N-(1H-imidazol-2-yl)benzamide compound and pharmaceutical composition containing the same as active ingredient

Abstract

The N-(1H-imidazole-2-yl)benzamide compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof is a novel compound that exhibits excellent inhibitory activity against IRAK-4 and can be used to effectively prevent and treat diseases mediated by the IRAK-4 receptor, particularly autoimmune diseases or lymphoma, without side effects.

Description

Technical Field

[0001] The present invention relates to an N-(1H-imidazol-2-yl)benzamide compound or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof that inhibits the activity of IRAK-4 (interleukin-1 receptor associated kinase 4), and a pharmaceutical composition comprising the same as an active ingredient. Background Art

[0002] Interleukin-1 receptor-associated kinase (IRAK) is critically involved in the regulation of intracellular signaling networks that control inflammation. IRAK is expressed in many cell types and can mediate signals from various cellular receptors including Toll-like receptors (TLRs).

[0003] The IRAK family consists of four family members, IRAK-1, IRAK-2, IRAK-3 / M and IRAK-4. These proteins are characterized by a typical N-terminal death domain that mediates interaction with the MyD88 (myeloid differentiation primary response gene 88) family adaptor proteins and a centrally located kinase domain.

[0004] MyD88 binds to a protein called IRAK (IL-1 receptor-associated kinase). IRAK is subsequently phosphorylated and dissociates from the receptor complex, interacting with tumor necrosis factor receptor-associated factor 6 (TRAF-6) to transmit the signal to downstream effectors. TRAF6 activates the transcription factor NF-κB by triggering the NIK / IKK kinase cascade. NF-κB regulates many genes, thereby modulating immune and inflammatory responses.

[0005] IRAK proteins, as well as MyD88, have been shown to play a role in transducing signals other than those originating from the IL-1R receptor, including those triggered by activation of the IL-18 receptor and the LPS (lipopolysaccharide) receptor. Among the four members of the IRAK family, IRAK-4 is a key mediator of the innate immune response coordinated by the IL-1R (interleukin-1 receptor), IL-18R (interleukin-18 receptor), IL-33R (interleukin-33 receptor), and TLRs. Since IRAK-4 is a serine / threonine kinase that plays an important role in signal transduction of the Toll / IL-1 receptor (TIR), it is considered the "master IRAK". Under overexpression conditions, all IRAKs can mediate the activation of nuclear factor-κB (NF-κB) and stress-induced mitogen-activated protein kinase (MAPK)-signaling cascades. However, IRAK-2 and IRAK-3 / M have no catalytic activity, while IRAK-1 and IRAK-4 have kinase activity.

[0006] Although IRAK-1 kinase activity may not be essential for IL-1-induced NF-kB activation, IRAK-4 requires its kinase activity for signal transduction. Given the central role of IRAK-4 in Toll-like / IL-1R signaling and immune protection, IRAK-4 inhibitors have been considered as valuable therapeutic agents for inflammatory diseases, sepsis, and immune-related diseases.

[0007] Meanwhile, although pyrazolo[1,5-a]pyrimidine and thieno[3,2-d]pyrimidine derivatives (WO 2012 / 007375), indazolyltriazole derivatives (WO 2012 / 084704), indazole derivatives (WO 2015 / 104662), bicyclic heterocyclyl derivatives (WO 2015 / 104688) and thiazolo[5,4-d]pyrimidine derivatives (WO 2015 / 048281) have been developed as IRAK-4 kinase inhibitors, there is still a need to develop novel IRAK-4 kinase inhibitors with excellent inhibitory activity. Summary of the invention

[0008] Technical issues

[0009] Therefore, the present inventors have endeavored to develop novel compounds showing excellent inhibitory activity against IRAK-4 and have found that N-(1-imidazol-2-yl)benzamide derivatives are useful as therapeutic agents for autoimmune diseases and lymphoma.

[0010] One object of the present invention is to provide an N-(1H-imidazol-2-yl)benzamide compound or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof that effectively inhibits IRAK-4 activity.

[0011] Another object of the present invention is to provide a pharmaceutical composition for preventing or treating diseases mediated by IRAK-4, comprising an N-(1H-imidazol-2-yl)benzamide compound or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof as an active ingredient.

[0012] Technical solutions to technical problems

[0013] According to one aspect of the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof:

[0014]

[0015] wherein R1, R2, R3, R4, A and X are as defined below.

[0016] According to another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a disease mediated by IRAK-4 (interleukin-1 receptor associated kinase 4), comprising a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof as an active ingredient.

[0017] Beneficial technical effects of the present invention

[0018] The N-(1H-imidazol-2-yl)benzamide compound or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof according to the present invention is a novel compound that exhibits excellent inhibitory activity against IRAK-4, and can be used for effectively preventing and treating diseases mediated by IRAK-4 receptors, particularly autoimmune diseases or lymphomas, without side effects. DETAILED DESCRIPTION

[0019] The present invention will be described in further detail below. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the subject matter of this invention belongs. Descriptions of known functions and configurations that may unnecessarily obscure the subject matter of the present invention will be omitted.

[0020] The term "alkyl" refers to a monovalent straight or branched chain saturated hydrocarbon group consisting only of carbon and hydrogen atoms, and exemplary alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, nonyl, etc., but are not limited thereto.

[0021] The term "aryl" refers to a monovalent group derived from an aromatic ring of an aromatic hydrocarbon by removing a hydrogen atom, including a monocyclic or condensed ring system containing appropriately 4 to 20, preferably 5 or 10 ring atoms in each ring, and even in the form of multiple aryl groups connected by a single bond. Exemplary aryl groups include phenyl, naphthyl, biphenyl, anthracenyl, indenyl, fluorenyl, etc., but are not limited thereto.

[0022] The term "heteroaryl" refers to a monovalent group of a heteroaromatic ring, which is an aryl group containing at least one heteroatom selected from N, O and S in the main skeleton and carbon atoms in the rest of the main skeleton. The heteroaryl group can be a 5-10-membered monocyclic or polycyclic ring, and its aromatic part is saturated. Exemplary heteroaryl groups include pyrrolyl, pyrazolyl, quinolyl, isoquinolyl, pyridyl, pyrimidinyl, oxazolyl, thiazolyl, thiadiazolyl, triazolyl, imidazolyl, benzimidazolyl, isoxazolyl, benzisoxazolyl, thienyl, benzothienyl, furyl, benzofuranyl, etc., but are not limited thereto.

[0023] The term "halo" or "halogen" refers to a fluorine, chlorine, bromine or iodine atom.

[0024] The term "haloalkyl" refers to an alkyl group substituted with one or more halogens, examples include trifluoromethyl and the like.

[0025] The term "arylalkyl" or "aralkyl" refers to an alkyl group substituted with an aryl group, and examples include benzyl and the like.

[0026] The term "hydroxyalkyl" refers to an alkyl group substituted with one or more hydroxy groups, and examples include hydroxymethyl and the like.

[0027] The term "alkoxy" refers to -O-alkyl, wherein alkyl is as described above. Exemplary alkoxy groups include methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, and the like, but are not limited thereto.

[0028] The term "cycloalkyl" refers to a monovalent saturated carbocyclic group consisting of one or more rings. Exemplary cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc., but are not limited thereto.

[0029] The term "heterocycle" or "heterocyclic ring" refers to an aromatic or non-aromatic ring having at least one heteroatom selected from N, O and S, which may be saturated or unsaturated and may be monocyclic or polycyclic.

[0030] The term "heterocycloalkyl" refers to a monovalent group of a non-aromatic heterocyclic ring containing at least one heteroatom selected from N, O and S, the non-aromatic heterocyclic ring including saturated or unsaturated monocyclic, polycyclic or spirocyclic forms, and may be connected through heteroatoms or carbon atoms. Exemplary heterocycloalkyls include monovalent groups of non-aromatic heterocyclic rings, such as aziridine, pyrrolidine, azetidine, piperidine, tetrahydropyridine, piperazine, morpholine, thiomorpholine, etc., but are not limited thereto.

[0031] According to one aspect of the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof:

[0032]

[0033] in:

[0034] X is =CH- or =N-;

[0035] R1 and R2 are each independently selected from H or a 5-10 membered heteroaryl; or R1 and R2 together with the carbon atoms to which they are attached form a 5-7 membered heterocyclic ring;

[0036] R3 is C 6-10 Aryl, 5-10 membered heteroaryl, C 6-10 Aryl-C 1-3 Alkyl, C 3-10Cycloalkyl or C 3-10 Cycloalkyl-C 1-3 alkyl;

[0037] A is a single bond, C 1-6 Alkylene, -C(=O)-(CH2) n -、-OC(=O)-(CH2) n -、-N(-Rx)-(CH2) n -、-N(-Rx)-C(=O)-(CH2) n -、-C(=O)-N(-Rx)-(CH2) n -or-(CH2) m -N(-Rx)-C(=O)-(CH2) n -, wherein n is an integer from 0 to 6, m is an integer from 0 to 6, and Rx is H or C 1-6 alkyl;

[0038] R4 is hydroxyl, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-10 Alkoxy, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl or C 6-10 Aryl-(CH2) p -4-10 membered heterocycloalkyl, wherein p is an integer from 0 to 3;

[0039] The aryl, cycloalkyl, heteroaryl and heterocycloalkyl groups each optionally have at least one selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkoxy, hydroxycarbonyl, halogenated C 1-3 Alkyl, oxido, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, hydroxyl C 1-6 Alkyl, cyano, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, oxo, nitro, C 1-6 Alkoxycarbonyloxy-C 1-6 alkyl and trimethylsilylethoxymethyl substituents; and

[0040] The heterocyclic ring, heteroaryl group and heterocycloalkyl group each contain at least one heteroatom selected from N, O and S.

[0041] In one embodiment of the compound of formula (I), R1 is H; and R2 is H or a 5-10 membered heteroaryl containing at least one nitrogen atom, wherein the heteroaryl optionally has one or two atoms selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkyl, amino, nitro, C 1-6 Alkoxycarbonyloxy-C 1-6 alkyl and trimethylsilylethoxymethyl substituents; or R1 and R2 together with the carbon atoms to which they are attached form a 5-7 membered heterocyclic ring containing one or two nitrogen atoms.

[0042] In one embodiment of R1 and R2, the heteroaryl is pyrazolyl, isoxazolyl, pyridinyl, indolyl, indazolyl, benzotriazolyl or benzothiazolyl, each of which optionally has one or two substituents selected from fluoro, methyl, 1-ethoxyethyl, 2-ethoxyprop-2-yl, fluoromethyl, difluoromethyl, trifluoromethyl, amino, nitro, methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl and trimethylsilylethoxymethyl.

[0043] In one embodiment, R3 is C 6-10 Aryl, C 6-10 Aryl-C 1-3 Alkyl, 5-6 membered heteroaryl containing nitrogen atom, C 5-7 Cycloalkyl or C 5-7 Cycloalkyl-C 1-3 Alkyl, wherein the aryl group optionally has one or two substituents selected from halogen.

[0044] In another embodiment of the compounds of formula (I), R3 is phenyl, fluorophenyl, difluorophenyl, chlorophenyl, bromophenyl, benzyl, pyridyl, cyclohexyl or cyclohexylmethyl.

[0045] In one embodiment of the compound of formula (I), R4 is hydroxyl, C 1-3 Alkyl, hydroxyl C 1-6 Alkyl, hydroxy-halogenated C 1-6 Alkyl, C 1-6 Alkoxy, amino, C 1-3 Alkylamino, di-C 1-3 Alkylamino, C 3-8 Cycloalkyl, C 6-10aryl, 5-9 membered heteroaryl, 4-9 membered heterocycloalkyl, phenyl-5-7 membered heterocycloalkyl or benzyl-5-7 membered heterocycloalkyl, wherein the aryl, cycloalkyl, heteroaryl and heterocycloalkyl each optionally have at least one selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkoxy, hydroxycarbonyl, halogenated C 1-3 Alkyl, oxide, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, hydroxyl C 1-6 Alkyl, cyano, C 1-3 Alkylcarbonyl, C 1-3 The substituents of the alkylsulfonyl and oxo groups, and the heteroaryl and heterocycloalkyl groups each contain at least one heteroatom selected from N, O and S.

[0046] In one embodiment of R4, the aryl is phenyl; the cycloalkyl is cyclopropyl, cyclobutyl or cyclohexyl; the heteroaryl is pyridinyl, triazolyl, pyrazinyl, pyrazolyl or indazolyl; and the heterocycloalkyl is piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrofuranyl, azepanyl or diazepanyl.

[0047] In another embodiment of R4, the substituents are selected from fluoro, methyl, tert-butoxy, methoxy, methoxymethyl, trifluoromethoxy, hydroxycarbonyl, trifluoromethyl, oxidized, amino, methylamino, dimethylamino, cyclopropyl, cyclohexyl, pyrrolidinyl, hydroxyethyl, cyano, methylcarbonyl, methylsulfonyl and oxo.

[0048] In one embodiment of the compound of formula (I), R4 may have at least one N atom, in which case it may be attached to group A via any one of the N atoms. Examples of such R4 include ((1R,4R)-4-hydroxycyclohexyl)amino, ((tetrahydro-2H-pyran-4-yl)methyl)amino, ((tetrahydrofuran-3-yl)methyl)amino, (2-(4-methylpiperazin-1-yl)ethyl)amino, (2-(dimethylamino)ethyl)amino, (2-(piperidin-1-yl)ethyl)amino, (2-fluorophenyl)amino, (2-hydroxy-2-methylpropyl)amino, (2-hydroxyethyl)amino, (2-morpholinylethyl)amino, (2R,5R)-2,5-dimethylpyrrolidin-1-yl, (2S,6R)-2,6 -dimethylpiperidin-1-yl, (3-(4-methylpiperazin-1-yl)propyl)amino, (3-(dimethylamino)propyl)amino, (3-(piperidin-1-yl)propyl)amino, (3-hydroxy-3-methylbutyl)amino, (3-hydroxypropyl)amino, (4-(dimethylamino)cyclohexyl)amino, (4-(dimethylamino)phenyl)amino, (4-(trifluoromethoxy)benzyl)piperazin-1-yl, (4-methoxycyclohexyl)amino, (4-methylpiperazin-1-yl)amino, piperidin-1-yl, (R)-(2-(methoxymethyl)pyrrolidin-1-yl)amino, (R)-(2-fluoro-3-hydroxy-3-methylbutyl)amino, (R)-(2-hydroxyethyl)piperidin-1-yl, (R)-2-(methoxymethyl)pyrrolidin-1-yl)amino, (R)-2-(trifluoromethyl)piperidin-1-yl, (R)-2-methylpiperidin-1-yl, (R)-3-aminopiperidin-1-yl, (R)-piperidin-1-yl-3-carboxylic acid, (S)-(2-(methoxymethyl)pyrrolidin-1-yl)amino, (S)-2-(methoxymethyl)pyrrolidin-1-yl, (S)-2-(methoxymethyl)pyrrolidin-1-yl)amino, (S) -2-(methoxymethyl)pyrrolidine, (S)-2-(trifluoromethyl)piperidin-1-yl, (S)-2-2-methylpiperidin-1-yl, (S)-2-methylpiperidin-1-yl, (S)-piperidin-1-yl-3-carboxylic acid, (S)-piperidin-1-yl-3-carboxylic acid, (S)-piperidin-1-yl-3-carboxylic acid, (S)-pyrrolidin-1-yl-3-carboxylic acid, (tetrahydrofuran-3-yl)amino, 2-methylpiperidin-1-yl, 2-oxopiperidin-1-yl, 2,5-dioxopyrrolidin-1-yl, 3-hydroxypiperidin-1-yl, 3,3-difluoropiperidin-1-yl, 3,3-dimethylpiperidin-1-yl, 4-(1-methylpiperidin-4-yl)amino, 4-(dimethylamino)piperidin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-(pyrrolidin-1-yl)piperidin-1-yl, 4-(tert-butyl)piperazin-1-yl, 4-acetylpiperazin-1-yl, 4-aminopiperidin-1-yl, 4-cyanopiperidin-1-yl, 4-cyclohexylpiperazin-1-yl, 4-cyclopropylpiperazin-1-yl, 4-ethylpiperazin-1-yl, 4-hydroxypiperidin-1-yl, 4-isopropylpiperazin-1-yl, 4-methoxypiperidin-1-yl, 4-methyl-1,4-diazepanyl-1-yl, 4-methylpiperazin-1-yl, 4-morpholinyl, 4-phenylpiperazin-1-yl, 4,4-dimethylpiperidin-1-yl, cyclobutylamino, cyclohexylamino, cyclopropanecarboxamido, cyclopropyl(methyl)amino, cyclopropylamino, methyl(4-methylpiperazin-1-yl)amino, methylamino, morpholinyl-N-oxide, N-morpholinyl, piperazin-1-yl, piperidin-1-yl-N-oxide, piperidin-1-ylamino, pyrrolidin-1-yl, pyrrolidin-1-ylamino, thiomorpholinyl, etc., but not limited thereto. ,

[0049] In one embodiment of the compound of formula (I), at least one of R1, R2, R3, R4 may include a heteroaryl group containing one or more heteroatoms selected from N, S and O. Examples of such moieties include pyridin-4-yl, pyridin-3-yl, pyridin-2-yl, isoxazol-4-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-5-yl, 7-(5-fluoro-1H-pyrazole), 6-aminopyridin-3-yl, 5-fluoro-1H-pyrazol-4-yl, 5-fluoro-1H-pyrazol-4-yl, 5-fluoro-1-methyl-1H-pyrazol-4-yl, 5-(1H-indazole), 4-pyridine, 4-(1H-pyrazole), 4-(1H-pyrazol-3-amine), 4-(1H-indazole), 4-(1-methyl-1H-pyrazole), 4-(1-ethoxyethyl)-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-ethoxyethyl)-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole), 4-(1-methyl-1H-pyrazole). 1H-pyrazol-1-yl)methylethyl carboxylate), 3-nitro-1H-pyrazol-4-yl, 3-(trifluoromethyl)-1H-pyrazol-4-yl, 1H-pyrazol-4-yl, 1H-indol-5-yl, 1H-indazol-6-yl, 1H-indazol-5-yl, 1H-indazol-4-yl, 1H-benzo[d][1,2,3]triazol-5-yl, 1-methyl-1H -pyrazol-4-yl, 1-methyl-1H-indazol-5-yl, 1-(trifluoromethyl)-1H-pyrazol-4-yl, 1-(fluoromethyl)-1H-pyrazol-4-yl, 1-(difluoromethyl)-1H-pyrazol-4-yl, 1-(2-ethoxyprop-2-yl)-1H-pyrazol-4-yl, 1-(1-ethoxyethyl)-1H-pyrazol-4-yl, and the like, but are not limited thereto.

[0050] Exemplary compounds of the present invention are:

[0051] 1) 3-(3-nitro-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0052] 2) 3-(3-amino-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0053] 3) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide;

[0054] 4) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1H-pyrazol-4-yl)nicotinamide;

[0055] 5) 3-(isoxazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0056] 6) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0057] 7) 3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoic acid;

[0058] 8) N-(4-(3-oxo-3-(piperidin-1-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0059] 9) N-(4-(3-((4-methylpiperazin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0060] 10) N-(4-(3-((4-fluorophenyl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0061] 11) N-(4-(3-morpholinyl-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0062] 12) N-(4-(3-oxo-3-(piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0063] 13) (S)-N-(4-(3-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0064] 14) N-(4-(3-oxo-3-(4-(4-(trifluoromethoxy)benzyl)piperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0065] 15) N-(4-(3-oxo-3-(pyridin-2-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0066] 16) N-(4-(3-((2,4-difluorophenyl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0067] 17) (R)-N-(4-(3-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0068] 18) methyl 3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoate;

[0069] 19) (S)-N-(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0070] 20)(R)-N-(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0071] 21) N-(4-(3-((4H-1,2,4-triazol-4-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0072] 22) N-(4-(3-oxo-3-(pyrazin-2-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0073] 23) (R)-N-(4-(3-(2-methylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0074] 24)(S)-N-(4-(3-(2-methylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0075] 25) (R)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)pyrrolidine-3-carboxylic acid;

[0076] 26)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)pyrrolidine-3-carboxylic acid;

[0077] 27) N-(4-(3-oxo-3-(pyrrolidin-1-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0078] 28) N-(4-(3-oxo-3-(pyrrolidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0079] 29) N-(4-(3-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0080] 30) (R)-N-(4-(3-(2-methylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0081] 31)(S)-N-(4-(3-(2-methylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0082] 32) N-(4-(3-((2R,6S)-2,6-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0083] 33) N-(4-(3-(methylamino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0084] 34) N-(4-(3-(3,3-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0085] 35) N-(4-(3-(4,4-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0086] 36)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)piperidine-3-carboxylic acid;

[0087] 37)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)piperidine-3-carboxylic acid;

[0088] 38) (S)-N-(4-(3-oxo-3-(2-(trifluoromethyl)piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0089] 39) (R)-N-(4-(3-oxo-3-(2-(trifluoromethyl)piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0090] 40) (R)-N-(4-(3-(3-aminopiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0091] 41) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0092] 42) methyl 2-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)acetate;

[0093] 43) 2-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)acetic acid;

[0094] 44)(S)-N-(4-(2-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0095] 45) (R)-N-(4-(2-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0096] 46)(S)-N-(4-(2-(2-(methoxymethyl)pyrrolidin-1-yl)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0097] 47) (R)-N-(4-(2-(2-(methoxymethyl)pyrrolidin-1-yl)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0098] 48) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1H-pyrazol-4-yl)benzamide;

[0099] 49) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1H-indazole-5-carboxamide;

[0100] 50) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0101] 51) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)nicotinamide;

[0102] 52) N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0103] 53)(S)-N-(4-(4-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0104] 54) (R)-N-(4-(4-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0105] 55)(S)-N-(4-(4-(2-(methoxymethyl)pyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0106] 56) (R)-N-(4-(4-(2-(methoxymethyl)pyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0107] 57) 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid;

[0108] 58) methyl 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate;

[0109] 59) N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0110] 60) N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0111] 61) (R)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0112] 62)(S)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0113] 63) N-(4-(4-((2R,6S)-2,6-dimethylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0114] 64) N-(4-(4-((4-fluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0115] 65) N-(4-(4-((2-fluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0116] 66) N-(4-(4-((2,4-difluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0117] 67) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide;

[0118] 68) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0119] 69) N-(4-(4-(cyclobutylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0120] 70) isopropyl 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate;

[0121] 71) N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0122] 72) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)benzamide;

[0123] 73) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(2-ethoxypropan-2-yl)-1H-pyrazol-4-yl)benzamide;

[0124] 74)(4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methyl methyl carboxylate;

[0125] 75)(4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methylethylcarboxylate;

[0126] 76) N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0127] 77) methyl 5-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoate;

[0128] 78) 5-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoic acid;

[0129] 79) N-(4-(5-oxo-5-(piperidin-1-yl)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0130] 80) N-(4-(5-(methylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0131] 81) N-(4-(5-((2R,6S)-2,6-dimethylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0132] 82)(S)-N-(4-(5-(2-methylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0133] 83) (R)-N-(4-(5-(2-methylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0134] 84)(S)-N-(4-(5-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0135] 85)(R)-N-(4-(5-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0136] 86)(S)-N-(4-(5-(2-(methoxymethyl)pyrrolidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0137] 87) (R)-N-(4-(5-(2-(methoxymethyl)pyrrolidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0138] 88) N-(4-(5-(cyclopropylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0139] 89) N-(4-(5-(cyclohexylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0140] 90) N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0141] 91) methyl 6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate;

[0142] 92) 6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid;

[0143] 93) N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0144] 94) N-(4-(6-(methylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0145] 95)(S)-N-(4-(6-(2-methylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0146] 96) (R)-N-(4-(6-(2-methylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0147] 97) N-(4-(6-((2R,6S)-2,6-dimethylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0148] 98)(S)-N-(4-(6-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0149] 99) (R)-N-(4-(6-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0150] 100)(S)-N-(4-(6-(2-(methoxymethyl)pyrrolidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0151] 101) (R)-N-(4-(6-(2-(methoxymethyl)pyrrolidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0152] 102) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0153] 103) N-(4-(2-hydroxyethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0154] 104) N-(1-phenyl-4-(2-(piperidin-1-yl)ethyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0155] 105) N-(4-(3-hydroxypropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0156] 106) N-(1-phenyl-4-(3-(piperidin-1-yl)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0157] 107) N-(4-(3-morpholinopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0158] 108) N-(4-(3-(4-methylpiperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0159] 109) N-(1-phenyl-4-(3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0160] 110) N-(1-phenyl-4-(3-thiomorpholinylpropyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0161] 111) N-(4-(4-hydroxybutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0162] 112) N-(1-phenyl-4-(4-(phenylamino)butyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0163] 113) N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0164] 114) N-(4-(4-morpholinylbutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0165] 115) N-(1-phenyl-4-(4-thiomorpholinylbutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0166] 116) N-(4-(5-hydroxypentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0167] 117) N-(1-phenyl-4-(5-(phenylamino)pentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0168] 118) N-(1-phenyl-4-(5-(piperidin-1-yl)pentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0169] 119) N-(4-(5-morpholinylpentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0170] 120) N-(1-phenyl-4-(5-thiomorpholinylpentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0171] 121) N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0172] 122) N-(1-phenyl-4-(6-(phenylamino)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0173] 123) N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0174] 124) N-(1-phenyl-4-(6-thiomorpholinylhexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0175] 125) 1-(6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl)piperidine 1-oxide;

[0176] 126) 4-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propyl)morpholine 4-oxide;

[0177] 127) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide hydrochloride;

[0178] 128) N-(4-(3-morpholinopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide hydrochloride;

[0179] 129) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide hydrochloride;

[0180] 130) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide hydrochloride;

[0181] 131) N-(4-(4-((4-(dimethylamino)cyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide hydrochloride;

[0182] 132) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((1-methylpiperidin-4-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide hydrochloride;

[0183] 133) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide citrate;

[0184] 134) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide fumarate;

[0185] 135) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (2R,3R)-2,3-dihydroxysuccinate;

[0186] 136) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide succinate;

[0187] 137) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide fumarate;

[0188] 138) 3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0189] 139) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0190] 140) 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid;

[0191] 141) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0192] 142) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0193] 143) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0194] 144) N-(4-(4-(4-ethylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0195] 145) N-(4-(4-(4-isopropylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0196] 146) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0197] 147) N-(4-(4-((4-(dimethylamino)cyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0198] 148) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((1-methylpiperidin-4-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0199] 149) N-(4-(4-(4-cyclopropylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0200] 150) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(pyridin-4-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0201] 151) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(pyrrolidin-1-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0202] 152) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0203] 153) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0204] 154) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0205] 155) N-(4-(4-((4-(dimethylamino)phenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0206] 156) N-(4-(4-(((1R,4R)-4-hydroxycyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0207] 157) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((tetrahydro-2H-pyran-4-yl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0208] 158) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((3-(piperidin-1-yl)propyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0209] 159) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((2-(piperidin-1-yl)ethyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0210] 160) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-morpholinyl-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0211] 161) N-(4-(4-((4-methoxycyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0212] 162) N-(4-(4-((2-(dimethylamino)ethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0213] 163) N-(4-(4-((3-(dimethylamino)propyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0214] 164) N-(4-(4-((2-hydroxyethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0215] 165) N-(4-(4-((3-hydroxypropyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0216] 166) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0217] 167) N-(4-(4-(4,4-dimethylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0218] 168) N-(4-(4-(4-cyanopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0219] 169) N-(4-(4-(4-hydroxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0220] 170) N-(4-(4-((2-hydroxy-2-methylpropyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0221] 171) N-(4-(4-((3-hydroxy-3-methylbutyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0222] 172) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0223] 173) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-(4-(trifluoromethoxy)benzyl)piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0224] 174) (R)-N-(4-(4-(2-(2-hydroxyethyl)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0225] 175) N-(4-(4-(3,3-difluoropiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0226] 176) (R)-3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(2-(trifluoromethyl)piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0227] 177) N-(4-(4-(4-methoxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0228] 178) N-(4-(4-(3-hydroxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0229] 179) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((tetrahydrofuran-3-yl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0230] 180) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(((tetrahydrofuran-3-yl)methyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0231] 181) N-(4-(4-(4-(tert-butyl)piperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0232] 182) N-(4-(4-(4-cyclohexylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0233] 183) N-(4-(4-(4-methyl-1,4-diazepan-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0234] 184) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((2-morpholinylethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0235] 185) (R)-N-(4-(4-((2-fluoro-3-hydroxy-3-methylbutyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0236] 186) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0237] 187) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0238] 188) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-phenylpiperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0239] 189) N-(4-(4-amino-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0240] 190) N-(4-(4-((1-methyl-1H-pyrazol-3-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0241] 191) N-(4-(4-((1-methyl-1H-indazol-5-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0242] 192) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0243] 193) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0244] 194) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-(4-methylpiperazin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0245] 195) N-(4-(3-(4-methyl-1,4-diazepan-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0246] 196) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-(4-methylpiperazin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0247] 197) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-oxo-5-((tetrahydro-2H-pyran-4-yl)amino)pentyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0248] 198) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-((2-morpholinylethyl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0249] 199) N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0250] 200) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0251] 201) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0252] 202) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0253] 203) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(piperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0254] 204) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-oxo-5-(piperazin-1-yl)pentyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0255] 205) N-(4-(4-(4-acetylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0256] 206) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-(methylsulfonyl)piperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0257] 207)(S)-1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylic acid;

[0258] 208) (S)-1-(5-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoyl)piperidine-3-carboxylic acid;

[0259] 209) N-(4-(4-(4-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0260] 210) (R)-N-(4-(4-(3-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0261] 211)(S)-N-(4-(4-(3-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0262] 212) (R)-N-(4-(4-(3-aminopyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0263] 213) N-(4-(5-(4-aminopiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0264] 214) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-4-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0265] 215) N-(4-(4-(((1R,4R)-4-aminocyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0266] 216) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-(methylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0267] 217) N-(4-(4-((1H-pyrazol-3-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0268] 218) N-(4-(4-(methyl(4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0269] 219) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide;

[0270] 220) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0271] 221) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0272] 222) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(pyrrolidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0273] 223) N-(4-(6-(azepan-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0274] 224) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0275] 225) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0276] 226) N-(4-(6-(2,5-dioxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0277] 227) N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0278] 228) N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0279] 229) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide;

[0280] 230) 3-(5-fluoro-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0281] 231) 3-(5-fluoro-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0282] 232) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide;

[0283] 233) N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide;

[0284] 234) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamide;

[0285] 235) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(difluoromethyl)-1H-pyrazol-4-yl)benzamide;

[0286] 236) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide;

[0287] 237) 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0288] 238) N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide;

[0289] 239) 3-(1H-indazol-5-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0290] 240) 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(pyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0291] 241) N-(4-(6-(azepan-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide;

[0292] 242) 3-(1H-benzo[d][1,2,3]triazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0293] 243) 3-(1H-indazol-5-yl)-N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0294] 244) 3-(1H-indazol-5-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0295] 245) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide;

[0296] 246) 3-(1H-indazol-5-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0297] 247) 3-(1H-indazol-5-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0298] 248) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-7-yl)benzamide;

[0299] 249) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-4-yl)benzamide;

[0300] 250) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-6-yl)benzamide;

[0301] 251) 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0302] 252) 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0303] 253) 3-(1H-indol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0304] 254) 3-(1H-indazol-5-yl)-N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0305] 255) 3-(1H-indazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0306] 256) 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide;

[0307] 257) 3-(1H-indazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide;

[0308] 258) 3-(1H-indazol-5-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0309] 259) 3-(1H-indazol-5-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0310] 260) 3-(1H-indazol-5-yl)-N-(4-(6-(2-oxopiperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0311] 261) N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide;

[0312] 262) N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide;

[0313] 263) 3-(1-methyl-1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0314] 264) 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0315] 265) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide;

[0316] 266) N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide;

[0317] 267) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide;

[0318] 268) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide;

[0319] 269) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-2-yl)benzamide;

[0320] 270) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-3-yl)benzamide;

[0321] 271) 3-(6-aminopyridin-3-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0322] 272) 3-(6-aminopyridin-3-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0323] 273) 3-(6-aminopyridin-3-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0324] 274) 3-(6-aminopyridin-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0325] 275) 3-(6-aminopyridin-3-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide;

[0326] 276) 3-(6-aminopyridin-3-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0327] 277) 3-(6-aminopyridin-3-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0328] 278) 3-(6-aminopyridin-3-yl)-N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0329] 279) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0330] 280) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0331] 281) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0332] 282) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0333] 283) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0334] 284) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0335] 285) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0336] 286) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0337] 287) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(4-(dimethylamino)piperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0338] 288) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0339] 289) N-(4-(6-(azepan-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(benzo[d]thiazol-5-yl)benzamide;

[0340] 290) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0341] 291) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(4-(dimethylamino)piperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide;

[0342] 292) N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0343] 293) N-(1-(3-chlorophenyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0344] 294) N-(1-(3-bromophenyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0345] 295) N-(1-(cyclohexylmethyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0346] 296) N-(1-cyclohexyl-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0347] 297) N-(1-(4-fluorophenyl)-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0348] 298) N-(1-(2,4-difluorophenyl)-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0349] 299) N-(1-(4-fluorophenyl)-4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0350] 300) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide;

[0351] 301) N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide;

[0352] 302) N-(1-(2,4-difluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; and

[0353] 303) N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide.

[0354] N-(1H-imidazoles-2-yl) benzamide compound according to the present invention can be used in the form of its pharmaceutically acceptable salt, prodrug or stereoisomer, for increasing absorption in vivo or increasing solubility. Therefore, prodrug, solvate and pharmaceutically acceptable salt also fall within the scope of the present invention. In addition, since N-(1H-imidazoles-2-yl) benzamide compound may have chiral carbon, there is a stereoisomer thereof, which also falls within the scope of the present invention.

[0355] The N-(1H-imidazole-2-yl)benzamide compound according to the present invention can be used in the form of its pharmaceutically acceptable salt, and the pharmaceutically acceptable salt can be prepared by conventional methods in the art, and may include, for example, salts formed with inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, sodium bisulfate, phosphoric acid, nitric acid or carbonic acid, and salts formed with organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid, malonic acid, mandelic acid, cinnamic acid, stearic acid, palmitic acid, Salts formed with glycolic acid, glutamic acid, tartaric acid, gluconic acid, lactic acid, fumaric acid, lactobionic acid, ascorbic acid, salicylic acid or acetylsalicylic acid (aspirin), salts formed with amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine or proline, salts formed with sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or toluenesulfonic acid, metal salts formed by reaction with alkali metals such as sodium or potassium, salts formed with ammonium ions, etc.

[0356] In one embodiment of the present invention, the pharmaceutically acceptable salt is a hydrochloride, citrate, fumarate, dihydroxysuccinate or succinate salt of the compound of formula (I).

[0357] The N-(1H-imidazol-2-yl)benzamide compound of the present invention may exist in a solvated form (e.g., a hydrated form) and a non-solvated form, and the solvates of the N-(1H-imidazol-2-yl)benzamide compound according to the present invention include all solvated forms having pharmaceutical activity.

[0358] The N-(1H-imidazole-2-yl)benzamide compounds of the present invention may have chiral centers and may exist as racemates, racemic mixtures and individual enantiomers or diastereomers. These isomers may be separated or split by conventional methods, and optionally predetermined isomers may be obtained by conventional synthetic methods or stereospecific synthesis or asymmetric synthesis. These stereoisomeric forms and mixtures thereof are all included within the scope of the present invention.

[0359] The N-(1H-imidazol-2-yl)benzamide compounds of the present invention can be administered in the form of prodrugs that decompose in the human or animal body to provide the compounds of the present invention. Prodrugs can be used to change or improve the physical and (or) pharmacokinetic characteristics of the parent compound and can be formed when the parent compound contains appropriate groups or substituents that can be derived to form prodrugs.

[0360] The N-(1H-imidazol-2-yl)benzamide compound according to the present invention is a novel compound which has a high inhibitory activity against IRAK4 (interleukin-1 receptor associated kinase 4) and is therefore useful as a therapeutic and preventive agent for diseases mediated by IRAK4, particularly autoimmune diseases or lymphoma.

[0361] In one embodiment of the present invention, the autoimmune disease can be selected from atopic dermatitis, alopecia areata, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriasis, arthritis, osteoarthritis, rheumatoid arthritis, frozen shoulder, tendinitis, tendonitis, peritonitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome and multiple sclerosis.

[0362] In one embodiment of the present invention, the lymphoma may be activated B-cell-like diffuse large B-cell lymphoma.

[0363] Therefore, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof, for use in preventing or treating a disease mediated by IRAK4.

[0364] The present invention further provides a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof, for use in inhibiting IRAK4.

[0365] The present invention further provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof in the preparation of a medicament for preventing or treating a disease mediated by IRAK4.

[0366] The present invention further provides use of a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof in the preparation of a medicament for inhibiting IRAK4.

[0367] The present invention further provides a method for preventing or treating a disease mediated by IRAK4, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof to a subject in need thereof.

[0368] The present invention further provides a method for inhibiting IRAK4, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof to a subject in need thereof.

[0369] The present invention further provides a pharmaceutical composition for preventing or treating a disease mediated by IRAK4, comprising a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof as an active ingredient, and a pharmaceutically acceptable carrier or excipient.

[0370] The present invention further provides a pharmaceutical composition for preventing or treating a disease mediated by IRAK4, comprising a compound of formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof as an active ingredient.

[0371] In one embodiment of the present invention, the disease mediated by IRAK4 is an autoimmune disease or lymphoma. Specifically, the disease mediated by IRAK4 is selected from atopic dermatitis, alopecia areata, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriasis, arthritis, osteoarthritis, rheumatoid arthritis, frozen shoulder, tendinitis, tendinitis, peritonitis, myositis, hepatitis, cystitis, nephritis, Sjögren's syndrome, or multiple sclerosis, or activated B-cell-like diffuse large B-cell lymphoma.

[0372] The pharmaceutical composition of the present invention inhibits the activity of serine / threonine kinase IRAK-4.

[0373] According to the present invention, the N-(1H-imidazol-2-yl)benzamide compound represented by formula (I) effectively inhibits the activity of IRAK-4, which is involved in the signal transduction of the innate immune response from Toll-like receptors (TLRs) and Toll / IL-1 receptors (TIRs).

[0374] The term "inhibit" refers to reducing the expression level or biological activity of a target substance in vivo to a significant level.

[0375] In addition, by adding conventional non-toxic pharmaceutically acceptable carriers, excipients, etc. to the N-(1H-imidazole-2-yl)benzamide compound represented by formula (I) or its pharmaceutically acceptable salt, prodrug, solvate or stereoisomer, the pharmaceutical composition of the present invention can be formulated into commonly used preparations in the medical field, for example, preparations for oral administration, such as tablets, pills, hard / soft capsules, liquids, suspensions, emulsions, syrups, granules and elixirs, or parenteral preparations with sterile aqueous or oily solvents for intravenous, subcutaneous, sublingual or intramuscular administration.

[0376] Pharmaceutically acceptable carriers commonly used in preparations can be used in the pharmaceutical composition of the present invention, including lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methylcellulose, hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and / or mineral oil, etc., but are not limited thereto.

[0377] The excipients that can be used in the pharmaceutical composition of the present invention can be sweeteners, adhesives, solubilizers, cosolvents, wetting agents, emulsifiers, isotonic agents, adsorbents, disintegrants, antioxidants, preservatives, lubricants, fillers, spices, etc., and the ratio and properties of the excipients can be determined by the solubility and chemical properties of the selected tablets, the selected route of administration, and standard pharmaceutical practice. The example of the excipient can include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, silicon dioxide, talc, stearic acid, glyceryl stearate, magnesium stearate, magnesium aluminum silicate, starch, gelatin, tragacanth, alginic acid, sodium alginate, methylcellulose, sodium carboxymethylcellulose, agar, water, ethanol, polyethylene glycol, polyvinyl pyrrolidone, sodium chloride, calcium chloride, orange flavor, strawberry flavor, vanilla flavor, etc.

[0378] In addition, the pharmaceutical composition of the present invention can be formulated into a parenteral administration form, in which case, intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, topical administration, etc. can be used, but are not limited thereto. In the preparation for parenteral administration, the pharmaceutical composition can be prepared into a solution or suspension by mixing the active ingredient, i.e., the N-(1H-imidazol-2-yl)benzamide compound represented by formula (I) or a pharmaceutically acceptable salt, prodrug, solvate or stereoisomer thereof, with a stabilizer or buffer in water, and the solution or suspension can be prepared into a unit dosage form of an ampoule or a vial.

[0379] In addition, the pharmaceutical composition of the present invention may be sterilized, or further contain adjuvants such as preservatives, stabilizers, hydrating agents or emulsifying promoters, salts for adjusting osmotic pressure, and / or buffers, as well as other therapeutically useful materials, and may be formulated according to conventional methods of mixing, granulating or coating.

[0380] In addition, according to the pharmaceutical composition for mammals including people of the present invention, the N-(1H-imidazole-2-yl) benzamide compound represented by formula (I) or its pharmaceutically acceptable salt, prodrug, solvate or stereoisomer can be changed according to the patient's age, body weight, sex, dosage form, health status and disease severity as the dosage of active ingredient. The compound of the present invention can be included in the pharmaceutical composition with an effective amount of 0.001-500mg / kg (body weight) per day, preferably 0.01-100mg / kg (body weight), and can be administered via oral or parenteral route, with separate portions once or twice a day. However, the dosage can be increased or decreased according to the route of administration, the severity of the disease, sex, body weight, age, etc., so the scope of the present invention is not limited thereto.

[0381] The N-(1H-imidazol-2-yl)benzamide compounds according to the present invention can be prepared by various known methods depending on the substituents.

[0382] The following schemes 1 and 2 can be illustrated, but they do not limit the scope of the method for preparing the compounds of the present invention. It is obvious to those skilled in the art that the preparation methods shown in the following schemes 1 and 2 can be easily modified according to specific substituents.

[0383] [Solution 1]

[0384]

[0385] i) 1N-NaOH, MeOH, ii) HATU or HBTU, DIPEA, iii) LiAlH4, THF, iv) oxalyl chloride, DMSO, TEA, MC, v) NaBH3CN, THF.

[0386] [Solution 2]

[0387]

[0388] In Schemes 1 and 2, the definitions of the substituents in the schemes are the same as those in formula (I).

[0389] Invention method

[0390] Hereinafter, the present invention is more specifically described by the following examples, but these examples are provided only for illustrative purposes, and the present invention is not limited thereto.

[0391] Unless otherwise stated, all reactions were carried out under nitrogen atmosphere. The progress of the reactions was monitored by thin layer chromatography (TLC). 1 H NMR spectrum (BRUKER 300 MHz spectrometer).

[0392] The abbreviations of chemical materials used in the examples are defined as follows.

[0393] -AcOH: acetic acid

[0394] -ACN: acetonitrile

[0395] -n-BuLi: n-butyllithium

[0396] -DCM: dichloromethane

[0397] -DIPEA: N,N-diisopropylethylamine

[0398] -DMAP: 4-dimethylaminopyridine

[0399] -DMF: dimethylformamide

[0400] -DMSO: dimethyl sulfoxide

[0401] -EA: Ethyl acetate

[0402] -EDCl: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

[0403] -EtOH: ethanol

[0404] -HATU: azabenzotriazole tetramethyluronium hexafluorophosphate

[0405] -HBTU: Benzotriazole tetramethyluronium hexafluorophosphate

[0406] -HOBt: Hydroxybenzotriazole

[0407] -KOAc: Potassium acetate

[0408] -LDA: lithium diisopropylamide

[0409] -MeOH: methanol

[0410] -NFSI: N-Fluorobenzenesulfonamide

[0411] -Pd(dppf)Cl2:1-cyclopenta-1,4-dienyl(diphenyl)phosphine

[0412] -Pd(PPh3)4:Tetrakis(triphenylphosphine)palladium(0)

[0413] -SEM: 2-(trimethylsilyl)ethoxymethyl

[0414] -TBAF: Tetra-n-butylammonium fluoride

[0415] -TEA: triethylamine

[0416] -TFA: trifluoroacetic acid

[0417] -THF: Tetrahydrofuran

[0418] Intermediates

[0419] Intermediate 1, 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0420]

[0421] Step 1: 4-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0422] To a solution of 4-bromopyrazole (4.00 g, 27.2 mmol) in anhydrous THF (25 mL) was added NaH (60% dispersion in mineral oil, 1.63 g, 40.8 mmol) at 0°C. The reaction mixture was stirred at 0°C for 30 min, then 2-(trimethylsilyl)ethoxymethyl chloride (5.06 mL, 28.6 mmol) was added dropwise. The reaction mixture was stirred overnight at room temperature, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (1.20 g, 50%). 1 H NMR (CDCl3, 400MHz): δ7.59(s,1H),7.49(s,1H),5.38(s,2H),3.60-3.53(m,2H),0.93-0.89(m,2H),-0.02(s,9H).

[0423] Step 2: Methyl 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate

[0424] A mixture of 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (20.4 g, 73.60 mmol), (3-(methoxycarbonyl)phenyl)boronic acid (13.25 g, 73.60 mmol), Pd(PPh3)4 (4.25 g, 3.68 mmol) and K2CO3 (30.52 g, 220.80 mmol) in 1,4-dioxane / H2O (4 / 1, 500 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (15.6 g, 58%). 1 H NMR (CDCl3, 400MHz): δ8.19-8.15(m,1H),7.94-7.85(m,3H),7.72-7.65(m,1H),7. 49-7.41(m,1H),5.46(s,2H),3.65-3.54(m,2H),0.98-0.87(m,2H),-0.02(s,9H).

[0425] Step 3: 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0426] To a solution of methyl 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate (15.6 g, 46.9 mmol) in MeOH (200 mL) was added 1N-NaOH (187.6 mL, 187.6 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (13.6 g, 91%). 1 H NMR (CDCl3, 400MHz): δ8.29-8.22(m,1H),8.04-7.96(m,1H),7.95-7.88(m,2H),7.79-7.71(m,1 H),7.54-7.445(m,1H),5.50(s,2H),3.62(t,J=8.4Hz,2H),0.94(t,J=8.4Hz,2H),-0.01(s,9H).

[0427] Intermediate 2, 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0428]

[0429] Step 1: Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

[0430] At 100°C, methyl 4-bromobenzoate (5.0 g, 23.25 mmol), bis(pinacolato)diboron (7.67 g, 30.23 mmol), Pd(dppf)Cl 2· A mixture of CH2Cl2 (950 mg, 1.16 mmol) and KOAc (6.84 g, 69.75 mmol) in DMF (50 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (4.4 g, 72%).

[0431] Step 2: Methyl 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate

[0432] A mixture of methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2.0 g, 7.63 mmol), 4-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (2.54 g, 9.15 mmol), Pd(PPh3)4 (440 mg, 0.38 mmol) and K2CO3 (3.2 g, 22.89 mmol) in 1,4-dioxane / H2O (4 / 1, 50 mL) was stirred at 100°C for 4 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (1.38 g, 54%). 1 H NMR (CDCl3, 400MHz): δ8.05-8.03(m,2H),7.89(s,1H),7.88(s,1H),7.57-7.55(m, 2H),5.47(s,2H),3.92(s,3H),3.62-3.58(m,2H),0.95-0.91(m,2H),-0.01(s,9H).

[0433] Step 3: 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0434] To a solution of methyl 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate (1.35 g, 4.06 mmol) in MeOH (30 mL) was added 1N-NaOH (8.12 mL, 8.12 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (0.93 g, 72%).

[0435] Intermediate 3, 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0436]

[0437] Step 1: 4-Bromo-3-nitro-1H-pyrazole

[0438] To a solution of 3-nitropyrazole (500 mg, 4.42 mmol) in anhydrous DMF (10 mL) was added N-bromosuccinimide (1.02 g, 5.75 mmol). The reaction mixture was stirred at 40 ° C for 3 h. The mixture was diluted with ethyl acetate and washed with water (30 mL x 3). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (710 mg, 84%).

[0439] Step 2: 4-Bromo-3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0440] To a solution of 4-bromo-3-nitro-1H-pyrazole (700 mg, 3.65 mmol) in anhydrous THF (10 mL) was added NaH (60% dispersion in mineral oil, 220 mg, 5.47 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then 2-(trimethylsilyl)ethoxymethyl chloride (0.75 mL, 3.83 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (820 mg, 70%). 1 H NMR (CDCl3, 400MHz): δ7.74 (s, 1H), 5.45 (s, 2H), 3.61-3.57 (m, 2H), 0.93-0.89 (m, 2H), -0.02 (s, 9H).

[0441] Step 3: Methyl 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate

[0442] A mixture of 4-bromo-3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (800 mg, 2.48 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (TCI) (750 mg, 2.85 mmol), Pd(PPh3)4 (143 mg, 0.124 mmol) and K2CO3 (1.03 g, 7.45 mmol) in 1,4-dioxane / H2O (4 / 1, 20 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (850 mg, 91%). 1H NMR (CDCl3, 400MHz): δ8.11-8.05(m,2H),7.74(s,1H),7.68-7.63(m,1H),7.54-7.48 (m,1H),5.53(s,2H),3.93(s,3H),3.70-3.66(m,2H),1.00-0.93(m,2H),0.02(s,9H).

[0443] Step 4: 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0444] To a solution of methyl 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate (840 mg, 2.22 mmol) in MeOH (20 mL) was added 1N-NaOH (4.45 mL, 4.45 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (730 mg, 90%). 1 H NMR(DMSO-D6,400MHz): δ8.47(s,1H),8.02(s,1H),7.99-7.72(m,1H),7.78-7.72(m,1H) ),7.59-7.55(m,1H),5.55(s,2H),3.70-3.60(m,2H),0.99-0.86(m,2H),-0.01(s,9H).

[0445] Intermediate 4, 3-(3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0446]

[0447] Intermediate 4 was prepared in a similar manner to Intermediate 3 (350 mg, 87%).

[0448] Intermediate 5: 3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0449]

[0450] Step 1: 1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0451] To a solution of pyrazole (5.0 g, 73.44 mmol) in anhydrous THF (100 mL) was added NaH (60% dispersion in mineral oil, 4.4 g, 110.16 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then 2-(trimethylsilyl)ethoxymethyl chloride (14.4 mL, 77.11 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (13.2 g, 91%). 1 H NMR (CDCl3, 400MHz): δ7.57-7.55(m,1H),7.55-7.53(m,1H),6.33-6.31(m,1H),5.43(s,2H),3.56-3.52(m,2H),0.91-0.87(m,2H),-0.02(s,9H).

[0452] Step 2: 5-Fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0453] A solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (1.0 g, 5.04 mmol) in anhydrous THF was cooled to -65°C. To the stirred solution was added LDA (1.0 M in THF, 6.0 mL, 6.0 mmol) dropwise and stirred at the same temperature for 45 min. Then, it was cooled to -78°C and a solution of NFSI (1.67 g, 5.29 mmol) in anhydrous THF was added dropwise. The mixture was stirred at -78°C for 2 h, stirred at room temperature overnight, diluted with saturated aqueous NH4Cl solution and concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with saturated aqueous NaHCO3 solution (50 mL x 3). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (230 mg, 21%). 1 H NMR (CDCl3, 400MHz): δ7.41-7.37(m,1H),5.78-5.72(m,1H),5.34(s,2H),3.63-3.59(m,2H),0.93-0.88(m,2H),-0.02(s,9H).

[0454] Step 3: 4-Bromo-5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0455] To a solution of 5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (197.5 mg, 0.91 mmol) in ACN (10 mL) was added N-bromosuccinimide (170 mg, 0.95 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and extracted with saturated aqueous NaHCO3 / DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (63 mg, 23%).

[0456] Step 4: Methyl 3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate

[0457] A mixture of 4-bromo-5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (350 mg, 1.33 mmol), 4-bromo-1-methyl-1H-pyrazole (0.16 mL, 1.53 mmol), Pd(PPh3)4 (77 mg, 0.066 mmol) and K2CO3 (553 mg, 4.0 mmol) in 1,4-dioxane / H2O (4 / 1, 10 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (150 mg, 52%). 1 H NMR (CDCl3, 400MHz): δ8.18(s,1H),7.94-7.91(m,1H),7.76-7.74(m,2H),7.48-7.44( m,1H),5.31(s,2H),3.94(s,3H),3.64-3.60(m,2H),0.96-0.92(m,2H),-0.01(s,9H).

[0458] Step 5: 3-(5-Fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid

[0459] To a solution of methyl 3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoate (310 mg, 0.88 mmol) in MeOH (10 mL) was added 1N-NaOH (3.54 mL, 3.54 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (290 mg, 97%).1 H NMR (CD3OD, 400MHz): δ8.22(s,1H),8.17-8.15(m,1H),7.93-7.90(m,1H),7.81-7.78(m, 1H),7.52-7.49(m,1H),5.33(s,2H),3.67-3.63(m,2H),0.94-0.90(m,2H),-0.01(s,9H).

[0460] Intermediate 6, 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinic acid

[0461]

[0462] Step 1: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

[0463] At 100°C, 4-bromo-1H-pyrazole (1.0 g, 6.80 mmol), bis(pinacolato)diboron (2.07 g, 8.16 mmol), Pd(dppf)Cl 2· A mixture of CH2Cl2 (278 mg, 0.34 mmol) and KOAc (2.0 g, 20.41 mmol) in DMF (30 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (330 mg, 25%). 1 H NMR (CDCl3, 400MHz): δ7.90 (s, 2H), 1.33 (s, 12H).

[0464] Step 2: 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

[0465] To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (200 mg, 1.03 mmol) in anhydrous THF (10 mL) was added NaH (60% dispersion in mineral oil, 62 mg, 1.54 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then 2-(trimethylsilyl)ethoxymethyl chloride (0.21 mL, 1.08 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (153 mg, 46%). 1 H NMR (CDCl3, 400MHz): δ7.85(s,1H),7.80(s,1H),5.43(s,2H),3.57-3.53(m,2H),1.32(s,12H),0.92-0.87(m,2H),-0.03(s,9H).

[0466] Step 3: 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinate

[0467] A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (150 mg, 0.46 mmol), methyl 5-bromonicotinate (120 mg, 0.55 mmol), Pd(PPh3)4 (27 mg, 0.023 mmol) and K2CO3 (192 mg, 1.38 mmol) in 1,4-dioxane / H2O (4 / 1, 5 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (123 mg, 80%). 1 H NMR(CDCl3,400MHz): δ9.08(s,1H),8.93(s,1H),8.37(s,1H),7.94(s,1H),7.90(s, 1H),5.48(s,2H),3.98(s,3H),3.64-3.60(m,2H),0.96-0.92(m,2H),-0.01(s,9H).

[0468] Step 4: 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinic acid

[0469] To a solution of methyl 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinate (110 mg, 0.33 mmol) in MeOH (10 mL) was added 1N-NaOH (0.66 mL, 0.66 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (84 mg, 79%).

[0470] Intermediate 7, 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid

[0471]

[0472] Step 1: Methyl 3-(1-methyl-1H-pyrazol-4-yl)benzoate

[0473] At 100 ° C, a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester (TCI) (350 mg, 1.33 mmol), 4-bromo-1-methyl-1H-pyrazole (0.16 mL, 1.53 mmol), Pd(PPh3)4 (77 mg, 0.066 mmol) and K2CO3 (553 mg, 4.0 mmol) in 1,4-dioxane / H2O (4 / 1, 10 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (150 mg, 52%). 1 H NMR (CDCl3, 400MHz): δ8.16-8.12(m,1H),7.91-7.85(m,1H),7.80(s,1H),7 .68(s,1H),7.67-7.62(m,1H),7.44-7.38(m,1H),3.95(s,3H),3.93(s,3H).

[0474] Step 2: 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid

[0475] To a solution of methyl 3-(1-methyl-1H-pyrazol-4-yl)benzoate (135 mg, 0.62 mmol) in MeOH (10 mL) was added 1N-NaOH (1.25 mL, 1.25 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (85 mg, 67%).1 H NMR(DMSO-D6,400MHz): δ13.03(s,1H),8.24(s,1H),8.08(s,1H),7.92(s, 1H),7.82-7.79(s,1H),7.76-7.73(s,1H),7.49-7.45(s,1H),3.86(s,3H).

[0476] Intermediate 8: 3-(1-(Fluoromethyl)-1H-pyrazol-4-yl)benzoic acid

[0477]

[0478] Step 1: 4-Bromo-1-(fluoromethyl)-1H-pyrazole

[0479] To a solution of 4-bromo-1H-pyrazole (500 mg, 3.40 mmol) in anhydrous THF (10 mL) was added NaH (60% dispersion in mineral oil, 204 mg, 5.10 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then iodomethane (0.25 mL, 3.74 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (420 mg, 69%). 1 H NMR (CDCl3, 400MHz): δ7.68 (s, 1H), 7.61 (s, 1H), 6.03-5.90 (m, 2H).

[0480] Step 2: Methyl 3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzoate

[0481] At 100 ° C, a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester (417 mg, 2.33 mmol), 4-bromo-1-(fluoromethyl)-1H-pyrazole (610 mg, 2.33 mmol), Pd(PPh3)4 (135 mg, 0.12 mmol) and K2CO3 (966 mg, 6.99 mmol) in 1,4-dioxane / H2O (4 / 1, 10 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (400 mg, 73%). 1H NMR (CDCl3, 400MHz): δ8.17(s,1H),7.98-7.93(m,3H),7.70-7.67(m,1H),7.49-7.45(m,1H),6.13-6.00(m,2H),3.94(s,3H).

[0482] Step 3: 3-(1-(Fluoromethyl)-1H-pyrazol-4-yl)benzoic acid

[0483] To a solution of methyl 3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzoate (400 mg, 1.71 mmol) in MeOH (10 mL) was added 1N-NaOH (6.83 mL, 6.83 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (309 mg, 82%).

[0484] Intermediate 9, 3-(1-(difluoromethyl)-1H-pyrazol-4-yl)benzoic acid

[0485]

[0486] Intermediate 9 was prepared in a similar manner to Intermediate 8 (742.7 mg, 92.5%). 1 H NMR(CD3OD,400MHz)δ8.50(d,J=0.8Hz,1H),8.29-8.24(m,1H),8.14(s,1H),7 .95(m,1H),7.866(m,1H),7.52(t,J=59.6Hz,1H),7.52(td,J=7.2,0.4Hz,1H).

[0487] Intermediate 10, 3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)benzoic acid

[0488]

[0489] Step 1: Methyl 3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)benzoate

[0490] At 100 ° C, a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester (TCI) (500 mg, 2.33 mmol), 4-bromo-1-(trifluoromethyl)-1H-pyrazole (610 mg, 2.33 mmol), Pd(PPh3)4 (135 mg, 0.12 mmol) and K2CO3 (966 mg, 6.99 mmol) in 1,4-dioxane / H2O (4 / 1, 10 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (540 mg, 86%). 1 H NMR (CDCl3, 400MHz): δ8.18(s,1H),8.10(s,1H),8.08(s,1H),8.00-7.98(m,1H),7.71-7.68(m,1H),7.52-7.47(m,1H),3.95(s,3H).

[0491] Step 2: 3-(1-(Trifluoromethyl)-1H-pyrazol-4-yl)benzoic acid

[0492] To a solution of methyl 3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)benzoate (540 mg, 2.0 mmol) in MeOH (10 mL) was added 1N-NaOH (8.0 mL, 8.0 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (470 mg, 92%).

[0493] Intermediate 11, 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzoic acid

[0494]

[0495] Step 1: 5-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

[0496] To a solution of 5-bromoindazole (500 mg, 2.53 mmol) in anhydrous THF (20 mL) at 0°C was added NaH (60% dispersion in mineral oil, 152 mg, 3.82 mmol). The reaction mixture was stirred at 0°C for 30 min, then 2-(trimethylsilyl)ethoxymethyl chloride (0.49 mL, 2.79 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 3 h, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (581 mg, 70%). 1 H NMR (CDCl3, 400MHz): δ7.95(s,1H),7.89(s,1H),7.51-7.45(m,2H),5.71(s,2H),3.53-3.49(m,2H),0.89-0.84(m,2H),-0.07(s,9H).

[0497] Step 2: Methyl 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzoate

[0498] A mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (464 mg, 1.77 mmol), 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (Intermediate 11, Step 1) (580 mg, 1.77 mmol), Pd(PPh3)4 (102 mg, 0.088 mmol) and K2CO3 (735 mg, 5.31 mmol) in 1,4-dioxane / H2O (4 / 1, 20 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (458 mg, 67%). 1 H NMR (CDCl3, 400MHz): δ8.35-8.30(m,1H),8.10-8.06(m,1H),8.05-8.00(m,1H),7.99-7.95(m,1H),7.86-7.80(m,1H) ,7.74-7.63(m,2H),7.57-7.49(m,1H),5.77(s,2H),3.96(s,3H),3.61-3.53(m,2H),0.95-0.85(m,2H),-0.06(s,9H).

[0499] Step 3: 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzoic acid

[0500] To a solution of methyl 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzoate (458 mg, 1.19 mmol) in MeOH (10 mL) was added 1N-NaOH (4.8 mL, 4.8 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (430 mg, 97%). 1 HNMR (CD3OD, 400MHz): δ8.34-8.29(m,1H),8.14(s,1H),8.07-8.03(m,1H),8.03-7.97(m,1H),793-7.87(m,1H),7 .80-7.73(m,2H),7.56(t,J=7.6Hz,1H),5.78(s,2H),3.58(t,J=8.0Hz,2H),0.86(t,J=8.0Hz,2H),-0.08(s,9H).

[0501] The following compounds were prepared in a similar manner to Intermediate 11.

[0502] [Table 1]

[0503]

[0504] Intermediate 17, 3-(1-methyl-1H-indazol-5-yl)benzoic acid

[0505]

[0506] Step 1: Methyl 3-(1-methyl-1H-indazol-5-yl)benzoate

[0507] At 100 ° C, a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester (TCI) (2.0 g, 7.63 mmol), 5-bromo-1-methyl-1H-indazole (1.61 g, 7.63 mmol), Pd(PPh3)4 (441 mg, 0.38 mmol) and K2CO3 (3.16 g, 22.88 mmol) in 1,4-dioxane / H2O (4 / 1, 50 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (1.44 g, 71%). 1H NMR(CDCl3,400MHz):8.31(s,1H),8.04(s,1H),8.02-8.00(m,1H),7.95(s,1H),7 .86-7.80(m,1H),7.69-7.65(m,1H),7.55-7.45(m,2H),4.11(s,3H),3.96(s,3H).

[0508] Step 2: 3-(1-methyl-1H-indazol-5-yl)benzoic acid

[0509] To a solution of methyl 3-(1-methyl-1H-indazol-5-yl)benzoate (1.44 g, 5.40 mmol) in MeOH (20 mL) was added 1N-NaOH (21.6 mL, 21.6 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (1.2 g, 88%).

[0510] Intermediate 18, 3-(pyridin-3-yl)benzoic acid

[0511]

[0512] Step 1: Methyl 3-(pyridin-3-yl)benzoate

[0513] At 100 ° C, a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid methyl ester (TCI) (2.0 g, 7.63 mmol), 3-bromopyridine (1.20 g, 7.63 mmol), Pd(PPh3)4 (441 mg, 0.38 mmol) and K2CO3 (3.16 g, 22.88 mmol) in 1,4-dioxane / H2O (4 / 1, 50 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (1.94 g, 98%). 1 H NMR(CDCl3,400MHz):8.87(s,1H),8.63-8.60(m,1H),8.26(s,1H),8.09-8.06(m,1H),7 .92-7.88(m,1H),7.79-7.76(m,1H),7.58-7.54(m,1H),7.40-7.37(m,1H),3.95(s,3H).

[0514] Step 2: 3-(Pyridin-3-yl)benzoic acid

[0515] To a solution of methyl 3-(pyridin-3-yl)benzoate (1.9 g, 5.40 mmol) in MeOH (30 mL) was added 1N-NaOH (35.6 mL, 35.6 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (1.6 g, 90%).

[0516] The following compounds were prepared in a similar manner to Intermediate 18.

[0517] [Table 2]

[0518]

[0519] Intermediate 21, 3-(6-((tert-butyloxycarbonyl)amino)pyridin-3-yl)benzoic acid

[0520]

[0521] Step 1: tert-Butyl (5-bromopyridin-2-yl)carbamate

[0522] A solution of 5-bromopyridin-2-amine (5.0 g, 28.9 mmol) in DCM (150 mL) was cooled to 0 ° C, and TEA (8.8 mL, 63.5 mmol), di-tert-butyl dicarboxylate (8.6 mL, 37.5 mmol) and 4-(dimethylamino)pyridine (353 mg, 2.89 mmol) were added thereto. The reaction mixture was stirred for 3 h at room temperature. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM and dried over anhydrous Na2SO4. The solvent was concentrated to form a crude product, which was recrystallized from hexane to give the title compound (5.60 g, 70%). 1 H NMR (CDCl3, 400MHz): δ8.29-8.27(m,1H),7.91-7.87(m,1H),7.77-7.73(m,1H),7.58(bs,1H),1.53(s,9H).

[0523] Step 2: Methyl 3-(6-((tert-Butyloxycarbonyl)amino)pyridin-3-yl)benzoate

[0524] At 100 ° C, a mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (TCI) (2.5 g, 9.53 mmol), tert-butyl (5-bromopyridin-2-yl)carbamate (2.60 g, 9.53 mmol), Pd(PPh3)4 (1.10 g, 0.95 mmol) and K2CO3 (1.97 g, 14.29 mmol) in 1,4-dioxane / H2O (4 / 1, 120 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (2.19 g, 70%). 1 H NMR (CDCl3, 400MHz): δ8.49-8.48(m,1H),8.24-8.22(m,1H),8.04-8.02(m,2H),7 .93-7.90(m,1H),7.76-7.73(m,1H),7.53-7.51(m,1H),3.95(s,3H),1.54(s,9H).

[0525] Step 3: 3-(6-((tert-Butyloxycarbonyl)amino)pyridin-3-yl)benzoic acid

[0526] To a solution of methyl 3-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)benzoate (2.0 g, 6.09 mmol) in MeOH (30 mL) was added 1N-NaOH (24.0 mL, 24.0 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (1.5 g, 78%).

[0527] Intermediate 22, 3-(Benzo[d]thiazol-6-yl)benzoic acid

[0528]

[0529] Step 1: Methyl 3-(Benzo[d]thiazol-6-yl)benzoate

[0530] A mixture of 6-bromobenzo[d]thiazole (5.0 g, 23.35 mmol), (3-(methoxycarbonyl)phenyl)boronic acid (4.62 g, 25.69 mmol), Pd(PPh3)4 (1.35 g, 1.17 mmol) and K2CO3 (9.70 g, 70.07 mmol) in 1,4-dioxane / H2O (4 / 1, 100 mL) was stirred overnight at 100°C. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was solidified with ethyl acetate and hexane and filtered to give the title compound (5.2 g, 83%). 1 H NMR(CDCl3,400MHz):9.03(s,1H),8.34(s,1H),8.24-8.18(m,2H),8.08-8.02 (m,1H),7.88-7.87(m,1H),7.82-7.77(m,1H),7.58-7.50(m,1H),3.95(s,3H).

[0531] Step 2: 3-(Benzo[d]thiazol-6-yl)benzoic acid

[0532] To a solution of methyl 3-(benzo[d]thiazol-6-yl)benzoate (5.2 g, 5.40 mmol) in MeOH (70 mL) was added 1N-NaOH (77.0 mL, 77.0 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (1.6 g, 32%).

[0533] Intermediate 23, 3-(Benzo[d]thiazol-5-yl)benzoic acid

[0534]

[0535] Intermediate 23 (5.0 g, 42%) was prepared in a similar manner to Intermediate 22.

[0536] Intermediate 24, 3-(2-amino-1-phenyl-1H-imidazol-4-yl)propionic acid methyl ester

[0537]

[0538] Step 1: Methyl 5-bromo-4-oxopentanoate

[0539] To stirring and heating (70 ℃) levulinic acid (10g, 86.12mmol) MeOH (100mL) solution through 10min add Br (4.43mL, 86.12mmol) MeOH (20mL) solution and reflux 2h.Reaction mixture is cooled to room temperature, and desolventizes under reduced pressure.Resistates is diluted with DCM and washed with saturated NaHCO The aqueous solution (50mL x 3).Organic phase is through anhydrous Na SO Dry and concentrate under reduced pressure to obtain title compound (obtain crude product).

[0540] Step 2: 4-oxo-5-(phenylamino)pentanoic acid methyl ester

[0541] To a solution of methyl 5-bromo-4-oxopentanoate (1.9 g, 9.09 mmol) and aniline (0.85 g, 9.09 mmol) in DMF (45 mL) was added NaHCO (3.8 g, 27.26 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate and washed with water (30 mL x 3) and brine (30 mL). The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure to give the title compound (crude product).

[0542] Step 3: Methyl 3-(2-amino-1-phenyl-1H-imidazol-4-yl)propanoate

[0543] By MeOH (20mL) solution of 4-oxo-5-(phenylamino)pentanoic acid methyl ester (2.2g, 7.75mmol) and cyanamide (3.06g, 72.91) reflux overnight. Remove solvent under reduced pressure, the residue is diluted with DCM, washed with water (30mL x 3). The organic phase is through anhydrous Na2SO4 dry and concentrated under reduced pressure. Use DCM / MeOH as eluent, by silica gel column chromatography purification, obtain title compound (1.20g, 50%). 1 H NMR (CDCl3, 400MHz): δ7.51-7.46(m,2H),7.39-7.35(m,3H),6.45(s,1H),3.69(s,3H),2.84-2.78(m,2H),2.71-2.65(m,2H).

[0544] The following compounds were prepared in a similar manner to Intermediate 24.

[0545] [Table 3]

[0546]

[0547] Example

[0548] Example 1, 3-(3-nitro-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Scheme 2)

[0549]

[0550] Step 1: Methyl 5-bromo-4-oxopentanoate

[0551] To stirring and heating (70 ℃) levulinic acid (2g, 17.22mmol) MeOH (20mL) solution through 10min add Br (0.89mL, 17.22mmol) MeOH (5mL) solution and reflux 2h.Reaction mixture is cooled to room temperature, and desolventizes under reduced pressure.Resistates is diluted with DCM and washed with saturated NaHCO The aqueous solution (50mL x 3).Organic phase is through anhydrous Na SO Dry and concentrate under reduced pressure to obtain title compound (obtain crude product).

[0552] Step 2: 4-oxo-5-(phenylamino)pentanoic acid methyl ester

[0553] To a solution of methyl 5-bromo-4-oxopentanoate (1.9 g, 9.09 mmol) and aniline (0.85 g, 9.09 mmol) in DMF (45 mL) was added NaHCO (3.8 g, 27.26 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate and washed with water (30 mL x 3) and brine (30 mL). The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure to give the title compound (crude product).

[0554] Step 3: 4-oxo-5-(phenylamino)pentanoic acid

[0555] 1N-NaOH (5.70 mL, 5.70 mmol) was added to a solution of methyl 4-oxo-5-(phenylamino)pentanoate (970 mg, 4.38 mmol) in MeOH (10 mL). The reaction mixture was stirred for 3 h at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (710 mg, 78%). 1H NMR (CDCl3, 400MHz): δ7.50-7.43(m,2H),7.40(bs,1H),7.35-7.28(m,2H),7.22-7.15(m,2H),7.13-7.07(m, 1H),6.75-6.71(m,1H),6.62-6.56(m,2H),4.53(bs,1H),4.10(s,2H),2.94-2.91(m,2H),2.78-2.73(m,2H).

[0556] Step 4: 4-Oxo-N-phenyl-5-(phenylamino)pentanamide

[0557] A mixture of 4-oxo-5-(phenylamino)pentanoic acid (4.126 g, 19.91 mmol), aniline (1.73 mL, 18.96 mmol), HBTU (10.78 g, 228.44 mmol) and DIPEA (10.2 mL, 56.88 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (2.19 g, 41%).

[0558] Step 5: 3-(2-amino-1-phenyl-1H-imidazol-4-yl)-N-phenylpropanamide

[0559] By 4-oxo-N-phenyl-5-(phenylamino) valeramide (200mg, 0.708mmol) and cyanamide (280mg, 6.66mmol) MeOH (10mL) solution reflux overnight. Remove solvent under reduced pressure, the residue is diluted with DCM, washed with water (30mL x 3). The organic phase is through anhydrous Na2SO4 dry and concentrated under reduced pressure. Use DCM / MeOH as eluent, by silica gel column chromatography purification, obtain title compound (70mg, 32%). 1 H NMR(CDCl3,400MHz): δ9.19(bs,1H),7.55-7.53(m,2H),7.53-7.46(m,2H),7.45-7.4 3(m,1H),7.43-7.20(m,4H),7.10-6.99(m,1H),2.88-2.85(m,2H),2.75-2.71(m,2H).

[0560] Step 6: 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0561] A mixture of 3-(2-amino-1-phenyl-1H-imidazol-4-yl)-N-phenylpropanamide (135 mg, 0.44 mmol) and 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 3) (208 mg, 0.57 mmol), EDCI (126.7 mg, 0.66 mmol), HOBt (89.3 mg, 0.66 mmol) and DIPEA (0.23 mL, 1.32 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (187 mg, 65%). 1 H NMR (CDCl3, 400MHz): δ8.29(s,1H),8.23-8.18(m,1H),7.68(s,1H),7.67-7.64(m,2H),7.55-7.48(m,5H),7.48-7.39(m,2H),7.39-7.25(m, 5H),7.12-7.08(m,1H),6.69(s,1H),5.50(s,2H),3.65-3.60(m,2H),3 .08-3.00(m,2H),2.78-2.70(m,2H),1.00-0.90(m,2H),-0.02(s,9H).

[0562] Step 7: 3-(3-nitro-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0563] TFA (1.0 mL) was added to a solution of 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide (80 mg, 0.12 mmol) in DCM and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (40 mg, 62%). 1H NMR(DMSO-D6,400MHz): δ10.03(s,1H),8.20-8.00(m,2H),7.75-7.58(m,4H),7.50-7.36(m,5 H),7.31-7.27(m,2H),7.20(s,1H),7.05-7.01(m,1H),2.95-2.85(m,2H),2.74-2.70(m,2H).

[0564] Example 2, 3-(3-amino-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0565]

[0566] Step 1: 3-(3-amino-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0567] To a MeOH solution of 3-(3-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 1, Step 6) (150 mg, 0.23 mmol) was added palladium on carbon (15 mg). Hydrogen gas was charged into the mixture via a hydrogen balloon, and then stirred at room temperature overnight. The reaction mixture was filtered through celite, washed with MeOH, and concentrated under reduced pressure to give the title compound (145 mg, 99%).

[0568] Step 2: 3-(3-amino-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0569] TFA (1.0 mL) was added to a solution of 3-(3-amino-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide (140 mg, 0.22 mmol) in DCM (5 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (10 mg, 10%). 1H NMR (CD3OD, 400MHz): δ8.28(s,1H),7.89-7.87(m,1H),7.80-7.76(m,2H),7.57-7.42(m,7H),7.39-7.36(m,1H),7 .31-7.27(m,2H),7.09-7.04(m,2H),5.56-5.53(m,1H),5.00-4.97(m,1H),3.01-2.98(m,2H),2.79-2.76(m,2H).

[0570] Example 3, N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide

[0571]

[0572] Step 1: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0573] A mixture of 3-(2-amino-1-phenyl-1H-imidazol-4-yl)-N-phenylpropanamide (Example 1, Step 5) (150 mg, 0.49 mmol), 3-(3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 3) (208 mg, 0.54 mmol), HBTU (278.5 mg, 0.73 mmol) and DIPEA (0.26 mL, 1.47 mmol) in DCM (10 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (275 mg, 83%). 1 H NMR (CDCl3, 400MHz): δ8.28(s,1H),8.17-8.14(m,1H),7.84(s,1H),7.70-7.62(m,3H),7.60-7.52(m,2H),7.52-7.30(m,7H),7.15 -7.07(m,1H),6.68(s,1H),5.48(s,2H),3.67-3.62(m,2H),3.08-3.00(m,2H),2.78-2.70(m,2H),1.00-0.90(m,2H),0.01(s,9H).

[0574] Step 2: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide

[0575] TFA (2.0 mL) was added to a solution of N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (265 mg, 0.39 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (58 mg, 27%). 1 H NMR(DMSO-D6,400MHz): δ13.78(s,1H),12.65(bs,0.6H),10.52(bs,0.4H),10.00(s,1H),8.2 2-7.65(m,4H),7.60-7.15(m,10H),7.05-7.01(m,1H),2.95-2.80(m,2H),2.74-2.70(m,2H).

[0576] Example 4, N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1H-pyrazol-4-yl)nicotinamide

[0577]

[0578] Step 1: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinamide

[0579] A mixture of 3-(2-amino-1-phenyl-1H-imidazol-4-yl)-N-phenylpropanamide (Example 1, Step 5) (73 mg, 0.238 mmol), 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinic acid (Intermediate 6) (83.6 mg, 0.26 mmol), HBTU (135 mg, 0.35 mmol) and DIPEA (0.12 mL, 0.71 mmol) in DCM (10 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (77 mg, 53%). 1 HNMR(CDCl3,400MHz): δ9.24(s,1H),8.79(s,1H),8.52(s,1H),7.90-7.87(m,2H),7.70-7.65(m,2H),7.56-7.48(m,4H),7.42-7.30(m,4H) ),7.16-7.10(m,1H),6.69(s,1H),5.47(s,2H),3.63-3.59(m,2H),3.07-3.03(m,2H),2.78-2.75(m,2H),0.96-0.91(m,2H),-0.02(s,9H).

[0580] Step 2: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1H-pyrazol-4-yl)nicotinamide

[0581] TFA (0.5 mL) was added to a solution of N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)nicotinamide (77 mg, 0.126 mmol) in DCM (5 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (45 mg, 75%). 1H NMR (CD3OD, 400MHz): δ8.95-8.94(m,1H),8.82-8.81(m,1H),8.54(s,1H),8.07(s,2H),7.64-7.41 (m,8H),7.32-7.27(m,2H),7.10-7.06(m,1H),7.02(s,1H),3.05-3.00(m,2H),2.82-2.78(m,2H).

[0582] Example 5, 3-(isoxazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0583]

[0584] Step 1: 3-Bromo-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0585] A mixture of 3-(2-amino-1-phenyl-1H-imidazol-4-yl)-N-phenylpropanamide (Example 1, Step 5) (200 mg, 0.653 mmol), 3-bromobenzoic acid (144 mg, 0.718 mmol), HBTU (371 mg, 0.98 mmol) and DIPEA (0.34 mL, 1.96 mmol) in DCM (10 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (150 mg, 47%).

[0586] Step 2: 3-(Isoxazolyl-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0587] A mixture of 3-bromo-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide (70 mg, 0.14 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (Alfa Aesar) (33 mg, 0.17 mmol), Pd(PPh3)4 (8.0 mg, 0.007 mmol) and K2CO3 (38 mg, 0.28 mmol) in 1,4-dioxane / H2O (4 / 1, 100 mL). The reaction mixture was heated to 100 °C in a sealed tube in a microwave for 2 h. The reaction mixture was diluted with DCM and washed with water. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (2.8 mg, 4%). 1 H NMR (CDCl3, 400MHz): δ8.68(s,1H),8.57(s,1H),8.33(s,1H),8.16-8.13(m,1H),7.70-7.60(m,2H),7.58-7.47(m, 4H),7.43-7.38(m,2H),7.38-7.29(m,3H),7.18-7.09(m,1H),6.69(s,1H),3.10-3.03(m,2H),2.78-72.73(m,2H).

[0588] Example 6, N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Scheme 1)

[0589]

[0590] Step 1: Methyl 3-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate

[0591] A mixture of methyl 3-(2-amino-1-phenyl-1H-imidazol-4-yl)propanoate (Intermediate 24) (2 g, 8.15 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (2.85 g, 8.96 mmol), HATU (4.65 g, 12.22 mmol) and DIPEA (4.25 mL, 24.45 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (3.0 g, 67%). 1 H NMR (400MHz, CDCl3) δ8.41-8.34(m,1H),8.11-8.02(m,1H),7.90-7.82(m,2H),7.79-7.70(m,2H),7.61-7.49(m,3H),7.45-7.34(m,2 H),6.63(s,1H),5.46(s,2H),3.71(s,3H),3.64-3.59(m,2H),2.75-2.62(m,2H),2.52-2.39(m,2H),1.00-0.87(m,2H),-0.02(s,9H).

[0592] Step 2: 3-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid

[0593] To a solution of methyl 3-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate (3.0 g, 5.50 mmol) in MeOH (20 mL) was added 1N-NaOH (22 mL, 22 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (2.5 g, 85%). 1H NMR (400MHz, CDCl3) δ8.35-8.24(m,1H),8.02-7.91(m,1H),7.89-7.77(m,2H),7.71-7.59(m,2H),7.59-7.44(m,3H),7.44-7.2 8(m,2H),6.62(s,1H),5.43(s,2H),3.65-3.52(m,2H),2.84-2.67(m,2H),2.58-2.42(m,2H),1.00-0.87(m,2H),-0.02(s,9H).

[0594] Step 3: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0595] A mixture of 3-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid (2 g, 8.15 mmol), aniline (2.85 g, 8.96 mmol), HATU (4.65 g, 12.22 mmol) and DIPEA (4.25 mL, 24.45 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (3.0 g, 67%). 1 H NMR (400MHz, CDCl3): δ8.39-8.33(m,1H),8.08-8.01(m,1H),7.89-7.81(m ,2H),7.75-7.66(m,2H),7.60-7.48(m,5H),7.47-7.35(m,3H),7.35-7.28( m,2H),7.15-7.07(m,1H),6.66(s,1H),5.45(s,2H),3.59(t,J=8.4Hz,2H), 2.78-2.68(m,2H),2.54-2.42(m,2H),0.93(t,J=8.4Hz,2H),-0.02(s,9H).

[0596] Step 4: N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0597] TFA (0.5 mL) was added to a solution of N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (77 mg, 0.126 mmol) in DCM (5 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (50 mg, 83%). 1 H NMR (CD3OD, 400MHz): δ8.26-7.83(m,3H),7.83-7.62(m,2H),7.62-7.34(m,8H ),7.34-7.23(m,2H),7.18-7.02(m,2H),3.01-2.98(m,2H),2.79-2.76(m,2H).

[0598] The following compounds were prepared in a similar manner as described in Example 6 and General Scheme 1.

[0599] [Table 4]

[0600]

[0601]

[0602]

[0603]

[0604]

[0605]

[0606]

[0607] Example 41, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0608]

[0609] Step 1: Methyl 2-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetate

[0610] A mixture of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (2.62 g, 11.35 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (3.8 g, 11.92 mmol), HBTU (6.45 g, 17.02 mmol) and DIPEA (5.9 mL, 34.05 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (5.7 g, 95%). 1 H NMR (CDCl3, 400MHz): δ8.33(s,1H),8.03-8.01(s,1H),7.85(s,1H),7.84(s,1H),7.76-7.66(m,2H),7.58-7.48(m,3H),7. 42-7.34(m,2H),6.84(s,1H),5.45(s,2H),3.80(s,3H),3.67(s,2H),3.60-3.57(m,2H),0.95-0.91(m,2H),-0.02(s,9H).

[0611] Step 2: 2-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid

[0612] To a solution of methyl 2-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetate (2.84 g, 5.34 mmol) in MeOH (30 mL) was added 1N-NaOH (10.7 mL, 10.7 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (2.41 g, 87%). 1 H NMR(DMSO-D6,400MHz): δ8.34(s,1H),8.30-8.10(m,1H),7.97(s,1H),7.88-7.30(m ,8H),7.26(s,1H),5.43(s,2H),3.60-3.55(m,4H),0.87-0.83(m,2H),-0.04(s,9H).

[0613] Step 3: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0614] A mixture of 2-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid (150 mg, 0.29 mmol), methylamine hydrochloride (23.5 mg, 0.35 mmol), EDCI (83.3 mg, 0.43 mmol), HOBt (58.7 mg, 0.43 mmol) and DIPEA (0.3 mL, 1.73 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (111 mg, 72%). 1 H NMR (CDCl3, 400MHz): δ8.21(s,1H),7.91-7.83(m,1H),7.79(s,1H),7.78(s,1H),7.61-7.51(m,3H),7.48-7.40(m,2H),7.39-7.30( m,2H),6.85(s,1H),6.80-6.70(m,1H),5.41(s,2H),3.60-3.55(m,2H),3.53(s,2H),2.75(s,3H),0.93-0.89(m,2H),-0.02(s,9H).

[0615] Step 4: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0616] TFA (0.5 mL) was added to a solution of N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (110 mg, 0.21 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (37 mg, 45%). 1H NMR (CD3OD, 400MHz): δ8.18-7.85(m,3H),7.85-7.35(m,8H),7.27(s,1H),3.56(s,2H),2.78(s,3H).

[0617] The following compounds were prepared in a similar manner as described in Example 41 and General Scheme 1.

[0618] [Table 5]

[0619]

[0620]

[0621] Example 48, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1H-pyrazol-4-yl)benzamide

[0622]

[0623] Step 1: Methyl 2-(1-phenyl-2-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetate

[0624] A mixture of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (300 mg, 1.29 mmol), 4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 2) (495 mg, 1.55 mmol), HBTU (738 mg, 1.93 mmol) and DIPEA (0.68 mL, 3.89 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (472 mg, 68%). 1 H NMR (CDCl3, 400MHz): δ8.18-8.10(m,2H),7.85(s,2H),7.71-7.65(m,2H),7.52-7.48(m,4H),7.41-7.38(m,1 H),6.84(s,1H),5.45(s,2H),3.77(s,3H),3.66(s,2H),3.62-3.55(m,2H),0.94-0.90(m,2H),-0.03(s,9H).

[0625] Step 2: 2-(1-phenyl-2-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid

[0626] To a solution of methyl 2-(1-phenyl-2-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetate (460 mg, 0.86 mmol) in MeOH (10 mL) was added 1N-NaOH (3.5 mL, 3.5 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (320 mg, 71%).

[0627] Step 3: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0628] A mixture of 2-(1-phenyl-2-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid (150 mg, 0.29 mmol), methylamine hydrochloride (23.5 mg, 0.35 mmol), EDCI (83.3 mg, 0.43 mmol), HOBt (58.7 mg, 0.43 mmol) and DIPEA (0.3 mL, 1.73 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (102 mg, 68%). 1 H NMR (CDCl3, 400MHz): δ8.08-7.98(m,2H),7.85(s,2H),7.61-7.58(m,2H),7.52-7.48(m,4H),7.41-7.38(m,1H),6.89( s,1H),6.36(bs,1H),5.45(s,2H),3.63-3.56(m,2H),3.54(s,2H),2.84-2.80(m,3H),0.94-0.90(m,2H),-0.03(s,9H).

[0629] Step 4: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1H-pyrazol-4-yl)benzamide

[0630] TFA (1.0 mL) was added to a solution of N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (95 mg, 0.18 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (13.2 mg, 18%). 1 H NMR (CD3OD, 400MHz): δ8.10-8.02(m,2H),7.90-7.80(m,2H),7.69-7.67(m,2H),7.53-7.40(m,5H),7.26(s,1H),3.56(s,2H),2.77(s,3H).

[0631] Example 49, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1H-indazole-5-carboxamide

[0632]

[0633] Step 1: Ethyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylate

[0634] To a solution of ethyl 1H-indazole-5-carboxylate (500 mg, 2.63 mmol) in anhydrous THF (20 mL) was added NaH (60% dispersion in mineral oil, 158 mg, 3.94 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then 2-(trimethylsilyl)ethoxymethyl chloride (0.51 mL, 2.76 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (285 mg, 34%). 1 H NMR(CDCl3,400MHz): δ8.53(s,1H),8.14-8.08(m,2H),7.61-7.56(m,1H),5.76(s,2H),4 .42-4.39(m,2H),3.62-3.52(m,2H),1.44-1.40(m,2H),0.90-0.85(m,2H),-0.07(s,9H).

[0635] Step 2: 1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylic acid

[0636] To a solution of ethyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylate (285 mg, 0.89 mmol) in MeOH (10 mL) was added 1N-NaOH (3.6 mL, 3.6 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (235 mg, 90%).

[0637] Step 3: Methyl 2-(1-phenyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamido)-1H-imidazol-4-yl)acetate

[0638] A solution of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (186 mg, 0.80 mmol), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxylic acid (235 mg, 0.80 mmol), HATU (305 mg, 1.20 mmol) and DIPEA (0.42 mL, 2.41 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (307 mg, 76%). 1 H NMR (CDCl3, 400MHz): δ8.60(s,1H),8.32-8.25(m,1H),8.07(s,1H),7.77-7.68(m,2H),7.60-7.51(m,3H),7.46-7. 39(m,1H),6.82(s,1H),5.72(s,2H),3.80(s,3H),3.67(s,2H),3.60-3.52(m,2H),0.90-0.80(m,2H),-0.10(s,9H).

[0639] Step 4: 2-(1-phenyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamido)-1H-imidazol-4-yl)acetic acid

[0640] To a solution of methyl 2-(1-phenyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamido)-1H-imidazol-4-yl)acetate (307 mg, 0.607 mmol) in MeOH (10 mL) was added 1N-NaOH (2.43 mL, 2.43 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (290 mg, 97%).

[0641] Step 5: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamide

[0642] A mixture of 2-(1-phenyl-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamido)-1H-imidazol-4-yl)acetic acid (300 mg, 0.61 mmol), methylamine hydrochloride (49 mg, 0.73 mmol), EDCI (175 mg, 0.92 mmol), HOBt (124 mg, 0.92 mmol) and DIPEA (0.53 mL, 3.05 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (206 mg, 67%). 1 H NMR (CDCl3, 400MHz): δ8.51(s,1H),8.21-8.14(m,2H),8.05(s,1H),7.68-7.62(m,2H),7.56-7.48(m, 3H),7.42-7.38(m,1H),6.87(s,1H),5.73(s,2H),3.60-3.51(m,4H),0.88-0.83(m,2H),-0.06(s,9H).

[0643] Step 6: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1H-indazole-5-carboxamide

[0644] TFA (1.0 mL) was added to a solution of N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carboxamide (206 mg, 0.41 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (50.4 mg, 33%). 1 H NMR (CD3OD, 400MHz): δ8.35(s,1H),8.17(s,1H),7.98-7.80(m,1H),7.78-7.38(m,6H),7.29(s,1H),5.81(s,1H),3.58(s,2H),2.77(s,3H).

[0645] Example 50, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0646]

[0647] Step 1: Methyl 2-(2-benzamido-1-phenyl-1H-imidazol-4-yl)acetate

[0648] A mixture of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (300 mg, 1.29 mmol), benzoic acid (190 mg, 1.55 mmol), HBTU (738 mg, 1.94 mmol) and DIPEA (0.68 mL, 3.89 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (382 mg, 88%). 1 H NMR (CDCl3, 400MHz): δ8.18-8.10(m,2H),7.72-7.65(m,2H),7.55-7.48(m,2H),7.48-7.33(m,4H),6.84(s,1H),3.79(s,3H),3.66(s,2H).

[0649] Step 2: 2-(2-Benzamido-1-phenyl-1H-imidazol-4-yl)acetic acid

[0650] To a solution of methyl 2-(2-benzamido-1-phenyl-1H-imidazol-4-yl)acetate (370 mg, 1.10 mmol) in MeOH (10 mL) was added 1N-NaOH (4.4 mL, 4.4 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (340 mg, 96%).

[0651] Step 3: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0652] A mixture of 2-(2-benzamido-1-phenyl-1H-imidazol-4-yl)acetic acid (150 mg, 0.29 mmol), methylamine hydrochloride (38.0 mg, 0.56 mmol), EDCI (134 mg, 0.70 mmol), HOBt (95 mg, 0.70 mmol) and DIPEA (0.4 mL, 2.33 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (65 mg, 42%). 1 H NMR(CDCl3,400MHz): δ7.99-7.97(m,2H),7.55-7.53(m,2H),7.46-7.41(m,3 H),7.37-7.32(m,3H),6.86(s,1H),6.77(bs,1H),3.52(s,2H),2.74(d,2H).

[0653] Example 51, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)nicotinamide

[0654]

[0655] Step 1: Methyl 2-(2-(nicotinylamino)-1-phenyl-1H-imidazol-4-yl)acetate

[0656] A mixture of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (300 mg, 1.29 mmol), nicotinic acid (191.6 mg, 1.55 mmol), HBTU (738 mg, 1.94 mmol) and DIPEA (0.68 mL, 3.89 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (320 mg, 73%). 1 H NMR (CDCl3, 400MHz): δ8.70-8.63(m,2H),8.00-7.92(m,2H),7.70-7.62(m,2H) ,7.58-7.50(m,2H),7.48-7.40(m,1H),6.84(s,1H),3.80(s,3H),3.68(m,2H).

[0657] Step 2: 2-(2-(nicotinylamino)-1-phenyl-1H-imidazol-4-yl)acetic acid

[0658] To a solution of methyl 2-(2-(nicotinylamino)-1-phenyl-1H-imidazol-4-yl)acetate (313 mg, 0.93 mmol) in MeOH (10 mL) was added 1N-NaOH (3.72 mL, 3.72 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (200 mg, 67%).

[0659] Step 3: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)nicotinamide

[0660] A mixture of 2-(2-(nicotinylamino)-1-phenyl-1H-imidazol-4-yl)acetic acid (100 mg, 0.31 mmol), methylamine hydrochloride (25.1 mg, 0.37 mmol), EDCI (89 mg, 0.465 mmol), HOBt (63 mg, 0.465 mmol) and DIPEA (0.16 mL, 0.93 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (40 mg, 40%). 1H NMR (CD3OD, 400MHz): δ9.17(s,1H),8.62-8.42(m,2H),7.71-7.46(m,6H),7.13(s,1H),3.61(s,2H),2.78(s,3H).

[0661] Example 52, N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Scheme 1)

[0662]

[0663] Step 1: Methyl 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoate

[0664] A mixture of methyl 4-(2-amino-1-phenyl-1H-imidazol-4-yl)butanoate (Intermediate 26) (5.35 g, 20.67 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (6.72 g, 21.09 mmol), HATU (12.03 g, 31.63 mmol) and DIPEA (11.02 mL, 63.27 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (8.6 g, 74%). 1 H NMR (400MHz, CDCl3) δ8.41-8.34(m,1H),8.11-8.02(m,1H),7.90-7.82(m,2H),7.79-7.70(m,2H),7.61-7.49(m,3H),7.45-7.34(m,2H),6.63( s,1H),5.46(s,2H),3.71(s,3H),3.64-3.59(m,2H),2.75-2.62(m,2H), 2.52-2.39(m,2H),2.12-1.96(m,2H),1.00-0.87(m,2H),-0.02(s,9H).

[0665] Step 2: 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoic acid

[0666] To a solution of methyl 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoate (6.00 g, 10.72 mmol) in MeOH (54 mL) was added 1N-NaOH (53.60 mL, 53.60 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (3.35 g, 57%). 1 H NMR (400MHz, CDCl3) δ8.35-8.24(m,1H),8.02-7.91(m,1H),7.89-7.77(m,2H),7.71-7.59(m,2H),7.59-7.44(m,3H),7.44-7.28(m,2H), 6.62(s,1H),5.43(s,2H),3.65-3.52(m,2H),2.84-2.67(m,2H),2.58-2.42(m,2H),2.16-1.98(m,2H),1.00-0.87(m,2H),-0.02(s,9H).

[0667] Step 3: N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0668] A mixture of 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoic acid (500 mg, 0.916 mmol), aniline (93.9 mg, 1.008 mmol), HATU (525 mg, 1.374 mmol) and DIPEA (0.48 mL, 2.749 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (438 mg, 77%). 1H NMR (400MHz, CDCl3): δ8.39-8.33(m,1H),8.08-8.01(m,1H),7.89-7.81(m,2H) ,7.75-7.66(m,2H),7.60-7.48(m,5H),7.47-7.35(m,3H),7.35-7.28(m,2H),7. 15-7.07(m,1H),6.66(s,1H),5.45(s,2H),3.59(t,J=8.4Hz,2H),2.78-2.68(m, 2H), 2.54-2.42 (m, 2H), 2.17-2.07 (m, 2H), 0.93 (t, J = 8.4Hz, 2H), -0.02 (s, 9H).

[0669] Step 4: N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0670] TFA (1.0 mL) was added to a solution of N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (87 mg, 0.140 mmol) in DCM (5.0 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (18 mg, 27%). 1H NMR (CD3OD, 400MHz): δ8.26-7.83(m,3H),7.83-7.62(m,2H),7.62-7.34(m,8H),7.34-7 .23(m,2H),7.18-7.02(m,2H),2.79-2.67(m,2H),2.55-2.45(m,2H),2.17-2.05(m,2H).

[0671] The following compounds were prepared in a similar manner to that described in Example 52 and General Scheme 1.

[0672] [Table 6]

[0673]

[0674]

[0675]

[0676] Example 70, 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butyric acid isopropyl ester

[0677]

[0678] Step 1: Isopropyl 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoate

[0679] A mixture of phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoic acid (100 mg, 0.183 mmol), DMAP (22 mg, 0.183 mmol) and EDCl (35 mg, 0.183 mmol) in isopropanol (2 mL) was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure. The reaction mixture was extracted with ethyl acetate, dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (38 mg, 36%). 1 H NMR (CDCl 3, 400MHz): δ8.41-3.36(m,1H),8.10-8.03(m,1H),7.89-7.83(m,2H),7.78-7.71( m,2H),7.60-7.50(m,3H),7.43-7.35(m,2H),6.66-6.60(m,1H),5.46(s,2H),5. 10-4.99(m,1H),3.60(t,J=8.4Hz,2H),2.72-2.62(m,2H),2.45-2.35(m,2H),2. 09-1.96(m,2H),1.26(s,3H),1.25(s,3H),0.93(t,J=8.4Hz,2H),-0.01(s,9H).

[0680] Step 2: Isopropyl 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate

[0681] TFA (1.0 mL) was added to a solution of isopropyl 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoate (36 mg, 0.061 mmol) in DCM (1.0 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (24 mg, 85%). 1 H NMR (CDCl 3, 400MHz): δ8.38(s,1H),8.12-8.01(m,1H),7.95-7.82(m,2H),7.78-7.69(m,2H),7.64-7.49(m,3H),7.47-7.30(m,2H),6 .63(s,1H),5.11-4.97(m,1H),2.67(t,J=7.2Hz,2H),2.40(t,J=7.2Hz,2H),2.09-1.94(m,2H),1.26(s,3H),1.24(s,3H).

[0682] Example 71, N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0683]

[0684] Step 1: tert-Butyl cyclopropylcarbamate

[0685] To a solution of cyclopropylamine (1.0 g, 17.51 ​​mmol) in DCM (150 mL) was added di-tert-butyl dicarboxylate (4.4 mL, 19.26 mmol) at 0°C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (2.61 g, 95%). 1 H NMR (CDCl3, 400MHz): δ4.70 (bs, 1H), 2.55-2.49 (m, 1H), 1.44 (s, 9H), 0.72-0.67 (m, 2H), 0.52-0.46 (m, 2H).

[0686] Step 2: tert-Butyl cyclopropyl(methyl)carbamate

[0687] To a solution of tert-butyl cyclopropylcarbamate (1.0 g 6.36 mmol) in THF (12 mL) was added n-BuLi (2.5 M, 2.8 mL, 6.99 mmol) and iodomethane (0.8 mL, 12.72 mmol) in hexane at -78 ° C. The mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with EA, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (700 mg, 64%). 1 H NMR (CDCl3, 400MHz): δ2.83 (s, 3H), 2.53-2.46 (m, 1H), 1.46 (s, 9H), 0.75-0.68 (m, 2H), 0.62-0.57 (m, 2H).

[0688] Step 3: N-Methylcyclopropylamine hydrochloride

[0689] The acid chloride (0.27 mL) was added to a solution of tert-butyl cyclopropyl(methyl)carbamate (131 mg, 0.76 mmol) in MeOH (2 mL) and stirred at room temperature for 4 h. The mixture was evaporated under reduced pressure to give the title compound (80 mg, 98%).

[0690] Step 4: N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0691] A mixture of 4-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)butanoic acid (140 mg, 0.25 mmol), N-methylcyclopropylamine hydrochloride (80 mg, 0.74 mmol), HBTU (195 mg, 0.51 mmol) and DIPEA (0.22 mL, 1.28 mmol) in DCM (3 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (105 mg, 68%). 1H NMR(CDCl3,400MHz): δ8.38(bs,1H),8.08-8.05(m,1H),8.02(s,1H),7.8 8-7.85(m,2H),7.78-7.73(m,2H),7.59-7.52(m,3H),7.43-7.37(m,2H),6 .65(s,1H),5.46(s,2H),3.63-3.56(m,2H),2.96(s,3H),2.70-2.62(m,5H ),2.10-2.03(m,2H),0.97-0.86(m,4H),0.76-0.72(m,2H),-0.02(s,9H).

[0692] Step 5: N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0693] TFA (3.0 mL) was added to a solution of N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (105 mg, 0.17 mmol) in DCM (6 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (48 mg, 58%). 1 H NMR (CD3OD, 400MHz): δ8.07(s,1H),8.01-7.99(m,2H),7.86-7.83(m,1H),7.72-7.69(m,1H),7.64-7.57(m,5H),7.52-7.47(m,1H) ),7.42-7.38(m,1H),2.93(s,3H),2.83-2.78(m,3H),2.76-2.72(m,2H),2.11-2.02(m,2H),0.95-0.90(m,2H),0.82-0.79(m,2H).

[0694] Example 72, N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)benzamide

[0695]

[0696] To a solution of N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazole-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 68) (40 mg, 0.08 mmol) in DCM (4 mL) was added TFA (2 mg, 0.01 mmol) and ethyl vinyl ether, and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (13 mg, 28%). 1 H NMR(CDCl3,400MHz): δ8.38(s,1H),8.06-8.04(m,1H),7.89(s,1H),7.83(s,1H),7.76-7 .73(m,2H),7.59-7.51(m,3H),7.42-7.37(m,2H),6.65(s,1H),5.65(bs,1H),5.56-5.51( m,1H),3.53-3.46(m,1H),3.42-3.36(m,1H),2.76-2.66(m,3H),2.27-2.23(m,2H),2.08- 2.00(m,2H),1.73-1.70(m,3H),1.19-1.15(m,3H),0.81-0.77(m,2H),0.54-0.50(m,2H).

[0697] Example 73, N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(2-ethoxypropan-2-yl)-1H-pyrazol-4-yl)benzamide

[0698]

[0699] To a solution of N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 68) (50 mg, 0.110 mmol) in chloroform (1.1 mL) was added 2-ethoxy-1-propene (19 mg, 0.220 mmol). p-Toluenesulfonic acid (1.4 mg, 0.006 mmol) was added to the reaction solution at 0°C, followed by stirring for 1 h. At the same temperature, TEA (55.7 mg, 0.550 mmol) was added to the reaction solution, followed by stirring for 30 min. The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was extracted with DCM / water, dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (18 mg, 30%). 1 H NMR (CDCl 3, 400MHz): δ8.40-8.35(m,1H),8.09-8.01(m,1H),7.97(d,J=0.8Hz,1H),7.82(d,J= 0.8Hz,1H),7.77-7.71(m,2H),7.60-7.50(m,3H),7.44-7.35(m,2H),6.64(s,1H),5 .71(s,1H),3.28(q,J=6.8Hz,2H),2.68-2.62(m,2H),2.28-2.17(m,2H),2.11-1.9 4(m,2H),1.83(s,6H),1.14(t,J=6.8Hz,3H),0.80-0.71(m,2H),0.52-0.44(m,2H).

[0700] Example 74, (4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methyl methyl carboxylate

[0701]

[0702] To a solution of chloromethyl chloroformate (62 mg, 0.48 mmol) in THF (3 mL) was added MeOH (17 mg, 0.53 mmol) and DIPEA (0.25 mL, 1.45 mmol) at 0°C and stirred for 1 h. N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 68) (100 mg, 0.22 mmol) and DMAP (5.3 mg, 0.04 mmol) were added to the reaction mixture. The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (40 mg, 33%). 1 H NMR(CDCl3,400MHz): δ8.36(s,1H),8.08-8.05(m,1H),7.97(s,1H),7.92(s,1H),7.75-7.72(m,2H),7.57-7.53(m,3H),7.43-7.37(m,2H),6.65 (s,1H),6.07(s,2H),5.67(bs,1H),3.83(s,3H),2.75-2.66(m,3H),2.2 7-2.23(m,2H),2.08-2.01(m,2H),0.81-0.76(m,2H),0.53-0.50(m,2H).

[0703] Example 75, (4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methylethylcarboxylate

[0704]

[0705] To a solution of chloromethyl chloroformate (90 mg, 0.70 mmol) in THF (3 mL) was added EtOH (45 mg, 0.98 mmol) and DIPEA (0.37 mL, 2.11 mmol) at 0°C and stirred for 1 h. N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 68) (80 mg, 0.17 mmol) and DMAP (4.3 mg, 0.03 mmol) were added to the reaction mixture. The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (38 mg, 40%). 1 H NMR(CDCl3,400MHz): δ8.36(s,1H),8.07-8.05(m,1H),7.97(s,1H),7.91(s,1H),7 .75-7.72(m,2H),7.57-7.52(m,3H),7.44-7.36(m,2H),6.64(s,1H),6.06(s,2H),5 .73(bs,1H),4.59-4.53(m,1H),4.27-4.22(m,1H),2.75-2.65(m,3H),2.27-2.22( m,2H),2.07-1.99(m,2H),1.33-1.29(m,3H),0.81-0.76(m,2H),0.53-0.49(m,2H).

[0706] Example 76, N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0707]

[0708] Step 1: Methyl 5-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)pentanoate

[0709] A mixture of methyl 5-(2-amino-1-phenyl-1H-imidazol-4-yl)pentanoate (Intermediate 27) (2.5 g, 9.14 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (2.7 g, 8.46 mmol), HBTU (4.81 g, 12.69 mmol) and DIPEA (3.68 mL, 21.15 mmol) in DCM (100 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (3.0 g, 63%). 1 HNMR (CDCl3, 400MHz): δ8.38(s,1H),8.08-8.04(m,1H),7.88-7.84(m,2H),7.77-7.72(m,2H),7.58-7.51(m,3H),7.43-7.36(m,2H),6.62(s, 1H),5.45(s,2H),3.69(s,3H),3.62-3.56(m,2H),2.66-2.60(m,2H),2 .43-2.37(m,2H),1.79-1.72(m,4H),0.98-0.91(m,2H),-0.01(s,9H).

[0710] Step 2: 5-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)pentanoic acid

[0711] To a solution of methyl 5-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)pentanoate (2.0 g, 3.48 mmol) in MeOH (35 mL) was added 1N-NaOH (17.0 mL, 17.0 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (1.3 g, 67%). 1H NMR (CDCl3, 400MHz): δ8.34-8.32(m,1H),8.04-7.98(m,1H),7.86-7.84(m,2H),7.73-7.68(m,2H),7.58-7.48(m,3H),7.43-7.36(m,2H) ,6.64(s,1H),5.45(s,2H),3.63-3.56(m,2H),2.74-2.67(m,2H),2.48-2.43(m,2H),1.84-1.78(m,4H),0.97-0.91(m,2H),-0.01(s,9H).

[0712] Step 3: N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0713] A mixture of 5-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)pentanoic acid (100 mg, 0.17 mmol), aniline (24 mg, 0.26 mmol), EDCI (51 mg, 0.26 mmol), HOBt (36 mg, 0.26 mmol) and DIPEA (0.07 mL, 0.44 mmol) in DMF (2.0 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (60 mg, 53%). 1 HNMR(CDCl3,400MHz): δ8.37(s,1H),8.08-8.03(m,2H),7.84(s,1H),7.79(s,1H), 7.72-7.67(m,2H),7.58-7.53(m,3H),7.53-7.47(m,2H),7.39-7.34(m,2H),7.32-7 .25(m,1H),7.10-7.03(m,1H),6.65(s,1H),5.42(s,2H),3.61-3.57(m,2H),2.56-2 .50(m,2H),2.37-2.31(m,2H),1.80-1.64(m,4H),0.96-0.91(m,2H),-0.02(s,9H).

[0714] Step 4: N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0715] TFA (1.8 mL) was added to a solution of N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (66 mg, 0.09 mmol) in DCM (3.6 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (23.7 mg, 50%). 1 H NMR(CD3OD,400MHz,): δ8.08(s,1H),8.00-7.98(m,2H),7.83-7.79(m,1H),7.72-7.69(m,1H),7.59-7.52(m,7H), 7.49-7.44(m,1H),7.31-7.26(m,3H),7.09-7.05(m,1H),2.79-2.75(m,2H),2.48-2.43(m,2H),1.85-1.80(m,4H).

[0716] The following compounds were prepared in a similar manner to that described in Example 76 and General Scheme 1.

[0717] [Table 7]

[0718]

[0719]

[0720]

[0721] Example 90, N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0722]

[0723] Step 1: Methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate

[0724] A mixture of methyl 6-(2-amino-1-phenyl-1H-imidazol-4-yl)hexanoate (Intermediate 28) (2.0 g, 6.69 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (2.43 g, 7.65 mmol), HATU (3.97 g, 10.44 mmol) and DIPEA (3.63 mL, 20.88 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (2.0 g, 49%). 1 H NMR(CDCl3,400MHz): δ8.38(s,1H),8.07-8.04(m,1H),7.86(s,1H),7.85(s, 1H),7.75-7.00(m,2H),7.57-7.50(m,3H),7.42-7.32(m,2H),6.58(s,1H),5. 43(s,2H),3.67(s,3H),3.62-3.57(m,2H),2.60-2.55(m,2H),2.38-2.30(m, 2H),1.74-1.62(m,4H),1.50-1.40(m,2H),,0.99-0.90(m,2H),-0.01(s,9H).

[0725] Step 2: 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoic acid

[0726] To a solution of methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate (2.0 g, 3.40 mmol) in MeOH (20 mL) was added 1N-NaOH (6.80 mL, 6.80 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (900 mg, 46%). 1H NMR (CDCl3, 400MHz): δ8.31(s,1H),7.99-7.96(m,1H),7.88-7.85(m,2H),7. 71-7.65(m,2H),7.58-7.56(m,1H),7.56-7.48(m,2H),7.41-7.35(m,2H),6. 62(s,1H),5.46(s,1H),3.62-3.56(m,2H),2.69-2.62(m,2H),2.48-2.41(m, 2H),1.82-1.75(m,4H),1.60-1.51(m,2H),0.95-0.91(m,2H),-0.01(s,9H).

[0727] Step 3: N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0728] A mixture of 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoic acid (120 mg, 0.21 mmol), aniline (23.4 mg, 0.25 mmol), EDCI (60 mg, 0.31 mmol), HOBt (42.4 mg, 0.31 mmol) and DIPEA (0.15 mL, 0.83 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (3.0 g, 67%). 1 H NMR(CDCl3,400MHz): δ8.37(s,1H),8.10-8.06(m,1H),7.85(s,1H),7.80(s,1 H),7.77-7.71(m,2H),7.60-7.50(m,6H),7.43-7.38(m,2H),7.32-7.24(m,2H) ,6.62(s,1H),5.44(s,1H),3.62-3.56(m,2H),2.69-2.62(m,2H),2.48-2.41( m,2H),1.90-1.70(m,4H),1.58-1.48(m,2H),0.95-0.91(m,2H),-0.01(s,9H).

[0729] Step 4: N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0730] TFA (1.0 mL) was added to a solution of N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (84 mg, 0.129 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (24 mg, 36%). 1 H NMR (CDCl3, 400MHz): δ8.37(s,1H),8.07-8.05(m,1H),7.87(s,2H),7.73-7.71(m,2H),7.64(s,1H),7.60-7.50(m,5H),7.41-7.37(m ,2H),7.30-7.27(m,2H),7.09-7.06(m,1H),6.61(s,1H),2.64-2.61(m,2H),2.42-2.38(m,2H),1.83-1.70(m,4H),1.52-1.48(m,2H).

[0731] The following compounds were prepared in a similar manner to that described in Example 90 and General Scheme 1.

[0732] [Table 8]

[0733]

[0734]

[0735]

[0736] Example 102, N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0737]

[0738] Step 1: N-(4-(6-Hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0739] To a solution of methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate (Example 90, Step 1) (1.36 g, 2.3 mmol) in anhydrous THF (25 mL) was added LiAlH4 (1.0 M in THF, 2.3 mL, 2.3 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (814 mg, 63%). 1 H NMR(CDCl3,400MHz): δ8.38(s,1H),8.10-8.04(m,1H),7.86(s,1H),7.85(s,1 H),7.80-7.70(m,2H),7.59-7.50(m,3H),7.42-7.35(m,2H),6.59(s,1H),5.46 (s,2H),3.70-3.65(m,2H),3.61-3.55(m,2H),2.64-2.57(m,2H),1.78-1.68( m,2H),1.66-1.56(m,2H),1.50-1.40(m,4H),0.95-0.91(m,2H),-0.02(s,9H).

[0740] Step 2: N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0741] To a solution of oxalyl chloride (92 μL, 1.072 mmol) in anhydrous DCM was added a solution of DMSO (0.15 mL, 2.14 mmol) in DCM at -78 °C. After 15 min, a solution of N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (500 mg, 0.893 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (0.62 mL, 4.46 mmol) was added and the reaction mixture was warmed to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (480 mg, 96%).

[0742] Step 3: N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0743] To a solution of N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (250 mg, 0.448 mmol) and piperidine (88.5 μL, 0.896 mmol) in THF was added NaBH3CN (56.3 mg, 0.896 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (126 mg, 45%). 1 H NMR(CDCl3,400MHz): δ8.38(s,1H),8.10-8.04(m,1H),7.87(s,1H),7.85(s,1 H),7.76-7.72(m,2H),7.59-7.50(m,3H),7.42-7.35(m,2H),6.58(s,1H),5.45 (s,2H),3.62-3.54(m,2H),2.62-2.58(m,2H),2.48-2.22(m,6H),1.75-1.65( m,2H),1.62-1.48(m,6H),1.48-1.30(m,6H),0.95-0.88(m,2H),-0.02(s,9H).

[0744] Step 4: N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[0745] TFA (1.0 mL) was added to a solution of N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (126 mg, 0.20 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (24 mg, 36%). 1H NMR (CDCl3, 400MHz): δ8.33(s,1H),8.08-8.02(m,1H),7.87(s,2H),7.74-7.68(m,2H),7.60-7.58(m,1H),7.54-7.50(m,2H),7 .43-7.37(m,2H),6.66(s,1H),3.05-2.88(m,6H),2.64-2.58(m,2H),1.92-1.80(m,4H),1.80-1.63(m,5H),1.50-1.38(m,5H).

[0746] The following compounds were prepared in a similar manner as described in Example 102 and General Scheme 1.

[0747] [Table 9]

[0748]

[0749]

[0750]

[0751]

[0752]

[0753] Example 125, 1-(6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl)piperidine 1-oxide

[0754]

[0755] Step 1: 1-(6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexyl)piperidine 1-oxide

[0756] To a solution of N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (Example 102, Step 3) (266 mg, 0.424 mmol) in DCM was added m-CPBA (125 mg, 0.509 mmol) at 0°C. The reaction mixture was stirred at 0°C for 1 h. The mixture was evaporated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (223 mg, 82%).

[0757] Step 2: 1-(6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl)piperidine 1-oxide

[0758] TFA (1.0 mL) was added to a solution of 1-(6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexyl)piperidine 1-oxide (117 mg, 0.182 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (60 mg, 64%). 1 H NMR (CD3OD, 400MHz): δ8.22-7.82(m,3H),7.80-7.68(m,2H),7.62-7.32(m,6H),7.07(s,1H),3.30-3.10 (m,6H),2.67-2.64(m,2H),2.18-2.09(m,2H),1.92-1.80(m,2H),1.80-1.60(m,5H),1.60-1.40(m,5H).

[0759] Example 126, 4-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propyl)morpholine 4-oxide

[0760]

[0761] Example 126 (26.8 mg, 41%) was prepared in a similar manner to Example 125. 1 H NMR (CD3OD, 400MHz): δ8.08(s,1H),7.99(s,2H),7.80-7.70(m,1H),7.70-7.62(m,1H),7.54-7.41(m,6H),7 .21(s,1H),4.22-4.18(m,2H),3.85-3.81(m,2H),3.56-3.48(m,4H),3.30-3.17(m,2H),2.32-2.28(m,2H).

[0762] Example 127, N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide hydrochloride

[0763]

[0764] To a solution of acetyl chloride (8.5 μL, 0.12 mmol) in MeOH (25.5 μL) was added a solution of N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 102) (40 mg, 0.08 mmol) in MeOH (1.0 mL) at 0°C. The reaction mixture was stirred at room temperature for 1 h. The mixture was evaporated under reduced pressure. The residue was washed with DCM and freeze-dried to give the title compound (30 mg, 70%). 1 H NMR(D2O,400MHz): δ7.99(s,2H),7.84(s,1H),7.79-7.77(m,1H),7.62-7.55(m,3H),7.52-7.48(m,2H),7.45-7.40(m,1H),7.21(s,1H) ,3.44-3.41(m,2H),3.01-2.97(m,2H),2.84-2.78(m,2H),2.70-2.60(m,2H),1.86-1.82(m,2H),1.78-1.58(m,7H),1.40-1.38(m,5H).

[0765] The following compounds were prepared in a similar manner to that described in Example 127 and General Scheme 1.

[0766] [Table 10]

[0767]

[0768]

[0769] Example 133, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide citrate

[0770]

[0771] A mixture of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazine-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 143) (1.0 g, 1.95 mmol) and citric acid (0.36 g, 1.85 mmol) in MeOH (5 mL) was heated. The reaction mixture was evaporated under reduced pressure. Acetone (10 mL) was added to the residue, stirred for 30 min, and the solid was filtered to give the title compound (1.14 g, 83%).1 H NMR(D2O,400MHz): δ7.63(s,2H),7.56(s,1H),7.48-7.46(d,1H),7.39-7.3 7(s,1H),7.31-7.29(m,5H),7.23-7.19(t,1H),6.86(s,1H),4.42-4.40(br, 1H),4.02-3.99(br,1H),3.38(br,3H),2.95-2.87(m,3H),2.73(s,3H),2.6 9-2.65(d,2H),2.57-2.54(d,2H),2.46(br,2H),2.37(br,2H),1.74(m,2H).

[0772] The following compounds were prepared in a similar manner to that described in Example 133.

[0773] [Table 11]

[0774]

[0775]

[0776] Example 138, 3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[0777]

[0778] To a solution of N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide (Example 102) (80 mg, 0.161 mmol) in DCM (10 mL) was added TFA (15 μL, 0.193 mmol) and ethyl vinyl ether (46 μL, 0.483 mmol). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (62 mg, 68%). 1H NMR(CDCl3,400MHz): δ8.38(s,1H),8.06-8.04(m,1H),7.88(s,1H),7.82(s,1H) ,7.76-7.74(m,2H),7.57-7.51(m,3H),7.41-7.36(m,2H),6.60(s,1H),5.53-5.5 2(m,1H),3.51-3.47(m,1H),3.39-3.35(m,1H),2.90-2.50(m,8H),1.82-1.78(m, 2H),1.78-1.60(m,8H),1.60-1.50(m,2H),1.50-1.30(m,4H),1.18-1.15(m,3H).

[0779] Example 139, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0780]

[0781] Step 1: Methyl 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate

[0782] A mixture of methyl 4-(2-amino-1-phenyl-1H-imidazol-4-yl)butanoate (Intermediate 26) (10.0 g, 38.57 mmol), 3-(1-methyl-1H-pyrazol-4-yl)benzoic acid (Intermediate 7) (6.0 g, 29.67 mmol), HATU (16.90 g, 44.51 mmol) and DIPEA (15.5 mL, 89.02 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (10.0 g, 76%). 1 H NMR (CDCl3, 400MHz): δ8.33(s,1H),8.03-8.01(s,1H),7.85(s,1H),7.84(s,1H),7.76-7.66(m,2H),7.58-7.48(m,3H),7. 42-7.34(m,2H),6.84(s,1H),5.45(s,2H),3.80(s,3H),3.67(s,2H),3.60-3.57(m,2H),0.95-0.91(m,2H),-0.02(s,9H).

[0783] Step 2: 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid

[0784] To a solution of methyl 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate (10.0 g, 22.54 mmol) in MeOH (90 mL) was added 1N-NaOH (90.2 mL, 90.2 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (9.0 g, 93%). 1 H NMR(DMSO-D6,400MHz): δ8.04(s,1H),8.00(s,1H),7.83(s,1H),7.78-7.75(s,1H),7.73-7.68(m,1H),7.62-7.5 0(m,5H),7.48-7.44(m,1H),7.28(s,1H),3.94(s,3H),2.78-2.75(m,2H),2.48-2.43(m,2H),2.08-2.01(m,2H).

[0785] Step 3: 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0786] A mixture of 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (150 mg, 0.349 mmol), methylamine hydrochloride (28.0 mg, 0.42 mmol), HATU (200 mg, 0.52 mmol) and DIPEA (0.3 mL, 1.75 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (111 mg, 72%). 1H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.03-8.01(m,1H),7.79(s,1H),7.74-7.72(m,2H),7.64(s,1H),7.55-7.51(m,3H),7.42- 7.33(m,2H),6.64(s,1H),5.52(bs,1H),3.94(s,3H),2.83(d,3H),2.68.-2.65(m,2H),2.30-2.26(m,2H),2.06-2.02(m,2H).

[0787] The following compounds were prepared in a similar manner to that described in Example 139 and General Scheme 1.

[0788] [Table 12]

[0789]

[0790]

[0791]

[0792]

[0793]

[0794]

[0795]

[0796]

[0797]

[0798]

[0799]

[0800]

[0801]

[0802]

[0803] Example 202, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0804]

[0805] Step 1: tert-Butyl 4-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperazine-1-carboxylate

[0806] A mixture of 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (Example 139, Step 2) (600 mg, 1.397 mmol), tert-butyl piperazine-1-carboxylate (312 mg, 1.076 mmol), HATU (800 mg, 2.095 mmol) and DIPEA (0.73 mL, 4.191 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (770 mg, 92%). 1 H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.05-8.02(m,1H),7.79(s,1H),7.78-7.71(m,2H),7.64(s,1H),7.58-7.50(m,3H),7.41-7.32(m,2H) ),6.64(s,1H),3.94(s,3H),3.68-3.56(m,4H),3.50-3.40(m,4H),2.72-2.64(m,2H),2.50-2.40(m,2H),2.10-2.00(m,2H),1.44(s,9H).

[0807] Step 2: 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0808] TFA (0.5 mL) was added to a solution of tert-butyl 4-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperazine-1-carboxylate (770 mg, 1.288 mmol) in DCM (20 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (400 mg, 62%). 1H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.04-8.02(m,1H),7.80(s,1H),7.75-7.73(m,2H),7.64(s,1H),7.55-7.51(m,3H),7.41-7.34(m,2H), 6.65(s,1H),3.94(s,3H),3.64-3.60(m,2H),3.46-3.41(m,2H),2.90 -2.82(m,4H),2.72-2.64(,2H),2.48-2.40(m,2H),2.10-2.00(m,2H).

[0809] The following compounds were prepared in a similar manner as described in Example 202 and General Scheme 1.

[0810] [Table 13]

[0811]

[0812] Example 205, N-(4-(4-(4-acetylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0813]

[0814] To a solution of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-oxo-5-(piperazin-1-yl)pentyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 202) (150 mg, 0.3 mmol) in DCM was added TEA (63 μL, 0.45 mmol). The reaction mixture was cooled to 0°C, and then acetyl chloride (26 μL, 0.36 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (59 mg, 36%). 1H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.05-8.02(m,1H),7.80(s,1H),7.75-7.73(m,2H),7.65(s,1H),7.55-7.51(m,3H),7.41-7.34 (m,2H),6.64(s,1H),3.94(s,3H),3.72-3.58(m,4H),3.50-3.40(m,4H),2.74-2.66(m,2H),2.50-2.39(m,2H),2.18-2.00(m,5H).

[0815] Example 206, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-(methylsulfonyl)piperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0816]

[0817] To a solution of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 202) (150 mg, 0.3 mmol) in DCM was added TEA (63 μL, 0.45 mmol). The reaction mixture was cooled to 0°C, and then methanesulfonyl chloride (28 μL, 0.36 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (118 mg, 68%). 1 H NMR(CDCl3,400MHz): δ8.33(s,1H),8.03-8.01(m,1H),7.80(s,1H),7.75 -7.73(m,2H),7.65(s,1H),7.55-7.51(m,3H),7.41-7.34(m,2H),6.65(s ,1H),3.95(s,3H),3.80-3.72(m,2H),3.60-3.52(m,2H),3.26-2.59(m,4 H),2.76(s,3H),2.72-2.68(m,2H),2.46-2.42(m,2H),2.07-2.02(m,2H).

[0818] Example 207, (S)-1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylic acid

[0819]

[0820] Step 1: (S)-1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylic acid ethyl ester

[0821] A mixture of 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (Example 139, Step 2) (140 mg, 0.32 mmol), (S)-(+)-ethyl 3-piperidinecarboxylate (102 mg, 0.65 mmol), HATU (186 mg, 0.48 mmol) and DIPEA (0.14 mL, 0.81 mmol) in DCM (3 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (80 mg, 44%). 1 H NMR (CDCl3, 400MHz): δ8.33(s,1H),8.07-8.02(m,1H),7.80-7.73(m,3H),7.65(s,1H),7.57-7 .50(m,3H),7.46-7.33(m,2H),6.66(s,1H),4.20-4.06(m,2H),3.94(s,3H),3.76-3.68(m,1H), 3.50-3.33(m,1H),3.22-3.10(m,1H),3.00-2.92(m,1H),2.72-2.66(m,1H),2.51-2.41(m,2H), 2.28-2.14(m,1H),2.10-2.00(m,1H),1.93-1.80(m,2H),1.70-1.44(m,4H),1.28-1.20(m,3H).

[0822] Step 2: (S)-1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylic acid

[0823] To a solution of (S)-ethyl 1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylate (80 mg, 0.14 mmol) in MeOH (2 mL) was added 1N-NaOH (0.7 mL, 0.70 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (45 mg, 59%). 1 H NMR(CDCl3,400MHz): δ8.13(s,1H),7.83-7.79(m,1H),7.73(s,1H),7.71-7 .68(m,1H),7.58-7.54(m,2H),7.52-7.44(m,3H),7.40-7.30(m,2H),6.80(s ,1H),3.80(s,3H),3.72-3.64(m,1H),3.60-3.50(m,3H),2.73-2.58(m,3H), 2.54-2.36(m,2H),2.02-1.88(m,4H),1.80-1.74(m,1H),1.68-1.62(m,1H).

[0824] Example 208, (S)-1-(5-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoyl)piperidine-3-carboxylic acid

[0825]

[0826] Example 208 (50 mg, 20% yield over 2 steps) was prepared in a similar manner to Example 207. 1 H NMR (CDCl3, 400MHz): δ8.25(s,1H),7.97-7.93(m,1H),7.77(s,1H),7.70-7.67(m,2H),7.62( s,1H),7.54-7.50(m,3H),7.42-7.33(m,2H),6.62(s,1H),4.76-4.72(m,1H),4.57-4.52(m,1H ),3.95(s,3H),3.40-3.34(m,1H),3.14-3.09(m,1H),2.87-2.77(m,2H),2.56-2.48(m,3H),2 .32-2.24(m,1H),2.09-2.02(m,1H),1.84-1.70(m,2H),1.66-1.57(m,3H),1.53-1.44(m,1H).

[0827] Example 209, N-(4-(4-(4-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0828]

[0829] Step 1: tert-Butyl (1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidin-4-yl)carbamate

[0830] A mixture of 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (Example 139, Step 2) (140 mg, 0.32 mmol), 4-(tert-butoxycarbonylamino)piperidine (130 mg, 0.65 mmol), HATU (186 mg, 0.48 mmol) and DIPEA (0.14 mL, 0.81 mmol) in DCM (3 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (75 mg, 38%).

[0831] Step 2: N-(4-(4-(4-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0832] TFA (0.5 mL) was added to a solution of tert-butyl (1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidin-4-yl)carbamate (75 mg, 0.12 mmol) in DCM (3 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (45 mg, 73%). 1H NMR(CDCl3,400MHz): δ8.34(s,1H),8.06-8.02(m,1H),7.80(s,1H),7.76-7.73 (m,2H),7.65(s,1H),7.56-7.51(m,3H),7.42-7.34(m,2H),6.65(s,1H),4.56-4 .50(m,1H),3.94(s,3H),3.84-3.78(m,1H),3.11-3.03(m,1H),2.97-2.89(m,1 H),2.76-2.66(m,3H),2.47-2.42(m,2H),2.08-1.99(m,2H),1.92-1.82(m,4H).

[0833] The following compounds were prepared in a similar manner to that described in Example 209 and General Scheme 1.

[0834] [Table 14]

[0835]

[0836]

[0837]

[0838] Example 218, N-(4-(4-(methyl(4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0839]

[0840] Step 1: 4-Methyl-N-methylenepiperazin-1-amine

[0841] To a solution of 4-methylpiperazine-1-amine (1.0 g, 8.68 mmol) and Na2SO4 (1.0 g) in DCM (10 mL) was added paraformaldehyde (217 mg, 7.23 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure to give the title compound (797 mg, 72%).

[0842] Step 2: N,4-dimethylpiperazine-1-amine

[0843] To a solution of 4-methyl-N-methylenepiperazin-1-amine (600 mg, 4.72 mmol) in anhydrous THF (20 mL) was added LiAlH4 (1.0 M in THF, 4.72 mL, 4.72 mmol) at -78°C. The reaction mixture was stirred at 80°C for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure to give the title compound (crude product obtained).

[0844] Step 3: N-(4-(4-(methyl(4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0845] A mixture of 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (Example 139, Step 2) (200 mg, 0.465 mmol), N,4-dimethylpiperazin-1-amine (120 mg, 0.93 mmol), HATU (265 mg, 0.698 mmol) and DIPEA (0.25 mL, 1.39 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (60 mg, 24%). 1 H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.05-8.03(m,1H),7.79(s,1H),7.76-7.74(m,2H),7.64(s,1H),7.55-7.51(m,3H),7.41-7.34 (m,2H),6.64(s,1H),3.94(s,3H),3.00-2.90(m,5H),2.82-2.74(m,2H),2.70-2.60(m,6H),2.30-2.20(m,5H),2.22-1.94(m,2H).

[0846] Example 219, 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide

[0847]

[0848] Step 1: N-(4-(4-Hydroxybutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0849] To a solution of methyl 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate (Example 139, Step 1) (6.0 g, 13.5 mmol) in anhydrous THF (200 mL) was added LiAlH4 (1.0 M in THF, 13.5 mL, 13.5 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (1.37 g, 24%).

[0850] Step 2: 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0851] To a solution of oxalyl chloride (0.4 mL, 4.62 mmol) in anhydrous DCM was added a solution of DMSO (0.66 mL, 9.24 mmol) in DCM at -78 °C. After 15 min, a solution of N-(4-(4-hydroxybutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (1.6 g, 3.85 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (2.7 mL, 19.25 mmol) was added and the reaction mixture was warmed to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (756 mg, 47%).

[0852] Step 3: 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide

[0853] To a solution of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (100 mg, 0.24 mmol) and piperidine (41 mg, 0.48 mmol) in THF was added NaBH3CN (30.4 mg, 0.48 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (30 mg, 26%).1 H NMR(CDCl3,400MHz):(CDCl3,400MHz): δ8.33(s,1H),8.05-8.03(m,1H),7.80(s,1H),7.77-7.73(m,2H),7.64(s,1H),7. 55-7.51(m,3H),7.41-7.34(m,2H),6.61(s,1H),3.95(s,3H),2.64-2.59(m,2H),2.58-2.10(m,6H),1.78-1.50(m,10H).

[0854] The following compounds were prepared in a similar manner to that described in Example 219 and General Scheme 1.

[0855] [Table 15]

[0856]

[0857] Example 224, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0858]

[0859] To a MeOH solution of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 219, Step 2) (100 mg, 0.24 mmol) was added 4-aminobutyric acid ethyl ester hydrochloride (48.7 mg, 0.29 mmol), TEA (44 mL, 0.31 mmol). The reaction mixture was stirred at room temperature for 30 min, and then NaBH3CN was added. The reaction mixture was stirred at 45°C overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (22 mg, 19%). 1 H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.08-8.03(m,1H),7.79(s,1H),7.75-7.70(m,2H),7.64(s,1H),7.58-7.51(m,3H),7.41-7.34 (m,2H),6.64(s,1H),3.94(s,3H),3.40-3.32(m,4H),2.66-2.60(m,2H),2.42-2.38(m,2H),2.06-2.00(m,2H),1.80-1.60(m,4H).

[0860] Example 225, 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0861]

[0862] Example 225 (64 mg, 35%) was prepared in a similar manner to Example 224. 1 H NMR(CDCl3,400MHz): δ8.34(s,1H),8.06-8.03(m,1H),7.80(s,1H),7.75-7.70 (m,2H),7.64(s,1H),7.58-7.51(m,3H),7.41-7.34(m,2H),6.59(s,1H),3.94(s ,3H),3.40-3.35(m,2H),3.29-3.26(m,2H),2.62-2.56(m,2H),2.42-2.36(m,2 H),2.06-2.00(m,2H),1.71-1.65(m,2H),1.62-1.50(m,2H),1.50-1.30(m,4H).

[0863] Example 226, N-(4-(6-(2,5-dioxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0864]

[0865] Step 1: 6-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate

[0866] To a solution of N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (Example 220, Step 1) (430 mg, 0.97 mmol) in DCM was added TEA (0.27 mL, 1.94 mmol). The reaction mixture was cooled to 0°C and then sulfonyl chloride (0.11 mL, 1.45 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (crude product obtained).

[0867] Step 2: N-(4-(6-azidohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0868] To a solution of 6-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate (580 mg, 1.11 mmol) in DMF was added sodium azide (144 mg, 2.22 mmol). The reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (210 mg, 44%).

[0869] Step 3: N-(4-(6-aminohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0870] To a MeOH solution of N-(4-(6-azidohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (210 mg, 0.45 mmol) was added palladium on carbon (50 mg). Hydrogen was charged into the mixture via a hydrogen balloon and then stirred at room temperature overnight. The reaction mixture was filtered through celite, washed with MeOH and concentrated under reduced pressure to give the title compound (197 mg, 99%).

[0871] Step 4: N-(4-(6-(2,5-dioxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0872] To a solution of N-(4-(6-aminohexyl)-1-phenyl-1H-imidazole-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (120 mg, 0.27 mmol), succinic anhydride (30 mg, 0.3 mmol) in AcOH (5 mL) was added DMAP (6.6 mg, 0.054 mmol). The reaction mixture was refluxed overnight. The mixture was evaporated under reduced pressure and extracted with DCM / saturated NaHCO3 aqueous solution. The organic phase was washed with 1N-HCl and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (54 mg, 38%). 1H NMR (CDCl3, 400MHz): δ8.34(s,1H),8.06-8.03(m,1H),7.80(s,1H),7.75-7.70(m,2H),7.64(s,1H),7.58-7.51(m,3H ),7.41-7.34(m,2H),6.59(s,1H),3.94(s,3H),3.55-3.49(m,2H),2.72(s,4H),2.61-2.58(m,2H),1.72-1.30(m,8H).

[0873] Example 227, N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0874]

[0875] Step 1: N-(4-(4-(isonitroso)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0876] To a solution of 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (Example 219, Step 2) (100 mg, 0.242 mmol) in EtOH (5 mL) were added TEA (80 μL, 0.58 mmol), hydroxylamine hydrochloride (32 mg, 0.46 mmol). The reaction mixture was stirred at room temperature for 3 h. The solid was filtered and washed with EtOH (5 mL) to give the title compound (80 mg, 77%).

[0877] Step 2: N-(4-(4-aminobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0878] To a THF solution of N-(4-(4-(isonitroso)butyl)-1-phenyl-1H-imidazole-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (80 mg, 0.186 mmol) was added 2N-HCl (2.0 mL), zinc powder (244 mg, 3.73 mmol). The reaction mixture was refluxed for 2 h. The reaction mixture was extracted with DCM / water and concentrated under reduced pressure to give the title compound (crude product).

[0879] Step 3: N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0880] A mixture of N-(4-(4-aminobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (55 mg, 0.13 mmol), cyclopropanecarboxylic acid (13.7 mg, 0.16 mmol), EDCI (38.2 mg, 0.20 mmol), HOBt (27 mg, 0.20 mmol) and DIPEA (0.12 mL, 0.66 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (7.0 mg, 11%). 1 H NMR (CDCl3, 400MHz): δ8.33(s,1H),8.05-8.03(m,1H),7.80(s,1H),7.77-7.73(m,2H),7.64(s,1H),7.55-7.51(m,3H),7.41-7.34(m,2H),6 .61(s,1H),3.93(s,3H),3.36-3.30(m,2H),2.64-2.60(m,2H),1.80- 1.60(m,4H),1.38-1.28(m,1H),0.98-0.92(m,2H),0.78-0.70(m,2H).

[0881] Example 228, N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0882]

[0883] Example 228 (64 mg, 35%) was prepared in a similar manner to Example 227. 1 H NMR(CDCl3,400MHz): δ8.29(s,1H),7.99-7.97(m,1H),7.80(s,1H),7.70-7.65( m,3H),7.55-7.49(m,3H),7.41-7.34(m,2H),6.61(s,1H),3.95(s,3H),3.29-3.2 4(m,2H),2.61-2.57(m,2H),1.72-1.67(m,2H),1.63-1.59(m,2H),1.56-1.51(m, 2H),1.37-1.31(m,1H),1.06-1.02(m,2H),0.96-0.94(m,2H),0.72-0.67(m,2H).

[0884] Example 229, N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide

[0885]

[0886] Step 1: Methyl 4-(2-(3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate

[0887] A mixture of methyl 4-(2-amino-1-phenyl-1H-imidazol-4-yl)butanoate (Intermediate 26) (220 mg, 0.847 mmol), 3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 5) (285 mg, 0.847 mmol), HATU (483 mg, 1.27 mmol) and DIPEA (0.44 mL, 2.54 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (300 mg, 61%). 1 H NMR(CDCl3,400MHz): δ8.45(s,1H),8.09-8.06(m,1H),7.78-7.72(m,1H) ,7.70(s,1H),7.62-7.58(m,1H),7.58-7.50(m,2H),7.41-7.35(m,2H),6. 63(s,1H),5.29(s,2H),3.70(s,3H),3.63-3.59(m,2H),2.68-2.64(m,2H ),2.46-2.42(m,2H),2.04-2.00(m,2H),0.95-0.91(m,2H),-0.01(s,9H).

[0888] Step 2: 4-(2-(3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid

[0889] To a solution of methyl 4-(2-(3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate (285 mg, 0.493 mmol) in MeOH (10 mL) was added 1N-NaOH (2.0 mL, 2.0 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (190 mg, 68%).

[0890] Step 3: N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[0891] A mixture of 4-(2-(3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (190 mg, 0.337 mmol), cyclopropylamine (23 mg, 0.404 mmol), HATU (192 mg, 0.505 mmol) and DIPEA (0.18 mL, 1.011 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (149 mg, 73%). 1 H NMR (CDCl3, 400MHz): δ8.44(s,1H),8.08-8.04(m,1H),7.76-7.72(m,2H),7.70(s,1H),7.62-7.58(m,1H),7.55-7.50(m,2H),7.42 -7.36(m,2H),6.64(s,1H),5.90(bs,1H),5.29(s,2H),3.64-3.59(m,2H),2.78-2.64(m,3H),2.25-2.20(m,2H),2.10-1.98(m,2H).

[0892] Step 4: N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide

[0893] To a solution of N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazole-2-yl)-3-(5-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (205 mg, 0.34 mmol) in THF (20 mL) was added TBAF (1.0 M in THF, 1.7 mL, 1.7 mmol). The reaction mixture was refluxed overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (59 mg, 37%). 1 H NMR (CD3OD, 400MHz): δ8.10-7.82(m,2H),7.80-7.40(m,8H),7.06(s,1H),2.72-2.58 (m,3H),2.30-2.20(m,2H),2.10-1.95(m,2H),0.78-0.60(m,2H),0.50-0.40(m,2H).

[0894] The following compounds were prepared in a similar manner to that described in Example 229 and General Scheme 1.

[0895] [Table 16]

[0896]

[0897] Example 232, N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide

[0898]

[0899] To a solution of N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide (Example 229) (40 mg, 0.084 mmol) in anhydrous THF (5 mL) was added NaH (60% dispersion in mineral oil, 4.0 mg, 0.101 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then iodomethane (13.2 mg, 0.093 mmol) was added dropwise. The reaction mixture was stirred for 1 h at room temperature, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (7 mg, 17%). 1H NMR(CDCl3,400MHz): δ8.39(s,1H),8.05-8.03(m,1H),7.75-7.72(m,2H),7.60-7.48(m,3H),7.41-7.35(m,2H),6.65(s,1H) ,5.72(bs,1H),3.81(s,3H),2.80-2.54(m,3H),2.30-2.10(m,2H),2.10-1.90(m,2H),0.90-0.64(m,2H),0.62-0.40(m,2H).

[0900] Example 233, N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide

[0901]

[0902] To a solution of N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide (Example 229) (40 mg, 0.084 mmol) in anhydrous THF (5 mL) was added NaH (60% dispersion in mineral oil, 8.0 mg, 0.203 mmol) at 0°C. The reaction mixture was stirred for 30 min at 0°C, and then iodomethane (26.4 mg, 0.186 mmol) was added dropwise. The reaction mixture was stirred for 3 h at room temperature, quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (10 mg, 23%). 1 H NMR (CDCl3, 400MHz): δ8.40(s,1H),8.06-8.04(m,1H),7.76-7.74(m,2H),7.60-7.49(m,3H),7.45-7.35(m,2H),6.65(s,1H) ),3.81(s,3H),2.93(s,3H),2.80-2.60(m,3H),2.50-2.20(m,2H),2.10-1.90(m,2H),0.90-0.80(m,2H),0.78-0.60(m,2H).

[0903] Example 234, N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamide

[0904]

[0905] Step 1: Methyl 4-(2-(3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate

[0906] A mixture of methyl 4-(2-amino-1-phenyl-1H-imidazol-4-yl)butanoate (Intermediate 26) (364 mg, 1.40 mmol), 3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzoic acid (309 mg, 1.40 mmol), HATU (799 mg, 2.10 mmol) and DIPEA (0.73 mL, 4.20 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (425 mg, 66%). 1 H NMR(CDCl3,400MHz): δ8.36(s,1H),8.10-8.08(m,1H),7.97(s,1H),7.90(s,1H),7.74-7.71(m,2H),7.57-7.50(m,3H),7 .42-7.38(m,2H),6.63(s,1H),6.12-5.99(m,2H),3.70(s,3H),2.69-2.65(m,2H),2.46-2.40(m,2H),2.08-2.00(m,2H).

[0907] Step 2: 4-(2-(3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid

[0908] To a solution of methyl 4-(2-(3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate (420 mg, 0.91 mmol) in MeOH (10 mL) was added 1N-NaOH (3.64 mL, 3.64 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (330 mg, 71%).

[0909] Step 3: N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamide

[0910] A mixture of 4-(2-(3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (200 mg, 0.447 mmol), cyclopropylamine (30.6 mg, 0.536 mmol), HATU (255 mg, 0.670 mmol) and DIPEA (0.23 mL, 1.341 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (116 mg, 53%). 1 H NMR(CDCl3,400MHz): δ8.36(s,1H),8.10-8.08(m,1H),7.95(s,1H),7.90(s,1H),7.74-7.69(m,2H),7.56-7.50(m,3H),7.42-7.36(m,2H),6. 64(s,1H),6.12-5.99(m,2H),5.68(bs,1H),2.78-2.60(m,3H),2.26-2 .20(m,2H)),2.10-2.01(m,2H),0.82-0.76(m,2H),0.60-0.48(m,2H).

[0911] The following compounds were prepared in a similar manner to that described in Example 234 and General Scheme 1.

[0912] [Table 17]

[0913]

[0914] Example 237, 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0915]

[0916] Step 1: Methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamido)-1H-imidazol-4-yl)hexanoate

[0917] A mixture of methyl 6-(2-amino-1-phenyl-1H-imidazol-4-yl)hexanoate (Intermediate 28) (4.05 g, 14.11 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzoic acid (Intermediate 11) (4.0 g, 10.85 mmol), HATU (6.19 g, 16.28 mmol) and DIPEA (5.67 mL, 32.56 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (4.7 g, 68%). 1 H NMR(CDCl3,400MHz): δ8.53(s,1H),8.20-8.14(m,1H),8.05(s,1H),7.99(s,1H),7.80 -7.74(m,3H),7.74-7.68(m,1H),7.66-7.61(m,1H),7.56-7.42(m,3H),7.41-7.35(m, 1H),6.60(s,1H),5.77(s,2H),3.67(s,3H),3.62-3.58(m,2H),2.62-2.58(m,2H),2.3 6-2.32(m,2H),1.76-1.64(m,4H),1.50-1.40(m,2H),0.93-0.88(m,2H),-0.05(s,9H).

[0918] Step 2: 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamido)-1H-imidazol-4-yl)hexanoic acid

[0919] To a solution of methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamido)-1H-imidazol-4-yl)hexanoate (1.9 g, 2.98 mmol) in MeOH (20 mL) was added 1N-NaOH (11.92 mL, 11.92 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (900 mg, 46%).

[0920] Step 3: N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0921] A mixture of 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamido)-1H-imidazol-4-yl)hexanoic acid (200 mg, 0.321 mmol), piperidine (41 mg, 0.481 mmol), HATU (183 mg, 0.481 mmol) and DIPEA (0.17 mL, 0.962 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (150 mg, 68%). 1 H NMR(CDCl3,400MHz): δ8.53(s,1H),8.20-8.12(m,1H),8.06(s,1H),7.99(s,1H),7.80- 7.72(m,3H),7.72-7.69(m,1H),7.66-7.61(m,1H),7.54-7.50(m,2H),7.49-7.45(m,1H) ,7.41-7.38(m,1H),6.62(s,1H),5.77(s,2H),3.60-3.50(m,4H),3.42-3.36(m,2H),2.6 6-2.58(m,2H),2.38-2.30(m,2H),1.80-1.40(m,12H),0.93-0.88(m,2H),-0.05(s,9H).

[0922] Step 4: 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0923] To a solution of N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazole-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-yl)benzamide (300 mg, 0.434 mmol) in THF (20 mL) was added TBAF (1.0 M in THF, 2.17 mL, 2.17 mmol). The reaction mixture was refluxed overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (55 mg, 23%). 1 H NMR (CDCl3, 400MHz): δ8.45(s,1H),8.10-8.07(m,1H),8.05(s,1H),7.96(s,1H),7.77-7.62(m,4H),7.56-7.42(m,4H),7.4 0-7.38(m,1H),6.61(s,1H),3.51-3.48(m,2H),3.39-3.35(m,2H),2.62-2.59(m,2H),2.35-2.31(m,2H),1.8-1.4(m,12H).

[0924] The following compounds were prepared in a similar manner to that described in Example 237 and General Scheme 1.

[0925] [Table 18]

[0926]

[0927]

[0928]

[0929] Example 251, 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0930]

[0931] Step 1: Methyl 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate

[0932] A mixture of methyl 6-(2-amino-1-phenyl-1H-imidazol-4-yl)hexanoate (Intermediate 28) (1.0 g, 3.48 mmol), 3-(1-methyl-1H-indazol-5-yl)benzoic acid (Intermediate 11) (878 mg, 3.48 mmol), HATU (1.98 g, 5.22 mmol) and DIPEA (1.82 mL, 10.44 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (1.05 g, 58%). 1 H NMR (CDCl3, 400MHz): δ8.52(s,1H),8.17-8.14(m,1H),8.02(s,1H),7.97(s,1H),7.78-7.68(m,4H),7.54-7.45(m,4H),7.41-7 .37(m,1H),6.60(s,1H),4.10(s,3H),3.65(s,3H),2.65-2.58(m,2H),2.39-2.31(m,2H),1.78-1.65(m,4H),1.52-1.39(m,2H).

[0933] Step 2: 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid

[0934] To a solution of methyl 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate (535 mg, 1.025 mmol) in MeOH (20 mL) was added 1N-NaOH (4.1 mL, 4.1 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (366 mg, 70%).

[0935] Step 3: 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0936] A mixture of 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid (130 mg, 0.256 mmol), piperidine (33 mg, 0.384 mmol), HATU (146 mg, 0.384 mmol) and DIPEA (0.13 mL, 0.768 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (80 mg, 54%). 1 H NMR (CDCl3, 400MHz): δ8.53(s,1H),8.17-8.15(m,1H),8.02(s,1H),7.96(s,1H),7.77-7.69(m,4H),7.54-7.50(m,2H),7.46-7.38 (m,3H),6.61(s,1H),4.11(s,3H),3.55-3.53(m,2H),3.41-3.37(m,2H),2.62-2.59(m,2H),2.35-2.31(m,2H),1.80-1.40(m,12H).

[0937] Example 252, 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[0938]

[0939] Step 1: N-(4-(6-Hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0940] To a solution of methyl 6-(1-phenyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamido)-1H-imidazol-4-yl)hexanoate (Example 237, Step 1) (410 mg, 0.643 mmol) in anhydrous THF (10 mL) was added LiAlH4 (1.0 M in THF, 0.65 mL, 0.65 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (274 mg, 70%). 1H NMR(CDCl3,400MHz): δ8.53(s,1H),8.20-8.15(m,1H),8.06(s,1H),7.99(s,1H),7.80-7.72 (m,3H),7.73-7.70(m,1H),7.66-7.6(m,1H),7.55-7.49(m,2H),7.49-7.42(m,1H),7.42-7. 38(m,1H),6.60(s,1H),5.78(s,2H),3.68-3.62(m,2H,3.60-3.56(m,2H),2.64-2.58(m,2H) ,1.75-1.68(m,2H),1.62-1.50(m,2H),1.50-1.38(m,4H),0.92-0.86(m,2H),-0.05(s,9H).

[0941] Step 2: N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0942] To a solution of oxalyl chloride (93 μL, 1.082 mmol) in anhydrous DCM was added a solution of DMSO (0.15 mL, 2.165 mmol) in DCM at -78 °C. After 15 min, a solution of N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (550 mg, 0.902 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (0.63 mL, 4.509 mmol) was added and the reaction mixture was warmed to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (380 mg, 69%).

[0943] Step 3: N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0944] To a solution of N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (180 mg, 0.296 mmol) and piperidine (58 μL, 0.593 mmol) in THF was added NaBH3CN (37.3 mg, 0.593 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (110 mg, 55%). 1 H NMR(CDCl3,400MHz): δ8.53(s,1H),8.20-8.16(m,1H),8.06(s,1H),7.99(s,1H),7 .80-7.70(m,4H),7.68-7.62(m,1H),7.54-7.42(m,3H),7.41-7.37(m,1H),6.59(s, 1H),5.77(s,2H),3.62-3.56(m,2H),2.62-2.58(m,2H),2.50-2.30(m,6H),1.75-1 .68(m,2H),1.68-1.50(m,6H),1.50-1.30(m,6H),0.93-0.88(m,2H),-0.05(s,9H).

[0945] Step 4: 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[0946] To a solution of N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazole-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-yl)benzamide (100 mg, 0.418 mmol) in THF (20 mL) was added TBAF (1.0 M in THF, 0.74 mL, 0.74 mmol). The reaction mixture was refluxed overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (55 mg, 23%). 1H NMR (CD3OD, 400MHz): δ8.22(s,1H),8.12(s,1H),8.03(s,1H),7.86-7.84(m,2H),7.77-7.48(m,7H),7.43 -7.42(m,1H),7.08(s,1H),3.28-2.92(m,6H),2.68-2.64(m,2H),1.82-1.58(m,10H),1.58-1.40(m,4H).

[0947] The following compounds were prepared in a similar manner to that described in Example 252 and General Scheme 1.

[0948] [Table 19]

[0949]

[0950]

[0951] Example 258, 3-(1H-indazol-5-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0952]

[0953] Step 1: N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0954] To a solution of N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (Example 256, Step 2) (340 mg, 0.586 mmol) in MeOH (20 mL) was added ethyl 4-aminobutyrate hydrochloride (118 mg, 0.703 mmol), TEA (0.11 mL, 0.762 mmol). The reaction mixture was stirred at room temperature for 30 min, and then NaBH3CN was added. The reaction mixture was stirred at 45°C overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (100 mg, 26%).

[0955] Step 2: 3-(1H-indazol-5-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0956] To a solution of N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazole-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-yl)benzamide (100 mg, 0.154 mmol) in THF (10 mL) was added TBAF (1.0 M in THF, 0.77 mL, 0.77 mmol). The reaction mixture was refluxed overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (30 mg, 37%). 1 H NMR (CDCl3, 400MHz): δ8.51(s,1H),8.18-8.16(m,1H),8.12(s,1H),8.00(s,1H),7.76-7.74(m,2H),7.72-7.69(m,2H),7.57-7.44(m ,4H),7.40-7.38(m,1H),6.62(s,1H),3.40-3.32(m,4H),2.66-2.60(m,2H),2.43-2.39(m,2H),2.06-2.00(m,2H),1.80-1.60(m,4H).

[0957] The following compounds were prepared in a similar manner to that described in Example 258 and General Scheme 1.

[0958] [Table 20]

[0959]

[0960] Example 261, N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide

[0961]

[0962] Step 1: N-(4-(4-(isonitroso)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0963] To a solution of N-(4-(4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (Example 256, Step 2) (300 mg, 0.517 mmol) in EtOH (15 mL) were added TEA (0.18 mL, 1.242 mmol), hydroxylamine hydrochloride (68.3 mg, 0.983 mmol). The reaction mixture was stirred at room temperature for 3 h. The solid was filtered and washed with EtOH (5 mL) to give the title compound (280 mg, 90%).

[0964] Step 2: N-(4-(4-aminobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide

[0965] To a THF solution of N-(4-(4-(isonitroso)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (280 mg, 0.47 mmol) was added 2N-HCl (6.0 mL), zinc powder (615 mg, 9.41 mmol). The reaction mixture was refluxed for 2 h. The reaction mixture was extracted with DCM / water and concentrated under reduced pressure to give the title compound (crude product).

[0966] Step 3: N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide

[0967] A mixture of N-(4-(4-aminobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yl)benzamide (300 mg, 0.52 mmol), cyclopropanecarboxylic acid (54 mg, 0.62 mmol), EDCI (150 mg, 0.77 mmol), HOBt (105 mg, 0.77 mmol) and DIPEA (0.45 mL, 2.58 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (53 mg, 20%).

[0968] Step 4: N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide

[0969] To a solution of N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazole-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide (53 mg, 0.082 mmol) in THF (10 mL) was added TBAF (1.0 M in THF, 0.41 mL, 0.41 mmol). The reaction mixture was refluxed overnight. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (16.5 mg, 39%). 1 H NMR(CDCl3,400MHz): δ8.49(s,1H),8.16-8.14(m,1H),8.10(s,1H),7.98(s,1H),7.76-7.64(m,4H),7.58-7.42(m,4H),7.40-7.37(m,1H),6 .60(s,1H),5.72(bs,1H),3.36-3.30(m,2H),2.64-2.60(m,2H),1.80- 1.60(m,4H),1.38-1.28(m,1H),0.98-0.92(m,2H),0.78-0.70(m,2H).

[0970] Example 262, N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide

[0971]

[0972] Example 262 (31 mg, 45%) was prepared in a similar manner to Example 261. 1 H NMR (CDCl3, 400MHz): δ8.52(s,1H),8.18-8.16(m,1H),8.13(s,1H),8.00(s,1H),7.76-7.74(m,2H),7.72-7.69(m,2H),7.57-7.45(m,4H),7 .40-7.38(m,1H),6.60(s,1H),5.76(bs,1H),3.32-3.26(m,2H),2.64- 2.58(m,2H),1.80-1.30(m,9H),0.98-0.82(m,2H),0.78-0.60(m,2H).

[0973] Example 263, 3-(1-methyl-1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[0974]

[0975] Step 1: N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-indazol-5-yl)benzamide

[0976] To a solution of methyl 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate (Example 251, Step 1) (500 mg, 0.96 mmol) in anhydrous THF (10 mL) was added LiAlH4 (1.0 M in THF, 0.96 mL, 0.96 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (220 mg, 46%).

[0977] Step 2: 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate

[0978] To a solution of N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-indazol-5-yl)benzamide (120 mg, 0.243 mmol) in DCM was added TEA (68 μL, 0.45 mmol). The reaction mixture was cooled to 0°C, and then methanesulfonyl chloride (28 μL, 0.36 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (97 mg, 70%).

[0979] Step 3: 3-(1-methyl-1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[0980] To a solution of piperidine (90 mg, 0.157 mmol) and K2CO3 (44 mg, 0.315 mmol) in ACN was added a solution of 6-(2-(3-(1-methyl-1H-indazol-5-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate (90 mg, 0.157 mmol). The reaction mixture was stirred overnight at 70°C. The reaction mixture was extracted with water / DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (46 mg, 52%). 1 H NMR (CDCl3, 400MHz): δ8.55(s,1H),8.38(s,1H),8.13-8.11(m,1H),7.92(s,1H),7.77-7.72(m,3H),7.54-7.50(m,3H),7.46-7.44(m,2H),7 .41-7.38(m,1H),7.23-7.20(m,1H),6.61(s,1H),6.58(s,1H),2.62- 2.57(m,2H),2.56-2.30(m,6H),1.72-1.60(m,8H),1.50-1.30(m,6H).

[0981] Example 264, 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[0982]

[0983] Example 264 (20 mg, 24%) was prepared in a similar manner to Example 263. 1 H NMR(CDCl3,400MHz): δ8.53(s,1H),8.17-8.15(m,1H),8.02(s,1H),7.96(s,1H),7.76-7.69(m,4H),7.54-7.50 (m,2H),7.46-7.44(m,3H),6.58(s,1H),4.10(s,3H),3.71-3.57(m,4H),2.62-2.10(m,8H),1.80-1.30(m,8H).

[0984] Example 265, N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[0985]

[0986] Step 1: Methyl 2-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)acetate

[0987] A mixture of methyl 2-(2-amino-1-phenyl-1H-imidazol-4-yl)acetate (Intermediate 25) (300 mg, 1.297 mmol), 3-(pyridin-4-yl)benzoic acid (310 mg, 1.556 mmol), HBTU (738 mg, 1.946 mmol) and DIPEA (0.68 mL, 3.892 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (490 mg, 92%).

[0988] Step 2: 2-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid

[0989] To a solution of methyl 2-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)acetate (490 mg, 1.188 mmol) in MeOH (20 mL) was added 1N-NaOH (4.75 mL, 4.75 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (280 mg, 59%).

[0990] Step 3: N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[0991] A mixture of 2-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)acetic acid (100 mg, 0.251 mmol), methylamine hydrochloride (20.3 mg, 0.30 mmol), EDCI (72 mg, 0.376 mmol), HOBt (51 mg, 0.376 mmol) and DIPEA (0.26 mL, 1.506 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (22.8 mg, 22%). 1H NMR (CD3OD, 400MHz): δ8.64-8.62(m,2H),8.29(s,1H),8.01-7.95(m,2H),7.79-7.77 (m,2H),7.63-7.49(m,5H),7.45-7.43(m,1H),7.24(s,1H),3.58(s,2H),2.79(s,3H).

[0992] The following compounds were prepared in a similar manner to that described in Example 265 and General Scheme 1.

[0993] [Table 21]

[0994]

[0995] Example 268, N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[0996]

[0997] Step 1: Methyl 6-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate

[0998] A mixture of methyl 6-(2-amino-1-phenyl-1H-imidazol-4-yl)hexanoate (Intermediate 28) (600 mg, 2.088 mmol), 3-(pyridin-4-yl)benzoic acid (416 mg, 2.088 mmol), HATU (1.20 g, 3.132 mmol) and DIPEA (1.10 mL, 6.264 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (570 mg, 58%). 1 H NMR (CDCl3, 400MHz): δ8.67-8.62(m,2H),8.53(s,1H),8.27-8.24(m,1H),7.78-7.69(m,3H),7.58-7.43(m,5H),7.43 -7.35(m,1H),6.60(s,1H),3.67(s,3H),2.63-2.58(m,2H),2.37-2.30(m,2H),1.75-1.63(m,4H),1.50-1.40(m,2H).

[0999] Step 2: N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[1000] To a solution of methyl 6-(1-phenyl-2-(3-(pyridin-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate (570 mg, 1.22 mmol) in anhydrous THF (20 mL) was added LiAlH4 (1.0 M in THF, 1.22 mL, 1.22 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (380 mg, 70%). 1 H NMR (CDCl3, 400MHz): δ8.67-8.62(m,2H),8.53(s,1H),8.27-8.24(m,1H),7.78-7.69(m,3H),7.58-7.43(m,5H) ),7.43-7.35(m,1H),6.60(s,1H),3.70-3.65(m,2H),2.63-2.58(m,2H),1.78-1.68(m,2H),1.68-1.40(m,6H).

[1001] Step 3: N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[1002] To a solution of oxalyl chloride (88 μL, 1.022 mmol) in anhydrous DCM was added a solution of DMSO (0.15 mL, 2.043 mmol) in DCM at -78 °C. After 15 min, a solution of N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide (375 mg, 0.851 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (0.60 mL, 4.256 mmol) was added and the reaction mixture was warmed to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (240 mg, 64%).

[1003] Step 4: N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide

[1004] To a solution of N-(4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide (240 mg, 0.547 mmol) and piperidine (100 μL, 1.094 mmol) in THF was added NaBH3CN (68.0 mg, 1.094 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (73 mg, 26%). 1 H NMR (CD3OD, 400MHz): δ8.62-8.60(m,2H),8.36(s,1H),8.18-8.12(m,1H),7.91-7.89(m,1H),7.74-7.73(m,2H),7.63-7.50(m,5H),7.44-7 .42(m,2H),7.04(s,1H),2.68-2.64(m,2H),2.60-2.47(m,4H),2.42- 2.38(m,2H),1.76-1.72(m,2H),1.63-1.55(m,6H),1.51-1.40(m,6H).

[1005] The following compounds were prepared in a similar manner to that described in Example 268 and General Scheme 1.

[1006] [Table 22]

[1007]

[1008] Example 271, 3-(6-aminopyridin-3-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1009]

[1010] Step 1: Methyl 6-(2-(3-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate

[1011] A mixture of 3-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)benzoic acid (500 mg, 1.59 mmol), methyl 6-(2-amino-1-phenyl-1H-imidazol-4-yl)hexanoate (Intermediate 28) (685 mg, 2.38 mmol), HATU (907 mg, 2.38 mmol) and DIPEA (0.83 mL, 4.77 mmol) in DCM (18 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (490 mg, 53%). 1 H NMR (CDCl3, 400MHz): δ8.54-8.52(m,1H),8.43(s,1H),8.19-8.16(m,1H),8.04- 8.01(m,1H),7.96-7.91(m,1H),7.77-7.73(m,2H),7.65-7.61(m,2H),7.56-7.50 (m,2H),7.49-7.44(m,1H),7.42-7.38(m,1H),6.60(s,1H),3.67(s,3H),2.65-2. 57(m,2H),2.37-2.33(m,2H),1.76-1.67(m,4H),1.54(s,9H),1.50-1.43(m,2H).

[1012] Step 2: 6-(2-(3-(6-((tert-Butyloxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid

[1013] To a solution of methyl 6-(2-(3-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate (490 mg, 0.83 mmol) in MeOH (4 mL) was added 1N-NaOH (4.2 mL, 4.20 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (400 mg, 84%).

[1014] Step 3: tert-Butyl (5-(3-((4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1015] A mixture of 6-(2-(3-(6-((tert-butyloxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid (140 mg, 0.24 mmol), piperidine (30 mg, 0.36 mmol), EDCI (70.5 mg, 0.36 mmol), HOBt (50 mg, 0.36 mmol) and DIPEA (0.13 mL, 0.73 mmol) in DCM (4 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (70 mg, 45%). 1 H NMR (CDCl3, 400MHz): δ8.53-8.52(m,1H),8.43(s,1H),8.21-8.17(m,1H),8.03-7.99(m, 1H),7.96-7.92(m,1H),7.77-7.73(m,2H),7.70-7.65(m,1H),7.65-7.61(m,1H),7.56-7. 50(m,2H),7.49-7.44(m,1H),7.42-7.38(m,1H),6.61(s,1H),3.58-3.53(m,2H),3.41-3 .37(m,2H),2.65-2.60(m,2H),2.37-2.33(m,2H),1.76-1.67(m,4H),1.64-1.50(m,17H).

[1016] Step 4: 3-(6-aminopyridin-3-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1017] TFA (0.7 mL) was added to a solution of tert-butyl (5-(3-((4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (70 mg, 0.10 mmol) in DCM (3 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (33 mg, 61%). 1H NMR (CDCl3, 400MHz): δ8.39-8.36(m,2H),8.15-8.12(m,1H),7.77-7.71(m,3H),7.59-7.50(m,3H),7.45-7.36(m,2H),6.61-6.57(m, 2H),4.56(bs,2H),3.57-3.53(m,2H),3.41-3.37(m,2H),2.63-2.58(m,2H),2.36-2.31(m,2H),1.75-1.60(m,6H),1.56-1.42(m,6H).

[1018] The following compounds were prepared in a similar manner to that described in Example 271 and General Scheme 1.

[1019] [Table 23]

[1020]

[1021] Example 275, 3-(6-aminopyridin-3-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[1022]

[1023] Step 1: tert-Butyl (5-(3-((4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1024] To a solution of methyl 6-(2-(3-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate (Example 271, Step 1) (520 mg, 0.89 mmol) in anhydrous THF (10 mL) was added LiAlH4 (1.0 M in THF (0.9 mL, 0.9 mmol)) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (240 mg, 48%). 1H NMR (CDCl3, 400MHz): δ8.49-8.47(m,1H),8.39(s,1H),8.16-8.13(m,1H),8.05-8. 02(m,1H),7.97-7.93(m,1H),7.74-7.70(m,2H),7.66-7.61(m,1H),7.56-7.50(m, 2H),7.49-7.44(m,1H),7.42-7.39(m,1H),6.63(s,1H),3.65-3.60(m,2H),2.66-2 .60(m,2H),1.78-1.70(m,2H),1.64-1.58(m,2H),1.55(s,9H),1.50-1.43(m,4H).

[1025] Step 2: 6-(2-(3-(6-((tert-Butyloxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate

[1026] To a solution of tert-butyl (5-(3-((4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (110 mg, 0.19 mmol) and TEA (0.07 mL, 0.49 mmol) in anhydrous DCM (6 mL) was added methanesulfonyl chloride (0.02 mL, 0.25 mmol). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The title compound (110 mg, 91%) was obtained.

[1027] Step 3: tert-Butyl (5-(3-((1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1028] A mixture of 6-(2-(3-(6-((tert-butyloxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate (110 mg, 0.17 mmol), piperidine (50 mg, 0.59 mmol) and KCO (35.5 mg, 0.25 mmol) in ACN (6 mL) was stirred overnight at 80°C. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous NaSO and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (95 mg, 90%). 1H NMR (CDCl3, 400MHz): δ8.53-8.51(m,1H),8.42(s,1H),8.19-8.16(m,1H),8.05-8.01(m,1H),7.9 6-7.92(m,1H),7.77-7.74(m,2H),7.66-7.62(m,1H),7.56-7.51(m,2H),7.49-7.44(m,1H),7.42 -7.38(m,1H),6.63(s,1H),2.97-2.83(m,4H),2.79-2.73(m,2H),2.63-2.57(m,2H),1.96-1.87( m,4H),1.86-1.76(m,2H),1.75-1.67(m,2H),1.62-1.57(m,2H),1.54(s,9H),1.48-1.37(m,4H).

[1029] Step 4: 3-(6-aminopyridin-3-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide

[1030] TFA (0.6 mL) was added to a solution of tert-butyl (5-(3-((1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (80 mg, 0.12 mmol) in DCM (3 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (30 mg, 44%). 1 H NMR (CDCl3, 400MHz): δ8.39-8.36(m,2H),8.15-8.12(m,1H),7.76-7.71(m, 3H),7.59-7.49(m,3H),7.45-7.36(m,2H),6.59-6.56(m,2H),4.54(bs,2H), 2.60-2.55(m,2H),2.44-2.37(m,4H),2.33-2.29(m,2H),1.72-1.65(m,2H), 1.63-1.57(m,4H),1.55-1.50(m,2H),1.46-1.40(m,4H),1.38-1.32(m,2H).

[1031] Example 276, 3-(6-aminopyridin-3-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1032]

[1033] Step 1: tert-Butyl (5-(3-((4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1034] To a solution of oxalyl chloride (0.1 mL, 1.25 mmol) in anhydrous DCM was added a solution of DMSO (0.13 mL, 1.84 mmol) in DCM at -78 °C. After 15 min, a solution of tert-butyl (5-(3-((4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (Example 275, Step 1) (410 mg, 0.73 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (0.51 mL, 3.68 mmol) was added and the reaction mixture was warmed to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (265 mg, 65%).

[1035] Step 2: tert-Butyl (5-(3-((4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1036] To a solution of tert-butyl (5-(3-((4-(6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (265 mg, 0.47 mmol) in MeOH (5 mL) was added ethyl 4-aminobutyrate hydrochloride (180 mg, 1.07 mmol), TEA (0.20 mL, 1.43 mmol). The reaction mixture was stirred at room temperature for 30 min, and then NaBH3CN (90 mg, 1.43 mmol) was added. The reaction mixture was stirred overnight at 45 ° C. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (120 mg, 40%). 1H NMR (CDCl3, 400MHz): δ8.54-8.52(m,1H),8.43(s,1H),8.21-8.17(m,1H),8.04-8.00(m,1H),7.96-7. 92(m,1H),7.77-7.74(m,2H),7.66-7.61(m,1H),7.56-7.50(m,3H),7.49-7.44(m,1H),7.42-7.39(m, 1H),6.60(s,1H),3.40-3.36(m,2H),3.30-3.27(m,2H),2.61-2.57(m,2H),2.42-2.38(m,2H),2.07-1 .98(m,2H),1.74-1.66(m,2H),1.62-1.58(m,2H),1.54(s,9H),1.50-1.42(m,2H),1.40-1.34(m,2H).

[1037] Step 3: 3-(6-aminopyridin-3-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1038] TFA (0.7 mL) was added to a solution of tert-butyl (5-(3-((4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (120 mg, 0.19 mmol) in DCM (3 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (43 mg, 43%). 1 H NMR (CDCl3, 400MHz): δ8.39-8.37(m,2H),8.15-8.12(m,1H),7.77-7.72(m,3H), 7.60-7.50(m,3H),7.46-7.37(m,2H),6.61-6.58(m,2H),4.50(bs,2H),3.40-3.3 6(m,2H),3.31-3.26(m,2H),2.61-2.57(m,2H),2.41-2.36(m,2H),2.06-1.99(m, 2H),1.73-1.66(m,2H),1.58-1.50(m,2H),1.48-1.40(m,2H),1.39-1.32(m,2H).

[1039] Example 277, 3-(6-aminopyridin-3-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1040]

[1041] Example 277 (31 mg, 45%) was prepared in a similar manner to Example 276. 1 H NMR(CDCl3,400MHz)δ8.39-8.37(m,2H),8.15-8.12(m,1H),7.76-7.72(m,3H),7.60-7.50(m,3H),7.46-7.37(m,2H),6.63-6.62(m,1 H),6.61-6.58(m,1H),4.51(bs,2H),3.41-3.32(m,4H),2.67-2.63(m,2H),2.44-2.38(m,2H),2.08-2.00(m,2H),1.74-1.62(m,4H).

[1042] Example 278, 3-(6-aminopyridin-3-yl)-N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1043]

[1044] Step 1: tert-Butyl (5-(3-((4-(6-azidohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1045] To a solution of 6-(2-(3-(6-((tert-butyloxycarbonyl)amino)pyridin-3-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl methanesulfonate (Example 275, Step 2) (298 mg, 0.47 mmol) in DMF (9.5 mL) was added sodium azide (46.7 mg, 0.71 mmol). The reaction mixture was stirred at 90° C. for 3 h. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (210 mg, 77%). 1H NMR (CDCl3, 400MHz): δ8.56-8.54(m,1H),8.43(s,1H),8.20-8.18(m,1H),8.04-8. 01(m,1H),7.97-7.93(m,1H),7.77-7.74(m,2H),7.65-7.61(m,1H),7.56-7.50(m, 2H),7.49-7.44(m,1H),7.42-7.38(m,1H),6.60(s,1H),3.33-3.27(m,2H),2.64-2 .59(m,2H),1.78-1.69(m,2H),1.67-1.58(m,2H),1.54(s,9H),1.47-1.43(m,4H).

[1046] Step 2: tert-Butyl (5-(3-((4-(6-aminohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1047] To a solution of tert-butyl (5-(3-((4-(6-azidohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (210 mg, 0.36 mmol) in MeOH (7 mL) was added palladium on carbon (38 mg). Hydrogen gas was charged into the mixture via a hydrogen balloon and then stirred at room temperature overnight. The reaction mixture was filtered through celite, washed with MeOH, and concentrated under reduced pressure to give the title compound (195 mg, 98%).

[1048] Step 3: tert-Butyl (5-(3-((4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate

[1049] A mixture of tert-butyl (5-(3-((4-(6-aminohexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (195 mg, 0.35 mmol), cyclopropanecarboxylic acid (46 mg, 0.54 mmol), EDCI (103 mg, 0.54 mmol), HOBt (73 mg, 0.54 mmol) and DIPEA (0.19 mL, 1.10 mmol) in DCM (4 mL) was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (120 mg, 55%). 1H NMR (CDCl3, 400MHz): δ8.56-8.54(m,1H),8.43(s,1H),8.21-8.18(m,1H),8.04-8.01(m,1H),7.9 5-7.92(m,1H),7.77-7.73(m,2H),7.65-7.62(m,2H),7.56-7.50(m,2H),7.49-7.44(m,1H),7.42 -7.38(m,1H),6.60(s,1H),3.33-3.24(m,2H),2.62-2.57(m,2H),1.74-1.68(m,2H),1.66-1.60( m,2H),1.54(s,9H),1.48-1.37(m,4H),1.35-1.30(m,1H),0.98-0.95(m,2H),0.74-0.69(m,2H).

[1050] Step 4: 3-(6-aminopyridin-3-yl)-N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1051] TFA (0.7 mL) was added to a solution of tert-butyl (5-(3-((4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)pyridin-2-yl)carbamate (120 mg, 0.19 mmol) in DCM (3 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (40 mg, 40%). 1 H NMR (CDCl3, 400MHz): δ8.39-8.37(m,2H),8.15-8.12(m,1H),7.77-7.72(m,3H) ,7.60-7.50(m,3H),7.46-7.37(m,2H),6.61-6.58(m,2H),5.74(bs,1H),4.48(b s,2H),3.31-3.25(m,2H),2.62-2.58(m,2H),1.75-1.66(m,2H),1.58-1.51(m,2 H),1.46-1.39(m,4H),1.36-1.30(m,1H),0.98-0.93(m,2H),0.73-0.68(m,2H).

[1052] Example 279, 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1053]

[1054] Step 1: Methyl 4-(2-(3-(Benzo[d]thiazol-6-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate

[1055] A mixture of methyl 4-(2-amino-1-phenyl-1H-imidazol-4-yl)butanoate (Intermediate 26) (1.0 g, 4.074 mmol), 3-(benzo[d]thiazol-6-yl)benzoic acid (800 mg, 3.133 mmol), HATU (1.78 g, 4.70 mmol) and DIPEA (1.64 mL, 9.40 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (740 mg, 47%). 1 H NMR (CDCl3, 400MHz): δ9.01(s,1H),8.55(s,1H),8.22-8.18(m,3H),7.83-7.79(m,1H),7.76-7.72(m,3H),7.55-7 .47(m,3H),7.42-7.39(m,1H),6.64(s,1H),3.71(s,3H),2.71-2.65(m,2H),2.48-2.43(m,2H),2.08-2.02(m,2H).

[1056] Step 2: 4-(2-(3-(Benzo[d]thiazol-6-yl)benzoylamino)-1-phenyl-1H-imidazol-4-yl)butanoic acid

[1057] To a solution of methyl 4-(2-(3-(benzo[d]thiazol-6-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate (740 mg, 1.50 mmol) in MeOH (10 mL) was added 1N-NaOH (6.0 mL, 6.0 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (590 mg, 82%).

[1058] Step 3: 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide

[1059] A mixture of 4-(2-(3-(benzo[d]thiazol-6-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid (120 mg, 0.248 mmol), cyclopropylamine (17 mg, 0.298 mmol), HATU (142 mg, 0.373 mmol) and DIPEA (0.13 mL, 0.746 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (77 mg, 59%). 1 H NMR (CDCl3, 400MHz): δ9.01(s,1H),8.55(s,1H),8.22-8.18(m,3H),7.83-7.80(m,1H),7.77-7.72(m,3H)7.54-7.49(m,3H),7.41-7. 38(m,1H),6.65(s,1H),5.65(bs,1H),2.80-2.65(m,3H),2.28-2.21(m,2H),2.10-2.00(m,2H),0.84-0.78(m,2H),0.60-0.50(m,2H).

[1060] The following compounds were prepared in a similar manner to that described in Example 279 and General Scheme 1.

[1061] [Table 24]

[1062]

[1063]

[1064]

[1065]

[1066] Example 292, N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1067]

[1068] Step 1: Methyl 5-bromo-4-oxopentanoate

[1069] To stirring and heating (70 ℃) levulinic acid (10g, 86.12mmol) MeOH (100mL) solution through 10min add Br (4.43mL, 86.12mmol) MeOH (20mL) solution and reflux 2h.Reaction mixture is cooled to room temperature, and desolventizes under reduced pressure.Resistates is diluted with DCM (100mL) and washed with saturated NaHCO The aqueous solution (50mL x 3).Organic phase is through anhydrous Na SO Dry and concentrate under reduced pressure to obtain title compound (obtain crude product).

[1070] Step 2: Methyl 5-(benzylamino)-4-oxopentanoate

[1071] To a solution of methyl 5-bromo-4-oxopentanoate (1.0 g, 4.78 mmol) and benzylamine (614 mg, 5.73 mmol) in dry DMF (30 mL) was added NaHCO (603 mg, 7.17 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate (40 mL) and washed with water (30 mL x 3) and brine (30 mL). The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure to give the title compound (840 mg, 75%).

[1072] Step 3: Methyl 3-(2-amino-1-benzyl-1H-imidazol-4-yl)propanoate

[1073] By 5-(benzylamino)-4-oxopentanoic acid methyl ester (840mg, 3.57mmol) and cyanamide (1.41g, 33.56) MeOH (20mL) solution reflux overnight.Desolventizing under reduced pressure, residue is diluted with DCM (20mL), washed with water (30mLx 3).Organic phase is through anhydrous Na2SO4 dry and concentrated under reduced pressure.Use DCM / MeOH as eluent, by silica gel column chromatography purification, obtain title compound (109mg, 12%).

[1074] Step 4: Methyl 3-(1-benzyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate

[1075] A mixture of methyl 3-(2-amino-1-benzyl-1H-imidazol-4-yl)propanoate (109 mg, 0.42 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (147 mg, 0.46 mmol), HBTU (239 mg, 0.63 mmol) and DIPEA (0.22 mL, 1.26 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (170 mg, 72%). 1 H NMR (CDCl3, 400MHz): δ8.40(s,1H),8.18-8.14(m,1H),7.89(s,2H),7.61-7.57(m,1H),7.43-7.36(m,1H),7.34-7.30(m,5H),6.25(s, 1H),5.47(s,2H),5.17(s,2H),3.70(s,3H),3.62-3.58(m,2H),2.84-2.80(m,2H),2.64-2.61(m,2H),0.94-0.90(m,2H),-0.02(s,9H).

[1076] Step 5: 3-(1-Benzyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid

[1077] To a solution of methyl 3-(1-benzyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate (160 mg, 0.28 mmol) in MeOH (10 mL) was added 1N-NaOH (0.57 mL, 0.57 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was evaporated under reduced pressure and acidified with 1N-HCl, and the solid was filtered to give the title compound (148 mg, 95%).

[1078] Step 6: N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[1079] A mixture of 3-(1-benzyl-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid (148 mg, 0.27 mmol), aniline (25.3 mg, 0.27 mmol), HBTU (154 mg, 0.41 mmol) and DIPEA (0.14 mL, 0.81 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (84 mg, 50%). 1 H NMR(CDCl3,400MHz): δ8.38(s,1H),8.20-8.14(m,1H),7.86(s,1H),7.83(s, 1H),7.59-7.55(m,1H),7.52-7.43(m,3H),7.42-7.38(m,1H),7.35-7.25(m, 7H),7.12-7.06(m,1H),6.29(s,1H),5.44(s,2H),5.14(s,2H),3.62-3.57(m ,2H),2.88-2.82(m,2H),2.52-2.48(m,2H),0.94-0.90(m,2H),-0.02(s,9H).

[1080] Step 7: N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1081] TFA (1.0 mL) was added to a solution of N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (133 mg, 0.21 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (59 mg, 56%). 1H NMR(DMSO-D6,400MHz): δ9.96(s,1H),8.30(s,1H),8.20-7.90(m,3H),7.75-7.60(m,1H),7.59-7.57(m,2 H),7.31-7.27(m,8H),7.05-7.01(M,1H),6.82(s,1H),5.15(s,2H),2.85-2.81(m,2H),2.65-2.61(m,2H).

[1082] The following compounds were prepared in a similar manner to that described in Example 292 and General Scheme 1.

[1083] [Table 25]

[1084]

[1085]

[1086] Example 301, N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1087]

[1088] Step 1: Methyl 8-bromo-7-oxooctanoate

[1089] In MeOH (250mL) solution of 7-oxooctanoic acid (25g, 158.04mmol) stirring and heating (70 ℃), add Br through 10min (8.15mL, MeOH (50mL) solution of 158.04mmol) and reflux 2h.Reaction mixture is cooled to room temperature, and desolventizes under reduced pressure.Resistates is diluted with DCM (100mL) and washed with saturated NaHCO3 aqueous solution (50mL x 3).Organic phase is through anhydrous Na2SO4 dry and under reduced pressure, concentrate, obtain title compound (obtain crude product).

[1090] Step 2: 8-((4-fluorophenyl)amino)-7-oxooctanoic acid methyl ester

[1091] To a solution of methyl 8-bromo-7-oxooctanoate (3.0 g, 11.95 mmol) and 4-fluoroaniline (0.96 mL, 10.15 mmol) in dry DMF (50 mL) was added NaHCO (1.2 g, 14.33 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate (40 mL) and washed with water (30 mL x 3) and brine (30 mL). The organic phase was dried over anhydrous NaSO and concentrated under reduced pressure to give the title compound (3.18 g, 95%).

[1092] Step 3: Methyl 6-(2-amino-1-(4-fluorophenyl)-1H-imidazol-4-yl)hexanoate

[1093] By 8-((4-fluorophenyl) amino)-7-oxooctanoic acid methyl ester (3.18g, 11.3mmol) and cyanamide (2.37g, 56.52mmol) MeOH (50mL) solution reflux overnight. Remove solvent under reduced pressure. Residue is diluted with DCM (20mL), washed with water (30mL x 3). Organic phase is through anhydrous Na2SO4 dry and concentrated under reduced pressure. Use DCM / MeOH as eluent, by silica gel column chromatography purification, obtain title compound (1.19g, 34%). 1 H NMR (CDCl3, 400MHz): δ7.38-7.32(m,2H),7.18-7.13(m,2H),6.37(s,1H),3.66(s ,3H),2.50-2.42(m,2H),2.34-2.28(m,2H),1.70-1.60(m,4H),1.46-1.38(m,2H).

[1094] Step 4: Methyl 6-(1-(4-fluorophenyl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate

[1095] A mixture of methyl 6-(2-amino-1-(4-fluorophenyl)-1H-imidazol-4-yl)hexanoate (500 mg, 1.637 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (573 mg, 1.80 mmol), HATU (934 mg, 2.456 mmol) and DIPEA (0.86 mL, 4.912 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (730 mg, 74%). 1 H NMR(CDCl3,400MHz): δ8.33(s,1H),8.04-8.00(m,1H),7.87(s,1H),7.86(s,1H), 7.70-7.67(m,2H),7.58-7.56(m,1H),7.40-7.37(m,1H),7.22-7.18(m,2H),6.56 (s,1H),5.46(s,2H),3.67(s,3H),3.62-3.57(m,2H),2.62-2.58(m,2H),2.36-2. 32(m,2H),1.74-1.66(m,4H),1.46-1.42(m,2H),0.95-0.91(m,2H),-0.02(s,9H).

[1096] Step 5: N-(1-(4-fluorophenyl)-4-(6-hydroxyhexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[1097] To a solution of methyl 6-(1-(4-fluorophenyl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)hexanoate (730 mg, 1.20 mmol) in anhydrous THF (20 mL) was added LiAlH4 (1.0 M in THF, 1.20 mL, 1.20 mmol) at -78°C. The reaction mixture was stirred at room temperature for 1 h, quenched with water, 15%-NaOH, and stirred for 1 h. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (486 mg, 70%). 1H NMR(CDCl3,400MHz): δ8.34(s,1H),8.04-8.00(m,1H),7.86(s,1H),7.85(s,1 H),7.70-7.67(m,2H),7.58-7.56(m,1H),7.40-7.37(m,1H),7.22-7.18(m,2H) ,6.54(s,1H),5.46(s,2H),3.68-3.65(m,2H),3.62-3.57(m,2H),2.62-2.58( m,2H),1.74-1.65(m,2H),1.65-1.40(m,6H),0.95-0.91(m,2H),-0.02(s,9H).

[1098] Step 6: N-(1-(4-fluorophenyl)-4-(6-oxohexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[1099] To a solution of oxalyl chloride (86 μL, 0.997 mmol) in anhydrous DCM was added a solution of DMSO (0.155 mL, 1.994 mmol) in DCM at -78 °C. After 15 min, a solution of N-(1-(4-fluorophenyl)-4-(6-hydroxyhexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (480 mg, 0.831 mmol) in DCM was added dropwise to the mixture over 10 min. After 1 h, TEA (0.58 mL, 4.154 mmol) was added and the reaction mixture was allowed to warm to room temperature. The reaction mixture was quenched with water and extracted with DCM. The organic phase was washed with 1N-HCl, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (460 mg, 96%).

[1100] Step 7: N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[1101] To a solution of N-(1-(4-fluorophenyl)-4-(6-oxohexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (460 mg, 0.799 mmol) and piperidine (0.16 mL, 1.598 mmol) in THF was added NaBH3CN (100 mg, 1.598 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (260 mg, 50%). 1 H NMR(CDCl3,400MHz): δ8.34(s,1H),8.06-8.02(m,1H),7.86(s,1H),7.85(s,1H),7 .72-7.68(m,2H),7.58-7.52(m,1H),7.40-7.35(m,1H),7.24-7.20(m,2H),6.53(s, 1H),5.46(s,2H),3.62-3.57(m,2H),2.62-2.52(m,2H),2.43-2.25(m,6H),1.72-1 .62(m,2H),1.62-1.50(m,6H),1.50-1.30(m,6H),0.95-0.91(m,2H),-0.02(s,9H).

[1102] Step 8: N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1103] TFA (1.0 mL) was added to a solution of N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (260 mg, 0.40 mmol) in DCM (10 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (124 mg, 60%). 1H NMR (CD3OD, 400MHz): δ8.13-7.90(m,3H),7.80-7.70(m,2H),7.68-7.50(m,2H),7.48-7.42(m,1H),7.27-7.22(m, 2H),7.06(s,1H),3.30-2.98(m,6H),2.69-2.62(m,2H),1.88-1.70(m,8H),1.70-1.58(m,2H),1.58-1.40(m,4H).

[1104] Example 302, N-(1-(2,4-difluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1105]

[1106] Example 302 (155 mg, 62%) was prepared in a similar manner to Example 301. 1 H NMR (CD3OD, 400MHz): δ8.13-7.85(m,3H),7.80-7.70(m,1H),7.70-.65(m,1H),7.65-7.55(m,1H),7.44-7.40(m,1H),7.26-7.21(m, 1H),7.15-7.08(m,1H),6.99(s,1H),3.30-2.98(m,6H),2.67-2.63(m,2H),1.88-1.70(m,8H),1.70-1.58(m,2H),1.58-1.40(m,4H).

[1107] Example 303, N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1108]

[1109] Step 1: Methyl 5-bromo-4-oxopentanoate

[1110] To stirring and heating (70 ℃) levulinic acid (10g, 86.12mmol) MeOH (100mL) solution through 10min add Br (4.43mL, 86.12mmol) MeOH (20mL) solution and reflux 2h.Reaction mixture is cooled to room temperature, and desolventizes under reduced pressure.Resistates is diluted with DCM (100mL) and washed with saturated NaHCO The aqueous solution (50mL x 3).Organic phase is through anhydrous Na SO Dry and concentrate under reduced pressure to obtain title compound (obtain crude product).

[1111] Step 2: tert-Butyl 2-amino-4-(3-methoxy-3-oxopropyl)-1H-imidazole-1-carboxylate

[1112] To a THF solution of methyl 5-bromo-4-oxopentanoate (1.0 g, 4.78 mmol) was added 1-Boc-guanidine (2.28 g, 14.35 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure. Purification by silica gel column chromatography using ethyl acetate / hexane as eluent gave the title compound (955 mg, 74%). 1 H NMR (CDCl3, 400MHz): δ6.55(s,1H),5.58(bs,2H),3.68(s,3H),2.72-2.68(m,2H),2.68-2.60(m,2H),1.58(s,9H).

[1113] Step 3: Methyl 3-(2-amino-1H-imidazol-4-yl)propanoate

[1114] TFA (2.0 mL) was added to a solution of tert-butyl 2-amino-4-(3-methoxy-3-oxopropyl)-1H-imidazole-1-carboxylate (450 mg, 1.67 mmol) in DCM (10 mL) and stirred at room temperature overnight. The mixture was evaporated under reduced pressure to give the title compound (crude product). 1 H NMR (CDCl3, 400MHz): δ11.11(bs,1H),10.87(bs,1H),6.37(s,1H),3.70(s,3H),2.81-2.76(m,2H),2.78-2.60(m,2H).

[1115] Step 4: Methyl 3-(2-amino-1-(pyridin-4-yl)-1H-imidazol-4-yl)propanoate

[1116] 3-(2-amino-1H-imidazole-4-yl)propionic acid methyl ester (710mg, 1.787mmol), 4-iodopyridine (403mg, 1.966mmol), CuI (34mg, 0.179mmol), 8-hydroxyquinoline (40mg, 0.268mmol), Cs2CO3 (2.4mg, 7.149mmol) and t-BuOH (6mL) were added to the sealed tube. The mixture was heated overnight in a sealed tube at 100°C. The reaction mixture was cooled, diluted with ethyl acetate / MeOH (10 / 1), filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure. Using DCM / MeOH as eluent, purified by silica gel column chromatography to obtain the title compound (148mg, 34%). 1 H NMR (CDCl3, 400MHz): δ8.69-8.65(m,2H),7.38-7.33(m,2H),6.52(s,1H),4.50(bs,2H),3.67(s,3H),2.82-2.77(m,2H),2.70-2.62(m,2H).

[1117] Step 4: Methyl 3-(1-(pyridin-4-yl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate

[1118] A mixture of methyl 3-(2-amino-1-(pyridin-4-yl)-1H-imidazol-4-yl)propanoate (147 mg, 0.597 mmol), 3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzoic acid (Intermediate 1) (228 mg, 0.716 mmol), HBTU (340 mg, 0.895 mmol) and DIPEA (0.31 mL, 1.791 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (245 mg, 75%). 1H NMR (CDCl3, 400MHz): δ8.80-8.75(m,2H),8.37(s,1H),2.12-8.08(m,1H),7.90-7.82(m,4H),7.62-7.59(m,1H),7.44-7.40(m,1H) ,6.71(s,1H),5.46(s,2H),3.76(s,3H),3.62-3.58(m,2H),2.95-2.90(m,2H),2.73-2.70(m,2H),0.95-0.90(m,2H),-0.02(s,9H).

[1119] Step 5: 3-(1-(pyridin-4-yl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid

[1120] To a solution of methyl 3-(1-(pyridin-4-yl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoate (228 mg, 0.417 mmol) in MeOH (10 mL) was added 1N-NaOH (0.84 mL, 0.84 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was evaporated under reduced pressure and acidified with 1N-HCl and extracted with DCM. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the title compound (31 mg, 14%).

[1121] Step 6: N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide

[1122] A mixture of 3-(1-(pyridin-4-yl)-2-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamido)-1H-imidazol-4-yl)propanoic acid (31 mg, 0.0582 mmol), aniline (6.5 mg, 0.0698 mmol), HBTU (33.1 mg, 0.0873 mmol) and DIPEA (30 μL, 0.175 mmol) in DCM was stirred overnight at room temperature. The reaction mixture was quenched with water and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (18 mg, 51%).

[1123] Step 7: N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide

[1124] TFA (0.3 mL) was added to a solution of N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide (38 mg, 0.06 mmol) in DCM (5 mL) and stirred at room temperature overnight. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel column chromatography using DCM / MeOH as eluent gave the title compound (8.2 mg, 27%). 1 H NMR (CD3OD, 400MHz): δ8.58-8.56(m,2H),8.22(s,1H),7.97(s,2H),7.86-7.83(m,1H),7.76-7.75(m,2H),7.69-7.68(m,1H),7 .54-7.53(m,2H),7.42-7.38(m,1H),7.29-7.25(m,2H),7.15(s,1H),7.08-7.04(m,1H),2.99-2.95(m,2H),2.78-2.75(m,2H).

[1125] Test Case

[1126] Test Example 1: In vitro IRAK4 phosphorylation activity assay

[1127] In vitro IRAK4 analysis was performed using the N-(1H-imidazole-2-yl)benzamide compounds according to the present invention. All compounds were prepared by dissolving in DMSO. The N-(1H-imidazole-2-yl)benzamide compounds according to the present invention and other elements for the reaction were added to the test wells. In the standard Kinase Profiler service, a pre-incubation step between the N-(1H-imidazole-2-yl)benzamide compound and the kinase was not performed before the reaction.

[1128] All reactants except the N-(1H-imidazol-2-yl)benzamide compound according to the present invention were added to the positive control wells, and DMSO was added to eliminate the solvent effect. A known control inhibitor having the following structure was added to the blank wells to inhibit kinase activity and determine the baseline.

[1129]

[1130] IRAK4 was incubated with 8mM MOPS pH 7.0, 0.2mM EDTA, 0.33mg / mL myelin basic protein, 10mM magnesium acetate and [γ-33P]-ATP (specific activity about 500cpm / pmol, concentration as needed). The reaction was initiated by adding the MgATP mixture. After incubation at room temperature for 40 minutes, the reaction was terminated by adding 3% phosphoric acid solution. Then 10μL of the reaction solution was spotted onto a P30 filter pad and washed three times for 5 minutes in 75mM phosphoric acid and once in methanol before drying and scintillation counting.

[1131] The results are shown in Table 26 below, where the IC values ​​for phosphorylation activity against IRAK4 are 50 The values ​​are shown in categories (A: <50 nM, B: 50-100 nM, C: >100 nM).

[1132] [Table 26]

[1133]

[1134]

[1135]

[1136]

[1137] As shown in Table 26, the N-(1H-imidazol-2-yl)benzamide compounds according to the present invention exhibit excellent inhibitory activity against IRAK-4, which makes the compounds useful for effectively preventing and treating diseases mediated by IRAK-4 receptors, particularly autoimmune diseases and lymphomas.

[1138] Although the present invention has been described with respect to the above specific embodiments, it will be appreciated that various modifications and variations may be made by those skilled in the art which fall within the scope of the present invention as defined by the appended claims.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof: in X is =CH- or =N-; R1 and R2 are each independently H or a 5-10 membered heteroaryl; or R1 and R2 together with the carbon atoms to which they are attached form a 5-7 membered heterocyclic ring; R3 is C 6-10 Aryl, 5-10 membered heteroaryl, C 6-10 Aryl-C 1-3 Alkyl, C 3-10 Cycloalkyl or C 3-10 Cycloalkyl-C 1-3 alkyl; A is -C(=O)-(CH2) n -, -O-C(=O)-(CH2) n -, -N(-Rx)-(CH2) n -, -N(-Rx)-C(=O)-(CH2) n -, -C(=O)-N(-Rx)-(CH2) n -or-(CH2) m -N(-Rx)-C(=O)-(CH2) n -, wherein n is an integer from 0 to 6, m is an integer from 0 to 6, and Rx is H or C 1-6 alkyl; R4 is hydroxyl, hydroxyl C 1-6 Alkyl, C 1-10 Alkoxy, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl or C 6-10 Aryl-(CH2) p -4-10 membered heterocycloalkyl, wherein p is an integer from 0 to 3; The aryl, cycloalkyl, heteroaryl and heterocycloalkyl groups each optionally have at least one selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkoxy, hydroxycarbonyl, halogenated C 1-3 Alkyl, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, hydroxyl C 1-6 Alkyl, cyano, C 1-6 Alkylcarbonyl, C 1-6 Alkylsulfonyl, oxo, nitro, C 1-6 Alkoxycarbonyloxy-C 1-6 alkyl and trimethylsilylethoxymethyl substituents; and The heterocyclic ring, heteroaryl group and heterocycloalkyl group each contain at least one heteroatom selected from N, O and S.

2. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: R1 is H; and R2 is H or a 5-10 membered heteroaryl group containing at least one nitrogen atom, wherein the heteroaryl group optionally has one or two selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkyl, amino, nitro, C 1-6 Alkoxycarbonyloxy-C 1-6 Alkyl and trimethylsilylethoxymethyl substituents; or R1 and R2 together with the carbon atoms to which they are attached form a 5-7 membered heterocyclic ring containing one or two nitrogen atoms.

3. The compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: The heteroaryl group is pyrazolyl, isoxazolyl, pyridyl, indolyl, indazolyl, benzotriazolyl or benzothiazolyl, each of which optionally has one or two substituents selected from fluorine, methyl, 1-ethoxyethyl, 2-ethoxyprop-2-yl, fluoromethyl, difluoromethyl, trifluoromethyl, amino, nitro, methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl and trimethylsilylethoxymethyl.

4. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: R3 is C 6-10 Aryl, C 6-10 Aryl-C 1-3 Alkyl, 5-6 membered heteroaryl containing nitrogen atom, C 5-7 Cycloalkyl or C 5-7 Cycloalkyl-C 1-3 Alkyl, wherein the aryl group optionally has one or two substituents selected from halogen.

5. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: R3 is phenyl, fluorophenyl, difluorophenyl, chlorophenyl, bromophenyl, benzyl, pyridyl, cyclohexyl or cyclohexylmethyl.

6. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: R4 is hydroxyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, amino, C 1-3 Alkylamino, di-C 1-3 Alkylamino, C 3-8 Cycloalkyl, C 6-10 aryl, 5-9 membered heteroaryl, 4-9 membered heterocycloalkyl, phenyl-5-7 membered heterocycloalkyl or benzyl-5-7 membered heterocycloalkyl, wherein the aryl, cycloalkyl, heteroaryl and heterocycloalkyl each optionally have at least one selected from halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy-C 1-6 Alkyl, halogenated C 1-3 Alkoxy, hydroxycarbonyl, halogenated C 1-3 Alkyl, amino, C 1-6 Alkylamino, di-C 1-6 Alkylamino, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl, hydroxyl C 1-6 Alkyl, cyano, C 1-3 Alkylcarbonyl, C 1-3 The substituents of the alkylsulfonyl and oxo groups, and the heteroaryl and heterocycloalkyl groups each contain at least one heteroatom selected from N, O and S.

7. The compound of formula (I) according to claim 6 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: The aryl group is phenyl; the cycloalkyl group is cyclopropyl, cyclobutyl or cyclohexyl; the heteroaryl group is pyridyl, triazolyl, pyrazinyl, pyrazolyl or indazolyl; and the heterocycloalkyl group is piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrofuranyl, azepanyl or diazepanyl.

8. The compound of formula (I) according to claim 6 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: The substituents are selected from fluorine, methyl, tert-butoxy, methoxy, methoxymethyl, trifluoromethoxy, hydroxycarbonyl, trifluoromethyl, amino, methylamino, dimethylamino, cyclopropyl, cyclohexyl, pyrrolidinyl, hydroxyethyl, cyano, methylcarbonyl, methylsulfonyl and oxo.

9. The compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: The pharmaceutically acceptable salt is the hydrochloride, citrate, fumarate, dihydroxysuccinate or succinate of the compound of formula (I).

10. A compound or a pharmaceutically acceptable salt or stereoisomer thereof selected from: 1) 3-(3-nitro-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 2) 3-(3-amino-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 3) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(3-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide; 4) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-5-(1H-pyrazol-4-yl)nicotinamide; 5) 3-(isoxazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 6) N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 7) 3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoic acid; 8) N-(4-(3-oxo-3-(piperidin-1-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 9) N-(4-(3-((4-methylpiperazin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 10) N-(4-(3-((4-fluorophenyl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 11) N-(4-(3-morpholinyl-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 12) N-(4-(3-oxo-3-(piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 13) (S)-N-(4-(3-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 14) N-(4-(3-oxo-3-(4-(4-(trifluoromethoxy)benzyl)piperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 15) N-(4-(3-oxo-3-(pyridin-2-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 16) N-(4-(3-((2,4-difluorophenyl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 17) (R)-N-(4-(3-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 18) methyl 3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoate; 19) (S)-N-(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 20)(R)-N-(4-(3-(2-(methoxymethyl)pyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 21) N-(4-(3-((4H-1,2,4-triazol-4-yl)amino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 22) N-(4-(3-oxo-3-(pyrazin-2-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 23) (R)-N-(4-(3-(2-methylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 24)(S)-N-(4-(3-(2-methylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 25) (R)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)pyrrolidine-3-carboxylic acid; 26)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)pyrrolidine-3-carboxylic acid; 27) N-(4-(3-oxo-3-(pyrrolidin-1-ylamino)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 28) N-(4-(3-oxo-3-(pyrrolidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 29) N-(4-(3-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 30) (R)-N-(4-(3-(2-methylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 31)(S)-N-(4-(3-(2-methylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 32) N-(4-(3-((2R,6S)-2,6-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 33) N-(4-(3-(methylamino)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 34) N-(4-(3-(3,3-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 35) N-(4-(3-(4,4-dimethylpiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 36)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)piperidine-3-carboxylic acid; 37)(S)-1-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propanoyl)piperidine-3-carboxylic acid; 38) (S)-N-(4-(3-oxo-3-(2-(trifluoromethyl)piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 39) (R)-N-(4-(3-oxo-3-(2-(trifluoromethyl)piperidin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 40) (R)-N-(4-(3-(3-aminopiperidin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 41) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 42) methyl 2-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)acetate; 43) 2-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)acetic acid; 44)(S)-N-(4-(2-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 45) (R)-N-(4-(2-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 46)(S)-N-(4-(2-(2-(methoxymethyl)pyrrolidin-1-yl)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 47) (R)-N-(4-(2-(2-(methoxymethyl)pyrrolidin-1-yl)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 48) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-4-(1H-pyrazol-4-yl)benzamide; 49) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-1H-indazole-5-carboxamide; 50) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 51) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)nicotinamide; 52) N-(4-(4-oxo-4-(phenylamino)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 53)(S)-N-(4-(4-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 54) (R)-N-(4-(4-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 55)(S)-N-(4-(4-(2-(methoxymethyl)pyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 56) (R)-N-(4-(4-(2-(methoxymethyl)pyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 57) 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid; 58) methyl 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate; 59) N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 60) N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 61) (R)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 62)(S)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 63) N-(4-(4-((2R,6S)-2,6-dimethylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 64) N-(4-(4-((4-fluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 65) N-(4-(4-((2-fluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 66) N-(4-(4-((2,4-difluorophenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 67) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)benzamide; 68) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 69) N-(4-(4-(cyclobutylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 70) isopropyl 4-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoate; 71) N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 72) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)benzamide; 73) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(2-ethoxypropan-2-yl)-1H-pyrazol-4-yl)benzamide; 74)(4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methyl methyl carboxylate; 75)(4-(3-((4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)carbamoyl)phenyl)-1H-pyrazol-1-yl)methylethylcarboxylate; 76) N-(4-(5-oxo-5-(phenylamino)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 77) methyl 5-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoate; 78) 5-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoic acid; 79) N-(4-(5-oxo-5-(piperidin-1-yl)pentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 80) N-(4-(5-(methylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 81) N-(4-(5-((2R,6S)-2,6-dimethylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 82)(S)-N-(4-(5-(2-methylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 83) (R)-N-(4-(5-(2-methylpiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 84)(S)-N-(4-(5-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 85)(R)-N-(4-(5-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 86)(S)-N-(4-(5-(2-(methoxymethyl)pyrrolidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 87) (R)-N-(4-(5-(2-(methoxymethyl)pyrrolidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 88) N-(4-(5-(cyclopropylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 89) N-(4-(5-(cyclohexylamino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 90) N-(4-(6-oxo-6-(phenylamino)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 91) methyl 6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoate; 92) 6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexanoic acid; 93) N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 94) N-(4-(6-(methylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 95)(S)-N-(4-(6-(2-methylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 96) (R)-N-(4-(6-(2-methylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 97) N-(4-(6-((2R,6S)-2,6-dimethylpiperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 98)(S)-N-(4-(6-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 99) (R)-N-(4-(6-((2-(methoxymethyl)pyrrolidin-1-yl)amino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 100)(S)-N-(4-(6-(2-(methoxymethyl)pyrrolidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 101) (R)-N-(4-(6-(2-(methoxymethyl)pyrrolidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 102) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 103) N-(4-(2-hydroxyethyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 104) N-(1-phenyl-4-(2-(piperidin-1-yl)ethyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 105) N-(4-(3-hydroxypropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 106) N-(1-phenyl-4-(3-(piperidin-1-yl)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 107) N-(4-(3-morpholinopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 108) N-(4-(3-(4-methylpiperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 109) N-(1-phenyl-4-(3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 110) N-(1-phenyl-4-(3-thiomorpholinylpropyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 111) N-(4-(4-hydroxybutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 112) N-(1-phenyl-4-(4-(phenylamino)butyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 113) N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 114) N-(4-(4-morpholinylbutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 115) N-(1-phenyl-4-(4-thiomorpholinylbutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 116) N-(4-(5-hydroxypentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 117) N-(1-phenyl-4-(5-(phenylamino)pentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 118) N-(1-phenyl-4-(5-(piperidin-1-yl)pentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 119) N-(4-(5-morpholinylpentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 120) N-(1-phenyl-4-(5-thiomorpholinylpentyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 121) N-(4-(6-hydroxyhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 122) N-(1-phenyl-4-(6-(phenylamino)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 123) N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 124) N-(1-phenyl-4-(6-thiomorpholinylhexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 125) 1-(6-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)hexyl)piperidine 1-oxide; 126) 4-(3-(2-(3-(1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)propyl)morpholine 4-oxide; 127) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide hydrochloride; 128) N-(4-(3-morpholinopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide hydrochloride; 129) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide hydrochloride; 130) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide hydrochloride; 131) N-(4-(4-((4-(dimethylamino)cyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide hydrochloride; 132) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((1-methylpiperidin-4-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide hydrochloride; 133) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide citrate; 134) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide fumarate; 135) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide (2R,3R)-2,3-dihydroxysuccinate; 136) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide succinate; 137) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide fumarate; 138) 3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 139) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 140) 4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoic acid; 141) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 142) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 143) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 144) N-(4-(4-(4-ethylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 145) N-(4-(4-(4-isopropylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 146) N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 147) N-(4-(4-((4-(dimethylamino)cyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 148) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((1-methylpiperidin-4-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 149) N-(4-(4-(4-cyclopropylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 150) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(pyridin-4-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 151) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(pyrrolidin-1-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 152) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 153) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 154) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 155) N-(4-(4-((4-(dimethylamino)phenyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 156) N-(4-(4-(((1R,4R)-4-hydroxycyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 157) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((tetrahydro-2H-pyran-4-yl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 158) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((3-(piperidin-1-yl)propyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 159) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((2-(piperidin-1-yl)ethyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 160) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-morpholinyl-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 161) N-(4-(4-((4-methoxycyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 162) N-(4-(4-((2-(dimethylamino)ethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 163) N-(4-(4-((3-(dimethylamino)propyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 164) N-(4-(4-((2-hydroxyethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 165) N-(4-(4-((3-hydroxypropyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 166) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(2-methylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 167) N-(4-(4-(4,4-dimethylpiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 168) N-(4-(4-(4-cyanopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 169) N-(4-(4-(4-hydroxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 170) N-(4-(4-((2-hydroxy-2-methylpropyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 171) N-(4-(4-((3-hydroxy-3-methylbutyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 172) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 173) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-(4-(trifluoromethoxy)benzyl)piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 174) (R)-N-(4-(4-(2-(2-hydroxyethyl)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 175) N-(4-(4-(3,3-difluoropiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 176) (R)-3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(2-(trifluoromethyl)piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 177) N-(4-(4-(4-methoxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 178) N-(4-(4-(3-hydroxypiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 179) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-((tetrahydrofuran-3-yl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 180) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(((tetrahydrofuran-3-yl)methyl)amino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 181) N-(4-(4-(4-(tert-butyl)piperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 182) N-(4-(4-(4-cyclohexylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 183) N-(4-(4-(4-methyl-1,4-diazepan-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 184) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((2-morpholinylethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 185) (R)-N-(4-(4-((2-fluoro-3-hydroxy-3-methylbutyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 186) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 187) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 188) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(4-phenylpiperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 189) N-(4-(4-amino-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 190) N-(4-(4-((1-methyl-1H-pyrazol-3-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 191) N-(4-(4-((1-methyl-1H-indazol-5-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 192) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 193) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(phenylamino)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 194) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-(4-methylpiperazin-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 195) N-(4-(3-(4-methyl-1,4-diazepan-1-yl)-3-oxopropyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 196) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-(4-methylpiperazin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 197) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-oxo-5-((tetrahydro-2H-pyran-4-yl)amino)pentyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 198) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-((2-morpholinylethyl)amino)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 199) N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 200) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 201) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 202) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 203) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(3-oxo-3-(piperazin-1-yl)propyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 204) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(5-oxo-5-(piperazin-1-yl)pentyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 205) N-(4-(4-(4-acetylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 206) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-(methylsulfonyl)piperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 207)(S)-1-(4-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)butanoyl)piperidine-3-carboxylic acid; 208) (S)-1-(5-(2-(3-(1-methyl-1H-pyrazol-4-yl)benzamido)-1-phenyl-1H-imidazol-4-yl)pentanoyl)piperidine-3-carboxylic acid; 209) N-(4-(4-(4-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 210) (R)-N-(4-(4-(3-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 211)(S)-N-(4-(4-(3-aminopiperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 212) (R)-N-(4-(4-(3-aminopyrrolidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 213) N-(4-(5-(4-aminopiperidin-1-yl)-5-oxopentyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 214) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-4-ylamino)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 215) N-(4-(4-(((1R,4R)-4-aminocyclohexyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 216) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-(methylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 217) N-(4-(4-((1H-pyrazol-3-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 218) N-(4-(4-(methyl(4-methylpiperazin-1-yl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 219) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide; 220) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 221) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 222) 3-(1-methyl-1H-pyrazol-4-yl)-N-(1-phenyl-4-(6-(pyrrolidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 223) N-(4-(6-(azepan-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 224) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 225) 3-(1-methyl-1H-pyrazol-4-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 226) N-(4-(6-(2,5-dioxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 227) N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 228) N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 229) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1H-pyrazol-4-yl)benzamide; 230) 3-(5-fluoro-1H-pyrazol-4-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 231) 3-(5-fluoro-1H-pyrazol-4-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 232) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide; 233) N-(4-(4-(cyclopropyl(methyl)amino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(5-fluoro-1-methyl-1H-pyrazol-4-yl)benzamide; 234) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(fluoromethyl)-1H-pyrazol-4-yl)benzamide; 235) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(difluoromethyl)-1H-pyrazol-4-yl)benzamide; 236) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide; 237) 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 238) N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide; 239) 3-(1H-indazol-5-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 240) 3-(1H-indazol-5-yl)-N-(4-(6-oxo-6-(pyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 241) N-(4-(6-(azepan-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide; 242) 3-(1H-benzo[d][1,2,3]triazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 243) 3-(1H-indazol-5-yl)-N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 244) 3-(1H-indazol-5-yl)-N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 245) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide; 246) 3-(1H-indazol-5-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 247) 3-(1H-indazol-5-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 248) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-7-yl)benzamide; 249) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-4-yl)benzamide; 250) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-6-yl)benzamide; 251) 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 252) 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 253) 3-(1H-indol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 254) 3-(1H-indazol-5-yl)-N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 255) 3-(1H-indazol-4-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 256) 3-(1H-indazol-5-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide; 257) 3-(1H-indazol-4-yl)-N-(1-phenyl-4-(4-(piperidin-1-yl)butyl)-1H-imidazol-2-yl)benzamide; 258) 3-(1H-indazol-5-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 259) 3-(1H-indazol-5-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 260) 3-(1H-indazol-5-yl)-N-(4-(6-(2-oxopiperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 261) N-(4-(4-(cyclopropanecarboxamido)butyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide; 262) N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)-3-(1H-indazol-5-yl)benzamide; 263) 3-(1-methyl-1H-indazol-5-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 264) 3-(1-methyl-1H-indazol-5-yl)-N-(4-(6-morpholinylhexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 265) N-(4-(2-(methylamino)-2-oxoethyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide; 266) N-(4-(4-(methylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide; 267) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide; 268) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-4-yl)benzamide; 269) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-2-yl)benzamide; 270) N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(pyridin-3-yl)benzamide; 271) 3-(6-aminopyridin-3-yl)-N-(4-(6-oxo-6-(piperidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 272) 3-(6-aminopyridin-3-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 273) 3-(6-aminopyridin-3-yl)-N-(4-(4-oxo-4-(piperidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 274) 3-(6-aminopyridin-3-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 275) 3-(6-aminopyridin-3-yl)-N-(1-phenyl-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)benzamide; 276) 3-(6-aminopyridin-3-yl)-N-(4-(6-(2-oxopyrrolidin-1-yl)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 277) 3-(6-aminopyridin-3-yl)-N-(4-(4-(2-oxopyrrolidin-1-yl)butyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 278) 3-(6-aminopyridin-3-yl)-N-(4-(6-(cyclopropanecarboxamido)hexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 279) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 280) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 281) 3-(Benzo[d]thiazol-6-yl)-N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 282) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(4-(dimethylamino)piperidin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 283) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 284) 3-(Benzo[d]thiazol-5-yl)-N-(4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 285) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 286) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 287) 3-(Benzo[d]thiazol-6-yl)-N-(4-(6-(4-(dimethylamino)piperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 288) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(4-methylpiperazin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 289) N-(4-(6-(azepan-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)-3-(benzo[d]thiazol-5-yl)benzamide; 290) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(cyclopropylamino)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 291) 3-(Benzo[d]thiazol-5-yl)-N-(4-(6-(4-(dimethylamino)piperidin-1-yl)-6-oxohexyl)-1-phenyl-1H-imidazol-2-yl)benzamide; 292) N-(1-benzyl-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 293) N-(1-(3-chlorophenyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 294) N-(1-(3-bromophenyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 295) N-(1-(cyclohexylmethyl)-4-(3-oxo-3-(phenylamino)propyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 296) N-(1-cyclohexyl-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 297) N-(1-(4-fluorophenyl)-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 298) N-(1-(2,4-difluorophenyl)-4-(4-(methylamino)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 299) N-(1-(4-fluorophenyl)-4-(4-(4-methylpiperazin-1-yl)-4-oxobutyl)-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 300) N-(4-(4-(cyclopropylamino)-4-oxobutyl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)-3-(1-methyl-1H-pyrazol-4-yl)benzamide; 301) N-(1-(4-fluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; 302) N-(1-(2,4-difluorophenyl)-4-(6-(piperidin-1-yl)hexyl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide; and 303) N-(4-(3-oxo-3-(phenylamino)propyl)-1-(pyridin-4-yl)-1H-imidazol-2-yl)-3-(1H-pyrazol-4-yl)benzamide.

11. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 10 or a pharmaceutically acceptable salt or stereoisomer thereof as an active ingredient, and a pharmaceutically acceptable carrier or excipient.

12. A pharmaceutical composition for preventing or treating a disease mediated by IRAK4 (interleukin-1 receptor associated kinase 4), comprising a compound of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof according to any one of claims 1 to 10 as an active ingredient. 13 . The pharmaceutical composition according to claim 12 , wherein the disease mediated by IRAK4 is an autoimmune disease or lymphoma.

14. The pharmaceutical composition according to claim 12, wherein the disease mediated by IRAK4 is selected from atopic dermatitis, alopecia areata, allergy, asthma, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia, psoriasis, arthritis, frozen shoulder, tendonitis, peritonitis, hepatitis, cystitis, nephritis, Sjögren's syndrome, multiple sclerosis or activated B-cell-like diffuse large B-cell lymphoma.

15. The pharmaceutical composition according to claim 12, wherein the disease mediated by IRAK4 is selected from osteoarthritis and rheumatoid arthritis.

16. The pharmaceutical composition according to claim 12, wherein the disease mediated by IRAK4 is selected from tendinitis and myositis.

17. Use of the compound (I) or a pharmaceutically acceptable salt or stereoisomer thereof according to any one of claims 1 to 10 in the preparation of a medicament for preventing or treating a disease mediated by IRAK4.

18. Use of the compound (I) or a pharmaceutically acceptable salt or stereoisomer thereof according to any one of claims 1 to 10 in the preparation of a medicament for inhibiting IRAK4.

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