Novel pyrazole derivatives

Abstract

The present invention provides a novel pyrazole derivative compound represented by Chemical Formula I, a stereoisomer, a solvate, an isotope variant, a tautomer or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same (in Chemical Formula I, A, B and R are the same as defined in the description of the present invention). # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a novel pyrazole derivative having excellent oxidative stress inhibitory activity, and more particularly to a novel pyrazole derivative which exhibits the ability to prevent, improve or treat various related diseases due to its excellent oxidative stress inhibitory ability, and its optical isomers, stereoisomers, solvates, isotopic variants, tautomers or pharmaceutically acceptable salts, methods for preparing the same and pharmaceutical compositions containing the same. Background Art

[0002] Oxidative stress refers to the imbalance between the production of reactive oxygen species or reactive nitrogen species and the antioxidant defense mechanism in biological molecules, cells and tissues in the body, and the relatively excessive production of reactive oxygen species or reactive nitrogen species, which usually leads to cell damage and tissue damage.

[0003] Reactive oxygen species (ROS) are oxygen free radicals generated by the chemical properties of oxygen and oxygen compounds derived from it, such as superoxide anion (O 2 -·), hydrogen peroxide (H 2 O 2 ), hydroxyl (OH·), alkoxy (RO·), peroxy (ROO·), etc.

[0004] Since these reactive oxygen species are chemically very unstable and highly active, they cause extensive oxidative damage to biomolecules, cells, tissues, etc. in the body, causing enzyme catalytic reactions, electron transfer in mitochondria, cell signaling systems and gene expression, activation of transcription factors, and peripheral inflammation, and act as a major factor in tissue fibrosis. This oxidative damage can lead to various diseases in all tissues of the human body. Specifically, it is known to be involved in the occurrence of cancer in tissues such as the skin, kidneys, heart, joints, lungs, brain, blood vessels, intestines, and eyes, as well as the progression of the resulting cancers, and it is known to play an important role in almost all diseases including cardiovascular disease, inflammation, fibrotic diseases, diabetes, etc.

[0005] In recent years, the interaction between the tumor microenvironment and cancer cells plays an important role in tumor growth, metastasis and expression of anti-tumor drug resistance, and in this context, cancer-associated fibroblasts (CAFs) play an important role. It is known that cancer-associated fibroblasts are activated by ROS and promote tumor immune evasion, thereby acting on tumor malignancy and metastasis. Therefore, in recent years, cancer-associated fibroblasts are becoming a new target for cancer therapy.

[0006] It has been reported that in liver tissues of patients experiencing liver fibrosis, increased ROS generation in hepatocytes is caused by TGF-β stimulation, thereby increasing the expression of collagen and αSMA, which are important for fibrosis. It has been reported that ROS can aggravate pulmonary fibrosis in lung tissues of patients with idiopathic pulmonary fibrosis.

[0007] The brain is a highly metabolic tissue and is therefore very susceptible to oxidative damage. Therefore, many studies have been conducted to effectively remove ROS to treat various neurodegenerative diseases (Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury, etc.), but without success. Recently, since ROS were found to be an important factor in these brain diseases, the possibility of treating these brain diseases through ROS inhibition has been reported.

[0008] Keloid is a benign tumor disease in which the connective tissue of the skin proliferates pathologically, forming a hard mass with a thin, shiny, and reddish epidermis. It has been reported that one of the causes of the occurrence and deterioration of keloid is the overexpression of connective tissue growth factor (CTGF) due to ROS produced by TGF-β stimulation.

[0009] In the case of diabetes, complications such as diabetic nephropathy and diabetic retinopathy may be associated with long-term hyperglycemia, and ROS are known to play an important role in the development of complications. In other words, hyperglycemia leads to increased ROS generation, and the ROS generated at this time can cause diabetic nephropathy and diabetic retinopathy through a series of processes including the death of renal cells and retinal cells.

[0010] Furthermore, it has been reported that when the CTGF gene is overexpressed in the retina of the eye, keloid disease can lead to retinal fibrosis and macular degeneration, among other things.

[0011] Therefore, the present inventors focused on the development of therapeutic agents for cancer, inflammatory diseases, fibrotic diseases, neurodegenerative diseases, liver diseases, skin diseases or retinal diseases caused by oxidative stress by using a molecular mechanism for inhibiting the generation of oxidative stress. As a result, it was found that the novel pyrazole derivatives of the present invention have excellent inhibitory activity for ROS generation and have been confirmed to be useful for treating various diseases associated with oxidative stress, thereby completing the present invention.

[0012] Prior art

[0013] Patent Literature

[0014] (Patent Document 1) WO 2016-207785 Summary of the invention

[0015] Technical issues

[0016] One object of the present invention is to provide a pyrazolyl compound of Formula I, an optical isomer, stereoisomer, solvate, isotopic variant, tautomer or pharmaceutically acceptable salt thereof.

[0017] One object of the present invention is to provide a pharmaceutical composition comprising a compound of Formula I, or a stereoisomer, solvate, isotope variant, tautomer or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0018] An object of the present invention is to provide a method for controlling ROS generation using the compound of formula I, or a stereoisomer, solvate, isotopic variant, tautomer or pharmaceutically acceptable salt thereof.

[0019] One object of the present invention is to provide a method for preventing, improving or treating oxidative stress-related diseases by administering to a subject a compound of Formula I, or a stereoisomer, solvate, isotope variant, tautomer or pharmaceutically acceptable salt thereof.

[0020] An object of the present invention is to provide a method for preparing the compound of formula I, or a stereoisomer, solvate, isotopic variant, tautomer or pharmaceutically acceptable salt thereof.

[0021] One object of the present invention is to provide a compound of formula I, or use of a solvate, stereoisomer or pharmaceutically acceptable salt thereof in the preparation of a pharmaceutical composition for preventing, improving or treating oxidative stress-related diseases.

[0022] Technical Solution

[0023] In order to achieve the above object, as one aspect of the present invention, a novel pyrazole derivative may be provided, namely, a compound represented by the following Chemical Formula 1, or a stereoisomer, solvate, isotope variant, tautomer or pharmaceutically acceptable salt thereof.

[0024] [Chemical formula 1]

[0025]

[0026] In the above formula, A, B and R are defined as follows.

[0027] As one aspect of the present invention, the present invention provides a compound represented by Chemical Formula 1, a solvate, a stereoisomer or a pharmaceutically acceptable salt thereof for preventing, improving or treating oxidative stress-related diseases.

[0028] As one aspect of the present invention, the present invention provides a pharmaceutical composition for treating oxidative stress-related diseases, comprising as an active ingredient a compound represented by Chemical Formula 1, a solvate, a stereoisomer or a pharmaceutically acceptable salt and an acceptable carrier.

[0029] In addition, the present invention provides a method for treating oxidative stress-related diseases, comprising administering an effective dose of the compound represented by Chemical Formula 1, a solvate, a stereoisomer or a pharmaceutically acceptable salt to a subject in need of treatment.

[0030] In addition, the present invention provides use of a compound represented by Chemical Formula I, a solvate, a stereoisomer or a pharmaceutically acceptable salt thereof in preparing a pharmaceutical composition for preventing or treating an oxidative stress-related disease.

[0031] Beneficial Effects

[0032] The novel pyrazole derivatives and the pharmaceutical compositions containing the novel pyrazole derivatives of the present invention provide excellent therapeutic effects for diseases related to oxidative stress.

[0033] In addition, the novel pyrazole derivatives effectively inhibit oxidative stress and the production of αSMA in various cells, and are particularly effective in improving cancer, inflammatory diseases, fibrotic diseases, neurodegenerative diseases, liver diseases, skin diseases or retinal diseases caused by oxidative stress.

[0034] BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 The effect of the synthetic example compounds on inhibiting ROS production induced by PMA in LX-2 and NHLF cells is shown.

[0036] Figure 2 The effect of the compound of Synthesis Example 3 on inhibiting ROS generation induced by α-synuclein preformed fibrils (PFFs) in N27 cells is shown.

[0037] Figure 3a and 3b The synthesis example compounds ( Figure 3a : Compounds 1, 23 and 12, Figure 3b : Compounds 5, 14 and 33) inhibit the expression of αSMA induced by TGFβ1 in HFF cells.

[0038] Figure 4 The effect of Synthesis Example Compound 1 on inhibiting the expression of αSMA induced by TGFβ1 in various cells is shown.

[0039] Figure 5 The effect of the synthetic example compounds on inhibiting IL6 expression in P.CAF cells is shown.

[0040] Figure 6 The effect of the synthetic example compounds on inhibiting IL8 expression in P.CAF cells is shown.

[0041] Figure 7 The results show the effect of the compounds of Synthesis Examples on inhibiting the contraction of collagen gel induced by TGFβ1 in HFF cells.

[0042] Figure 8 The effect of the synthetic example compounds on inhibiting the LPS-induced IL1β expression in LX2, NHLF, ARPE19 and KEL-Fib cells is shown. DETAILED DESCRIPTION

[0043] Hereinafter, the present invention will be described in more detail.

[0044] 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, unless otherwise explicitly stated, the numerical values ​​disclosed herein are intended to include the meaning of "about". All publications and other references mentioned herein are fully incorporated herein by reference.

[0045] The definitions of the residues used herein are as follows. In addition, unless there is a separate definition of a residue, it is used with the meaning commonly understood by those skilled in the art.

[0046] As used herein, the term "independently" means that when more than one substituent is selected from a plurality of possible substituents, the substituents may be the same as or different from each other.

[0047] The term "alkyl" as used herein refers to an aliphatic hydrocarbon group and refers to a straight chain, branched monovalent saturated hydrocarbon group. Unless otherwise specified, the alkyl group generally includes 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 tert-butyl), pentyl (e.g., n-pentyl, isopentyl and neopentyl), n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl.

[0048] The term "alkenyl" as used herein refers to an aliphatic hydrocarbon group containing one or more carbon-carbon double bonds, and includes straight and branched hydrocarbon groups. For example, "alkenyl" is vinyl, allyl, but-1-enyl or but-2-enyl. The number of carbon atoms of the alkenyl or alkynyl group is not particularly limited, and is preferably 1 to 10, 1 to 8, 1 to 6, 1 to 4 or 1 to 3 carbon atoms.

[0049] The term "alkynyl" as used herein refers to an aliphatic hydrocarbon group containing one or more carbon-carbon triple bonds, and includes all straight and branched hydrocarbon groups. For example, "alkynyl" is ethynyl, alkynyl or butynyl.

[0050] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents. 3 , -C 2 F 5 , -CHF 2 , -CCl 3 , -CHCl 2 and -C 2 Cl 5 Unless otherwise defined, a haloalkyl group typically contains 1 to 6, 1 to 5, 1 to 4, or 1 to 3 carbon atoms, and may be further substituted with other substituents.

[0051] The term "alkoxy" used herein may be a straight chain, a branched chain or a cyclic chain. The carbon number of the alkoxy group is not particularly limited, but the carbon number is preferably 1 to 10, 1 to 8, 1 to 6, 1 to 4 or 1 to 3. Specifically, it may be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a tert-butoxy group, a sec-butoxy group, a n-pentoxy group, a neopentoxy group, an isopentoxy group, etc., but is not limited thereto.

[0052] As used herein, the term "hydroxy" or "hydroxyl" refers to -HO, alone or in combination with other terms.

[0053] The term "amino" as used herein refers to -NH 2 .

[0054] As used herein, the terms "halo," "halogen," and "halide" refer to fluorine, chlorine, bromine, and iodine.

[0055] As used herein, the term "cycloalkyl" refers to a non-aromatic carbocyclic ring comprising cyclized alkyl, alkenyl and alkynyl. The cycloalkyl may comprise a monocyclic or polycyclic ring. Polycyclic rings have, for example, 2, 3 or 4 fused rings. Unless otherwise defined, the cycloalkyl generally comprises 3 to 10 or 3 to 7 ring carbon atoms. The cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclohexadienyl, cycloheptatrienyl, etc., and may be further substituted with other substituents.

[0056] Herein, the term "aryl" refers to an aromatic hydrocarbon group with a monocyclic or polycyclic ring, and can be further substituted by other substituents. Herein, polycyclic refers to wherein the aryl is directly connected to another cyclic group or fused with another cyclic group. Herein, another cyclic group can be an aryl, but can be other types of cyclic groups, such as cycloalkyl, heteroaryl, etc. Polycyclic can have, for example, 2, 3 or 4 rings. Unless otherwise specified, the aryl group generally has 5 to 20, 6 to 15, 6 to 12 or 6 to 10 carbon ring atoms. Aryl includes, for example, phenyl, naphthyl (such as naphthyl-1-base and naphthyl-2-base), non-phenyl, anthracenyl (anthracenyl), phenanthreneyl (phenanthreneyl), etc.

[0057] As used herein, "heterocycle" means an aromatic, saturated or partially unsaturated mono-, bi-, di- or polycyclic ring system containing the specified number of ring atoms and including one or more heteroatoms selected from N, O and S. Ring members, heterocycles herein are connected to the base molecule via ring atoms (which may be C or N). Bicyclic ring systems may be connected via 1,1-fusion (spiro), 1,2-fusion (fused) or 1,>2-fusion (bridged).

[0058] 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 includes monocyclic or polycyclic structures. Polycyclic rings may have, for example, 2, 3 or 4 fused rings. Unless otherwise defined, heteroaryl groups typically contain 3 to 10, 3 to 7 or 3 to 5 ring atoms. Heteroaryl groups may contain 1, 2 or 3 heteroatoms. The heteroaryl groups include, for example, furanyl, pyridyl, N-oxypyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolyl, isoquinolyl, dihydroisoquinolyl, thienyl, imidazolyl, furanyl, thiazolyl, indolyl, pyrrole, oxazolyl, benzofuranyl, benzothiophenyl, benzothiazolyl, isobutyl oxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, benzothienyl, furanyl, benzimidazolyl, indolyl and the like, and may be further substituted by other substituents.

[0059] As used herein, "heterocycloalkyl" refers to a monocyclic, bicyclic, tricyclic or polycyclic alkyl group having 3 to 10 carbon ring members, wherein the carbon ring members contain one or more, for example, 1 to 4, 1 to 3 or 1 to 2 heteroatoms selected from N, O and S. In addition, the heterocycle according to the present invention may also be a fused or cross-linked heterocycloalkyl group. Examples of non-aromatic rings may be azetidinyl, oxolanyl, tetrahydrofuran, pyrrolyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, Oxazoline, oxazolidinyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyrazolopyridinyl, morpholinyl, indolyl, azathiomorpholinyl and the like.

[0060] The connection of the heterocycloalkyl substituent can occur through a carbon atom or a heteroatom. Heterocycloalkyl can be randomly substituted with one or more suitable groups by one or more of the above groups. Unless otherwise defined, heterocycloalkyl refers to 4 to 12-membered heterocycloalkyl, preferably 4 to 10-membered heterocycloalkyl, more preferably 4 to 7-membered heterocycloalkyl.

[0061] As used herein, the term "aralkyl" refers to an alkyl group substituted with an aryl group. "Aryl" and "alkyl" are as defined above.

[0062] As used herein, the term "heteroaralkyl" refers to an alkyl group substituted by a heteroaryl group. "Heteroaryl" and "alkyl" are as defined above.

[0063] As used herein, the term "alkylheterocycloalkyl" refers to a heterocycloalkyl group substituted by an alkyl group. "Alkyl" and "heterocycloalkyl" are as defined above.

[0064] In this context, the "substituted or unsubstituted amino group" may be selected from monoalkylamino, -NH 2 and dialkylamino, and the definition of "alkyl" is the same as defined above. Specific examples of the substituted or unsubstituted amino group include NH 2 , methylamino, dimethylamino, ethylamino, diethylamino, etc., but are not limited thereto.

[0065] Herein, "alkylene" refers to an alkyl group having two bonding sites, that is, a divalent group. The description of the aforementioned alkyl group can be applied to them, except that each of them is a divalent group.

[0066] Herein, the term "substituted" means that a hydrogen atom bonded to a carbon atom of a compound is replaced by another substituent, and the position to be substituted is not limited, as long as the position to which the hydrogen atom is substituted, that is, the position where the substituent can be substituted is not limited, and when two or more substituents are substituted, the two or more substituents may be the same or different from each other, and two or more same or different substituents may be connected and substituted.

[0067] As used herein, the term "substituted alkyl", "substituted alkenyl", "substituted alkynyl" or "substituted alkoxy" refers to the following substituents in the C 1 -C 10 Straight or branched alkyl, C 2 -C 10 Alkenyl, C 2 -C 10 Alkynyl or C 1 -C 10 The carbon atom of the alkoxy group is substituted. Specifically, the substituent is a group selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 Aryl or C 5 -C 20 Heteroaryl, C 1 -C 5 Alkoxy and C 1 -C 5 One or more substituents in the haloalkyl, or the same or different two or more substituents are connected and substituted. As exemplary substituents, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl substituted imidazole, pyridine, substituted or unsubstituted sulfonyl etc. can be used, but are not limited thereto.

[0068] The term "substituted cycloalkyl" as used herein refers to a cycloalkyl group which is selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 Aryl or C 5 -C 20 Heteroaryl, C 1 -C 5 Alkoxy and C 1 -C 5 One or more substituents, or two or more substituents that are the same or different, in the haloalkyl group are linked and substituted with C 3 -C 8As exemplary substituents, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl, substituted imidazole, substituted or unsubstituted sulfonyl, etc. can be used, but are not limited thereto.

[0069] The term "substituted aryl" or "substituted heteroaryl" as used herein is a group in which a radical is selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, C 1 -C 5 Alkoxy, C 1 -C 5 Haloalkyl, C 1 -C 10 Alkyl, C 3 -C 8 Cycloalkyl or C 3 -C 8 Heterocycloalkyl, C 3 -C 8 Cycloalkyl C 1 -C 10 Alkyl, C 5 -C 20 Aryl C 1 -C 10 One or more substituents, or two or more substituents that are the same or different, in the alkyl group are linked and substituted with C 5 -C 20 Aryl or C 5 -C 50 As exemplary substituents, trifluoromethyl, halogen, cyano, methoxy, carboxyl, methyl, amino, nitro, dimethylamino, cyclopropyl substituted imidazole, methylpiperazine, substituted imidazopyrimidine, substituted or unsubstituted sulfonyl, etc. can be used, but are not limited thereto.

[0070] In this article, "adjacent" groups can refer to substituents substituted on the atom directly connected to the corresponding substituent, the substituent closest to the corresponding substituent in space, or another substituent substituted on the atom on which the corresponding substituent is substituted. For example, two substituents substituted at the ortho position of a benzene ring and two substituents substituted on the same carbon of an aliphatic ring can be interpreted as groups "adjacent" to each other.

[0071] When applied to a compound, "effective dose" refers to an amount effective to treat or prevent a disease in a subject as described herein.

[0072] Compound

[0073] In order to achieve the above object, the present invention provides a compound of the following chemical formula I, or a stereoisomer, solvate, isotope variant, tautomer or pharmaceutically acceptable salt thereof:

[0074]

[0075] In the formula,

[0076] A is a substituted or unsubstituted 5- to 20-membered heteroaryl group or a substituted or unsubstituted C 5 -C 20 aryl; and

[0077] Among them, 5- to 20-membered heteroaryl or C 5 -C 20 The aryl group may be unsubstituted or may be substituted by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 20-membered heteroaryl and substituted or unsubstituted 5- to 20-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium or C 1 -C 10 Alkyl; and

[0078] Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 5 -C 10 Aromatic rings; and

[0079] R is hydrogen, deuterium, cyano, halogen, nitro, C 1 -C 6 Haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 20-membered heteroaryl, or -C(=O)R 2 , where R 2 It is C 3 -C 8Cycloalkyl, C 1 -C 10 Alkyl, C 2 -C 10 Alkenyl or C 6 -C 10 aryl; and

[0080] B is -NKM or substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and

[0081] K is hydrogen, deuterium, cyano, halogen, nitro, haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroarylC 1 -C 10 alkyl;

[0082] M is cyano, halogen, nitro, haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroarylC 1 -C 10 alkyl,

[0083] Among them, C 1 -C 10The alkyl group may be unsubstituted or selected from deuterium, halogen, hydroxyl, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Haloalkyl, substituted or unsubstituted C 1 -C 10 Hydroxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, C 1 -C 10 Alkoxy, C 1 -C 10 Alkylsulfonyl, C 5 -C 20 Arylsulfonyl, C 5 -C 20 Aryloxy, substituted or unsubstituted C 5 -C 20 substituted with 1, 2, 3 or 4 substituents selected from the group consisting of aryl, substituted or unsubstituted 5- to 20-membered heteroaryl and substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and

[0084] C 3 -C 8 The cycloalkyl group may be unsubstituted or selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 Aryl or 5- to 20-membered heteroaryl, C 1 -C 10 Alkoxy and C 1 -C 10 substituted with 1, 2, 3 or 4 substituents selected from the group consisting of haloalkyl; and

[0085] 5- to 20-membered heteroaryl, 5- to 20-membered heterocycloalkyl or C 5 -C 20 The aryl group may be unsubstituted or selected from deuterium, halogen, cyano, nitro, -C(=O)R', -C(=O)OR', -NH-C(=O)R", substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Haloalkyl, substituted or unsubstituted C 1 -C 10 Hydroxyalkyl, substituted or unsubstituted C 1 -C10 Alkylsulfonyl, substituted or unsubstituted C 5 -C 20 Arylsulfonyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl C 1 -C 10 Aryl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 12-membered heterocycloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl C 3 -C 8 Cycloalkyl and substituted or unsubstituted C 1 -C 10 Alkyl is substituted with 1, 2, 3 or 4 substituents selected from the group consisting of 5-membered to 20-membered heterocycloalkyl; and

[0086] wherein R' and R" are each independently hydrogen, deuterium, substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 6 Alkyl, substituted or unsubstituted C 2 -C 6 Alkenyl, substituted or unsubstituted C 2 -C 6 Alkynyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 6 -C 10 Aryl or substituted or unsubstituted C 6 -C 10 Aryl or C 1 -C 6 Alkyl, wherein the C 2 -C 6 Alkenyl or C 2 -C 6 The alkynyl group may be unsubstituted or may be substituted with a single C 1 -C 6 Alkylamino or di-C 1 -C 6 1, 2, 3 or 4 substitutions in alkylamino;

[0087] and

[0088] The substituted amino group can be C 1 -C10 Alkyl, C 6 -C 10 Aryl C 1 -C 6 1 or 2 substitutions in the alkyl group; and

[0089] The heteroatom of the heterocycloalkyl or heteroaryl ring may be one or more selected from N, S and O.

[0090] As a specific aspect,

[0091] A is an unsubstituted or substituted 5- to 12-membered heteroaryl group or C 6 -C 10 Aryl, wherein 5- to 12-membered heteroaryl or C 6 -C 10 The aryl group may be selected from cyano, halogen, C 1 -C 6 Haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 6 Alkyl, C 1 -C- 6 Alkoxy, C 3 -C 6 Cycloalkyl, amino, C 6 -C 10 aryl, 5- to 12-membered heteroaryl and 5- to 12-membered heterocycloalkyl, wherein R 1 is hydrogen, deuterium or C 1 -C 6 Alkyl; and

[0092] Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 7-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 9 Aromatic ring.

[0093] As a specific aspect, A can be a 5- to 10-membered heteroaryl group having 1, 2, 3 or 4 heteroatoms selected from N, O and S or a C 6 -C 9 Aryl.

[0094] As a specific aspect, A can be pyridyl, pyrimidinyl, pyrazolyl, triazolyl, thiazolyl, phenyl or thieno[3,2]pyridine.

[0095] As a specific aspect, A can be1 -C 6 Alkyl, C 1 -C 6 Alkoxy, F, Cl, Br, I, cyano, amino, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , 5- to 12-membered heterocycloalkyl, wherein Ra can be hydrogen, deuterium, C 1 -C 6 alkyl.

[0096] As a specific aspect, A can be methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, F, Cl, Br, I, cyano, amino, nitro, -C(=O)OH, -C(=O)CH 3 、-NH-C(=O)CH 3 , morpholinyl or piperidinyl, 1, 2, 3 or 4 of them are substituted.

[0097] As a specific aspect, R is hydrogen, deutrium, cyano, halogen, nitro, unsubstituted or C 3 -C 6 Cycloalkyl substituted C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 3 -C 6 Cycloalkyl, C 6 -C 10 Aryl, 5- to 12-membered heteroaryl, -C(=O)R 2 , where R 2 It is C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 6 -C 10 Aryl.

[0098] As a specific aspect, R 2 It may be cyclopropyl, methyl, ethyl, propyl, vinyl, propenyl or phenyl.

[0099] As a specific aspect, R can be hydrogen, deuterium, cyano, halogen, nitro, methyl, ethyl, propyl, butyl, cyclopropylmethyl, CF 3 , -C(=O)-cyclopropyl, -C(=O)-vinyl or benzoyl.

[0100] As a specific aspect, 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 by deuterium, halogen, cyano, nitro, -NR 3 R 4 , C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, -C(=O)R 5 、-SO 2 -R 6 1, 2, 3 or 4 substitutions in

[0101] Among them, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 The aryl group may be unsubstituted or substituted with hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 1, 2, 3 or 4 substituted or unsubstituted aryloxy groups 1 -C 6 Alkyl, C 6 -C 10 Aryl C 1 -C 6 Alkyl or C 1 -C 6 alkylcarbonyl-substituted 4- to 12-membered heterocycloalkyl, and

[0102] R 3 and R 4 are independently hydrogen, deuterium, -C(=O)-R a , C 1 -C 6 Alkyl or C 6 -C 10 Aryl, and C 1 -C 6 Alkyl or C 6 -C 10 Aryl is unsubstituted or substituted by halogen, hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 101, 2, 3 or 4 substitutions in aryloxy, wherein Ra is hydrogen, deuterium, C 1 -C 6 Alkyl or C 1 -C 6 haloalkyl; and

[0103] R 5 Yes-OR b 、-NR c R d , C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 8 Cycloalkyl, wherein C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 2 -C 6 Alkynyl groups may be unsubstituted or substituted with a single C 1 -C 6 Alkylamino or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamino group, wherein R b , R c and R d Each independently is hydrogen, deuterium, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 Alkyl, and

[0104] R 6 It is C 1 -C 6 Alkyl, unsubstituted or substituted with 1, 2, 3 or 4 C 1 -C 6 Alkyl substituted C 6 -C 10 Aryl, and

[0105] K is hydrogen, deuterium, cyano, halogen, nitro, C 1 -C 6 Haloalkyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", C 3-C 8 Cycloalkyl, C 6 -C 10 Aryl, C 6 -C 10 Aryl C 1 -C 6 alkyl, 5- to 12-membered heteroaryl, 5- to 12-membered heteroarylC 1 -C 6 Alkyl, where C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, C 3 -C 8 The cycloalkyl or 5- to 12-membered heteroaryl may be substituted with cyano, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Alkylsulfonyl, C 6 -C 10 Arylsulfonyl, -NR 7 R 8 、-C(=O)R 9 , 5- to 12-membered heterocyclic group, hydroxyl, nitro, C 6 -C 10 1, 2, 3 or 4 substitutions in the aryl group, wherein the 5- to 12-membered heterocyclic group or the C 6 -C 10 The aryl group may be unsubstituted or substituted with C 1 -C 6 Alkyl substitution,

[0106] M is cyano, halogen, nitro, C 1 -C 6 Haloalkyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", C 3 -C 8 Cycloalkyl, C 6 -C 10 Aryl, C 6 -C 10 Aryl C 1-C 6 alkyl, 5- to 12-membered heteroaryl, 5- to 12-membered heteroarylC 1 -C 6 Alkyl, where C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, C 3 -C 8 The cycloalkyl or 5- to 12-membered heteroaryl may be substituted with cyano, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Alkylsulfonyl, C 6 -C 10 Arylsulfonyl, -NR 7 R 8 、-C(=O)R 9 , 5- to 12-membered heterocyclic group, hydroxyl, nitro, C 6 -C 10 1, 2, 3 or 4 substitutions in the aryl group, wherein the 5- to 12-membered heterocyclic group or the C 6 -C 10 The aryl group may be unsubstituted or substituted with C 1 -C 6 Alkyl substitution,

[0107] R 7 and R 8 Each independently is hydrogen, deuterium, C 1 -C 6 Alkyl, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 alkyl,

[0108] and

[0109] R 9 Yes-OR e 、-NR e R f , unsubstituted or substituted with 1, 2, 3 or 4 kinds of -NR e R f -substituted C 2 -C6 Alkenyl or C 6 -C 10 Aryl, wherein R e and R f Each independently is hydrogen, deuterium, C 1 -C 6 Alkyl, C 6 -C 10 Aryl or C 1 -C 6 alkyl.

[0110] As a specific aspect, B may be a 5- to 10-membered heteroaryl group or a 5- to 10-membered heterocycloalkyl group having 1 to 3 heteroatoms selected from the group consisting of N, O and S, and they may be substituted with the aforementioned substituents or be unsubstituted.

[0111] As a specific aspect, B may be pyrrolidine, piperazine, dihydroisoquinoline, morpholine or piperidine, and they may be substituted with the aforementioned substituents or may be unsubstituted.

[0112] As a specific aspect, the compound of Chemical Formula I can be the compound of the following Chemical Formula I-1:

[0113] [Chemical Formula I-1]

[0114]

[0115] In the formula,

[0116] K, M and R are the same as those in Formula I; and

[0117] D is for CR 10 , N, O or S, or E is CR 11 , N, O or S, or F is CR 12 , N, O or S, or G is CR 13 , N, O or S, or J is CR 14 , N, O or S, but N, O and S are one or more; and

[0118] R 10 To R 14 are the same or different and may be independently replaced by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 12-membered heteroaryl and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium, C 1 -C 10 Alkyl; and

[0119] Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 10 Aromatic ring.

[0120] As a specific aspect, the compound of Chemical Formula I can be a compound of the following Chemical Formula I-2:

[0121] [Chemical Formula I-2]

[0122]

[0123] In the formula,

[0124] R, D, E, F, G and J are as defined in Formula I-1; and

[0125] n is an integer of 0, 1 or 2; and

[0126] L is CH 2 , NH or O; and

[0127] It may be unsubstituted or substituted with deuterium, halogen, cyano, nitro, -NR 3 R 4 , C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, -C(=O)R 5 、-SO 2 -R 6 1, 2, 3 or 4 substitutions in

[0128] When the number of substituents is 2 or more, two or more adjacent groups may be combined with each other to form a substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and

[0129] Among them, C1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 The aryl group may be unsubstituted or substituted with hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryloxy, unsubstituted or substituted with C 1 -C 6 Alkyl, C 6 -C 10 Aryl C 1 -C 6 Alkyl or C 1 -C 6 1, 2, 3 or 4 substitutions in 4- to 12-membered heterocycloalkyl substituted with alkylcarbonyl, and

[0130] R 3 and R 4 are independently hydrogen, deuterium, -C(=O)-R a , C 1 -C 6 Alkyl or C 6 -C 10 Aryl, and C 1 -C 6 Alkyl or C 6 -C 10 The aryl group may be unsubstituted or may be substituted by halogen, hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 1, 2, 3 or 4 substitutions in the aryloxy group, wherein R a For hydrogen, deuterium, C 1 -C 6 Alkyl or C 1 -C 6 haloalkyl; and

[0131] R 5 Yes-OR b 、-NR c R d , C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C8 Cycloalkyl, wherein C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 2 -C 6 Alkynyl groups may be unsubstituted or substituted with a single C 1 -C 6 Alkylamino or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamino group, and R b , R c and R d are independently hydrogen, deuterium, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 Alkyl, and

[0132] R 6 It is C 1 -C 6 Alkyl, unsubstituted or substituted with 1, 2, 3 or 4 C 1 -C 6 Alkyl substituted C 6 -C 10 Aryl.

[0133] In one specific aspect, when L is substituted When L is CH 2 or NH, wherein one or two H groups may be substituted by the above substituents.

[0134] As a specific aspect, the compound of Chemical Formula I can be a compound of the following Chemical Formula I-3:

[0135] [Chemical Formula I-3]

[0136]

[0137] In the formula,

[0138] K, M, R, D, E, F and G are as defined in Chemical Formula I-1.

[0139] As a specific aspect, the compound of Chemical Formula I can be a compound of the following Chemical Formula I-4:

[0140] [Chemical Formula I-4]

[0141]

[0142] In the formula,

[0143] L, n, R, D, E, F and G are as defined in Chemical Formula I-2.

[0144] As one aspect, the compound of Chemical 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.

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

[0146] 2) 5-(Benzylcyclopropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0147] 3) 4-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile;

[0148] 4) 5-[(4-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0149] 5) 5-[(2,4-difluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0150] 6) 5-[(2-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0151] 7) 5-[(3-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0152] 8) 5-[methyl-(4-trifluoromethylbenzyl)amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0153] 9) 5-[methyl-(3-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0154] 10) 5-[methyl-(3-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0155] 11) 5-[methyl-(2-trifluoromethylbenzyl)-amino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0156] 12) 5-[(4-methylsulfonylbenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0157] 13) 5-[(3-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0158] 14) 5-piperidin-1-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0159] 15) 5-morpholin-4-yl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0160] 16) 5-(4-methylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0161] 17) 5-(4-(2-(2-hydroxymethoxy)ethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0162] 18) 5-(3,4-dihydro-1H-isoquinolin-2-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0163] 19) 5-[(4-chlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0164] 20) 5-(Benzylethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0165] 21) 5-(Benzylpropylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0166] 22) 5-(Benzylbutylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0167] 23) 5-[methyl(3-methylsulfonylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0168] 24) 5-[methyl-(4-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0169] 25) 3-{[(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)methylamino]methyl}benzonitrile;

[0170] 26) 5-[(2-methoxybenzyl)-methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0171] 27) 5-[(3-fluorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0172] 28) 5-[(4-methoxybenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0173] 29) 5-[methyl-(2-methylbenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0174] 30) 5-[(2,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0175] 31) 5-[(3,4-dichlorobenzyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0176] 32) 5-(3,4-difluorophenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0177] 33) 5-[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0178] 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;

[0179] 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;

[0180] 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;

[0181] 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;

[0182] 38) [4-(3-Hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2-indazol-5-yl)piperazin-1-yl]cyclopropylmethanone;

[0183] 39) 5-(Benzylmethylamino)-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0184] 40) 5-(Benzylmethylamino)-2-(5-chloropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0185] 41) 5-(Benzylmethylamino)-2-(6-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0186] 42) 5-(Benzylmethylamino)-2-(6-methylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0187] 43) 5-(Benzylmethylamino)-2-(3-fluoropyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0188] 44) 6-(5-(Benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinonitrile;

[0189] 45) 5-(Benzylmethylamino)-2-(6-methyl-4-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0190] 46) 5-(Benzylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0191] 47) 2-(pyridin-2-yl)-5-[(pyridin-2-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0192] 48) 5-[methyl(pyridin-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0193] 49) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(5-trifluoromethylpyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0194] 50) 2-(5-chloropyridin-2-yl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0195] 51) 5-[methyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0196] 52) 2-(4-bromophenyl)-5-[methyl(pyridin-4-ylmethyl)amino]-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0197] 53) 5-(Benzylmethylamino)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0198] 54) 2-(6-aminopyridin-2-yl)-5-(benzylmethylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0199] 55) 5-phenylamino-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0200] 56) 5-[(2,5-dimethylphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0201] 57) 5-[(4-nitrophenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0202] 58) 5-[(4-methoxyphenyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0203] 59) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0204] 60) 2-(pyridin-2-yl)-5-(quinolin-3-ylamino)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0205] 61) 5-[methyl(naphthalen-2-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0206] 62) 5-[(Isoquinolin-3-ylmethyl)methylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0207] 63) 5-[methyl(quinolin-6-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0208] 64) 5-[(Isoquinolin-3-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0209] 65) 5-[Methyl(pyridin-2-ylmethyl)amino]-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0210] 66) 5-[ethyl(pyridin-4-ylmethyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0211] 67) 5-[(3-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0212] 68) 5-[(4-dimethylaminobenzyl)amino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-2-ol;

[0213] 69) 5-[(3-dimethylaminobenzyl)methylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0214] 70) 5-[(4-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0215] 71) 5-[(2-dimethylamino)benzylmethylamino]-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0216] 72) 5-(Benzylmethylamino)-2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0217] 73) 4-[(5-Benzylmethylamino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl]benzoic acid;

[0218] 74) 5-(Benzylmethylamino)-2-(4-bromophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0219] 75) 5-(Benzylmethylamino)-2-(2-chlorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0220] 76) 5-(Benzylmethylamino)-2-(2-methoxyphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0221] 77) 2-(2-chlorophenyl)-5-[(3-dimethylaminobenzyl)methylamino]-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0222] 78) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzoic acid;

[0223] 79) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)benzamide;

[0224] 80) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N-methylbenzamide;

[0225] 81) 4-(((3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)(methyl)amino)methyl)-N,N-dimethylbenzamide;

[0226] 82) 5-(4-methylpiperazin-1-yl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0227] 83) 2-(6-chloropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0228] 84) 2-(6-methyl-4-(trifluoromethyl)pyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0229] 85) 5-(4-methylpiperazin-1-yl)-2-(thieno[3,2-c]pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0230] 86) 2-(3-fluoropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0231] 87) 2-(pyridin-2-yl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0232] 88) 5-((4-methoxybenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0233] 89) 1-(4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazin-1-yl)but-2-yn-1-one;

[0234] 90) 2-(pyridin-2-yl)-5-(4-(quinolin-6-ylmethyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0235] 91) 5-(4-ethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0236] 92) 5-(phenylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0237] 93) 5-(phenethylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0238] 94) 2-(4-chlorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0239] 95) 5-(4-methylpiperazin-1-yl)-2-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0240] 96) 2-(pyridin-2-yl)-5-(pyrrolidin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0241] 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;

[0242] 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;

[0243] 99) (E)-4-(dimethylamino)-N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-methylbut-2-enamide;

[0244] 100) 5-(4-propylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0245] 101) 2-(4-bromophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0246] 102) 2-(4-fluorophenyl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0247] 103) 4-(3-hydroxy-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzonitrile;

[0248] 104) 5-(4-phenethylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0249] 105) 5-(4-benzylpiperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0250] 106) 5-(4-(cyclohexylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0251] 107) 5-(4-(3-phenylpropyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0252] 108) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0253] 109) 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0254] 110) 5-(4-(methylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0255] 111) 5-(4-(phenylsulfonyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0256] 112) 2-(pyridin-2-yl)-5-(4-tosylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0257] 113) 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-N-phenylpiperazine-1-carboxamide;

[0258] 114) benzyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate;

[0259] 115) 2-(1-methyl-1H-pyrrol-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0260] 116) 5-(4-methylpiperazin-1-yl)-2-(thiazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0261] 117) 5-(4-methylpiperazin-1-yl)-2-( oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0262] 118) 2-(1-methyl-1H-pyrazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0263] 119) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0264] 120) 2-(1-methyl-1H-imidazol-5-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0265] 121) 5-(Benzyl(methyl)amino)-2-(pyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0266] 122) 5-(Benzyl(methyl)amino)-2-(1-methyl-1H-pyrrol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0267] 123) 5-(Benzyl(methyl)amino)-2-(1-methyl-1H-pyrazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0268] 124) 5-(Benzyl(methyl)amino)-2-(1-methyl-1H-imidazol-5-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0269] 125) 5-(Benzyl(methyl)amino)-2-( oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0270] 126) 2-(pyridin-2-yl)-5-(4-(p-tolyl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0271] 127) 5-(4-(4-hydroxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0272] 128) 5-(4-(3,4-difluorophenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0273] 129) 5-(4-(4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0274] 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;

[0275] 131) 5-(4-(4-(methylsulfonyl)phenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0276] 132) 5-(4-(4-phenoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0277] 133) 5-(4-(piperidin-4-ylmethyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0278] 134) 5-(4-((1-methylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0279] 135) 5-(4-((1-benzylpiperidin-4-yl)methyl)piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0280] 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;

[0281] 137) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzamide;

[0282] 138) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-2-phenylacetamide;

[0283] 139) 1-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-3-phenylurea;

[0284] 140) 1-benzyl-3-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)urea;

[0285] 141) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)benzenesulfonamide;

[0286] 142) N-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)-4-methylbenzenesulfonamide;

[0287] 143)benzyl (3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)carbamate;

[0288] 144) 2-(5-fluoro-4-morpholinopyrimidin-2-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0289] 145) N-benzyl-3-methoxy-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine;

[0290] 146) N-benzyl-3-(cyclopropylmethoxy)-N-methyl-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-amine;

[0291] 147) 5-(Benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ylcyclopropanecarboxylate;

[0292] 148) 5-(Benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl acrylate;

[0293] 149) 5-(Benzyl(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-yl benzoate;

[0294] 150) 2-(5-(Benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyrimidine-5-carboxylic acid;

[0295] 151) 2-(5-(Benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)nicotinate;

[0296] 152) N-(6-(5-(Benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyridin-2-yl)acetamide;

[0297] 153) 5-(Benzyl(methyl)amino)-2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0298] 154) 5-(4-methylpiperazin-1-yl)-2-(pyrimidin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0299] 155) 2-(5-chloropyridazin-3-yl)-5-(4-methylpiperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0300] 156) 2-(pyridin-2-yl)-5-(4-(pyrimidin-2-yl)piperazin-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0301] 157) 5-(Benzyl(methyl)amino)-2-(5-nitropyrimidin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0302] 158) 5-((4-hydroxybenzyl)(methyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0303] 159) 5-(methyl(4-nitrobenzyl)amino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol;

[0304] 160) 5-(3-(ethyl(methyl)amino)pyrrolidin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol; and

[0305] 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.

[0306] Unless otherwise specified, the chemical formulae or nomenclature given in the present specification and claims refer to tautomers and all stereo, optical and geometric isomers (e.g., enantiomers, diastereomers and E / Z isomers, etc.) and racemates thereof, as well as mixtures of different enantiomers in different proportions, diastereomeric mixtures, or mixtures in which any of the above forms of isomers and enantiomers are present, and pharmaceutically acceptable salts and solvates thereof, such as hydrates (including, for example, solvates and hydrates of free compounds, or solvates and hydrates of salts of corresponding compounds).

[0307] In one embodiment, the compounds of the present invention may be present in the form of pharmaceutically acceptable salts. Salts refer to salts commonly used in the medical field to which the present invention belongs, and acid addition salts formed from pharmaceutically acceptable free acids are useful. The term "pharmaceutically acceptable salt" of the present invention refers to any organic or inorganic addition salt of a compound, wherein the side effects caused by the salt do not reduce the beneficial effects of the compounds according to the present invention, and its concentration has an effective effect that is relatively nontoxic and harmless to the patient.

[0308] Acid addition salts are prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent (e.g., methanol, ethanol, acetone or acetonitrile). Equimolar amounts of the compound and acid or alcohol (e.g., ethylene glycol monoethyl ether) can be heated in water and the mixture then evaporated to dryness, or the precipitated salt can be filtered with suction.

[0309] Among them, organic acids and inorganic acids can be used as free acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, hydrobromic acid, etc. can be used as inorganic acids, and methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, hydroxybenzoic acid, salicylic acid, tartaric acid, fumaric acid, malic acid, citric 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, hydroiodic acid, etc. can be used as organic acids, but are not limited to these.

[0310] In addition, pharmaceutically acceptable metal salts can be prepared using a base. Alkali metal salts or alkaline earth metal salts can be obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. Among them, as metal salts, pharmaceutically suitable for preparing sodium, potassium or calcium salts, but not limited thereto. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0311] Unless otherwise indicated, the pharmaceutically acceptable salts of the compounds of the present invention include salts of acidic or basic groups that may be present in the compounds described in the above chemical formula I. For example, as pharmaceutically acceptable salts, sodium salts, calcium salts and potassium salts of hydroxyl groups may be included, while pharmaceutically acceptable salts of other amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (methoxide) and p-toluenesulfonate (p-toluenesulfonate), which can be prepared by salt preparation methods known in the art.

[0312] As the salt of the compound of the above Chemical Formula I of the present invention, any pharmaceutically acceptable salt may be used without limitation, which is a salt of the compound of the above Chemical Formula I that exhibits the same pharmacological activity as the compounds shown in Table 1.

[0313] In addition, the compounds of the present invention may also be in the form of stereoisomers thereof. Stereoisomers include 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. The separation of a specific stereoisomer may be carried out by one of the common methods known in the art. Some examples of the compounds of the present invention may have a greater inhibitory effect on the oxidative stress of a specific stereoisomer. In this case, by using a specific stereoisomer, the dosage can be reduced. Therefore, a specific stereoisomer, such as an enantiomer or a diastereomer, which has a great inhibitory effect on oxidative stress can be separated, thereby effectively treating oxidative stress-related diseases.

[0314] The compounds of the present invention may be in the form of solvates thereof. "Solvate" refers to a complex or aggregate of one or more solute molecules (i.e., a compound of Formula I or a pharmaceutically acceptable salt thereof) and one or more solvent molecules. Solvates may be, for example, complexes or aggregates formed by various solvent molecules such as water, methanol, ethanol, isopropanol or acetate.

[0315] Solvates with water as the solvent molecule are called hydrates. Hydrates include compositions containing stoichiometric amounts of water as well as compositions containing varying amounts of water.

[0316] The compounds of the present invention may also be in the form of tautomers.

[0317] The term "tautomer" or "tautomeric form" refers to different compositional isomers of different energies that are interconvertible via a low energy barrier. Some non-limiting examples of proton tautomers (also known as proton tautomers) include interconversions via proton transfer, such as ketoenol and imine-enamine isomerizations. Valence tautomers include interconversions that occur via reorganization of some of the bonding electrons.

[0318] The compounds of the present invention may also be in the form of isotopic variations thereof.

[0319] The term "isotopic variant" refers to a compound having the same atomic number as any compound, but having at least one atom replaced by another atom having an atomic mass different from the usual or normal atomic mass found in nature.

[0320] Solvates, stereoisomers, tautomers and isotopic variations of the compound of the above-mentioned Formula I can be prepared from the compound using methods known in the art.

[0321] In the preparation method of the present invention, as the reactant used in the above reaction formula, a commercially available compound can be purchased and used as it is, or they can be synthesized by performing one or more reactions known in the art as they are or by appropriately changing them and using them. For example, considering the presence, type and / or position of reactive functional groups and / or heteroelements included in the framework structure, they can be synthesized by performing one or more reactions in a tandem order, but are not limited thereto.

[0322] In one embodiment, compared with the control group, the compounds of the synthetic examples of the present invention showed 30%, 50%, 70% or more inhibition of ROS production by treating ROS produced by PMA in HL-60 cells (human leukemia cells), and also showed concentration-dependent inhibition ability. Therefore, the compounds of the present invention can be used to prevent or treat oxidative stress-related diseases.

[0323] It is reported that as fibroblasts differentiate into myofibroblasts, cancer-associated fibroblasts (CAFs) form or induce various tissue fibrosis. As a result of treating HFF-1 (human foreskin fibroblasts) cells with the synthetic example compounds of the present invention (where fibrosis is induced by TGF-β1 treatment), the expression effect of inhibiting αSMA (an indicator of fibrosis) was shown. Therefore, the compounds of the present invention can be used to prevent or treat fibrosis-related diseases, and can be used to treat cancer by regulating cancer-associated fibroblasts, which are important indicators of tumor microenvironment interactions.

[0324] When ROS levels in neurons are elevated, lipid oxidation is induced, which is considered an important factor in neuronal cell death. When N27 cells (rat dopaminergic neurons) were treated with 1-(1-methyl-4-phenylptridinium) and the compound of the synthesis example, the generation of ROS was effectively inhibited. Therefore, the compound of the present invention can be used to prevent or treat diseases related to neuronal cell death caused by oxidative stress.

[0325] One of the main causes of skin fibrosis is that CTGF of keloid fibroblasts produces extracellular matrix, such as type I collagen, etc. When the synthetic example compound treats KEL-FIB (keloid fibroblast) cells and then TGF-β1 is treated to induce fibrosis, the expression of CTGF gene and type I collagen gene is effectively inhibited. Therefore, the compound of the present invention can be used to prevent or treat skin keloid disease.

[0326] Pharmaceutical compositions and medical uses

[0327] The compound of the present invention, its optical isomer, its stereoisomer, its solvate, its isotopic variant, its tautomer or its pharmaceutically acceptable salt is suitable for preventing, improving or treating various diseases caused by oxidative stress due to its biological properties.

[0328] The pharmaceutical composition of the present invention can be used to treat oxidative stress-related diseases. The disease can be cancer, inflammatory diseases, fibrotic diseases, neurodegenerative diseases, nervous system diseases, liver diseases, skin diseases, mitochondrial diseases, aging, chronic alcoholism, stem cell dysfunction, lameness, metabolic syndrome, Down syndrome, infertility, excessive production of lipid peroxides in tissues, muscle-related diseases, accumulation of lipid peroxides in cell membranes, chronic fatigue or retinal diseases.

[0329] The cancer may be selected from the group consisting of liver cancer, hepatocellular carcinoma, gastrointestinal cancer, gastric cancer, neurofibroma-related intracranial meningioma, pancreatic cancer, leukemia, myeloid and extramedullary myeloproliferative / myelodysplastic diseases, cutaneous fibrosarcoma, breast cancer, lung cancer, thyroid cancer, colorectal cancer, prostate cancer, breast cancer, ovarian cancer, brain tumor, head and neck cancer, glioblastoma, etc. In addition, the cancer may be a secondary cancer that has metastasized to another organ from various types of cancer.

[0330] Metabolic syndrome can be obesity, diabetes, hypertension, hyperlipidemia, arteriosclerosis, peripheral vascular disease, ischemic perfusion, myocardial infarction or stroke, etc.

[0331] Inflammatory diseases may be inflammation-associated rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory colorectal disease, enterocolitis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, inflammation in ischemia-reperfusion injury and inflammation caused by immune rejection after tissue and organ transplantation, various inflammations occurring on the skin (such as burns, allergic contact dermatitis, etc.), inflammation caused by multi-organ diseases, diabetic inflammation including diabetic nephropathy, infectious inflammation caused by viral or bacterial infection, or autoimmune diseases (such as atopic diseases, lupus, psoriasis, atherosclerosis, etc.).

[0332] The fibrotic disease may be liver fibrosis or cirrhosis induced by metabolic diseases, liver fibrosis or cirrhosis induced by NAFLD, liver fibrosis or cirrhosis induced by NASH, liver fibrosis or cirrhosis induced by alcohol, liver fibrosis or cirrhosis induced by drugs, liver fibrosis or cirrhosis induced by infectious pathogens, liver fibrosis or cirrhosis induced by parasitic infections, liver fibrosis or cirrhosis induced by bacterial infections, liver fibrosis or cirrhosis induced by viral infections, liver fibrosis or cirrhosis induced by HBV infections, liver fibrosis or cirrhosis induced by HCV infections, liver fibrosis or cirrhosis induced by HIV infections, liver fibrosis or cirrhosis induced by dual HCV and HIV infections, liver fibrosis or cirrhosis induced by radiotherapy or chemotherapy, biliary fibrosis, liver fibrosis or cirrhosis caused by any chronic cholestatic disease, digestive tract fibrosis caused by any etiology, fibrosis induced by Crohn's disease, fibrosis induced by ulcerative colitis, small intestine Fibrosis, colonic fibrosis, gastric fibrosis, pulmonary fibrosis, skin fibrosis, epidermal fibrosis, endothelial fibrosis, skin fibrosis due to sclerosis / systemic sclerosis, chronic obstructive pulmonary disease (COPD), asthma, emphysema, smoker's lung, tuberculosis, pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF) secondary to pulmonary fibrosis, cardiac fibrosis, renal fibrosis, nephrogenic systemic fibrosis, muscle fibrosis, soft tissue fibrosis, myelofibrosis, arthrofibrosis, tendon 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, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis as a complication of pneumoconiosis, proliferative fibrosis, tumor fibrosis, perigraft fibrosis, asbestosis, arthrofibrosis or adhesive pericranitis.

[0333] The neurodegenerative disease may be Alzheimer's disease (including mild or early Alzheimer's disease, mild to moderate Alzheimer's disease, moderate to intermediate Alzheimer's disease, moderate to severe Alzheimer's disease, moderate to severe Alzheimer's disease, severe Alzheimer's disease, and Alzheimer's disease with Lewy bodies), Parkinson's disease (including chemically induced Parkinson's disease due to exposure to environmental factors such as pesticides, insecticides 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's disease-related or LRRK2-related Parkinson's disease), autosomal dominant Parkinson's disease, diffuse Lewy body disease (DLBD) (also called dementia with Lewy bodies (DLB)), pure autonomic imbalance, dysphagia with Lewy bodies, random LBD, inherited LBD (e.g., mutations in the alpha-synuclein gene, PARK3, and PARK4), multiple system atrophy (including olivopontocerebellar atrophy, striatonigral degeneration, Shy-Drager syndrome symptoms (MSA), complex Alzheimer's disease 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 (ALS), dementias (including vascular dementia, dementia with Lewy bodies, Parkinson's dementia, and frontotemporal dementia), psychosis (including anxiety caused by neurodegenerative diseases or associated with dopamine treatment, such as Parkinson's psychosis, Alzheimer's psychosis, dementia with Lewy bodies psychosis (without limitation)), movement disorders (including anxiety caused by neurodegenerative diseases or associated with dopamine treatment), anxiety (anxiety caused by neurodegenerative diseases or associated with dopamine treatment), conditions associated with dopamine treatment (including dystonia, myoclonus, or tremor), synucleinopathies, diseases associated with abnormal expression of alpha synuclein, ischemic brain diseases, Creutzfeldt-Jakob disease, Machado-Joseph disease Joseph disease or spinocerebellar ataxia or Pick disease.

[0334] The liver disease can be a metabolic liver disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), drug-induced liver disease, alcohol-induced liver disease, infectious pathogen-induced liver disease, inflammatory liver disease, liver disease mediated by immune system dysfunction, or dyslipidemia.

[0335] The skin disease may be keloid disease, psoriasis or psoriasis, and the retinopathy may be retinal fibrosis, macular degeneration, diabetic retinopathy, diabetic macular degeneration, retinopathy of prematurity, ischemia-reperfusion related retinal damage, retinitis pigmentosa, cataract or neovascular glaucoma.

[0336] The mitochondrial disease can be an inherited mitochondrial disease, Alpers disease, Barth syndrome, chronic progressive external ophthalmoplegia (CPEO), long-chain acyl-CoA dehydrogenase deficiency (LCAD), melas syndrome, Leber hereditary optic neuropathy (LHON), Leigh disease, Leigh-like syndrome, Luft disease, Pearson syndrome, neuropathy, ataxia and retinitis pigmentosa (NARP), Co-Q10 deficiency, MERRF syndrome (MERRF), mitochondrial DNA depletion syndrome (MDS), fatal infantile cardiomyopathy (LIC), mitochondrial neurogastrointestinal encephalomyopathy, beta oxidation defect, Friedrich's ataxia (Friedrich's ataxia FA), Kearns-Sayre syndrome (KSS), or lactic acidosis.

[0337] Neurological diseases can be bipolar disorder, developmental disorders, autism, Asperger's syndrome, Rett syndrome, visual impairment, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorders, Tourette syndrome or schizophrenia, etc. Muscle-related diseases can be myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy or spinal muscular atrophy, etc.

[0338] Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective dose of a compound of the above-defined chemical formula I, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof, and a pharmaceutically acceptable carrier.

[0339] In the composition of the present invention, the compound or its pharmaceutically acceptable salt or solvate or stereoisomer is as defined above.

[0340] In the composition of the present invention, "pharmaceutically acceptable carrier" means a substance used in combination with an active ingredient to help apply the active ingredient, usually an inert substance. The carrier includes common pharmaceutically acceptable excipients, additives or diluents. The carrier may include, for example, one or more selected from fillers, binders, disintegrants, buffers, preservatives, surfactants, antioxidants, lubricants (glydent), flavoring agents, thickeners, colorants, emulsifiers, suspending agents, stabilizers, pH adjusters and isotonic agents.

[0341] As diluents, sugar, starch, microcrystalline cellulose, lactose (hydrated lactose), glucose, dimannitol, alginate, alkaline earth metal salts, clay, polyethylene glycol, anhydrous calcium hydrogen phosphate or a mixture thereof can be used; as binders, starch, microcrystalline cellulose, highly dispersed silicon dioxide, mannitol, dimannitol, sucrose, lactose hydrate, polyethylene glycol, polyvinyl pyrrolidone (povidone), polyvinyl pyrrolidone copolymer (copovidone), hydroxypropyl methylcellulose, hydroxypropyl cellulose, natural gum, synthetic gum, gelatin or a mixture thereof can be used.

[0342] As disintegrants, starch or modified starch, such as sodium starch glycolate, corn starch, potato starch, pregelatinized starch, etc., clay, such as bentonite, montmorillonite or magnesium aluminum silicate, etc., cellulose, such as microcrystalline cellulose, hydroxypropyl cellulose or carboxymethyl cellulose, etc., alginic acid, such as sodium alginate or alginic acid, etc., cross-linked cellulose, such as cross-linked carboxymethyl cellulose, etc., gum, such as guar gum, xanthan gum, etc., cross-linked polymers, such as cross-linked polyvinyl pyrrolidone (cross-linked polyvinyl pyrrolidone), etc., effervescent agents, such as sodium bicarbonate, citric acid, etc., or mixtures thereof, can be used.

[0343] As the lubricant, talc, stearate, magnesium stearate, calcium stearate, sodium lauryl sulfate, hydrogenated vegetable oil, sodium benzoate, sodium stearyl fumarate, glyceryl monostearate, glyceryl monostearate, glyceryl palmitostearate, colloidal silicon dioxide or a mixture thereof or the like can be used.

[0344] As pH adjusters, acidulants such as acetate, ascorbic acid, sodium ascorbate, sodium acetate, malic acid, succinic acid, tartaric acid, fumaric acid and citric acid (citrate) and alkaline agents such as precipitated calcium carbonate, ammonia water, meglumine, sodium carbonate, magnesium oxide, magnesium carbonate, sodium citrate and tribasic calcium phosphate can be used.

[0345] As antioxidants, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol acetate, tocopherol, propyl gallate, sodium bisulfite, sodium pyrosulfite, etc. can be used. In the pre-release chamber of the present invention, as solubilizers, sodium lauryl sulfate, polyoxyethylene sorbitan fatty acid esters (such as polysorbate), docusate sodium, poloxamer, etc. can be used.

[0346] Furthermore, to prepare a sustained-release preparation, enteric polymers, water-insoluble polymers, hydrophobic compounds and hydrophilic polymers may be included.

[0347] Enteric polymers refer to polymers that are insoluble or stable under acidic conditions of pH less than 5 and dissolve or degrade under specific pH conditions above pH 5, and include, for example, enteric cellulose derivatives such as hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate (hydroxypropylmethylcellulose phthalate), hydroxymethylethylcellulose phthalate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate malate, cellulose benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalate, carboxymethylethylcellulose and ethylhydroxyethylcellulose phthalate, methylhydroxyethylcellulose; enteric acrylate copolymers such as styrene-acrylate copolymers, methyl acrylate-acrylate copolymers, acrylate-methyl methacrylate copolymers (e.g., acryl-IS), butyl acrylate-styrene-acrylate copolymers and acrylate-methyl methacrylate-octyl acrylate copolymers; enteric polymethacrylate copolymers such as poly(methacrylate methyl methacrylate) copolymers (e.g., Eudragit L, Eudragit S, Evonik, Germany) and poly (methacrylate ethyl acrylate) copolymers (e.g., Eudragit L100-55); enteric maleic acid-based copolymers, such as vinyl acetate-maleic anhydride copolymers, styrene-maleic anhydride copolymers, styrene-maleic anhydride monoester copolymers, vinyl methyl ether-maleic anhydride copolymers, ethylene-maleic anhydride copolymers, vinyl butyl ether-maleic anhydride copolymers, acrylonitrile-methyl acrylate-maleic anhydride copolymers and butyl acrylate-styrene-maleic anhydride copolymers; and enteric polyethylene derivatives, such as polyvinyl phthalate, polyvinylacetalphthalate, polyvinylbutylatephthalate and polyvinylacetacetalphthalate.

[0348] Water-insoluble polymers refer to pharmaceutically acceptable polymers that are insoluble in water and control the release of the drug. For example, water-insoluble polymers include 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, etc.), ethyl cellulose, cellulose esters, cellulose ethers, acylated cellulose, diacylated cellulose, triacylated cellulose, cellulose acetate, diacetate cellulose, and triacetate cellulose, etc.

[0349] Hydrophobic compounds refer to pharmaceutically acceptable substances that are insoluble in water and control the release of drugs. For example, they include fatty acids and fatty acid esters, such as glyceryl palmitostearate, glyceryl stearate, glyceryl behenate, palmitic acid hexadecyl, glyceryl monooleate and glyceryl stearate; fatty acid alcohols, such as cetearyl alcohol, cetyl alcohol and stearyl alcohol; waxes, such as carnauba wax, beeswax and microcrystalline wax; and minerals, such as talc, precipitated calcium carbonate, calcium monohydrogen phosphate, zinc oxide, titanium oxide, kaolin, bentonite, montmorillonite and magnesium aluminum silicate.

[0350] Hydrophilic polymers refer to pharmaceutically acceptable polymer substances that are soluble in water and control the release of drugs. For example, it includes carbohydrates such as dextrin, polydextrin, dextran, pectin and pectin derivatives, alginates, polygalacturonic acid, xylan, arabinoxylan, arabinogalactan, starch, hydroxypropyl starch, amylose and amylopectin; cellulose derivatives such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose and sodium carboxymethyl cellulose; gums such as guar gum, locust bean gum, baical gum, carrageenan, acacia gum, gum arabic, gellan gum and xanthan gum; proteins such as gelatin, casein and zein; polyvinyl alcohol derivatives such as polyvinyl alcohol, polyvinyl pyrrolidone and polyvinyl alcohol acetal diethylamine acetate; hydrophilic polymethacrylate copolymers such as poly(butyl methacrylate-(2-dimethylaminoethyl) methacrylate-methyl methacrylate) copolymer (e.g., Eudragit E100, Evonik, Germany), poly(ethyl acrylate-methyl methacrylate-triethylaminoethyl methacrylate chloride) copolymer (e.g., Eudragit RL, RS, Evonik, Germany); polyethylene derivatives such as polyethylene glycol and polyethylene oxide; and carbomer, etc.

[0351] Furthermore, as various additives selected from coloring agents and flavoring agents, the preparation of the present invention can be formulated by selecting and using pharmaceutically acceptable additives.

[0352] In the present specification, the range of additives is not limited to the use of the above-mentioned additives, and it can be formulated by controlling the dosage within a conventional range by selecting the above-mentioned additives.

[0353] The pharmaceutical composition of the present invention can be formulated in the form of oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, as well as external preparations, suppositories or sterile injection solutions.

[0354] The composition of the present invention may be administered orally, or parenterally including intravenous, intraperitoneal, subcutaneous, rectal and topical administration.

[0355] Another aspect of the present invention provides a method for treating a disease in a subject, comprising administering to the subject a therapeutically effective dose of a compound of Formula I or a pharmaceutically acceptable salt or solvate or stereoisomer thereof.

[0356] In this method, those skilled in the art can appropriately select the route of administration according to the patient's condition when administering. Oral or parenteral administration is possible. Parenteral administration includes intravenous, intraperitoneal, subcutaneous, rectal and topical administration.

[0357] In this method, the dosage can be adjusted in various ways according to various factors (such as the patient's condition, route of administration, judgment of the family doctor, etc.), as described above. The effective dose can be estimated based on the dose-response curve obtained from in vitro experiments or animal model experiments. The proportion and concentration of the compound of the present invention present in the composition to be administered can be determined based on chemical properties, route of administration, therapeutic dose, etc. The dose can be administered to the subject at an effective dose of about 1 μg / kg to about 1g / kg / day or about 0.1mg / kg to about 500mg / kg / day. The dosage can be adjusted according to the age, weight, sensitivity or symptoms of the subject.

[0358] In addition, the pharmaceutical composition comprising the compound of the present invention or its stereoisomer, solvate, isotopic variant, tautomer or pharmaceutically acceptable salt as an active ingredient can be used in a method for preventing, improving or treating a disease selected from the group consisting of: cancer; an inflammatory disease selected from rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory colorectal disease, enterocolitis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, allergic contact dermatitis, diabetic inflammation, infectious inflammation and autoimmune diseases; an inflammatory disease selected from liver fibrosis, cirrhosis, small intestinal fibrosis, large intestinal fibrosis, gastric fibrosis, pulmonary fibrosis fibrotic diseases selected from the group consisting of Parkinson's disease, Huntington's disease, amyloid lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury; neurological diseases selected from the group consisting of bipolar disorder, developmental disorder, autistic disorder, Asperger's syndrome, Rett syndrome, visual disorder, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorder, Tourette syndrome and schizophrenia; liver disease; skin disease; selected from the group consisting of inherited mitochondrial disease, Alpers disease, Barrett's disease, th syndrome, chronic progressive external ophthalmoplegia (CPEO), long-chain acyl-CoA dehydrogenase deficiency (LCAD), melas syndrome, Leber hereditary optic neuropathy (LHON), Leigh disease, Leigh-like syndrome, Luft disease, Pearson syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP), Co-Q10 deficiency, MERRF syndrome (MERRF), mitochondrial DNA depletion syndrome (MDS), fatal infantile cardiomyopathy (LIC), mitochondrial neurogastrointestinal encephalomyopathy, beta-oxidation defect, Friedrich's ataxia (Friedrich's mitochondrial diseases such as ataxia (FA), Kearns-Sayre syndrome (KSS) or lactic acidosis; aging; chronic alcoholism; stem cell dysfunction; claudication; metabolic syndrome selected from obesity, diabetes, hypertension, hyperlipidemia, atherosclerosis, peripheral vascular disease, ischemic perfusion, myocardial infarction and stroke; Down syndrome; infertility; excessive production of lipid peroxides in tissues; muscle-related diseases selected from myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy and back muscle atrophy; accumulation of cell membrane lipid peroxides; chronic fatigue; and retinal diseases selected from retinal fibrosis, macular degeneration, diabetic retinopathy, cataracts and neovascular glaucoma,

[0359] The method comprises administering it to a subject in need thereof.

[0360] Implementation

[0361] [Example]

[0362] Hereinafter, the present invention will be described in more detail by way of examples. These examples are intended to illustrate the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited by these examples.

[0363] <Reference Example - Preparation of Intermediates 1 to 3>

[0364] Intermediate 1: Preparation of methyl 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylate

[0365] 4-dioxaspiro [4.5] decane-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 then added at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and dimethyl carbonate (11.5 g, 128 mmol, 2 eq) was then added. After stirring at room temperature for 12 hours, 200 mL of saturated aqueous ammonium chloride solution was added to terminate the reaction. The reaction mixture was extracted with ethyl acetate (100 mL × 3) and brine, dried over anhydrous sodium sulfate, and then 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.

[0366] 1 H NMR (400 MHz, CDCl 3 ): 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).

[0367] 4-dioxaspiro [4.5] decane-8-one (15.0 g, 96.04 mmol) was dissolved in 250 mL of anhydrous tetrahydrofuran, and sodium hydride (9.22 g, 192.08 mmol, 2 eq) was then 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, then cooled to room temperature, and then 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 then 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.

[0368] Intermediate 2: Preparation of 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazole]-3'-ol

[0369] 8-Oxo-1,4-dioxaspiro[4,5]decane-7-carboxylic acid methyl ester (2.0 g, 10.3 mmol) was dissolved in 20 mL of ethanol, and then 2-hydrazinopyridine (1.1 g, 10.3 mol, 1.0 eq) was added. The reaction mixture was refluxed for 12 hours 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.

[0370] 1 H NMR (400 MHz, DMSO-d 6 ): 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).

[0371] 8-Oxo-1,4-dioxaspiro[4,5]decane-7-carboxylic acid methyl ester (18.1 g, 84.53 mmol) was dissolved in 120 mL of ethanol, and then 2-hydrazinopyridine (9.22 g, 84.5 mmol, 1.0 eq) was added. The reaction mixture was refluxed at 100° C. for 4 hours 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.

[0372] Intermediate 3: Preparation of 3-hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one

[0373] 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 trifluoroacetate (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 then adjusted to pH 6 with sodium bicarbonate. The reaction mixture was extracted with dichloromethane and water, then 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.

[0374] 1 H NMR (400 MHz, 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 calculated value: 229.2; MS found value: 230.2([M+H] + ).

[0375] 2'-(Pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazole]-3'-ol (12,99 g, 47,56 mmol) was dissolved in 120 mL of dichloromethane, and trifluoroacetate (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 ether to give the title compound (10.88 g, 99%) as a light brown solid.

[0376] <Synthesis example>

[0377] Synthesis Example 1. Preparation of 8-oxo-1,4-dioxaspiro[4,5]decane-7-carboxylic acid methyl ester

[0378] 4-dioxaspiro [4.5] decane-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 then added at room temperature. The reaction mixture was stirred at room temperature for 30 minutes, and dimethyl carbonate (11.5 g, 128 mmol, 2 eq) was then added. After stirring at room temperature for 12 hours, 200 mL of saturated aqueous ammonium chloride solution was added to terminate the reaction. The reaction mixture was extracted with ethyl acetate (100 mL × 3) and brine, dried over anhydrous sodium sulfate, and then 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.

[0379] 1 H NMR (400 MHz, CDCl 3 ): 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).

[0380] 4-dioxaspiro [4.5] decane-8-one (15.0 g, 96.04 mmol) was dissolved in 250 mL of anhydrous tetrahydrofuran, and sodium hydride (9.22 g, 192.08 mmol, 2 eq) was then 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, then cooled to room temperature, and then 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 then 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.

[0381] Synthesis Example 2. Preparation of 2'-(pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazole]-3'-ol

[0382] 8-Oxo-1,4-dioxaspiro[4,5]decane-7-carboxylic acid methyl ester (2.0 g, 10.3 mmol) was dissolved in 20 mL of ethanol, and then 2-hydrazinopyridine (1.1 g, 10.3 mol, 1.0 eq) was added. The reaction mixture was refluxed for 12 hours 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.

[0383] 1 H NMR (400 MHz, DMSO-d 6 ): 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).

[0384] 8-Oxo-1,4-dioxaspiro[4,5]decane-7-carboxylic acid methyl ester (18.1 g, 84.53 mmol) was dissolved in 120 mL of ethanol, and then 2-hydrazinopyridine (9.22 g, 84.5 mmol, 1.0 eq) was added. The reaction mixture was refluxed at 100° C. for 4 hours. The residue was recrystallized from ethyl acetate to give the title compound (16.39 g, 71%) as a yellow solid.

[0385] Synthesis Example 3. Preparation of 3-hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one

[0386] 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 trifluoroacetate (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 then adjusted to pH 6 with dichloromethane and water. The reaction mixture was extracted with dichloromethane and water, then 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 yellow solid.

[0387] 1 H NMR (400 MHz, DMSO-d 6 ):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 calculated value: 229.2; MS found value: 230.2([M+H] + ).

[0388] 2'-(Pyridin-2-yl)-2',4',6',7'-tetrahydrospiro[[1,3]dioxolane-2,5'-indazole]-3'-ol (12.99 g, 47.56 mmol) was dissolved in 120 mL of dichloromethane, and then trifluoroacetate (240 mL) was added. The reaction mixture was recrystallized from ether to give the title compound (10.88 g, 99%) as a light brown solid.

[0389] Synthesis Example 4. Preparation of 5-(Benzylpropylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 21)

[0390] 3-hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazole-5-one (500mg, 2.18mmol, 1.0eq) was dissolved in 30mL dichloromethane, and then tert-butyldimethylsilyl chloride (494mg, 3.27mmol, 1.5eq) and triethylamine (0.6mL, 4.36mmol, 2.0eq) were slowly added under a nitrogen stream. The reaction mixture was stirred at room temperature for 12 hours, then extracted with water and brine. The organic layer was dried over anhydrous sodium sulfate, and then the mixture was used for the next step without additional purification.

[0391] N-benzylpropane-1-amine (649 mg, 4.36 mmol, 2.0 eq), sodium triacetoxyborohydride (1.39 g, 6.54 mmol, 3.0 eq) and acetate (4 drops) were added to the compound obtained in the reaction, and then stirred at room temperature for 12 hours. Saturated sodium bicarbonate aqueous solution (50 mL) was added to the reaction mixture to adjust the pH to about 8, and then extracted with dichloromethane (30 mL × 3). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified once by a silica gel column (solvent: dichloromethane / methanol=20 / 1) to obtain a mixture 6 (400 mg). The mixture purified once was purified twice by sorting high performance liquid chromatography to obtain the title compound (104 mg, 13.1%) as a yellow solid.

[0392] 1 H NMR (400MHz, CD 3 OD): δ8.40(s,1H),8.15-8.11(m,1H),8.08-8.01(m,1H),7.56-7.53(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), 1.60-1.57 (m, 1H), 0.90-0.81 (m, 3H). MS calculated value: 362.2; MS found value: 363.3 ([M+H] + ).

[0393] Synthesis Example 5. Preparation of 5-(Benzylethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 20)

[0394] According to the preparation method of Compound 21, the title compound (120 mg, 15.8%) was obtained as a yellow solid.

[0395] 1 H NMR (400MHz, CD 3OD): 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,4H),7.23(t,J=6.8Hz,1H),4.68(t,J=13.6Hz,1H),4.50-4.44(m,1 H), 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 calculated value: 347.5; MS found value: 349.2 ([M+H] + ).

[0396] Synthesis Example 6. Preparation of 5-(Benzylbutylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 22)

[0397] According to the preparation method of Compound 21, the title compound (100 mg, 12.1%) was obtained as a yellow solid.

[0398] 1 H NMR (400MHz, CD 3 OD): 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),7.6 0-7.45(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 calculated value: 376.2; MS found value: 377.2([M+H] + ).

[0399] 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)

[0400] 3-Hydroxy-2-pyridin-2-yl-2,4,6,7-tetrahydroindazol-5-one (500mg, 2.18mmol, 1.0eq) was dissolved in 30mL of dichloromethane, and then 1-(2-methoxyphenyl)-N-methylmethaneamine (658mg, 4.36mmol, 2.0eq) and sodium triacetoxyborohydride (1.39g, 6.54mmol, 3.0eq) were added, and 4 drops of acetate were added. The reaction mixture was stirred at room temperature for 12 hours. Saturated aqueous sodium bicarbonate solution (50mL) was added to the reaction mixture, and then extracted with dichloromethane (50mL×2). After washing the organic layer with brine, it was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by sorting high performance liquid chromatography to obtain the title compound (200mg, 34.0%) as a yellow solid. Compounds 39 to 60, 64 to 68, 72 to 76, 78 to 81, 121 to 125, 146 to 153 and 157 to 159 were also prepared by the above method.

[0401] 1 H NMR (400MHz, CD 3 OD): 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,J 1 =12.8Hz,J 2 =19.2Hz,1H),4.20(dd,J 1 =12.8Hz,J 2 =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 calculated value: 364.2; MS found value: 365.3([M+H] + ).

[0402] Synthesis Example 8. Preparation of 5-(Benzylmethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 1)

[0403] According to the preparation method of compound 26, the title compound (200 mg, 27.4%) was obtained as a white solid.

[0404] 1 H NMR (400 MHz, DMSO-d 6): 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,J 1 =18.4Hz,J 2 =34.4 Hz, 2H), 2.80-2.70 (m, 1H), 2.65-2.55 (m, 1H), 2.52-2.50 (m, 1H), 2.48-2.30 (m, 1H), 2.31-2.25 (m, 1H), 2.16 (s, 3H), 2.05-1.85 (m, 1H), 1.71-1.65 (m, 1H). MS calculated value: 334.2; MS found value: 335.2 ([M+H] + ).

[0405] Synthesis Example 9. Preparation of 5-(Benzylcyclopropylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 2)

[0406] According to the preparation method of Compound 26, the title compound (94 mg, 11.9%) was obtained as a yellow solid.

[0407] 1 H NMR (400 MHz, DMSO-d 6 ):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 calculated value: 360.2; MS found value: 361.0([M+H] + ).

[0408] 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)

[0409] According to the preparation method of Compound 26, the title compound (103 mg, 16.4%) was obtained as a yellow solid.

[0410] 1 H NMR (400 MHz, DMSO-d 6):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 calculated value: 359.4; MS found value: 360.2([M+H] + ).

[0411] Synthesis Example 11. Preparation of 5-[(4-fluorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 4)

[0412] According to the preparation method of compound 26, the title compound (189 mg, 30.8%) was obtained as a white solid.

[0413] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =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 calculated value: 352.2; MS found value: 353.1 ([M+H] + ).

[0414] 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)

[0415] According to the preparation method of compound 26, the title compound (150 mg, 23.3%) was obtained as a brown solid.

[0416] 1 H NMR (400 MHz, DMSO-d 6): δ11.60-11.45(br,1H),8.50-8.36(m,2H),7.96-7.92(m,1H),7.46(q,J 1 =11.2Hz,J 2 =20.4Hz,2H),7.22-7.16(m,2H),7.10-7.05(m,1H),3.63(q,J 1 =9.6Hz,J 2 =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), 1.72-1.68 (m, 1H). MS calculated value: 370.2; MS found value: 371.1 ([M+H] + )

[0417] Synthesis Example 13. Preparation of 5-[(2-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 6)

[0418] According to the preparation method of compound 26, the title compound (270 mg, 42.0%) was obtained as a brown solid.

[0419] 1 H NMR (400 MHz, DMSO-d 6 ): 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 calculated value: 368.9; MS found value: 369.1 ([M+H] + )

[0420] Synthesis Example 14. Preparation of 5-[(3-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 7)

[0421] According to the preparation method of compound 26, the title compound (150 mg, 23.4%) was obtained as a white solid.

[0422] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =14.0Hz,J 2 =32.0 Hz, 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 calculated value: 368.1; MS found value: 369.1 ([M+H] + )

[0423] 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)

[0424] According to the preparation method of compound 26, the title compound (304 mg, 43.5%) was obtained as a white solid.

[0425] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =14.4Hz,J 2 =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 calculated value: 402.4; MS found value: 403.1 ([M+H] + )

[0426] 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)

[0427] According to the preparation method of Compound 26, the title compound (103 mg, 17.0%) was obtained as a brown solid.

[0428] 1 H NMR (400 MHz, DMSO-d 6 ):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 calculated value: 348.4; MS found value: 349.2([M+H] + )

[0429] 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)

[0430] According to the preparation method of compound 26, the title compound (292 mg, 57.5%) was obtained as a white solid.

[0431] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =12.0Hz,J 2 =30.4 Hz, 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 calculated value: 402.4; MS found value: 403.2 ([M+H] + )

[0432] 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)

[0433] According to the preparation method of compound 26, the title compound (117 mg, 16.7%) was obtained as a brown solid.

[0434] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =10.0Hz,J 2 =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), 1.72-1.68 (m, 1H). MS calculated value: 402.4; MS found value: 403.1 ([M+H] + )

[0435] Synthesis Example 19. Preparation of 5-[(4-methylsulfonylbenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 12)

[0436] According to the preparation method of Compound 26, the title compound (100 mg, 11.1%) was obtained as a white solid.

[0437] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =14.8Hz,J 2=31.2 Hz, 2H), 3.19 (s, 3H), 2.84-2.80 (m, 1H), 2.65-2.55 (m, 1H), 2.55-2.50 (m, 1H), 2.42-2.32 (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 calculated value: 412.1; MS found value: 413.1 ([M+H] + )

[0438] Synthesis Example 20. Preparation of 5-[(3-methylsulfonylbenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 23)

[0439] According to the preparation method of compound 26, the title compound (50 mg, 5.5%) was obtained as a white solid.

[0440] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =14.0Hz,J 2 =31.6 Hz, 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 calculated value: 412.5; MS found value: 413.1 ([M+H] + ).

[0441] 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)

[0442] According to the preparation method of compound 26, the title compound (50 mg, 5.5%) was obtained as a bright yellow solid.

[0443] 1 H NMR (400MHz, CD 3OD): δ8.51-8.50 (m, 1H), 8.35-8.20 (m, 2H), 7.65-7.47 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 4.63 (t, J = 13.2 Hz, 1H), 4.34 (t, J = 13.6 Hz, 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 calculated value: 348.2; MS found value: 349.2 ([M+H] + ).

[0444] Synthesis Example 22. Preparation of 5-[(3-methoxybenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 13)

[0445] According to the preparation method of compound 26, the title compound (105 mg, 13.2%) was obtained as a brown solid.

[0446] 1 H NMR (400 MHz, CDCl 3 )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 calculated value: 364.2; MS found value: 365.1([M+H] + )

[0447] Synthesis Example 23. Preparation of 5-piperidin-1-yl-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 14)

[0448] According to the preparation method of compound 26, the title compound (70 mg, 10.7%) was obtained as a brown solid.

[0449] 1 H NMR (400 MHz, DMSO-d 6):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 calculated value: 298.2; MS found value: 299.2([M+H] + )

[0450] Synthesis Example 24. Preparation of 5-morpholin-4-yl-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 15)

[0451] According to the preparation method of compound 26, the title compound (80 mg, 11.3%) was obtained as a brown solid.

[0452] 1 H NMR (400 MHz, DMSO-d 6 ):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 calculated value: 300.4; MS found value: 301.2([M+H] + )

[0453] 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)

[0454] According to the preparation method of compound 26, the title compound (195 mg, 28.5%) was obtained as a gray solid.

[0455] 1 H NMR (400 MHz, DMSO-d 6):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,1H),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 calculated value: 313.4; MS found value: 314.2([M+H] + )

[0456] 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)

[0457] According to the preparation method of Compound 26, the title compound (120 mg, 16.0%) was obtained as a white solid.

[0458] 1 H NMR (400 MHz, DMSO-d 6 ):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,4H),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 calculated value: 346.2; MS found value: 347.2([M+H] + )

[0459] 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)

[0460] According to the preparation method of Compound 26, the title compound (104 mg, 13.3%) was obtained as a yellow solid.

[0461] 1 H NMR (400MHz, CD 3OD): 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,1 H),8.08-8.00(m,1H),7.90(d,J=8.0Hz,1H),7.72(t,J=8.0Hz,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 calculated value: 359.1,MS found value: 360.1([M+H] + ).

[0462] Synthesis Example 28. Preparation of 5-[(4-chlorobenzyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 19)

[0463] According to the preparation method of compound 26, the title compound (144 mg, 22.5%) was obtained as a brown solid.

[0464] 1 H NMR (400 MHz, DMSO-d 6 ): 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,J 1 =13.6Hz,J 2 =30.4 Hz, 2H), 2.83-2.80 (m, 1H), 2.65-2.55 (m, 1H), 2.55-2.50 (m, 1H), 2.42-2.32 (m, 1H), 2.28-2.20 (m, 1H), 2.16 (s, 3H), 2.05-1.98 (m, 1H), 1.72-1.68 (m, 1H). MS calculated value: 368.1; MS found value: 369.1 ([M+H] + )

[0465] 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)

[0466] According to the preparation method of Compound 26, the title compound (95 mg, 12.3%) was obtained as a yellow solid.

[0467] 1 H NMR (400MHz, CD 3 OD): δ8.44 (d, J = 5.6 Hz, 1H), 8.25-8.15 (m, 1H), 8.15-8.10 (m, 1H), 7.50-7.45 (m, 2H), 7.39 (d, J = 8.4 Hz, 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 calculated value: 352.2; MS found value: 353.1 ([M+H] + ).

[0468] 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)

[0469] According to the preparation method of Compound 26, the title compound (80 mg, 10.7%) was obtained as a yellow oil.

[0470] 1 H NMR (400MHz, CD 3 OD): δ8.44 (d, J = 5.2 Hz, 1H), 8.30-8.20 (m, 1H), 8.15-8.05 (m, 1H), 7.55-7.40 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 4.50 (t, J = 12.8 Hz, 1H), 4.22 (t, J = 14.0 Hz, 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 calculated value: 364.2; MS found value: 365.2 ([M+H] + ).

[0471] 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)

[0472] According to the preparation method of compound 26, the title compound (300 mg, 39.5%) was obtained as a white solid.

[0473] 1 H NMR (400MHz, CD 3OD): 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,J 1 =13.6Hz,J 2 =23.6Hz,1H),4.21(dd,J 1 =13.2Hz,J 2 =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 calculated value: 348.2; MS found value: 349.2 ([M+H] + ).

[0474] 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)

[0475] According to the preparation method of Compound 26, the title compound (127 mg, 13.3%) was obtained as a white solid.

[0476] 1 H NMR (400MHz, CD 3 OD): δ8.42 (d, J = 5.2 Hz, 1H), 8.20-8.07 (m, 2H), 7.71 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 2.0 Hz, 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 calculated value: 402.1; MS found value: 403.1 ([M+H] + ).

[0477] Synthesis Example 33. Preparation of 5-[(3,4-dichlorophenyl)methylamino]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol hydrochloride (Compound 31)

[0478] According to the preparation method of compound 26, the title compound (144 mg, 16.4%) was obtained as a yellow solid.

[0479] 1H NMR (400MHz, CD 3 OD): δ8.54 (d, J = 5.2 Hz, 1H), 8.30-8.20 (m, 2H), 7.93 (d, J = 1.6 Hz, 1H), 7.75-7.60 (m, 2H), 7.58-7.50 (m, 1H), 4.75-4.60 (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 calculated value: 402.1; MS found value: 403.1 ([M+H] + ).

[0480] 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)

[0481] 1) Preparation of N-methyl-5,6,7,8-tetrahydroquinolin-8-amine

[0482] 6,7-Dihydroquinolin-8(5H)-one (2.0 g, 13.59 mmol) was dissolved in 40 mL of dichloroethane, and then methylamine (3.39 mL, 27.18 mmol, 2.0 eq) and 7 drops of acetate were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (5.7 g, 27.18 mmol, 2.0 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 (60 mL × 2), and the organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the title compound (1.98 g, 90.0%).

[0483] 1 H NMR (600 MHz, CDCl 3 ): δ8.33(d,J=4.1Hz,1H),7.25-7.32(m,1H),7.01(q,J=4.1Hz,1H),3.66(m,1H),2.73-2.78(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).

[0484] 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

[0485] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (0.03g, 0.13mmol) was dissolved in 8mL of dichloroethane, and then N-methyl-5,6,7,8-tetrahydroquinoline-8-amine (0.02g, 0.13mmol, 1.0eq) and 2 drops of acetate were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium cyanoborohydride (0.01g, 0.16mmol, 1.2eq) 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 (20mL×2), and the organic layer was then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (dichloromethane / methanol=5 / 1+0.1% triethylamine) to give the title compound (0.05g, 11.0%) as a brown solid.

[0486] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 375.2; MS found value: 376.1([M+H] + ).

[0487] 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)

[0488] 3-Hydroxy-2-(pyridin-2-yl)-2,4,6,7-tetrahydro-5H-indazol-5-one (2.5 g, 10.9 mmol) was dissolved in 100 mL of dichloromethane / dichloroethane (1 / 1), and then cyclopropyl(piperazine-1-yl)methanone hydrochloride (3.1 g, 16.4 mmol, 1.5 eq), diisopropylethylamine (2.8 mL, 16.4 mmol, 1.5 moles), acetate (1.0 mL, 16.4 mmol, 1.5 eq) were added. The reaction mixture was stirred at room temperature for 3 hours, and then sodium triacetoxyborohydride (4.6 g, 21.8 mmol, 2.0 eq) was added. The reaction mixture was stirred at room temperature for 48 hours, and then a 2M aqueous sodium hydroxide solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL×2), and then the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was preliminarily 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.

[0489] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 367.2; MS found value: 368.1([M+H] + ).

[0490] 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)

[0491] 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, 3.03 mmol, 1.0 eq) and acetate (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 a 2M aqueous sodium hydroxide solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL×2), and then 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.

[0492] 1 H NMR (600MHz, CD 3 OD): 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,2 H),2.63(s,3H),2.58–2.47(m,2H),2.34–2.25(m,1H),2.02–1.92(m,1H).

[0493] MS calculated value: 377.2; MS found value: 378.3 ([M+H] + ).

[0494] Synthesis Example 37. Preparation of 2-pyridin-2-yl-5-pyrrolidin-1-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 96)

[0495] 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 pyrrolidine (0.32 mL, 3.91 mmol, 3.0 eq) and acetate (0.16 mL, 2.61 mmol, 2.0 eq) were added. The reaction mixture was stirred at room temperature for 12 hours, and 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 a 10% aqueous sodium bicarbonate solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 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) to give the title compound (0.085 g, 23.0%) as a brown gel. Compounds 17, 160 and 161 were prepared by the same method as described above.

[0496] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 284.2; MS found value: 285.4([M+H] + ).

[0497] Synthesis Example 38. Preparation of 5-(4-methoxybenzylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 88)

[0498] According to the preparation method of compound 96, the title compound (0.30 g, 39.3%) was obtained as a dark grey solid.

[0499] 1 H NMR (600 MHz, CDCl 3): δ8.23(d,J=4.8Hz,1H),7.93–7.85(m,1H),7.83–7.77(m,1H),7.36(d,J=8.6Hz,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(ddd,J=12.3,5.1,2.6Hz,1H), 2.90 (dd, J = 14.7, 5.0 Hz, 1H), 2.78 (ddd, J = 16.7, 4.9, 3.9 Hz, 1H), 2.58 (ddd, J = 16.8, 11.1, 5.7 Hz, 1H), 2.50 (dd, J = 14.6, 9.6 Hz, 1H), 2.26–2.14 (m, 1H), 1.91–1.81 (m, 1H). MS calculated value: 350.2; MS found value: 351.3 ([M+H] + ).

[0500] Synthesis Example 39. Preparation of 5-phenylethylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 93)

[0501] According to the preparation method of compound 96, the title compound (0.30 g, 39.3%) was obtained as a dark grey solid.

[0502] 1 H NMR (600 MHz, DMSO-d 6 ):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 calculated value: 334.2; MS found value: 335.3([M+H] + ).

[0503] Synthesis Example 40. Preparation of 5-phenylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 92)

[0504] According to the preparation method of compound 96, the title compound (0.21 g, 53.2%) was obtained as a brown solid.

[0505] 1 H NMR (600 MHz, CDCl3 OD): 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, 4.5 Hz, 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 calculated value: 306.2; MS found value: 307.3 ([M+H] + ).

[0506] Synthesis Example 41. Preparation of 5-(3,4-difluorophenylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 32)

[0507] According to the preparation method of compound 96, the title compound (0.22 g, 74.2%) was obtained as a dark grey solid.

[0508] 1 H NMR (600 MHz, DMSO-d 6 ): 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=9.1H z, 1H), 5.80 (d, J = 8.1 Hz, 1H), 3.62-3.50 (m, 1H), 2.64-2.55 (m, 2H), 2.51 (dd, J = 15.1, 5.1 Hz, 1H), 2.06-2.00 (m, 1H), 2.00-1.93 (m, 1H), 1.64-1.53 ​​(m, 1H). MS calculated value: 342.1; MS found value: 343.2 ([M+H] + ).

[0509] Synthesis Example 42. Preparation of 5-(4-ethylpiperazine-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 91)

[0510] According to the preparation method of compound 96, the title compound (0.20 g, 47.0%) was obtained as a brown gel.

[0511] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 327.2; MS found value: 328.4([M+H] + ).

[0512] 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)

[0513] 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 × 2), followed by drying the organic layer with anhydrous sodium sulfate and concentrating 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. Compounds 127 and 128 were also prepared by the same method as above.

[0514] 1 H NMR (600 MHz, CDCl 3 OD): 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, 4.7 Hz, 1H), 2.68–2.57 (m, 3H), 2.39 (dd, J = 14.3, 10.8 Hz, 1H), 2.21–2.12 (m, 1H), 1.75–1.65 (m, 3H), 0.93 (t, J = 7.4 Hz, 3H). MS calculated value: 341.2; MS found value: 342.4 ([M+H] + ).

[0515] 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)

[0516] According to the preparation method of compound 100, the title compound (0.14 g, 33.1%) was obtained as a brown solid.

[0517] 1 H NMR (600MHz, CD 3 OD): δ8.45-8.20 (m, 2H), 7.87 (dd, J = 12.7, 5.3 Hz, 1H), 7.19 (dd, J = 7.1, 5.3 Hz, 1H), 3.55-3.35 (m, 1H), 3.09–2.53 (m, 10H), 2.40-2.25 (m, 1H), 2.25–2.07 (m 1H), 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 calculated value: 395.3; MS found value: 396.3 ([M+H] + ).

[0518] 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)

[0519] According to the preparation method of compound 100, the title compound (0.20 g, 47.1%) was obtained as a brown solid.

[0520] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 389.2; MS found value: 390.3([M+H] + ).

[0521] Synthesis Example 46. Preparation of 5-(4-phenethylpiperazine-1-yl)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 104)

[0522] According to the preparation method of compound 100, the title compound (0.18 g, 40.9%) was obtained as a brown solid.

[0523] 1 H NMR (600 MHz, CDCl 3 ): δ10.24(brs,1H),8.24–8.11(m,1H),8.04–7.81(m,1H),7.81–7.69(m,1H),7.27–7.2 2(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, 5.2 Hz, 1H). MS calculated value: 403.2; MS found value: 404.3 ([M+H] + ).

[0524] Synthesis Example 47. Preparation of 5-[4-(3-phenylpropyl)-piperazine-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 107)

[0525] According to the preparation method of compound 100, the title compound (0.11 g, 24.2%) was obtained as a brown solid.

[0526] 1 H NMR (600MHz, CD 3 OD): 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, 5.3,3.2 Hz,3H), 2.67–2.55 (m,4H), 2.31–2.23 (m,1H), 2.13 (ddtdd, J=8.1,5.4,2.7,1.3,0.6 Hz,1H), 1.96–1.88 (m,3H), 1.76–1.66 (m,1H). MS calculated value: 417.3; MS found value: 418.3 ([M+H] + ).

[0527] 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)

[0528] 5-(Methylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazole-3-ol (0.20g, 0.82mmol) was dissolved in 15mL dichloroethane, and 2-(dimethylamino)benzaldehyde (0.18g, 1.23mmol, 1.5eq) and 2 drops of acetate were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (0.35g, 1.63mmol, 2.0eq) was added. The reaction mixture was stirred at room temperature for 16 hours, and then a 2M aqueous sodium hydroxide solution was added. The reaction mixture was extracted with dichloromethane (20mL×2), and the organic layer was then 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 (0.09g, 29%) as a light brown solid. Compounds 69 and 77 were also prepared by the same method as above.

[0529] 1 H NMR (600MHz, CD 3 OD): 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=7.4 Hz,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 calculated value: 377.2; MS found value: 378.3([M+H] + ).

[0530] Synthesis Example 49. Preparation of 5-(methylquinolin-6-ylmethylamino)-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 63)

[0531] 5-Methylamino-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazole-3-ol (0.25 g, 1.02 mmol) was dissolved in 20 mL of dichloromethane / dichloroethane (1 / 1), and then quinoline-6-carboxaldehyde (0.24 g, 1.5 mmol, 1.5 eq) and acetate (0.06 mL, 1.0 mmol, 1 eq) were added. The reaction mixture was stirred at room temperature for 1 hour, and then sodium triacetoxyborohydride (0.09 g, 1.5 mmol, 1.5 eq) was added. The reaction mixture was stirred at room temperature for 12 hours, and then 10% aqueous sodium hydroxide solution was added to adjust the pH to about 8.0. The reaction mixture was extracted with dichloromethane (20 mL × 2), and then 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. Compound 61 was also prepared by the same method as above.

[0532] 1 H NMR (600 MHz, DMSO-d 6 ): 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, 2.7 Hz, 1H), 2.72–2.61 (m, 1H), 2.57–2.47 (m, 1H), 2.40 (tddd, J = 7.9, 6.7, 3.5, 2.1 Hz, 1H), 2.30–2.14 (m, 1H), 2.19 (s, 3H), 2.09–1.99 (m, 1H), 1.70 (qd, J = 12.0, 5.4 Hz, 1H). MS calculated value: 385.2; MS found value: 386.2 ([M+H] + ).

[0533] 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)

[0534] According to the preparation method of compound 63, the title compound (0.02 g, 6.1%) was obtained as a brown solid.

[0535] 1 H NMR (600 MHz, DMSO-d 6 ): δ11.45(brs,1H),9.21(s,1H),8.47–8.31(m,2H),8.05(d,J=8.2Hz,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,1H),7.10-7.20(m,1H),3.88( dd, J = 41.3, 14.7 Hz, 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 calculated value: 385.2; MS found value: 386.2 ([M+H] + ).

[0536] 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)

[0537] 5-(Methylamino)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazole-3-ol (0.13 g, 0.55 mmol) was dissolved in 6 mL of dichloromethane / dichloroethane (1 / 1), and then 5-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-2-carbaldehyde (0.20 g, 0.82 mmol, 1.5 eq) was added, and 3 drops of acetate were added. The reaction mixture was stirred at 45 ° C for 16 hours, and then sodium cyanoborohydride (0.07 g, 1.09 mmol, 2.0 eq) was added. The reaction mixture was stirred at 45 ° C for 24 hours, and then a 2M aqueous sodium hydroxide solution was added. The reaction mixture was extracted with dichloromethane (20 mL×2), and then the organic layer was dried over anhydrous sodium sulfate and concentrated 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 also prepared by the same method as above.

[0538] 1 H NMR (600MHz, CD 3OD): 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, 5.4 Hz, 1H). MS calculated value: 472.2; MS found value: 473.4 ([M+H] + ).

[0539] 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)

[0540] According to the preparation method of compound 37, the title compound (0.03 g, 12.7%) was obtained as a brown solid.

[0541] 1 H NMR (600MHz, CD 3 OD): δ8.40–8.32 (m, 2H), 8.27 (d, J=8.4 Hz, 1H), 7.87–7.79 (m, 1H), 7.16 (dd, J=7.2, 5.0 Hz, 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, 5.4 Hz, 1H). MS calculated value: 434.3; MS found value: 435.5 ([M+H] + ).

[0542] 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)

[0543] 1) Preparation of tert-butyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl)piperazine-1-carboxylate

[0544] 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 acetate (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 then stirred at room temperature for 3 hours. Saturated aqueous sodium bicarbonate solution (20 mL) was added to the reaction mixture to adjust the pH to about 7, and then extracted with dichloromethane (30 mL×3). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column (solvent: dichloromethane / methanol = 10 / 1) to obtain the title compound (1.59 g, 58.8%) as a yellow solid. Compound 109 was also prepared by the same method as above.

[0545] 1 H NMR (600 MHz, CDCl 3 )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,4H),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).

[0546] 2) Preparation of 5-(piperazin-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol dihydrochloride

[0547] Tert-butyl 4-(3-hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazole-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 isopropanol solution was added under a nitrogen stream. The reaction mixture was stirred at room temperature for 1 day and concentrated under reduced pressure. The residue was recrystallized from ethanol and ether to give the title compound (1.31 g, 87.8%) as a yellow solid.

[0548] 1 H NMR (600MHz, CD 3 OD)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=14.2,5.1Hz,1H), 3.01(ddd,J=17.4,5.4,2.3Hz,1H),2.89(ddd,J=17.4,11.6,5.7Hz,1H),2.78–2.70(m,1H),2.61–2.53(m,1H),2.13(qd,J=12.1,5.5Hz,1H).

[0549] 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

[0550] 2-Butenoic acid 2,5-dioxopyrrolidin-1-yl ester (0.12g, 0.65mmol), 5-(piperazine-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazole-3-ol dihydrochloride (0.24g, 0.65mmol, 1.0eq) were dissolved in 5mL acetonitrile, and N,N-diisopropylethylamine (0.6mL, 3.25mmol, 5.0eq) 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 (20mL×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 (0.25g, 92.6%) as a green solid.

[0551] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 365.2; MS found value: 367.2([M+H] + ).

[0552] 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)

[0553] 5-(Piperazine-1-yl)-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazole-3-ol dihydrochloride (0.038g, 0.10mmol) was dissolved in 3mL of dichloromethane, and triethylamine (0.04mL, 0.30mmol, 3.0eq) was added. The reaction mixture was stirred at 0°C for 10 minutes. Acryloyl chloride (0.01mL, 0.10mmol, 1.0eq) was added and stirred at 0°C for 30 minutes, and then neutralized with sodium bicarbonate aqueous solution. The reaction mixture was extracted with dichloromethane (10mL×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% ammonia water) to give the title compound (19mg, 53.7%) as a brown solid.

[0554] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 353.2; MS found value: 354.3([M+H] + ).

[0555] Synthesis Example 57b. Synthesis of Reaction Amide, Carbonate, Urea and Sulfonamide Derivatives 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 mixed solution of 5 mL of acetonitrile and 1 mL of water, and NaHCO was added. 3 Saturated solution (200uL). To synthesize each derivative, one of carboxyl chloride, chloroformate, isocyanate and sulfonyl chloride was added at room temperature. The reaction mixture solution was stirred at room temperature for 1 hour, and the reaction was confirmed to be complete by LC-MS, and then ethyl acetate 50mL was added and diluted, and the mixture was washed with brine and NaHCO 3The product was separated and purified by TLC with a yield in the range of 10 to 70%. In addition, data of synthetic examples prepared according to general synthetic methods and synthetic methods using specific materials are described. Compounds 110 to 114 were prepared by the same method as above.

[0556] 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)

[0557] 5-(Piperazine-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. For the reaction mixture, sodium bicarbonate aqueous solution was used to adjust the neutralization, 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 give the title compound (0.27 g, 65.8%) as a brown solid. Compound 99 was also prepared by the same method as above.

[0558] 1 H NMR (600 MHz, CDCl 3 ): δ8.25(d,J=5.0Hz,1H),7.83(dt,J=14.3,7.8Hz,2H),7.13–7.07(m,1H),6.84(dt,J=1 5.2,6.3Hz,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 calculated value: 410.2; MS found value: 411.3([M+H]+ ).

[0559] 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)

[0560] 5-(4-methylpiperazine-1-yl)-2-oxocyclohexane-1-methylformate (0.19 g, 0.75 mmol) was dissolved in 15 mL of ethanol, followed by the addition of 5 drops of acetate and 2-hydrazine-5-(trifluoromethyl)pyridine (0.13 g, 0.75 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for 1 hour, stirred at 100 ° C for 4 hours, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate / diethyl ether to give the title compound (0.092 g, 32%) as a light brown solid. Compounds 115 to 120, 132, 137 to 145, 154 to 156 were also prepared by the same method as above.

[0561] 1 H NMR (600MHz, CD 3 OD): δ8.69 (s, 1H), 8.57 (d, J = 8.5 Hz, 1H), 8.15 (dd, J = 8.9, 2.4 Hz, 1H), 3.55–2.86 (m, 8H), 2.84 (s, 3H), 2.76 (dd, J = 5.1, 3.3 Hz, 1H), 2.70–2.61 (m, 2H), 2.59–2.51 (m, 1H), 2.31 (dd, J = 14.5, 10.1 Hz, 1H), 2.16–2.09 (m, 1H), 1.80 (qd, J = 11.2, 5.5 Hz, 1H). MS calculated value: 381.2; MS found value: 382.3 ([M+H] + ).

[0562] 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)

[0563] According to the preparation method of compound 82, the title compound (0.11 g, 59.8%) was obtained as a light grey solid.

[0564] 1 H NMR (600MHz, D 2O): δ7.91 (d, J = 8.2 Hz, 1H), 7.80 (t, J = 7.9 Hz, 1H), 7.23 (d, J = 7.9 Hz, 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, 3.3 Hz, 1H), 1.93 (qd, J = 11.9, 5.6 Hz, 1H). MS calculated value: 347.1; MS found value: 348.2 ([M+H] + ).

[0565] Synthesis Example 57. Preparation of 5-(4-methyl-piperazine-1-yl)-2-(6-methyl-4-trifluoromethyl-pyridin-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 84)

[0566] According to the preparation method of compound 82, the title compound (0.12 g, 73.8%) was obtained as a grey solid.

[0567] 1 H NMR (600MHz, CD 3 OD): 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 (ddd, J=18.6, 10.1, 3.7 Hz, 1H), 2.84 (s, 3H), 2.91–2.77 (m, 1H), 2.74–2.67 (m, 1H), 2.30 (qd, J=12.0, 5.6 Hz, 1H). MS calculated value: 395.2; MS found value: 396.3 ([M+H] + ).

[0568] Synthesis Example 58. Preparation of 5-(4-methyl-piperazine-1-yl)-2-thieno[3,2-c]pyridin-4-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 85)

[0569] According to the preparation method of compound 82, the title compound (0.11 g, 43.0%) was obtained as a grey solid.

[0570] 1 H NMR (600MHz, CD 3OD): δ8.22 (d, J = 5.6 Hz, 1H), 8.03 (d, J = 5.3 Hz, 1H), 7.90 (d, J = 5.6 Hz, 1H), 7.74 (d, J = 5.7 Hz, 1H), 3.22–2.86 (m, 9H), 2.81 (ddd, J = 16.9, 5.0, 3.2 Hz, 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, 5.4 Hz, 1H). MS calculated value: 369.1; MS found value: 370.2 ([M+H] + ).

[0571] 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)

[0572] According to the preparation method of compound 82, the title compound (0.41 g, 86.3%) was obtained as a brown solid.

[0573] 1 H NMR (600MHz, CD 3 OD): δ8.34 (d, J = 4.6 Hz, 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, 10.7 Hz, 1H), 2.20–2.13 (m, 1H), 1.83–1.70 (m, 1H), 0.92–0.79 (m, 1H). MS calculated value: 331.2; MS found value: 332.3 ([M+H] + ).

[0574] Synthesis Example 60. Preparation of 2-pyridin-2-yl-5-(4-pyridin-2-ylmethyl-piperazine-1-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 87)

[0575] According to the preparation method of compound 82, the title compound (0.064 g, 23.6%) was obtained as a brown solid.

[0576] 1 H NMR (600MHz, CD 3OD): δ8.47 (d, J = 4.4 Hz, 1H), 8.36 (d, J = 4.6 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.87–7.77 (m, 2H), 7.52 (d, J = 7.8 Hz, 1H), 7.31 (dd, J = 7.3, 5.2 Hz, 1H), 7.16 (dd, J = 7.1, 5.1 Hz, 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 calculated value: 390.2; MS found value: 391.3 ([M+H] + ).

[0577] 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)

[0578] According to the preparation method of compound 82, the title compound (0.064 g, 23.6%) was obtained as a brown solid.

[0579] 1 H NMR (600 MHz, DMSO-d 6 ): 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=8.6,1.6H z, 1H), 7.47 (dd, J=8.3,4.1 Hz, 1H), 7.17–7.11 (m, 1H), 3.62 (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 calculated value: 440.2; MS found value: 441.4 ([M+H] + ).

[0580] 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)

[0581] According to the preparation method of compound 82, the title compound (0.048 g, 39.8%) was obtained as a beige solid.

[0582] 1 H NMR (600 MHz, DMSO-d 6 ):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,10H),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 calculated value:382.1(Free Base:346.2);MS found value:347.3([M+H] + ).

[0583] Synthesis Example 63. Preparation of 5-(4-methyl-piperazine-1-yl)-2-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 95)

[0584] According to the preparation method of compound 82, the title compound (0.072 g, 68.8%) was obtained as a brown solid.

[0585] 1 H NMR (600MHz, CD 3 OD): δ7.97 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 7.8 Hz, 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 calculated value: 380.2; MS found value: 381.2 ([M+H] + ).

[0586] 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)

[0587] According to the preparation method of compound 82, the title compound (0.005 g, 6%) was obtained as a brown solid.

[0588] 1 H NMR (600MHz, CD 3OD): δ7.65 (d, J = 8.9 Hz, 2H), 7.50 (d, J = 8.9 Hz, 2H), 2.89-2.46 (m, 11 Hz), 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, 5.4 Hz, 1H). MS calculated value: 390.1; MS found value: 391.2 ([M+H] + ).

[0589] 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)

[0590] According to the preparation method of compound 82, the title compound (0.10 g, 55.8%) was obtained as a brown solid.

[0591] 1 H NMR (600MHz, CD 3 OD): δ8.53 (dd, J = 9.1, 4.8 Hz, 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, 5.4 Hz, 1H). MS calculated value: 330.2; MS found value: 331.4 ([M+H] + ).

[0592] Synthesis Example 66. Preparation of 4-[3-hydroxy-(4-methylpiperazine-1-yl)-4,5,6,7-tetrahydroindazol-2-yl]-benzonitrile (Compound 103)

[0593] According to the preparation method of compound 82, the title compound (0.035 g, 17.6%) was obtained as a brown solid.

[0594] 1 H NMR (600MHz, CD 3OD): δ8.04 (d, J = 8.9 Hz, 2H), 7.68 (d, J = 8.9 Hz, 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, 5.3 Hz, 1H). MS calculated value: 337.2; MS found value: 338.2 ([M+H] + ).

[0595] 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)

[0596] According to the preparation method of compound 82, the title compound (0.10 g, 40.5%) was obtained as a brown solid.

[0597] 1 H NMR (600MHz, CD 3 OD): δ8.71 (d, J = 4.9 Hz, 2H), 7.23 (t, J = 4.9 Hz, 1H), 2.79–2.68 (m, 6H), 2.67–2.52 (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, 5.3 Hz, 1H). MS calculated value: 314.2; MS found value: 315.3 ([M+H] + ).

[0598] 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)

[0599] According to the preparation method of compound 96, the title compound (0.14 g, 32.9%) was obtained as a beige solid.

[0600] 1 H NMR (600 MHz, CDCl 3): 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=5.0H z, 4H), 2.94–2.73 (m, 6H), 2.70–2.59 (m, 2H), 2.32 (dd, J=13.9, 10.9 Hz, 1H), 2.27-2.22 (m, 1H), 2.22 (s, 3H), 1.75 (qd, J=11.8, 5.4 Hz, 1H). MS calculated value: 389.2; MS found value: 390.3 ([M+H] + ).

[0601] Synthesis Example 69. Preparation of 5-[4-(4-methoxyphenyl)-piperazine-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 129)

[0602] According to the preparation method of compound 96, the title compound (0.10 g, 23.7%) was obtained as a brown solid.

[0603] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 405.2; MS found value: 406.3([M+H] + ).

[0604] 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)

[0605] According to the preparation method of compound 96, the title compound (0.14 g, 30.1%) was obtained as a grey solid.

[0606] 1H NMR (600 MHz, CDCl 3 ):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 calculated value: 417.2; MS found value: 418.3([M+H] + ).

[0607] Synthesis Example 71. Preparation of 5-[4-(4-methylsulfonylphenyl)-piperazine-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 131)

[0608] According to the preparation method of compound 96, the title compound (0.09 g, 18.1%) was obtained as a light grey solid.

[0609] 1 H NMR (600 MHz, CDCl 3 ): δ8.25–8.20(m,1H),7.86–7.79(m,2H),7.76(d,J=9.0Hz,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, 0.7 Hz, 1H). MS calculated value: 453.2; MS found value: 454.2 ([M+H] + ).

[0610] Synthesis Example 72. Preparation of 5-[4-(1-benzylpiperidin-4-ylmethyl)-piperazine-1-yl]-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 135)

[0611] 5-(Piperazine-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-carboxaldehyde (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. After sodium triacetoxyborohydride (0.79 g, 3.76 mmol, 2.0 eq) was added at 0°C, the reaction mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate aqueous solution (20 mL) was added to the reaction mixture to adjust the pH to about 7, and then extracted with dichloromethane (30 mL×3). The organic layer was dried over anhydrous sodium sulfate and then 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 also prepared by the same method as above.

[0612] 1 H NMR (600 MHz, CDCl 3 ):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 calculated value: 486.3; MS found value: 487.4([M+H] + ).

[0613] Synthesis Example 73. Preparation of 5-{4-[2-(2-hydroxyethoxy)-ethyl]-piperazine-1-yl}-2-pyridin-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol (Compound 17)

[0614] According to the preparation method of compound 96, the title compound (0.15 g, 29.5%) was obtained as a yellow solid.

[0615] 1 H NMR (600 MHz, CDCl 3):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 calculated value: 387.2; MS found value: 388.3([M+H] + ).

[0616] The structures, MS results and IUPAC names of the prepared Synthesis Example compounds 1-161 are shown in Table 1 below.

[0617] Table 1

[0618]

[0619]

[0620]

[0621]

[0622]

[0623]

[0624]

[0625]

[0626]

[0627]

[0628]

[0629]

[0630]

[0631]

[0632]

[0633]

[0634]

[0635]

[0636]

[0637]

[0638] <Example 1> Analysis of changes in ROS generation induced by PMA treatment in HL-60 cells differentiated into neutrophils by DMSO treatment

[0639] In order to confirm the effect of the synthetic example compounds on ROS generation of fibroblasts and specific stromal cells, HL-60 cells differentiated into neutrophils by DMSO treatment, NHLF (normal human lung fibroblasts (Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cells, ATCC) and KEL-FIB (keloid fibroblasts (Keloid fibroblasts, ATCC)) were stimulated with PMA (phorbol 12-myristic acid 13-acetate), TGF-β1, palmitate or high concentration of glucose to induce ROS generation, and the inhibitory effect of the synthetic example compounds on ROS generation was observed under these conditions.

[0640] HL-60 cells (human leukemia cells, ATCC) were suspended in a medium containing 1.25% DMSO (RPMI + 10% FBS) and incubated in 5% CO 2 , 37°C for 6 days to induce differentiation into neutrophils. HL-60 cells differentiated into neutrophils were cultured at 2×10 4 The concentration of cells / well was equally divided in a 96-well plate, and the synthetic example compound was treated with cells at a concentration of 0.5 mM for 30 minutes. Then, 200 mM PMA was treated in each well containing cells and drugs to induce ROS generation, and this ROS generation was measured by observing the luminescence level of each well using 100 μM L-012.

[0641] NHLF (normal human lung fibroblasts, Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cells, ATCC), and KEL-FIB (keloid fibroblasts, ATCC) cells were suspended in a medium containing 10% FBS, aliquoted in 96-well plates, and then incubated in 5% CO 2 , 37°C for 24 hours. After pretreatment with the synthetic example compound at concentrations of 10, 20, 30, 40, 60, and 80 μM for 30 minutes to 1 hour, each well containing cells and drugs was subjected to ROS stimulation. After an additional 48 hours of culture, the level of ROS generation was confirmed using L-012 or DCF-DA.

[0642] The experimental results showed that the synthesis example compound inhibited ROS generation by ROS stimulation in all NHLF, LX-2, ARPE19, and KEL-FIB cells. The results in Table 2 show that the generation of ROS induced by PMA was inhibited when the synthesis example compound (0.5 μm) was treated with HL-60 cells induced to be neutrophils. Figure 1 The results show that when LX-2 and NHLF cells were treated with Synthesis Example Compounds 1 and 17, the generation of ROS induced by PMA was completely inhibited.

[0643] Therefore, it was confirmed that when differentiated HL-60 cells or various fibroblasts or specific stromal cells that induce ROS generation were treated with the Synthesis Example compounds, ROS generation was effectively suppressed.

[0644] Table 2 [Inhibitory effect on ROS generation in differentiated HL-60 cells]

[0645]

[0646]

[0647]

[0648] <*:<30%,**:30<<50%,***:50<<70%,****:>70%>

[0649] <Example 2> Analysis of changes in αSMA expression induced by TGF-β1

[0650] It has been reported that when fibroblasts differentiate into myofibroblasts, cancer-associated fibroblasts (CAFs) are formed or cause fibrosis of various tissues.

[0651] In order to confirm whether the synthetic example compounds of the present invention affect the differentiation of fibroblasts into myofibroblasts, the synthetic example compounds were observed to inhibit the increased expression of αSMA (a biomarker for confirming differentiation into myofibroblasts) induced by TGF-β1 in HFF-1 (human foreskin fibroblasts, ATCC), NHLF (normal human lung fibroblasts, Lonza), LX-2 (human hepatic stellate cells, Sigma), ARPE19 (human retinal pigment epithelial cells, ATCC) and KEL-FIB (keloid fibroblasts, ATCC) cells.

[0652] Each cell was suspended in DMEM medium containing 10% FBS and cultured at 1 × 10 4 -1.5×10 5The concentration of cells / well was aliquoted on a 4-well chamber slide (Nunc), and the synthetic example compound and TGF-β1 (TGF-β1 and TGF-β have the same meaning) were treated to prepare cells for confirming the expression of αSMA. The expression of αSMA in the prepared cells was confirmed by immunocytochemistry as shown below. For the cells, after fixing with 4% paraformaldehyde for 10 minutes and permeabilizing the cells with 0.1% Triton x-100, the process of treating with a primary antibody against αSMA (anti-αSMA antibody, 1:200, at 4°C for 16 hours) and a secondary antibody (antibody conjugated to Alexa-594, 1:800, at room temperature for 1 hour) was carried out in sequence, and then the expression level of αSMA was observed by fluorescence microscopy.

[0653] Figure 3 observed the effect of treating HFF cells with 10, 20 and 40 μM of each compound of the synthesis example after inducing αSMA expression by treating HFF cells with TGF-β1 (10 ng / mL). Compound 1, Compound 23, Compound 12, Compound 5, Compound 14 and Compound 33 in the synthesis example all showed the effect of inhibiting αSMA expression by 35% to 70%, although the degree was different.

[0654] In addition, in LX-2, NHLF, ARPE19, and KEL-FIB cells, it was confirmed that the increase in αSMA expression induced by TGF-β1 (10 ng / mL) was significantly inhibited by treatment with 10 μM of Synthetic Example Compound 1, as shown in FIG. Figure 4 Confirmed in.

[0655] <Example 3> Analysis of TGF-β1-induced gel contraction changes

[0656] In order to confirm the effect of the synthetic example compound on the differentiation of fibroblasts into myofibroblasts, the inhibitory effect of the synthetic example compound on the gel contraction phenomenon induced by the interaction between human foreskin fibroblasts (HFF-1, ATCC) and collagen was observed.

[0657] Will be 3×10 6 The mixed solution of HFF-1 cells and collagen (bovine type I collagen) prepared at a concentration of 1 cell / mL was aliquoted into 24-well plates and then incubated in 5% CO 2 , 37°C for 1 hour to induce gel polymerization. Then, after the gel attached to the plate was suspended from the plate using a spoon, a medium containing TGF-β1 and a synthetic example compound was added to each well. After 72 hours of culture, the size of the gel was measured by treating with 10, 20, 30, 40, 60, and 80 μM of the synthetic example compound to confirm the degree of gel shrinkage by drug treatment.

[0658] As a result of the experiment, Figure 7As demonstrated in the results, it was observed that treatment with Synthetic Example Compound 1, Compound 5, Compound 12, Compound 13, Compound 14, Compound 16, Compound 23, Compound 33, Compound 38, Compound 63 and Compound 62 effectively inhibited the gel contraction induced by TGF-β1 (10 ng / mL).

[0659] <Example 4> Analysis of changes in ROS generation in dopaminergic neurons

[0660] In order to confirm the effect of the synthetic example compounds on ROS generation in dopaminergic neurons, ROS generation was induced by stimulating N27 (rat dopaminergic neurons, Sigma) cells with α-synuclein preformed fibrils (PFFs), and under this condition, the inhibitory effect of the synthetic example compounds on ROS generation was observed.

[0661] N27 cells were cultured in RPMI medium containing 10% FBS and 1 μM angiotensin II. The prepared cells were plated on a 6-well plate at 4 × 10 3 The cells were treated with ROS generation stimulants, PFFs (preformed fibrils) and Synthetic Example compounds. After 24 hours of Synthetic Example compound treatment, the fluorescence of each well was measured using CellROX Deep Red reagent to confirm the extent of ROS generation.

[0662] As the experimental results, Figure 2 As shown, it was confirmed that the treatment with 0.001 μM of synthetic example compounds 12, 16, 32 and 82 could effectively inhibit the generation of ROS induced by PFF.

[0663] <Example 5> Analysis of changes in LPS-induced IL-1β expression

[0664] In order to confirm the effect of the compounds of Synthesis Examples of the present invention on the inflammatory response in human-derived fibroblasts, it was observed whether the IL-1β expression increased by LPS treatment was inhibited by the compounds of Synthesis Examples in fibroblasts derived from various tissues.

[0665] 2 × 10 5 After culturing for 24 hours, the cells were further cultured in serum-free medium for 16 hours, and then the synthetic compound 1 was pretreated for 20 minutes according to each condition, and the inflammatory response was induced with LPS (1 μg / mL) for 6 hours. The expression of IL-1β was confirmed by RT-PCR. Total RNA was isolated from the cells using the RNeasy mini kit (Qiagen), and for the isolated RNA 2ug, PrimeScript TM II First-Strand cDNA Synthesis Kit (TaKaRa) was used to synthesize cDNA, and then PCR PreMix (Bioneer) was used to amplify the gene by PCR. The nucleotide sequences of the target primers are as follows. IL-1β (forward: 5'-CCCACAGACCTTCCAGGAGAGATG-3' (SEQ ID NO: 1), reverse: 5'-GGCAGTTCAGTGATCGTACAGG-3'); GAPDH (forward: 5'-GTGGGCTGGCTCAGAAAAAGG-3' (SEQ ID NO: 3), reverse: 5'-GGTGGTCCAGGGGTCTTACT-3' (SEQ ID NO: 4)); β-actin (forward: 5'-CCACCATTGGCAATGAGCGGTTC-3' (SEQ ID NO: 5), reverse: 5'-AGGTCTTTGCGGATGTCCACGT-3' (SEQ ID NO: 6)). The PCR product was confirmed by electrophoresis in 1.5% agarose gel.

[0666] As the experimental results, Figure 8 As demonstrated in FIG. 1 , it was observed that LPS-induced IL-1β was effectively inhibited in a concentration-dependent manner by treatment with 10 μM of Synthetic Example Compound 1.

[0667] <Example 6> Analysis of changes in IL-6 and IL8 expression in cancer-associated fibroblasts

[0668] In order to confirm the effect of the compounds of Synthesis Examples of the present invention on the inflammatory response in cancer-associated fibroblasts, it was observed whether the expression of IL6 and IL8 was inhibited by the compounds of Synthesis Examples in pancreatic cancer-associated fibroblasts (P.CAF).

[0669] 1.5 × 10 5 The cells were then cultured in P.CAF complete medium for 48 h and then treated with 10, 20, 30, 40, 60, and 80 μM of the synthetic example compounds for 48 h according to each condition, and then the expression of IL-6 and IL-8 was confirmed by ELISA using a Quantkine ELISA kit (R&D systems), as shown below.

[0670] 100 μl of culture fluid treated with the compound of the synthetic example for 48 hours was added to a microwell strip including 100 μl of the assay diluent for analysis and placed at room temperature for 2 hours, then the contents were removed and then washed 4 times with 400 μl of washing buffer. 200 μl of human IL-6 or IL-8 conjugate was added and placed at room temperature for 2 hours, then the contents were removed and then washed 4 times with 400 μl of washing buffer. 200 μl of substrate solution was added and placed at room temperature for 20 minutes, then placed at room temperature for 20 minutes, 50 μl of stop solution was added, and the absorbance at a wavelength of 450 nm was measured within 30 minutes to confirm the expression level of IL-6 and IL-8.

[0671] As the experimental results, Figure 5 and 6 As confirmed, it was observed that the treatment with Compound 1, Compound 5, Compound 12 to Compound 16, Compound 23, Compound 33, Compound 38, Compound 63 and Compound 62 of Synthesis Example could effectively inhibit IL-6 and IL-8 expressed in P.CAF.

[0672] <Example 7> Confirmation of brain injury treatment effect

[0673] In order to test the effect of the synthesized example compounds in preventing or treating brain diseases or disorders, they were evaluated using the α-synuclein preformed fibril (PFF) injection Parkinson's disease mouse model.

[0674] C57Bl / 6 mice were used, and all mice were maintained under standard conditions. The experiment was conducted by dividing the experimental animals into a normal control group (negative control) that was orally administered with distilled water, an α-synuclein preformed fibril (PFF) injected with Parkinson's disease induction group (vehicle control), and an experimental group (25 mg / kg of Synthesis Example Compound 16 was orally administered daily to the α-synuclein preformed fibril (PFF) injected with Parkinson's disease induction group), with 8 animals in each group. The normal control group was given physiological saline, and the Synthesis Example compound was orally administered once a day for 7 weeks, and then behavioral change experiments and histopathological experiments were performed.

[0675] Behavioral changes were analyzed by rotarod test, pole test and hindlimb clasping, and the average of three tests for each animal was measured.

[0676] After the experiment was completed, the animals were anesthetized to extract the brain tissue of each animal, and the tissue was fixed in 4% buffered neutral formalin solution (10% buffered neutral formalin). After the fixed tissue was cut to a certain thickness, it was embedded in paraffin by a conventional tissue processing process to prepare 4-5 μm tissue sections. Then, in order to confirm whether the pathological index of Parkinson's disease was improved according to the protein aggregation level in the striatum, it was first labeled with phosphorylated serine 129 α-synuclein, and then thioflavin T staining was performed to observe the histopathological results.

[0677] As a result of the experiment, as a result of analyzing the behavioral changes (such as climbing time, rotarod test, hind limb clenching, etc.) of the group administered with Synthesis Example Compound 16, it was observed that Parkinson's-like behavioral symptoms improved by 50% or more, and the aggregation and accumulation of a-synuclein, an important pathological indicator of Parkinson's disease, improved by 50% or more.

[0678] In conclusion, it was confirmed that the compounds of the synthesis examples of the present invention effectively improved Parkinson's disease.

Claims

1. A compound of the following chemical formula I, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof: In the formula, A is a substituted or unsubstituted 5- to 20-membered heteroaryl group or a substituted or unsubstituted C 5 -C 20 aryl; and in ， 5- to 20-membered heteroaryl or C 5 -C 20 The aryl group may be unsubstituted or may be substituted by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 20-membered heteroaryl and substituted or unsubstituted 5- to 20-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium or C 1 -C 10 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 5 -C 10 Aromatic rings; and R is hydrogen, deuterium, cyano, halogen, nitro, haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 20-membered heteroaryl, or -C(=O)R 2 , where R 2 It is C 3 -C 8 Cycloalkyl, C 1 -C 10 Alkyl, C 2 -C 10 Alkenyl or C 6 -C 10 aryl; and B is -NKM or substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and K is hydrogen, deuterium, cyano, halogen, nitro, haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroarylC 1 -C 10 alkyl, M is cyano, halogen, nitro, haloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 20-membered heteroarylC 1 -C 10 alkyl, Among them, C 1 -C 10 The alkyl group is unsubstituted or is selected from deuterium, halogen, hydroxyl, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Haloalkyl, substituted or unsubstituted C 1 -C 10 Hydroxyalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, C 1 -C 10 Alkoxy, C 1 -C 10 Alkylsulfonyl, C 5 -C 20 Arylsulfonyl, C 5 -C 20 Aryloxy, substituted or unsubstituted C 5 -C 20 substituted with 1, 2, 3 or 4 substituents selected from the group consisting of aryl, substituted or unsubstituted 5- to 20-membered heteroaryl and substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and C 3 -C 8 The cycloalkyl group may be unsubstituted or selected from deuterium, halogen, cyano, nitro, carboxyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 Aryl or 5- to 20-membered heteroaryl, C 1 -C 10 Alkoxy and C 1 -C 10 substituted with 1, 2, 3 or 4 substituents selected from the group consisting of haloalkyl; and 5- to 20-membered heteroaryl, 5- to 20-membered heterocycloalkyl or C 5 -C 20 The aryl group may be unsubstituted or selected from deuterium, halogen, cyano, nitro, -C(=O)R', -C(=O)OR', -NH-C(=O)R", substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Haloalkyl, substituted or unsubstituted C 1 -C 10 Hydroxyalkyl, substituted or unsubstituted C 1 -C 10 Alkylsulfonyl, substituted or unsubstituted C 5 -C 20 Arylsulfonyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl C 1 -C 10 Aryl, substituted or unsubstituted C 5 -C 20 Aryl, substituted or unsubstituted C 5 -C 20 Aryl C 1 -C 10 alkyl, substituted or unsubstituted 5- to 12-membered heterocycloalkyl, substituted or unsubstituted C 1 -C 10 Alkyl C 3 -C 8 Cycloalkyl and substituted or unsubstituted C 1 -C 10 Alkyl is substituted with 1, 2, 3 or 4 substituents selected from the group consisting of 5-membered to 20-membered heterocycloalkyl; and wherein R' and R" are each independently hydrogen, deuterium, substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 6 Alkyl, substituted or unsubstituted C 2 -C 6 Alkenyl, substituted or unsubstituted C 2 -C 6 Alkynyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 6 -C 10 Aryl or substituted or unsubstituted C 6 -C 10 Aryl C 1 -C 6 Alkyl, wherein the C 2 -C 6 Alkenyl or C 2 -C 6 The alkynyl group may be unsubstituted or may be substituted with a single C 1 -C 6 Alkylamine or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamine; and The substituted amino group is C 1 -C 10 Alkyl, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 1 or 2 substitutions in the alkyl group; and The heteroatom of the heterocycloalkyl or heteroaromatic ring is one or more selected from N, S and O.

2. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer or a pharmaceutically acceptable salt thereof, wherein A is an unsubstituted or substituted 5- to 12-membered heteroaryl or C 6 -C 10 Aryl, in, 5- to 12-membered heteroaryl or C 6 -C 10 The aryl group may be selected from cyano, halogen, C 1 -C 6 Haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 6 Alkyl, C 1 -C- 6 Alkoxy, C 3 -C 6 Cycloalkyl, amino, C 6 -C 10 aryl, 5- to 12-membered heteroaryl and 5- to 12-membered heterocycloalkyl, wherein R 1 is hydrogen, deuterium or C 1 -C 6 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 7-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 9 Aromatic ring.

3. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer or a pharmaceutically acceptable salt thereof, Where R is hydrogen, deuterium, cyano, halogen, nitro, unsubstituted or replaced by C 3 -C 6 Cycloalkyl substituted C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 3 -C 6 Cycloalkyl, C 6 -C 10 Aryl, 5- to 12-membered heteroaryl, -C(=O)R 2 , in, R 2 It is C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 6 -C 10 Aryl.

4. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, wherein B is -NKM or a 5- to 12-membered heteroaryl or a 5- to 12-membered heterocycloalkyl, in, The 5- to 12-membered heteroaryl or 5- to 12-membered heterocycloalkyl is unsubstituted or substituted by deuterium, halogen, cyano, nitro, -NR 3 R 4 , C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, -C(=O)R 5 、-SO 2 -R 6 1, 2, 3 or 4 substitutions in Among them, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 The aryl group may be unsubstituted or substituted with hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 1, 2, 3 or 4 substituted, unsubstituted or C 1 -C 6 Alkyl, C 6 -C 10 Aryl C 1 -C 6 Alkyl or C 1 -C 6 alkylcarbonyl-substituted 4- to 12-membered heterocycloalkyl, and R 3 and R 4 are independently hydrogen, deuterium, -C(=O)-R a , C 1 -C 6 Alkyl or C 6 -C 10 Aryl, and C 1 -C 6 Alkyl or C 6 -C 10 Aryl is unsubstituted or substituted by halogen, hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 1, 2, 3 or 4 substitutions in the aryloxy group, wherein Ra is hydrogen, deuterium, C 1 -C 6 Alkyl or C 1 -C 6 haloalkyl; and R 5 Yes-OR b 、-NR c R d , C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 8 Cycloalkyl, wherein C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 2 -C 6 Alkynyl groups may be unsubstituted or substituted with a single C 1 -C 6 Alkylamine or di-C 1 -C 6 1, 2, 3 or 4 substitutions in an alkylamine, wherein R b , R c and R d Each independently is hydrogen, deuterium, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 Alkyl, and R 6 It is C 1 -C 6 Alkyl, unsubstituted or substituted with 1, 2, 3 or 4 C 1 -C 6 Alkyl substituted C 6 -C 10 Aryl, and K is hydrogen, deuterium, cyano, halogen, nitro, C 1 -C 6 Haloalkyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", C 3 -C 8 Cycloalkyl, C 6 -C 10 Aryl, C 6 -C 10 Aryl C 1 -C 6 alkyl, 5- to 12-membered heteroaryl, 5- to 12-membered heteroarylC 1 -C 6 Alkyl, where C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, C 3 -C 8 The cycloalkyl or 5- to 12-membered heteroaryl may be substituted with cyano, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Alkylsulfonyl, C 6 -C 10 Arylsulfonyl, -NR 7 R 8 、-C(=O)R 9 , 5- to 12-membered heterocyclic group, hydroxyl, nitro, C 6 -C 10 1, 2, 3 or 4 substitutions in the aryl group, wherein the 5- to 12-membered heterocyclic group or the C 6 -C 10 The aryl group may be unsubstituted or substituted with C 1 -C 6 Alkyl substituted, M is cyano, halogen, nitro, C 1 -C 6 Haloalkyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, -C(=O)R', -C(=O)OR', -SO 2 -R", C 3 -C 8 Cycloalkyl, C 6 -C 10 Aryl, C 6 -C 10 Aryl C 1 -C 6 alkyl, 5- to 12-membered heteroaryl, 5- to 12-membered heteroarylC 1 -C 6 Alkyl, where C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, C 3 -C 8 The cycloalkyl or 5- to 12-membered heteroaryl may be substituted with cyano, halogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Alkoxy, C 1 -C 6 Alkylsulfonyl, C 6 -C 10 Arylsulfonyl, -NR 7 R 8 、-C(=O)R 9 , 5- to 12-membered heterocyclic group, hydroxyl, nitro, C 6 -C 10 1, 2, 3 or 4 substitutions in the aryl group, wherein the 5- to 12-membered heterocyclic group or the C 6 -C 10 The aryl group may be unsubstituted or substituted with C 1 -C 6 Alkyl substitution, wherein R' and R" are each independently hydrogen, deuterium, substituted or unsubstituted amino, substituted or unsubstituted C 1 -C 6 Alkyl, substituted or unsubstituted C 2 -C 6 Alkenyl, substituted or unsubstituted C 2 -C 6 Alkynyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted C 6 -C 10 Aryl or substituted or unsubstituted C 6 -C 10 Aryl or C 1 -C 6 Alkyl, wherein the C 2 -C 6 Alkenyl or C 2 -C 6 Alkynyl is unsubstituted or substituted with a single C 1 -C 6 Alkylamino or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamino group, The substituted amino group can be C 1 -C 10 Alkyl, C 6 -C 10 Aryl C 1 -C 6 1 or 2 substitutions in the alkyl group; R 7 and R 8 are independently hydrogen, deuterium, C 1 -C 6 Alkyl, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 alkyl, and R 9 Yes-OR e 、-NR e R f , unsubstituted or substituted with 1, 2, 3 or 4 kinds of -NR e R f -substituted C 2 -C 6 Alkenyl or C 6 -C 10 Aryl, wherein R e and R f Each independently is hydrogen, deuterium, C 1 -C 6 Alkyl, C 6 -C 10 Aryl or C 1 -C 6 alkyl.

5. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, The compound of Chemical Formula I is the compound of the following Chemical Formula I-1: [Chemical Formula I-1] In the formula, K, M and R are as defined in Formula I; and D is for CR 10 , N, O or S, or E is CR 11 , N, O or S, or F is CR 12 , N, O or S, or G is CR 13 , N, O or S, or J is CR 14 , N, O or S, but N, O and S are one or more; and R 10 To R 14 are the same or different and may be independently replaced by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 12-membered heteroaryl and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium, C 1 -C 10 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 10 Aromatic ring.

6. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, The compound of Chemical Formula I is the compound of the following Chemical Formula I-2: [Chemical Formula I-2] In the formula, R is as defined in Formula I; and D is for CR 10 , N, O or S, or E is CR 11 , N, O or S, or F is CR 12 , N, O or S, or G is CR 13 , N, O or S, or J is CR 14 , N, O or S, but N, O and S are one or more; and R 10 To R 14 are the same or different and may be independently replaced by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 12-membered heteroaryl and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium, C 1 -C 10 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, in, The aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S or a C 6 -C 10 Aromatic rings, and n is an integer of 0, 1 or 2; and L is CH 2 , NH or O; and It may be unsubstituted or substituted with deuterium, halogen, cyano, nitro, -NR 3 R 4 , C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, -C(=O)R 5 、-SO 2 -R 6 1, 2, 3 or 4 substitutions, wherein when the substituents are 2 or more, two or more adjacent groups may be combined with each other to form a substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and Among them, the C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 The aryl group may be unsubstituted or may be substituted by hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryloxy, unsubstituted or substituted with C 1 -C 6 Alkyl, C 6 -C 10 Aryl C 1 -C 6 Alkyl or C 1 -C 6 1, 2, 3 or 4 substitutions in 4- to 12-membered heterocycloalkyl substituted with alkylcarbonyl, and R 3 and R 4 are independently hydrogen, deuterium, -C(=O)-R a , C 1 -C 6 Alkyl or C 6 -C 10 Aryl, and C 1 -C 6 Alkyl or C 6 -C 10 The aryl group may be unsubstituted or may be substituted by halogen, hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 1, 2, 3 or 4 substitutions in the aryloxy group, wherein R a For hydrogen, deuterium, C 1 -C 6 Alkyl or C 1 -C 6 haloalkyl; and R 5 Yes-OR b 、-NR c R d , C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 8 Cycloalkyl, wherein the C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 2 -C 6 The alkynyl group may be unsubstituted or may be substituted with a single C 1 -C 6 Alkylamine or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamine, and R b , R c and R d are independently hydrogen, deuterium, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 Alkyl, and R 6 It is C 1 -C 6 Alkyl, unsubstituted or substituted with 1, 2, 3 or 4 C 1 -C 6 Alkyl substituted C 6 -C 10 Aryl.

7. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, The compound of Chemical Formula I is the compound of the following Chemical Formula I-3: [Chemical Formula I-3] In the formula, K, M and R are as defined in Formula I; and D is for CR 10 , N, O or S, or E is CR 11 , N, O or S, or F is CR 12 , N, O or S, or G is CR 13 , N, O or S, but N, O and S are one or more; and R 10 To R 13 are the same or different and may be independently replaced by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amine, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 12-membered heteroaryl and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium, C 1 -C 10 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 10 Aromatic ring.

8. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, The compound of Chemical Formula I is the compound of the following Chemical Formula I-4: [Chemical Formula I-4] In the formula, R is as defined in Formula I; and D is for CR 10 , N, O or S, or E is CR 11 , N, O or S, or F is CR 12 , N, O or S, or G is CR 13 , N, O or S, but N, O and S are one or more; and R 10 To R 13 are the same or different and may be independently replaced by cyano, halogen, haloalkyl, nitro, -C(=O)R 1 、-C(=O)OR 1 、-NH-C(=O)R 1 , C 1 -C 10 Alkoxy, substituted or unsubstituted C 1 -C 10 Alkyl, substituted or unsubstituted C 3 -C 8 Cycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted C 5 -C 20 aryl, substituted or unsubstituted 5- to 12-membered heteroaryl and substituted or unsubstituted 5- to 12-membered heterocycloalkyl, wherein R 1 It can be hydrogen, deuterium, C 1 -C 10 Alkyl; and Two or more adjacent groups may be combined with each other to form a substituted or unsubstituted aromatic hydrocarbon ring, wherein the aromatic hydrocarbon ring may form a 5- to 10-membered heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms selected from N, O and S, or a C 6 -C 10 Aromatic rings, and n is an integer of 0, 1 or 2 ； and L is CH 2 , NH or O; and It may be unsubstituted or may be substituted with deuterium, halogen, cyano, nitro, -NR 3 R 4 , C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryl, -C(=O)R 5 、-SO 2 -R 6 1, 2, 3 or 4 substitutions in the formula (a), wherein when the substituents are 2 or more, two or more adjacent groups are combined with each other to form a substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 20-membered heterocycloalkyl; and Among them, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 The aryl group may be unsubstituted or may be substituted by hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, C 6 -C 10 Aryloxy, unsubstituted or substituted with C 1 -C 6 Alkyl, C 6 -C 10 Aryl C 1 -C 6 Alkyl or C 1 -C 6 1, 2, 3 or 4 substitutions in 4- to 12-membered heterocycloalkyl substituted with alkylcarbonyl, and R 3 and R 4 are independently hydrogen, deuterium, -C(=O)-R a , C 1 -C 6 Alkyl or C 6 -C 10 Aryl, and C 1 -C 6 Alkyl or C 6 -C 10 The aryl group may be unsubstituted or may be substituted by halogen, hydroxyl, C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy or C 6 -C 10 1, 2, 3 or 4 substitutions in the aryloxy group, wherein R a For hydrogen, deuterium, C 1 -C 6 Alkyl or C 1 -C 6 haloalkyl; and R 5 Yes-OR b 、-NR c R d , C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 8 Cycloalkyl, wherein C 1 -C 6 Alkyl, C 2 -C 6 Alkenyl or C 2 -C 6 The alkynyl group may be unsubstituted or may be substituted with a single C 1 -C 6 Alkylamine or di-C 1 -C 6 1, 2, 3 or 4 substitutions in the alkylamine, and R b , R c and R d are independently hydrogen, deuterium, C 6 -C 10 Aryl or C 6 -C 10 Aryl C 1 -C 6 Alkyl, and R 6 It is C 1 -C 6 Alkyl, unsubstituted or substituted with 1, 2, 3 or 4 C 1 -C 6 Alkyl substituted C 6 -C 10 Aryl.

9. The compound according to claim 1, or a stereoisomer, a solvate, an isotopic variant, a tautomer, or a pharmaceutically acceptable salt thereof, Wherein the compound represented by Chemical Formula I is selected from the following compounds 1) to 161): 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-methylsulfonylbenzyl)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-morpholin-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-(((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; 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) [4-(3-Hydroxy-2-(pyridin-2-yl)-4,5,6,7-tetrahydro-2-indazol-5-yl)piperazin-1-yl]cyclopropylmethanone; 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-yn-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-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; 150) 2-(5-(Benzyl(methyl)amino)-3-hydroxy-4,5,6,7-tetrahydro-2H-indazol-2-yl)pyrimidine-5-carboxylic acid; 151) 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-chloropyridazin-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. The compound or a salt thereof according to claim 1, in, The salt is in the form of a salt induced by 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, ethanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, hydroxybenzoic acid, salicylic acid, tartaric acid, fumaric acid, malic acid, citric 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, hydrogen sulfate, hydrogen phosphate, dihydrogen phosphate, succinate, citrate, methanesulfonate (methoxide) or p-toluenesulfonate (p-toluenesulfonate).

11. A pharmaceutical composition for preventing, improving or treating oxidative stress-related diseases, comprising as an active ingredient a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition according to claim 11, The pharmaceutically acceptable carrier is one or more selected from the group consisting of excipients, diluents, disintegrants, binders, lubricants, surfactants, emulsifiers, suspending agents and diluents.

13. The pharmaceutical composition according to claim 11, wherein the oxidative stress-related disease is selected from the group consisting of: cancer; an inflammatory disease selected from rheumatoid arthritis, osteoarthritis, pneumonia, hepatitis, inflammatory colorectal disease, enterocolitis, glomerulonephritis, gastritis, vasculitis, pancreatitis, peritonitis, bronchitis, myocarditis, encephalitis, allergic contact dermatitis, diabetic inflammation, infectious inflammation and autoimmune diseases; a fibrotic disease selected from liver fibrosis, cirrhosis, small intestinal fibrosis, large intestinal fibrosis, gastric fibrosis, pulmonary fibrosis, skin fibrosis, epidermal fibrosis, dermal sclerosis / systemic sclerosis, cardiac fibrosis and renal fibrosis; a neurodegenerative disease selected from Parkinson's disease, Huntington's disease, amyloid lateral sclerosis, Alzheimer's disease, multiple sclerosis, ischemic and traumatic brain injury; a bipolar disorder, developmental disorders, autism spectrum disorders , Asperger's syndrome, Rett syndrome, visual impairment, optic neuropathy, attention deficit hyperactivity disorder (ADHD), epilepsy, mood disorders, Tourette syndrome and schizophrenia; liver disease; skin disease; mitochondrial disease; aging; chronic alcoholism; stem cell dysfunction; claudication; metabolic syndrome selected from obesity, diabetes, hypertension, hyperlipidemia, arteriosclerosis, peripheral vascular disease, ischemic perfusion, myocardial infarction and stroke; Down syndrome; infertility; excessive production of lipid peroxides in tissues; muscle-related diseases selected from myopathy, muscular dystrophy, cardiomyopathy, encephalomyopathy and back muscle atrophy; accumulation of cell membrane lipid peroxides; chronic fatigue; and retinal diseases selected from retinal fibrosis, macular degeneration, diabetic retinopathy, cataracts and neovascular glaucoma.

14. A method for preventing, improving or treating oxidative stress-related diseases, comprising administering to a subject the compound according to any one of claims 1 to 9, or a stereoisomer, a solvate, an isotopic variant, a tautomer or a pharmaceutically acceptable salt thereof.

15. Use of the compound according to any one of claims 1 to 9, or its stereoisomer, solvate, isotopic variant, variant or pharmaceutically acceptable salt in the preparation of a pharmaceutical composition for preventing, improving or treating oxidative stress-related diseases.

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