IKK inhibitor

Abstract

The present invention relates to an IKK alpha inhibitory compound having the structural formula (I) shown below, or a pharmaceutically acceptable salt, hydrate or solvate thereof: 【Chemical 1】 JPEG2025521099000682.jpg55127(wherein R1, X, R3, R4 and X1 are as defined herein respectively) The present invention also relates to methods for preparing these compounds, pharmaceutical compositions containing them, and their use in the treatment of proliferative disorders such as cancer, and other diseases or conditions in which IKK-alpha activity is involved.

Description

Technical Field

[0001] The present invention relates to certain compounds that function as inhibitors of inhibitor of κB kinase (IKK) activity, particularly the alpha subunit of IKK (IKKα). Accordingly, the compounds of the present invention can be used, at least in part, to treat diseases or conditions mediated by abnormal or inappropriate IKK (particularly IKKα) activity. Cancer is an example of a condition associated with abnormal or inappropriate IKK (particularly IKKα) activity. The present invention further relates to the use of the compounds for treating diseases or conditions in which IKK (particularly IKKα) activity is involved, methods for preparing these compounds, and pharmaceutical compositions containing these compounds.

Background Art

[0002] Cancer is caused by changes in cell proliferation. Exactly what causes cells to become malignant and proliferate in an uncontrolled and disorderly manner has been the focus of intensive research over the past few decades. This research has led to the identification of molecular targets associated with the major pathways that permit such malignancies.

[0003] Nuclear factor kappa B (NF-κB) derived from the nuclear factor kappa light-chain enhancer of activated B cells represents a family of five transcription factors involved in diverse biological responses that underlie the phenotypic consequences of inflammation, regulation of the immune response, cell growth, proliferation, apoptosis, and aspects of differentiation and development [1-5]. NF-κB signaling is currently recognized as either a canonical (classical) or non-canonical (alternative) pathway through the recruitment of both homodimeric and heterodimeric complexes of these family members (Figure 1; [1-5]). Collectively, the NF-κB proteins are five different isoforms of RelA (p65), RelB, c-Rel, NF-κB1 (p105 / p50), and NF-κB2 (p100 / p52) [1-5]. In the inactive state, these proteins typically associate with inhibitory κB (IκB) proteins, including the isoforms of IκBα, IκBβ, and IκBε, and in the case of the p105 and p100 proteins, their C-terminal IκB-like structures composed of ankyrin repeats (IκBδ and IκBγ, respectively) maintain them in a self-association inhibitory form due to their intrinsic protein structure [1-5]. Activation and release of the NF-κB proteins typically occur in response to several extracellular ligands and agents that induce the DNA damage response (DDR), resulting in the nuclear localization of the DNA-binding protein dimers after dissociation from the IκB molecules [1-5].

[0004] The canonical pathway can be activated in response to cytokines such as TNFα and IL-1β, as well as pathogen-associated molecular patterns (PAMPs) such as bacterial endotoxin lipopolysaccharide (LPS) [6, 7]. This response is typically rapid and transient and is mediated by the classical inhibitor of κB kinase (IKK) complex (IKKα / β / γ), which requires IKKβ-mediated phosphorylation of selected IκB proteins [6, 7]. In contrast, activation of the non-canonical NF-κB pathway is relatively slow and results in the IKKα-mediated release of mainly the p52-RelB dimer over several hours, driving gene transcription [1-7]. This slow response reflects the dependence on protein expression / stabilization within the upstream components of the pathway. TNFα and IL-1β have the ability to activate the non-canonical NF-κB pathway, but it is typically alternative members of the larger TNF superfamily that drive activation [3, 4]. These include lymphotoxin β (LT-β), the related tumor necrosis factor superfamily member 14 (TNFSF14) known as LIGHT, TNF-like weak apoptosis inducer (TWEAK), CD40 ligand (CD40L), receptor activator of NF-κB ligand (RANKL), and B cell activating factor (BAFF) [1, 3, 4].

[0005] Molecular and genetic studies have shown that receptor-mediated non-canonical NF-κB activation is built around a paradigm of TNF superfamily ligands that activate their cognate receptors through the recruitment of a series of identifiable adapter molecules that modulate ubiquitination and the accompanying proteolysis in the form of the TNF receptor-associated factor (TRAF) family, particularly TRAF2 and TRAF3, and cellular inhibitor of apoptosis (cIAP). These proteins enable the involvement and activation of the cellular kinase NF-κB-inducing kinase (NIK), the 14th member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, and IKKα, determining the release of the p52-RelB protein complex (Figure 1; [1-5]).

[0006] In the cellular environment, under quiescent and unstimulated conditions, NIK is maintained at low expression levels based on proteasome degradation focused on NIK. However, when the receptor is activated, NIK is stabilized, protein expression increases, and pathway activation becomes possible

[16] . By controlling the degree of proteasome-mediated degradation, TRAF3 acts as an important regulator of NIK expression

[16] . When the receptor is activated, the focus of proteasome-mediated protein degradation switches from NIK to that of TRAF2 and TRAF3, NIK expression is stabilized, and a series of signaling events leading to p100 processing are initiated [17 - 20]. Subsequently, the cIAP protein, which functions as a ubiquitin ligase for ubiquitinating NIK, targets TRAF3 for degradation and raises the NIK protein level.

[0007] When the NIK protein is stabilized, as the first component of the non-canonical NF-κB pathway, it catalyzes the phosphorylation of IKKα, supports the recruitment of IKKα to p100 and the phosphorylation of p100, and then drives the subsequent ubiquitination and proteasome-mediated degradation of p100 to release p52

[16] . Under basal conditions, p100 typically exists as a dimer complex with RelB, and upon stimulation of degradation, it generates a p52-RelB dimer that can translocate to the nucleus and initiate the transcription of different genes (Figure 1).

[0008] Both NIK and IKKα play important roles in the phosphorylation of p100 to liberate the mature p52-RelB protein dimer. However, although IKKα is currently regarded as the major regulator of p100 phosphorylation, there is co-dependence on NIK, resulting in the coupled phosphorylation and processing of p100 to generate the transcriptionally active mature p52

[22] . In transfected cells, NIK can stimulate the phosphorylation, ubiquitination, and processing of p100 [23, 24], but recombinant NIK itself does not show p100 phosphorylation in vitro [24, 25]. In a cell-based environment, NIK mediates downstream signaling through the involvement and activation of IKKα, resulting in the phosphorylation of the C-terminal region of p100

[25] , which is independent of the other IKK isoforms, β and γ, associated with canonical NF-κB activation [26, 27]. IKKα phosphorylated p100 and regulated only non-canonical NF-κB activation, but was less effective than NIK in inducing p100 processing

[23] . Under these findings, further studies then identified that NIK has an important role in the regulation of p100 processing through the recruitment of p100 as a protein substrate of IKKα and its binding to p100

[22] . In summary, the NIK-IKKα interaction with p100 results in the phosphorylation of p100 at specific serine residues, mainly Ser868 / 870

[24] . These sites are components of a phosphodegron within the p100 C-terminal NIK-responsive domain (NRD), and when phosphorylated, drive the final processing of p100 to generate p52 by the SCF βTrCP Resulting in βTrCP binding as part of the ubiquitin ligase complex.

[0009] Independent of the non-canonical NF-κB pathway, several studies have confirmed that there are also examples of signal bifurcation at the level of NIK-IKKα kinases. These can depend on different extracellular conditions

[29] , demonstrating that p100 is not the only substrate for IKKα-mediated phosphorylation. IKKα directly regulates several cellular proteins via catalytic phosphorylation, thereby directly or indirectly regulating cellular transcription [6, 7]. This includes transcription factors different from the NF-κB family, such as E2F1 [30, 31], β-catenin

[32] , CBP

[33] , as well as silencing mediators of retinoic acid and thyroid hormone receptors (SMRT)

[34] , and transcription repressors such as the cell cycle regulator cyclin D1

[35] . Additional substrates include the protein inhibitor of activated STAT1 (PIAS1)

[36] as a regulator of transcription / inflammation, estrogen receptor (ER)

[37] and androgen receptor (AR)

[38] of the steroid hormone family receptors and their associated steroid receptor cofactor (SRC)-3 [37, 39, 40], as well as aurora kinase A [41, 42] that contributes to the mitotic process. The direct regulation of the state of these proteins by IKKα is related to the transcription of additional regulatory proteins such as p53 [43, 44] and EZH2

[44] and the additional mitotic kinase polo-like kinase (PLK) 4

[45] . Therefore, IKKα functions as an important switch for the coordinated regulation of both NF-κB-dependent gene transcription and NF-κB-independent gene transcription, which supports the results related to events that initiate and / or perpetuate acquired traits or phenotypes, and are recognized here as cancer "hallmarks" as defined and identified by Hanahan & Weinberg [46, 47].Transcriptional regulation driven by IKKα-mediated signaling, elucidated using several experimental approaches such as gene deletion and rearrangement [48, 49], siRNA “knockdown”

[35] , and overexpression strategies

[50] , may involve over 200 genes, and the induction / suppression events of these genes / proteins support the acquisition of characteristics of specific “hallmarks”, particularly the ability of tumors to “maintain proliferative signaling”, “resist cell death”, “evade growth suppressors”, and “promote genomic instability and mutation”. More strikingly, the role of IKKα in the regulation of genes / proteins that support “induction of angiogenesis” and “activation of invasion and metastasis”, phenotypic manifestations associated with long-term tumorigenesis, by regulating the induction of cytokines (e.g., IL-1β, IL-6 [48, 49]) and chemokines (e.g., CCL19, CCL21, CXCL12, CXCL13, and BAFF [27, 51, 52]) as well as the expression of adhesion molecules (e.g., VCAM; [48 - 50]), maspin [50; 53], and MMP

[50] in different cell / tissue contexts. Also, in specific subtypes of cancer, it is clear that a specific mutation, the acquisition of C250T, in the hTERT promoter that supports tumor reactivation causes tumors to become “addicted” to IKKα-mediated non-canonical NF-κB signaling, thus identifying the potential to “enable replicative capacity”. In summary, disruption of this enzyme could have a wide range of effects on multiple hallmarks of the above-mentioned tumor cells. Furthermore, considering the influence of IKKα on the regulation of major cytokines, chemokines, and matrix metalloproteinase isoforms, intervention against this enzyme could have a significant effect on tumor-stroma communication and matrix composition in the tumor microenvironment and could define a better understanding of “tumor-promoting inflammation”.

[0010] It is now recognized that this transcription process is not entirely driven by receptor-mediated activation, and thus the additional complexity of the regulation of IKKα-dependent, NF-κB-dependent, and -independent gene transcription in the cancer environment is also revealed here. For both solid tumors (e.g., pancreatic adenocarcinoma) and the hematological environment (e.g., multiple myeloma), constitutive activation of IKKα-mediated signaling has been reported as a result of the regulation of the expression of upstream TRAF and cIAP components in the pathway or mutations in these same components, ultimately leading to constitutive activation of the pathway in the absence of an agonist. Furthermore, the cleaved p45 form of IKKα has been identified in some colorectal cancers, particularly those with a V600E B-Raf mutant background [55, 56]. This drives p45 IKKα-mediated nuclear signaling in a TNF superfamily member-independent manner, providing additional mechanisms and transcriptional diversity in tumorigenesis and therapeutically influencing potential interventions.

[0011] In recent years, the non-canonical NF-κB pathway and the role of IKKα within it have become increasingly implicated in the development and progression of multiple solid tumors and hematological cancers. As a result, there is a need and desire to identify potentially useful IKKα inhibitors.

[0012] The present invention has been devised with the foregoing in mind. References [1] Sun SC. Non-canonical NF-κB signaling pathway. Cell Res. 2011 Jan;21(1):71-85. [2] Razani B, Reichardt AD, Cheng G. Non-canonical NF-κB signaling activation and regulation: principles and perspectives. Immunol Rev. 2011 Nov;244(1):44-54. [3] Cildir G, Low KC, Tergaonkar V. Noncanonical NF-κB Signaling in Health and Disease. Trends Mol Med. 2016 May;22(5):414-429. [4] Sun SC. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol. 2017 Sep;17(9):545-558. [5] Xia L, Tan S, Zhou Y, Lin J, Wang H, Oyang L, Tian Y, Liu L, Su M, Wang H, Cao D, Liao Q. Role of the NFκB-signalingpathway in cancer. Onco Targets Ther. 2018 Apr 11;11:2063-2073. [6] Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007 Jan;8(1):49-62. [7] Gamble C, McIntosh K, Scott R, Ho KH, Plevin R, Paul A. Inhibitory kappa B Kinases as targets for pharmacological regulation. Br J Pharmacol. 2012 Feb;165(4):802-19.

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SUMMARY OF THE INVENTION

[0013] According to a first aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0014] According to a further aspect of the present invention, there is provided a pharmaceutical composition comprising a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, admixed with a pharmaceutically acceptable diluent or carrier.

[0015] According to a further aspect of the present invention, there is provided a method of inhibiting IKKα activity in vitro or in vivo, the method comprising contacting a cell with an effective amount of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0016] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder involving IKKα activity in a patient in need of treatment for a disease or disorder involving IKKα activity, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0017] According to a further aspect of the present invention, there is provided a method of treating a proliferative disorder in a patient in need of treatment for a proliferative disorder, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0018] According to a further aspect of the present invention, there is provided a method of treating cancer in a patient in need of treatment for cancer, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0019] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition for use in therapy.

[0020] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition for use as a medicament.

[0021] According to a further aspect of the present invention, there is provided a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition for use in the treatment of a proliferative disorder.

[0022] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition for use in the treatment of cancer. In certain embodiments, the cancer is a human cancer.

[0023] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the inhibition of IKKα activity.

[0024] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of a disease or disorder in which IKKα activity is involved.

[0025] According to a further aspect of the present invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating a proliferative disorder.

[0026] According to a further aspect of the present invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating cancer.

[0027] According to a further aspect of the present invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for inhibiting IKKα activity.

[0028] According to a further aspect of the present invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating a disease or disorder in which IKKα activity is involved.

[0029] According to a further aspect of the present invention, there is provided a method for preparing a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0030] According to a further aspect of the invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, which can be obtained, or has been obtained, or is directly obtained, by a method for preparing a compound as defined herein.

[0031] According to a further aspect of the invention, there is provided a novel intermediate as defined herein, which is suitable for use in any one of the synthetic methods shown herein.

[0032] Features including optional, suitable and preferred features relating to one aspect of the invention may also be features including optional, suitable and preferred features relating to any other aspect of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0033]

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Modes for Carrying Out the Invention

[0034] Definitions Unless otherwise specified, the following terms used in this specification and the claims have the following meanings as set forth below.

[0035] References to "treating" or "treatment" include the prevention and alleviation of established symptoms of a condition. Thus, "treating" or "treatment" of a situation, disorder or condition includes (1) preventing or delaying the appearance of clinical symptoms of a situation, disorder or condition that may afflict or be predisposed to a situation, disorder or condition but in which neither the clinical nor subclinical symptoms of the situation, disorder or condition have yet been experienced or manifested in a human who has not yet experienced or manifested them, (2) inhibiting a situation, disorder or condition, i.e., stopping, reducing or delaying the onset or recurrence of a disease (in the case of maintenance treatment) or at least one of its clinical or subclinical symptoms, or (3) alleviating or attenuating a disease, i.e., causing at least one regression of a situation, disorder or condition or its clinical or subclinical symptoms.

[0036] "Therapeutically effective amount" means an amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect treatment of such disease. A "therapeutically effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, etc., of the mammal being treated. For example, in humans or other mammals, a therapeutically effective amount can be determined experimentally in a laboratory or clinical setting, or a therapeutically effective amount can be the amount required by the guidelines of the U.S. Food and Drug Administration (FDA) or equivalent foreign regulatory agencies for the particular disease and subject being treated. It should be understood that the determination of the appropriate dosage form, dosage, and route of administration is within the skill of those in the pharmaceutical and medical arts.

[0037] When used alone or in combination with another term in this specification, "subject" and "patient" refer to an animal (e.g., a mammal), particularly a human. Appropriately, "subject" and "patient" may be a non-human animal (e.g., livestock and household pets) or a human.

[0038] As used herein, either alone or in combination with another term, "pharmaceutically acceptable" refers to a material that is generally chemically and / or physically compatible with other ingredients (e.g., with respect to a formulation, etc.) and / or that is generally physiologically compatible with its recipient (e.g., a subject, etc.).

[0039] As used herein, the term "alkyl" includes both straight-chain alkyl groups and branched-chain alkyl groups. References to individual alkyl groups such as "propyl" are specific only to the straight-chain version, and references to individual branched-chain alkyl groups such as "isopropyl" are specific only to the branched-chain version. For example, "(1-6C)alkyl" includes (1-4C)alkyl, (1-3C)alkyl, propyl, isopropyl, and t-butyl.

[0040] The term "(m-nC)" or "(m-nC) group", used either alone or as a prefix, refers to any group having from m to n carbon atoms.

[0041] An "alkylene" group is an alkyl group that is positioned between and serves to connect two other chemical groups. For example, "(1-6C)alkylene" means a straight-chain saturated divalent hydrocarbon group of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon group of 3 to 6 carbon atoms, such as methylene (-CH2-), ethylene isomers (-CH(CH3)- and -CH2CH2-), propylene isomers (-CH(CH3)CH2-, -CH(CH2CH3)-, -C(CH3)2-, and -CH2CH2CH2-), pentylene (-CH2CH2CH2CH2CH2-), etc.

[0042] The term "alkenyl" refers to straight-chain and branched-chain alkyl groups containing two or more carbon atoms in which at least one carbon-carbon double bond is present within the group. Examples of alkenyl groups include ethenyl, propenyl, and buta-2,3-enyl, including all possible geometric (E / Z) isomers.

[0043] The term "alkynyl" refers to straight-chain and branched-chain alkyl groups containing two or more carbon atoms in which at least one carbon-carbon triple bond is present within the group. Examples of alkynyl groups include ethynyl and propynyl.

[0044] "(m - nC) cycloalkyl" means a saturated hydrocarbon ring system containing m to n carbon atoms. Exemplary cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and bicyclo[2.2.1]heptyl.

[0045] The term "alkoxy" refers to O-bonded straight-chain and branched-chain alkyl groups. Examples of alkoxy groups include methoxy, ethoxy and t-butoxy.

[0046] The term "haloalkyl" is used herein to refer to an alkyl group in which one or more hydrogen atoms are replaced by halogen (e.g., fluorine) atoms. Examples of haloalkyl groups include -CH2F, -CHF2 and -CF3.

[0047] The terms "halo" and "halogeno" refer to fluoro, chloro, bromo and iodo, suitably fluoro, chloro and bromo, more suitably fluoro and chloro.

[0048] The term "carbocyclyl", "carbocyclic" or "carbocycle" means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic carbon-containing ring system. Monocyclic carbocyclic rings contain about 3 to 12 (suitably 3 to 7) ring atoms. Bicyclic carbocycles contain 6 to 17 member atoms, suitably 7 to 12 member atoms within the ring. Bicyclic carbocyclic rings can be fused, spiro, or bridged ring systems. Examples of carbocyclic groups include cyclopropyl, cyclobutyl, cyclohexyl, cyclohexenyl and spiro[3.3]heptanyl.

[0049] The terms "heterocyclyl", "heterocyclic", or "heterocycle" mean a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system. A monocyclic heterocyclic ring contains about 3 to 12 (appropriately 3 to 7) ring atoms and 1 to 5 (appropriately 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur within the ring. A bicyclic heterocycle contains 7 to 17 ring atoms, appropriately 7 to 12 ring atoms. The bicyclic heterocyclic ring can be a fused, spiro, or bridged ring system. Examples of heterocyclic groups include cyclic ethers such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Heterocycles containing nitrogen include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, etc. Typical sulfur-containing heterocycles include tetrahydrothienyl, dihydro-1,3-dithiol, tetrahydro-2H-thiopyran, and hexahydrothiepin. Other heterocycles include dihydro-oxathiolyl, tetrahydro-oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro-oxathiazolyl, hexahydrotriazinyl, tetrahydro-oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl. For sulfur-containing heterocycles, sulfur oxide heterocycles containing SO or SO2 groups are also included. Examples include sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl such as tetrahydrothiene 1,1-dioxide and thiomorpholinyl 1,1-dioxide. The heterocycle may contain one or two oxo (=O) substituents or thioxo (=S) substituents. Suitable values for a heterocyclyl group having one or two oxo (=O) substituents or thioxo (=S) substituents are, for example, 2-oxopyrrolidinyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl, or 2,6-dioxopiperidinyl.Specific heterocyclic groups are saturated monocyclic 3- to 7-membered heterocyclyls containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, or sulfur, such as azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1,1-dioxide, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, piperidinyl, homopiperidinyl, piperazinyl, or homopiperazinyl. As will be recognized by those skilled in the art, any heterocycle may be attached to another group via any suitable atom, such as via a carbon atom or a nitrogen atom. However, references herein to piperidino or morpholino refer to a piperidin-1-yl or morpholin-4-yl ring attached via the ring nitrogen.

[0050] By "bridged ring system" is meant a ring system in which two rings share three or more atoms. See, for example, Advanced Organic Chemistry, Jerry March, 4th Edition, Wiley Interscience, pages 131-133, 1992. Examples of bridged heterocyclyl ring systems include azabicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, azabicyclo[2.2.2]octane, azabicyclo[3.2.1]octane, and quinuclidine.

[0051] By "spiro bicyclic ring system" is meant that two ring systems share one common spiro carbon atom, i.e., a heterocyclic ring is attached to a further carbocyclic or heterocyclic ring through a single common spiro carbon atom. Examples of spiro ring systems include 6-azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.4]octane, 2-azaspiro[3.3]heptane, 2-oxa-6-azaspiro[3.3]heptane, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7-azaspiro[3.5]nonane, and 2-oxa-6-azaspiro[3.5]nonane.

[0052] As used herein, alone or in combination with another term, "aromatic" refers to a monocyclic or polycyclic ring system containing 4n + 2 π electrons (where n is an integer). Aromatics refer to ring systems containing only carbon atoms (i.e., aryl), and ring systems containing at least one heteroatom selected from N, O, or S (i.e., "heteroaromatic" or "heteroaryl"), and are to be understood as including these. Aromatic ring systems may be substituted or unsubstituted.

[0053] As used herein, alone or in combination with another term, "non-aromatic" refers to a monocyclic or polycyclic ring system having at least one double bond that is not part of an extended conjugated π system. As used herein, non-aromatic refers to ring systems containing only carbon atoms, and ring systems containing at least one heteroatom selected from N, O, or S, and includes these. Non-aromatic ring systems may be substituted or unsubstituted.

[0054] The term "heteroaryl" or "heteroaromatic" means a monocyclic, bicyclic or polycyclic aromatic ring incorporating one or more (e.g., 1 to 4, particularly 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur. The term heteroaryl includes both monovalent and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing 5 to 12 ring members, more usually 5 to 10 ring members. A heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10-membered bicyclic ring, for example a bicyclic structure formed from a fused 5- and 6-membered ring or two fused 6-membered rings. Each ring can typically contain up to about 4 heteroatoms selected from nitrogen, sulfur and oxygen. Typically, a heteroaryl ring contains up to 3 heteroatoms, more usually up to 2, for example a single heteroatom. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atoms within the heteroaryl ring can be basic, as in the case of imidazole or pyridine, or essentially non-basic, as in the case of the nitrogen of indole or pyrrole. Generally, the number of basic nitrogen atoms present in a heteroaryl group, including any amino group substituents of the ring, is less than 5.

[0055] Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthyridinyl, carbazolyl, phenazinyl, benzoisoquinolinyl, pyridopyrazinyl, thieno[2,3-b]furanyl, 2H-furo[3,2-b]-pyranyl, 5H-pyrido[2,3-d]-oxazinyl, 1H-pyrazolo[4,3-d]-oxazolyl, 4H-imidazo[4,5-d]thiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-b][1,2,4]triazinyl. "Heteroaryl" also encompasses partially aromatic bicyclic or polycyclic ring systems in which at least one ring is an aromatic ring and one or more other rings are non-aromatic, saturated or partially saturated rings, provided that at least one ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur. Examples of partially aromatic heteroaryl groups include, for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydrobenzothienyl, dihydrobenzofuranyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,3]dioxolyl, 2,2-dioxo-1,3-dihydro-2-benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, 1,2,3,4-tetrahydropyrido[2,3-b]pyrazinyl and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl.

[0056] Examples of 5-membered heteroaryl groups include, but are not limited to, pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, and tetrazolyl groups.

[0057] Examples of 6-membered heteroaryl groups include, but are not limited to, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, and triazinyl.

[0058] Bicyclic heteroaryl groups include, for example, a benzene ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; a pyridine ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; a pyrimidine ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; a pyrrole ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; a pyrazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; a pyrazine ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; an imidazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; an oxazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; an isoxazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; a thiazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; an isothiazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; a thiophene ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; A furan ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; A cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms; and A cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms may be a group selected from.

[0059] Specific examples of bicyclic heteroaryl groups containing a 6-membered ring fused to a 5-membered ring include, but are not limited to, benzofuranyl, benzothiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl and pyrazolopyridinyl groups.

[0060] Specific examples of bicyclic heteroaryl groups containing two fused 6-membered rings include, but are not limited to, quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolidinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.

[0061] The term "aryl" means a cyclic or polycyclic aromatic ring having 5 to 12 carbon atoms. The term aryl includes both monovalent and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl and the like. In certain embodiments, aryl is phenyl.

[0062] This specification also uses several compound terms to describe groups containing two or more functional groups. Such terms will be understood by those skilled in the art. For example, (3-6C) cycloalkyl(m-nC) alkyl includes (m-nC) alkyl substituted by (3-6C) cycloalkyl.

[0063] The term "optionally substituted" refers to either a substituted group, structure, or molecule or an unsubstituted group, structure, or molecule. "R 1 The term "one or any CH group, CH2 group, CH3 group, or heteroatom (i.e., NH) within the group is optionally substituted" properly means that (any) one of the hydrogen groups of the R 1 group is substituted by a properly defined group.

[0064] When an optional substituent is selected from "one or more" groups, this definition should be understood to include all substituents selected from one of the specified groups or substituents selected from two or more of the specified groups. In some embodiments, one or more refers to one, two, or three. In another embodiment, one or more refers to one or two. In a particular embodiment, one or more refers to one.

[0065] The phrase "the compounds of the present invention" means, both generally and specifically, the compounds disclosed herein.

[0066] "About", as used herein in connection with a measurable value such as an amount or a period, is intended to encompass reasonable variations of the value, for example, to account for experimental error in the measurement of the value.

[0067] Compound In one aspect, the present invention provides a compound having the following structural formula (I), or a pharmaceutically acceptable salt, hydrate, or solvate thereof:

Chemical formula

[0068] In a further aspect, the invention provides that R3 is hydrogen, cyano, (1-8C)alkyl, (3-7C)cycloalkyl, (CH2) 1~3 (3-7C)cycloalkyl, 4-7 membered carbon-bonded heterocyclyl, 5-6 membered carbon-bonded heteroaryl, -C(O)-(1-8C)alkyl, -C(O)(CH2) 0~3(3 - 7C) cycloalkyl, -C(O)[5 - or 6 - membered heteroaryl], -C(O)phenyl, -C(O)O(1 - 8C)alkyl, -C(O)O(3 - 7C)cycloalkyl, -C(O)O(CH2) 1~3 (3 - 7C) cycloalkyl, -C(O)NH2, -C(O)NH-(1 - 8C)alkyl, -C(O)NH-(CH2) 0~3 (3 - 7C) cycloalkyl, -C(O)NH-(CH2) 0~3 Heterocyclyl, -C(O)NH-(CH2) 0~3 [5 - or 6 - membered heteroaryl], -C(O)NH-(CH2) 0~3 Selected from phenyl, -S(O)2H or -S(O)2-(1 - 8C)alkyl; any alkyl, cycloalkyl, phenyl, heteroaryl or heterocyclyl moiety may also be optionally substituted by one or more R substituents as defined herein 300 Relates to a compound of formula I as defined above, optionally substituted by one or more substituents as defined herein.

[0069] Certain compounds of the present invention are, for example, of the structural formulas (Ia), (Ib), (Ic), (Id) or (Ie) shown below:

Chemical formula

[0070] Certain compounds of the present invention are, for example, unless otherwise specified, each of R1, X, R2, R3, R4, X1, R5 and Q and any attendant substituents has any of the meanings defined in any of the above or the following paragraphs (1) - (43), a compound of formula (I) [including sub - formulas (Ia), (Ib), (Ic), (Id), (Ie) or (If)], or a pharmaceutically acceptable salt, hydrate and / or solvate thereof. (1) R1 is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, 5- or 6-membered heteroaryl or 4-7-membered heterocyclyl, wherein said (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, heteroaryl and heterocyclyl are optionally substituted by one or more R 100 substituents; R 100 is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH2) z OR f , (CH2) z C(O)R f , (CH2) z C(O)OR f , (CH2) z OC(O)R f , (CH2) z C(O)N(R j )R h , (CH2) z N(R g )C(O)R f , (CH2) z S(O) y R f , (CH2) z SO2N(R j )R h , (CH2) z N(R g )SO2R f , (CH2) z NR j R h , (CH2) z (3-7C) cycloalkyl, (CH2) z heterocyclyl, (CH2) z heteroaryl, or (CH2) z phenyl; (i) R f and R g are each independently selected from hydrogen or (1-2C) alkyl; R h and R jis independently selected from hydrogen or (1-2C) alkyl, or R h and R j together with the nitrogen atom to which they are attached, optionally form a 3- to 7-membered ring optionally containing further heteroatoms; (ii) Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl or phenyl moiety in the R 100 substituent group is also halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR k , C(O)R k , C(O)OR k , OC(O)R k , C(O)N(R l )R k , N(R l )C(O)R k , S(O) y R k , SO2N(R l )R k , N(R l )SO2R k , or NR l R k and is optionally further substituted by one or more substituents selected from, R k and R l are selected from hydrogen or (1-2C) alkyl; (2) R1 is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, phenyl or 5- or 6-membered heteroaryl, wherein said (2-6C) alkynyl, phenyl or heteroaryl is optionally substituted by one or more R 100 substituents; R 100 is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH2) z OR f , (CH2) z C(O)R f, (CH2) z C(O)OR f , (CH2) z OC(O)R f , (CH2) z C(O)N(R j )R h , (CH2) z N(R g )C(O)R f , (CH2) z S(O) y R f , (CH2) z SO2N(R j )R h , (CH2) z N(R g )SO2R f , (CH2) z NR j R h , (CH2) z (3 - 7C) cycloalkyl, (CH2) z - [4 - 6 membered heterocyclyl], (CH2) z - [5 - or 6 - membered heteroaryl] or (CH2) z selected from phenyl; (i) R f and R g are each independently selected from hydrogen or (1 - 2C) alkyl; R h and R j are each independently selected from hydrogen or (1 - 2C) alkyl, or R h and R j together with the nitrogen atom to which they are attached, optionally form a 3 - 7 membered ring optionally containing further heteroatoms; (ii) Any (1 - 4C) alkyl, (3 - 7C) cycloalkyl, heterocyclyl, heteroaryl or phenyl moiety in the R 100 substituent group is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1 - 2C) alkyl, (1 - 2C) haloalkyl, (1 - 2C) hydroxyalkyl, OR k , C(O)R k , C(O)OR k , OC(O)R k, C(O)N(R l )R k , N(R l )C(O)R k , S(O) y R k , SO2N(R l )R k , N(R l )SO2R k , or NR l R k is optionally further substituted by one or more substituents selected from k R l and R (3) R1 is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, phenyl or 5- or 6-membered heteroaryl, wherein said (2-6C) alkynyl, phenyl or heteroaryl is optionally substituted by one or more R 100 substituents; R 100 is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH2) z OR f , (CH2) z C(O)R f , (CH2) z C(O)OR f , (CH2) z OC(O)R f , (CH2) z C(O)N(R j )R h , (CH2) z N(R g )C(O)R f , (CH2) z S(O) y R f , (CH2) z SO2N(R j )R h , (CH2) z N(R g )SO2R f , (CH2) z NR jR h and (CH2) z (3 to 7C) cycloalkyl, (CH2) z -[4 to 6-membered heterocyclyl], (CH2) z -[5-membered or 6-membered heteroaryl] or (CH2) z selected from phenyl; (i) R f and R g are each independently selected from hydrogen or (1 to 2C) alkyl; (ii) Any (1 to 4C) alkyl, (3 to 7C) cycloalkyl, heterocyclyl, heteroaryl or aryl moiety in the R 100 substituent group is further optionally substituted by one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1 to 2C) alkyl, (1 to 2C) haloalkyl, (1 to 2C) hydroxyalkyl or OR k and R k is selected from hydrogen or (1 to 2C) alkyl; (4) R1 is selected from hydrogen, (2 to 6C) alkynyl, phenyl or 5-membered or 6-membered heteroaryl, wherein said (2 to 6C) alkynyl, phenyl or heteroaryl is optionally substituted by one or more R 100 substituents; R 100 is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1 to 4C) alkyl, (1 to 4C) hydroxyalkyl, (CH2) z OR f , C(O)R f , C(O)OR f , OC(O)R f , C(O)N(R j )R h , N(R g )C(O)R f , S(O) y R f , SO2N(R j )R h , N(R g )SO2R f, NR j R h , (CH2) z -[4 - 6 membered heterocyclyl], or (CH2) z selected from phenyl; (i) R f and R g are each independently selected from hydrogen or (1 - 2C) alkyl; (ii) Any (1 - 4C) alkyl, heterocyclyl, or phenyl moiety in the R 100 substituent group is further optionally substituted by one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1 - 2C) alkyl, (1 - 2C) haloalkyl, (1 - 2C) hydroxyalkyl or OR k , and R k is selected from hydrogen or (1 - 2C) alkyl; (5) R1 is (i) hydrogen; (ii) halo; (iii) methyl; (iv) CF3; (v) ethynyl optionally substituted by R 100 , i.e., [Chemical formula] (vi) phenyl optionally substituted by R 100 ; (vii) 5 - or 6 - membered heteroaryl optionally substituted by R 100 selected from ; R 100 is halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1 - 4C) alkyl, (1 - 4C) hydroxyalkyl, (CH2) z OR f , C(O)R f , C(O)OR f , OC(O)R f , C(O)N(R j )R h , N(Rg )C(O)R f 、S(O) y R f 、SO2N(R j )R h 、N(R g )SO2R f 、NR j R h 、(CH2) z -[4- to 6-membered heterocyclyl], or (CH2) z selected from phenyl; (i)R f and R g are each independently selected from hydrogen or (1-2C) alkyl; (ii)Any (1-4C) alkyl, heterocyclyl or phenyl moiety in the substituent group is optionally further substituted by one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl or OR 100 and R k is selected from hydrogen or (1-2C) alkyl; (6)R1 is (i) hydrogen; (ii) ethynyl optionally substituted by R 100 , i.e.,

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0071] Suitably, R1 is as defined in any one of the numbered paragraphs (1)-(9) above. More suitably, R1 is as defined in any one of the numbered paragraphs (5)-(9) above. Most suitably, R1 is as defined in any one of the numbered paragraphs (7)-(9) above.

[0072] Suitably, X is as defined in any one of the numbered paragraphs (10) to (18) above. More suitably, X is as defined in any one of the numbered paragraphs (14) to (18) above. Most suitably, X is as defined in any one of the numbered paragraphs (16) to (18) above.

[0073] Suitably, R2 is as defined in any one of the numbered paragraphs (10) to (17) above, R3 is as defined in any one of the numbered paragraphs (19) to (21) (including (19a) and (20a)) above, or R2 and R3 are joined together to form a -CH=CQ- group, where Q is as defined in any one of paragraphs (31) to (35) above. More suitably, R2 is as defined in any one of the numbered paragraphs (14) to (17) above, R3 is as defined in either of the numbered paragraphs (20) or (21) above, or R2 and R3 are joined together to form a -CH=CQ- group, where Q is as defined in any one of paragraphs (33) to (35) above. Most suitably, R2 is as defined in either of the numbered paragraphs (16) or (17) above, R3 is as defined in either of the numbered paragraphs (20) or (21) above, or R2 and R3 are joined together to form a -CH=CQ- group, where Q is as defined in either of paragraphs (34) or (35) above.

[0074] Suitably, R4 is as defined in paragraph (23) above.

[0075] Suitably, X1 is as defined in any one of the numbered paragraphs (24)-(30) above. More suitably, X1 is as defined in the numbered paragraphs (28)-(30) above. Most suitably, X1 is as defined in either one of the numbered paragraphs (29) or (30) above.

[0076] Suitably, R5 is as defined in any one of the numbered paragraphs (28)-(30) above. More suitably, R5 is as defined in paragraph (29) or (30) numbered above. Most suitably, R5 is as defined in paragraph (30) numbered above.

[0077] Suitably, y is as defined in paragraph (36) numbered above.

[0078] Suitably, x is as defined in paragraph (40) numbered above.

[0079] As shown above, specific compounds of the present invention are, for example, the following structural formulas (Ia), (Ib), (Ic), (Id) or (Ie): [Chemical formula] (wherein R1, X, R3, R4, R5 and Q are each as defined herein) include a compound of formula (I) as defined herein having one of the above, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof.

[0080] In a particular group of the compounds of the present invention, the compound has a structure according to formula Ia (a sub-definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein X, R4 and R5 each have any one of the definitions shown herein.

[0081] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in any one of paragraphs (10) to (18) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in any one of paragraphs (28) to (30) numbered above.

[0082] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in any one of paragraphs (14) to (18) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (29) or (30) numbered above.

[0083] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in paragraph (14) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (28) numbered above.

[0084] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in paragraph (15) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (28) numbered above.

[0085] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (16) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (29) above.

[0086] In certain embodiments of the compound of formula Ia, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (17) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (30) above.

[0087] In certain groups of the compounds of the invention, the compounds have the structure of formula Ib (a sub - definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein R1, R3, R4, and R5 each have any one of the definitions shown herein.

[0088] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of numbered paragraphs (1) to (9) above; R3 is as defined in any one of numbered paragraphs (19) to (21) (including (19a) and (20a)) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in any one of numbered paragraphs (28) to (30) above.

[0089] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of paragraphs (5) to (9) numbered above; R3 is as defined in any one of paragraphs (19) to (21) (including (19a) and (20a)) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (29) or (30) numbered above.

[0090] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in paragraph (5) numbered above; R3 is as defined in paragraph (19) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (28) numbered above.

[0091] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in paragraph (6) numbered above; R3 is as defined in paragraph (20) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (29) numbered above.

[0092] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in paragraph (7) numbered above; R3 is as defined in the numbered paragraph (20) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0093] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (8) above; R3 is as defined in the numbered paragraph (21) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0094] In certain embodiments of the compound of formula Ib, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (9) above; R3 is as defined in the numbered paragraph (21) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0095] In certain groups of the compounds of the present invention, the compounds have the structure of formula Ic (a sub - definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein R1, R4, and R5 each have any one of the definitions shown herein.

[0096] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (1)-(9) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in any one of the numbered paragraphs (28)-(30) above.

[0097] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (5)-(9) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) or (30) above.

[0098] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (5) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (28) above.

[0099] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (6) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0100] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (7) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0101] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (8) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0102] In certain embodiments of the compound of formula Ic, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (9) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0103] In certain groups of the compounds of the present invention, the compounds have the structure of formula Id (a sub - definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein R1, Q, R4, and R5 each have any one of the definitions shown herein.

[0104] In certain embodiments of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (1) to (9) above; Q is as defined in any one of the numbered paragraphs (32) to (35) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in any one of the numbered paragraphs (28) to (30) above.

[0105] In an embodiment of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (5) to (9) above; Q is as defined in any one of the numbered paragraphs (33) to (35) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) or (30) above.

[0106] In an embodiment of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (5) above; Q is as defined in the numbered paragraph (32) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (28) above.

[0107] In an embodiment of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (6) above; Q is as defined in the numbered paragraph (33) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0108] In certain embodiments of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in numbered paragraph (7) above; Q is as defined in numbered paragraph (33) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (29) above.

[0109] In certain embodiments of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in numbered paragraph (8) above; Q is as defined in numbered paragraph (34) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (30) above.

[0110] In certain embodiments of the compound of formula Id, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in numbered paragraph (9) above; Q is as defined in numbered paragraph (35) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (30) above.

[0111] In certain groups of the compounds of the invention, the compounds have the structure of formula Ie (a sub - definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein X, R3, R4 and R5 each have any one of the definitions shown herein.

[0112] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in any one of paragraphs (10)-(18) numbered above; R3 is as defined in any one of paragraphs (19)-(21) (including (19a) and (20a)) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in any one of paragraphs (28)-(30) numbered above.

[0113] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in any one of paragraphs (14)-(18) numbered above; R3 is as defined in any one of paragraphs (19)-(21) (including (19a) and (20a)) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (29) or (30) numbered above.

[0114] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in paragraph (14) numbered above; R3 is as defined in paragraph (19) numbered above; R4 is as defined in paragraph (23) numbered above; R5 is as defined in paragraph (28) numbered above.

[0115] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (14) above; R3 is as defined in numbered paragraph (20) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (29) above.

[0116] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (15) above; R3 is as defined in numbered paragraph (20) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (29) above.

[0117] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (16) above; R3 is as defined in numbered paragraph (21) above; R4 is as defined in numbered paragraph (23) above; R5 is as defined in numbered paragraph (30) above.

[0118] In certain embodiments of the compound of formula Ie, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, X is as defined in numbered paragraph (17) above; R3 is as defined in numbered paragraph (21) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0119] In certain groups of the compounds of the present invention, the compound has a structure according to formula If (a sub - definition of formula I), or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, wherein R1, Q, R4, and R5 each have any one of the definitions shown herein.

[0120] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (1) to (9) above; Q is as defined in any one of the numbered paragraphs (32) to (35) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in any one of the numbered paragraphs (28) to (30) above.

[0121] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in any one of the numbered paragraphs (5) to (9) above; Q is as defined in any one of the numbered paragraphs (33) to (35) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) or (30) above.

[0122] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (5) above; Q is as defined in the numbered paragraph (32) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (28) above.

[0123] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (6) above; Q is as defined in the numbered paragraph (33) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0124] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (7) above; Q is as defined in the numbered paragraph (33) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (29) above.

[0125] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (8) above; Q is as defined in the numbered paragraph (34) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0126] In certain embodiments of the compound of formula If, or a pharmaceutically acceptable salt, hydrate and / or solvate thereof, R1 is as defined in the numbered paragraph (9) above; Q is as defined in the numbered paragraph (35) above; R4 is as defined in the numbered paragraph (23) above; R5 is as defined in the numbered paragraph (30) above.

[0127] Particular compounds of the invention are any of the compounds exemplified in this application, or a pharmaceutically acceptable salt or solvate thereof, in particular, 5-(2-Aminopyridin-4-yl)-7-chloro-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-methyl-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(trifluoromethyl)-1H-indazole-3-amine; 7-Chloro-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-Bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-Ethynyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-Phenyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(tert-Butyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid; 7-Bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indazol-3-amine 5-(2-(Ethylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Propylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Isopropylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-((Cyclopropylmethyl)amino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Isopentylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Hexylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Cyclohexylamino)pyridin-4-yl)-1H-indazol-3-amine; 5-{2-[(Trans-4-methylcyclohexyl)amino]pyridin-4-yl}-1H-indazol-3-amine; 2-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)ethan-1-ol; 3-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)propan-1-ol; 4-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)butan-1-ol; 5-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)pentan-1-ol; 5-{2-[(trans-4-Hydroxycyclohexyl)amino]pyridin-4-yl}-1H-indazol-3-amine; 5-(2-((2-Methoxyethyl)amino)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-((3-Methoxypropyl)amino)pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((3-Isopropoxypropyl)amino)pyridin-4-yl)-1H-indazole-3-amine; 3-((4-(3-Amino-1H-indazol-5-yl)pyrimidin-2-yl)amino)propan-1-ol; 3-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)(methyl)amino)propan-1-ol; 5-(2-((2-Morpholinoethyl)amino)pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((2-(Piperidin-1-yl)ethyl)amino)pyridin-4-yl)-1H-indazole-3-amine; N 1 -(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-N3-methylpropane-1,3-diamine; N-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide; N-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)benzamide; Ethyl (4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)carbamate; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-ethylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-ethylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-propylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-isopentylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-cyclopentylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-cyclohexylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(2-hydroxyethyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-hydroxypropyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(2-methoxyethyl)urea; 3-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-1-(2-hydroxyethyl)-1-methylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-benzylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-phenethylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(pyridin-2-ylmethyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(pyridin-3-ylmethyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(pyridin-4-ylmethyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-phenylurea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-fluorophenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-chlorophenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-isopropylphenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-(hydroxymethyl)phenyl)urea; 3-(3-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)ureido)benzamide; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-phenoxyphenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-(benzyloxy)phenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-((4-fluorobenzyl)oxy)phenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-((3-fluorobenzyl)oxy)phenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-((2-fluorobenzyl)oxy)phenyl)urea; 3-(3-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)ureido)-N-phenylbenzamide; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(4-fluorophenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(4-chlorophenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(4-(tert-butyl)phenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(4-(methylsulfonyl)phenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(o-tolyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(2-ethylphenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(2-isopropylphenyl)urea; 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(pyridin-3-yl)urea; 5-(2-Amino-3-ethynylpyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(cyclopropylethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(3,3-dimethylbut-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(cyclopentylethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(cyclohexylethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(phenylethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-((4-aminophenyl)ethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-((3-aminophenyl)ethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-((2-aminophenyl)ethynyl)pyridin-4-yl)-1H-indazol-3-amine; Methyl 3-((2-amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethynyl)benzoate; Methyl 4-((2-amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethynyl)benzoate; 5-(2-Amino-3-((2-methoxyphenyl)ethynyl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)-1-phenylpent-4-yn-1-one; 3-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)prop-2-yn-1-ol; 4-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)but-3-yn-1-ol; 5-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)penta-4-yn-1-ol; 6-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)-2-methylhex-5-yn-2-ol; 4-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)-2-methylbut-3-yn-2-ol; 5-(2-Amino-3-(3-(tert-butoxy)prop-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 1-((2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethynyl)cyclopentan-1-ol; 1-((2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethynyl)cyclohexan-1-ol; 1-((2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethynyl)cycloheptan-1-ol; 5-(2-Amino-3-(3-amino-3-methylbut-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(4-(piperidin-1-yl)but-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(4-morpholinobut-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(5-(piperidin-1-yl)penta-1-yn-1-yl)pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Amino-3-(5-morpholinopent-1-yn-1-yl)pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Amino-3-(3-(piperidin-4-yl)prop-1-yn-1-yl)pyridin-4-yl)-1H-indazole-3-amine; 3-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)-N-methylprop-2-ynamide; 5-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)-1-morpholinopent-4-yn-1-one; 5-(2-Amino-3-cyclopropylpyridin-4-yl)-1H-indazole-3-amine; 4-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)butan-1-ol; 1-(2-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)ethyl)cyclohexan-1-ol; 5-(2-Amino-4-(3-amino-1H-indazol-5-yl)pyridin-3-yl)pentan-1-ol; 5-(2-Aminopyridin-4-yl)-7-phenyl-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3-fluorophenyl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3-(trifluoromethyl)phenyl)-1H-indazole-3-amine; 7-(3-Aminophenyl)-5-(2-aminopyridin-4-yl)-1H-indazole-3-amine; 3-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)phenol; 5-(2-Aminopyridin-4-yl)-7-(3-methoxyphenyl)-1H-indazole-3-amine; (3-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)phenyl)methanol; 3-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzaldehyde; Ethyl 3-(3-amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzoate; 3-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzamide; 3-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzenesulfonamide; 5-(2-Aminopyridin-4-yl)-7-(3-(methylsulfonyl)phenyl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3-(morpholinomethyl)phenyl)-1H-indazol-3-amine; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)phenol; (4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)phenyl)methanol; 5-(2-Aminopyridin-4-yl)-7-(4-(dimethylamino)phenyl)-1H-indazol-3-amine; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzamide; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)benzenesulfonamide; 5-(2-Aminopyridin-4-yl)-7-(4-(morpholinomethyl)phenyl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(4-(tert-butyl)phenyl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(2-chlorophenyl)-1H-indazol-3-amine; (2-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)phenyl)methanol; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)-3-methylbenzenesulfonamide; 5-(2-Aminopyridin-4-yl)-7-(pyridin-3-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(pyridin-4-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(furan-3-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(thiophen-3-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(thiophen-2-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(thiazol-5-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(1H-pyrazol-5-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3-methylbut-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(pent-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(cyclopropylethynyl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-Aminopyridin-4-yl)-7-(phenylethynyl)-1H-indazol-3-amine; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)but-3-yn-1-ol; 4-(3-Amino-5-(2-aminopyridin-4-yl)-1H-indazol-7-yl)-2-methylbut-3-yn-2-ol; 5-(2-Aminopyridin-4-yl)-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazole-3-amine; 5-(2-Aminopyrimidin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(3,3-dimethylbutyl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(2-cyclohexylethyl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-(2-cyclopropylethyl)-1H-indazole-3-amine; 5-(2-Aminopyridin-4-yl)-7-phenethyl-1H-indazole-3-amine; 5-(2-Amino-5-fluoropyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-Amino-3-fluoropyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-Amino-6-fluoropyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridine-2,6-diamine; 6-Amino-4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)nicotinonitrile; 5-(2-(Cyclopropylamino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-(Cyclobutylamino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-(oxetan-3-ylamino)pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Cyclopentylamino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-((Cyclopropylmethyl)amino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((2,2,2-trifluoroethyl)amino)pyridin-4-yl)-1H-indazole-3-amine; 3-((4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)amino)propanenitrile; 2-((4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)amino)ethan-1-ol; N1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)ethane-1,2-diamine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((2-methoxyethyl)amino)pyridin-4-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((3-methoxypropyl)amino)pyridin-4-yl)-1H-indazole-3-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)acetamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)propionamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3,3,3-trifluoropropanamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)isobutyramide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)pivalamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-2-cyclopropylacetamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3-methylbutanamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)cyclobutanecarboxamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)cyclopentanecarboxamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-2-hydroxyacetamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-2-methoxyacetamide; 5-(2-(Cyclopropylamino)pyridin-4-yl)-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazole-3-amine; N-(4-(3-Amino-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazol-5-yl)pyridin-2-yl)acetamide; N-(4-(3-Amino-7-(phenylethynyl)-1H-indazol-5-yl)pyridin-2-yl)acetamide; Methyl (4-(3-amino-7-(cyclopropylethynyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-hydroxy-3-methylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-amino-3-methylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-methoxy-3-methylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-morpholinoprop-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(4-morpholinobut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; 1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)urea; 1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3-methylurea; 1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3-ethylurea; 1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3-propylurea; 1-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3-phenylurea; Methyl (4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Ethyl (4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; tert-Butyl (4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; (4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)sulfamic acid; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)methanesulfonamide; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)-6-fluoropyridin-2-yl)acetamide; N-(4-(3-Amino-7-phenyl-1H-indazol-5-yl)pyridin-2-yl)acetamide; N-(4-(3-Amino-7-(pyridin-4-yl)-1H-indazol-5-yl)pyridin-2-yl)acetamide; 7-(Furan-3-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 7-Ethynyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(Cyclopropylethynyl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(Cyclopentylethynyl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(Cyclohexylethynyl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 3-(3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)prop-2-yn-1-ol; 4-(3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)-2-methylbut-3-yn-2-ol; 1-((3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)ethynyl)cyclopentan-1-ol; 1-((3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)ethynyl)cyclohexan-1-ol; 1-((3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)ethynyl)cycloheptan-1-ol; 7-(5-Morpholinopent-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(4-(Piperidin-1-yl)but-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(5-(Piperidin-1-yl)pent-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(6-(Piperidin-1-yl)hex-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 6-(3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)hex-5-ynoic acid; 7-(3-Amino-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-7-yl)hept-6-ynoic acid; 7-(4-Phenoxybut-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 7-(6-Phenoxyhex-1-yn-1-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(tert-Butyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Cyclohexyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Neopentyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Cyclohexylmethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(2-Cyclohexylethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-Benzyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; (4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)methanol; 2-(4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)propan-2-ol; 3-(4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)pentan-3-ol; 5-(2-(tert-Butoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 5-(2-(Tetrahydro-2H-pyran-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 5-(2-((Tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; 4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid; Methyl 4-(3-amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; Ethyl 4-(3-amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; 4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; (4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)(pyrrolidin-1-yl)methanone; 4-(3-Amino-1H-indazol-5-yl)-N-cyclopentyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-isopentyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-phenethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(3-phenylpropyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(2-methoxyethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(2-aminoethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(2-(dimethylamino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; (4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)(4-methylpiperazin-1-yl)methanone; 4-(3-Amino-1H-indazol-5-yl)-N-(2-(piperidin-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(2-(butyl(ethyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(2-(diisopropylamino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-Amino-1H-indazol-5-yl)-N-(3-(dimethylamino)propyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 5-(2-((tert-Butylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine 5-(2-((Isopentylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Piperidin-2-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((Cyclohexylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((Phenylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((((2-(Benzyloxy)phenyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((((2-Methoxyethyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; N 1 -((4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)methyl)-N 2 ,N 2 -dimethyl ethane-1,2-diamine; 5-(2-((((3-Methoxypropyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((((3-Isopropoxypropyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; N 1 -((4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)methyl)-N 3 ,N 3 -dimethyl propane-1,3-diamine; 5-(2-((Isopropyl(methyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Piperidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((4,4-Difluoropiperidin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Morpholinomethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((4-Methylpiperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((4-(tert-Butyl)piperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Azepan-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((4-Methyl-1,4-diazepan-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(2-(Piperidin-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(2-Morpholinoethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(3-(Piperidin-1-yl)propyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(3-(Cyclohexylamino)propyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(3-Morpholinopropyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(Piperidin-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((1-Benzylpiperidin-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)oxazole-2-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((3,3,3-trifluoropropyl)amino)pyridin-4-yl)-1H-indazol-3-amine; 7-(Cyclopropylethynyl)-5-(2-(oxetan-3-ylamino)pyridin-4-yl)-1H-indazol-3-amine; Methyl (4-(3-amino-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; 4-(3-Amino-5-(2-(oxetan-3-ylamino)pyridin-4-yl)-1H-indazol-7-yl)-2-methylbut-3-yn-2-ol; 5-(2-(Oxetan-3-ylamino)pyridin-4-yl)-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazol-3-amine; N-(4-(3-Amino-7-(cyclopropylethynyl)-1H-indazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide; N-(4-(3-Amino-7-(3-hydroxy-3-methylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide; Methyl (4-(3-amino-7-(5-morpholinopent-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; N-(4-(3-Amino-7-(3-hydroxy-3-methylbutyl)-1H-indazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide; Methyl (4-(3-amino-7-(3,3-dimethylbutyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; 5-(2-Cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-Cyclopentyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-(tert-Butyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; (4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)methanol; 2-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)propan-2-ol; Methyl 4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; 5-(2-(Difluoromethyl)-3H-imidazo[4,5-b]pyridin-7-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; 5-(2-Cyclobutyl-3H-imidazo[4,5-b]pyridin-7-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-3-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)cyanamide; 5-(2-((1H-Pyrazol-3-yl)amino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-((1H-Pyrazol-4-yl)amino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((5-methyl-1H-pyrazol-3-yl)amino)pyridin-4-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((3-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)-1H-indazole-3-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)thiazole-2-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-4-methyloxazole-2-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-4-(trifluoromethyl)oxazole-2-amine; N-(4-(3-Amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)pyridin-2-yl)-3,5-dimethylisoxazole-4-amine; 5-(2-((1H-Imidazol-4-yl)amino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 5-(2-((4H-1,2,4-triazol-3-yl)amino)pyridin-4-yl)-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((2-methyl-2H-tetrazol-5-yl)amino)pyridin-4-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-(pyrimidin-2-ylamino)pyridin-4-yl)-1H-indazole-3-amine; 7-(3,3-Dimethylbut-1-yn-1-yl)-5-(2-((tetrahydrofuran-3-yl)amino)pyridin-4-yl)-1H-indazole-3-amine; Methyl (4-(3-amino-7-(4-hydroxyphenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; 4-(3-Amino-5-(2-(oxetan-3-ylamino)pyridin-4-yl)-1H-indazol-7-yl)phenol; Methyl (4-(3-amino-7-(4-aminophenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(7-(4-acetamidophenyl)-3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(4-carbamoylphenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(4-(morpholinomethyl)phenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; 5-(2-Aminopyridin-4-yl)-7-(4-(2-morpholinoethyl)phenyl)-1H-indazole-3-amine; Methyl (4-(3-amino-7-(4-(2-morpholinoethyl)phenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(4-(methylsulfonyl)phenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-hydroxyphenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-carbamoylphenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; Methyl (4-(3-amino-7-(3-(morpholinomethyl)phenyl)-1H-indazol-5-yl)pyridin-2-yl)carbamate; N-(4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)-2-cyclohexylacetamide; or 6-Amino-4-(3-amino-7-(3,3-dimethylbut-1-yn-1-yl)-1H-indazol-5-yl)nicotinonitrile comprises any one of them.

[0128] The various functional groups and substituents constituting the compounds of formula (I) or the sub-formulas (Ia) to (Ie) are typically selected such that the molecular weight of the compounds of formula (I) does not exceed 1000. More usually, the molecular weight of the compound is less than 900, for example less than 800, or less than 750, or less than 700, or less than 650. More preferably, the molecular weight is less than 600, for example, 550 or less.

[0129] Suitable pharmaceutically acceptable salts of the compounds of the present invention are, for example, acid addition salts of the compounds of the present invention that are sufficiently basic, for example, acid addition salts with inorganic acids or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, formic acid, citric methane sulfonate or maleic acid. Furthermore, suitable pharmaceutically acceptable salts of the compounds of the present invention that are sufficiently acidic are alkali metal salts, such as sodium salts or potassium salts, alkaline earth metal salts, such as calcium or magnesium salts, ammonium salts, or salts with organic bases that give pharmaceutically acceptable cations, such as salts with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.

[0130] Compounds that have the same molecular formula but differ in the nature or sequence of the bonds between their atoms or in the arrangement of those atoms in space are called "isomers". Isomers that differ in the arrangement of those atoms in space are called "stereoisomers". Stereoisomers that are not mirror images of each other are called "diastereomers", and stereoisomers that are mirror images that cannot be superimposed on each other are called "enantiomers". If a compound has, for example, an asymmetric center, it is bonded to four different groups and a pair of enantiomers is possible. Enantiomers can be characterized by the absolute configuration of their asymmetric centers and are described by the Cahn - Prelog R and S ranking rules or by the manner in which the molecule rotates the plane of polarization and are designated as dextrorotatory or levorotatory (i.e., as the (+)-isomer or (-)-isomer, respectively). Chiral compounds can exist as either individual enantiomers or as mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture".

[0131] The compounds of the present invention may have one or more asymmetric centers; thus, such compounds can be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof. Unless otherwise indicated, the description or naming of a particular compound in the specification and claims is intended to include both the individual enantiomers and mixtures thereof (racemic or otherwise). Methods for the determination of stereochemistry and the separation of stereoisomers are well known in the art (see the discussion in Chapter 4 of "Advanced Organic Chemistry", 4th Edition, J. March, John Wiley and Sons, New York, 2001) and are, for example, by synthesis from optically active starting materials or by resolution of the racemic form. Some of the compounds of the present invention may have geometric isomer centers (E - isomers and Z - isomers).

[0132] It should be understood that the present invention encompasses all optical isomers, diastereoisomers and geometric isomers having activity, and mixtures thereof.

[0133] The present invention also encompasses compounds of the invention as defined herein that contain one or more isotope substitutions. For example, H can be in any isotopic form including 1H, 2H (D), and 3H (T); C can be in any isotopic form including 12C, 13C, and 14C; O can be in any isotopic form including 16O and 18O, and so on.

[0134] It should also be understood that certain compounds of formula (I) or sub-formulas (Ia)-(Ie) may exist in solvated and non-solvated forms, such as hydrated forms. It should be understood that the present invention encompasses all such solvated forms having activity.

[0135] It should also be understood that certain compounds of formula (I) or sub-formulas (Ia)-(Ie) may exhibit polymorphism, and that the present invention encompasses all such forms having activity.

[0136] The compounds of formula (I) or sub-formulas (Ia)-(Ie) may exist in several different tautomeric forms, and reference to a compound of formula (I) or sub-formulas (Ia)-(Ie) includes all such forms. To avoid doubt, if a compound may exist in one of several tautomeric forms and only one is explicitly described or shown, nevertheless all others are encompassed by formula (I) or sub-formulas (Ia)-(Ie). Examples of tautomeric forms include, for example, keto / enol (illustrated below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and keto forms, enol forms, enolate forms such as the nitro / acyinitro tautomeric pairs.

[0137]

Chemical Formula

[0138] Compounds of formula (I) or sub-formulas (Ia) to (Ie) containing an amine functional group also form N-oxides. References herein to compounds of formula (I) or sub-formulas (Ia) to (Ie) containing an amine functional group include N-oxides as well. When a compound contains several amine functional groups, one or more nitrogen atoms may be oxidized to form N-oxides. Specific examples of N-oxides are N-oxides of tertiary amines or nitrogen atoms of nitrogen-containing heterocycles. N-oxides can be formed by treating the corresponding amine with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., percarboxylic acid). See, for example, Advanced Organic Chemistry, Jerry March, 4th Edition, Wiley Interscience, pages. More specifically, N-oxides can be produced by the procedure of L.W. Deady (Syn. Comm. 1977, 7, 509 - 514) in which the amine compound is reacted with m-chloroperbenzoic acid (mCPBA) in an inert solvent such as dichloromethane.

[0139] Compounds of formula (I) or sub-formulas (Ia) to (Ie) can be administered in the form of prodrugs that are decomposed in the human or animal body to release the compounds of the present invention. The use of prodrugs can change the physical properties and / or pharmacokinetic properties of the compounds of the present invention. When the compounds of the present invention contain suitable groups or substituents to which a property-modifying group can be attached, prodrugs can be formed. Examples of prodrugs include in vivo cleavable ester derivatives that can be formed from carboxy groups or hydroxy groups in compounds of formula (I) or sub-formulas (Ia) to (Ie), and in vivo cleavable amide derivatives that can be formed from carboxy groups or amino groups in compounds of formula (I) or sub-formulas (Ia) to (Ie).

[0140] Accordingly, the present invention includes compounds of formula (I) or sub-formulas (Ia)-(Ie) as defined above when made available by organic synthesis and when made available in the human or animal body by cleavage of their prodrugs. Accordingly, the present invention also includes compounds of formula (I) or sub-formulas (Ia)-(Ie) produced by organic synthesis means and also compounds produced in the human or animal body by metabolism of precursor compounds, i.e., the compounds of formula (I) or sub-formulas (Ia)-(Ie) can be synthetically produced compounds or metabolically produced compounds.

[0141] Suitable pharmaceutically acceptable prodrugs of the compounds of formula (I) or sub-formulas (Ia)-(Ie) are based on reasonable medical judgment as being suitable for administration to the human or animal body without undesirable pharmacological activity and without undue toxicity.

[0142] Various forms of prodrugs are, for example, a) Methods in Enzymology, Volume 42, pages 309 - 396, edited by K. Widder et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 "Design and Application of Pro-drugs", pages 113 - 191 by H. Bundgaard (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1 - 38 (1992); e) H. Bundgaard et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, "Pro-Drugs as Novel Delivery Systems", A.C.S. Symposium Series, Volume 14; and h) E. Roche (editor), "Bioreversible Carriers in Drug Design", Pergamon Press, 1987 are described in.

[0143] Suitable pharmaceutically acceptable prodrugs of the compounds of formula (I) or sub-formulas (Ia)-(Ie) having a carboxy group are, for example, their in vivo cleavable esters. In vivo cleavable esters of the compounds of formula I or sub-formulas (Ia)-(Ie) containing a carboxy group are pharmaceutically acceptable esters that are cleaved in the body of a human or animal to produce the parent acid or parent alcohol. Pharmaceutically acceptable esters suitable for carboxy include (1-6C) alkyl esters such as methyl, ethyl and tert-butyl, (1-6C) alkoxymethyl esters such as methoxymethyl ester, (1-6C) alkanoyloxymethyl esters such as pivaloyloxymethyl ester, 3-phthalidyl ester, (3-8C) cycloalkylcarbonyl-oxy-(1-6C) alkyl esters such as cyclopentylcarbonyl-oxymethyl ester and 1-cyclohexylcarbonyl-oxyethyl ester, 2-oxo-1,3-dioxolenylmethyl esters such as 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl ester, and (1-6C) alkoxycarbonyl-oxy-(1-6C) alkyl esters such as methoxycarbonyl-oxymethyl ester and 1-methoxycarbonyl-oxyethyl ester.

[0144] Suitable pharmaceutically acceptable prodrugs of the compounds of formula (I) or sub-formulas (Ia) to (Ie) having a hydroxy group are, for example, their in vivo cleavable esters or ethers. In vivo cleavable esters or ethers of the compounds of formula (I) or sub-formulas (Ia) to (Ie) containing a hydroxy group are, for example, pharmaceutically acceptable esters or ethers that are cleaved in the human or animal body to produce the parent hydroxy compound. Pharmaceutically acceptable ester-forming groups suitable for a hydroxy group include inorganic esters such as phosphate esters (including phosphoramidic acid cyclic esters). Further pharmaceutically acceptable ester-forming groups suitable for a hydroxy group include (1-10C) alkanoyl groups such as acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, (1-10C) alkoxycarbonyl groups such as ethoxycarbonyl, N,N-(1-6C)2 carbamoyl, 2-dialkylaminoacetyl and 2-carboxyacetyl groups. Examples of ring substituents on the phenylacetyl group and benzoyl group include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(1-4C) alkylpiperazin-1-ylmethyl. Pharmaceutically acceptable ether-forming groups suitable for a hydroxy group include α-acyloxyalkyl groups such as acetoxymethyl group and pivaloyloxymethyl group.

[0145] Suitable pharmaceutically acceptable prodrugs of the compounds of formula (I) or sub-formulas (Ia) to (Ie) having a carboxy group are, for example, their in vivo cleavable amides, for example amides formed by amines such as ammonia, (1-4C) alkylamines such as methylamine, [(1-4C) alkyl]2 amines such as dimethylamine, N-ethyl-N-methylamine or diethylamine, (1-4C) alkoxy-(2-4C) alkylamines such as 2-methoxyethylamine, phenyl-(1-4C) alkylamines such as benzylamine, and amino acids such as glycine or its esters.

[0146] Suitable pharmaceutically acceptable prodrugs of the compounds of formula (I) or sub-formulas (Ia) to (Ie) having an amino group are, for example, their in vivo cleavable amide derivatives. Suitable pharmaceutically acceptable amides from the amino group include, for example, (1-10C) alkanoyl groups such as acetyl, benzoyl, phenylacetyl and amides formed by substituted benzoyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl group and benzoyl group include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(1-4C) alkyl) piperazin-1-ylmethyl.

[0147] The in vivo effect of the compound of formula (I) or sub-formulas (Ia) to (Ie) can be exerted, in part, by one or more metabolites formed in the human or animal body after administration of the compound of formula (I) or sub-formulas (Ia) to (Ie). As described above, the in vivo effect of the compound of formula (I) or sub-formulas (Ia) to (Ie) can also be exerted by the metabolism of the precursor compound (prodrug).

[0148] The present invention can relate to any compound or specific group of compounds defined herein by optional, preferred or suitable features, or with respect to specific embodiments, but the present invention can also relate to any compound or specific group of compounds that specifically excludes said optional, preferred or suitable features or specific embodiments.

[0149] Suitably, the present invention excludes any individual compound that does not have the biological activity defined herein.

[0150] Synthesis The compounds of the present invention can be prepared by any suitable technique known in the art. Specific methods for preparing these compounds are further described in the accompanying examples.

[0151] In any reference synthetic method used to prepare the starting materials and the description of the synthetic method described in this specification, it should be understood that all proposed reaction conditions, including the selection of solvents, reaction atmosphere, reaction temperature, duration of the experiment, and work-up procedures, can be selected by those skilled in the art.

[0152] Those skilled in the art of organic synthesis understand that the functional groups present in various parts of the molecule must be compatible with the reagents and reaction conditions used.

[0153] It will be recognized that during the synthesis of the compounds of the present invention or during the synthesis of certain starting materials in the methods defined herein, it may be desirable to protect certain substituents to prevent unwanted reactions. One skilled in the art will recognize when such protection is necessary and how to place such protecting groups at a given position and later remove them.

[0154] For examples of protecting groups, see one of the many general texts on this subject, such as "Protective Groups in Organic Synthesis", Theodora Green (Publisher: John Wiley & Sons). The protecting groups can be removed by any convenient method described in the literature or known to those skilled in the art as suitable for the removal of the protecting group in question, and such methods are selected to effect the removal of the protecting group with minimal perturbation of other groups within the molecule.

[0155] Thus, for example, if the reactants contain groups such as amino, carboxy or hydroxy, it may be desirable to protect the groups in some of the reactions referred to herein.

[0156] As an example, protecting groups suitable for amino or alkylamino groups are, for example, acyl groups such as alkanoyl groups like acetyl, alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl groups, arylmethoxycarbonyl groups such as benzyloxycarbonyl, or aroyl groups such as benzoyl. The deprotection conditions for the above protecting groups necessarily vary depending on the choice of the protecting group. Thus, for example, an acyl group or an aroyl group such as an alkanoyl or alkoxycarbonyl group can be removed by hydrolysis with a suitable base such as an alkali metal hydroxide like lithium hydroxide or sodium hydroxide. Alternatively, an acyl group such as a tert-butoxycarbonyl group can be removed by treatment with a suitable acid such as hydrochloric acid, sulfuric acid or phosphoric acid or trifluoroacetic acid, and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group can be removed by, for example, hydrogenation on a catalyst such as palladium carbon or by treatment with a Lewis acid such as boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group that can be removed by treatment with an alkylamine such as dimethylaminopropylamine or hydrazine.

[0157] Protecting groups suitable for hydroxy groups are, for example, acyl groups such as alkanoyl groups like acetyl, aroyl groups such as benzoyl, or arylmethyl groups such as benzyl. The deprotection conditions for the above protecting groups necessarily vary depending on the choice of the protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group can be removed by hydrolysis with a suitable base such as an alkali metal hydroxide like lithium hydroxide, sodium hydroxide or ammonia. Alternatively, an arylmethyl group such as a benzyl group can be removed by, for example, hydrogenation on a catalyst such as palladium carbon.

[0158] Protecting groups suitable for carboxy groups are, for example, esterifying groups such as methyl or ethyl groups which can be removed by hydrolysis with a base such as sodium hydroxide, or t-butyl groups which can be removed by treatment with an acid such as an organic acid such as trifluoroacetic acid, or benzyl groups which can be removed by hydrogenation on a catalyst such as palladium carbon.

[0159] Resins can also be used as protecting groups.

[0160] The methodology used to synthesize the compounds of formula (I) or sub-formulae (Ia)-(Ie) varies depending on the nature of R 1 , R 2 , R 3 , R 4 , R 6 and R 10 and any substituent groups or subgroups associated therewith. Suitable methods for preparing these are further described in the accompanying examples.

[0161] Once the compounds of formula (I) or sub-formulae (Ia)-(Ie) have been synthesized by any one of the methods defined herein, these methods may (i) further include the step of removing any protecting groups present; (ii) the step of converting a compound of formula (I) into another compound of formula (I); (iii) the step of forming its pharmaceutically acceptable salt, hydrate or solvate; and / or (iv) the step of forming its prodrug Additional steps of.

[0162] An example of the above (ii) is when a compound of formula (I) is synthesized and then one or more of the groups are further reacted to change the nature of the group, providing an alternative compound of formula (I).

[0163] The resulting compounds of formula (I) or sub-formulae (Ia)-(Ie) can be isolated and purified using techniques well known in the art.

[0164] The compounds of formula (I) can be synthesized by the synthetic routes shown in the Examples section below.

[0165] Biological activity Using the biological assays described in the Examples section herein, the pharmacological effects of the compounds of the present invention can be measured.

[0166] The pharmacological properties of the compounds of formula (I) are expected to vary with structural changes, but the compounds of the present invention were found to be active in the IKK-alpha in vitro assay described in the Examples section, and the preferred compounds showed selectivity for IKK-alpha over IKK-beta.

[0167] Pharmaceutical composition According to a further aspect of the present invention, there is provided a pharmaceutical composition comprising a compound of the present invention as defined above, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in combination with a pharmaceutically acceptable diluent or carrier.

[0168] The compositions of the present invention may be in a form suitable for oral use (e.g., as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), topical use (e.g., as creams, ointments, gels, or aqueous or oily solutions or suspensions), administration by inhalation (e.g., as fine powders or liquid aerosols), administration by insufflation (e.g., as fine powders), or parenteral administration (e.g., as sterile aqueous or oily solutions for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular injection, or as suppositories for rectal administration).

[0169] The compositions of the present invention can be obtained by conventional procedures using conventional pharmaceutical excipients well known in the art. Thus, compositions intended for oral use may contain, for example, one or more coloring agents, sweetening agents, flavoring agents and / or preservatives.

[0170] An effective amount of a compound of the invention for use in therapy is an amount sufficient to treat or prevent the proliferative conditions referred to herein, delay their progression, and / or reduce the symptoms associated with the conditions.

[0171] For the manufacture of a single dosage form, the amount of the active ingredient combined with one or more excipients will necessarily vary depending on the individual being treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain from about 5 to about 98 weight percent of the total composition of suitable and conventional amounts of excipients, and, for example, from 0.5 mg to 0.5 g of the active agent (more suitably from 0.5 to 100 mg, for example 1 to 30 mg).

[0172] The dosage size for therapeutic or prophylactic purposes of the compounds of formula I will of course vary according to well-known medical principles according to the nature and severity of the condition, the age and sex of the animal or patient, and the route of administration.

[0173] When using a compound of the invention for therapeutic or prophylactic purposes, it is generally administered in divided doses as necessary so that, for example, a daily dose in the range of from 0.1 mg / kg body weight to 75 mg / kg body weight is received. Generally, when parenteral administration is used, a lower dose is administered. Thus, for example, in the case of intravenous or intraperitoneal administration, doses in the range of from 0.1 mg / kg body weight to 30 mg / kg body weight are generally used. Similarly, in the case of administration by inhalation, doses in the range of from 0.05 mg / kg body weight to 25 mg / kg body weight are used. Oral administration may also be suitable, particularly in tablet form. Typically, a unit dosage form contains from about 0.5 mg to 0.5 g of a compound of the invention.

[0174] Therapeutic use and applications The present invention provides compounds that function as inhibitors of IKK activity, particularly IKKα activity. Accordingly, the compounds of the invention are suitable for the treatment of any disease or condition in which inhibition of IKKα activity is potentially beneficial.

[0175] IKKα activity is known to play a role in cancer.

[0176] Role of IKKα in Cancer IKKα in Solid Tumors In recent years, the role of the non-canonical NF-κB pathway and IKKα within it has become increasingly associated with the development and progression of multiple solid tumors. The non-canonical NF-κB pathway is associated with poor prognosis in glioblastoma

[57] , and mouse orthotopic models have demonstrated that upregulation of this pathway is associated with aggressive glioblastoma subtypes

[57] . In prostate cancer, nuclear localization of RelB is associated with high-grade tumors

[58] , and treatment of prostate cancer cells with androgen induces accumulation of nuclear p52

[59] . Furthermore, silencing of IKKα decreases androgen receptor activity and gene expression, providing evidence that IKKα is associated with prostate cancer growth

[58] . Therefore, since the androgen receptor is a major driver of prostate cancer proliferation and inhibition of cell death, IKKα is an attractive target for prostate cancer.

[0177] In pancreatic cancer, the non-canonical NF-κB pathway is constitutively activated and associated with increased cell proliferation

[60] . NIK is elevated in pancreatic cancer and associated with increased proliferation [61, 62], upregulation of RelB and p52 is associated with mutant KRAS pancreatic cancer

[63] , and IKKα-dependent gene expression has been observed. In gastrointestinal tumors, NF-κB2 DCT / DCT Mouse models provide evidence that tumors develop spontaneously and that p100 / p52 drives carcinogenesis in this context

[64] . In renal cancer, members of the non-canonical NF-κB pathway are associated with poor prognosis, increased stage, and decreased local inflammation

[65] . In lung cancer, RelB is associated with short overall survival, differentiation, tumor invasion, lymph node metastasis, distant metastasis, and tumor, node, metastasis (TNM) stage

[68] . In bladder cancer, upregulation of RelB and p52 correlates with histological grade, stage, and lymph node metastasis

[69] .

[0178] There are also numerous studies investigating IKKα in breast cancer. IKKα, RelB, and p52 are associated with a decrease in cancer-specific survival in ER-positive breast diseases [70, 71]. Bcl3 can form a DNA-binding complex with p52 and has been observed to be overexpressed in breast cancer samples. IKKα has been demonstrated to play an essential role in the proliferation of mammary epithelium, and thus, it is not surprising that abnormal IKKα signaling has been reported in breast cancer

[72] . Yang et al. 2013 reported that in HER2-positive epithelial cells, nuclear IKKα can promote progression to tumorigenesis via p27

[73] . In transgenic mice, overexpression of p100 / 52 results in delayed mammary gland development, accompanied by overexpression of cyclin D1, MMP2, MMP9, and COX-2, and as a result, the mice develop multiple tumors

[74] . Furthermore, constitutive RANK signaling causes an increase in non-canonical NF-κB signaling in breast cancer cell lines, which then stimulates cell proliferation via an increase in the transcription of cyclin D1 [75 - 77], and nuclear IKKα expression has been observed in invasive ductal carcinoma and is associated with disease-free survival. Immunohistochemical studies have demonstrated that the p52 subunit is expressed at high levels in breast cancer tissue compared to normal adjacent tissue

[78] , and Western blots of nuclear fractions extracted from cancerous and adjacent normal breast tissue confirm an increase in p52 levels in tumor cells

[78] . This is accompanied by an increase in the mRNA levels of p52, Bcl-3, and cyclin D1, all of which are genes regulated by IKKα

[78] . Additionally, IKKα has been demonstrated to regulate mTORC1 and mTORC2, which control tumor cell proliferation, in cervical, lung, prostate, and pancreatic cell lines

[79] . Overall, there is now a substantial amount of evidence supporting the role of the IKKα-NF-κB non-canonical pathway in the development and progression of solid tumors.

[0179] IKKα Signaling Independent of the NF-κB Pathway in Solid Tumors In addition to the role played by IKKα in the NF-κB pathway, it has also been reported that IKKα has a role independent of both the canonical and non-canonical NF-κB pathways. IKKα accumulates in the nucleus and can phosphorylate various substrates including histone H3, SMRT, and nuclear receptor corepressor (NCoR)

[80] . In colorectal cancer, IKKα phosphorylates SMRT, leading to increased expression of Notch-dependent genes

[80] . Furthermore, IKKα has been reported to be associated with NOTCH activation in the presence of anti-estrogen drugs in breast cancer, resulting in upregulation of ER-dependent gene expression and providing a mechanism for hormone resistance in an NF-κB-independent manner [81, 82]. Bennett et al. reported that neither NIK nor RelB is associated with IKKα expression in relation to recurrence in luminal A-type breast cancer, suggesting that it is independent of the non-canonical NF-κB pathway

[71] . In a second cohort of tamoxifen-treated patients, the authors reported that cytoplasmic IKKα is associated with the disease-free and recurrence-free survival of tamoxifen in luminal A-type disease, which can predict patients who are likely to develop resistance to tamoxifen or IKKα-targeted therapy

[71] , and supports the role of IKKα in tamoxifen-resistant breast cancer once again. However, in contrast, Roseweir et al. reported that low IKKα expression is associated with an increased risk of recurrence with continuous tamoxifen / exemestane therapy in the tamoxifen and exemestane adjuvant multinational (TEAM) clinical trial cohort, suggesting that the role of IKKα in hormone therapy resistance may vary depending on the mechanism of action of the therapy the patient receives

[83] .

[0180] In gastric cancer, Helicobacter pylori-mediated NF-κB activation occurs through an IKKα-binding pathway involving both IKKα and NIK, which is independent of the non-canonical NF-κB pathway but upregulates inflammatory infiltration and is thought to promote tumorigenesis

[84] . Studies on IKKα independent of the non-canonical NF-κB pathway in colorectal cancer and cutaneous squamous cell carcinoma have focused on a truncated form of IKKα (p45 IKKα) that is constitutively active and specifically present in the nucleus [55, 56]. Bennett et al. observed that nuclear IKKα in breast cancer has a stronger predictive power than cytoplasmic IKKα, and proposed that this may be due to the detection of the truncated activated form of p45 IKKα because the antibodies used could not distinguish between full-length IKKα and the truncated p45 IKKα form

[71] . Other studies on IKKα signaling independent of the non-canonical NF-κB pathway in colorectal cancer have shown that IKKα binds to Notch-dependent gene promoters and upregulates them, releases chromatin-bound SMRT, which can be restored by IKKα inhibition, and provides additional evidence that the size of colorectal cancer xenografts is reduced

[56] . Truncated p45 IKKα has been reported to form a complex with full-length IKKα and NEMO and is responsible for regulating the phosphorylation of SMRT and histone H3 in an NF-κB-independent manner. Furthermore, p45 IKKα V600E In mutant-type colorectal tumors, it can be phosphorylated in a TAK1-dependent but NF-κB-independent manner

[56] , supporting the role of nuclear IKKα independent of non-canonical NF-κB signaling.

[0181] The nuclear role of IKKα has been consistently reported as being independent of NF-κB by activating alternative pathways such as NOTCH

[85] . This has been observed in breast cancer, skin cancer, and osteosarcoma

[86] . In liver cancer, hepatitis B virus X protein downregulates maspin expression via nuclear IKKα, leading to chemotherapy resistance, suggesting that targeting IKKα can resensitize HCC tumors to chemotherapy

[87] . In a transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer, IKKα can translocate to the nucleus in a maspin-dependent manner and promote the metastasis and development of castration-resistant disease, which is associated with a local inflammatory response

[88] . Similar to breast cancer, in prostate cancer, since IKKα is associated with the development of castration-resistant prostate cancer

[53] , nuclear IKKα seems to provide a mechanism of hormone resistance, and deletion of BAG3 required for IKKα nuclear translocation delays the development of castration-resistant disease

[89] .

[0182] Association of IKKα with cancer hallmarks in human tumors The NF-κB pathway regulates the transcription of a wide range of genes involved in inflammation, proliferation, and apoptosis. Many of these processes are hallmarks of cancer [46, 47], and NF-κB is hypothesized to link inflammation and tumorigenesis. Whether IKKα functions as a member of the non-canonical NF-κB pathway or in its NF-κB-independent role, it is clear that it is involved in multiple hallmarks of cancer, including important roles in innate and adaptive immune responses, cell survival, cell death, and inflammation [90, 91]. The non-canonical NF-κB pathway plays an important role in the regulation of processes including the production of lymphoid organs (responsible for the production of B and T lymphocytes), B cell development and survival, dendritic cell function, and bone metabolism

[92] , and has been reported to promote cancer development and progression through the promotion of inflammatory infiltration. Mouse model studies have demonstrated that mice with dominant negative, catalytically inactive IKKα have reduced adenoma formation and small colorectal tumors with a low proliferation index when treated with carcinogens, which was associated with an increase in the recruitment of macrophages and other immune cell types

[93] . In skin cancer research, IKKα has been demonstrated to induce inflammation-related genes

[94] . Additional studies using a model of peritoneal metastasis in immunocompetent mice showed that intraperitoneal injection of IκBα-suppressed colon cancer induced an M1-like macrophage phenotype with reduced liver and peritoneal metastases in vivo. This was associated with an increase in intratumoral activated CD4 + and CD8 + T cells, as well as a decrease in angiogenesis

[93] , demonstrating that the NF-κB pathway acts together with local inflammatory infiltration to promote the progression of colorectal cancer. In renal cancer, the inflammatory effects of the NF-κB pathway are mainly attributed to the canonical p65 / p50 subunits in combination with STAT3. However, NIK and RelB have previously been shown to be important for B cell development [2], suggesting that the non-canonical NF-κB pathway also plays a role and that RelB can regulate local inflammatory infiltration in renal cell carcinoma. IKKα is also associated with the promotion of the expression of pro-inflammatory cytokines such as IL-8 in prostate cancer

[95] .

[0183] Kong et al. suggested that IKKα can be phosphorylated via deleted in breast cancer 1 (DBC1) to regulate B cell activation via RelB activity, which can cause an increase in cell proliferation in mice

[96] . Furthermore, polymerase chain reaction (PCR) array-based gene transcription profiling experiments demonstrated that a decrease in cellular IKKα expression significantly affected the increase in the expression of genes related to apoptosis induction, particularly BAK1 and BBC3, providing evidence that IKKα is involved in the regulation of both cell proliferation and apoptosis in ER-positive breast cancer. Dan et al. showed that IKKα can induce cell proliferation in cervical, lung, prostate, and pancreatic cell lines via mTORC

[79] , and demonstrated that in basal cell carcinoma, IKKα is associated with proliferation and EMT

[94] . In vitro studies have also demonstrated that the proliferation, migration, and invasive cancer phenotype of ovarian cancer epithelial cells were promoted via upregulation of IKKα. Furthermore, NIK levels are associated with the regulation of both cell proliferation and apoptosis in colorectal cancer, demonstrating that the non-canonical NF-κB pathway is involved in cell survival and tumor growth

[97] .

[0184] IKKα in Hematological Malignancies Aberrant NF-κB signaling and associated gene transcription, which regulate cellular processes involved in the initiation, maintenance, and progression of human malignancies, are also common to blood cells and cancer. In this regard, many B-cell leukemias and lymphomas exhibit aberrant NF-κB activation, implicating this transcription factor family in these diseases and suggesting that the regulation of these proteins could be a promising therapeutic target. Furthermore, it is now recognized that conventional cytotoxic agents increase NF-κB activation and can contribute to the development of drug resistance through several different mechanisms. Thus, inhibitors targeting NIK-IKKα-mediated signaling may prove clinically useful as monotherapies and also to re-sensitize patients to chemotherapeutic agents. Considering the frequency of gene mutations in the non-canonical NF-κB pathway and its important role in tumor microenvironment signaling, IKKα is an attractive anti-cancer target.

[0185] Chronic lymphocytic leukemia (CLL) is the most common leukemia in Europe and North America. It is characterized by the presence of mature-appearing CD5 + / CD19 +Characterized by the accumulation of B lymphocytes [

[0105] ]. NF-κB is constitutively activated in many CLL patients, which is associated with a more aggressive disease [106, 107]. Several recurrent genetic mutations in NF-κB-related genes have been described in CLL. The most common of these is the inactivating mutation of NFKBIE, which encodes IκBε, a negative NF-κB regulator. These NFKBIE abnormalities are found in approximately 7% of CLL cases and occur mainly in the poor-prognosis subgroup. Mutations in NFKBIE result in an increase in the nuclear translocation of RelA, which can be causative [

[0108] ]. NOTCH1 mutations occur at an even higher frequency in CLL (approximately 11%). These activating mutations are associated with a poor response to chemotherapy [

[0109] ], which can be caused by NOTCH1-mediated NF-κB pathway activation [110 - 112]. BIRC3 mutations are seen in a smaller proportion of CLL patients (approximately 4%), but due to the premature cleavage of cIAP2, the BIRC3-encoded protein product, they affect the non-canonical NF-κB pathway and result in the loss of its E3 ubiquitin ligase activity, which is essential for NIK proteasomal degradation. As a result, NIK levels increase, leading to the phosphorylation of IKKα, NF-κB2, the processing of p100 to p52, and the constitutive activation of non-canonical NF-κB signaling [

[0113] ]. Importantly, BIRC3 mutations are associated with a loss of sensitivity to chemotherapy and a poor prognosis [

[0114] ].

[0186] In addition to the genetic causes of NF-κB dysregulation in CLL, the lymph node microenvironment is now understood to play an important role in the regulation of the natural pathology of this disease. Signaling through the B cell receptor (BCR), toll-like receptors (TLRs) and CD40, as well as the involvement of the BAFF and proliferation-inducing ligand (APRIL) receptors TACI, BAFF-R and BCMA, generate survival- and proliferation-promoting niches mediated by NF-κB activation [116, 117]. The importance of this microenvironment is perhaps best exemplified by the marked clinical efficacy of the Bruton's tyrosine kinase inhibitor ibrutinib. Treatment with this drug results in a marked tissue redistribution effect, with leukemic cells being eliminated from lymphoid tissues

[0118] . The fraction of tumors distant from sites of increased NF-κB signaling results in a durable remission that is reversed by drug withdrawal.

[0187] Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. These are divided into three molecular subtypes: ABC (activated B cell), GCB (germinal center B cell), and PMBL (primary mediastinal large B-cell lymphoma). Initial evidence regarding the role of the canonical NF-κB pathway in DLBCL was obtained from gene expression profiling studies showing enrichment of NF-κB target genes in the ABC subtype. This group has the worst prognosis, suggesting NF-κB as a modulator of the clinical outcome of DLBCL

[0123] . Constitutive NF-κB activation in the ABC subtype can result from mutations in components of the BCR signaling cascade that lead to chronic BCR activation. These mutations often occur not only in the immunoreceptor tyrosine-based motif (ITAM) but also in the coiled-coil domain of the CARD11 / CARMA1 gene

[0124] . Finally, MYD88 gene mutations are found in approximately 30% of the ABC subtype, resulting in spontaneous activation of the downstream IRAK complex and NF-κB activation

[0125] . The non-canonical NF-κB pathway is also abnormally dysregulated in 10-15% of DLBCL cases due to TRAF2 and TRAF3 mutations

[0126] , identifying a subpopulation of tumors that can be targeted via IKKα.

[0188] Multiple myeloma (MM) is an incurable plasma cell malignancy that accounts for approximately 13% of all blood cancers. Disease progression is accompanied by clonal expansion of transformed plasma cells in the bone marrow. Overall, genetic abnormalities resulting in constitutive NF-κB activation are seen in approximately 20% of MM patients and 40% of MM cell lines [127-129]. Most of the genetic abnormalities associated with NF-κB dysregulation in MM involve the non-canonical NF-κB pathway, including abnormal expression of NIK, CD40, TRAF2, TRAF3, transmembrane activator and CAML interactor (TACI), and cIAP1 / 2 [127, 128]. In these studies, the majority of MM cases had either overexpression of the positive NF-κB regulators NIK, TACI, and CD40, or reduced or silenced activity of the negative NF-κB regulators TRAF2, TRAF3, and cIAP1 / 2. All of these phenotypes contribute to increased NF-κB signaling through a preference for non-canonical NF-κB signaling [128, 129]. Additionally, other less common genetic abnormalities that similarly result in constitutive NF-κB signaling in MM have been identified. These included, respectively, overexpression of the NFΚB1 gene (p105) and abnormalities within the NFΚB2 gene (p100), which result in increased canonical and non-canonical NF-κB signaling [127-129].

[0189] Gene abnormalities can account for some of the high NF-κB activity in MM, but a large proportion of NF-κB signaling in this disease is likely to result from interactions within the bone marrow microenvironment

[0129] . One such mechanism for NF-κB activation is through the CD40-CD40L interaction [130, 131]. CD40 is a cell surface marker that is not normally expressed on normal plasma cells but has been shown to increase in the early stages of MM

[0132] . Furthermore, blocking the interaction between CD40 and CD40L reduces NF-κB activation

[0127] . This leads to inhibition of IL-6 and vascular endothelial growth factor (VEGF) secretion, which in turn results in growth arrest and cell death of MM cells

[0133] . Additionally, bone marrow stromal cells (BMSCs) found in the MM tumor microenvironment have also been found to express high levels of NF-κB activation that helps support the proliferation, survival, and drug resistance of malignant plasma cells within the bone marrow niche

[0134] . Adhesion of MM cells to BMSCs induces NF-κB-dependent cytokine transcription as well as the secretion of TNFα, IL-6, VEGF, RANKL, and BAFF, promoting the survival and growth of MM cells through NF-κB activation of MM cells [135, 136].

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[0191] Accordingly, according to a further aspect of the present invention, there is provided a method of inhibiting IKKα activity in vitro or in vivo, the method comprising contacting a cell with an effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0192] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder in which IKKα activity is involved in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0193] According to a further aspect of the present invention, there is provided a method of treating a proliferative disorder in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0194] According to a further aspect of the present invention, there is provided a method of treating cancer in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound as defined herein or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein.

[0195] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition, for use in therapy.

[0196] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition, for use as a medicament.

[0197] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition, for use in the treatment of a proliferative disorder.

[0198] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition, for use in the treatment of cancer. In certain embodiments, the cancer is a human cancer.

[0199] According to a further aspect of the present invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the inhibition of IKKα activity.

[0200] According to a further aspect of the invention, there is provided a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of a disease or disorder in which IKKα activity is involved.

[0201] According to a further aspect of the invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating a proliferative disorder.

[0202] According to a further aspect of the invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating cancer.

[0203] According to a further aspect of the invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for inhibiting IKKα activity.

[0204] According to a further aspect of the invention, there is provided the use of a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for treating a disease or disorder in which IKKα activity is involved.

[0205] According to a further aspect of the invention, there is provided a method for preparing a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0206] According to a further aspect of the invention, there is provided a compound obtainable by, or obtained by, or directly obtained by, a method for preparing a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

[0207] According to a further aspect of the invention, there is provided a novel intermediate as defined herein suitable for use in any one of the synthetic methods shown herein.

[0208] The terms "proliferative disorder", "proliferative state", and "proliferative disease" are used interchangeably herein and relate to unwanted or uncontrolled cell proliferation of undesirable excess or abnormal cells, such as neoplasms or hyperplastic growth, whether in vitro or in vivo.

[0209] In the aspects outlined above of the present invention, the proliferative disorder is suitably cancer, and the cancer is suitably human cancer. In particular, the compounds of the present invention will be useful for the treatment of any cancer for which mismatch repair inhibition is beneficial.Any suitable cancer (e.g., adenoid cystic carcinoma, adrenal tumor, amyloidosis, anal cancer, appendiceal cancer, astrocytoma, ataxia telangiectasia, Beckwith-Wiedemann syndrome, bile duct cancer (cholangiocarcinoma), Birt-Hogg-Dubé syndrome, bladder cancer, bone cancer, brainstem glioma, brain tumor, breast cancer, Carney complex, central nervous system tumor, cervical cancer, colorectal cancer, Cowden syndrome, craniopharyngioma, desmoplastic infantile ganglioglioma, ependymoma, esophageal cancer, Ewing sarcoma, eye cancer, eyelid cancer, familial adenomatous polyposis, familial GIST, familial melanoma, familial non-VHL clear cell renal cell carcinoma, familial pancreatic cancer, gallbladder cancer, gastrointestinal stromal tumor - GIST, germ cell tumor, gestational trophoblastic disease, head and neck cancer, hereditary breast and ovarian cancer, hereditary diffuse gastric cancer, hereditary leiomyomatosis and renal cell cancer, hereditary mixed polyposis syndrome, hereditary pancreatitis, hereditary papillary renal cell carcinoma, juvenile polyposis syndrome, kidney cancer, lacrimal gland tumor, laryngeal and hypopharyngeal cancer, leukemia (acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), B-cell prolymphocytic leukemia, hairy cell leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic T-cell lymphocytic leukemia, eosinophilic leukemia), Li-Fraumeni syndrome, liver cancer, lung cancer (non-small cell lung cancer, small cell lung cancer), lymphoma (Hodgkin, non-Hodgkin), Lynch syndrome, mastocytosis, medulloblastoma, melanoma, meningioma, mesothelioma, multiple endocrine neoplasia type 1 and 2, multiple myeloma, MUTYH (or MYH)-associated polyposis, myelodysplastic syndrome (MDS), nasal and paranasal cancer, nasopharyngeal cancer, neuroblastoma, neuroendocrine tumor (e.g., of the gastrointestinal tract, lung or pancreas), neurofibromatosis type 1 and 2, nevoid basal cell carcinoma syndrome, oral and oropharyngeal cancer, osteosarcoma, ovarian / fallopian tube / peritoneal cancer, pancreatic cancer, parathyroid cancer, penile cancer, Peutz-Jeghers syndrome, pheochromocytoma, paraganglioma, pituitary tumor, pleuropulmonary blastoma, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma (e.g., Kaposi or soft tissue), skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymoma and thymic carcinoma, thyroid cancer, tuberous sclerosis, uterine cancer, vaginal cancer, von Hippel-Lindau syndrome, vulvar cancer, Waldenström macroglobulinemia, Werner syndrome, Wilms tumor as well as xeroderma pigmentosum) can be targeted.Particularly interesting cancers include hematologic cancers such as lymphoma (including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL), and angioimmunoblastic T-cell lymphoma (AITL)), leukemia (including acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML)), multiple myeloma, breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastroesophageal cancer, neuroendocrine cancer, osteosarcoma, prostate cancer, pancreatic cancer, small intestine cancer, bladder cancer, rectal cancer, cholangiocarcinoma, CNS cancer, thyroid cancer, head and neck cancer, esophageal cancer, and ovarian cancer.

[0210] Specific cancers in which IKKα inhibition is expected to be beneficial include advanced prostate cancer, multiple myeloma, pancreatic cancer, colorectal cancer (particularly metastatic colorectal cancer), and breast cancer (particularly triple-negative breast cancer).

[0211] Prostate cancer is of particular interest as a potential therapeutic target for IKKα inhibitors. Without wishing to be bound by any particular theory, in prostate cancer, effective targeting of IKKα may enhance the chemotherapeutic response to androgen deprivation therapy (ADT) by simultaneously inhibiting androgen-driven AR (androgen receptor) activity and androgen-independent AR activity. IKKα inhibition may also suppress inflammatory microenvironment signaling and eliminate tumor-promoting stimuli from adjacent stroma and infiltrating monocytes. Thus, IKKα inhibitors have the potential to alter the disease course, restore / extend sensitivity to AR-targeted therapy, and improve survival. Furthermore, their use in hormone-sensitive de novo metastatic disease may significantly extend the benefit period of conventional therapy and reduce the overall incidence of castration-resistant prostate cancer (CRPC). As a result, IKKα inhibitors are · The ultimate treatment for CRPC patients who have failed standard treatment · Combination therapy with ADT to prevent the emergence of CRPC / extend sensitivity to ADT · Combination therapy in CRPC patients to restore sensitivity to ADT / reduce the development of resistance to chemotherapy ·Monotherapy for preventing the emergence of CRPC Uses can be found in clinical scenarios such as

[0212] Route of administration The compounds of the present invention or pharmaceutical compositions containing these compounds can be administered to a subject by any convenient route of administration, regardless of whether it is systemic, peripheral, or local (i.e., the desired site of action).

[0213] Routes of administration include, but are not limited to, oral (e.g., by ingestion); buccal; sublingual; transdermal (e.g., including those by patch, plaster, etc.); transmucosal (e.g., including those by patch, plaster, etc.); intranasal (e.g., by nasal spray); intraocular (e.g., by eye drops); pulmonary (e.g., by inhalation or insufflation therapy via an aerosol, e.g., through the mouth or nose); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral (e.g., by injection including intratumoral, subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intramedullary, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, and intrasternal; by implantation of a depot or reservoir, e.g., subcutaneous or intramuscular).

[0214] Combination therapy The compounds of the present invention may be administered as monotherapy, or in addition to the compounds of the present invention, may be accompanied by conventional surgery or radiotherapy or chemotherapy or targeted agents. Such chemotherapeutic agents or targeted agents are (i) But not limited thereto, alkylating agents (e.g., cisplatin, oxaliplatin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulfan, temozolomide and nitrosourea); antimetabolites (e.g., gemcitabine and folic acid antimetabolites, such as fluoropyrimidines like 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside, and hydroxyurea); antitumor antibiotics (e.g., anthracyclines such as doxorubicin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mitramycin); antimitotic agents (e.g., vinca alkaloids such as vincristine, vinblastine, vindesine and vinorelbine and taxoids such as paclitaxel and docetaxel, and polo kinase inhibitors); and topoisomerase inhibitors (e.g., epipodophyllotoxins such as etoposide and teniposide, amsacrine, topotecan and camptothecin), such as antiproductive / antineoplastic drugs and their combinations used in medical oncology; (ii) But not limited thereto, cell growth inhibitors including antiestrogen drugs (e.g., tamoxifen, fulvestrant, toremifene, raloxifene, droloxifene and iodoxyfene), antiandrogen drugs (e.g., bicalutamide, flutamide, nilutamide and cyproterone acetate), LHRH antagonists or LHRH agonists (e.g., goserelin, leuprorelin and buserelin), progestogens (e.g., megestrol acetate) and corticosteroids (e.g., dexamethasone, prednisone and prednisolone), aromatase inhibitors (e.g., as exemestane, anastrozole, letrozole, vorozole), and inhibitors of 5α-reductase such as finasteride; (iii) but not limited thereto, c-Src kinase family inhibitors such as 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-tetrahydropyran-4-yloxyquinazoline (AZD0530; International Publication No. 01 / 94341), N-(2-chloro-6-methylphenyl)-2-{6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-ylamino}thiazole-5-carboxamide (dasatinib, BMS-354825; J. Med. Chem., 2004, 47, 6658-6661), bosutinib (SKI-606), and metalloproteinase inhibitors such as marimastat, anti-invasion agents such as inhibitors of urokinase plasminogen activator receptor function or antibodies against heparanase; (iv) but not limited thereto, inhibitors of growth factor function such as growth factor antibodies and growth factor receptor antibodies (e.g., anti-erbB2 antibody trastuzumab [Herceptin (trademark)], anti-EGFR antibody panitumumab, anti-erbB1 antibody cetuximab [Erbitux, C225] and any growth factor or growth factor receptor antibody disclosed by Stern et al. (Critical reviews in oncology / haematology, 2005, Vol. 54, pp. 11-29)); such inhibitors include tyrosine kinase inhibitors, e.g., inhibitors of the epidermal growth factor family (e.g., N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine (gefitinib, ZD1839), N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (erlotinib, OSI-774) and 6-acrylamido-N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-quinazolin-4-amine (CI1033) and other EGFR family tyrosine kinase inhibitors, erbB2 tyrosine kinase inhibitors such as lapatinib); inhibitors of the hepatocyte growth factor family; inhibitors of the insulin growth factor family; inhibitors of the platelet-derived growth factor family such as imatinib and / or nilotinib (AMN107); inhibitors of serine / threonine kinases (e.g., farnesyltransferase inhibitors, e.g., Ras / Raf signal transduction inhibitors such as sorafenib (BAY43-9006), tipifarnib (R115777) and lonafarnib (SCH66336)), inhibitors of cell signal transduction through MEK and / or AKT kinases, c-kit inhibitors, abl kinase inhibitors, PI3 kinase inhibitors, Plt3 kinase inhibitors, CSF-1R kinase inhibitors, IGF receptor (insulin-like growth factor) kinase inhibitors; aurora kinase inhibitors and cyclin-dependent kinase inhibitors such as CDK2 and / or CDK4 inhibitors are also included; (v) but not limited thereto, anti-angiogenic agents that inhibit the effects of vascular endothelial growth factor, such as anti-vascular endothelial growth factor antibody bevacizumab (Avastin (trademark)), and VEGF receptor tyrosine kinase inhibitors such as vandetanib (ZD6474), batatinib (PTK787), sunitinib (SU11248), axitinib (AG-013736), and pazopanib (GW786034); (vi) but not limited thereto, vascular damaging agents such as combretastatin A4 and the compounds disclosed in WO 99 / 02166, WO 00 / 40529, WO 00 / 41669, WO 01 / 92224, WO 02 / 04434, and WO 02 / 08213; (vii) endothelin receptor antagonists, such as dibotentan (ZD4054) or atrasentan; (viii) but not limited thereto, antisense therapies such as ISIS2503, anti-ras antisense, etc., directed to the targets listed above; (ix) immunotherapy approaches, such as cancer vaccines, antibodies, viruses (oncolytic viruses), and small molecules or cell therapy approaches, for increasing the immunogenicity of a patient's tumor cells and / or promoting a cell-mediated anti-tumor response. Such therapies include, but are not limited to, OX40 agonists, cGAS-STING agonists, A2a receptor antagonists, PI3 kinase inhibitors, TLR7 / 8 agonists, IDO inhibitors, arginase inhibitors, BTK inhibitors, and bromodomain inhibitors; transduction of cancer antigens by microbial vectors, direct introduction of cancer antigens into antigen-presenting cells, treatment with immune cells specific for cancer antigens (e.g., CAR-T), treatment with antibodies, antibody fragments, and antibody-drug conjugates that enable the immune system to recognize tumor cells may include one or more of the categories of.

[0215] The compounds of the present invention are expected to be particularly useful in combination with androgen deprivation therapy (ADT) and standard chemotherapy used to treat prostate cancer, particularly castration-resistant prostate cancer (CRPC).

[0216] Such conjoint treatment can be achieved by administering the individual components of the treatment simultaneously, sequentially, or separately. Such combination products use the compounds of the present invention within the dosage ranges described herein and other pharmaceutically active agents within their approved dosage ranges.

[0217] According to this aspect of the present invention, there is provided a combination for use in the treatment of cancer (e.g., cancer with solid tumors) comprising a compound of the present invention as defined herein, or a pharmaceutically acceptable salt or solvate thereof, and an anti-tumor agent.

[0218] According to this aspect of the present invention, there is provided a combination for use in the treatment of a proliferative condition such as cancer (e.g., cancer with solid tumors) comprising a compound of the present invention as defined herein, or a pharmaceutically acceptable salt or solvate thereof, and any one of the anti-tumor agents listed above in this specification.

[0219] In a further aspect of the present invention, there is provided a compound of the present invention or a pharmaceutically acceptable salt or solvate thereof for use in the treatment of cancer, optionally in combination with another anti-tumor agent selected from those listed above in this specification.

[0220] In a further aspect of the present invention, there is provided a compound of the present invention or a pharmaceutically acceptable salt or solvate thereof for use in the treatment of cancer, optionally in combination with a tyrosine kinase inhibitor selected from those listed above in this specification.

[0221] In this specification, when the term "combination" is used, it should be understood to refer to simultaneous, separate, or sequential administration. In one aspect of the invention, "combination" refers to simultaneous administration. In another aspect of the invention, "combination" refers to separate administration. In a further aspect of the invention, "combination" refers to sequential administration. When the administration is sequential or separate, the delay in the administration of the second component should not be such as to lose the beneficial effects of the combination.

[0222] According to a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of the invention, or a pharmaceutically acceptable salt or solvate thereof, in combination with an anti-tumor agent (optionally selected from those listed above in this specification), together with a pharmaceutically acceptable diluent or carrier.

Examples

[0223] Experimental Section General methods. Unless otherwise specified, commercially available materials were used without further purification. Air- or moisture-sensitive reactions were carried out under a nitrogen atmosphere. Anhydrous solvents were obtained from Sigma-Aldrich. Flash chromatography was performed using standard techniques 1 (Acros, 60 Å, 35 - 70 μm) using silica gel, or on a Biotage SP4 automated chromatography system (SNAP KP-Sil, 60 Å, 40 - 63 μm cartridge; detection wavelength: 254 nm; monitoring: 280 nm). NMR spectra ( 1 H and 13C) was recorded on either a JEOL ECX-400 (400 MHz); Bruker Avance3 / DPX400 (400 MHz) or Bruker Avance / DPX500 (500 MHz) instrument. Chemical shifts (δ) are quoted in parts per million (ppm) relative to an internal solvent standard. Coupling constants (J) are recorded in Hertz. Low-resolution mass spectrometry was performed on a ThermoFinnigan LCQ Duo by direct injection and high-resolution mass spectrometry was performed on an Exactive (thermo scientific) LCMS mass spectrometer. Reverse-phase HPLC purification was performed using a semi-preparative (50 × 21.2 mm) Luna 5μ C18 column (eluting with an acetonitrile / water gradient containing 0.1% TFA in each solvent using the following gradient) on a Waters 1525 binary HPLC pump, Waters 717 autosampler, Waters 2487 dual λ absorbance detector (254 nm) Waters HPLC system.

[0224]

Table 1

[0225] General procedure All commercially available reagents and solvents used were obtained from Sigma-Aldrich, Fluorochem Fisher Scientific, Acros, Alfa Aesar, Apollo scientific and Advand ChemBlocks and used without further purification. Air or moisture-sensitive reactions were carried out under an argon or nitrogen atmosphere. The microwave reaction was carried out using a Biotage Initiator system. Flash chromatography was performed using a Biotage SP4 automated chromatography system with a silica stationary phase (Fisher Scientific, 60 Å, 35 - 70 microns; detection wavelength: 254 nm; monitoring: 280 nm), and the mobile phase used is detailed in the text. Reverse-phase HPLC purification was performed on a Shimadzu Prominance HPLC at 40 °C; flow rate: 6 ml / min; detection wavelength: 254 nm, eluting with an acetonitrile / water gradient containing 0.1% TFA, using a semi-preparative (50×21.2 mm) Luna 5μm C18 column. NMR spectra were recorded on either a Bruker Avance3 / DPX400 (400 MHz), Bruker DRX500 (500 MHz), Bruker AV400 (400 MHz), Bruker AV500HD (500 MHz) or Bruker AV600 (600 MHz) instrument and analyzed using Advanced Chemistry Development Labs (ACD / labs) NMR Processor 12.00 or MestReNova 10.0 software. Chemical shifts (δ) are reported in parts per million (ppm) relative to an internal solvent standard (tetramethylsilane) and coupling constants (J) in Hertz (Hz). Splitting patterns are indicated as singlet (s), broad singlet (br.s), doublet (d), doublet of doublets (dd), triplet (t), quartet (q) and multiplet (m). LCMS was performed on an Agilent Technologies 1220 series LC system equipped with an Agilent 6100 series quadrupole mass spectrometer in ESI / APCI mode. Separation was achieved using an Agilent Eclipse C18 4.6×50 mm column; flow rate: 1 ml / min; detection: 254 nm; sample volume: 10 μl; mobile phase: acetonitrile / 5 mM ammonium acetate: water / 5 mM ammonium acetate; 5%, 1.48 min; 5 - 100%, 8 min; 100%, 13.5 min; 100 - 5%, 16.5 min; 18 min. HRMS was performed using an Exactive (Thermo scientific) or LTQ orbitrap (Thermo scientific).

[0226] Section 1 - Formula: [Chemical formula] Compound of

[0227] [Example 1] 3-Chloro-2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

[0228] [Chemical formula] 7.2 mL was taken from a 25 mL catalytic solution of [Ir(OMe)cod]2 (104 mg, 0.312 mmol [Ir]), bis(pinacolato)diboron (2644 mg, 10.4 mmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (84 mg, 0.312 mmol) dissolved in pre-prepared tert-butyl methyl ether, and this was added to a 10 - 20 mL microwave vial. 3-Chloro-2-fluorobenzonitrile (934 mg, 6 mmol) was added thereto, and the solution was heated at 90 °C for 90 minutes under microwave conditions. The solution was filtered through celite using CH2Cl2:methanol 10:1 and used without further purification. 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-7-chloro-3-amino-1H-indazole

[0229]

Chem.

[0230]

Chem.

[0231] [Example 2] (E)-5-Bromo-2-fluoro-3-methylbenzaldoxime

[0232]

Chem.

[0233]

Chem.

[0234]

Chemical formula

[0235] [Example 3] 5-Bromo-2-fluoro-3-(trifluoromethyl)benzonitrile

[0236]

Chem.

[0237]

Chem.

[0238]

Chemical formula

[0239]

Chemical Structure

[0240] Section 2 - Formula: [Chem.] compound of

[0241] [Example 4] 7-Chloro-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine

[0242] [Chem.] 4-Bromo-1H-pyrrolo[2,3-b]pyridine (0.291 g, 1.50 mmol) was placed in a 20 ml microwave vial together with 7-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-amine (0.502 g, 1.5 mmol), dioxane (8 ml) and potassium phosphate (4 ml of 1 M solution). The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (118) (0.118 g, 0.17 mmol, 5 mol%) was added, the vial was sealed and heated at 90 °C for 16 h. The solution was then cooled and the solvent was removed under reduced pressure to give the crude product, which was purified by flash chromatography to give the desired product. (321 mg, 0.98 mmol, 65 %), δ H(d6-DMSO): 5.57 (s, 1H), 5.69 (s, 2H), 6.70 (q, J = 1.72 1H), 7.21 (d, J = 5.00, 1H) 7.56 (t, J = 2.76, 1H), 7.84 (d, J = 1.24, 1H), 8.22 (d, J = 1.28 Hz, 1H), 8.27 (d, J = 5.00 Hz, 1H), 11.76 (s, 1H), 11.96 (s, 1H). LRMS: found: 283.2 (M+1), calculated C 14 H 10 ClN5: 284.2.

[0243] [Example 5] 7-Bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine

[0244] [Chemical formula] 4-Bromo-1H-pyrrolo[2,3-b]pyridine (0.291 g, 1.50 mmol) was placed in a 20 ml microwave vial together with 7-bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-amine (0.502 g, 1.5 mmol), dioxane (8 ml) and potassium phosphate (4 ml of 1 M solution). The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.118 g, 0.17 mmol, 5 mol%) was added, the vial was sealed and heated at 90 °C for 16 hours. The solution was then cooled and the solvent was removed under reduced pressure to give the crude product, which was purified by flash chromatography to give the desired product. (321 mg, 0.98 mmol, 65 %), δ H(d6-DMSO): 5.57 (s, 1H), 5.69 (s, 2H), 6.70 (q, J = 1.72 1H), 7.21 (d, J = 5.00, 1H) 7.56 (t, J = 2.76, 1H), 7.84 (d, J = 1.24, 1H), 8.22 (d, J = 1.28 Hz, 1H), 8.27 (d, J = 5.00 Hz, 1H), 11.76 (s, 1H), 11.96 (s, 1H). LRMS: found: 328.17 (M+1), calculated C 14 H 10 BrN5: 327.01.

[0245] [Example 6] 7-Ethynyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine

[0246] [Chemical Formula] 7-Bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine (0.200 g, 0.61 mmol) and ethynyltrimethylsilane (0.169 ml, 1.2 mmol) were added to a sealable vial containing triethylamine (2 ml) and DMF (2 ml), and the solution was degassed with N2 for 10 minutes. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) catalyst (0.064 g, 0.08 mmol) and CuI (0.017 g, 0.08 mmol) were added, the vial was sealed, and heated at 60 °C for 16 h. The solution was then cooled, and the solvent was removed under reduced pressure to give the crude product, which was purified by flash chromatography to give the desired product. (64 mg, 0.23 mmol, 38 %), δ H(d6-DMSO): 5.10 (s, 1H), 5.66 (s, 2H), 6.69 (q, J = 1.48 1H), 7.20 (d, J = 4.76, 1H) 7.55 (t, J = 3.28, 1H), 7.75 (d, J = 1.48, 1H), 8.25 (m, 2H), 11.76 (s, 1H), 11.96 (s, 1H). LRMS: found: 274.2 (M+1), calculated C 14 H 10 BrN5: 273.1.

[0247] [Example 7] 7-Phenyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine

[0248] [Chemical Formula] Into a 2 - 5 mL MW tube, a mixture of 7-chloro-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine (Example 4) (57 mg, 0.2 mmol, 1 equiv), phenylboronic acid (49 mg, 1.2 equiv, 2 equiv), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (6.5 mg, 5 mol%) in 1,4-dioxane (1.2 mL) was placed and stirred under argon. Then, 1M K3PO4 aqueous solution (0.6 mL, 3 equiv) was added. The reaction mixture was heated at 50 °C for 10 minutes and then at 110 °C for 17 hours under a gentle argon stream. During this time, the initial orange solution became a suspension. Then, the stirred reaction mixture was cooled to room temperature, slowly diluted with water (15 mL), and filtered. The filtered solid was washed with water (3 × 5 mL) and hexane (3 × 5 mL) to obtain the crude product (63 mg). Purification by flash chromatography (80 - 100% AcOEt in hexane) gave the title compound as an off-white solid (19 mg). 11H NMR (400 MHz, DMSO-D6) δ 5.60 (s, 2H), 6.76 (dd, J = 3.5, 1.8 Hz, 1H), 7.28 (d, J = 5.1 Hz, 1H), 7.39 - 7.47 (m, 1H), 7.49 - 7.58 (m, 3H), 7.69 (d, J = 1.7 Hz, 1H), 7.75 - 7.81 (m, 2H), 8.20 (d, J = 1.6 Hz, 1H), 8.27 (d, J = 5.1 Hz, 1H), 11.71 (s, 1H), 11.74 (s, 1H).

[0249] [Example 8] 5-(2-Methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-3-amine

[0250] [Chemical formula] A suspension of 4-chloro-2-methyl-7-azaindole (0.058 g, 0.35 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-amine (0.136 g, 0.53 mmol), 1 M potassium phosphate solution (0.87 ml, 0.87 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.011 g, 0.0175 mmol) in 1.5 ml of ethanol / water (1:1) was deoxygenated with nitrogen in a sealed tube, and the mixture was stirred at 90 - 100 °C for 18 hours. After the reaction mixture was cooled to room temperature, EtOAc and water were added. The extracted organic layer was dried over magnesium sulfate and concentrated under reduced pressure, and the residue was purified by column chromatography (80 - 90% EtOAc and 1% triethylamine in petroleum ether 60 - 80%) to obtain the title compound as a white solid (35 mg, 38%). 11H NMR (400 MHz, DMSO-d6) δ ppm 2.63 (s, 3 H) 5.53 ( s, 2 H) 6.37 (d, J=2.20 Hz, 1 H) 7.12 (d, J= 4.83 Hz, 1 H) 7.37 (d, J=8.35 Hz, 1 H) 7.62 (dd, J=8.79,1.76 Hz, 1 H) 8.12 (s, 1 H) 8.17 (d, J=5.27 Hz, 1 H) 11.53 (s, 1 H) 11.62 (s, 1 H). m / z (ESI-HRMS) calculated for C 15 H 14 N5(M+H + ) 264.1249 found= 264.1253 (M+H + )

[0251] [Example 9] 2-(tert-Butyl)-7-oxide-7-azaindole

[0252] [Chemical Structure] To an ice-cooled solution of 2-tert-butylazaindole (0.1 g, 0.57 mmol) in EtOAc was slowly added meta-chloroperbenzoic acid (0.16 g, 0.91 mmol). The reaction mixture was then warmed to room temperature and stirred for 1 hour. After completion of the reaction, the solvent was evaporated, treated with 1 M sodium carbonate solution, and extracted with EtOAc. The residue was then concentrated under vacuum to give the product as a yellow solid (68.4 mg, 63%). 1 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (s, 9 H) 6.26 (d, J=1.76 Hz, 1 H) 7.01 (dd, J=7.91, 6.15 Hz, 1 H) 7.51 (d, J=7.91 Hz, 1 H) 8.04 (d, J=6.15 Hz, 1 H) 12.25 (br. s., 1 H). 1313C NMR (100 MHz, DMSO-d6) δ ppm 29.93, 32.67, 97.14, 116.54, 119.27, 124.58, 130.97, 139.38, 151.47. m / z (ESI-MS) [M] + 191.1. 2-(tert-Butyl)-4-(3-amino-1H-indazol-5-yl)-7-azaindole

[0253]

Chem.

[0254] [Example 10] 4-(3-Amino-1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

[0255] [Chemical formula] The reactants were purified by HPLC to synthesize 4-(3-amino-1H-indazol-5-yl)-N-isopentyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (Example 237), and the title compound was also obtained as a yellow solid (0.0091 g, 0.0175 mmol, 22%). 1 1H NMR (400 MHz, DMSO-d6) δ 7.27 (d, J = 5.0 Hz, 1H), 7.34 (s, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.70 (dd, J = 8.7, 1.6 Hz, 1H), 8.24 (s, 1H), 8.43 (d, J = 5.0 Hz, 1H), 12.45 (s, 1H). HRMS: Calculated for C 15 H 12 O2N5(M + H + ) = 294.0986; Found: 294.0987

[0256] Section 3 - Formula: [Chemical formula] compounds of

[0257] [Example 11] 7-Bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indazole-3-amine

[0258] [Chemical formula] 4-Bromo-7H-pyrrolo[2,3-d]pyrimidine (0.200 g, 1.02 mmol) was placed in a 20 ml microwave vial together with 7-bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-amine (0.401 g, 1.20 mmol), dioxane (6 ml) and potassium phosphate (3 ml of 1 M solution). The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.118 g, 0.17 mmol) was added, the vial was sealed and heated at 90 °C for 16 hours. The solution was then cooled and the solvent was removed under reduced pressure to give the crude product, which was purified by flash chromatography to give the desired product. (180 mg, 0.55 mmol, 53 %), δ H (d6-DMSO): 5.85 (s, 2H), 7.14 (d, J = 3.5, 1H) 7.67 (d, J = 2.90, 1H), 8.40 (s, 1H), 8.67 (s, 1H), 8.79 (s, 1H), 12.07 (s, 1H), 12.22 (s, 1H). LRMS: found: 329.15 (M+1), calculated C 13 H9BrN6: 328.01.

[0259] Section 4 - Formula: [Chemical formula] of the compound

[0260] [Example 12] 5-[2-(Ethylamino)pyridin-4-yl]-1H-indazole-3-amine

[0261]

Chem.

[0262] [Example 13] 5-(2-(Propylamino)pyridin-4-yl)-1H-indazole-3-amine

[0263] [Chemical formula] A suspension of 4-bromo-N-propylpyridin-2-amine (0.094 g, 0.44 mmol), 3-cyano-4-fluorophenylboronic acid (0.122 g, 0.54 mmol), t-butylamine (138 μL, 1.31 mmol), [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.024 g, 0.04 mmol), isopropanol (2 mL) and H2O (1 mL) was degassed with nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. When cooled to room temperature, the reaction mixture was concentrated under reduced pressure and then suspended in EtOH (2 mL). Hydrazine hydrate (57 μL, 1.17 mmol) and NaHCO3 (0.030 g) were added to this suspension. The resulting suspension was heated at 80 °C for 2 days, at which point additional hydrazine hydrate (28.5 μL, 2.5 equivalents) and EtOH (1 mL) were added. Heating was continued for 1.5 days. The reaction mixture was then cooled to 40 °C, diluted with water (6 mL), stirred at room temperature for 30 minutes and left standing in the refrigerator overnight. The resulting precipitate was collected by filtration and washed with cold H2O (2 × 20 mL) and EtOH / H2O 1:1 (2 × 20 mL). The aqueous filtrates were combined and extracted with EtOAc (50 mL). The organic layer was combined with the first precipitate, concentrated on silica gel and purified by flash chromatography (Biotage SP4, 50 g SiO4, EtOAc to remove impurities, followed by 7% MeOH - 1% triethylamine in EtOAc) to give the title compound as a pale yellow solid (0.028 g, 0.105 mmol, 45%). 11H NMR (400 MHz, DMSO-d6): δ 0.93 (t, J = 7.4 Hz, 1H), 1.50 - 1.61 (m, 1H), 3.18 - 3.28 (m, 1H), 5.47 (s, 1H), 6.49 (t, J = 5.7 Hz, 1H), 6.69 (s, 1H), 6.75 (dd, J = 5.4, 1.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.52 (dd, J = 8.7, 1.9 Hz, 1H), 7.98 (d, J = 5.4 Hz, 1H), 8.06 (s, 1H), 11.50 (br s, 1H).

[0264] [Example 14] 5-(2-(Isopropylamino)pyridin-4-yl)-1H-indazole-3-amine

[0265] [Chemical formula] A suspension of 4-bromo-N-isopropylpyridin-2-amine (0.050 g, 0.23 mmol), 3-cyano-4-fluorophenylboronic acid pinacol ester (0.115 g, 0.5 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.030 g, 0.05 mmol) in IPA / H2O (2:1 mL) was degassed with nitrogen. t-Butylamine (0.25 mL, 2.32 mmol) was added, and the mixture was heated in a microwave at 160 °C for 40 minutes. The reaction mixture was concentrated, dissolved in EtOH (4 mL), and degassed with nitrogen. Hydrazine hydrate (0.34 mL, 7.0 mmol) was added, and the mixture was heated in a microwave at 165 °C for 30 minutes. The reaction mixture was concentrated and purified by flash column chromatography (silica gel using EtOAc (50 - 100%) in hexane) to obtain the title compound as an off-white solid. 11H NMR (400 MHz, DMSO-d6): 1.16 (s, 3H), 1.17 (s, 3H), 3.98 - 4.08 (m, 1H), 5.46 (br s, 2H), 6.30 (d, J = 7.6 Hz, 1H), 6.67 (s, 1H), 6.74 (dd, J = 5.4, 1.0 Hz, 1H), 7.30 (d, J = 8.7 Hz, 1H), 7.51 (dd, J = 8.7, 1.5 Hz, 1H), 7.98 (d, J = 5.4 Hz, 1H), 8.05 (s, 1H), 11.50 (br s, 1H). HRMS: C 15 H 18 N5 requires 268.1557, found 268.1553 (M+H) + .

[0266] [Example 15] 5-(2-((Cyclopropylmethyl)amino)pyridin-4-yl)-1H-indazole-3-amine

[0267] [Chemical formula] A suspension of 4-bromo-N-(cyclopropylmethyl)pyridin-2-amine (0.020 g, 0.09 mmol), 3-cyano-4-fluorophenylboronic acid (0.04, 0.16 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.010 g, 0.02 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t-butylamine (0.25 mL, 2.38 mmol) was added and degassed using nitrogen. The reaction was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction was diluted with EtOAc and concentrated under reduced pressure. EtOH (4 mL) was subsequently added followed by hydrazine hydrate (0.20 mL, 5.00 mmol), and the mixture was irradiated at 165 °C for 30 minutes. The reaction mixture was then concentrated under reduced pressure and purified using column chromatography (100% EtOAc) to obtain the desired product as a yellow solid (0.004 g, 0.02 mmol, 17%). 1 1H NMR (400 MHz, DMSO-d6): δ 0.22 (d, J = 4.4 Hz, 2H), 0.44 (d, J = 8.0 Hz, 2H), 1.07 (br s, 1H), 3.17 (t, J = 5.8 Hz, 2H), 5.47 (br s, 2H), 6.57 (br s, 1H), 6.73 (s, 1H), 6.77 (d, J = 5.2 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 4.8 Hz, 1H), 8.06 (s, 1H), 11.51 (br s, 1H).

[0268] [Example 16] 5-(2-(Isopentylamino)pyridin-4-yl)-1H-indazol-3-amine

[0269] [Chemical formula] A suspension of 4-bromo-N-isopentylpyridin-2-amine (0.05 g, 0.23 mmol), 3-cyano-4-fluorophenylboronic acid pinacol ester (0.115 g, 0.50 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.030 g, 0.05 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. t-Butylamine (0.25 mL, 2.32 mmol) was added, and the mixture was heated in a microwave at 160 °C for 40 minutes. The reaction mixture was concentrated, dissolved in EtOH (4 mL), and degassed with nitrogen. Hydrazine hydrate (0.34 mL, 7.00 mmol) was added, and the mixture was heated in a microwave at 165 °C for 30 minutes. The reaction mixture was concentrated and purified by flash column chromatography (silica gel using EtOAc (50 - 100%) in hexane) to give the title compound as an off-white solid (0.011 g, 0.04 mmol, 16%). 11H NMR (400 MHz, DMSO-d6): 0.91 (s, 3H), 0.93 (s, 3H), 1.64 - 1.72 (m, 1H), 3.24 - 3.30 (m, 2H), 5.47 (br s, 2H), 6.42 (t, J = 5.5 Hz, 1H), 6.68 (s, 1H), 6.76 (dd, J = 4.7, 1.3 Hz, 1H), 7.30 (d, J = 8.5 Hz, 1H), 7.52 (dd, J = 7.3, 1.6 Hz, 1H), 7.99 (d, J = 5.3, 1H), 8.06 (s, 1H), 11.50 (br s, 1H). HRMS: C 17 H 22 N5requires 296.1870, found 296.1867 (M+H) + .

[0270] [Example 17] 5-(2-(Hexylamino)pyridin-4-yl)-1H-indazole-3-amine

[0271] [Chemical formula] A suspension of 4-bromo-N-hexylpyridin-2-amine (0.090 g, 0.35 mmol), 3-cyano-4-fluorophenylboronic acid (0.148 g, 0.60 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.028 g, 0.04 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t-butylamine (0.25 mL, 2.38 mmol) was added and the mixture was degassed using nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. EtOH (4 mL) and then hydrazine hydrate (0.2 mL, 5.0 mmol) were added and the mixture was irradiated at 165 °C for 30 minutes. The reaction mixture was then concentrated under reduced pressure and purified using column chromatography (100% hexane to 100% EtOAc). The resulting solid was triturated with diethyl ether, filtered, and dried to give the title compound as an off-white solid (0.061 g, 0.20 mmol, 56.2%). 1 H NMR (400 MHz, DMSO-d6): δ 0.88 (br s, 3H), 1.30 - 1.35 (m, 6H), 1.54 (br s, 2H), 3.26 (br s, 2H), 5.47 (br s, 2H), 6.46 (br s, 1H), 6.68 (br s, 1H), 6.75 (br s, 1H), 7.29 - 7.31 (m, 1H), 7.50 - 7.53 (m, 1H), 7.99 (m, 1H), 8.06 (s, 1H), 11.50 (br s, 1H). HRMS: For C 18 H 24 N5requires 310.2026 found 310.2023.

[0272] [Example 18] 5-(2-(Cyclohexylamino)pyridin-4-yl)-1H-indazol-3-amine

[0273] [Chemical formula] A suspension of 4-bromo-N-cyclohexylpyridin-2-amine (0.108 g, 0.43 mmol), 3-cyano-4-fluorophenylboronic acid (0.168 g, 0.68 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.029 g, 0.04 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t-butylamine (0.25 mL, 2.38 mmol) was added and degassed using nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. EtOH (4 mL) was subsequently added followed by hydrazine hydrate (0.25 mL, 5.5 mmol), and the mixture was irradiated at 165 °C for 30 minutes. The reaction mixture was then concentrated under reduced pressure and purified using column chromatography (100% EtOAc). The resulting solid was triturated from diethyl ether, filtered, and dried to give the title compound as an off-white solid (0.059 g, 0.19 mmol, 45%). 1 H NMR (400 MHz, DMSO-d6): δ 1.16 - 1.24 (m, 3H), 1.29 - 1.38 (m, 2H), 1.58 - 1.61 (m, 1H), 1.71 - 1.74 (m, 2H), 1.92 - 1.95 (m, 2H), 3.70 - 3.77 (m, 1H), 5.47 (br s, 1H), 6.33 (d, J = 8.0 Hz, 1H), 6.69 (s, 1H), 6.71 (dd, J = 1.6, 5.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.50 (dd, J = 1.6, 8.8 Hz, 1H), 7.97 (d, J = 5.6 Hz, 1H), 8.04 (s, 1H), 11.50 (br s, 1H).

[0274] [Example 19] 4-Bromo-N-(trans-4-methylcyclohexyl)pyridin-2-amine

[0275]

Chemical Structure

[0276]

Chemical Structure

[0277] [Example 20] 2-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)ethan-1-ol

[0278]

Chem.

[0279] [Example 21] 3 - ((4 - (3 - Amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)amino)propan - 1 - ol

[0280] [Chemical formula] A suspension of 3 - ((4 - bromopyridin - 2 - yl)amino)propan - 1 - ol (0.116 g, 0.72 mmol), 3 - cyano - 4 - fluorophenylboronic acid (0.246 g, 1.00 mmol), and [1,1’ - bis(di - tert - butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.037 g, 0.057 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t - butylamine (0.38 mL, 3.62 mmol) was added and degassed using nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. Subsequently, EtOH (4 mL) and hydrazine hydrate (0.25 mL, 5.0 mmol) were added, and the mixture was irradiated at 165 °C for 30 minutes. Then the reaction mixture was concentrated under reduced pressure and purified using column chromatography (100% EtOAc ~ 20% MeOH / EtOAc). The resulting solid was triturated with Et2O, filtered, and dried to obtain the title compound as an off - white solid (0.0676 g, 0.239 mmol, 47.3%). 1 H NMR (400 MHz, DMSO - d6): δ 1.79 (qt, 2H, J = 6.4 Hz), 3.45 (q, 2H, J = 6.4 Hz), 3.55 (t, 2H, J = 6.0 Hz), 7.18 (d, 1H, J = 6.8 Hz), 7.24 (s, 1H), 7.39 (d, 1H, J = 8.8 Hz), 7.67 (d, 1H, J = 8.4 Hz), 7.98 (d, 1H, J = 6.8 Hz), 8.33 (s, 1H), 8.51 (br s, 1H), 11.80 (br s, 1H). HRMS: For C 15 H 18ON5 requires 284.1506 found 284.1504.

[0281] [Example 22] 4-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-ylamino)butan-1-ol

[0282] [Chemical formula] A suspension of 4-((3-bromopyridin-2-yl)amino)butan-1-ol (0.093 g, 0.38 mmol), 3-cyano-4-fluorophenylboronic acid pinacol ester (0.187 g, 0.76 mmol), and [[1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.040 g, 0.061 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. t-Butylamine (0.4 mL, 3.8 mmol) was added and the mixture was heated in a microwave at 160 °C for 45 minutes. The reaction mixture was concentrated, dissolved in EtOH (4 mL), and degassed with nitrogen. Hydrazine hydrate (0.55 mL, 11.38 mmol) was added and the mixture was heated in a microwave at 165 °C for 30 minutes. The reaction mixture was concentrated and purified by flash column chromatography (silica gel using 50% EtOAc in hexane to 10% MeOH in EtOAc) to give the title compound as a pale solid (0.070 g, 0.24 mmol, 62%). 11H NMR (400 MHz, DMSO-d6): 1.57 (m, 4H), 3.28 (q, J = 6.8 Hz, 2H), 3.44 (q, J = 6.4 Hz, 2H), 4.39 (t, J = 5.2 Hz, 1H), 5.45 (br s, 2H), 6.45 (t, J = 5.2 Hz, 1H), 6.70 (s, 1H), 6.76 (dd, J = 1.6, 5.6 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.53 (dd, J = 1.6, 8.8 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 8.07 (s, 1H), 11.49 (br s, 1H).

[0283] [Example 23] 5-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)amino)pentan-1-ol

[0284] [Chemical formula] 5-[(4-Bromopyridin-2-yl)amino]pentan-1-ol (0.150 g, 0.58 mmol), 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.240 g, 0.96 mmol), and a suspension of [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.047 g, 0.072 mmol) in IPA / H2O (3:1.5 mL) were degassed for 5 minutes using a constant stream of nitrogen. t-Butylamine (0.3 mL, 2.9 mmol) was added and the mixture was degassed for 5 minutes under nitrogen. The reaction mixture was reacted in a microwave at 160 °C for 40 minutes, then cooled to room temperature and concentrated under reduced pressure. The reaction mixture was suspended in EtOH (4.5 mL), hydrazine hydrate (0.3 mL, 5.99 mmol) was added thereto, and then the mixture was reacted in a microwave at 165 °C for 30 minutes. When cooled to room temperature, the reaction mixture was concentrated under reduced pressure. Purification by column chromatography (100% EtOAc~15% MeOH / EtOAc) was followed by recrystallization from MeOH (15 mL) and hexane (150 mL), and filtration to obtain the desired compound as a yellow solid (0.099 g, 0.32 mmol, 55%). 1 H NMR (DMSO-d6): δ 1.37-1.40 (2H, m), 1.41-1.5 (2H, m), 1.52-1.59 (2H, m), 3.26 (q, J = 6.5 Hz, 2H), 3.40 (q, J = 6.0 Hz, 2H), 4.37 (t, J = 5.2 Hz, 1H), 5.48 (2H, br s), 6.55 (1H, br s), 6.77 (d, J = 5.2 Hz, 1H,), 7.30 (d, J = 8.8 Hz, 1H), 7.53 (dd, J = 8.8, 1.6 Hz, 1H), 7.98 (d, J = 5.6 Hz, 1H), 8.07 (1H, s), 11.52 (1H, br s). HRMS: For C 17 H 22 ON5requires 312.1813, found 312.1819.

[0285] [Example 24] 4-Bromo-N-(trans-4-hydroxycyclohexyl)pyridin-2-amine

[0286] [Chemical formula] 4-Bromo-2-fluoropyridine (0.5 ml, 4.52 mmol), (1r,4r)-4-aminocyclohexanol (1.200 g, 10.60 mmol) and triethylamine (0.7 ml, 5.02 mmol) were placed in a round-bottom flask containing n-butanol (15 ml), and then the solution was heated for 16 hours. Then the solvent was removed under reduced pressure, the residue was dissolved in EtOAc (50 ml), and extracted with water (2 × 50 ml). Then the organic layer was dried (Mg2SO4) and the solvent was removed under reduced pressure. Then the residue was purified by flash chromatography using hexane~hexane:ethyl acetate (2:1) to obtain the desired product. (0.879 g, 3.2 mmol, 72.3 %), δ H (d6-DMSO): 1.19 (4H, m), 1.82 (4H, m), 3.40 (1H, m), 3.57 (1H, m), 4.51 (d, J = 4.0 Hz, 1H), 6.58 (2H, m), 6.62 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 5.5 Hz, 1H), 9.32 (t, J = 5.1 Hz, 1H). δ C (d6-DMSO): 30.8, 34.4, 49.0, 68.8, 110.7, 114.2, 131.9, 149.5, 159.7, LRMS: found: 273.00, 275.00 (M+1), calculated C 11 H 15 BrN2O: 270.03. 5-{2-[(trans-4-hydroxycyclohexyl)amino]pyridin-4-yl}-1H-indazole-3-amine

[0287] [Chemical formula] 4-Bromo-N-(trans-4-hydroxycyclohexyl)pyridin-2-amine (0.143 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. The solution was then cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in the microwave at 100 °C for 1 hour. The solution was then cooled, and the solvent was removed under reduced pressure to obtain a crude product, which was purified by HPLC to obtain the desired product. (0.029 g, 0.09 mmol, 16.9 %) δ H (d6-DMSO): 1.32 (4H, m), 1.88 (4H, m), 3.47 (1H, m), 3.64 (1H, m), 7.15 (dd, J = 6.9, 1.7 Hz, 1H), 7.21 (d, J = 1.0 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 8.65 Hz, 1H), 7.96 (d, J = 6.9 Hz, 1H), 8.30 (1H, s), 8.55 (1H, s). HRMS: C 18 H 21 N5O requires 323.1746, found 324.1819 (M+H).

[0288] [Example 25] 5-(2-((2-Methoxyethyl)amino)pyridin-4-yl)-1H-indazole-3-amine

[0289] [Chemical formula] 4-Bromo-N-(2-methoxyethyl)pyridin-2-amine (0.040 g, 0.17 mmol), 3-cyano-4-fluorophenylboronic acid (0.075 g, 0.30 mmol), and a suspension of [[1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.015 g, 0.02 mmol) in IPA / H2O (3:1.5 mL) were degassed with nitrogen. Then t-butylamine (0.15 mL, 1.43 mmol) was added and the mixture was degassed with nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. EtOH (4 mL) was added, followed by hydrazine hydrate (0.2 mL, 5.0 mmol), and the mixture was irradiated at 165 °C for 30 minutes. The reaction mixture was then concentrated under reduced pressure and purified using column chromatography (100% EtOAc to 20% methanol / EtOAc). The resulting solid was recrystallized from methanol and hexane, filtered, and dried to give the title compound as an off-white solid (0.037 g, 0.13 mmol, 49%). 1 H NMR (400 MHz, DMSO-d6): δ 3.28 (s, 3H), 3.48 (br s, 2H), 5.47 (br s, 2H), 6.55 (br s, 1H), 6.76 (s, 1H), 6.78 (d, J = 5.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 1H), 7.51 (dd, J = 1.2, 8.4 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 8.06 (s, 1H), 11.51 (br s, 1H).

[0290] [Example 26] 5-(2-((3-Methoxypropyl)amino)pyridin-4-yl)-1H-indazol-3-amine

[0291]

Chemical Structure

[0292] [Example 27] 4-Bromo-N-[3-(propan-2-yloxy)propyl]pyridin-2-amine

[0293] [Chemical formula] 4-Bromo-2-fluoropyridine (0.1 mL, 0.98 mmol), triethylamine (0.55 mL, 3.95 mmol), and 3-(propan-2-yloxy)propan-1-amine (0.68 mL, 4.90 mmol) in 1,4-dioxane (2.5 mL) were heated in a microwave at 160 °C for 30 minutes. When cooled to room temperature, the reaction mixture was concentrated under reduced pressure. Purification by column chromatography (100% hexane to 75 / 25 hexane / EtOAc) gave the title compound as an off-white solid (0.21 g, 0.77 mmol, 79%). 1 H NMR (DMSO-d6): δ 1.07 (d, J = 6.0 Hz, 6H), 1.69 (2H, m), 3.24 (q, J = 6.5 Hz, 2H), 3.41 (t, J = 2.8 Hz, 2H), 3.49 (2H, m), 6.63 (dd, J = 5.2, 1.6 Hz, 1H), 6.66 (d, J = 1.6 Hz, 1H), 6.73 (t, J = 10.8 Hz, 1H), 7.83 (d, J = 5.6 Hz, 1H). LRMS: found: 273.00, 274.93 (M+1), calculated C 11 H 17 BrN2O: 272.05. 5-(2-((3-Isopropoxypropyl)amino)pyridin-4-yl)-1H-indazole-3-amine

[0294] [Chemical formula] 4-Bromo-N-[3-(propan-2-yloxy)propyl]pyridin-2-amine (0.196 g, 0.72 mmol), 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.280 g, 1.14 mmol), and a suspension of [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.050 g, 0.08 mmol) in IPA / H2O (3:1.5 mL) were degassed for 5 minutes using a constant stream of nitrogen. t-Butylamine (0.38 mL, 3.6 mmol) was added, and the mixture was degassed for 5 minutes under nitrogen. The reaction mixture was reacted in a microwave at 160 °C for 40 minutes, then cooled to room temperature and concentrated under reduced pressure. The reaction mixture was suspended in EtOH (4.5 mL), hydrazine hydrate (0.38 mL, 7.60 mmol) was added thereto, and then the mixture was reacted in a microwave at 165 °C for 30 minutes. When cooled to room temperature, the reaction mixture was concentrated under reduced pressure. Purification by column chromatography (100% hexane ~ 50 / 50 hexane / EtOAc ~ 100% EtOAc ~ 10% MeOH / EtOAc) was followed by recrystallization from MeOH (15 mL) and hexane (150 mL), and filtration to obtain the desired compound as a yellow solid (0.114 g, 0.35 mmol, 48.7%). 1 H NMR (DMSO-d6): δ 1.09 (d, J = 6.0 Hz, 6H), 1.77 (qt, J = 6.5 Hz, 2H), 3.46 (t, J = 12.4 Hz, 2H), 3.53 (qt, J = 6.1 Hz, 1H), 5.50 (1H, br s), 6.81 (1H, s), 6.89 (d, J = 3.2 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 8.12 (1H, s). 11.56 (1H, br s). HRMS: For C 18 H 24 ON5 requires 326.1977, found 326.1975.

[0295] [Example 28] 3-((4-Chloropyrimidin-2-yl)amino)propan-1-ol

[0296] [Chemical formula] 2,4-Dichloropyrimidine (2 g, 13.42 mmol) and triethylamine (1.5 ml, 21.21 mmol) were placed in a round-bottom flask together with dichloromethane (30 ml). Then 3-aminopropan-1-ol (2.5 ml, 33.50 mmol) was added dropwise, and the solution was stirred overnight at room temperature. Then water (20 ml) was added, the organic layer was dehydrated over sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain a crude product, which was purified by flash chromatography (100% hexane to 50 / 50 hexane / EtOAc) to obtain the desired products (I) and (II). (0.562 g, 3.00 mmol, 22 %), δ H (d6-DMSO): 1.65 (q, J = 6.5 Hz, 2H), 3.28 (2H, m), 3.44 (t, J = 6.5 Hz, 2H), 4.43 (1H, s), 6.61 (d, J = 5.0 Hz, 1H), 7.58 (t, J = 5.5 Hz, 1H), 8.21 (1H, s). LRMS: found: 188.00 (M+1), calculated C7H 10 ClN3O: 187.05 3-((4-(3-Amino-1H-indazol-5-yl)pyrimidin-2-yl)amino)propan-1-ol

[0297] [Chemical formula] 3-((4-Chloropyrimidin-2-yl)amino)propan-1-ol (0.103 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then, [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. The solution was then cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in the microwave at 100 °C for 1 hour. The solution was then cooled, and the solvent was removed under reduced pressure to obtain the crude product, which was purified by HPLC to obtain the desired product. (32 mg, 0.1 mmol, 20.8 %) δ H (d6-DMSO): 1.77 (t, J = 6.1 Hz, 2H), 3.53 (4H, m), 4.48 (1H, s), 7.27 (1H, s), 7.39 (d, J = 6.2 Hz, 1H), 8.06 (1H, s), 8.16 (1H, m), 8.35 (d, J = 6.2 Hz, 1H), 8.73 (1H, s). HRMS: C 14 H 16 N6O requires 284.1386, found 285.1458 (M+H) +

[0298] [Example 29] 3-((4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)(methyl)amino)propan-1-ol

[0299] [Chemical formula] 3-((4-Bromopyridin-2-yl)(methyl)amino)propan-1-ol (0.027 g, 0.11 mmol), 3-cyano-4-fluorophenylboronic acid pinacol ester (0.054 g, 0.22 mmol), and a suspension of [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.014 g, 0.02 mmol) in IPA / H2O (3:1.5 mL) were degassed with nitrogen. t-Butylamine (0.12 mL, 1.10 mmol) was added, and the mixture was heated in a microwave at 160 °C for 45 minutes. The reaction mixture was concentrated, dissolved in EtOH (4 mL), and degassed with nitrogen. Hydrazine hydrate (0.16 mL, 3.30 mmol) was added, and the mixture was heated in a microwave at 165 °C for 30 minutes. The reaction mixture was concentrated and purified by flash column chromatography (silica gel using 50% EtOAc in hexane to 10% MeOH in EtOAc) to give the title compound as an off-white solid (0.008 g, 0.03 mmol, 24%). 1 H NMR - (500 MHz, DMSO-d6): 1.72 (m, 2H), 3.06 (m, 3H), 3.44 (q, J = 6.0 Hz, 2H), 3.62 (t, J = 7.1 Hz, 2H), 6.81 (s, 1H), 6.83 (dd, J = 1.5, 5.5 Hz, 1H), 7.29 (d, J = 9.0 Hz, 1H), 7.61 (dd, J = 1.5, 8.5 Hz, 1H), 8.08 (d, J = 5.0 Hz, 1H), 8.12 (s, 1H), 11.49 (br s, 1H). HRMS: C 16 H 19 ON5requires 297.1590, found 298.1662 (M+H) +

[0300] [Example 30] 5-(2-((2-Morpholinoethyl)amino)pyridin-4-yl)-1H-indazol-3-amine

[0301] [Chemical Structure] A suspension of 4-bromo-N-(2-morpholinoethyl)pyridin-2-amine (0.100 g, 0.35 mmol), 3-cyano-4-fluorophenylboronic acid (0.151 g, 0.61 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.021 g, 0.032 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t-butylamine (0.20 mL, 1.90 mmol) was added and degassed using nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. EtOH (4.5 mL) was then added followed by hydrazine hydrate (0.3 mL, 6.0 mmol), and the mixture was irradiated at 165 °C for 30 minutes. The reaction mixture was then concentrated under reduced pressure and purified using column chromatography (100% EtOAc~20% MeOH / EtOAc). The resulting solid was triturated with Et2O, filtered, and dried to give the title compound as an off-white solid (0.0379 g, 0.11 mmol, 32.1%). 1 H NMR (400 MHz, DMSO-d6): δ 2.40-2.44 (m, 4H), 3.41 (q, J = 6.4, 12.4 Hz, 2H), 3.59 (m, 4H), 5.48 (br s, 2H), 6.35 (t, 1H), 6.74 (s, 1H), 6.78 (dd, J = 1.2, 5.2 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.54 (dd, J = 1.6, 8.8 Hz, 1H), 7.99 (d, J = 5.6 Hz, 1H), 8.08 (s, 1H), 11.52 (br s, 1H). HRMS: For C 18 H 23 ON6requires 339.1928 found 339.1927

[0302] [Example 31] 5-(2-((2-(Piperidin-1-yl)ethyl)amino)pyridin-4-yl)-1H-indazol-3-amine

[0303]

Chem.

[0304] [Example 32] tert-Butyl 3-(3-(3-amino-1H-indazol-5-yl)phenylamino)propyl(methyl)carbamate

[0305] [Chemical formula] A suspension of tert-butyl 3-(3-bromophenylamino)propyl(methyl)carbamate (0.105 g, 0.31 mmol), 3-cyano-4-fluorophenylboronic acid pinacol ester (0.150 g, 0.61 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.040 g, 0.06 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. t-Butylamine (0.32 mL, 3.05 mmol) was added, and the mixture was heated in a microwave at 160 °C for 45 minutes. The reaction mixture was concentrated, dissolved in EtOH (4 mL), and degassed with nitrogen. Hydrazine hydrate (0.44 mL, 9.15 mmol) was added, and the mixture was heated in a microwave at 165 °C for 30 minutes. The reaction mixture was concentrated and purified by flash column chromatography (silica gel using 50% EtOAc in hexane to 10% MeOH in EtOAc) to give the title compound as an off-white solid (0.032 g, 0.08 mmol, 26%). 11H NMR (400 MHz, DMSO-d6): 1.37 (br s, 9H), 1.75 (m, 2H), 2.80 (s, 3H), 3.26 (m, 4H), 5.45 (br s, 2H), 6.45 (br s, 1H), 6.69 (s, 1H), 6.78 (dd, J = 1.6, 5.6 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 8.0 (d, J = 5.2 Hz, 1H), 8.07 (s, 1H), 11.50 (br s, 1H). HRMS: C 21 H 28 O2N5requires 396.2274, found 397.2347 (M+H) N 1 -(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-N 3 -methylpropane-1,3-diamine

[0306]

Chemical formula

[0307] Section 5 - Formula: [Chemical formula] Compound of

[0308] [Example 33] N-[4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl]cyclopropanecarboxamide

[0309] [Chemical formula] A suspension of N-(4-chloropyridin-2-yl)cyclopropanecarboxamide (0.133 g, 0.678 mmol), 3-cyano-4-fluorophenylboronic acid (0.205 g, 0.791 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.043 g, 0.066 mmol) in IPA / H2O (3:1.5 mL) was degassed with nitrogen. Then t-butylamine (0.60 mL, 5.71 mmol) was added and degassed using nitrogen. The reaction mixture was placed in a microwave and irradiated at 160 °C for 40 minutes. The reaction mixture was diluted with EtOAc and concentrated under reduced pressure. Ethanol (5 mL) and hydrazine hydrate (0.25 mL, 5.0 mmol) were added to this residue, and the reaction mixture was placed in a microwave and irradiated at 165 °C for 30 minutes. Purification was performed using HPLC as described in the General Experimental Section. The peak was collected at 9 minutes (0.01229 g, 0.04 mmol, 6.2%). 1 H NMR (400 MHz, DMSO-d6): δ 0.83 - 0.86 (m, 4H), 2.04 - 2.07 (m, 1H), 7.36 - 7.40 (m, 2H), 7.63 (d, J = 8.4 Hz, 1H), 8.19 (s, 1H), 8.34 (d, J = 5.2 Hz, 1H), 8.43 (s, 1H), 10.84 (s, 1H), 11.72 (br s, 1H). LRMS: found: 294.13 (M+1), calculated C 16 H 15 N5O: 293.13

[0310] [Example 34] N-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)benzamide

[0311] [Chemical formula] A suspension of N-(4-bromopyridin-2-yl)benzamide (0.097 g, 0.35 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-amine (0.136 g, 0.525 mmol) and tetrakis(triphenylphosphine)palladium(0) catalyst (0.02 g, 0.0175 mmol) in EtOH / water (1:1, 1.5 mL, degassed under nitrogen) was added with K3PO4 (1 M, 0.88 mL), and the reaction mixture was heated at 80 °C for 24 h. The reaction mixture was cooled to room temperature, filtered, and the obtained solid was washed with water (10 mL) and Et2O (8 mL), and then dried. Purification by column chromatography (100% hexane ~ 2 / 1 hexane / EtOAc ~ 100% EtOAc) and trituration with MeOH and hexane gave the title compound as a gray solid (0.05 g, 43%). 11H NMR (500 MHz, DMSO) δ 11.60 (s, 1H), 10.81 (s, 1H), 8.57 (d, J = 1.7 Hz, 1H), 8.43 (d, J = 5.3 Hz, 1H), 8.24 (d, J = 1.7 Hz, 1H), 8.11 - 8.06 (m, 2H), 7.70 - 7.62 (m, 1H), 7.61 (s, 1H), 7.55 (t, J = 7.6 Hz, 2H), 7.48 (dd, J = 5.2, 1.8 Hz, 1H), 7.39 (d, J = 8.7 Hz, 1H), 5.56 (s, 2H). LRMS: found: 330.13 (M+1), calculated C 19 H 16 N5O: 330.14 (M+1)

[0312] [Example 35] Ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate

[0313] [Chemical formula] Ethyl (4-bromopyridin-2-yl)carbamate (0.437 g, 1.82 mmol) was placed in a 5 ml microwave vial containing ethanol (10 ml) together with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-amine (0.722 g, 2.16 mmol) and potassium phosphate (945 mg in water (4 ml)). The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (118) (0.060 g, 0.10 mmol, 5 mol%) was added, the vial was sealed, and heated at 90 °C for 16 h. The solution was then cooled and the solvent removed under reduced pressure to give the crude product, which was purified by HPLC to give the desired product. (569 mg, 1.70 mmol, 94 %), δ H(d6-DMSO): 1.25 (t, J = 7.0 Hz, 3H), 4.02 (q, J = 7.0 Hz, 2H), 5.52 (s, 2H) 7.32 (m, 2H), 7.59 (dd, J = 8.5 and 1.5 Hz, 1H), 8.15 (m, 2H), 8.27 (d, J = 5.5 Hz, 1H), 10.08 (s, 1H), 11.56 (s, 1H). LRMS: found: 298.10 (M+1), calculated C 15 H 15 N5O2: 297.12.

[0314] [Example 36] 1-(4-Chloropyridin-2-yl)-3-ethylurea

[0315] [Chemical formula] To a 2 - 5 mL microwave vial were added 4-chloropyridin-2-amine (437 mg, 3.40 mg, 1 equivalent) and chloroform (1.6 mL). Isocyanatoethane (483 mg, 538 μL, 6.80 mmol, 2 equivalents) was added to the resulting suspension. The reaction mixture was heated at 100 °C for 1 hour under microwave irradiation. The resulting pale yellow solution was cooled to room temperature and diluted by dropwise addition of hexane (8 mL), and left standing overnight. The white precipitate was then filtered and washed with hexane (8 mL × 3) to obtain the title compound (480 mg, 71%) as a white solid. 1 1H NMR (DMSO-D6) δ: 1.07 (t, J = 7.2 Hz, 3H), 3.21 - 3.12 (m, 2H), 7.04 (dd, J = 5.5, 1.9 Hz, 1H), 7.59 (d, J = 1.6 Hz, 1H), 7.62 (br s, 1H), 8.16 (d, J = 5.5 Hz, 1H), 9.30 (s, 1H) 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-ethylurea

[0316] [Chemical formula] Into a 2 - 5 mL microwave vial, add 1-(4 - chloropyridin - 2 - yl)-3 - ethylurea (200 mg, 1 mmol, 1 equivalent), 5-(4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl)-1H - indazole - 3 - amine (259 mg, 1.2 mmol, 1.2 equivalents), [1,1’ - bis(di - tert - butylphosphino)ferrocene]dichloropalladium(II) catalyst (33 mg, 0.05 mmol, 5 mol%). Seal it with an aluminum crimp cap equipped with a disposable PTFE / silicone septum and purge with nitrogen. Add ethanol (4 mL), stir the mixture under nitrogen for several minutes, then add 1M aqueous K3PO4 solution (2.0 mL, O2 - free). Heat the mixture to about 50 °C, purge with nitrogen for 10 minutes, and then stir at 60 °C for 24 hours. Then dilute the reaction mixture with EtOAc (200 mL), wash with water (40 ml × 3), dry (MgSO4), and purify by flash chromatography (Biotage SP4, 50 g SiO4, 5% MeOH in EtOAc) to obtain the title compound (53 mg, 18%) as an off - white solid. 1 H NMR (DMSO - D6) δ: 1.11 (t, J = 7.2 Hz, 3H), 3.25 - 3.17 (m, 2H), 5.53 (s, 2H), 7.20 (dd, J = 5.4, 1.6 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 8.7, 1.6 Hz, 1H), 7.67 (s, 1H), 8.12 (s, 1H), 8.15 (br s, 1H), 8.20 (d, J = 5.4 Hz, 1H), 9.17 (s, 1H), 11.58 (s, 1H). HRMS: Calculated for C15H17ON6 (M + H + ): 297.1458; Found: 297.1450

[0317] [Example 37] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-propylurea

[0318]

Chem.

[0319] [Example 38] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-isopentylurea

[0320] [Chemical] Ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate (Example 35) (0.030 g, 0.10 mmol, 1 equiv), 3-methylbutan-1-amine (0.264 g, 352 μL, 3.03 mmol, 30 equiv), and dioxane (650 μL) were placed in a 0.5–2 mL microwave vial, sealed with an aluminum crimp cap fitted with a disposable PTFE / silicone septum, and purged with nitrogen. The reaction mixture was heated at 180 °C for 30 min under microwave irradiation. The reaction mixture was then cooled to about 40 °C and diluted by dropwise addition of water (5 mL) with a syringe. The mixture was stirred, sonicated for 30 min, and cooled to room temperature. The stopper was then removed, the solid was filtered, washed with water (2 × 4 mL), and dried to give the title compound (32 mg, 0.09 mmol, 94%). 1 H NMR (DMSO-D6) δ: 0.91 (d, J = 6.6 Hz, 6H), 1.39 (dd, J = 14.3, 7.1 Hz, 2H), 1.67 - 1.57 (m, 1H), 3.26 - 3.15 (m, 2H), 5.53 (s, 2H), 7.20 (d, J = 5.5 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.54 (d, J = 8.6 Hz, 1H), 7.67 (s, 1H), 8.23 - 8.09 (m, 3H), 9.16 (s, 1H), 11.58 (s, 1H), HRMS: Calculated for C 18 H 23 ON6(M+H + ): 339.1928; Found: 339.1925

[0321] [Example 39] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-cyclopentylurea

[0322] [Chemical formula] 1-(4-Bromopyridin-2-yl)-3-cyclopentylurea (0.149 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then, [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. The solution was then cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in a microwave at 100 °C for 1 hour. The solution was then cooled, and the solvent was removed under reduced pressure to obtain a crude product, which was purified by HPLC to obtain the desired product. (0.028 g, 0.08 mmol, 16 %) δ H (d6-DMSO): 1.43 (m, 2H), 1.56 (m, 2H), 1.66 (m, 2H), 1.89 (m, 2H), 4.02 (h, J = 6.5 Hz, 1H), 7.29 (s, 1H), 7.39 (d, J = 9.0 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.72 (s, 1H), 8.22 (m, 2H). HRMS: C 18 H 20 N6O requires 336.1699, found 337.1771 (M+H) + .

[0323] [Example 40] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-cyclohexylurea

[0324] [Chemical formula] 1-(4-Bromopyridin-2-yl)-3-cyclopentylurea (0.157 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. The solution was then cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in the microwave at 100 °C for 1 hour. The solution was then cooled, and the solvent was removed under reduced pressure to obtain the crude product, which was purified by HPLC to obtain the desired product. (0.043 g, 0.12 mmol, 22 %) δ H (d6-DMSO): 1.18 (m, 6H), 1.67 (m, 2H), 1.86 (m, 2H), 3.58 (m, 1H), 7.32 (s, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.62 (dd, J = 8.8 and 1.4 Hz, 1H), 7.71 (s, 1H), 8.24 (m, 2H). HRMS: C 19 H 22 N6O requires 350.1855, found 351.1928 (M+H) + .

[0325] [Example 41] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(2-hydroxyethyl)urea

[0326] [Chemical formula] In a 0.5 - 2 mL microwave vial, ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate (Example 35) (0.030 g, 0.10 mmol, 1 equivalent), 2-aminoethanol (0.025 g, 24.4 μL, 0.40 mmol, 4 equivalents) and dioxane (650 μL) were added, sealed with an aluminum crimp cap fitted with a disposable PTFE / silicone septum, and purged with nitrogen. The reaction mixture was heated to 160 °C for 90 minutes under microwave irradiation. The reaction mixture was then concentrated in vacuo, and the resulting crude product was dissolved in water (3 mL). The mixture was stirred, sonicated for 30 minutes, then the solid was filtered, washed with water (2×3 mL), and dried to give the title compound (27 mg, 0.08 mmol, 84%). 1 H NMR (400 MHz, DMSO-D6) δ 3.25 (app q, J = 5.6 Hz, 2H), 3.48 (m, 2H), 4.78 (t, J = 5.1 Hz, 1H), 5.53 (s, 2H), 7.20 (dd, J = 5.4, 1.5 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.54 (dd, J = 8.7, 1.5 Hz, 1H), 7.68 (s, 1H), 8.12 (s, 1H), 8.20 (d, J = 5.4 Hz, 1H), 8.27 (br s, 1H), 9.24 (s, 1H), 11.58 (s, 1H). HRMS: Calculated for C 15 H 17 O2N6(M+H + ): 313.1408; Found: 313.1400

[0327] [Example 42] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-hydroxypropyl)urea

[0328]

Chemical Structure

[0329] [Example 43] 1-(4-(3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)-3-(2 - methoxyethyl)urea

[0330] [Chemical formula] Into a 0.5 - 2 mL microwave vial, ethyl (4-(3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)carbamate (Example 35) (0.030 g, 0.10 mmol, 1 equivalent), 2 - methoxyethanamine (0.264 g, 352 μL, 3.03 mmol, 30 equivalents) and dioxane (650 μL) were added, sealed with an aluminum crimp cap fitted with a disposable PTFE / silicone septum, and purged with nitrogen. The reaction mixture was heated to 180 °C for 30 minutes under microwave irradiation. Then the reaction mixture was cooled to about 40 °C and diluted by dropwise addition of water (5 mL) with a syringe. The mixture was stirred, sonicated for 30 minutes, and cooled to room temperature. Then the stopper was removed, the solid was filtered, washed with water (2×4 mL), and dried to obtain the title compound. (0.029 g, 0.09 mmol, 88 %), 1 H NMR (DMSO - D6) δ: 3.29 (s, 3H), 3.38 - 3.34 (m, 2H), 3.45 - 3.40 (m, 2H), 5.53 (s, 2H), 7.21 (d, J = 5.3 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 8.12 (s, 1H), 8.20 (d, J = 5.4 Hz, 1H), 8.24 (br s, 1H), 9.24 (s, 1H), 11.58 (s, 1H)

[0331] [Example 44] 3 - (4 - (3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)-1 - (2 - hydroxyethyl)-1 - methylurea

[0332]

Chemical formula

[0333] [Example 45] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-benzylurea

[0334] [Chemical Structure] 1-Benzyl-3-(4-bromopyridin-2-yl)urea (0.161 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then, [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. The solution was then cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in a microwave at 100 °C for 1 hour. The solution was then cooled, and the solvent was removed under reduced pressure to obtain a crude product, which was purified by HPLC to obtain the desired product. (0.034 g, 0.10 mmol, 18 %) δ H (d6-DMSO): 4.41 (d, J = 5.5 Hz, 2H), 7.23 (m, 1H), 7.26 (m, 5H),7.42 (d, J = 9.0 Hz, 1H), 7.64 (dd, J = 8.8 and 1.4 Hz, 1H), 7.72 (s, 1H), 8.22 (m, 2H), 8.38 (s, 1H), 9.70 (s, 1H). HRMS: C 20 H 18 N6O requires 358.1542, found 359.1615 (M+H) + .

[0335] [Example 46] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-phenethylurea

[0336] [Chemical formula] 1-(4-Bromopyridin-2-yl)-3-phenethylurea (0.169 g, 0.53 mmol) was placed in a 5 ml microwave vial together with 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.132 g, 0.53 mmol) and t-butylamine (150 μl), and IPA:H2O (2:1) (4 ml) was added thereto. The solution was then degassed with N2 for 10 minutes. Then [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) catalyst (0.020 g, 0.03 mmol, 5 mol%) was added, the vial was sealed, and heated at 140 °C for 40 minutes. After the solution was cooled, hydrazine hydrate (1 ml) was added, and the solution was heated in a microwave at 100 °C for 1 hour. After the solution was cooled, the solvent was removed under reduced pressure to obtain a crude product, which was purified by HPLC to obtain the desired product. (0.023 g, 0.06 mmol, 12 %) δ H (d6-DMSO): 2.81 (t, J = 7.0 Hz, 2H), 3.44 (q, J = 5.5 Hz, 2H), 7.27 (m, 6H), 7.44 (d, J = 9.0 Hz, 1H), 7.68 (m, 2H), 8.19 (d, J = 7.5 Hz, 1H), 8.27 (s, 1H), HRMS: C 21 H 20 N6O requires 372.1699, found 373.1771 (M+H) + .

[0337] [Example 47] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-(pyridin-2-ylmethyl)urea

[0338]

Chemical formula

[0339] [Example 48] 1-(4-(3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)-3-(pyridin - 3 - ylmethyl)urea

[0340] [Chemical Structure] Into a 0.5 - 2 mL microwave vial, ethyl (4-(3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)carbamate (Example 35) (0.030 g, 0.10 mmol, 1 equivalent), pyridin - 3 - ylmethanamine (0.044 g, 41.6 μL, 0.40 mmol, 4 equivalents) and dioxane (650 μL) were added, sealed with an aluminum crimp cap equipped with a disposable PTFE / silicone septum, and purged with nitrogen. The reaction mixture was heated at 180 °C for 40 minutes under microwave irradiation. Then the reaction mixture was cooled to about 40 °C and diluted by dropwise addition of water (5 mL) with a syringe. The mixture was stirred, sonicated for 30 minutes, and cooled to room temperature. Then the stopper was removed, the solid was filtered, washed with water (2 × 4 mL), and dried to obtain the title compound. (29 mg, 0.08 mmol, 81%) 1 H NMR (400 MHz, DMSO - D6) δ 4.45 (d, J = 5.9 Hz, 2H), 5.53 (s, 2H), 7.23 (d, J = 5.4 Hz, 1H), 7.42 - 7.30 (m, 2H), 7.54 (d, J = 8.7 Hz, 1H), 7.69 (s, 1H), 7.74 (d, J = 7.7 Hz, 1H), 8.12 (s, 1H), 8.21 (d, J = 5.4 Hz, 1H), 8.47 (d, J = 4.7 Hz, 1H), 8.56 (s, 1H), 8.69 (br s, 1H), 9.37 (s, 1H), 11.59 (s, 1H). HRMS: Calculated for C 19 H 18 ON7(M + H + ): 360.1567; Found: 360.1564

[0341] [Example 49] 1-(4-(3 - amino - 1H - indazol - 5 - yl)pyridin - 2 - yl)-3-(pyridin - 4 - ylmethyl)urea

[0342] [Chemical formula] In a 0.5 - 2 mL microwave vial, ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate (Example 35) (0.030 g, 0.101 mmol, 1 equiv), pyridin-4-ylmethanamine (0.044 g, 41.6 μL, 0.40 mmol, 4 equiv) and dioxane (650 μL) were added, sealed with an aluminum crimp cap fitted with a disposable PTFE / silicone septum, and purged with nitrogen. The reaction mixture was heated to 180 °C for 40 minutes under microwave irradiation. Then the reaction mixture was cooled to about 40 °C and diluted by dropwise addition of water (5 mL) with a syringe. The mixture was stirred, sonicated for 30 minutes and cooled to room temperature. Then the stopper was removed, the solid was filtered, washed with water (2 × 4 mL) and dried to obtain the title compound. (32 mg, 0.09 mmol, 89%) 1 H NMR (400 MHz, DMSO-D6) δ 4.46 (d, J = 6.0 Hz, 2H), 5.53 (s, 2H), 7.24 (d, J = 5.3 Hz, 1H), 7.38 - 7.28 (m, 3H), 7.54 (d, J = 9.5 Hz, 1H), 7.69 (s, 1H), 8.12 (s, 1H), 8.23 (d, J = 5.4 Hz, 1H), 8.51 (d, J = 5.8 Hz, 2H), 8.77 (br s, 1H), 9.44 (s, 1H), 11.58 (s, 1H).

[0343] [Example 50] 1-(4-(3-Amino-1H-indazol-5-yl)pyridin-2-yl)-3-phenylurea

[0344] [Chemical formula] Ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate (Example 35) (0.050 g, 0.17 mmol) and aniline (16 μl, 0.20 mmol, 1.2 eq) were placed in a 0.5 - 2 ml microwave vial together with dioxane (2 ml). The solution was then degassed with nitrogen for 5 minutes, followed by the addition of bismuth triflate (0.006 g, 0.009 mmol, 5 mol%). The vial was then sealed and heated at 120 °C for 60 minutes. The solution was cooled and the solvent was removed under reduced pressure. The crude residue was then dissolved in DMF (0.5 ml) and purified by HPLC to give the desired product. (5 mg, 0.02 mmol, 9 %) δ H (d6-DMSO): 7.01 (t, J = 7.5 Hz, 1H), 7.30 (m, 3H), 7.40 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 7.5 Hz, 2H), 7.64 (dd, J = 8.5 and 1.5 Hz, 1H), 7.85 (s, 1H), 8.21 (s, 1H), 8.32 (d, J = 5.5Hz, 1H), 9.50 (s, 1H), 10.38 (s, 1H). HRMS: C 19 H 16 N6O requires 344.1386, found 345.1458 (M+H) + .

[0345] [Example 51] 1-(4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)-3-(3-fluorophenyl)urea

[0346] [Chemical formula] A suspension of ethyl (4-(3-amino-1H-indazol-5-yl)pyridin-2-yl)carbamate (0.050 g, 0.17 mmol) and 3-fluoroaniline (60 μL) in dioxane (3 mL) was degassed with nitrogen. Bismuth triflate (0.008 g) was added and the mixture was heated in a microwave at 120 °C for 80 minutes. The re...

Claims

1. Compounds having the structural formula (I) shown below, or pharmaceutically acceptable salts, hydrates, or solvates thereof: 【Chemistry 1】 (In the formula, R １ These are selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, (3-7C) cycloalkyl, aryl, heteroaryl and heterocyclyl. The (1-6C) alkyl, (2-6C) alkynyl, (3-7C) cycloalkyl, aryl, heteroaryl, and heterocyclyl are one or more R １００ It is optionally substituted by substituents; R １００ is selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C)alkyl, (1-4C)hydroxyalkyl, (CH ２ ) ｚ OR ｆ , (CH ２ ) ｚ C(O)R ｆ , (CH ２ ) ｚ C(O)OR ｆ , (CH ２ ) ｚ OC(O)R ｆ , (CH ２ ) ｚ C(O)N(R ｊ )R ｈ , (CH ２ ) ｚ N(R ｇ )C(O)R ｆ、 (CH ２ ) ｚ S(O) ｙ R ｆ , (CH ２ ) ｚ SO ２ N(R ｊ )R ｈ , (CH ２ ) ｚ N(R ｇ )SO ２ R ｆ , (CH ２ ) ｚ NR ｊ R ｈ , (CH ２ ) ｚ (3-7C)cycloalkyl, (CH ２ ) ｚ heterocyclyl, (CH ２ ) ｚ heteroaryl, or (CH ２ ) ｚ aryl; (i) R ｆ and R ｇ R is independently selected from hydrogen, (1-6C) alkyl, or phenyl; ｈ and R ｊ is independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｈ and R ｊ These, together with the nitrogen atom to which they are bonded, form a 3- to 7-membered ring that may optionally contain further heteroatoms and is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R １００ Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or aryl in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｋ , C(O)R ｋ , C(O)OR ｋ OC(O)R ｋ , C(O)N(R ｌ ) R ｋ , N(R ｌ ) C(O)R ｋ , S(O) ｙ R ｋ SO ２ N(R) ｌ ) R ｋ , N(R ｌ ) SO ２ R ｋ , or NR ｌ R ｋ It is further optionally substituted by one or more substituents selected from R ｋ and R ｌ is selected from hydrogen or (1-2C) alkyl; X is N or CR ２ And; R ２ These are selected from hydrogen, halogen, (1-8C) alkyl, (2-8C) alkenyl, (2-8C) alkynyl, (3-7C) cycloalkyl, aryl, heteroaryl and heterocyclyl. The (1-8C) alkyl, (2-8C) alkenyl, (2-8C) alkynyl, (3-7C) cycloalkyl, aryl, heteroaryl, and heterocyclyl are one or more R ２００ It is optionally substituted by substituents; R ２００ is selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C)alkyl, (1-4C)hydroxyalkyl, (CH ２ ) ｚ OR ｍ , (CH ２ ) ｚ C(O)R ｍ , (CH ２ ) ｚ C(O)OR ｍ , (CH ２ ) ｚ OC(O)R ｍ , (CH ２ ) ｚ C(O)N(R ｏ )R ｐ , (CH ２ ) ｚ N(R ｎ )C(O)R ｍ , (CH ２ ) ｚ S(O) ｙ R ｍ , (CH ２ ) ｚ SO ２ N(R ｏ )R ｐ , (CH ２ ) ｚ N(R ｎ )SO ２ R ｍ , (CH ２ ) ｚ NR ｏ R ｐ , (CH ２ ) ｚ (3-7C)cycloalkyl, (CH ２ ) ｚ heterocyclyl, (CH ２ ) ｚ heteroaryl, or (CH ２ ) ｚ aryl; (i) R ｍ and R ｎ R is independently selected from hydrogen, (1-6C) alkyl, or phenyl; ｏ and R ｐ is independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ These, together with the nitrogen atom to which they are bonded, form a 3- to 7-membered ring that may optionally contain further heteroatoms and is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or aryl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ R is hydrogen, (1-2C) alkyl, or phenyl. ｒ is selected from hydrogen or (1-2C) alkyl; R ３ These are hydrogen, cyano, (1-8C) alkyl, (3-7C) cycloalkyl, (CH ２ ) １～３ (3-7C) cycloalkyl, 4-7 membered heterocyclyl with carbon bonds, 5-6 membered heteroaryl with carbon bonds, -C(O)-(1-8C) alkyl, -C(O)(CH ２ ) ０～３ (3-7C) cycloalkyl, -C(O) [5-membered or 6-membered heteroaryl], -C(O) phenyl, -C(O)O(1-8C) alkyl, -C(O)O(3-7C) cycloalkyl, -C(O)O(CH ２ ) １～３ (3-7C) Cycloalkyl, -C(O)NH ２ , -C(O)NH-(1-8C)alkyl, -C(O)NH-(CH ２ ) ０～３ (3-7C) Cycloalkyl, -C(O)NH-(CH ２ ) ０～３ Heterocyclyl, -C(O)NH-(CH ２ ) ０～３ [5-membered or 6-membered heteroaryl], -C(O)NH-(CH ２ ) ０～３ Phenyl, -S(O) ２ H or -S(O) ２ - Selected from (1-8C) alkyl groups; Each alkyl, cycloalkyl, phenyl, heteroaryl, or heterocyclyl moiety contains one or more R ３００ It is optionally substituted by substituents; R ３００ This includes halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｓ , (CH ２ ) ｚ C(O)R ｓ , (CH ２ ) ｚ C(O)OR ｓ , (CH ２ ) ｚ OC(O)R ｓ , (CH ２ ) ｚ C(O)N(R) ｖ ) R ｕ , (CH ２ ) ｚ N(R) ｔ ) C(O)R ｓ , (CH ２ ) ｚ N(R) ｔ ) C(O)OR ｓ , (CH ２ ) ｚ S(O) ｙ R ｓ , (CH ２ ) ｚ SO ２ N(R) ｖ ) R ｕ , (CH ２ ) ｚ N(R) ｔ ) SO ２ R ｓ , (CH ２ ) ｚ NR ｕ R ｖ Selected from; (i) R ｓ and R ｔ is hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Each is independently selected from phenyl; R ｕ and R ｖ These are hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Either independently selected from phenyl, or R ｕ and R ｖ These, together with the nitrogen atom to which they are bonded, form a 3- to 7-membered ring which may optionally contain further heteroatoms, and any 3- to 7-membered ring formation R ｏ and R ｐ , and R ｓ , R ｔ , R ｕ and R ｖ Any alkyl or phenyl group present is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl groups; (ii) R ３００ Any alkyl, cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, OR ｗ , C(O)R ｗ , C(O)OR ｗ OC(O)R ｗ , C(O)N(R ｗ ) R ｘ , N(R ｘ ) C(O)R ｗ , S(O) ｙ R ｗ SO ２ N(R) ｘ ) R ｗ , N(R ｘ ) SO ２ R ｗ , or NR ｗ R ｘ It is further optionally substituted by one or more substituents selected from R ｗ R is hydrogen, (1-2C) alkyl, or phenyl. ｘ is selected from hydrogen or (1-2C) alkyl; or R ２ and R ３ They are bonded together to form a -CH=CQ- or -N=CQ- group; Q is hydrogen, halo, cyano or formula: -L １ -Y １ -L ２ -Q １ (In the formula, L １ It either does not exist or is (1-3C)alkylene; Y １ It does not exist, or O, S, SO, SO ２ , N(R ｙ１ ), C(O), C(O)O, OC(O), C(O)N(R ｙ１ ), or N (R ｙ１ ) C(O), R ｙ１ is selected from hydrogen or (1-4C) alkyl; L ２ It either does not exist or is (1-3C)alkylene; Q １ (These are hydrogen, (1-6C) alkyl, (2-6C) alkenyl, (2-6C) alkynyl, phenyl, (3-8C) cycloalkyl, heteroaryl, or heterocyclyl.) It is the basis of; Q is one or more substituent groups independently selected from oxo, hydroxy, (1-6C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)aminoalkyl, (1-4C)hydroxyalkyl, cyano, or formula: -L ３ -Y ２ -L ４ -W １ (In the formula, L ３ It either does not exist or is (1-3C)alkylene; Y ２ It does not exist, or O, S, SO, SO ２ , N(R ｙ２ ), C(O), C(O)O, OC(O), C(O)N(R ｙ２ ), or N (R ｙ２ )C(O), S(O) ２ N(R) ｙ２ ), N (R ｙ２ ) SO ２ Selected from, R ｙ２ is selected from hydrogen or (1-3C) alkyl; L ４ It either does not exist or is (1-3C)alkylene; W １ These are hydrogen, (1-6C) alkyl, phenyl, (3-8C) cycloalkyl, heteroaryl, or heterocyclyl; W １ These are oxo, (1-4C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)alkoxy, amino, (1-4C)alkylamino, di[(1-4C)alkyl]aminoC(O)OH, C(O)O(1-4C)alkyl, (CH ２ ) ０～３ - Optionally substituted with one or more substituents selected from heterocyclyl or cyano compounds. It is further optionally substituted by one or more of the following groups; R ４ is selected from hydrogen, halo, cyano, or amino; X １ R ２ and R ３ When they are bonded together to form a -CH=CH- group, N; or CR ５ And R ５ is selected from hydrogen, halo, cyano, or amino; y is independently selected from 0, 1, or 2; z is independently selected from 0, 1, 2, or 3; however, (i) R ２ and R ３ If both are hydrogen, R １ It is not hydrogen; (ii) R １ and R ３ If both are hydrogen, R ２ It is not hydrogen; (iii) R ２ and R ３ When they bond to form a -CH=CH- group, R １ It is not hydrogen; (iv) X is N, R ３ If R is hydrogen, １ It is not hydrogen; (v) L １ , Y １ and L ２ If none of the above exist, Q １ (It is neither an aryl nor a heteroaryl.)

2. The following structural formulas are shown: (Ia), (Ib), (Ic), (Id), or (Ie): 【Chemistry 2】 (In the formula, R １ X, R ３ , R ４ , R ５ (and Q are as defined in claim 1, respectively.) The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is a compound having [the specified compound].

3. R １ However, it is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, 5- or 6-membered heteroaryl, or 4- to 7-membered heterocyclyl. The (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, heteroaryl, and heterocyclyl are one or more R １００ It is optionally substituted by substituents; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , (CH ２ ) ｚ C(O)R ｆ , (CH ２ ) ｚ C(O)OR ｆ , (CH ２ ) ｚ OC(O)R ｆ , (CH ２ ) ｚ C(O)N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) C(O)R ｆ , (CH ２ ) ｚ S(O) ｙ R ｆ , (CH ２ ) ｚ SO ２ N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) SO ２ R ｆ , (CH ２ ) ｚ NR ｊ R ｈ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ Heterocyclyl, (CH ２ ) ｚ Heteroaryl, or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C) alkyl are independently selected; R ｈ and R ｊ However, hydrogen or (1-2C) alkyl may be independently selected, or R ｈ and R ｊ However, together with the nitrogen atom to which these are bonded, they form a 3- to 7-membered ring which may optionally contain further heteroatoms; (ii) R １００ Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｋ , C(O)R ｋ , C(O)OR ｋ OC(O)R ｋ , C(O)N(R ｌ ) R ｋ , N(R ｌ ) C(O)R ｋ , S(O) ｙ R ｋ SO ２ N(R) ｌ ) R ｋ , N(R ｌ ) SO ２ R ｋ , or NR ｌ R ｋ It is further optionally substituted by one or more substituents selected from R ｋ and R ｌ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

4. R １ However, it is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, phenyl, or 5-membered or 6-membered heteroaryl, The (2-6C) alkynyl, phenyl, or heteroaryl is one or more R １００ It is optionally substituted by substituents; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , (CH ２ ) ｚ C(O)R ｆ , (CH ２ ) ｚ C(O)OR ｆ , (CH ２ ) ｚ OC(O)R ｆ , (CH ２ ) ｚ C(O)N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) C(O)R ｆ , (CH ２ ) ｚ S(O) ｙ R ｆ , (CH ２ ) ｚ SO ２ N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) SO ２ R ｆ , (CH ２ ) ｚ NR ｊ R ｈ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ - [4-6 member heterocyclyl], (CH ２ ) ｚ - [5-membered or 6-membered heteroaryl] or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C) alkyl are independently selected; R ｈ and R ｊ However, hydrogen or (1-2C) alkyl may be independently selected, or R ｈ and R ｊ However, together with the nitrogen atom to which these are bonded, they form a 3- to 7-membered ring which may optionally contain further heteroatoms; (ii) R １００ Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｋ , C(O)R ｋ , C(O)OR ｋ OC(O)R ｋ , C(O)N(R ｌ ) R ｋ , N(R ｌ ) C(O)R ｋ , S(O) ｙ R ｋ SO ２ N(R) ｌ ) R ｋ , N(R ｌ ) SO ２ R ｋ , or NR ｌ R ｋ It is further optionally substituted by one or more substituents selected from R ｋ and R ｌ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

5. R １ However, it is selected from hydrogen, halogen, (1-6C) alkyl, (2-6C) alkynyl, phenyl, or 5-membered or 6-membered heteroaryl, The (2-6C) alkynyl, phenyl, or heteroaryl is one or more R １００ It is optionally substituted by substituents; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , (CH ２ ) ｚ C(O)R ｆ , (CH ２ ) ｚ C(O)OR ｆ , (CH ２ ) ｚ OC(O)R ｆ , (CH ２ ) ｚ C(O)N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) C(O)R ｆ , (CH ２ ) ｚ S(O) ｙ R ｆ , (CH ２ ) ｚ SO ２ N(R) ｊ ) R ｈ , (CH ２ ) ｚ N(R) ｇ ) SO ２ R ｆ , (CH ２ ) ｚ NR ｊ R ｈ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ - [4-6 member heterocyclyl], (CH ２ ) ｚ - [5-membered or 6-membered heteroaryl] or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C)alkyl is independently selected; (ii) R １００ Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or aryl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, or OR ｋ It is further optionally substituted by one or more substituents selected from R ｋ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

6. R １ However, it is selected from hydrogen, (2-6C)alkynyl, phenyl, or 5-membered or 6-membered heteroaryl, The (2-6C) alkynyl, phenyl, or heteroaryl is one or more R １００ It is optionally substituted by substituents; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , C(O)R ｆ , C(O)OR ｆ OC(O)R ｆ , C(O)N(R ｊ ) R ｈ , N(R ｇ ) C(O)R ｆ , S(O) ｙ R ｆ SO ２ N(R) ｊ ) R ｈ , N(R ｇ ) SO ２ R ｆ , NR ｊ R ｈ , (CH ２ ) ｚ - [4-6 member heterocyclyl], or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C)alkyl is independently selected; (ii) R １００ Any (1-4C)alkyl, heterocyclyl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, or OR ｋ It is further optionally substituted by one or more substituents selected from R ｋ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

7. R １ but, (i) Hydrogen; (ii) Hello; (iii) Methyl; (iv)CF ３ ; (v) R １００ Ethynyl, which is optionally substituted by, 【Transformation 3】 (vi)R １００ Phenyl compounds that are optionally substituted by; (vii)R １００ Five-membered or six-membered heteroaryl compounds that are optionally substituted by Selected from; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , C(O)R ｆ , C(O)OR ｆ OC(O)R ｆ , C(O)N(R ｊ ) R ｈ , N(R ｇ ) C(O)R ｆ , S(O) ｙ R ｆ SO ２ N(R) ｊ ) R ｈ , N(R ｇ ) SO ２ R ｆ , NR ｊ R ｈ , (CH ２ ) ｚ - [4-6 member heterocyclyl], or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C)alkyl is independently selected; (ii) R １００ Any (1-4C) alkyl, (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or aryl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, or OR ｋ It is further optionally substituted by one or more substituents selected from R ｋ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

8. R １ but, (i) Hydrogen; (ii) Hello; (iii) Methyl; (iv)CF ３ ; (v) R １００ Ethynyl, which is optionally substituted by, 【Chemistry 4】 (vi)R １００ Phenyl compounds that are optionally substituted by; (vii)R １００ Five-membered or six-membered heteroaryl compounds that are optionally substituted by Selected from; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , C(O)R ｆ , C(O)OR ｆ OC(O)R ｆ , C(O)N(R ｊ ) R ｈ , N(R ｇ ) C(O)R ｆ , S(O) ｙ R ｆ SO ２ N(R) ｊ ) R ｈ , N(R ｇ ) SO ２ R ｆ , NR ｊ R ｈ , (CH ２ ) ｚ - [4-6 member heterocyclyl], or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C)alkyl is independently selected; (ii) R １００ Any (1-4C)alkyl, heterocyclyl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, or OR ｋ It is further optionally substituted by one or more substituents selected from R ｋ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

9. R １ but, (i) Hydrogen; (ii) R １００ Ethynyl, which is optionally substituted by, 【Transformation 5】 (iii) R １００ Phenyl compounds that are optionally substituted by; (iv) 5-membered or 6-membered heteroaryl Selected from; R １００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｆ , C(O)R ｆ , C(O)OR ｆ OC(O)R ｆ , C(O)N(R ｊ ) R ｈ , N(R ｇ ) C(O)R ｆ , S(O) ｙ R ｆ SO ２ N(R) ｊ ) R ｈ , N(R ｇ ) SO ２ R ｆ , NR ｊ R ｈ , (CH ２ ) ｚ - [4-6 member heterocyclyl], or (CH ２ ) ｚ Selected from phenyl; (i) R ｆ and R ｇ However, hydrogen or (1-2C)alkyl is independently selected; (ii) R １００ Any (1-4C)alkyl, heterocyclyl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)hydroxyalkyl, or OR ｋ It is further optionally substituted by one or more substituents selected from R ｋ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

10. X is N or CR ２ And; R ２ However, it is selected from hydrogen, halogen, (1-8C) alkyl, (2-8C) alkenyl, (2-8C) alkynyl, (3-7C) cycloalkyl, phenyl, 5- or 6-membered heteroaryl, or 4- to 7-membered heterocyclyl. The (1-6C) alkyl, (2-6C) alkenyl, (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, 5- or 6-membered heteroaryl, or 4- to 7-membered heterocyclyl is one or more R ２００ It is optionally substituted by substituents; R ２００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｍ , (CH ２ ) ｚ C(O)R ｍ , (CH ２ ) ｚ C(O)OR ｍ , (CH ２ ) ｚ OC(O)R ｍ , (CH ２ ) ｚ C(O)N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) C(O)R ｍ , (CH ２ ) ｚ S(O) ｙ R ｍ , (CH ２ ) ｚ SO ２ N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) SO ２ R ｍ , (CH ２ ) ｚ NR ｏ R ｐ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ Heterocyclyl, (CH ２ ) ｚ Heteroaryl, or (CH ２ ) ｚ Selected from phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

11. X is N or CR ２ And; R ２ However, it is selected from hydrogen, halogen, (1-8C) alkyl, (2-8C) alkynyl, (3-7C) cycloalkyl, phenyl, 5- or 6-membered heteroaryl, or 4- to 7-membered heterocyclyl. The (2-6C) alkynyl, (3-7C) cycloalkyl, phenyl, heteroaryl, and heterocyclyl are one or more R ２００ It is optionally substituted by substituents; R ２００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｍ , (CH ２ ) ｚ C(O)R ｍ , (CH ２ ) ｚ C(O)OR ｍ , (CH ２ ) ｚ OC(O)R ｍ , (CH ２ ) ｚ C(O)N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) C(O)R ｍ , (CH ２ ) ｚ S(O) ｙ R ｍ , (CH ２ ) ｚ SO ２ N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) SO ２ R ｍ , (CH ２ ) ｚ NR ｏ R ｐ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ Heterocyclyl, (CH ２ ) ｚ Heteroaryl, or (CH ２ ) ｚ Selected from phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

12. X is N or CR ２ And; R ２ However, it is selected from hydrogen, fluoro, (1-8C)alkyl, (2-8C)alkynyl, (3-7C)cycloalkyl, phenyl, or 5-membered or 6-membered heteroaryl, The (1-6C) alkynyl, (3-7C) cycloalkyl, phenyl, heteroaryl, and heterocyclyl are one or more R ２００ It is optionally substituted by substituents; R ２００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｍ , (CH ２ ) ｚ C(O)R ｍ , (CH ２ ) ｚ C(O)OR ｍ , (CH ２ ) ｚ OC(O)R ｍ , (CH ２ ) ｚ C(O)N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) C(O)R ｍ , (CH ２ ) ｚ S(O) ｙ R ｍ , (CH ２ ) ｚ SO ２ N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) SO ２ R ｍ , (CH ２ ) ｚ NR ｏ R ｐ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ Heterocyclyl, (CH ２ ) ｚ Heteroaryl, or (CH ２ ) ｚ Selected from phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

13. X is N or CR ２ And; R ２ However, it is selected from hydrogen, fluoro, (1-8C)alkyl, (3-7C)cycloalkyl, or (2-6C)alkynyl, The above (2-6C) alkynyl is one or more R ２００ It is optionally substituted by substituents; R ２００ is selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C)alkyl, (1-4C)hydroxyalkyl, (CH ２ ), ｚ OR ｍ , (CH ２ ), ｚ C(O)R ｍ , (CH ２ ), ｚ C(O)OR ｍ , (CH ２ ), ｚ OC(O)R ｍ , (CH ２ ), ｚ C(O)N(R ｏ )R ｐ , (CH ２ ), ｚ N(R ｎ )C(O)R ｍ , (CH ２ ), ｚ S(O) ｙ R ｍ , (CH ２ ), ｚ SO ２ N(R ｏ )R ｐ , (CH ２ ), ｚ N(R ｎ )SO ２ R ｍ , (CH ２ ), ｚ NR ｏ R ｐ , (CH ２ ), ｚ (3-7C)cycloalkyl, (CH ２ ), ｚ heterocyclyl, (CH ２ ), ｚ heteroaryl, or (CH ２ ), ｚ phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

14. X is N or CR ２ And; R ２ but, (i) Hydrogen; (ii) Fluoro; (iii) R ２００ Ethynyl, which is optionally substituted by, 【Transformation 6】 (iv)R ２００ Phenyl compounds that are optionally substituted by; (v) R ２００ Five-membered or six-membered heteroaryl compounds that are optionally substituted by Selected from; R ２００ is selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C)alkyl, (1-4C)hydroxyalkyl, (CH ２ ), ｚ OR ｍ , (CH ２ ), ｚ C(O)R ｍ , (CH ２ ), ｚ C(O)OR ｍ , (CH ２ ), ｚ OC(O)R ｍ , (CH ２ ), ｚ C(O)N(R ｏ )R ｐ , (CH ２ ), ｚ N(R ｎ )C(O)R ｍ , (CH ２ ), ｚ S(O) ｙ R ｍ , (CH ２ ), ｚ SO ２ N(R ｏ )R ｐ , (CH ２ ), ｚ N(R ｎ )SO ２ R ｍ , (CH ２ ), ｚ NR ｏ R ｐ , (CH ２ ), ｚ a (3-7C)cycloalkyl, (CH ２ ),<00 / sup> ｚ heterocyclyl, (CH ２ ),<00 / sup> ｚ heteroaryl, or (CH ２ ), <00 / sup> ｚ phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

15. X is N or CR ２ And; R ２ but, (i) hydrogen; or (ii) R ２００ Ethynyl, which is optionally substituted by, 【Transformation 7】 Selected from; R ２００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, (CH ２ ) ｚ OR ｍ , (CH ２ ) ｚ C(O)R ｍ , (CH ２ ) ｚ C(O)OR ｍ , (CH ２ ) ｚ OC(O)R ｍ , (CH ２ ) ｚ C(O)N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) C(O)R ｍ , (CH ２ ) ｚ S(O) ｙ R ｍ , (CH ２ ) ｚ SO ２ N(R) ｏ ) R ｐ , (CH ２ ) ｚ N(R) ｎ ) SO ２ R ｍ , (CH ２ ) ｚ NR ｏ R ｐ , (CH ２ ) ｚ (3-7C) Cycloalkyl, (CH ２ ) ｚ Heterocyclyl, (CH ２ ) ｚ Heteroaryl, or (CH ２ ) ｚ Selected from phenyl; (i) R ｍ and R ｎ However, each is independently selected from hydrogen, (1-6C) alkyl, or phenyl; R ｏ and R ｐ However, these are independently selected from hydrogen, (1-6C) alkyl, or phenyl, or R ｏ and R ｐ However, together with the nitrogen atom to which these are bonded, they may optionally contain further heteroatoms, forming a 3- to 7-membered ring that is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl; (ii) R ２００ Any (3-7C) cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group may be halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-2C) alkyl, (1-2C) haloalkyl, (1-2C) hydroxyalkyl, OR ｑ , C(O)R ｑ , C(O)OR ｑ OC(O)R ｑ , C(O)N(R ｑ ) R ｒ , N(R ｒ ) C(O)R ｑ , S(O) ｙ R ｑ SO ２ N(R) ｒ ) R ｑ , N(R ｒ ) SO ２ R ｑ , or NR ｒ R ｑ It is further optionally substituted by one or more substituents selected from R ｑ However, R is hydrogen, (1-2C) alkyl, or phenyl. ｒ However, selected from hydrogen or (1-2C)alkyl, The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

16. X is CR ２ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

17. R ３ However, hydrogen, cyano, (1-8C) alkyl, (3-7C) cycloalkyl, carbon-bonded 4-7 member heterocyclyl, carbon-bonded 5-6 member heteroaryl, -(CH ２ ) １～３ (3-7C) cycloalkyl, -C(O)-(1-8C) alkyl, -C(O)(CH ２ ) ０～３ (3-7C)cycloalkyl, -C(O)phenyl, -C(O)O(1-8C)alkyl, -C(O)NH ２ , -C(O)NH-(1-8C)alkyl, -C(O)NH-(CH ２ ) ０～３ (3-7C) Cycloalkyl, -C(O)NH-(CH ２ ) ０～３ [5-membered or 6-membered heteroaryl], -C(O)NH-(CH ２ ) ０～３ Phenyl, -S(O) ２ H or -S(O) ２ - Selected from (1-6C) alkyl groups; Each alkyl, cycloalkyl, phenyl, or heteroaryl moiety contains one or more R ３００ It is optionally substituted by substituents; R ３００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, OR ｓ , C(O)R ｓ , C(O)OR ｓ OC(O)R ｓ , C(O)N(R ｖ ) R ｕ , N(R ｔ ) C(O)R ｓ , N(R ｔ ) C(O)OR ｓ , S(O) ｙ R ｓ SO ２ N(R) ｖ ) R ｕ , N(R ｔ ) SO ２ R ｓ , (CH ２ ) ｚ NR ｕ R ｖ Selected from; (i) R ｓ and R ｔ However, hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Each is independently selected from phenyl; R ｕ and R ｖ However, hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Either independently selected from phenyl, or R ｕ and R ｖ However, these, together with the nitrogen atom to which they are bonded, form a 3- to 7-membered ring which may optionally contain further heteroatoms, and any 3- to 7-membered ring formation R ｏ and R ｐ , and R ｓ , R ｔ , R ｕ and R ｖ Any alkyl or phenyl group present is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, carboxyl, carbamoyl, sulfamoyl, and (1-2C)alkyl groups; (ii) R ３００ Any cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or (1-2C)alkyl. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

18. R ３ However, hydrogen, cyano, (1-8C) alkyl, (3-7C) cycloalkyl, -(CH ２ ) １～３ (3-7C) cycloalkyl, 4-7 membered heterocyclyl with carbon bonds, 5-6 membered heteroaryl with carbon bonds, -C(O)-(1-8C) alkyl, -C(O)(3-7C) cycloalkyl, -C(O) phenyl, -C(O)O(1-8C) alkyl, -C(O)NH ２ , -C(O)NH-(1-8C)alkyl, -C(O)NH-(CH ２ ) ０～３ (3-7C) Cycloalkyl, -C(O)NH-(CH ２ ) ０～３ [5-membered or 6-membered heteroaryl], -C(O)NH-(CH ２ ) ０～３ Phenyl, -S(O) ２ H or -S(O) ２ - Selected from (1-6C) alkyl groups; Each alkyl, cycloalkyl, phenyl, or heteroaryl moiety contains one or more R ３００ It is optionally substituted by substituents; R ３００ However, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, (1-4C) alkyl, (1-4C) hydroxyalkyl, OR ｓ , C(O)N(R ｖ ) R ｕ , S(O) ｙ R ｓ , (CH ２ ) ｚ NR ｕ R ｖ Selected from; (i) R ｓ and R ｔ However, hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Each is independently selected from phenyl; R ｕ and R ｖ However, hydrogen, (1-6C) alkyl or (CH ２ ) ｚ Either independently selected from phenyl, or R ｕ and R ｖ However, these, together with the nitrogen atom to which they are bonded, form a 3- to 7-membered ring which may optionally contain further heteroatoms. (ii) R ３００ Any cycloalkyl, heterocyclyl, heteroaryl, or phenyl moiety in the substituent group is optionally further substituted with one or more substituents selected from halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, or (1-2C)alkyl. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

19. R ３ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from hydrogen or acetyl.

20. R ４ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from hydrogen or fluoro.

21. R ５ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from hydrogen, cyano, or fluoro.

22. Q is hydrogen, or formula: -L １ -Y １ -L ２ -Q １ (In the formula, L １ It either does not exist or is (1-3C)alkylene; Y １ It does not exist, or O, S, SO, SO ２ , N(R ｙ１ ), C(O), C(O)O, C(O)N(R ｙ１ ), or N (R ｙ１ ) C(O), R ｙ１ is selected from hydrogen or (1-4C) alkyl; L ２ It either does not exist or is (1-3C)alkylene; Q １ (These are hydrogen, (1-6C) alkyl, phenyl, (3-8C) cycloalkyl, heteroaryl, or heterocyclyl.) It is the basis of; Q is one or more substituent groups independently selected from oxo, hydroxy, (1-6C)alkyl, halo, (1-4C)haloalkyl, (1-4C)haloalkoxy, (1-4C)aminoalkyl, (1-4C)hydroxyalkyl, cyano, or formula: -L ３ -Y ２ -L ４ -W １ (In the formula, L ３ It does not exist; Y ２ It does not exist, or O, S, SO, SO ２ , N(R ｙ２ ), C(O), C(O)O, OC(O), C(O)N(R ｙ２ ), or N (R ｙ２ )C(O), S(O) ２ N(R) ｙ２ ), N (R ｙ２ ) SO ２ Selected from, R ｙ２ is selected from hydrogen or (1-3C) alkyl; L ４ It either does not exist or is (1-3C)alkylene; W １ is hydrogen, (1-6C) alkyl, or phenyl; W １ (The atom is optionally substituted with one or more substituents selected from (1-2C) alkyl or halo.) It is further optionally substituted by one or more of the following groups; However, L １ , Y １ and L ２ If Q does not exist, １ It is neither an aryl nor a heteroaryl. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

23. 5-(2-aminopyridine-4-yl)-7-chloro-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-methyl-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(trifluoromethyl)-1H-indazole-3-amine; 7-Chloro-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-bromo-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-Ethinyl-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-phenyl-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-methyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(tert-butyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid; 7-bromo-5-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)-1H-indazole-3-amine 5-(2-(ethylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(propylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(isopropylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((cyclopropylmethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(isopentylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(hexylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(cyclohexylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-{2-[(Trans-4-methylcyclohexyl)amino]pyridine-4-yl}-1H-indazole-3-amine; 2-((4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)amino)ethane-1-ol; 3-((4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)amino)propan-1-ol; 4-((4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)amino)butan-1-ol; 5-((4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)amino)pentan-1-ol; 5-{2-[(trans-4-hydroxycyclohexyl)amino]pyridine-4-yl}-1H-indazole-3-amine; 5-(2-((2-methoxyethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((3-methoxypropyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((3-isopropoxypropyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 3-((4-(3-amino-1H-indazole-5-yl)pyrimidine-2-yl)amino)propan-1-ol; 3-((4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)(methyl)amino)propan-1-ol; 5-(2-((2-morpholinoethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((2-(piperidine-1-yl)ethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; N １ -(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-N3-methylpropane-1,3-diamine; N-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)cyclopropanecarboxamide; N-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)benzamide; Ethyl (4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)carbamate; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-ethylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-ethylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-propylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-isopentylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-cyclopentylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-cyclohexylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(2-hydroxyethyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-hydroxypropyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(2-methoxyethyl)urea; 3-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-1-(2-hydroxyethyl)-1-methylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-benzylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-phenethylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(pyridine-2-ylmethyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(pyridine-3-ylmethyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(pyridine-4-ylmethyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-phenylurea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-fluorophenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-chlorophenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-isopropylphenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-(hydroxymethyl)phenyl)urea; 3-(3-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)ureido)benzamide; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-phenoxyphenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-(benzyloxy)phenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-((4-fluorobenzyl)oxy)phenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-((3-fluorobenzyl)oxy)phenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(3-((2-fluorobenzyl)oxy)phenyl)urea; 3-(3-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)ureido)-N-phenylbenzamide; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(4-fluorophenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(4-chlorophenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(4-(tert-butyl)phenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(4-(methylsulfonyl)phenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(o-tolyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(2-ethylphenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(2-isopropylphenyl)urea; 1-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-3-(pyridine-3-yl)urea; 5-(2-amino-3-ethynylpyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(cyclopropylethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(3,3-dimethylbuta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(cyclopentylethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(cyclohexylethinyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(phenylethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-((4-aminophenyl)ethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-((3-aminophenyl)ethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-((2-aminophenyl)ethynyl)pyridine-4-yl)-1H-indazole-3-amine; Methyl 3-((2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethynyl)benzoate; Methyl 4-((2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethynyl)benzoate; 5-(2-amino-3-((2-methoxyphenyl)ethynyl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)-1-phenylpenta-4-in-1-one; 3-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)propa-2-in-1-ol; 4-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)buta-3-in-1-ol; 5-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)penta-4-in-1-ol; 6-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)-2-methylhexa-5-in-2-ol; 4-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)-2-methylbuta-3-in-2-ol; 5-(2-amino-3-(3-(tert-butoxy)propa-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 1-((2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethinyl)cyclopentan-1-ol; 1-((2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethynyl)cyclohexane-1-ol; 1-((2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethinyl)cycloheptan-1-ol; 5-(2-amino-3-(3-amino-3-methylbuta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(4-(piperidine-1-yl)buta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(4-morpholinbuta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(5-(piperidine-1-yl)penta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(5-morpholinopenta-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-amino-3-(3-(piperidine-4-yl)propa-1-in-1-yl)pyridine-4-yl)-1H-indazole-3-amine; 3-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)-N-methylpropioamide; 5-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)-1-morpholinopenta-4-in-1-one; 5-(2-amino-3-cyclopropylpyridine-4-yl)-1H-indazole-3-amine; 4-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)butan-1-ol; 1-(2-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)ethyl)cyclohexane-1-ol; 5-(2-amino-4-(3-amino-1H-indazole-5-yl)pyridine-3-yl)pentan-1-ol; 5-(2-aminopyridine-4-yl)-7-phenyl-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3-fluorophenyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3-(trifluoromethyl)phenyl)-1H-indazole-3-amine; 7-(3-aminophenyl)-5-(2-aminopyridine-4-yl)-1H-indazole-3-amine; 3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)phenol; 5-(2-aminopyridine-4-yl)-7-(3-methoxyphenyl)-1H-indazole-3-amine; (3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)phenyl)methanol; 3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzaldehyde; Ethyl 3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzoate; 3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzamide; 3-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzenesulfonamide; 5-(2-aminopyridine-4-yl)-7-(3-(methylsulfonyl)phenyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3-(morpholinomethyl)phenyl)-1H-indazole-3-amine; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)phenol; (4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)phenyl)methanol; 5-(2-aminopyridine-4-yl)-7-(4-(dimethylamino)phenyl)-1H-indazole-3-amine; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzamide; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)benzenesulfonamide; 5-(2-aminopyridine-4-yl)-7-(4-(morpholinomethyl)phenyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(4-(tert-butyl)phenyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(2-chlorophenyl)-1H-indazole-3-amine; (2-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)phenyl)methanol; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)-3-methylbenzenesulfonamide; 5-(2-aminopyridine-4-yl)-7-(pyridine-3-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(pyridine-4-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(furan-3-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(thiophen-3-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(thiophen-2-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(thiazole-5-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(1H-pyrazole-5-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3-methylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(penta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(cyclopropylethynyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(phenylethynyl)-1H-indazole-3-amine; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)buta-3-in-1-ol; 4-(3-amino-5-(2-aminopyridine-4-yl)-1H-indazole-7-yl)-2-methylbuta-3-in-2-ol; 5-(2-aminopyridine-4-yl)-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazole-3-amine; 5-(2-aminopyrimidine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(3,3-dimethylbutyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(2-cyclohexylethyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-(2-cyclopropylethyl)-1H-indazole-3-amine; 5-(2-aminopyridine-4-yl)-7-phenethyl-1H-indazole-3-amine; 5-(2-amino-5-fluoropyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-amino-3-fluoropyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-amino-6-fluoropyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2,6-diamine; 6-amino-4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)nicotinonitrile; 5-(2-(cyclopropylamino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-(cyclobutylamino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-(oxetan-3-ylamino)pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(cyclopentylamino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-((cyclopropylmethyl)amino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((2,2,2-trifluoroethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 3-((4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)amino)propanenitrile; 2-((4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)amino)ethane-1-ol; N1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)ethane-1,2-diamine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((2-methoxyethyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((3-methoxypropyl)amino)pyridine-4-yl)-1H-indazole-3-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)acetamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)propionamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3,3,3-trifluoropropanamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)cyclopropanecarboxamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)isobutylamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)pivaramide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-2-cyclopropylacetamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3-methylbutanamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)cyclobutanecarboxamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)cyclopentanecarboxamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-2-hydroxyacetamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-2-methoxyacetamide; 5-(2-(cyclopropylamino)pyridine-4-yl)-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazole-3-amine; N-(4-(3-amino-7-((3-methyloxetan-3-yl)ethinyl)-1H-indazole-5-yl)pyridine-2-yl)acetamide; N-(4-(3-amino-7-(phenylethynyl)-1H-indazole-5-yl)pyridine-2-yl)acetamide; Methyl (4-(3-amino-7-(cyclopropylethynyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl (4-(3-amino-7-(3-hydroxy-3-methylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(3-amino-3-methylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(3-methoxy-3-methylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(3-morpholinopropane-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(4-morpholinbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; 1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)urea; 1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3-methylurea; 1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3-ethylurea; 1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3-propylurea; 1-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3-phenylurea; Methyl(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Ethyl (4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; tert-butyl(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; (4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)sulfamic acid; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)methanesulfonamide; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)-6-fluoropyridine-2-yl)acetamide; N-(4-(3-amino-7-phenyl-1H-indazole-5-yl)pyridine-2-yl)acetamide; N-(4-(3-amino-7-(pyridine-4-yl)-1H-indazole-5-yl)pyridine-2-yl)acetamide; 7-(furan-3-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-Ethinyl-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(cyclopropylethynyl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(cyclopentylethynyl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(cyclohexylethynyl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 3-(3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)propa-2-in-1-ol; 4-(3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)-2-methylbuta-3-in-2-ol; 1-((3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)ethinyl)cyclopentan-1-ol; 1-((3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)ethynyl)cyclohexane-1-ol; 1-((3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)ethinyl)cycloheptan-1-ol; 7-(5-morpholinopenta-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(4-(piperidine-1-yl)buta-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(5-(piperidine-1-yl)penta-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(6-(piperidine-1-yl)hexa-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 6-(3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)hexa-5-ic acid; 7-(3-amino-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-7-yl)hepta-6-ic acid; 7-(4-phenoxybuta-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 7-(6-phenoxyhexa-1-in-1-yl)-5-(1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-methyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(tert-butyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-neopentyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(cyclohexylmethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(2-cyclohexylethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-benzyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; (4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)methanol; 2-(4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)propan-2-ol; 3-(4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)pentan-3-ol; 5-(2-(tert-butoxymethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(tetrahydro-2H-pyran-2-yl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid; Methyl 4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; Ethyl 4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; 4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; (4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)(pyrroridine-1-yl)methanone; 4-(3-amino-1H-indazole-5-yl)-N-cyclopentyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-isopentyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-phenethyl-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(3-phenylpropyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(2-methoxyethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(2-aminoethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(2-(dimethylamino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; (4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)(4-methylpiperazine-1-yl)methanone; 4-(3-amino-1H-indazole-5-yl)-N-(2-(piperidine-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(2-(butyl(ethyl)amino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(2-(diisopropylamino)ethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 4-(3-amino-1H-indazole-5-yl)-N-(3-(dimethylamino)propyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide; 5-(2-((tert-butylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine 5-(2-((isopentylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(piperidine-2-yl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((cyclohexylamino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((phenylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(((2-(benzyloxy)phenyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(((2-methoxyethyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; N １ -((4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)methyl)-N ２ , N ２ -dimethylethane-1,2-diamine; 5-(2-(((3-methoxypropyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(((3-isopropoxypropyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; N １ -((4-(3-amino-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)methyl)-N ３ , N ３ -Dimethylpropane-1,3-diamine; 5-(2-((isopropyl(methyl)amino)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(piperidine-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((4,4-difluoropiperidine-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(morpholinomethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-((4-methylpiperazine-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((4-(tert-butyl)piperazine-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(azepan-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((4-methyl-1,4-diazepan-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(2-(piperidine-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(2-morpholinoethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazole-3-amine; 5-(2-(3-(piperidine-1-yl)propyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(3-(cyclohexylamino)propyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(3-morpholinopropyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-(piperidine-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; 5-(2-((1-benzylpiperidine-4-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-1H-indazole-3-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)oxazole-2-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((3,3,3-trifluoropropyl)amino)pyridine-4-yl)-1H-indazole-3-amine; 7-(cyclopropylethynyl)-5-(2-(oxetan-3-ylamino)pyridine-4-yl)-1H-indazole-3-amine; Methyl(4-(3-amino-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-((3-methyloxetan-3-yl)ethynyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; 4-(3-amino-5-(2-(oxetan-3-ylamino)pyridine-4-yl)-1H-indazole-7-yl)-2-methylbuta-3-in-2-ol; 5-(2-(oxetan-3-ylamino)pyridine-4-yl)-7-((tetrahydro-2H-pyran-4-yl)ethynyl)-1H-indazole-3-amine; N-(4-(3-amino-7-(cyclopropylethynyl)-1H-indazole-5-yl)pyridine-2-yl)cyclopropanecarboxamide; N-(4-(3-amino-7-(3-hydroxy-3-methylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)cyclopropanecarboxamide; Methyl(4-(3-amino-7-(5-morpholinopenta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; N-(4-(3-amino-7-(3-hydroxy-3-methylbutyl)-1H-indazole-5-yl)pyridine-2-yl)cyclopropanecarboxamide; Methyl (4-(3-amino-7-(3,3-dimethylbutyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; 5-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-cyclopentyl-1H-pyrrolo[2,3-b]pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-(tert-butyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; (4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)methanol; 2-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-yl)propan-2-ol; Methyl 4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate; 5-(2-(difluoromethyl)-3H-imidazo[4,5-b]pyridine-7-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-cyclobutyl-3H-imidazo[4,5-b]pyridine-7-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)cyanamide; 5-(2-((1H-pyrazole-3-yl)amino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-((1H-pyrazole-4-yl)amino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((5-methyl-1H-pyrazole-3-yl)amino)pyridine-4-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((3-methyl-1H-pyrazole-4-yl)amino)pyridine-4-yl)-1H-indazole-3-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)thiazole-2-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-4-methyloxazole-2-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-4-(trifluoromethyl)oxazole-2-amine; N-(4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)pyridine-2-yl)-3,5-dimethylisoxazole-4-amine; 5-(2-((1H-imidazole-4-yl)amino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 5-(2-((4H-1,2,4-triazole-3-yl)amino)pyridine-4-yl)-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((2-methyl-2H-tetrazole-5-yl)amino)pyridine-4-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-(pyrimidine-2-ylamino)pyridine-4-yl)-1H-indazole-3-amine; 7-(3,3-dimethylbuta-1-in-1-yl)-5-(2-((tetrahydrofuran-3-yl)amino)pyridine-4-yl)-1H-indazole-3-amine; Methyl (4-(3-amino-7-(4-hydroxyphenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; 4-(3-amino-5-(2-(oxetan-3-ylamino)pyridine-4-yl)-1H-indazole-7-yl)phenol; Methyl (4-(3-amino-7-(4-aminophenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl (4-(7-(4-acetamidophenyl)-3-amino-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(4-carbamoylphenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(4-(morpholinomethyl)phenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; 5-(2-aminopyridine-4-yl)-7-(4-(2-morpholinoethyl)phenyl)-1H-indazole-3-amine; Methyl(4-(3-amino-7-(4-(2-morpholinoethyl)phenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl(4-(3-amino-7-(4-(methylsulfonyl)phenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl (4-(3-amino-7-(3-hydroxyphenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl (4-(3-amino-7-(3-carbamoylphenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; Methyl (4-(3-amino-7-(3-(morpholinomethyl)phenyl)-1H-indazole-5-yl)pyridine-2-yl)carbamate; N-(4-(3-amino-1H-indazole-5-yl)pyridine-2-yl)-2-cyclohexylacetamide; 6-amino-4-(3-amino-7-(3,3-dimethylbuta-1-in-1-yl)-1H-indazole-5-yl)nicotinonitrile A compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

24. A pharmaceutical composition comprising the compound described in Claim 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

25. (i) For use in treatment; (ii) For use in the treatment of diseases or conditions responsive to IKK alpha regulation; (iii) For use in the treatment of proliferative disorders (e.g., cancer); or (iv) For use in treating inflammation, A compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical formulation according to claim 24.

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