Novel pyrazole derivatives

Abstract

The present invention provides novel pyrazole derivative compounds represented by chemical formula I, stereoisomers thereof, solvates thereof, isotopic variations thereof, tautomers thereof, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing the same. [Chemical formula I] TIFF2023536764000044.tif36149 (In the above formula, A, B, R, etc. are as defined in the description of the invention.)

Description

[Technical field]

[0001] The present invention relates to a novel pyrazole derivative having excellent oxidative stress-suppressing activity, more specifically, to a novel pyrazole derivative exhibiting preventive, ameliorative or therapeutic activity against various related diseases due to its excellent oxidative stress-suppressing activity, its optical isomer, its stereoisomer, its solvate, its isotopic variant, its tautomer, or its pharma- ceutically acceptable salt, methods for producing these, and pharmaceutical compositions containing these. [Background technology]

[0002] Oxidative stress refers to the phenomenon in which the production of reactive oxygen species or reactive nitrogen species in biological molecules, cells, and tissues in the body becomes relatively excessive as a result of a loss of balance between the production of reactive oxygen species or reactive nitrogen species and the antioxidant defense mechanisms, which usually results in cell and tissue damage.

[0003] Reactive oxygen species (ROS) are a collective term for oxygen free radicals produced by the chemical properties of oxygen and oxygen compounds derived from them, such as superoxide anion (O2-·), hydrogen peroxide (H2O2), hydroxyl group (OH·), alkoxyl group (RO·), and peroxyl group (ROO·).

[0004] These reactive oxygen species are chemically very unstable and highly reactive, and thus induce inflammation in the surrounding area by inducing a wide range of oxidative damage to enzyme catalysis, electron transport in mitochondria, cell signaling and gene expression, activation of transcription factors, and biomolecules, cells, tissues, etc. in the body, and are involved as a major factor in tissue fibrosis. Such oxidative damage induces various diseases in all tissues of the human body. Specifically, it is known that reactive oxygen species are involved in the development and progression of cancer in tissues such as the skin, kidneys, heart, joints, lungs, brain, blood vessels, intestines, and eyes, as well as playing an important role in almost all diseases such as cardiovascular disease, inflammation, fibrotic disease, and diabetes.

[0005] Recently, it has been known that the interaction between the tumor microenvironment and cancer cells plays a major role in tumor growth, metastasis, and the expression of anticancer drug resistance, in which cancer associated fibroblasts (CAFs) play an important role. CAFs are known to promote tumor immune evasion by being activated by ROS, which contributes to the malignant progression and metastasis of cancer. Therefore, CAFs have recently emerged as a new target for cancer therapy.

[0006] It has been reported that in liver tissue from patients with progressive liver fibrosis, TGF-β1 stimulation induces increased ROS production in liver cells, leading to increased expression of collagen and αSMA, which are important in fibrosis. It has been reported that ROS aggravate pulmonary fibrosis in lung tissue from patients with idiopathic pulmonary fibrosis.

[0007] The brain is a tissue with a very high metabolic rate and is therefore highly vulnerable to oxidative damage. Therefore, many studies have been conducted to effectively remove ROS for the treatment of various neurodegenerative diseases (Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury, etc.), but they have not been successful. Recently, ROS has been identified as a key factor in these brain diseases, and the possibility of treatment by inhibiting ROS has been reported.

[0008] Keloids are a type of benign tumor disease in which connective tissue in the skin grows abnormally, forming hard bumps, thinning the epidermis, making it shiny and slightly red. It has been reported that one of the reasons for the onset and exacerbation of keloids is the overexpression of connective tissue growth factor (CTGF) due to ROS generated by TGF-β stimulation.

[0009] In the case of diabetes, as hyperglycemic conditions persist for a long period of time, complications such as diabetic nephropathy and diabetic retinopathy can occur, and it is known that ROS play an important role in the development of these complications. In other words, hyperglycemia leads to increased production of ROS, and the ROS generated at this time can induce diabetic nephropathy and diabetic retinopathy through a series of processes that induce the death of kidney and retinal cells. In addition, as observed in keloid diseases, it has been reported that overexpression of the CTGF gene in the retina of the eye induces retinal fibrosis and macular degeneration.

[0010] Therefore, the present inventors conducted research focusing on the possibility of developing therapeutic agents for cancer, inflammatory diseases, fibrotic diseases, degenerative neurological diseases, liver diseases, skin diseases, retinal diseases, and the like caused by oxidative stress by utilizing the molecular mechanism of inhibiting the generation of oxidative stress. As a result, they found that the novel pyrazole derivatives of the present invention have excellent ROS generation inhibitory activity and confirmed that they can be used to treat various diseases related to oxidative stress, thereby completing the present invention. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] International Publication No. 2016-207785 Summary of the Invention [Problem to be solved by the invention]

[0012] The present invention aims to provide a pyrazole-based compound of formula I, its optical isomers, its stereoisomers, its solvates, its isotopic variations, its tautomers, or pharma- ceutically acceptable salts thereof.

[0013] The present invention aims to provide a pharmaceutical composition comprising a compound of formula I, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier.

[0014] The present invention aims to provide a method for modulating the production of ROS using a compound of Formula I, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof.

[0015] The present invention aims to provide a method for treating diseases associated with oxidative stress by administering to an individual a compound of formula I, or a stereoisomer, solvate, isotopic variant, tautomer, or a pharma- ceutically acceptable salt thereof.

[0016] The present invention aims to provide a method for preparing a compound of formula I, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof.

[0017] The present invention aims to provide a use of a compound of formula I, a solvate, a stereoisomer or a pharma- ceutically acceptable salt thereof for the preparation of a pharmaceutical composition for the prevention, amelioration or treatment of diseases associated with oxidative stress. [Means for solving the problem]

[0018] In order to achieve the above object, one aspect of the present invention provides a compound represented by the following chemical formula I, which is a novel pyrazole derivative, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof. [Chemical formula 1] [ka] In the above formula, A, B and R are defined as follows.

[0019] One aspect of the present invention provides a compound represented by the above chemical formula I, a solvate, a stereoisomer or a pharma- ceutically acceptable salt thereof for use in the prevention, amelioration or treatment of a disease associated with oxidative stress.

[0020] One aspect of the present invention provides a pharmaceutical composition for treating a disease associated with oxidative stress, comprising as an active ingredient a compound represented by formula I, a solvate, a stereoisomer or a pharma- ceutically acceptable salt thereof, and an acceptable carrier.

[0021] The present invention also provides a method for treating a disease associated with oxidative stress, comprising administering to a subject in need of treatment an effective amount of a compound represented by formula I, a solvate, a stereoisomer, or a pharma- ceutically acceptable salt thereof.

[0022] The present invention also provides the use of a compound of formula I, a solvate, a stereoisomer or a pharma- ceutically acceptable salt thereof for the preparation of a pharmaceutical composition for the prevention or treatment of a disease associated with oxidative stress. Effect of the Invention

[0023] The novel pyrazole derivative according to the present invention and the pharmaceutical composition containing the same provide excellent effects on diseases associated with oxidative stress.

[0024] In addition, the novel pyrazole derivative effectively suppresses oxidative stress and the production of αSMA in various cells, and in particular has the effect of effectively improving cancer, inflammatory diseases, fibrotic diseases, degenerative neurological diseases, liver diseases, skin diseases, retinal diseases, etc. caused by oxidative stress. [Brief description of the drawings]

[0025] [Figure 1] FIG. 1 shows the effect of the compounds of the Synthesis Examples in suppressing PMA-induced ROS production in LX-2 and NHLF cells. [Diagram 2] FIG. 1 shows the effect of the compound of Synthesis Example 3 in suppressing ROS production induced by alpha-synuclein preformed fibril (PFF) in N27 cells. [Figure 3a] FIG. 3 shows the effect of the compounds of the synthesis examples (FIG. 3a: compounds 1, 23 and 12) in suppressing the expression of αSMA induced by TGF β1 in HFF cells. [Figure 3b] FIG. 3 shows the effect of the compounds of the synthesis examples (FIG. 3b: 5, 14 and 33) in suppressing the expression of αSMA induced by TGF β1 in HFF cells. [Figure 4] FIG. 1 shows the effect of Compound 1 of Synthesis Example in suppressing the expression of αSMA induced by TGF β1 in various cells. [Diagram 5] FIG. 1 shows the effect of the compounds of the synthesis examples in suppressing the expression of IL6 in P.CAF cells. [Figure 6] FIG. 1 shows the effect of the compounds of the synthesis examples in suppressing the expression of IL8 in P.CAF cells. [Figure 7] FIG. 1 shows the effect of the compounds of the synthesis examples in suppressing collagen gel contraction induced by TGF β1 in HFF cells. [Figure 8] FIG. 1 shows the effect of the compounds of the synthesis examples in suppressing the expression of IL1β induced by LPS in LX2, NHLF, ARPE19 and KEL-Fib cells. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The present invention will now be described in more detail.

[0027] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. In addition, numerical values ​​described herein are considered to include the meaning of "about" unless otherwise specified. All publications and other references mentioned herein are incorporated herein by reference in their entirety. The definitions of residues used herein are set forth below, and unless otherwise defined, residues are used as generally understood by those of skill in the art.

[0028] As used herein, the term "independently" means that when one or more substituents are selected from a number of possible substituents, those substituents are either the same or different from one another.

[0029] As used herein, the term "alkyl" refers to an aliphatic hydrocarbon radical and means a linear or branched, monovalent, saturated hydrocarbon group. Unless otherwise defined, the alkyl group generally contains 1 to 10, 1 to 8, 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, and t-butyl), pentyl (e.g., n-pentyl, isopentyl, and neopentyl), n-hexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

[0030] As used herein, the term "alkenyl" refers to an aliphatic hydrocarbon radical containing one or more carbon-carbon double bonds, and includes all linear and branched hydrocarbon radicals. For example, "alkenyl" is vinyl, allyl, but-1-enyl, or but-2-enyl.

[0031] As used herein, the term "alkynyl" refers to an aliphatic hydrocarbon radical containing one or more carbon-carbon triple bonds, and includes all linear and branched hydrocarbon radicals. For example, "alkynyl" is ethynyl, propynyl, or butynyl.

[0032] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents. Haloalkyl includes -CF3, -C2F5, -CHF2, -CCl3, -CHCl2, and -C2Cl5. Unless otherwise defined, the haloalkyl group generally contains 1 to 6, 1 to 5, 1 to 4, or 1 to 3 carbon atoms and may be additionally substituted with other substituents.

[0033] In the present specification, the term "alkoxy" may be a straight chain, a branched chain, or a cyclic chain. The number of carbon atoms of the alkoxy group is not particularly limited, but it is preferable that the number of carbon atoms is 1 to 10, 1 to 8, 1 to 6, 1 to 4, or 1 to 3. Specifically, it may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, isopentyloxy, etc., but is not limited thereto. The terms "hydroxy" or "hydroxyl," as used herein, alone or in combination with other terms, refer to --OH. As used herein, the term "amino" refers to --NH.sub.2. As used herein, the terms "halo," "halogen" and "halogen" refer to fluorine, chlorine, bromine and iodine.

[0034] As used herein, the term "cycloalkyl" refers to non-aromatic carbocyclic rings, including cyclized alkyl, alkenyl, and alkynyl groups. The cycloalkyl groups can include a single ring or multiple rings. The multiple rings can have, for example, 2, 3, or 4 fused rings. Unless otherwise defined, the cycloalkyl groups generally include 3 to 10, or 3 to 7 ring carbon atoms. Cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclohexadienyl, cycloheptatrienyl, and the like, and may be further substituted with other substituents.

[0035] In the present specification, the term "aryl" refers to an aromatic hydrocarbon group having a single ring or multiple rings, which may be additionally substituted by other substituents. Here, the multiple rings refer to a group in which an aryl group is directly linked to or condensed with another ring group. Here, the other ring group may be an aryl group, but may also be other types of ring groups, such as a cycloalkyl group, a heteroaryl group, etc. The multiple rings may have, for example, 2, 3, or 4 rings. Unless otherwise defined, the aryl group generally has 5 to 20, 6 to 15, 6 to 12, or 6 to 10 carbon ring atoms. The aryl group includes, for example, phenyl, naphthyl (e.g., naphthyl-1-yl and naphthyl-2-yl), biphenyl, anthracenyl, phenanthrenyl, etc.

[0036] As used herein, the term "heterocycle" refers to an aromatic, saturated or partially unsaturated mono-, bi-, di- or poly-ring system containing the specified number of ring atoms, including one or more heteroatoms selected from N, O and S. The ring members, where the heterocycle, are linked to the base molecule via a ring atom, which may be C or N. The bicyclic systems may be linked in a 1,1-fused (spiro), 1,2-fused (fused) or 1,>2-fused (bridgehead) configuration.

[0037] As used herein, the term "heteroaryl" refers to a monovalent aromatic group having one or more heteroatoms selected from N, O, and S as ring members. Heteroaryl groups include monocyclic or polycyclic structures. The polycyclic ring may have, for example, 2, 3, or 4 fused rings. Unless otherwise defined, the heteroaryl group generally contains 3 to 10, 3 to 7, or 3 to 5 ring atoms. The heteroaryl group may contain 1, 2, or 3 heteroatoms. Heteroaryl groups include, for example, furanyl, pyridyl, N-oxopyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, quinolyl, isoquinolyl, dihydroisoquinolyl, thienyl, imidazolyl, furanyl, thiazolyl, indolyl, pyrryl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, benzothienyl, purinyl, benzimidazolyl, indolinyl, and the like, and may be further substituted with other substituents.

[0038] As used herein, the term "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic or heterocycloalkyl having 3-10 carbon ring members containing one or more, e.g., 1-4, 1-3, or 1-2, heteroatoms selected from N, O and S. The heterocyclo of the present invention may also be a fused or bridged heterocycloalkyl. Examples of non-aromatic rings include azetidinyl, oxetanyl, tetrahydrofuran, pyrrole, pyrrolidinyl, imidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyrazolopyridinyl, morpholinyl, indolinyl, azethiomorpholinyl, and the like.

[0039] The bond of the heterocycloalkyl substituent is bonded via a carbon atom or a heteroatom. The heterocycloalkyl group is optionally substituted via one or more of the above-mentioned groups with one or more preferred groups. Unless otherwise defined, the heterocycloalkyl is a 4-12 membered heterocycloalkyl, preferably a 4-10 membered heterocycloalkyl, more preferably a 4-7 membered heterocycloalkyl.

[0040] As used herein, the term "arylalkyl" refers to an alkyl group substituted with an aryl group, where "aryl" and "alkyl" are defined above.

[0041] As used herein, the term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl group, where "heteroaryl" and "alkyl" are defined above.

[0042] As used herein, the term "alkylheterocycloalkyl" refers to a heterocycloalkyl group substituted with an alkyl group, where "alkyl" and "heterocycloalkyl" are defined above.

[0043] In the present specification, the "substituted or unsubstituted amine group" is selected from the group consisting of a monoalkylamine group, -NH2, and a dialkylamine group, where "alkyl" is as defined above. Specific examples of the substituted or unsubstituted amine group include, but are not limited to, NH2, a methylamine group, a dimethylamine group, an ethylamine group, and a diethylamine group.

[0044] In this specification, the term "alkylene group" refers to an alkyl group having two bonding positions, i.e., a divalent group. The above description of the alkyl group is applicable to these groups, except that they are both divalent groups.

[0045] As used herein, the term "substituted" means that a hydrogen atom bonded to a carbon atom of a compound is replaced with another substituent, and the position of the substitution is not limited as long as it is the position of a hydrogen atom to be replaced, i.e., a position substitutable by a substituent, and when two or more substituents are replaced, the two or more substituents may be the same or different from each other, and two or more identical or different substituents may be linked to form a substitution.

[0046] In the present specification, the term "substituted alkyl" refers to a form in which the carbon atom of a linear or branched alkyl having 1 to 10 carbon atoms is substituted with the following substituents. Specifically, it refers to a form in which one or more substituents selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms or heteroaryl having 5 to 20 carbon atoms, alkoxy having 1 to 5 carbon atoms, and haloalkyl having 1 to 5 carbon atoms are linked to substitute, or two or more identical or different substituents are linked to substitute. Exemplary substituents that can be used include, but are not limited to, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl-substituted imidazole, pyridine, substituted or unsubstituted sulfonyl, and the like.

[0047] The term "substituted cycloalkyl" as used herein refers to a cycloalkyl having 3 to 8 carbon atoms, which is substituted by one or more substituents selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms or heteroaryl having 5 to 20 carbon atoms, alkoxy having 1 to 5 carbon atoms, and haloalkyl having 1 to 5 carbon atoms, or two or more identical or different substituents. Exemplary substituents that can be used include, but are not limited to, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl-substituted imidazole, substituted or unsubstituted sulfonyl, and the like.

[0048] The term "substituted aryl" or "substituted heteroaryl" as used herein refers to a form in which an aryl having 5 to 20 carbon atoms or a heteroaryl having 5 to 50 carbon atoms is substituted by one or more substituents selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amine, alkoxy having 1 to 5 carbon atoms, haloalkyl having 1 to 5 carbon atoms, alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms or heterocycloalkyl having 3 to 8 carbon atoms, cycloalkyl having 1 to 10 carbon atoms, alkyl having 1 to 10 carbon atoms, and aryl having 5 to 20 carbon atoms and alkyl having 1 to 10 carbon atoms, or two or more identical or different substituents. Exemplary substituents that can be used include, but are not limited to, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl-substituted imidazole, methylpiperazine-substituted imidazopyrimidine, substituted or unsubstituted sulfonyl, and the like.

[0049] In this specification, the term "adjacent" refers to a substituent substituted on an atom directly connected to the atom on which the substituent is substituted, a substituent sterically closest to the substituent, or another substituent substituted on the atom on which the substituent is substituted. For example, two substituents substituted at the ortho positions on a benzene ring and two substituents substituted on the same carbon on an aliphatic ring are considered to be "adjacent" to each other. An "effective amount," when used in reference to a compound, is an amount that is effective to treat or prevent a disease in a subject as described herein. compound

[0050] In order to achieve the above object, the present invention provides a compound of formula I, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof: [ka] In the above formula, A is a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted aryl having 5 to 20 carbon atoms;

[0051] In this case, the 5- to 20-membered heteroaryl or the aryl having 5 to 20 carbon atoms is unsubstituted or substituted with one, two, three or four kinds of substituents consisting of cyano, halo, haloalkyl, nitro, -C(=O)R1, -C(=O)OR1, -NH-C(=O)R1, alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl and substituted or unsubstituted 5- to 20-membered heterocycloalkyl, in which case R1 is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms;

[0052] Two or more adjacent groups may be bonded to each other to form a substituted or unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5-10 membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 5 to 10 carbon atoms;

[0053] R is hydrogen, deuterium, cyano, halo, nitro, haloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5-membered to 20-membered heteroaryl, or -C(=O)R2, wherein R2 is cycloalkyl having 3 to 8 carbon atoms, alkyl having 1 to 10 carbon atoms, alkenyl having 2 to 10 carbon atoms, or aryl having 6 to 10 carbon atoms; B is -NKM or a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl;

[0054] K and M are each independently hydrogen, deuterium, cyano, halo, nitro, haloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted aryl alkyl having 1 to 10 carbon atoms having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroaryl alkyl having 1 to 10 carbon atoms.

[0055] The alkyl having 1 to 10 carbon atoms may be unsubstituted or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of deuterium, halo, hydroxy, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkoxy having 1 to 10 carbon atoms, alkylsulfonyl having 1 to 10 carbon atoms, arylsulfonyl having 5 to 20 carbon atoms, aryloxy having 5 to 20 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, and substituted or unsubstituted 5- to 20-membered heterocycloalkyl.

[0056] the cycloalkyl having 3 to 8 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms or 5-membered to 20-membered heteroaryl, alkoxy having 1 to 10 carbon atoms, and haloalkyl having 1 to 10 carbon atoms;

[0057] The 5- to 20-membered heteroaryl, 5- to 20-membered heterocycloalkyl, or aryl having 5 to 20 carbon atoms is unsubstituted or is selected from the group consisting of deuterium, halo, cyano, nitro, -C(=O)R', -C(=O)OR', -NH-C(=O)R'', substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to 10 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to 2 ... substituted or unsubstituted arylsulfonyl, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkyl having 1 to 10 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted aryl alkyl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heterocycloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, and substituted or unsubstituted alkyl 5- to 20-membered heterocycloalkyl having 1 to 10 carbon atoms;

[0058] wherein R' and R'' are each independently hydrogen, deuterium, a substituted or unsubstituted amine, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, a substituted or unsubstituted alkynyl having 2 to 6 carbon atoms, a substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, a substituted or unsubstituted aryl having 6 to 10 carbon atoms, or a substituted or unsubstituted aryl having 6 to 10 carbon atoms and an alkyl having 1 to 6 carbon atoms; the substituted amino group is substituted with one or two alkyl groups having 1 to 10 carbon atoms; The heteroatoms in the heterocycloalkyl and heteroaryl rings may be one or more, or 1 to 4, 1 to 3, or 1 to 2 types selected from N, S and O. As a specific embodiment,

[0059] A is an unsubstituted or substituted 5- to 12-membered heteroaryl or aryl having 6 to 10 carbon atoms, wherein the 5- to 12-membered heteroaryl or aryl having 6 to 10 carbon atoms is substituted with one, two, three or four substituents selected from the group consisting of cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, -C(=O)R1, -C(=O)OR1, -NH-C(=O)R1, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, amino, aryl having 6 to 10 carbon atoms, 5- to 12-membered heteroaryl, and 5- to 12-membered heterocycloalkyl, wherein R1 is hydrogen, deuterium, or alkyl having 1 to 6 carbon atoms;

[0060] Two or more adjacent types of substituents can be bonded to each other to form a substituted or unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring can form a 5- to 7-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 9 carbon atoms.

[0061] In a specific embodiment, A may be a 5- to 10-membered heteroaryl having 1, 2, 3, or 4 heteroatoms selected from the group consisting of N, O, and S, or an aryl having 6 to 9 carbon atoms.

[0062] In a specific embodiment, A can be pyridinyl, pyrimidinyl, pyrazinyl, triazolyl, thiazolyl, phenyl, or thieno[3,2]pyridinyl.

[0063] In a specific embodiment, A is substituted with one, two, three or four types of alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, F, Cl, Br, I, cyano, amino, nitro, -C(=O)R1, -C(=O)OR1, -NH-C(=O)R1, or 5- to 12-membered heterocycloalkyl, and in this case, Ra can be hydrogen, deuterium, or alkyl having 1 to 6 carbon atoms.

[0064] In a specific embodiment, A may be substituted with one, two, three or four of methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, F, Cl, Br, I, cyano, amino, nitro, -C(=O)OH, -C(=O)CH3, -NH-C(=O)CH3, morpholino, or piperidino.

[0065] In a specific embodiment, R is hydrogen, deuterium, cyano, halo, nitro, alkyl having 1 to 6 carbon atoms which is unsubstituted or substituted with cycloalkyl having 3 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, 5- to 12-membered heteroaryl, -C(=O)R2, in which R2 is cycloalkyl having 3 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms. In a specific embodiment, R2 can be cyclopropyl, methyl, ethyl, propyl, ethenyl, propenyl, or phenyl.

[0066] In a specific embodiment, R can be hydrogen, deuterium, cyano, halo, nitro, methyl, ethyl, propyl, butyl, cyclopropylmethyl, CF3, -C(=O)-cyclopropyl, -C(=O)-ethenyl, or benzoyl.

[0067] In a specific embodiment, B is -NKM or 5- to 12-membered heteroaryl or 5- to 12-membered heterocycloalkyl, wherein the 5- to 12-membered heteroaryl or 5- to 12-membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, or 4 deuterium, halo, cyano, nitro, -NR3R4, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R5, or -SO2-R6;

[0068] In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms;

[0069] wherein R3 and R4 are each independently hydrogen, deuterium, -C(=O)-Ra, alkyl having 1 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms or aryl having 6 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or aryloxy having 6 to 10 carbon atoms, wherein Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, or haloalkyl having 1 to 6 carbon atoms;

[0070] The R5 is -OR b , -NR c R d , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of monoalkylamine having 1 to 6 carbon atoms or dialkylamine having 1 to 6 carbon atoms, wherein the R b , R c and R d each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, or an aryl having 6 to 10 carbon atoms and an alkyl having 1 to 6 carbon atoms; R6 is an alkyl having 1 to 6 carbon atoms, or an aryl having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3, or 4 kinds of alkyl having 1 to 6 carbon atoms,

[0071] K and M are each independently hydrogen, deuterium, cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, 5-membered to 12-membered heteroaryl, 5-membered to 12-membered heteroaryl alkyl having 1 to 6 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or 5-membered to 12-membered heteroaryl alkyl having 1 to 6 carbon atoms is the membered heteroaryl is substituted with one, two, three or four of cyano, halo, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, hydroxyalkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, alkylsulfonyl having 1 to 6 carbon atoms, arylsulfonyl having 6 to 10 carbon atoms, -NR7R8, -C(=O)R9, 5- to 12-membered heterocyclyl, hydroxy, nitro, or aryl having 6 to 10 carbon atoms, in which the 5- to 12-membered heterocyclyl or aryl having 6 to 10 carbon atoms is unsubstituted or substituted with alkyl having 1 to 6 carbon atoms;

[0072] R9 is -OR e , -NR e R f , unsubstituted or one, two, three or four of -NR e R f or aryl having 6 to 10 carbon atoms, each of which is substituted with R e and R f are each independently hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, or alkyl having 1 to 6 carbon atoms.

[0073] In a specific embodiment, B is a 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl having one to three heteroatoms selected from the group consisting of N, O, and S, which may be substituted or unsubstituted by the substituents mentioned above.

[0074] In one specific embodiment, B is pyrrolidine, piperazine, dihydroisoquinoline, morpholine, or piperidine, which may be substituted or unsubstituted with the substituents mentioned above. In a specific embodiment, the compound of formula I may be a compound of formula I-1: [Chemical formula I-1] [ka] In the above formula, K, M and R are as defined above for Formula I.

[0075] D is CR 10 , N, O or S, E is CR 11 , N, O or S, F is CR 12 , N, O or S, G is CR 13 , N, O or S, J is CR 14 , N, O or S, with the proviso that N, O and S are one or more;

[0076] R 10 ~R 14 are the same or different and each independently substituted with one, two, three or four types of substituents consisting of cyano, halo, haloalkyl, nitro, -C(=O)R1, -C(=O)OR1, -NH-C(=O)R1, alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5 to 12 membered heteroaryl and substituted or unsubstituted 5 to 12 membered heterocycloalkyl, wherein R1 is hydrogen, deuterium or alkyl having 1 to 10 carbon atoms;

[0077] Two or more adjacent groups can be bonded to each other to form a substituted or unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring can form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 10 carbon atoms. In a specific embodiment, the compound of formula I may be a compound of formula I-2: [Chemical formula I-2] [ka] In the above formula, R, D, E, F, G and J are as defined above in formula I-1; n is an integer of 0, 1, or 2; L is CH2, NH or O; [ka] is unsubstituted or substituted with one, two, three or four of deuterium, halo, cyano, nitro, -NR3R4, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R5, -SO2-R6; In this case, when there are two or more kinds of substituents, adjacent two or more kinds of substituents are bonded to each other. [ka] together with a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl,

[0078] In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms;

[0079] R3 and R4 each independently represent hydrogen, deuterium, -C(=O)-R a, an alkyl having 1 to 6 carbon atoms or an aryl having 6 to 10 carbon atoms, said alkyl having 1 to 6 carbon atoms or aryl having 6 to 10 carbon atoms being unsubstituted or substituted with 1, 2, 3 or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms or aryloxy having 6 to 10 carbon atoms, wherein said Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms or haloalkyl having 1 to 6 carbon atoms;

[0080] The R5 is -OR b , -NR c R d , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of monoalkylamine having 1 to 6 carbon atoms or dialkylamine having 1 to 6 carbon atoms, wherein the R b , R c and R d each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, or an aryl having 6 to 10 carbon atoms and an alkyl having 1 to 6 carbon atoms; The R6 is an alkyl group having 1 to 6 carbon atoms, or an aryl group having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3 or 4 kinds of alkyl groups having 1 to 6 carbon atoms. In a specific embodiment, [ka] When L is substituted, L is CH2 or NH, in which one or two of the H's may be substituted by the above-mentioned substituents. In a specific embodiment, the compound of formula I can be a compound of formula I-3: [Chemical formula I-3] [ka] In the above formula, K, M, R, D, E, F and G are as defined above in formula I-1. In a specific embodiment, the compound of formula I can be a compound of formula I-4: [Chemical formula I-4] [ka] In the above formula, L, n, R, D, E, F and G are as defined above in formula I-2.

[0081] In a specific embodiment, the compound of formula I according to the present invention may be one or more selected from the group consisting of the following compounds 1) to 161), but is not limited thereto. 1) 5-(benzylmethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 2) 5-(benzylcyclopropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0082] 3) 4-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile; 4) 5-[(4-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 5) 5-[(2,4-difluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 6) 5-[(2-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 7) 5-[(3-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0083] 8) 5-[methyl-(4-trifluoromethylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 9) 5-[methyl-(3-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0084] 10) 5-[methyl-(3-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0085] 11) 5-[methyl-(2-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0086] 12) 5-[(4-methanesulfonylbenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 13) 5-[(3-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 14) 5-piperidin-1-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 15) 5-morpholino-4-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 16) 5-(4-methylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0087] 17) 5-(4-(2-(2-hydroxymethoxy)ethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0088] 18) 5-(3,4-dihydro-1H-isoquinolin-2-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 19) 5-[(4-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 20) 5-(benzylethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 21) 5-(benzylpropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 22) 5-(benzylbutylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0089] 23) 5-[methyl(3-methylsulfonylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 24) 5-[methyl-(4-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0090] 25) 3-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile; 26) 5-[(2-methoxybenzyl)-methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 27) 5-[(3-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 28) 5-[(4-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 29) 5-[methyl-(2-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 30) 5-[(2,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 31) 5-[(3,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 32) 5-(3,4-difluorophenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0091] 33) 5-[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0092] 34) 5-(((3-(hydroxymethyl)-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl)methyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0093] 35) 5-{[(3-(hydroxymethyl)-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl)methyl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0094] 36) 5-{methyl[3-methyl-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0095] 37) 5-{methyl[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0096] 38) Cyclopropyl[4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2-indazol-5-yl)piperazin-1-yl]methanone;

[0097] 39) 5-(benzylmethylamino)-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 40) 5-(benzylmethylamino)-2-(5-chloropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0098] 41) 5-(benzylmethylamino)-2-(6-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 42) 5-(benzylmethylamino)-2-(6-methylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 43) 5-(benzylmethylamino)-2-(3-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 44) 6-(5-(benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinonitrile;

[0099] 45) 5-(benzylmethylamino)-2-(6-methyl-4-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 46) 5-(benzylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 47) 2-(pyridin-2-yl)-5-[(pyridin-2-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol; 48) 5-[methyl(pyridin-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0100] 49) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0101] 50) 2-(5-chloropyridin-2-yl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol; 51) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0102] 52) 2-(4-bromophenyl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7,-tetrahydro-2H-indazol-3-ol; 53) 5-(benzylmethylamino)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 54) 2-(6-aminopyridin-2-yl)-5-(benzylmethylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 55) 5-Phenylamino-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 56) 5-[(2,5-dimethylphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 57) 5-[(4-nitrophenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 58) 5-[(4-methoxyphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 59) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 60) 2-(pyridin-2-yl)-5-(quinolin-3-ylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0103] 61) 5-[methyl(naphthalen-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0104] 62) 5-[(isoquinolin-3-ylmethyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 63) 5-[methyl(quinolin-6-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 64) 5-[(isoquinolin-3-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 65) 5-[Methyl(pyridin-2-ylmethyl)amino]-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 66) 5-[ethyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 67) 5-[(3-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 68) 5-[(4-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-2-ol;

[0105] 69) 5-[(3-dimethylaminobenzyl)methylamino)]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0106] 70) 5-[(4-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0107] 71) 5-[(2-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 72) 5-(benzylmethylamino)-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 73) 4-[(5-benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]benzoic acid; 74) 5-(benzylmethylamino)-2-(4-bromophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 75) 5-(benzylmethylamino)-2-(2-chlorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 76) 5-(benzylmethylamino)-2-(2-methoxyphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0108] 77) 2-(2-chlorophenyl)-5-[(3-dimethylaminobenzyl)methylamino]-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0109] 78) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzoic acid;

[0110] 79) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzamide;

[0111] 80) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N-methylbenzamide;

[0112] 81) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N,N-dimethylbenzamide;

[0113] 82) 5-(4-methylpiperazin-1-yl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 83) 2-(6-chloropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0114] 84) 2-(6-methyl-4-(trifluoromethyl)pyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0115] 85) 5-(4-methylpiperazin-1-yl)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0116] 86) 2-(3-fluoropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0117] 87) 2-(pyridin-2-yl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 88) 5-((4-methoxybenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0118] 89) 1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)but-2-en-1-one;

[0119] 90) 2-(pyridin-2-yl)-5-(4-(quinolin-6-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 91) 5-(4-ethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 92) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 93) 5-(phenethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 94) 2-(4-chlorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0120] 95) 5-(4-methylpiperazin-1-yl)-2-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 96) 2-(pyridin-2-yl)-5-(pyrrolidin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0121] 97) 1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)prop-2-en-1-one;

[0122] 98) (E)-4-(dimethylamino)-1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)but-2-en-1-one;

[0123] 99) (E)-4-(Dimethylamino)-N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-methylbut-2-enamide; 100) 5-(4-propylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 101) 2-(4-bromophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 102) 2-(4-fluorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 103) 4-(3-hydroxy-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzonitrile; 104) 5-(4-phenethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 105) 5-(4-benzylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0124] 106) 5-(4-(cyclohexylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0125] 107) 5-(4-(3-phenylpropyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 108) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 109) 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0126] 110) 5-(4-(methylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0127] 111) 5-(4-(phenylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 112) 2-(pyridin-2-yl)-5-(4-tosylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0128] 113) 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-phenylpiperazine-1-carboxamide;

[0129] 114) Benzyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate;

[0130] 115) 2-(1-methyl-1H-pyrrol-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 116) 5-(4-methylpiperazin-1-yl)-2-(thiazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 117) 5-(4-methylpiperazin-1-yl)-2-(oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0131] 118) 2-(1-methyl-1H-pyrazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0132] 119) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0133] 120) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 121) 5-(benzyl(methyl)amino)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0134] 122) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-pyrrol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0135] 123) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-pyrazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0136] 124) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-imidazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 125) 5-(benzyl(methyl)amino)-2-(oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 126) 2-(pyridin-2-yl)-5-(4-(p-tolyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0137] 127) 5-(4-(4-hydroxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0138] 128) 5-(4-(3,4-difluorophenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0139] 129) 5-(4-(4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0140] 130) 1-(4-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)phenyl)ethan-1-one;

[0141] 131) 5-(4-(4-(methylsulfonyl)phenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0142] 132) 5-(4-(4-phenoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0143] 133) 5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0144] 134) 5-(4-((1-methylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0145] 135) 5-(4-((1-benzylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0146] 136) 1-(4-((4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)ethan-1-one; 137) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzamide; 138) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-2-phenylacetamide; 139) 1-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-3-phenylurea; 140) 1-Benzyl-3-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)urea; 141) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzenesulfonamide;

[0147] 142) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-4-methylbenzenesulfonamide; 143) Benzyl (3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)carbamate;

[0148] 144) 2-(5-fluoro-4-morpholinopyrimidin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 145) N-benzyl-3-methoxy-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine;

[0149] 146) N-benzyl-3-(cyclopropylmethoxy)-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine;

[0150] 147) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ylcyclopropanecarboxylate; 148) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl acrylate; 149) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl benzoate;

[0151] 150) 2-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyrimidine-5-carboxylic acid; 151) Methyl 2-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinate;

[0152] 152) N-(6-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyridin-2-yl)acetamide;

[0153] 153) 5-(benzyl(methyl)amino)-2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 154) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0154] 155) 2-(5-chloropyridin-3-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0155] 156) 2-(pyridin-2-yl)-5-(4-(pyrimidin-2-yl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 157) 5-(benzyl(methyl)amino)-2-(5-nitropyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0156] 158) 5-((4-hydroxybenzyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 159) 5-(Methyl(4-nitrobenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0157] 160) 5-(3-(ethyl(methyl)amino)pyrrolidin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; and

[0158] 161) 2,2,2-trifluoro-N-(1-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)pyrrolidin-3-yl)acetamide.

[0159] Unless otherwise specified, the chemical formulae or names given in the specification and claims encompass tautomers and all stereo, optical and geometric isomers (e.g., enantiomers, partial stereoisomers, E / Z isomers, etc.) and racemates thereof as well as mixtures of different ratios of the different enantiomers, mixtures of partial stereoisomers, or any of the above forms in which isomers and enantiomers are present, and pharma- ceutically acceptable salts thereof and salts thereof, including, for example, solvates and hydrates of the free compounds or solvates and hydrates of the salts of the compounds.

[0160] In one embodiment, the compound of the present invention can be in the form of a pharmaceutically acceptable salt. The salt means a salt commonly used in the pharmaceutical industry to which the present invention belongs, and an acid addition salt formed with a pharmaceutically acceptable free acid is useful. The term "pharmaceutically acceptable salt" in the present invention means any organic or inorganic addition salt of the compound, which has a concentration that is relatively non-toxic and harmless to patients and does not reduce the beneficial efficacy of the compound of the present invention due to side effects caused by the salt.

[0161] The acid addition salts can be prepared in the usual manner, for example by dissolving the compound in an excess of aqueous acid and precipitating the salt with a water-miscible organic solvent, for example methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and an acid in water or an alcohol (for example glycol monomethyl ether) are heated, and then the mixture is evaporated to dryness or the precipitated salt can be filtered off with suction.

[0162] In this case, the free acid may be an organic acid or an inorganic acid. Examples of the inorganic acid include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and tartaric acid. Examples of the organic acid include, but are not limited to, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, and hydroiodic acid.

[0163] Also, pharma- ceutically acceptable metal salts can be prepared using bases. Alkali metal salts or alkaline earth metal salts can be obtained, for example, by dissolving a compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. In this case, as the metal salt, it is particularly preferable to prepare sodium, potassium, or calcium salts, but the metal salts are not limited to these. Corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0164] Pharmaceutically acceptable salts of the compounds of the present invention, unless otherwise specified, include salts of acidic or basic groups that may be present in the compounds of formula I. For example, pharma- ceutically acceptable salts include sodium, calcium, and potassium salts of hydroxy groups, and other pharma-ceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (methylated), and p-toluenesulfonate (tosylate) salts, which may be prepared by methods known in the art for preparing salts.

[0165] As the salt of the compound represented by the formula I of the present invention, any salt of the compound represented by the formula I that is pharma- ceutically acceptable and has pharmacological activity equivalent to that of the compound listed in Table 1 may be used without limitation.

[0166] The compound of the present invention may also be in the form of its stereoisomer. The stereoisomer includes all stereoisomers, such as enantiomers and diastereomers. The compound may be in a stereoisomerically pure form or a mixture of one or more stereoisomers, such as a racemic mixture. Separation of a specific stereoisomer is carried out by one of the conventional methods known in the art. Some examples of the compound of the present invention may be such that a specific stereoisomer has a greater oxidative stress suppressing effect than the racemic mixture. In this case, the dosage can be reduced by using a specific stereoisomer. Therefore, by separating a specific stereoisomer, such as an enantiomer or a partial structural isomer, that has a greater suppressive effect against oxidative stress, diseases associated with oxidative stress can be effectively treated.

[0167] The compound of the present invention may further be in the form of its solvate. "Solvate" refers to a complex or aggregate formed by one or more solute molecules, i.e., the compound of formula I or its pharma- ceutically acceptable salt, and one or more solvent molecules. The solvate may be a complex or aggregate formed with various solvent molecules, such as, for example, water, methanol, ethanol, isopropanol, or acetic acid. Solvates in which water is the solvent molecule are referred to as hydrates. Hydrates include compositions that contain stoichiometric amounts of water as well as compositions that contain variable amounts of water. The compounds of the invention may also be in the form of their tautomers.

[0168] The term "tautomer" or "tautomeric form" refers to structural isomers of different energies that are interconvertible via a low energy barrier. Some non-limiting examples of proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions via reorganization of some of the bonding electrons. The compounds of the invention may also be in the form of their isotopic variations.

[0169] The term "isotopic variant" refers to a compound in which at least one atom in any compound has been replaced by another atom having the same atomic number but an atomic mass different from the atomic mass usually or predominantly occurring in nature. Solvates, stereoisomers, tautomers, and isotopic variations of the compounds of formula I may be prepared from the compounds using methods known in the art.

[0170] In the production method according to the present invention, the reactants used in the reaction scheme may be purchased from a commercial source and used as they are, or may be synthesized by carrying out one or more reactions known in the art as they are or with appropriate modifications. For example, one or more reactions may be carried out in a series of steps in consideration of the presence, type and / or position of reactive functional groups and / or heteroatoms contained in the skeletal structure, but are not limited thereto.

[0171] In one embodiment, the compound of the synthetic example of the present invention not only exhibits an inhibitory effect on ROS generation of 30%, 50%, 70% or more compared to the control group by treating ROS generated by PMA in HL-60 cells (human leukemia cells), but also exhibits a concentration-dependent inhibitory effect, and therefore the compound of the present invention can be used for the prevention or treatment of diseases associated with oxidative stress.

[0172] It has been reported that differentiation of fibroblasts into myofibroblasts leads to the formation of cancer associated fibroblasts (CAFs) or the induction of fibrosis in various tissues. When the compound according to the present invention was treated with HFF-1 cells (human foreskin fibroblasts) in which fibrosis was induced by treatment with TGF-β1, the expression of αSMA, an indicator of fibrosis, was suppressed. Therefore, the compound according to the present invention can be used for the prevention or treatment of diseases associated with fibrosis, and can be used for the treatment of cancer by regulating cancer associated fibroblasts, which are an important indicator of tumor microenvironment interactions.

[0173] When ROS levels in nerve cells are high, lipid oxidation is induced, which is known to be an important factor in the death of nerve cells. When ROS-inducing MPP+ (1-methyl-4-phenylptridinium) and the compound of the synthetic example were treated simultaneously in N27 cells (rat dopaminergic neural cells), the production of ROS was effectively inhibited. Therefore, the compound of the present invention can be used for the prevention or treatment of diseases related to the death of nerve cells due to oxidative stress.

[0174] One of the main causes of skin fibrotic diseases is the production of extracellular matrix such as collagen type I by keloid fibroblasts due to CTGF. When KEL-FIB (keloid fibroblast) cells were treated with the compound of the synthesis example and then treated with TGF-β1 to induce fibrosis, the expression of CTGF gene and collagen type I gene was effectively inhibited. Therefore, the compound of the present invention can be used for the prevention or treatment of skin keloid diseases. Pharmaceutical Compositions and Medical Uses

[0175] Due to their biological properties, the compounds according to the present invention, their optical isomers, their stereoisomers, their solvates, their isotopic variants, their tautomers or their pharma- ceutically acceptable salts are suitable for preventing, ameliorating or treating a variety of diseases induced by oxidative stress.

[0176] The pharmaceutical composition of the present invention may be for treating a disease associated with oxidative stress, which may be cancer, an inflammatory disease, a fibrotic disease, a degenerative neurological disease, a neurological disease, a liver disease, a skin disease, a mitochondrial disease, aging, chronic alcoholism, stem cell dysfunction, claudication, metabolic syndrome, Down's syndrome, infertility, overproduction of lipid peroxides in tissues, muscle disease, accumulation of lipid peroxides in cell membranes, chronic fatigue, or a retinal disease.

[0177] The cancer may be selected from the group consisting of liver cancer, hepatocellular carcinoma, gastrointestinal cancer, gastric cancer, brain meningioma associated with neurofibromatosis, pancreatic cancer, leukemia, myeloproliferative / myelodysplastic disorders, dermatofibrosarcoma, lung cancer, thyroid cancer, colon cancer, prostate cancer, breast cancer, ovarian cancer, brain tumor, head and neck cancer, glioblastoma, etc. The cancer may also be a secondary cancer metastasized to other organs from the various types of cancer.

[0178] The metabolic syndrome includes obesity, diabetes, hypertension, hyperlipidemia, arteriosclerosis, myocardial infaction, ischemic perfusion, myocardial infarction, and stroke.

[0179] The inflammatory disease may be inflammation-related rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory bowel disease, enteritis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, inflammation in postischemic reperfusion injury, inflammation caused by immune rejection after tissue and organ transplantation, various inflammations occurring on the skin such as burns and allergic contact dermatitis, inflammation occurring during multiple organ disorders, diabetic inflammation including diabetic nephropathy, infectious inflammation caused by viral or bacterial infection, or autoimmune diseases such as atopic disease, lupus, psoriasis, and sclerosis.

[0180] The fibrotic disease may be metabolic disease-induced liver fibrosis or cirrhosis, NAFLD-induced fibrosis or cirrhosis, NASH-induced fibrosis or cirrhosis, alcohol-induced liver fibrosis or cirrhosis, drug-induced liver fibrosis or cirrhosis, infectious agent-induced liver fibrosis or cirrhosis, parasitic infection-induced liver fibrosis or cirrhosis, bacterial infection-induced liver fibrosis or cirrhosis, viral infection-induced fibrosis or cirrhosis, HBV-infection-induced liver fibrosis or cirrhosis, HCV-infection-induced liver fibrosis or cirrhosis, HI HCV-infection induced liver fibrosis or cirrhosis, dual HCV and HIV-infection induced liver fibrosis or cirrhosis, radiation- or chemotherapy-induced fibrosis or cirrhosis, bile duct fibrosis, liver fibrosis or cirrhosis due to any chronic cholestatic disease, gastrointestinal fibrosis of any etiology, Crohn's disease-induced fibrosis, ulcerative colitis-induced fibrosis, small intestinal fibrosis, colonic fibrosis, gastric fibrosis, lung fibrosis, skin fibrosis, epidermal fibrosis, endothelial fibrosis, skin fibrosis due to dermatosclerosis / systemic sclerosis, chronic inflammatory airway disease The fibrosis may be from COPD (Obstructive Pulmonary Disease), asthma, emphysema, smoker's lung, tuberculosis, pulmonary fibrosis, lung fibrosis secondary to idiopathic pulmonary fibrosis (IPF), cardiac fibrosis, renal fibrosis, nephrogenic systemic fibrosis, muscle fibrosis, soft tissue fibrosis, bone marrow fibrosis, arthrofibrosis, liver fibrosis, cartilage fibrosis, pancreatic fibrosis, uterine fibrosis, nervous system fibrosis, testicular fibrosis, ovarian fibrosis, adrenal fibrosis, arterial fibrosis, venous fibrosis, ocular fibrosis, endomyocardial fibrosis, mediastinal fibrosis, bone marrow fibrosis, retroperitoneal fibrosis, progressive giant fibrosis as a complication of pneumoconiosis, proliferative fibrosis, neoplastic fibrosis, peri-implant fibrosis, asbestosis, arthrofibrosis, or adhesive capsulitis.

[0181] The degenerative neurological disease may be Alzheimer's disease (including mild or early Alzheimer's disease, mild to moderate Alzheimer's disease, moderate or intermediate stage Alzheimer's disease, moderate to severe Alzheimer's disease, moderately severe Alzheimer's disease, severe Alzheimer's disease, Alzheimer's disease with Lewy bodies), Parkinson's disease (including Parkinson's disease chemically induced by exposure to environmental agents such as insecticides, pesticides, or herbicides and / or metals such as manganese, aluminum, cadmium, copper, or zinc, SNCA gene-associated Parkinson's disease, sporadic or idiopathic Parkinson's disease, or Parkinson- or LRRK2-associated Parkinson's disease), autosomal dominant Parkinson's disease, Diffuse Lewy Body Disease (DLBD) (or Dementia with Lewy Bodies), or Dementia with Lewy Bodies (DLBD). (also known as Degenerative Disorders of Autonomic Bodies; DLB), pure dysautonomia, Lewy body dysphagia, incidental LBD, genetic LBD (e.g., mutations in the alpha-synuclein gene, PARK3 and PARK4), multiple system atrophy (including olivopontocerebellar atrophy, striatonigral degeneration, Shy-Drager syndrome (MSA)), combined Alzheimer's and Parkinson's disease and / or MSA, Huntington's disease, synucleinopathies, disorders or conditions characterized by the presence of Lewy bodies, multiple sclerosis, amyotrophic lateral sclerosis (AMSC),ALS), dementia (including vascular dementia, dementia with Lewy bodies, Parkinson's dementia, frontotemporal dementia), psychosis (including anxiety caused by a neurodegenerative disease or associated with dopamine therapy, e.g., but not limited to, Parkinson's disease psychosis, Alzheimer's disease psychosis, dementia with Lewy bodies psychosis), dyskinesia (including anxiety caused by a neurodegenerative disease or associated with dopamine therapy), anxiety (including anxiety caused by a neurodegenerative disease or associated with dopamine therapy), conditions associated with dopamine therapy (including abnormalities in muscle tone, muscle spasms, or tremors), synucleinopathies, diseases associated with abnormal expression of alpha-synuclein, ischemic cerebrovascular disease, Creutzfeldt-Jakob disease, Machado-Joseph disease, or spinocerebellar ataxia ataxia, Pick's disease;

[0182] The liver disease can be metabolic liver disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), drug-induced liver disease, alcohol-induced liver disease, infectious agent-induced liver disease, inflammatory liver disease, immune system dysfunction-mediated liver disease, or dyslipidemia.

[0183] The skin disease can be keloid disease, psoriasis or vitiligo, and the retinal disease can be retinal fibrosis, macular degeneration, diabetic retinopathy, diabetic macular degeneration, retinopathy of prematurity, retinal ischemia-reperfusion injury, retinitis pigmentosa, cataract or neovascular glaucoma.

[0184] The mitochondrial diseases include mitochondrial disease, Alpers Disease, Barth syndrome, chronic progressive external ophthalmoplegia syndrome (CPEO), long-chain acyl-CoA dehydrogenase deficiency (LCAD), MELAS syndrome, Leber's hereditary optic neuropathy (LHON), Leigh disease, MEGDEL syndrome, Luft disease, Pearson syndrome, neurogenic ataxia retinitis pigmentosa (NARP), Co-Q10 deficiency, myoclonus epilepsy with ragged-red fibers (MERRF), mitochondrial DNA depletion syndrome (MDS), fatal infantile cardiomyopathy (LIC), mitochondrial neurogastrointestinal encephalopathy syndrome, β-oxidation disorder, Friedreich's ataxia FA, Kearns-Sayre syndrome, The condition may be pulmonary edema, pulmonary edema (KSS), or lactic acidosis.

[0185] The nervous system disease may be bipolar disorder, developmental disorder, autistic disorder, Asperger's syndrome, Rett's disorder, visual impairment, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorder, Tourette's disorder, or schizophrenia, etc. The muscle-related disease may be myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy, or spinal muscular atrophy, etc.

[0186] Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I as defined above, or a pharma- ceutically acceptable salt or solvate or stereoisomer thereof, and a pharma- ceutically acceptable carrier. In the composition of the present invention, the compound or a pharma- ceutically acceptable salt, solvate or stereoisomer thereof is as described above.

[0187] In the composition of the present invention, "a pharma-ceutically acceptable carrier" refers to a substance, generally an inactive substance, used in combination with an active ingredient to facilitate application of the active ingredient. The carrier includes a conventional pharma-ceutically acceptable excipient, additive, or diluent. The carrier may include, for example, one or more selected from fillers, binders, disintegrants, buffers, preservatives, antioxidants, lubricants, flavorings, thickeners, coloring agents, emulsifiers, suspending agents, stabilizers, pH adjusters, and isotonicity agents.

[0188] The diluent may be sugar, starch, microcrystalline cellulose, lactose (lactose hydrate), glucose, D-mannitol, alginate, alkaline earth metal salts, clay, polyethylene glycol, anhydrous calcium hydrogen phosphate, or mixtures thereof; the binder may be starch, microcrystalline cellulose, highly dispersible silica, mannitol, D-mannitol, sucrose, lactose hydrate, polyethylene glycol, polyvinylpyrrolidone (povidone), polyvinylpyrrolidone copolymer (copovidone), hypromellose, hydroxypropyl cellulose, natural gums, synthetic gums, gelatin, or mixtures thereof.

[0189] Disintegrants may be starches or modified starches such as sodium starch gluconate, corn starch, potato starch, pregelatinized starch; clays such as bentonite, montmorillonite or veegum; celluloses such as microcrystalline cellulose, hydroxypropyl cellulose or carboxymethyl cellulose; algins such as sodium alginate or alginic acid; cross-linked celluloses such as croscarmellose sodium; gums such as guar gum, xanthan gum; cross-linked polymers such as cross-linked polyvinylpyrrolidone (crospovidone); effervescent agents such as sodium bicarbonate, citric acid or mixtures thereof.

[0190] Lubricants that can be used include talc, stearic acid, magnesium stearate, calcium stearate, sodium lauryl sulfate, hydrogenated vegetable oils, sodium benzoate, sodium stearyl fumarate, glyceryl monolate, glyceryl monostearate, glyceryl palmitostearate, colloidal silicon dioxide, or mixtures thereof.

[0191] Examples of pH adjusters that can be used include acidifiers such as acetic acid, ascorbic acid, sodium ascorbate, sodium etherate, malic acid, succinic acid, tartaric acid, fumaric acid, and citric acid (citric acid), and basifiers such as precipitated calcium carbonate, aqueous ammonia, meglumine, sodium carbonate, magnesium oxide, magnesium carbonate, sodium citrate, and tribasic calcium phosphate.

[0192] The antioxidant may be dibutylhydroxytoluene, butylated hydroxyanisole, tocopherol acetate, tocopherol, propyl gallate, sodium hydrogen sulfite, sodium pyrosulfite, etc. In the advance-release compartment of the present invention, the solubilizing agent may be sodium lauryl sulfate, polyoxyethylene sorbitan fatty acid esters such as polysorbate, docusate sodium, poloxamer, etc. Additionally, enteric polymers, water-insoluble polymers, hydrophobic compounds, and hydrophilic polymers may be included to prepare delayed release formulations.

[0193] The enteric polymer refers to a polymer that is insoluble or stable under acidic conditions of less than pH 5, and dissolves or decomposes under specific pH conditions of more than pH 5. Examples of the enteric polymer include enteric cellulose derivatives such as hypromellose acetate succinate, hypromellose phthalate (hydroxypropyl methylcellulose phthalate), hydroxymethylethylcellulose phthalate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalate, carboxymethylethylcellulose and ethylhydroxyethylcellulose phthalate, and methylhydroxyethylcellulose; styrene-acrylic acid copolymers, methyl acrylate-acrylic acid copolymers, methyl acrylate-methyl methacrylate copolymers (e.g., Acryloylase), butyl acrylate-styrene-acrylic acid copolymers, and methyl acrylate-methyl methacrylate-acrylic acid copolymers. enteric acrylic copolymers such as octyl acetate copolymer; enteric polymethacrylate copolymers such as poly(methyl methacrylate) copolymers (e.g., Eudragit L, Eudragit S, Evonik, Germany) and poly(ethyl methacrylate) copolymers (e.g., Eudragit L100-55); enteric maleic copolymers such as vinyl acetate-maleic anhydride copolymer, styrene-maleic anhydride copolymer, styrene-maleic monoester copolymer, vinyl methyl ether-maleic anhydride copolymer, ethylene-maleic anhydride copolymer, vinyl butyl ether-maleic anhydride copolymer, acrylonitrile-methyl acrylate·maleic anhydride copolymer, and butyl acrylate-styrene-maleic anhydride copolymer; and enteric polyvinyl derivatives such as polyvinyl alcohol phthalate, polyvinyl acetal phthalate, polyvinyl butyrate phthalate, and polyvinyl acetoacetal phthalate.

[0194] The water-insoluble polymer refers to a pharma- ceutically acceptable polymer that does not dissolve in water and controls the release of a drug. For example, the water-insoluble polymer includes polyvinyl acetate (e.g., Kollicoat SR30D), water-insoluble polymethacrylate copolymers [e.g., poly(ethyl acrylate-methyl methacrylate) copolymers (e.g., Eudragit NE30D, poly(ethyl acrylate-methyl methacrylate-trimethylaminoethyl methacrylate) copolymers (e.g., Eudragit RSPO)], ethyl cellulose, cellulose esters, cellulose ethers, cellulose acylates, cellulose diacylates, cellulose triacylates, cellulose acetates, cellulose diacetates, and cellulose triacetates.

[0195] The hydrophobic compound refers to a pharma- ceutically acceptable water-insoluble substance that controls the release of drugs.For example, fatty acids and fatty acid esters such as glyceryl palmitostearate, glyceryl stearate, glyceryl behenate, cetyl palmitate, glyceryl monooleate and threaic acid; fatty acid alcohols such as cetostearyl alcohol, cetyl alcohol and stearyl alcohol; waxes such as carnauba wax, beeswax and microcrystalline wax; inorganic substances such as talc, precipitated calcium carbonate, calcium hydrogen phosphate, zinc oxide, titanium oxide, kaolin, bentonite, montmorillonite and veegum.

[0196] The hydrophilic polymer refers to a pharma- ceutically acceptable water-soluble polymeric substance that controls the release of a drug. For example, saccharides such as dextrin, polydextrin, dextran, pectin and pectin derivatives, alginate, polygalacturonic acid, xylan, arabinoxylan, arabinogalactan, starch, hydroxypropyl starch, amylose, and amylopectin; cellulose derivatives such as hypromellose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose, and sodium carboxymethyl cellulose; gums such as guar gum, locust bean gum, tragacanth, carrageenan, acacia gum, gum arabic, gellan gum, and xanthan gum; gelatin, casein, and zeyl. proteins such as methacrylate; polyvinyl derivatives such as polyvinyl alcohol, polyvinylpyrrolidone, and polyvinyl acetal diethylaminoacetate; hydrophilic polymethacrylate copolymers such as poly(butyl methacrylate-(2-dimethylaminoethyl) methacrylate-methyl methacrylate) copolymers (e.g., Eudragit E100, Evonik, Germany), poly(ethyl acrylate-methyl methacrylate-triethylaminoethyl-methacrylate chloride) copolymers (e.g., Eudragit RL, RS, Evonik, Germany); polyethylene derivatives such as polyethylene glycol, and polyethylene oxide; carbomer, and the like. In addition, various additives selected from coloring agents and flavoring agents, which are pharma- ceutical acceptable additives, can be selected and used to formulate the preparation of the present invention.

[0197] In the present invention, the range of additives is not limited to the above additives, and the additives can be selected to be contained in a dosage range within the normal range.

[0198] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations, suppositories or sterile injection solutions by conventional methods. The compositions of the present invention may be administered orally or parenterally, including intravenous, intraperitoneal, subcutaneous, rectal and topical administration.

[0199] Another aspect of the invention provides a method of treating a disease in an individual comprising administering to the individual a therapeutically effective amount of a compound of formula I, or a pharma-ceutically acceptable salt or solvate or stereoisomer thereof.

[0200] In the above method, those skilled in the art can appropriately select the administration route depending on the condition of the patient. The administration may be oral or parenteral. Parenteral administration includes intravenous, intraperitoneal, subcutaneous, rectal and topical administration.

[0201] In the method, the dosage may vary depending on various factors such as the condition of the patient, the route of administration, and the judgment of the attending physician, as described above. The effective dosage may be estimated from dose-response curves obtained from in vitro experiments or animal model studies. The ratio and concentration of the compound of the present invention present in the administered composition may be determined depending on the chemical properties, the route of administration, the therapeutic dose, and the like. The dosage may be administered to an individual in an effective amount of about 1 μg / kg to about 1 g / kg / day, or about 0.1 mg / kg to about 500 mg / kg / day. The dosage may vary depending on the age, weight, sensitivity, or symptoms of the individual.

[0202] Furthermore, a pharmaceutical composition comprising a compound of the present invention or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof as an active ingredient can be administered to an individual in need thereof, comprising:

[0203] cancer; inflammatory diseases selected from rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory bowel disease, enterocolitis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, allergic contact dermatitis, diabetic inflammation, infectious inflammation, and autoimmune diseases; fibrotic diseases selected from liver fibrosis, liver cirrhosis, small intestinal fibrosis, large intestinal fibrosis, gastric fibrosis, pulmonary fibrosis, dermal fibrosis, epidermal fibrosis, dermatosclerosis / systemic sclerosis, cardiac fibrosis, and renal fibrosis; degenerative neurological diseases selected from Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury; bipolar disorder, developmental disorders, autistic disorder, Asperger's syndrome, Rett's disorder nervous system disease selected from: visual impairment, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorder, Tourette's disorder or schizophrenia; liver disease; skin disease; mitochondrial disease of any cause, Alpers syndrome, Barth syndrome, chronic progressive external ophthalmoplegia syndrome (CPEO), long-chain acyl-CoA dehydrogenase deficiency (LCAD), MELAS syndrome, Leber's hereditary optic neuropathy (LHON), Leigh disease, MEGDEL syndrome (Leigh-like syndrome), Luft disease, Pearson syndrome, neurogenic ataxia retinitis pigmentosa (NARP), Co-Q10 deficiency, myoclonus epilepsy with ragged red fibers (MERRF), mitochondrial DNA depletion syndrome (MDS), fatal infantile cardiomyopathy (LIC), mitochondrial neurogastrointestinal encephalopathy syndrome, beta-oxidation disorder, Friedreich's ataxia mitochondrial diseases selected from ataxia FA, Kearns-Sayre syndrome (KSS), and lactic acidosis; aging; chronic alcoholism; stem cell dysfunction; claudication; metabolic syndromes selected from obesity, diabetes, hypertension, hyperlipidemia, arteriosclerosis, myocardial infaction, ischemic perfusion, myocardial infarction, or stroke; Down's syndrome; infertility, excessive production of lipid peroxides in tissues;It may be used in a method for preventing or treating a disease selected from the group consisting of muscle-related diseases selected from myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy, and spinal muscular atrophy; accumulation of lipid peroxides in cell membranes; chronic fatigue; and retinal diseases selected from retinal fibrosis, macular degeneration, diabetic retinopathy, cataract, and neovascular glaucoma. EXAMPLES

[0204] The present invention will be described in more detail below with reference to examples. These examples are provided to more specifically explain the present invention, and it will be obvious to those skilled in the art that the scope of the present invention is not limited to these examples according to the gist of the present invention. <Reference Example - Production of Intermediates 1 to 3> Intermediate 1: Preparation of methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate

[0205] 4-Dioxaspiro[4.5]decan-8-one (10.0 g, 64 mmol) was dissolved in 250 mL of tetrahydrofuran, and sodium hydride (1.84 g, 77 mmol, 1.2 eq) was added at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and then dimethyl carbonate (11.5 g, 128 mmol, 2 eq) was added. After stirring at room temperature for 12 hours, the reaction was quenched by adding 200 mL of saturated aqueous ammonium chloride solution. The reaction mixture was extracted with ethyl acetate (100 mL x 3) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 18 / 1) to give the title compound (6.94 g, 56%) as a colorless oil.

[0206] 1 H NMR (400MHz, CDCl3): δ12.19(s, 1H), 4.04(s, 4H), 3.79(s, 3H), 2.60-2.50(m, 4H), 2.30-2.05(m, 1H), 1.88(t, J=4.8Hz, 2H).

[0207] 4-Dioxaspiro[4.5]decan-8-one (15.0 g, 96.04 mmol) was dissolved in 250 mL of anhydrous tetrahydrofuran, and then sodium hydride (9.22 g, 192.08 mmol, 2 eq) was added at room temperature. The reaction mixture was refluxed at 50° C. for 30 minutes, and then dimethyl carbonate (17.3 g, 192.08 mmol, 2 eq) was added. The reaction mixture was refluxed for 4 hours, cooled to room temperature, and neutralized with 2M aqueous hydrochloric acid at 0° C. The reaction mixture was extracted with ethyl acetate (100 mL×3) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate=3 / 1) to give the title compound (18.10 g, 88%) as a white solid.

[0208] Intermediate 2: Preparation of 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazol]-3'-ol

[0209] Methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate (2.0 g, 10.3 mmol) was dissolved in 20 mL of ethanol, followed by the addition of 2-hydrazinylpyridine (1.1 g, 10.3 mmol, 1.0 eq). The reaction mixture was refluxed for 12 h and then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (1.5 g, 54%) as a yellow solid.

[0210] 1 H NMR (400MHz, DMSO-d6): δ11.56(s, 1H), 8.41(t, J=4.8Hz, 2H), 7.88(t, J=8.0Hz, 1H), 7.19(t , J=6.0Hz, 1H), 3.95-3.90(m, 4H), 2.60-2.52(m, 2H), 2.38-2.33(m, 2H), 1.89-1.84(m, 2H).

[0211] Methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate (18.1 g, 84.53 mmol) was dissolved in 120 mL of ethanol, followed by the addition of 2-hydrazinylpyridine (9.22 g, 84.53 mmol, 1.0 eq). The reaction mixture was refluxed at 100° C. for 4 h and then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (16.39 g, 71%) as a yellow solid. Intermediate 3: Preparation of 3-hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one

[0212] 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazol]-3'-ol (5.0 g, 18.3 mmol, 1.0 eq) was dissolved in 40 mL of dichloromethane, and trifluoroacetic acid (80 mL) was added. The reaction mixture was refluxed at 50° C. for 12 hours and then concentrated under reduced pressure. The reaction mixture was diluted with dichloromethane and adjusted to pH 6 with sodium bicarbonate. The reaction mixture was extracted with dichloromethane and water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent: dichloromethane / methanol=20 / 1) to give the title compound (2.3 g, 54.9%) as a brown solid.

[0213] 1 H NMR (400MHz, DMSO-d6): δ8.48-8.40(m, 1H), 8.31(d, J=8.4Hz, 1H), 8.00-7.90(m, 1H), 7.25-7.22(m, 1H), 3.09(s, 2H), 2.93(t, J=6.8Hz, 2H), 2.62(t, J=6.8Hz, 2H). MS Calcd.:229.2;MS Found:230.2([M+H] + ).

[0214] 2'-(Pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazol]-3'-ol (12.99 g, 47.56 mmol) was dissolved in 120 mL of dichloromethane, and trifluoroacetic acid (240 mL) was added. The reaction mixture was refluxed at 60° C. for 12 hours and then concentrated under reduced pressure. The reaction mixture was recrystallized from diethyl ether to give the title compound (10.88 g, 99%) as a light brown solid. <Synthesis Example> Synthesis Example 1. Preparation of methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate

[0215] 4-Dioxaspiro[4.5]decan-8-one (10.0 g, 64 mmol) was dissolved in 250 mL of tetrahydrofuran, and sodium hydride (1.84 g, 77 mmol, 1.2 eq) was added at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and then dimethyl carbonate (11.5 g, 128 mmol, 2 eq) was added. After stirring at room temperature for 12 hours, the reaction was quenched by adding 200 mL of saturated aqueous ammonium chloride solution. The reaction mixture was extracted with ethyl acetate (100 mL x 3) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 18 / 1) to give the title compound (6.94 g, 56%) as a colorless oil.

[0216] 1 H NMR (400MHz, CDCl3): δ12.19(s, 1H), 4.04(s, 4H), 3.79(s, 3H), 2.60-2.50(m, 4H), 2.30-2.05(m, 1H), 1.88(t, J=4.8Hz, 2H).

[0217] 4-Dioxaspiro[4.5]decan-8-one (15.0 g, 96.04 mmol) was dissolved in 250 mL of anhydrous tetrahydrofuran, and then sodium hydride (9.22 g, 192.08 mmol, 2 eq) was added at room temperature. The reaction mixture was refluxed at 50° C. for 30 minutes, and then dimethyl carbonate (17.3 g, 192.08 mmol, 2 eq) was added. The reaction mixture was refluxed for 4 hours, cooled to room temperature, and neutralized with 2M aqueous hydrochloric acid at 0° C. The reaction mixture was extracted with ethyl acetate (100 mL×3) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate=3 / 1) to give the title compound (18.10 g, 88%) as a white solid.

[0218] Synthesis Example 2. Preparation of 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazol]-3'-ol

[0219] Methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate (2.0 g, 10.3 mmol) was dissolved in 20 mL of ethanol, followed by the addition of 2-hydrazinylpyridine (1.1 g, 10.3 mmol, 1.0 eq). The reaction mixture was refluxed for 12 h and then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (1.5 g, 54%) as a yellow solid.

[0220] 1 H NMR (400MHz, DMSO-d6): δ11.56(s, 1H), 8.41(t, J=4.8Hz, 2H), 7.88(t, J=8.0Hz, 1H), 7.19(t , J=6.0Hz, 1H), 3.95-3.90(m, 4H), 2.60-2.52(m, 2H), 2.38-2.33(m, 2H), 1.89-1.84(m, 2H).

[0221] Methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate (18.1 g, 84.53 mmol) was dissolved in 120 mL of ethanol, followed by the addition of 2-hydrazinylpyridine (9.22 g, 84.53 mmol, 1.0 eq). The reaction mixture was refluxed at 100° C. for 4 h and then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (16.39 g, 71%) as a yellow solid. Synthesis Example 3. Preparation of 3-hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one

[0222] 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazole]-3'-ol (5.0 g, 18.3 mmol, 1.0 eq) was dissolved in 40 mL of dichloromethane, and trifluoroacetic acid (80 mL) was added. The reaction mixture was refluxed at 50° C. for 12 hours and then concentrated under reduced pressure. The reaction mixture was diluted with dichloromethane and adjusted to pH 6 using sodium bicarbonate. The reaction mixture was extracted with dichloromethane and water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent: dichloromethane / methanol=20 / 1) to give the title compound (2.3 g, 54.9%) as a brown solid.

[0223] 1 H NMR (400MHz, DMSO-d6): δ8.48-8.40(m, 1H), 8.31(d, J=8.4Hz, 1H), 8.00-7.90(m, 1H), 7.25-7.22(m, 1H), 3.09(s, 2H), 2.93(t, J=6.8Hz, 2H), 2.62(t, J=6.8Hz, 2H). MS Calcd.:229.2;MS Found:230.2([M+H] + ).

[0224] 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazol]-3'-ol (12.99 g, 47.56 mmol) was dissolved in 120 mL of dichloromethane, and trifluoroacetic acid (240 mL) was added. The reaction mixture was refluxed at 60° C. for 12 hours and then concentrated under reduced pressure. The reaction mixture was recrystallized with diethyl ether to give the title compound (10.88 g, 99%) as a light brown solid.

[0225] Synthesis Example 4. Preparation of 5-(benzylpropylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 21)

[0226] 3-Hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one (500 mg, 2.18 mmol, 1.0 eq) was dissolved in 30 mL of dichloromethane, followed by slow addition of tert-butyldimethylsilyl chloride (494 mg, 3.27 mmol, 1.5 eq) and triethylamine (0.6 mL, 4.36 mmol, 2.0 eq) under a nitrogen stream. The reaction mixture was stirred at room temperature for 12 h and then extracted with water and brine. The organic layer was dried over anhydrous sodium sulfate and the mixture was used in the next step without further purification.

[0227] To the compound obtained from the above reaction, N-benzylpropan-1-amine (649 mg, 4.36 mmol, 2.0 eq), sodium triacetoxyborohydride (1.39 g, 6.54 mmol, 3.0 eq) and acetic acid (4 drops) were added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was adjusted to pH 8 by adding saturated aqueous sodium bicarbonate solution (50 mL), and then extracted with dichloromethane (30 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was first purified using a silica gel column (solvent: dichloromethane / methanol = 20 / 1) to obtain mixture 6 (400 mg). The first purified mixture was secondarily purified using preparative high performance liquid chromatography to obtain the title compound (104 mg, 13.1%) as a yellow solid.

[0228] 1 H NMR (400MHz, CD3OD): δ8.40(s, 1H), 8.15-8.11(m, 1H), 8.08-8.01(m, 1H), 7.56-7.5 3(m, 2H), 7.41(s, 3H), 7.34(t, J=6.4Hz, 1H), 4.58-4.51(m, 1H), 4.38-4.31(m, 1H), 3 .72-3.68(m, 1H), 3.25-3.18(m, 1H), 3.15-2.83(m, 3H), 2.80-2.70(m, 2H), 2.50-2. 42(m, 1H), 2.20-2.08(m, 1H), 1.75-1.60(m, 1H), 1.-1.57(m, 1H), 0.90-0.81(m, 3H). MS Calcd.:362.2;MS Found:363.3([M+H] + ).

[0229] Synthesis Example 5. Preparation of 5-(benzylethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 20) The title compound (120 mg, 15.8%) was obtained as a yellow solid by the preparation of compound 21 described above.

[0230] 1 H NMR (400MHz, CD3OD): δ9.55-9.40(m, 1H), 8.42(d, J=4.0Hz, 1H), 8.40-8.30(br, 1 H), 7.92(t, J=8.0Hz, 1H), 7.60-7.45(m, 4H), 7.23(t, J=6.8Hz, 1H), 4.68(t, J=13 .6Hz, 1H), 4.50-4.44(m, 1H), 3.90-3.86(m, 1H), 3.47-3.37(m, 2H), 3.20-3.02(m , 2H), 2.95-2.90(m, 2H), 2.60-2.50(m, 1H), 2.35-2.25(m, 1H), 1.47-1.37(m, 3H). MS Calcd.:347.5;MS Found:349.2([M+H]+).

[0231] Synthesis Example 6. Preparation of 5-(benzylbutylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 22) The title compound (100 mg, 12.1%) was obtained as a yellow solid by the preparation of compound 21 described above.

[0232] 1 H NMR (400MHz, CD3OD): δ9.55-9.40(m, 1H), 8.42(d, J=4.0Hz, 1H), 8.40-8.30(br, 1H), 7.92 (t, J=8.0Hz, 1H), 7.60-7.45(m, 5H), 7.23(t, J=6.8Hz, 1H), 4.61-4.50(m, 1H), 4.40-4.35 (m, 1H), 3.66-3.50(m, 2H), 3.30-3.15(m, 2H), 3.10-2.90(m, 1H), 2.80-2.55(m, 4H), 2.45 -2.30(m, 1H), 2.15-1.80(m, 1H), 1.75-1.60(m, 1H), 1.60-1.40(m, 1H), 1.35-1.22(m, 3H). MS Calcd.:376.2;MS Found:377.2([M+H] + ).

[0233] Synthesis Example 7. Preparation of 5-[(2-methoxybenzyl)-methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 26)

[0234] 3-Hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one (500 mg, 2.18 mmol, 1.0 eq) was dissolved in 30 mL of dichloromethane, followed by the addition of 1-(2-methoxyphenyl)-N-methylmethanamine (658 mg, 4.36 mmol, 2.0 eq) and sodium triacetoxyborohydride (1.39 g, 6.54 mmol, 3.0 eq), and 4 drops of acetic acid. The reaction mixture was stirred at room temperature for 12 hours. Saturated aqueous sodium bicarbonate solution (50 mL) was added to the reaction mixture, followed by extraction with dichloromethane (50 mL x 2). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative high performance liquid chromatography to give the title compound (200 mg, 34.0%) as a yellow solid. In this manner, compounds 39-60, 64-68, 72-76, 78-81, 121-125, 146-153, and 157-159 were prepared.

[0235] 1 H NMR (400MHz, CD3OD): δ8.56(d, J=5.2Hz, 1H), 8.30-8.22(m, 2H), 7.59-7.52(m , 3H), 7.19(d, J=8.4Hz, 1H), 7.10(t, J=7.6Hz, 1H), 4.78(dd, J1=12.8Hz, J2=19 .2Hz, 1H), 4.20(dd, J1=12.8Hz, J2=27.6Hz, 1H), 4.00(s, 3H), 3.90-3.85(m, 1H) ), 3.15-3.08(m, 2H), 3.00-2.85(m, 5H), 2.60-2.50(m, 1H), 2.40-2.10(m, 1H). MS Calcd.:364.2;MS Found:365.3([M+H] + ). Synthesis Example 8. Preparation of 5-(benzylmethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 1) The title compound (200 mg, 27.4%) was obtained as a white solid by the preparation of compound 26 described above.

[0236] 1H NMR (400MHz, DMSO-d6): δ10.8-10.50(br, 1H), 8.45-8.38(m, 2H), 7.88(t, J=11.2Hz, 1H), 7.40-7.15(m, 6H), 3.63(q, J1=18.4Hz, J2=34.4Hz, 2H), 2.80-2.70(m, 1H), 2.65-2.55(m, 1H), 2.52-2.50(m, 1H), 2.48-2.30(m, 1 H), 2.31-2.25(m, 1H), 2.16(s, 3H), 2.05-1.85(m, 1H), 1.71-1.65(m, 1H). MS Calcd.:334.2;MS Found:335.2([M+H] + ).

[0237] Synthesis Example 9. Preparation of 5-(benzylcyclopropylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 2) The title compound (94 mg, 11.9%) was obtained as a yellow solid by the preparation of compound 26 described above.

[0238] 1 H NMR (400MHz, DMSO-d6): δ11.39(s, 1H), 8.42-8.37(m, 2H), 7.92-7.85(m, 1H), 7.31-7.15(m, 6H), 3.82(s, 2H), 2.80-2.70( m, 1H), 2.60-2.52(m, 1H), 2.50-2.35(m, 2H), 2.13-2.00(m, 2H), 1.77-1.72(m, 1H), 0.48-0.43(m, 2H), 0.30-0.26(m, 2H). MS Calcd.:360.2;MS Found:361.0([M+H] + ).

[0239] Synthesis Example 10. Preparation of 4-{[(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile (Compound 3) The title compound (103 mg, 16.4%) was obtained as a yellow solid by the preparation of compound 26 described above.

[0240] 1 H NMR (400MHz, DMSO-d6): δ8.40(s, 1H), 7.96-7.60(m, 4H), 7.60-7.55(m, 2H), 7.22-7.18(m, 0.5H), 6.95-6.90(m, 0.5H), 3.80-3 .62(m, 2H), 2.90-2.75(m, 1H), 2.75-2.60(m, 2H), 2.50-2.22(m, 2H), 2.21-2.04(m, 3H), 2.05-1.92(m, 1H), 1.75-1.62(m, 1H). MS Calcd.:359.4;MS Found:360.2([M+H] + ).

[0241] Synthesis Example 11. Preparation of 5-[(4-fluorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 4) The title compound (189 mg, 30.8%) was obtained as a white solid by the preparation of Compound 26 described above.

[0242] 1 H NMR (400MHz, DMSO-d6): δ8.40-8.33(m, 2H), 7.90-7.83(m, 1H), 7.40-7.30(m, 2H), 7.22-7.10(m, 3H), 3.58(q, J1=13.6Hz, J 2=30.0Hz, 2H), 2.75-2.60(m, 2H), 2.50-2.22(m, 1H), 2.21-2.04(m, 1H), 2.15(s, 3H), 2.03-1.96(m, 1H), 1.68-1.52(m, 1H). MS Calcd.:352.2;MS Found:353.1([M+H] + ).

[0243] Synthesis Example 12. Preparation of 5-[(2,4-difluorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 5) The title compound (150 mg, 23.3%) was obtained as a brown solid by the preparation of compound 26 described above.

[0244] 1H NMR (400MHz, DMSO-d6): δ11.60-11.45(br, 1H), 8.50-8.36(m, 2H), 7.96-7.92(m , 1H), 7.46(q, J1=11.2Hz, J2=20.4Hz, 2H), 7.22-7.16(m, 2H), 7.10-7.05(m, 1H), 3.63(q, J1=9.6Hz, J2=28.0Hz, 2H), 2.75-2.60(m, 2H), 2.60-2.50(m, 1H), 2.50- 2.42(m, 1H), 2.42-2.20(m, 1H), 2.20(s, 3H), 2.03-1.96(m, 1H), 1.-1.68(m, 1H). MS Calcd.:370.2;MS Found:371.1([M+H] + ).

[0245] Synthesis Example 13. Preparation of 5-[(2-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 6) The title compound (270 mg, 42.0%) was obtained as a brown solid by the preparation of Compound 26 described above.

[0246] 1 H NMR (400MHz, DMSO-d6): δ11.60-11.45 (br, 1H), 8.50-8.38 (m, 2H), 7.92-7.90 (m, 1H) ), 7.53(d, J=7.2Hz, 1H), 7.42(d, J=7.6Hz, 1H), 7.40-7.35(m, 1H), 7.35-7.30(m, 1H) ), 7.20-7.17(m, 1H), 3.76-3.68(m, 2H), 2.85-2.70(m, 2H), 2.65-2.55(m, 1H), 2.55 -2.50(m, 1H), 2.42-2.20(m, 2H), 2.20(s, 3H), 2.03-1.96(m, 1H), 1.72-1.68(m, 1H). MS Calcd.:368.9;MS Found:369.1([M+H] + ).

[0247] Synthesis Example 14. Preparation of 5-[(3-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 7) The title compound (150 mg, 23.4%) was obtained as a white solid by the preparation of Compound 26 described above.

[0248] 1 H NMR (400MHz, DMSO-d6): δ11.50-11.42(br, 1H), 8.50-8.38(m, 2H), 7.90-7.80(m, 1H), 7.40-7.23(m, 4H), 7.30-7.23(m, 1H), 3.65(q, J1=14.0Hz, J2=32.0Hz, 2H), 2.85-2.70(m, 1H), 2.65-2.55(m, 1H), 2.55-2.50(m, 1H) ), 2.42-2.20(m, 1H), 2.20(s, 3H), 2.03-1.96(m, 1H), 1.68-1.60(m, 1H). MS Calcd.:368.1;MS Found:369.1([M+H] + ).

[0249] Synthesis Example 15. Preparation of 5-[methyl-(4-trifluoromethylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 8) The title compound (304 mg, 43.5%) was obtained as a white solid by the preparation of compound 26 described above.

[0250] 1 H NMR (400MHz, DMSO-d6): δ11.43(s, 1H), 8.44-8.38(m, 2H), 7.92-7.90(m, 1H) 7.67 (d, J=8.0Hz, 2H), 7.58(d, J=8.0Hz, 2H), 7.17(t, J=5.6Hz, 1H), 3.70(q, J1=14.4Hz , J2=31.2Hz, 2H), 2.85-2.70(m, 1H), 2.65-2.55(m, 1H), 2.55-2.50(m, 1H), 2.42-2 .30(m, 1H), 2.30-2.20(m, 1H), 2.20(s, 3H), 2.03-1.96(m, 1H), 1.72-1.68(m, 1H). MS Calcd.:402.4;MS Found:403.1([M+H] + ).

[0251] Synthesis Example 16. Preparation of 5-[methyl-(3-methylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 9) The title compound (103 mg, 17.0%) was obtained as a brown solid by the preparation of Compound 26 described above.

[0252] 1 H NMR (400MHz, DMSO-d6): δ11.43(s, 1H), 8.44-8.38(m, 2H), 7.92-7.90(m, 1H), 7.21-7.04(m, 4H), 7.04-7.02(m, 1H), 3.60-3.48(m, 2H), 2. 80-2.72(m, 1H), 2.70-2.66(m, 1H), 2.48-2.40(m, 1H), 2.29(s, 3H), 2 .20-2.16(m, 1H), 2.19(s, 3H), 2.03-1.96(m, 2H), 1.70-1.62(m, 1H). MS Calcd.:348.4;MS Found:349.2([M+H] + ).

[0253] Synthesis Example 17. Preparation of 5-[methyl-(3-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 10) The title compound (292 mg, 57.5%) was obtained as a white solid by the preparation of Compound 26 described above.

[0254] 1 H NMR (400MHz, DMSO-d6): δ11.43(s, 1H), 8.44-8.38(m, 2H), 7.92-7.90(m, 1H), 7.71-7.52(m, 4H), 7.19-7.16(m, 1H), 3.70(q, J1=12.0Hz, J2= 30.4Hz, 2H), 2.85-2.70(m, 1H), 2.65-2.55(m, 1H), 2.55-2.50(m, 1H), 2.45-2.20(m, 2H), 2.20(s, 3H), 2.03-1.96(m, 1H), 1.73-1.68(m, 1H). MS Calcd.:402.4;MS Found:403.2([M+H] + ).

[0255] Synthesis Example 18. Preparation of 5-[methyl-(2-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 11) The title compound (117 mg, 16.7%) was obtained as a brown solid by the preparation of compound 26 described above.

[0256] 1 H NMR (400MHz, DMSO-d6): δ11.52-11.47(br, 1H), 8.50-8.38(m, 2H), 7.89-7.83(m , 2H), 7.70-7.65(m, 2H), 7.45(t, J=7.6Hz, 1H), 7.18(br, 1H), 3.80(q, J1=10.0Hz , J2=25.0Hz, 2H), 2.86-2.70(m, 1H), 2.65-2.55(m, 1H), 2.53-2.50(m, 1H), 2.42- 2.31(m, 1H), 2.29-2.20(m, 1H), 2.20(s, 3H), 2.05-1.96(m, 1H), 1.-1.68(m, 1H). MS Calcd.:402.4;MS Found:403.1([M+H] + ).

[0257] Synthesis Example 19. Preparation of 5-[(4-methanesulfonylbenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 12) The title compound (100 mg, 11.1%) was obtained as a white solid by the preparation of compound 26 described above.

[0258] 1H NMR (400MHz, DMSO-d6): δ11.45(s, 1H), 8.44-8.38(m, 2H), 7.89(d, J=8.0Hz, 3H) , 7.60(d, J=8.0Hz, 2H), 7.19-7.16(m, 1H), 3.72(q, J1=14.8Hz, J2=31.2Hz, 2H), 3.19(s, 3H), 2.84-2.80(m, 1H), 2.65-2.55(m, 1H), 2.55-2.50(m, 1H), 2.42-2.3 2(m, 1H), 2.28-2.20(m, 1H), 2.20(s, 3H), 2.05-1.98(m, 1H), 1.72-1.68(m, 1H). MS Calcd.:412.1;MS Found:413.1([M+H] + ).

[0259] Synthesis Example 20. Preparation of 5-[(3-methanesulfonylbenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 23) The title compound (50 mg, 5.5%) was obtained as a white solid by the preparation of compound 26 described above.

[0260] 1 H NMR (400MHz, DMSO-d6): δ8.51-8.30(m, 2H), 7.95-7.85(m, 2H), 7.81(d, J=8.0Hz, 1H ), 7.70(d, J=8.0Hz, 1H), 7.60(t, J=8.0Hz, 1H), 7.25-7.15(m, 1H), 3.76(dd, J1=14. 0Hz, J2=31.6Hz, 2H), 3.21(s, 3H), 2.90-2.80(m, 1H), 2.70-2.60(m, 1H), 2.60-2.50 (m, 1H), 2.50-2.40(m, 1H), 2.30-2.15(m, 4H), 2.10-2.00(m, 1H), 1.70-1.60(m, 1H). MS Calcd.:412.5;MS Found:413.1([M+H] + ).

[0261] Synthesis Example 21. Preparation of 5-[methyl-(4-methylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 24) The preparation of compound 26 described above afforded the title compound (50 mg, 5.5%) as a bright yellow solid.

[0262] 1 H NMR (400MHz, CD3OD): δ8.51-8.50(m, 1H), 8.35-8.20(m, 2H), 7.65-7.47(m, 3H), 7.34(d, J=8.0Hz, 2H), 4.63(t, J=13.2Hz, 1H), 4. 34(t, J=13.6Hz, 1H), 3.90-3.70(m, 1H), 3.20-3.00(m, 2H), 3.00-2.75(m, 5H), 2.65-2.52(m, 1H), 2.41(s, 3H), 2.25-2.10(m, 1H). MS Calcd.:348.2;MS Found:349.2([M+H] + ).

[0263] Synthesis Example 22. Preparation of 5-[(3-methoxybenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 13) The title compound (105 mg, 13.2%) was obtained as a brown solid by the preparation of Compound 26 described above.

[0264] 1 H NMR (400MHz, CDCl3) δ8.24(br, 1H), 7.82(m, 2H), 7.26-7.22(m, 1H), 7.14-7.02(m, 1H), 7.00-6.90(m, 2H), 6.80-6.75(m, 1H), 3.85-3.80 (m, 3H), 3.65(s, 2H), 2.95-2.78(m, 2H), 2.65-2.52(m, 2H), 2.50-2.40(m, 1H), 2.32-2.28(m, 3H), 2.27-2.16(m, 1H), 1.72-1.58(m, 1H). MS Calcd.:364.2;MS Found:365.1([M+H] + ). Synthesis Example 23. Preparation of 5-piperidin-1-yl-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 14) The title compound (70 mg, 10.7%) was obtained as a brown solid by the preparation of compound 26 described above.

[0265] 1 H NMR (400MHz, DMSO-d6): δ9.74(br, 1H), 8.42(d, J=4.4Hz, 1H), 8.35(d, J=8.0Hz, 1H), 7.92(t, J=8.4Hz, 1H), 7.23(t, J=6.8Hz, 1H), 3 .60-3.40(m, 3H), 3.12-3.02(m, 2H), 2.75-2.60(m, 3H), 2.55-2.48(m, 1H), 2.30-2.27(m, 1H), 1.90-1.70(m, 6H), 1.50-1.42(m, 1H). MS Calcd.:298.2;MS Found:299.2([M+H] + ). Synthesis Example 24. Preparation of 5-morpholin-4-yl-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 15) The title compound (80 mg, 11.3%) was obtained as a brown solid by the preparation of compound 26 described above.

[0266] 1 H NMR (400MHz, DMSO-d6): δ11.65-11.47(br, 1H), 8.39-8.33(m, 2H), 7.89(t, J=7.2Hz, 1H), 7.18(t, J=5.6Hz, 1H), 3.59-3.53 (m, 4H), 2.60-2.55(m, 2H), 2.55-2.45(m, 4H), 2.45-2.40(m, 1H), 2.20-2.05(m, 1H), 2.01-1.98(m, 1H), 1.62-1.50(m, 1H). MS Calcd.:300.4;MS Found:301.2([M+H] + ).

[0267] Synthesis Example 25. Preparation of 5-(4-methylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 16) The title compound (195 mg, 28.5%) was obtained as a gray solid by the method for preparing compound 26 described above.

[0268] 1 H NMR (400MHz, DMSO-d6): δ8.42(d, J=4.4Hz, 1H), 8.35(d, J=8.4Hz, 1H), 7.91(t, J=7.6Hz, 1H), 7.22(t, J=5.6Hz, 1 H), 3.70-3.20(br, 9H), 2.88(s, 3H), 2.74-2.51(m, 3H), 2.42-2.37(m, 1H), 2.26-2.23(m, 1H), 1.82-1.72(m, 1H). MS Calcd.:313.4;MS Found:314.2([M+H] + ).

[0269] Synthesis Example 26. Preparation of 5-(3,4-dihydro-1H-isoquinolin-2-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 18) The title compound (120 mg, 16.0%) was obtained as a white solid by the preparation of compound 26.

[0270] 1 H NMR (400MHz, DMSO-d6): δ11.47(s, 1H), 8.44-8.38(m, 2H), 7.91-7.88(m, 1H), 7.19-7.16(m, 1H), 7.10-7.04(m, 4 H), 3.76(s, 2H), 2.91-2.50(m, 7H), 2.50-2.40(m, 1H), 2.40-2.25(m, 1H), 2.20-2.02(m, 1H), 1.78-1.70(m, 1H). MS Calcd.:346.2;MS Found:347.2([M+H] + ).

[0271] Synthesis Example 27. Preparation of 3-{[(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile hydrochloride (Compound 25) The title compound (104 mg, 13.3%) was obtained as a yellow solid by the preparation of Compound 26 described above.

[0272] 1 H NMR (400MHz, CD3OD): δ8.5(d, J=6.0Hz, 1H), 8.40-8.32(m, 1H), 8.21(d, J=8.4Hz , 1H), 8.16-8.10(m, 1H), 8.08-8.00(m, 1H), 7.90(d, J=8.0Hz, 1H), 7.72(t, J=8.0 Hz, 1H), 7.66-7.56(m, 1H), 4.80-4.75(m, 1H), 4.62-4.45(m, 1H), 4.00-3.80(m, 1H), 3.25-3.00(m, 2H), 3.00-2.80(m, 5H), 2.70-2.60(m, 1H), 2.30-2.15(m, 1H). MS Calcd.:359.1, MS Found:360.1([M+H] + ).

[0273] Synthesis Example 28. Preparation of 5-[(4-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 19) The title compound (144 mg, 22.5%) was obtained as a brown solid by the preparation of Compound 26 described above.

[0274] 1H NMR (400MHz, DMSO-d6): δ11.42(s, 1H), 8.44-8.38(m, 2H), 7.87(m, 1H), 7.39-7.33(m, 4H), 7.19-7.16(m, 1H), 3.72(q, J1=13.6Hz, J2=30.4Hz, 2H), 2.83-2.80(m, 1H), 2.65-2.55(m, 1H), 2.55-2.50(m, 1H), 2.42-2.32(m, 1 H), 2.28-2.20(m, 1H), 2.16(s, 3H), 2.05-1.98(m, 1H), 1.72-1.68(m, 1H). MS Calcd.:368.1;MS Found:369.1([M+H] + ).

[0275] Synthesis Example 29. Preparation of 5-[(3-fluorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 27) The title compound (95 mg, 12.3%) was obtained as a yellow solid by the preparation of compound 26 described above.

[0276] 1 H NMR (400MHz, CD3OD): δ8.44(d, J=5.6Hz, 1H), 8.25-8.15(m, 1H), 8.15-8.10(m, 1H), 7.50-7.45(m, 2H), 7.39(d, J=8.4Hz, 2H), 7.25-7.10(m , 1H), 4.65-4.55(m, 1H), 4.40-4.28(m, 1H), 3.80-3.65(m, 1H), 3.10- 2.90(m, 2H), 2.85-2.65(m, 5H), 2.50-2.40(m, 1H), 2.15-2.00(m, 1H). MS Calcd.:352.2;MS Found:353.1([M+H] + ).

[0277] Synthesis Example 30. Preparation of 5-[(4-methoxybenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 28) The title compound (80 mg, 10.7%) was obtained as a yellow oil by the preparation of compound 26 described above.

[0278] 1 H NMR (400MHz, CD3OD): δ8.44(d, J=5.2Hz, 1H), 8.30-8.20(m, 1H), 8.15-8.05(m, 1H), 7.55-7.40(m, 3H), 6.94(d, J=8.4Hz, 2H), 4.50(t, J=12.8Hz, 1H), 4.22(t, J=14.0Hz, 1H), 3.76-3.64(m, 4H), 3.10-2.93(m, 2H), 2.92-2.70(m, 5H), 2.50-2.42(m, 1H), 2.10-2.00(m, 1H). MS Calcd.:364.2;MS Found:365.2([M+H] + ).

[0279] Synthesis Example 31. Preparation of 5-[methyl-(2-methylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 29) The title compound (300 mg, 39.5%) was obtained as a white solid by the preparation of compound 26 described above.

[0280] 1 H NMR (400MHz, CD3OD): δ8.43(d, J=5.2Hz, 1H), 8.20-8.10(m, 2H), 7.50-7.37(m, 2H), 7.35-7.20(m, 3H), 4.68(dd, J1=13.6Hz, J2=23.6Hz, 1H), 4. 21(dd, J1=13.2Hz, J2=32.8Hz, 1H), 3.90-3.73(m, 1H), 3.10-2.85(m, 2H ), 2.84-2.65(m, 5H), 2.51-2.45(m, 1H), 2.43(s, 3H), 2.30-2.00(m, 1H). MS Calcd.:348.2;MS Found:349.2([M+H] + ).

[0281] Synthesis Example 32. Preparation of 5-[(2,4-dichlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 30) The title compound (127 mg, 13.3%) was obtained as a white solid by the preparation of compound 26 described above.

[0282] 1 H NMR (400MHz, CD3OD): δ8.42(d, J=5.2Hz, 1H), 8.20-8.07(m, 2H), 7.71(d, J=8.0Hz, 1H), 7.61(d, J=2.0Hz, 1H), 7.49-7.35(m, 2H), 4. 78-4.68(m, 1H), 4.50-4.30(m, 1H), 3.90-3.70(m, 1H), 3.10-2.90(m, 2H), 2.90-2.65(m, 5H), 2.55-2.45(m, 1H), 2.30-2.05(m, 1H). MS Calcd.:402.1;MS Found:403.1([M+H] + ).

[0283] Synthesis Example 33. Preparation of 5-[(3,4-dichlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 31) The title compound (144 mg, 16.4%) was obtained as a yellow solid by the preparation of compound 26 described above.

[0284] 1 H NMR (400MHz, CD3OD): δ8.54(d, J=5.2Hz, 1H), 8.30-8.20(m, 2H), 7.93(d, J=1.6Hz, 1H), 7.75-7.60(m, 2H), 7.58-7.50(m, 1H), 4.7 5-4.60(m, 1H), 4.50-4.35(m, 1H), 3.95-3.76(m, 1H), 3.20-3.00(m, 2H), 3.00-2.77(m, 5H), 2.62-2.55(m, 1H), 2.23-2.15(m, 1H). MS Calcd.:402.1;MS Found:403.1([M+H] + ).

[0285] Synthesis Example 34. Preparation of 5-(methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 33) 1) Preparation of N-methyl-5,6,7,8-tetrahydroquinolin-8-amine

[0286] 6,7-Dihydroquinolin-8(5H)-one (2.0g, 13.59mmol) was dissolved in 40mL of dichloroethane, and then methylamine (3.39mL, 27.18mmol, 2.0eq) and 7 drops of acetic acid were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (5.7g, 27.18mmol, 2.0eq) was added. The reaction mixture was stirred at room temperature for 12 hours, and then 10% aqueous ammonium chloride solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (60mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the title compound (1.98g, 90.0%).

[0287] 1 H NMR (600MHz, CDCl3): δ8.33(d, J=4.1Hz, 1H), 7.25-7.32(m, 1H), 7.01(q, J=4.1Hz, 1H), 3.66(m, 1H), 2.7 3-2.78(m, 1H), 2.66-2.70(m, 1H), 2.49(s, 3H), 2.07-2.11(m, 1H), 1.91-1.96(m, 1H), 1.66-1.76(m, 2H).

[0288] 2) Preparation of 5-(methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol

[0289] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (0.03 g, 0.13 mmol) was dissolved in 8 mL of dichloroethane, and then N-methyl-5,6,7,8-tetrahydroquinolin-8-amine (0.02 g, 0.13 mmol, 1.0 eq) and 2 drops of acetic acid were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium cyanoborohydride (0.01 g, 0.16 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 12 hours, and then 10% aqueous ammonium chloride solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol=5 / 1+0.1% triethylamine) to give the title compound (0.05 g, 11.0%) as a brown solid.

[0290] 1 H NMR (600MHz, CDCl3): δ8.50-8.44(m, 1H), 8.23-8.17(m, 1H), 7.90-7.70(m, 2H), 7.33(d, J=7.4Hz, 1H), 7.10-6.97(m, 2H), 4.20-4.12(m, 1H), 3. 15-2.95(m, 1H), 2.85-2.77(m, 3H), 2.71-2.65(m, 1H), 2.60-2.42(m, 2H) ), 2.29(s, 3H), 2.27-2.20(m, 1H), 2.05-1.95(m, 2H), 1.83-1.67(m, 3H). MS Calcd.:375.2;MS Found:376.1([M+H] + ).

[0291] Synthesis Example 35. Preparation of cyclopropyl(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)methanone (Compound 38)

[0292] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (2.5g, 10.9mmol) was dissolved in 100mL of dichloromethane / dichloroethane (1 / 1), followed by the addition of cyclopropyl(piperazin-1-yl)methanone hydrochloride (3.1g, 16.4mmol, 1.5eq), diisopropylethylamine (2.8ml, 16.4mmol, 1.5eq), and acetic acid (1.0ml, 16.4mmol, 1.5eq). The reaction mixture was stirred at room temperature for 3 hours, followed by the addition of sodium triacetoxyborohydride (4.6g, 21.8mmol, 2.0eq). The reaction mixture was stirred at room temperature for 48 hours, followed by the addition of 2M aqueous sodium hydroxide solution to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was primarily purified by silica gel column chromatography (dichloromethane / methanol=5 / 1) and then recrystallized from diethyl ether to give the title compound (2.8 g, 70.0%) as a light brown solid.

[0293] 1 H NMR (600MHz, CDCl3): δ8.23(d, J=5.5Hz, 1H), 7.82(t, J=3.4Hz, 2H), 7.10(q, J=4.1Hz, 1H), 3.74-3.61(m, 4H), 2.91-2.81( m, 1H), 2.81-2.52(m, 8H), 2.44-2.35(m, 1H), 2.15-2.07(m, 1H), 1.76-1.70(m, 1H), 1.04-0.95(m, 2H), 0.79-0.70(m, 2H). MS Calcd.:367.2;MS Found:368.1([M+H] + ).

[0294] Synthesis Example 36. Preparation of 5-((4-(dimethylamino)benzyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 70)

[0295] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (0.70 g, 3.04 mmol) was dissolved in 40 mL of dichloromethane / dichloroethane (1 / 1), and then N,N-dimethyl-4-((methylamino)methyl)aniline (0.50 g, 3.04 mmol, 1.0 eq) and acetic acid (0.19 ml, 3.04 mmol, 1.0 eq) were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (0.64 g, 3.04 mmol, 1.0 eq) was added. The reaction mixture was stirred at room temperature for 18 hours, and then 2 M aqueous sodium hydroxide solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol=5 / 1) to give the title compound (0.094 g, 8.0%) as a black solid.

[0296] 1 H NMR (600MHz, CD3OD): δ8.42-8.34(m, 1H), 8.25(d, J=8.8Hz, 1H), 7.90-7.79(m , 1H), 7.27(d, J=9.0Hz, 2H), 7.18(dd, J=8.0, 5.4Hz, 1H), 6.77(d, J=9.1Hz, 2H ), 4.11(dd, J=23.9, 13.5Hz, 2H), 3.55-3.37(m, 1H), 2.93(s, 6H), 2.87-2.72( m, 2H), 2.63(s, 3H), 2.58-2.47(m, 2H), 2.34-2.25(m, 1H), 2.02-1.92(m, 1H). MS Calcd.:377.2;MS Found:378.3([M+H] + ). Synthesis Example 37. Preparation of 2-pyridin-2-yl-5-pyrrolidin-1-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 96)

[0297] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (0.30 g, 1.30 mmol) was dissolved in 10 mL of dichloromethane, and then pyrrolidine (0.32 ml, 3.91 mmol, 3.0 eq) and acetic acid (0.16 ml, 2.61 mmol, 2.0 eq) were added. The reaction mixture was stirred at room temperature for 12 hours, and then sodium triacetoxyborohydride (0.35 g, 1.65 mmol, 1.3 eq) was added. The reaction mixture was stirred at room temperature for 12 hours, and then 10% aqueous sodium bicarbonate was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 5 / 1) to obtain the title compound (0.085 g, 23.0%) as a brown jelly. In this manner, compounds 17, 160 and 161 were prepared.

[0298] 1 H NMR (600MHz, CDCl3): δ10.45(brs, 1H), 8.23(s, 1H), 7.98-7.75(m, 2H), 7.21-7.05(m, 1H), 3. 51-3.20(m, 5H), 3.00-2.80(m, 2H), 2.77-2.59(m, 2H), 2.45-2.30(m, 1H), 2.15-2.00(m, 5H). MS Calcd.:284.2;MS Found:285.4([M+H] + ).

[0299] Synthesis Example 38. Preparation of 5-(4-methoxybenzylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 88) The title compound (0.30 g, 39.3%) was obtained as a dark gray solid by the same method as described above for preparing compound 96.

[0300] 1H NMR (600MHz, CDCl3): δ8.23(d, J=4.8Hz, 1H), 7.93-7.85(m, 1H), 7.83-7.77(m, 1H), 7.36(d, J=8.6 Hz, 2H), 7.09(dd, J=7.5, 5.3Hz, 1H), 6.86(d, J=8.7Hz, 2H), 3.93(dd, J=50.4, 13.1Hz, 2H), 3.06(dd d, J=12.3, 5.1, 2.6Hz, 1H), 2.90(dd, J=14.7, 5.0Hz, 1H), 2.78(ddd, J=16.7, 4.9, 3.9Hz, 1H), 2.58( ddd, J=16.8, 11.1, 5.7Hz, 1H), 2.50(dd, J=14.6, 9.6Hz, 1H), 2.26-2.14(m, 1H), 1.91-1.81(m, 1H). MS Calcd.:350.2;MS Found:351.3([M+H] + ). Synthesis Example 39. Preparation of 5-phenethylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 93) The title compound (0.30 g, 39.3%) was obtained as a dark gray solid by the same method as described above for preparing compound 96.

[0301] 1 H NMR (600MHz, DMSO-d6): δ8.44-8.23(m, 2H), 7.85(t, J=7.1Hz, 1H), 7.27-7.23(m, 2H), 7.21-7.18(m, 2H), 7.15-7.12(m, 2H), 2.90-2.75(m, 3H), 2.72-2.65(m, 2H), 2.60-2.50(m, 1H), 2.48-2.35(m, 2H), 1.95-1.89(m, 2H), 1.56-1.44(m, 1H). MS Calcd.:334.2;MS Found:335.3([M+H] + ). Synthesis Example 40. Preparation of 5-phenylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 92) The title compound (0.21 g, 53.2%) was obtained as a brown solid by the preparation of Compound 96 described above.

[0302] 1 H NMR (600MHz, CDCl3OD): δ8.27-8.21(m, 1H), 7.87-7.79(m, 2H), 7.20-7.13(m, 2H), 7.13-7.03(m, 1H), 6.74-6.66(m, 1H), 6.66-6.58(m, 2H), 3.90-3.73(m, 1H), 2.95(ddd, J=16.0, 9.0, 4.5Hz, 1H), 2.85-2.69(m, 2H), 2.45-2.33(m, 1H), 2.23-2.07(m, 1H), 1.95-1.79(m, 1H). MS Calcd.:306.2;MS Found:307.3([M+H] + ).

[0303] Synthesis Example 41. Preparation of 5-(3,4-difluorophenylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 32) The title compound (0.22 g, 74.2%) was obtained as a dark gray solid by the same method as used for preparing compound 96.

[0304] 1 H NMR (600MHz, DMSO-d6): δ11.50(s, 1H), 8.39(d, J=8.4Hz, 1H), 8.36(d, J=4.0Hz, 1H), 7.84( t, J=7.2Hz, 1H), 7.14(dd, J=6.9, 5.2Hz, 1H), 7.06(q, J=9.7Hz, 1H), 6.58(ddd, J=13.7, 6.8 , 2.4Hz, 1H), 6.37(d, J=9.1Hz, 1H), 5.80(d, J=8.1Hz, 1H), 3.62-3.50(m, 1H), 2.64-2.55(m , 2H), 2.51(dd, J=15.1, 5.1, 1H), 2.06-2.00(m, 1H), 2.00-1.93(m, 1H), 1.64-1.53(m, 1H). MS Calcd.:342.1;MS Found:343.2([M+H] + ).

[0305] Synthesis Example 42. Preparation of 5-(4-ethylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 91) The title compound (0.20 g, 47.0%) was obtained as a brown jelly by the preparation of Compound 96.

[0306] 1 H NMR (600MHz, CDCl3): δ8.28-8.00(m, 1H), 7.95-7.80(m, 1H), 7.80-7.65(m, 1H), 7.10-6.95(m, 1H), 2.85-2. 50(m, 12H), 2.35-2.25(m, 1H), 2.15-2.05(m, 1H), 2.05-1.95(m, 2H), 1.70-1.55(m, 1H), 1.50-1.15(m, 3H). MS Calcd.:327.2;MS Found:328.4([M+H] + ).

[0307] Synthesis Example 43. Preparation of 5-(4-propylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 100)

[0308] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (0.25 g, 1.09 mmol) was dissolved in 14 mL of dichloromethane / dichloroethane (1 / 1), followed by the addition of 1-propylpiperazine dihydrobromide (0.41 g, 1.42 mmol, 1.3 eq) and diisopropylethylamine (0.50 ml, 2.84 mmol, 2.6 eq). The reaction mixture was stirred at room temperature for 1 hour, followed by the addition of sodium triacetoxyborohydride (0.30 g, 1.42 mmol, 1.3 eq). The reaction mixture was extracted with dichloromethane (20 mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 5 / 1) to give the title compound (0.11 g, 29.0%) as a brown solid. In this manner, compounds 127 and 128 were prepared.

[0309] 1H NMR (600MHz, CDCl3OD): δ8.28-8.16(m, 1H), 8.00-7.58(m, 2H), 7.17-6.97(m, 1H), 3.05-2.87(m, 8H), 2.85-2.75(m, 2H), 2.71(dd, J=14.5, 4.7Hz, 1H), 2.68-2.57(m, 3H), 2.39(dd, J=14.3, 10.8Hz, 1H), 2.21-2.12(m, 1H), 1.75-1.65(m, 3H), 0.93(t, J=7.4Hz, 3H). MS Calcd.:341.2;MS Found:342.4([M+H] + ).

[0310] Synthesis Example 44. Preparation of 5-(4-cyclohexylmethylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 106) The title compound (0.14 g, 33.1%) was obtained as a brown solid by the preparation of Compound 100 described above.

[0311] 1 H NMR (600MHz, CD3OD): δ8.45-8.20(m, 2H), 7.87(dd, J=12.7, 5.3Hz, 1H), 7.19(dd, J=7.1, 5.3Hz, 1H), 3.55-3.35(m, 1H), 3.09-2 .53(m, 10H), 2.40-2.25(m, 1H), 2.25-2.07(m1H), 1.92-1.61(m, 8H), 1.37-1.28(m, 4H), 1.26-1.19(m, 1H), 1.10-0.90(m, 2H). MS Calcd.:395.3;MS Found:396.3([M+H] + ).

[0312] Synthesis Example 45. Preparation of 5-(4-benzylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 105) The title compound (0.20 g, 47.1%) was obtained as a brown solid by the preparation of Compound 100 described above.

[0313] 1H NMR (600MHz, CDCl3): δ8.22 (d, J=5.1Hz, 1H), 7.90-7.70 (m, 2H), 7.39-7.27 (m, 5H), 7.11 (dd, J=7.5, 5.4Hz, 1H), 3.75(brs, 2H), 3.31-2.75(m, 10H), 2.74-2.61(m, 2H), 2.60-2.42(m, 1H), 2.41-2.24(m, 1H), 1.89-1.67(m, 1H). MS Calcd.:389.2;MS Found:390.3([M+H] + ).

[0314] Synthesis Example 46. Preparation of 5-(4-phenethylpiperazin-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 104) The title compound (0.18 g, 40.9%) was obtained as a brown solid by the preparation of Compound 100 described above.

[0315] 1 H NMR (600MHz, CDCl3): δ10.24 (brs, 1H), 8.24-8.11 (m, 1H), 8.04-7.81 (m, 1H), 7.81- 7.69(m, 1H), 7.27-7.22(m, 2H), 7.18-7.14(m, 3H), 7.07-7.02(m, 1H), 3.70(ddd, J= 6.6, 4.2, 2.5Hz, 1H), 2.88-2.64(m, 12H), 2.63-2.52(m, 2H), 2.36(dd, J=14.3, 10.7 Hz, 1H), 2.19-2.10(m, 1H), 1.84-1.76(m, 1H), 1.68(ddd, J=23.9, 12.2, 5.2Hz, 1H). MS Calcd.:403.2;MS Found:404.3([M+H] + ).

[0316] Synthesis Example 47. Preparation of 5-[4-(3-phenylpropyl)-piperazin-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 107) The title compound (0.11 g, 24.2%) was obtained as a brown solid by the preparation of Compound 100 described above.

[0317] 1 H NMR (600MHz, CD3OD): δ8.36 (ddd, J=5.0, 1.9, 0.9Hz, 1H), 8.27 (d, J=8.4Hz, 1H), 7. 83(ddd, J=8.4, 7.4, 1.9Hz, 1H), 7.28-7.22(m, 2H), 7.21-7.12(m, 4H), 3.05-2.78( m, 8H), 2.75(ddd, J=16.1, 5.3, 3.2Hz, 3H), 2.67-2.55(m, 4H), 2.31-2.23(m, 1H), 2 .13(ddtdd, J=8.1, 5.4, 2.7, 1.3, 0.6Hz, 1H), 1.96-1.88(m, 3H), 1.76-1.66(m, 1H). MS Calcd.:417.3;MS Found:418.3([M+H] + ).

[0318] Synthesis Example 48. Preparation of 5-((2-(dimethylamino)benzyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 71)

[0319] 5-(Methylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (0.20 g, 0.82 mmol) was dissolved in 15 mL of dichloroethane, followed by the addition of 2-(dimethylamino)benzaldehyde (0.18 g, 1.23 mmol, 1.5 eq) and two drops of acetic acid. The reaction mixture was stirred at room temperature for 1 hour, followed by the addition of sodium triacetoxyborohydride (0.35 g, 1.63 mmol, 2.0 eq). The reaction mixture was stirred at room temperature for 16 hours, followed by the addition of 2M aqueous sodium hydroxide solution. The reaction mixture was extracted with dichloromethane (20 mL x 2), followed by the organic layer being dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 5 / 1) to give the title compound (0.09 g, 29%) as a pale brown solid. Compounds 69 and 77 were prepared in this manner.

[0320] 1H NMR (600MHz, CD3OD): δ8.38-8.35(m, 1H), 8.23(d, J=8.4Hz, 1H), 7.86-7.81(m, 1H), 7.44-7.37(m , 2H), 7.34(d, J=7.4Hz, 1H), 7.20-7.14(m, 2H), 4.31(s, 2H), 3.38(tdd, J=5.2, 4.5, 2.7Hz, 1H), 2 .83(ddd, J=16.8, 5.3, 2.5Hz, 1H), 2.80-2.74(m, 1H), 2.71(s, 6H), 2.69-2.64(m, 1H), 2.65(s, 3H) ), 2.61 (dd, J=13.8, 11.1Hz, 1H), 2.29 (ddd, J=7.0, 5.2, 2.7Hz, 1H), 2.02 (qd, J=11.9, 5.5Hz, 1H). MS Calcd.:377.2;MS Found:378.3([M+H] + ).

[0321] Synthesis Example 49. Preparation of 5-(methylquinolin-6-ylmethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 63)

[0322] 5-Methylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (0.25g, 1.02mmol) was dissolved in 20mL of dichloromethane / dichloroethane (1 / 1), and then quinoline-6-carboxaldehyde (0.24g, 1.5mmol, 1.5eq) and acetic acid (0.06ml, 1.0mmol, 1eq) were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium cyanoborohydride (0.09g, 1.5mmol, 1.5eq) was added. The reaction mixture was stirred at room temperature for 12 hours, and then 10% aqueous sodium hydroxide was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol=5 / 1+0.1% triethylamine) to give the title compound (0.058 g, 14.7%) as a brown solid. In this manner, compound 61 was prepared.

[0323] 1 H NMR (600MHz, DMSO-d6): δ11.42(brs, 1H), 8.81(dd, J=4.2, 1.8Hz, 1H), 8.42-8.33(m, 2H), 8.30(d, J=7.7Hz, 1H), 7.94(d, J=8.6Hz, 1H), 7.84(s, 2H), 7.72(dd, J=8.6, 1.7Hz, 1H), 7.46(dt, J=4.1,3.0Hz, 1H), 7.10-7.20(m, 1H), 3.78 (dd, J=43.2, 13.9Hz, 2H), 2.84 (ddd, J=10.8, 5.0, 2.7Hz, 1H), 2.72-2.61 (m, 1H) 2.57-2.47 (m, 1H), 2.40 (td dd, J=7.9, 6.7, 3.5, 2.1Hz, 1H), 2.30-2.14(m, 1H), 2.19(s, 3H), 2.09-1.99(m, 1H), 1.70(qd, J=12.0, 5.4Hz, 1H). MS Calcd.:385.2;MS Found:386.2([M+H] + ).

[0324] Synthesis Example 50. Preparation of 5-(isoquinolin-3-ylmethyl-methylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 62) The title compound (0.02 g, 6.1%) was obtained as a brown solid by the same method as described above for preparing compound 63.

[0325] 1H NMR (600MHz, DMSO-d6): δ11.45(brs, 1H), 9.21(s, 1H), 8.47-8.31(m, 2H), 8.05(d, J=8.2H) z, 1H), 7.92(d, J=8.2Hz, 1H), 7.89-7.79(m, 2H), 7.70(t, J=7.5Hz, 1H), 7.58(t, J=7.4Hz, 1 H), 7.10-7.20(m, 1H), 3.88(dd, J=41.3, 14.7Hz, 2H), 2.93-2.81(m, 1H), 2.71-2.59(m, 1H) , 2.56-2.36(m, 2H), 2.27(s, 3H), 2.25-2.14(m, 1H), 2.09-1.99(m, 1H), 1.75-1.64(m, 1H). MS Calcd.:385.2;MS Found:386.2([M+H] + ).

[0326] Synthesis Example 51. Preparation of 5-(methyl((5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl)methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 37)

[0327] 5-(Methylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (0.13 g, 0.55 mmol) was dissolved in 6 ml of dichloromethane / dichloroethane (1 / 1), followed by the addition of 5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-2-carbaldehyde (0.20 g, 0.82 mmol, 1.5 eq) and 3 drops of acetic acid. The reaction mixture was stirred at 45°C for 16 hours, followed by the addition of sodium cyanoborohydride (0.07 g, 1.09 mmol, 2.0 eq). The reaction mixture was stirred at 45°C for 24 hours, followed by the addition of 2M aqueous sodium hydroxide. The reaction mixture was extracted with dichloromethane (20 mL x 2), followed by drying the organic layer over anhydrous sodium sulfate and concentrating under reduced pressure. The residue was purified by silica gel column chromatography (solvent: dichloromethane / methanol=5 / 1) to give the title compound (0.059 g, 15%) as a light brown solid. Compounds 35 and 36 were prepared in this manner.

[0328] 1 H NMR (600MHz, CD3OD): δ8.39-8.33(m, 1H), 8.27(d, J=8.8Hz, 1H), 7.88-7.78(m, 1H), 7.67(s , 1H), 7.28(ddd, J=31.9, 16.9, 6.7Hz, 2H), 7.15(dd, J=8.1, 5.3Hz, 1H), 6.52-6.40(m, 1H), 3.94(dd, J=26.0, 14.0Hz, 2H), 3.24-3.01(m, 4H), 3.02-2.93(m, 1H), 2.82-2.56(m, 7H), 2. 43(s, 3H), 2.37(s, 3H), 2.41-2.35(m, 1H), 2.26-2.19(m, 1H), 1.80(qd, J=11.9, 5.4Hz, 1H). MS Calcd.:472.2;MS Found:473.4([M+H] + ).

[0329] Synthesis Example 52. Preparation of 5-{methyl-[6-(4-methyl-piperazin-1-yl)-pyrimidin-4-ylmethyl]-amino}-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 34) The title compound (0.03 g, 12.7%) was obtained as a brown solid by the preparation of compound 37 described above.

[0330] 1 H NMR (600MHz, CD3OD): δ8.40-8.32(m, 2H), 8.27(d, J=8.4Hz, 1H), 7.87-7.79 (m, 1H), 7.16(dd, J=7.2,5.0Hz, 1H), 6.87(s, 1H), 3.76-3.54(m, 6H), 2.94-2 .87(m, 1H), 2.80-2.70(m, 1H), 2.65-2.53(m, 2H), 2.53-2.42(m, 5H), 2.35( s, 3H), 2.29(s, 3H), 2.15-2.08(m, 1H), 1.81(dtd, J=22.2, 11.0, 5.4Hz, 1H). MS Calcd.:434.3;MS Found:435.5([M+H] + ).

[0331] Synthesis Example 53. Preparation of 1-[4-(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-piperazin-1-yl]-2-butyn-1-one (Compound 89)

[0332] 1) Preparation of tert-butyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate

[0333] 3-Hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one (1.55 g, 6.78 mmol, 1.0 eq) was dissolved in 80 mL of dichloromethane / dichloroethane (1 / 1), and then tert-butyl piperazine-1-carboxylate (3.65 g, 16.97 mmol, 2.5 eq) and acetic acid (0.4 ml, 6.77 mmol, 1.0 eq) were added under a nitrogen stream. The reaction mixture was stirred at room temperature for 2 hours, and then sodium triacetoxyborohydride (4.31 g, 20.3 mmol, 3.0 eq) was added at 0°C, and the mixture was stirred at room temperature for 3 days. The reaction mixture was adjusted to pH 7 by adding saturated aqueous sodium bicarbonate (20 mL), and then extracted with dichloromethane (30 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column (solvent: dichloromethane / methanol=10 / 1) to give the title compound (1.59 g, 58.8%) as a yellow solid. In this manner, compound 109 was prepared.

[0334] 1 H NMR (600MHz, CDCl3) δ8.23(dt, J=5.0, 1.2Hz, 1H), 7.81(dd, J=11.0, 4.4Hz, 2H), 7.09(dd, J=8.3, 5.1Hz, 1H), 3.49(brt, 4 H), 2.88-2.78(m, 2H), 2.73-2.61(m, 6H), 2.42-2.31(m, 1H), 2.15(dd, J=8.4, 5.1Hz, 1H), 1.77-1.64(m, 1H), 1.46(s, 9H). 2) Preparation of 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride

[0335] tert-Butyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate (1.59 g, 3.98 mmol, 1.0 eq) was dissolved in 30 mL of methanol, and then 10 ml of 4.6 N hydrochloric acid in isopropanol was added under a nitrogen stream. The reaction mixture was stirred at room temperature for 1 day and then concentrated under reduced pressure. The residue was recrystallized from ethyl alcohol and ethyl ether to give the title compound (1.31 g, 87.8%) as a yellow solid.

[0336] 1 H NMR (600MHz, CD3OD) δ8.51-8.44(m, 1H), 8.26(dd, J=8.5, 0.8Hz, 1H), 8.17-8.11(m, 1H), 7.47-7.35(m, 1H), 4.01-3.61(m, 9H), 3.08(dd, J=14.2,5.1 Hz, 1H), 3.01(ddd, J=17.4, 5.4, 2.3Hz, 1H), 2.89(ddd, J=17.4, 11.6, 5.7H z, 1H), 2.78-2.70(m, 1H), 2.61-2.53(m, 1H), 2.13(qd, J=12.1, 5.5Hz, 1H).

[0337] 3) Preparation of 1-[4-(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-piperazin-1-yl]-2-butyn-1-one

[0338] 2-Butynoic acid 2,5-dioxopyrrolidin-1-yl ester (0.12 g, 0.65 mmol) was dissolved in 5 mL of acetonitrile with 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride (0.24 g, 0.65 mmol, 1.0 eq), and then N,N-diisopropylethylamine (0.6 mL, 3.25 mmol, 5.0 eq) was added. The reaction mixture was stirred at room temperature for 1 day, and then extracted with water and brine. The reaction mixture was extracted with dichloromethane (20 mL x 2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 5 / 1) to give the title compound (0.25 g, 92.6%) as a green solid.

[0339] 1 H NMR (600MHz, CDCl3): δ8.22(d, J=3.3Hz, 1H), 7.80(s, 2H), 7.08(s, 1H), 3.74(dd, J=10.3, 5.8Hz, 2H), 3.70-3.58(m, 2H), 2.89 -2.69(m, 2H), 2.69-2.51(m, 6H), 2.40-2.27(m, 1H), 2.07(d, J=10.4Hz, 1H), 2.01-1.92(m, 3H), 1.69(dt, J=11.4, 7.0Hz, 1H). MS Calcd.:365.2;MS Found:367.2([M+H] + ).

[0340] Synthesis Example 57a. Preparation of 1-[4-(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-piperazin-1-yl]-propenone (Compound 97)

[0341] 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride (0.038 g, 0.10 mmol) was dissolved in 3 mL of dichloromethane, and triethylamine (0.04 ml, 0.30 mmol, 3.0 eq) was added. The reaction mixture was stirred at 0° C. for 10 minutes. Acryloyl chloride (0.01 mL, 0.10 mmol, 1.0 eq) was added, and the mixture was stirred at 0° C. for 30 minutes, and then neutralized using aqueous sodium bicarbonate. The reaction mixture was extracted with dichloromethane (10 mL×2), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol=5 / 1+1% aqueous ammonia) to give the title compound (19 mg, 53.7%) as a brown solid.

[0342] 1 H NMR (600MHz, CDCl3): δ8.23(s, 1H), 7.82(s, 2H), 7.10(s, 1H), 6.64-6.48(m, 1H), 6.28(dd, J=16.8, 1.6Hz, 1H), 5.76-5.59(m, 1H), 3.85-3.40(m, 4H), 2.95-2.50(m, 7H), 2.44-2.28(m, 1H), 2.09(s, 1H), 1.84-1.61(m, 1H), 0.86(dd, J=17.6, 10.5Hz, 1H). MS Calcd.:353.2;MS Found:354.3([M+H] + ). Synthesis Example 57b. Reactions: Synthesis of amide, carbonate, urea, and sulfonamide derivatives

[0343] 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride (0.038 g, 0.10 mmol) was dissolved in a mixture of 5 mL of acetonitrile and 1 mL of water, and NaHCO3 saturated solution (200 uL) was added. For the synthesis of each derivative, a carboxylic acid chloride, chloroformic acid, isocyanate, or sulfonyl chloride was selected and added at room temperature. The reaction mixture was stirred at room temperature for 1 hour, and after confirming the completion of the reaction by LC-MS, it was diluted with 50 mL of ethyl acetate and washed with a mixture of salt water and NaHCO3 saturated solution. The product was separated and purified by TLC for purification, and the yield was in the range of 10 to 70%. In addition, data on synthesis examples prepared by the general synthesis method and the synthesis method using specific substances are described. Compounds 110 to 114 were prepared by this method.

[0344] Synthesis Example 54. Preparation of 4-dimethylamino-1-[4-(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-piperazin-1-yl]-2-buten-1-one (Compound 98)

[0345] 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride (0.37 g, 1.00 mmol) was dissolved in 15 mL of dichloromethane, and then (E)-4-(dimethylamino)-2-butenoic acid hydrochloride (0.20 g, 1.20 mmol, 1.2 eq), hydroxybenzotriazole (0.18 g, 1.30 mmol, 1.3 eq), and N,N-diisopropylethylamine (1.74 mL, 10.0 mmol, 10.0 eq) were added. The reaction mixture was stirred at 0° C. for 10 minutes, and then 1,3-diisopropylcarbodiimide (0.19 mL, 1.20 mmol, 1.2 eq) was added and stirred at room temperature for 8 hours. The reaction mixture was neutralized using an aqueous solution of sodium bicarbonate, and then extracted with dichloromethane (10 mL×2). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol=5 / 1+0.1% aqueous ammonia) to obtain the title compound (0.27 g, 65.8%) as a brown solid. In this manner, compound 99 was prepared.

[0346] 1 H NMR (600MHz, CDCl3): δ8.25 (d, J=5.0Hz, 1H), 7.83 (dt, J=14.3, 7.8Hz, 2H), 7.13-7.0 7(m, 1H), 6.84(dt, J=15.2, 6.3Hz, 1H), 6.50-6.43(m, 1H), 3.70(d, J=0.9Hz, 2H), 3.52 (s, 2H), 3.30-3.22(m, 2H), 2.84(d, J=16.5Hz, 1H), 2.77-2.69(m, 1H), 2.69-2.60(m, 4H), 2.57(s, 2H), 2.41-2.33(m, 7H), 2.11-2.04(m, 1H), 1.70(qd, J=12.1, 5.3Hz, 1H). MS Calcd.:410.2;MS Found:411.3([M+H] + ).

[0347] Synthesis Example 55. Preparation of 5-(4-methylpiperazin-1-yl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 82)

[0348] Methyl 5-(4-methylpiperazin-1-yl)-2-oxocyclohexane-1-carboxylate (0.19 g, 0.75 mmol) was dissolved in 15 mL of ethanol, followed by the addition of 5 drops of acetic acid and 2-hydrazinyl-5-(trifluoromethyl)pyridine (0.13 g, 0.75 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for 1 h and at 100 °C for 4 h, and then concentrated under reduced pressure. The residue was recrystallized with ethyl acetate / diethyl ether to give the title compound (0.092 g, 32%) as a pale brown solid. Compounds 115-120, 132, 137-145, and 154-156 were prepared in this manner.

[0349] 1 H NMR (600MHz, CD3OD): δ8.69(s, 1H), 8.57(d, J=8.5Hz, 1H), 8.15(dd, J=8.9, 2.4Hz, 1H), 3.55-2.86(m, 8H), 2.84(s, 3H), 2.76(dd, J=5 .1, 3.3Hz, 1H), 2.70-2.61(m, 2H), 2.59-2.51(m, 1H), 2.31(dd, J=14.5, 10.1Hz, 1H), 2.16-2.09(m, 1H), 1.80(qd, J=11.2,5.5Hz, 1H). MS Calcd.:381.2;MS Found:382.3([M+H] + ).

[0350] Synthesis Example 56. Preparation of 2-(6-chloro-pyridin-2-yl)-5-(4-methyl-piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 83) The title compound (0.11 g, 59.8%) was obtained as a light grey solid by the preparation of compound 82 described above.

[0351] 1H NMR (600MHz, D2O): δ7.91(d, J=8.2Hz, 1H), 7.80(t, J=7.9Hz, 1H), 7.23(d, J=7.9Hz, 1H), 3.82-3.30(m, 8H), 2.97-2.87(m, 1H), 2 .93(s, 3H), 2.84-2.75(m, 2H), 2.74-2.65(m, 1H), 2.48-2.40(m, 1H), 2.33(dd, J=8.4, 3.3Hz, 1H), 1.93(qd, J=11.9, 5.6Hz, 1H). MS Calcd.:347.1;MS Found:348.2([M+H] + ).

[0352] Synthesis Example 57. Preparation of 5-(4-methyl-piperazin-1-yl)-2-(6-methyl-4-trifluoromethyl-pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 84) The title compound (0.12 g, 73.8%) was obtained as a grey solid by the method for preparing compound 82 described above.

[0353] 1 H NMR (600MHz, CD3OD): δ8.41(s, 1H), 7.73(s, 1H), 4.16-3.59(m, 9H), 3.30(s, 3H), 3.33-3.24(m, 2H), 3.19(dd d, J=18.6, 10.1,3.7Hz, 1H), 2.84(s, 3H), 2.91-2.77(m, 1H), 2.74-2.67(m, 1H), 2.30(qd, J=12.0, 5.6Hz, 1H). MS Calcd.:395.2;MS Found:396.3([M+H] + ).

[0354] Synthesis Example 58. Preparation of 5-(4-methyl-piperazin-1-yl)-2-thieno[3,2-c]pyridin-4-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 85) The title compound (0.11 g, 43.0%) was obtained as a gray solid by the method for preparing compound 82 described above.

[0355] 1H NMR (600MHz, CD3OD): δ8.22(d, J=5.6Hz, 1H), 8.03(d, J=5.3Hz, 1H), 7.90(d, J=5.6Hz, 1H), 7.74(d, J=5.7Hz, 1H), 3.22-2.86(m, 9H), 2 .81(ddd, J=16.9, 5.0, 3.2Hz, 1H), 2.76(s, 3H), 2.73-2.62(m, 2H), 2.42-2.34(m, 1H), 2.19-2.12(m, 1H), 1.79(qd, J=11.6, 5.4Hz, 1H). MS Calcd.:369.1;MS Found:370.2([M+H] + ).

[0356] Synthesis Example 59. Preparation of 2-(3-fluoro-pyridin-2-yl)-5-(4-methyl-piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 86) The title compound (0.41 g, 86.3%) was obtained as a brown solid by the preparation of compound 82 described above.

[0357] 1 H NMR (600MHz, CD3OD): δ8.34(d, J=4.6Hz, 1H), 7.81-7.76(m, 1H), 7.51-7.43(m, 1H), 3.00-2.69(m, 9H), 2.68-2. 59(m, 2H), 2.52(s, 3H), 2.32(dd, J=14.8, 10.7Hz, 1H), 2.20-2.13(m, 1H), 1.83-1.70(m, 1H), 0.92-0.79(m, 1H). MS Calcd.:331.2;MS Found:332.3([M+H] + ).

[0358] Synthesis Example 60. Preparation of 2-pyridin-2-yl-5-(4-pyridin-2-ylmethyl-piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 87) The title compound (0.064 g, 23.6%) was obtained as a brown solid by the same method as described above for preparing compound 82.

[0359] 1H NMR (600MHz, CD3OD): δ8.47(d, J=4.4Hz, 1H), 8.36(d, J=4.6Hz, 1H), 8.26(d, J=8.4Hz, 1H), 7.87-7.77(m, 2H), 7.52(d, J=7.8Hz, 1H), 7.31(dd, J=7.3, 5.2Hz, 1H), 7.16(dd, J=7.1, 5.1Hz, 1H), 3.69(s, 2H), 2.90-2.69(m, 6H), 2 .69-2.50(m, 6H), 2.34-2.23(m, 1H), 2.22-2.14(m, 1H), 1.76-1.64(m, 1H). MS Calcd.:390.2;MS Found:391.3([M+H] + ).

[0360] Synthesis Example 61. Preparation of 2-pyridin-2-yl-5-(4-quinolin-6-ylmethylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 90) The title compound (0.064 g, 23.6%) was obtained as a brown solid by the same method as described above for preparing compound 82.

[0361] 1 H NMR (600MHz, DMSO-d6): δ11.40(s, 1H), 8.83(dd, J=4.2, 1.8Hz, 1H), 8.38(d, J=8.5Hz, 1H), 8.36-8.34(m, 1H), 8.31(d, J=8.2Hz, 1H), 7.94(d, J=8.6Hz, 1H), 7.83(d, J=10.9Hz , 2H), 7.69(dd, J=8.6, 1.6Hz, 1H), 7.47(dd, J=8.3, 4.1Hz, 1H), 7.17-7.11(m, 1H), 3.6 2(s, 2H), 2.67-2.23(m, 12H), 2.14-2.01(m, 1H), 2.00-1.90(m, 1H), 1.60-1.45(m, 1H). MS Calcd.:440.2;MS Found:441.4([M+H] + ).

[0362] Synthesis Example 62. Preparation of 2-(4-chlorophenyl)-5-(4-methyl-piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 94) The title compound (0.048 g, 39.8%) was obtained as a beige solid by the same procedure as described above for compound 82.

[0363] 1 H NMR (600MHz, DMSO-d6): δ12.47-11.52(brd, 1H), 7.72(d, J=9.0Hz, 2H), 7.45(d, J=8.9Hz, 2H), 3.79-3.24(m, 10 H), 2.80(s, 3H), 2.75-2.65(m, 1H), 2.60-2.55(m, 1H), 2.47-2.40(m, 1H), 2.38-2.21(m, 1H), 1.90-1.75(m, 1H). MS Calcd.:382.1(FreeBase:346.2;MS Found:347.3([M+H] + ).

[0364] Synthesis Example 63. Preparation of 5-(4-methyl-piperazin-1-yl)-2-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 95) The title compound (0.072 g, 68.8%) was obtained as a brown solid by the same method as described above for preparing compound 82.

[0365] 1 H NMR (600MHz, CD3OD): δ7.97(d, J=8.3Hz, 2H), 7.70(d, J=7.8Hz, 2H), 3.00-2.61 (m, 8H), 2.77-2.66(m, 4H), 2.55(s, 3H), 2.41-2.11(m, 2H), 1.75-1.65(m, 1H). MS Calcd.:380.2;MS Found:381.2([M+H] + ).

[0366] Synthesis Example 64. Preparation of 2-(4-bromophenyl)-5-(4-methyl-piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 101) The title compound (0.005 g, 6%) was obtained as a brown solid by the same procedure as above for compound 82.

[0367] 1 H NMR (600MHz, CD3OD): δ7.65(d, J=8.9Hz, 2H), 7.50(d, J=8.9Hz, 2H), 2.89-2.46(m, 11Hz), 2.34 (s, 3H), 2.2-2.30(m, 1H), 2.19-2.11(m, 1H), 2.05-1.95(m, 1H), 1.67(qd, J=11.8, 5.4Hz, 1H). MS Calcd.:390.1;MS Found:391.2([M+H] + ).

[0368] Synthesis Example 65. Preparation of 2-(4-methyl-piperazin-1-yl)-2-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 102) The title compound (0.10 g, 55.8%) was obtained as a brown solid by the same procedure as above for compound 82.

[0369] 1 H NMR (600MHz, CD3OD): δ8.53(dd, J=9.1, 4.8Hz, 2H), 8.06-8.00(m, 2H), 3.76-3.61(m, 4H), 3.61-3. 42(m, 8H), 3.26(s, 3H), 3.19-3.13(m, 1H), 3.08-3.02(m, 1H), 2.59(ddd, J=24.0, 11.5, 5.4Hz, 1H). MS Calcd.:330.2;MS Found:331.4([M+H] + ).

[0370] Synthesis Example 66. Preparation of 4-[3-hydroxy-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-indazol-2-yl]-benzonitrile (Compound 103) The title compound (0.035 g, 17.6%) was obtained as a brown solid by the same method as described above for preparing compound 82.

[0371] 1H NMR (600MHz, CD3OD): δ8.04(d, J=8.9Hz, 2H), 7.68(d, J=8.9Hz, 2H), 2.78-3.00(m, 5H), 2.77-2.66(m, 4H), 2.66-2.52(m, 3H), 2.44(s, 3H), 2.34-2.22(m, 1H), 2.11-2.17(m, 1H), 1.69(ddd, J=24.0, 11.8, 5.3Hz, 1H). MS Calcd.:337.2;MS Found:338.2([M+H] + ).

[0372] Synthesis Example 67. Preparation of 5-(4-methylpiperazin-1-yl)-2-pyrimidin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 108) The title compound (0.10 g, 40.5%) was obtained as a brown solid by the same method as described above for preparing compound 82.

[0373] 1 H NMR (600MHz, CD3OD): δ8.71(d, J=4.9Hz, 2H), 7.23(t, J=4.9Hz, 1H), 2.79-2.68(m, 6H), 2.67-2.5 2(m, 5H), 2.36(s, 3H), 2.34-2.23(m, 2H), 2.18-2.11(m, 1H), 1.68(ddd, J=23.9, 11.8, 5.3Hz, 1H). MS Calcd.:314.2;MS Found:315.3([M+H] + ).

[0374] Synthesis Example 68. Preparation of 2-pyridin-2-yl-5-(4-p-tolylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 126) The title compound (0.14 g, 32.9%) was obtained as a beige solid by the same procedure as described above for compound 96.

[0375] 1H NMR (600MHz, CDCl3): δ8.40-8.34(m, 1H), 8.32-8.26(m, 1H), 7.85(ddd, J=8.6, 7.4 , 1.9Hz, 1H), 7.17(ddd, J=7.3, 5.0, 0.8Hz, 1H), 7.04(d, J=8.3Hz, 2H), 6.87(d, J=8 .6Hz, 2H), 3.16(t, J=5.0Hz, 4H), 2.94-2.73(m, 6H), 2.70-2.59(m, 2H), 2.32(dd, J =13.9, 10.9Hz, 1H), 2.27-2.22(m, 1H), 2.22(s, 3H), 1.75(qd, J=11.8, 5.4Hz, 1H). MS Calcd.:389.2;MS Found:390.3([M+H] + ).

[0376] Synthesis Example 69. Preparation of 5-[4-(4-methoxyphenyl)-piperazin-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 129) The title compound (0.10 g, 23.7%) was obtained as a brown solid by the preparation of Compound 96 described above.

[0377] 1 H NMR (600MHz, CDCl3): δ8.28-8.19(m, 1H), 7.90-7.70(m, 2H), 7.10(ddd, J=8.4, 4.3, 3.2Hz, 1H), 6.91(d, J=9.1Hz, 2H), 6.83(d, J=9.1Hz, 2H) , 3.76(s, 3H), 3.20-3.10(m, 4H), 3.01-2.72(m, 7H), 2.73-2.60(m, 1H) ), 2.52-2.36(m, 1H), 2.32-2.19(m, 1H), 1.76(qd, J=12.2,5.1Hz, 1H). MS Calcd.:405.2;MS Found:406.3([M+H] + ).

[0378] Synthesis Example 70. Preparation of 1-{4-[4-(3-hydroxy-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-piperazin-1-yl]-phenyl}-ethanone (Compound 130) The title compound (0.14 g, 30.1%) was obtained as a gray solid by the same method as used for preparing compound 96.

[0379] 1 H NMR (600MHz, CDCl3): δ8.30-8.22(m, 1H), 7.89-7.75(m, 4H), 7.12-7.05(m, 1H), 6.91-6.80(m, 2H), 3.40 -3.30(m, 4H), 2.92-2.59(m, 8H), 2.50(s, 3H), 2.45-2.33(m, 1H), 2.19-2.07(m, 1H), 1.80-1.65(m, 1H). MS Calcd.:417.2;MS Found:418.3([M+H] + ).

[0380] Synthesis Example 71. Preparation of 5-[4-(4-methanesulfonylphenyl)-piperazin-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 131) The title compound (0.09 g, 18.1%) was obtained as a light gray solid by the same method as described above for preparing Compound 96.

[0381] 1 H NMR (600MHz, CDCl3): δ8.25-8.20(m, 1H), 7.86-7.79(m, 2H), 7.76(d, J=9.0H z, 2H), 7.11(ddd, J=6.8, 5.2, 2.0Hz, 1H), 6.93(d, J=9.0Hz, 2H), 3.43-3.27(m , 4H), 3.00(s, 3H), 2.91-2.83(m, 1H), 2.82-2.75(m, 6H), 2.70-2.59(m, 1H), 2 .47-2.37(m, 1H), 2.19-2.10(m, 1H), 1.74(dddd, J=12.6, 7.1, 3.3, 0.7Hz, H). MS Calcd.:453.2;MS Found:454.2([M+H] + ).

[0382] Synthesis Example 72. Preparation of 5-[4-(1-benzylpiperidin-4-ylmethyl)-piperazin-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 135)

[0383] 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride (0.70 g, 1.88 mmol) was dissolved in 30 mL of dichloromethane / dichloroethane (1 / 1), and then 1-benzylpiperidine-4-carbaldehyde (0.35 mL, 1.88 mmol, 1.0 eq) and triethylamine (0.77 mL, 5.64 mmol, 3.0 eq) were added under a nitrogen stream. The reaction mixture was added with sodium triacetoxyborohydride (0.79 g, 3.76 mmol, 2.0 eq) at 0°C, and then stirred at room temperature for 2 hours. The reaction mixture was adjusted to pH 7 by adding saturated aqueous sodium bicarbonate solution (20 mL), and then extracted with dichloromethane (30 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column (solvent: chloroform / methanol=5 / 1+1% aqueous ammonia) to give the title compound (0.65 g, 70.3%) as a brown solid. Compounds 133, 134 and 136 were prepared in this manner.

[0384] 1 H NMR (600MHz, CDCl3): δ8.26-8.19(m, 1H), 7.90-7.80(m, 2H), 7.27-7.17(m, 5H), 7.10-7.00(m, 1H), 3.51(s, 2H), 2.96-2.80(m , 2H), 2.80-2.27(m, 11H), 2.17(d, J=7.1Hz, 2H), 2.00-1.90(m, 3H), 1.75-1.64(m, 2H), 1.55-1.40(m, 1H), 1.34-1.16(m, 5H). MS Calcd.:486.3;MS Found:487.4([M+H] + ).

[0385] Synthesis Example 73. Preparation of 5-{4-[2-(2-hydroxyethoxy)-ethyl]-piperazin-1-yl}-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 17) The title compound (0.15 g, 29.5%) was obtained as a yellow solid by the same procedure as described above for compound 96.

[0386] 1 H NMR (600MHz, CDCl3): δ8.25-8.19(m, 1H), 7.99-7.73(m, 2H), 7.11-7.02(m, 1H), 3.76-3. 50(m, 6H), 2.89-2.55(m, 14H), 2.39-2.30(m, 1H), 2.16-2.09(m, 1H), 1.72-1.60(m, 1H). MS Calcd.:387.2;MS Found:388.3([M+H] + ). The structures, MS results and IUPAC names of the compounds 1 to 161 of the synthesis examples prepared above are shown in Table 1 below.

[0387] [Table 1] TIFF0007634083000011.tif255170TIFF0007634083000012.tif243170TIFF000763408300001 3.tif255170TIFF0007634083000014.tif233170TIFF0007634083000015.tif237170TIFF0007 634083000016.tif230170TIFF0007634083000017.tif253170TIFF0007634083000018.tif254 170TIFF0007634083000019.tif234170TIFF0007634083000020.tif234170TIFF0007634083000 021.tif248170TIFF0007634083000022.tif253170TIFF0007634083000023.tif239170TIFF00 07634083000024.tif239170TIFF0007634083000025.tif240170TIFF0007634083000026.tif2 47170TIFF0007634083000027.tif241170TIFF0007634083000028.tif235170TIFF0007634083000029.tif222170<Example 1> Analysis of changes in ROS generation induced by PMA treatment in HL-60 cells differentiated into neutrophilic cells by DMSO treatment

[0388] In order to confirm the effect of the compound of the synthesis example on ROS generation from fibroblasts and specific stromal cells, ROS generation was induced in HL-60 cells (Korea Cell Line Bank), NHLF (normal human lung fibroblast, Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cell, ATCC), and KEL-FIB (keloid fibroblast, ATCC) cells, which were differentiated into neutrophil cells by treatment with DMSO, by stimuli such as PMA (phorbol 12-myristate 13-acetate), TGF-β1, palmitate, or high-concentration glucose, and the ROS generation inhibitory effect of the compound of the synthesis example was observed under these conditions.

[0389] HL-60 cells (human leukemia cells, ATCC) were suspended in a medium (RPMI + 10% FBS) containing 1.25% DMSO and cultured at 5% CO2 and 37°C for 6 days to induce differentiation into neutrophilic cells. HL-60 cells differentiated into neutrophilic cells were cultured at 2 × 10 4 The cells were treated with the compound of the synthesis example at a concentration of 0.5 mM for 30 minutes. After that, each well containing the cells and drug was treated with 200 nM PMA to induce ROS generation, and the ROS generation was measured by observing the luminescence level of each well using 100 μM L-012.

[0390] NHLF (normal human lung fibroblast, Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cells, ATCC), and KEL-FIB (keloid fibroblast, ATCC) cells were suspended in culture medium containing 10% FBS and distributed into 96-well plates, and then cultured for 24 hours under conditions of 5% CO2 and 37°C. After pretreatment with the compound of the synthesis example at concentrations of 10, 20, 30, 40, 60, and 80 μM for 30 minutes to 1 hour, the ROS stimulus source was applied to each well containing the cells and drug. After additional culture for 48 hours, the level of ROS generation was confirmed using L-012 or DCF-DA.

[0391] As a result of the experiment, the compound of the synthetic example suppressed ROS generation caused by ROS stimuli in all cells of NHLF, LX-2, ARPE19, and KEL-FIB. Specifically, the results in Table 2 show that when HL-60 cells induced with neutrophils were treated with the compound of the synthetic example at 0.5uM, ROS generation induced by PMA was suppressed. Figure 1 shows that when LX-2 and NHLF cells were treated with compound 1 and compound 17 of the synthetic example, all ROS generation induced by PMA was suppressed.

[0392] Therefore, it was confirmed that when the compounds of the synthetic examples were treated with differentiated HL-60 cells or various fibroblasts or specific stromal cells in which ROS production was induced, ROS production was effectively inhibited.

[0393] [Table 2] TIFF0007634083000031.tif254148TIFF0007634083000032.tif254148TIFF0007634083000033.tif62148<*:<30%, **:30< <50%, ***:50< <70%, ****:>70%> Example 2: Analysis of changes in αSMA expression induced by TGF-β1

[0394] It has been reported that differentiation of fibroblasts into myofibroblasts can form cancer associated fibroblasts (CAFs) or induce fibrosis in various tissues.

[0395] In order to confirm whether the compounds of the synthetic examples of the present invention have an effect on the differentiation of fibroblasts into myofibroblasts, the inhibitory effect of the compounds of the synthetic examples on the increase in expression of αSMA (a biomarker for confirming differentiation into myofibroblasts) induced by TGF-β1 was observed in HFF-1 (human foreskin fibroblast, ATCC), NHLF (normal human lung fibroblast, Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cell, ATCC), and KEL-FIB (keloid fibroblast, ATCC) cells.

[0396] Each type of cell was suspended in DMEM medium containing 10% FBS and plated on a 4-well chamber slide (Nunc) at 1 × 10 4 ~1.5×10 5The cells were dispensed at a concentration of 1000 cells / well and treated with the compound of the synthesis example and TGF-β1 (TGFβ1 and TGF-β are all the same meaning) to prepare cells to be used for confirming the expression of αSMA. The expression of αSMA in the prepared cells was confirmed by immunocytochemistry as follows. The cells were fixed with 4% paraformaldehyde for 10 minutes, permeabilized with 0.1% Triton x-100, and then treated with a primary antibody against αSMA (anti-αSMA Ab, 1:200, 16 hours at 4℃) and a secondary antibody (Alexa-594 conjugated Ab, 1:800, 1 hour at room temperature), and the expression level of αSMA was observed using a fluorescent microscope.

[0397] Figure 3 shows the effect of treating HFF cells with 10, 20 and 40 μM of various synthetic example compounds after inducing αSMA expression by TGF-β1 (10 ng / ml). Although there were differences in the degree, synthetic example compounds 1, 23, 12, 5, 14 and 33 all showed the effect of suppressing αSMA expression by 35% to 70% or more.

[0398] Furthermore, as can be seen from Figure 4, in LX-2, NHLF, ARPE19, and KEL-FIB cells, it was observed that the increase in αSMA expression induced by TGF-β1 (10 ng / ml) was significantly suppressed by treatment with 10 μM of compound 1 (synthetic example). Example 3: Analysis of gel contraction changes induced by TGF-β1

[0399] To confirm whether the compound of the synthetic example has an effect on the differentiation of fibroblasts into myofibroblasts, the inhibitory effect of the compound of the synthetic example on the gel contraction phenomenon induced by the interaction between human foreskin fibroblasts (HFF-1, ATCC) and collagen was observed.

[0400] 3×10 6A mixture of HFF-1 cells and collagen (bovine type I collagen) prepared at a concentration of 10 ...

[0401] As a result of the experiment, as can be seen from Figure 7, it was observed that gel contraction induced by TGF-β1 (10 ng / ml) was effectively inhibited by treatment with synthetic examples Compound 1, Compound 5, Compound 12, Compound 13, Compound 14, Compound 16, Compound 23, Compound 33, Compound 38, Compound 63 and Compound 62. Example 4: Analysis of changes in ROS production in dopaminergic neurons

[0402] To confirm the effect of the compound in the synthesis example on ROS generation from dopaminergic neurons, ROS generation was induced in N27 (rat dopaminergic neural cell, Sigma) cells by stimulation with alpha-synuclein preformed fibril (PFF), and the ROS generation inhibitory effect of the compound in the synthesis example was observed under these conditions.

[0403] N27 cells were cultured in RPMI medium containing 10% FBS and 1 μM angiotensin II. The cells were cultured at 4 × 10 3The cells were then treated with PFF (preformed fibril), a ROS generating stimulus, and the compound in the synthesis example. After 24 hours of treatment with the compound in the synthesis example, the fluorescence in each well was measured using CellROX-Deep Red reagent to confirm the level of ROS generation.

[0404] As a result of the experiment, as can be seen from Figure 2, it was confirmed that the generation of ROS induced by PFF was effectively suppressed by treatment with 0.001 μM of the synthetic examples, Compound 12, Compound 16, Compound 32 and Compound 82. Example 5: Analysis of changes in IL-1β expression induced by LPS

[0405] In order to confirm the effect of the compounds of the synthetic examples of the present invention on inflammatory responses in human fibroblasts, it was observed whether the expression of IL-1β, which was increased by LPS treatment in fibroblasts derived from various tissues, was suppressed by the compounds of the synthetic examples.

[0406] 2×10 in a 6-well plate 5 After inoculation, the cells were cultured for 24 hours, and then further cultured in serum-free culture medium for 16 hours. After pretreatment with the compound of Synthesis Example 1 for 30 minutes according to each condition, an inflammatory response was induced with LPS (1 μg / ml) for 6 hours. IL-1β expression was confirmed using RT-PCR. Total RNA was isolated from the cells using RNeasy mini kit (Qiagen), and 2 μg of the isolated RNA was analyzed using PrimeScript PCR. TM II 1 stcDNA was synthesized using a 3-strand cDNA synthesis kit (TaKaRa), and then PCR was performed using AccuPower® PCR PreMix (Bioneer) to amplify the gene. The base sequences for the target primers were as follows: IL-1β (forward: 5'-CCACAGACCTTCCAGGAGAATG-3' (SEQ ID NO: 1), reverse: 5'-GTGCAGTTCAGTGATCGTACAGG-3' (SEQ ID NO: 2); GAPDH (forward: 5'-GTGGCTGGCTCAGAAAAAGG-3' (SEQ ID NO: 3), reverse: 5'-GGTGGTCCAGGGGTCTTACT-3' (SEQ ID NO: 4); β-actin (forward: 5'-CACCATTGGCAATGAGCGGTTC-3' (SEQ ID NO: 5), reverse: 5'-AGGTCTTTGCGGATGTCCACGT-3' (SEQ ID NO: 6)). The PCR products were confirmed by electrophoresis on a 1.5% agarose gel.

[0407] As a result of the experiment, as can be seen from FIG. 8, it was observed that IL-1β induced by LPS was effectively suppressed in a concentration-dependent manner by treatment with 10 μM of Compound 1 (Synthesis Example). Example 6: Analysis of changes in expression of IL-6 and IL8 in cancer-associated fibroblasts

[0408] In order to confirm the effect of the compounds of the synthetic examples of the present invention on the inflammatory response in cancer-associated fibroblasts, it was observed whether the expression of IL6 and IL8 was suppressed by the compounds of the synthetic examples in pancreatic cancer associated fibroblasts (P.CAF).

[0409] 1.5×10 in a 6-well plate 5After inoculation, the cells were cultured in P.CAF complete media for 48 hours, and then treated with 10, 20, 30, 40, 60, or 80 μM of the compound of the synthetic example according to each condition for 48 hours. The expression of IL-6 and IL-8 was confirmed by ELISA using a Quantkine ELISA kit (R&D systems) as follows.

[0410] 100μl of culture medium treated with the compound of the synthesis example for 48 hours was added to an analytical microplate strip containing 100μl of assay diluent, and left at room temperature for 2 hours, after which the contents were removed and washed 4 times with 400μl of wash buffer. 200μl of human IL-6 or IL-8 conjugate was added and left at room temperature for 2 hours, after which the contents were removed and washed 4 times with 400μl of wash buffer. 200μl of substrate solution was added and left at room temperature for 20 minutes, after which 50μl of stop solution was added and the absorbance was measured at a wavelength of 450nm within 30 minutes to confirm the expression levels of IL-6 and IL-8.

[0411] As a result of the experiment, as can be seen from Figures 5 and 6, it was observed that IL-6 and IL-8 expressed in P.CAF were effectively suppressed by treatment with synthetic examples Compound 1, Compound 5, Compound 12 to Compound 16, Compound 23, Compound 33, Compound 38, Compound 63 and Compound 62. <Example 7> Confirmation of the therapeutic effect of brain injury

[0412] To test the efficacy of the compounds of the synthetic examples in preventing or treating brain disorders or diseases, they were evaluated using alpha-synuclein preformed fibril (PFF)-injected Parkinson's disease model mice.

[0413] C57Bl / 6 mice were used, and all mice were maintained under standard conditions. Experimental animals were divided into groups of eight animals, and were divided into three groups: a normal control group orally administered distilled water (negative control), a Parkinson's disease patient group injected with alpha-synuclein preformed fibril (PFF) (vehicle control), and an experimental group (synthetic example) in which the compound of synthetic example 16 was orally administered daily at 25 mg / kg to the Parkinson's disease patient group injected with alpha-synuclein preformed fibril (PFF). The normal control group was administered saline, and the compound of synthetic example was orally administered once a day for 7 weeks, after which behavioral change experiments and histopathological experiments were performed.

[0414] Behavioral changes were analyzed by Rota rod, pole test and hindlimb clasping, and the mean values ​​of three experiments per animal were determined.

[0415] After the test, the animals were anesthetized, and brain tissue was removed from each individual and fixed in 4% neutral buffered formalin. The fixed tissue was cut to a certain thickness, and then embedded in paraffin through a general tissue processing process to prepare 4-5 μm tissue sections. Then, to confirm whether or not there was an improvement in the pathological indicators of Parkinson's disease according to the protein aggregation level in the striatum, the tissue was first labeled with phosphorylated -Serin-129 alpha-synuclein, and then Thioflavin-T staining was performed to observe the histopathological findings.

[0416] As a result of the experiment, in the group administered the compound of Synthesis Example 16, the results of the analysis of behavioral changes such as climbdown time, Rota rod, pole test, and hindlimb clasping showed that Parkinson's-like behavioral symptoms were improved by more than 50%, and the aggregation and accumulation of a-synuclein, which is an important pathological indicator of Parkinson's disease, was improved by more than 50%. In conclusion, it was confirmed that the compounds of the synthetic examples of the present invention effectively improve the symptoms of Parkinson's disease. (Additional Note) (Appendix 1) A compound of formula I, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharma- ceutically acceptable salt thereof: [ka] In the above formula, A is a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted aryl having 5 to 20 carbon atoms; In this case, the 5-20 membered heteroaryl or the aryl having 5 to 20 carbon atoms is unsubstituted or is selected from the group consisting of cyano, halo, haloalkyl, nitro, -C(=O)R 1 , -C(=O)OR 1 , -NH-C(=O)R 1 , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amine, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5-membered to 20-membered heteroaryl, and substituted or unsubstituted 5-membered to 20-membered heterocycloalkyl, 1 is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form a substituted or unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5-10 membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 5 to 10 carbon atoms; R is hydrogen, deuterium, cyano, halo, nitro, haloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, or -C(=O)R 2 At this time, the R 2 is a cycloalkyl having 3 to 8 carbon atoms, an alkyl having 1 to 10 carbon atoms, an alkenyl having 2 to 10 carbon atoms, or an aryl having 6 to 10 carbon atoms; B is -NKM or a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl; K and M are each independently hydrogen, deuterium, cyano, halo, nitro, haloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted aryl alkyl having 1 to 10 carbon atoms having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroaryl alkyl having 1 to 10 carbon atoms; The alkyl having 1 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of deuterium, halo, hydroxy, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkoxy having 1 to 10 carbon atoms, alkylsulfonyl having 1 to 10 carbon atoms, arylsulfonyl having 5 to 20 carbon atoms, aryloxy having 5 to 20 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5-membered to 20-membered heteroaryl, and substituted or unsubstituted 5-membered to 20-membered heterocycloalkyl; the cycloalkyl having 3 to 8 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amine, substituted or unsubstituted aryl having 5 to 20 carbon atoms or 5-membered to 20-membered heteroaryl, alkoxy having 1 to 10 carbon atoms, and haloalkyl having 1 to 10 carbon atoms; The 5- to 20-membered heteroaryl, 5- to 20-membered heterocycloalkyl, or aryl having 5 to 20 carbon atoms is unsubstituted or is selected from the group consisting of deuterium, halo, cyano, nitro, -C(=O)R', -C(=O)OR', -NH-C(=O)R'', substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to 10 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to 2 ... substituted or unsubstituted arylsulfonyl, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkyl having 1 to 10 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted aryl alkyl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heterocycloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, and substituted or unsubstituted alkyl 5- to 20-membered heterocycloalkyl having 1 to 10 carbon atoms; wherein R' and R'' are each independently hydrogen, deuterium, a substituted or unsubstituted amine, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, a substituted or unsubstituted alkynyl having 2 to 6 carbon atoms, a substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, a substituted or unsubstituted aryl having 6 to 10 carbon atoms, or a substituted or unsubstituted aryl having 6 to 10 carbon atoms and an alkyl having 1 to 6 carbon atoms; the substituted amino group is substituted with one or two alkyl groups having 1 to 10 carbon atoms; The heteroatom of the heterocycloalkyl or heteroaryl ring is at least one selected from N, S and O. (Appendix 2) The A is an unsubstituted or substituted 5- to 12-membered heteroaryl or an aryl having 6 to 10 carbon atoms, and the 5- to 12-membered heteroaryl or the aryl having 6 to 10 carbon atoms is cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, -C(=O)R 1 , -C(=O)OR 1 , -NH-C(=O)R 1 , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, amino, aryl having 6 to 10 carbon atoms, 5-membered to 12-membered heteroaryl, and 5-membered to 12-membered heterocycloalkyl, wherein R 1 is hydrogen, deuterium, or alkyl having 1 to 6 carbon atoms; or a phenyl group, wherein two or more adjacent groups can be bonded to each other to form a substituted or unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring forms a 5- to 7-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 9 carbon atoms; (Appendix 3) R is hydrogen, deuterium, cyano, halo, nitro, alkyl having 1 to 6 carbon atoms which is unsubstituted or substituted with cycloalkyl having 3 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, 5-membered to 12-membered heteroaryl, -C(=O)R 2 At this time, the R 2 is cycloalkyl having 3 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof, of the compound according to Appendix 1. (Appendix 4) B is -NKM or a 5- to 12-membered heteroaryl or a 5- to 12-membered heterocycloalkyl, wherein the 5- to 12-membered heteroaryl or the 5- to 12-membered heterocycloalkyl is unsubstituted or substituted with one, two, three or four of deuterium, halo, cyano, nitro, -NR 3 R 4 , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R 5 , -SO 2 -R 6 is replaced by In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms; R 3 and R4 are each independently hydrogen, deuterium, -C(=O)-Ra, alkyl having 1 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms, said alkyl having 1 to 6 carbon atoms or aryl having 6 to 10 carbon atoms being unsubstituted or substituted with 1, 2, 3, or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or aryloxy having 6 to 10 carbon atoms, wherein said Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, or haloalkyl having 1 to 6 carbon atoms; R 5 -OR b , -NR c R d , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of monoalkylamine having 1 to 6 carbon atoms or dialkylamine having 1 to 6 carbon atoms, wherein the R b 、R c and R d each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, or an aryl having 6 to 10 carbon atoms and an alkyl having 1 to 6 carbon atoms; R 6 is an alkyl group having 1 to 6 carbon atoms, or an aryl group having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3 or 4 alkyl groups having 1 to 6 carbon atoms, K and M each independently represent hydrogen, deuterium, cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, 5-membered to 12-membered heteroaryl, 5-membered to 12-membered heteroaryl alkyl having 1 to 6 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or 5-membered to 12-membered heteroaryl is one, two, three, or four of cyano, halo, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, hydroxyalkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, alkylsulfonyl having 1 to 6 carbon atoms, arylsulfonyl having 6 to 10 carbon atoms, -NR 7 R 8 , -C(=O)R 9 , substituted by 5- to 12-membered heterocyclyl, hydroxy, nitro, or aryl having 6 to 10 carbon atoms, in which the 5- to 12-membered heterocyclyl or aryl having 6 to 10 carbon atoms is unsubstituted or substituted by alkyl having 1 to 6 carbon atoms; R 9 -OR e , -NR e R f , unsubstituted or one, two, three or four of -NR e R f or aryl having 6 to 10 carbon atoms, each of which is substituted with R e and R f are each independently hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, or alkyl having 1 to 6 carbon atoms, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof, of the compound according to Appendix 1. (Appendix 5) The compound of formula I is a compound of formula I-1, which is described in Appendix 1, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof: [Chemical formula I-1]

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Claims

1. A compound of formula I: or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharma- ceutically acceptable salt thereof: [Chemical formula I] 【Chemistry 1】 In the above formula, A is a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted aryl having 5 to 20 carbon atoms; In this case, the 5- to 20-membered heteroaryl or the aryl having 5 to 20 carbon atoms is unsubstituted or is selected from the group consisting of cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amino, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, and substituted or unsubstituted 5- to 20-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 5 to 10 carbon atoms; R is hydrogen, deuterium, cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, or -C(=O)R ２ At this time, the R ２ is a cycloalkyl having 3 to 8 carbon atoms, an alkyl having 1 to 10 carbon atoms, an alkenyl having 2 to 10 carbon atoms, or an aryl having 6 to 10 carbon atoms; B is -NKM or a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl; K is hydrogen, deuterium, cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, unsubstituted alkoxy having 1 to 10 carbon atoms, -C(=O)R', -C(=O)OR', -SO ２ -R'', a substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, a substituted or unsubstituted aryl having 5 to 20 carbon atoms, a substituted or unsubstituted aryl having 5 to 20 carbon atoms and an alkyl having 1 to 10 carbon atoms, a substituted or unsubstituted 5- to 20-membered heteroaryl, or a substituted or unsubstituted 5- to 20-membered heteroaryl and an alkyl having 1 to 10 carbon atoms; M is cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms substituted or unsubstituted alkyl having 1 to 10 carbon atoms, unsubstituted alkoxy having 1 to 10 carbon atoms, -C(=O)R', -C(=O)OR', -SO ２ -R'', a substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, a substituted or unsubstituted aryl having 5 to 20 carbon atoms, a substituted or unsubstituted aryl having 5 to 20 carbon atoms and an alkyl having 1 to 10 carbon atoms, a substituted or unsubstituted 5- to 20-membered heteroaryl, or a substituted or unsubstituted 5- to 20-membered heteroaryl and an alkyl having 1 to 10 carbon atoms; The alkyl having 1 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of substituents selected from the group consisting of deuterium, halo, hydroxy, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkoxy having 1 to 10 carbon atoms, alkylsulfonyl having 1 to 10 carbon atoms, arylsulfonyl having 5 to 20 carbon atoms, aryloxy having 5 to 20 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 20-membered heteroaryl, and substituted or unsubstituted 5- to 20-membered heterocycloalkyl; The cycloalkyl having 3 to 8 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted aryl having 5 to 20 carbon atoms or 5- to 20-membered heteroaryl, alkoxy having 1 to 10 carbon atoms, and haloalkyl having 1 to 10 carbon atoms; The 5- to 20-membered heteroaryl, 5- to 20-membered heterocycloalkyl, or aryl having 5 to 20 carbon atoms is unsubstituted or is selected from the group consisting of deuterium, halo, cyano, nitro, -C(=O)R', -C(=O)OR', -NH-C(=O)R'', substituted or unsubstituted amino, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, unsubstituted alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted haloalkyl having 1 to 10 carbon atoms, substituted or unsubstituted hydroxyalkyl having 1 to 10 carbon atoms, substituted or unsubstituted alkylsulfonyl having 1 to 10 carbon atoms, substituted or unsubstituted arylsulfonyl having 5 to 20 carbon atoms, and the like. substituted by one, two, three or four kinds of substituents selected from the group consisting of arylsulfonyl, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, alkyl having 1 to 10 carbon atoms, substituted or unsubstituted aryl having 5 to 20 carbon atoms, substituted or unsubstituted aryl alkyl having 5 to 20 carbon atoms, alkyl having 1 to 10 carbon atoms, substituted or unsubstituted 5- to 12-membered heterocycloalkyl, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, and substituted or unsubstituted alkyl having 1 to 10 carbon atoms, 5- to 20-membered heterocycloalkyl; wherein R' and R'' are each independently hydrogen, deuterium, a substituted or unsubstituted amino, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, a substituted or unsubstituted alkynyl having 2 to 6 carbon atoms, a substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, a substituted or unsubstituted aryl having 6 to 10 carbon atoms, or a substituted or unsubstituted aryl alkyl having 1 to 6 carbon atoms having 6 to 10 carbon atoms, wherein the alkenyl having 2 to 6 carbon atoms or the alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of monoalkylamine having 1 to 6 carbon atoms or dialkylamine having 1 to 6 carbon atoms; the substituted amino group is substituted with one or two alkyl groups having 1 to 10 carbon atoms, aryl groups having 6 to 10 carbon atoms, or aryl groups having 6 to 10 carbon atoms and alkyl groups having 1 to 6 carbon atoms; The heteroatom of the heterocycloalkyl or heteroaryl ring is at least one selected from N, S and O.

2. A is an unsubstituted or substituted 5- to 12-membered heteroaryl or an aryl having 6 to 10 carbon atoms, and the 5- to 12-membered heteroaryl or the aryl having 6 to 10 carbon atoms is cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, amino, aryl having 6 to 10 carbon atoms, 5- to 12-membered heteroaryl, and 5- to 12-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 6 carbon atoms; The compound according to claim 1, wherein two or more adjacent groups can be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring forms a 5- to 7-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 9 carbon atoms, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof.

3. R is hydrogen, deuterium, cyano, halo, nitro, alkyl having 1 to 6 carbon atoms which is unsubstituted or substituted with cycloalkyl having 3 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, 5- to 12-membered heteroaryl, -C(=O)R ２ At this time, the R ２ is cycloalkyl having 3 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof, of the compound according to claim 1.

4. B is -NKM or a 5- to 12-membered heteroaryl or a 5- to 12-membered heterocycloalkyl, wherein the 5- to 12-membered heteroaryl or the 5- to 12-membered heterocycloalkyl is unsubstituted or substituted with one, two, three or four of deuterium, halo, cyano, nitro, -NR ３ R ４ , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R ５ , -SO ２ -R ６ is replaced by In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms; The R ３ and R ４ are each independently hydrogen, deuterium, -C(=O)-Ra, an alkyl having 1 to 6 carbon atoms, or an aryl having 6 to 10 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or aryloxy having 6 to 10 carbon atoms, wherein the Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, or haloalkyl having 1 to 6 carbon atoms; The R ５ Yes - OR ｂ , -NR ｃ R ｄ , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 monoalkylamines having 1 to 6 carbon atoms or dialkylamines having 1 to 6 carbon atoms, wherein the R ｂ , R ｃ and R ｄ each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, an aryl having 6 to 10 carbon atoms, and an alkyl having 1 to 6 carbon atoms; The R ６ is an alkyl group having 1 to 6 carbon atoms, or an aryl group having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3 or 4 alkyl groups having 1 to 6 carbon atoms, K is hydrogen, deuterium, cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, -C(=O)R', -C(=O)OR', -SO ２ -R", cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, 5-membered to 12-membered heteroaryl, or 5-membered to 12-membered heteroaryl alkyl having 1 to 6 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or 5-membered to 12-membered heteroaryl is one, two, three, or four of cyano, halo, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, hydroxyalkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, alkylsulfonyl having 1 to 6 carbon atoms, arylsulfonyl having 6 to 10 carbon atoms, -C(=O)R ９ , substituted by 5- to 12-membered heterocyclyl, hydroxy, nitro, or aryl having 6 to 10 carbon atoms, wherein the 5- to 12-membered heterocyclyl or aryl having 6 to 10 carbon atoms is unsubstituted or substituted by alkyl having 1 to 6 carbon atoms; M is cyano, halo, nitro, haloalkyl having 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, -C(=O)R', -C(=O)OR', -SO ２ -R", cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, 5-membered to 12-membered heteroaryl, or 5-membered to 12-membered heteroaryl alkyl having 1 to 6 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or 5-membered to 12-membered heteroaryl is one, two, three, or four of cyano, halo, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, hydroxyalkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, alkylsulfonyl having 1 to 6 carbon atoms, arylsulfonyl having 6 to 10 carbon atoms, -C(=O)R ９ , substituted by 5- to 12-membered heterocyclyl, hydroxy, nitro, or aryl having 6 to 10 carbon atoms, wherein the 5- to 12-membered heterocyclyl or aryl having 6 to 10 carbon atoms is unsubstituted or substituted by alkyl having 1 to 6 carbon atoms; The R ９ Yes - OR ｅ , -NR ｅ R ｆ , unsubstituted or 1, 2, 3 or 4 of -NR ｅ R ｆ or an aryl having 6 to 10 carbon atoms substituted with R ｅ and R ｆ are each independently hydrogen, deuterium, alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, or alkyl having 1 to 6 carbon atoms, or a stereoisomer, solvate, isotopic variant, tautomer, or pharma- ceutically acceptable salt thereof, of the compound according to claim 1.

5. The compound of formula I is a compound of formula I-1, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof, according to claim 1: [Chemical formula I-1] 【Chemistry 2-1】 In the above formula, K, M and R are as defined above in Formula I. D is CR １０ , or N, E is CR １１ , or N, F is CR １２ , or N, G is CR １３ , or N, J is CR １４ or N, where 【Chemistry 2-2】 in which N is 1 or more; The R １０ ~R １４ are the same or different, and each independently represents cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, or -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amino, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heteroaryl, and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 10 carbon atoms.

6. The compound of formula I is a compound of formula I-2, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof, according to claim 1: [Chemical formula I-2] 【Chemistry 3-1】 In the above formula, R is as defined above in Formula I; D is CR １０ , or N, E is CR １１ , or N, F is CR １２ , or N, G is CR １３ , or N, J is CR １４ or N, where 【Chemistry 3-2】 in which N is 1 or more; The R １０ ~R １４ are the same or different, and each independently represents cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, or -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amino, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heteroaryl, and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 10 carbon atoms; n is an integer of 0, 1 or 2; L is CH ２ , NH or O; 【Chemistry 4】 is unsubstituted or has one, two, three or four deuterium, halo, cyano, nitro, -NR ３ R ４ , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R ５ , -SO ２ -R ６ In this case, when there are two or more kinds of substituents, adjacent two or more kinds of groups are bonded to each other. 【Chemistry 5】 together with a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl, In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms; The R ３ and R ４ are each independently hydrogen, deuterium, or -C(=O)-R ａ , an alkyl having 1 to 6 carbon atoms or an aryl having 6 to 10 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms or aryloxy having 6 to 10 carbon atoms, wherein Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms or haloalkyl having 1 to 6 carbon atoms; The R ５ Yes - OR ｂ , -NR ｃ R ｄ , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 monoalkylamines having 1 to 6 carbon atoms or dialkylamines having 1 to 6 carbon atoms, wherein the R ｂ , R ｃ and R ｄ each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, an aryl having 6 to 10 carbon atoms, and an alkyl having 1 to 6 carbon atoms; The R ６ is alkyl having 1 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3 or 4 alkyl groups having 1 to 6 carbon atoms.

7. The compound of formula I is a compound of formula I-3, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof, according to claim 1: [Chemical formula I-3] 【Chemistry 6-1】 In the above formula, K, M and R are as defined above for Formula I; D is O or S, E is CR １１ , or N, F is CR １２ , or N, G is CR １３ or N, where 【Chemistry 6-2】 in which N is 1 or more; The R １０ ~R １３ are the same or different, and each independently represents cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, or -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amino, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heteroaryl, and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 10 carbon atoms.

8. The compound of formula I is a compound of formula I-4, or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof, according to claim 1: [Chemical formula I-4] 【Chemistry 7-1】 In the above formula, R is as defined above in Formula I; D is O or S, E is CR １１ , or N, F is CR １２ , or N, G is CR １３ or N, where 【Chemistry 7-2】 in which N is 1 or more; The R １０ ~R １３ are the same or different, and each independently represents cyano, halo, haloalkyl having 1 to 6 carbon atoms, nitro, or -C(=O)R １ , -C(=O)OR １ , -NH-C(=O)R １ , alkoxy having 1 to 10 carbon atoms, substituted or unsubstituted alkyl having 1 to 10 carbon atoms, substituted or unsubstituted cycloalkyl having 3 to 8 carbon atoms, substituted or unsubstituted amino, aryl having 5 to 20 carbon atoms, substituted or unsubstituted 5- to 12-membered heteroaryl, and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R １ is hydrogen, deuterium, or alkyl having 1 to 10 carbon atoms; Two or more adjacent groups may be bonded to each other to form an unsubstituted aromatic hydrocarbon ring, and the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaryl ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or an aryl ring having 6 to 10 carbon atoms; n is an integer of 0, 1 or 2; L is CH ２ , NH or O; 【Chemistry 8】 is unsubstituted or has one, two, three or four deuterium, halo, cyano, nitro, -NR ３ R ４ , alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, -C(=O)R ５ , -SO ２ -R ６ In this case, when there are two or more kinds of substituents, adjacent two or more kinds of groups are bonded to each other. 【Chemistry 9】 together with a substituted or unsubstituted 5- to 20-membered heteroaryl or a substituted or unsubstituted 5- to 20-membered heterocycloalkyl, In this case, the alkyl having 1 to 6 carbon atoms, the alkoxy having 1 to 6 carbon atoms, or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with one, two, three, or four of hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, aryloxy having 6 to 10 carbon atoms, or a 4- to 12-membered heterocycloalkyl unsubstituted or substituted with alkyl having 1 to 6 carbon atoms, aryl having 6 to 10 carbon atoms, alkyl having 1 to 6 carbon atoms, or alkylcarbonyl having 1 to 6 carbon atoms; The R ３ and R ４ are each independently hydrogen, deuterium, or -C(=O)-R ａ , an alkyl having 1 to 6 carbon atoms or an aryl having 6 to 10 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms or the aryl having 6 to 10 carbon atoms is unsubstituted or substituted with 1, 2, 3 or 4 kinds of halo, hydroxy, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms or aryloxy having 6 to 10 carbon atoms, wherein Ra is hydrogen, deuterium, alkyl having 1 to 6 carbon atoms or haloalkyl having 1 to 6 carbon atoms; The R ５ Yes - OR ｂ , -NR ｃ R ｄ , alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms, wherein the alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, or alkynyl having 2 to 6 carbon atoms is unsubstituted or substituted with 1, 2, 3, or 4 monoalkylamines having 1 to 6 carbon atoms or dialkylamines having 1 to 6 carbon atoms, wherein the R ｂ , R ｃ and R ｄ each independently represents hydrogen, deuterium, an aryl having 6 to 10 carbon atoms, an aryl having 6 to 10 carbon atoms, and an alkyl having 1 to 6 carbon atoms; The R ６ is alkyl having 1 to 6 carbon atoms, or aryl having 6 to 10 carbon atoms which is unsubstituted or substituted with 1, 2, 3 or 4 alkyl groups having 1 to 6 carbon atoms.

9. The compound according to claim 1, wherein the compound represented by the chemical formula I is selected from the following compounds 1) to 161), or a stereoisomer thereof, a solvate thereof, an isotopic variant thereof, a tautomer thereof, or a pharma- ceutically acceptable salt thereof: 1) 5-(benzylmethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 2) 5-(benzylcyclopropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 3) 4-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile; 4) 5-[(4-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 5) 5-[(2,4-difluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 6) 5-[(2-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 7) 5-[(3-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 8) 5-[methyl-(4-trifluoromethylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 9) 5-[methyl-(3-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 10) 5-[methyl-(3-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 11) 5-[methyl-(2-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 12) 5-[(4-methanesulfonylbenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 13) 5-[(3-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 14) 5-piperidin-1-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 15) 5-morpholino-4-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 16) 5-(4-methylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 17) 5-(4-(2-(2-hydroxymethoxy)ethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 18) 5-(3,4-dihydro-1H-isoquinolin-2-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 19) 5-[(4-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 20) 5-(benzylethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 21) 5-(benzylpropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 22) 5-(benzylbutylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 23) 5-[methyl(3-methylsulfonylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 24) 5-[methyl-(4-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 25) 3-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile; 26) 5-[(2-methoxybenzyl)-methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 27) 5-[(3-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 28) 5-[(4-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 29) 5-[methyl-(2-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 30) 5-[(2,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 31) 5-[(3,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 32) 5-(3,4-difluorophenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 33) 5-[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 34) 5-{methyl-[6-(4-methyl-piperazin-1-yl)-pyrimidin-4-ylmethyl]-amino}-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 35) 5-{[(3-(hydroxymethyl)-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl)methyl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 36) 5-{methyl[3-methyl-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 37) 5-{methyl[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methylamino}-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 38) Cyclopropyl[4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2-indazol-5-yl)piperazin-1-yl]methanone; 39) 5-(benzylmethylamino)-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 40) 5-(benzylmethylamino)-2-(5-chloropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 41) 5-(benzylmethylamino)-2-(6-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 42) 5-(benzylmethylamino)-2-(6-methylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 43) 5-(benzylmethylamino)-2-(3-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 44) 6-(5-(benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinonitrile; 45) 5-(benzylmethylamino)-2-(6-methyl-4-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 46) 5-(benzylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 47) 2-(pyridin-2-yl)-5-[(pyridin-2-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol; 48) 5-[methyl(pyridin-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 49) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 50) 2-(5-chloropyridin-2-yl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol; 51) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 52) 2-(4-bromophenyl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7,-tetrahydro-2H-indazol-3-ol; 53) 5-(benzylmethylamino)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 54) 2-(6-aminopyridin-2-yl)-5-(benzylmethylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 55) 5-phenylamino-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 56) 5-[(2,5-dimethylphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 57) 5-[(4-nitrophenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 58) 5-[(4-methoxyphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 59) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 60) 2-(pyridin-2-yl)-5-(quinolin-3-ylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 61) 5-[methyl(naphthalen-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 62) 5-[(isoquinolin-3-ylmethyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 63) 5-[methyl(quinolin-6-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 64) 5-[(isoquinolin-3-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 65) 5-[methyl(pyridin-2-ylmethyl)amino]-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 66) 5-[ethyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 67) 5-[(3-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 68) 5-[(4-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-2-ol; 69) 5-[(3-dimethylaminobenzyl)methylamino)]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 70) 5-[(4-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 71) 5-[(2-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 72) 5-(benzylmethylamino)-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol; 73) 4-[(5-benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]benzoic acid; 74) 5-(benzylmethylamino)-2-(4-bromophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 75) 5-(benzylmethylamino)-2-(2-chlorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 76) 5-(benzylmethylamino)-2-(2-methoxyphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 77) 2-(2-chlorophenyl)-5-[(3-dimethylaminobenzyl)methylamino]-4,5,6,7-tetrahydro-2H-indazol-3-ol; 78) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzoic acid; 79) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzamide; 80) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N-methylbenzamide; 81) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N,N-dimethylbenzamide; 82) 5-(4-methylpiperazin-1-yl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 83) 2-(6-chloropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 84) 2-(6-methyl-4-(trifluoromethyl)pyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 85) 5-(4-methylpiperazin-1-yl)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 86) 2-(3-fluoropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 87) 2-(pyridin-2-yl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 88) 5-((4-methoxybenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 89) 1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)but-2-en-1-one; 90) 2-(pyridin-2-yl)-5-(4-(quinolin-6-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 91) 5-(4-ethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 92) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 93) 5-(phenethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 94) 2-(4-chlorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 95) 5-(4-methylpiperazin-1-yl)-2-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 96) 2-(pyridin-2-yl)-5-(pyrrolidin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 97) 1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)prop-2-en-1-one; 98) (E)-4-(dimethylamino)-1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)but-2-en-1-one; 99) (E)-4-(dimethylamino)-N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-methylbut-2-enamide; 100) 5-(4-propylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 101) 2-(4-bromophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 102) 2-(4-fluorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 103) 4-(3-hydroxy-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzonitrile; 104) 5-(4-phenethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 105) 5-(4-benzylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 106) 5-(4-(cyclohexylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 107) 5-(4-(3-phenylpropyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 108) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 109) 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 110) 5-(4-(methylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 111) 5-(4-(phenylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 112) 2-(pyridin-2-yl)-5-(4-tosylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 113) 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-phenylpiperazine-1-carboxamide; 114) benzyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate; 115) 2-(1-methyl-1H-pyrrol-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 116) 5-(4-methylpiperazin-1-yl)-2-(thiazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 117) 5-(4-methylpiperazin-1-yl)-2-(oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 118) 2-(1-methyl-1H-pyrazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 119) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 120) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 121) 5-(benzyl(methyl)amino)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 122) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-pyrrol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 123) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-pyrazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 124) 5-(benzyl(methyl)amino)-2-(1-methyl-1H-imidazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 125) 5-(benzyl(methyl)amino)-2-(oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 126) 2-(pyridin-2-yl)-5-(4-(p-tolyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 127) 5-(4-(4-hydroxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 128) 5-(4-(3,4-difluorophenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 129) 5-(4-(4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 130) 1-(4-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)phenyl)ethan-1-one; 131) 5-(4-(4-(methylsulfonyl)phenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 132) 5-(4-(4-phenoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 133) 5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 134) 5-(4-((1-methylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 135) 5-(4-((1-benzylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 136) 1-(4-((4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)ethan-1-one; 137) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzamide; 138) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-2-phenylacetamide; 139) 1-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-3-phenylurea; 140) 1-benzyl-3-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)urea; 141) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzenesulfonamide; 142) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-4-methylbenzenesulfonamide; 143) Benzyl (3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)carbamate; 144) 2-(5-fluoro-4-morpholinopyrimidin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 145) N-benzyl-3-methoxy-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine; 146) N-benzyl-3-(cyclopropylmethoxy)-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine; 147) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl cyclopropanecarboxylate; 148) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl acrylate; 149) 5-(benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ylbenzoate; 150) 2-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyrimidine-5-carboxylic acid; 151) Methyl 2-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinate; 152) N-(6-(5-(benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyridin-2-yl)acetamide; 153) 5-(benzyl(methyl)amino)-2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 154) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 155) 2-(5-chloropyridin-3-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 156) 2-(pyridin-2-yl)-5-(4-(pyrimidin-2-yl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 157) 5-(benzyl(methyl)amino)-2-(5-nitropyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 158) 5-((4-hydroxybenzyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 159) 5-(methyl(4-nitrobenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; 160) 5-(3-(ethyl(methyl)amino)pyrrolidin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; and 161) 2,2,2-trifluoro-N-(1-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)pyrrolidin-3-yl)acetamide.

10. 2. The compound according to claim 1 or a salt thereof, characterized in that the salt is a salt form derived from one or more acids selected from the group consisting of hydrochloric acid, tartaric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, and hydroiodic acid; sodium salt; potassium salt; calcium salt; silver salt; hydrobromide salt; hydrogen sulfate salt; hydrogen phosphate salt; dihydrogen phosphate salt; succinate salt, citrate salt; mesylate salt, or tosylate salt.

11. A pharmaceutical composition for preventing, ameliorating or treating a disease associated with oxidative stress, comprising the compound according to any one of claims 1 to 9 or a pharma- ceutical acceptable salt thereof as an active ingredient and a pharma- ceutical acceptable carrier, The diseases associated with oxidative stress are selected from cancer; inflammatory diseases selected from rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory bowel disease, enterocolitis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, allergic contact dermatitis, diabetic inflammation, infectious inflammation, and autoimmune diseases; fibrotic diseases selected from liver fibrosis, liver cirrhosis, small intestinal fibrosis, large intestinal fibrosis, gastric fibrosis, pulmonary fibrosis, dermal fibrosis, epidermal fibrosis, dermal / systemic sclerosis, cardiac fibrosis, and renal fibrosis; degenerative neurological diseases selected from Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury; bipolar disorder, developmental disorder, autistic disorder, Asperger's syndrome, Rett's syndrome, and the like. nervous system disease selected from: visual impairment, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorder, Tourette's syndrome or schizophrenia; liver disease; skin disease; mitochondrial disease, Alpers syndrome, Barth syndrome, chronic progressive external ophthalmoplegia syndrome (CPEO), long-chain acyl-CoA dehydrogenase deficiency (LCAD), MELAS syndrome, Leber's hereditary optic neuropathy (LHON), Leigh syndrome, MEGDEL syndrome, Luft disease, Pearson's disease mitochondrial diseases selected from neurogenic ataxia retinitis pigmentosa (NARP), Co-Q10 deficiency, myoclonus epilepsy with ragged red fibers (MERRF), mitochondrial DNA depletion syndrome (MDS), fatal infantile cardiomyopathy (LIC), mitochondrial neurogastrointestinal encephalopathy syndrome, β-oxidation disorders, Friedreich's ataxia (FA), Kearns-Sayre syndrome (KSS), and lactic acidosis; aging; chronic alcoholism; stem cell dysfunction; claudication; obesity, diabetes, hypertension, hyperlipidemia, arteriosclerosis, peripheral vascular disease metabolic syndrome selected from: metabolic syndrome selected from: ischemic perfusion, myocardial infarction or stroke; Down's syndrome; infertility;A pharmaceutical composition selected from the group consisting of muscle-related diseases selected from myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy and spinal muscular atrophy; chronic fatigue; and retinal diseases selected from retinal fibrosis, macular degeneration, diabetic retinopathy, cataracts and neovascular glaucoma.

12. The pharmaceutical composition according to claim 11, wherein the pharma- ceutically acceptable carrier is at least one selected from the group consisting of excipients, diluents, disintegrants, binders, lubricants, surfactants, emulsifiers, suspending agents, and diluents.

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