)-1H-indazol-3-amine;

5-(3-benzisoxazol-5-yl)-1H-indazol-3-amine;

N-{2-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]ethyl}-N,N-dimethylamine;

5-[4-(4-forfinal)-1-(3-morpholine-4-ylpropyl)-1H-indazol-5-yl]-1H-indazol;

5-[4-(4-forfinal)-1-(3-pyrrolidin-1-ylpropyl)-1H-indazol-5-yl]-1H-indazol;

5-{4-(4-forfinal)-1-[2-(4-methylpiperidin-1-yl)ethyl]-1H-imidazol-5-yl}-1H-indazol;

5-[1-(1-benzylpiperidine-4-yl)-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol;

5-[4-(4-forfinal)-1-(2-morpholine-4-retil)-1H-imidazol-5-yl]-1H-indazol;

5-[1-(1-benzylpyrrolidine-3-yl)-4-(4-fluoro who enyl)-1H-imidazol-5-yl]-1H-indazol;

2-{4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]piperidine-1-yl}-2-oxoethyl;

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol;

5-[4-(methoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;

1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]-1-phenylethanol;

5-(4-propyl-1H-1,2,3-triazole-1-yl)-1H-indazol;

1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol;

3-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-1-ol;

1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-1,2,3-benzotriazol;

5-{4-[(phenylthio)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;

5-(4-cyclopropyl-1H-1,2,3-triazole-1-yl)-1H-indazol;

5-[4-(2-phenylethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;

5-[4-(cyclohexylmethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;

5-(4-cyclopentyl-1H-1,2,3-triazole-1-yl)-1H-indazol;

1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]cyclohexanol;

5-[4-(phenoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;

5-{4-[(1,1-diocletianopolis-4-yl)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;

5-[4-(3-phenylpropyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](phenyl)methanon;

N,N-diethyl-N-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}amine;

ethyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-yl]-beta-alaninate;

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol;

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

N3-[2-(1H-indazol-5-yl)imidazo[1,2-α]pyrimido the-3-yl]-β-alaninate;

5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}-N'-(3-were)urea;

5-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)isoxazol-3-carboxamide;

5-[3-(morpholine-4-ylcarbonyl)isoxazol-5-yl]-1H-indazol;

5-(1H-indazol-5-yl)-N-(3-morpholine-4-ylpropyl)isoxazol-3-carboxamide;

N-[2-(1H-indazol-4-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

(3R)-1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperidine-3-ol;

1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperidine-3-carboxamide;

2-[2-(4-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperazine-1-yl)ethoxy]ethanol;

5-{3-[(4-methyl-1,4-diazepan-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;

N-(3-hydroxypropyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1R)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[3-(1H-indazol-1-yl)propyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[3-(2-oxopyrrolidin-1-yl)propyl]isoxazol-3-carboxamide;

N-{2-[4-(aminosulfonyl)phenyl]ethyl}-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](3-chlorophenyl)methanon;

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](cyclopropyl)methanon;

5-[5-cyclopropyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

N1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]methyl}glycinamide;

(4-forfinal)[4-(lΗ-indazol-5-yl)-1-(tetrahydro-2Η-Piran-4-ylmethyl)-lΗ-1,2,3-triazole-5-yl]metano;

(4-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;

(3-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;

(2-chlorophenyl) [4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}meanon;

cyclopentyl[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}meanon;

1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxylic acid;

5-{5-(4-forfinal)-1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;

5-[1-benzyl-5-(4-forfinal)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl](tetrahydro-2H-Piran-4-yl)methanon;

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-{1-benzyl-5-[(4-methylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-ol;

1-acetyl-5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

1-benzyl-4-(1H-indazol-5-yl)-N,N-dimethyl-1H-1,2,3-triazole-5-carboxamide;

N,1-dibenzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

N-(2-hydroxy-2-phenylethyl)-5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide;

N-[(1S)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-3-methyl-1H-indazol;

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

2-{2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]ethyl}-1H-isoindole-1,3(2H)-dione;

5-{4-[(2,4-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;

5-{4-[(2,6-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;

5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-indazol;

5-[1-benzyl-5-(piperidine-1-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

5-[1-benzyl-5-(morpholine-4-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;

5-[1-benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

N-[(1S)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-{3-[(3-phenylmorpholine-4-yl)carbonyl]isoxazol-5-yl}-1H-indazol;

N-benzyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

((1S)-2-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-yl)methanol;

N-[(1R)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1S)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)itxas the l-3-carboxamide;

N-2,3-dihydro-1H-inden-1-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-2,3-dihydro-1H-inden-2-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(1-phenylpropyl)isoxazol-3-carboxamide;

5-{1-benzyl-5-[3-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;

5-{1-benzyl-5-[4-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;

N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide;

N-{4-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide;

5-{1-benzyl-5-[3-(1H-pyrazole-1-yl)phenyl]-lH-1,2,3-triazole-4-yl}-1H-indazol-3-amine;

5-[1-benzyl-5-(1-methyl-1H-pyrazole-4-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-phenylbenzene;

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-benzylbenzamide;

5-[1-benzyl-5-(1-methyl-1H-indol-5-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

5-[1-benzyl-5-(3-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

5-[1-benzyl-5-(3-morpholine-4-ylphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;

5-[3-(1,3-dihydro-2H-isoindole-2-ylcarbonyl)isoxazol-5-yl]-1H-indazol;

5-{3-[(4-methyl-2-phenylpiperazin-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-amine;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]bansilal UNAMID;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(4-methoxyphenyl)urea;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]butanamide;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-methylpropanamide;

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]cyclopropanecarboxamide;

N-[1-benzoyl-5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl}benzamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-perbenzoic;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide;

N-benzyl-5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;

N-[(1R)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol;

N-[(1R)-3-hydroxy-1-phenylpropyl]-5-(3-methyl-1H-indazol-5-yl)isoxazol-3-carboxamide;

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenol;

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]benzamide;

5-{1-benzyl-5-[4-(methylsulphonyl)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-chlorobenzamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-chlorobenzamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]econsultant;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzosulfimide;

N-[5-(1-gasoline is-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-chlorobenzenesulfonamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-chlorobenzenesulfonamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-chlorobenzenesulfonamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2,5-dimethylfuran-3-sulfonamide;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(2-Chlorobenzyl)-1H-indazol-3-amine;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(3-Chlorobenzyl)-1H-indazol-3-amine;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-chlorobenzamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-furamide;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-ethyl-1H-indazol-3-amine;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(4-Chlorobenzyl)-1H-indazol-3-amine;

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(3-furylmethyl)-1H-indazol-3-amine;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-[5-methyl-2-(trifluoromethyl)-3-furyl]urea;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-furamide;

5-(1H-indazol-5-yl)-N-[(1S)-1-phenylpropyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-phenylpropyl]isoxazol-3-carboxamide;

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-amine;

1-benzyl-4-(1H-indazol-5-yl)-N-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-in the azole-5-yl)-N-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-(tetrahydrofuran-3-ylmethyl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-cyclopentyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-(cyclopentylmethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-ethyl-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-isopropyl-N-methyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-phenyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-(4-chlorophenyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-4-(1H-indazol-5-yl)-N-(2-morpholine-4-retil)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-[2-(dimethylamino)ethyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-N-propyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-[3-(dimethylamino)propyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-[2-(diethylamino)ethyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;

N,1-dibenzyl-N-ethyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

N,1-dibenzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

(3R)-1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-3-ol;

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-carboxamide;

5-{1-benzyl-5-[(,6-dimethylmorpholine-4-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{5-[(4-acetylpiperidine-1-yl)carbonyl]-1-benzyl-1H-1,2,3-triazole-4-yl}-1H-indazol;

5-{1-benzyl-5-[(4-phenylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;

1-benzyl-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

1-benzyl-N-[3-(1H-indazol-1-yl)propyl]-4(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-utilmately;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-prilocaine;

N-benzyl-N'-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]urea;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(2-chlorophenyl)urea;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(3-chlorophenyl)urea;

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(4-chlorophenyl)urea;

N-[5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide;

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanenitrile;

2-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]ndimethylacetamide;

methyl 3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanoate;

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanamide;

[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]acetonitrile;

4-(3-amino-1H-indazol-5-yl)-N,N-dimethyl-1H-indazol-1-sulfonamide;

5-PI is Azin-2-yl-1H-indazol-3-amine;

5-Tien-2-yl-1H-indazol-3-amine;

5-(2-aminopyrimidine-4-yl)-1H-indazol-3-amine;

5-(2-methoxypyridine-3-yl)-1H-indazol-3-amine;

5-imidazo[1,2-a]pyridine-3-yl-1H-indazol-3-amine;

N2N2-dimethyl-N1-[5-(1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]glycinamide;

5-(1H-pyrazole-5-yl)-1H-indazol-3-amine;

5-(4-methyl-1H-indazol-5-yl)-1H-indazol-3-amine;

5-(1H-indazol-4-yl)-1H-indazol-3-amine;

N2N2-dimethyl-N1-{5-[1-(3-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide;

5-(1-benzyl-1H-indazol-4-yl)-1H-indazol-3-amine;

N1-{5-[1-(4-tert-butylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}-N2N2-dimethylglycinamide;

N2N2-dimethyl-N1-{5-[1-(2-piperidine-1-retil)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide;

N2N2-dimethyl-N1-{5-[1-(2-morpholine-4-retil)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide;

N1-(5-{1-[2-(3,5-dimethylisoxazol-4-yl)ethyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-yl)-N2N2-dimethylglycinamide;

N1-(5-{1-[2-(3,5-dimethyl-1H-pyrazole-4-yl)ethyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-yl)-N2N2-dimethylglycinamide;

2-(4-{3-[(N,N-dimethylphenyl)amino]-1H-indazol-5-yl}-1H-1,2,3-triazole-1-yl)-2-methylpropanoyl acid;

ethyl (4-{3-[(N,N-dimethylphenyl)amino]-1H-indazol-5-yl}-1H-1,2,3-triazole-1-yl)acetate;

N2N2-dimethyl-N1-(5-{1-[(trimethylsilyl)methyl]-1H-1,2,3-triazole-4-yl}-1H-shall indazol-3-yl)glycinamide;

N1-[5-(3-furyl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

N2N2-dimethyl-N1-[5-(1H-pyrazole-5-yl)-1H-indazol-3-yl]glycinamide;

N2N2-dimethyl-N1-(5-pyrimidine-5-yl-1H-indazol-3-yl)glycinamide;

N1-[5-(2,1,3-benzoxadiazole-5-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

N2N2-dimethyl-N1-[5-(1H-pyrazole-4-yl)-1H-indazol-3-yl]glycinamide;

N2N2-dimethyl-N1-[5-(1-methyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]glycinamide;

N1-[5-(3,5-dimethyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

N1-{5-[2-(dimethylamino)pyrimidine-5-yl]-1H-indazol-3-yl}-N2N2-dimethylglycinamide;

N2N2-dimethyl-N1-[5-(2-morpholine-4-Yeremey-5-yl)-1H-indazol-3-yl]glycinamide;

N2N2-dimethyl-N1-{5-[1-(2-morpholine-4-retil)-1H-pyrazole-4-yl]-1H-indazol-3-yl}glycinamide;

N1-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

N1-[5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-methylglycine;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-pyrrolidin-1-ylacetamide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclopentylamine the amide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclopropylidene;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-tetrahydro-2H-Piran-4-anglicanae;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(3-hydroxypyrrolidine-1-yl)ndimethylacetamide;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(3-hydroxypiperidine-1-yl)ndimethylacetamide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N3N3-dimethyl-beta-alaninate;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-morpholine-4-ylacetamide;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(4-methylpiperazin-1-yl)ndimethylacetamide;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(3-oxopiperidin-1-yl)ndimethylacetamide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-isopropylpyridine;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclohexylglycine;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]ndimethylacetamide;

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclobutylamine;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-propylacetic;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]econsultant;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-N-(cyclopropylmethyl)-1H-indazol-3-amine;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-atilmotin;

1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol--yl]pyrrolidin-2-he;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-(dimethylamino)butanamide;

N-3,4-dihydro-1H-isochroman-4-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-(cyclohexylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-(3-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-methoxybenzyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[2-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[3-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[4-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(pyridine-2-ylmethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(pyridine-3-ylmethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(pyridine-4-ylmethyl)isoxazol-3-carboxamide;

N-(2-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-(4-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(1-phenyl-2-piperidine-1-retil)isoxazol-3-carboxamide;

N-[2-(1H-indazol-1-yl)-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-morpholine-4-yl-1-phenylethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[2-(4-methylpiperazin-1-yl)-1-phenylethyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(1-phenyl-2-pyrrolidin-1-retil)isoxazol-3-carboxamide;

tert-butyl 2-({[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}amino)-2-generationbased;

5(1H-indazol-5-yl)-N-(1-naphthylmethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-phenylethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-pyridin-2-retil)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-pyridin-3-retil)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-(2-pyridin-4-retil)isoxazol-3-carboxamide;

N-[2-(2-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[2-(3-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[2-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-benzyl-N-ethyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-methyl-N-(1-naphthylmethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-methyl-N-(2-phenylethyl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-methyl-N-(2-pyridin-2-retil)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-phenylethyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-1,2,3,4-tetrahydronaphthalen-1 - isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1S)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide;

N-[3-(dimethylamino)-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-(3,4-dihydro-2H-1,5-benzodioxepin-6-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1-methyl-1H-indol-4-yl)methyl]isoxazol-3-carboxamide;

5-{3-[(3-phenylpyrrolidine-1-the l)carbonyl]isoxazol-5-yl}-1H-indazol;

5-{3-[(2-phenylpyrrolidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;

5-{3-[(2-phenylpiperidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;

5-(1H-indazol-5-yl)-N-[(1S)-1-phenylethyl]isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-(4-were)ethyl]-isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1S)-1-(4-were)ethyl]-isoxazol-3-carboxamide;

N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1R)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1S)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1R)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[(1S)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1S)-1-(2-naphthyl)ethyl]isoxazol-3-carboxamide;

N-[1-(4-ethoxyphenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[2-hydroxy-1-(4-isopropylphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[1-(3,4-dimetilfenil)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[2-hydroxy-1-(2-methoxyphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[2-hydroxy-1-(4-were)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-(2-methoxyphenyl)ethyl]-isoxazol-3-carboxamide;

N-[(1S)-1-(3,4-differeni is)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]-isoxazol-3-carboxamide;

5-(1H-indazol-5-yl)-N-{(1R)-1-[3-(trifluoromethyl)-phenyl]ethyl}isoxazol-3-carboxamide;

N-[1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

N-[1-(3,5-dichlorophenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;

tert-butyl 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-[({[6-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]-1H-indazol-1-carboxylate;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(1-methylpiperidin-2-yl)carbonyl]-1H-indazol-3-amine;

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(dimethylamino)acetyl]-1H-indazol-3-amine;

tert-butyl 3-amino-5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate;

N-[5-(1-benzyl-1Η-1,2,3-triazole-4-yl)-1Η-indazol-3-yl]-2-piperidine-1-ylacetamide;

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-morpholine-4-ylacetamide; and

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-1-methylpiperidin-2-carboxamide.

All patents, patent applications and reference documents, known from the literature referenced in this description are incorporated in this application by reference in their entirety. In case of inconsistencies, the present disclosure, including definitions, will take precedence.

As used in this description and the accompanying claims, the following terms shall have the following malignancies is implemented:

The term "alkenyl"as used in this application, means a hydrocarbon with a linear or branched chain containing from 2 to 10 carbon atoms and containing at least one carbon-carbon double bond formed by removing two hydrogen atoms. Representative examples of alkenyl include, but are not limited to, ethynyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-1-Heptene and 3-decenyl.

The term "alkoxy", as used in this application, means an alkyl group as defined in this application, attached to the original molecular group through an oxygen atom. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy.

The term "alkoxyalkane as used in this application means alkoxygroup defined in this application, attached to the original molecular group through another alkoxygroup defined in this application. Representative examples of alkoxyalkyl include, but are not limited to, tert-butoxyethoxy, 2-ethoxyethoxy, 2-methoxyethoxy, ethoxyethoxy.

The term "alkoxyalkyl as used in this application means alkoxyalkyl defined in the us is oasa application attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkoxyalkyl include, but are not limited to, tert-butoxyethoxyethanol, ethoxyethoxy, (2 methoxyethoxy)methyl and 2-(2-methoxyethoxy)ethyl.

The term "alkoxyalkyl as used in this application means alkoxygroup defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkoxyalkyl include, but are not limited to, tert-butoxymethyl, 2-ethoxyethyl, 2-methoxyethyl and ethoxymethyl.

The term "alkoxycarbonyl as used in this application means alkoxygroup defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples of alkoxycarbonyl include, but are not limited to, methoxycarbonyl, etoxycarbonyl and tert-butoxycarbonyl.

The term "alkoxycarbonyl as used in this application means alkoxycarbonyl group that is defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. A representative example is alkoxycarbonylmethyl include, but not limited to, 3-methoxycarbonylpropionyl, 4-ethoxycarbonylbutyl and 2-tert-butoxycarbonylmethyl.

The term "alkyl", as used in this application, means a hydrocarbon with a linear or branched chain containing from 1 to 10 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-etylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl and n-decyl.

The term "alkylaryl"as used in this application, means an alkyl group as defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples of alkylcarboxylic include, but are not limited to, acetyl, 1-oxopropyl, 2,2-dimethyl-1-oxopropyl, 1-oxobutyl and 1-oxopent.

The term "alkylcarboxylic as used in this application means alkylcarboxylic group that is defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkylcarboxylic include, but are not limited to, 2-oxopropyl, 3,3-dimethyl-2-oxopropyl, 3-oxobutyl and 3-oxopent.

the Term "alkylcarboxylic", as used in this application means alkylcarboxylic group that is defined in this application, attached to the original molecular group through an oxygen atom. Representative examples of alkylcarboxylic include, but are not limited to, atomic charges, ethylcarbonate and tert-BUTYLCARBAMATE.

The term "alkylene" means a divalent group formed from a hydrocarbon with a linear or branched chain comprising from 1 to 10 carbon atoms. Representative examples of alkylene include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2- and-CH2CH(CH3)CH2-.

The term "alkylene-NRg-as used in this application means alkylenes group that is defined in this application, attached to the original molecular group through an-NRggroup defined in this application.

The term "alkylsulfonyl"as used in this application, means an alkyl group as defined in this application, attached to the original molecular group through sulfonyloxy group that is defined in this application. Representative examples of alkylsulfonyl include, but are not limited to, methylsulfinyl and ethylsulfinyl.

The term "and calculationally", as used in this application means alkylsulfonyl group that is defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkylsulfonyl include, but are not limited to, methylsulfonylmethyl and ethylsulfinyl.

The term "alkylsulfonyl"as used in this application, means an alkyl group as defined in this application, attached to the original molecular group through sulfonyloxy group that is defined in this application. Representative examples alkylsulfonyl include, but are not limited to, methylsulphonyl and ethylsulfonyl.

The term "alkylsulfonyl as used in this application means alkylsulfonyl group that is defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkylsulfonyl include, but are not limited to, methylsulfonylmethyl and ethylsulfonyl.

The term "alkylthio"as used in this application, means an alkyl group as defined in this application, attached to the original molecular group through a sulfur atom. Representative examples of alkylthio include, but is not limited to this, methylthio, ethylthio, tert-butylthio and hexylthio.

The term "alkylthiomethyl as used in this application means allylthiourea defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of alkylthiomethyl include, but are not limited to, methylthiomethyl and 2-(ethylthio)ethyl.

The term "quinil"as used in this application, means a linear or branched hydrocarbon group containing from 2 to 10 carbon atoms and containing at least one carbon-carbon triple bond. Representative examples of quinil include, but are not limited to, acetylenyl, 1-PROPYNYL, 2-PROPYNYL, 3-butynyl, 2-pentenyl and 1-butynyl.

The term "aryl", as used in this application, means phenyl, bicyclic aryl or tricyclic aryl. Bicyclic aryl represents naphthyl or phenyl condensed with cycloalkyl, or phenyl condensed with cycloalkenyl, or phenyl condensed with a monocyclic heteroaryl ring, as defined in this application, or phenyl fused with a monocyclic heterocycle, as defined in this application. Bicyclic aryl of the present invention must be attached to the original molecular groups is through any available carbon atom, contained in the phenyl ring. Representative examples of bicyclic aryl include, but are not limited to, 2,3-dihydro-1,4-benzodioxin-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl, 3,4-dihydro-2H-1,5-benzodioxepin-6-yl, dihydroindeno, indenyl, indol-4-yl, naphthyl, dihydronaphthalene and tetrahydronaphthalene. Tricyclic aryl represents an anthracene or phenanthrene, or a bicyclic aryl fused with cycloalkyl or bicyclic aryl condensed with cycloalkenyl, or a bicyclic aryl fused with a phenyl. Tricyclic aryl attached to the original molecular group via any carbon atom contained in the tricyclic aryl. Representative examples of tricyclic aryl ring include, but are not limited to, azulene, dihydroanthracene, fluorenyl and tetrahydropyranyl.

Aryl groups of the present invention optionally are substituted by 1, 2, 3, 4 or 5 substituents, independently selected from alkenyl, alkoxy, alkoxyalkyl, alkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylmethyl, alkyl, alkylsulphonyl, alkylcarboxylic, alkylcarboxylic, alkylsulfonyl, alkylsulfanyl, alkylsulfonyl, alkylsulfonyl, alkylthio, alkylthiomethyl, quinil, aryl*NC(O)-, aryl*NHC(O)NH-, carboxy, carboxyamide, cyan is, zainoulline, formyl, formylalkyl, halogen, halogenoalkane, heteroaryl, hydroxy, hydroxyalkyl, mercapto, morpholino, nitro, Z1Z2N - or (Z3Z4N)carbonyl. Aryl*optionally is substituted by 1, 2 or 3 substituents, independently selected from alkyl, halogen, cyano or nitro. Z1and Z2each independently selected from hydrogen, alkyl or alkylsulphonyl.

The term "aryloxy"as used in this application, means an aryl group that is defined in this application, attached to the original molecular group through an oxygen atom. Representative examples of aryloxy include, but are not limited to, phenoxy, naphthyloxy, 3 bromophenoxy, 4-chlorophenoxy, 4-methylphenoxy and 3.5-dimethoxyphenoxy.

The term "aryloxyalkyl as used in this application means alloctype defined in this application, attached to the original molecular group through an alkyl group as defined in this application. Representative examples of aryloxyalkyl include, but are not limited to, 2-phenoxyethyl, 3-naphthas-2-aloxiprin and 3-bromperoxidase.

The term "arylalkyl"as used in this application, means an aryl group that is defined in this application, attached to the original molecular group through alkylenes group, defined the th in this application. Representative examples of arylalkyl include, but are not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl and 2-naphthas-2-ileti.

The term "aryl(hydroxy)alkyl", as used in this application, means an aryl group that is defined in this application, attached to the original molecular group through alkylenes group containing one hydroxy-group defined in this application. Representative examples of aryl(hydroxy)alkyl include, but are not limited to, 2-phenylethanol-2-yl and 2-hydroxy-2-phenylethanol.

The term "arylcarbamoyl"as used in this application, means an aryl group that is defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples of arylcarbamoyl include, but are not limited to, benzoyl and naphtol.

The term "aristeo"as used in this application, means an aryl group that is defined in this application, attached to the original molecular group through a sulfur atom. Representative examples of aaltio include, but are not limited to, phenylthio and 2 naphthylthio.

The term "alltoall as used in this application means killigrew defined in this application, attached to the original molecular group cerealkiller group, defined in this application. Representative examples of alltoall include, but are not limited to, phenylthiomethyl, 2-naphthas-2-indiatel and 5-phenylthiomethyl.

The term "azido"as used in this application, means-N3group.

The term "azidoethyl as used in this application means sidegroup defined in this application, attached to the original molecular group through alkylenes group that is defined in this application.

The term "carbonyl"as used in this application, means-C(O)-group.

The term "carboxy"as used in this application, means-CO2H group.

The term "carboxylic as used in this application means carboxypropyl defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of carboxyethyl include, but are not limited to, carboxymethyl, 2-carboxyethyl and 3-carboxypropyl.

The term "cyano"as used in this application, means-CN group.

The term "cianelli as used in this application means a cyano defined in this application, attached to the original molecular group through alkylenes group that is defined in this bid, medium, small is. Representative examples of cyanoalanine include, but are not limited to, cyanomethyl, 2-cyanoethyl and 3-cyanopropyl.

The term "cycloalkenyl"as used in this application, means a monocyclic or bicyclic ring system containing from 3 to 10 carbon atoms and containing at least one carbon-carbon double bond formed by removing two hydrogen atoms. Representative examples of monocyclic ring systems include, but are not limited to, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl, 2,4-cyclohexadiene-1-yl and 3-cyclopenten-1-yl. Bicyclic ring system presents, as an example, monocyclic cycloalkenyl ring system, which is condensed with another monocyclic cycloalkyl ring defined in this application, monocyclic aryl ring as defined in this application, a monocyclic heterocycle, as defined in this application, or a monocyclic heteroaryl defined in this application. Bicyclic ring system of the present invention must be attached to the original molecular group through an available carbon atom in cycloalkenyl ring. Representative examples of bicyclic ring systems include, but are not limited to, 4,5-dihydro-benzo[1,2,5]OK diazol, 3a,4,5,6,7,7a-hexahydro-1H-indenyl, 1,2,3,4,5,6-hexahydro-pentalen, 1,2, 3,4,4a,5,6,8a-octahydro-pentalene.

The term "cycloalkyl"as used in this application, means a monocyclic, bicyclic or spirocyclic ring system. Monocyclic ring systems are presented, as an example, a saturated cyclic hydrocarbon group containing from 3 to 8 carbon atoms. Examples of monocyclic ring systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Bicyclic cycloalkyl group of the present invention presents, as an example, monocyclic cycloalkyl ring condensed with another monocyclic cycloalkyl ring, or monocyclic cycloalkyl ring condensed with cycloalkenyl, or monocyclic cycloalkyl ring condensed with a phenyl ring, or monocyclic cycloalkyl ring condensed with a monocyclic heteroaryl ring, as defined in this application, or monocyclic cycloalkyl ring condensed with a monocyclic heterocycle, as defined in this application. Bicyclic cycloalkyl ring system according to the present invention must be attached to the original molecular group through access is hydrated carbon atom in monocyclohexyl ring.

Cycloalkyl group of the present invention optionally are substituted by 1, 2, 3 or 4 substituents, selected from alkenyl, alkoxy, alkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonyl, alkyl, alkylsulphonyl, alkylcarboxylic, alkylsulfonyl, alkylthio, alkylthiomethyl, quinil, carboxy, cyano, formyl, halogenoalkane, halogenoalkane, halogen, hydroxy, hydroxyalkyl, mercapto, oxo, Z1Z2N - or (Z3Z4N)carbonyl.

The term "cycloalkenyl as used in this application means cycloalkyl group attached to the original molecular group through an alkyl group as defined in this application.

The term "cycloalkylcarbonyl as used in this application means cycloalkyl group that is defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples of cycloalkylcarbonyl include, but are not limited to, cyclopropylmethyl, 2-cyclobutanecarbonyl and cyclohexylcarbonyl.

The term "formyl"as used in this application, means-C(O)H group.

The term "formylalkyl as used in this application means a formyl group, defined in this application, attached to source the th molecular group through alkylenes group, defined in this application. Representative examples of formylalkyl include, but are not limited to, formylmethyl and 2-formylated.

The term "halo" or "halogen"as used in this application, means-Cl, -Br, -I or-F.

The term "halogenoalkane as used in this application means at least one halogen atom, as defined in this application, attached to the original molecular group through alkoxygroup defined in this application. Representative examples of halogenoalkane include, but are not limited to, chloromethoxy, 2-floratone, triptoreline, pentaverate.

The term "halogenated as used in this application means at least one halogen atom, as defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of halogenoalkane include, but are not limited to, chloromethyl, 2-foretel, trifluoromethyl, pentafluoroethyl and 2-chloro-3-terpencil.

The term "heteroaryl"as used in this application, means a monocyclic heteroaryl or bicyclic heteroaryl. Monocyclic heteroaryl represents a 5-or 6-membered ring containing at least one heteroatom independently selected from O, N or S. the 5-membered ring which ring contains two double bonds and may contain one, two, three or four heteroatoms. 6-membered ring contains three double bonds and may contain one, two, three or four heteroatoms. 5 - or 6-membered heteroaryl linked to the original molecular group via any carbon atom or any nitrogen atom contained in heteroaryl. Representative examples of monocyclic heteroaryl include, but are not limited to, furyl, indazoles, isoxazolyl, isothiazolin, oxadiazolyl, oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl and triazinyl. Bicyclic heteroaryl consists of a monocyclic of heteroaryl condensed with a monocyclic aryl ring as defined in this application, monocyclic cycloalkyl ring defined in this application, monocyclic cycloalkenyl ring defined in this application, other monocyclic heteroaryl or monocyclic heterocyclyl ring defined in this application. Bicyclic heteroaryl ring system of the present invention must be attached to the original molecular group through an available carbon atom in the heteroaryl ring. Bicyclic heteroaryl linked to the original molecular group via any carbon atom or any nitrogen atom, containing the different in the bicyclic heteroaryl. Representative examples of bicyclic heteroaryl include, but are not limited to, benzofuranyl, benzoxazolyl, 1,3-benzothiazolyl, benzimidazolyl, benzodioxolyl, benzothiophene, bromanil, cinnoline, properidine, indolyl, indazoles, isoindolyl, ethenolysis, naphthyridine, oxazolopyridine, chinoline, thienopyridine and thienopyridines.

Heteroaryl groups of the present invention optionally are substituted by 1, 2, 3 or 4 substituents, independently selected from alkenyl, alkoxy, alkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylmethyl, alkoxycarbonyl, alkyl, alkylsulphonyl, alkylcarboxylic, alkylcarboxylic, alkylthio, alkylthiomethyl, quinil, benzyl, carboxy, carboxyamide, cyano, cyanoalanine, formyl, halogenoalkane, halogenoalkane, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, Z1Z2N - or (Z3Z4N)carbonyl. Heteroaryl groups of the present invention, which are substituted, may be present in the form of tautomers. The present invention includes all tautomers, including nonaromatic tautomers.

The term "heteroaromatic"as used in this application, means a heteroaryl group attached to the original molecular group through an alkyl group as defined in this bid, medium, small is.

The term "heterocycle" or "heterocyclic"as used in this application, refers to monocyclic, bicyclic, tricyclic or spiritlessly ring system that contains at least one heteroatom. Monocyclic heterocycle is a 3, 4, 5, 6 or 7-membered ring containing at least one heteroatom independently selected from the group consisting of O, N and S. the 3-or 4-membered ring contains 1 heteroatom selected from the group consisting of O, N and S. the 5-membered ring does not contain or contains one double bond and one, two or three heteroatoms selected from the group consisting of O, N and S. the 6 or 7-membered ring contains no or very contains one or two double bonds and one, two or three heteroatoms selected from the group consisting of O, N and S. the Monocyclic heterocycle is linked to the original molecular group via any carbon atom or any nitrogen atom contained within the monocyclic heterocycle. Representative examples of monocyclic heterocycle include, but are not limited to, azetidine, azepane, aziridinyl, diazepan, 1,3-dioxane, 1,3-DIOXOLANYL, 1,3-dithiolane, 1,3-ditional, imidazolines, imidazolidinyl, isothiazolines, isothiazolinones, isoxazolyl, isoxazolidine, isoindoline-1,3-dione, morpholinyl, oxadiazolyl, oxadiazolidine, oxazol the Nile, oxazolidinyl, piperazinil, piperidinyl, pyranyl, pyrazolyl, pyrazolidine, pyrrolidyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothieno, thiadiazolyl, thiadiazolidine, thiazolyl, diazolidinyl, thiomorpholine, 1,1-dioxythiophene (thiomorpholine), tiopronin and tritional. The bicyclic heterocycle of the present invention is defined as a monocyclic heterocycle fused to the phenyl group, cycloalkyl group defined in this application, cycloalkenyl group defined in this application, another monocyclic heterocyclyl group defined in this application, or spirocycles ring, where one carbon atom monocyclic heterocycle linked to form a bridge two ends alkalinous chain. The bicyclic heterocycle of the present invention is associated with a source of molecular group via any carbon atom or any nitrogen atom contained in a heterocyclic ring. Representative examples of bicyclic heterocycle include, but are not limited to, 1,3-benzodioxolyl, 1,3-benzodithiol, 2,3-dihydro-1,4-benzodioxolyl, 2,3-dihydro-1-benzofuranyl, 2,3-dihydro-1-benzothieno, 3,4-dihydro-1H-isochroman-4-yl, 2,3-dihydro-1H-indolyl, Succinimidyl and 1,2,3,4-tetrahydroquinoline. Tetracyclic heterocycle is bellicheck the th heterocycle, condensed with phenyl, or the bicyclic heterocycle condensed with cycloalkyl, or the bicyclic heterocycle condensed with cycloalkenyl, or the bicyclic heterocycle fused to a monocyclic heterocycle. Tetracyclic heterocycle linked to the original molecular group via any carbon atom or any nitrogen atom contained in tricyclic heterocycle. Representative examples of tricyclic heterocycle include, but are not limited to, 2,3,4,4a,9,9a-hexahydro-1H-carbazolyl, 5a,6,7,8,9,9a-hexahydrobenzo[b,d]furanyl and 5a,6,7,8,9,9a-hexahydrobenzo[b,d]thienyl.

The heterocycles of the present invention optionally are substituted by 1, 2 or 3 substituents, independently selected from alkenyl, alkoxy, alkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylmethyl, alkoxycarbonyl, alkyl, alkylsulphonyl, alkylcarboxylic, alkylcarboxylic, alkylthio, alkylthiomethyl, quinil, aryl, benzyl, carboxy, carboxyamide, cyano, cyanoalanine, formyl, halogenoalkane, halogenoalkane, halogen, hydroxy, hydroxyalkyl, hydroxycarbonyl, hydroxyethoxyethyl, mercapto, oxo, Z1Z2N - or (Z3Z4N)carbonyl.

The term "heterocyclyl as used in this application means heterocyclyl group, to recognize the military to the original molecular group through an alkyl group, defined in this application.

The term "heterocyclicamines"as used in this application, means a heterocycle, as defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application.

The term "hydroxy"as used in this application, means-OH group.

The term "hydroxyalkyl as used in this application means at least one hydroxy-group defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of hydroxyalkyl include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxybutyl and 2-ethyl-4-hydroxyethyl.

The term "hydroxycarbonyl as used in this application means a hydroxyalkyl group that is defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples include, but are not limited to, 2-hydroxyacetic and 4-hydroxybutanoic.

The term "hydroxyalkoxy as used in this application means hydroxyalkoxy defined in this application, attached to the original molecule the Noah group through alkylenes group, defined in this application. Representative examples of hydroxyethoxyethyl include, but are not limited to, (2-hydroxy-ethoxy)-ethyl 3-hydroxy-propoxy)-ethyl.

The term "hydroxy-protective group" or "O-protective group" means the Deputy, which protects hydroxyl groups against undesirable reactions during synthetic procedures. Examples of hydroxy-protecting groups include, but are not limited to, substituted simple methyl esters, for example, methoxymethyl, benzoyloxymethyl, 2-methoxyethoxymethyl, 2-(trimethylsilyl)-ethoxymethyl, benzyl and triphenylmethyl; tetrahydropyranyl ethers; substituted ethyl simple esters, for example, 2,2,2-trichlorethyl and tert-butyl; Silovye esters, for example, trimethylsilyl, tert-butyldimethylsilyl and tert-butyldiphenylsilyl; cyclic acetals and ketals, for example, metronatural, acetonide and benzylideneacetone; cyclic complex of ortho-esters, for example, methoxymethyl; cyclic carbonates; cyclic boronate. Traditionally used hydroxy-protective group are disclosed in T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons, New York (1999).

The term "mercapto"as used in this application, means-SH group.

The term "nitrogen-protective group"as used in this application means a group, which are designed to protect aminopropyl undesirable reactions during synthetic procedures. The preferred nitrogen-protective groups are acetyl, benzoyl, benzyl, benzyloxycarbonyl (Cbz), formyl, phenylsulfonyl, tert-butoxycarbonyl (Boc), tert-butylacetyl, TRIFLUOROACETYL and triphenylmethyl (trityl).

The term "nitro"as used in this application, means-NO2group.

The term "trialkylsilyl as used in this application means three independently chosen alkyl groups as defined in this application, attached to the original molecular group through an atom of silicon. Representative examples trialkylsilyl include, but are not limited to, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl and triisopropylsilyl.

The term "trialkylsilyl as used in this application means trialkylsilyl group that is defined in this application, attached to the original molecular group through alkylenes group that is defined in this application. Representative examples of trialkylsilyl include, but are not limited to, trimethylsilylmethyl, 2-trimethylsilylmethyl and 2-tert-butyldimethylsilyl.

The term "Z1Z2N", as used in this application, means two groups, Z1and Z2that are attached to the original molecular group through a nitrogen atom. Z1and Z2, each independently, represent with the battle hydrogen, alkoxycarbonyl, alkyl, alkylaryl, aryl, arylalkyl and formyl. In some cases, in the present invention, Z1and Z2taken together with the nitrogen atom to which they are linked, form a heterocyclic ring. Representative examples of Z1Z2N include, but are not limited to, amino, methylamino, acetylamino, acetylecholine, phenylamino, benzylamino, azetidine, pyrrolidine and piperidine.

The term " Z3Z4N", as used in this application, means two groups, Z3and Z4that are attached to the original molecular group through a nitrogen atom. Z3and Z4, each independently, represent hydrogen, alkyl, aryl and arylalkyl. Representative examples of Z3Z4N include, but are not limited to, amino, methylamino, phenylamino, benzylamino.

The term "(Z3Z4N)carbonyl"as used in this application means NZ3Z4the group defined in this application, attached to the original molecular group through a carbonyl group that is defined in this application. Representative examples (Z3Z4N)carbonyl include, but are not limited to, aminocarbonyl, (methylamino)carbonyl, (dimethylamino)carbonyl, and (ethylmethylamino)carbonyl.

The term "oxo"as used in this application means the s =O group.

The term "sulfinil"as used in this application, means-S(O)- group.

The term "sulfonyl"as used in this application, means-SO2group.

The term "sulfonamide"as used in this application, means-SO2NH2group.

The term "tautomer"as used in this application means a shift of a proton from one atom in connection to another atom in the same connection, where two or more structurally different compounds are in equilibrium with each other.

Compounds of the present invention can exist as stereoisomers, where there are asymmetric or chiral centers. These stereoisomers are "R" or "S" depending on the configuration of substituents around the chiral carbon atom. The terms "R" and "S"used in this application means the configuration defined in the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem., 1976, 45:13-30. The present invention contemplates various stereoisomers and mixtures thereof, and they are specifically included in the scope of the present invention. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of compounds of the present invention can be obtained by synthetic methods from commercially available starting compounds to the e contain asymmetric or chiral centers, or by obtaining racemic mixtures followed by separation, which is well known to specialists in this field. Such methods of separation are, as example, (1) the accession of a mixture of enantiomers to a chiral auxiliary substance, separating the resulting mixture of diastereomers by recrystallization or chromatography and isolation of optically pure product from the auxiliary substance; or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns.

Compounds and methods of the present invention will be better understood by reference to the following Examples, which are intended to illustrate and not to limit the scope of the present invention. In addition, all references available in this application, incorporated by reference.

The names of the compounds are indicated using the program name Name Pro, a provider which is ACD/Labs. Alternatively, the names of the compounds are indicated using the AUTONOM name, a provider which is a company MDL Information Systems GmbH (formerly known as Beilstein Informationssysteme), Frankfurt, Germany, and it is part of the set of programs CHEMDRA W® ULTRA v. 6.0.2 and ISIS Draw v. 2.5. Also, the names of the compounds are indicated using the algorithm name Struct=Name, which is part of a set of programs CHEMDRA W® ULTRA v. 9.0.7.

Abbreviations

Abbreviations used in the descriptions of the Schemes and in the Examples below, the following: DMF for N,N-dimethylformamide, DMSO for dimethyl sulfoxide, EtOAc for ethyl acetate, CHCl3for chloroform, CH2Cl2for dichloromethane, CH3CN for acetonitrile, THF for tetrahydrofuran, HATU for hexaphosphate O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea, EDC or EDCI hydrochloride for 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, LC/MS liquid chromatography/mass spectroscopy, NH4OAc for acetate of ammonium, NaBH(OAc)3for triacetoxyborohydride sodium PBS for bovine serum albumin, PBS for phosphate buffered saline, TMS for trimethylsilyl, MW for microwave irradiation, DMAP for 4-(dimethylamino)pyridine, dppf for 1,1'-bis(diphenylphosphino)ferrocene, TFU for triperoxonane acid, BINAP for 2,2'-bis(diphenylphosphino)-1,1'-binfile, TBAF for tetrabutylammonium, Tween for polyoxyethylenesorbitan, HPLC for high performance liquid chromatography, DME for 1,2-dimethoxyethane, Boc for tert-butoxycarbonyl, BSA for bovine serum albumin, DTT for dithiothreitol, ATP for ATP, EDTA for ethylenediaminetetraacetic acid, HPMC for hydroxypropylmethylcellulose, TMB for 3,3',5,5'-tetramethylbenzidine and HEPES for 4-(2-hydroxyethyl)-1-PIP is reinacastellano acid.

Obtaining the compounds of the present invention

Compounds and methods of the present invention will be better understood in connection with the following synthesis Schemes and Examples that illustrate the means by which it is possible to obtain the compounds of the present invention.

Scheme 1

As shown in Scheme 1, compounds of formula 2, which are typical representatives of compounds of formula (I)can be obtained as follows. The compounds of formula 1, where R1and R2defined in formula (I) and X1represents iodine, bromine or chlorine, and which can be obtained from commercial sources or can be synthesized in accordance with methods known from the literature, when processing reagent And-M1where A has the meaning given in formula (I), and M1represents-Sn(Rz)3or-B(ORy)2where Rzrepresents alkyl or aryl and Ryrepresents hydrogen, alkyl, aryl, or two groups Rytogether with the boron atom to which they are bound, form a 1,3-dioxaborolane, in the presence of palladium catalyst to provide compounds of formula 2. In such reactions between the compounds of formula 1 and compounds of the formula Sn(Rz)3widely known as combination method Steele is e, use a palladium catalyst, such as, but not limited to, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), Tris(dibenzylideneacetone)dipalladium or palladium diacetate, in the presence or in the absence of ligand, such as tri(2-furyl)phosphine or triphenylarsine, in a solvent such as toluene or DMF, at a temperature from about 25°C to about 150°C. in Addition, can be added to salt Li(I), Cu(I) or Mn(II) to improve the reactivity or specificity. In the reaction between compounds of formula 1 and compounds of the formula B(ORy)2widely known as binding by the method of Suzuki, the use of palladium catalysts, such as, but not limited to, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), Tris(dibenzylideneacetone)dipalladium or palladium diacetate. You can add a ligand of palladium, such as 2-(dicyclohexylphosphino)biphenyl, tri-tert-butylphosphine or Tris(2-furyl)phosphine, and a base, such as, but not limited to, water K3PO4, cesium carbonate, potassium carbonate or Na2CO3,in solvents such as toluene, dimethoxyethane, dioxane, water or DMF, at a temperature from about 25°C to about 150°C. the Reaction can also be carried out by heating in the reactor, which represents a microwave.

Hot the many organostannic are commercially available or described in the literature, you can also get additional stannane from A-halides or-triflates by processing hexa-alkylbetaine formula ((Rz)3Sn)2in the presence of Pd(Ph3P)4. Similarly, in the absence of commercially available organoboron reagents, -B(ORy)2can be obtained from the corresponding halides or triflates (A-halogen or-triplet) via metallome with organolithium compound and then adding alkylborane.

Scheme 2

The compounds of formula 2 where R1and R2defined in formula (I), and A is a heteroaryl ring, associated with the original group through the nitrogen atom, can be obtained as illustrated in Scheme 2. Treatment of compounds of formula I with a reagent of formula A-H, where H is a hydrogen on a nitrogen atom contained in the heteroaryl ring A, in the presence of a base such as, but not limited to, tert-piperonyl sodium or cesium carbonate, and a metal catalyst, such as, but not limited to, metallic copper, CuI or palladium diacetate, and optionally with a ligand such as, but not limited to, BINAP or three-tert-butylphosphine, will provide compounds of formula 2.

Scheme 3

As described above for Scheme 1, compound f is rmula (I) can be synthesized by using the keyboard according to the method of the Steele, as described in Scheme 3. The compounds of formula 3, where Riihas the meaning given in formula (I), and compounds of formula 4 where R1has the meaning given in formula (I), and P1is a nitrogen protective group, such as, but not limited to, tert-butyloxycarbonyl or acetyl, in the presence of dichlorobis(triphenylphosphine)palladium(II) and (thiophene-2-carbonyloxy)copper, in toluene, in conditions of heat, will provide compounds of formula 5. The compounds of formula 5, processing conditions, known as used for removal of the protective group, such as hydrochloric acid or triperoxonane acid in a solvent such as acetic acid or dioxane, when the protective group is a tert-butyloxycarbonyl, or sodium hydroxide, lithium hydroxide or potassium hydroxide in an aqueous mixture of THF, isopropanol or dioxane, when the protective group is an acetyl, will provide compounds of formula 6, which are typical representatives of compounds of formula (I) where A is a (ii).

Scheme 4

The compounds of formula 3 used in Scheme 3 to obtain the compounds of formula (I)can be obtained as shown in Scheme 4. The compounds of formula 7, which is obtained from commercial sources or which can is about to receive in accordance with the methods, well-known experts in this field, while processing them or 1,1,1-tributyl-N,N-dimethylethanamine or methyl ethyl(tributylstannyl)carbamate, will provide compounds of formula 8. Alkynes of formula 8, when heated in the presence of compounds of formula 9, where Riihas the meaning given in formula (I), and N3represents azide, will provide compounds of formula 3.

Scheme 5

As shown in Scheme 5, compounds of formula 12, which are typical representatives of compounds of formula (I), where A is a (ii)can be obtained as follows. The compounds of formula 10, where R1has the meaning given in formula (I), and X1represents iodine, bromine, chlorine or triflate, and TMS-acetylene in the presence of copper iodide, dichlorobis(triphenylphosphine)palladium(II) and triethylamine, followed by treatment with tetrabutylammonium or potassium hydroxide, will provide compounds of formula 11. The reaction can be carried out in a solvent such as, but not limited to, DMF, at ambient temperature or under conditions of heating. The compounds of formula 11, and Rii-Cl, sodium azide, copper sulfate and metallic copper, in terms of heating, in a solvent such as dioxane, will provide compounds f is rmula 12, which are the typical representatives of compounds of formula (I), where A is a (ii).

Scheme 6

Alternatively, the compounds of formula 13, and TMS-acetylene in the presence of copper iodide, dichlorobis(triphenylphosphine)palladium(II) and triethylamine, followed by treatment with tetrabutylammonium or potassium hydroxide, will provide compounds of formula 14. The reaction can be carried out in a solvent such as, but not limited to, DMF, at ambient temperature or under conditions of heating. The compounds of formula 14, when treating compounds of formula 9, where Riihas the meaning given in formula (I), or sodium azide, copper sulfate and metallic copper in the heating conditions will provide compounds of formula 15. The compounds of formula 15, when heated in the presence of hydrazine in ethanol, will provide compounds of formula 16. The compounds of formula 16, and di-tert-BUTYLCARBAMATE and catalytic amount of DMAP in a solvent such as THF or acetonitrile, will provide compounds of formula 17. The compounds of formula 17, when treating compounds of formula 18 in the presence of a base such as, but not limited to, pyridine, in a solvent such as dichloromethane, followed by treatment triperoxonane Ki is LOTOS will provide compounds of formula 19. The compounds of formula 16, when processing carboxylic acid using the conditions of the binding of carboxylic acid-amine, known to specialists in this field, will provide compounds of formula 19A. Standard conditions for the binding of carboxylic acid-amine include the addition of a binding reagent, such as, but not limited to, hydrochloride, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 1,3-dicyclohexylcarbodiimide (DCC), the acid chloride of bis(2-oxo-3-oxazolidinyl)phosphinic acid (BOPCl), hexaflurophosphate O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea (HATU) or tetrafluoroborate O-benzotriazol-1-yl-N,N,N',N'-tetramethylurea (TBTU), with or without excipients, such as, but not limited to, 1-hydroxy-7-asobancaria (HOAT) or the hydrate of 1-hydroxybenzotriazole (HOBT), in a solvent such as, but not limited to, dichloromethane.

Scheme 7

The compounds of formula 24, which are typical representatives of compounds of formula (I)can be obtained as follows. The compounds of formula 20 where X1represents a halogen or triflate, when treating a compound of formula 21, acetic anhydride and a base such as, but not limited to, potassium acetate, in the conditions of the heating will provide compounds of formula 22. Link the formula 22, when handling sodium azide, copper sulfate, base, such as sodium carbonate, and compounds of formula 23, where Riihas the meaning given in formula (I), and are either available from commercial sources or can be obtained by specialists in this field, will provide compounds of formula 24.

Scheme 8

As shown in Scheme 8, compounds of formula 29 and 30, which are typical representatives of compounds of formula (I)can be obtained as follows. The compounds of formula 25, where R1has the meaning given in formula (I), and X1represents a halogen or triflate, when treating compounds of formula 23, copper iodide, dichlorobis(triphenylphosphine)palladium(II) and triethylamine in DMF, at ambient temperature or heating conditions will provide compounds of formula 27. The compounds of formula 27, when treating compounds of formula 9 in the conditions of heating and either without solvent or in a solvent such as, but not limited to, dioxane, will provide compounds of formula 29 and 30.

Scheme 9

The compounds of formula 32, which are typical representatives of compounds of formula (I), where A is a (vii) and R1and RViidefined in formula (I), could the t can be obtained as follows. Aldehydes of formula 31, where Rviihas the meaning given in formula (I), which can be obtained from commercial sources, as they are processed by the hydroxylamine hydrochloride and an aqueous solution of sodium hydroxide, will provide an intermediate oxime compound, which, when oxidized by Chloramine T trihydrate, followed by treatment with copper sulphate and copper wire and compounds of the formula 11, will provide compounds of formula 32.

Scheme 10

The compounds of formula 38, which are typical representatives of compounds of formula (I), where A is a (x), obtained as follows. The compounds of formula 33, where R1has the meaning given in formula (I), which can be obtained from commercial sources or can be obtained by specialists in this field, and N,O-dimethylhydroxylamine using acidic conditions binding, well-known experts in this field, will provide compounds of formula 34. Standard conditions for the binding of carboxylic acid-amine include the addition of a binding reagent, such as, but not limited to, hydrochloride, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 1,3-dicyclohexylcarbodiimide (DCC), the acid chloride of bis(2-oxo-3-oxazolidinyl)phosphinic acid (BOPCl), Huck is atorvastat O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea (HATU) or tetrafluoroborate O-benzotriazol-1-yl-N N,N',N'-tetramethylurea (TBTU), with or without excipients, such as, but not limited to, 1-hydroxy-7-asobancaria (HOAT) or the hydrate of 1-hydroxybenzotriazole (HOBT), in a solvent such as, but not limited to, dichloromethane. The compounds of formula 34, and a Grignard reagent, such as benzylacrylamide, in a solvent such as tetrahydrofuran, at a temperature below the ambient temperature will provide compounds of formula 35. The compounds of formula 35, and a reagent, which represents a protective group such as, but not limited to, di-tert-BUTYLCARBAMATE, and a catalytic amount of DMAP in a solvent such as THF or acetonitrile, will provide compounds of formula 36. The compounds of formula 36, when they are processed by tribromide pyridinium in a solvent such as, but not limited to, THF, with heating or without heating will provide compounds of formula 36 A. the compounds of formula 36 A, and compounds of formula 37 with heating or without heating, with subsequent processing of the product, subjecting it to conditions that remove nitrogen protective group, will provide compounds of formula 38. Traditionally used nitrogen-protective groups and methods for their removal are disclosed in T.W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons, New York (1999).

<> Scheme 11

The compounds of formula 36, where R1has the meaning given in formula (I), and P1is a nitrogen protective group, and compounds of formula 39 under conditions of heat, with subsequent processing of the product, subjecting it to the conditions which, as is known to experts in this field, remove the nitrogen protective group, or as shown in the literature, will provide compounds of formula 40, which are typical representatives of compounds of formula (I), where A is a (xvii).

Scheme 12

As shown in Scheme 12, compounds of formula 47, which are typical representatives of compounds of formula (I), where A is a (x)can be obtained as follows. The compounds of formula 41, where R1has the meaning given in formula (I), and di-tert-BUTYLCARBAMATE and catalytic amount of DMAP in a solvent such as THF or acetonitrile, will provide compounds of formula 42. Treatment of compounds of formula 42 tributyl(1-ethoxyphenyl)stannane and dichlorobis(triphenylphosphine)palladium(II) will provide compounds of formula 44. The compounds of formula 44, when they are processed by tribromide pyridinium in THF will provide compounds of formula 45. The compounds of formula 45, when their processing is TKE compounds of formula 46 in the solvent, such as, but not limited to, ethanol, where Rxhas the meaning given in formula (I), will provide compounds of formula 47.

Scheme 13

As shown in Scheme 13, compounds of formula 51, which are typical representatives of compounds of formula (I), where A is a (iv)can be obtained as follows. The compounds of formula 48, where R1has the meaning given in formula (I), and which are either available through commercial sources or can be obtained in accordance with the procedures described in the literature, or as shown in this application, when heated in the presence of compounds of formula 49 and the compounds of formula 50, which are either commercially available or can be obtained by specialists in this field, using the procedures described in the literature, will provide compounds of formula 51.

Scheme 14

As shown in Scheme 14, compounds of formula 55, which are typical representatives of compounds of formula (I), where A is a (xiv), (xv), (xvi) or (xvii)can be obtained as follows. The compounds of formula (52), where R1has the meaning given in formula (I), when they are processed by butyllithium with subsequent processing of DMF, and then the acid treatment is rigid, will provide compounds of formula 48. The compounds of formula 48, when treating compounds of formula 51 where X represents-CH-, -N - or-S-, Y is-CH-, -N - or connection, and three(triplet)ω scandium, followed by treatment of compounds of formula 54, where Zadefined in formula (I), will provide compounds of formula 55.

Scheme 15

As shown in Scheme 15, compounds of formula 56, which are typical representatives of compounds of formula (I), where A is a (vii)can be obtained as follows. The compounds of formula (11), where R1has the meaning given in formula (I), when their treatment with a reagent such as, but not limited to, ethyl 2-chloro-2-(hydroxyimino)acetate, a base such as, but not limited to, triethylamine, will provide compounds of formula 56. The reaction can be carried out in a solvent such as, but limited to, toluene, and may require the application of heat.

Scheme 16

As shown in Scheme 16, compounds of formula 29, which are typical representatives of compounds of formula (I), where A is a (ii)can be obtained as follows. The compounds of formula (27), where R1has the meaning given in formula (I), and the connection form is s 9, RiiC(O)Cl or ICl, CuI and triethylamine in a solvent such as, but not limited to, tetrahydrofuran (THF will provide compounds of formula 29. The reaction may be carried out at ambient temperature or with heating.

Scheme 17

As shown in Scheme 17, compounds of formula 57, which are typical representatives of compounds of formula (I), where A is a (vi)can be obtained as follows. The compounds of formula 45, where R1has the meaning given in formula (I), when they are processed by ammonium formate and formic acid, will provide a compound of formula 57.

Scheme 18

As shown in Scheme 18, compounds of formula 58, which are typical representatives of compounds of formula (I), where A is a (vii)can be obtained as follows. The compounds of formula 48, where R1has the meaning given in formula (I), and nitromethane, will provide compounds of formula 58 (Organic Preparations and Procedures International, 2001, 33, 381-386).

Scheme 19

As shown in figure 19, the compounds of formula 60, which are typical representatives of compounds of formula (I), where A is a (vi)can be obtained as follows. Connection formula, where R1has the meaning given in formula (I), and 1-(isocyanatomethyl)-4-methylbenzoate, 59, and a suitable base, such as, but not limited to, potassium carbonate, in a solvent such as methanol or tetrahydrofuran, followed by treatment with a suitable acid, such as hydrochloric acid will provide compounds of formula 60.

Scheme 20

As shown in Scheme 20, the compounds of formula 63, which are typical representatives of compounds of formula (I), where A is a (vi)can be obtained as follows. The compounds of formula 33, where R1has the meaning given in formula (I), and suitable gloriouse agent such as thionyl chloride, will provide compounds of formula 61. The compounds of formula 61, and 2-(trimethylsilyl)-2H-1,2,3-triazole, 62, in a solvent such as sulfolane, will provide a compound of formula 63.

Scheme 21

As shown in Scheme 21, the compounds of formula 66, which are typical representatives of compounds of formula (I), where A is a (ix)can be obtained as follows. The compounds of formula 61, where R1has the meaning given in formula (I), when treatment with hydrazine in a suitable solvent is, such as tetrahydrofuran, will provide compounds of formula 64. The compounds of formula 64, when they are processed by triethylorthoformate, 65, in the presence of catalytic amount of p-toluensulfonate acid in a solvent such as tetrahydrofuran, will provide compounds of formula 66.

Scheme 22

As shown in Scheme 22, the compounds of formula 69, which are typical representatives of compounds of formula (I), where A is defined in formula (I)can be obtained as follows. The compounds of formula 67, where Ryrepresents hydrogen, alkyl, aryl, or two groups Rytogether with the boron atom to which they are bound, form a 1,3-dioxaborolane, in the presence of a palladium catalyst using Suzuki reaction conditions described in Scheme 1 in the presence of heteroaromatic (A-I) to provide the compounds of formula 68. The compounds of formula 68 is converted into the compounds of formula 69 by treatment with hydrazine, as described in Scheme 6.

Scheme 23

As shown in Scheme 23, the compounds of formula 74, which are typical representatives of compounds of formula (I), where Riiand R4have the meanings given for formula (I)receive, from the compounds of formula 70, where X1represents iodine, bromine or chlorine. Processing the connection is s formula 70 first hydrazine, and then di-tert-BUTYLCARBAMATE as described in Scheme 6, gives the compounds of formula 71. The compounds of formula 71, in their interaction with the anhydrides of the acids of formula 18 in the presence of a base such as potassium carbonate in tetrahydrofuran, at ambient temperature, for 2 to 8 hours to provide compounds of formula 72. Alternatively, the compounds of formula 72 can be obtained from compounds of formula 71 using conditions described in Scheme 6. The compounds of formula 72 is subjected to interaction with (trimethylsilyl)acetylene in the conditions described in Schemes 5 and 6, to obtain the compounds of formula 73. The compounds of formula 74 obtained from compounds of formula 73 by processing Rii-N3in aqueous tert-butanol, in the presence of copper sulfate(II) and (R)-2-((S)-1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydrofuran-3-olate sodium at 40-80°C for a time from 1 to 6 hours.

Scheme 24

As shown in Scheme 24, the compounds of formula 76, which are typical representatives of compounds of formula (I), where A and R4defined for formula (I), are obtained from compounds of formula 75. The compounds of formula 75 you can handle-B(ORy)2where A has the values defined for formula (I), and Ryrepresents hydrogen, alkyl, aryl, or two groups Rytogether with the boron atom, with the cat is the ring they are attached, form a 1,3-dioxaborolane, in the presence of a palladium catalyst, using Suzuki reaction conditions described in Scheme 1, to obtain the compounds of formula 76.

Scheme 25

As shown in Scheme 25, the compounds of formula 80, which are typical representatives of compounds of formula (I), where Riiand R4defined for formula (I), obtained as follows. The compounds of formula 77 and 78 are subjected to interaction in terms of the binding according to the method of the Steele described in Scheme 3 to give compounds of formula 79. The compounds of formula 79, in the interaction, as described in Scheme 6, to provide the compounds of formula 80.

Scheme 26

As shown in figure 26, the compounds of formula 82, 83., 84 and 85, which are typical representatives of compounds of formula (I), where A, R4, R5, Raand Rjhave the meanings given for formula (I), are obtained from compounds of formula 81. The compounds of formula 81 can be treated with the acid chloride of the acid, 18, in a solvent such as tetrahydrofuran, in the presence of a base such as potassium carbonate or triethylamine, to obtain the compounds of formula 82. Alternative solvent is dichloromethane and the alternative base is pyridine. The anhydrides of the acids can be obtained from suitable the carboxylic acid by treatment with oxalylamino with a catalytic amount of N,N-dimethylformamide. To obtain the compounds of formula 83, the compounds of formula 81 can be processed RjNCO in hot pyridine. The compounds of formula 84 obtained from compounds of formula 81 by processing R5SO2Cl in pyridine at room temperature or so. The compounds of formula 85 also obtained from compounds of formula 81 in the reaction of reductive amination with RaCHO in the presence of a reducing agent, such as triacetoxyborohydride sodium or cyanoborohydride sodium and acetic acid in a solvent such as 1,2-dichloroethane at room temperature or so, and with the subsequent processing triperoxonane acid in dichloromethane to remove the tert-butoxycarbonyl protective group.

Scheme 27

As shown in figure 27, the compounds of formula 87, where A, Rjand Rkdefined for formula (I)can be obtained from compounds of formula 86. The compounds of formula 86 receive, as described for compounds of formula 82 in Scheme 26. The compounds of formula 86 can then be subjected to heat in the presence of amine, HNRjRkand the base, such as triethylamine, in a solvent such as acetonitrile, to obtain the compounds of formula 87. Alternatively, the amine can be substituted heterocycles, such as pyrrolidine, piperidine, piperazine and morpholine.

Scheme 28

As shown in Scheme 28, the compounds of formula 89, where A, R1, R2, R3, m, Zcand Zddefined for formula (I)can be obtained from compounds of formula 88. The compounds of formula 88 can be obtained as described in Schemes 1-4, 7-9, 22, 24 and 26. In the process of producing compounds of formula 88, carbonisation group as the side chain in A can be protected in the form of ester and then hydrolyzed, leaving the carboxylic acid of the open without protection, by methods known to experts in the field of organic synthesis. The compounds of formula 88, and Amin (HNZcZd) using the conditions of the binding of carboxylic acid-amine, known to specialists in this field, will provide compounds of formula 89. Standard terms and conditions binding the carboxylic acid - amine include the addition of a binding reagent, such as, but not limited to, hydrochloride, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 1,3-dicyclohexylcarbodiimide (DCC), the acid chloride of bis(2-oxo-3-oxazolidinyl)phosphinic acid (BOPCl), hexaflurophosphate O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea (HATU) or tetrafluoroborate O-benzotriazol-1-yl-N,N,N',N'-tetramethylurea (TBTU), optionally in the presence of a base such as triethylamine or diisopropylethylamine, with or without excipients, t is whom, but not limited to, 1-hydroxy-7-asobancaria (HOAT) or the hydrate of 1-hydroxybenzotriazole (HOBT), in a solvent such as, but not limited to, dichloromethane or N,N-dimethylformamide.

EXAMPLES

Compounds and methods of the present invention will be better understood by reference to the following examples, which are intended to illustrate and not limit the scope of the present invention.

Example 1

5-(1-benzyl-1H-1,2,3-triazole-5-yl)-1H-indazol connection with 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazole

Example 1A

tert-Butyl 5-iodine-1H-indazol-1-carboxylate

It chilled in an ice bath to a solution of 4-iodine-2-methylaniline (20 g, 83,24 mmol) in chloroform (250 ml) was added dropwise a solution of acetic anhydride (21.2 g, 208,11 mmol) in chloroform (50 ml). Upon completion of the addition the mixture was stirred at room temperature for 1 hour. Was added potassium acetate (2.5 g, 24,97 mmol) and isoenergetic (22,3 ml, 166,48 mmol) and the mixture was heated at 70°C for 20 hours. The mixture was cooled and extinguished saturated aqueous NaHCO3to pH 7. The mixture was extracted with dichloromethane and the organic phase was dried over sodium sulfate and filtered. The solvent is evaporated under reduced pressure. The crude solid was washed with methanol, was dissolved in tetrahydrofuran (200 ml) and treated with a warm solution of KOH (0 g) in water (200 ml). The mixture was stirred for 15 minutes and was treated with 6N HCl solution to pH 1. The layers were separated, the organic layer was dried over sodium sulfate and filtered and the solvent evaporated under reduced pressure. The crude solid was dissolved in dichloromethane (500 ml) was added triethylamine (23 ml, 166,48 mmol) and di-tert-BUTYLCARBAMATE (23,6 g to 108.2 mmol) and a catalytic amount of dimethylaminopyridine (~ 5 mg). The mixture was stirred at room temperature for 2 hours, diluted with water, was extracted with dichloromethane, dried with sodium sulfate and filtered. The solvent is evaporated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 344,9 (M+H)+.

Example 1B

tert-Butyl 5-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate

The compound of Example 1A (10,81 g of 31.4 mmol), dichlorobis(triphenylphosphine)palladium(II) (1.1 g, 1.57 mmol) and copper iodide(I) (365 mg, 1.92 mmol) were combined in triethylamine (70 ml) in an inert atmosphere. Added trimethylsilylacetamide (5.0 ml, 36,0 mmol) and the mixture was stirred at 60°C over night. The solvent was removed under reduced pressure and the obtained residue was dissolved in methylene chloride and washed with 1 n hydrochloric acid. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% e is racette in hexane, obtaining specified in the connection header. MS (ESI+) m/z 215,0 (M-99)+.

Example 1C

5-Ethinyl-1H-indazol

The compound of Example 1B (of 7.93 g of 25.2 mmol) was dissolved in methanol (150 ml). Added 1 n solution of potassium hydroxide (50 ml) and the mixture was stirred at ambient temperature for 1 hour. The solvent was removed under reduced pressure and the resulting slurry was dissolved in ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over sodium sulfate and filtered and the solvent was removed under reduced pressure to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,24 (s, 1H), 8,10 (s, 1H), 7,95 (s, 1H), 7,55 (d, J=8,82 Hz, 1H), 7,39 (DD, J=8,48, of 1.36 Hz, 1H), 4,03 (s, 1H).

Example 1D

5-(1-benzyl-1H-1,2,3-triazole-5-yl)-1H-indazol connection with 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazole

In a container for microwave heating was added to 100.0 mg (0.70 mmol) of the compound of Example 1C and 94 mg (0.70 mmol) benserazide. The mixture was heated at 160°C for 20 minutes using microwave irradiation (CEM-Discover, 100 Watts, time temperature rises to the specified level is 1 minute). The mixture was dissolved in ethyl acetate and was purified using chromatography on silica gel by elution with 75% ethyl acetate in hexane, to obtain specified in the header connections. H NMR (300 MHz, DMSO-d6) δ ppm 13,28 (s, 1H, 13,12 (s, 1H), 8,61 (s, 1H), 8,23 (s, 1H), 8,13 (s, 1H), 8,11 (s, 1H), 7,94 (s, 1H), 7,82-7,89 (m, 2H), 7,56-of 7.70 (m, 2H), 7,20-7,44 (m, 9H), 6,97-7,02 (m, 2H), 5,69 (s, 2H), 5,65 (s, 2H). MS (CI) m/z 276 (M+H)+.

Example 2

5-(1H-1,2,3-triazole-5-yl)-1H-indazol

In a container for microwave heating was added to 100.0 mg (0.70 mmol) of the compound of Example 1C, 81 mg (0.7 mmol) trimethylsilane, CuI (4 mg) and dimethylformamide/methanol (1 ml, 9:1). The mixture was heated at 160°C for 20 minutes using microwave irradiation (CEM-Discover, 100 Watts, time temperature rises to the specified level is 1 minute). The mixture was dissolved in ethyl acetate and the organic layer was washed with water. The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure and was purified using chromatography on silica gel by elution with 80% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,16 (s, 1H), 8,31 (s, 1H), of 8.25 (s, 1H), 8,13 (s, 1H), 7,87 (d, J=8,82 Hz, 1H), 7.62mm (d, J=8,82 Hz, 1H). MS (CI) m/z 186 (M+H)+.

Example 3

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Example 3A

tert-Butyl 5-iodine-1H-indazol-1-carboxylate

It chilled in an ice bath to a solution of 4-iodine-2-methylaniline (20 g, 83,24 mmol) in chloroform (250 ml) was added dropwise via an addition funnel a solution of acetic anhydride (21.2 g, 208,11 mmol) in chloroform (50 ml). Upon completion of the addition the mixture peremeshivaniya room temperature for 1 hour. Was added potassium acetate (2.5 g, 24,97 mmol) and isoenergetic (22,3 ml, 166,48 mmol) and the mixture was heated at 70°C for 20 hours. The mixture was then cooled and extinguished saturated aqueous NaHCO3to pH 7. The mixture was extracted with dichloromethane, dried over sodium sulfate, filtered and the solvent evaporated under reduced pressure. The crude solid was washed with methanol, was dissolved in tetrahydrofuran (200 ml) and treated with a warm solution of KOH (60 g) in water (200 ml). The mixture was stirred for 15 minutes and was treated with 6N HCl solution to pH 1. The layers were separated, the organic layer was dried over sodium sulfate and filtered and the solvent evaporated under reduced pressure. The crude substance was dissolved in dichloromethane (500 ml) and triethylamine (23 ml, 166,48 mmol) was added di-tert-BUTYLCARBAMATE (23,6 g to 108.2 mmol) and a catalytic amount of dimethylaminopyridine (~5 mg). The mixture was stirred at room temperature for 2 hours, extinguished with water, was extracted with dichloromethane and dried over sodium sulfate and filtered. The solvent is evaporated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 344,9 (M+H)+.

Example 3B

tert-Butyl 5-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate

The compound of Example 3A, (10,81 g of 31.4 mmol), dichlorobis(triphenylphosphine)palladium(II) (1.1 g, 1.57 mmol) and iodide is a single(I) (365 mg, 1.92 mmol) were combined in triethylamine (70 ml) in an inert atmosphere. Added trimethylsilylacetamide (5.0 ml, 36,0 mmol) and the mixture was stirred at 60°C over night. The solvent was removed under reduced pressure and the obtained residue was dissolved in methylene chloride and washed with 1 n hydrochloric acid. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 215,0 (M-99)+.

Example 3C

5-Ethinyl-1H-indazol

The compound of Example 3B (of 7.93 g of 25.2 mmol) was dissolved in methanol (150 ml). Added a 1N solution of potassium hydroxide (50 ml) and the mixture was stirred at ambient temperature for 1 hour. The solvent was removed under reduced pressure and the resulting slurry was dissolved in ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over sodium sulfate, filtered and the solvent was removed under reduced pressure to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,24 (s, 1H), 8,10 (s, 1H), 7,95 (s, 1H), 7,55 (d, J=8,82 Hz, 1H), 7,39 (DD, J=8,48, of 1.36 Hz, 1H), 4,03 (s, 1H).

Example 3D

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol

The compound of Example 3C (40 mg, 0.28 mmol), benzilate (37 mg, 0.28 mmol), CuSO4(14 mg, 0,056 mmol) and menu the wire (14 mg) were combined in tert-butanol (0.5 ml) and water (0.5 ml) and heated in a microwave reactor CEM-Discover for 10 minutes at 125°C and 100 Watts. To the mixture was added 1M HCl and water, the product was extracted with dichloromethane and purified via chromatography on silica gel (50% ethyl acetate in hexane) to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), at 8.60 (s, 1H), 8,23 (s, 1H), 8,11 (s, 1H), a 7.85 (d, J=8,59, of 1.53 Hz, 1H), to 7.59 (d, J=8,59 Hz, 1H), 7,26-7,49 (m, 5H), the 5.65 (s, 2H). MS (ESI+) m/z 276,0 (M+H)+.

Example 4

5-[1-(2-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

A 5-ml microwave reaction tube CEM Microwave, which was equipped with a rod stirrer from micro-flea with Teflon coating was added to 17.6 mg (0,124 mmol) of the compound of Example 3C, 300 μl of an aqueous solution containing 7,80 mg (amount of 0.118 mmol) of sodium azide; and then adding 15,79 μl (amount of 0.118 mmol; 21,80 mg 0.95 equivalent) of 2-methyl-benzylbromide (added without solvent). To the suspension was then added 300 μl of tert-butanol; 25 mg copper wire; and finally 50 μl of 1 n aqueous solution of pentahydrate copper sulfate. Microwave reaction vessel was then closed with a lid and heated under stirring for 10 minutes at 125°C at a power of 100 Watts in a microwave device CEM-Discover. After cooling to ambient temperature the mixture was diluted with 0.25 n aqueous solution of HCl; and the aqueous suspension was extracted with dichloromethane. The organic layer was washed with distilled water, saturated aqueous NaCl, and then with the sewed over anhydrous sodium sulfate and filtered. The dried solution was diluted with acetonitrile; and soluble organic matter was then filtered through a plug of glass wool on top of which was applied an extra layer of anhydrous sodium sulfate. An aliquot of the filtrate was then selected for subsequent LC/MS analysis. Those solutions which contained the desired triazole product, then was evaporated in vacuum and then dissolved in 1.50 ml of a mixture 1:1 DMSO/methanol. A solution of the crude triazole product was then purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU obtaining specified in the connection header.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm is 2.37 (s, 3H), to 5.66 (s, 2H), 7,16-7,34 (m, 4H), 7,63 (d, J=8.54 in Hz, 1H), 7,87 (d, J=8,70, to 1.37 Hz, 1H), 8,14 (s, 1H), of 8.25 (s, 1H), 8,49 (s, 1H). MS (ESI+) m/z 289,9 (M+H)+.

Example 5

5-[1-(3-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-methylbenzylamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,58 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=cent to 8.85, of 1.53 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,30 (t, J=7,63 Hz, 1H), 7,14-7,24 (m, 3H), ceiling of 5.60 (s, 2H), 2,31 (s, 3H). MS (ESI+) m/z 289,8 (M+H)+.

Example 6

5-[1-(4-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained in accordance with procedures is Oh, described in Example 4, substituting 2-methylbenzylamine 4-methylbenzylamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,55 (s, 1H), 8,24 (s, 1H), 8,14 (s, 1H), 7,86 (d, J=8,54, of 1.53 Hz, 1H), 7,63 (d, J=cent to 8.85 Hz, 1H), 7,25-7,33 (m, 2H), 7.18 in-7,24 (m, 2H), 5,59 (s, 2H), to 2.29 (s, 3H). MS (ESI+) m/z 290,1 (M+H)+.

Example 7

5-[1-(3-methoxybenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-methoxybenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,59 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=8,54, of 1.53 Hz, 1H), to 7.64 (d, J=cent to 8.85 Hz, 1H), 7,33 (t, J=to 7.93 Hz, 1H), 6.89 in-7,00 (m, 3H), 5,62 (s, 2H), 3,76 (s, 3H). MS (ESI+) m/z 306,1 (M+H)+.

Example 8

5-[1-(2-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-farbensymposium.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.57 (s, 1H), of 8.25 (s, 1H), 8,12-8,17 (m, 1H), 7,87 (d, J=8,54, of 1.53 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,41-7,49 (m, J=7,32, to 7.32 Hz, 2H), 7,22-7,33 (m, J=7,02 Hz, 2H), 5,71 (s, 2H). MS (ESI+) m/z 293,9 (M+H)+.

Example 9

5-[1-(3-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-farbensymposium. H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,61 (s, 1H), of 8.25 (s, 1H), 8,15 (s, 1H), 787 (d, J=cent to 8.85, of 1.53 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,41-7,51 (m, 1H), 7,15-7,28 (m, 3H), of 5.68 (s, 2H). MS (ESI+) m/z 293,8 (M+H)+.

Example 10

5-[1-(4-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-farbensymposium.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,58 (s, 1H), 8,24 (s, 1H), 8,14 (s, 1H), 7,86 (d, J=cent to 8.85, of 1.53 Hz, 1H), to 7.64 (d, J=cent to 8.85 Hz, 1H), 7,46 (d, J=cent to 8.85, 5,49 Hz, 2H), 7,24 (t, J=9,00 Hz, 2H), 5,64 (s, 2H). MS (ESI+) m/z 293,9 (M+H)+.

Example 11

5-[1-(2-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-chlorobenzylamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,56 (s, 1H), compared to 8.26 (s, 1H), 8,14 (s, 1H), 7,88 (d, J=8,54, of 1.53 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,55 (d, J=7,63, of 1.53 Hz, 1H), 7,32-of 7.48 (m, 3H), USD 5.76 (s, 2H). MS (ESI+) m/z 309,8 (M+H)+.

Example 12

5-[1-(3-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-chlorobenzylamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.62 (s, 1H), compared to 8.26 (s, 1H), 8,15 (s, 1H), 7,87 (d, J=8,54, of 1.53 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,40-7,49 (m, J=7,63 Hz, 3H), 7,35 (d, J=6,41 Hz, 1H), 5,67 (s, 2H). MS (ESI+) m/z 309,8 (M+H)+.

Example 13

5-[1-(4-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Listed is in the title compound was obtained in accordance with the procedure described in Example 4, substituting 2-methylbenzylamine 4-chlorobenzylamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,58 (s, 1H), 8,24 (s, 1H), 8,15 (s, 1H), 7,86 (d, J=8,54, of 1.53 Hz, 1H), to 7.64 (d, J=cent to 8.85 Hz, 1H), 7,45-7,52 (m, 2H), 7,38-7,44 (m, 2H), 5,65 (s, 2H). MS (ESI-) m/z 307,7 (M-H)-.

Example 14

5-[1-(2-bromobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-bromobenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,55 (s, 1H), compared to 8.26 (s, 1H), 8,14 (s, 1H), 7,88 (d, J=8,54, of 1.53 Hz, 1H), 7,72 (d, J=to 7.93 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,41-to 7.50 (m, 1H), 7,27-7,40 (m, 2H), 5,74 (s, 2H). MS (ESI+) m/z 353,5 (M+H)+.

Example 15

5-[1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-nitrobenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.57 (s, 1H), of 8.27 (s, 1H), 8,12 were 8.22 (m, 2H), 7,88 (d, J=8,54, of 1.53 Hz, 1H), 7,75-7,83 (m, 1H), 7,60-7,72 (m, 2H), 7,27 (d, J=7,63 Hz, 1H), 6,02 (s, 2H). MS (ESI+) m/z 320,8 (M+H)+.

Example 16

5-[1-(3-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-nitrobenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,65 (s, 1H), 8,21-of 8.28 (m, 3H), of 8.15 (s, 1H), 7,80-to $ 7.91 (m, 2H), ,73 (t, J=7,78 Hz, 1H), 7,65 (d, J=8.54 in Hz, 1H), of 5.83 (s, 2H). MS (ESI+) m/z 320,8 (M+H)+.

Example 17

5-[1-(4-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-nitrobenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,64 (s, 1H), they were 8.22-8,31 (m, 3H), of 8.15 (s, 1H), 7,88 (d, J=8,70, to 1.37 Hz, 1H), EUR 7.57-to 7.68 (m, 3H), of 5.83 (s, 2H). MS (ESI+) m/z 320,7 (M+H)+.

Example 18

2-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl} benzonitrile

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-cyanobenzaldehyde.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,61 (s, 1H), compared to 8.26 (s, 1H), 8,15 (s, 1H), to 7.93 (d, J=7,63 Hz, 1H), 7,88 (d, J=8,54, of 1.53 Hz, 1H), 7,72-7,80 (m, 1H), EUR 7.57-to 7.68 (m, 2H), 7,53 (d, J=to 7.93 Hz, 1H), 5,86 (s, 2H). MS (ESI+) m/z 300,9 (M+H)+.

Example 19

3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl} benzonitrile

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-cyanobenzaldehyde.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,63 (s, 1H), compared to 8.26 (s, 1H), 8,15 (s, 1H), 7,85-to 7.93 (m, 2H), 7,83 (d, J=7,63 Hz, 1H), 7,72 (d, J=8,24 Hz, 1H), 7,56-to 7.68 (m, 2H), 5,74 (s, 2H). MS (ESI+) m/z 300,9 (M+H)+.

Example 20

4-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl} benzonitrile

Specified in the title compound was obtained is in accordance with the procedure described in Example 4, substituting 2-methylbenzylamine 4-cyanobenzaldehyde.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.62 (s, 1H), compared to 8.26 (s, 1H), 8,15 (s, 1H), 7,82-to 7.93 (m, J=8,24 Hz, 3H), of 7.65 (d, J=8.54 in Hz, 1H), 7,54 (d, J=8,24 Hz, 2H), 5,78 (s, 2H). MS (ESI+) m/z to 300.7 (M+H)+.

Example 21

5-{1-[2-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2-cryptomethodoverrides.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,56 (s, 1H), of 8.27 (s, 1H), 8,15 (s, 1H), 7,89 (d, J=cent to 8.85, of 1.53 Hz, 1H), a 7.85 (d, J=to 7.93 Hz, 1H), 7,72 (t, J=7,63 Hz, 1H), 7,55-to 7.68 (m, 2H), 7,33 (d, J=to 7.93 Hz, 1H), to 5.85 (s, 2H). MS (ESI+) m/z to 300.7 (M+H)+.

Example 22

5-{1-[3-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-cryptomethodoverrides.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,65 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=8,70, to 1.37 Hz, 1H), to 7.77 (s, 1H), 7,71-7,76 (m, 1H), to 7.61-of 7.69 (m, 3H), 5,78 (s, 2H). MS (ESI+) m/z 344,0 (M+H)+.

Example 23

5-{1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-cryptomethodoverrides.1H NMR (500 MHz, DMSO-d6/D2O) δ m is. 8,63 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=8.54 in Hz, 1H), 7,78 (d, J=to 7.93 Hz, 2H), 7,63 (d, J=8.54 in Hz, 1H), 7,58 (d, J=to 7.93 Hz, 2H), 5,78 (s, 2H). MS (ESI+) m/z 344,2 (M+H)+.

Example 24

5-{1-[3-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-cryptomethodoverrides.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,64 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=8.54 in Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,56 (t, J=8,24 Hz, 1H), 7,31 was 7.45 (m, 3H), 5,73 (s, 2H). MS (ESI+) m/z to 359.9 (M+H)+.

Example 25

5-{1-[4-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-cryptomethodoverrides.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,61 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,87 (d, J=8,70, to 1.37 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,52 (d, J=cent to 8.85 Hz, 2H), 7,40 (d, J=8,24 Hz, 2H), 5,70 (s, 2H). MS (ESI+) m/z to 359.9 (M+H)+.

Example 26

5-[1-(4-tert-butylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-tert-butylbenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,58 (s, 1H), 8,24 (s, 1H), 8,13 (s, 1H), 7,86 (d, J=cent to 8.85, of 1.53 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,42 (d, J=8,24 Hz, 2H), 7,32 (d, J=8,24 Hz, 2H), ceiling of 5.60 (s, 2H), 1.26 in (s, 9H). MS (ESI+) m/z 32,1 (M+H) +.

Example 27

methyl 3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl} benzoate

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3-carbomethoxyamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.62 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), 7,92-to 7.99 (m, 2H), 7,87 (d, J=8,54, of 1.53 Hz, 1H), 7,68 (d, J=7,63 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,58 (t, J=7,63 Hz, 1H), of 5.75 (s, 2H), 3,86 (s, 3H). MS (ESI+) m/z 333,9 (M+H)+.

Example 28

methyl 4-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzoate

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 4-carbomethoxyamino.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.62 (s, 1H), of 8.25 (s, 1H), 8,14 (s, 1H), to 7.99 (d, J=8,24 Hz, 2H), 7,87 (d, J=cent to 8.85 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,49 (d, J=8,24 Hz, 2H), USD 5.76 (s, 2H), 3,85 (s, 3H). MS (ESI+) m/z 333,9 (M+H)+.

Example 29

5-[1-(2,4-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2,4-dimethylbenzylidene.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.45 (s, 1H), 8,24 (s, 1H), 8,13 (s, 1H), 7,86 (d, J=8.54 in Hz, 1H), 7.62mm (d, J=8.54 in Hz, 1H), 7,12 (d, J=to 7.93 Hz, 1H), 7,07 (s, 1H),? 7.04 baby mortality (d, J=7,63 Hz, 1H), ceiling of 5.60 (s, 2H), 2,32 (s, 3H), and 2.26 (s, 3H). MS (ESI+) m/z 304,0 (M+H)+.

Example 30

5-[1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-Inda is ol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3,5-dimethylbenzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,56 (s, 1H), 8,24 (s, 1H), 8,13 (s, 1H), 7,87 (d, J=8.54 in Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 6,95-7,01 (m, 3H), of 5.55 (s, 2H), and 2.26 (s, 6H). MS (ESI+) m/z 304,2 (M+H)+.

Example 31

5-[1-(2,3-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2,3-dichlorobenzylchloride.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,59 (s, 1H), compared to 8.26 (s, 1H), 8,14 (s, 1H), 7,88 (d, J=8,70, to 1.37 Hz, 1H), 7,69 (d, J=8,09, to 1.37 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,44 (t, J=7,78 Hz, 1H), 7,31 (d, J=7,78, 1.07 Hz, 1H), of 5.81 (s, 2H). MS (ESI+) m/z 343,8 (M+H)+.

Example 32

5-[1-(2,4-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2,4-dichlorobenzylchloride.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,56 (s, 1H), of 8.25 (s, 1H), 8,13 (s, 1H), 7,87 (d, J=8.54 in Hz, 1H), 7,72 (d, J=2,14 Hz, 1H), 7,63 (d, J=8.54 in Hz, 1H), 7,50 (d, J=8,39, to 1.98 Hz, 1H), 7,40 (d, J=8,24 Hz, 1H), 5,74 (s, 2H). MS (ESI-) m/z 341,8 (M-H)-.

Example 33

5-[1-(2,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylb is sybreed 2,5-dichlorobenzylchloride. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,59 (s, 1H), compared to 8.26 (s, 1H), 8,14 (s, 1H), 7,88 (d, J=cent to 8.85 Hz, 1H), 7,63 (d, J=cent to 8.85 Hz, 1H), 7,56-to 7.61 (m, 1H), 7,49-of 7.55 (m, 1H), 7,47 (d, J=2,44 Hz, 1H), of 5.75 (s, 2H). MS (ESI+) m/z 343,8 (M+H)+.

Example 34

5-[1-(3,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 3,5-dichlorobenzylchloride.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,64 (s, 1H), compared to 8.26 (s, 1H), 8,15 (s, 1H), 7,87 (d, J=cent to 8.85 Hz, 1H), EUR 7.57-7,71 (m, 2H), 7,44 (d, J=1,53 Hz, 2H), 5,69 (s, 2H). MS (ESI+) m/z 344,1 (M+H)+.

Example 35

5-{1-[2,4-bis(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained according to the procedure described in Example 4, substituting 2-methylbenzylamine 2,4-bis(trifluoromethyl)bromide.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 8.62 (s, 1H), of 8.27 (s, 1H), 8.07-a 8,18 (m, 3H), 7,89 (d, J=8,70, to 1.37 Hz, 1H), to 7.64 (d, J=8.54 in Hz, 1H), 7,49 (d, J=to 7.93 Hz, 1H), 5,96 (s, 2H). MS (ESI+) m/z 411,7 (M+H)+.

Example 36

N-cyclohexyl-6-(1H-indazol-5-yl)imidazo[2,1-b][1,3]thiazole-5-amine

Example 36A

1H-indazol-5-carbaldehyde

To a solution of 5-brominate (5 g, 25,38 mmol) in tetrahydrofuran (100 ml), cooled at -50°C under argon atmosphere was added dropwise a solution of 1.6 M n-utility in hexane (40 ml, 63,44 mmol). Added dimethylformamide (3.9 ml, 50,75 mmol) and the mixture was allowed to warm to room so the temperature and was stirred for 15 minutes. The mixture was then extinguished with water, was extracted with ethyl acetate, pre-absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-30% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (500 MHz, DMSO-d6) δ ppm there is a 10.03 (s, 1H), 8,45 (s, 1H), 8,35 (s, 1H), a 7.85 (DD, J=8,70, to 1.37 Hz, 1H), 7,69 (d, J=8.54 in Hz, 1H).

Example 36B

N-cyclohexyl-6-(1H-indazol-5-yl)imidazo[2,1-b][1,3]thiazole-5-amine

The compound of Example 36A (50 mg, 0.34 mmol) and 2-aminothiazole (28 mg, 0.34 mmol) was combined with scandicraft (8 mg, of 0.017 mmol) in anhydrous methanol (1 ml) in 4-ml vessel. The vessel was tightly closed and shaken at ambient temperature for 30 minutes. Added cyclohexylethane (42 ml, 0.34 mmol) and the mixture was shaken for 2 days at room temperature. The mixture was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU obtaining specified in the connection header in the form of a salt TFU.1H NMR (500 MHz, DMSO-d6) δ ppm 13,12 (s, 1H), 8,32 (s, 1H), 8,13 (s, 1H), with 8.05 (d, J=cent to 8.85, 1,22 Hz, 1H), 7,92 (d, J=4,27 Hz, 1H), 7,60 (d, J=8.54 in Hz, 1H), 7,37 (d, J=3,66 Hz, 1H), 4,89 (s, 1H), 2,78-to 2.94 (m, 1H), 1,73 of-1.83 (m, 2H), 1,58 by 1.68 (m, 2H), 1,45-of 1.53 (m, 1H), 1,16-of 1.29 (m, 2H), 1.04 million-to 1.14 (m, 3H). MS (ESI+) m/z 338,1 (M+H)+.

Example 37

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine

Specified in the header with the unity received in accordance with the procedure described in Example 36B, with the substitution of 2-aminothiazole 2-aminopyridine.1H NMR (500 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), to 8.57 (s, 1H), 8,23-8,39 (m, 2H), 8,11 (s, 1H), EUR 7.57 (d, J=8.54 in Hz, 1H), 7,46 (d, J=cent to 8.85 Hz, 1H), 7,12-7,21 (m, 1H), to 6.88 (t, J=of 6.71 Hz, 1H), 4,78 (d, J=5,80 Hz, 1H), 2,78-only 2.91 (m, 1H), 1,69-to 1.77 (m, J=10,98 Hz, 2H), 1,57-to 1.67 (m, 2H), 1,45-of 1.53 (m, 1H), 1,21-of 1.34 (m, 2H), 1,01 is 1.16 (m, 3H). MS (ESI+) m/z 332,1 (M+H)+.

Example 38

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrazin-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 36B, with the substitution of 2-aminothiazole 2-aminopyrazine.1H NMR (500 MHz, DMSO-d6) δ ppm 13,12 (s, 1H), 8,90 (d, J=1,22 Hz, 1H), 8,61 (s, 1H), of 8.37 (d, J=4,58, of 1.53 Hz, 1H), 8,29 (d, J=8,70, to 1.37 Hz, 1H), 8,15 (s, 1H), a 7.85 (d, J=4,58 Hz, 1H), 7.62mm (d, J=cent to 8.85 Hz, 1H), of 5.05 (d, J=of 6.71 Hz, 1H), 2,81-2,99 (m, 1H), 1.70 to 1.77 in (m, J=is 10.68 Hz, 2H), 1,58-to 1.67 (m, 2H), 1,47 (s, 1H), 1,24-to 1.38 (m, 2H), 1.00 and is 1.16 (m, 3H). MS (ESI+) m/z 333,1 (M+N)+.

Example 39

5- [1-benzyl-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol

A 20-ml scintillation vessel was added 50.0 mg (0.34 mmol) of the compound of Example 36A. This solid matter was added to 2.0 ml of dimethylformamide, containing 0.46 mmol (49 mg) benzylamine and 50 mg of powdered activated 4Å molecular sieves. The vessel was then closed with a lid and heated at 60°C for 4 hours on an orbital shaker device. The vessel was allowed to cool to ambient temperature; and the lid opened. To a suspension of relax is whether 32 mg (0.23 mmol) of anhydrous potassium carbonate followed by the addition of 66 mg (0.23 mmol) of α-(p-toluensulfonyl)-4-farbenindustrie. The vessel was then closed with a lid and heated overnight at 60°C on a shaking device. The vessel was removed from shaking the device was allowed to cool to ambient temperature; and the resulting suspension was filtered. The filtrate was evaporated under reduced pressure at moderate heat on a Savant Speed Vac. The crude residues were again dissolved in a mixture of 1:1 DMSO/methanol and purified using reverse-phase HPLC using a gradient elution of acetonitrile/water TFU method of obtaining specified in the connection header in the form of a salt TFU.1H NMR (300 MHz, DMSO-d6) δ ppm 9,01 (s, 1H), 8,12 (s, 1H), 7,76 (s, 1H), 7,60 (d, J=8,48 Hz, 2H), 7,32 was 7.45 (m, 2H), 7,09-7,30 (m, 6N), of 6.96 (d, J=6,61, 2,88 Hz, 2H), 5,23 (s, 2H). MS (ECI) m/z 369 (M+N)+.

Example 40

N-{3-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-indazol-1-yl]propyl}-N,N-dimethylamine

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 39, substituting benzylamine N1N1-DIMETHYLPROPANE-1,3-diamine.1H NMR (300 MHz, DMSO-d6) δ ppm 9,49 (s, 1H), 8,88 (s, 1H), 8,19 (s, 1H), 7,94 (s, 1H), 7,73 (d, J=8,81 Hz, 1H), 7,29-7,44 (m, 3H), 7,17 (t, J=8,98 Hz, 2H), 4,01 (t, J=7,12 Hz, 2H), 2,89 totaling 3.04 (m, J=10,51 Hz, 2H), 2,68 (s, 3H), 2,67 (, 3H), 1,87-2,02 (m, 2H). MS (ECI) m/z 364 (M+H)+.

Example 41

N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine

Specified in the title compound was obtained in the form of a salt TFU in the accordance with the procedure described in Example 36B, using pyrimidine-2-amine instead of thiazole-2-amine.1H NMR (500 MHz, DMSO-d6) δ ppm 13,21-13,41 (m, 1H), 9,07 (d, J=5,80 Hz, 1H), cent to 8.85 (d, J=3,05 Hz, 1H), 8,51 (s, 1H), 8,24 (s, 1H), 8,14 (d, J=8,70, to 1.37 Hz, 1H), 7,73 (d, J=cent to 8.85 Hz, 1H), 7,47-7,56 (m, 1H), 5.25 to 5,41 (m, J=2,75 Hz, 1H), 2,81-only 2.91 (m, J=10,53, 10,53 Hz, 1H), 1,74 of-1.83 (m, 2H), 1.56 to of 1.66 (m, 2H), 1,43 of 1.50 (m, 1H), 1,24 (sq, J=1 1,09 Hz, 2H), and 1.00-1.14 in (m, 3H). MS (ESI+) m/z 333,1 (M+H)+.

Example 42

5-[4-(4-forfinal)-1-(1-phenylethyl)-1H-indazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 1-fenilalanina instead of benzylamine.1H NMR (300 MHz, CDCl3) δ ppm of 8.04 (s, 1H), 7,75-to 7.84 (m, 1H), 7,35-of 7.55 (m, 4H), 7,20-7,31 (m, 5H), 6,76-7,01 (m, 4H), 5,09 (sq, J=7,12 Hz, 1H), equal to 1.82 (d, 3H). MS (ECI) m/z 383 (M+H)+.

Example 43

2-(1H-indazol-5-yl)-N-isopropylimidazole[1,2-a]pyrimidine-3-amine

The compound of Example 36A (42 mg, 0,287 mmol) and 2-aminopyrimidine (27 mg, 0,284 mmol) was combined with scandicraft (7 mg, 0.014 mmol) in anhydrous methanol (2 ml) in 4-ml vessel. The vessel was tightly closed and shaken at ambient temperature for 30 minutes. Added isopropyltoluene (27 ml, 0,286 mmol) and the mixture was shaken at ambient temperature overnight and then at 40°C for 2 hours. The mixture was absorbed on silica gel and purified by chromatography on silica gel with elution gradient of 0-5% methanol is dichloromethane, obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), up 8.75 (d, J=6,95, to 1.86 Hz, 1H), at 8.60 (s, 1H), 8,31 (d, J=8,82, of 1.36 Hz, 1H), to 8.20 (d, J=4,75 Hz, 1H), 8,14 (s, 1H), 7,60 (d, J=8,82 Hz, 1H), 7,03 (d, J=6,78, 4,07 Hz, 1H), is 6.54 (d, J=4,75 Hz, 1H), a 4.86 (d, J=5,09 Hz, 1H), of 1.05 (d, J=6,10 Hz, 6H). MS (ESI+) m/z 293,0 (M+H)+.

Example 44

4-(1H-indazol-5-yl)-N-phenyl-1,3-thiazol-2-amine

Example 44A

tert-Butyl 5-bromo-1H-indazol-1-carboxylate

5-Brominator (and 4.40 g of 22.3 mmol) and a catalytic amount of dimethylaminopyridine (~50 mg) was dissolved in dichloromethane (100 ml). Was added di-tert-BUTYLCARBAMATE (5,43 g, 24,9 mmol) and the mixture was stirred at ambient temperature overnight. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 297,2 (M+H)+.

Example 44B

tert-Butyl 5-acetyl-1H-indazol-1-carboxylate

The compound of Example 44A (5,12 g, and 17.2 mmol), tributyl(1-ethoxyphenyl)tin (7,0 ml of 20.7 mmol) and dichlorobis(triphenylphosphine)palladium(II) (672 mg, 0,957 mmol) were combined in toluene (85 ml). The mixture barbotirovany nitrogen for 5 minutes and the mixture was heated to 100°C in a sealed tube overnight. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 0-4% ethyl acetate in hexane, obtaining specified in the connection header. MS (ESI+) m/z 283,0 (M+Na)+.

Example 44C

tert-Butyl 5-(2-bromoacetyl)-1H-indazol-1-carboxylate

The compound of Example 44B (1.60 g, x 6.15 mmol) and tribromide pyridinium (1.98 g, to 6.19 mmol) were combined in tetrahydrofuran and heated to 40°C for 2 hours. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 360,9 (M+Na)+.

Example 44D

4-(1H-indazol-5-yl)-N-phenyl-1,3-thiazol-2-amine

The compound of Example 44C (71 mg, 0,208 mmol) and 1-phenyl-2-thiourea (33 mg, 0,217 mmol) were combined in ethanol (300 ml) in 4-ml vessel. The vessel was shaken at 80°C during the night. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of methanol in dichloromethane (0-5%), obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), 10,23 (s, 1H), 8,32 (s, 1H), 8,14 (s, 1H), to 7.93 (d, J=8,59, of 1.53 Hz, 1H), of 7.75 (d, J=8,75, 1.07 Hz, 1H), 7,58 (d, J=8,90 Hz, 1H), was 7.36 (d, J=8,59, of 7.36 Hz, 1H), 7,25 (s, 1H), 6,92-7,02 (m, 1H). MS (ESI+) m/z 292,9 (M+H)+.

Example 45

5-(2-methyl-1,3-thiazol-4-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 44D, with substitution of 1-phenyl-2-thiourea thioacetamide.1H YAM who (300 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), 8.34 per (s, 1H), 8,12 (s, 1H), 7,94 (d, J=8,82, 1.70 Hz, 1H), a 7.85 (s, 1H), EUR 7.57 (d, J=8,82 Hz, 1H), 2,73 (s, 3H). MS (ESI+) m/z 215,9 (M+H)+.

Example 46

N-ethyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 44D, with substitution of 1-phenyl-2-thiourea by ethyltoluidines.1H NMR (300 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), 8,21 (s, 1H), of 8.09 (s, 1H), 7,83 (d, J=8,65, of 1.53 Hz, 1H), 7,58 (t, J=5.43 Hz, 1H), 7,51 (d, J=8,82 Hz, 1H), of 6.96 (s, 1H), 3,22-to 3.34 (m, 2H), 1,21 (t, J=7.29 trend Hz, 3H). MS (ESI+) m/z 244,9 (M+H)+.

Example 47

N-benzyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 44D, with substitution of 1-phenyl-2-thiourea 1-benzyl-2-thiourea.1H NMR (400 MHz, DMSO-d6) δ ppm 13,02 (s, 1H), 8,21 (s, 1H), 8,12 (t, J=of 5.83 Hz, 1H), 8,08 (s, 1H), 7,83 (d, J=8,90, of 1.53 Hz, 1H), 7,50 (d, J=8,90 Hz, 1H), 7,39 was 7.45 (m, 2H), 7,35 (t, J=7,52 Hz, 2H), 7,26 (t, J=7,21 Hz, 1H), 6,97 (s, 1H), of 4.54 (d, J=5.83 in Hz, 1H). MS (ESI+) m/z 306,9 (M+H)+.

Example 48

4-(1H-indazol-5-yl)-1,3-thiazol-2-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 44D, with substitution of 1-phenyl-2-thiourea thiourea.1H NMR (300 MHz, DMSO-d6) δ ppm 13,03 (s, 1H), 8,17 (s, 1H), 8,07 (s, 1H), 7,81 (d, J=8,82, of 1.36 Hz, 1H), 7,50 (d, J=8,82 Hz, 1H), 7,01 (s, 2H), 6,92 (s, 1H). MS (ESI+) m/z 216,9 (M+H)+.

Example 49

4-(1H-indazol-5-yl)-N-(2-phenylethyl)-1,3-thiazol-2-amine

Indicated the data in the title compound was obtained in accordance with the procedure described in Example 44D with substitution of 1-phenyl-2-thiourea 1-penicillioides.1H NMR (300 MHz, DMSO-d6) δ ppm 13,03 (s, 1H), 8,23 (s, 1H), of 8.09 (s, 1H), a 7.85 (d, J=8,65, of 1.53 Hz, 1H), 7,71 (t, J=5.43 Hz, 1H), 7,51 (d, J=8,82 Hz, 1H), 7,26 and 7.36 (m, 4H), 7.18 in-7,26 (m, 1H), 6,97 (s, 1H), 3,47-3,59 (m, 1H), 2,94 (t, J=7,44 Hz, 1H). MS (ESI+) m/z 321,0 (M+H)+.

Example 50

N-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 43, using benzylideneamino instead of isopropyltoluene.1H NMR (300 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), 8,50-8,58 (m, 2H), 8,39 (d, J=4,07, 2,03 Hz, 1H), 8,25 (d, J=8,81, of 1.36 Hz, 1H), 8,13 (s, 1H), to 7.61 (d, J=8,81 Hz, 1H), 7,24 (s, 5H), 6,92 (d, J=6,78, 4,07 Hz, 1H), 5,44 (t, J=6,27 Hz, 1H), 4,13 (d, J=6,10 Hz, 2H). MS (ESI+) m/z 341,0 (M+H)+.

Example 51

N-butyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 43, using utilizationa instead of isopropyltoluene.1H NMR (300 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), to 8.70 (d, J=6,78, 2,03 Hz, 1H), 8,55 (s, 1H), 8,44 (d, J=4,07, 2,03 Hz, 1H), 8,25 (d, J=8,82, of 1.36 Hz, 1H), 8,14 (s, 1H), to 7.61 (d, J=8,82 Hz, 1H), 7,03 (d, J=6,78, 4,07 Hz, 1H), 4,90 (t, J=5,93 Hz, 1H), 2,96 (s, 2H), 1,49 (s, 2H), 1,34 (s, 2H), of 0.82 (t, J=7.29 trend Hz, 3H). MS (ESI+) m/z 307,0 (M+H)+.

Example 52

N-(4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine

Specified in the title compound was obtained in accordance with procedures is th, described in Example 43, using 4-chlorophenylalanine instead of isopropyltoluene.1H NMR (500 MHz, DMSO-d6) δ ppm 13,12 (s, 1H), 8,58 (DD, J=4,12, to 1.98 Hz, 1H), 8,46 (d, J=trend of 15.87 Hz, 2H), 8,40 (DD, J=of 6.71 and 1.83 Hz, 1H), 8,06-8,16 (m, 2H), 7,58 (d, J=cent to 8.85 Hz, 1H), 7,18 (d, J=cent to 8.85 Hz, 2H), 7,05 (DD, J=of 6.71, of 3.97 Hz, 1H), 6,57 (d, J=cent to 8.85 Hz, 2H). MS (ESI+) m/z 361,0 (M+H)+.

Example 53

2-(1H-indazol-5-yl)-N-(4-methoxyphenyl)imidazo[1,2-a]pyrimidine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 43, using 4-methoxyphenylalanine instead of isopropyltoluene.1H NMR (500 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), 8,56 (DD, J=3,97, with 2.14 Hz, 1H), of 8.47 (s, 1H), at 8.36 (DD, J=6,56, to 1.98 Hz, 1H), 8,15 (DD, J=8,70, to 1.37 Hz, 1H), 8,10 (s, 1H), to 7.99 (s, 1H), EUR 7.57 (d, J=8.54 in Hz, 1H), 7,03 (DD, J=of 6.71, 4,27 Hz, 1H), 6,76 (d, J=cent to 8.85 Hz, 2H), 6,50 (d, J=cent to 8.85 Hz, 2H), 3,63 (s, 3H). MS (ESI+) m/z 357,4 (M+H)+.

Example 54

2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine

Specified in the title compound was obtained in accordance with the procedure described in Example 44D, using a 2-aminopyrimidine instead of 1-phenyl-2-thiourea.1H NMR (300 MHz, DMSO-d6) δ ppm 13,13 (s, 1H), 8,96 (DD, J=6,78, 2,03 Hz, 1H), 8,51 (DD, J=to 4.41, 2,03 Hz, 1H), 8,42 (s, 1H), at 8.36 (s, 1H), 8,15 (s, 1H), 8,01 (DD, J=8,82, 1.70 Hz, 1H), 7.62mm (d, J=8,48 Hz, 1H),? 7.04 baby mortality (DD, J=6,61, 4,24 Hz, 1H). MS (ESI+) m/z 236,1 (M+H)+.

Example 55

methyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-yl]glycinate

Specified in the title compound was obtained in a salt form TF is in accordance with the procedure described in Example 36B, using 2-aminopyridine instead of 2-aminothiazole and methyl 2-isocyanoacetate instead of cyclohexyldiamine.1H NMR (400 MHz, DMSO-d6) δ ppm 13,41 (s, 1H), 8,90 (d, J=6.75 Hz, 1H), scored 8.38 (s, 1H), of 8.27 (s, 1H), 7,84-7,98 (m, 3H), to 7.77 (d, J=8,90 Hz, 1H), 7,55 (TD, J=6.75 in, 1.23 Hz, 1H), 5,95-the 6.06 (m, 1H), a 3.87 (d, J=4,60 Hz, 2H), 3,51 (s, 3H). MS (ESI+) m/z 340,1 (M+H)+.

Example 56

N-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 36B, using 2-aminopyridine instead of 2-aminothiazole and benzylideneamino instead of cyclohexyldiamine. The final product was precipitated from solution with obrazovanie sediment and it was isolated after filtration.1H NMR (400 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), 8,49 (s, 1H), 8,16-of 8.27 (m, 2H), of 8.09 (s, 1H), 7,58 (d, J=8,90 Hz, 1H), 7,44 (d, J=8,90 Hz, 1H), 7,19-to 7.35 (m, 5H), 7,13 (DDD, J=8,98, 6,67, to 0.92 Hz, 1H), 6,80 (TD, J=6.75 in, to 0.92 Hz, 1H), 5,32 (t, J=6,14 Hz, 1H), 4,12 (d, J=6,14 Hz, 2H). MS (ESI+) m/z 322,1 (M+H)+.

Example 57

N-(4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 36B, using 2-aminopyridine instead of 2-aminothiazole and 1-chloro-4-isocyanate instead of cyclohexyldiamine.1H NMR (400 MHz, DMSO-d6) δ ppm 13,06 (s, 1H), 8,39 (s, 2H), 8,05-to 8.14 (m, 2H), 7,94 (d, J=6.75 Hz, 1H), 7.62mm (d, J=8,90 Hz, 1H), 7,55 (d, J=8,59 Hz, 1H), 7,28-7,34 (m, 1H), 7,17 (q, j =8,90 Hz, 2H), 6,88-of 6.96 (m, J=6.75 in, 6.75 Hz, 1H), 6,53 (d, J=8,59 Hz, 2H). MS (ESI+) m/z 360,0 (M+H)+.

Example 58

2-(1H-indazol-5-yl)-N-(4-methoxyphenyl)imidazo[1,2-a]pyridine-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 36B, using 2-aminopyridine instead of 2-aminothiazole and 1 isocyano-4-methoxybenzoyl instead of cyclohexyldiamine.1H NMR (400 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), 8,44 (s, 1H), 8,14 (d, J=8,90, 1.23 Hz, 1H), of 8.06 (s, 1H), 7,87-of 7.96 (m, 2H), to 7.59 (d, J=8,90 Hz, 1H), 7,54 (d, J=8,59 Hz, 1H), 7.24 to 7,33 (m, 1H), 6,86-6,93 (m, J=6.75 in, 6.75 Hz, 1H), 6.75 in (d, J=of 9.21 Hz, 2H), 6,47 (d, J=of 9.21 Hz, 2H), 3,63 (s, 3H). MS (ESI+) m/z 356,1 (M+H)+.

Example 59

tert-butyl 4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]piperidine-1-carboxylate

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using tert-butyl 4-aminopiperidine-1-carboxylate instead of benzylamine.1H NMR (400 MHz, DMSO-d5) δ ppm 13,32 (s, 1H), 8,14 (s, 1H), 8,01 (s, 1H), 7,79 (s, 1H), 7,68 (d, J=8,59 Hz, 2H), 7.24 to 7,39 (m, 2H), 6,97 (t, J=8,90 Hz, 2H), 3,91-of 4.05 (m, 2H), 3,71-a-3.84 (m, 1H), 2,53-2,69 (m, 2H), 1,76-of 1.94 (m, 4H), 1,35-1,40 (m, 9H). MS (DCI) m/z 462 (M+H)+.

Example 60

3,5-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Example 60A

tert-Butyl 5-bromo-3-iodine-1H-indazol-1-carboxylate

To a solution of 5-brominate (10 g, 50,75 mmol) in dimethylformamide (100 ml) was added KOH (10 g, 177,63 mmol). Within 2 hours was added iodine (20 g, 78,80 mmol). The mixture clicks sativali solution of Na 2S2O3(20 g) in water (200 ml), extracted with ethyl acetate, washed with saturated saline solution, dried over sodium sulfate and filtered and the solvent was removed under reduced pressure. The solid was dissolved in dichloromethane (350 ml) and was treated with di-tert-BUTYLCARBAMATE (14.4 g, 65,98 mmol) and dimethylaminopyridine (10 mg, 0.08 mmol). The mixture was stirred for 20 minutes at room temperature and passed directly through a layer of silica gel to obtain specified in the connection header. MS (DCI/NH3) m/z 422,9 (M+H)+.

Example 60B

tert-butyl 5-bromo-3-phenyl-1H-indazol-1-carboxylate and tert-butyl 5-bromo-3-iodine-1H-indazol-1-carboxylate

To a solution of compound of Example 60A (2.1 g, 5 mmol) in toluene (10 ml) was added Pd(PPh3)4(173 mg, 0.15 mmol), a solution of Na2CO3(1.1 g, 10 mmol) in water (5 ml) and a solution of phenylboronic acid (671 mg, 5.5 mmol) in methanol (3 ml). The mixture was stirred at room temperature for 5 days, extinguished with water, was extracted with ethyl acetate and was purified using chromatography on silica gel by elution of a mixture of 5% ethyl acetate/hexane, obtaining mentioned in the title compounds as a mixture.1H NMR (500 MHz, DMSO-d6) δ ppm of 8.28 (d, J=1,53 Hz, 1H), 8,12 (d, J=cent to 8.85 Hz, 1H), 7,97-of 8.04 (m, 3H), 7,80-7,86 (m, 2H), of 7.75 (d, J=1,83 Hz, 1H), 7,54-7,63 (m, 3H), by 1.68 (s, 9H), of 1.64 (s, 9H). MS (ESI+) m/z 373,9 (M+H)+./p>

Example 60C

tert-Butyl 3,5-bis((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate and tert-butyl 5-bromo-3-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate

The compound of Example 60B (1 g, 2.55 mmol), dichlorobis(triphenylphosphine)palladium(II) (89 mg, 0.13 mmol), triethylamine (1,78 ml, 12.75 mmol), trimethylsilylacetamide (0,432 ml of 3.06 mmol) and CuI (24 mg, 0.13 mmol) were combined in dimethylformamide (10 ml) and stirred at room temperature for 20 hours. The mixture was diluted with ethyl acetate, washed with water and purified using chromatography on silica gel with getting listed in the title compounds.1H NMR (500 MHz, DMSO-d6) δ ppm 8,10 (d, J=cent to 8.85 Hz, 1H), 8,07 (d, J=cent to 8.85 Hz, 1H), of 7.97 (d, J=1,83 Hz, 1H), to 7.84 (s, 1H), 7,82 (DD, J=cent to 8.85 and 1.83 Hz, 1H), 7,71 (DD, J=8,54, of 1.53 Hz, 1H), 1,65 (s, 18H), 0,33 (d, J=0,92 Hz, 18H).

Example 60D

tert-butyl 3, 5-diethynyl-1H-indazol-1-carboxylate and tert-butyl 5-bromo-3-ethinyl-1H-indazol-1-carboxylate

To a solution of compound of Example 60C (350 mg, 0.85 mmol) in tetrahydrofuran (5 ml) solution was added 1M TBAF in tetrahydrofuran (2 ml, 2 mmol). After 10 minutes the solvent is evaporated under reduced pressure and the crude mixture was purified using chromatography on silica gel, elwira a mixture of 5% ethyl acetate in hexane, to obtain specified in the header connections.1H NMR (500 MHz, DMSO-d6) δ ppm to 8.12 (d, J=to 7.93 Hz, 1H), 8,07 (d, J=cent to 8.85 Hz, 1H), 8,01 (d, J=1,53 Hz, 1H), of 7.90 (s, 1H), 7,83 (DD, J=cent to 8.85 and 1.83 Hz, 1H), 7,74 (DD,J=cent to 8.85, of 1.53 Hz, 1H), 4,91 (s, 1H), 4,90 (s, 1H), 4,29 (s, 1H), of 1.66 (s, 9H), of 1.65 (s, 9H).

Example 60E

3,5-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 3D, using the compound of Example 60D instead of the compound of Example 3C.1H NMR (500 MHz, DMSO-d6) δ ppm 13,35 (s, 1H), 8,76 (s, 1H), 8,71 (s, 1H), to 8.70 (s, 1H), 7,92 (d, J=8,61, of 1.28 Hz, 1H), to 7.64 (d, J=8,79 Hz, 1H), 7,38-the 7.43 (m, 8H), 7,33-7,37 (m, 2H), 5,73 (s, 2H), to 5.66 (s, 2H). MS (ESI+) m/z 433,2 (M+H)+.

Example 61

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-phenyl-1H-indazol

Example 61A

tert-Butyl 3-phenyl-5-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate and tert-butyl 5-bromo-3-phenyl-1H-indazol-1-carboxylate

The compound of Example 60B (1 g, 2.55 mmol), dichlorobis(triphenylphosphine)palladium(II) (89 mg, 0.13 mmol), triethylamine (1,78 ml, 12.75 mmol), trimethylsilylacetamide (0,432 ml of 3.06 mmol) and CuI (24 mg, 0.13 mmol) were combined in dimethylformamide (10 ml) and stirred at room temperature for 20 hours. The mixture was diluted with ethyl acetate and was purified using chromatography on silica gel with obtaining specified in the connection header.1H NMR (500 MHz, DMSO-d6) δ ppm 8,29 (d, J=1,53 Hz, 1H), 8,09-8,19 (m, 3H), of 7.96-8,03 (m, 4H), 7,83 (DD, J=cent to 8.85 and 1.83 Hz, 1H), 7,72 (DD, J=cent to 8.85, of 1.53 Hz, 1H), 7,50-the 7.65 (m, 6H), 1,68 (s, 18H), 0,26 is 0.27 (m, 9H).

Example 61B

tert-Butyl 5-ethinyl-3-phenyl-1H-indazol-1-carboxylate and tert-butyl 5-bromo-3-phenyl-1H-indazol-1-carboxylate

1H NMR (500 MHz, DMSO-d6) δ ppm of 8.28 (d, J=1,53 Hz, 1H), 8,21 (s, 1H), 8,16 (d, J=8.54 in Hz, 1H), 8,12 (d, J=cent to 8.85 Hz, 1H), 7,97-with 8.05 (m, 4H), 7,83 (DD, J=cent to 8.85 and 1.83 Hz, 1H), of 7.75 (DD, J=cent to 8.85, of 1.53 Hz, 1H), 7,53-to 7.64 (m, 6H), 4,27 (s, 1H), 1,68 (s, 9H), by 1.68 (s, 9H).

Example 61C

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-phenyl-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 3D, using the compound of Example 61B instead of the compound of Example 3C.1H NMR (500 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,77 (s, 1H), charged 8.52 (s, 1H), of 8.06 (d, J=7,33 Hz, 2H), 7,98 (d, J=8,79 Hz, 1H), 7,69 (d, J=8,79 Hz, 1H), 7,53-to 7.61 (m, J=7,51, 7,51 Hz, 2H), 7,33-of 7.48 (m, 6H), of 5.68 (s, 2H). MS (ESI+) m/z 352,0 (M+H)+.

Example 62

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Example 62A

2-Fluoro-5-((trimethylsilyl)ethinyl)benzonitrile

5-Bromo-2-perbenzoate (5,01 g 25,0 mmol), dichlorobis(triphenylphosphine)palladium(II) (652 mg, 0,929 mmol) and copper iodide(I) (413 mg, 2,17 mmol) were combined in triethylamine (15 ml) under nitrogen atmosphere. Added trimethylsilylacetamide (4,2 ml, 29.7 mmol) and the mixture was heated to 100°C. the Mixture was aterials, and the reaction was monitored by LC/MS. After completion of the reaction the mixture was diluted with methylene chloride and washed with 1 n HCl solution. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel, elwira using the m gradient of ethyl acetate in hexane (5-45%), obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm of 8.09 (DD, J=6,10, 2,03 Hz, 1H), to 7.77-of 7.97 (m, 1H), 7,54 (t, J=9.15, with Hz, 1H), 0,15-0,32 (m, 9H).

Example 62B

5-Ethinyl-2-perbenzoate

Tetrabutylammonium (a 1.0 M solution in tetrahydrofuran 70 ml) was added to a solution of compound of Example 62A (of 5.05 g, 23.2 mmol) in tetrahydrofuran (50 ml) and left to stir for 20 minutes. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel, elwira with a gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 8,13 (DD, J=6,27, 2.20 Hz, 1H), 7,82-to 7.95 (m, 1H), 7,56 (t, J=8,99 Hz, 1H), and 4.40 (s, 1H).

Example 62C

5-(1-Benzyl-1H-1,2,3-triazole-4-yl)-2-perbenzoate

The compound of Example 62B (1.68 g, 11.6 mmol) was dissolved in tert-butanol (14 ml). Added benzilate (2.14 g, 15.8 mmol) and the mixture was transferred into a 14 microwave vessels (1.0 ml each). In each microwave vessel was added water (0.5 ml), a small piece of copper wire and a 1 M solution of copper sulfate(II) (0.5 ml) and the vessel was heated in a microwave reactor CEM-Discover at 125°C with a power of 100 Watts for 10 minutes each. The contents of the vessels were combined, diluted with ethyl acetate and washed with water and saturated saline R is the target. Organic matter was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-50% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 8,73 (s, 1H), 8,33-8,44 (m, 1H), 8,19-8,32 (m, 1H), 7,56-of 7.70 (m, 1H), 7,28-7,47 (m, 5H), of 5.68 (s, 2H).

Example 62D

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Hydrazinehydrate (18 ml) was added to the compound of Example 62C (1,93 g, 6,94 mmol) in ethanol (10 ml). The mixture was heated to 95°C during the night. The mixture was diluted with ethyl acetate and washed with water. A certain amount of product deposited in a separating funnel, and it was filtered to obtain specified in the connection header. An ethyl acetate layer was concentrated under reduced pressure and the resulting solid was ground into powder with methanol to obtain additional quantities specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,43 (s, 1H), 8,42 (s, 1H), 8,21 (s, 1H), to 7.67 (d, J=8,82, 1.70 Hz, 1H), 7,38 (s, 5H), 7,26 (d, J=8,48 Hz, 1H), 5,64 (s, 2H), 5,38 (s, 2H). MS (ESI+) m/z 291,0 (M+H)+.

Example 63

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(1-methylpiperidin-4-yl)carbonyl]-1H-indazol-3-amine

Connection Example 62D (44 mg, 0,152 mmol), hydrochloride of 1-methylpiperidin-4-carboxylic acid (27 mg, 0,150 mmol) and HATU (61 mg, 0,160 mmol) were combined in tetrahydrofuran (2 ml). added diisopropylate the Lamin (110 ml, 0,631 mmol) and the mixture was heated to 90°C for 30 minutes. The mixture was diluted with methylene chloride and washed with 1 n sodium hydroxide solution. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-15% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 8,58 (s, 1H), of 8.47 (s, 1H), compared to 8.26 (d, J=8,48 Hz, 1H), of 7.97 (d, J=8,48, 1.70 Hz, 1H), 7,38 (s, 5H), to 6.58 (s, 2H), 5,67 (s, 2H), 3,35-3,47 (m, 1H), 2,95 (d, J=1 1,19 Hz, 2H), 2,28 (s, 3H), 2,03-of 2.20 (m, 2H,), with 1.92 (s, 2H), 1.77 in (s, 2H). MS (ESI+) m/z 416,2 (M+H)+.

Example 64

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-methoxyacetate

Example 64A

tert-Butyl 3-amino-5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

Connection Example 62D (1,80 g of 6.20 mmol) suspended in methylene chloride (100 ml) with a catalytic amount of dimethylaminopyridine. Solution was added di-tert-BUTYLCARBAMATE (1,36 g, 6,23 mmol) in methylene chloride (50 ml) dropwise over 1 hour. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header. MS (ESI+) m/z to € 391.1 (M+H)+.

Example 64B

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-methoxyacetate

The compound of Example 64A (45 mg, 0,115 mmol) was dissolved in metranil the Ried im Innkreis (1.5 ml) and pyridine (0.5 ml). Added methoxyacetanilide (18 μl, 0,197 mmol) and the mixture was stirred at ambient temperature for 2 hours. The solvents were removed using a warm stream of nitrogen, and the mixture was introduced into a column with silica gel and the product was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain tert-butyl 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-(2-methoxyacetyl)-1H-indazol-1-carboxylate (58 mg). Promezhutochnoe compound was dissolved in methylene chloride (2 ml) and triperoxonane acid (1 ml) and stirred at ambient temperature overnight. The solvents were removed under reduced pressure and the mixture was purified using preparative HPLC on a C8 column using a gradient from 10% to 100% acetonitrile/water containing 0.1% triperoxonane acid, obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 12,79 (s, 1H), 10,16 (s, 1H), 8,59 (s, 1H), to 8.20 (s, 1H), 7,83 (d, J=8,65, of 1.53 Hz, 1H), 7,51 (d, J=8,82 Hz, 1H), 7,37 (s, 5H), 5,64 (s, 2H), 4,12 (s, 2H), 3,42 (s, 3H). MS (ESI+) m/z 363,0 (M+H)+.

Example 65

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

The compound of Example 64A (81 mg, 0,207 mmol) was dissolved in methylene chloride (2 ml) and pyridine (0.5 ml). Added hydrochloride dimethylaminoacetonitrile, 80% (120 mg, 0,607 mmol) in three portions over 2 h the owls and the mixture was stirred at ambient temperature overnight. Added triperoxonane acid (2 ml) and the mixture was stirred for 3 hours. The mixture was diluted with methylene chloride and washed with 1 n sodium hydroxide solution. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-15% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 12,77 (s, 1H), of 10.05 (s, 1H), 8,58 (s, 1H), 8,24 (s, 1H), 7,82 (d, J=8,65, of 1.53 Hz, 1H), 7,50 (d, J=8,82 Hz, 1H), 7,30-7,44 (m, 5H), 5,64 (s, 2H), 3,16-3,20 (m, 2H), 2,34 (s, 6H). MS (ESI+) m/z 376,1 (M+H)+.

Example 66

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]butanamide

The compound of Example 64A (76 mg, of € 0.195 mmol) was dissolved in methylene chloride (2 ml) and pyridine (0.2 ml). Added butyrylcholine (26 μl, of 0.250 mmol) and the mixture was stirred at ambient temperature for 2 hours. Added triperoxonane acid (1 ml) and the mixture was stirred for 3 hours. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 1-8% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 12,70 (s, 1H), 10.30 a.m. (s, 1H), to 8.57 (s, 1H), 8,23 (s, 1H), 7,81 (d, J=8,82 Hz, 1H), 7,49 (d, J=8,82 Hz, 1H), 7,37 (s, 5H), 5,64 (s, 2H), 2,39 (t, J=7.29 trend Hz, 2H), 1,67 (s, 2H) 0,97 (t, J=7,46 Hz, 3H). MS (ESI+) m/z 361,1 (M+H)+.

Example 67

5-[4-(4-forfinal)-1-piperidine-4-yl-1H-indazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using piperidine-4-amine instead of benzylamine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,28 (s, 1H), 8,14 (s, 1H), 7,94 (s, 1H), 7,78 (s, 1H), 7,63-7,72 (m, 2H), 7,21-the 7.43 (m, 2H), 6.90 to? 7.04 baby mortality (m, 2H), 4,14 (d, J=5,59, to 1.86 Hz, 1H), 3,53-3,74 (m, J=5,76 Hz, 1H), 2,94 (d, J=12,21 Hz, 2H), 2.21 are to 2.35 (m, 2H), 1,74-of 1.88 (m, 3H). MS (DCI) m/z 362 (M+H)+.

Example 68

5-{4-(4-forfinal)-1-[2-(1-methylpyrrolidine-2-yl)ethyl]-1H-indazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 2-(1-methylpyrrolidine-2-yl)ethanamine instead of benzylamine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,30 (s, 1H), 8,14 (s, 1H), 7,86 (s, 1H), 7,82 (s, 1H), 7,68 (d, J=8,48 Hz, 1H), 7.24 to 7,47 (m, 3H), 6,92-was 7.08 (m, 2H), 3,83 (t, J=7,80 Hz, 2H), 2.71 to at 2.93 (m, 1H), 1,88 is 2.01 (m, 3H), 1,74-of 1.88 (m, 1H), 1,00 of-1.83 (m, 7H). MS (DCI) m/z 390 (M+H)+.

Example 69

5-{4-(4-forfinal)-1-[3-(4-methylpiperazin-1-yl)propyl]-1H-imidazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 3-(4-methylpiperazin-1-yl)propan-1-amine instead of benzylamine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 8,13 (s, 1H), 7,81 (s, 2H), to 7.67 (d, J=8,48 Hz, 1H), 7,32 was 7.45 (m, 2H), 7,27 (d, J=8,48, of 1.36 Hz, 1H), 6.87 in-7,06 (m, 2H), 3.72 points-3,91 (m, 2H), 1,92-of 2.21 (m, 10H), 1,1-of 2.20 (s, 3H), 1,51-of 1.66 (m, 2H). MS (ESI+) m/z 419 (M+H)+.

Example 70

ethyl 5-(1H-indazol-5-yl)isoxazol-3-carboxylate

The compound of Example 3C (1,83 g, 12.9 mmol) was dissolved in toluene (60 ml) and triethylamine (2.2 ml) and was heated to 90°C. Ethyl 2-chloro-2-(hydroxyimino)acetate (1.89 g, 12.5 mmol) was dissolved in toluene (15 ml) and added dropwise within 30 minutes. Once added, the mixture was diluted with ethyl acetate and washed with 1 n hydrochloric acid. The organic layer was concentrated under reduced pressure and the obtained residue was ground into powder with methanol to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,43 (s, 1H), 8,23 (s, 1H), 7,92 (d, J=8,82, of 1.36 Hz, 1H), of 7.70 (d, J=8,82 Hz, 1H), 7,44 (s, 1H), to 4.41 (sq, J=7,12 Hz, 2H), 1,35 (t, J=7,12 Hz, 3H). MS (ESI+) m/z 257,9 (M+H)+.

Example 71

5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide

Example 71 A

5-(1H-indazol-5-yl)isoxazol-3-carboxylic acid

The compound of Example 70 (1.50 g, 5.83 mmol) was dissolved in tetrahydrofuran (100 ml), methanol (10 ml) and water (10 ml). Was added potassium hydroxide (680 mg, 12.1 mmol) and the mixture was stirred at ambient temperature for 2 hours. The solvents were removed under reduced pressure and the obtained residue was ground into powder with a mixture of 1 n hydrochloric acid and methanol to obtain solid, which was filtered to obtain specified the title compound. 1H NMR (300 MHz, DMSO-dd) δ ppm 13,37 (s, 1H), 8,39 (s, 1H), they were 8.22 (s, 1H), of 7.90 (DD, J=8,81, of 1.36 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,30 (s, 1H).

Example 71B

5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide

The compound of Example 71A (46 mg, 0,201 mmol), HATU (88 mg, 0,231 mmol) and diisopropylethylamine (133 μl, 0,764 mmol) were combined in tetrahydrofuran (2 ml). Added monomethylamine (40% solution in water) (50 μl) and the reaction mixture was stirred at 50°C for 2 hours. The mixture was diluted with methylene chloride and washed with 1 n sodium hydroxide solution, 1 n hydrochloric acid and saturated saline. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 8,72 (sq, J=4,30 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,65, of 1.53 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,28 (s, 1H), 2,80 (d, J=4,75 Hz, 3H). MS (ESI+) m/z 243,0 (M+H)+.

Example 72

5-(3-benzisoxazol-5-yl)-1H-indazol

Phenylacetaldehyde (90+ %) (266 mg, of 2.38 mmol) was dissolved in tert-butanol (1 ml) and water (1 ml). Added gidroxinimesoulid (79 mg, to 1.14 mmol) followed by addition of 6 n sodium hydroxide solution (19 μl, and 31.7 mmol). The mixture was stirred for 30 minutes. Was slowly added chloramine-T trihydrate (308 mg, of 1.09 mmol) for 5 minutes, is followed by the addition of copper sulfate (II) and a small piece of copper wire. Added the compound of Example 3C (154 mg, of 1.08 mmol) and the mixture was stirred at 50°C for 2 hours, then at a temperature of acrawsa environment during the night. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,31 (s, 1H), 8,28 (s, 1H), 8,18 (s, 1H), 7,79 (DD, J=8,65, of 1.53 Hz, 1H), to 7.64 (d, J=8,81 Hz, 1H), 7,13-7,46 (m, 5H), 6,83 (s, 1H), Android 4.04 (s, 2H). MS (ESI+) m/z 275,7 (M+H)+.

Example 73

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide

The compound of Example 64A (72 mg, 0,184 mmol) was dissolved in methylene chloride (2 ml) and pyridine (0.2 ml). Added benzoyl chloride (36 μl, 0,310 mmol) and the mixture was stirred at ambient temperature for 2 hours. Added triperoxonane acid (1 ml) and the mixture was stirred for 3 hours. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and purified by chromatography on silica gel by elution gradient 1-8% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 12,88 (s, 1H), 10,81 (s, 1H), 8,63 (s, 1H), 8,16 (s, 1H), 8,06-8,13 (m, 2H), 7,88 (d, J=8,82, of 1.36 Hz, 1H), to 7.59-to 7.64 (m, J=7,12 Hz, 1H), 7,51-to 7.59 (m, 3H), 7,31-7,42 (m, 5H), 5,63(s, 2H). MS (ESI+) m/z 395,1 (M+H)+.

Example 74

5-(3-propylenoxide-5-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 72, using Butyraldehyde instead of phenylacetaldehyde.1H NMR (300 MHz, DMSO-d<j) δ ppm 13,31 (s, 1H), 8,28 (s, 1H), to 8.20 (s, 1H), 7,76-a 7.85 (m, 1H), 7,63-of 7.70 (m, 1H), to 6.88 (s, 1H), 2.63 in (t, J=7,46 Hz, 2H), 1,61-to 1.79 (m, 2H), of 0.96 (t, J=7.29 trend Hz, 3H). MS (ESI+) m/z 228,0 (M+H)+.

Example 75

N-benzyl-4-(1H-indazol-5-yl)-5-phenyl-1,3-thiazol-2-amine

Example 75A

1H-indazol-5-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in Example 3A, using methyl 4-amino-3-methylbenzoate instead of 4-iodine-2-methylaniline. In the process of finishing the addition of 6 n HCl to achieve pH 6 resulted in the formation of solid, which was filtered, washed twice with water and dried in vacuum to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,32 (s, 1H), 12,83 (s, 1H), 8,46 (s, 1H), 8,24 (s, 1H), 7,92 (DD, J=8,82, 1.70 Hz, 1H), 7,60 (d, J=8,82 Hz, 1H).

Example 75B

N-Methoxy-N-methyl-1H-indazol-5-carboxamid

To a suspension of compound of Example 75A (1.6 g, 10 mmol) and N,O-dimethylhydroxylamine (1.1 g, 11 mmol) in dichloromethane (40 ml) and dimethylformamide (10 ml) was added triethylamine (rate of 1.67 ml, 12 mmol) and EDC (2.1 g, 11 mmol) and the mixture was stirred at room temperature is round within 24 hours. The solvents are evaporated under reduced pressure and the obtained residue was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate and purified using column chromatography on silica gel in ethyl acetate to obtain specified in the connection header. MS (ESI+) m/z 206,0 (M+H)+.

Example 75C

1-(1H-indazol-5-yl)-2-phenylethanone

A solution of compound of Example 75B (900 mg, 4,39 mmol) in tetrahydrofuran (10 ml) was cooled in an argon atmosphere using an ice bath and treated using a 2M solution of benzylmagnesium in tetrahydrofuran (6.6 ml, 13,16 mmol). The reaction mixture was stirred overnight at room temperature followed by the addition of one equivalent of benzylaniline. The mixture was heated at 70°C for 9 hours. Added another equivalent of benzylaniline and the reaction mixture was heated at 70°C for 90 minutes and allowed to cool to room temperature. Was added a saturated aqueous solution of ammonium chloride and the product was extracted with ethyl acetate and was purified using column chromatography on silica gel using 30% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 237,1 (M+H)+.

Example 75D

tert-Butyl 5-(2-phenylacetyl)-1H-indazol-1-carboxylate

To a suspension of compound of Example 75C (236 mg, 1 is the mole) in dichloromethane (2 ml) was added di-tert-BUTYLCARBAMATE (327 mg, 1.5 mmol) and a pinch of dimethylaminopyridine (~2 mg). The mixture was stirred for 15 minutes and passed through a layer of silica gel and was suirable dichloromethane. The solvent is evaporated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 337,0 (M+H)+.

Example 75E

2-Bromo-1-(1H-indazol-5-yl)-2-phenylethanone

To a solution of compound of Example 75D (336 mg, 1 mmol) in tetrahydrofuran (20 ml), heated at 40°C in an oil bath, was added dropwise via an addition funnel a solution of tribromide pyridinium (352 mg, 1.1 mmol) in tetrahydrofuran (20 ml) for 10 minutes. The reaction mixture was heated for another 2 hours and then was cooled, filtered and the filtrate was evaporated to obtain specified in the connection header. MS (ESI-) m/z 212,9 (M-H)".

Example 75F

N-benzyl-4-(1H-indazol-5-yl)-5-phenyl-1,3-thiazol-2-amine

The vessel containing the compound of Example 75E (50 mg, 0.16 mmol) and 1-benzyltoluene (26 mg, 0.16 mmol) in ethanol (1 ml), covered with a lid and heated in a heating device with shaking at 80°C for 2 hours. A solution of the crude product was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header in the form of a salt TFU.1H NMR (400 MHz, DMSO-d6) δ ppm 12,99 (s, 1H), 8,33-of 8.37 (m, 1H), 8,01 (s, 1H), 7,92-to 7.99 (m, 1H), 7,82 (s, 1H), ,60-7,67 (m, J=7,83, 7,83 Hz, 1H), 7,31 was 7.45 (m, 5H), 7,17-7,30 (m, 5H), 4,53 (d, J=4,60 Hz, 2H). MS (ESI+) m/z of 383.0 (M+H)+.

Example 76

4-(1H-indazol-5-yl)-N,5-diphenyl-1,3-thiazole-2-amine

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 75F, using 1-phenyltoloxamine instead of 1-benzyltoluene.1H NMR (400 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), 10,29 (s, 1H), with 8.05 (d, J=0,92 Hz, 1H), 7,89 (d, J=1,53, to 0.92 Hz, 1H), 7,69 (d, J=8,59, 1,23 Hz, 2H), 7,47 (dt, J=8,59, to 0.92 Hz, 1H), 7,40-7,44 (m, 1H), 7,26-7,37 (m, 7H), 6,94-7,02 (m, J=of 7.36, of 7.36 Hz, 1H). MS (ESI+) m/z 369,0 (M+H)+.

Example 77

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Example 77A

tert-butyl 5-(cyclopropylmethyl)-1H-indazol-1-carboxylate

The compound of Example 44A (2,31 g, to 7.77 mmol), cyclopropylacetylene (620 mg, 9,37 mmol), dichlorobis(triphenylphosphine)palladium(II) (170 mg, 0,242 mmol) and copper iodide(I) (92 mg, 0,483 mmol) were combined in triethylamine (10 ml) in an inert nitrogen atmosphere. The mixture was heated to 100°C in a sealed tube for 4 hours. The mixture was diluted with methylene chloride and washed with 1 n hydrochloric acid. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 283,0 (M+H)+.

Example 77B

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-three is evil-4-yl)-1H-indazol

The compound of Example 77A (145 mg, 0.51 mmol) and benserazide (82 mg, of 0.62 mmol) was heated without solvent in a microwave reactor CEM-Discover at 150°C and 150 Watts for 10 minutes. The crude mixture was dissolved in dichloromethane and purified using column chromatography on silica gel using 50% ethyl acetate in hexane as eluent.1H NMR (400 MHz, DMSO-d6) δ ppm 13,12 (s, 1H), 8,11 (d, J=5,52 Hz, 2H), 7,79 (d, J=8,59, of 1.53 Hz, 1H), 7,60 (d, J=8,59 Hz, 1H), 7,26 was 7.45 (m, 5H), 5,69 (s, 2H), 1,78-of 1.92 (m, 1H), 0,98-of 1.09 (m, 2H), 0,31-of 0.45 (m, 2H). MS (ESI+) m/z was 316.0 (M+H)+.

Example 78

5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol

Specified in the title compound was isolated as a side product in accordance with the procedure described in Example 77B.1H NMR (500 MHz, DMSO-d6) δ ppm to 13.29 (s, 1H), 8,14 (s, 1H), 7,80 (s, 1H), 7,65 (d, J=cent to 8.85 Hz, 1H), 7,29 (d, J=8,54, of 1.53 Hz, 1H), 7,21-7,27 (m, 3H), 6,93 (d, J=of 7.48, to 1.98 Hz, 2H), 5,49 (s, 2H), 1,70-1,80 (m, 1H), 0,81 to 0.92 (m, 4H). MS (ESI+) m/z was 316.0 (M+H)+.

Example 79

2-(1H-indazol-5-yl)-3-phenylimidazo[1,2-a]pyrimidine

The vessel containing the compound of Example 75E (80 mg, 0.25 mmol) and pyrimidine-2-amine (23 mg, 0.25 mmol) in ethanol (1 ml), covered with a lid and heated in a heating device with shaking at 80°C for 21 hours. A solution of the crude product was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8,69 (DD, J=4,30, of 1.84 Hz, 1H), 8,59 (DD, J=6.75 in, of 1.84 Hz, 1H), 8,07 (s, 1H), 8,02 (s, 1H), 7,46-the 7.65 (m, 7H), 7,16 (DD, J=6.75 in, 3,99 Hz, 1H). MS (ESI+) m/z 312,0 (M+H)+.

Example 80

5-[1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Example 80A

4-(azidomethyl)tetrahydro-2H-Piran

4-(Iodomethyl)tetrahydro-2H-Piran (4,76 g, 21.1 mmol) was dissolved in dimethyl sulfoxide (25 ml). Was added sodium azide (2.70 g, 41.5 mmol) and the mixture was stirred at ambient temperature overnight. The resulting suspension was diluted simple diethyl ether and washed with water. The organic layer was concentrated under reduced pressure to obtain specified in the connection header. The product was used directly in subsequent reactions without his identification.

Example 80B

5-[1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

The compound of Example 80A (122 mg, 0,864 mmol) and the compound of Example 3C (150 mg, 0,619 mmol) were combined in a microwave vessel with tert-butanol (1 ml) and water (1 ml). Added a small piece of copper wire with the subsequent addition of copper sulfate(II) (5 mg, 0.02 mmol) and the contents of the vessel were stirred in a microwave system (CEM-Discover) at 125°C at 100 W for 10 minutes. The mixture was diluted with methylene chloride and washed with 1 n hydrochloric acid. The organic layer was absorbed on silica gel which was purified using chromatography on silica gel, using elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMS(MJ) δ ppm 13,11 (s, 1H), 8,53 (s, 1H), they were 8.22 (s, 1H), 8,12 (s, 1H), a 7.85 (d, J=8,48, of 1.36 Hz, 1H), 7,60 (d, J=8,82 Hz, 1H), 4,32 (d, J=7,12 Hz, 2H), 3,85 (d, J=1 1,70, of 2.54 Hz, 2H), 3,21-to 3.36 (m, 2H), and 2.14 (s, 1H), of 1.47 (s, 2H), 1,30 (s, 2H). MS (ESI+) m/z 284,0 (M+H)+.

Example 81

5-[3-(piperidine-1-ylcarbonyl)isoxazol-5-yl]-1H-indazol

Example 81A

5-(1H-indazol-5-yl)isoxazol-3-carboxylic acid

The compound of Example 70 (1.50 g, 5.83 mmol) was dissolved in tetrahydrofuran (100 ml), methanol (10 ml) and water (10 ml). Was added potassium hydroxide (680 mg, 12.1 mmol) and the mixture was stirred at ambient temperature for 2 hours. The solvents were removed under reduced pressure and the obtained residue was ground into powder with a mixture of 1 n hydrochloric acid and methanol to obtain solid, which was filtered to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), to 8.41 (s, 1H), 8,23 (s, 1H), to $ 7.91 (DD, J=8,82, 1.70 Hz, 1H), of 7.70 (d, J=8,82 Hz, 1H), was 7.36 (s, 1H).

Example 81B

5-[3-(piperidine-1-ylcarbonyl)isoxazol-5-yl]-1H-indazol

The compound of Example 81A (110 mg, to 0.480 mmol), piperidine (55 μl, 0,556 mmol) and HATU (101 mg, 0,266 mmol) were combined in dimethylformamide (2 ml). Added diisopropylethylamine (133 μl, 0,764 mmol) and the reaction mixture was stirred at 45°C for 2 hours the Mixture was diluted with ethyl acetate and washed with 1 n sodium hydroxide solution, 1 n hydrochloric acid solution, water (3 times) and saturated salt solution. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 8.34 per-of 8.40 (m, 1H), 8,21-of 8.25 (m, 1H), 7,84-to $ 7.91 (m, 1H), 7,66-7,72 (m, 1H), 7,20 (s, 1H), 3,59 at 3.69 (m, 2H), 3,48-to 3.58 (m, 2H), 1,47-1,72 (m, 6H). MS (ESI+) m/z 297,0 (M+H)+.

Example 82

5-(1H-indazol-5-yl)-N-phenylisoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using aniline instead of piperidine.1H NMR (500 MHz, DMSO-d6) δ ppm 13,40 (s, 1H), a 10.74 (s, 1H), 8,44 (s, 1H), of 8.25 (s, 1H), to 7.93 (d, J=cent to 8.85, of 1.53 Hz, 1H), 7,82 (d, J=7,63 Hz, 2H), 7,72 (d, J=cent to 8.85 Hz, 1H), 7,44 (s, 1H), 7,35-7,42 (m, 2H), 7,16 (t, J=7,32 Hz, 1H). MS (ESI+) m/z 304,9 (M+H)+.

Example 83

N-cyclohexyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

The compound of Example 81A (53 mg, 0,231 mmol), cyclohexylamine (29 μl, 0,253 mmol) and HATU (101 mg, 0,266 mmol) were combined in dimethylformamide (2 ml). Added diisopropylethylamine (133 μl, 0,764 mmol) and the reaction mixture was stirred at 45°C for 2 hours. The mixture was diluted with ethyl acetate and washed with 1 n sodium hydroxide solution, 1 n hydrochloric acid solution, water (3 times) and saturated salt solution. the content of inorganic fillers layer was absorbed on silica gel and was purified using chromatography on silica gel, using elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 8,58 (d, J=8,14 Hz, 1H), scored 8.38 (s, 1H), they were 8.22 (s, 1H), 7,88 (d, J=8,81, 1.70 Hz, 1H), 7,69 (d, J=8,81 Hz, 1H), 7,28 (s, 1H), 3,69-3,86 (m, 1H), 1.77 in (s, 4H), 1,60 (d, J=12,21 Hz, 1H), 1,20-1,46 (m, 4H), 1.06 a-1,20 (m, 1H). MS (ESI+) m/z 311,0 (M+H)+.

Example 84

5-[3-(piperidine-1-ylmethyl)isoxazol-5-yl]-1H-indazol

The compound of Example 81B (22 mg, 0,0742 mmol) was dissolved in tetrahydrofuran (2.5 ml) in an inert nitrogen atmosphere. Added sociallyengaged (a 1.0 M solution in tetrahydrofuran) (250 μl) and the mixture was heated to 70°C for 20 minutes. Was added methanol and the mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of methanol in dichloromethane (0-7%), obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,30 (s, 1H), 8,31 (s, 1H), to 8.20 (s, 1H), to 7.84 (d, J=8,59, of 1.53 Hz, 1H), 7,66 (d, J=8,59 Hz, 1H), 6,92 (s, 1H), 3,54 (s, 2H), 2,32 is 2.46 (m, 2H), 1,47-to 1.59 (m, 4H), 1,33 of 1.46 (m, 2H). MS (ESI+) m/z 283,0 (M+H)+.

Example 85

[5-(1H-indazol-5-yl)isoxazol-3-yl]methanol

The compound of Example 70 (84 mg, 0,366 mmol) was dissolved in tetrahydrofuran (8 ml). Added sociallyengaged (a 1.0 M solution in tetrahydrofuran (THF) (3.0 ml) and 1.0-ml portions over 2 hours. Upon completion of the addition, the mixture was stirred for another 30 minutes. The mixture was diluted with methylene what chloridum and washed with water and the organic layer was absorbed on silica gel and was purified using chromatography on silica gel, using elution gradient of 0-20% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,31 (s, 1H), 8,31 (s, 1H), 8,21 (s, 1H), 7,83 (d, J=8,59, of 1.53 Hz, 1H), to 7.67 (d, J=8,90 Hz, 1H), 6,93 (s, 1H), 5,51 (s, 1H), 4,56 (d, J=2,45 Hz, 1H). MS (ESI+) m/z 215,9 (M+H)+.

Example 86

5-(1H-indazol-5-yl)-N-(2-methoxyethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using a 2-methoxyethylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), total of 8.74 (t, J=4,92 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,65, of 1.53 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,30 (s, 1H), 3,38-of 3.53 (m, 4H), of 3.28 (s, 3H). MS (ESI+) m/z 287,0 (M+H)+.

Example 87

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Example 87A

1-(5-Iodine-1H-indazol-1-yl)alanon

4-Iodine-2-methylaniline (30,2 g, 130 mmol) was dissolved in chloroform (300 ml) and was cooled to 5°C. was Added dropwise acetic anhydride (35 ml, 343 mmol) and the mixture was allowed to warm to ambient temperature. Was added potassium acetate (4,21 g, 42,9 mmol) and isoenergetic (37 ml, 277 mmol) and the mixture was heated to 70°C during the night. The mixture was neutralized with saturated aqueous sodium bicarbonate solution and was extracted with methylenechloride. The solvents were removed under reduced pressure and the obtained residue was ground into powder with methanol to obtain specified in the header is the connection. 1H NMR (300 MHz, DMSO-d6) δ ppm to 8.41 (s, 1H), with 8.33 (s, 1H), 8,05-8,21 (m, 1H), of 7.90 (DD, J=8,48, 1.70 Hz, 1H), 2,71 (s, 3H).

Example 87B

1-Benzyl-5-phenyl-4-(tributylstannyl)-1H-1,2,3-triazole

Phenylethynyl-tri-n-botillo (8,25 g, 21.1 mmol) and benserazide (2.3 ml, 18.4 mmol) were combined and heated to 150°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 526,3 (M+H)+.

Example 87C

1-(5-(1-Benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-yl)alanon

The compound of Example 87A (139 mg, 0,486 mmol), the compound of Example 87B (284 mg, 0,542 mmol), dichlorobis(triphenylphosphine)palladium(II) (40 mg, 0,057 mmol) and thiophene-2-carboxylate copper (167 mg, 0,876 mmol) were combined in toluene (1.5 ml) in a microwave vessel in an inert atmosphere of nitrogen. The vessel was heated in a microwave system (CEM-Discover) up to 150°C at 125 Watts for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 394,1 (M+H)+.

Example 87D

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Connection Example 87C (95 mg, 0,242 mmol) was dissolved in tetrahydrofuran (2.0 ml), methanol (1.0 ml) and water (1.0 ml) was added potassium hydroxide (64 mg, 1,14 m is ol). The mixture was stirred for 2 hours and was diluted with ethyl acetate and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), 8,00 (s, 1H), 7,79 (s, 1H), 7,44-7,56 (m, 5H), 7,24 and 7.36 (m, 5H), 6,95-7,03 (m, 2H), 5,49 (s, 2H). MS (ESI+) m/z 252,1 (M+H)+.

Example 88

5-(4-benzyl-1H-1,2,3-triazole-1-yl)-1H-indazol

The compound of Example 87A (969 mg, 3,39 mmol), 3-phenyl-1-propyne (392 mg, 3,37 mmol), sodium azide (278 mg, 4,28 mmol), sodium ascorbate (68 mg, of 3.43 mmol), sodium carbonate (75 mg, 0,708 mmol) and L-Proline (78 mg, 8.98 mmol) were combined in 1:1 mixture of dimethyl sulfoxide and water (10 ml). Added copper sulfate(II) pentahydrate (46 mg, 0,184 mmol) and the mixture was stirred at 65°C for 3 hours. Added a 6N solution of sodium hydroxide (1 ml) and the mixture was stirred for 30 minutes to remove protection from andazola. The mixture was diluted with ethyl acetate and washed with 1 n hydrochloric acid. The organic layer was concentrated under reduced pressure and the obtained residue was ground into powder with methanol. The remaining solid particles absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, received the eat specified in the connection header. 1H NMR (300 MHz, DMSO-d6) δ ppm 13,35 (s, 1H), 8,58 (s, 1H), 8.17-a of 8.27 (m, 1H), 7,86 (d, J=8,82, 2,03 Hz, 1H), to 7.67-to 7.77 (m, 1H), 7,27 was 7.36 (m, 2H), 7.18 in-7,27 (m, 1H), 4,10 (s, 1H). MS (ESI+) m/z 276,0 (M+H)+.

Example 89

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Example 89A

5-(Cyclopropylamino)-2-perbenzoate

5-Bromo-2-perbenzoate (of 3.06 g of 15.3 mmol), dichlorobis(triphenylphosphine)palladium(II) (478 mg, 0,681 mmol) and copper iodide(I) (165 mg, 0,866 mmol) were combined in triethylamine (15 ml) in an inert nitrogen atmosphere. Added cyclopropylacetylene (1.8 ml) and the mixture was heated to 60°C, until she turned into a black solid. The mixture was diluted with methylene chloride and washed with 1 n hydrochloric acid. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 319,0 (M+H)+.

Example 89B

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

The compound of Example 89A (211 mg, to 1.14 mmol) and benserazide (143 μl, to 1.14 mmol) were combined in a microwave (CEM-Discover) the vessel and was heated to 160°C, using a power of 100 Watts, for 26 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 20-60% ethyl acetate in hexane, with the doctrine of inseparable mixture of triazole regimeof. A mixture of regimeof were treated with hydrazinehydrate (3.0 ml) and ethanol (3.0 ml) and heated to 90°C for 1 hour. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 1-6% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,43 (s, 1H), 8,07 (s, 1H), 7,63 (d, J=8,65, of 1.53 Hz, 1H), 7,32 was 7.45 (m, 3H), 7.24 to to 7.32 (m, 3H), of 5.68 (s, 2H), of 5.40 (s, 2H), 1,69 of-1.83 (m, 1H), 0,98-1,08 (m, 2H), 0,32 at 0.42 (m, 2H). MS (ESI+) m/z 331,1 (M+H)+.

Example 90

5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol-3-amine

Specified in the title compound was isolated as a side product in accordance with the procedure described in Example 89B.1H NMR (300 MHz, DMSO-d6) δ ppm are 11.62 (s, 1H), 7,79 (s, 1H), 7,32 (d, J=8,48 Hz, 1H), 7,20-7,27 (m, 3H), 7,15 (d, J=8,65, of 1.53 Hz, 1H), 6,93 (d, J=7,12, 2.37 Hz, 2H), 5,49 (s, 2H), of 5.45 (s, 2H), 1,71-to 1.82 (m, 1H), 0,80-0,89 (m, 4H). MS (ESI+) m/z 331,1 (M+H)+.

Example 91

5-(3-isobutylthiazole-5-yl)-1H-indazol-3-amine

Example 91A

2-fluoro-5-(3-isobutylthiazole-5-yl)benzonitrile

Specified in the title compound was obtained in accordance with the procedure described in Example 72, using isovaleraldehyde instead of phenylacetaldehyde and using the compounds of Example 62B instead of the compound of Example 3C.1H NMR (300 MHz, DMSO-d6) δ ppm 847 (DD, J=6,10, 2,03 Hz, 1H), 8,19-8,29 (m, 1H), 7,71 (t, J=8,99 Hz, 1H), was 7.08 (s, 1H), 2,56 (d, J=7,12 Hz, 2H), 1,86 is 2.10 (m, 1H), 0,94 (d, J=is 6.78 Hz, 6H).

Example 91B

5-(3-isobutylthiazole-5-yl)-1H-indazol-3-amine

To the compound of Example 91A (75 mg, 0,307 mmol) was added hydrazinehydrate (1.5 ml) in ethanol (1.0 ml). The mixture was heated to 70°C overnight in a tightly closed container. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header

1H NMR (300 MHz, DMSO-d6) δ ppm 11,67 (s, 1H), compared to 8.26 (s, 1H), 7,66 (DD, J=8,82, 1.70 Hz, 1H), 7,32 (d, J=8,48 Hz, 1H), to 6.67 (s, 1H), 5.56mm (s, 2H), of 2.51-of 2.58 (m, 2H), 1,89-2,11 (m, 1H), 0,95 (d, J=6,44 Hz, 6H). MS (ESI+) m/z to 257.0 (M+H)+.

Example 92

5-(3-benzisoxazol-5-yl)-1H-indazol-3-amine

Example 92A

5-(3-benzisoxazol-5-yl)-2-perbenzoate

Specified in the title compound was obtained in accordance with the procedure described in Example 72, using the compound of Example 62B instead of the compound of Example 3C. The crude product was used in the next stage without additional purification or determine its characteristics.

Example 92B

5-(3-benzisoxazol-5-yl)-1H-indazol-3-amine

To the compound of Example 92A (65 mg, 0,234 mmol) was added hydrazinehydrate (1.5 ml) in ethanol (1.0 ml). The mixture was heated is about 70°C overnight in a tightly closed container. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-20% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,67 (s, 1H), compared to 8.26 (s, 1H), 7,66 (d, J=8,82, 1.70 Hz, 1H), 7,32 (d, J=8,48 Hz, 1H), to 6.67 (s, 1H), 5.56mm (s, 2H), 2,45-to 2.57 (m, 2H), 1,91-of 2.08 (m, 1H), 0,95 (d, J=6,44 Hz, 6H). MS (ESI+) m/z 291,0 (M+H)+.

Example 93

N-{2-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]ethyl}-N,N-dimethylamine

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using a 2-diethylaminoethylamine instead of benzylamine.1H NMR (500 MHz, c) δ ppm 13,28 (s, 1H), 8,14 (s, 1H), 7,78-7,87 (m, 2H), 7,68 (d, J=8.54 in Hz, 1H), 7,33-7,41 (m, 2H), 7,28 (d, J=8,54, of 1.53 Hz, 1H), 6,95-7,05 (m, 2H), 3,86 (t, J=6,56 Hz, 2H), 2,31 (t, J=of 6.71 Hz, 2H), a 2.00 (s, 6H).

Example 94

5-[4-(4-forfinal)-1-(3-morpholine-4-ylpropyl)-1H-imidazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 3-morpholinopropan instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 13,28 (s, 1H), 8,14 (s, 1H), 7,79-7,87 (m, 2H), 7,68 (d, J=8,24 Hz, 1H), 7,34-7,42 (m, 2H), 7,28 (d, J=8,54, of 1.53 Hz, 1H), 6,92-7,03 (m, 2H), of 3.77-to 3.89 (m, 2H), 3,24-3,30 (m, 4H), 2,10 (t, J=6,56 Hz, 2H), 1,96-2,05 (m, 4H), 1,54-of 1.66 (m, 2H). MS (ESI+) m/z 406,1 (M+H)+.

Example 95

5-[4-(4-forfinal)--(3-pyrrolidin-1-ylpropyl)-1H-imidazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 3-pyrrolidinedione instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,13 (d, J=0,92 Hz, 1H), 7,79-a 7.85 (m, 2H), 7,68 (d, J=8.54 in Hz, 1H), 7,38 (d, J=cent to 8.85, 5,49 Hz, 2H), 7,27 (d, J=8,54, of 1.53 Hz, 1H), 6,99 (t, J=9,00 Hz, 2H), 3,82-3,90 (m, 2H), of 2.21 (t, J=of 6.71 Hz, 2H), 2,08-to 2.18 (m, 4H), 1.56 to of 1.65 (m, 2H), 1,44-of 1.53 (m, 4H). MS (ESI+) m/z 390,2 (M+H)+.

Example 96

5-{4-(4-forfinal)-1-[2-(4-methylpiperidin-1-yl)ethyl]-1H-imidazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 2-(4-methylpiperidin-1-yl)ethanamine instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 13.29 (s, 1H), 8,14 (s, 1H), 7,83 (s, 1H), 7,81 (s, 1H), to 7.67 (d, J=8.54 in Hz, 1H), 7,32-7,40 (m, 2H), 7,28 (DD, J=8,54, of 1.53 Hz, 1H), 6,93? 7.04 baby mortality (m, 2H), 3,85 (t, J=6,56 Hz, 2H), 2,60 (d, J=1 to 1.60 Hz, 2H)that is 2.37 (t, J=6,56 Hz, 2H), 1,71-of 1.85 (m, 2H), 1,45 (d, J=1 1,29 Hz, 2H), 1,15-1,30 (m, 1H), 0,95-of 1.07 (m, 2H), or 0.83 (d, J=of 6.71 Hz, 3H) MS (ESI+) m/z 404,1 (M+H)+.

Example 97

5-[1-(1-benzylpiperidine-4-yl)-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 4-amino-N-benzylpiperidine instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 13,32 (s, 1H), 8,14 (s, 1H), 8,02 (s, 1H), 7,78 (s, 1H), 7,69 (d, J=8.54 in Hz, 1H), 7,17-7,40 (m, 8H), 6,97 (t, J=cent to 8.85 Hz, 2H), 3,50-3,63 (m, 1H), 3,40 (s, 2H), 2,82 (d, J=1 1,90 G is, 2H), 1,90-2,05 (m, 2H), 1,72-1,89 (m, 4H). MS (ESI+) m/z 452,2 (M+H)+.

Example 98

5-[4-(4-forfinal)-1-(2-morpholine-4-retil)-1H-imidazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using a 2-morpholinoethyl instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm of 13.27 (s, 1H), 8,14 (s, 1H), 7,86 (s, 1H), 7,81 (s, 1H), to 7.67 (d, J=8.54 in Hz, 1H), 7,33-7,42 (m, 2H), 7,29 (d, J=8.54 in Hz, 1H), 6,95-7,06 (m, 2H), a 3.87 (t, J=6,41 Hz, 2H), 3,42-3,51 (m, 4H), 2.40 a (t, J=6,56 Hz, 2H), 2,21 (d, J=3,97 Hz, 4H). MS (ESI+) m/z 392,1 (M+H)+.

Example 99

5-[1-(1-benzylpyrrolidine-3-yl)-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 3-pyrrolidinedione instead of benzylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm to 13.29 (s, 1H), 8,13 (s, 1H), 8,03 (s, 1H), 7,76 (s, 1H), to 7.67 (d, J=8.54 in Hz, 1H), 7,29-7,38 (m, 6H), 7,20-7,28 (m, 2H), 6,98 (t, J=9,00 Hz, 2H), 4,25-4,34 (m, 1H), 3,53 at 3.69 (m, 2H), 2,89-of 2.97 (m, 1H), 2,84 (d, J=9,76, of 3.05 Hz, 1H), 2,55 (d, J=10,07, of 6.71 Hz, 1H), 2,17-of 2.34 (m, 2H), 1,92-2,03 (m, 1H). MS (ESI+) m/z 438,1 (M+H)+.

Example 100

Example 100 is removed and is not part of this document.

Example 101

2-{4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]piperidine-1-yl}-2-oxoethyl

Specified in the title compound was obtained in accordance with the procedure described in Example 39, using 1-(4-aminopiperidin-1-yl)-2-hydroxyethane is on instead of benzylamine. 1H NMR (300 MHz, DMSO-d6/D2O) δ ppm of 13.27 (s, 1H), 8,14 (s, 1H), to 7.99 (s, 1H), 7,81 (s, 1H), 7,69 (d, J=8,48 Hz, 1H), 7,25-7,39 (m, 4H), 6,91-7,03 (m, 2H), 4,48 (t, J=5.43 Hz, 1H), 4,34-of 4.44 (m, 1H), 4,07 (t, J=5,59 Hz, 1H), 3,79-3,91 (m, 1H), 3,64-of 3.77 (m, 1H), 2,85 (m, 1H), 2.77-to 2,90 (m, 5H). MS (DCI) m/z 420 (M+H)+.

Example 102

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Example 102A

5-(1-Benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-2-perbenzoate

The compound of Example 87B (415 mg, 0,792 mmol), 5-bromo-2-perbenzoate (158 mg, 0,790 mmol), dichlorobis(triphenylphosphine)palladium(II) (52 mg, 0,074 mmol) and thiophene-2-carboxylate copper (226 mg, 1,19 mmol) were combined in toluene (2 ml) in a microwave vessel in an inert atmosphere of nitrogen. The vessel was heated in a microwave system (CEM-Discover) up to 150°C at 125 Watts for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of ethyl acetate in hexane (5-40%), obtaining specified in the connection header. MS (ESI+) m/z 355,1 (M+H)+.

Example 102B

5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

The compound of Example 102A (120 mg, 0,339 mmol) was treated with hydrazinehydrate (1.0 ml) in ethanol (1.0 ml) and was heated to 60°C over night. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 0-5% m is canola in dichloromethane, obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), of 8.06 (s, 1H), 7,42-of 7.55 (m, 3H), 7.23 percent-7,33 (m, 5H), 7,02-7,10 (m, 2H), 6,94-7,02 (m, 2H), 5,49 (s, 2H), of 5.34 (s, 2H). MS (ESI+) m/z 367,1 (M+H)+.

Example 103

2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 88 using 2-methyl-3-butyn-2-ol instead of 3-phenyl-1-propene, except that the crude reaction mixture was extinguished using 2 ml of 1 n aqueous NaOH, and stirred for 1.5 hours at ambient temperature. The slurry is then dried by evaporation using a flow of heated nitrogen gas before the implementation of atrakchi.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,51 (s, 1H), they were 8.22-8,29 (m, 2H), 7,88 (d, J=9,00, to 1.98 Hz, 1H), to 7.77 (d, J=cent to 8.85 Hz, 1H), 1.57 in (s, 6H). MS (ESI+) m/z 244,0 (M+H)+.

Example 104

5-[4-(methoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using methylpropanamide ester instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,73 (s, 1H), 8,23-8,29 (m, J=1,83 Hz, 2H), 7,88 (d, J=cent to 8.85, and 2.14 Hz, 1H), 7,78 (d, J=9.15, with Hz, 1H), 4,57 (s, 2H), 3,35 (s, 3H). MS (ESI+) m/z 230,0 (M+H)+.

Example 105

1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]-1-phenylethanol

Specified in the header with the unity received in accordance with the procedure described in Example 88 using 2-phenyl-3-butyn-2-ol instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm charged 8.52 (s, 1H), 8,21-of 8.28 (m, 2H), 7,87 (d, J=cent to 8.85, and 2.14 Hz, 1H), 7,76 (d, J=9.15, with Hz, 1H), 7,51-EUR 7.57 (m, 2H), 7,34 (t, J=7,78 Hz, 2H), 7,24 (t, J=7,32 Hz, 1H), 1,92 (s, 3H). MS (ESI+) m/z 306,0 (M+H)+.

Example 106

5-(4-propyl-1H-1,2,3-triazole-1-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1-pentene instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm and 8.50 (s, 1H), 8,20-8,30 (m, 2H), 7,87 (d, J=9,00, to 1.98 Hz, 1H), to 7.77 (d, J=cent to 8.85 Hz, 1H), 2,71 (t, J=of 7.48 Hz, 2H), 1,64-of 1.78 (m, 2H), 0,97 (t, J=to 7.32 Hz, 3H). MS (ESI+) m/z 228,0 (M+H)+.

Example 107

1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using the Penta-4-in-2-ol instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,49 (s, 1H), 8,20-of 8.33 (m, 2H), 7,88 (DD, J=9,00, to 1.98 Hz, 1H), 7,74-of 7.82 (m, 1H), 3.95 to 4,08 (m, 1H), 2,74-2,89 (m, 2H), 1,16 (d, J=6,10 Hz, 3H). MS (ESI+) m/z 244,0 (M+H)+.

Example 108

3-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-1-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 88 using 4-pentyn-1-ol instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm and 8.50 (s, 1H), 8,28 (s, 1H), 8,23 (d, J=1,83 Hz, 1H), 7,83-to $ 7.91 (m, 1H), 7,74-,82 (m, 1H), 4,50 (t, J=6,41 Hz, 1H), 3,51 (t, J=6,41 Hz, 2H), 2,77 (t, J=7,63 Hz, 2H), 1,80-1,90 (m, 2H). MS (ESI+) m/z 244,0 (M+H)+.

Example 109

1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-1,2,3-benzotriazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1-propargyl-1H-benzotriazole instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,91 (s, 1H), 8,21-8,29 (m, 2H), 8,07 (d, J=8.54 in Hz, 1H), to 7.99 (d, J=8.54 in Hz, 1H), to 7.84 (d, J=9,00, to 1.98 Hz, 1H), 7,72-7,81 (m, 1H), EUR 7.57-the 7.65 (m, 1H), 7,41-7,52 (m, 1H), 6,16 (s, 2H). MS (ESI-) m/z 315,0 (M-H)-.

Example 110

5-{4-[(phenylthio)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using phenylpropanolamine instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,59 (s, 1H), compared to 8.26 (s, 1H), 8,21 (d, J=1,22 Hz, 1H), 7,80-7,86 (m, 1H), 7,72-7,79 (m, 1H), 7,43 (d, J=8,39, to 1.37 Hz, 2H), 7,35 (t, J=7,78 Hz, 2H), 7,22 (t, J=7,32 Hz, 1H), to 4.38 (s, 2H). MS (ESI+) m/z 308,3 (M+H)+.

Example 111

5-(4-cyclopropyl-1H-1,2,3-triazole-1-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using cyclopropylacetylene instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,46 (s, 1H), of 8.25 (s, 1H), to 8.20 (d, J=1,53 Hz, 1H), to 7.84 (d, J=9,00, to 1.98 Hz, 1H), 7,76 (d, J=cent to 8.85 Hz, 1H), 1,97 with 2.14 (m, 1H), 0,93 was 1.06 (m, 2H), 0.77-a of 0.91 (m, 2H). MS (ESI+) m/z 226,0 (M+H)+./p>

Example 112

5-[4-(2-phenylethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1-phenyl-1-butyne instead of 3-phenyl-1-propyne. The product was a 1:1 mixture of original substances and specified in the connection header.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,48 (s, 1H), of 8.25 (s, 1H), 8,21 (d, J=1,53 Hz, 1H), of 8.06 (s, 1H), 7,81-7,89 (m, 1H), 7,73-7,80 (m, 1H), to 7.61 (DD, J=cent to 8.85, of 1.53 Hz, 1H), 7,45 (d, J=8.54 in Hz, 1H), 7,25 was 7.36 (m, 4H), 7,17-7,25 (m, 1H), 3.04 from (s, 4H). MS (ESI+) m/z 290,1 (M+H)+.

Example 113

5-[4-(cyclohexylmethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 3-cyclohexyl-1-propene instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,49 (s, 1H), 8,21-8,29 (m, 2H), 7,88 (d, J=9,00, to 1.98 Hz, 1H), to 7.77 (d, J=cent to 8.85 Hz, 1H), 2,61 (d, J=of 6.71 Hz, 2H), and 1.54-1.77 in (m, 6H), 1,08-of 1.30 (m, 3H), 0,91-of 1.05 (m, 2H). MS (ESI+) m/z 282,2 (M+H)+.

Example 114

5-(4-cyclopentyl-1H-1,2,3-triazole-1-yl)-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using cyclopentylamine instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm charged 8.52 (s, 1H), 8,19-8,30 (m, 2H), 7,88 (d, J=9,00, to 1.98 Hz, 1H), to 7.77 (d, J=cent to 8.85 Hz, 1H), 3,13-of 3.27 (m, 1H), 1,98-of 2.15 (m, 2H), 1,57-of 1.84 (m, 6H). MS (ESI+) m/z 254,0 (M+H)+.

Example 115

1-[1-(1H-ind is evil-5-yl)-1H-1,2,3-triazole-4-yl]cyclohexanol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1-ethinyl-1-cyclohexanol instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm charged 8.52 (s, 1H), 8,21-8,30 (m, J=1,53 Hz, 2H), 7,89 (DD, J=9,00, to 1.98 Hz, 1H), to 7.77 (d, J=cent to 8.85 Hz, 1H), 2,16 is 2.46 (m, 1H), 1,92-2,05 (m, 2H), 1.77 in is 1.86 (m, 2H), 1,61-to 1.77 (m, 2H), 1,51-to 1.59 (m, 1H), 1,42-1,51 (m, 2H), 1,28-of 1.40 (m, J=9,92, 2,90 Hz, 1H). MS (ESI+) m/z 284,0 (M+H)+.

Example 116

5-[4-(phenoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using fenilpropionova ester instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,87 (s, 1H), they were 8.22-to 8.34 (m, 2H), 7,89 (d, J=cent to 8.85 and 1.83 Hz, 1H), 7,79 (d, J=9.15, with Hz, 1H), 7,29-7,41 (m, 2H), to 7.09 (d, J=7,63 Hz, 2H), 6,99 (t, J=7,32 Hz, 1H), 5.25 in (s, 2H). MS (ESI+) m/z 292,0 (M+H)+.

Example 117

5-{4-[(1,1-diocletianopolis-4-yl)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using N-propylthiouracil-sulfone instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 8,81 (s, 1H), 8,24-at 8.36 (m, 2H), 7,89 (d, J=9,00, to 1.98 Hz, 1H), 7,80 (d, J=9.15, with Hz, 1H), to 4.38 (s, 2H), 3,30 of 3.56 (m, J=39,36 Hz, 8H). MS (ESI+) m/z 332,9 (M+H)+.

Example 118

5-[4-(3-phenylpropyl)-1H-1,2,3-triazole-1-yl]-1H-indazol

Specified in the title compound was obtained according to the following procedure, described in Example 88, using 1-phenyl-1-pentyne instead of 3-phenyl-1-propyne.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm charged 8.52 (s, 1H), compared to 8.26 (s, 1H), 8,23 (d, J=1,53 Hz, 1H), 7,87 (d, J=9,00, to 1.98 Hz, 1H), 7,76 (d, J=9.15, with Hz, 1H), 7,31 (t, J=to 7.32 Hz, 2H), 7.23 percent-7,28 (m, 2H), 7,20 (t, J=7,32 Hz, 1H), 2,74 (t, J=7,63 Hz, 2H), 2,65-of 2.72 (m, 2H), 1,95-2,05 (m, 2H). MS (ESI+) m/z 304,2 (M+H)+.

Example 119

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](phenyl)metano

Example 119A

tert-Butyl 5-ethinyl-1H-indazol-1-carboxylate

To a solution of compound of Example 3C (230 mg, of 1.62 mmol) in dichloromethane (10 ml) was added di-tert-BUTYLCARBAMATE (459 mg, 2.1 mmol) and a pinch of dimethylaminopyridine (~3 mg) and the mixture was stirred for 30 minutes at room temperature. Added water and the product was extracted with dichloromethane, dried over sodium sulfate, filtered and the solvent evaporated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 265,0 (M+Na)+.

Example 119B

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](phenyl)metano

In argon atmosphere, the vessel containing the compound of Example 119A (90 mg, and 0.37 mmol), benzilate (0,047 ml of 0.37 mmol), tetrahydrofuran (3 ml), triethylamine (holding 0.062 ml, 0.44 mmol), CuI (71 mg, and 0.37 mmol) and benzoyl chloride (0,059 ml, 0.51 mmol), closed with a lid and shaken for 16 hours. The solvents are evaporated and the product was purified using column chromatography on silica gel in 5-30 ethyl acetate in hexane. The crude substance was processed using TFU (0.5 ml) in dichloromethane (1 ml) and purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 13,08 (s, 1H), 7,98 (s, 1H), to 7.77 (s, 1H), 7,54 (d, J=8,24, 1,22 Hz, 2H), 7,43-of 7.48 (m, 1H), 7,33-7,40 (m, 2H), 7,22-7,30 (m, 5H), 7,17-7,21 (m, 2H), 5,74 (s, 2H). MS (ESI+) m/z 380,1 (M+H)+.

Example 120

N,N-diethyl-N-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}amine

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1,1-diethylproprion instead of 3-phenyl-1-propyne.1H NMR (300 MHz, DMSO-d6) δ ppm 8,98 (s, 1H), 8,30 (d, J=1,36 Hz, 1H), of 8.27 (s, 1H), 7,85-to 7.93 (m, 1H), 7,75-7,83 (m, 1H), 4,53 (d, J=4,07 Hz, 2H), 3,11-of 3.23 (m, 4H), to 1.31 (t, J=7,12 Hz, 6H). MS (ESI+) m/z 271,0 (M+H)+.

Example 121

ethyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-yl]-beta-alaninate

Specified in the title compound was obtained in accordance with the procedure described in Example 43, using utilizationoriented instead of isopropyltoluene.1H NMR (300 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), 8,71 (d, J=6,78, 2,03 Hz, 1H), 8,54 (s, 1H), 8,46 (d, J=4,24, to 1.87 Hz, 1H), 8,23 (d, J=8,82, of 1.36 Hz, 1H), 8,14 (s, 1H), to 7.61 (d, J=8,82 Hz, 1H), 7,05 (d, J=6,78, 4,07 Hz, 1H), 5,03 (t, J=5,93 Hz, 1H), 3.96 points (sq, J=7,12 Hz, 2H), 3,23 (sq, J=6.22 per Hz, 2H), 2,47 is 2.55 (m, 2H), only 1.08 (t, J=7,12 Hz, 3H). MS (ESI+) m/z 351,1 (M+H)+.

Example 122/p>

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Example 122A

1-Benzyl-5-methyl-4-(tributylstannyl)-1H-1,2,3-triazole

Tributyl(1-PROPYNYL)tin (a 3.87 g of 11.8 mmol) and benserazide (2.2 ml, 17.6 mmol) were combined and heated to 150°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 464,2 (M+H)+.

Example 122B

1-(5-(1-Benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-yl)alanon

The compound of Example 87A (235 mg, 0,821 mmol), the compound of Example 122A (380 mg, 0,822 mmol), dichlorobis(triphenylphosphine)palladium(II) (60 mg, of 0.085 mmol) and thiophene-2-carboxylate copper (325 mg, of 1.23 mmol) were combined in toluene (2.0 ml) in a microwave vessel in an inert atmosphere of nitrogen. The vessel was heated in a microwave system (CEM-Discover) up to 150°C at 125 Watts for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 332,2 (M+H)+.

Example 122C

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol

Connection Example 122B (109 mg, 0,329 mmol) was dissolved in tetrahydrofuran (3.0 ml) and water (0.5 ml) was added potassium hydroxide (53 mg, 0,945 mmol). The mixture was stirred for 2 hours, diluted atilas what tatom and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-5% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,13 (s, 1H), 8,12 (s, 1H), 8,01 (s, 1H), 7,71 for 7.78 (m, 1H), to 7.59-7,66 (m, 1H), 7,31 was 7.45 (m, 3H), 7.23 percent-7,29 (m, 2H), 5,65 (s, 2H), 2,43 (s, 3H). MS (ESI+) m/z 290,1 (M+H)+.

Example 123

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Example 123A

5-(1-Benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-2-perbenzoate

Connection Example 122A (415 mg, 0,792 mmol), 5-bromo-2-perbenzoate (158 mg, 0,790 mmol), dichlorobis(triphenylphosphine)palladium(II) (52 mg, 0,074 mmol) and thiophene-2-carboxylate copper (226 mg, 1,19 mmol) were combined in toluene (2 ml) in a microwave vessel in an inert atmosphere of nitrogen. The vessel was heated in a microwave system (CEM-Discover) at 150°C at 125 Watts for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 293,0 (M+H)+.

Example 123B

5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

The compound of Example 123A (120 mg, 0,339 mmol) was treated with hydrazinehydrate (1.0 ml) in ethanol (1.0 ml) and was heated to 60°C over night. The mixture was diluted with methylene chloride and washed vadasy layer was absorbed on silica gel and was purified using chromatography on silica gel, using elution gradient of methanol in dichloromethane (0-5%), obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,43 (s, 1H), 7,98 (s, 1H), 7,60 (d, J=8,65, of 1.53 Hz, 1H), 7,27-7,44 (m, 4H), 7,21-7,27 (m, 2H), 5,65 (s, 2H), 5,41 (s, 2H), 2,41 (s, 3H). MS (ESI+) m/z 305,1 (M+H)+.

Example 124

N3-[2-(1H-indazol-5-yl)imidazo[1,2-α]pyrimidine-3-yl]-β-albumid

The compound of Example 121 (42 mg, 0,120 mmol) and 7 n ammonia solution in methanol (1.0 ml) were combined and heated to 60°C over night. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of methanol in dichloromethane (1-7%), obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), 8,76 (d, J=6,78, 2,03 Hz, 1H), 8,56 (s, 1H), 8,45 (d, J=4,07, 2,03 Hz, 1H), 8,24 (d, J=8,82, of 1.36 Hz, 1H), 8,15 (s, 1H), to 7.61 (d, J=8,48 Hz, 1H), 7,32 (s, 1H), 7,03 (d, J=6,78, 4,07 Hz, 1H), 6,85 (s, 1H), is 4.93 (t, J=6,10 Hz, 1H), 3,11-of 3.23 (m, 2H), 2,32 (t, J=is 6.78 Hz, 2H). MS (ESI+) m/z 322,0 (M+H)+.

Example 125

5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Example 125A

5-(1-Benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-2-perbenzoate

A mixture of compound of Example 62B (200 mg, 1.38 mmol), benserazide (0,176 ml, 1.38 mmol), tetrahydrofuran (12 ml), triethylamine (0,230, 1.56 mmol), CuI (263 mg, 1.38 mmol) and ICl (0,069 ml, 1.38 mmol) in an argon atmosphere was stirred at room temperature for 24 hours. The solvent is evaporated and neojidannostei was dissolved in dichloromethane, downloaded directly to a column of silica gel and was suirable a mixture of ethyl acetate/hexane (10-20%) to obtain specified in the connection header. MS (ESI+) m/z 404,9 (M+H)+.

Example 125B

5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

The compound of Example 125A (50 mg, 0.12 mmol) and hydrazinoacetate (1 ml) in ethanol (1 ml) was heated at 95°C for 2 hours. Added water and the solid is collected by filtration and then purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header in the form of a salt TFU.1H NMR (500 MHz, DMSO-d6) δ ppm 12,07 (s, 1H), 8.30 to (s, 1H), 7,83 (d, J=cent to 8.85, of 1.53 Hz, 1H), 7,44 (d, J=8.54 in Hz, 1H), 7,38-the 7.43 (m, J=7,32, to 7.32 Hz, 2H), 7,32-7,37 (m, 1H), 7.23 percent-7,27 (m, J=7,02 Hz, 2H), 5,74 (s, 2H), 4.00 points (s, 2H). MS (ESI+) m/z 417,0 (M+H)+.

Example 126

N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}-N'-(3-were)urea

Example 126A

1-(3-(1-Benzyl-4-(3-cyano-4-forfinal)-1H-1,2,3-triazole-5-yl)phenyl)-3-m-trilochana

In argon atmosphere, the vessel containing the compound of Example 125A (94 mg, 0.23 mmol), 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-m-tolylacetic (obtained in accordance with the procedure described in WO2004/113304) (990 mg, 0.26 mmol), PdCl2dppf. (19 mg, 0.02 mmol), potassium carbonate (64 mg, 0.46 mmol), DME (2 ml) and water (0.2 ml), covered with a lid and heated in naked is Evelina device with shaking at 80°C for 90 minutes. The solvents are evaporated and the product was extracted with methanol/dichloromethane. Purification using column chromatography on silica gel using 10% ethyl acetate in hexane gave specified in the header connection. MS (ESI+) m/z 503,2 (M+H)+.

Example 126B

N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}-N'-(3-were)urea

The compound of Example 126A (25 mg, 0.05 mmol) and hydrazinoacetate (0.5 ml) in ethanol (2 ml) was heated at 80°C for 1 hour. The crude mixture was loaded onto a column of silica gel and was suirable with a gradient of 0-5% methanol in dichloromethane to obtain specified in the connection header.1H NMR (500 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 8,79 (s, 1H), 8,63 (s, 1H), 8,12 (s, 1H), EUR 7.57 (d, J=8,24, 1,22 Hz, 1H), 7,43 (t, J=1,83 Hz, 1H), 7,38 (t, J=to 7.93 Hz, 1H), 7.23 percent-7,34 (m, 4H), 7,08-7,22 (m, 4H), 7,03 (d, J=of 6.71 Hz, 2H), 6,88 (d, J=7,63 Hz, 1H), 6,78 (d, J=7,32 Hz, 1H), 5,50 (s, 2H), are 5.36 (s, 2H), and 2.26 (s, 3H). MS (ESI+) m/z 515,3 (M+H)+.

Example 127

5-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)isoxazol-3-carboxamide

A 20-ml vessel was added a solution of compound of Example 81A (37 mg, 0.18 mmol)dissolved in dimethylformamide (0.8 ml), followed by addition of HATU (61 mg, 0.18 mmol)dissolved in dimethylformamide (0.8 ml). Then was added a solution of 2-isopropoxyaniline (20 mg, 0.20 mmol)dissolved in dimethylformamide (0.9 ml), followed by the addition of diisopropylethylamine (42 mg, 0.36 mmol)dissolved in dimethylformamide (0.8 ml). The mixture was then shaken at 40°C for three hours. The crude reaction mixture was filtered through Si-carbonate cartridge (6 ml, 2 g), supplied by Silicycle Chemical Division, using methanol, controlled by LC/MS and concentrated to dryness. The residue was dissolved in a mixture of 1:1 DMSO/methanol and purified using reverse-phase HPLC (Agilent, gradient 5%-100% TFU/water over 8 minutes).1H NMR (300 MHz, DMSO-d6/D2O) δ ppm scored 8.38-8,43 (m, 1H), they were 8.22-8.30 to (m, 1H), of 7.90 (d, 1H), 7,73 (d, 1H), 7,21-7,29 (m, 1H), 3,56-the 3.65 (m, 1H), 3,52 (t, 2H), 3.43 points (t, 2H), 1,10 (d, 6H). MS (ESI+) m/z 315 (M+H)+.

Example 128

5-[3-(morpholine-4-ylcarbonyl)isoxazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using the research instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm at 8.36-8,43 (m, 1H), they were 8.22-8,29 (m, 1H), 7,89 (d, 1H), 7,72 (d, 1H), 7,11-7,22 (m, 1H), 3,68-and 3.72 (m, 4H), 3,61-3,68 (m, 4H). MS (ESI+) m/z 299 (M+H)+.

Example 129

5-(1H-indazol-5-yl)-N-(3-morpholine-4-ylpropyl)isoxazol-3-carboxamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 127, using 3-morpholinopropan-1-amine instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm of 8.37-8,46 (m, 1H), 8,20-8,31 (m, 1H), to $ 7.91 (d, 1H), 7,73 (d, 1H), 7,17 and 7.36 (m, 1H), 3,98-4,08 (m, 2H), 3,57-to 3.73 (m, 2H), 3,42-3,51 (m, 2H), 3,3-to 3.41 (m, 2H), 3,14-up 3.22 (m, 2H), 3,01-3,14 (m, 2H), 1,88-to 2.06 (m, 2H). MS (ESI+) m/z 356 (M+H)+.

Example 130

N-[2-(1H-imidazol-4-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using 2-(1H-imidazol-4-yl)ethanamine instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 8,90-8,97 (m, 1H), 8.34 per-8,46 (m, 1H), 8,20-8,32 (m, 1H), of 7.90 (d, 1H), 7,72 (d, 1H), 7,38-7,49 (m, 1H), 7,14-7,28 (m, 1H), only 3.57 (t, 2H), 2,96 (t, 2H). MS (ESI+) m/z 323 (M+H)+.

Example 131

(3R)-1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]-carbonyl}piperidine-3-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using the hydrochloride of (R)-piperidine-3-ol instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 8.34 per-to 8.45 (m, 1H), 8,19-8,30 (m, 1H), 7,89 (d, 1H), 7,72 (d, 1H), 7,13 (d, 1H), 4,03-4,19 (m, 1H), 3,64-and 3.72 (m, 1H), 3,54-3,62 (m, 1H), 3,34-3,44 (m, 1H), 3,20-of 3.32 (m, 1H), 2,99-3,10 (m, 1H), 1,67-2,03 (m, 2H), 1,36-to 1.61 (m, 2H). MS (ESI+) m/z 313 (M+H)+.

Example 132

1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperidine-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using piperidine-3-carboxamide instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm at 8.36-to 8.45 (m, 1H), they were 8.22-8,32 (m, 1H), of 7.90 (d, 1H), 7,72 (d, 1H), 7,07-of 7.23 (m, 1H), 4,27-4,56 (m, 1H), 3,91-of 4.05 (m, 1H), 3,09-3,37 (m,1H), 2,85 totaling 3.04 (m, 1H), 2,31 at 2.45 (m, 1H), 1,89-2,05 (m, 1H), 1,73 is 1.86 (m, 1H), 1.60-to 1,72 (m, 1H), 1,36-of 1.55 (m, 1H). MS (ESI-) m/z 338 (M-H)-.

Example 133

2-[2-(4-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperazine-1-yl)ethoxy]ethanol

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 127, using 2-(2-(piperazine-1-yl)ethoxy)ethanol instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 8,39-8,48 (m, 1H), 8,19-8,32 (m, 1H), 7,92 (d, 1H), 7,74 (d, 1H), 7,17-7,27 (m, 1H), 4,49-4,60 (m, 1H), 3,94-4,01 (m, 1H), 3,76-3,81 (m, 4H), 3,56-3,63 (m, 2H), 3,51 of 3.56 (m, 2H), 3.33 and-of 3.43 (m, 3H), 3,13 is 3.23 (m, 1H), 2,65 is 2.75 (m, 2H). MS (ESI+) m/z 386 (M+H)+.

Example 134

5-{3-[(4-methyl-1,4-diazepan-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 127, using 1-methyl-1,4-diazepan instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm scored 8.38-8,46 (m, 1H), they were 8.22-8,32 (m, 1H), 7,85-7,98 (m, 1H), of 7.75 (d, 1H), 7,22 (d, 1H), 4,07-4,19 (m, 1H), 3,69-of 3.77 (m, 2H), 3,59-to 3.67 (m, 1H), 3,44-3,59 (m, 1H), 3,35-3,44 (m, 1H), 3,24-to 3.35 (m, 2H), 2,84-2,95 (m, 3H), 2,66-to 2.74 (m, 1H), 2,10-of 2.26 (m, 2H). MS (ESI+) m/z 326 (M+H)+.

Example 135

N-(3-hydroxypropyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using 3-aminopropan-1-ol instead of 2-isopropoxyaniline.1H the Mr (300 MHz, DMSO-d6/D2O) δ ppm at 8.36-to 8.45 (m, 1H), 8,20-8,30 (m, 1H), 7,84-7,94 (m, 1H), 7,71 (d, 1H), 7.18 in-7,28 (m, 1H), 3,48 (t, 2H), 3,35 (t, 2H), 1,64-of 1.78 (m, 2H). MS (ESI+) m/z 387 (M+H)+.

Example 136

N-[(1R)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using (R)-2-amino-2-phenylethanol instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 9,11 (d, 1H), of 8.37-8,46 (m, 1H), 8,23-of 8.28 (m, 1H), to $ 7.91 (d, 1H), 7,73 (d, 1H), 7,40 was 7.45 (m, 2H), 7,32-7,39 (m, 2H), 7.23 percent-to 7.32 (m, 2H), of 5.05-5,13 (m, 1H), 3,66-and 3.72 (m, 2H). MS (ESI+) m/z 349 (M+H)+.

Example 137

N-[3-(1H-indazol-1-yl)propyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using 3-(1H-indazol-1-yl)propan-1-amine instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 9,02-9,10 (m, 1H), 8,40-8,44 (m, 1H), 8,25-8,29 (m, 1H), 7,87-to 7.95 (m, 1H), 7,71-of 7.82 (m, 2H), to 7.61-of 7.69 (m, 1H), 7,20-7,29 (m, 1H), 4,28 (t, 2H), 3.33 and (t, 2H), 2.06 to 2,19 (m, 2H). MS (ESI+) m/z 337 (M+H)+.

Example 138

5-(1H-indazol-5-yl)-N-[3-(2-oxopyrrolidin-1-yl)propyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using 1-(3-aminopropyl)pyrrolidin-2-it instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm scored 8.38-8,43 m, 1H), 8,24-8,30 (m, 1H), 7,87-to 7.93 (m, 1H), 7,73 (d, 1H), 7,22-7,26 (m, 1H), 3,39 (t, 2H), 3,21-3,30 (m, 4H), and 2.26 (t, 2H), 1,90-2,00 (m, 2H), 1.70 to to 1.79 (m, 2H). MS (ESI+) m/z 354 (M+H)+.

Example 139

N-{2-[4-(aminosulfonyl)phenyl]ethyl}-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 127, using 4-(2-amino-ethyl)benzosulfimide instead of 2-isopropoxyaniline.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm of 8.37-8,42 (m, 1H), 8,24-8,29 (m, 1H), 7,86-to 7.93 (m, 1H), 7,70-7,80 (m, 3H), 7,47 (d, 2H), 7,20-7,24 (m, 1H), only 3.57 (t, 2H), 2,96 (t, 2H). MS (ESI+) m/z 412 (M+H)+.

Example 140

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](3-chlorophenyl)metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using 3-chlorobenzylchloride instead of benzoyl chloride.1H NMR (500 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), to 7.99 (s, 1H), to 7.77 (s, 1H), 7,38-7,51 (m, 4H), 7,28-7,37 (m, 3H), 7,20-7,27 (m, 4H), 5,78 (s, 2H). MS (ESI+) m/z 414,1 (M+H)+.

Example 141

[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl] (cyclopropyl)metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using cyclopropanecarbonitrile instead of benzoyl chloride.1H NMR (500 MHz, DMSO-d6) δ ppm 13,26 (s, 1H), 8,18 (s, 1H), 8,08 (s, 1H), to 7.61-of 7.70 (m, 2H), 7,29-7,40 (m, 3H), from 7.24 (d, J=7,02 Hz, 2H), 5,79 (s, 2H), 1,86 is 2.00 (m, 1H), 0,98 by 1.12 (m, 2H), 0.77-a of 0.93 (m, 2H). MS (ESI+) m/z 344,1 (M+H) +.

Example 142

5-[5-cyclopropyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Example 142A

5-Cyclopropyl-1-((tetrahydro-2H-Piran-4-yl)methyl)-4-(tributylstannyl)-1H-1,2,3-triazole

Cyclopropylacetylene (142 mg, of 2.15 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (716 mg, 2.14 mmol) in hexane (3.0 ml) and stirred in a tightly closed vessel at 70°C for 2 hours. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added the compound of Example 80A (455 mg, up 3.22 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of ethyl acetate in hexane (5-50%), obtaining specified in the connection header. MS (ESI+) m/z 498,3 (M+H)+.

Example 142B

1-(5-(5-Cyclopropyl-1-((tetrahydro-2H-Piran-4-yl)methyl)-1H-1,2,3-triazole-4-yl)-1H-indazol-1-yl)alanon

Connection Example 142A (220 mg, 0,444 mmol), the compound of Example 87A (128 mg, 0,447 mmol), dichlorobis(triphenylphosphine)palladium(II) (33 mg, 0,047 mmol) and thiophene-2-carboxylate copper (127 mg, 0,666 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated to 150°C for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel, using the UYa for elution gradient of 5-70% ethyl acetate in hexane, obtaining specified in the connection header. MS (ESI+) m/z 366,0 (M+H)+.

Example 142C

5-[5-cyclopropyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Connection Example 142B (46 mg, 0,126 mmol) was dissolved in tetrahydrofuran (2.0 ml) and water (0.5 ml) was added potassium hydroxide (80 mg, was 1.43 mmol). The mixture was stirred for 2 hours, diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-8% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, CDCl3) δ ppm 8,19 (s, 1H), of 7.96 (d, J=8,82 Hz, 1H), to 7.61 (d, J=7,80 Hz, 1H), 7,25-7,28 (m, 1H), 4,34 (d, J=6,44 Hz, 2H), was 4.02 (d, J=1 1,36, of 3.56 Hz, 2H), 3,42 (t, J=1 1,53 Hz, 2H), 2,33 is 2.46 (m, 1H), 1,81-of 1.95 (m, 1H), 1,59 is 1.70 (m, 2H), 1,43 is 1.58 (m, 2H), 1,23 of 1.28 (m, 1H), 1,10-1,20 (m, 2H), 0,47-of 0.62 (m, 2H). MS (ESI+) m/z 324,1 (M+H)+.

Example 143

N1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]methyl}glycinamide

Example 143A

2-((1-Benzyl-4-(tributylstannyl)-lΗ-1,2,3-triazole-5-yl)methyl)isoindoline-1,3-dione

N-Propargylamine (2.35 mg, 12.7 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (to 4.23 mg, 12.7 mmol) in hexane (3.0 ml) and stirred in a tightly closed vessel at 70°C for 2 hours. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 mine is. Added benzilate (2.0 ml, 16.0 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 609,3 (M+H)+.

Example 143B

2-((4-(1-Acetyl-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl)methyl)isoindoline-1,3-dione

The compound of Example 143A (567 mg, 0,934 mmol), the compound of Example 87A (268 mg, 0,934 mmol), dichlorobis(triphenylphosphine)palladium(II) (67 mg, 0,095 mmol) and thiophene-2-carboxylate copper (268 mg, of 1.41 mmol) were combined in toluene (2.5 ml) in a microwave vessel in an inert atmosphere of nitrogen. The vessel was heated in a microwave system (CEM-Discover) up to 150°C at 125 Watts for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 477,2 (M+H)+.

Example 143C

(1-Benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl)methanamine

Connection Example 143B (140 mg, 0,294 mmol) was treated with hydrazinehydrate (0.7 ml) in ethanol (0.7 ml) and stirred at ambient temperature overnight. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 1-6% met the Nola in dichloromethane, obtaining specified in the connection header. MS (ESI+) m/z 305,0 (M+H)+.

Example 143D

N1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]methyl}glycinamide

Connection Example 143C (66 mg, 0,217 mmol), N-(tert-butoxycarbonyl)-glycine (39 mg, 0,223 mmol) and ΗATU (85 mg, 0,224 mmol) were combined in methylene chloride (2.5 ml). Added diisopropylethylamine (150 μl, 0,865 mmol) and the mixture was stirred at ambient temperature overnight. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-6% methanol in dichloromethane, to obtain tert-butyl 2-((1-benzyl-4-(lΗ-indazol-5-yl)-lΗ-1,2,3-triazole-5-yl)methylamino)-2-oxoethylidene. This carbamate was dissolved in tetrahydrofuran (2 ml) was added to 0.5 ml of a 1 n hydrochloric acid in diethyl ether and the mixture was stirred for 20 minutes at room temperature. The solvents were removed under reduced pressure and to the mixture was added diethyl ether and stirred at room temperature overnight. The solvent decantation, and the obtained residue was dried under a stream of nitrogen to obtain specified in the connection header in the form of cleaners containing hydrochloride salt.1H NMR (300 MHz, DMSO-d6) δ ppm 13,21 (s, 1H), 9,02 (t, J=5,09 Hz, 1H), 8,11-8,16 (m, 2H), of 8.06 (s, 2H), 7,75-of 7.82 (m, 1H), to 7.64 (d, J=8,82 Hz, 1H), 7,30 was 7.45 (m, 3H), 7.23 percent-7,31 (m, 2H), 5,72 (s, 2H), 4,57 (d, J=5,09 Hz, 2H), 3,1 (square, J=USD 5.76 Hz, 2H). MS (ESI+) m/z 362,1 (M+H)+.

Example 144

(4-forfinal) [4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using 4-tormentilla instead of benzoyl chloride and using the compounds of Example 80A instead benserazide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), 8,00 (s, 1H), 7,72-7,80 (m, 3H), 7,38-7,44 (m, 1H), 7,30 and 7.36 (m, 1H), 7,09-7,19 (m, 2H), to 4.41 (d, J=7,12 Hz, 2H) 3,80 (d, J=1 1,36, of 2.54 Hz, 2H), 3,14-3,26 (m, 2H), 2,04-2,19 (m, 1H), 1,38-1,49 (m, 2H), 1,19-of 1.35 (m, 2H). MS (ESI+) m/z 406,1 (M+H)+.

Example 145

(4-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using 4-chlorobenzylchloride instead of benzoyl chloride and using the compounds of Example 80A instead benserazide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,10 (s, 1H), 8,00 (s, 1H), to 7.77 (s, 1H), 7,68 (d, J=8,48 Hz, 2H), 7.29 trend was 7.45 (m, 4H), 4,42 (d, J=7,12 Hz, 2H), 3,81 (d, J=1 1,19, 2,71 Hz, 2H), 3,14-of 3.27 (m, 2H), 2,03-2,19 (m, 1H), 1,38-is 1.51 (m, 2H), 1,22-of 1.36 (m, 2H). MS (ESI+) m/z 422,1 (M+H)+.

Example 146

(3-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using 3-chlorobenzoyl is Yes instead of benzoyl chloride and using the compounds of Example 80A instead benserazide. 1H NMR (300 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), 7,95 (s, 1H), to 7.64 (s, 1H), of 7.48-rate of 7.54 (m, 1H), 7,29-7,35 (m, 1H), 7,22-7,28 (m, 1H), 7,13-7,22 (m, 3H), 4,58 (d, J=7,12 Hz, 2H), 3,86 (d, J=1 1,53, 2.37 Hz, 2H), 3,20-3,30 (m, 2H), 2,11-2,24 (m, 1H), 1,45-and 1.54 (m, 2H), 1,33-1,44 (m, 2H). MS (ESI+) m/z 422,1 (M+H)+.

Example 147

(2-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using a 2-chlorobenzylchloride instead of benzoyl chloride and using the compounds of Example 80A instead benserazide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), to 7.99 (s, 1H), of 7.75 (s, 1H), 7,66 (t, J=1,86 Hz, 1H), 7,56 (d, J=7,80 Hz, 1H), 7,47-7,53 (m, 1H), was 7.36-7,42 (m, 1H), 7.23 percent-7,34 (m, 2H), 4,45 (d, J=is 6.78 Hz, 2H), 3,82 (d, J=1 l,19, 2.37 Hz, 2H), 3,18 to be 3.29 (m, 2H), 2,09-of 2.23 (m, 1H), 1.41 to 1,53 (m, 2H), 1,28-to 1.38 (m, 2H). MS (ESI+) m/z 422,1 (M+H)+.

Example 148

cyclopentyl[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl}metano

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using cyclopentanecarbonitrile instead of benzoyl chloride and using the compounds of Example 80A instead benserazide.1H NMR (300 MHz, DMSO-d6) δ ppm of 13.27 (s, 1H), 8,18 (s, 1H), 7,95 (s, 1H), 7,68 (d, J=8,48 Hz, 1H), 7,52 (d, J=8,48, 1.70 Hz, 1H), 4,47 (d, J=7,12 Hz, 2H), 3,85 (d, J=1 1,53, 2.37 Hz, 2H), 3,18-3,30 (m, 2H), 3,02-3,14 (m, 1H), 2,00-2,17 (m, 1H), 1,19 to 1.76 (m, 12H). MS (ESI+) m/z 380,1 (M+H)+.

Example 149

1-ensil-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxylic acid

Example 149A

Methyl 1-benzyl-4-(tributylstannyl)-1H-1,2,3-triazole-5-carboxylate

Methylpropionate (5.75 g and 68.4 mmol) was added to methylethyl(tributylstannyl)carbamate (26,9 g, only 68.6 mmol) in a sealed tube. The mixture was heated to 70°C during the night. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added benzilate (10,2 ml of 81.6 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 508,3 (M+H)+.

Example 149B

methyl 4-(1-acetyl-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-carboxylate

The compound of Example 149A (7,17 g, 14.1 mmol), the compound of Example 87A (as 4.02 g, 14.1 mmol), dichlorobis(triphenylphosphine)palladium(II) (1,01 mg, 1.44 mmol) and thiophene-2-carboxylate copper (4,07 mg of 21.3 mmol) were combined in toluene (55 ml) in a sealed tube in an inert atmosphere of nitrogen. The tube was tightly closed and heated at 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 376,1 (M+H)+.

Example 149C

1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxylic acid

Connection Example 149B (3,40 mg, 9,06 mmol) was dissolved in tetrahydrofuran (100 ml), methanol (10 ml) and water (10 ml) was added potassium hydroxide (1.63 g, of 29.1 mmol). The mixture was stirred for 3 hours, diluted with ethyl acetate and washed with 1 n hydrochloric acid, washed with saturated brine and the combined organic layers were dried over sodium sulfate. After filtration the solvent was removed under reduced pressure to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,16 (s, 1H), 8,11-8,18 (m, 2H), 7,66-7,76 (m, 1H), 7,54 to 7.62 (m, 1H), 7,31-the 7.43 (m, 3H), 7,22-7,29 (m, 2H), to 5.93 (s, 2H). MS (ESI+) m/z 320,0 (M+H)+.

Example 150

5-{5-(4-forfinal)-1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Example 150A

1-(azidomethyl)-4-(trifluoromethyl)benzene

Sodium azide (2.30 g, of 35.4 mmol) was added to a solution of 4-(trifluoromethyl)benzylbromide (4.26 deaths / g, 17.8 mmol), dissolved in dimethyl sulfoxide (15 ml), and stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate, washed with water and saturated saline and dried over sodium sulfate. After filtration the solvent was removed under reduced pressure to obtain specified in the connection header. The crude product was used for next the stage without additional analysis.

Example 150B

5-(4-forfinal)-4-(tributylstannyl)-1-(4-(trifluoromethyl)benzyl)-1H-1,2,3-triazole

4-Perforation (524 mg, 4,36 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (1,46 g, 4,37 mmol) and the mixture was stirred in a tightly closed vessel at 50°C for 30 minutes. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added the compound of Example 150A (1.28 g, 6,30 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient 5-35% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 612,3 (M+H)+.

Example 150C

2-fluoro-5-(5-(4-forfinal)-1-(4-(trifluoromethyl)benzyl)-1H-1,2,3-triazole-4-yl)benzonitrile

Connection Example 150B (485 mg, 0,795 mmol), 5-bromo-2-perbenzoate (143 mg, 0,715 mmol), dichlorobis(triphenylphosphine)palladium(II) (49 mg, 0,070 mmol) and thiophene-2-carboxylate copper (205 mg, of 1.08 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated at 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 441,2 (M+H)+ .

Example 150D

5-{5-(4-forfinal)-1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Connection Example 150C treated hydrazinehydrate (1.0 ml) in ethanol (1.0 ml) and the reaction mixture was stirred and heated to 65°C for 3 hours. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-6% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,42 (s, 1H), 8,04 (s, 1H), to 7.67 (d, J=8,14 Hz, 2H), 7,26-7,41 (m, 4H), 7,22 (d, J=8,48 Hz, 2H), 7.03 is-to 7.15 (m, 2H), 5,62 (s, 2H), are 5.36 (s, 2H). MS (ESI+) m/z 453,1 (M+H)+.

Example 151

5-[1-benzyl-5-(4-forfinal)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Example 151A

1-benzyl-5-(4-forfinal)-4-(tributylstannyl)-1H-1,2,3-triazole

4-Perforation (525 mg, 4,37 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (1,46 g, 4,37 mmol) and the mixture was stirred in a tightly closed vessel at 50°C for 2 hours. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added benzilate (850 μl, to 6.80 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient 5-35% ethyl acetate is hexane, obtaining specified in the connection header. MS (ESI+) m/z 544,4 (M+H)+.

Example 151B

5-(1-Benzyl-5-(4-forfinal)-1H-1,2,3-triazole-4-yl)-2-perbenzoate

Connection Example 151A (361 mg, 0,666 mmol), 5-bromo-2-perbenzoate (119 mg, 0,595 mmol), dichlorobis(triphenylphosphine)palladium(II) (45 mg, 0,064 mmol) and thiophene-2-carboxylate copper (193 mg, 1.01 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated to 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 373,0 (M+H)+.

Example 151C

5-[1-benzyl-5-(4-forfinal)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Connection Example 151B (135 mg, 0,363 mmol) was treated with hydrazinehydrate (1.0 ml) in ethanol (1.0 ml) and was stirred and heated to 65°C for 3 hours. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 0-6% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 8,02 (s, 1H), 7.24 to 7,38 (m, 7H), 7.03 is-7,14 (m, 2H), 6,98 (d, J=7,29, 2.20 Hz, 2H), 5,50 (s, 2H), to 5.35 (s, 2H). MS (ESI+) m/z 385,1 (M+H)+.

Example 152

[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl](tetrahydro-2H-Piran-4-yl)methanon

Specified in the title compound was obtained in accordance with the procedure described in Example 119B, using the compound of Example 80A instead benserazide and using tetrahydro-2H-Piran-4-carbonylchloride instead of benzoyl chloride.1H NMR (300 MHz, DMSO-d6) δ ppm 13,30 (s, 1H), 8,18 (s, 1H), 8,00 (s, 1H), 7,69 (d, J=8,48 Hz, 1H), 7,53 (d, J=8,65, of 1.53 Hz, 1H), 4,48 (d, J=7,12 Hz, 2H), 3,79-3,90 (m, 2H), 3,62-3,74 (m, 2H), 3,18-3,30 (m, 2H), was 2.76-is 2.88 (m, 1H), 2,64-was 2.76 (m, 2H), 2.00 in 2,17 (m, 1H), 1,20 is 1.58 (m, 8H). MS (ESI+) m/z 396,0 (M+H)+.

Example 153

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol

Example 153A

1-benzyl-5-o-tolyl-4-(tributylstannyl)-1H-1,2,3-triazole

2-Ethnicolor (456 μl, 3.62 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (1,21 g, 3.62 mmol) and the mixture was stirred in a tightly closed vessel at 70°C for 3 hours. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added benzilate (678 μl, 5,42 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-45% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 539,8 (M+H)+.

Example 153B

1-(5-(1-Benzyl-5-o-tolin-1,2,3-triazole-4-yl)-1H-indazol-1-yl)alanon

Connection Example 153A (119 mg, 0,221 mmol), the compound of Example 87A (63 mg, 0,221 mmol), dichlorobis(triphenylphosphine)palladium(II) (16 mg, is 0.023 mmol) and thiophene-2-carboxylate copper (65 mg, 0,341 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated at 150°C for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-45% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 408,7 (M+H)+.

Example 153C

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol

Connection Example 153B (42 mg, 0,103 mmol) was dissolved in tetrahydrofuran (2.0 ml) and water (0.3 ml) was added potassium hydroxide (48 mg, 0,856 mmol). The mixture was stirred for 1 hour, diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 1-6% methanol in dichloromethane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,07 (s, 1H), of 7.97 (s, 1H), 7,73 (s, 1H), 7,44-7,53 (m, 3H), 7,39 (t, J=6,95 Hz, 1H), 7,28-7,35 (m, 2H), 7,21-7,29 (m, 3H), 6,86-to 6.95 (m, 2H), 5,28-of 5.45 (m, 2H), 1,59 (s, 3H). MS (ESI+) m/z 366,1 (M+H)+.

Example 154

5-{1-benzyl-5-[(4-methylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the header connect the tion received in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A and using 1-methylpiperazine instead of piperidine and tetrahydrofuran instead of dimethylformamide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,20 (s, 1H), 8,16 (s, 1H), of 7.96 (s, 1H), EUR 7.57-of 7.69 (m, 2H), 7,31-7,44 (m, 3H), 7.23 percent-7,30 (m, 2H), are 5.36-of 5.83 (m, 2H), 3.40 in-the 3.65 (m, J=4,75 Hz, 2H), 2,38-2,49 (m, 2H), 2,10-2,22 (m, 2H), 1,89 (s, 3H), 1,40 (t, J=4,92 Hz, 2H). MS (ESI+) m/z 402,2 (M+H)+.

Example 155

5-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A and using 4-hydroxypiperidine instead of piperidine and tetrahydrofuran instead of dimethylformamide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,15-13,24 (m, 1H), 8,16 (s, 1H), of 7.97 (s, 1H), 7,55-to 7.68 (m, 2H), 7,32-the 7.43 (m, 3H), 7.23 percent-7,30 (m, 2H), 5,41-of 5.83 (m, J=65,10 Hz, 2H), 4,58 (d, J=3,39 Hz, 1H), 3,74-3,91 (m, 1H), 3,37-of 3.48 (m, 2H), 2,66-2,79 (m, 1H), 2,25-2,47 (m, 1H), 1,54 by 1.68 (m, 1H), 1,20-of 1.36 (m, 1H), 0.74 and-of 0.90 (m, 1H), 0,40-0,60 (m, 1H). MS (ESI+) m/z 403,1 (M+H)+.

Example 156

1-acetyl-5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Example 156A

5-(4-forfinal)-1-((tetrahydro-2H-Piran-4-yl)methyl)-4-(tributylstannyl)-1H-1,2,3-triazole

4-Perforation (440 μl, 3.88 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (1.30 grams, with 3.89 mmol) and the mixture was stirred in ermetico a closed vessel at 50°C for 40 minutes. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added the compound of Example 80A (710 μl, of 5.68 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 552,4 (M+H)+.

Example 156B

1-acetyl-5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

The compound of Example 156A (433 mg, 0,787 mmol), the compound of Example 87A (205 mg, 0,717 mmol), dichlorobis(triphenylphosphine)palladium(II) (55 mg, 0,078 mmol) and thiophene-2-carboxylate copper (224 mg, 1,17 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated to 150°C for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 5-45% ethyl acetate in hexane, and was ground into powder with methanol to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 8,40-8,48 (m, J=0.68 Hz, 1H), 8,25 (d, J=8,82 Hz, 1H), 7,82-to $ 7.91 (m, 1H), 7,73 (d, J=8,48, 1.70 Hz, 1H), 7,50-of 7.60 (m, 2H), 7,38-7,49 (m, 2H), 4,13 (d, J=7,12 Hz, 2H), 3,76 (d, J=1 1,36, of 2.54 Hz, 2H), 3,10-3,25 (m, 2H), 2,70 (s, 3H), 1,86-of 2.08 (m, 1H), 1,37 (d, J=12,55, 1.70 Hz, 2H), 1,03 is 1.23 (m, 2H). MS (ESI+) m/z 420,2 (M+H)+.

Por the measures 157

1-benzyl-4-(1H-indazol-5-yl)-N,N-dimethyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A and using dimethylamine instead of piperidine and tetrahydrofuran instead of dimethylformamide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,19 (s, 1H), 8,15 (s, 1H), of 7.96 (t, J=1,19 Hz, 1H), 7.62mm (d, J=1,36 Hz, 2H), 7,33-7,44 (m, 3H), 7.24 to 7,33 (m, 2H), 5,59 (s, 2H), 2,92 (s, 3H), of 2.21 (s, 3H). MS (ESI+) m/z 347,1 (M+H)+.

Example 158

N,1-dibenzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A and using benzylamine instead of piperidine and tetrahydrofuran instead of dimethylformamide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,15 (s, 1H), 9,35 (t, J=6,10 Hz, 1H), 8,01 (d, J=12,55 Hz, 2H), 7,68 (d, J=8,82, of 1.36 Hz, 1H), 7,53 (d, J=8,82 Hz, 1H), 7,17-7,41 (m, 10H), to 5.66 (s, 2H), to 4.41 (d, J=6,10 Hz, 2H). MS (ESI+) m/z 409,1 (M+H)+.

Example 159

N-(2-hydroxy-2-phenylethyl)-5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using DL-alpha-(methylaminomethyl)benzyl alcohol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,01 (s, 1H), 8,29 (1H), 8,17 (s, 1H), 7,73-a 7.85 (m, 1H), 7,62-7,72 (m, 1H), 7,16-the 7.43 (m, 5H), 6,86 (s, 1H), 5,17 (d, J=4,39 Hz, 1H), 4,89 (s, 1H), 3,71 (d, J=5,49 Hz, 2H), 3,10 (s, 3H). MS (ESI+) m/z 363,1 (M+H)+.

Example 160

N-[(1S)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (S)-2-amino-2-phenylethanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,05 (d, J=8,14 Hz, 1H), 8,40 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,65, of 1.53 Hz, 1H), of 7.70 (d, J=8,82 Hz, 1H), 7,20-7,46 (m, 6H), 5,02-5,13 (m, 1H), to 4.98 (t, J=5,59 Hz, 1H), 3,61-3,82 (m, 2H). MS (ESI+) m/z 349,0 (M+H)+.

Example 161

N-benzyl-N-(2-hydroxyethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 2-(benzylamino)ethanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,05 (d, J=8,48 Hz, 1H), 8,40 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,65, of 1.53 Hz, 1H), of 7.70 (d, J=8,82 Hz, 1H), 7,22 was 7.45 (m, 6H), 5,02-5,14 (m, 1H), to 4.98 (t, J=5,76 Hz, 1H), 3,61-3,81 (m, 2H). MS (ESI+) m/z 349,0 (M+H)+.

Example 162

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-3-methyl-1H-indazol

Example 162A

1-(5-Bromo-3-methyl-1H-indazol-1-yl)alanon

5-Bromo-3-methyl-1H-indazol (838 mg, of 3.97 mmol) was dissolved in methylene chloride (15 ml) and diisopropylethylamine (0.7 ml). Was added acetic anhydride (500 μl, of 5.29 mmol) and the mixture was stirred at ambient temperature over night. The mixture was diluted with ethyl acetate, washed with 1 n sodium hydroxide solution, and then 1 n hydrochloric acid, then with saturated salt solution. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z to 252.7 (M+H)+.

Example 162B

1-(5-(1-Benzyl-5-o-tolyl-1H-1,2,3-triazole-4-yl)-3-methyl-1H-indazol-1-yl)alanon

Connection Example 153A (436 mg, 0,808 mmol), Example 162A (205 mg, 0,810 mmol), dichlorobis(triphenylphosphine)palladium(II) (56 mg, 0,080 mmol) and thiophene-2-carboxylate copper (239 mg, 1.25 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated to 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 422,6 (M+H)+.

Example 162C

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-3-methyl-1H-indazol

Connection Example 162B (202 mg, 0,548 mmol) was dissolved in tetrahydrofuran (5.0 ml), methanol (0.5 ml) and water (0.5 ml) was added potassium hydroxide (133 mg, is 2.37 mmol). The mixture was stirred for 1 hour and then was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and purified using the cromatografia on silica gel, using elution gradient of 30-80% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 12,63 (s, 1H), of 7.70 (s, 1H), 7,44-7,52 (m, 1H), 7,38-the 7.43 (m, 1H), 7,29-7,38 (m, 4H), 7,22-7,29 (m, 3H), 6,89-of 6.96 (m, J=6,44, of 3.05 Hz, 2H), and 5.30-of 5.48 (m, 2H), 2,32 (s, 3H), 1,58 (s, 3H). MS (ESI+) m/z 380,1 (M+H)+.

Example 163

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Example 163 A

5-(1-Benzyl-5-o-tolyl-1H-1,2,3-triazole-4-yl)-2-perbenzoate

Connection Example 153A (450 mg, 0,834 mmol), 5-bromo-2-perbenzoate (167 mg, 0,835 mmol), dichlorobis(triphenylphosphine)palladium(II) (56 mg, 0,080 mmol) and thiophene-2-carboxylate copper (242 mg, of 1.27 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated at 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 369,2 (M+H)+.

Example 163B

5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

The compound of Example 163A (202 mg, 0,548 mmol) was treated with hydrazinehydrate (1.0 ml) in ethanol (1.0 ml) and was stirred and heated to 60°C over night. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and purified by using chromate is graphy on silica gel, using elution gradient 35-85% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,38 (s, 1H), 8,11 (s, 1H), 7,41-7,49 (m, 1H), 7,33-7,40 (m, J=6,95, to 6.95 Hz, 1H), 7,28-to 7.32 (m, 2H), 7,21-7,28 (m, 3H), 7,00-7,06 (m, 1H), 6,86-to 6.95 (m, 3H), 5,27-5,44 (m, 4H), 1,58 (s, 3H). MS (ESI+) m/z 381,1 (M+H)+.

Example 164

2-{2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]ethyl}-1H-isoindole-1,3(2H)-dione

Specified in the title compound was obtained in accordance with the procedure described in Example 88 using 2-(but-3-inyl)isoindoline-1,3-dione instead of 3-phenyl-1-propyne. The crude product was subjected to processing 25% TFU/dichloromethane and was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,33 (s, 1H), 8,65 (s, 1H), they were 8.22 (s, 1H), 8,18 (d, J=1,53 Hz, 1H), 7,78-of 7.90 (m, 5H), 7,71 to 7.75 (m, 1H), 3,92 (t, J=7,21 Hz, 2H), is 3.08 (t, J=7,21 Hz, 2H). MS (ESI+) m/z 359,0 (M+H)+.

Example 165

5-{4-[(2,4-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 2,4-dichloro-1-(prop-2-ynyloxy)benzene instead of 3-phenyl-1-propyne. The crude product was subjected to processing 25% TFU/dichloromethane and was purified using reverse-phase HPLC using the method of gradient elution of ACE nitril/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,93 (s, 1H), 8,28 (d, J=1,53 Hz, 1H), 8,23 (s, 1H), 7,88 (d, J=8,90, of 1.84 Hz, 1H), 7,76 (d, J=8,90 Hz, 1H), to 7.59 (d, J=2,46 Hz, 1H), 7,39-7,49 (m, 2H), lower than the 5.37 (s, 2H). MS (ESI+) m/z to 359.9 (M+H)+.

Example 166

5-{4-[(2,6-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using 1,3-dichloro-2-(prop-2-ynyloxy)benzene instead of 3-phenyl-1-propyne. The crude product was subjected to processing 25% TFU/dichloromethane and was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (500 MHz, DMSO-d6) δ ppm 13,39 (s, 1H), 8,97 (s, 1H), 8,29 (d, J=1,53 Hz, 1H), 8,24 (s, 1H), 7,89 (d, J=9,00, to 1.98 Hz, 1H), 7,76 (d, J=cent to 8.85 Hz, 1H), 7,51-of 7.55 (m, 2H), 7,19-7,26 (m, J=8,24, 8,24 Hz, 1H), 5,23 (s, 2H). MS (ESI+) m/z to 359.9 (M+H)+.

Example 167

5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

The compound of Example 156B (168 mg, 0,401 mmol) was dissolved in tetrahydrofuran (5.0 ml), methanol (0.5 ml) and water (0.5 ml) was added potassium hydroxide (138 mg, of 2.46 mmol). The mixture was stirred for 1 hour and was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel using suirou is of gradient 0-7% methanol in dichloromethane, obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), 8,02 (s, 1H), to 7.77 (s, 1H), 7,50-7,58 (m, 2H), 7,37-7,49 (m, 4H), 4,11 (d, J=7,12 Hz, 2H), 3,76 (d, J=1 1,53, 2,71 Hz, 2H), 3,11-3,24 (m, 2H), 1,88-2,03 (m, 1H), 1,30 was 1.43 (m, J=12,72, to 1.86 Hz, 2H), 1.04 million-1,22 (m, 2H). MS (ESI+) m/z 378,1 (M+H)+.

Example 168

1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-indazol

Example 168A

1-(Prop-2-inyl)-1H-indazol

Indazol (530 mg, of 4.49 mmol) was dissolved in dimethylformamide (4 ml). Was slowly added sodium hydride (60% suspension in mineral oil, 231 mg, 5,78 mmol) and the mixture was stirred for 10 minutes. Added propylbromide (80% of the mass. in toluene, 5.0 ml) and the mixture was stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate, washed with excess amount of water was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 5-30% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 157,1 (M+H)+.

Example 168B

1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 88, using the compound of Example 168A instead of 3-phenyl-1-propyne.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 8,78 (s, 1H), they were 8.22 (d, J=2,03, 0.68 Hz, 1H), to 8.20 (s, 1H), 8,10 (d, J=1,02 Hz, 1H), 7,80-7,87 (m, 2H), 7,75-7,80 (m, 1H), 7.68 per-7,74 (m, 1H, 7,39-7,46 (m, 1H), 7,13-7,19 (m, 1H), of 5.81 (s, 2H). MS (ESI+) m/z was 316.0 (M+H)+.

Example 169

5-[1-benzyl-5-(piperidine-1-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A and using tetrahydrofuran instead of dimethylformamide.1H NMR(300 MHz, DMSO-d6) δ ppm 13,20 (s, 1H), 8,16 (s, 1H), 7.95 is-8,00 (m, J=1,02 Hz, 1H), 7,62-to 7.68 (m, 1H), EUR 7.57-7,63 (m, 1H), 7,31-7,44 (m, 3H), 7.24 to 7,30 (m, 2H), are 5.36 of 5.84 (m, J=69,17 Hz, 2H), 3,43-3,59 (m, 2H), 2,43 at 2.59 (m, 2H), 1,17 of 1.46 (m, J=39,67 Hz, 4H), 0,49 is 0.65 (m, 2H). MS (ESI+) m/z 387,1 (M+H)+.

Example 170

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Example 170A

1-((Tetrahydro-2H-Piran-4-yl)methyl)-5-o-tolyl-4-(tributylstannyl)-1H-1,2,3-triazole

2-Ethnicolor (576 mg, of 4.57 mmol) was added to 1,1,1-tributyl-N,N-dimethylethanolamine (1,53 g, 4,58 mmol) and the mixture was stirred in a tightly closed vessel at 70°C for 2 hours. The mixture was cooled to ambient temperature and the contents of the vessel were stirred without sealing within 10 minutes. Added the compound of Example 80A (648 mg, 4,59 mmol) and the vessel again tightly closed and heated to 130°C during the night. The mixture was purified using chromatography on silica gel by elution gradient of 5-50% ethyl acetate in hexane, to obtain specified in the header connections. MS (ESI+) m/z 548,4 (M+H)+.

Example 170B

1-(5-(1-((Tetrahydro-2H-Piran-4-yl)methyl)-5-o-tolyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-yl)alanon

Connection Example 170A (432 mg, 0,791 mmol), the compound of Example 87A (222 mg, 0,776 mmol), dichlorobis(triphenylphosphine)palladium(II) (58 mg, 0,083 mmol) and thiophene-2-carboxylate copper (231 mg, to 1.21 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated at 150°C for 20 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 20-70% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 416,2 (M+H)+.

Example 170C

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Connection Example 170B (184 mg, 0,443 mmol) was dissolved in tetrahydrofuran (3.0 ml), methanol (0.3 ml) and water (0.3 ml) was added potassium hydroxide (140 mg, of 2.50 mmol). The mixture was stirred for 3 hours and was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 35-100% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,08 (s, 1H), 7,98 (s, 1H), 7.68 per-7,74 (m, J=1,02, of 1.02 Hz, 1H), 7,49-7,56 (m, 1H), 7,45-7,49 (m, 3H), 7,41 was 7.45 (m, J=7,46 Hz, 2H), 4,10(d, J=13,73, to 6.95 Hz, 1H), 3,89 (d, J=13,90, 7,80 Hz, 1H), of 3.77 (d, J=10,51, 2,71 Hz, 2H), 3,10-3,24 (m, 2H), 1,92 (s, 3H), 1,88-to 1.98 (m, 1H), 1,26 was 1.43 (m, 2H), 1.04 million-to 1.21 (m, 2H). MS (ESI+) m/z 374,1 (M+H)+.

Example 171

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Example 171A

2-fluoro-5-(1-((tetrahydro-2H-Piran-4-yl)methyl)-5-o-tolyl-1H-1,2,3-triazole-4-yl)benzonitrile

Connection Example 170A (411 mg, 0,752 mmol), 5-bromo-2-perbenzoate (151 mg, 0,755 mmol), dichlorobis(triphenylphosphine)palladium(II) (52 mg, 0,074 mmol) and thiophene-2-carboxylate copper (223 mg, 1,17 mmol) were combined in toluene (2.0 ml) in 4-ml vessel in an inert atmosphere of nitrogen. The vessel was tightly closed and heated to 150°C for 30 minutes. The mixture was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 377,6 (M+H)+.

Example 171B

5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Connection Example 171A (175 mg, 0,465 mmol) was treated with hydrazinehydrate (2.0 ml) in ethanol (2.0 ml) and the mixture was stirred and heated to 65°C for 2 hours. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient 1-8% methanol in dichloro is not, obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm is 11.39 (s, 1H), 8,08 (s, 1H), 7,45-of 7.55 (m, 1H), 7,37 was 7.45 (m, 3H), 7,01-was 7.08 (m, J=8,48 Hz, 1H), 6.89 in-6,97 (m, 1H), of 5.34 (s, 2H), 4.09 to (d, J=13,73, to 6.95 Hz, 1H), 3,89 (d, J=13,73, 7,63 Hz, 1H), 3,70-3,81 (m, 2H,), is 3.08-3.24 in (m, 2H), 1.91 a (s, 3H), 1,84 of 1.99 (m, 1H), 1,22-of 1.41 (m, 2H), 1.04 million-1,20 (m, 2H). MS (ESI+) m/z 389,1 (M+H)+.

Example 172

5-[1-benzyl-5-(morpholine-4-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81A, the research instead of piperidine and tetrahydrofuran instead of dimethylformamide.1H NMR (300 MHz, DMSO-d6) δ ppm 13,22 (s, 1H), 8,18 (s, 1H), 7.95 is-8,03 (m, 1H), of 7.64-of 7.70 (m, 1H), EUR 7.57-to 7.64 (m, 1H), 7,33 was 7.45 (m, 3H), 7.24 to 7,31 (m, 2H), USD 5.76 (s, 1H), 5,52 (s, 1H), 3.33 and-3,59 (m, 4H), 2,61-to 2.74 (m, 2H), 2,45 at 2.59 (m, 2H). MS (ESI+) m/z 389,1 (M+H)+.

Example 173

5-[1-benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

In argon atmosphere, the vessel containing the compound of Example 125B (50 mg, 0.12 mmol), 4-methoxyphenylalanine acid (20 mg, 0.13 mmol), PdCl2(dppf)dichlormethane (10 mg, 0.01 mmol) and potassium carbonate (33 mg, 0.24 mmol) in DME (2 ml) and water (0.2 ml), covered with a lid and heated at 80°C in a heating device with shaking for 48 hours. The solvent is evaporated under reduced pressure and the product was purified using reverse-phase HPLC using the method is ravintola elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 11,85 (s, 1H), 8,18 (s, 1H), 7,26-7,34 (m, 3H), 7,19-7,25 (m, 2H), 7,16-7,19 (m, 2H), 7,02 (t, J=8,13 Hz, 4H), vs. 5.47 (s, 2H), 3,80 (s, 3H). MS (ESI+) m/z 397,1 (M+H)+.

Example 174

N-[(1S)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (S)-(-)-2-amino-3-phenyl-1-propanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), of 8.47 (d, J=8,82 Hz, 1H), scored 8.38 (s, 1H), they were 8.22 (s, 1H), 7,87 (d, J=8,82, 1.70 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7.23 percent-7,31 (m, 3H), 7,22 (s, 1H), 7,12-7,21 (m, 1H), 4,90 (t, J=5,59 Hz, 1H), 4,07-to 4.28 (m, 1H), 3,40-to 3.58 (m, 2H), 2,89-3,00 (m, 1H), 2,75-of 2.86 (m, 1H). MS (ESI+) m/z 363,0 (M+H)+.

Example 175

N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (1S,2R)-(-)-CIS-1-amino-2-indanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,42 (s, 1H), 8,24 (s, 1H), 8,16 (d, J=8,48 Hz, 1H), to $ 7.91 (d, J=8,82, 1.70 Hz, 1H), 7,71 (d, J=8,48 Hz, 1H), 7,45 (s, 1H), 7,16-to 7.32 (m, 4H), are 5.36-vs. 5.47 (m, 2H), 4,50-br4.61 (m, 1H), 3,14 (d, J=15,43, 5,26 Hz, 1H), 2,90 (d, J=16.28 per, 1.70 Hz, 1H). MS (ESI+) m/z 361,0 (M+H)+.

Example 176

5-{3-[(3-phenylmorpholine-4-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in the Use of the e 81B, using the hydrochloride of 3-phenylmorpholine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,32-8,46 (m, 1H), 8,24 (s, 1H), 7,81-of 7.96 (m, 1H), of 7.70 (d, J=8,82 Hz, 1H), 7,37-of 7.55 (m, 4H), 7,26-7,37 (m, 2H), 5,34-5,71 (m, 1H), 4,51 (d, J=13,22 Hz, 1H), 3,78-4,39 (m, 3H)and 3.59 (t, J=1 to 1.36 Hz, 1H), 3.33 and-to 3.41 (m, 1H). MS (ESI+) m/z 375,0 (M+H)+.

Example 177

N-benzyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using benzylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 9,35 (t, J=6,27 Hz, 1H), 8,40 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,82, 1.70 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,33-7,40 (m, 4H), 7,32 (s, 1H), 7,22-7,30 (m, 1H), 4,48 (d, J=6,10 Hz, 2H). MS (ESI+) m/z 319,0 (M+H)+.

Example 178

((1S)-2-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (S)-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-yl)methanol instead of piperidine. MS (ESI+) m/z 435,1 (M+H)+.

Example 179

N-[(1R)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (R)-3-amino-3-phenylpropanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,24 (d, J=8,48 Hz, 1H), 8,39 (s, 1H),8,23 (s, 1H), 7,88 (d, J=8,82, 1.70 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,38-7,46 (m, 2H), 7,34 (t, J=7,46 Hz, 2H), 7,19-7,30 (m, 2H), 5,09 at 5.27 (m, 1H), to 4.62 (t, J=4,92 Hz, 1H), 3,37-to 3.52 (m, 2H), 2.00 in of 2.16 (m, 1H), 1,84-2,00 (m, 1H). MS (ESI+) m/z 363,1 (M+H)+.

Example 180

N-[(1S)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (S)-3-amino-3-phenylpropanol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 9,24 (d, J=8,14 Hz, 1H), 8,39 (s, 1H), they were 8.22 (s, 1H), 7,88 (d, J=8,65, of 1.53 Hz, 1H), 7,69 (d, J=8,81 Hz, 1H), 7,37 was 7.45 (m, 2H), 7,29-7,37 (m, 2H), 7,19-7,29 (m, 2H), 5.08 to and 5.30 (m, 1H), 4,55-and 4.68 (m, 1H), 3,37-3,51 (m, 2H), 2.00 in and 2.14 (m, 1H), 1,83 of 1.99 (m, 1H). MS (ESI+) m/z 363,0 (M+H)+.

Example 181

N-2,3-dihydro-1H-inden-1-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-aminoindane instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,13 (d, J=8,14 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,82, of 1.36 Hz, 1H), of 7.70 (d, J=8,82 Hz, 1H), 7,35 (s, 1H), 7,15-to 7.32 (m, 4H), 5,55 (sq, J=to $ 7.91 Hz, 1H), 2.95 and-is 3.08 (m, 1H), was 2.76 vs. 2.94 (m, 1H), 2,37-2,49 (m, 1H), 2,01-of 2.15 (m, 1H). MS (ESI+) m/z 345,0 (M+H)+.

Example 182

N-2,3-dihydro-1H-inden-2-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using a 2-aminoindane instead of piperidine.1H NMR (300 M is C, DMSO-d6) δ ppm 13,37 (s, 1H), remaining 9.08 (d, J=7,46 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,89 (d, J=8,82, 1.70 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,31 (s, 1H), 7,10-7,28 (m, 4H), 4.63 to-4,79 (m, 1H), 3,24 (d, J=15,77, 7,63 Hz, 2H), 2,96-is 3.08 (m, 2H). MS (ESI+) m/z 345,0 (M+H)+.

Example 183

5-(1H-indazol-5-yl)-N-(1-phenylpropyl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using alpha ethylbenzylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 9,18 (d, J=8,82 Hz, 1H), scored 8.38 (s, 1H), they were 8.22 (s, 1H), 7,88 (d, J=8,82, of 1.36 Hz, 1H), 7,69 (d, J=8,48 Hz, 1H), 7,39-of 7.48 (m, 2H), 7,34 (t, J=7.29 trend Hz, 2H), 7,19-7,29 (m, 2H), 4,84-5,00 (m, 1H), 1,69-2,04 (m, 2H), of 0.91 (t, J=7.29 trend Hz, 3H). MS (ESI+) m/z 347,1 (M+H)+.

Example 184

5-{1-benzyl-5-[3-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 173, using 3-(dimethylamino)phenylboronic acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm to 11.52 (s, 1H), 8,17 (s, 1H), 7,22-7,35 (m, 4H), 7,08-to 7.15 (m, 2H), 7,03 (d, J=of 6.71 Hz, 2H), PC 6.82 (d, J=8,39, to 2.29 Hz, 1H), 6.48 in-6,54 (m, 2H), vs. 5.47 (s, 2H), 2,78 (s, 6H). MS (ESI+) m/z 410,2 (M+H)+.

Example 185

5-{1-benzyl-5-[4-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 173, using 4-(dimethylamino)is anivorano acid instead of 4-methoxyphenylacetic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 11,65 (s, 1H), 8,17 (s, 1H), 7.23 percent-7,38 (m, 3H), 7,12-7,16 (m, 2H), 7,01-to 7.09 (m, 4H), 6,74-of 6.78 (m, 2H), of 5.45 (s, 2H), 2.95 and (s, 6H). MS (ESI+) m/z 410,2 (M+H)+.

Example 186

N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 3-acetaminophenydrocodone acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm of 10.05 (s, 1H), 8,14 (s, 1H), 7,69 (d, J=8.54 in Hz, 1H), 7,54 (s, 1H), 7,41 (t, J=to 7.93 Hz, 1H), 7.24 to to 7.32 (m, 3H), 7,08-7,16 (m, 2H), 6,93? 7.04 baby mortality (m, 3H), of 5.48 (s, 2H), a 2.01 (s, 3H). MS (ESI+) m/z 424,2 (M+H)+.

Example 187

N-{4-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 4-acetaminophenydrocodone acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 10,14 (s, 1H), 8,07 (s, 1H), 7,66 (d, J=cent to 8.85 Hz, 2H), 7.24 to to 7.32 (m, 3H), 7.18 in-7,22 (m, 2H),? 7.04 baby mortality-7,11 (m, 2H), 6,98-7,02 (m, 2H), 5,48 (s, 2H), to 5.35 (s, 2H), 2,04 is 2.10 (m, 3H). MS (ESI+) m/z 424,1 (M+H)+.

Example 188

5-{1-benzyl-5-[3-(1H-pyrazole-1-yl)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 3-(1H-pyrazole-1-yl)phenylboronic acid instead of 4-methoxyphenylacetic acid.1H I Is R (500 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 8,45 (d, J=2,75 Hz, 1H), of 8.09 (s, 1H), to 7.99 (d, J=8,24, of 1.53 Hz, 1H), 7,80-a 7.85 (m, 1H), 7,74 (d, J=1,83 Hz, 1H), 7,56 (t, J=to 7.93 Hz, 1H), 7,20-7,30 (m, 3H), 7,06-7,16 (m, 3H), 6,98? 7.04 baby mortality (m, 2H), 6,53-is 6.54 (m, 1H), of 5.55 (s, 2H), to 5.35 (s, 2H). MS (ESI+) m/z 433,2 (M+H)+.

Example 189

5-[1-benzyl-5-(1-methyl-1H-pyrazole-4-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 1-methyl-1H-pyrazole-4-Voronovo acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,78 (s, 1H), 8,11 (s, 1H), 7,87 (s, 1H), 7,43 (s, 1H), 7,27-7,41 (m, 4H), from 7.24 (d, J=8.54 in Hz, 1H), 7,05-7,11 (m, J=7,02 Hz, 2H), 5,54 (s, 2H), 3,86 (s, 3H). MS (ESI+) m/z 370,9 (M+H)+.

Example 190

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-phenylbenzene

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 3-(phenylcarbamoyl)phenylboronic acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,41 (s, 1H), 10,22 (s, 1H), 8.07-a to 8.12 (m, 2H), 7,95 (s, 1H), 7,73 (d, J=7,63 Hz, 2H), 7,60 (t, J=7,78 Hz, 1H), 7,43 (d, J=7,63 Hz, 1H), 7,32-7,39 (m, 2H), 7,21-7,30 (m, 3H), 7,05-to 7.15 (m, 3H), 7,00 (d, J=of 6.71 Hz, 2H), 5,54 (s, 2H), are 5.36 (s, 2H). MS (ESI+) m/z 486,2 (M+H)+.

Example 191

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-benzylbenzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using EQ is whether the 3-(benzylcarbamoyl)phenylboronic acid instead of 4-methoxyphenylacetic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 11,41 (s, 1H), 9,04 (t, J=5,95 Hz, 1H), 8,07 (s, 1H), 8,01 (d, J=to 7.93 Hz, 1H), a 7.85 (s, 1H), 7,56 (t, J=7,78 Hz, 1H), 7,41 (d, J=7,63 Hz, 1H), 7,21-7,35 (m, 8H), 7,01-7,11 (m, 2H), of 6.96 (d, J=7,32, 2,14 Hz, 2H), 5,52 (s, 2H), to 5.35 (s, 2H), 4,45 (d, J=5,80 Hz, 2H). MS (ESI+) m/z 500,2 (M+H)+.

Example 192

5-[1-benzyl-5-(1-methyl-1H-indol-5-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 173, using 1-methyl-1H-indol-5-Voronovo acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,35 (s, 1H), 8,14 (s, 1H), 7,54 (d, J=8.54 in Hz, 1H), 7,50 (d, J=1,53 Hz, 1H), 7,42 (d, J=3,05 Hz, 1H), 7.24 to 7,33 (m, 3H), 6,97-7,05 (m, 5H), 6,44 (d, J=2,75 Hz, 1H), 5,46 (s, 2H), 5,33 (s, 2H), 3,83 (, 3H). MS (ESI+) m/z 420,1 (M+H)+.

Example 193

5-[1-benzyl-5-(3-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 3-methoxyphenylacetic acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 8,08 (s, 1H), 7,34-7,40 (m, 1H), 7.24 to to 7.32 (m, 3H), 7.03 is-7,11 (m, 3H), 6,98-7,02 (m, 2H), 6,80-6,85 (m, 2H), 5,49 (s, 2H), to 5.35 (s, 2H), 3,66 (s, 3H). MS (ESI+) m/z 397,1 (M+H)+.

Example 194

5-[1-benzyl-5-(3-morpholine-4-ylphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine

In argon atmosphere, the vessel containing the compound of Example 125B (35 mg, 0.09 mmol), 3-morpholinobutyrophenone to the slot (21 mg, 0.09 mmol), PdCl2(dppf)dichlormethane (7 mg, 0,009 mmol) and potassium carbonate (24 mg, 0.18 mmol) in DME (1 ml) and water (0.1 ml), covered with a lid and heated at 80°C in a heating device with shaking for 3 days. The solvent is evaporated under reduced pressure and the product was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header in the form of a salt TFU.1H NMR (500 MHz, DMSO-d6) δ ppm to 11.52 (s, 1H), 8,14 (s, 1H), 7,26-7,34 (m, 4H), 6,98 for 7.12 (m, 5H), 6,67 to 6.75 (m, 2H), vs. 5.47 (s, 2H), 3,57-to 3.73 (m, 4H), 2.91 in-3,03 (m, 4H). MS (ESI+) m/z 452,2 (M+H)+.

Example 195

5-[3-(1,3-dihydro-2H-isoindole-2-ylcarbonyl)isoxazol-5-yl]-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using isoindoline instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,38 (s, 1H), 8,43 (s, 1H), of 8.25 (s, 1H), to 7.93 (d, J=8,82, of 1.36 Hz, 1H), 7,71 (d, J=8,48 Hz, 1H), 7,30-7,47 (m, 5H), is 5.18 (s, 2H), 4.92 in (s, 2H). MS (ESI+) m/z 331,0 (M+H)+.

Example 196

5-{3-[(4-methyl-2-phenylpiperazin-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-methyl-3-phenylpiperazine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,12 (s, 1H), 8,28-at 8.36 (m, 1H), 8,18 (s, 1H), 7,83 (d, J=8,79, 1,46 Hz, 1H), to 7.67 (d, J=8,79 Hz, 1H), of 7.48 (d, J=7,69 G is, 2H), 7,30-7,40 (m, 2H), 7,21-7,29 (m, 1H), 7,14 (s, 1H), 5,56-5,73 (m, J=5,86 Hz, 1H), 3,99-4,19 (m, J=8,42 Hz, 1H), 3,38-3,47 (m, 1H), 3,05-is 3.21 (m, J=of 7.69 Hz, 1H), 2,80 (d, J=1 1,72 Hz, 1H), 2,41 (d, J=12,08, 4,39 Hz, 1H), 2,24 (s, 3H), 2,02-of 2.16 (m, 1H). MS (ESI+) m/z 388,1 (M+H)+.

Example 197

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-amine

Example 197A

tert-Butyl 1-(1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carbonyl)piperidine-4-ylcarbamate

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 149C instead of the compound of Example 81B and using 4-Boc-aminopiperidine instead of piperidine. MS (ESI+) m/z 502,3 (M+H)+.

Example 197B

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-amine

Connection Example 197A (101 mg, 0,201 mmol) was dissolved in 4 M hydrochloric acid in dioxane (4 ml) and methanol (1 ml) and stirred at ambient temperature for 2 hours. The solvents were removed under reduced pressure to obtain specified in the connection header in the form of the HCl salt.1H NMR (300 MHz, DMSO-d6) δ ppm 8,18 (s, 1H), 7,92-8,08 (m, J=1,36 Hz, 3H), 7,53-of 7.70 (m, 2H), 7.24 to 7,47 (m, 5H), 5.40 to-5,73 (m, J=3,39 Hz, 2H), 4,34-4,63 (m, 1H), 3,44-of 3.53 (m, J=3,39 Hz, 1H), 2.95 and-3,17 (m, 2H), was 2.76 vs. 2.94 (m, J=1 1,02, 11,02 Hz, 1H), 1,87-2,03 (m, J=1 to 1.87 Hz, 1H), 1.30 and of 1.52 (m, J=10,85 Hz, 2H), 0,66-of 0.91 (m, J=10,17 Hz, 1H). MS (ESI+) m/z 402,2 (M+H)+.

Example 198

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]be Samid

Example 198A

tert-butyl 3-amino-5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

The compound of Example 102B (200 mg, 0.55 mmol) and N,N-dimethylpyridin-4-amine (5 mg, 0.04 mmol) was dissolved in methylene chloride. The mixture was stirred at room temperature while adding dropwise a solution of di-tert-BUTYLCARBAMATE (120 mg, 0.55 mmol) in 5 ml of methylene chloride. The reaction mixture was left for stirring at room temperature for 8 hours, concentrated under vacuum, dissolved in methylene chloride (10 ml) and washed with diluted aqueous HCl solution (1N, 10 ml) and saturated aqueous NaHCO3(10 ml). The organic layer was concentrated and purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 8,29 (s, 2H), 7,43-to 7.59 (m, 3H), 7.23 percent-7,38 (m, 6H), 6,98 (d, J=7,17, 2,39 Hz, 2H), 6,38 (s, 2H), 5,52 (s, 2H), of 1.55 (s, 9H). MS (ESI+) m/z 467 (M+H)+.

Example 198B

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide

Connection Example 198A (37.5 mg, 0.08 mmol) and pyridine (12.7mm mg, 0.16 mmol) was dissolved in methylene chloride (2 ml). The mixture was left for stirring at room temperature. To the mixture was added benzoyl chloride (14 mg, 0.1 mmol). The reaction mixture was left to stir at room temperature overnight, concentrated in the condition is s vacuum and was purified using reverse-phase-HPLC (CH 3CN/H2O/NH4OAc) to give the Boc-protected precursor. The precursor was treated with a mixture of 1:1 TFU/dichloromethane (2 ml) for 1 hour and concentrated under vacuum to obtain specified in the connection header in the form of a salt TFU.1H NMR (300 MHz, DMSO-d6) δ ppm 12,84 (s, 1H), 10,70 (s, 1H), 8,01 (d, J=6,99 Hz, 2H), 7,87 (s, 1H), 7,50-of 7.69 (m, 3H), of 7.36-of 7.48 (m, 5H), 7.18 in-7,35 (m, 5H), 6,92-7,03 (m, 2H), 5,48 (s, 2H). MS (ESI+) m/z 471 (M+H)+.

Example 199

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzosulfimide

Specified in the title compound was obtained in accordance with the procedure described in Example 198B, using benzosulfimide instead of benzoyl chloride.1H NMR (300 MHz, DMSO-d6) δ ppm 12,69 (s, 1H), 10,61 (s, 1H), to 7.99 (s, 1H), 7,70-7,76 (m, 2H), 7,45 to 7.62 (m, 6H), 7,24 and 7.36 (m, 7H), of 6.99 (d, J=6,99, of 2.21 Hz, 2H), 5,50 (s, 2H). MS (ESI+) m/z 507 (M+H)+.

Example 200

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(4-methoxyphenyl)urea

Connection Example 198A (25 mg, 0.54 mmol) was dissolved in dioxane (2 ml) and to the solution was added 1-isocyanato-4-methoxybenzo (24 mg, 0.16 mmol). The reaction mixture was stirred at 80°C for 12 hours, concentrated and purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) to give the Boc-protected precursor. The precursor was treated with a mixture of 1:1 TFU/dichloromethane (2 ml) for 1 hour and the oxygen which has demonstrated under vacuum to obtain specified in the connection header in the form of a salt TFU. 1H NMR (300 MHz, DMSO-d6) δ ppm 12,54 (s, 1H), 9,51 (s, 1H), 9,42 (s, 1H), 8,28 (s, 1H), 7,45-7,51 (m, 3H), of 7.36-7,42 (m, 2H), 7.24 to 7,35 (m, 7H), 6,98 (d, J=7,17, 2,39 Hz, 2H), 6.87 in-6,94 (m, 2H), 5,50 (s, 2H), 3,74 (s, 3H). MS (ESI+) m/z 516 (M+H)+.

Example 201

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]butanamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 198B, using butyrylcholine instead of benzoyl chloride.1H NMR (300 MHz, DMSO-d6) δ ppm 10,77-10,84 (m, 1H), 8,07 (s, 1H), of 7.97 (d, J=8,82 Hz, 1H), to 7.64 (d, J=8,82, to 1.47 Hz, 1H), 7,43-EUR 7.57 (m, 3H), 7,22-7,38 (m, 5H), 6,91-7,06 (m, 2H), 5,50 (s, 2H), 2,33 (t, J=7,17 Hz, 2H), 1,54-to 1.60 (m, 2H), of 0.91 (t, J=7,35 Hz, 3H). MS (ESI+) m/z 437 (M+H)+.

Example 202

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-methylpropanamide

Specified in the title compound was obtained in accordance with the procedure described in Example 198B, using isobutyramide instead of benzoyl chloride.1H NMR (300 MHz, DMSO-d6) δ ppm 12,66 (s, 1H), 10,12 (s, 1H), 7,80 (s, 1H), 7,42-of 7.55 (m, 4H), 7,33-7,39 (m, 1H), 7,22-to 7.32 (m, 5H), 6,97 (d, J=6,99, to 2.57 Hz, 2H), 5,48 (s, 1H), 2,59-2,69 (m, 1H), 1,07 (d, J=6,99 Hz, 6H). MS (ESI+) m/z 437 (M+H)+.

Example 203

N-[5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]cyclopropanecarboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 198B, using cyclopropanecarbonitrile instead of benzoyl chloride.1H NMR (30 MHz, DMSO-d6) δ ppm 10,45-at 10.64 (s, 1H), to $ 7.91 (s, 1H), 7,43-of 7.55 (m, 3H), 7,31-the 7.43 (m, 2H), 7.23 percent-7,30 (m, 5H), 6,97 (d, J=7,17, 2,39 Hz, 2H), 5,48 (s, 2H), 1.77 in is 1.91 (m, 1H), 0,69-0.87 (m, 4H). MS (ESI+) m/z 435 (M+H)+.

Example 204

N-[1-benzoyl-5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl}benzamide

The compound of Example 89B (33 mg, 0.1 mmol) was dissolved in tetrahydrofuran (0.6 ml) in a microwave tube CEM. Added benzoyl chloride (28 mg, 0.2 mmol) and the mixture was heated at 120°C for 15 minutes in a microwave device CEM-Discover. The reaction mixture was cooled to room temperature and concentrated. The residue was purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 11,35 (s, 1H), 8,55 (d, J=8,82 Hz, 1H), at 8.36 (s, 1H), 8,17 (d, J=8,64, 1.65 Hz, 1H), of 8.06 (d, J=7,54, 2,39 Hz, 4H), 7,51-7,72 (m, 6H), 7,26 was 7.45 (m, 5H), 5,71 (s, 2H), 1,76-to 1.87 (m, 1H), 1,11 (d, J=6,62 Hz, 2H), 0,44 (d, J=to 4.41 Hz, 2H). MS (ESI+) m/z 539 (M+H)+.

Example 205

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-perbenzoic

Example 205A

tert-Butyl 3-amino-5-(1-benzyl-S-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

Specified in the title compound was obtained in accordance with the procedure described in Example 198A, using the compound of Example 89B instead of the compound of Example 102A.1H NMR (300 MHz, DMSO-d6) δ ppm compared to 8.26 (s, 1H), of 7.96-8,07 (m, 1H), 7,86-to 7.95 (m, 1H), 7,35-7,46 (m, 3H), 7,28-7,35 (who, 2H), 6,35-6,47 (m, 2H), 5,70 (s, 2H), 1,72-of 1.84 (m, 1H), 1,60 (s, 9H), 0,99-1,10 (d, J=1,84 Hz, 2H), 0,38 (d, J=3,68 Hz, 2H). MS (ESI+) m/z 431 (M+H)+.

Example 205B

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-perbenzoic

Connection Example 205A (25 mg, 0,058 mmol) and pyridine (9,2 mg, 0,116 mmol) was dissolved in methylene chloride (1 ml). The mixture was left for stirring at room temperature and to the mixture was added 3-perbenzoate (11,1 mg of 0.58 mmol). The reaction mixture was left to stir at room temperature overnight, concentrated and purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) to give the Boc-protected precursor. The precursor was treated with a mixture of 1:1 TFU/dichloromethane (2 ml) for 1 hour and concentrated under vacuum to obtain specified in the connection header in the form of a salt TFU.1H NMR (300 MHz, DMSO-d6) δ ppm of 10.58 (s, 1H), of 7.75 (s, 1H), 7,51-of 7.60 (m, 1H), 7,46 (d, J=8,82, to 1.47 Hz, 1H), 7,15-7,28 (m, 2H), 7,10 (d, J=2,21 Hz, 1H), 6,88-7,05 (m, 6H), 5,31 (s, 2H), of 1.35 to 1.47 (m, J=5,15 Hz, 1H), 0,68 (d, J=8,27, 1,65 Hz, 2H), 0,03 (d, J=5,52 Hz, 2H). MS (ESI+) m/z 453 (M+H)+.

Example 206

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using benzoyl chloride instead of 3-tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 12,89 (s, 1H), 10,3 (s, 1H), 8,02-of 8.15 (m, 3H), 7,83 (d, J=8,82, to 1.47 Hz, 1H), 7,50-7,66 (m, 4H), 7.24 to the 7.43 (m, 5H), 5,67 (s, 2H), 1.77 in (m, 1H), 0,99-1,10 (m, 2H), 0,39 (m, 2H). MS (ESI+) m/z 435 (M+H)+.

Example 207

N-benzyl-5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

To a solution of compound of Example 89B (18.3 mg, 0.05 mmol) in dimethylformamide (2 ml) was added acetic acid (15 mg, 0.25 mmol) and benzaldehyde (6.4 mg, 0.06 mmol). The reaction mixture was stirred at room temperature overnight. To the mixture was added triacetoxyborohydride sodium (NaBH(OAc)3, 32 mg, 0.15 mmol). The reaction mixture was stirred at room temperature for 3 hours, concentrated and purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) obtaining specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm to 13.09 (s, 1H), 9,24 (s, 1H), 8,02-8,10 (m, 3H), 7,84-of 7.90 (m, 1H), 7,49-to 7.67 (m, 4H), 7,25 was 7.45 (m, 5H), 5,70 (s, 2H), 3,30 (s, 2H), 1,88-of 1.95 (m, 1H), 1,01 (PI)-1.09 (m, 2H), 0,43 (d, J=Android 4.04 Hz, 2H). MS (ESI+) m/z 421 (M+H)+.

Example 208

N-[(1R)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (R)-(+)-2-amino-3-phenyl-1-propanol (37 mg, 0,245 mmol) in place of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm made 13.36 (s, 1H), 8,46 (d, J=8,82 Hz, 1H), of 8.37 (s, 1H), they were 8.22 (s, 1H), 7,87 (DD, J=8,82, of 1.36 Hz, 1H), 7,69 (d, J=8,82 Hz, 1H), 7,12-7,35 (m, 6H), 4,89 (t, J=5,59 Hz, 1H), 4,13-of 4.25 (m, 1H), 3,40 to 3.8 (m, 2H), 2,90-2,99 (m, 1H), 2,74-2,87 (m, 1H). MS (ESI+) m/z 363,0 (M+H)+.

Example 209

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol

Example 209A

1-(5-Bromo-1H-indazol-1-yl)alanon

4-Bromo-2-methylaniline (25,0 g, 134 mmol) was dissolved in chloroform (250 ml) and the mixture was cooled to 5°C. was Added dropwise acetic anhydride (35 ml, 343 mmol) and the mixture was allowed to warm to ambient temperature. Was added potassium acetate (of 3.97 g of 40.4 mmol) and isoenergetic (35 ml, 262 mmol) and the mixture was heated at 70°C during the night. The mixture was neutralized with saturated sodium bicarbonate solution and was extracted with methylenechloride. The combined organic layers were concentrated under reduced pressure and the obtained residue was ground into powder with methanol to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm to 8.45 (s, 1H), compared to 8.26 (d, J=8,82 Hz, 1H), 8,17 (d, J=1.70 Hz, 1H), to 7.77 (DD, J=8,82, 2,03 Hz, 1H), 2,72 (s, 3H).

Example 209B

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol

Connection Example 209A (425 mg, 1.78 mmol), 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (508 mg, to 1.79 mmol), dichlorobis(triphenylphosphine)palladium(II) (133 mg, 0,189 mmol) and potassium carbonate (742 mg, 5.37 mmol) were combined in a tightly closed container with dioxane (10 ml) and water (1 ml) in an inert nitrogen atmosphere and the mixture was heated to 110°C over night. The mixture was diluted with methylene chloride and washed with water. The organic layer absor Aravali on silica gel and was purified using chromatography on silica gel, using elution gradient 45-90% ethyl acetate in hexane, to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm 13,00 (s, 1H), of 8.25 (s, 1H), 8,02 (s, 1H), 7,92 (s, 2H), 7,55-to 7.61 (m, 1H), of 7.48-rate of 7.54 (m, 1H), 7,25-7,40 (m, 5H), to 5.35 (s, 2H). MS (ESI+) m/z to 274.9 (M+H)+.

Example 210

N-[(1R)-3-hydroxy-1-phenylpropyl]-5-(3-methyl-1H-indazol-5-yl)isoxazol-3-carboxamide

Example 210A

tert-Butyl 5-bromo-3-methyl-1H-indazol-1-carboxylate

5-Bromo-3-methyl-1H-indazol (5,11 g, and 24.2 mmol) and a catalytic amount of dimethylaminopyridine (~30 mg) was dissolved in methylene chloride (100 ml). Was added di-tert-BUTYLCARBAMATE (5.9 g, of 27.0 mmol) and the mixture was stirred at ambient temperature for 3 hours. The solvent was removed under reduced pressure and the obtained residue was diluted with ethyl acetate and washed with 1 n solution of sodium hydroxide (twice), 0,1N solution of hydrochloric acid and saturated saline. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 210,8 (M-Boc)+.

Example 210B

tert-Butyl 3-methyl-5-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate

Connection Example 210A (of 7.55 g, a 24.3 mmol), dichlorobis(triphenylphosphine)palladium(II) (870 mg, 1,24 mmol) and copper iodide(I) (250 mg, 1,31 mmol) were combined in triethylamine (60 ml) is inert atmosphere of nitrogen. Added trimethylsilylacetamide (4,0 ml of 28.9 mmol) and the mixture was heated at 60°C over night. The mixture was diluted with methylene chloride and washed using 0.1 M hydrochloric acid. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-40% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 228,9 (M-Boc)+.

Example 210C

5-Ethinyl-3-methyl-1H-indazol

Connection Example 210B (7,26 g, 22,1 mmol) was dissolved in methanol (170 ml). Added a 1N solution of potassium hydroxide (45 ml) and the mixture was stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the obtained residue was diluted with ethyl acetate and washed with water and saturated salt solution. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header. MS (ESI+) m/z 157,1 (M+H)+.

Example 210D

ethyl 5-(3-methyl-1H-indazol-5-yl)isoxazol-3-carboxylate

Connection Example 210C (411 mg, 2,63 mmol) was dissolved in toluene (15 ml) and triethylamine (478 μl) and heated to 90°C. was Added ethylchlorothioformate (480 mg, 3,17 mmol)dissolved in toluene (15 ml)slowly dropwise within 30 minutes. Once added, the mixture was diluted with ethyl acetate and washed with 1 n rest the rum hydrochloric acid. The organic layer was concentrated under reduced pressure and the obtained residue was ground into powder with methanol to obtain specified in the connection header. MS (ESI+) m/z 271,9 (M+H)+.

Example 210E

5-(3-methyl-1H-indazol-5-yl)isoxazol-3-carboxylic acid

Connection Example 210D (325 mg, 1.20 mmol) was dissolved in tetrahydrofuran (10 ml), methanol (1 ml) and water (1 ml) was added potassium hydroxide (150 mg, or 2.67 mmol). The mixture was stirred at ambient temperature for 3 hours. The mixture was diluted with ethyl acetate and washed with 1 n hydrochloric acid. The product was deposited in a separating funnel, and it was filtered to obtain specified in the connection header. MS (ESI+) m/z 243,9 (M+H)+.

Example 210F

N-[(1R)-3-hydroxy-1-phenylpropyl]-5-(3-methyl-1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the compound of Example 210E instead of the compound of Example 81A and using (R)-3-amino-3-phenylpropane-1-ol instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 12,93 (s, 1H), 8,45 (d, J=8,82 Hz, 1H), with 8.33 (s, 1H), to 7.84 (d, J=8,82, 1.70 Hz, 1H), to 7.59 (d, J=9,16 Hz, 1H), 7,21-7,29 (m, 5H), 7,13-7,21 (m, 1H), 4,89 (t, J=5,59 Hz, 1H), 4,10-4.26 deaths (m, 1H), 3,42 of 3.56 (m, 2H), 2,88-3,00 (m, 1H), 2,75-2,87 (m, 1H), to 2.55 (s, 3H). MS (ESI+) m/z 377,1 (M+H)+.

Example 211

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenol

In argon atmosphere, the vessel containing the compound of Example 125B (35 mg, 0.09 mmol), 3-hydroxyphenylarsonic acid (12 mg, 0.09 mmol), PdCl2(dppf)dichlormethane (7 mg, 0,009 mmol) and potassium carbonate (24 mg, 0.18 mmol) in DME (1 ml) and water (0.1 ml), covered with a lid and heated at 80°C in a heating device with shaking for 3 days. The solvent is evaporated and the product was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water with 0.1% TFU, obtaining specified in the connection header.1H NMR (500 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 9,68 (s, 1H), of 8.09 (s, 1H), 7.24 to 7,35 (m, 5H), 6,98-7,13 (m, 3H), to 6.88 (d, J=8,09, to 1.98 Hz, 1H), 6.73 x (s, 1H), 6,60 of 6.66 (m, 1H), vs. 5.47 (s, 2H), to 5.35 (s, 2H). MS (ESI+) m/z 383,1 (M+H)+.

Example 212

3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]benzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 173, using 3-carbamoilirovaniem acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,41 (s, 1H), 8,07 (s, 1H), 7,97-8,03 (m, 2H), 7,83-7,87 (m, 1H), 7,53 (t, J=7,78 Hz, 1H), 7,45 (s, 1H), 7,38 (d, J=7,63 Hz, 1H), 7.23 percent-7,30 (m, 3H), 7,00-7,10 (m, 2H), of 6.96 (d, J=of 7.48, to 1.98 Hz, 2H), 5,51 (s, 2H), to 5.35 (s, 2H). MS (ESI+) m/z 410,1 (M+H)+.

Example 213

5-{1-benzyl-5-[4-(methylsulphonyl)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine

Specified in the title compound was obtained according to the procedure described is Oh in Example 173, using 4-(methylsulphonyl)phenylboronic acid instead of 4-methoxyphenylacetic acid.1H NMR (500 MHz, DMSO-d6) δ ppm 11,44 (s, 1H), 7,94 shed 8.01 (m, 3H), 7,58 (d, J=8.54 in Hz, 2H), 7,22-7,30 (m, 3H),? 7.04 baby mortality-7,13 (m, 2H), 6,98 (d, J=of 7.48, to 1.98 Hz, 2H), to 5.56 (s, 2H), lower than the 5.37 (s, 2H), or 3.28 (s, 3H). MS (ESI+) m/z 445,2 (M+H)+.

Example 214

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-chlorobenzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using a 2-chlorobenzylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 10,94 (s, 1H), 8,24 (s, 1H), a 7.85 (d, J=8,82, to 1.47 Hz, 1H), 7,65 (d, J=6,99, of 1.84 Hz, 1H), 7,43-to 7.61 (m, 4H), 7,26-7,42 (m, 5H), of 5.68 (s, 2H), 1,71 of-1.83 (m, 1H), 1.04 million-1,12 (m, 2H), from 0.37 to 0.45 (m, 2H). MS (ESI+) m/z 469 (M+H)+.

Example 215

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-chlorobenzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using 4-chlorobenzylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 10,53 (s, 1H), 7,65-7,71 (m, 3H), 7,42 (d, J=8,82, to 1.47 Hz, 1H), 7.18 in-7,24 (m, 2H), 7,12-to 7.18 (m, 1H), 6,93-7,02 (m, 3H), 6,83-6,92 (m, 3H), at 5.27 (s, 2H), 1.30 and the 1.44 (m, 1H), 0,59 is 0.67 (m, 2H), -0,07-0,04 (m, 2H). MS (ESI+) m/z 469 (M+H)+.

Example 216

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]econsultant

Specified in the title compound was obtained in accordance with the procedure opican the th in the Example 205B, using acanaloniidae instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 10,19 (s, 1H), 8,15 (s, 1H), 7,82 (d, J=8,64, 1.65 Hz, 1H), 7,53 (d, J=8,82 Hz, 1H), 7,35-7,45 (m, 3H), 7,27-7,35 (m, 2H), 5,69 (s, 2H), 3,30 (sq, J=7,35 Hz, 2H), 1,74, to 1.87 (m, 1H), 1,27-of 1.36 (m, 3H), 1,02-of 1.12 (m, 2H), 0,34 to 0.44 (m, 2H). MS (ESI+) m/z 423 (M+H)+.

Example 217

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzosulfimide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using benzosulfimide instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm was 12.75 (s, 1H), 10,69 (s, 1H), 8,02 (s, 1H), 7,71-7,83 (m, 3H), 7,43-of 7.60 (m, 4H), 7,34-the 7.43 (m, 3H), 7,27-7,34 (m, 2H), 5,69 (s, 2H), 1,69 of-1.83 (m, 1H), 0,99-1,11 (m, 2H), 0,31-of 0.45 (m, 2H). MS (ESI+) m/z 471 (M+H)+.

Example 218

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-chlorobenzenesulfonamide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using 2-chlorobenzene-1-sulphonylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 12,36 (s, 1H), or 10.60 (s, 1H), to 7.67 (s, 1H), 7.62mm (d, J=to $ 7.91, 1.65 Hz, 1H), 7,40 (d, J=8,82, to 1.47 Hz, 1H), 7,14-7,27 (m, 2H), 7,00 for 7.12 (m, 4H), of 6.96-7,00 (m, 1H), 6.90 to-to 6.95 (m, 2H), 5,31 (s, 2H), 1,29-of 1.44 (m, 1H), and 0.61-0.74 and (m, 2H), be-0.05 to 0.05 (m, 2H). MS (ESI+) m/z 505 (M+H)+.

Example 219

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-chlorobenzenesulfonamide

Specified in zag is lowke compound was obtained in the form of an HCl salt according to the procedure described in Example 205B, using 3-chlorobenzene-1-sulphonylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 12,84 (s, 1H), 10,86 (s, 1H), 8,00 (s, 1H), 7,82 (s, 1H), 7,72 (d, J=7,72 Hz, 1H), to 7.64 (d, J=1,84 Hz, 1H), EUR 7.57 (d, J=7,72 Hz, 1H), 7,50 (d, J=8,82 Hz, 1H), 7,34 was 7.45 (m, 3H), 7,28-7,34 (m, 2H), 5,69 (, 2H), 1,71 of-1.83 (m, 1H), 1.06 a (m, 2H), and 0.37 (m, 2H). MS (ESI+) m/z 505 (M+H)+.

Example 220

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-chlorobenzenesulfonamide

Specified in the title compound was obtained in the form of an HCl salt according to the procedure described in Example 205B, using 4-chlorobenzene-1-sulphonylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 12,80 (s, 1H), 10,79 (s, 1H), 8,00 (s, 1H), 7,73-7,83 (m, 3H), 7,56-to 7.64 (m, 2H), 7,49 (d, J=8,82 Hz, 1H), 7,34 was 7.45 (m, 3H), 7,28-7,34 (m, 2H), 5,69 (s, 2H), 1,71 is 1.86 (m, 1H), 0,99 by 1.12 (m, 2H), 0,31-0,43 (m, 2H). MS (ESI+) m/z 505 (M+H)+.

Example 221

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2,5-dimethylfuran-3-sulfonamide

Specified in the title compound was obtained in the form of an HCl salt according to the procedure described in Example 205B, using 2.5-dimethylfuran-3-sulphonylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 12,82 (s, 1H), 10,48 (s, 1H), 8,00 (s, 1H), 7,78 (d, J=8,64, 1.65 Hz, 1H), 7,50 (d, J=9,19 Hz, 1H), 7,34 was 7.45 (m, 3H), 7,28-7,33 (m, 2H), of 6.20 (s, 1H), 5,69 (s, 2H), 2,11 (s, 6H), 1,71-of 1.84 (m, 1H), 1,01-a 1.11 (m, 2H), 0,32-0,41 (m, 2H). MS (ESI+) m/z 489 (M+H)+.

Example 222

5-(-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(2-Chlorobenzyl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 207 using 2-chlorobenzaldehyde instead of benzaldehyde.1H NMR (300 MHz, DMSO-d6) δ ppm for 11.55 (s, 1H), to 8.20 (s, 1H), 7,69 (d, J=8,46, to 1.47 Hz, 1H), 7,49 (d, J=8,82 Hz, 1H), 7,34-7,46 (m, 4H), 7.23 percent-7,33 (m, 5H), 5,69 (s, 2H), 4,56 (s, 2H), 1,72 of-1.83 (m, 1H), 0,99 (PI)-1.09 (m, 2H), 0,35-0,42 (m, 2H,). MS (ESI+) m/z 455 (M+H)+.

Example 223

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(3-Chlorobenzyl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 207 using 3-chlorobenzaldehyde instead of benzaldehyde.1H NMR (300 MHz, DMSO-d6) δ ppm 11,53 (s, 1H), 8,15 (s, 1H), to 7.59-to 7.77 (m, 1H), 7,25-of 7.48 (m, 10H), of 5.68 (s, 2H), 4,49 (s, 2H), 1,71 and 1.80 (m, 1H), 1.04 million (s, 2H), 0,38 (s, 2H).

Example 224

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-chlorobenzamide

Specified in the title compound was obtained in accordance with the procedure described in Example 205B, using 3-chlorobenzylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 10,99 (s, 1H), 8,12 (s, 2H), 8,03 (d, J=7,72 Hz, 1H), 7,83 (d, J=8,46 Hz, 1H), 7,68 (s, 1H), 7,58 (t, J=8,09 Hz, 2H), 7,33-7,44 (m, 3H), 7,25-7,33 (m, 2H), of 5.68 (s, 2H), 1,72 is 1.86 (m, 1H), 0,99 by 1.12 (m, 2H), 0,34-of 0.45 (m, 2H). MS (ESI+) m/z 470 (M+H)+.

Example 225

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-furamide

Specified in the title compound was obtained in accordance with paragraph what ocedures, described in Example 205B, using furan-2-carbonylchloride instead of 3 tormentilla.1H NMR (300 MHz, DMSO-d6) δ ppm 10,36 (s, 1H), 7,71 (s, 1H), 7,42 (d, J=8,82, to 1.47 Hz, 1H), 7,15 (d, J=8,82 Hz, 1H), 7,06 (d, J=3,31 Hz, 1H), 6,93-7,03 (m, 3H), 6,86-6,93 (m, 2H), of 6.31 (d, J=3,49, 1.65 Hz, 1H), 5,28 (s, 1H), 1,31-of 1.45 (m, 1H), 0,59 is 0.71 (m, 2H), be-0.05 to 0.05 (m, 2H). MS (ESI+) m/z 425 (M+H)+.

Example 226

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-ethyl-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 207 using acetaldehyde instead of benzaldehyde.1H NMR (300 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8.30 to-8,42 (m, 1H), of 7.90-8,17 (m, 2H), 7,20 was 7.45 (m, 5H), 5,70 (s, 2H), 1,78-of 1.93 (m, 2H), 1,67 (s, 1H), 1.06 a (m, 3H), of 0.95 (m, 2H), of 0.29 to 0.48 (m, 2H). MS (ESI+) m/z 359 (M+H)+.

Example 227

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(4-Chlorobenzyl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 207 using 4-chlorobenzaldehyde instead of benzaldehyde.1H NMR (300 MHz, DMSO-d6) δ ppm of 10.01 (s, 1H), 9,25 (s, 1H), 8,25-of 8.33 (m, 1H), of 8.09 (d, J=8,46 Hz, 1H), 7,84-of 7.97 (m, 2H), EUR 7.57-7,73 (m, 2H), 7,26-7,51 (m, 6H), 5,70 (s, 2H), 1,71-of 1.84 (m, 1H), 0,97-of 1.15 (m, 2H), 0,36 of 0.47 (m, 2H). MS (ESI+) m/z 455 (M+H)+.

Example 228

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-N-(3-furylmethyl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 207, IP is the use of furan-3-carbaldehyde instead of benzaldehyde. 1H NMR (300 MHz, DMSO-d6) δ ppm 8,21 (s, 1H), of 7.90 (s, 1H), 7,71-of 7.82 (m, 1H), 7,55-to 7.68 (m, 2H), 7.24 to 7,51 (m, 6H), of 5.68 (s, 2H), 4,33 (s, 2H), 1,67-of 1.85 (m, 1H), 0,95-of 1.13 (m, 2H), 0,30 at 0.42 (m, 2H). MS (ESI+) m/z 411 (M+H)+.

Example 229

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-[5-methyl-2-(trifluoromethyl)-3-furyl]urea

Connection Example 205A (30 mg, 0.07 mmol) was dissolved in dioxane (2 ml) and to the solution was added 3-isocyanato-5-methyl-2-(trifluoromethyl)furan (40 mg, 0.21 mmol). The reaction mixture was stirred at 80°C for 12 hours, concentrated and purified using reverse-phase-HPLC (CH3CN/H2O/NH4OAc) to give the Boc-protected precursor. The precursor was dissolved in methanol and treated with excess amount of HCl in dioxane (4 M, 0.5 mmol). The reaction mixture was left to stir for 5 hours and concentrated under vacuum to obtain specified in the connection header in the form of the HCl salt.1H NMR (300 MHz, DMSO-d6) δ ppm of 12.73 (s, 1H), 10,19 (s, 1H), 8,40 (s, 1H), 7,83 (d, J=8,82, to 1.47 Hz, 1H), of 7.64 to 7.75 (m, 1H), 7,49 (d, J=8,82 Hz, 1H), 7,35-7,45 (m, 3H), 7,27-7,35 (m, 2H), 5,69 (s, 2H), 2,33 (s, 3H), 1,73-of 1.84 (m, 1H), 1,02-1,11 (m, 2H), 0,35-of 0.43 (m, 2H). MS (ESI+) m/z 522 (M+H)+.

Example 230

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-3-furamide

Specified in the title compound was obtained in the form of an HCl salt according to the procedure described in Example 205B, using furan-3-to the of bonyhard instead of 3 tormentilla. 1H NMR (300 MHz, DMSO-d6) δ ppm at 10.64 (s, 1H), 8,46 (s, 1H), 8,13 (s, 1H), 7,74-to 7.84 (m, 2H), 7,52-7,58 (m, 1H), 7,33-7,46 (m, 3H), 7.24 to 7,33 (m, 3H), 7,06 (s, 1H), of 5.68 (s, 2H), 1.70 to to 1.86 (m, 1H), 0,99 (PI)-1.09 (m, 2H), of 0.33 to 0.44 (m, 2H). MS (ESI+) m/z 425 (M+H)+.

Example 231

5-(1H-indazol-5-yl)-N-[(1S)-1-phenylpropyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (S)-(-)-1-phenylpropylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,20 (d, J=8,48 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,88 (d, J=8,81, 1.70 Hz, 1H), 7,69 (d, J=8,81 Hz, 1H), 7,38-7,49 (m, 2H), 7.18 in-7,38 (m, 4H), of 4.83-5,02 (m, 1H), 1,73-of 1.97 (m, 2H), 0,86-to 0.97 (m, 3H). MS (ESI+) m/z 347,0 (M+H)+.

Example 232

5-(1H-indazol-5-yl)-N-[(1R)-1-phenylpropyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (R)-(-)-1-phenylpropylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,37 (s, 1H), 9,20 (d, J=8,48 Hz, 1H), 8,39 (s, 1H), 8,23 (s, 1H), 7,88 (d, J=8,65, of 1.53 Hz, 1H), 7,69 (d, J=8,81 Hz, 1H), 7,39-of 7.48 (m, 2H), 7.18 in-7,38 (m, 4H), 4,85-4,99 (m, 1H), 1,74-of 1.97 (m, 2H), 0,91 (t, J=7.29 trend Hz, 3H). MS (ESI+) m/z 347,0 (M+H)+.

Example 233

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-amine

Example 233A

5-(1-Benzyl-1H-pyrazole-4-yl)-2-perbenzoate

5-Bromo-2-perbenzoate (484 mg, 2,42 mmol), 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (736 mg, at 2.59 mmol), dichlorobis(triphenylphosphine)palladium(II) (174 mg ,248 mmol) and potassium carbonate (1,36 g, 9,84 mmol) were combined in a tightly closed container with dioxane (10 ml) and water (1 ml) in an inert nitrogen atmosphere and the mixture was heated to 110°C over night. The mixture was diluted with methylene chloride and washed with water. The organic layer was absorbed on silica gel and was purified using chromatography on silica gel by elution gradient of 10-50% ethyl acetate in hexane, to obtain specified in the connection header. MS (ESI+) m/z 290,0 (M+H)+.

Example 233B

5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-amine

Connection Example 233A (591 mg, 2,13 mmol) was treated with hydrazinehydrate (4,0 ml) in ethanol (3.0 ml) and stirred and heated to 70°C during the night. The mixture was diluted with methylene chloride and washed with water. The organic layer was concentrated under reduced pressure and the obtained residue was ground into powder with methanol to obtain specified in the connection header.1H NMR (300 MHz, DMSO-d6) δ ppm made 11.32 (s, 1H), 8,10 (s, 1H), a 7.85 (s, 1H), 7,80 (s, 1H), 7,44 (d, J=8,48, 1.70 Hz, 1H), 7,25-7,41 (m, 5H), 7,21 (d, J=8,82 Hz, 1H), to 5.35 (s, 2H), 5,24-and 5.30 (m, 2H). MS (ESI+) m/z 290,0 (M+H)+.

Example 234

1-benzyl-4-(1H-indazol-5-yl)-N-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide

A 20-ml vessel was added a solution of compound of Example 149C (51 mg, 0.16 mmol)dissolved in dimethylformamide (0.5 ml), followed by addition of (S)-(+)-tetrahydrofurfurylamine (18.2 mg, 0.18 mmol)dissolved dimethylformamide (0.9 ml). Added HATU (68 mg, 0.18 mmol)dissolved in dimethylformamide (0.5 ml), followed by the addition of a solution of diisopropylethylamine (0,087 ml, 0.5 mmol)dissolved in dimethylformamide (0.5 ml). The mixture was shaken at 50°C during the night. The reaction mixture was filtered through Si-carbonate cartridge (6 ml 1 g), supplied by Silicycle Chemical Division, and the filtrate was transferred into a 20-ml vessels. The reaction mixture was monitored by LC/MS and concentrated to dryness. The residue was dissolved in a mixture of 1:1 DMSO/methanol and purified using reverse-phase HPLC (Agilent, gradient 5%-100% TFU/water over 8 minutes).1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1,35-and 1.54 (m, 1H), 1,64 is 1.96 (m, 3H), 3,17-3,26 (m, 1H), 3,32-to 3.38 (m, 1H), 3,50-of 3.77 (m, 2H), 3,81-4,00 (m, 1H), 5,58-5,74 (m, 2H), 7,21-7,41 (m, 5H), 7,54-7,66 (m, 1H), 7.68 per-to 7.84 (m, 1H), 8,01-8,19 (m, 2H). MS (ESI-) m/z 401 (M-H)-.

Example 235

1-benzyl-4-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, 2-aminomethylpropanol ester instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm and 0.98 (d, 6H), 3,31 is-3.45 (m, 4H), 3.45 points is 3.57 (m, 1H), 5,61-5,74 (m, 2H), 7,25-7,46 (m, 5H), EUR 7.57-the 7.65 (m, 1H), 7.68 per-7,80 (m, 1H), 8,04-8,13 (m, 2H). MS (ESI+) m/z 405 (M+H)+.

Example 236

1-benzyl-4-(1H-indazol-5-yl)-N-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide

Specified the title compound was obtained in accordance with the procedure described in Example 234, using (R)-(-)-tetrahydrofurfurylamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1,34 is 1.60 (m, 1H), 1,65-of 1.94 (m, 3H), 3,16-3,26 (m, 1H), 3.33 and-3,39 (m, 1H), 3,51-of 3.77 (m, 2H), 3,78-4,00 (m, 1H), ceiling of 5.60-5,73 (m, 2H), 7,26 was 7.45 (m, 5H), 7,56-to 7.68 (m, 1H), 7,71-7,79 (m, 1H), 8,01-8,15 (m, 2H). MS (ESI-) m/z 401 (M-H)-.

Example 237

1-benzyl-4-(1H-indazol-5-yl)-N-(tetrahydrofuran-3-ylmethyl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 3-aminomethyltransferase instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1,36-to 1.59 (m, 1H), 1,67-2,00 (m, 1H), 2,19 at 2.45 (m, 1H), 3,11-of 3.23 (m, 2H), 3.45 points-of 3.77 (m, 2H), 5,45-6,14 (m, 2H), 7,16-7,44 (m, 5H), 7,50-to 7.84 (m, 2H), of 7.96-of 8.25 (m, 2H). MS (ESI+) m/z 403 (M+H)+.

Example 238

1-benzyl-N-cyclopentyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using cyclopentylamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1,19-to 1.63 (m, 6H), 1,71 of 1.99 (m, 2H), 3,99-4,37 (m, 1H), 5,52 is 5.77 (m, 2H), 7,22 was 7.45 (m, 5H), 7,55-7,83 (m, 2H), 7.95 is-to 8.20 (m, 2H). MS (ESI-) m/z 385 (M-H)-.

Example 239

1-benzyl-N-(cyclopentylmethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with procedures is th, described in Example 234, using aminomethylation instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1,02 of 1.28 (m, 2H), 1,34-of 1.73 (m, 6H), 1,83-2,17 (m, 1H), 3,03-3,17 (m, 2H), 5,51-5,80 (m, 2H), 7,20-7,42 (m, 5H), 7,52-7,81 (m, 2H), 7,93-8,19 (m, 2H). MS (ESI+) m/z 401 (M+H)+.

Example 240

1-benzyl-N-ethyl-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using the hydrochloride of N-methylethylamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 0,33-0,56 (m, 1H), 0,90-to 1.14 (m, 2H), 2,15 was 2.25 (m, 2H), 2,58-2,69 (m, 1H), 2,82-a 3.01 (m, 1H), 3,35-to 3.52 (m, 1H), 5.40 to-5,67 (m, 2H), 7,14-of 7.48 (m, 5H), 7,56-7,79 (m, 2H), of 7.90-8,24 (m, 2H). MS (ESI+) m/z 361 (M+H)+.

Example 241

1-benzyl-4-(1H-indazol-5-yl)-N-isopropyl-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using methylisobutylketone instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 0,22-of 0.51 (m, 2H), 0,84-of 1.09 (m, 4H), 1,96 and 2.13 (m, 2H), 2,74-2,87 (m, 1H), of 4.44 to 4.92 (m, 1H), 5,43-5,67 (m, 2H), 7,20-7,44 (m, 5H), 7,51-7,73 (m, 2H), 7,84-to 8.14 (m, 2H). MS (ESI+) m/z 375 (M+H)+.

Example 242

1-benzyl-4-(1H-indazol-5-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained according to the procedure described is Oh in Example 234, using N-(2-methoxyethyl)methylamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 2,25-to 2.42 (m, 2H), 2,74-of 3.06 (m, 4H), 3,40 of 3.75 (m, 3H), 5,38-5,73 (m, 2H), 7.18 in was 7.45 (m, 5H), 7,53-7,74 (m, 2H), a 7.85-8,19 (m, 2H). MS (ESI+) m/z 391 (M+H)+.

Example 243

1-benzyl-4-(1H-indazol-5-yl)-N-phenyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using aniline instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 5,65-5,79 (m, 2H),? 7.04 baby mortality-at 7.55 (m, 10H), 7,54-to 7.84 (m, 2H), 7.95 is-8,21 (m, 2H). MS (ESI+) m/z 395 (M+H)+.

Example 244

1-benzyl-N-(4-chlorophenyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 4-Chloroaniline instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 5,70-5,74 (m, 2H), 7,25-7,42 (m, 7H), 7,43-7,52 (m, 2H), 7,54-7,66 (m, 1H), 7.68 per-to 7.77 (m, 1H), 8,03-of 8.15 (m, 2H). MS (ESI-) m/z 427 (M-H)-.

Example 245

1-benzyl-4-(1H-indazol-5-yl)-N-(2-morpholine-4-retil)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using N-(3-aminopropyl)the research instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 2,94-3,13 (m, 6H), 3.46 in-3,61 (m, 2H), 3,63-3,79 m, 4H), 5,61-5,88 (m, 2H), 7,19-7,46 (m, 5H), 7,56-7,88 (m, 2H), 7,88-8,30 (m, 2H). MS (ESI-) m/z 430 (M-H)-.

Example 246

1-benzyl-N-[2-(dimethylamino)ethyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 234, using N,N,N-trimethylethylenediamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 2,28-to 2.42 (m, 3H), 2,73-3,00 (m, 6H), 3,07-3,19 (m, 2H), 3,56-of 3.80 (m, 2H), 5,55-of 5.68 (m, 2H), 7.24 to 7,47 (m, 5H), 7,56 for 7.78 (m, 2H), to $ 7.91-8,02 (m, 1H), 8,10-8,17 (m, 1H). MS (ESI+) m/z 404 (M+H)+.

Example 247

1-benzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-N-propyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, 2-(propylamino)ethanol instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm is 0.22 to 0.39 (m, 1H), 0,80 was 1.06 (m, 3H), 1,50-1,75 (m, 1H), 2,65-2,78 (m, 1H), 2,80-to 2.94 (m, 1H), 2,97-to 3.09 (m, 1H), 3,37-to 3.50 (m, 1H), 3,51-3,63 (m, 1H), 3,61-to 3.73 (m, 1H), 5,39-5,74 (m, 2H), 7,20-7,44 (m, 5H), 7,50-a 7.85 (m, 2H), 7,86 is 8.25 (m, 2H). MS (ESI+) m/z 405 (M+H)+.

Example 248

1-benzyl-N-[3-(dimethylamino)propyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 234, using N,N,N-trimethyl-1,3-propandiamine instead of (S)-(+)-tetrahydrofurfuryl is on. 1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 8,06-8,23 (m, 1H), 7,85-with 8.05 (m, 1H), EUR 7.57-7,73 (m, 2H), 7,19-of 7.48 (m, 5H), 5,41-5,74 (m, 2H), 3,36 is-3.45 (m, 2H), 2,88-3,10 (m, 3H), 2,60-of 2.86 (m, 5H), 2,24-to 2.42 (m, 4H), 1,73 is 1.91 (m, 1H). MS (ESI+) m/z 418 (M+H)+.

Example 249

1-benzyl-N-[2-(diethylamino)ethyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 234, using N,N-diethyl-N-methylethylenediamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,82-8,24 (m, 2H), 7,56-7,76 (m, 2H), 7,15-7,49 (m, 5H), 5,54-5,71 (m, 2H), 3,60-of 3.77 (m, 2H), 3,20-3,24 (m, 2H), 3,13-3,18 (m, 2H), 3,03-3,11 (m, 2H), 2,32 is 2.44 (m, 3H), 0,63-of 1.41 (m, 6H). MS (ESI+) m/z 432 (M+H)+.

Example 250

N,1-dibenzyl-N-ethyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using N-ethylbenzylamine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,81-to 8.20 (m, 2H), 7,49-7,71 (m, 2H), 7.24 to 7,51 (m, 9H), 6,39-to 7.18 (m, 2H), 5,41-5,74 (m, 2H), 4.53-in-4,84 (m, 1H), 3,82-4,00 (m, 1H), 3,37-of 3.54 (m, 1H), 2,61-2,78 (m, 1H), 0,91-1,08 (m, 1H), 0,27-0,45 (m, 2H). MS (ESI+) m/z 437 (M+H)+.

Example 251

N,1-dibenzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using N-benzilate is alumina instead of (S)-(+)-tetrahydrofurfurylamine. MS (ESI+) m/z 453 (M+H)+.

Example 252

(3R)-1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-3-ol

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using the hydrochloride of (R)-(+)-3-hydroxypiperidine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,83 is 8.22 (m, 2H), 7,51 for 7.78 (m, 2H), 7.23 percent was 7.45 (m, 5H), 5,46-of 5.75 (m, 2H), 3,80-or 4.31 (m, 1H), 3,40-3,68 (m, 1H), 2,58 is 3.15 (m, 2H), 2,19-2,49 (m, 1H), 0,31-2,14 (m, 4H). MS (ESI+) m/z 403 (M+H)+.

Example 253

1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using isonipecotamide instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,86-8,24 (m, 2H), 7,53-of 7.70 (m, 2H), 7,22-7,46 (m, 5H), 5,42 is 5.77 (m, 2H), 4,19-4,48 (m, 1H), 2,65-3,10 (m, 2H), 2,27-2,47 (m, 1H), 2,05-of 2.24 (m, 1H), 1,65-1,89 (m, 1H), 1,29-of 1.55 (m, 1H), 0,98-of 1.27 (m, 1H), 0,52-0.87 (m, 1H). MS (ESI+) m/z 430 (M+H)+.

Example 254

5-{1-benzyl-5-[(2,6-dimethylmorpholine-4-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 2,6-dimethylmorpholine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,87-of 8.27 (m, 2H), 7,50-7,76 (m, 2H), 7,12 was 7.45 (m, 5H), 5,46-of 5.68 (m, 2H), 4,16-4,43 (m, 1H), 2,61-2,98 (who, 1H), 2,16-to 2.41 (m, 2H), 1.77 in and 2.13 (m, 1H), 0,86-of 1.39 (m, 3H), 0,38-of 0.83 (m, 3H). MS (ESI+) m/z 417 (M+H)+.

Example 255

5-{5-[(4-acetylpiperidine-1-yl)carbonyl]-1-benzyl-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 1-acetylpiperidine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,89-to 8.41 (m, 2H), 7,55-7,86 (m, 2H), 7,07-7,51 (m, 5H), 5,44-of 5.82 (m, 2H), 3.46 in-3,70 (m, 3H), 3,35-to 3.49 (m, 2H), 2.57 m-of 2.93 (m, 3H), 1,61-2,03 (m, 3H). MS (ESI+) m/z 430 (M+H)+.

Example 256

5-{1-benzyl-5-[(4-phenylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 1-phenylpiperazine instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (SOO MHZ, DMSO-d6/D2O) δ ppm 7,79 is 8.38 (m, 2H), 7,53-7,73 (m, 2H), 7,22-7,46 (m, 5H), 7,05-7,19 (m, 2H), 6,64-6,79 (m, 3H), 5,54-of 5.68 (m, 2H), 3,50-3,90 (m, 2H), 2.93 which is 3.15 (m, 2H), 2,62-2,89 (m, 2H), 2,19 is 2.43 (m, 2H). MS (ESI-) m/z 462 (M-H)-.

Example 257

1-benzyl-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using (R)-(+)-2-amino-3-methyl-1-butanol instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7.95 is-8,31 (m, 2H), 7,52-of 7.96 (m, 2H), 7.18 in-7,46 (m, 5H), 5,42 and 5.86 (m, 2H), 3,68-of 3.94(m, 1H), 3,38-3,59 (m, 2H), 1,49-of 2.08 (m, 1H), 0,50-1,20 (m, 6H). MS (ESI+) m/z 405 (M+H)+.

Example 258

1-benzyl-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using (S)-(-)-2-amino-3-methyl-1-butanol instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 7,94-at 8.36 (m, 2H), 7,52-to 7.84 (m, 2H), 7.18 in-7,51 (m, 5H), 5,57-USD 5.76 (m, 2H), 3.75 to of 3.94 (m, 1H), 3,35-of 3.54 (m, 2H), 1.70 to was 1.94 (m, 1H), 0,54 (PI)-1.09 (m, 6H). MS (ESI+) m/z 405 (M+H)+.

Example 259

1-benzyl-N-[3-(1H-indazol-1-yl)propyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 234, using 1-(3-aminopropyl)indazole instead of (S)-(+)-tetrahydrofurfurylamine.1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 8,57 cent to 8.85 (m, 1H), 7,92-8,16 (m, 2H), 7,60-7,80 (m, 2H), 7,47-of 7.55 (m, 2H), 7,19-7,40 (m, 5H), 5,54-of 5.75 (m, 2H), 3,83-is 4.21 (m, 2H), 3,19-3,26 (m, 2H), 1,79-to 2.06 (m, 2H). MS (ESI+) m/z 427 (M+H)+.

Example 260

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-atilmotin

Specified in the title compound was obtained in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using isocyanatomethyl instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,38 (s, 1H), for 9.47 (s, 1H) scored 8.38 (s, 1H), a 7.85-of 7.97 (m, 1H), 7,78 (d, J=8,82, to 1.47 Hz, 1H), 7,34-to 7.50 (m, 4H), 7.24 to 7,33 (m, 2H), 5,69 (s, 2H), 3,17-3,29 (m, 2H), 1.70 to to 1.83 (m, 1H), 1,12 (t, J=7,17 Hz, 3H), 1.00 and-a 1.08 (m, 2H), and 0.37 (d, J=3,68 Hz, 2H,). MS (ESI+) m/z 402 (M+H)+.

Example 261

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-prilocaine

Specified in the title compound was obtained in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using isocyanatobenzene instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,47-12,78 (m, 1H), for 9.64 (s, 1H), 8,39 (s, 1H), 7,70-to 7.95 (m, 1H), 7,45-of 7.60 (m, 3H), 7,27 was 7.45 (m, 7H), 7,02 (m, 1H), 5,69 (s, 2H), 1,79 (m, 1H), 1,07 (m, 2H), and 0.40 (m, 2H). MS (ESI+) m/z 450 (M+H)+.

Example 262

N-benzyl-N'-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]urea

Specified in the title compound was obtained in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using (isocyanatomethyl)benzene instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,42 (s, 1H), being 9.61 (s, 1H), of 8.37 (s, 1H), 8,23-of 8.33 (m, 1H), 7,79 (d, J=8,82, to 1.47 Hz, 1H), was 7.36-to 7.50 (m, 4H), 7,28 and 7.36 (m, 6H), 7,21-7,27 (m, 1H), 5,69 (s, 2H), 4,45 (d, J=5,88 Hz, 2H), 1,65-to 1.79 (t, J=8,27, of 8.27 Hz, 1H), 0,99-1,08 (m, 2H), 0,30-0,43 (m, 2H). MS (ESI+) m/z 464 (M+H)+.

Example 263

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(2-chlorophenyl)urea

Specified in the title compound was obtained is in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using 1-chloro-2-isocyanatobenzene instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,74 (s, 1H), 10,23 (s, 1H), 8,44 (s, 1H), 8.34 per (d, J=8,09 Hz, 1H), 7,83 (d, J=8,82, to 1.47 Hz, 1H), 7,46-of 7.55 (m, 2H), 7,35-7,45 (m, 3H), 7,28-7,35 (m, 3H), 7.03 is for 7.12 (m, 1H), 5,70 (s, 2H), 1.70 to to 1.86 (m, 1H), and 1.00-1,12 (m, 2H), 0,33-of 0.45 (m, 2H). MS (ESI+) m/z 484 (M+H)+.

Example 264

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(3-chlorophenyl)urea

Specified in the title compound was obtained in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using 1-chloro-3-isocyanatobenzene instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,66 (s, 1H), 10,02 (s, 1H), 9,71 (s, 1H), they were 8.22-8,48 (m, 1H), 7,71-to $ 7.91 (m, 2H), 7,51 (d, J=8,46 Hz, 1H), 7,37-7,46 (m, 2H), 7,26-7,37 (m, 5H), 7,02-7,11 (m, 1H), 5,69 (s, 2H), 1,73-1,89 (m, 1H), 0,99-1,11 (m, 2H), 0,33-of 0.48 (m, 2H). MS (ESI+) m/z 484 (M+H)+.

Example 265

N-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-(4-chlorophenyl)urea

Specified in the title compound was obtained in the form of a salt of hydrochloric acid in accordance with the procedure described in Example 229 using 1-chloro-4-isocyanatobenzene instead of 3-isocyanato-5-methyl-2-(trifluoromethyl)furan.1H NMR (300 MHz, DMSO-d6) δ ppm 12,65 (s, 1H), 9,96 (s, 1H), 9,68 (s, 1H), of 8.37 (s, 1H), 7,81 (d, J=8,82, to 1.47 Hz, 1H), 7,53-of 7.60 (m, 2H), 7,50 (d, J=8,82 Hz, 1H), 7,39-7,44 (m, 1H), 7,33-,40 (m, 4H), 7,27-to 7.32 (m, 2H), 5,69 (s, 2H), 1,71-to 1.87 (m, 1H), 1.00 and by 1.12 (m, 2H), 0,34 to 0.44 (m, 2H). MS (ESI+) m/z 484 (M+H)+.

Example 266

N-[5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide

Example 266A

tert-butyl 3-amino-5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

Specified in the title compound was obtained in accordance with the procedure described in Example 198A, using the compound of Example 125B instead of the compound of Example 102B. The product was used directly in subsequent reactions without defining its characteristics.

Example 266B

N-[5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]benzamide

Specified in the title compound was obtained in the form of a salt TFU in accordance with the procedure described in Example 205B, using the compound of Example 266A instead of the compound of Example 205A.1H NMR (300 MHz, DMSO-d6) δ ppm 12,97 (s, 1H), 10,89 (s, 1H), 8,28 (s, 1H), 8,05-to 8.14 (m, 2H), 7,88 (d, J=8,82, to 1.47 Hz, 1H), 7,58-to 7.67 (m, 2H), 7,54 (t, J=7,35 Hz, 2H), 7.29 trend was 7.45 (m, 3H), of 7.23 (d, J=6,99 Hz, 2H), 5,73 (s, 2H). MS (ESI+) m/z 521 (M+H)+.

Example 267

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanenitrile

Example 267A

3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)propanenitrile

To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5,00 g for 25.8 mmol) in acetonitrile (50 ml) was added Acrylonitrile (3.4 ml, 52 mmol) followed by the addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (1,94 ml, 12,mmol). After about 2 hours the reaction mixture was concentrated under reduced pressure. The crude substance was then dissolved in minimum amount of dichloromethane and purified via chromatography on silica gel by elution gradient of 10-50% ethyl acetate in heptane, to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 8,03 (s, 1H), to 7.64 (s, 1H), and 4.40 (t, J=6.4 Hz, 2H), 3,06 (t, J=6.4 Hz, 2H), 1.26 in (s, 12H). MS (ESI+) m/z 247,3 (M+H)+.

Example 267B

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanenitrile

In a microwave vessel was added 5-bromo-1H-indazol-3-amine (0.14 g, 0.66 mmol), tetrakis(triphenylphosphine)palladium(0) (0,076 g of 0.066 mmol) and sodium carbonate (0,147 g of 1.39 mmol) followed by the addition of a solution of the compound of Example 267A (0,212 g, 0,858 mmol) in 1,2-dimethoxyethane (2,50 ml) and then water (1.25 ml). The mixture was heated in a CEM microwave system at 150°C for about 20 minutes (maximum pressure 275 psi (19 kg/cm2), while increasing the temperature to a specified level of about 2 minutes, maximum power 200 watts) and then the mixture was concentrated under reduced pressure. Was added methanol (20 ml) and the resulting mixture was stirred for about 1 hour. The insoluble substance was removed by filtration. The filtrate was concentrated under reduced pressure over silica gel and was purified using chromatography on silica gel, using the UYa for the elution step gradient of dichloromethane/methanol/ammonium hydroxide(990:9:1→985:13,5:1,5→980:18:2), obtaining a solid substance. This solid was dissolved in minimum amount of hot acetonitrile (~2 ml), filtered to remove minor amounts of insoluble substances, while washing with methanol (<0.5 ml)and left to precipitate at ambient temperature. The obtained solid substance, which was formed during the night, collected by filtration, washing with additional amount of acetonitrile, and dried in a vacuum oven at about 60°C for about 2 hours with obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 11,35 (s, 1H), 8,10 (s, 1H), 7,86 (s, 1H), to 7.84 (s, 1H), 7,44 (DD, J=8,54, of 1.26 Hz, 1H), 7.23 percent (d, J=8,62 Hz, 1H), 5,32 (s, 2H), 4,42 (t, J=6,36 Hz, 2H), 3,10 (t, J=to 6.43 Hz, 2H). MS (ESI+) m/z 253,2 (M+H)+.

Example 268

2-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]ndimethylacetamide

Example 268A

2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)ndimethylacetamide

A suspension of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.00 g, or 10.3 mmol), 2-bromoacetamide (2.14 g, a 15.5 mmol) and potassium carbonate (2.14 g, a 15.5 mmol) in acetone (60 ml) was heated at about 50°C for about 3.5 days. The reaction mixture then was cooled to ambient temperature, filtered through diatomaceous earth, rinsing with additional amount of acetone, and then concentrated under reduced pressure. The crude substance is then R who was storyli in a minimum amount of dichloromethane and purified via chromatography on silica gel, using elution gradient of 80-100% ethyl acetate in heptane, to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 7,88 (s, 1H), EUR 7.57 (s, 1H), 7,46 (s, 1H), 7,24 (s, 1H), of 4.77 (s, 2H), 1.26 in (s, 12H). MS (ESI+) m/z 252,2 (M+H)+.

Example 268B

2-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]ndimethylacetamide

Specified in the title compound was obtained in accordance with the procedure described in Example 267B, using the compound of Example 268A instead of the compound of Example 267A and heating at about 120°C for about 10 minutes.1H NMR (400 MHz, DMSO-d6) δ ppm made 11.32 (s, 1H), 7,98 (s, 1H), 7,87 (s, 1H), to 7.77 (s, 1H), of 7.48 (s, 1H), 7,45 (d, J=8.6 Hz, 1H), 7,26 (s, 1H), 7,22 (d, J=8.7 Hz, 1H), 5,28 (s, 2H), 4,78 (s, 2H). MS (ESI+) m/z 257,2 (M+H)+.

Example 269

methyl 3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl}propanoate

Example 269A

methyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)propanoate

Specified in the title compound was obtained in accordance with the procedure described in Example 267A, using methyl acrylate instead of Acrylonitrile.1H NMR (400 MHz, DMSO-d6) δ ppm to $ 7.91 (s, 1H), EUR 7.57 (s, 1H), 4,35 (t, J=6.73 x Hz, 2H), 2,87 (t, J=6.75 Hz, 2H)and 3.59 (s, 3H), 1,24 (s, 12H). MS (ESI+) m/z 281,2 (M+H)+.

Example 269B

methyl 3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanoate

Specified in the title compound was obtained in accordance with the procedure described in Example 267B, with the use the of the compounds of Example 269A instead of the compound of Example 267A and heating at about 120°C for about 20 minutes. 1H NMR (400 MHz, DMSO-d6) δ ppm made 11.32 (s, 1H), 8,00 (s, 1H), a 7.85 (s, 1H), 7,76 (s, 1H), 7,42 (d, J=8,50 Hz, 1H), 7,21 (d, J=8,61 Hz, 1H), 5,28 (s, 2H), 4,37 (t, J=of 6.71 Hz, 2H), 3,61 (s, 3H), of 2.92 (t, J=6.69 in Hz, 2H). MS (ESI+) m/z of 286.2 (M+H)+.

Example 270

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanamide

Example 270A

3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)propanamide

Specified in the title compound was obtained in accordance with the procedure described in Example 267A, using acrylamide instead of Acrylonitrile (0,72 g, 53%).1H NMR (400 MHz, DMSO-d6) δ ppm to 7.84 (s, 1H), 7,56 (s, 1H), 7,37 (s, 1H), to 6.88 (s, 1H), 4,30 (t, J=6,80 Hz, 2H), 2,60 (t, J=6,79 Hz, 2H), 1,24 (s, 12H). MS (ESI+) m/z 266,2 (M+H)+.

Example 270B

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanamide

Specified in the title compound was obtained in accordance with the procedure described in Example 267B, using the compound of Example 270A instead of the compound of Example 267A and heating at about 120°C for about 15 minutes (0,056 g, 22%).1H NMR (400 MHz, DMSO-d6) δ ppm made 11.32 (s, 1H), 7,94 (d, J=0,53 Hz, 1H), to 7.84 (s, 1H), of 7.75 (d, J=0.54 Hz, 1H), 7,42 (m, 2H), 7,20 (d, J=compared to 8.26 Hz, 1H), 6.89 in (s, 1H), 5,27 (s, 2H), 4,32 (t, J=6,89 Hz, 2H), 2,65 (t, J=6,89 Hz, 2H). MS (ESI+) m/z 271,0 (M+H)+.

Example 271

[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl}acetonitrile

Example 271A

2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)acetonitrile

Specified in the title compound was obtained the accordance with the procedure described in Example 268A, using a 2-bromoacetonitrile instead of 2-bromoacetamide.1H NMR (400 MHz, DMSO-d6) δ ppm to 7.99 (s, 1H), 7,66 (s, 1H), the 5.45 (s, 2H), 1,25 (s, 12H).

Example 271B

tert-butyl 3-(bis(tert-butoxycarbonyl)amino)-5-bromo-1H-indazol-1-carboxylate

To 5-bromo-1H-indazol-3-amine (2.00 g, 9.43 mmol) in tetrahydrofuran (20 ml) was added 4-(dimethylamino)pyridine (0,230 g, 1,886 mmol) and di-tert-BUTYLCARBAMATE (6,18 g, 28.3 mmol). The reaction mixture was heated at 50°C for about 2 hours, cooled to ambient temperature and concentrated under reduced pressure. The residue was dissolved in diethyl ether (100 ml) and then washed sequentially 1 n solution of hydrochloric acid (2×25 ml), 1 n solution of sodium hydroxide (2×25 ml) and saturated brine (25 ml). The organic layer was then dried over sodium sulfate, filtered, concentrated under reduced pressure and dried in a vacuum oven at about 60°C to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) with 8.05 (d, J=8,95 Hz, 1H), to 7.99 (d, J=1.90 Hz, 1H), 7,81 (DD, J=8,94, 1.89 Hz, 1H), 1,65 (s, 9H), of 1.40 (s, 18H). MS (ESI+) m/z 512,2 (M+H)+.

Example 271C

tert-butyl 3-(bis(tert-butoxycarbonyl)amino)-5-(1-(cyanomethyl)-1H-pyrazole-4-yl)-1H-indazol-1-carboxylate

The vessel was loaded connection Example 271A (0,682 g of 2.93 mmol), the compound of Example 271B (1,25 g of 2.44 mmol), cesium carbonate (1.9 g, 6,10 mmol), 1,4-dioxane (12.5 ml) and water (2,50 ml). After cycle vacuum/nitrogen purging through the membranous septum, was added Tris(dibenzylideneacetone)dipalladium(0) (0,112 g, 0,122 mmol) and tetrafluoroborate three-tert-butylphosphine (of 0.085 g, 0.29 mmol) and the vessel was closed with a lid after purging with nitrogen. After about 6 hours at ambient temperature the reaction mixture was distributed between saturated aqueous sodium bicarbonate and dichloromethane (each 50 ml). The layers were separated and the aqueous layer was extracted with additional dichloromethane (2×50 ml). The combined organic layers were washed with saturated salt solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude oil was dissolved in minimum amount of dichloromethane and purified via chromatography on silica gel by elution gradient of 20-60% ethyl acetate in heptane, to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 8,43 (s, 1H), 8,19 (s, 1H), 8,08 (d, J=which 9.22 Hz, 1H), to 7.93 (m, 2H), of 5.53 (s, 2H), 1,67 (s, 9H), of 1.39 (s, 18H). MS (ESI+) m/z to 539.3 (M+H)+.

Example 271D

[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl}acetonitrile

To a solution of tert-butyl 3-(bis(tert-butoxycarbonyl)amino)-5-(1-(cyanomethyl)-1H-pyrazole-4-yl)-1H-indazol-1-carboxylate (0,30 g, 0,557 mmol) in dichloromethane (4.0 ml) was added triperoxonane Ki the lot (2.0 ml). After about 45 minutes the reaction mixture is slowly extinguished saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane (3×25 ml). The combined organic layers were washed with saturated salt solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure to get crude solid. A white precipitate, which was suspended in the original aqueous layer and in the layer of saturated salt solution, was filtered and was added to the crude solid substance. The obtained solid was ground into powder with dichloromethane/methanol (19:1). The remaining solid was collected by filtration under vacuum and dried in a vacuum oven at about 70°C to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 11,37 (s, 1H), 8,12 (s, 1H), 7,92 (s, 1H), 7,89 (s, 1H), 7,49-7,41 (m, 1H), 7,24 (d, J=8,71 Hz, 1H), 5,52 (s, 2H), 5,31 (s, 2H). MS (ESI+) m/z 239,1 (M+H)+.

Example 272

4-(3-amino-1H-indazol-5-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

3-Cyano-4-ftorhinolonovy acid (0.083 g, 0,503 mmol), 4-iodine-N,N-dimethyl-1H-imidazole-1-sulfonamide (0.167 g, 0,554 mmol), sodium carbonate (0,128 g, 1,208 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.035 g, being 0.030 mmol) were combined in dimethoxyethane (4 ml) and water (1.5 ml). The reaction mixture was heated in a microwave system (CEM-Discover) at about 150°C in ECENA about 25 minutes. The organic layer was separated and the solvent was removed under reduced pressure. To the residue was added ethanol (0.7 ml) and hydrazinoacetate (1 ml). The reaction mixture was heated at about 80°C for about 20 hours. The reaction mixture was distributed between water (5 ml) and dichloromethane (100 ml). The organic layer was separated and concentrated under reduced pressure. The residue was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 11,42 (s, 1H), of 8.25 (s, 1H), 8,21 (d, J=1,36 Hz, 1H), 7,92 (d, J=1,37 Hz, 1H), 7,74 (DD, J=8,66, 1,58 Hz, 1H), 7.23 percent (d, J=8,68 Hz, 1H), to 5.35 (s, 2H), 2,87 (s, 6H). MS (ESI+) m/z 307,2 (M+H)+.

Example 273

5-pyrazin-2-yl-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 2-iodopyrazine instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm of 11.61 (s, 1H), 9,18 (d, 1H, J=1,6), 8,66 (DD, 1H, J=1,7, 2,4), 8,59 (d, 1H, J=1,0), 8,51 (d, 1H, J=2,5), of 8.04 (DD, 1H, J=1,8, 8,8), 7,35 (d, 1H, J=9,2), 5,54 (s, 2H). MS (ESI+) m/z 212,2 (M+H)+.

Example 274

5-Tien-2-yl-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 2-idioten instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H I Is R (400 MHz, DMSO-d6) δ ppm 11,47 (s, 1H), to 7.99 (d, 1H, J=1,4), 7,55 (DD, 1H, J=1,8, 8,8), the 7.43 (DD, 1H, J=1,0, 5,1), 7,35 (DD, 1H, J=1,1, 3,6), 7,26 (d, 1H, J=8,6), 7,10 (DD, 1H, J=3,5, 5,1), 5,42 (d, 2H, J=8,8). MS (ESI+) m/z 216,1 (M+H)+.

Example 275

5-(2-aminopyrimidine-4-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 5-iodopyrimidine-2-amine instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm 11,40 (s, 1H), 8,53 (s, 2H), to $ 7.91 (DD, 1H, J=0,7, 1,5), 7,47 (DD, 1H, J=1,8, 8,6), 7,28 (DD, 1H, J=0,7, 8,7), only 6.64 (s, 2H), are 5.36 (s, 2H),1H NMR (400 MHz, DMSO-d6) δ ppm 11,41 (s, 1H), 8,53 (s, 2H), 7,92 (m, 1H), 7,47 (DD, J=8,66, 1,74 Hz, 1H), 7,28 (DD, J=8,63, of 0.65 Hz, 1H), only 6.64 (s, 2H), are 5.36 (s, 2H). MS (ESI+) m/z 227,2 (M+H)+.

Example 276

5-(2-methoxypyridine-3-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 3-iodine-2-methoxypyridine instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm 11,43 (s, 1H), 8,14 (DD, 1H, J=1,9, 5,0), 7,86 (s, 1H), 7,71 (DD, 1H, J=2.0 a, 7,2), 7,42 (DD, 1H, J=1,7, 8,7), 7,26 (d, 1H, J=8,6), to 7.09 (DD, 1H, J=5,0, 7,3), 5,38 (s, 2H), with 3.89 (s, 3H). MS (ESI+) m/z 241,2 (M+H)+.

Example 277

5-imidazo[1,2-a]pyridine-3-yl-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 3-bromoimidazo[1,2-a]pyridine instead of 4-iodine-N,N-dimethyl-1H-imidazole 1-Sul is vanamide. 1H NMR (400 MHz, DMSO-d6) δ ppm charged 8.52 (dt, 1H, J=1,2, 7,0), to 7.99 (DD, 1H, J=0,7, 1,7), 7,68 (s, 1H), 7,65 (dt, 2H, J=1,2, 9,0), 7,46 (DD, 1H, J=1,8, 8,6), 7,39 (DD, 1H, J=0,8, 8,6), 7,28 (DDD, 1H, J=1,2, 6,6, 9,2), 6,96 (TD, 1H, J=1,3, 6,7), vs. 5.47 (s, 2H). MS (ESI+) m/z 250,2 (M+H)+.

Example 278

N2N2-dimethyl-N1-[5-(1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]glycinamide

The compound of Example 65 (257 mg, 0,685 mmol) was dissolved in ethanol (15 ml). The reaction mixture was first made in the apparatus of the H-Cube using palladium hydroxide (20%on carbon at a temperature of about 80°C and a pressure of about 60 psi (4,29 kg/cm2within about 8 hours. The solvent was removed under reduced pressure and the residue was purified using reverse-phase HPLC using a gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 8,16-of 8.37 (m, 1H), 7,10-7,46 (users, 2H), 7,00-7,34 (users, 2H), 6.87 in-7,24 (users, 2H), 3.33 and-to 3.34 (m, 2H). MS (ESI+) m/z of 286.2 (M+H)+.

Example 279

5-(1H-pyrazole-5-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 5-iodine-1H-pyrazole instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm 7,87-7,94 (m, 3H), 7,60-7,63 (m, 1H), of 7.48 (DD, J=8,55, of 1.62 Hz, 1H), 7,19-to 7.32 (m, 2H), 5.25-inch is 5.28 (m, 2H). MS (ESI+) m/z 200,1 (M+H)+.

Example 280

5-(4-methyl-1H-imidazol-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 5-iodine-4-methyl-1H-imidazole instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm a 7.85 (s, 1H), 7,52 (d, 2H, J=6,6), 7,22 (m, 1H), 5,3 2 (users, 2H), is 2.37 (s, 3H). MS (ESI+) m/z 214,1 (M+H)+.

Example 281

5-(1H-imidazol-4-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 4-iodine-1H-imidazole instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm 8,07 (s, 1H), 7,66 (s, 1H), 7,63 (d, 1H, J=8,6), 7,37 (s, 1H), 7,20 (d, 1H, J=8,8), 5,28 (s, 2H). MS (ESI+) m/z 200,1 (M+H)+.

Example 282

N2N2-dimethyl-N1-{5-[1-(3-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide

Example 282A

5-bromo-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 62D, using 5-bromo-2-perbenzoate instead of the compound of Example 62C.1H NMR (400 MHz, DMSO-d6) δ ppm for 11.55 (s, 1H), 7,92 (d, J=1,87 Hz, 1H), 7,30 (DD, J=8,79, 1.89 Hz, 1H), 7,19 (d, J=8,78 Hz, 1H), 5,41 (s, 2H).

Example 282B

tert-butyl 3-amino-5-bromo-1H-indazol-1-carboxylate

Specified in the title compound was obtained in accordance with the procedure described in Example 64A, using the compound of Example 282A instead of connecting the Application is and 62D. 1H NMR (400 MHz, DMSO-d6) δ ppm to 8.12 (d, J=1,93 Hz, 1H), 7.95 is-7,81 (m, 1H), 7,65 (DD, J=cent to 8.85, a 1.96 Hz, 1H), to 6.39 (d, J=of 4.44 Hz, 1H), 1,58 (m, 9H).

Example 282C

tert-butyl 5-bromo-3-(2-(dimethylamino)acetamido)-1H-indazol-1-carboxylate

To a mixture of compound of Example 282B (24,43 g, 78 mmol), potassium carbonate (81 g, 587 mmol) and hydrochloride of 2-(dimethylamino)acetylchloride (43,3 g, 274 mmol) was added tetrahydrofuran (200 ml). The reaction mixture was stirred at room temperature for about 2 hours. The reaction mixture was filtered and the filtrate washed with water (50 ml). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified using chromatography on silica gel, elwira methanol in dichloromethane (5%), obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm of 10.72 (s, 1H), 8,19 (d, 1H, J=1,6), 8,03 (d, 1H, J=9,0), 7,76 (DD, 1H, J=2.0 a, 9,0), up 3.22 (s, 2H), 2,32 (s, 6H), and 1.63 (s, 9H).

Example 282D

tert-butyl 3-(2-(dimethylamino)acetamido)-5-((trimethylsilyl)ethinyl)-1H-indazol-1-carboxylate

To a mixture of compound of Example 282C (2,56 g, 6,44 mmol), chloride bis(triphenylphosphine)palladium(II) (0,225 g, 0,321 mmol) and copper iodide(I) (0,073 g, 0,383 mmol) was added triethylamine (20 ml, 144 mmol) followed by the addition of amenitieseven (0,760 g, 7,73 mmol. The reaction mixture was heated at 60°C for about 3 hours. The reaction mixture was diluted with dichloromethane (100 ml), washed with water (20 ml) and saturated saline (20 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified using chromatography on silica gel by elution ethyl acetate in dichloromethane (10%), obtaining specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 10,69 (s, 1H), 8,08 (s, 1H), 8,04 (d, 1H, J=9,0), a 7.62 (d, 1H, J=8,8), 3,21 (s, 2H), 2,30 (s, 6H), to 1.61 (s, 9H), of 0.23 (s, 9H).

Example 282E

2-(dimethylamino)-N-(5-ethinyl-1H-indazol-3-yl)ndimethylacetamide

To the compound of Example 282D (0,303 g, 0,731 mmol) in methanol (5 ml) was added an aqueous solution of potassium hydroxide (1,46 ml of 1.46 mmol, 1.0 n solution). The reaction mixture was stirred at room temperature for about 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (80 ml). The organic layer was separated and washed with water (10 ml) and saturated saline (10 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 12,89 (s, 1H), 10,14 (s, 1H), 8,00 (d, 1H, J=12,1), 7,44 (s, 2H), 7,38 (d, 1H, J=8,6), was 4.02 (s, 1H), 3,17 (s, 2H), 2,33 (s, 6H).

Example 282F

N2N2-dimethyl-N1-{5-[1-(3-methylbenzo is)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide

To a suspension of compound of Example 282E (0.16 g, 0,660 mmol) in tert-butanol (1.2 ml) was added 1-(azidomethyl)-3-methylbenzo (0,098 g, 0,667 mmol), then water (1.2 ml). Solution was added (R)-2-((S)-1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydrofuran-3-olate sodium (0,057 ml of 0.066 mmol, 1,6 M in water) and an aqueous solution of copper sulfate (II) pentahydrate is 0.019 ml, 6.6 mmol, 0,34M). The reaction mixture was heated at 60°C for about 2 hours. The solvent was removed under reduced pressure and the residue was purified using reverse-phase HPLC using a gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 12,77 (s, 1H), of 10.05 (s, 1H), 8,56 (s, 1H), 8,24 (s, 1H), 7,82 (d, 1H, J=8,6), to 7.50 (d, 1H, J=8,8), 7,28 (t, 1H, J=7,6), 7,16 (m, 4H), 5,59 (s, 2H), 3,18 (s, 2H), 2,34 (s, 6H), is 2.30 (s, 3H). MS (ESI+) m/z 390,3 (M+H)+.

Example 283

5-(1-benzyl-1H-imidazol-4-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 272 using 1-benzyl-4-iodine-1H-imidazole instead of 4-iodine-N,N-dimethyl-1H-imidazol-1-sulfonamida.1H NMR (400 MHz, DMSO-d6) δ ppm of 11.29 (s, 1H), 8,07 (s, 1H), 7,79 (s, 1H), to 7.61 (d, 1H, J=8,6), 7,46 (s, 1H), was 7.36 (m, 5H), 7,17 (d, 1H, J=8,8), 5,28 (s, 2H), with 5.22 (s, 2H). MS (ESI+) m/z 290,2 (M+H)+.

Example 284

N1-{5-[1-(4-tert-butylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}-N2N2-dimetallic named

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 1-(azidomethyl)-4-tert-butylbenzoyl instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 12,88 (s, 1H), of 10.05 (s, 1H), to 8.57 (s, 1H), 8,23 (s, 1H), 7,81 (d, 1H, J=8,8), to 7.50 (d, 1H, J=8,8), 7,41 (d, 2H, J=8,2), 7,30 (d, 2H, J=8,2), 3,18 (s, 2H), 2,34 (s, 6H), 1.26 in (s, 9H). MS (ESI+) m/z 432,2 (M+H)+.

Example 285

N2N2-dimethyl-N1-{5-[1-(2-piperidine-1-retil)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 1-(2-azidoethyl)piperidine instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 12,91 (s, 1H), 10,07 (s, 1H), of 8.47 (s, 1H), they were 8.22 (s, 1H), 7,80 (DD, 1H, J=1,2, 8,7), 7,52 (d, 1H, J=8,8), of 4.49 (t, 2H, J=6,4), 3,19 (s, 2H), was 2.76 (t, 2H, J=6,4), is 2.41 (s, 4H), to 2.35 (s, 6H), 1.69 in (s, 3H), of 1.47 (m, 4H), to 1.37 (DD, 2H, J=5,2, 10,2). MS (ESI-) m/z 395,3 (M-H)-.

Example 286

N2N2-dimethyl-N1-{5-[1-(2-morpholine-4-retil)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-yl}glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 4-(2-azidoethyl)the research instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 12,83 (s, 1H), 10,07 (s, 1H), 8,49 (s, 1H), 8,23 (s, 1H), 7,81 (DD, 1H, J=1,3, 8,7), 7,52 (d, 1H, J=8,8), a 4.53 (t, 2H, J=6,3), 3,55 (m, 4H), 3,19 (s, 2H), 2,80 (t, 2H, J=6,3), a 2.45 (m, 4H), 2,35 (s, 6H). MS (ESI - m/z 397,3 (M-H) -.

Example 287

N1-(5-{1-[2-(3,5-dimethylisoxazol-4-yl)ethyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-yl)-N2N2-dimethylglycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 4-(2-azidoethyl)for 3,5-dimethylisoxazole instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 12,90 (s, 1H), 10,07 (s, 1H), 8,44 (s, 1H), 8,21 (s, 1H), 7,78 (DD, 1H, J=1,3, 8,7), 7,52 (d, 1H, J=8,8), 4,51 (t, 2H, J=6,7), 3,19 (s, 2H), with 2.93 (t, 2H, J=6,7), to 2.35 (s, 6H), 2,08 (d, 6H, J=4,3). MS (ESI-) m/z 407,2 (M-H)-.

Example 288

N1-(5-{1-[2-(3,5-dimethyl-1H-pyrazole-4-yl)ethyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-yl)-N2N2-dimethylglycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 4-(2-azidoethyl)for 3,5-dimethyl-1H-pyrazole instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm is 12.85 (s, 1H), 10,06 (s, 1H), of 8.37 (s, 1H), 8,21 (s, 1H), 7,78 (d, 1H, J=8,8), 7,51 (d, 1H, J=8,8), was 4.42 (t, 2H, J=6,9), 3,19 (s, 2H), 2,89 (t, 2H, J=7,0), to 2.35 (s, 6H), of 1.97 (s, 6H). MS (ESI-) m/z 406,2 (M-H)-.

Example 289

2-(4-{3-[(N,N-dimethylphenyl)amino]-1H-indazol-5-yl}-1H-1,2,3-triazole-1-yl)-2-methylpropanoate acid

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using 2-azido-2-methylpropanoic acid instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) the ppm 12,77 (s, 1H), there is a 10.03 (s, 1H), of 8.47 (s, 1H), they were 8.22 (s, 1H), a 7.85 (DD, 1H, J=0,9, 8,7), 7,49 (d, 1H, J=8,6), 3,21 (s, 2H), a 2.36 (s, 6H), 1.77 in (s, 6H). MS (ESI-) m/z 370,2 (M-H)-.

Example 290

ethyl (4-{3-[(N,N-dimethylphenyl)amino]-1H-indazol-5-yl}-1H-1,2,3-triazole-1-yl)acetate

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using ethyl 2-azidoaniline instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 12,87 (s, 1H), 10,08 (s, 1H), 8,51 (s, 1H), compared to 8.26 (s, 1H), 7,82 (DD, 1H, J=1,4, 8,7), 7,53 (d, 1H, J=8,8), 5,44 (s, 2H), 4,21 (square, 2H, J=7,0), 3,19 (s, 2H), 2,35 (s, 6H), of 1.24 (t, 3H, J=7,1). MS (ESI+) m/z 372,2 (M+H)+.

Example 291

N2N2-dimethyl-N1-(5-{1-[(trimethylsilyl)methyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-yl)glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 282F, using (azidomethyl)trimethylsilane instead of 1-(azidomethyl)-3-methylbenzene.1H NMR (400 MHz, DMSO-d6) δ ppm 13,04 (s, 1H), and 10.20 (s, 1H), 8,46 (s, 1H), at 8.36 (s, 1H), 7,94 (DD, 1H, J=1,3, 8,7), the 7.65 (d, 1H, J=8,8), 4,18 (s, 2H), 3.33 and (s, 2H), 2.49 USD (s, 6H), 0.25 in (m, 9H). MS (ESI+) m/z 372,2 (M+H)+.

Example 292

N1-[5-(3-furyl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using furan-3-Voronovo acid VM is one hundred 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (600 MHz, DMSO-d6) δ ppm 12,70 (s, 1H), 9,98 (s, 1H), 8,08 (s, 1H), of 7.90 (s, 1H), 7,72 (t, 1H, J=1,6), to 7.59 (DD, 1H, J=1,4, 8,7), was 7.45 (d, 1H, J=8,8), 6.87 in (s, 1H), 3,17 (s, 2H), 2,33 (s, 6H). MS (ESI+) m/z RUB 285.2 (M+H)+.

Example 293

N2N2-dimethyl-N1-[5-1H-pyrazole-5-yl)-1H-indazol-3-yl]glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 1H-pyrazole-5-Voronovo acid instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (400 MHz, DMSO-d6) δ ppm 12,68 (s, 1H), 10,01 (s, 1H), 8,12 (s, 1H), 7,80 (d, 1H, J=9,0), of 7.69 (s, 1H), 7,46 (d, 1H, J=8,6), 6,60 (d, 1H, J=2,0), 3,17 (d, 2H, J=6,4), was 2.34 (s, 6H). MS (ESI+) m/z RUB 285.2 (M+H)+.

Example 294

N2N2-dimethyl-N1-(5-pyrimidine-5-yl-1H-indazol-3-yl)glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using pyrimidine-5-Voronovo acid instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,87 (s, 1H), 10,11 (s, 1H), 9,16 (s, 1H), which is 9.09 (s, 2H), 8,16 (s, 1H), of 7.75 (DD, 1H, J=1,5, 8,8), 7,60 (d, 1H, J=8,8), 3,18 (s, 2H), 2,33 (s, 6H). MS (ESI+) m/z 297,2 (M+H)+.

Example 295

N1-[5-(2,1,3-benzoxadiazole-5-yl)-1H-indazol-3-yl]-N2N2-DIMET glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using benzo[c][1,2,5]oxadiazol-5-Voronovo acid instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,87 (s, 1H), 10,15 (s, 1H), 8,29 (s, 1H), 8,21 (s, 1H), 8,16 (d, 1H, J=9,4), to 7.99 (DD, 1H, J=1,1, 9,4), a 7.85 (m, 1H), to 7.59 (d, 1H, J=8,8), 3,19 (s, 2H), 2,34 (s, 6H). MS (ESI+) m/z 337,2 (M+H)+.

Example 296

N2N2-dimethyl-N1-[5-(1H-pyrazole-4-yl)-1H-indazol-3-yl]glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm br12.62 (s, 1H), 9,94 (s, 1H), 7,95 (s, 2H), 7,87 (s, 1H), 7,58 (d, 1H, J=8,8), 7,42 (d, 1H, J=8,8), and 3.16 (s, 2H), 2,34 (s, 6H). MS (ESI+) m/z RUB 285.2 (M+H)+.

Example 297

N2N2-dimethyl-N1-[5-(1-methyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 1-methyl-4-(4,4,5,5-tetrame the Il-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 1H NMR (600 MHz, DMSO-d6) δ ppm 12,64 (s, 1H), 9,98 (s, 1H), 8,04 (s, 1H), 7,86 (s, 1H), 7,76 (s, 1H), 7,55 (DD, 1H, J=1,6, 8,6), the 7.43 (d, 1H, J=8,8), a 3.87 (s, 3H), 3,17 (s, 2H), 2,35 (s, 6H). MS (ESI+) m/z 299,2 (M+H)+.

Example 298

N1-[5-(3,5-dimethyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,63 (s, 1H), 10,02 (s, 1H), 7,63 (s, 1H), 7,46 (m, 1H), 7,27 (DD, 1H, J=1,6, 8,6), and 3.16 (s, 2H), 2,32 (s, 6H), to 2.18 (s, 6H). MS (ESI+) m/z 323,2 (M+H)+.

Example 299

N1-{5-[2-(dimethylamino)pyrimidine-5-yl]-1H-indazol-3-yl}-N2N2-dimethylglycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-amine instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,72 (s, 1H), there is a 10.03 (s, 1H), to 8.62 (s, 2H), to $ 7.91 (s, 1H), 7,58 (DD, 1H, J=1,6, 8,6), 7,51 (d, 1H, J=8,5), and 3.16 (s, 8H), of 2.33 (s, 6H). MS (ESI+) m/z 340,2 (M+H)+.

Example 300

N2,N 2-dimethyl-N1-[5-(2-morpholine-4-Yeremey-5-yl)-1H-indazol-3-yl]glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-yl)research instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,74 (s, 1H), there is a 10.03 (s, 1H), 8,67 (s, 2H), 7,94 (s, 1H), 7,60 (DD, 1H, J=1,8, 8,8), 7,52 (d, 1H, J=8,5), 3,74 (m, 4H), to 3.67 (m, 4H), 3,17 (s, 2H), 2,33 (s, 6H). MS (ESI+) m/z 382,2 (M+H)+.

Example 301

N2N2-dimethyl-N1-{5-[1-(2-morpholine-4-retil)-1H-pyrazole-4-yl]-1H-indazol-3-yl}glycinamide

Specified in the title compound was obtained in accordance with the procedure described in Example 233A, using the compound of Example 282C instead of 5-bromo-2-perbenzoate and using 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-yl)ethyl)research instead of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.1H NMR (600 MHz, DMSO-d6) δ ppm 12,63 (s, 1H), 9,96 (s, 1H), of 8.09 (s, 1H), a 7.85 (s, 1H), to 7.77 (s, 1H), 7,54 (DD, 1H, J=1,5, 8,8), the 7.43 (d, 1H, J=8,5), 4,24 (t, 2H, J=6,6), of 3.54 (m, 4H), and 3.16 (s, 2H), by 2.73 (t, 2H, J=6,6), 2,41 (s, 4H), of 2.34 (s, 6H). MS (ESI+) m/z 398,3 (M+H)+.

Example 302

N1-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

1-benzyl-5-cyclopropyl-4-(tributylstannyl)-1H-1,2,3-triazole

Specified in the title compound was obtained in accordance with the procedure described in Example 142A, using toluene instead of hexane and using (azidomethyl)benzene instead of the compound of Example 80A. The crude product was used in the next stage without purification.

Example 302B

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-2-perbenzoate

Specified in the title compound was obtained in accordance with the procedure described in Example 142B, using the compound of Example 302A instead of the compound of Example 142A and using 2-fluoro-5-iodobenzonitrile instead of the compound of Example 87A. MS (ESI+) m/z spreads for about 319.2 (M+H)+.

Example 302C

5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine

Specified in the title compound was obtained in accordance with the procedure described in Example 62D, using the compound of Example 302B instead of the compound of Example 62C. MS (ESI-) m/z 299,2 (M-H)-.

Example 302D

tert-butyl 3-amino-5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

Specified in the title compound was obtained in accordance with the procedure described in Example 64A, using the compound of Example 302C instead of the compound of Example 62D.

Example 302E

N1-[5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2N2

Specified in the title compound was obtained in accordance with the procedure described in Example 64B, using the compounds of Example 302D instead of the compound of Example 64A and using hydrochloride dimethylaminoacetonitrile instead of methoxyacetanilide.1H NMR (400 MHz, DMSO-d6) δ ppm of 12.76 (s, 1H), 10,06 (s, 1H), 8,18 (s, 1H), 7,79 (d, 1H, J=8,8), to 7.50 (d, 1H, J=8,8), 7,34 (m, 5H), of 5.68 (s, 2H), and 3.16 (s, 2H), 2,32 (s, 6H), to 1.76 (m, 1H), 1,05 (square, 2H, J=6,1), 0,39 (square, 2H, J=5,4). MS (ESI+) m/z 416,3 (M+H)+. MS (ESI+) m/z 416,3 (M+H)+.

Example 303

N1[5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

Example 303A

tert-butyl ester 3-amino-5-(1-benzyl-1H-pyrazole-4-yl)-indazol-1-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in Example 64A, using the compound of Example 233B instead of the compound of Example 62D (0,925 g, 100%).1H NMR (400 MHz, DMSO-d6) δ ppm 8,19 (s, 1H), 8,04 (s, 1H), of 7.90-to 7.95 (m, 1H), 7,87 (s, 1H), 7,74 (d, J=1.6 Hz, 1H), 7,28 and 7.36 (m, 5H), 6,27 (s, 2H), lower than the 5.37 (s, 2H), 1,58 (s, 9H). MS (ESI+) m/z 390 (M+H)+.

Example 303B

N1-[5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-yl]-N2N2-dimethylglycinamide

A suspension of 2-(dimethylamino)acetic acid (32 mg, 0,308 mmol) and oxalicacid (0,31 ml, 0.61 mmol) in dichloromethane (5 ml) and dimethylformamide (2 drops) was stirred at ambient temperature for about 1 hour, then conc who was narrowly under reduced pressure. The residue is suspended in tetrahydrofuran (3 ml) was added to a suspension of compound of Example 303A (40 mg, 0,103 mmol) and potassium carbonate (43 mg, 0,308 mmol) in tetrahydrofuran (5 ml). The reaction mixture was stirred at ambient temperature for about 30 minutes, then added triperoxonane acid (4 ml) and the reaction mixture was heated at 60°C for about 20 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure, diluted with dichloromethane (20 ml) and washed with 15% aqueous solution of sodium hydroxide (20 ml). The organic extract was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm becomes 9.97 (s, 1H), 8,21 (s, 1H), 7,83 (s, 1H), 7,82 (s, 1H), 7,56 (d, J=8.7 Hz, 1H), 7,43 (d, J=8.6 Hz, 1H), 7,32-7,40 (m, 2H), 7,25-to 7.32 (m, 3H), to 5.35 (s, 2H), and 3.16 (s, 2H), 2,33 (s, 6H), 1.91 a (s, 3H). MS (ESI+) m/z 375 (M+H)+.

Example 304

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-methylglycine

Specified in the title compound was obtained in accordance with the procedure described in Example 303B, using 2-(tert-butoxycarbonylmethyl)amino)acetic acid instead of 2-(dimethylamino)acetic acid using the compound of Example 64A instead of the compound of Example 303A. 1H NMR (400 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8,28 (s, 1H), 7,78-7,88 (m, 1H), 7,45-7,56 (m, 1H), 7,28 was 7.45 (5H, m), 5,64 (2H, s), is 2.37 (s, 2H), 1,89 (s, 3H). MS (ESI+) m/z 362 (M+H)+.

Example 305

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-pyrrolidin-1-ylacetamide

Example 305A

tert-butyl 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-(2-bromoacetamide)-1H-indazol-1-carboxylate

To a suspension of compound of Example 64A (500 mg, 1.28 mmol) in tetrahydrofuran (12 ml) was added diisopropylethylamine (to 0.22 ml, 1.28 mmol). The reaction mixture was stirred at ambient temperature for about 15 minutes, then was added 2-bromocatechol (of 0.11 ml, 1.2 mmol). The reaction mixture was stirred at ambient temperature for about 16 hours, then was added an additional amount of 2-bromoacetanilide (of 0.11 ml, 1.2 mmol). The reaction mixture was stirred for 15 minutes, then concentrated under reduced pressure to obtain specified in the title compound as a brown solid. This substance was used without further purification.

Example 305B

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-pyrrolidin-1-ylacetamide

To a solution of compound of Example 305A (44 mg, 0,086 mmol) and diisopropylethylamine (of 0.015 ml, 0,086 mmol) in acetonitrile (1 ml) was added pyrrolidine (0,021 ml, 0.25 mmol) and the reaction mixture was heated at 60°C for about 15 minutes. Reactio the ing the mixture was cooled to ambient temperature and was added triperoxonane acid (1 ml). The reaction mixture was heated at 60°C for about 48 hours. The reaction mixture was concentrated under reduced pressure, diluted with dichloromethane (20 ml) and washed with 15% aqueous sodium hydroxide solution (20 ml). The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header.1H NMR (400 MHz, DMSO-d6) δ ppm 8,58 (s, 1H), 8,24 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,27 was 7.45 (m, 5H), 5,64 (s, 2H), 3,35 (s, 2H), 2,65 (s, 4H), to 1.76 (s, 4H). MS (ESI+) m/z 402 (M+H)+.

Example 306

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclopentylphenol

Specified in the title compound was obtained in accordance with the procedure described in Example 305B, using cyclopentylamine instead of pyrrolidine (0.004 g, 12%).1H NMR (400 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8,31 (s, 1H), 7,73-7,86 (d, J=8,8 Hz, 1H), 7,49 (d, J=8.7 Hz, 1H), 7.29 trend was 7.45 (m, 5H), 5,64 (s, 2H), 3,37 (s, 2H), 2,99-3,14 (m, 1H), 1,60-1,80 (m, 4H), 1,30-1,50 (m, 4H). MS (ESI+) m/z 416 (M+H)+.

Example 307

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclopropylalanine

To a solution of compound of Example 305 A (100 mg, 0,196 mmol) and diisopropylethylamine (0,034 ml to 0.19 mmol) acetonitrile (1 ml) was added cyclopropylamine (11 mg, 0,19 mmol) and the reaction mixture was heated at 60°C for about 1 hour. The reaction mixture was cooled to ambient temperature and was added hydrochloric acid (solution of 4 n in dioxane, 1 ml). The reaction mixture was stirred at ambient temperature for about 16 hours. The reaction mixture was concentrated under reduced pressure and the crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain specified in the connection header acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 10,18 (s, 1H), 8,28 (s, 1H), 8,56 (s, 1H), 7,81 (d, J=8.6 Hz, 1H), 7,49 (d, J=8.7 Hz, 1H), 7,30 was 7.45 (m, 5H), 5,64 (s, 2H), 3.45 points (s, 2H), 2,18-of 2.26 (m, 1H), 1,89 (s, 3H), from 0.37 to 0.45 (m, 2H), 0.29 to 0,37 (m, 2H). MS (ESI+) m/z 388 (M+H)+.

Example 308

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-tetrahydro-2H-Piran-4-illiterated

Specified in the title compound was obtained in the form of the acetate salt according to the procedure described in Example 307 using tetrahydro-2H-Piran-4-amine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8,31 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,31 was 7.45 (m, 5H), 5,64 (s, 2H), 3,84 (d, J=11.2 Hz, 2H), 3.43 points (s, 2H), 3,30 (t, J=10,8 Hz, 2H), 2,62-to 2.74 (m, 1H), 1,88 (, 3H), 1,75-of 1.85 (m, 2H), 1,24-of 1.39 (m, 2H). MS (ESI+) m/z 432 (M+H)+.

Example 309

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-shall indazol-3-yl]-2-(3-hydroxy pyrrolidin-1-yl)ndimethylacetamide

Specified in the title compound was obtained in the form of a salt diacetate in accordance with the procedure described in Example 307 using pyrrolidin-3-ol instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm of 10.09 (s, 1H), they were 8.22 (s, 1H), 8,58 (s, 1H), 7,82 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,28 was 7.45 (m, 5H), 5,64 (s, 2H), 4,16-4.26 deaths (m, 1H), 3,34 (s, 2H), 2.77-to of 2.93 (m, 2H), 2,52-to 2.65 (m, 2H), 1,98-to 2.13 (m, 1H), 1,87 (s, 6H), 1.56 to 1.69 in (m, 1H). MS (ESI+) m/z 418 (M+H)+.

Example 310

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(3-hydroxy piperidine-1-yl)ndimethylacetamide

Specified in the title compound was obtained in the form of the acetate salt according to the procedure described in Example 307 using piperidine-3-ol instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm of 10.05 (s, 1H), 8,56 (s, 1H), 8,23 (s, 1H), 7,82 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,29-7,44 (m, 5H), 5,64 (s, 2H), 3,55-to 3.67 (m, 1H), 3,20 (s, 2H), 2.77-to is 2.88 (m, 1H), 2,60-2,70 (m, 1H), 2,22-to 2.35 (m, 1H), 2,12-of 2.23 (m, 1H), of 1.88 (s, 3H), 1,66-of 1.78 (m, 2H), 1,43-to 1.59 (m, 1H), 1,13-of 1.27 (m, 1H). MS (ESI+) m/z 432 (M+H)+.

Example 311

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N3N3-dimethyl-beta-alaninemia

Specified in the title compound was obtained in the form of the acetate salt according to the procedure described in Example 307 using dimethylamine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 10,48 (s, 1H), 8,54 (s, 1H), compared to 8.26 (s, 1H), 7,80 (d, J=8.7 Hz, 1H), of 7.48 (d, J=8.7 Hz, 1H), 7,30-7,44 (m, 5H), 5,64 (s, 2H), 2,60 (d, J=6,1 Hz, 2), of 2.54 (d, J=6.3 Hz, 2H), of 2.21 (s, 6H), 1,90 (s, 3H). MS (ESI+) m/z 390 (M+H)+.

Example 312

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-morpholine-4-ylacetamide

Specified in the title compound was obtained in accordance with the procedure described in Example 307 using the research instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 10,10 (s, 1H), to 8.57 (s, 1H), 8,23 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,29-7,46 (m, 5H), 5,64 (s, 2H), 3,59-3,71 (m, 4H), 3,22 of 3.28 (m, 2H), 2,54-of 2.64 (m, 4H). MS (ESI+) m/z 418 (M+H)+.

Example 313

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(4-methylpiperazin-1-yl)ndimethylacetamide

Specified in the title compound was obtained in the form diacetate salt according to the procedure described in Example 307 using 1-methylpiperazine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm to 8.57 (s, 1H), of 8.25 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,32-the 7.43 (m, 5H), 5,64 (s, 2H), up 3.22 (s, 2H), 2,53-to 2.65 (m, 4H), 2,31 at 2.45 (m, 4H), 2,17 (s, 3H), of 1.85 (s, 6H). MS (ESI+) m/z 431 (M+H)+.

Example 314

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-(3-oxopiperidin-1-yl)ndimethylacetamide

Specified in the title compound was obtained in accordance with the procedure described in Example 307 using piperazine-2-it instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm of 10.21 (s, 1H), to 8.57 (s, 1H), they were 8.22 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,50 (d, J=8.7 Hz, 1H), 7,31-7,46 (m, 5H), 5,64 (s, 2H), 3,36 (s, 2H), 3,24 (s, 2H), 3,17 (s, 2H), 2,78 (s, 2H). MS (ESI+) m/z 431 M+H) +.

Example 315

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-isopropylpyridine

Specified in the title compound was obtained in the form of the acetate salt according to the procedure described in Example 307 using propane-2-amine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8,31 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,49 (d, J=8.7 Hz, 1H), 7,31-7,44 (m, 5H), 5,64 (s, 2H), 3,39 (s, 2H), 2,73-of 2.86 (m, 1H), 1,90 (s, 3H), was 1.04 (d, J=6,1 Hz, 6H). MS (ESI+) m/z 390 (M+H)+.

Example 316

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclohexylglycine

Specified in the title compound was obtained in the form of the acetate salt according to the procedure described in Example 307 using cyclohexanamine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 8,55 (s, 1H), 8,31 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,49 (d, J=8.7 Hz, 1H), 7,30-7,44 (m, 5H), 5,64 (s, 2H), 3,40 (s, 2H), 1,90 (s, 3H), 1,80-of 1.88 (m, 2H), 1,63 - of 1.73 (m, 2H), 1,50-1,60 (m, 1H), 1,02-of 1.29 (m, 5H). MS (ESI+) m/z 430 (M+H)+.

Example 317

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]ndimethylacetamide

To a mixture of compound of Example 64A (20 mg, 0,051 mmol) and diisopropylethylamine (0,063 ml, 0.35 mmol) in tetrahydrofuran (1.5 ml) was added acetylchloride (0,013 ml of 0.17 mmol) and the reaction mixture was stirred at ambient temperature for about 1.5 hours. Added hydrochloric acid (solution of 4 n in dioxane, 1.5 ml) and see what camping was stirred at ambient temperature for about 16 hours. The solvent was removed under reduced pressure and the crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain the specified title compound as the acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 10,35 (s, 1H), to 8.57 (s, 1H), they were 8.22 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), of 7.48 (d, J=8.7 Hz, 1H), 7,33-7,42 (m, 5H), 5,64 (s, 2H), 2.13 and (s, 3H). MS (ESI-) m/z 331 (M-H)-.

Example 318

N1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N2-cyclobutylamine

Specified in the title compound was obtained in accordance with the procedure described in Example 307 using cyclobutylamine instead of cyclopropylamine.1H NMR (400 MHz, DMSO-d6) δ ppm 8,56 (s, 1H), 8,29 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), 7,49 (d, J=8.7 Hz, 1H), 7,31 was 7.45 (m, 5H), 5,64 (s, 2H), and 3.31 (s, 2H), 2,01-of 2.20 (m, 2H), 1,48 of-1.83 (m, 5H). MS (ESI+) m/z 402 (M+H)+.

Example 319

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-proprotein

To a solution of compound of Example 64A (75 mg, 0,19 mmol) in pyridine (2 ml) was added 1-isocyanatopropyl (16 mg, 0,19 mmol) and the reaction mixture was stirred at ambient temperature for about 3 hours. Added additional amount of isocyanate (0.1 ml) was added and the mixture was heated at about 80°C for about 16 hours. The reaction mixture was cooled to ambient temperature and was added water ( ml). The precipitate was collected by filtration, then was treated with hydrochloric acid (4 n solution in dioxane, 3 ml) and stirred at room temperature for about 4.5 hours. Added diethyl ether (5 ml) and the precipitate was collected by filtration. The crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain the specified title compound as the acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 9,34 (s, 1H), and 8.50 (s, 1H), 8,42 (s, 1H), 7,80 (d, J=8.7 Hz, 1H), 7,38 (d, J=8.7 Hz, 1H), 7,31-of 7.48 (m, 5H), the 5.65 (s, 2H), 3,18 (DD, J=6,6, a 12.7 Hz, 2H)and 1.51 (DD, J=7,1, and 14.3 Hz, 2H), of 0.91 (t, J=7,3 Hz, 3H). MS (ESI+) m/z 376 (M+H)+.

Example 320

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]econsultant

To a solution of compound of Example 64A (75 mg, 0,19 mmol) in pyridine (2 ml) was added acanaloniidae (25 mg, 0,19 mmol) and the reaction mixture was stirred at room temperature for about 3 hours. Added more sulphonylchloride (25 mg, 0,19 mmol) and the reaction mixture was stirred for about 48 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane (10 ml) and washed with 1 n aqueous hydrochloric acid solution (10 ml). The organic portion was separated, dried under reduced pressure and operationalisation acid (4 n solution in dioxane, 5 ml) and stirred at room temperature for about 12 hours. The reaction mixture was concentrated under reduced pressure and the crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain the specified title compound as the acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 10,12 (s, 1H), 8,61 (s, 1H), 8,24 (s, 1H), 7,83 (d, J=8.7 Hz, 1H), 7,52 (d, J=8.7 Hz, 1H), 7,29-of 7.48 (m, 5H), 5,64 (s, 2H), 3,29 (d, J=9,2 Hz, 2H), 1,31 (t, J=7,3 Hz, 3H). MS (ESI+) m/z 383 (M+H)+.

Example 321

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-N-(cyclopropylmethyl)-1H-indazol-3-amine

A mixture of compound of Example 64A (100 mg, 0,256 mmol), cyclopropanecarboxaldehyde (0,057 ml, from 0.76 mmol), triacetoxyborohydride sodium (163 mg, from 0.76 mmol) and acetic acid (0,044 ml, from 0.76 mmol) in 1,2-dichloroethane (5 ml) was stirred at ambient temperature for about 2.5 hours. Added hydrochloric acid (4 n solution in dioxane, 4 ml) and the reaction mixture was stirred for about 16 hours. The precipitate was collected by filtration, rinsing with simple ether (10 ml). The solid was dissolved in dichloromethane (10 ml) and treated triperoxonane acid (0.1 ml) and the reaction mixture was stirred at room temperature for about 2 hours. The reaction mixture was neutralized by addition of 15% aqueous solution of hydroc the IDA sodium (about 15 ml) and the organic layer was separated, was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain the specified title compound as the acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 11,43 (s, 1H), to 8.41 (s, 1H), 8,28 (s, 1H), 7,68 (d, J=8.7 Hz, 1H), 7,32 was 7.45 (m, 5H), 7,26 (d, J=8.6 Hz, 1H), between 6.08 (t, J=5.7 Hz, 1H), 5,64 (s, 2H), 3,12 (t, J=6.2 Hz, 2H), 1.04 million-1,22 (m, 1H), 0.35 to 0.53 per share (m, 2H), 0,17-0,32 (m, 2H). MS (ESI+) m/z 345 (M+H)+.

Example 322

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-N'-utilmately

Specified in the title compound was obtained in accordance with the procedure described in Example 319, using isocyanatomethyl instead of 1-isocyanatopropyl.1H NMR (400 MHz, DMSO-d6) δ ppm to 9.32 (s, 1H), 8,49 (s, 1H), 8,42 (s, 1H), 7,81 (d, J=8.7 Hz, 1H), of 7.70 (d, J=8.7 Hz, 1H), 7,31-7,49 (m, 5H), the 5.65 (s, 2H), 3,23 (d, J=6,9 Hz, 2H), 1,12 (t, J=7,1 Hz, 3H). MS (ESI+) m/z 362 (M+H)+.

Example 323

1-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]pyrrolidin-2-he

A suspension of compound of Example 64A (200 mg, 0.51 mmol) and diisopropylethylamine (0,089 ml, 0.51 mmol) in tetrahydrofuran (5 ml) was stirred for about 15 minutes at ambient temperature, then added 4-bromobutyrate (0,059 ml, 0.51 mmol). The reaction mixture was stirred for about 16 hours. The precipitate was removed by filtering and the filtrate was concentrated under reduced pressure. The residue was absorbed in acetonitrile (5 ml) and treated with diisopropylethylamine (0,089 ml, 0.51 mmol) and was heated at about 60°C for about 16 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was treated with hydrochloric acid (4 n solution in dioxane, 5 ml) and the reaction mixture was stirred at room temperature for about 2 hours. The reaction mixture was concentrated under reduced pressure and the crude substance was purified using reverse-phase HPLC using the method of gradient elution of acetonitrile/water (of 0.05 M ammonium acetate) to obtain the specified title compound as the acetate salt.1H NMR (400 MHz, DMSO-d6) δ ppm 12,84 (s, 1H), 8,56 (s, 1H), 8,49 (s, 1H), to 7.84 (d, J=8.6 Hz, 1H), 7,51 (d, J=8.7 Hz, 1H), 7,29-7,46 (m, 5H), 5,64 (s, 2H), 3.96 points (t, J=6.9 Hz, 2H), has 2.56 (t, J=7.9 Hz, 2H), 2,25-2,12 (m, 2H). MS (ESI+) m/z 359 (M+H)+.

Example 324

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-4-(dimethylamino)butanamide

Specified in the title compound was obtained in the form diacetate salt according to the procedure described in Example 303B, using 4-(dimethylamino)butane acid instead of 2-(dimethylamino)acetic acid using the compound of Example 64A instead of the compound of Example 303A.1H NMR (400 MHz, DMSO-d6) δ ppm 10,34 (s, 1H), 8,53 (s, 1H), they were 8.22 (s, 1H), 7,78 (d, J=8,7 the C, 1H), 7,47 (d, J=8.7 Hz, 1H), 7,30-7,41 (m, 5H), 5,62 (s, 2H), 2,41 (t, J=7.2 Hz, 2H), 2,28 (t, J=6,8 Hz, 2H), and 2.14 (s, 6H), of 1.84 (s, 6H), 1,74-to 1.77 (m, 2H). MS (ESI-) m/z 462 (M-H)-.

Example 325

N-3,4-dihydro-1H-isochroman-4-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 3,4-dihydro-1H-isochroman-4-amine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,02 (d, 1H), and 8.4 (m, 1H), they were 8.22 (m, 1H), to 7.75 (m, 2H), 7,2-7,4 (m, 5H), of 5.24 (m, 1H), 4.75 in (m, 2H), was 4.02 (m, 1H), and 3.8 (m, 1H). MS m/z (ESI+) 361 (M+H)+.

Example 326

N-(cyclohexylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

5-(1H-Indazol-5-yl)isoxazol-3-carboxylic acid (35 mg, 0.15 mmol, Example 71A) was dissolved in N,N-dimethylformamide (0.8 ml) followed by addition of HATU (60 mg, 0.15 mmol)dissolved in N,N-dimethylformamide (0.8 ml). Then was added a solution of 1-cyclohexylethylamine (17 mg, 0,17 mmol)dissolved in N,N-dimethylformamide (0.8 ml), followed by the addition of diisopropylethylamine (56 μl, 0.31 mmol)dissolved in N,N-dimethylformamide (0.8 ml). The resulting mixture was shaken for 3 hours at 40°C. the Reaction mixture was filtered, monitored by LC/MS and concentrated to dryness. The residues were dissolved in a mixture of 1:1 dimethyl sulfoxide/methanol and purified using reverse-phase HPLC (column Phenomenex® Luna® C8 (2) 5 µm 100Å AXIA™ (30 mm × 75 mm), 50 ml/min, 10-10% acetonitrile/0.1% of triperoxonane acid in water) to produce specified in the header of the product. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,91-0,97 (m, 2H), 1,12-of 1.27 (m, 4H), 1,61 is 1.75 (m, 5H), is 3.08-and 3.16 (m, 2H), 7,22-7,24 (m, 1H), 7,71 to 7.75 (m, 1H), 7,87-a 7.92 (m, 1H), 8,23-of 8.27 (m, 1H), scored 8.38-to 8.41 (m, 1H). MS (ESI+) m/z 325 (M+H)+; (ESI-) m/z 323 (M-H)-.

Example 327

N-(3-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-(3-chlorophenyl)methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,47-to 4.52 (m, 2H), 7,27-7,29 (m, 1H), 7,30-7,42 (m, 4H), 7,72 to 7.75 (m, 1H), 7,89-to 7.93 (m, 1H), 8,25-of 8.28 (m, 1H), to 8.41-8,42 (m, 1H). MS (ESI+) m/z 353 (M+H)+; (ESI-) m/z 351 (M-H)-.

Example 328

5-(1H-indazol-5-yl)-N-(2-methoxybenzyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-(2-methoxyphenyl)methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,82-3,86 (m, 3H), 4,45-4,50 (m, 2H), 6,92-6,97 (m, 1H), 7,01? 7.04 baby mortality (m, 1H), 7,19-7,24 (m, 1H), 7,26-7,31 (m, 2H), 7,69-to 7.77 (m, 1H), 7,88-to 7.93 (m, 1H), 8,24-of 8.28 (m, 1H), scored 8.38-8,44 (m, 1H). MS (ESI+) m/z 349 (M+H)+; (ESI-) m/z 347 (M-H)-.

Example 329

5-(1H-indazol-5-yl)-N-[2-(trifluoromethyl)benzyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-[2-(Tr is permitil)phenyl]methanamine instead of 1-cyclohexylethylamine. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,66-to 4.73 (m, 2H), 7,29-7,33 (m, 1H), 7,49-of 7.60 (m, 2H), to 7.67-7,79 (m, 3H), to $ 7.91-7,94 (m, 1H), compared to 8.26-of 8.28 (m, 1H), to 8.41-to 8.45 (m, 1H). MS (ESI+) m/z 387 (M+H)+; (ESI-) m/z 385 (M-H)-.

Example 330

5-(1H-indazol-5-yl)-N-[3-(trifluoromethyl)benzyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-[3-(trifluoromethyl)phenyl]methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,57-br4.61 (m, 2H), 7,28-7,31 (m, 1H), to 7.59-to 7.77 (m, 5H), of 7.90-7,94 (m, 1H), 8,27-of 8.28 (m, 1H), 8,40-8,43 (m, 1H). MS (ESI-) m/z 385 (M-H)-.

Example 331

5-(1H-indazol-5-yl)-N-[4-(trifluoromethyl)benzyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-[4-(trifluoromethyl)phenyl]methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,55-4,60 (s, 2H), 7,27-7,30 (m, 1H), 7,54-to 7.59 (m, 2H), 7,70-7,76 (m, 3H), 7,88-7,94 (m, 1H), 8,24-of 8.28 (m, 1H), 8,40-8,44 (m, 1H). MS (ESI+) m/z 387 (M+H)+; (ESI-) m/z 385 (M-H)-.

Example 332

5-(1H-indazol-5-yl)-N-(pyridine-2-ylmethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-pyridine-2-ylmethanone instead of 1-cyclohexylethylamine.1NAMR (500 MHz, DMSO-d6/D2O) δ ppm 4,74-4,84 (s, 2H), 7,30-7,34 (m, 1H), 7.68 per-7,81 (m, 3H), 7,89-of 7.97 (m, 1H), they were 8.22-of 8.33 (m, 2H), 8,40-to 8.45 (m, 1H), 8,67-8,76 (m, 1H). MS (ESI+) m/z 320 (M+H)+; (ESI-) m/z 318 (M-H)-.

Example 333

5-(1H-indazol-5-yl)-N-(pyridine-3-ylmethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-pyridine-3-ylmethanone instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm br4.61-and 4.68 (s, 2H), 7,27-7,31 (m, 1H), 7,70 to 7.75 (m, 1H), 7,83-7,94 (m, 2H), 8,24-of 8.28 (m, 1H), 8,31-of 8.37 (m, 1H), 8,40-8,44 (m, 1H), 8,69-a total of 8.74 (m, 1H), 8,77-8,82 (m, 1H). MS (ESI+) m/z 320 (M+H)+; (ESI-) m/z 318 (M-H)-.

Example 334

5-(1H-indazol-5-yl)-N-(pyridine-4-ylmethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-pyridine-4-ylmethanone instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,73-4,80 (s, 2H), 7,30-7,33 (m, 1H), 7,73 for 7.78 (m, 1H), 7,89-of 7.97 (m, 3H), 8,25-8,30 (m, 1H), 8,40-8,46 (m, 1H), 8,76-8,83 (m, 2H). MS (ESI-) m/z 318 (M-H)-.

Example 335

N-(2-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-(2-chlorophenyl)methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d 6/D2O) δ ppm 4,54-4,58 (s, 2H), 7,27-7,32 (m, 1H), 7,33-7,42 (m, 3H), 7,47-7,49 (m, 1H), 7,71-to 7.77 (m, 1H), 7,88-7,98 (m, 1H), 8,24-of 8.27 (m, 1H), to 8.41-8,44 (m, 1H). MS (ESI+) m/z 353 (M+H)+; (ESI-) m/z 351 (M-H)-.

Example 336

N-(4-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-(4-chlorophenyl)methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,42 figure-4.49 (m, 2H), 7,22-7,31 (m, 1H), 7,34-7,49 (m, 4H), 7,70-7,76 (m, 1H), 7,84-a 7.92 (m, 1H), 8.17-a 8,30 (m, 1H), 8,35-of 8.47 (m, 1H). MS (ESI-) m/z 351 (M-H)-.

Example 337

5-(1H-indazol-5-yl)-N-(1-phenyl-2-piperidine-1-retil)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-phenyl-2-piperidine-1-retinamide instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,12 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,9 (d, 1H), 7.7 (d, 1H), 7,2-7,4 (m, 6H), and 5.2 (m, 1H), 3,2 (m, 2H), 2,3 (m, 4H), 1,2-1,4 (m, 6H). MS (ESI+) m/z 416 (M+H)+.

Example 338

N-[2-(1H-indazol-1-yl)-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 2-(1H-indazol-1-yl)-1-fenilalanina instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 9.5 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,78 (m, 1H), 7,52(d, 2H), 7,72 (d, 2H), 7,2-7,4 (m, 5H), 6,85 (s, 1H), 5,44 (m, 1H), of 4.44 (m, 2H). MS (ESI+) m/z 399 (M+H)+.

Example 339

5-(1H-indazol-5-yl)-N-(2-morpholine-4-yl-1-phenylethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 2-morpholine-4-yl-1-fenilalanina instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 9.2 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,9 (d, 1H), 7.7 (d, 1H), 7,2-7,4 (m, 6H), and 5.2 (m, 1H), 3,6 (m, 4H), 3,4 (m, 2H), 2,4 (m, 4H). MS (ESI+) m/z 418 (M+H)+.

Example 340

5-(1H-indazol-5-yl)-N-[2-(4-methylpiperazin-1-yl)-1-phenylethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 2-(4-methylpiperazin-1-yl)-1-fenilalanina instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,6 (users, 1H), 9,14 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,9 (d, 1H), 7.7 (d, 1H), 7,2-7,4 (m, 6H), and 5.2 (m, 1H), 3,2 (m, 2H), 2,4 (m, 4H), 2,2 (m, 4H), 2,1 (m, 3H). MS (ESI+) m/z 432 (M+H)+.

Example 341

5-(1H-indazol-5-yl)-N-(1-phenyl-2-pyrrolidin-1-retil)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-phenyl-2-pyrrolidin-1 retinamide instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,14 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,9 (d, 1H), 7.7 (d, 1H), 7,2-7,4 (m, 6H), is 5.18 (m, 1H), 3,2 (m, 2H), 2,4 (m, 4H), 1.8 m (m, 3H). MS (ESI+) m/z 402,5 (M+H)+

Example 342

tert-butyl 2-({[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl} amino)-2-generationbased

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using tert-butyl 2-amino-2-phenylethylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,14 (d, 1H), and 8.4 (s, 1H), they were 8.22 (s, 1H), 7,9 (d, 1H), 7.7 (d, 1H), 7,2-7,4 (m, 6H), of 7.00 (t, 1H), 5,18 (m, 1H), 3,2 (m, 2H), and 1.4 (s, 9H). MS (ESI+) m/z 449 (M+H)+.

Example 343

5-(1H-indazol-5-yl)-N-(1-naphthylmethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1-(1-naphthyl)methanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,93-4,99 (m, 2H), 7,28-7,32 (m, 1H), of 7.48-7,66 (m, 4H), 7,70-7,76 (m, 1H), 7,86-a 7.92 (m, 2H), of 7.96-of 8.00 (m, 1H), 8,18-8,23 (m, 1H), 8,24-of 8.27 (m, 1H), scored 8.38-8,44 (m, 1H). MS (ESI-) m/z 367 (M-H)-.

Example 344

5-(1H-indazol-5-yl)-N-(2-phenylethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-fenilatilamin instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,84 of 2.92 (t, 2H), 3,47 is 3.57 (t, 2H), 7.18 in-7,35 (m, 6H), 7,69-to 7.77 (m, 1H), 7,86-to $ 7.91 (m, 1H), they were 8.22-8,29 (m, 1H), of 8.37-8,44 (m, 1H). MS (ESI+) m/z 333 (M+H)+; (ESI-) m/z 331 (M-H)-.

Example 345

5-(1H-indazol-5-is)-N-(2-pyridin-2-retil)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-pyridine-2-elatonin instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,22 be 3.29 (t, 2H), 3,71 of 3.75 (t, 2H), 7,14-7,26 (m, 1H), 7,70 to 7.75 (m, 1H), 7,81-7,94 (m, 3H), 8,23-8,29 (m, 1H), 8,35-8,44 (m, 2H), 8,71-8,83 (m, 1H). MS (ESI+) m/z 334 (M+H)+; (ESI-) m/z 332 (M-H)-.

Example 346

5-(1H-indazol-5-yl)-N-(2-pyridin-3-retil)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-pyridine-3-elatonin instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,01-3,13 (t, 2H), 3,55-3,70 (t, 2H), 7,14-7,26 (m, 1H), 7,70-to 7.77 (m, 1H), 7,84-to 7.95 (m, 2H), 8,25-8,29 (m, 1H), at 8.36-to 8.45 (m, 2H), 8,69 is 8.75 (m, 1H), 8,77-8,84 (m, 1H). MS (ESI+) m/z 334 (M+H)+; (ESI-) m/z 332 (M-H)-.

Example 347

5-(1H-indazol-5-yl)-N-(2-pyridin-4-retil)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-pyridine-4-elatonin instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,12 is 3.23 (t, 2H), 3,67-3,71 (t, 2H), 7,20-7,21 (m, 1H), 7,69-7,76 (m, 1H), 7,86-to $ 7.91 (m, 3H), 8,25-of 8.27 (m, 1H), scored 8.38-to 8.41 (m, 1H), 8,70-8,77 (m, 2H). MS (ESI+) m/z 334 (M+H)+; (ESI-) m/z 332 (M-H)-.

Example 348

N-[2-(2-chlorophenyl)ethyl]-5-(1H-and dasol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-(2-chlorophenyl)ethanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,99 was 3.05 (t, 2H), 3,54-3,61 (t, 2H), 7,21-of 7.23 (m, 1H), 7,26-7,33 (m, 2H), 7,35-7,40 (m, 1H), 7,41-7,47 (m, 1H), 7,70 to 7.75 (m, 1H), 7,87-to 7.93 (m, 1H), 8,23-8,31 (m, 1H), of 8.37-8,44 (m, 1H). MS (ESI+) m/z 367 (M+H)+; (ESI-) m/z 365 (M-H)-.

Example 349

N-[2-(3-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-(3-chlorophenyl)ethanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,89 (t, 2H), 3,54 (t, 2H), 7,19-7,42 (m, 5H), 7,69-to 7.77 (m, 1H), 7,86-7,94 (m, 1H), they were 8.22-8,29 (m, 1H), scored 8.38-8,42 (m, 1H). MS (ESI-) m/z 365 (M-H)-.

Example 350

N-[2-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 2-(4-chlorophenyl)ethanamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm of 2.86 (t, 2H), 3,50 (t, 2H), 7,17-7,24 (m, 1H), 7,27-7,41 (m, 4H), 7,71-7,76 (m, 1H), a 7.85 to $ 7.91 (m, 1H), 8,21-8,29 (m, 1H), 8.34 per-8,44 (m, 1H). MS (ESI-) m/z 365 (M-H)-.

Example 351

N-benzyl-N-ethyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in is the head of the connection is received, using the procedure described in Example 326, except that used N-benzyl-N-ethylamine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.06 a-1,19 (m, 3H), 3,37-to 3.49 (m, 2H), 4,69 was 4.76 (m, 2H), 7,21-7,28 (m, 1H), 7,28-7,49 (m, 5H), 7,69 for 7.78 (m, 1H), 7,83-of 7.97 (m, 1H), 8,24-8,32 (m, 1H), at 8.36-8,46 (m, 1H). MS (ESI+) m/z 347 (M+H)+; (ESI-) m/z 345 (M-H)-.

Example 352

5-(1H-indazol-5-yl)-N-methyl-N-(1-naphthylmethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used N-methyl-N-(1-naphthylmethyl)amine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3.04 from-3,11 (m, 3H), 5,20 to 5.35 (m, 2H), 7,20-7,31 (m, 1H), 7,33-7,66 (m, 4H), 7,66-to 7.77 (m, 1H), 7,81-8,18 (m, 4H), 8,20-of 8.28 (m, 1H), 8,31-to 8.45 (m, 1H). MS (ESI+) m/z 383 (M+H)+; (ESI-) m/z 381 (M-H)-.

Example 353

5-(1H-indazol-5-yl)-N-methyl-N-(2-phenylethyl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used N-methyl-N-(2-phenylethyl)amine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,86-of 2.97 (m, 2H), 3,06-3,13 (m, 3H), 3,70-3,74 (m, 2H), 6,64-7,39 (m, 6H), 7,69-a 7.92 (m, 2H), 8,24-8,44 (m, 2H). MS (ESI+) m/z 347 (M+H)+; (ESI-) m/z 345 (M-H)-.

Example 354

5-(1H-indazol-5-yl)-N-methyl-N-(2-pyridin-2-retil)isoxazol-3-carboxamide

Specified in C is the cylinder, a connection was received, using the procedure described in Example 326, except that used N-methyl-N-(2-pyridin-2-retil)amine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,07-up 3.22 (m, 3H), 3,26-3,39 (m, 2H), 3,92-Android 4.04 (m, 2H), 6,85-7,14 (m, 1H), 7,65-with 8.05 (m, 4H), 8,23-8,56 (m, 3H), 8,65-8,86 (m, 1H). MS (ESI+) m/z 348 (M+H)+; (ESI-) m/z 346 (M-H)-.

Example 355

5-(1H-indazol-5-yl)-N-[(1R)-1-phenylethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that he used (1R)-1-fenilatilamin instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1,49-and 1.54 (m, 3H), 5,12-5,20 (m, 1H), 7.23 percent-7,29 (m, 2H), 7,33-7,46 (m, 4H), 7,71 to 7.75 (m, 1H), 7,87-to $ 7.91 (m, 1H), they were 8.22-of 8.28 (m, 1H), of 8.37-8,42 (m, 1H). MS (ESI+) m/z 333 (M+H)+; (ESI-) m/z 331 (M-H)-.

Example 356

5-(1H-indazol-5-yl)-N-1,2,3,4-tetrahydronaphthalen-1 - isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 326, except that used 1,2,3,4-tetrahydronaphthalen-1-amine instead of 1-cyclohexylethylamine.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1,72-of 2.09 (m, 4H), 2,68-to 2.85 (m, 2H), 5,19-of 5.26 (m, 1H), 7,12-7,24 (m, 4H), 7,29-7,35 (m, 1H), 7,69-to 7.77 (m, 1H), 7,86-to 7.93 (m, 1H), 8,25-8,30 (m, 1H), scored 8.38-8,43 (m, 1H). MS (ESI-) m/z 357 (M-H)-.

Example 357

5-(1H-indazol-5-yl)-N-[(1S)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide

Specified in the header is VCE compound was obtained in accordance with the procedure described in Example 81B, using (1S)-1-(1-naphthyl)ethanamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 9.4 (d, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), they were 8.22 (users, 1H), 7,95 (d, 1H), a 7.85 (m, 2H), 7,65 (m, 2H), 7.5 (m, 3H), and 7.3 (s, 1H)and 5.9 (m, 1H), 1,65 (d, 3H). MS (ESI+) m/z 382,9 (M+H)+.

Example 358

5-(1H-indazol-5-yl)-N-[(1R)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (1R)-1-(1-naphthyl)ethanamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 9.4 (d, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), they were 8.22 (users, 1H), 7,95 (d, 1H), a 7.85 (m, 2H), 7,65 (m, 2H), 7.5 (m, 3H), and 7.3 (s, 1H)and 5.9 (m, 1H), 1,65 (d, 3H). MS (ESI+) m/z 382,9 (M+H)+.

Example 359

N-[3-(dimethylamino)-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using the N3N3-dimethyl-1-phenylpropane-1,3-diamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 9.4 (d, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), 7,92 (m, 1H), and 7.7 (m, 1H), and 7.3-7.5 (m, 6H), of 5.15 (m, 1H), 3,2 (m, 2H), of 7.75 (s, 6H), to 2.35 (m, 1H), 2,15 (m, 1H). MS (ESI+) m/z 390 (M+H)+.

Example 360

Ν-(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-(2,3-dihyd the on-1,4-benzodioxin-5-yl)methanamine instead of piperidine. 1H NMR (SOO MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,24 (t, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), 7.7 (d, 1H), 7,24 (s, 1H), 6,9 (m, 3H), 4,4 (d, 2H), 4,3 (d, 2H), 4.25 in (d, 2H). MS (ESI+) m/z 377 (M+H)+.

Example 361

N-(3,4-dihydro-2H-1,5-benzodioxepin-6-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)methanamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,2 (t, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), 7.7 (d, 1H), 7,24 (s, 1H), 6,9 (m, 3H), 4,42 (d, 2H), 4,15 (m, 4H), 2,2 (m, 2H). MS (ESI+) m/z 391 (M+H)+.

Example 362

5-(1H-indazol-5-yl)-N-[(1-methyl-1H-indol-4-yl)methyl]isoxazol-3-carboxamide

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using (1-methyl-1H-indol-4-yl)methylamine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), 9,24 (t, 1H), and 8.4 (s, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), 7.7 (d, 1H), 7,38 (m, 3H), 7,18 (m, 1H), 7,0 (d, 1H), and 6.6 (s, 1H), 4,7 (d, 2H), and 3.8 (s, 3H). MS (ESI+) m/z 372 (M+H)+.

Example 363

5-{3-[(3-phenylpyrrolidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 3-phenylpyrrolidine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 8.4 (m, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), and 7.8 (d, 1H),7,24 (m, 6H), 4,4 (m, 1H), 3,4 (m, 2H), 2,4 (m, 2H), 2.0 (m, 2H). MS (ESI+) m/z 359 (M+H)+.

Example 364

5-{3-[(2-phenylpyrrolidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using a 2-phenylpyrrolidine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 8.4 (m, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), and 7.8 (d, 1H), 7,24 (m, 6H), 5,6 (m, 0,3H), 5,2 (m, 0,7H), 4,0 (m, 2H), 1,8-2,0 (m, 4H). MS (ESI+) m/z 390 (M+H)+.

Example 365

5-{3-[(2-phenylpiperidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol

Specified in the title compound was obtained in accordance with the procedure described in Example 81B, using 2-phenylpiperidine instead of piperidine.1H NMR (300 MHz, DMSO-d6) δ ppm 13,4 (users, 1H), and 8.4 (m, 1H), of 8.25 (s, 1H), 7,92 (d, 1H), and 7.8 (d, 1H), 7,24 (m, 6H), 5,6 (m, 0,3H), 5,2 (m, 0,7H), 4,0 (m, 2H), 1,8-2,0 (m, 6H). MS (ESI+) m/z 373 (M+H)+.

Example 366

5-(1H-indazol-5-yl)-N-[(1S)-1-phenylethyl]isoxazol-3-carboxamide

5-(1H-Indazol-5-yl)isoxazol-3-carboxylic acid (36 mg, 0.16 mmol, Example 71A) was dissolved in N,N-dimethylformamide (1.0 ml) followed by addition of HATU (60 mg, 0.16 mmol)dissolved in N,N-dimethylformamide (0.5 ml). Then solution was added (S)-1-fenilalanina (22 mg, 0.18 mmol)dissolved in N,N-dimethylformamide (0.6 ml) followed by the addition of diisopropylethylamine (56 μl, 0.32 mmol)dissolved in N,N-dimethylformamide (0.2 ml). Poluchenno the mixture was shaken for 3 hours at 40°C. The reaction mixture was filtered, monitored by LC/MS and concentrated to dryness. The residues were dissolved in a mixture of 1:1 dimethyl sulfoxide/methanol and purified using reverse-phase HPLC (column Phenomenex® Luna® C8(2) 5 µm 100Å AXIA™ (30 mm × 75 mm), 50 ml/min, 10-100% acetonitrile/0.1% of triperoxonane acid in water) to produce specified in the header of the product.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 in (d, 3H), 5,06 with 5.22 (m, 1H), 7.23 percent-7,29 (m, 2H), 7,34-7,38 (m, 2H), 7,40 was 7.45 (m, 2H), 7,70 to 7.75 (m, 1H), 7,87-a 7.92 (m, 1H), 8,25-of 8.27 (m, 1H), 8,39-to 8.41 (m, 1H), 9.28 are (d, 1H). MS (ESI+) m/z 333 (M+H)+; (ESI-) m/z 331 (M-H)-.

Example 367

5-(1H-indazol-5-yl)-Ν-[(1R)-1-(4-were)ethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)-1-(4-were)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm for 1.49 (d, 3H), 2,25-2,31 (m, 3H), 5,09-by 5.18 (m, 1H), 7,14-to 7.18 (m, 2H), 7.23 percent-of 7.24 (m, 1H), 7,28-to 7.32 (m, 2H), 7,70 to 7.75 (m, 1H), 7,86-a 7.92 (m, 1H), they were 8.22-8,29 (m, 1H), of 8.37-8,42 (m, 1H), 9,19 (d, 1H). MS (ESI+) m/z 347 (M+H)+; (ESI-) 345 (M-H)-.

Example 368

5-(1H-indazol-5-yl)-N-[(1S)-1-(4-were)ethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1S)-1-(4-were)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d /D2O) δ ppm to 1.48 (d, 3H), 2.26 and-2,30 (m, 3H), of 5.05-5,23 (m, 1H), 7,15-7,17 (m, 2H), 7,22-7,25 (m, 1H), 7,28-to 7.32 (m, 2H), to 7.67-7,79 (m, 1H), 7,86-to 7.93 (m, 1H), they were 8.22-8.30 to (m, 1H), scored 8.38-to 8.41 (m, 1H), of 9.21 (d, 1H). MS (ESI-) m/z 345(M-H)-.

Example 369

N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used the (1R,2S)-1-aminoindan-2-ol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,89-2,96 (m, 1H), 3,13-is 3.21 (m, 1H), 4,55-br4.61 (m, 1H), 5.40 to-5,47 (m, 1H), 7,21-7,34 (m, 4H), 7,39-7,42 (m, 1H), 7,72-to 7.77 (m, 1H), to $ 7.91-to 7.95 (m, 1H), 8,25-8,29 (m, 1H), 8,42-to 8.45 (m, 1H). MS (ESI-) m/z 359 (M-H)-.

Example 370

N-[(1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used the (1R,2R)-1-aminoindan-2-ol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,72-and 2.83 (m, 1H), 3,13-3,30 (m, 1H), of 4.44-4.53-in (m, 1H), 5,24-5,32 (m, 1H), 7,10-to 7.18 (m, 1H), 7,20-7,27 (m, 3H), 7,30-7,33 (m, 1H), 7,72 for 7.78 (m, 1H), to $ 7.91-to 7.93 (m, 1H), 8,24-8,29 (m, 1H), to 8.41-to 8.45 (m, 1H), 9,17 (d, 1H). MS (ESI-) m/z 359 (M-H)-.

Example 371

N-[(1R)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)--(4-bromophenyl)ethanamine instead of (S)-1-fenilalanina. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 in (d, 3H), 5.08 to by 5.18 (m, 1H), 7,21-7,27 (m, 1H), was 7.36-7,41 (m, 2H), 7,50-to 7.59 (m, 2H), 7,70-7,76 (m, 1H), 7,86-to 7.93 (m, 1H), 8,23-8,29 (m, 1H), scored 8.38-to 8.41 (m, 1H), to 9.32 (d, 1H). MS (ESI+) m/z 411 (M+H)+.

Example 372

N-[(1S)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (lS)-1-(4-bromophenyl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm for 1.49 (d, 3H), 5,09-5,19 (m, 1H), 7.23 percent-of 7.25 (m, 1H), 7,37-7,40 (m, 2H), 7,53-EUR 7.57 (m, 2H), 7,71 to 7.75 (m, 1H), 7,87-a 7.92 (m, 1H), 8,25-of 8.27 (m, 1H), scored 8.38-to 8.41 (m, 1H), to 9.32 (d, 1H). MS (ESI) negative ion 409 (M-H)-.

Example 373

N-[(1R)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)-1-(4-chlorophenyl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 in (d, 3H), 5,10-to 5.21 (m, 1H), 7,22-7,26 (m, 1H), 7,38-7,47 (m, 4H), 7,70 to 7.75 (m, 1H), 7,87-a 7.92 (m, 1H), 8,20-of 8.28 (m, 1H), scored 8.38-to 8.41 (m, 1H), was 9.33 (d, 1H). MS (ESI-) m/z 365 (M-H)-.

Example 374

N-[(1S)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1S)-1-(4-chlorophenyl)ethanamine instead of(S)-1-fenilalanina. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm for 1.49 (d, 3H), 5,12-5,19 (m, 1H), 7.23 percent-of 7.25 (m, 1H), 7,39-7,47 (m, 4H), 7,71-7,74 (m, 1H), 7,87-to $ 7.91 (m, 1H), 8,25-of 8.27 (m, 1H), of 8.37-8,43 (m, 1H), to 9.32 (d, 1H). MS (ESI-) m/z 365 (M-H)-.

Example 375

5-(1H-indazol-5-yl)-N-[(1S)-1-(2-naphthyl)ethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1S)-1-(2-naphthyl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm of 1.61 (d, 3H), 5,30 is 5.38 (m, 1H), 7,25-7,26 (m, 1H), of 7.48-of 7.55 (m, 2H), 7,60-7,63 (m, 1H), 7,72 to 7.75 (m, 1H), 7,88-to 7.95 (m, 5H), 8,25-of 8.28 (m, 1H), 8,39-8,43 (m, 1H), 9,39 (d, 1H). MS (ESI-) m/z 381 (M-H)-.

Example 376

N-[1-(4-ethoxyphenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 2-amino-2-(4-ethoxyphenyl)ethanol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.32 to (t, 3H), 3,62-to 3.67 (m, 1H), 3,70-to 3.73 (m, 1H), 3.96 points-4,06 (m, 2H), 4,98-of 5.06 (m, 1H), 6.87 in-6,91 (m, 2H), 7.23 percent and 7.36 (m, 3H), 7,70 to 7.75 (m, 1H), 7,88-to $ 7.91 (m, 1H), 8,25-of 8.27 (m, 1H), 8,39-8,42 (m, 1H). MS (ESI-) m/z 391 (M-H)-.

Example 377

N-[2-hydroxy-1-(4-isopropylphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 2-amino-2-(4-ISO is propylphenyl)ethanol instead of (S)-1-fenilalanina. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm of 1.18 (d, 6H), of 2.81-2.91 in (m, 1H), 3,65-3,70 (m, 1H), 3.72 points-3,74 (m, 1H), 5,01-5,09 (m, 1H), 7,20-7,28 (m, 3H), 7,29-7,35 (m, 2H), 7,72-7,80 (m, 1H), 7,87-to 7.95 (m, 1H), 8,24-8,29 (m, 1H), scored 8.38-8,44 (m, 1H). MS (ESI-) m/z 389 (M-H)-.

Example 378

N-[1-(3,4-dimetilfenil)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 2-amino-2-(3,4-dimetilfenil)ethanol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2,30 (d, 6H), 3,56-3,63 (m, 1H), 3,65-to 3.73 (m, 1H), 5,32-5,42 (m, 1H), 7,06-was 7.08 (m, 2H), 7.23 percent-7,28 (m, 2H), 7,69-7,76 (m, 1H), 7,87-to 7.95 (m, 1H), 8,25-of 8.28 (m, 1H), 8,39-8,43 (m, 1H). MS (ESI-) m/z 375 (M-H)-.

Example 379

N-[2-hydroxy-1-(2-methoxyphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 2-amino-2-(2-methoxyphenyl)ethanol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,60-3,66 (m, 2H), 3,84-3,88 (m, 3H), lower than the 5.37-of 5.48 (m, 1H), 6,95 (t, 1H), 7,00-7,06 (m, 1H), 7.24 to 7,31 (m, 2H), to 7.32 and 7.36 (m, 1H), 7,71-to 7.77 (m, 1H), 7,85-of 7.97 (m, 1H), 8,24-of 8.28 (m, 1H), 8,40-to 8.45 (m, 1H). MS (ESI+) m/z 379 (M+H)+; negative ion 377 (M-H)-.

Example 380

N-[2-hydroxy-1-(4-were)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using PR the procedures, described in Example 366 except that used 2-amino-2-(4-were)ethanol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 2.26 and of-2.32 (m, 3H), 3,65-3,70 (m, 1H), 3.72 points of 3.75 (m, 1H), 5,01-5,08 (m, 1H), 7,10-7,21 (m, 2H), 7,25-7,35 (m, 3H), 7,70-to 7.77 (m, 1H), 7,86-to 7.95 (m, 1H), compared to 8.26-of 8.28 (m, 1H), 8,39-8,46 (m, 1H). MS (ESI+) m/z 363 (M+H)+; (ESI-) m/z 361 (M-H)-.

Example 381

5-(1H-indazol-5-yl)-N-[(1R)-1-(2-methoxyphenyl)ethyl]isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)-1-(2-methoxyphenyl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm was 1.43 (d, 3H), 3,82-3,86 (m, 3H), 5,41-of 5.50 (m, 1H), 6,95 (t, 1H), 7,00-7,05 (m, 1H), 7.23 percent-7,29 (m, 2H), 7,35-7,39 (m, 1H), 7,71-7,76 (m, 1H), 7,88-a 7.92 (m, 1H), 8,25-of 8.27 (m, 1H), of 8.37-8,43 (m, 1H). MS (ESI+) m/z 363 (M+H)+; (ESI-) m/z 361 (M-H)-.

Example 382

N-[(1S)-1-(3,4-differenl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1S)-1-(3,4-differenl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 in (d, 3H), 5,09-5,24 (m, 1H), 7,21-7,30 (m, 2H), 7,35-7,44 (m, 1H), 7,44-7,53 (m, 1H), 7.68 per-of 7.82 (m, 1H), 7,86-7,94 (m, 1H), compared to 8.26-of 8.27 (m, 1H), 8,39-8,42 (m, 1H). MS (ESI-) m/z 367 (M-H)-.

Example 383

5-(1H-indazol-5-yl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]isoxazol-3-CT is the oksamid

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)-1-(3-methoxyphenyl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 1.50 in (d, 3H), 3.75 to of 3.77 (m, 3H), 5,01-5,19 (m, 1H), 6,80-6,87 (m, 1H), 6,97-7,02 (m, 2H), 7,21-to 7.32 (m, 2H), 7,70 to 7.75 (m, 1H), 7,87-to 7.95 (m, 1H), they were 8.22-8,31 (m, 1H), of 8.37-8,43 (m, 1H). MS (ESI-) m/z 361 (M-H)-.

Example 384

5-(1H-indazol-5-yl)-N-{(1R)-1-[3-(trifluoromethyl)phenyl]ethyl} isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that he used (1R)-1-[3-(trifluoromethyl)phenyl]ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm and 1.54 (d, 3H), 5,22-of 5.29 (m, 1H), 7.23 percent-7,27 (m, 1H), 7,58-of 7.69 (m, 2H), 7,71 to 7.75 (m, 2H), to 7.77-7,83 (m, 1H), 7,87-a 7.92 (m, 1H), 8,24-8,29 (m, 1H), scored 8.38-8,42 (m, 1H). MS (ESI-) m/z 399 (M-H)-.

Example 385

N-[1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethanamine instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm of 1.46 (d, 3H), 4,18-of 4.25 (m, 4H), 5,01-5,10 (m, 1H), 6,80-to 6.95 (m, 3H), 7,22-7,24 (m, 1H), 7,70-7,74 (m, 1H), 7,87-to $ 7.91 (m, 1H), compared to 8.26-of 8.27 (m, 1H), 8,39-to 8.41 (m, 1H). MS (ESI-) m/z 389 (M-H)-.

Example 386

N-[1-(3-dichlorophenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide

Specified in the title compound was obtained using the procedure described in Example 366 except that used 2-amino-2-(3,5-dichlorophenyl)ethanol instead of (S)-1-fenilalanina.1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 3,68-and 3.72 (m, 1H), 3,76-of 3.78 (m, 1H), 5,02-5,10 (m, 1H), 7,26-7,29 (m, 1H), 7,47-7,52 (m, 3H), 7,72 to 7.75 (m, 1H), 7,89-to 7.93 (m, 1H), 8,25-of 8.28 (m, 1H), 8,39-8,44 (m, 1H). MS (ESI-) m/z 415 (M-H)-.

Example 387

tert-butyl 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-3-[({[6-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]-1H-indazol-1-carboxylate

The solution triphosgene in dichloromethane was cooled to 0°C in nitrogen atmosphere. Then slowly dropwise added a mixture of triethylamine (0,426 ml of 3.07 mmol) and compound of Example 64A (150 mg, 0.384 mmol) in dichloromethane (2 ml). The resulting mixture was stirred at room temperature for 1 hour. Then was added 6-(trifluoromethyl)pyridin-2-amine (62.3 mg, 0.384 mmol), followed by stirring overnight at room temperature. The precipitate was filtered and washed with dichloromethane and water. The product was dried under vacuum to obtain specified in the connection header. MS m/z 579,3 (M+Η)+.

Example 388

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(1-methylpiperidin-2-yl)carbonyl]-1H-indazol-3-amine

Hydrochloride 1 methylpiperidin-3-carboxylic acid was combined with a mixture of dimethylformamide and dichloromethane in a nitrogen atmosphere and was stirred over their 15 minutes. Then added in portions, carbonyldiimidazole. The resulting solution was stirred at room temperature for 1 hour. Then was added the compound of Example 62 with the subsequent addition by stirring at 60°C for 2 hours and then at room temperature overnight. The reaction mixture was poured into ice vodou and added a saturated salt solution. The cooled solution decantation and the residue was swallowed up in dichloromethane and washed with water (2×). The organic layer was dried using magnesium sulfate and the volatiles were removed under reduced pressure. Decanted solution was extracted with ethyl acetate (3×). The combined organic layers were washed with saturated brine (2×), dried with magnesium sulfate and concentrated. The residue was absorbed in a small amount of acetone and then added dropwise to distilled water. The precipitate was collected by filtration, washed with water and dried to obtain specified in the connection header. MS m/z 579,3 (M+Η)+.

Example 389

5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1-[(dimethylamino)acetyl]-1H-indazol-3-amine

2-(Dimethylamino)acetic acid was dissolved in dimethylformamide and pyridine in a nitrogen atmosphere at room temperature for 15 minutes. Was added in portions to carbonyldiimidazole. The resulting mixture was stirred at room temperature in the course is 1 hour. Then was added the compound of Example 62 and the mixture was stirred over night at room temperature. Volatile matter was removed under reduced pressure and the residue was added to ice water. Was added sodium chloride, and was the deposition of thick oil from the cooled solution. The solution decantation. The residue was washed with water (3×) and then dried. From the decanted solution is directly over night was the release of sludge from a mixture of water/dimethylformamide. It turned out that is a starting material, which was filtered and poured. The residue, containing the product, was led in dichloromethane, collected by filtration, washed with a small amount of dichloromethane and simple ether. The product was dried to obtain specified in the connection header. MS m/z 376.3 on (M+Η)+.

Example 390

tert-butyl 3-amino-5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-1-carboxylate

Example 62 suspended in dichloromethane together with a catalytic amount of dimethylaminopyridine. Solution was added di-tert-BUTYLCARBAMATE in dichloromethane (160 ml) for 1 hour. The reaction mixture was stirred for approximately 40 hours. Was added silica gel and the mixture was concentrated. This contains silicon dioxide and the mixture was introduced into a column with silica gel and substance suirable first dichloromethane and then a mixture of 1% methanol/dichloromethane and averseness 2% methanol/dichloromethane. The fractions containing the desired product were combined and concentrated to obtain specified in the connection header. MS m/z 391,3 (M+Η)+.

Example 391

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-piperidine-1-ylacetamide

2-(piperidine-1-yl)acetic acid was combined with dimethylformamide and pyridine. The mixture was stirred for 15 minutes at room temperature and then added in portions, carbonyldiimidazole. Continued stirring at room temperature for 1 hour and then was added the compound of Example 64A, continuing the stirring for 24 hours. The reaction mixture was heated to 60°C for 14 hours. Received a small amount specified in the connection header. MS m/z 416,3 (M+Η)+.

Example 392

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-2-morpholine-4-ylacetamide

2-Morpholinoethoxy acid was combined with dimethylformamide and pyridine. The mixture was stirred for 15 minutes at room temperature then added in portions, carbonyldiimidazole. Continued stirring at room temperature for 1 hour and then was added the compound of Example 64A, continuing the stirring for 28 hours. The reaction mixture was heated to 60°C for 4 hours and then continued stirring overnight at room temperature. The reaction mixture was again heated to 60°C during the course the e 7 o'clock. Received a small amount specified in the connection header. MS m/z 418,3 (M+Η)+.

Example 393

N-[5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-yl]-1-methylpiperidin-2-carboxamide

Hydrochloride 1 methylpiperidin-3-carboxylic acid was combined with dimethylformamide and pyridine. The mixture was stirred for 15 minutes at room temperature and then added in portions, carbonyldiimidazole. Continued stirring at room temperature for 1 hour and then was added the compound of Example 64A, continuing the stirring for 28 hours. The reaction mixture was heated to 60°C in a period of 4.25 hours and then continued stirring overnight at room temperature. The reaction mixture was again heated to 60°C for 7 hours. Received a small amount specified in the connection header. MS m/z 416,3 (M+H)+.

Biological data

Analysis of inhibition of ROCK-2

The compounds of formula (I) were tested for their ability to inhibit His6-labeled N-Termini of recombinant human ROCK-2, residues 11-552, expressed by baculovirus in Sf21 cells (Upstate). In 384-well having a v-shaped bottom polypropylene plates (Axygen) 1 nm (final concentration) in 10 μl of recombinant His6-tagged at the N end of the recombinant human ROCK-2, residues 11-552, expressed by baculovirus in Sf21 cells (Upstate), smesi is from 2 μm (final concentration) in 10 ál of biotinylated peptide substrate (Biotin-Aha-KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (SEQ ID NO:I)) (Genemed) and various concentrations of inhibitor (2% DMSO final concentration) in reaction buffer (25 mm HEPES, pH 7.5, 0.5 mm DTT, 10 mm MgCl2, 100 μm Na3VO4, 0.075 mg/ml Triton X-100) and the reaction was initiated by adding its 5 μm ATP containing a 0.01 µci of [33P]-ATP (Perkin Elmer). The reaction is extinguished after 1 hour by adding 50 μl of stop buffer (50 mm EDTA, 2M NaCl final concentration). 80 μl of reaction mixtures after stopping the reaction was transferred into a 384-well streptavidin coated tablets FlashPlates (Perkin Elmer), incubated for 10 minutes at room temperature, washed 3 times using 0.05% of Tween-20/PBS, using an automatic device for washing tablets ELX-405 (BioTek) and counted using a scintillation reader tablets TopCount (Packard).

Analysis of inhibition of ROCK-1

The compounds of formula (I) were tested for their ability to inhibit His6-labeled N-Termini of recombinant human ROCK-1, amino acids 17-535, expressed by baculovirus in Sf21 cells (Upstate). In 384-well having a v-shaped bottom polypropylene plates (Axygen) 2 nm (final concentration) in 10 μl of recombinant His6-tagged at the N end of the recombinant human ROCK-1, amino acids 17-535, expressed by baculovirus in Sf21 cells (Upstate), was mixed with 2 μm (final concentration) of the biotinylated peptide substrate (Biotin-Aha-VRRLRRLTAREAA (SEQ ID NO:2)) (Genemed) and various concentrations of inhibitor (2% DMSO con is CNA concentration) in 10 μl reaction buffer (25 mm HEPES, pH 7.5, 0.5 mm DTT, 10 mm MgCl2, 100 μm Na3VO4, 0.075 mg/ml Triton X-100) and the reaction was initiated by adding its 5 μm ATP containing a 0.01 µci of [33P]-ATP (Perkin Elmer). The reaction is extinguished after 1 hour by adding 50 μl of stop buffer (50 mm EDTA, 2M NaCl final concentration). 80 μl of reaction mixtures after stopping the reaction was transferred into a 384-well streptavidin coated tablets FlashPlates (Perkin Elmer), incubated for 10 minutes at room temperature, washed 3 times using 0.05% of Tween-20/PBS, using an automatic device for washing tablets ELX-405 (BioTek) and counted using a scintillation reader tablets TopCount (Packard).

Analysis of inhibition of GSK

The compounds of formula (I) were tested for their ability to inhibit His6-tagged at the N end of GSK-3, expressed by baculovirus in Sf21 cells (Upstate). In 384-well having a v-shaped bottom polypropylene plates (Axygen) 10 μl of recombinant His-tagged at the N end of GSK3, expressed by baculovirus in Sf21 cells (Upstate), was mixed with 10 μl of the biotinylated peptide substrate (Biotin-ahx-YRRAAVPPSPSLSRHSSPHQS(p)EDEEE (SEQ ID NO:3)), 2 μm final concentration (Genemed), and various concentrations of inhibitor (2% DMSO final concentration) in reaction buffer (20 mm HEPES, pH 7.5, 1 mm DTT, 10 mm MgCl2100 μm Na3VO4, 0.075 mg/ml Triton X-100) and p is the rally was initiated by adding 20 μm [ 33P]-ATP, 5 μm final concentration, 2 MCI/ mmol (Perkin Elmer). The reaction is extinguished after 1 hour by adding 50 μl of stop buffer (50 mm EDTA, 2M NaCl final concentration). 80 μl of reaction mixtures after stopping the reaction was transferred into a 384-well streptavidin coated tablets FlashPlates (Perkin Elmer), incubated for 10 minutes at room temperature, washed 3 times using 0.05% of Tween-20/PBS, using an automatic device for washing tablets ELX-405 (BioTek) and counted using a scintillation reader tablets TopCount (Packard).

Analysis of inhibition of GSK-3β person

Compounds were tested for their ability to inhibit human glikogensintetazy-kinase-3 beta (hGSK-3β), with regard to its ability to fosforilirovanii Biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE. Compounds were incubated with 0.5 µci33P-ATP, 10 μm ATP, 0,0125U hGSK-3β (solutions to identify cellular signaling activity from Upstate) and 1 μm substrate (Biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE (SEQ ID NO:3)) in 50 mm HEPES, 10 mm MgCl2, 100 μm Na3VO4, 1 mm DTT, 0,0075% Triton, 2% DMSO (total volume 50 μl) for 30 minutes at room temperature. The incubation was stopped by adding equal volume of 100 mm EDTA, 4 M NaCl2. 80 μl of this mixture was added to streptavidin coated tablets FlashPlates (PerkinElmer). After the stage of leaching,33P incorporation was determined with use is using a liquid scintillation counter for MicroBeta microplate (PerkinElmer). Values IR50was determined by fitting a sigmoidal curve dose-response to account for different concentrations in GraphPad Prism.

Analysis of inhibition of GSK-3α person

Compounds were tested for their ability to inhibit human glikogensintetazy-kinase-3 alpha (hGSK-3α), 0.5 nm final concentration, in relation to phosphorylation Biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE (SEQ ID NO:3). Compounds were incubated with 0.5 CI33P-ATP, 10 M ATP, 0,0125U hGSK-3 (solutions to identify cellular signaling activity from Upstate) and 2 μm of substrate (Biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE) in 50 mm HEPES, 10 mm MgCl2, 100 μm Na3VO4, 1 mm DTT, 0,0075% Triton, 2% DMSO (total volume 50 μl) for 30 minutes at room temperature. The incubation was stopped by adding equal volume of 100 mm EDTA, 4M NaCl2. 80 μl of this mixture was added to streptavidin coated tablets FlashPlates (PerkinElmer). After the stage of leaching was determined33P enable using a liquid scintillation counter for microplates (PerkinElmer). Values IR50was determined by fitting a sigmoidal curve dose-response to the number of pulses at various concentrations in GraphPad Prism.

Analysis of inhibition of JAK2

Activity against Jak2 kinase was determined using a homogeneous, with a time resolution of fluorescence (HTRF) kinase in vitro assays (Mathis, G., HTRF(R) Technology. J Biomol Screen 1999. 4(6):p. 309-34). Specifically, 10 μl of His6-tagged C-end, recombinant human JAK2, amino acids 808-end, expressed by baculovirus in Sf21 cells (Upstate), was mixed with 10 μl of inhibitor (various concentrations, the final concentration of DMSO 2%) and 10 μl of ATP (5 μm final concentration) in reaction buffer (50 mm HEPES, pH 7.5, 10 mm MgCl2, 2 mm MnCl2, 0,1% BSA and 1 mm DTT, final volume of 40 µl). The reaction mixture was initiated by adding 10 ál of Bio-PDK of peptid (Biotin-Ahx-KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC (SEQ ID NO:4), the final concentration of 0.5 mm) in a black 384-well the tablet (Packard). After 60 minutes incubation at room temperature the reaction was suppressed by adding 60 ál of stop/manifesting buffer with 30 mm EDTA, 1 μg/ml streptavidin-APC (Prozyme), 50 ng/ml anti-phosphotyrosine mAb PT66-K cryptit europium, 30 mm HEPES, pH 7.5, 120 mm BCF, of 0.005% Tween-20, 0.05% of BSA). Slaked the reaction mixture was left to stand at room temperature for 1 hour and then read in a fluorescence detector with a time resolution (Envision, Perkin Elmer) at 615 nm and 665 nm simultaneously. The relationship between the signals 615 nm and 665 nm was used to calculate the values IR50.

Methods - analysis of reporter gene β-catenin

Compounds were tested for their ability to modulate β-catenin-modulated gene transcription in LEF/TCF(T cell factor) analysis of the reporter gene. Cells neuroblast the ohms person SY-SY5Y was unstable transfusional using 80 ng/well TOPFLASH plasmid (solutions to identify cellular signaling activity from Upstate), containing two sets of three copies of the TCF binding site, which is located above from timeintensive minimal promoter and an open reading frame luciferase moth, or by using 80 ng/well FOPFLASH plasmids (solutions to identify cellular signaling activity from Upstate), containing three copies of a mutated TCF binding site, which is located above from timeintensive minimal promoter and an open reading frame luciferase borer. In addition, all cells were unstable transliterowany using 20 ng/well pRL-TK plasmid (Promega)containing timeintensity the promoter of the herpes simplex virus, to ensure the levels of expression of Renilla luciferase from low to medium. Environment for transfection was replaced with serum-free medium containing the test substance and incubated for 24 hours at 370C. the Incubation was stopped and the quantitative determination was carried out using the Dual Glo Luciferase Assay (Promega)as specified, and to calculate the used reader Pherastar (BMG).

The luciferase activity of the moth were normalized to the activity of Renilla luciferase per well. Then the normalized TOPFLASH response was compared with the normalized FOPFLASH response, thus receiving a specific signal LEF/TCF. The maximum response is the maximum ratio between normal is organised by the signals TOPFLASH and FOPFLASH. Sigmoidal curves dose-response constructed using the program Graphpad Prism.

Murine model of acute asthma

Female Balb/c mice were purchased from the company Taconic and placed in Abbott Bioresearch Center. Animals were used at the age of 8-12 weeks. All protocols were approved by the Institutional Animal Care and Use Committee (IACUC). Dexamethasone (Dex) and ovalbumin (OVA) was purchased from Sigma. Endotoxin was removed from ovalbumin using DetoxiGel (Pierce), according to the manufacturer's Protocol, and the target substance contained less than 0.1 EU/mg protein. Imject Alum bought the company Pierce.

Animals were senzibilizirani to OVA on day 0 and 7 by intraperitoneally injection of 8 μg OVA in 2 mg alum. On days 14 and 16 animals received intranasal stimulation of 0.3 μg OVA in 50 μl of sterile PBS. Animals administered intraperitoneally injected representative compound of the formula (I) (dissolved with 0.5% HMPC, 0,02% Tween 80 in water) twice a day at doses of 3, 10 and 30 mg/kg/dose, starting at day 13 in the daytime. The final dose of a compound was administered 30 minutes prior to measurement hyperresponsiveness of the Airways (AHR). Dexamethasone was administered orally once a day on days 13-17 at the dose of 3 mg/kg All outcomes were analyzed on day 17 through 24 hours after the second OVA stimulation. AHR was analyzed using whole body plethysmography combined with an unconscious immobilized animals. Briefly, surgically the level of anesthesia was provided by intraperitoneally injection of ketamine and xylazine. Surgically inserted tracheal cannula between the third and fourth tracheal rings. Spontaneous breathing was prevented by intravenous (IV) injection into the jugular vein of pancuronium. Animals were placed in plethysmograph for the study of the whole organism (Buxco) and was carried out by artificial ventilation with 0.2 ml of room air at 150 breaths per minute using an automatic ventilator with controlled volume (Harvard Apparatus). The pressure in the lung and the flow in plethysmography was measured using sensors and lung resistance was calculated as the ratio of pressure/flow using Biosystem Xa. Measured the resistance at baseline, as well as resistance after stimulation methacholine (3, 10 or 30 mg/ml), delivery of which was carried out by using built-in line of the ultrasonic nebulizer. After completion of tests of lung function, the lungs were washed 4 times using 0.5 ml of sterile PBS. The flushing liquid is analyzed for IL-13, Amazo, Muc5ac and cellular infiltrates. The effectiveness of the test compounds were tested at doses of 3, 10 and 30 mg/kg b.i.d (6, 20, 60 mg/kg/day). Stimulation by OVA caused the increase of the resistance of the lungs to 6.90 cm H2O/ml/sec against the 4.65 cm H2O/ml/sec in animals stimulated using PBS. Education is denied mice of the test compound significantly inhibited (p< 0.001) metacholine-induced respiratory resistance to 4,55 cm H2O/ml/sec and 4,77 cm H2O/ml/sec at doses ranging from 1 to 100 mg/kg For the preferred compounds necessary dose less than 50 mg/kg for the occurrence of a specified response. For the most preferred compounds necessary dose of less than 30 mg/kg for the occurrence of a specified response. This inhibition was equivalent to the values obtained in the group with PBS-stimulation (4,65 cm H2O/ml/sec) and in the processing group 3 mg/kg dexamethasone (4,76 cm H2O/ml/sec).

Measurement of IL-13: concentration of IL-13 in bronchoalveolar washing fluid (BAL) was measured using ELISA (R & D Systems)according to the manufacturer's instructions. The concentration of IL-13 in BAL fluid were significantly induced to 102.5 PG/ml in OVA-induced mice compared with the levels defined below in PBS-stimulated group. Significant inhibition of this induction (p<0,05) 60% was observed after administration of the test compounds at a dose of 30 mg/kg had No significant inhibition in groups a dose of 3 mg/kg or 10 mg/kg

Measurement Amazy: the activity of the acidic chitinases mammals (Amazy) was determined in 1:10 dilution of BAL fluid from 0.01% BSA, 30 mm sodium citrate, 60 mm sodium phosphate, pH 5.2, in the presence of 80 μm 4-methylumbelliferyl β-D-N,N'-deacetylate is Yoshida. The reaction mixture was incubated for 15 minutes at room temperature and the reaction was suppressed by adding 100 μl of 1 M glycine/NaOH pH of 10.6. The formation of the product was determined by the method of fluorescence emission at 460 nm with excitation at 385 nm, using fluorometry Fluorskan Ascent. Induction activity Amazy to 28,5U was observed in OVA-stimulated animals, compared with 2,17U in PBS-stimulated animals. Significant inhibition of this induction (p<0,01) 35% was observed after administration of the test compounds in group a dose of 30 mg/kg

Measurement of MUC5AC: the concentration of mucin gene MUC5AC was determined in the format of ELISA. Briefly, BAL samples were diluted 1:2 in buffer (2% BSA in PBS) and were sown in 96-well plates to high binding protein (Costar) and dried. After a series of washes for 1 hour was added a 1:100 dilution of biotinylated MUC5AC antibody (Clone 45M, Lab Vision). The tablets were washed and added to the tablet 1:3000 dilution of streptavidin-HRP (Southern Biotech) for 15 minutes. The tablets were then shown using TMB substrate (Sigma) for 30 minutes. The reaction was stopped using 1M H2SO4and then the tablets were read in a spectrophotometer at OD 450 nm. The levels of MUC5AC was reduced by more than 50% after administration of the test compounds.

Determination of antinociceptive effect: models of neuropathic pain

Model neuropathy eskay pain, caused by legirovaniem spinal nerve (L5/L6). As was described previously, Kim and Chung (Kim, S. H.; Chung J.M. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50, 355-363), did a 1.5 cm incision dorsal to lumbosacral plexus. The shot rats paraspinal muscles (left side) were separated from the spinous processes, L5 and L6 spinal nerves were isolated and tightly ligated 3-0 silk threads. After hemostasis, the wound was sutured and smeared ointment on the basis of the antibiotic. The rats were allowed to recover and then put it in a cage with soft bedding for 14 days before behavioral testing for mechanical allodynia.

Model of neuropathic pain caused by legirovaniem sciatic nerve. As has been described in detail previously (Bennett and Xie (Bennett G. J.; Xie Y-K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33, 87-107), shot rats did 1.5 cm incision of 0.5 cm below the pelvis and released the femoral biceps muscle and outer gluteal muscles (right side). The sciatic nerve was exposed, allocated and applied around him four loose ligatures (5-0 chromic catgut) with a separation of 1 mm, the Rats were allowed to recover and then put it in a cage with soft bedding for 14 days before behavioral testing for mechanical allodynia, as described above. In addition, animals were also tested on cold allodynia, is the kunai their hind foot bath with cold water (4,5°C) and determining the latency otdergivanija paws.

Selected analogs of compounds of formula (I), which was administered or administered intraperitoneally or orally, showed more than 30% inhibition of tactile-allodynia in models of neuropathic pain Chung and Bennett described in this application, at doses in the range 1-150 mg/kg

Summarizing the above, a representative compound of the formula (I) in a murine model of acute asthma was effective in the inhibition of airway resistance at a dose in the range from 1 to 100 mg/kg Treatment using high-dose (30 mg/kg) also inhibited IL-13 induction and activity Amazy and MUC5AC levels in BAL fluid.

Representative compounds of formula (I) in the rat models of neuropathic pain have been effective, as was demonstrated more than 30% inhibition of tactile-allodynia at doses in the range 1-150 mg/kg

The compounds of formula (I), has been found to inhibit human ROCK-2, His-tagged at the N end of GSK-3β, human GSK-3β, His6-tagged recombinant chelovecheski JAK2 and luciferase moth, demonstrating the value IR50from about 1.0 μm to about 10 μm, preferably, from about 100 nm to about 1.0 μm. More preferably, the compounds of formula (I), has been found to inhibit human ROCK-2, His-tagged at the N end of GSK-3β, human GSK-3β, His6-tagged, recombinant chelovecheski JAK2 and luciferase Motyl is a, demonstrating the value IR50from about 10 nm to about 100 nm and most preferably less than 10 nm. In addition, some compounds of formula (I) demonstrated inhibition of human ROCK-2 selectivity more than 10 times greater compared to a panel of 50 kinase targets. Some compounds of formula (I) demonstrated inhibition of human GSK-3β with a selectivity of more than 10 times greater compared to a panel of 50 kinase targets. Some compounds of formula (I) demonstrated inhibition of His6-tagged recombinant human JAK2 with a selectivity of more than 10 times greater compared to a panel of 50 kinase targets.

Methods introduction

The present invention also provides pharmaceutical compositions which include the compounds of the present invention. Pharmaceutical compositions include compounds of the present invention, formulated together with one or more non-toxic pharmaceutically acceptable carriers.

The pharmaceutical compositions of the present invention can enter humans and other mammals orally, rectally, parenterally, intracisternally, intrawaginalno local path (for example, in the form of powders, ointments or drops), buccal or oral or nasal spray. The term "p is interline", as used in this application relates to methods of introduction, which include intravenous, intramuscular, intraperitoneally, intrasternal, subcutaneous and intraarticular injection and infusion.

The term "pharmaceutically acceptable carrier", as used in this application, means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating substance or excipients for the formulation of any type. Some examples of substances which can serve as pharmaceutically suitable carriers include sugars, such as, but not limited to, lactose, glucose and sucrose; starches such as, but not limited to, corn starch and potato starch; cellulose and its derivatives, such as, but not limited to, sodium carboxymethyl cellulose, ethylcellulose and cellulose acetate; powdered tragakant; malt; gelatin; talc; excipients, such as, but not limited to, cocoa butter and waxes for suppositories; oils, such as, but not limited to, peanut oil, cotton seeds, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; esters, such as, but not limited to, etiloleat and tillaart; agar buffer substances, such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; ringer's solution; ethyl alcohol and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweeteners, fragrances and flavors, preservatives and antioxidants can also be present in the composition, at the discretion of the specialist, which is the composition.

The pharmaceutical compositions of the present invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for recovery in sterile solutions or dispersions for injection immediately before use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or excipients include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), vegetable oils (such as olive oil), organic esters for injection (such as etiloleat), and suitable mixtures of these substances. Proper fluidity can be maintained, for example, by use of which the materials of the coating, such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surface-active substances.

These compositions can also contain adjuvants such as preservatives, specialsee substances, emulsifiers and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, fenolcarbonove acid and the like. Also, it may be desirable inclusion isotonic substances, such as sugars, sodium chloride and the like. Prolonged absorption of a pharmaceutical preparation for injection can be achieved by inclusion of substances which delay absorption such as aluminum monostearate and gelatin.

In some cases, for the prolongation of drug action, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be done by using a liquid suspension of crystalline or amorphous material with poor water-solubility. The rate of absorption of the drug will depend on its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of parentera is LNA input of the dosage form provided by the dissolution or suspension of the drug in an oil medium.

Depot injections are produced by education microencapsulated matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending on the relationship of drug to polymer and the nature of the particular polymer used, you can kontrolirovat the rate of release of the drug. Examples of other biodegradable polymers include poly(orthoevra) and poly(anhydrides). Depot injections also produced by capture of the drug in liposomes or microemulsions which are compatible with body tissues.

Compositions for injection can be sterilized, for example, by filtration through a retaining bacteria filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersing in sterile water or other sterile environment for injection immediately before use.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms the active compound may be mixed with at least one inert, pharmaceutically suitable carrier or excipient, such as sodium citrate or dicalcium phosphate and/or a) fillers or creating about what to eat substances, such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and the Arabian gum; c) humectants such as glycerol; d) disintegrants, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; (e) slow dissolving agents such as paraffin; f) absorption accelerators such as Quaternary ammonium compounds; (g) socialsim agents such as cetyl alcohol and glycerylmonostearate; h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures of such substances. In the case of capsules, tablets and pills, the dosage form may also include a buffering agent.

Solid compositions of a similar type can also be used as fillers in gelatin capsules with hard and soft filling, using such media as lactose or milk sugar and high molecular weight glycols and similar substances.

Solid dosage forms such as tablets, coated tablets, capsules, pills and granules can be obtained with coatings and shells, tecimical intersolubility coatings and other coatings, well known in the formulation of pharmaceutical compositions. They optionally may contain substances that make the drug opaque, and may have such a composition that allows them to release the active ingredient(ingredients) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of compositions for filling a drug that can be used include polymeric substances and waxes.

The active compounds can also be microencapsulating form if it is appropriate, with one or more of the above media.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents conventionally used in this field, such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol, dimethylformamide, oils (in particular, oil seeds, cotton, peanut oil, corn oil, germ oil oilseeds, olive oil, castor m the words and sesame oil) glycerin, tetrahydrofurfuryl alcohol, polyethylene glycols and esters of fatty acids sorbitan, and mixtures of such substances.

Besides inert diluents, the oral compositions can also include adjuvants, such as specialsee substances, emulsifiers and suspendresume agents, sweeteners, fragrances and flavorings.

Suspensions, in addition to the active compounds, may contain suspendresume substances, for example, ethoxylated isostearyl alcohols, polyoxyethylenated and esters sorbitan, microcrystalline cellulose, Metagalaxy aluminum, bentonite, agar-agar, tragakant and mixtures of such substances.

Compositions for rectal or vaginal administration, preferably, are suppositories which can be obtained by mixing the compounds of the present invention with suitable non-irritating carriers or excipients, such as cocoa butter, polyethylene glycol or wax for suppositories, which are solid at room temperature, but liquid at body temperature and therefore melt in the rectum or vagina and release the active compound.

Compounds of the present invention can also be entered in the form of liposomes. As is known from the prior art, liposomes, generally derived from phospholipids or other lipid substances the TV. Liposomes formed from one layer or multi - layer of hydrated liquid crystals that are dispersed in the aquatic environment. You can use any non-toxic, physiologically acceptable and metabolisable a lipid capable of forming liposomes. The compositions of the present invention in the form of liposomes can contain, in addition to the compounds of the present invention, stabilizers, preservatives, excipients and the like substances. The preferred lipids are natural and synthetic phospholipids and phosphatidylcholine (lecithins), which are used separately or together.

The method of the formation of liposomes are known in the prior art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq.

Dosage forms for topical administration of the compounds of the present invention include powders, sprays, ointments and preparations for inhalation. The active compound can be mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffer substances or propellants that may be required. Preparations for introduction into the eye, eye ointments, powders and solutions are also provided as included in the scope of the present invention.

The actual dose levels of active ingredients in the pharmaceutical compositions of the present invention can in order to harirawati so, to get the number of active connections(connections), which is effective to achieve the desired therapeutic response for a particular patient, compositions and mode of administration. The choice of dose level will depend on the activity of the particular compound, the route of administration, the severity of the condition to be treated, and the condition and prior medical history of the patient to be treated.

When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be used in pure form, where such forms exist, in the form of a pharmaceutically acceptable salt of ester or prodrug. The phrase "therapeutically effective amount" of the compounds of the present invention means an amount of compound sufficient to treat disorders, at a reasonable relation to the benefit/risk applicable to any medical treatment. However, it should be clear that the total daily dose of the compounds and compositions of the present invention depends on the opinion of the attending physician, within reasonable medical practice. The specific level of therapeutically effective dose for any particular patient will depend on many factors including the disorder to be treated, and the severity of the disorder; activity of the specific the CSOs used connection; the specific composition; the age, body weight, General health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound; the duration of the treatment; drugs used in combination or simultaneously with the particular compound used; and like factors well known in medicine.

The term "pharmaceutically acceptable salt", as used in this application, refers to salts derived from inorganic or organic acids. Salts can be obtained in situ during the final isolation and purification of the compounds of formula (I), or they can be obtained separately by reacting the free base form of the compounds of formula (I) with inorganic or organic acid. Representative acid additive salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, bansilalpet, bisulfate, butyrate, comfort, camphorsulfonate, digluconate, glycyrrhizinate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic (isetionate), lactate, maleate, fumarate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, sulphate, (L) tartrate, (D) - tartrate, (DL) tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluensulfonate, undecanoate.

The term "pharmaceutically acceptable prodrug" or "prodrug", as used in this application is such prodrugs of the compounds of the present invention, which, in accordance with the common medical assessment, are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reactions and other Prodrugs of the present invention can quickly be converted in vivo into compounds of formula (I), for example, by hydrolysis in blood.

The present invention provides compounds of formula (I)formed by synthetic means or formed by biopreparation in vivo.

Compounds of the present invention may exist in resolutiony, as well as in solvated formic, including hydrated forms, such as polyhydrate. As a rule, the solvated forms with pharmaceutically acceptable solvents such as water and ethanol, among others, are equivalent nonsolvated forms for the purposes of the present invention.

The total daily dose of the compounds of the present invention for administration to a human or lower animal may be in before the lah from about 0.003 to about 30 mg/kg/day. For oral administration is preferable doses can be in the range of from about 0.01 to about 10 mg/kg/day. If desired, the effective daily dose can be divided into multiple doses for purposes of administration; therefore, the composition containing a single dose, may contain such amounts or fractional part of the dose that make up the daily dose.

Protein kinases can be divided into broad groups based on the identity of amino acids(amino acids)to which they are targeted (serine/threonine, tyrosine, lysine and histidine). For example, the tyrosine kinases include receptor of the tyrosine kinase (RTK), such as growth factors, and preceptories the tyrosine kinases, such as src family kinases. There are also protein kinase with dual specificity, which aimed at tyrosine and serine/threonine, such as cyclin-dependent kinase (CDK) and mitogenactivated protein kinase (MAPK).

The tyrosine protein kinase (PTK) form a large family of kinases, which regulate the transmission of signals from cell to cell, which are involved in growth, differentiation, adhesion, motility and death (Pearson, M. et al., In Protein Tyrosine Kinases; Fabbro, D., McCormick, F., Eds.; Humana Press Inc., 2006; pp 1-29.). Members of the family of tyrosine kinases include, but are not limited to this, Yes, BMX, Syk, EphA1, FGFR3, RYK, MUSK, JAK1 and EGFR. The tyrosine kinases are divided into two classes, and the time, the tyrosine kinase receptor type and precepting type. Interestingly, the entire family of tyrosine kinases consists of at least 90 characterized kinases, of which at least 58 kinase receptor type and at least 32 kinase precepting type, and includes at least a total of 30 subselect. The tyrosine kinases are associated with various human diseases, including diabetes and cancer (Pearson, M. et al., In Protein Tyrosine Kinases; Fabbro, D., McCormick, F., Eds.; Humana Press Inc., 2006; pp 1-29.). The tyrosine kinases are often involved in most forms of malignant diseases and are associated with a wide variety of congenital syndromes (Robertson et al., Trends Genet. 16:265-271, 2000). Preceptories the tyrosine kinases are a group of intracellular enzymes that do not have extracellular and transmembrane sequences. Currently identified more than 32 families preceptory of tyrosine kinases (Robinson et al., Oncogene 19, 5548-5557, 2000). Representative examples include Src, Btk, Csk, ZAP70 and Both families. In particular, the Src family is the largest family preceptory of tyrosine kinases, consisting of Src, Yes, Fyn, Lyn, Lck, Blk, Hck, Fgr and Yrk tyrosine protein kinases. Src family kinases is associated with oncogenesis, cell proliferation and tumor progression. It was found that many of tyrosine protein kinases Uch is contained in cell signaling pathways, associated with various pathological conditions including, but not limited to, cancer and hyperproliferative disorders and immune disorders.

Cyclin-dependent kinase CDK are a group of intracellular enzymes, which control the passage through the cell cycle and play an essential role in cell proliferation (Cohen, P. Nature Reviews Drug Discovery 1, 309-315, 2002). Representative examples of cancers include, but are not limited to, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 7 (CDK7), cyclin-dependent kinase 6 (CDK6) and protein 2, controlling cell division (CDC2). CDK involved in the regulation of transitions between different phases of the cell cycle, for example, the transition from the resting stage in G1 (gap between mitosis and the beginning of DNA replication for a new cell division cycle to the S phase (the period of active DNA synthesis), or the transition from G2 to M phase, in which there is an active mitosis and cell division (Rowell et al. Critical Reviews in Immunology 26(3), 189-212, 2006). CDK complexes are formed through the Association of regulatory cyclenbuy subunit (e.g., cyclin A, B1, B2, D1, D2, D3 and E) and a catalytic kinase subunit (e.g., cdc2 (CDK1), CDK2, CDK4, CDK5 and CDK6). CDK demonstrate absolute dependence on cyclenbuy subunit to fosforilirovanii their substrates on which they are aimed, and different pairs kinase/cyclin possess the function to regulate the Finance promotion through specific parts of the cell cycle. In addition, CDK involved in a variety of painful conditions, including but not limited to, state, showing the phenotype of the cancer, various neoplastic disorders, and neurological disorders (Pallas et al. Current Medicinal Chemistry: the Central Nervous System Agents 5(2), 101-109, 2005).

Mitogenactivated protein (MAP) kinase involved in signal transduction to the cell nucleus in response to extracellular stimuli. Representative examples of MAP kinases include, but are not limited to, mitogenactivated the protein kinase 3 (MAPK3), mitogenactivated the protein kinase 1 (ERK2), mitogenactivated the protein kinase 7 (MAPK7), mitogenactivated the protein kinase 8 (JNK1), mitogenactivated the protein kinase 14 (p38 alpha), mitogenactivated the protein kinase 10 (MAPK 10), JNK3 alpha protein kinase, straksaktivering the protein kinase JNK2 and mitogenactivated the protein kinase 14 (MAPK14). MAP kinases are a family of Proline-directed serine/treoninove kinases, which mediate signal transduction from extracellular receptors or heat shock or UV radiation (Barr et al., Trends in Pharmacological Sciences, 27(10), 525-530, 2006). MAP kinases are activated through phosphorylation of threonine and tyrosine with dual specificity by protein kinases, including the tyrosine kinases, such as growth factors. Cell proliferation and differentiation, as has been shown, under reg is Torno control different MAP kinase cascades (Sridhar et al., Pharmaceutical Research, 17:11 1345-1353, 2000). Thus, MAP kinase path plays a critical role in a variety of painful conditions, for example, defects in the activities of MAP kinases have been shown to lead to aberrant cell proliferation and carcinogenesis (Qi et al., Journal of Cell Science 118(16), 3569-3572, 2005). Moreover, the activity of MAP kinase is also associated with insulin resistance associated with type 2 diabetes (Fujishiro et al. Recent Research Developments in discrimination 1(Pt. 2), 801-812, 2003).

p90 Ribosomal S6 kinase (Rsk) are serine/threonine kinases that play a role in mitogenactivated cellular growth and proliferation, differentiation and cell survival. Examples of members of the Rsk family of kinases include, but are not limited to, the ribosomal S6 protein kinase, 90 kDa, polypeptide 2 (Rsk3), the ribosomal S6 protein kinase, 90 kDa, polypeptide 6 (Rsk4), the ribosomal S6 protein kinase, 90 kDa, polypeptide 3 (Rsk2) and the ribosomal S6 protein kinase, 90 kDa, polypeptide 1 (Rsk1/p90Rsk). Members of the Rsk family associated with activated extracellular signal kinase and phosphoinositidedependent protein kinase 1 (Frodin and Gammeltoft, Mol. Cell. Endocrinol. 151, 65-77, 1999). Under normal conditions RSK kinase localized in the cytoplasm of the cells, while stimulation of the mitogen-activated (fosforilirovaniye associated with extracellular signal kinase) RSK transient image moves to the plasma membrane is wound, where they become fully activated. Fully activated RSK phosphorylates substrates involved in cell growth, proliferation, differentiation and cell survival (Clark et al. Cancer Research 65, 3108-3116, 2005). RSK signaling pathway is also associated with modulation of the cell cycle (Gross et al., J. Biol. Chem. 276, 46099-46103, 2001). On currently available data suggest that small molecules that inhibit Rsk, can be useful therapeutic tools for the prevention and treatment of cancer and inflammatory diseases.

Members of the family of checkpoint kinases (CHK) are serine/threonine kinases that play an important role in the development of the cell cycle. Examples of family members of checkpoint kinases include, but are not limited to, CHK1 and CHK2. Kinase checkpoints are control systems that coordinate the development of the cell cycle, affecting the formation, activation and subsequent inactivation of cyclin-dependent kinases. Kinase checkpoint prevent the development of the cell cycle at the wrong time, maintain metabolic balance of cells in the “stop” cells at a particular point in the cell cycle and, in some cases, can induce apoptosis (programmed cell death)when is the requirement of the control points were not satisfied (Nurse, Cell, 91, 865-867, 1997; Hartwell et al., Science, 266, 1821-1828, 1994). Members of the family kinases control points associated with proliferative disorders phenotypes of cancer and other diseases associated with damage and DNA repair (Kumagai and Dunphy, Cell Cycle, 5, 1265-1268 (2006); Xiao et al., Molecular Cancer Therapeutics 5, 1935-1943, 2006).

Kinase Aurora are a multigene family of mitotic serine-treoninove kinase, which functions as a new class of oncogenes. These kinases include aurora-A and aurora-b Kinase Aurora hyperactivity and/or over-expressed in some ό tumors, including, but not limited to, breast cancer, ovarian, prostate, pancreas and colorectal cancer. In particular, aurora-A is centrosomal kinase, which plays an important role in the development of cell cycle and cell proliferation. Aurora-A is located in a region of chromosome 20q13, which often amplificates in some different types of malignant tumors, such as colorectal cancer, breast cancer and bladder. Also there is a strong correlation between aurora-A and high histo-prognostic level aneuploidy that makes this kinase is a potential prognostic vector. The inhibition activity of the aurora kinase may reduce cell proliferation, tumor growth and potentially carcinogenesis. P is a fractional function of the kinase aurora presented in the Journal of Cell Science, 119, 3664-3675, 2006.

Rho-associated, containing coiled spiral serine/threonine protein kinase ROCK-1 and ROCK-2, considered to play a major role in cytoskeletal dynamics, acting as below effectors of the Rho/Rac family is activated by cytokines and growth factors small GTP. ROCK phosphorylate a variety of substrates, including, but not limited to, phosphatase light chain of myosin, light chain of myosin, Ezrin-radixin-MouseMove proteins and LIM (Lin11, Is1l and Mec3) kinase. ROCK also mediate the formation of actin stress fibers and focal adhesion in different types of cells. ROCK play an important role in cell migration by enhancing cellular contractility, and they are necessary for retraction tails monocytes and cancer cells. Inhibitors of ROCK, as also was shown to reduce the spreading of tumor cells in vivo. Recent experiments have identified new features of ROCK in cells, including centrosomal the location and regulation of the size of the cells, which may contribute to various physiological and pathological conditions (Mueller et al, Nature Reviews Drug Discovery 4, 387-398, 2005). Members of the ROCK family are attractive targets for intervention in different pathologies, including cancer and cardiovascular disease. The ROCK inhibitors may be useful therapeutic environments is Tami for the treatment of hypertension, angina and asthma. In addition, Rho, assumed to play a role in peripheral circulatory disorders, arteriosclerosis, inflammation and autoimmune diseases and, thus, represents a useful target for therapy (Shimokawa et al, Arteriosclerosis, Thrombosis and Vascular Biology, 25, 1767-1775, 2005).

Limited success pharmacotherapeutic approaches in spinal cord injury attributed in large part to the inability of damaged nerve fibers in the white matter of the human spinal cord to restore growth and to re-establish synaptic contacts with their disjointed partners neurons. Aggressive microenvironment, characterized by the presence of a large diversity of molecular inhibitors of the growth of neuritis on the lesion, scar tissue and on the Central nervous system myelin, is the cause of this irreversible stopping of the growth of neuritis. In tissue culture, these inhibitors of the growth of neuritis often induce dramatic responses, including the collapse of education and the loss of neuritis. Scar tissue in the brain and spinal cord of the person is strong and persistent barrier to any regeneration growth of neuritis, and ROCK inhibitors could help damaged fibers to grow or spread beyond this inhibiting the regeneration of tissue. Various facts indicate that the result is avridine the brain and spinal cord there is a strong activation of the RhoA-ROCK pathway. Due to the constant presence of inhibitors of the growth of neuritis on the lesion or around it and in CNS myelin, such activation could potentially persist for a long time, making inhibition of ROCK an attractive target not only for the emergency treatment of acute and sub-acute cases, but also for the chronic treatment of spinal cord injury. Inhibition of ROCK in two different small molecules inhibitors ROCK (Y-27632 and fasudil) stimulated or accelerated functional recovery in various models of spinal cord injury in rats and mice at their local or systemic administration immediately after injury in the form of a single dose or in several weeks (Dergham, P. et al. Rho signaling pathway targeted to promote spinal cord repair. J. Neurosci. 22, 6570-6577, 2002; Hara, M. et al. Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J. Neurosurg. Spine 93, 94-101, 2000.; Fournier, A. E. et al. ROCK inhibition enhances axonal regeneration in the injured CNS. J. Neurosci. 23, 1416-1423, 2003; Sung, J. K. et al. A possible role of RhoA/Rho-kinase in experimental spinal cord injury in the rat. Brain Res. 959, 29-38, 2003; Tanaka, H. et al. Cytoplasmic p21(Cipl/WAFl) enhances axonal regeneration and functional recovery after spinal cord injury in rats. Neuroscience 127, 155-164, 2004). In these studies, inhibition of ROCK not only increased the growth of nerve fibers outside of the affected area, but also had a neuroprotective effect and reduced tissue damage and the formation of voids. Based on these studies in rodents inhibitors ROCK, which have neuroprotective and stimulating neuroregeneration action, could bring significant benefits to patients with spinal cord injury. In addition, they could normalize the blood flow in the spinal cord, due to their vasodilating effect, thus, further contributing to the conservation of the fabric.

Pathologically, Alzheimer's disease is characterized at the microscopic level of intracellular neurofibrillary plexuses and extracellular amyloid aggregates. Neurofibrillary plexus contain aberrant phosphorylated tau protein associated with the microtubule protein and substrate for ROCK, whereas amyloid aggregates are formed primarily through the use of toxic amyloid-β (Aβ) peptides having a length of 42-amino acids. Recently it was shown (Zhou, Y. et al. Nonsteroidal anti-inflammatory drugs can lower amiloidogenic Aβ42 by inhibiting Rho. Science 302, 1215-1217, 2003)that in cells secreting Aβ42, and transgenic PDAPP MICE, producing large amounts of Aβ42, some non-steroidal anti-inflammatory drug (NSAID) reduced the level of Aβ42 by inhibiting RhoA-ROCK pathway. The ROCK inhibitor, Y-27632, was effective in reducing the levels of Aβ42 in cell culture and in PDAPP transgenic mice when introduced by intracerebroventricular injection. Activation of Rho by geranylgeranylpyrophosphate, whether the home, required for membrane attachment Rho, increased Aβ42 levels; this increase was completely prevented by using Y-27632. The ROCK inhibitor, Y-27632, which is used in animal models of Alzheimer's disease, was effective, causing a reduction in the number of levels of toxic Aβ42, but had no effect on overall levels of Aβ, and the effect of inhibitors of Rho or ROCK is at least one mechanism by which NSAIDs reduce Aβ42 levels. In addition to many other therapeutic interventions, these inhibitors have such a well-confirmed documentary advantage, which is to stimulate renewed growth of neuritis, and therefore it is possible that inhibition of this pathway may lead to the recovery of amyloid-damaged neural circuits.

The most important in the pathogenesis of the disease is the migration of leukocytes outside the endothelial brain in the Central nervous system and the inflammatory cascade stimulated these cells, which ultimately leads to demyelination of the sections of the fibers of the Central nervous system and damage to and loss of neuritis. Leukocytes are in need of active RhoA and ROCK for them to progress beyond the endothelium of the brain, because of their TRANS-endothelial migration was prevented by the ROCK inhibitor Y-2763294.

Neuroprotective effect of ROCK inhibitors fasudil and hydroxybutyl not limited to models of spinal cord injury, but there have also been reports that the effect in cerebral multi-infarct models gerbils and rats (! Y, Satoh S, Ikegaki I, Asano T. A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor. Stroke 31, 2245-2250, 2000; Satoh, S. et al. Pharmacological profile of hydroxy fasudil as a selective ROCK inhibitor on ischemic brain damage. Life Of Si. 69, 1441-1453, 2001; Kitaoka, Y. et al. Involvement of RhoA and possible neuroprotective effect of fasudil, a ROCK inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res.l018, 111-118, 2004). In models of stroke in rodents, some inhibitors of regeneration, such as ROCK-activating NgR1 complex and one of its ligands, NOGO-A, were neutralized after 24 hours or even 1 week after the induction of cerebral stroke, and watched improved functional recovery (Lee, J. K., Kim, J. E., Sivula, M. & Strittmatter, S. M. Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J. Neurosci. 24, 6209-6217, 2004; Wiessner, C. et al. Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats. J. Cereb. Blood FlowMetab. 23, 154-165, 2003). Blocking ROCK is therefore achievable neuroregenerative strategy; in addition, this strategy has the advantage consisting in the fact that therapeutic window for the use of these inhibitors may be greater than for thrombolytic or neuroprotective treatment options blow.

Damage to nerve cells in the peripheral nervous system or Central nervous system can lead to chronic pain, known for the AK neuropathic pain. Recently it has been shown that inflammatory mediators, such as lysophosphatidic acid (LPA), which is produced in response to injury, involved in the initiation of neuropathic pain in rat models of peripheral nerve injury (Inoue, M. et al. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nature Med. 10, 712-718, 2004). LPA is present at sites of lesions in the peripheral nervous system and Central nervous system and exerts its function by binding to G-protein-coupled LPA receptors, leading to activation of the RhoA-ROCK pathway. The ROCK inhibitor, Y-27632, preventing the initiation of neuropathic pain after nerve damage or LPA injection, then another ROCK inhibitor H-1152, alleviates neuropathic pain model dissection of the spinal nerve L5 (Tatsumi, S. et al. Involvement of Rho-kinase in iflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS). Neuroscience 131, 491-498, 2005). The results of these tests show that the ROCK is a potential target for drugs, which is responsible for the induction and maintenance of chronic pain States.

Moreover, Schueller et al. (Abstract 1216, 8th World Congress on Inflammation, Copenhagen, DenMark, June 16-20, 2007) demonstrated that SLx-2119, orally bioavailable, potent and highly selective inhibitor of ROCK 2, reduces atherogenesis in the presence of highly elevated levels of lipids in groups of 8 with ApoE-Ko mice, what this suggests, that selective inhibition of ROCK 2 has the potential limitations of atherosclerosis.

70 kDa ribosomal S6 kinase (p70S6K) is activated by various mitogens, growth factors and hormones. The p70S6K activation occurs through phosphorylation at different sites, and the main target of the activated kinase is a 40S ribosomal protein S6, a major component of the mechanism that is involved in protein synthesis in mammalian cells. In addition, activation of p70S6K is associated with control of cell cycle, differentiation of nerve cells, regulation of cell motility and cell response, which is important for tumor metastasis, immune system and restore tissue. Modulation of the activity of p70S6 kinase may also have therapeutic application in disorders such as cancer, inflammation and various neuropathie. A detailed discussion of p70S6K kinases can be found in Prog. Cell Cycle Res., 1, 21-32, 1995, and in Immunol. Cell Biol. 78, 447-51, 2000.

Glikogensintetazy-kinase 3 (GSK-3) is a widely expressed, constitutively active serine/threonine kinase, which phosphorylate cellular substrates and thereby regulates a wide variety of cellular functions, including development, metabolism, gene transcription, protein translation, cytoskeletal organization, cell cycle regulation and apoptosis. GSK-3 was originally describe what and how key enzyme involved in the metabolism of glycogen, but it is now known that it regulates a wide range of cellular functions. Were previously identified two forms of this enzyme, GSK-3+ƒ and GSK-3+ƒ. The activity of GSK-3+ƒ negatively regulated by protein kinase B/Akt and signaling by Wnt. Therefore, small molecules that are inhibitors of GSK-3 may have some therapeutic applications, including treatment and prevention of neurodegenerative diseases and stimulation of neurogenerative with various neurological disorders (Gartner et al. J. Cell Science, 2006, 119, 3927-3934. Zhou et al. Neuron, 2004, 42, 897-912), diabetes type II, bipolar disorders, stroke, cancer, osteoarthritis, osteoporosis, rheumatoid arthritis (Cuzzocrea et al. Clinical Immunology, 2006, 120, 57-67) and chronic inflammatory disease. Overview: Kockeritz et al., Current Drug Targets, 7, 1377-1388, 2006. Overview neurological applications: Current Drug Targets, 7(11), 1389-1397 and 1399-1409, 2006.

Protein kinases have become attractive targets for cancer treatment (Fabbro et al., Pharmacology & Therapeutics 93:79-98, 2002). Assume that the participation of protein kinases in the development of human malignancies can occur through the following: (1) genomic rearrangement (e.g., BCR-ABL in chronic myelogenous leukemia), (2) mutations leading to constitutive active kinase activity, for example, acute myelogenous leukemia and gastrointestinal op is Holi, (3) impaired regulation of kinase activity by activation of oncogenes or loss of function of tumor suppressor gene, such as for cancer with oncogenic RAS, (4) impaired regulation of kinase activity as a result of over-expression, as in the case of EGFR, and (5) ectopic expression of growth factors, which may contribute to the development and preservation of tumor phenotype (Fabbro et al., Pharmacology & Therapeutics 93:79-98, 2002).

Some cancers are associated with angiogenesis. Angiogenesis is the growth of new capillary blood vessels from pre-existing vascular network (Risau, W., Nature 386:671-674, 1997). It was shown that protein kinases may contribute to the development and preservation of tumor phenotype (Fabbro et al., Pharmacology & Therapeutics 93:79-98, 2002). For example, A VEGF-D and their four receptor are associated with phenotypes that include neovascularization and increased vascular permeability, such as tumor angiogenesis and lymphangiogenesis (Matter, A., Drug Discov. Today 6:1005-1023, 2001).

It was recognized that the approach based on a single tool, which is specifically aimed at one kinase or one kinase a pathway may be insufficient for the treatment of diseases and disorders, in particular cancer, for some reason. Models suggest that you need from 5 to 7 mutations to transform normal cells in slok the quality. In addition, it is widely accepted that cancer is a result of changes in several ways, in particular, proteinkinase ways that are associated with such processes as cell growth, proliferation, apoptosis, motility or invasion. In most cancers, a common characteristic is the simultaneous overexpression and/or hyperactivation of various protein kinases, such as receptor and preceptories kinase, serine/threonine kinase, P13 kinase and associated with the cell cycle kinase. Actually, some of these kinases, either alone or in combination with other kinase involved in various processes important for cell survival, proliferation, growth and malignant transformation, motility and invasion, leading to metastasis and angiogenesis or inflammation, and diseases, disorders and conditions associated with them.

Therefore, blocking one of kinase targets may be clinically inadequate, because there are multiple targets, which are kinases that affect the progression of the condition, disease or disorder. In addition, blocking one of kinase targets may be clinically inadequate because of the excessive kinase-mediated pathways and alternative oncogenic or inflammatory mechanisms may compensate for nl is keravnou kinase target. Furthermore, the use of one tool may also increase the likelihood of developing resistance to this drug.

Cardiovascular disease is responsible for almost a quarter of the total annual mortality worldwide. Vascular disorders such as atherosclerosis and restenosis, are the result of violations of the growth of blood vessels and restrict blood flow to vital organs. Various kinase path, such as JNK, are activated atherogenic stimuli and regulated through the local production of cytokines and growth factors in cells of blood vessels (Yang et al., Immunity 9:575, 1998). Ischemia and ischemia with reperfusion in the heart, the kidney or the brain lead to cell death and scarring, which can result in congestive heart failure, renal failure or cerebral dysfunction. For organ transplant reperfusion of previously ischemic donor organs leads to acute leukocyte-mediated tissue damage and slow graft function. The way ischemia and reperfusion mediated by various kinases. For example, JNK path associated with leukocyte-mediated tissue damage (Li et al., Mol. Cell. Biol. 16:5947-5954, 1996). And finally, enhanced apoptosis in cardiac tissues is also associated with kinase activity (Pombo et al., J. Biol. Chem. 269:26546-26551, 1994).

1. The compound of formula (I)

or its pharmaceutically acceptable salt, where
But a


R1represents hydrogen or RaRbN;
R2represents hydrogen;
R3represents alkyl, alkoxy, aryl, cyano, cycloalkyl, halogen, halogenated, heteroaryl, nitro, or RgRhN-;
Raand Rbeach represents hydrogen;
Rgand Rheach independently represent hydrogen, C1-10alkyl or C1-10alkylsulphonyl;
Ri, Rii, Riii, Riv, Rv, Rvi, Rvii, Rviii, Rix, Rx, Rxi, Rxii, Rxiii, Rx1v, Rxv, Rxvi, Rxviiand Rxviiieach independently represent a1-10alkoxy, C1-10alkoxy-C1-10alkyl, C1-10alkoxycarbonyl,1-10alkoxycarbonyl-C1-10alkyl, aryl, aryl-C1-10alkyl, aryl-C1-10-(hydroxy)alkyl, aryloxyalkyl, arylcarbamoyl, alltoall, carboxy, carboxy-C1-10alkyl, C1-10cianelli,3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl, C3-8cycloalkylcarbonyl, halogen, heteroaryl, heteroaryl-C1-10alkyl, heterocycle, heterocycle-C1-10With1-10alkyl, heterocyclicamines,1-10hydroxyalkyl,1-10trials lilil-C 1-10alkyl, H2NC(O)-C1-10alkyl, ZaZbN-, ZaZbN-C1-10alkyl, ZcZdNC(O) -, or ZcZdNS(O)2; Zaand Zbeach independently represent hydrogen, C1-10alkyl, alkoxycarbonyl-C1-10alkyl, aryl, aryl-C1-10alkyl, C3-8cycloalkyl, H2NC(O)-, H2TN-C1-10alkyls(O)-, H2NC(O)-C1-10alkyl, C1-10N(O)- or1-10N(O)-alkyl-;
Zcand Zdeach independently represent hydrogen, C1-10alkyl, C1-10alkoxy-C1-10alkyl, aryl, aryl-C1-10alkyl, aryl - C1-10(hydroxy)alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl, heteroaryl-C1-10alkyl, heterocycle, heterocycle1-10alkyl, C1-10hydroxyalkyl, H2NC(O)-C1-10alkyl, C1-10N(Oh)1-10alkyl, C1-10the N-C1-10alkyl - or CHZeZf;
Zerepresents aryl or heteroaryl;
Zfis heteroaryl-C1-10alkyl or heterocycle-C1-10alkyl;
m has a value of 0;
and has a value of 0 or 1;
b is 0, 1 or 2;
C has a value of 0, 1, 2 or 3; d is 0, 1, 2, 3,or 4
where aryl means phenyl, dihydroindeno, indenyl, naphthyl,
dihydronaphthalene or tetrahydronaphthalene;
where heteroaryl oznachaet is furyl, imidazolyl, isoxazolyl, isothiazolin, oxadiazolyl, oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, triazinyl, benzofuranyl, benzoxazolyl, 1,3-benzothiazolyl, benzimidazolyl, benzodioxolyl, benzothiophene, bromanil, cinnoline, properidine, indolyl, indazoles, isoindolyl, ethenolysis, naphthyridine, oxazolopyridine, chinoline, thienopyridine or thienopyridines; and
where the heterocycle means azetidinol, azepane, aziridinyl, diazepan, 1,3-dioxane, 1,3-DIOXOLANYL, 1,3-dithiolane, 1,3-ditional, imidazolines, imidazolidinyl, isothiazolines, isothiazolinones, isoxazolyl, isoxazolidine, isoindoline-1,3-dione, morpholinyl, oxadiazolyl, oxadiazolidine, oxazolines, oxazolidinyl, piperazinil, piperidinyl, pyranyl, pyrazolyl, pyrazolidine, pyrrolidyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothieno, thiadiazolyl, thiadiazolidine, thiazolyl, diazolidinyl, thiomorpholine, 1,1-dioxythiophene, tiopronin, tritional, 1,3-benzodioxolyl, 1,3-benzodithiol, 2,3-dihydro-1,4-benzodioxolyl, 2,3-dihydro-1-benzofuranyl, 2,3-dihydro-1-benzothieno, 3,4-dihydro-1H-isochroman-4-yl, 2,3-dihydro-1H-indolyl, Succinimidyl, 1,2,3,4-tetrahydroquinoline, 2,3,4,4A,9,9a-hexahydro-1H-carbazolyl, 5A,6,7,8,9,9a-hexahydrobenzo[b,d]furanyl or 5A,6,7,8,9,and hexahydrobenzo[b,d]thienyl.

2. The compound according to claim 1, where a is a (ii), (iii), (iv), (vii), (x), (xiv), (xv), (xvi), (xvii) or (xviii).

3. The compound according to claim 2, where a is a (ii),

R11represents a C1-10alkoxy-C1-10alkyl, C1-10alkoxycarbonyl, aryl, aryl-C1-10alkyl, aryl-C1-10(hydroxy)alkyl, aryloxy-C1-10alkyl, arylcarbamoyl, alkoxycarbonyl-C1-10alkyl, aryl-C1-10thioalkyl, carboxy, carboxy-C1-10alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl, C3-8cycloalkylcarbonyl, halogen, heteroaryl, heteroaryl-C1-10alkyl, heterocycle, heterocycle-C1-10alkyl, heterocyclicamines,1-10hydroxyalkyl,1-10trialkylsilyl-C1-10alkyl, ZaZbN-, ZaZbN-C1-10alkyl - or ZcZdNC(O)-;
Zaand Zbeach independently represent hydrogen, C1-10alkyl or H2N-C1-10alkyls(O)-;
Zcand Zdeach independently represent hydrogen, C1-10alkyl, C1-10alkoxy-C1-10alkyl, aryl, aryl-C1-10alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl, heteroaryl-C1-10alkyl, heterocycle-C1-10alkyl, C1-10hydroxyalkyl or1-10the N-C1-10alkyl-; and
b is 0, 1 or 2.

4. The compound according to claim 3, where the
R11represents aryl, aryl-C1-10alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl or halogen;
b has a value of 1 or 2.

5. The compound according to claim 1, where a is a (iii),

Riiirepresents aryl-C1-10alkyl; and
C has a value of 1.

6. The compound according to claim 2, where a is a (iii)

Riiirepresents a C1-10alkoxycarbonyl-C1-10alkyl, aryl-C1-10alkyl, C1-10cianelli, heterocycle-C1-10alkyl or H2NC(O)-C1-10alkyl-;
C has a value of 0, 1 or 2.

7. The compound according to claim 2, where a is a (iv)

Rivrepresents aryl, aryl-C1-10alkyl, heterocycle, heterocycle-C1-10alkyl or ZaZbN-C1-10alkyl or ZcZdNS(O)2-;
Zaand Zbeach independently represent hydrogen or C1-10alkyl;
Zcand Zdeach represent a1-10alkyl; and
C has a value of 0 or 1.

8. The compound according to claim 2, where a is a (vii)

Rviirepresents a C1-10alkoxycarbonyl, aryl, aryl-C1-10alkyl, C3-8cycloalkyl, heterocycle-C1-10alkyl, heterocyclicamines,1-10hydroxyalkyl or Z cZdNC(O)-;
Zcand Zdeach independently represent hydrogen, C1-10alkyl, C1-10alkoxy-C1-10alkyl, aryl, aryl-C1-10alkyl, aryl-C1-10(hydroxy)alkyl, C3-8cycloalkyl,3-8cycloalkyl-C1-10alkyl, heteroaryl-C1-10alkyl, heterocycle, heterocycle-C1-10alkyl, C1-10hydroxyalkyl or CHZeZf;
Zerepresents aryl or heteroaryl;
Zfis heteroaryl-C1-10alkyl or heterocycle-C1-10alkyl; and b is set to 1.

9. The compound according to claim 2, where a is a (vii)

Rviirepresents a C1-10alkoxycarbonyl, aryl-C1-10alkyl, C3-8cycloalkyl, heterocycle-C1-10alkyl, heterocyclicamines,1-10hydroxyalkyl or ZcZdNC(O)-;
Zcand Zdeach independently represent hydrogen, C1-10alkyl, C1-10alkoxy-C1-10alkyl, aryl, aryl-C1-10alkyl, aryl-C1-10(hydroxy)alkyl, C3-8cycloalkyl, heteroaryl-C1-10alkyl, heterocycle - C1-10alkyl or C1-10hydroxyalkyl; and
b has a value of 1.

10. The method according to claim 2, where a is a (vii)

Rviirepresents aryl-C1-10alkyl; and
b has a value of 1.

11. The compound according to claim 2,where a is a (x)

R1represents hydrogen;
Rxrepresents aryl or ZaZbN-;
Zaand Zbeach independently represent hydrogen, C1-10alkyl, aryl or aryl-C1-10alkyl; and
b has a value of 1 or 2.

12. The compound according to claim 2, where a is a (xiv)

R1represents hydrogen;
Rxivis a ZaZbN-;
Zaand Zbeach independently represent hydrogen or C3-8cycloalkyl; and
C has a value of 1.

13. The compound according to claim 2, where a is a (xv)

Rxvis a ZaZbN-;
Zaand Zbeach independently represent hydrogen, C1-10alkoxycarbonyl-C1-10alkyl, aryl, aryl-C1-10alkyl or C3-8cycloalkyl; and
d is 0 or 1.

14. The compound according to claim 2, where a is a (xvi)

R1represents hydrogen;
Rxviiis a ZaZbN-;
Zaand Zbeach independently represent hydrogen or C3-8cycloalkyl; and
d has a value of 1.

15. The compound according to claim 2, where a is a (xvii)

R1represents hydrogen;
Rxvii is a ZaZbN - or aryl;
Zaand Zbeach independently represent hydrogen, C1-10alkyl, C1-10alkoxycarbonyl-C1-10alkyl, aryl, aryl-C1-10alkyl, C1-10cycloalkyl or H2NC(O)-C1-10alkyl; and
d is 0 or 1.

16. The compound according to claim 2, where a is a (xviii)

R1is an RaRbN-;
C has a value of 0.

17. A compound selected from the group including:
5-(1-benzyl-1H-1,2,3-triazole-5-yl)-1H-indazol connection with 5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazole;
5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol;
5-[1-(2-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(4-methylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3-methoxybenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(4-terbisil)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(4-Chlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2-bromobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(4-nitrobenzyl)-1H-1,2,3-triazole-4-yl]-1H-ind is angry;
2-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;
3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;
4-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzonitrile;
5-{1-[2-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{1-[3-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{1-[3-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{1-[4-(triptoreline)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-[1-(4-tert-butylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
methyl 3-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzoate;
methyl 4-{[4-(1H-indazol-5-yl)-1H-1,2,3-triazole-1-yl]methyl}benzoate;
5-[1-(2,4-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2,3-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2,4-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(2,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-(3,5-dichlorobenzyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-{1-[2,4-bis(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
N-cyclohexyl-6-(1H-indazol-5-yl)imidazo[2,1-b][1,3]thiazole-5-amine;
N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;
N-cyclohexyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrazin-3-amine;
5-[1-benzyl-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol;
N-{3-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]propyl}-N,N-dime the ylamine;
5-[4-(4-forfinal)-1-(1-phenylethyl)-1H-imidazol-5-yl]-1H-indazol;
4-(1H-indazol-5-yl)-N-phenyl-1,3-thiazol-2-amine;
N-ethyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;
N-benzyl-4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;
4-(1H-indazol-5-yl)-1,3-thiazol-2-amine;
4-(1H-indazol-5-yl)-N-(2-phenylethyl)-1,3-thiazol-2-amine;
N-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;
N-butyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;
N-(4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-amine;
2-(1H-indazol-5-yl)-N-(4-methoxyphenyl)imidazo[1,2-a]pyrimidine-3-amine;
2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine;
methyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-yl]glycinate;
N[-benzyl-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;
N - (4-chlorophenyl)-2-(1H-indazol-5-yl)imidazo[1,2-a]pyridine-3-amine;
2-(1H-indazol-5-yl)-N-(4-methoxyphenyl)imidazo[1,2-a]pyridine-3-amine;
tert-butyl 4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]piperidine-1-carboxylate;
5-(1-benzyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;
5-[4-(4-forfinal)-1-piperidine-4-yl-1H-imidazol-5-yl]-1H-indazol;
5-{4-(4-forfinal)-1-[2-(1-methylpyrrolidine-2-yl)ethyl]-1H-imidazol-5-yl}-1H-indazol;
5-{4-(4-forfinal)-1-[3-(4-methylpiperazin-1-yl)propyl]-1H-imidazol-5-yl}-1H-indazol;
ethyl 5-(1H-indazol-5-yl)isoxazol-3-carboxylate;
5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide;
5-(3-benzisoxazol-5-yl)-1H-indazol;
N-benzyl-4-(1H-indazol-5-yl)-5-phenyl-1,3-thiazol-2-amine
4-(1H-indazol-5-yl)-N,5-diphenyl-1,3-thiazole-2-amine;
5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol;
5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol;
2-(1H-indazol-5-yl)-3-phenylimidazo[1,2-a]pyrimidine;
5-[1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-imidazole;
5-[3-(piperidine-1-ylcarbonyl)isoxazol-5-yl]-1H-indazol;
5-(1H-indazol-5-yl)-N-phenylisoxazol-3-carboxamide;
N-cyclohexyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-[3-(piperidine-1-ylmethyl)isoxazol-5-yl]-1H-indazol;
[5-(1H-indazol-5-yl)isoxazol-3-yl]methanol;
5-(1H-indazol-5-yl)-N-(2-methoxyethyl)isoxazol-3-carboxamide;
5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol;
5-(4-benzyl-1H-1,2,3-triazole-1-yl)-1H-indazol;
5-(1-benzyl-5-cyclopropyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;
5-(1-benzyl-4-cyclopropyl-1H-1,2,3-triazole-5-yl)-1H-indazol-3-amine;
5-(3-benzisoxazol-5-yl)-1H-indazol-3-amine;
N-{2-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]ethyl}-N,N-dimethylamine;
5-[4-(4-forfinal)-1-(3-morpholine-4-ylpropyl)-1H-imidazol-5-yl]-1H-indazol;
5-[4-(4-forfinal)-1-(3-pyrrolidin-1-ylpropyl)-1H-imidazol-5-yl]-1H-indazol;
5-{4-(4-forfinal)-1-[2-(4-methylpiperidin-1-yl)ethyl]-1H-imidazol-5-yl}-1H-indazol;
5-[1-(1-benzylpiperidine-4-yl)-4-(4-forfinal)-1H-imidazol-5-yl]-1H-indazol;
5-[4-(4-forfinal)-1-(2-morpholine-4-retil)-1H-imidazol-5-yl]-1H-indazol;
5-[1-(1-benzylpyrrolidine-3-yl)-4-(4-forfinal)-1H-imidazol-yl]-1H-indazol;
2-{4-[4-(4-forfinal)-5-(1H-indazol-5-yl)-1H-imidazol-1-yl]piperidine-1-yl}-2-oxoethyl;
5-(1-benzyl-5-phenyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;
2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol;
5-[4-(methoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;
1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]-1-phenylethanol;
1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-2-ol;
3-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]propan-1-ol;
1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-1,2,3-benzotriazol;
5-{4-[(phenylthio)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;
5-(4-cyclopropyl-1H-1,2,3-triazole-1-yl)-1H-indazol;
5-[4-(2-phenylethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;
5-[4-(cyclohexylmethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;
5-(4-cyclopentyl-1H-1,2,3-triazole-1-yl)-1H-indazol;
1-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]cyclohexanol;
5-[4-(phenoxymethyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;
5-(4-[(1,1-diocletianopolis-4-yl)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;
5-[4-(3-phenylpropyl)-1H-1,2,3-triazole-1-yl]-1H-indazol;
[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](phenyl)methanon;
N,N-diethyl-N-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}amine;
ethyl N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-yl]-beta-alaninate;
5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol;
5-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-yl)-1H-indazol-3-amine;
N-[2-(1H-indazol-5-yl)imidazo[1,2-a]pyrimidine-3-yl]-β-alaninate;
5-(1-benzyl-5-iodine-1H-1,2,3-triazole-4-yl)-1H-indaz the l-3-amine;
N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}-N'-(3-were)urea;
5-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)isoxazol-3-carboxamide;
5-[3-(morpholine-4-ylcarbonyl)isoxazol-5-yl]-1H-indazol;
5-(1H-indazol-5-yl)-N-(3-morpholine-4-ylpropyl)isoxazol-3-carboxamide;
N-[2-(1H-imidazol-4-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
(3R)-1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperidine-3-ol;
1-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperidine-3-carboxamide;
2-[2-(4-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}piperazine-1-yl)ethoxy]ethanol;
5-{3-[(4-methyl-1,4-diazepan-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;
N-(3-hydroxypropyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1R)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[3-(1H-imidazol-1-yl)propyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[3-(2-oxopyrrolidin-1-yl)propyl]isoxazol-3-carboxamide;
N-{2-[4-(aminosulfonyl)phenyl]ethyl}-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](3-chlorophenyl)methanon;
[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl](cyclopropyl)methanon;
5-[5-cyclopropyl-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
N1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]methyl}glycinamide;
(4-forfinal)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,triazol-5-yl]metano;
(4-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;
(3-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;
(2-chlorophenyl)[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;
cyclopentyl[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl]metano;
1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxylic acid;
5-{5-(4-forfinal)-1-[4-(trifluoromethyl)benzyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;
5-[1-benzyl-5-(4-forfinal)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
[4-(1H-indazol-5-yl)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-5-yl](tetrahydro-2H-Piran-4-yl)methanon;
5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-{1-benzyl-5-[(4-methylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-ol;
1-benzyl-4-(1H-indazol-5-yl)-N,N-dimethyl-1H-1,2,3-triazole-5-carboxamide;
N,1-dibenzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
N-(2-hydroxy-2-phenylethyl)-5-(1H-indazol-5-yl)-N-methylisoxazole-3-carboxamide;
N-[(18)-2-hydroxy-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-benzyl-N-(2-hydroxyethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-[1-benzyl-5-(2-were)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
2-{2-[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]ethyl}-1H-isoi the Dol-1,3(2H)-dione;
5-{4-[(2,4-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;
5-{4-[(2,6-dichlorophenoxy)methyl]-1H-1,2,3-triazole-1-yl}-1H-indazol;
5-[5-(4-forfinal)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
1-{[1-(1H-indazol-5-yl)-1H-1,2,3-triazole-4-yl]methyl}-1H-indazol;
5-[1-benzyl-5-(piperidine-1-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[5-(2-were)-1 (tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[5-(2-were)-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
5-[1-benzyl-5-(morpholine-4-ylcarbonyl)-1H-1,2,3-triazole-4-yl]-1H-indazol;
5-[1-benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
N-[(1S)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-{3-[(3-phenylmorpholine-4-yl)carbonyl]isoxazol-5-yl}-1H-indazol;
N-benzyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
((1S)-2-{[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-yl)methanol;
N - [(1R)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N - [(1S)-3-hydroxy-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-2,3-dihydro-1H-inden-1-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-2,3-dihydro-1H-inden-2-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(1-phenylpropyl)isoxazol-3-carbox the ID;
5-{1-benzyl-5-[3-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;
5-{1-benzyl-5-[4-(dimethylamino)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;
N-{3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide;
N-{4-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenyl}ndimethylacetamide;
5-{1-benzyl-5-[3-(1H-pyrazole-1-yl)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;
5-[1-benzyl-5-(1-methyl-1H-pyrazole-4-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-phenylbenzene;
3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]-N-benzylbenzamide;
5-[1-benzyl-5-(1-methyl-1H-indol-5-yl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
5-[1-benzyl-5-(3-methoxyphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
5-[1-benzyl-5-(3-morpholine-4-ylphenyl)-1H-1,2,3-triazole-4-yl]-1H-indazol-3-amine;
5-[3-(1,3-dihydro-2H-isoindole-2-ylcarbonyl)isoxazol-5-yl]-1H-indazol;
5-{3-[(4-methyl-2-phenylpiperazin-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;
1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-amine;
N-[(1R)-1-benzyl-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol;
3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]phenol;
3-[4-(3-amino-1H-indazol-5-yl)-1-benzyl-1H-1,2,3-triazole-5-yl]benzamide;
5-{1-benzyl-5-[4-(methylsulphonyl)phenyl]-1H-1,2,3-triazole-4-yl}-1H-indazol-3-amine;
5-(1H-indazol-5-yl)-N-[(1S)-1-eliprodil]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-phenylpropyl]isoxazol-3-carboxamide;
5-(1-benzyl-1H-pyrazole-4-yl)-1H-indazol-3-amine;
1-benzyl-4-(1H-indazol-5-yl)-N-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-N-(2-isopropoxyphenyl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-N-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-N-(tetrahydrofuran-3-ylmethyl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-cyclopentyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-(cyclopentylmethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-ethyl-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-1-isopropyl-N-methyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1 H-indazol-5-yl)-N-phenyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-(4-chlorophenyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-4-(1H-indazol-5-yl)-N-(2-morpholine-4-retil)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-[2-(dimethylamino)ethyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-N-propyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-[3-(dimethylamino)propyl]-4-(1H-indazol-5-yl)-N-methyl-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-[2-(diethylamino)ethyl]-4-(1H-indazol-5-yl)--methyl-1H-1,2,3-triazole-5-carboxamide;
N,1-dibenzyl-N-ethyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
N,1-dibenzyl-N-(2-hydroxyethyl)-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
(3R)-1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-3-ol;
1-{[1-benzyl-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-yl]carbonyl}piperidine-4-carboxamide;
5-{1-benzyl-5-[(2,6-dimethylmorpholine-4-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{5-[(4-acetylpiperidine-1-yl)carbonyl]-1-benzyl-1H-1,2,3-triazole-4-yl}-1H-indazol;
5-{1-benzyl-5-[(4-phenylpiperazin-1-yl)carbonyl]-1H-1,2,3-triazole-4-yl}-1H-indazol;
1-benzyl-N-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
1-benzyl-N-[3-(1H-imidazol-1-yl)propyl]-4-(1H-indazol-5-yl)-1H-1,2,3-triazole-5-carboxamide;
3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanenitrile;
2-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]ndimethylacetamide;
methyl 3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanoate;
3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]propanamide;
[4-(3-amino-1H-indazol-5-yl)-1H-pyrazole-1-yl]acetonitrile;
4-(3-amino-1H-indazol-5-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide;
5-imidazo[1,2-a]pyridine-3-yl-1H-indazol-3-amine;
5-(1H-pyrazole-5-yl)-1H-indazol-3-amine;
5-(1H-imidazol-4-yl)-1H-indazol-3-amine;
5-(1-benzyl-1H-imidazol-4-yl)-1H-indazol-3-amine;
N-3,4-dihydro-1H-isochroman-yl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(cyclohexylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(3-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(2-methoxybenzyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[2-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[3-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[4-(trifluoromethyl)benzyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(pyridine-2-ylmethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(pyridine-3-ylmethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(pyridine-4-ylmethyl)isoxazol-3-carboxamide;
N-(2-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(4-Chlorobenzyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-]-N-[-(1-phenyl-2-piperidine-1-retil)isoxazol-3-carboxamide;
N-[2-(1H-imidazol-1-yl)-1-phenylethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-]-N-(2-morpholine-4-yl-1-phenylethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[2-(4-methylpiperazin-1-yl)-1-phenylethyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(1-phenyl-2-pyrrolidin-1-retil)isoxazol-3-carboxamide;
tert-butyl 2-({[5-(1H-indazol-5-yl)isoxazol-3-yl]carbonyl}amino)-2-generationbased;
5-(1H-indazol-5-yl)-N-(1-naphthylmethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(2-phenylethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(2-pyridin-2-retil)isoxazol-carboxamide;
5-(1H-indazol-5-yl)-N-(2-pyridin-3-retil)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-(2-pyridin-4-retil)isoxazol-3-carboxamide;
N-[2-(2-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[2-(3-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[2-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-benzyl-N-ethyl-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-methyl-N-(1-naphthylmethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-methyl-N-(2-phenylethyl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-methyl-N-(2-pyridin-2-retil)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-phenylethyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-1,2,3,4-tetrahydronaphthalen-1-isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1S)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-(1-naphthyl)ethyl]isoxazol-3-carboxamide;
N-[3-(dimethylamino)-1-phenylpropyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(3,4-dihydro-2H-1,5-benzodioxepin-6-ylmethyl)-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1-methyl-1H-indol-4-yl)methyl]isoxazol-3-carboxamide;
5-{3-[(3-phenylpyrrolidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;
5-{3-[(2-phenylpyrrolidine-1-yl)carbonyl]isoxazol-5-yl}-1H-indazol;
5-{3-[(2-phenylpiperidine-1-yl)carbonyl]isok the azole-5-yl}-1H-indazol;
5-(1H-indazol-5-yl)-N-[(1S)-1-phenylethyl]isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-(4-were)ethyl]-isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1S)-1-(4-were)ethyl]isoxazol-3-carboxamide;
N-[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1R)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1S)-1-(4-bromophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1R)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[(1S)-1-(4-chlorophenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1S)-1-(2-naphthyl)ethyl]isoxazol-3-carboxamide;
N-[1-(4-ethoxyphenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[2-hydroxy-1-(4-isopropylphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-(3,4-dimetilfenil)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[2-hydroxy-1-(2-methoxyphenyl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
N-[2-hydroxy-1-(4-were)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-(2-methoxyphenyl)ethyl]-isoxazol-3-carboxamide;
N-[(1S)-1-(3,4-differenl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]-isoxazol-3-carboxamide;
5-(1H-indazol-5-yl)-N-{(1R)-1-[3-(trif ormetal)phenyl]-ethyl}isoxazol-3-carboxamide;
N-[1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide; or
N-[1-(3,5-dichlorophenyl)-2-hydroxyethyl]-5-(1H-indazol-5-yl)isoxazol-3-carboxamide.

18. Pharmaceutical composition having inhibitory activity against the kinase, comprising a therapeutically effective amount of a compound according to any one of claims 1 to 17 in combination with a pharmaceutically acceptable carrier.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and salts thereof wherein R1 represents -A11-A12-; R2 represents tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl; A11 represents a single bond, methylene or 3,2-ethylene; A12 represents C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl containing methyl; R3 represents methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl; and R4 represents methoxy or chlorine. Also, the invention also refers to a pharmaceutical composition possessing corticotrophin-releasing factor (CRF) receptor antagonist activity, containing a compound of formula (I), to a therapeutic/preventive agent, and a method of treating the diseases specified in the patent claim.

EFFECT: there are presented the compounds of formula (I) as corticotropin-releasing factor (CRF) receptor antagonists.

20 cl, 2 dwg, 2 tbl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of general formula:

or its pharmaceutically acceptable salt wherein the ring A represents a phenyl group which can contain 1-3 substitutes specified in a group of substitutes, or a thienyl group which can contain 1-3 substitutes specified in a group of substitutes α; L represents a single bond or a group of formula -NRC CO- (wherein Re represents a hydrogen atom), the ring B represents C6-14 aryl group which can contain 1-3 substitutes specified in a group of substitutes α, or a 5-10-member heterocyclic group which can contain 1-3 substitutes specified in a group of substitutes α; the X, Y, Z , R1 and R2 , R3, R4, R5 and R6 radical values are presented in cl.1 of the patent claim which possess an effect of Aβ protein production inhibition or an effect of BACE1 inhibition.

EFFECT: preparing the compound which is applicable as a preventive or therapeutic agent for neurodegenerative disease caused by Aβ.

13 cl, 35 tbl, 285 ex

FIELD: chemistry.

SUBSTANCE: invention relates to bicyclosulphonyl acid (BCSA) compounds of formula: where: where each of -Rpw, -Rpx, -RPY, and -RPZ independently denotes H or -RRS1; each -RRS1 independently denotes -F, -Cl, -Br, -I, -RA1, -CF3, -OH, -OCF3 or -ORA1; where each RA1 independently denotes C1-4alkyl, phenyl or benzyl; and additionally, two neighbouring -RRS1 groups can together form -OCH2O-, -OCH2CH2O- or -OCH2CH2CH2O-; -RAK independently denotes a covalent bond, -(CH2)- or -(CH2)2-; -RN independently denotes -RNNN, or -LN-RNNN; the rest of the values of the radicals are given in claim 1, which act as inhibitors of inhibitors of tumor necrosis factor-α converting enzyme (TACE).

EFFECT: compounds are useful in treating TNF-α mediated conditions.

36 cl, 303 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-aza-bicyclo[3.3.0]octane derivatives of formula , where R1 and R2 are hydrogen, C1-4alkyl or fluorine; R3 is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl, trifluoromethoxy group and halogen; 2,3-dihydrobenzofuranyl; 2,3-dihydrobenzo[1,4]dioxynyl; or isoxazolyl, pyridyl, indazolyl, benzofuranyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, pyrrolo[2,1b]thiazolyl, imidazo[ 1,2-a]pyridinyl or imidazo[2,1-b]thiazolyl, where said groups are unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, halogen and trifluoromethyl; A is or ; R4 is C1-4alkyl or -NR6R7; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; and D is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl and halogen; or a pharmaceutically acceptable salt of such a compound. 3-aza-bicyclo[3.3.0]octane derivatives or a pharmaceutically acceptable salt thereof are used as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: novel 3-aza-bicyclo[3,3,0]octane derivatives as nonpeptide antagonists of human orexin receptors.

9 cl, 1 tbl, 85 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: medicine.

SUBSTANCE: invention refers to an agent for activation of lipoprotein lipase containing a benzene derivative of general formula (1) which is used for preventing and treating hyperlipidemia and obesity. The invention also refers to the benzene derivatives of general formula (1a).

EFFECT: composition improvement.

8 cl, 6 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: method is realised by mixing a compound of formula (B) with p-toluenesulphonic acid or a monohydrate of toluenesulphonic acid in less than 1 molar equivalent with respect to the compound of formula (B), in a solvent while heating. An additional amount of p-toluenesulphonic acid or monohydrate of p-toluenesulphonic acid is then added to the mixed solution while cooling in such an amount that their total molar equivalent with p-toluenesulphonic acid or monohydrate of p-toluenesulphonic acid at the mixing step is equal to 1 molar equivalent or more with respect to the compound of formula (B). At the last step, the obtained solution is crystallised to separate a compound of formula (A).

EFFECT: obtaining a compound of formula (A) with stable high output.

12 cl, 1 dwg, 3 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes the pyrrolo- and thiazolopyridinium compounds and their pharmaceutically acceptable salts covered by general structural formula I: wherein the values A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are those as presented in cl.1, and a pharmaceutical composition based on the given compound for inhibition of hypoxia-inducible factor (HIF) hydroxylase activity.

EFFECT: there are produced and described new compounds able to modulate hypoxia-inducible factor (HIF) stability and/or activity.

29 cl, 178 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), stereoisomers, trans- and cis-isomers, racemates or pharmaceutically acceptable salts thereof, having modulating activity on histamine H3-receptors. In formula (I) m equals 0; one of R1 and R2 is selected from a group which includes hydrogen, C1-10alkoxycarbonyl, amido-, carboxy-, C3-8cycloalkyl, halogen, -NRARB, (NRARB)carbonyl, or a group of formula -L2-R6; the other of R1 and R2 is selected from a group which includes hydrogen, halogen; each of R3a and R3b is independently selected from a group which includes hydrogen; each of R4 and R5 is independently selected from a group which includes C1-10alkyl and C1-10hydroxyalkyl; or R4 and R5, taken together with a nitrogen atom to which each is bonded, form a heteroaromatic ring of the type (a) or (b), where Q1 is O or C; Q2 is -N(R20)-; R20 is selected from a group which includes hydrogen and C1-10alkoxycarbonyl; each of p1 and p2 is independently equal to 1, 2 or 3; each of q1, q2, q3, q4 and q5 are independently equal to 0, 1 or 2; and wherein each carbon atom in the ring is substituted with hydrogen or 0, 1 or 2 substitutes, independently selected from a group which includes hydrogen, hydroxy group, fluorine, C1-10alkyl, C1-10hydroxyalkyl and C1-10fluoroalkyl; R6 is a phenyl, heterocycle or heterocycloC1-4alkyl, wherein the heterocycle is a 4-6-member aromatic or non-aromatic ring which contains 1 or 2 heteroatoms independently selected from N, O and S, optionally condensed with a benzene ring, wherein the phenyl or heterocycle can be unsubstituted or optionally substituted with one or more substitutes independently selected from a group which includes C1-4alkoxy, C1-4alkyl, cyano, halogen and oxo-; L is a bond or C1-4alkylene; L2 is a bond, C1-4alkylene, -C(=O)-, -SO2N(R14a)-, -N(R14a)SO2-, -C(O)N(R14a)-, -N(Rl4a)C(O)- or -N(R15)-; R10 is selected from a group which includes hydrogen; R14a is selected from a group which includes hydrogen; R15 is selected from a group which includes hydrogen; and RA and RB are independently selected from a group which includes hydrogen, C1-10alkyl, C1-10acyl, C1-4halogenalkyl, C1-10alkoxycarbonyl, C3-8cycloalkyl and C3-8cycloalkylcarbonyl. The invention also relates to a pharmaceutical composition which contains compounds of formula (I), a method for selective modulation of effects of histamine H3-receptors, use of said compounds in producing a medicament for treating a condition or disorder modulated by histamine H3-receptors, as well as specific compounds of formula (I).

EFFECT: improved properties of compounds.

18 cl, 2 tbl, 154 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) a pharmaceutically acceptable salt thereof wherein each dash line (represented as ---) represents a double bond; X represents N or CH; R1a and R1b independently represent hydrogen or C1-6-jalkyl; L represents -O-; R2 represents hydrogen; R3 represents hydrogen or C1-6-alkyl; R4 represents quinolinyl substituted by one, two or three substitutes specified in C1-6-alkyl, C1-6-alkyloxy, thiazolyl or pyrazolyl, wherein said thiazolyl or pyrazolyl are substituted on any carbon atom by C1-6-alkyl; n is equal to 3, 4, 5 or 6; p is equal to 1 or 2. The invention refers to a pharmaceutical composition possessing the properties of KS3/4a-protease HCV inhibitors, containing a carrier, and an virally effective amount of the compound of formula (I) as an active ingredient. The method for preparing the compound of formula (I), wherein the above method involves forming an amide bond of an intermediate product (2a) and sulphonylamide (2b), as presented by the diagram, wherein G represents a group Also, the invention refers to alternative methods for preparing the compound of formula (I).

EFFECT: there are presented macrocyclic compounds possessing inhibitory activity on hepatitis C virus (HCV) replication.

13 cl, 1 tbl, 17 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention provides new imidazo[1,2-b]pyridazine compounds covered by general structural formula (I) wherein the radicals and symbols have the values presented in the patent claim, and pharmaceutically acceptable salts thereof. The compounds of structural formula (I) are effective both for treating or preventing the diseases related to GABA receptor inhibition, anxiety, epilepsy, sleep disorders, including insomnia, and for inducing a sedative-hypnotic, anaesthetic effect, sleep and muscle relaxation.

EFFECT: there are presented methods for preparing the above compounds, and also intermediate compounds for preparing them.

21 cl, 4 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to octahydro-pyrrolo[3,4-b]pyrrol N-oxides or pharmaceutically acceptable salts thereof of general formula (I) wherein Z1 represents N or CH. Octahydro-pyrrolo[3,4-b]pyrrol N-oxides of formula (I) are prodrugs of histamine-3 antagonists, and effective in treating conditions and disorders that can be prevented or relieved by H3-histamine receptor ligands. The present paper discloses N-oxide derivatives of octahydro-pyrrolo[3,4-b]pyrrol, the use of these compounds, compositions thereof and methods of treating a mammal having a condition or disorder wherein the H3-histamine receptor modulation has a therapeutic effect.

EFFECT: new compounds are presented.

11 cl, 2 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are new triazolopyrimidine derivatives of general formula (I): wherein R1 means hydrogen or alkyl; R2 means hydrogen; R3 means optionally substituted C3-8cycloalkyl, optionally substituted bridged monocyclic C6-cycloalkyl, optionally substituted phenyl, optionally substituted 6-member heterocyclyl containing one or two heteroatoms specified in O and N, etc., a pharmaceutical composition containing them, and using the compounds and composition for inhibiting the enzyme type 1 diacylglycerol-O-acyltransferase (DGAT) for treating type 2 diabetes mellitus, obesity, high plasma triglycerides, metabolic syndrome, etc.

EFFECT: there are presented new triazolopyrimidine derivatives.

11 cl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to tetrahydroimidazo[1,5-a]pyrazine derivatives of formula I or to their pharmaceutically acceptable salts (I), wherein: Ar represents phenyl, wherein phenyl is additionally substituted by 1-3 substitutes independently specified in halogen; R1 represents trifluoromethyl; R2 is specified in a group consisting of hydrohyl, alkyl having 1 to 4 carbon atoms, alkoxyl having having 1 to 4 carbon atoms, cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely, and -NR4R5, wherein each alkoxyl is optionally substituted by one group specified in a group consisting of phenyl and -OC(O)OR8; R3 is specified in a group consisting of a hydrogen atom and alkyl having 1 to 4 carbon atoms; each of R4 and R5 is independently specified is a group consisting of a hydrogen atom, alkyl having 1 to 4 carbon atoms, cycloalkyl representing a 3-8-member monocyclic ring group consisting of carbon completely, phenyl and pyridinyl, wherein each alkyl or phenyl is optionally substituted by one or more group specified in a group consisting of halogen, a cyano group, -SO2R7, -NR4R5 and -C(=O)OCH3; or R4 and R5 together with an atom, whereto attached form a 5-6-member heterocycle wherein the 5-6-member heterocycle optionally contains one or more N, O or S atom, and each 5-6-member heterocycle is optionally substituted by one or more groups consisting of halogen, hydroxyl, an amino group, alkyl having 1 to 4 carbon atoms, hydroxyalkyl 1 to 4 carbon atoms, -SO2R7, -C(O)NR4R5, -C(O)R7, =O; R7 represents alkyl 1 to 4 carbon atoms; and R8 is specified in a group consisting of alkyl 1 to 4 carbon atoms, and cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely. The invention also refers to methods for preparing them, a pharmaceutical composition having dipeptidyl peptidase IV inhibitory activity and containing said derivatives.

EFFECT: there are produced new compounds and composition on their basis which can find application in medicine for treating type 2 diabetes mellitus or hyperglycemia.

17 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel azoindolizines or pharmaceutically acceptable salts thereof having Mek-kinase inhibitory activity in formula : ZA means CRA; RA means H or halogen; each of R1, R2 and R3 means H; W means: , each R4 and R5 means H; X1 represents -OR7; each R7 means C2-C12-hydroxyalkyl, 2,3-dihydroxypropyl, C2-C3-alkenoxyC1-C6-alkoxy, (2,2-dimethyl-[1,3]dioxalan-4-yl)-methyl or piperidinyl; X4 means: R6 means halogen or -SR16; R6 means halogen; p is equal to 1; R16 means C1-C12-alkyl.

EFFECT: invention relates to a pharmaceutical compositions containing these compounds, to a method of inhibiting the abnormal cell growth and the use of the compounds for preparing a drug preparation for inhibiting the abnormal cell growth.

9 cl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline compounds of formula (I) and physiologically acceptable acid addition salts and N oxides thereof, wherein R denotes a polycyclic group of formula (R) wherein * indicates the quinolinyl radical binding site; A denotes (CH2)a, where a equals 0, 1, 2 or 3; B denotes (CH2)b, where b equals 0, 1, 2 or 3; X' denotes (CH2)x where x equals 0, 1, 2 or 3; Y denotes (CH2)y where y equals 0, 1, 2 or 3; provided that a+b=1, 2, 3 or 4, x+y=1, 2, 3 or 4, and a+b+x+y=3, 4, 5, 6 or 7; Q denotes N; R1 denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, phenoxycarbonyl or benzyloxycarbonyl, where phenyl rings in last two said groups are unsubstituted or carry 1, 2 or 3 substitutes selected from halogen, C1-C4-alkyl or C1-C4-halogenalkyl; R2 denotes hydrogen; R3 denotes hydrogen; p=0, 1 or 2; R4, if present, denotes C1-C4-alkyl and is bonded with X and/or Y, if p=2, two radicals R4, which are bonded with adjacent carbon atoms of X or Y, together can also denote a straight C2-C5-alkylene; q=0; n=0; m=0; X denotes S(O)2; which is located in position 3 of quinoline; Ar denotes a radical Ar1, wherein Ar1 is a phenyl, wherein the phenyl can be unsubstituted or can carry 1 substitute Rx wherein Rx denotes halogen, CN, C1-C6-alkyl, C1-C6-halogenalkyl, C1-C6-alkoxy, C1-C6-halogenalkoxy, C1-C6-alkylthio, C1-C6-halogenalkylthio, NRx1 Rx2, wherein Rx1 and Rx2 independently denote hydrogen, C1-C6-alkyl, or Rx1 and Rx2 together with a nitrogen atom form an N-bonded 5-, 6- or 7-member saturated heteromonocyclic ring or an N-boned 7-, 8-, 9- or 10-member saturated heterobicyclic ring, which are unsubstituted or carry 1, 2, 3 or 4 radicals selected from C1-C4-alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treatment using the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel quinoline derivatives are obtained, which respond to modulation of the serotonin 5-HT6 receptor.

23 cl, 2 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new tetracyclic compounds of general formula (I), wherein is a single or double bond; no bonds or a single bond; or V means N; T and X as shown in structure fragments above; U and W independently mean C or N with one of them shall be N; R3, R4, R5 and R6 - H; Rv is absent; Ru and Rw are independently absent or mean (C1-12)alkyl; Y =N-OR1 or NP'1, wherein R1 - H, (C1-12)alkyl optionally substituted by phenyl, phenyloxy, carboxy, (C1-12)alkoxy, (C1-12)alkoxycarbonyl, or (C2-12)alkenyl; R'1 is phenyl, or pharmaceutically acceptable salts thereof, or diastereomers thereof, or regioisomers thereof, or: mixtures thereof, a pharmaceutical composition containing them, and specific compounds for cysteine protease inhibition.

EFFECT: compounds may be used in medicine in treating cancer, neurodegenerative diseases, inflammatory disorders, cardiovascular diseases, etc.

8 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to pharmacy and medicine, and concerns using the pyridopyrazine derivatives for preparing a drug for treating or preventing the physiological and/or pathophysiological conditions associated withPI3K kinase inhibition in mammals.

EFFECT: invention provides high clinical effectiveness.

7 cl, 4 tbl, 3 ex

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