Bicyclic compound and pharmaceutical use thereof

Abstract

Disclosed in the present invention are a bicyclic compound and pharmaceutical use thereof. The present invention provides a bicyclic compound represented by formula (I) or a pharmaceutically acceptable salt, ester, stereoisomer, deuterated substance, or solvate thereof. The compound described in the present invention has a potent inhibitory effect on TEAD, so that the compound or a pharmaceutically acceptable salt, tautomer, mesomer, racemate, stereoisomer, metabolite, metabolic precursor, prodrug, or solvate thereof can be used for preparing a TEAD inhibitor, and can be used for preparing a medicament for preventing or treating diseases mediated by TEAD, mediated by YAP / TAZ, or mediated by interaction between YAP / TAZ and TEAD.

Description

Bicyclic compounds and their pharmaceutical uses Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a bicyclic compound and its pharmaceutical uses. Background Technology

[0002] The Hippo signaling pathway is an evolutionarily conserved signaling cascade pathway, first discovered in Drosophila and highly conserved in mammals, regulating growth and development, cell homeostasis, cell proliferation, and differentiation of organisms or organs (Annu Rev Biochem, 2019, 88:577-604). This pathway may be involved in regulating the self-renewal and differentiation of stem cells and progenitor cells. In addition, the Hippo pathway may also be involved in wound healing and tissue regeneration (Cell Mol Life Sci, 2021, 78(2):497-512; Dev Cell, 2019, 50(3):264-282). The Hippo pathway also crosstalks with other signaling pathways such as Wnt, Notch, Hedgehog, and MAPK / ERK, which may affect a variety of biological events, and its dysfunction may be involved in other human diseases besides cancer (Genes Dev, 2019, 33(21-22): 1491-1505; Cell, 2014, 158(1): 157-70; Oncogene, 2014, 33(40): 4857-66; Cancer Cell, 2020, 37(1): 104-122).

[0003] The Hippo signaling pathway consists of the following core components: upstream regulators (such as NF2 / Merlin, SCRIBBLE, CRUMBS, and GPCRs), a core kinase cascade (MST1 / 2 and LATS1 / 2 and their adaptor proteins SAV1 and MOB1), and downstream effector factors (the transcriptional coactivator Yes-associated protein (YAP) and the transcriptional coactivator with the PDZ-binding motif (TAZ)). The Hippo signaling pathway is tightly regulated by both internal and external signals. NF2 / Merlin or other upstream regulators activate MST1 / 2 kinase and the scaffold protein SAV1. Activated MST1 / 2 promotes phosphorylation of LATS1 / 2 and MOB1. Phosphorylated LATS1 / 2 then further phosphorylates YAP / TAZ. Phosphorylated YAP / TAZ remains in the cytoplasm, isolated by the 14-3-3 protein, or degraded by the proteasome via ubiquitin-mediated degradation. When the kinase signaling cascade is inactivated, dephosphorylated YAP and TAZ are transported to the nucleus and bind to transcription factors TEAD1 / 2 / 3 / 4 of the transcriptional enhancer factor TEF with TEA / ATTS domain (TEAD) family. This regulates the transcription of target genes and initiates transcriptional programs that are crucial for cell proliferation, survival, and migration (Trends Cancer, 2019, 5(5): 283-296; Semin Cancer Biol, 2022, 85: 33-42; Front Immunol, 2020, 11: 323; Nat Rev Drug Discov, 2020, 19(7): 480-494).

[0004] The binding and activation of YAP or TAZ with TEAD induces the expression of various genes, including connective tissue growth factor (CTGF), cysteine-rich angiogenesis inducer 61 (CYR61), amphotericin G (AREG), proto-oncogene (MYC), GLI family zinc finger 2 (Gli2), AXL receptor tyrosine kinase (AXL), and B-cell lymphoma-2 gene (Bcl2). Many of these genes mediate cell survival and proliferation (Cell Death Discov, 2022, 8(1):213; Pharmacol Res, 2021, 169:105635). Therefore, the closed Hippo pathway may act as an oncogene through unphosphorylated YAP and TAZ, while the open Hippo pathway may act as a tumor suppressor through phosphorylated YAP and TAZ. In addition, the Hippo pathway also plays a role in the resistance mechanisms of cancer cells to oncology and immuno-oncology therapies (Cancer Res, 2023, 83(24): 4112-4129; Pharmaceuticals (Basel), 2023, 16(4): 553).

[0005] Therefore, dysfunction or abnormal regulation of the Hippo pathway as a tumor suppressor is believed to play an important role in the development of various cancer types and diseases. The pro-cancer transcriptional activity of YAP / TAZ-TEAD can be inhibited by suppressing palmitoylation of TEAD protein or by inhibiting the YAP / TAZ-TEAD protein interaction.

[0006] Therefore, inhibiting TEAD, YAP / TAZ, or the interaction between YAP / TAZ and TEAD through pharmacology may be a potential, rational, and valuable strategy for the prevention or treatment of cancer, organ fibrosis, metabolic diseases, or inflammatory diseases mediated by TEAD, YAP / TAZ, or the interaction between YAP / TAZ and TEAD. Summary of the Invention

[0007] Purpose of the invention: To address the problems existing in the prior art, the present invention provides a bicyclic compound and its pharmaceutical uses. The bicyclic compound or its pharmaceutically acceptable salts, esters, stereoisomers, deuterated derivatives or solvates can act as TEAD inhibitors and have excellent therapeutic effects on TEAD-mediated, YAP / TAZ-mediated or YAP / TAZ-TEAD-mediated diseases.

[0008] Technical solution: To achieve the above objectives, the present invention provides a bicyclic compound of formula (I) or a pharmaceutically acceptable salt thereof:

[0009] Where X is selected from CR aOr N, the R a Selected from H or halogens; Y is selected from CH or N;

[0010] Ring A is selected from C 6-10 Aryl, 5-10 heteroaryl or C 3-6 Cycloalkenyl, wherein the 5- to 10-membered heteroaryl group comprises 1 to 4 heteroatoms independently selected from N, O, or S;

[0011] Each R 1 They may be the same or different, and each is independently selected from H, D, halogen, -CN, -NO2, -NH2, -OR b1 -SR b2 -SF5, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl and phenyl groups are optionally substituted by 0 to 3 substituents independently selected from -OH, halogen, -CN, -NO2 or -NH2;

[0012] Ring B is selected from C 6-10 Aryl, 5-10 heteroaryl or C 3-6 Cycloalkenyl, wherein the 5- to 10-membered heteroaryl group comprises 1 to 4 heteroatoms independently selected from N, O, or S;

[0013] Each R 2 They may be the same or different, and each is independently selected from H, D, halogen, -CN, -NO2, -NH2, -OR b1 -SR b2 C, whether substituted or not 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl and phenyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH, halogen or -CN;

[0014] R b1 and R b2 Each time, the same or different, and each independently selected from H, D, substituted or unsubstituted C, are used. 1-6 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl and phenyl groups are optionally substituted with 0 to 3 substituents independently selected from halogens, -CN, -NH2 or -OH;

[0015] R 3 Selected from

[0016] R 4 and R 5 Each time it may be the same or different, and each is independently selected from H, D, -OH, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl group and phenyl group are optionally separated by 0 to 3 independently selected from halogen, -OR f or -NR f R g Substituents; R f and R g Each time the same or different, and each is independently selected from H and C. 1-6 Alkyl or C 3-6 cycloalkyl;

[0017] R c R d and R e Each time it may be the same or different, and each is independently selected from H, D, halogen, -CN, -OH or C. 1-6 Halogenated or non-halogenated alkyl groups;

[0018] m is selected from any integer from 0 to 3;

[0019] n is any integer from 0 to 3.

[0020] In some preferred embodiments, X is selected from CR a Or N, where the R a Selected from H; Y is selected from CH or N.

[0021] Furthermore, the ring A is specifically selected from any of the following structural segments:

[0022] Each R 1 Same or different, and each independently selected from H, halogen, -OR b1 -SR b2 -SF5, substituted or unsubstituted C 1-4 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-4 The alkyl and phenyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH or halogens;

[0023] R b1 and R b2 Each time, the same or different, and each independently selected from H, D, substituted or unsubstituted C, are used.1-6 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 The alkyl and phenyl groups are optionally substituted with 0 to 3 substituents independently selected from halogens, -CN, -NH2, or -OH. Further, ring B is specifically selected from any of the following structural segments:

[0024] Each R 2 Same or different, and each independently selected from halogen, -OR b1 -SR b2 C, either substituted or unsubstituted 1-3 Alkyl, wherein the substituted C 1-3 The alkyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH or halogens;

[0025] R b1 and R b2 Each time, the same or different, and each independently selected from H, or substituted or unsubstituted C. 1-3 Alkyl, wherein the substituted C 1-3 The alkyl group is optionally substituted by 0 to 3 independent substituents selected from halogens.

[0026] Furthermore, the R 3 Choose from any of the following structural fragments:

[0027] R 4 and R 5 Each time, the same or different, and each independently selected from H, or substituted or unsubstituted C. 1-3 Alkyl, wherein the substituted C 1-3 The alkyl groups are optionally substituted by 0 to 3 independent substituents selected from halogens;

[0028] R c R d and R e Each time it may be the same or different, and each is independently selected from H, halogen or C. 1-3 Halogenated or non-halogenated alkyl groups;

[0029] m is selected from any integer from 0 to 2;

[0030] n is any integer from 0 to 2.

[0031] In some preferred embodiments, the bicyclic compound further includes its pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate.

[0032] Preferably, the bicyclic compound of Formula I of the present invention, or its pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate, is selected from any one of the compounds shown in Table 1 below:

[0033] Table 1. Structure and Nomenclature of Compounds

[0034] The bicyclic compounds of the present invention can be used as pharmaceutical salts, which can be salts formed by the compounds of the present invention with metal ions (including sodium, potassium, calcium, etc.) or pharmaceutically acceptable amines (including ethylenediamine, tromethamine, diisopropylamine, meglumine, berberine, metformin, etc.) or ammonium ions.

[0035] The application of the bicyclic compounds or their pharmaceutically acceptable salts, tautomers, meso compounds, racemates, stereoisomers, metabolites, metabolic precursors, prodrugs, chelates, non-covalent complexes or solvates described in this invention in the preparation of TEAD inhibitors.

[0036] The bicyclic compounds described in this invention, or their pharmaceutically acceptable salts, tautomers, meso compounds, racemates, stereoisomers, metabolites, metabolic precursors, prodrugs, chelates, non-covalent complexes, or solvates, can be used as TEAD inhibitors to prepare drugs for the prevention or treatment of TEAD-mediated, YAP / TAZ-mediated, or YAP / TAZ-TEAD-mediated diseases.

[0037] Specifically, the compounds of the present invention can be used to prepare medicaments for the prevention or treatment of diseases mediated by TEAD, YAP / TAZ, or by the interaction between YAP / TAZ and TEAD.

[0038] The compounds of this invention can be used to prevent or treat cancers, including mesothelioma, glioma, medulloblastoma, myeloma, myelodysplastic syndrome, Hodgkin's lymphoma, non-Hodgkin's lymphoma, meningioma, sarcoma, melanoma, germ cell tumor (pineal tumor), astrocytoma, medulloblastoma, ependymoma, head and neck cancer, colorectal cancer, gastric cancer, thyroid cancer, lung cancer, leukemia, pancreatic cancer, hematologic malignancies, esophageal squamous cell carcinoma, bone cancer, vascular cancer, brain cancer, kidney cancer, liver cancer, squamous cell carcinoma, basal cell carcinoma, bladder cancer, prostate cancer, uterine cancer, testicular cancer, interstitial cell carcinoma, ovarian cancer, or breast cancer, etc.

[0039] The compounds of this invention can be used to prevent or treat organ fibrosis, metabolic diseases, or inflammatory diseases, including liver cirrhosis, liver fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, cystic fibrosis, systemic sclerosis, progressive nephropathy, diabetic nephropathy, cardiovascular fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic fatty liver, cirrhosis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), interstitial pneumonia, pulmonary tuberculosis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), Behcet's disease, asthma, chronic obstructive pulmonary disease, chronic bronchitis, and pulmonary emphysema. Swelling, obliterative bronchiolitis, allergic rhinitis, chronic rhinitis, sinusitis, systemic lupus erythematosus, rheumatoid arthritis, spondyloarthritis, osteoarthritis, synovitis, tendinitis, thromboangiitis obliterans, phlebitis, psoriasis, ichthyosis, dermatitis, contact dermatitis, pancreatitis, chronic nephritis, cystitis, meningitis, gastritis, sepsis, pyoderma gangrenosa, uveitis, Parkinson's disease, Alzheimer's disease, alpha-complexoprotein disease, depression, multiple sclerosis, amyotrophic lateral sclerosis, fibromyalgia syndrome, neuralgia, Down syndrome, Hallewarden-Scholes disease, Huntington's disease, or Wilson's disease, etc.

[0040] This invention also provides a pharmaceutical composition for the prevention or treatment of diseases mediated by TEAD, YAP / TAZ, or by the interaction between YAP / TAZ and TEAD, comprising a therapeutically effective amount of a bicyclic compound of formula (I) or a pharmaceutically acceptable salt thereof, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate as the active ingredient and a pharmaceutically acceptable carrier. The carrier can be varied depending on the dosage form, administration method, etc. Examples of carriers include excipients, binders, disintegrants, lubricants, flavoring agents, fragrances, colorants, and sweeteners. The pharmaceutical composition may be in pharmaceutically conventional forms such as capsules, powders, tablets, granules, pills, injections, syrups, oral solutions, inhalers, ointments, suppositories, or patches.

[0041] In addition to the active compound, the pharmaceutical composition of the present invention may contain one or more excipients selected from the following components: fillers, binders, wetting agents, disintegrants, or excipients. Depending on the method of administration, the composition may contain 0.1 to 99% by weight of the active compound.

[0042] The general chemical terms used in the above structural formulas have their usual meanings. For example, unless otherwise stated, the term "halogen" as used herein refers to F, Cl, Br, and I.

[0043] Unless otherwise stated, the term "alkyl" as used herein refers to a saturated monovalent hydrocarbon group having a straight-chain, branched, or cyclic moiety having 1 to 6 carbon atoms. Examples of such alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, n-pentyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, cyclopentyl, n-hexyl, 2-hexyl, 2-methylpentyl, and cyclohexyl.

[0044] Unless otherwise stated, the term "aryl" as used herein refers to a 6- to 10-membered monocyclic or polycyclic system containing a carbon ring atom, whether unsubstituted or substituted. Examples of such aryl groups include, but are not limited to, phenyl and naphthyl groups.

[0045] Unless otherwise stated, the term "heteroaryl" as used herein refers to an unsubstituted or substituted stable 5- or 6-membered monocyclic aromatic ring system, or an unsubstituted or substituted 8- to 10-membered benzo[a]-fused heteroaromatic ring system, or a bicyclic heteroaromatic ring system, consisting of a carbon atom and 1 to 4 heteroatoms selected from N, O, or S, wherein the N or S heteroatoms may optionally be oxidized, and the N heteroatoms may optionally be quaternized. Heteroaryl groups can be attached to any heteroatom or carbon atom to produce a stable structure. Examples of heteroaryl groups include, but are not limited to, pyrrole, thiophene, furanyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, azaindolyl, indolyl, azaindolyl, benzimidazolyl, benzofuranyl, benzothiophene, benzoisooxazolyl, benzooxazolyl, benzopyrazolyl, benzothiazolyl, quinolinyl, and isoquinolinyl.

[0046] Unless otherwise stated, the term "cycloalkyl" as used herein refers to a cyclic saturated alkyl group having 3 to 6 carbon atoms. Examples of such cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0047] As used herein, the term "composition" is intended to include products containing specific amounts of specific ingredients, as well as products directly or indirectly produced from combinations of specific amounts of specific ingredients. Therefore, pharmaceutical compositions containing compounds of the present invention as active ingredients, and methods for preparing the compounds of the present invention, are also part of this invention. Furthermore, some compounds can form solvates with water or common organic solvents, and such solvates are also included within the scope of this invention.

[0048] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium, potassium, calcium, aluminum, magnesium, bismuth, and ammonium salts. When a compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochlorides, acetates, trifluoroacetates, sulfates, and methanesulfonates.

[0049] The invention will be described in more detail through specific embodiments. The following embodiments are provided for illustrative purposes and are not intended to limit the invention in any way. Those skilled in the art will readily recognize that various non-critical parameters can be changed or modified to produce substantially the same results. According to at least one assay method described herein, the compounds of the examples were found to inhibit the transcriptional activity of YAP / TAZ and TEAD protein / protein interactions.

[0050] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0051] (1) The bicyclic compounds provided by the present invention or their pharmaceutically acceptable salts, esters, stereoisomers, deuterated compounds or solvates have strong TEADs inhibitory activity. Multiple compounds show an inhibition rate of more than 80% against TEADs at a concentration of 1 μM, inhibiting the transcriptional activity of YAP / TAZ and TEAD protein / protein interactions; they can be used to prepare or treat drugs for TEADs-mediated diseases.

[0052] (2) The bicyclic compounds of the present invention or their pharmaceutically acceptable salts, esters, stereoisomers, deuterated compounds or solvates are easy to prepare and inexpensive, and have simple structures, ingenious designs, cheap and readily available raw materials, safe and environmentally friendly synthesis processes, and are easy to scale up for production. Detailed Implementation

[0053] The following abbreviations were used in the examples:

[0054] Cu(OAc)₂: Copper acetate; NaHCO₃: Sodium bicarbonate; NH₄Cl: Ammonium chloride; CuI: Cuprous iodide; CuCl: Cuprous chloride; NaNO₂: Sodium nitrite; Cs₂CO₃: Cesium carbonate; K₂CO₃: Potassium carbonate; MeNH₂·HCl: Methylamine hydrochloride; LiOH·H₂O: Lithium hydroxide monohydrate; DPPA: Diphenyl azidophosphate; TEA or Et₃N: Triethylamine; Py: Pyridine; 4,4 '-Bipyridine: 4,4-Bipyridine; B2(OH)4: Tetrahydroxydiboron; SnCl2·2H2O: Stannous chloride dihydrate; STAB: Sodium triacetoxyborohydride; CDI: N,N'-carbonyldiimidazole; NaH: Sodium hydride; CH3I: Iodomethane; AcOH: Acetic acid; HCl: Hydrochloric acid; PhMe: Toluene; DMF: N,N-Dimethylformamide; DIPEA: N,N-Diisopropyl Ethylamine; 1,4-Dioxane: 1,4-dioxane; DCM: dichloromethane; MeOH: methanol; EtOH: ethanol; PE: petroleum ether; EA: ethyl acetate; THF: tetrahydrofuran; MeCN: acetonitrile; SOCl2: thionyl chloride; Tween 20: Tween 20; NBS: N-bromosuccinimide; NCS: N-chlorosuccinimide; HATU: 1-[bis(dimethylamino)methylene]-1 H-1,2,3-Triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate; h: hours; min: minutes; Pd(PPh3)4: tetrakis(triphenylphosphine)palladium; Pd(dppf)Cl2: 1,1-bis(diphenylphosphine)diferro-palladium dichloride; Pd2(dba)3: tris(dibenzylene-BASEacetone)dipalladium; Xantphos: 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene; rtor RT: room temperature.

[0055] Unless otherwise specified, reagents and solvents are used in the form obtained from the supplier. Anhydrous solvents and dried glassware are used for synthetic transformations sensitive to moisture and / or oxygen. Yields are not optimized. Reaction times are approximate and not optimized. Column chromatography and thin-layer chromatography (TLC) are performed on silica gel, with 200-300 mesh silica gel from Qingdao Ocean Chemical Plant Branch generally used as the support for column chromatography.

[0056] The structure of the compound was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). The NMR determination was performed using a Bruker NMR spectrometer with deuterated dimethyl sulfoxide (DMSO-d6) or deuterated chloroform (CDCl3) as the solvent and tetramethylsilane (TMS) as the internal standard.

[0057] The known starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as Leyan, Bidex Pharmaceuticals, Aladdin, and Anaiji.

[0058] The present invention will now be specifically illustrated through embodiments. In this invention, the embodiments described below are for better explanation and are not intended to limit the scope of the invention. Various changes and modifications can be made to the present invention without departing from its spirit and scope.

[0059] Example 1

[0060] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 1)

[0061] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0062] Py (165 μL, 2.0 mmol) was added dropwise to a mixture of 3-bromo-5-nitro-1H-indazole (242 mg, 1 mmol; Adamas, 01104143), 4-trifluoromethylphenylboronic acid (380 mg, 2 mmol; Adamas, 011468334), and Cu(OAc)₂ (272 mg, 1.5 mmol; Leyan, 1021293) in DCM (5.0 mL), and the mixture was stirred at room temperature for 6 h. TLC (PE:EA = 3:1, R f =0.9) indicates that the starting material was almost completely consumed and a new spot was detected. The residue was concentrated under reduced pressure and purified by column chromatography (PE:EA = 25:1) to give the title compound 1-1 (335 mg, 87% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ8.71(dd,J=2.1,0.6Hz,1H),8.42(dd,J=9.3,2.2Hz,1H),7.86(s,4H),7.83(dd,J=9.3,0.6Hz,1H).

[0063] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0064] Iron powder (192 mg, 3.4 mmol) was added to a mixture of 1-1 (330 mg, 0.85 mmol) and NH4Cl (51 mg, 0.95 mmol) in EtOH (2 mL) and water (1 mL), and the mixture was heated and stirred at 80 °C for 4 h. TLC (PE:EA = 3:1, R f=0.2) showed that 1-1 was completely consumed and a new spot was detected. The residue was concentrated under reduced pressure via anhydrous magnesium sulfate pad extraction. PE (2.0 mL) and EA (0.2 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 1-2 (135 mg, 44% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ7.83(d,J=8.6Hz,2H),7.76(d,J=8.7Hz,2H),7.60(dd,J=9.0 ,0.7Hz,1H),6.98(dd,J=9.0,2.2Hz,1H),6.87(dd,J=2.2,0.7Hz,1H),3.82(s,2H).

[0065] Step 3: Preparation of N-(3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0066] Under ice bath conditions, Py (45 μL, 0.51 mmol) and methanesulfonic anhydride (77 mg, 0.44 mmol; Adamas, 01108284) were added dropwise to a solution of 1-2 (130 mg, 0.34 mmol) dissolved in DCM (2.0 mL), and the mixture was stirred at room temperature for 1 h. TLC (PE:EA = 2:1, R f =0.2) showed that 1-2 was completely consumed and a new spot was detected. The residue was concentrated under reduced pressure and purified by column chromatography (PE:EA = 3:1) to give title compounds 1-3 (140 mg, 95% yield) as a pale yellow-white solid. 1 H NMR (300MHz, CDCl3) δ7.83(d,J=3.0Hz,4H),7.77(d,J=8.9Hz,1H),7.59(d,J=2.1Hz,1H),7.50–7.44(m,1H),6.66(s,1H),3.06(s,3H).

[0067] Step 4: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0068] To a mixture of 1-3 (86 mg, 0.2 mmol), 1-methyl-1H-pyrazole-4-boric acid (50 mg, 0.4 mmol; Leyan, 1062073), NaHCO3 (50 mg, 0.6 mmol), and Pd(PPh3)4 (12 mg, 0.01 mmol; Leyan, 14221-01-3), 1,4-Dioxane (1.0 mL) and water (0.25 mL) were added, and the mixture was heated and stirred at 100 °C for 1 h under an argon atmosphere. TLC (PE:EA = 1:1, R f =0.05) showed that 1-3 were completely consumed and a new spot was detected. After cooling to room temperature, the residue was concentrated under reduced pressure. The residue was purified by column chromatography (DCM:MeOH = 75:1) to give a crude product as a yellow solid. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded title compound 1 (78 mg, 90% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO-d6) δ9.73(s,1H),8.38(s,1H),8.07(d,J=8.6Hz,2H),8.01(d,J=7.4Hz,2H),7. 94(d,J=8.8Hz,2H),7.89(d,J=2.0Hz,1H),7.48(dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.01(s,3H).

[0069] Example 2

[0070] N-(3-(1H-imidazol-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 2)

[0071] Step 1: Preparation of N-(3-(1H-imidazol-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0072] Dry DMF (2.0 mL) was added to the mixture of 1-3 (86 mg, 0.2 mmol), imidazole (34 mg, 0.5 mmol; Leyan, 1028408), Cs2CO3 (251 mg, 0.8 mmol; Leyan, 1604853), and CuI (15 mg, 0.08 mmol; Leyan, 1042604) prepared in step 3 of Example 1, and the mixture was heated and stirred at 120 °C for 24 h under an argon atmosphere. TLC (DCM:MeOH = 25:1, R f=0.3) showed a small amount of residue 1-3 and a new spot was detected. Cool to room temperature, pour the reaction solution into water (20 mL), extract with EA (20 mL × 3), wash the organic layer with saturated brine (20 mL × 2), dry to anhydrous sodium sulfate, concentrate under reduced pressure to obtain the residue, and purify the residue by column chromatography (DCM:MeOH = 30:1) to give title compound 2 (9.5 mg, 11% yield) as a pale yellow solid: 1 H NMR(300MHz,DMSO-d6)δ9.92(s,1H),8.41(d,J=1.1Hz,1H),8.15–8.05(m,3H),7.98(d,J=8.7Hz,2H),7.8 9(t,J=1.3Hz,1H),7.76(d,J=1.3Hz,1H),7.54(dd,J=9.2,2.0Hz,1H),7.28(t,J=1.1Hz,1H),3.04(s,3H).

[0073] Example 3

[0074] N-(3-(pyridin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 3)

[0075] Example 3 used the same preparation method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pyridine-4-boric acid (Leyan, 1023404). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 3 (85 mg, 62% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.87 (s, 1H), 8.84–8.75 (m, 2H), 8.13 (d, J = 8.4Hz, 2H), 8.10–8.02(m,2H),8.02–7.95(m,4H),7.53(dd,J=9.1,2.0Hz,1H),3.02(s,3H).

[0076] Example 4

[0077] 1-(4-Methoxyphenyl)-N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-sulfonamide (Compound 4)

[0078] Step 1: Preparation of 3-bromo-1-(4-methoxyphenyl)-5-nitro-1H-indazole

[0079] Step 1 employs the same preparation method as Step 1 of Example 1, except that 4-trifluoromethylphenylboronic acid in Step 1 of Example 1 is replaced with 4-methoxyphenylboronic acid (Leyan, 1036309). The residue is purified by column chromatography (PE:EA = 25:1) to obtain the title compound 4-1:, which is a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.68(d,J=2.1Hz,1H),8.33(dd,J=9.3,2.1Hz,1H),7.65(d,J=9.3Hz,1H),7.59–7.53(m,2H),7.11–7.05(m,2H),3.90(s,3H).

[0080] Step 2: Preparation of 3-bromo-1-(4-methoxyphenyl)-1H-indazole-5-amine

[0081] Step 2 follows the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 4-1. The residue is concentrated under reduced pressure using anhydrous magnesium sulfate, and PE (5.0 mL) and EA (0.5 mL) are added to the residue. The mixture is stirred at room temperature for 2 hours and then filtered to obtain the title compound 4-2 (678 mg, 100% two-step yield) as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ7.58–7.52(m,2H),7.43(d,J=8.9Hz,1H),7.05–6.99(m,2H),6.91(dd,J=8.9,2.2Hz,1H),6.84(d,J=2.3Hz,1H),3.87(s,3H).

[0082] Step 3: Preparation of 3-bromo-1-(4-methoxyphenyl)-1H-indazole-5-sulfonyl chloride

[0083] At -15℃, SOCl2 (780 μL, 10.7 mmol; Macklin, T819486) was added dropwise to water (3.5 mL), followed by CuCl (4.5 mg, 0.05 mmol; Adamas, 013385471). The mixture was stirred at room temperature for 3 h to prepare reaction solution 1. At -15℃, an aqueous solution of NaNO2 (163 mg, 2.35 mmol; Macklin, S818033) was added dropwise to a solution of 4-2 (678 mg, 2.14 mmol) dissolved in concentrated HCl (3.0 mL). The mixture was stirred for 30 min to prepare reaction solution 2. At -15℃, reaction solution 2 was added dropwise to reaction solution 1, and the mixture was stirred at room temperature for 1 h. TLC (PE:EA = 10:1, R f=0.6) indicates that 4-2 was completely consumed and a new spot was detected. The reaction solution was poured into water (30 mL), extracted with EA (20 mL × 3), the organic layer was washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 4-3, which was a yellow-black oil. The crude product was used directly in the next step of the reaction without purification.

[0084] Step 4: Preparation of 3-bromo-1-(4-methoxyphenyl)-N-methyl-1H-indazole-5-sulfonamide

[0085] At -15°C, Et3N (42 μL, 0.3 mmol) was added dropwise to a solution of MeNH2·HCl (21 mg, 0.3 mmol; Adamas, 01092862) dissolved in DCM (2.0 mL), stirred for 15 min, and then crude product 4-3 (0.15 mmol) was added. The mixture was stirred at room temperature for 1 h. TLC (PE:EA = 3:1, R f =0.15) showed that 4-3 was completely consumed and a new spot was detected. The residue was concentrated under reduced pressure and purified by column chromatography (PE:EA = 2:1) to give the title compound 4-4 (56 mg, 7% two-step yield) as a white solid. 1 H NMR(300MHz, CDCl3) δ8.29(dd,J=1.7,0.7Hz,1H),7.89(dd,J=9.0,1.7Hz,1H),7.69(dd,J=9.0,0.7Hz ,1H),7.59–7.50(m,2H),7.11–7.02(m,2H),4.42(q,J=5.3Hz,1H),3.89(s,3H),2.70(d,J=5.2Hz,3H).

[0086] Step 5: Preparation of 1-(4-methoxyphenyl)-N-methyl-3-(1-methyl-1H-pyrazol-3-yl)-1H-indazole-5-sulfonamide

[0087] Step 5 uses the same preparation method as step 4 of Example 1, except that 1-4 in step 4 of Example 1 is replaced with 4-4. Purification by column chromatography (DCM:MeOH = 75:1) yields a crude product as a white solid. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtration yields title compound 4 (29 mg, 73% yield) as a white solid. 1H NMR (400MHz, DMSO-d6) δ8.48(d,J=0.8Hz,1H),8.44(s,1H),8.06(d,J=0.8Hz,1H),7.90–7.82(m,2H),7.7 3–7.67(m,2H),7.48(q,J=5.0Hz,1H),7.20–7.14(m,2H),3.98(s,3H),3.86(s,3H),2.43(d,J=4.8Hz,3H).

[0088] Example 5

[0089] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-sulfonamide (Compound 5)

[0090] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethoxy)phenyl)-1H-indazole

[0091] Step 1 employed the same preparation method as Step 1 of Example 1, except that 4-trifluoromethylphenylboronic acid in Step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid (BYD, BD4476). The residue was purified by column chromatography (PE:EA = 10:1) to obtain the title compound 5-1 (840 mg) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ8.70 (dd, J=2.2, 0.6Hz, 1H), 8.39 (dd, J=9.3, 2.1Hz, 1H), 7.78–7.71 (m, 3H), 7.48–7.41 (m, 2H).

[0092] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-amine

[0093] Step 2 follows the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 5-1. The residue is concentrated under reduced pressure using anhydrous magnesium sulfate, and PE (15 mL) and DCM (3.0 mL) are added to the residue. The mixture is stirred at room temperature for 2 hours and then filtered to obtain the title compound 5-2 (672 mg, 90% two-step yield) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ7.75–7.68(m,2H),7.52(dd,J=9.0,0.7Hz,1H),7.39–7.32(m,2H),6.96(dd,J=8.9,2.2Hz,1H),6.86(dd,J=2.2,0.7Hz,1H).

[0094] Step 3: Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-sulfonyl chloride

[0095] Step 3 uses the same preparation method as Step 3 in Example 4, except that 4-2 in Step 3 of Example 4 is replaced with 5-2. The reaction solution is poured into water (30 mL), extracted with EA (20 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 5-3, which is a yellow-black oil. The crude product is used directly in the next step of the reaction without purification.

[0096] Step 4: Preparation of 3-bromo-N-methyl-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-sulfonamide

[0097] Step 4 employs the same preparation method as Step 4 of Example 4, except that 4-3 in Step 4 of Example 4 is replaced with 5-3. The residue is concentrated under reduced pressure and purified by column chromatography (PE:EA = 2:1) to obtain the title compound 5-4 (313 mg, 35% two-step yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.31 (dd, J=1.7, 0.7Hz, 1H), 7.95 (dd, J=9.0, 1.7Hz, 1H), 7.79 (dd, J=9.0, 0.8Hz,1H),7.76–7.69(m,2H),7.43(dd,J=9.0,1.0Hz,2H),4.46(q,1H),2.71(d,J=4.6Hz,3H).

[0098] Step 5: Preparation of N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-sulfonamide

[0099] Step 5 follows the same preparation method as step 4 of Example 1, except that 1-4 in step 4 of Example 1 is replaced with 5-4. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (4.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 5 (28 mg, 62% yield) in the form of a pale yellow solid. 1H NMR(300MHz, DMSO-d6)δ8.53(s,1H),8.47(dd,J=1.7,0.7Hz,1H),8.12–8.03(m,2H),8.02–7.93(m,2H),7.89( dd,J=8.9,1.7Hz,1H),7.64(dt,J=7.8,1.0Hz,2H),7.54(q,J=4.8Hz,1H),3.99(s,3H),2.44(d,J=5.0Hz,3H).

[0100] Example 6

[0101] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-sulfonamide (Compound 6)

[0102] Example 6 used the same preparation method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid (Adamas, 011468334), and 3-bromo-5-nitro-1H-indazole was replaced with 3-bromo-6-nitro-1H-indazole (Bide, BD4141). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 6 (41 mg, 94% yield) in the form of a white solid. 1 H NMR(300MHz, CDCl3)δ8.34(dd,J=1.4,0.7Hz,1H),8.15–8.06(m,2H),8.01(s,1H),7.91(d,J=8.5Hz, 2H),7.83(d,J=8.6Hz,2H),7.75(dd,J=8.5,1.4Hz,1H),4.57(q,J=5.4Hz,1H),2.70(d,J=5.3Hz,3H).

[0103] Example 7

[0104] N-(1-(1-methyl-1H-imidazol-4-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 7)

[0105] Step 1: Preparation of 3-bromo-1-(1-methyl-1H-imidazol-4-yl)-6-nitro-1H-indazole

[0106] To a mixture of 3-bromo-6-nitro-1H-indazole (605 mg, 2.5 mmol; BD4141), 4-iodo-1-methylimidazole (624 mg, 3.0 mmol; BD2277), CuI (95 mg, 0.5 mmol), and Cs₂CO₃ (2036 mg, 6.26 mmol) dissolved in water (12.5 mL) and Tween 20 (250 μL; Adamas, 013641249), trans-(1R,2R)-N,N'-dimethyl-1,2-cyclohexanediamine (320 μL, 2.0 mmol; BD10761) was added, and the mixture was heated and stirred at 100 °C for 24 h. TLC (PE:EA = 4:1, R f =0.2) indicates a small amount of starting material remaining and a new spot was detected. After cooling to room temperature, the reaction solution was poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was then purified by column chromatography (PE:EA = 2:1) to give the title compound 7-1 (682 mg, 85% yield) as a pale yellowish-brown solid. 1 H NMR (400MHz, CDCl3) δ9.29(d,J=1.9Hz,1H),8.11(dd,J=8.9,2.0Hz,1H),7.74(dd,J=8.9,0.6Hz,1H),7.44(s,1H),7.24(s,1H),3.80(s,3H).

[0107] Steps 2, 3, and 4 follow the same preparation method as steps 2, 3, and 4 of Example 1. The starting material was changed from 1-1 to 7-1. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 7 (26.5 mg, 64% yield) in the form of a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ10.05(s,1H),8.32–8.17(m,3H),8.12(d,J=8.8Hz,1H),7.90(d,J=8.2Hz,2H) ,7.76(d,J=1.6Hz,1H),7.51(d,J=1.6Hz,1H),7.24(dd,J=8.8,2.0Hz,1H),3.77(s,3H),3.04(s,3H).

[0108] Example 8

[0109] N-(3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide (compound 8)

[0110] Step 1: Preparation of N-(3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide

[0111] Under ice bath conditions, Et3N (280 μL, 2 mmol) and acryloyl chloride (90 μL, 1.1 mmol; Adamas, 01156773) were added dropwise to the solution of 1-2 (355 mg, 1 mmol) prepared in step 2 of Example 1, dissolved in DCM (3.0 mL), and stirred at room temperature for 1 h. TLC (DCM:MeOH = 50:1, R f =0.4) showed that 1-2 was completely consumed and a new spot was detected. Concentration under reduced pressure yielded a residue, which was purified by column chromatography (DCM:MeOH = 1:0) to give title compound 8 (364.5 mg, 89% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.06 (s, 1H), 7.85 (d, J = 8.5Hz, 2H), 7.79 (d, J = 8.7Hz, 2H), 7.75–7.69 (m, 1H), 7.66 (d, J = 9. 2Hz,1H),7.47(s,1H),6.51(dd,J=16.8,1.2Hz,1H),6.30(dd,J=16.8,10.2Hz,1H),5.84(dd,J=10.2,1.2Hz,1H).

[0112] Example 9

[0113] N-(1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide (compound 9)

[0114] Step 1: Preparation of 5-nitro-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0115] Step 1 employed the same preparation method as Step 1 of Example 1, except that the 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 was replaced with 5-nitro-1H-indazole (Leyan, 1035160). After concentration under reduced pressure, a residue was obtained. This residue was purified by column chromatography (PE:EA = 40:1) to give the title compound 9-1 (2.76 g, 45% yield) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ8.82(dd,J=2.1,0.6Hz,1H),8.45(d,J=0.9Hz,1H),8.37(dd,J=9.3,2.1Hz,1H),7.92–7.81(m,5H).

[0116] Step 2: Preparation of 1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0117] Step 2 uses the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 9-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (DCM:MeOH = 1:0) to give the title compound 9-2 (1.467 g, 59% yield) as a yellow solid. 1 H NMR(400MHz, CDCl3)δ8.04(d,J=0.9Hz,1H),7.90–7.84(m,2H),7.77(d,J=8.6Hz,2H),7 .66–7.60(m,1H),7.01(dd,J=2.2,0.8Hz,1H),6.94(dd,J=8.9,2.2Hz,1H),3.72(s,2H).

[0118] Step 3: Preparation of N-(1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide

[0119] Step 3 uses the same preparation method as Step 1 of Example 8, except that 1-2 in Step 1 of Example 8 is replaced with 9-2. After concentration under reduced pressure, a residue is obtained. The residue is purified by column chromatography (DCM:MeOH = 150:1) to obtain a crude product as a pale yellow solid. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 9 (128 mg, 77% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ8.34–8.14(m,2H),7.88(d,J=8.5Hz,2H),7.84–7.72(m,3H),7.51(d,J=8.9Hz,1H) ,7.41(s,1H),6.50(dd,J=16.8,1.4Hz,1H),6.29(dd,J=16.8,10.2Hz,1H),5.82(dd,J=10.2,1.3Hz,1H).

[0120] Example 10

[0121] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide (compound 10)

[0122] Step 1: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0123] Step 1 employs the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 1-2 prepared in Step 2 of Example 1, and the temperature is 80°C. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (DCM:MeOH = 75:1) to obtain the title compound 10-1 (464 mg, 87% yield) as a pale yellow solid. 1 H NMR(400MHz, CDCl3)δ8.06(d,J=0.7Hz,1H),7.94(s,1H),7.92–7.86(m,2H),7.76(d,J=8.5Hz,2 H),7.66–7.61(m,1H),7.19–7.12(m,1H),6.96(dd,J=8.9,2.2Hz,1H),4.02(s,3H),3.79(s,2H).

[0124] Step 2: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide

[0125] Step 2 follows the same preparation method as Step 1 in Example 8, except that 1-2 in Step 1 of Example 8 is replaced with 10-1. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a pale yellow solid. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 10 (12.2 mg, 25% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.46(s,1H),8.11(s,1H),8.00(s,1H),7.90(d,J=8.4Hz,2H),7.76(dd,J=20.0,8.7Hz,3H),7.54(s,1H), 7.46(dd,J=9.0,2.0Hz,1H),6.51(dd,J=16.8,1.3Hz,1H),6.32(dd,J=16.8,10.2Hz,1H),5.84(d,J=10.2Hz,1H),4.02(s,3H).

[0126] Example 11

[0127] N-(1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 11)

[0128] Step 1: Preparation of N-(1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0129] Step 1 follows the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 9-2 prepared in Step 2 of Example 9. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (DCM:MeOH = 150:1) to obtain a crude product that is a pale yellow gel. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 11 (99 mg, 56% yield) as a white solid. 1 HNMR (300MHz, CDCl3) δ8.23(d,J=0.9Hz,1H),7.94–7.71(m,6H),7.38(dd,J=8.9,2.1Hz,1H),6.67(s,1H),3.03(s,3H).

[0130] Example 12

[0131] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide (compound 12)

[0132] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridine

[0133] Step 1 employs the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 is replaced with 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine (Bide, BD224019), and 4-trifluoromethylphenylboronic acid is replaced with 4-trifluoromethoxyphenylboronic acid. After concentration under reduced pressure, the residue was obtained. The residue was purified by column chromatography (PE:EA = 25:1) to give the title compound 12-1 (85 mg, 10.5% yield) as a yellow solid. 1 H NMR (300MHz, CDCl3) δ9.52(d,J=2.4Hz,1H),8.93(d,J=2.5Hz,1H),8.36–8.27(m,2H),7.46–7.38(m,2H).

[0134] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridine-5-amine

[0135] Step 2 uses the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 12-1. After concentration under reduced pressure, crude product 12-2, which is a yellow solid, is obtained and used directly in the next reaction without purification.

[0136] Step 3: Preparation of 3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridine-5-amine

[0137] Step 3 uses the same preparation method as step 1 of Example 10, except that 1-2 in step 1 of Example 10 is replaced with 12-2. After concentration under reduced pressure, a yellow gelatinous crude product 12-3 is obtained, which is used directly in the next reaction without purification.

[0138] Step 4: Preparation of N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide

[0139] Step 4 follows the same preparation method as step 2 in Example 10. The 10-1 in step 2 of Example 10 is replaced with 12-3. After purification by column chromatography (DCM:MeOH = 50:1), a crude product in the form of a yellow solid is obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 12 (2.1 mg, 2% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO-d6) δ10.65(s,1H),8.94(d,J=2.3Hz,1H),8.79(d,J=2.3Hz,1H),8.50–8.39(m,3H),8.06(s,1H),7.6 6–7.56(m,2H),6.51(dd,J=17.0,10.1Hz,1H),6.35(dd,J=17.0,2.0Hz,1H),5.86(dd,J=10.1,2.0Hz,1H),3.98(s,3H).

[0140] Example 13

[0141] Methyl 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylate (Compound 13)

[0142] Step 1: Preparation of methyl 3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylate

[0143] Step 1 employed the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 was replaced with methyl 3-bromo-1H-indazole-6-carboxylate (BYD, BD209901). After concentration under reduced pressure, the residue was obtained and purified by column chromatography (PE:EA = 20:1) to give the title compound 13-1 (310 mg, 78% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ8.47(t,J=1.0Hz,1H),8.00(dd,J=8.5,1.2Hz,1H),7.93–7.81(m,4H),7.77(dd,J=8.5,0.8Hz,1H),3.99(s,3H).

[0144] Step 2: Preparation of methyl 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylate

[0145] Step 2 follows the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 is replaced with 13-1. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (PE:EA = 3:1) to obtain a crude product that is a pale yellow solid. Diethyl ether (4.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 13 (157 mg, 78.5% yield) that is a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.50(t,J=1.1Hz,1H),8.12(s,1H),8.05–7.90(m,5H),7.84(d,J=8.5Hz,2H),4.04(s,3H),3.99(s,3H).

[0146] Example 14

[0147] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (Compound 14)

[0148] Step 1: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid

[0149] Compound 13 (80 mg, 0.2 mmol) prepared in Example 13 was dissolved in a solution of EtOH (2.0 mL) and water (1.0 mL). LiOH·H₂O (42 mg, 1 mmol; LY-TRCL469125) was added in portions, and the mixture was stirred at 80 °C for 4 h. TLC (PE:EA = 1.5:1, R f=0.2) indicates that compound 13 was completely consumed and a new spot was detected. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (5.0 mL) to adjust the pH to ~1. The mixture was stirred at room temperature for 30 min, and filtered to obtain a crude product as a white solid. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded a white solid, compound 14 (62 mg, 80% yield): 1 H NMR (300MHz, DMSO-d6) δ13.37(s,1H),8.58(d,J=0.8Hz,1H),8.44(t,J=1.0Hz,1H),8.29(dd,J=8.5,0.8Hz,1H) ,8.14(d,J=0.8Hz,1H),8.08(d,J=8.6Hz,2H),8.01(d,J=8.8Hz,2H),7.90(dd,J=8.5,1.3Hz,1H),3.97(s,3H).

[0150] Example 15

[0151] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-yl)acrylamide (compound 15)

[0152] Step 1: Preparation of 3-bromo-5-nitro-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole

[0153] Step 1 employed the same preparation method as Step 1 in Example 7, except that 3-bromo-6-nitro-1H-indazole in Step 1 of Example 7 was replaced with 3-bromo-5-nitro-1H-indazole, and 4-iodo-1-methylimidazole was replaced with 1-bromo-4-(trifluoromethylthio)benzene (Adamas; 013436328). After concentration under reduced pressure, the residue was obtained and purified by column chromatography (PE:EA = 50:1) to give the title compound 15-1 (196 mg, 23.5% yield) as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.70(dd,J=2.1,0.6Hz,1H),8.41(dd,J=9.3,2.2Hz,1H),7.91–7.86(m,2H),7.84(dd,J=9.3,0.6Hz,1H),7.82–7.78(m,2H).

[0154] Step 2: Preparation of 3-bromo-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-amine

[0155] Step 2 uses the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 15-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (PE:EA = 7.5:1) to obtain 15-2 (150 mg, 82% yield), a pale brownish-yellow solid. 1 H NMR (300MHz, CDCl3) δ7.78 (s, 4H), 7.60 (dd, J = 9.0, 0.7Hz, 1H), 6.97 (dd, J = 8.9, 2.2Hz, 1H), 6.87 (dd, J = 2.3, 0.7Hz, 1H), 3.82 (s, 2H).

[0156] Step 3: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-amine

[0157] Step 3 uses the same preparation method as step 1 of Example 10, except that 1-2 in step 1 of Example 10 is replaced with 15-2. After concentration under reduced pressure, a yellow gelatinous crude product 15-3 is obtained, which is used directly in the next reaction without purification.

[0158] Step 4: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-yl)acrylamide

[0159] Step 4 uses the same preparation method as step 2 of Example 10. The 10-1 in step 2 of Example 10 is replaced with 15-3. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a yellow solid is obtained. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 15 (73 mg, 55% yield) in the form of a yellow solid. 1 H NMR (400MHz, CDCl3) δ8.52–8.41(m,1H),8.10(d,J=0.8Hz,1H),8.00(s,1H),7.89–7.77(m,4H),7.73(d,J=9.0Hz,1H),7.64(s,1H), 7.45(dd,J=9.0,1.9Hz,1H), 6.51(dd,J=16.8,1.3Hz,1H), 6.32(dd,J=16.8,10.2Hz,1H), 5.83(dd,J=10.1,1.3Hz,1H), 4.01(s,3H).

[0160] Example 16

[0161] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-carboxylic acid methyl ester (Compound 16)

[0162] Example 16 used the same preparation method as Example 13, except that methyl 3-bromo-1H-indazole-6-carboxylate in step 1 of Example 13 was replaced with methyl 3-bromo-1H-indazole-5-carboxylate (Bide, BD210997), and 4-trifluoromethylphenylboronic acid was replaced with 4-trifluoromethoxyphenylboronic acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Hexane (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 16 (399 mg, 96% yield) in the form of a white solid. 1 H NMR(400MHz, CDCl3)δ8.69(dd,J=1.6,0.8Hz,1H),8.17–8.11(m,2H),8.04(s,1H),7.83–7.7 6(m,2H),7.71(dd,J=8.9,0.8Hz,1H),7.42(dt,J=8.0,1.0Hz,2H),4.05(s,3H),3.99(s,3H).

[0163] Example 17

[0164] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-carboxylic acid (Compound 17)

[0165] Example 17 was prepared using the same method as Example 14, except that 13 in step 1 of Example 14 was replaced with 16. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (6.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 17 (332 mg, 83% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ13.07 (s, 1H), 8.65 (dd, J = 1.6, 0.8Hz, 1H), 8.57 (d, J = 0. 8Hz,1H),8.11–8.05(m,2H),7.99–7.91(m,3H),7.66–7.59(m,2H),3.99(s,3H).

[0166] Example 18

[0167] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-carboxamide (Compound 18)

[0168] Step 1: Preparation of N-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-carboxamide

[0169] Under ice bath conditions, Et3N (30 μL, 0.2 mmol) and HATU (57 mg, 0.15 mmol; Adamas, 01025670) were added to a solution of compound 17 (40 mg, 0.1 mmol) prepared in Example 17 dissolved in DMF (2 mL). After stirring for 20 min, MeNH2·HCl (13.5 mg, 0.2 mmol) was added, and the mixture was stirred at room temperature for 2 h. TLC (PE:EA = 1:1, R f =0.05) indicates that compound 17 was completely consumed and a new spot was detected. The reaction solution was poured into water (20 mL), extracted with DCM (10 mL × 3), the organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (DCM:MeOH = 30:1) to obtain a white gel-like crude product. Diethyl ether (3.0 mL) was added to the crude product, stirred at room temperature for 1 h, and filtered to obtain the title compound 18 (39.3 mg, 95% yield) as a white solid: 1 H NMR(400MHz,DMSO-d6)δ8.65(q,J=4.3Hz,1H),8.61–8.56(m,1H),8.52(s,1H),8.19(d,J=0.8Hz,1H), 8.05(dd,J=9.0,1.6Hz,1H),8.00–7.89(m,3H),7.67–7.57(m,2H),3.99(s,3H),2.87(d,J=4.5Hz,3H).

[0170] Example 19

[0171] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)acrylamide (compound 19)

[0172] Example 19 used the same preparation method as Example 10, except that step 1-2 in Example 10 was replaced with step 2 of Example 5, which was prepared as 5-2. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 19 (61 mg, 36% yield) in the form of a white solid. 1 H NMR (400MHz, CDCl3) δ8.49–8.40(m,1H),8.09(d,J=0.8Hz,1H),7.99(s,1H),7.80–7.73(m,2H),7.65(d,J=8.9Hz,1H),7.58(s,1H),7.44(dd, J=8.9,2.0Hz,1H),7.42–7.35(m,2H),6.50(dd,J=16.8,1.3Hz,1H),6.31(dd,J=16.8,10.2Hz,1H),5.83(dd,J=10.1,1.3Hz,1H),4.01(s,3H).

[0173] Example 20

[0174] 1-Cyclopropyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)urea (Compound 20)

[0175] Step 1: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-formyl azide

[0176] Under ice bath conditions, Et3N (125 μL, 0.9 mmol) and DPPA (195 μL, 0.9 mmol; Adamas, 011141547) were added dropwise to a solution of compound 17 (302 mg, 0.75 mmol) prepared in Example 17 dissolved in DCM (3 mL), and the mixture was stirred at room temperature for 3 h. TLC (PE:EA = 2:1, R f =0.4) indicates that compound 17 was completely consumed and a new spot was detected. Concentration under reduced pressure yielded a residue, which was purified by column chromatography (PE:EA = 3:1) to give the title compound 20-1 as a white solid. 1H NMR (400MHz, CDCl3) δ8.69 (dd, J=1.7, 0.8Hz, 1H), 8.17–8.09 (m, 2H), 8.04 (s, 1H) ,7.82–7.75(m,2H),7.72(dd,J=9.0,0.8Hz,1H),7.46–7.40(m,2H),4.06(s,3H).

[0177] Step 2: Preparation of 1-cyclopropyl-3-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)urea

[0178] Dissolve 20-1 (64 mg, 0.15 mmol) in toluene (1.0 mL) and heat and stir at 100 °C for 3 h. TLC (PE:EA = 2:1, R f =0.05) showed complete consumption of 20-1 and a new spot was detected. The temperature was lowered to 60°C, and cyclopropylamine (11.5 μL, 0.165 mmol; Adamas, 011135491) was added dropwise, with stirring for 1 h. TLC (DCM:MeOH = 40:1, R f =0.1) indicates complete consumption of the intermediate and detection of a new spot. Cool to room temperature, add n-hexane (1.0 mL), stir at room temperature for 1 h, and filter to give title compound 20 (70 mg, 100% two-step yield) as a white solid: 1 H NMR (400MHz, DMSO-d6) δ8.48(s,1H),8.31(s,1H),8.22(d,J=1.9Hz,1H),7.98(d,J=0.8Hz,1H),7.96–7.89(m,2H),7.81(d,J=9.1Hz,1H),7.61–7.55 (m,2H),7.48(dd,J=9.1,2.0Hz,1H),6.48(d,J=2.7Hz,1H),3.98(s,3H),2 .57(tq,J=6.9,3.5Hz,1H),0.66(td,J=6.9,4.7Hz,2H),0.48–0.40(m,2H).

[0179] Example 21

[0180] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)methanesulfonamide (compound 21)

[0181] Example 21 was prepared using the same method as Example 1, except that 3-bromo-5-nitro-1H-indazole was replaced with 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine, and 4-trifluoromethylphenylboronic acid was replaced with 4-trifluoromethoxyphenylboronic acid. After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a yellow gel was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 21 (25 mg, 23% yield) as a yellow solid. 1 H NMR (300MHz, DMSO-d6) δ9.96(s,1H),8.59(d,J=2.2Hz,1H),8.54–8.23(m,4H),8.10(s,1H),7.60(d,J=8.6Hz,2H),3.98(s,3H),3.08(s,3H).

[0182] Example 22

[0183] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)methanesulfonamide (compound 22)

[0184] Example 22 was prepared using the same method as Example 1, except that the 3-bromo-5-nitro-1H-indazole in Example 1 was replaced with 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine. After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a yellow gel was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 22 (16 mg, 18.5% yield) as a yellow solid. 1 H NMR(400MHz,DMSO-d6)δ10.00(s,1H),8.65–8.58(m,3H),8.53(s,1H),8.36(d,J=2 .4Hz,1H),8.12(d,J=0.8Hz,1H),7.96(d,J=8.7Hz,2H),3.98(s,3H),3.09(s,3H).

[0185] Example 23

[0186] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-sulfonamide (Compound 23)

[0187] Example 23 used the same preparation method as Example 4, except that 4-2 in step 3 of Example 4 was replaced with 15-2 prepared in step 2 of Example 15. After purification by column chromatography (DCM:MeOH = 150:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 23 (11 mg, 23.5% yield) in the form of a pale yellow-white solid. 1 H NMR(300MHz, DMSO-d6)δ8.56(s,1H),8.48(dd,J=1.7,0.7Hz,1H),8.22–8.14(m,1H),8.11(d,J=0.8Hz ,1H),8.08–8.01(m,2H),8.00–7.88(m,3H),7.57(q,J=5.0Hz,1H),4.00(s,3H),2.44(d,J=5.0Hz,3H).

[0188] Example 24

[0189] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 24)

[0190] Example 24 was prepared using the same method as Example 1, except that step 3 of Example 1, 1-2, was replaced with step 2 of Example 15, 15-2. After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 24 (28 mg, 30% yield) in the form of a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ9.72(s,1H),8.37(s,1H),8.07–7.97(m,4H),7.96–7.87(m,3H),7.47(dd,J=9.0,2.0Hz,1H),3.98(s,3H),3.01(s,3H).

[0191] Example 25

[0192] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(3-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 25)

[0193] Example 25 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 3-trifluoromethylphenylboronic acid (Adamas, 01022844). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 25 (56 mg, 64% yield) as a white solid. 1 H NMR (300MHz, DMSO-d6) δ9.74(s,1H),8.40(s,1H),8.16(d,J=8.3Hz,1H),8.09(s,1H),8.03(d,J=0.8Hz,1H),7.94 (d,J=9.0Hz,1H),7.91–7.79(m,2H),7.75(d,J=7.8Hz,1H),7.47(dd,J=9.0,2.0Hz,1H),3.98(s,3H),3.00(s,3H).

[0194] Example 26

[0195] N-(1-(cyclohexyl-1-en-1-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)methanesulfonamide (compound 26)

[0196] Example 26 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with cyclohexene-1-ylboronic acid (BYD, BD2927). After purification by column chromatography (DCM:MeOH = 75:1), a white gel-like crude product was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 26 (34 mg, 46% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.59 (s, 1H), 8.25 (d, J = 0.8Hz, 1H), 7.91 (d, J = 0.8Hz, 1 H),7.77(d,J=1.9Hz,1H),7.72(d,J=9.0Hz,1H),7.34(dd,J=9.0,2.0Hz,1H),6. 03(dt,J=4.0,2.4Hz,1H),3.94(s,3H),2.96(s,3H),2.61(ddt,J=6.5,4.4,1.9H z,2H),2.29(ddt,J=8.7,6.0,2.6Hz,2H),1.88–1.77(m,2H),1.74–1.64(m,2H).

[0197] Example 27

[0198] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indazole-5-yl)methanesulfonamide (compound 27)

[0199] Example 27 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 5-(trifluoromethyl)-pyridine-2-boronic acid (BYD, BD232534). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 27 (14 mg, 32% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO-d6)δ9.81(s,1H),8.94(dt,J=2.0,1.0Hz,1H),8.81–8.74(m,1H),8.45(s,1H),8.37(dd,J=9.0,2.5Hz,1 H),8.18(d,J=8.8Hz,1H),8.09(d,J=0.8Hz,1H),7.94–7.87(m,1H),7.54(dd,J=9.0,2.1Hz,1H),3.99(s,3H),3.03(s,3H).

[0200] Example 28

[0201] N-(1-(4-(adamantane-1-yl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 28)

[0202] Example 28 was prepared using the same method as Example 7, except that 3-bromo-6-nitro-1H-indazole in step 1 of Example 7 was replaced with 3-bromo-5-nitro-1H-indazole, 4-iodo-1-methylimidazolium was replaced with 4-adamantylbromobenzene (Bide, BD233474), and 4-trifluoromethylphenylboronic acid in step 4 was replaced with 1-methyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 28 (15 mg, 18% yield) in the form of a white solid. 1H NMR(300MHz, DMSO-d6)δ9.67(s,1H),8.32(s,1H),7.98(d,J=0.8Hz,1H),7.89–7.80(m,2H),7.76–7.66(m,2H),7.62–7.53(m ,2H),7.40(dd,J=9.0,2.0Hz,1H),3.97(s,3H),2.99(s,3H),2.14–2.05(m,3H),1.93(d,J=2.9Hz,6H),1.77(d,J=3.1Hz,6H).

[0203] Example 29

[0204] N-(3-(quinolin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 29)

[0205] Example 29 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with quinoline-5-boric acid (Bide, BD7505). After purification by column chromatography (DCM:MeOH = 50:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 29 (32 mg, 56% yield) in the form of a yellow solid. 1 H NMR (300MHz, DMSO-d6) δ9.86 (s, 1H), 9.13 (d, J = 4.4Hz, 1H), 8.47 (d, J = 8.4Hz, 1H), 8.19 (d, J = 8.5Hz, 3H), 8.15 (d, J = 9.0Hz, 1H), 8.02(d,J=8.6Hz,2H),7.91(d,J=4.4Hz,1H),7.88(d,J=7.0Hz,1H),7.74–7.67(m,2H),7.56(dd,J=9.1,2.0Hz,1H),2.98(s,3H).

[0206] Example 30

[0207] N-(3-(furan-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 30)

[0208] Example 30 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with furan-2-boric acid (Leyan, 1020048). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 30 (24 mg, 48% yield) in the form of a yellow solid. 1 H NMR(300MHz, DMSO-d6)δ9.88(s,1H),8.09(d,J=8.6Hz,2H),8.07(d,J=4.1Hz,1H),8.03(s,1H),8.00–7.99(m,1H),7.9 7(d,J=8.5Hz,2H),7.52(dd,J=9.1,2.1Hz,1H),7.12(dd,J=3.5,0.8Hz,1H),6.78(dd,J=3.4,1.8Hz,1H),3.01(s,3H).

[0209] Example 31

[0210] N-(3-(cyclopenten-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 31)

[0211] Example 31 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with cyclopenten-1-ylboronic acid (BYD, BD122948). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 31 (23 mg, 46% yield) in the form of a white solid. 1 H NMR(300MHz, DMSO-d6)δ9.79(s,1H),8.02(dd,J=11.1,8.8Hz,3H),7.97–7.91(m,3H),7.46(dd,J=9.1,2.0H z,1H),6.60(t,J=2.2Hz,1H),3.00(s,3H),2.91(d,J=7.8Hz,2H),2.67(d,J=7.2Hz,2H),2.07–1.95(m,2H).

[0212] Example 32

[0213] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 32)

[0214] Example 32 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with thiophene-2-boric acid (Bide, BD9413). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a brownish-yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 32 (24 mg, 46% yield) in the form of a brownish-yellow solid. 1 H NMR(300MHz,DMSO-d6)δ9.89(s,1H),8.13–8.02(m,4H),7.98(d,J=8.6Hz,2H) ,7.77(d,J=2.8Hz,2H),7.51(d,J=9.2Hz,1H),7.37–7.28(m,1H),3.03(s,3H).

[0215] Example 33

[0216] N-(3-(pyrimidin-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 33)

[0217] Example 33 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 5-pyrimidineboric acid (Leyan, 1016490). After purification by column chromatography (DCM:MeOH = 25:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 33 (30 mg, 57% yield) in the form of a yellow solid. 1 H NMR(400MHz,DMSO-d6)δ9.88(s,1H),9.42(s,2H),9.35(s,1H),8.16(d,J=8.3Hz,2H) ,8.09(d,J=9.1Hz,1H),8.04–7.96(m,3H),7.54(dd,J=9.1,2.0Hz,1H),3.05(s,3H).

[0218] Example 34

[0219] N-(3-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 34)

[0220] Example 34 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with phenylboronic acid (BYD, BD3573). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 34 (38 mg, 74% yield) in the form of a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ9.82 (s, 1H), 8.13 (d, J = 8.4Hz, 2H), 8.07 (d, J = 9.1Hz, 1H),8.02–7.94(m,5H),7.62(t,J=7.5Hz,2H),7.56–7.50(m,2H),3.01(s,3H).

[0221] Example 35

[0222] N-(3-(naphth-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 35)

[0223] Example 35 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-naphthoboric acid (Leyan, 1020910). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 35 (25 mg, 43% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.79(s,1H),8.28(d,J=8.2Hz,1H),8.18(d,J=8.4Hz,2H),8.14(dd,J=8.5,3.1Hz,2H),8.10(d,J=7.9Hz,1H),8.00(d, J=8.7Hz,2H),7.88(dd,J=7.0,1.1Hz,1H),7.77–7.71(m,1H),7.66–7.61(m,1H),7.60–7.56(m,2H),7.54(dd,J=9.0,2.0Hz,1H),2.95(s,3H).

[0224] Example 36

[0225] N-(3-(naphth-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 36)

[0226] Example 36 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-naphthoboric acid (Bide, BD0424). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 36 (39 mg, 68% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO-d6)δ9.86(s,1H),8.55(s,1H),8.20–8.13(m,5H),8.10(d,J=8.9Hz,2H),8.06–8.02( m,1H),8.00(d,J=8.5Hz,2H),7.62(td,J=7.9,7.0,4.0Hz,2H),7.56(dd,J=9.1,2.0Hz,1H),3.03(s,3H).

[0227] Example 37

[0228] N-(3-(benzofuran-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 37)

[0229] Example 37 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with benzofuran-2-boric acid (Leyan, 1047654). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 37 (35 mg, 62% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.94(s,1H),8.20(d,J=2.0Hz,1H),8.14(d,J=8.4Hz,2H),8.08(d,J=9.1Hz,1H),8.01(d,J=8.5Hz,2H),7.81(d,J=7.7Hz,1H) ,7.75(d,J=8.0Hz,1H),7.59(d,J=1.0Hz,1H),7.56(dd,J=9.1,2.1Hz,1H), 7.44(td,J=8.3,7.8,1.4Hz,1H),7.36(td,J=7.4,1.1Hz,1H),3.06(s,3H).

[0230] Example 38

[0231] N-(3-(1-methyl-1H-pyrazole-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 38)

[0232] Example 38 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-methyl-1H-pyrazole-5-boric acid (BYD, BD164764). After purification by column chromatography (DCM:MeOH = 50:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 38 (41 mg, 47% yield) in the form of a white solid. 1 HNMR (400MHz, DMSO-d6) δ9.88(s,1H),8.14(d,J=8.4Hz,2H),8.09(d,J=9.1Hz,1H),7.99(d,J=8.6Hz,2H),7.85(d, J=2.0Hz,1H),7.69(d,J=1.9Hz,1H),7.53(dd,J=9.1,2.0Hz,1H),6.89(d,J=2.0Hz,1H),4.19(s,3H),3.02(s,3H).

[0233] Example 39

[0234] N-(3-(1-(methanesulfonyl)-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 39)

[0235] Example 39 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with 1-methylsulfonyl-4-(tetramethyl-1,3,2-dioxoboronyl-2-yl)-1H-pyrazole (Bide, BD01416355). After purification by column chromatography (DCM:MeOH = 20:1), a crude product in the form of a light yellow solid was obtained. DCM (1.0 mL) and diethyl ether (2.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 39 (38.3 mg, 51% yield) in the form of a light yellow solid. 1 H NMR (400MHz, DMSO) δ9.75(s,1H),8.24(s,2H),8.08(d,J=8.5Hz,2H),8.02(d,J=9.0Hz,1H ),7.95(s,1H),7.95–7.88(m,2H),7.48(dd,J=9.0,2.0Hz,1H),4.59(s,3H),3.01(s,3H).

[0236] Example 40

[0237] N-(1,3-bis(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 40)

[0238] Example 40 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 40 (37 mg, 62% yield) in the form of a yellow solid. 1 H NMR(300MHz,DMSO-d6)δ9.88(s,1H),8.23(d,J=8.1Hz,2H),8.14(d,J=8.4Hz,2H), 8.08(d,J=9.1Hz,1H),8.04–7.95(m,5H),7.53(dd,J=9.1,2.0Hz,1H),3.02(s,3H).

[0239] Example 41

[0240] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 41)

[0241] Example 41 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 41 (48 mg, 88% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.70(s,1H),8.36(s,1H),8.01(s,1H),7.96–7.93(m,2H),7.91(d,J=8.9Hz,1H ),7.89(d,J=1.9Hz,1H),7.60(d,J=8.3Hz,2H),7.45(dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.00(s,3H).

[0242] Example 42

[0243] N-(1-(4-cyclohexylphenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 42)

[0244] Example 42 uses the same preparation method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 is replaced with 4-cyclohexylphenylboronic acid (Bide, BD01391414). The crude product was purified by column chromatography (DCM:MeOH = 40:1) to obtain a white solid. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 42 (46 mg, 85% yield) as a white solid: ¹H NMR (400 MHz, DMSO-d6) δ 9.66 (s, 1H), 8.32 (s, 1H), 7.98 (s, 1H), 7.90–7.77 (m, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.43 (t, J = 9.8 Hz, 3H), 3.98 (s, 3H), 2.99 (s, 3H), 2.62 (d, J = 10.4 Hz, 1H), 1.87–1.71 (m, 4H), 1.56–1.15 (m, 6H).

[0245] Example 43

[0246] N-(1-(4-methoxyphenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 43)

[0247] Example 43 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 43 was replaced with 4-methoxyphenylboronic acid. After purification by column chromatography (DCM:MeOH = 30:1), a crude product in the form of a light pink solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 43 (40 mg, 78% yield) in the form of a light pink solid. 1 H NMR (300MHz, DMSO-d6) δ9.66(s,1H),8.33(s,1H),8.01–7.95(m,1H),7.85(d,J=1.9Hz,1H),7.73(d,J=9.1Hz, 1H),7.70–7.64(m,2H),7.40(dd,J=9.0,2.0Hz,1H),7.19–7.10(m,2H),3.97(s,3H),3.85(s,3H),2.99(s,3H).

[0248] Example 44

[0249] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-phenyl-1H-indazole-5-yl)methanesulfonamide (compound 44)

[0250] Example 44 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 44 was replaced with phenylboronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 44 (34 mg, 78% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.69(s,1H),8.35(s,1H),8.00(s,1H),7.87(dd,J=5.5,3.4Hz,2H ),7.82–7.77(m,2H),7.61(t,J=7.9Hz,2H),7.45–7.38(m,2H),3.98(s,3H),3.00(s,3H).

[0251] Example 45

[0252] N-(1-(4-fluorophenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 45)

[0253] Example 45 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 45 was replaced with 4-fluorophenylboronic acid (BYD, BD9939). After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 45 (39 mg, 84% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.69(s,1H),8.35(s,1H),8.00(s,1H),7.87(d,J=1 .9Hz,1H),7.85–7.79(m,3H),7.48–7.41(m,3H),3.98(s,3H),3.00(s,3H).

[0254] Example 46

[0255] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(naphth-1-yl)-1H-indazole-5-yl)methanesulfonamide (compound 46)

[0256] Example 46 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 1-naphthoboronic acid. After purification by column chromatography (DCM:MeOH = 75:1), a white, gel-like crude product was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 46 (10.4 mg, 17% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.64(s,1H),8.35(d,J=0.8Hz,1H),8.19–8.10(m,2H),8.00(d,J=0.8Hz,1H),7.93(dd,J=1.9,0.7Hz,1H),7.77–7.69(m ,2H),7.63(ddd,J=8.2,5.8,2.3Hz,1H),7.56–7.49(m,2H),7.34(dd,J=9.0,1.9Hz,1H),7.23(dd,J=9.0,0.7Hz,1H),3.97(s,3H),3.00(s,3H).

[0257] Example 47

[0258] 1,1,1-Trifluoro-N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (Compound 47)

[0259] Step 1: Preparation of 1,1,1-trifluoro-N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0260] Step 1 uses the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 10-1 prepared in Step 1 of Example 10, and the methanesulfonic anhydride is replaced with trifluoromethanesulfonic anhydride (Adamas, 01065791). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a light brown solid is obtained. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 47 (31.2 mg, 32% yield) in the form of a light brown solid. 1 H NMR (400MHz, DMSO-d6) δ12.02(s,1H),8.47(s,1H),8.18–8.01(m,4H),8.01–7.87(m,3H),7.45(dd,J=9.0,2.1Hz,1H),3.98(s,3H).

[0261] Example 48

[0262] 1,1,1-Trifluoro-N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)methanesulfonamide (Compound 48)

[0263] Example 48 was prepared using the same method as step 3 of Example 1, except that 1-2 in step 3 of Example 1 was replaced with 19-1 prepared in step 1 of Example 19, and the methanesulfonic anhydride was replaced with trifluoromethanesulfonic anhydride. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a light brown gel was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 48 (25.2 mg, 25% yield) in the form of a light brown solid. 1 H NMR(400MHz,DMSO-d6)δ11.99(s,1H),8.45(s,1H),8.02(d,J=0.8Hz,1H),7.99–7 .90(m,4H),7.60(dd,J=9.0,1.0Hz,2H),7.41(dd,J=9.0,2.0Hz,1H),3.98(s,3H).

[0264] Example 49

[0265] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)propane-1-sulfonamide (Compound 49)

[0266] Example 49 was prepared using the same method as Example 10, except that step 1-2 in Example 10 was replaced with step 2 of Example 5 (prepared as 5-2), and acryloyl chloride in step 2 was replaced with 1-propylsulfonyl chloride (BYD, BD60318). After purification by chromatography (DCM:MeOH = 100:1), a pale yellow gel-like crude product was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 49 (37 mg, 39% yield) as a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.78(s,1H),8.32(s,1H),8.02–7.81(m,5H),7.59(d,J=8.6Hz,2H),7.44 (dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.14–3.00(m,2H),1.79–1.64(m,2H),0.94(t,J=7.4Hz,3H).

[0267] Example 50

[0268] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)ethylenesulfonamide (compound 50)

[0269] Example 50 was prepared using the same method as Example 10, except that step 1-2 in Example 10 was replaced with step 2 of Example 5 (prepared as 5-2), and acryloyl chloride in step 2 was replaced with 2-chloroethanesulfonyl chloride (BYD, BD73577). After purification by column chromatography (DCM:MeOH = 75:1), a pale yellow gel-like crude product was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 50 (59 mg, 64% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.97 (s, 1H), 8.32 (s, 1H), 8.07–7.85 (m, 4H), 7.81 (d, J = 2.0Hz, 1H), 7.67–7. 52(m,2H),7.38(dd,J=9.0,2.0Hz,1H),6.83(dd,J=16.4,9.9Hz,1H),6.14–5.97(m,2H),3.98(s,3H).

[0270] Example 51

[0271] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethylenesulfonamide (compound 51)

[0272] Example 51 was prepared using the same method as Example 10, except that acryloyl chloride in step 2 of Example 10 was replaced with 2-chloroethanesulfonyl chloride. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (5.0 mL) and DCM (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 51 (21.6 mg, 24% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO-d6) δ10.02(s,1H),8.35(s,1H),8.08–7.97(m,4H),7.94(d,J=8.7Hz,2H),7.83(d,J =1.9Hz,1H),7.42(dd,J=9.1,2.0Hz,1H),6.84(dd,J=16.4,9.9Hz,1H),6.14–5.98(m,2H),3.98(s,3H).

[0273] Example 52

[0274] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethanesulfonamide (compound 52)

[0275] Example 52 was prepared using the same method as Example 10, except that acryloyl chloride in step 2 of Example 10 was replaced with ethylsulfonyl chloride (Adamas, 01093003). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale pink gel was obtained. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 52 (19.5 mg, 22% yield) in the form of a pale pink solid. 1 H NMR (400MHz, DMSO-d6) δ9.83(s,1H),8.35(s,1H),8.06(d,J=8.5Hz,2H),8.03–7.98(m,2H),7.94(d,J=8.5Hz,2H ),7.88(d,J=2.0Hz,1H),7.48(dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.11(q,J=7.3Hz,2H),1.23(t,J=7.3Hz,3H).

[0276] Example 53

[0277] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)ethanesulfonamide (compound 53)

[0278] Example 53 was prepared using the same method as Example 10, except that step 1-2 in Example 10 was replaced with 5-2 prepared in Example 5, and acryloyl chloride in step 2 was replaced with ethylsulfonyl chloride. After purification by column chromatography (DCM:MeOH = 100:1), a pale yellow gel-like crude product was obtained. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 53 (43 mg, 46% yield) as a creamy white solid. 1 H NMR(300MHz,DMSO-d6)δ9.82(s,1H),8.33(s,1H),8.05–7.81(m,5H),7.64–7.55(m,2H) ,7.44(dd,J=9.1,2.0Hz,1H),3.97(s,3H),3.10(q,J=7.3Hz,2H),1.22(t,J=7.3Hz,3H).

[0279] Example 54

[0280] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-carboxylic acid methyl ester (compound 54)

[0281] Step 1: Preparation of methyl 1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-carboxylate

[0282] Dry DMF (8 mL) was added to a mixture of methyl 1H-indole-5-carboxylate (700 mg, 4 mmol; BD12879), 1-iodo-4-(trifluoromethoxy)benzene (940 μL, 6 mmol; BD17369), CuI (76 mg, 0.4 mmol), Cs₂CO₃ (2608 mg, 8 mmol), and N,N'-dimethylethylenediamine (430 μL, 4 mmol; BD216125), and the mixture was heated and stirred at 120 °C for 8 h under an argon atmosphere. TLC (PE:EA = 4:1, R f =0.6) indicates partial consumption of the starting material and detection of a new spot. Cool to room temperature, pour the reaction solution into water (100 mL), extract with EA (50 mL × 3), wash the organic layer with saturated brine (30 mL × 2), dry with anhydrous sodium sulfate, concentrate under reduced pressure to obtain the residue, and purify the residue by column chromatography (PE:EA = 100:1) to obtain the title compound 54-1 (492 mg, 37% yield) as a yellow oil. 1 H NMR (400MHz, CDCl3) δ8.25–8.18(m,1H),7.88(dd,J=8.3,1.4Hz,1H),7.71(dd,J=8.2,0.7Hz,1H),7. 57–7.51(m,2H),7.45(d,J=3.2Hz,1H),7.44–7.38(m,2H),6.74(dd,J=3.2,0.9Hz,1H),3.93(s,3H).

[0283] Step 2: Preparation of methyl 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-carboxylate

[0284] Under ice bath conditions, NBS (311 mg, 1.75 mmol; Bio-Tech, BD40868) was added in portions to a solution of 54-1 (490 mg, 1.46 mmol) dissolved in DMF (10 mL), and the mixture was stirred at room temperature for 0.5 h. TLC (PE:EA = 10:1, R f=0.5) showed that 54-1 was completely consumed and a new spot was detected. After cooling to room temperature, the reaction mixture was poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was then purified by column chromatography (PE:EA = 150:1) to give the title compound 54-2 (512 mg, 85% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ8.18 (dd, J=1.4, 0.7Hz, 1H), 7.95 (dd, J=8.4, 1.4Hz, 1H), 7.67(dd,J=8.4,0.7Hz,1H),7.54–7.48(m,3H),7.45–7.39(m,2H),3.93(s,3H).

[0285] Step 3: Preparation of methyl 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-carboxylate

[0286] To a mixture of 54-2 (166 mg, 0.4 mmol), pinacol 1-methyl-4-pyrazoleboronic acid (126 mg, 0.6 mmol; BD59474), Pd(dppf)Cl2 (45 mg, 0.06 mmol; BD22387), and K2CO3 (110 mg, 0.8 mmol), 1,4-Dioxane (4.5 mL) and water (1.5 mL) were added, and the mixture was heated and stirred at 80 °C for 2 h under an argon atmosphere. TLC (PE:EA = 3:1, R f =0.05) showed that 54-2 was completely consumed and a new spot was detected. After cooling to room temperature and concentration under reduced pressure, the residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 150:1) to give the title compound 54 (94 mg, 57% yield) as a light brown solid. 1 H NMR (300MHz, CDCl3) δ8.23(d,J=1.3Hz,1H),7.93(dd,J=8.4,1.4Hz,1H),7.83(d,J=8.0H z,2H),7.72(s,1H),7.64–7.49(m,3H),7.43(d,J=8.4Hz,2H),4.04(s,3H),3.94(s,3H).

[0287] Example 55

[0288] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-carboxylic acid (Compound 55)

[0289] Example 55 was prepared using the same method as Example 14, except that compound 13 in step 1 of Example 14 was replaced with compound 54. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (6.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 55 (60 mg, 74% yield) as a pale yellowish-brown solid. 1 H NMR(400MHz,DMSO-d6)δ12.84(s,1H),8.24(s,1H),8.19–8.10(m,2H),8.00(d,J =8.4Hz,1H),7.90(s,1H),7.86–7.75(m,3H),7.66(d,J=8.4Hz,2H),3.92(s,3H).

[0290] Example 56

[0291] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indole-5-carboxylic acid methyl ester (Compound 56)

[0292] Example 56 was prepared using the same method as Example 54, except that 1-iodo-4-(trifluoromethoxy)benzene in Example 54 was replaced with 1-bromo-4-(trifluoromethylthio)benzene. After purification by column chromatography (PE:EA = 3:1), the title compound 56 (101 mg, 49% yield) was obtained as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.32 (dd, J=1.4, 0.7Hz, 1H), 7.94 (dd, J=8.4, 1.4Hz, 1H), 7.90– 7.78(m,4H),7.71(s,1H),7.65–7.59(m,2H),7.57(s,1H),4.02(s,3H),3.95(s,3H).

[0293] Example 57

[0294] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indole-5-carboxylic acid (Compound 57)

[0295] Example 57 was prepared using the same method as Example 14, except that compound 13 in step 1 of Example 14 was replaced with compound 56. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (6.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 57 (55 mg, 63% yield) as a pale yellow solid. 1 H NMR (300MHz, DMSO-d6) δ12.89(s,1H),8.25(d,J=4.8Hz,2H),8.21(d,J=1.4Hz,1H),8.00 (dd,J=8.4,5.9Hz,3H),7.91(d,J=0.8Hz,1H),7.84(dd,J=10.2,8.5Hz,3H),3.92(s,3H).

[0296] Example 58

[0297] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-yl)methanesulfonamide (compound 58)

[0298] Step 1: Preparation of 3-(1-methyl-1H-pyrazol-4-yl)-5-nitro-1H-indole

[0299] A mixture of 3-bromo-5-nitro-1H-indole (482 mg, 2 mmol; Adamas, 011002534), pinacol ester of 1-methyl-4-pyrazoleboronic acid (416 mg, 2 mmol), Pd(dppf)Cl2 (146 mg, 0.2 mmol), and K2CO3 (830 mg, 6 mmol) was added to 1,4-Dioxane (2 mL) and water (1.5 mL), and the mixture was heated and stirred at 85 °C for 4 h under an argon atmosphere. TLC (PE:EA = 1:1, R f =0.1) indicates partial consumption of the starting material and detection of a new spot. After cooling to room temperature and concentration under reduced pressure, the residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 150:1) to give the title compound 58-1 (164 mg, 34% yield) as an orange-red solid. 1H NMR (400MHz, CDCl3) δ8.72(d,J=2.2Hz,1H),8.54(s,1H),8.16(dd,J=9.0,2.2Hz,1H),7.74(d,J=12.6Hz,2H),7.48–7.40(m,2H),4.03(s,3H).

[0300] Step 2: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-5-nitro-1-(4-(trifluoromethoxy)phenyl)-1H-indole

[0301] Step 2 follows the same preparation method as Step 1 in Example 54, except that methyl 1H-indole-5-carboxylate in Step 1 of Example 54 is replaced with 58-1. After cooling to room temperature, the reaction solution is poured into water (30 mL), extracted with EA (30 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a yellow, gelatinous crude product 58-2, which is used directly in the next reaction without purification.

[0302] Step 3: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-amine

[0303] Under ice bath conditions, 4,4'-Bipyridine (0.5 mg, 0.0325 mmol; Leyan, 1035701) and B2(OH)4 (175 mg, 1.95 mmol; Leyan, 1062182) were added in portions to a solution of crude product 58-2 (0.65 mmol) dissolved in DMF (4.5 mL), and the mixture was stirred at room temperature for 5 min. TLC (PE:EA = 1:1, R f =0.05) showed that 58-2 was completely consumed and a new spot was detected. The reaction solution was poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (DCM:MeOH = 75:1) to give the title compound 58-3 (195 mg, 81% two-step yield) as a pale pink solid: 1 H NMR(300MHz, CDCl3)δ7.77(d,J=0.8Hz,1H),7.64(s,1H),7.55–7.49(m,2H),7.41–7.33(m,3H ),7.31(s,1H),7.09(d,J=2.3Hz,1H),6.73(dd,J=8.7,2.2Hz,1H),4.00(s,3H),3.64(s,2H).

[0304] Step 4: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-yl)methanesulfonamide

[0305] Step 4 uses the same preparation method as Step 3 of Example 1, except that steps 1-2 in Step 3 of Example 1 are replaced with 58-3. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 58 (65 mg, 97% yield) in the form of a pale yellow solid. 1 H NMR(400MHz,DMSO-d6)δ9.45(s,1H),8.03(s,1H),7.94(s,1H),7.82–7.74(m,3H),7.72(d, J=2.0Hz,1H),7.59(d,J=8.9Hz,3H),7.18(dd,J=8.9,2.1Hz,1H),3.93(s,3H),2.93(s,3H).

[0306] Example 59

[0307] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-yl)acrylamide (compound 59)

[0308] Example 59 was prepared using the same method as Example 10, except that 10-1 in step 2 of Example 10 was replaced with 58-3 prepared in step 3 of Example 58. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale purple solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 59 (40 mg, 63% yield) in the form of a white solid. 1 H NMR(400MHz, CDCl3)δ8.25(d,J=2.1Hz,1H),7.84–7.69(m,2H),7.57–7.51(m,2H),7.51–7.33(m,5H),7.29(dd,J=8.9 ,2.1Hz,1H),6.47(dd,J=16.8,1.3Hz,1H),6.30(dd,J=16.9,10.2Hz,1H),5.79(dd,J=10.1,1.3Hz,1H),3.99(s,3H).

[0309] Example 60

[0310] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)methacrylamide (compound 60)

[0311] Example 60 was prepared using the same method as Example 10, except that step 1-2 in Example 10 was replaced with step 2 of Example 19, and acryloyl chloride in step 2 was replaced with methacryloyl chloride (Adamas, 01124709). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 60 (40 mg, 60% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.41(d,J=1.9Hz,1H),8.10(d,J=0.8Hz,1H),8.00(s,1H),7.83–7.75(m,2H),7.74–7. 64(m,2H),7.49–7.36(m,3H),5.91–5.84(m,1H),5.53(d,J=1.7Hz,1H),4.02(s,3H),2.12(d,J=0.7Hz,3H).

[0312] Example 61

[0313] N-(3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide (compound 61)

[0314] Example 61 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boronic acid in step 1 of Example 10 was replaced with 1-cyclopropylpyrazole-4-boronic acid ester (Bide, BD211291). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 61 (51 mg, 47% yield) in the form of a white solid. 1HNMR (400MHz, CDCl3) δ8.45–8.35(m,1H),8.13–8.03(m,2H),7.88(d,J=8.4Hz,2H),7. 78(d,J=8.5Hz,2H),7.72(d,J=8.9Hz,1H),7.63(s,1H),7.51(dd,J=9.0,2.0Hz,1H),6 .51(dd,J=16.8,1.3Hz,1H),6.32(dd,J=16.9,10.2Hz,1H),5.83(dd,J=10.1,1.3Hz,1 H),3.70(tt,J=7.4,3.8Hz,1H),1.25–1.21(m,2H),1.09(ddd,J=7.3,2.5,1.3Hz,2H).

[0315] Example 62

[0316] N-(3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 62)

[0317] Example 62 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with 1-cyclopropylpyrazole-4-boronic acid ester. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (4 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 62 (22 mg, 19% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.73 (s, 1H), 8.44 (d, J = 0.8Hz, 1H), 8.07 (d, J = 8.4Hz, 2H), 8.04–7.99 (m, 2H), 7.95 (d, J = 8.6Hz, 2H), 7.9 0(d,J=2.0Hz,1H),7.48(dd,J=9.1,2.0Hz,1H),3.89(tt,J=7.4,3.9Hz,1H),3.01(s,3H),1.21–1.13(m,2H),1.08–1.00(m,2H).

[0318] Example 63

[0319] N-(3-(1-isopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide (compound 63)

[0320] Example 63 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with 1-isopropylpyrazole-4-boric acid (Adamas, 011145994). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (6.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 63 (13 mg, 16% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.39(s,1H),8.13(s,1H),8.06(s,1H),7.91(d,J=8.4Hz,2H),7.78(dd,J=13.1,8.8Hz,3H),7.56(d,J=8.8Hz,1H),7.45 (s,1H),6.51(dd,J=16.9,1.2Hz,1H),6.31(dd,J=16.8,10.2Hz,1H),5.84(d,J=10.2Hz,1H),4.62(hept,J=6.5Hz,1H),1.61(d,J=6.8Hz,6H).

[0321] Example 64

[0322] N-(3-(1-isopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 64)

[0323] Example 64 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-isopropylpyrazole-4-boric acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a brownish-yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 64 (46 mg, 52% yield) in the form of a pale yellow solid. 1 H NMR(300MHz,DMSO-d6)δ9.75(s,1H),8.41(d,J=0.8Hz,1H),8.12–7.99(m,4H),7.98–7.88(m,3 H),7.49(dd,J=9.1,2.0Hz,1H),4.66(hept,J=6.8Hz,1H),3.01(s,3H),1.51(d,J=6.7Hz,6H).

[0324] Example 65

[0325] N-(3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 65)

[0326] Example 65 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester (Leyan, 1052797). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 65 (38.2 mg, 57% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.75(s,1H),8.42(s,1H),8.11–7.99(m,4H),7.95(d,J=8.6Hz,2H),7.90(d, J=2.0Hz,1H),7.48(dd,J=9.0,2.0Hz,1H),4.27(q,J=7.3Hz,2H),3.01(s,3H),1.46(t,J=7.3Hz,3H).

[0327] Example 66

[0328] N-(1-(4-(trifluoromethyl)phenyl)-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 66)

[0329] Example 66 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with (1,3,5-trimethyl-1H-pyrazole-4-yl)boric acid (Bide, BD216381). After purification by column chromatography (DCM:MeOH=), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 66 (38.7 mg, 56% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ9.77(s,1H),8.05(dd,J=11.6,8.7Hz,3H),7.94(d,J=8.5Hz,2H),7.54(d ,J=1.9Hz,1H),7.45(dd,J=9.0,2.1Hz,1H),3.78(s,3H),2.95(s,3H),2.33(s,3H),2.22(s,3H).

[0330] Example 67

[0331] N-(3-(1,3-dimethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 67)

[0332] Example 67 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pinacol 1,3-dimethylpyrazole-4-boric acid (Bide, BD208999). After purification by column chromatography (DCM:MeOH=), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 67 (52.5 mg, 78% yield) in the form of a white solid. 1 H NMR(300MHz,DMSO-d6)δ9.69(s,1H),8.26(s,1H),8.06(dd,J=13.6,8.7Hz,3H),7.95(d,J=8.6Hz ,2H),7.80(d,J=1.9Hz,1H),7.48(dd,J=9.0,2.0Hz,1H),3.91(s,3H),2.99(s,3H),2.47(s,3H).

[0333] Example 68

[0334] 3-((1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid (Compound 68)

[0335] Step 1: Preparation of methyl 3-nitro-4-((4-(trifluoromethyl)phenyl)amino)benzoate

[0336] DIPEA (1050 μL, 6.0 mmol) was added dropwise to a solution of methyl 4-fluoro-3-nitrobenzene (796 mg, 4 mmol; Leyan, 1062139) and 4-trifluoromethylaniline (600 μL, 4.8 mmol; Bide, BD10447) dissolved in DMF (10 mL). The mixture was heated and stirred at 150 °C for 9 h. TLC (PE:EA = 10:1, R f =0.4) indicates that the starting material was completely consumed and a new spot was detected. After cooling to room temperature, the reaction mixture was poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was then purified by column chromatography (PE:EA = 30:1) to give the title compound 68-1 (509 mg, 37% yield) as a yellow solid. 1H NMR (300MHz, CDCl3) δ9.82 (s, 1H), 8.94 (d, J = 2.0Hz, 1H), 8.04 (ddd, J = 9.0, 2.0, 0.6Hz ,1H),7.71(d,J=8.4Hz,2H),7.41(d,J=8.3Hz,2H),7.31(d,J=9.0Hz,1H),3.93(s,3H).

[0337] Step 2: Preparation of methyl 3-amino-4-((4-(trifluoromethyl)phenyl)amino)benzoate

[0338] Add SnCl₂·2H₂O (1015 mg, 4.5 mmol; Biotin, BD154165) to a solution of 68-1 (340 mg, 1 mmol) dissolved in EtOH (10 mL), and heat and stir at 80 °C for 2 h. TLC (DCM:MeOH = 20:1, R f =0.5) showed that 68-1 was completely consumed and a new spot was detected. Cool to room temperature, slowly add saturated NaHCO3 aqueous solution to the reaction solution until no bubbles are generated, filter, dissolve the filter cake with EA (10 mL), filter again, collect the filtrate, concentrate under reduced pressure to obtain crude product 68-2 in the form of white solid. The crude product is used directly in the next step of the reaction without purification.

[0339] Step 3: Preparation of methyl 3-(((1H-imidazol-4-yl)methyl)amino)-4-((4-(trifluoromethyl)phenyl)amino)benzoate

[0340] Under ice bath conditions, catalytically added amounts of AcOH (2 drops) were added dropwise to a mixture of 68-2 (155 mg, 0.5 mmol), 1H-imidazolium-4-carboxaldehyde (48 mg, 0.5 mmol; Adamas, 01058105), and STAB (316 mg, 1.5 mmol; Leyan, 1036092) in dry DCM (2 mL), and stirred at room temperature for 1 h. TLC (DCM:MeOH = 20:1, R f =0.1) indicates that 68-2 was almost completely consumed and a new spot was detected. Saturated NaHCO3 aqueous solution was slowly added dropwise to the reaction solution until no more bubbles were generated. The reaction solution was poured into water (30 mL), extracted with DCM (30 mL × 3), the organic layer was washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (DCM:MeOH = 20:1) to give the title compound 68-3 (174 mg, 66% two-step yield) as a pale yellow solid. 1H NMR (400MHz, DMSO-d6) δ11.93(s,1H),8.11(s,1H),7.59(d,J=1.2Hz,1H),7.49(d,J=8.5Hz,2H),7.30(d,J=1.9Hz,1H),7.25( dd,J=8.1,1.8Hz,1H),7.20(d,J=8.1Hz,1H),6.95(d,J=9.0Hz,3H),5.38(t,J=5.5Hz,1H),4.23(d,J=5.2Hz,2H),3.80(s,3H).

[0341] Step 4: Preparation of methyl 3-((1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylate

[0342] Add CDI (141 mg, 0.88 mmol; Leyan, 1034792) to a solution of 68-3 (170 mg, 0.44 mmol) dissolved in DMF (4 mL), and heat and stir at 90 °C for 12 h. TLC (DCM:MeOH = 20:1, R f =0.15) showed that 68-3 was completely consumed and a new spot was detected. After cooling to room temperature, the reaction mixture was poured into water (40 mL), extracted with EA (20 mL × 3), the organic layer was washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was purified by column chromatography (DCM:MeOH = 20:1) to give the title compound 68-4 (141 mg, 78% yield) as a white solid. 1 H NMR (300MHz, DMSO-d6) δ12.03(s,1H),7.98(d,J=8.5Hz,2H),7.91(s,1H),7.85(d,J=8.3Hz,2H),7.74(dd ,J=8.4,1.6Hz,1H),7.60(d,J=1.2Hz,1H),7.26(d,J=8.3Hz,1H),7.15(s,1H),5.06(s,2H),3.85(s,3H).

[0343] Step 5: 3-((1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid

[0344] Step 5 uses the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 68-4. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (5.0 mL) to adjust the pH to approximately 7. The mixture is stirred at room temperature for 1 h, and then filtered to obtain the title compound 68 (70 mg, 88% yield) as a white solid. 1 H NMR (300MHz, DMSO-d6) δ12.82(s,1H),12.12(s,1H),7.98(d,J=8.4Hz,2H),7.91–7.81(m,3H),7.72(d d,J=8.3,1.6Hz,1H),7.61(d,J=1.2Hz,1H),7.23(d,J=8.3Hz,1H),7.15(d,J=1.2Hz,1H),5.06(s,2H).

[0345] Example 69

[0346] 3-((1-methyl-1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid (compound 69)

[0347] Step 1: Preparation of methyl 3-((1-methyl-1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylate

[0348] Under ice bath conditions, NaH (5.5 mg, 0.132 mmol; Adamas, 013474116) was added in portions to a solution of 68-4 (55 mg, 0.132 mmol) prepared in step 4 of Example 68 dissolved in DCM (2 mL). The mixture was stirred for 30 min, and then iodomethane (10 μL, 0.145 mmol; Adamas, 013554266) was added dropwise. The reaction was carried out at room temperature for 2 h. TLC (DCM:MeOH = 40:1, R f =0.3) showed that 68-4 was almost completely consumed and a new spot was detected. After cooling to room temperature, the reaction solution was poured into water (20 mL), extracted with DCM (20 mL × 3), the organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was then purified by column chromatography (DCM:MeOH = 40:1) to give the title compound 69-1 (30 mg, 53% yield) as a white solid. 1H NMR (300MHz, CDCl3) δ8.01(d,J=1.6Hz,1H),7.82(dd,J=9.8,8.3Hz,3H),7.71(d,J=8.4Hz,2H),7.38( d,J=1.4Hz,1H),7.13(d,J=8.4Hz,1H),6.95(d,J=1.4Hz,1H),5.10(s,2H),3.93(s,3H),3.63(s,3H).

[0349] Step 2: Preparation of 3-((1-methyl-1H-imidazol-4-yl)methyl)-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazol-5-carboxylic acid

[0350] Step 2 follows the same preparation method as Step 1 of Example 14, except that compound 13 in Example 14 is replaced with 69-1. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (3 mL) to adjust the pH to approximately 1. The mixture is stirred at room temperature for 1 h, and then filtered to obtain the title compound 69 (12 mg, 46% yield) as a white solid. 1 H NMR (400MHz, DMSO-d6) δ12.89(s,1H),7.97(d,J=8.5Hz,2H),7.89(d,J=1.6Hz,1H),7.85(d,J=8.3Hz,2H),7.72(dd ,J=8.3,1.6Hz,1H),7.54(d,J=1.3Hz,1H),7.24(d,J=8.3Hz,1H),7.13(d,J=1.3Hz,1H),5.01(s,2H),3.59(s,3H).

[0351] Example 70

[0352] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-yl)methanesulfonamide (compound 70)

[0353] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethyl)benzyl)-1H-indazole

[0354] 1-(bromomethyl)-4-(trifluoromethyl)benzene (340 μL, 2.2 mmol; Biotin, BD33583) was added dropwise to a solution of 3-bromo-5-nitro-1H-indazole (484 mg, 2 mmol) and K₂CO₃ (290 mg, 2.1 mmol) dissolved in DMF (10 mL), and the reaction was carried out at room temperature for 2 h. TLC (PE:EA = 5:1, R f=0.3) indicates that the starting material was almost completely consumed and a new spot was detected. The reaction solution was poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (PE:EA = 8:1) to give the title compound 70-1 (765 mg, 96% yield) as a yellow solid: 1 H NMR (400MHz, CDCl3) δ8.65 (dd, J=2.1, 0.6Hz, 1H), 8.30 (dd, J=9.2, 2.1Hz, 1H), 7 .61(d,J=8.0Hz,2H),7.39(d,J=9.3Hz,1H),7.34(d,J=8.0Hz,2H),5.66(s,2H).

[0355] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-amine

[0356] Step 2 uses the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 70-1. After vacuum concentration using anhydrous magnesium sulfate, a crude product 70-2 in the form of yellow oil is obtained. The crude product is used directly in the next reaction without purification.

[0357] Step 3: Preparation of N-(3-bromo-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-yl)methanesulfonamide

[0358] Step 3 uses the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 70-2. After purification by column chromatography (PE:EA = 1:1), the title compound 70-3 (156 mg, 54% two-step yield) is obtained as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ7.58(d,J=8.1Hz,2H),7.53–7.49(m,1H),7.36–7.32(m,2H),7.31(d,J=0.8Hz,2H),6.52(s,1H),5.60(s,2H),3.01(s,3H).

[0359] Step 4: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-yl)methanesulfonamide

[0360] Step 4 uses the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 70-3. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid is obtained. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. After filtration, the title compound 70 (78 mg, 87% yield) in the form of a creamy white solid is obtained. 1 H NMR (300MHz, DMSO-d6) δ9.55(s,1H),8.24(d,J=0.8Hz,1H),7.90(d,J=0.8Hz,1H),7.80–7.65(m ,4H),7.42(d,J=8.0Hz,2H),7.32(dd,J=9.0,1.9Hz,1H),5.77(s,2H),3.94(s,3H),2.95(s,3H).

[0361] Example 71

[0362] N-(3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methanesulfonamide (compound 71)

[0363] Step 1: Preparation of (1-methyl-1H-imidazol-4-yl)zinc(II) bromide

[0364] Under an argon atmosphere, ethyl magnesium bromide solution (2.3 mL, 4.6 mmol, 2.0 M in THF; Adamas, 01375896) was slowly added dropwise to a solution of 4-bromo-1-methyl-1H-imidazole (Bide, BD32904) dissolved in dry THF (5.0 mL). After stirring at room temperature for 10 min, zinc chloride solution (8.0 mL, 8 mmol, 1.0 M in THF; Adamas, 01375947) was slowly added dropwise, and the mixture was stirred at room temperature for 2 h. The resulting reaction solution 71-1 was used directly in the next reaction without further treatment.

[0365] Step 2: Preparation of 3-(1-methyl-1H-imidazol-4-yl)-5-nitro-1-(4-(trifluoromethyl)benzyl)-1H-indazole

[0366] Dry THF (5.0 mL) was added to a mixture of reaction solution 71-1, 70-1 (798 mg, 2 mmol) prepared in step 1 of Example 70, and Pd(PPh3)4 (115 mg, 0.1 mmol). The mixture was heated and stirred at 95 °C for 3 h under an argon atmosphere. TLC (PE:EA = 3:1, R f=0.15) indicates that 70-1 was completely consumed and a new spot was detected. After cooling to room temperature and concentrating under reduced pressure, crude product 71-2, which is yellow oil, was obtained. The crude product was used directly in the next reaction without purification.

[0367] Step 3: Preparation of 3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-amine

[0368] Step 3 employs the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 71-2. The residue is concentrated under reduced pressure using anhydrous magnesium sulfate, and then purified by column chromatography (DCM:MeOH = 150:1) to obtain the title compound 71-3 (63 mg, 9% two-step yield) as a yellow gel. 1 H NMR(400MHz, DMSO-d6)δ7.68(d,J=8.1Hz,2H),7.54–7.38(m,5H),7.37(d,J=2 .1Hz,1H),6.85(dd,J=8.9,2.2Hz,1H),5.73(s,2H),5.12(s,2H),3.98(s,3H).

[0369] Step 4: N-(3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-yl)methanesulfonamide

[0370] Step 4 uses the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 71-3. After purification by column chromatography (DCM:MeOH = 25:1), a crude product in the form of a brown solid is obtained. Diethyl ether (4.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. After filtration, the title compound 71 (35 mg, 46% yield) in the form of a light brown solid is obtained. 1 H NMR (300MHz, DMSO-d6) δ9.69(s,1H),8.16(dd,J=2.1,0.7Hz,1H),7.81(dd,J=9.0,0.7Hz,1H),7.70(d ,J=8.1Hz,2H),7.52–7.45(m,3H),7.42(dd,J=9.0,2.1Hz,1H),5.85(s,2H),4.00(s,3H),2.93(s,3H).

[0371] Example 72

[0372] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 72)

[0373] Example 72 was prepared using the same method as Example 4, except that step 3 of Example 4, 4-2, was replaced with 70-2 prepared in Example 70. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 72 (35 mg, 78% yield) in the form of a pale yellow solid. 1 H NMR (300MHz, DMSO-d6) δ8.40(dd,J=9.1,0.8Hz,2H),7.97(dd,J=10.0,0.8Hz,2H),7.79(dd,J=8.9,1 .6Hz,1H),7.70(d,J=8.1Hz,2H),7.49–7.38(m,3H),5.85(s,2H),3.95(s,3H),2.41(d,J=5.0Hz,3H).

[0374] Example 73

[0375] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(3-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 73)

[0376] Step 1: Preparation of 3-bromo-5-nitro-1-(3-(trifluoromethyl)benzyl)-1H-indazole

[0377] Step 1 employs the same preparation method as Step 1 in Example 70, except that 1-(bromomethyl)-4-(trifluoromethyl)benzene in Step 1 of Example 70 is replaced with 1-(bromomethyl)-3-(trifluoromethyl)benzene (BYD, BD33580). The reaction solution is poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 73-1, which is a yellow solid. The crude product is used directly in the next reaction without purification.

[0378] Step 2: Preparation of 3-bromo-1-(3-(trifluoromethyl)benzyl)-1H-indazole-5-amine

[0379] Step 2 uses the same preparation method as Step 2 of Example 1, except that 1-1 in Step 2 of Example 1 is replaced with 73-1. After filtration through anhydrous magnesium sulfate pad and concentration under reduced pressure, crude product 73-2, which is a brownish-yellow solid, is obtained. The crude product is used directly in the next reaction without purification.

[0380] Step 3: Preparation of 3-bromo-1-(3-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonyl chloride

[0381] Step 3 uses the same preparation method as Step 3 in Example 4, except that 4-2 in Step 3 of Example 4 is replaced with 73-2. The reaction solution is poured into water (30 mL), extracted with EA (20 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 73-3, which is a yellow solid. The crude product is used directly in the next step of the reaction without purification.

[0382] Step 4: Preparation of 3-bromo-N-methyl-1-(3-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide

[0383] Step 4 employs the same preparation method as Step 4 of Example 4, except that 4-3 in Step 4 of Example 4 is replaced with 73-3. The residue is concentrated under reduced pressure and purified by column chromatography (PE:EA = 1:1) to obtain the title compound 73-4 (72.7 mg, 10% four-step yield) as a pale pink solid. 1 H NMR(300MHz, CDCl3)δ8.26(d,J=0.9Hz,1H),7.86(dd,J=8.9,1.7Hz,1H),7.62–7.52( m,2H),7.50–7.35(m,3H),5.64(s,2H),4.37(q,J=5.7Hz,1H),2.68(d,J=5.1Hz,3H).

[0384] Step 5: Preparation of N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(3-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide

[0385] Step 5 uses the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 is replaced with 73-4. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid is obtained. Diethyl ether (5.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. After filtration, the title compound 73 (25 mg, 71% yield) in the form of a white solid is obtained. 1 H NMR (400MHz, DMSO-d6) δ7.56(dd,J=11.3,0.8Hz,2H),7.20–7.12(m,2H),6.96(dd,J=8.9,1.6Hz,1H),6.89(s,1H),6.82(d,J=7 .7Hz,1H),6.72(t,J=7.7Hz,1H),6.66(d,J=7.8Hz,1H),6.57(d,J=5.1Hz,1H),5.01(s,2H),3.12(s,3H),1.57(d,J=4.7Hz,3H).

[0386] Example 74

[0387] N-Methyl-3-(thien-3-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 74)

[0388] Example 74 was prepared using the same method as Example 72, except that 1-methyl-1H-pyrazole-4-boric acid in Example 72 was replaced with 3-thiopheneboric acid (Bide, BD9414). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a brown solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 74 (36 mg, 80% yield) in the form of a light brown solid. 1 H NMR (400MHz, DMSO-d6) δ8.48(dd,J=1.6,0.7Hz,1H),8.17(dd,J=2.8,1.3Hz,1H),8.02(dd,J=8.9,0.7Hz,1H),7.82(dd,J=8.9 ,1.6Hz,1H),7.77(dd,J=5.0,2.8Hz,1H),7.74–7.66(m,3H),7.46(dd,J=10.0,6.5Hz,3H),5.90(s,2H),2.41(d,J=5.0Hz,3H).

[0389] Example 75

[0390] N-Methyl-3-(1-Methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 75)

[0391] Example 75 was prepared using the same method as Example 72, except that the 1-methyl-1H-pyrazole-4-boric acid in Example 72 was replaced with 71-1 prepared in step 1 of Example 71. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a purple-red gel was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 75 (2 mg, 5% yield) as a pale purple solid. 1 H NMR (400MHz, DMSO-d6) δ8.89(d,J=1.7Hz,1H),7.93(d,J=8.9Hz,1H),7.81(d,J=1.3Hz,1H),7.76(dd,J=8.9, 1.8Hz,1H),7.70(dd,J=4.9,3.5Hz,3H),7.45–7.38(m,3H),5.84(s,2H),3.74(s,3H),2.39(d,J=5.0Hz,3H).

[0392] Example 76

[0393] N-Methyl-3-(pyridin-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 76)

[0394] Example 76 was prepared using the same method as Example 72, except that 1-methyl-1H-pyrazole-4-boric acid in Example 72 was replaced with pyridine-4-boric acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 76 (37 mg, 82% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO-d6) δ8.79–8.74(m,2H),8.54(d,J=0.9Hz,1H),8.12(dd,J=8.9,0.7Hz,1H),8.00–7.92(m ,2H),7.87(dd,J=8.9,1.6Hz,1H),7.74–7.69(m,2H),7.54–7.49(m,3H),5.98(s,2H),2.42(d,J=5.0Hz,3H).

[0395] Example 77

[0396] 1-(3-chloro-4-(trifluoromethyl)phenyl)-N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-sulfonamide (Compound 77)

[0397] Example 77 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 3-chloro-4-trifluoromethylphenylboronic acid (BYD, BD4275). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 77 (36 mg, 77% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO-d6)δ8.59(s,1H),8.49(dd,J=1.7,0.8Hz,1H),8.27–8.20(m,2H),8.15(d,J=0.8Hz,1H),8 .08(d,J=1.3Hz,2H),7.95(dd,J=9.0,1.7Hz,1H),7.58(q,J=5.0Hz,1H),4.00(s,3H),2.44(d,J=4.8Hz,3H).

[0398] Example 78

[0399] N-Methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)-1H-indazole-5-sulfonamide (Compound 78)

[0400] Example 78 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 2-trifluoromethyl-5-pyridineboronic acid (Adamas, 01233453). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 78 (36 mg, 83% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO-d6) δ9.34(d,J=2.5Hz,1H),8.58(d,J=9.4Hz,2H),8.50(d,J=0.9Hz,1H),8.27(dd,J=9.0,0.8H z,1H),8.20–8.10(m,2H),7.95(dd,J=9.0,1.7Hz,1H),7.58(q,J=5.0Hz,1H),4.00(s,3H),2.44(d,J=5.0Hz,3H).

[0401] Example 79

[0402] 1-(4-Cyclohexylphenyl)-N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-sulfonamide (Compound 79)

[0403] Example 79 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-cyclohexylphenylboronic acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 79 (31 mg, 87% yield) in the form of a pale yellow solid. 1H NMR (400MHz, DMSO-d6) δ8.50(s,1H),8.45(d,J=1.6Hz,1H),8.07(s,1H),7.98(d,J=9.0Hz,1H),7.85(dd,J=8.9,1.6Hz,1H),7.71(d,J=8.5Hz,2H),7.5 3–7.43(m,3H),3.99(s,3H),2.68–2.57(m,1H),2.43(d,J=4.9Hz,3H),1.91 –1.78(m,4H),1.73(d,J=12.6Hz,1H),1.54–1.34(m,4H),1.33–1.21(m,1H).

[0404] Example 80

[0405] 1-(3-fluoro-4-(trifluoromethyl)phenyl)-N-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-sulfonamide (Compound 80)

[0406] Example 80 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 3-fluoro-4-(trifluoromethyl)phenylboronic acid (Adamas, 01270215). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 80 (9.5 mg, 31% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ8.55(s,1H),8.47(d,J=1.6Hz,1H),8.23(dt,J=8.5,3.6Hz,1H),8.17(dd,J=6.3,2.7Hz,1H),8.11(s,1H),8 .04(d,J=8.9Hz,1H),7.90(dd,J=9.0,1.6Hz,1H),7.80(t,J=9.6Hz,1H),7.55(q,J=3.8Hz,1H),3.99(s,3H),2.44(d,J=4.3Hz,3H).

[0407] Example 81

[0408] N-Methyl-3-(1-methyl-1H-pyrazole-5-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-sulfonamide (Compound 81)

[0409] Example 81 was prepared using the same method as Example 72, except that 1-methyl-1H-pyrazole-4-boric acid in Example 72 was replaced with 1-methyl-1H-pyrazole-5-boric acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 81 (16 mg, 50% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ8.29(dd,J=1.6,0.7Hz,1H),8.09(dd,J=9.0,0.8Hz,1H),7.86(dd,J=8.9,1.6Hz,1H),7.72(d,J=8. 1Hz,2H),7.65(d,J=2.0Hz,1H),7.58–7.45(m,3H),6.90(d,J=2.0Hz,1H),5.96(s,2H),4.10(s,3H),2.39(d,J=5.0Hz,3H).

[0410] Example 82

[0411] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(2-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 82)

[0412] Example 82 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 2-trifluoromethylphenylboronic acid (Leyan, 1021256). After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 82 (39 mg, 74% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO-d6)δ9.64(s,1H),8.30(s,1H),8.05(d,J=7.2Hz,1H),7.97–7.89(m,2H),7.88–7.80(m ,2H),7.74(d,J=7.8Hz,1H),7.36(dd,J=8.9,1.9Hz,1H),7.29(d,J=8.9Hz,1H),3.97(s,3H),3.00(s,3H).

[0413] Example 83

[0414] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)-1H-indazole-5-yl)methanesulfonamide (compound 83)

[0415] Example 83 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 2-trifluoromethyl-5-pyridineboronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 83 (36 mg, 69% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ9.77(s,1H),9.31(d,J=2.5Hz,1H),8.52(dd,J=8.5,2.6Hz,1H),8.40(s,1H),8.10( d,J=8.8Hz,2H),8.05(s,1H),7.91(d,J=2.0Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.01(s,3H).

[0416] Example 84

[0417] N-(1-(4-(difluoromethoxy)phenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 84)

[0418] Example 84 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with p-difluoromethoxyphenylboronic acid (Leyan, 1067210). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 84 (31 mg, 60% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO-d6)δ9.70(s,1H),8.35(s,1H),8.00(s,1H),7.90–7.80( m,4H),7.45(d,J=2.0Hz,1H),7.44–7.32(m,3H),3.98(s,3H),3.00(s,3H).

[0419] Example 85

[0420] N-(1-(4-ethylphenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 85)

[0421] Example 85 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-ethylphenylboronic acid (BYD, BD10663). After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 85 (38 mg, 80% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ9.68(s,1H),8.34(s,1H),7.99(s,1H),7.86(d,J=2.0Hz,1H),7.83(d,J=9.0Hz,1H),7. 69(d,J=8.3Hz,2H),7.49–7.38(m,3H),3.98(s,3H),2.99(s,3H),2.71(d,J=7.6Hz,2H),1.25(t,J=7.6Hz,3H).

[0422] Example 86

[0423] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(p-tolyl)-1H-indazole-5-yl)methanesulfonamide (compound 86)

[0424] Example 86 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-methylphenylboronic acid (Leyan, 1036307). After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 86 (41 mg, 89% yield) in the form of a white solid. 1 H NMR(300MHz,DMSO-d6)δ9.67(s,1H),8.33(s,1H),7.98(s,1H),7.85(d,J=1.9Hz,1H),7.81(d, J=9.0Hz,1H),7.66(d,J=8.4Hz,2H),7.44–7.36(m,3H),3.97(s,3H),2.98(s,3H),2.40(s,3H).

[0425] Example 87

[0426] N-(1-(4-isopropylphenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 87)

[0427] Example 87 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-isopropylphenylboronic acid (Leyan, 1022889). After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 87 (47 mg, 95% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ9.67(s,1H),8.32(s,1H),8.01–7.94(m,1H),7.85(d,J=1.9Hz,1H),7.83(d,J=9.1Hz,1H),7.6 9(d,J=8.5Hz,2H),7.46(d,J=8.6Hz,2H),7.40(dd,J=9.0,2.0Hz,1H),3.97(s,3H),2.99(s,4H),1.27(d,J=6.9Hz,6H).

[0428] Example 88

[0429] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(2-(trifluoromethyl)pyrimidin-5-yl)-1H-indazole-5-yl)methanesulfonamide (compound 88)

[0430] Example 88 was prepared using the same method as Example 7, except that 4-iodo-1-methylimidazolium in step 1 of Example 7 was replaced with 5-bromo-2-trifluoromethylpyrimidine (Leyan, 1050316), and 4-trifluoromethylphenylboronic acid in step 4 was replaced with 1-methyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 88 (31 mg, 59% yield) in the form of a white solid. 1 H NMR(300MHz,DMSO-d6)δ9.85(s,1H),9.60(s,2H),8.45(s,1H),8.24(d,J=9.0Hz,1H ),8.09(s,1H),7.93(s,1H),7.52(dd,J=9.0,2.0Hz,1H),4.00(s,3H),3.03(s,3H).

[0431] Example 89

[0432] N-(1-(4-cyclopropylphenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 89)

[0433] Example 89 was prepared using the same method as Example 7, except that 4-iodo-1-methylimidazolium in step 1 of Example 7 was replaced with 4-bromocyclopropylbenzene (BYD, BD96719), and 4-trifluoromethylphenylboronic acid in step 4 was replaced with 1-methyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a pink solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 89 (42 mg, 86% yield) in the form of a pink solid. 1 H NMR(300MHz, DMSO-d6)9.68(s,1H),8.33(s,1H),7.98(s,1H),7.86(d,J=1.9Hz,1H),7.80(d,J=9.0Hz,1H),7.68–7.60(m,2H),7.41(dd,J= 9.0,2.0Hz,1H),7.29(d,J=8.5Hz,2H),3.97(s,3H),2.99(s,3H),2.03(ddd,J=13.3,8.5,5.0Hz,1H),1.06–0.98(m,2H),0.79–0.71(m,2H).

[0434] Example 90

[0435] N-Methyl-3-(pyridin-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 90)

[0436] Example 90 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with pyridine-4-boronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 90 (39 mg, 84% yield) in the form of a white solid. 1 H NMR(400MHz, CDCl3)δ8.81(d,J=6.1Hz,2H),8.70(s,1H),8.00(dd,J=9.0,1.6Hz,1H), 7.97–7.92(m,5H),7.89(d,J=8.7Hz,2H),4.66(q,J=5.4Hz,1H),2.72(d,J=5.4Hz,3H).

[0437] Example 91

[0438] 3-(cyclohexyl-1-en-1-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 91)

[0439] Example 91 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with cyclohexene-1-ylboronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 91 (39 mg, 84% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6)8.45(d,J=2.1Hz,1H),8.14(d,J=9.0Hz,1H),8.06(d,J=8.4Hz,2H),7.98(d,J=8.7Hz,2H),7.90(dd,J=8.9,1. 7Hz,1H),7.57(s,1H),6.75–6.68(m,1H),2.65(q,J=5.7Hz,2H),2.42(s,3H),2.40–2.33(m,2H),1.76(ddd,J=29.2,5.9,2.2Hz,4H).

[0440] Example 92

[0441] N-Methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 92)

[0442] Example 92 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with phenylboronic acid. After purification by column chromatography (DCM:MeOH = 40:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 92 (39 mg, 84% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ8.53(s,1H),8.23(d,J=9.0Hz,1H),8.17(d,J=8.5Hz,2H),8.07–8.00(m, 4H),7.96(dd,J=9.0,1.7Hz,1H),7.66(t,J=7.6Hz,2H),7.63–7.55(m,2H),2.44(d,J=4.5Hz,3H).

[0443] Example 93

[0444] N,3-Dimethyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 93)

[0445] Step 1: Preparation of 5-bromo-3-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0446] Step 1 uses the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 is replaced with 5-bromo-3-methyl-1H-indazole (Leyan, 1048785). After concentration under reduced pressure, crude product 93-1, which is dark green and gelatinous, is obtained and used directly in the next reaction without purification.

[0447] Step 2: Preparation of 5-((4-methoxybenzyl)thio)-3-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0448] Dry 1,4-Dioxane (3 mL) was added to a mixture of 93-1 (178 mg, 0.5 mmol), (4-methoxyphenyl)methanethiol (77 μL, 0.55 mmol; Adamas, 011145514), Pd2(dba)3 (92 mg, 0.1 mmol; Adamas, 014369210), Xantphos (58 mg, 0.1 mmol; Adamas, 01029728), and DIPEA (165 μL, 1 mmol). The mixture was heated and stirred at 110 °C for 2 h under an argon atmosphere. TLC (PE:EA = 15:1, R f =0.6) indicates that 93-1 was completely consumed and a new spot was detected. After cooling to room temperature and concentrating under reduced pressure, crude product 93-2, which is yellow-black gelatinous, was obtained and used directly in the next reaction without purification.

[0449] Step 3: 3-Methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonyl chloride

[0450] Under ice bath conditions, NCS (133 mg, 0.82 mmol; Biotin, BD40870) was added fractionally to a solution of 93-2 (86 mg, 0.2 mmol) dissolved in CH3CN (3.0 mL), AcOH (140 μL), and water (94 μL), and reacted at room temperature for 2 h. TLC (PE:EA = 15:1, R f=0.7) indicates that 93-2 was completely consumed and a new spot was detected. The reaction solution was poured into water (10 mL), extracted with EA (10 mL × 3), the organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 93-3, which was yellow-black and gelatinous. It was used directly in the next reaction without purification.

[0451] Step 4: Preparation of N,3-dimethyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide

[0452] Step 4 follows the same preparation method as step 4 of Example 4, except that 4-3 in step 4 of Example 4 is replaced with 93-3. After purification by column chromatography (DCM:MeOH = 150:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 93 (35.5 mg, 48% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ8.34(d,J=1.3Hz,1H),8.14(d,J=8.9Hz,1H),8.06(d,J=8.5Hz,2H),7.96(d, J=8.6Hz,2H),7.89(dd,J=9.0,1.8Hz,1H),7.52(q,J=5.0Hz,1H),2.68(s,3H),2.43(d,J=5.0Hz,3H).

[0453] Example 94

[0454] 3-(cyclopent-1-en-1-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 94)

[0455] Example 94 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with 1-cyclopentenylboronic acid (BYD, BD122948). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a pink solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 94 (38 mg, 75% yield) in the form of a light pink solid. 1H NMR (300MHz, DMSO-d6) δ8.50(s,1H),8.15(d,J=8.9Hz,1H),8.07(d,J=8.5Hz,2H),7.99(d,J=8.6Hz,2H),7.92(dd,J=8.9,1.7Hz,1 H),7.59(q,J=5.0,4.0Hz,1H),6.79(s,1H),2.95(t,J=6.6Hz,2H),2.68(t,J=5.6Hz,2H),2.43(d,J=4.8Hz,3H),2.10–1.94(m,2H).

[0456] Example 95

[0457] 3-([1,1'-biphenyl]-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 95)

[0458] Example 95 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with 4-biphenylboronic acid (Leyan, 1034198). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 95 (46 mg, 76% yield) in the form of a white solid. 1 H NMR(300MHz, CDCl3)δ8.72(s,1H),8.09(d,J=8.4Hz,2H),8.00–7.92(m,4H),7.91–7.83(m,2H),7.80(d, J=8.3Hz,2H),7.73–7.65(m,2H),7.50(t,J=7.4Hz,2H),7.41(t,J=7.3Hz,1H),4.51(s,1H),2.71(s,3H).

[0459] Example 96

[0460] 3-(4-cyclohexylphenyl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 96)

[0461] Example 96 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with 4-cyclohexylphenylboronic acid. After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a pink solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 96 (46 mg, 75% yield) in the form of a light pink solid. 1 H NMR (300MHz, DMSO-d6) δ8.51(s,1H),8.22(d,J=9.0Hz,1H),8.16(d,J=8.5Hz,2H),8.02(d,J=8.6Hz,2H),7.98–7.91(m,3H),7.59 (q,J=4.9Hz,1H),7.50(d,J=8.1Hz,2H),2.63(t,J=10.8Hz,1H),2.43(d,J=5.0Hz,3H),1.84(d,J=11.3Hz,4H),1.59–1.20(m,6H).

[0462] Example 97

[0463] 3-Chloro-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 97)

[0464] Example 97 was prepared using the same method as Example 93, except that 5-bromo-3-methyl-1H-indazole in step 1 of Example 93 was replaced with 5-bromo-3-chloro-1H-indazole (Leyan, 1121243). After purification by column chromatography (DCM:MeOH = 150:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 97 (37 mg, 54% yield) in the form of a white solid. 1 H NMR (300MHz, CDCl3) δ8.39 (dd, J=1.8, 0.8Hz, 1H), 7.98 (dd, J=9.0, 1.7Hz, 1H), 7 .87(d,J=0.8Hz,1H),7.85(s,4H),4.48(q,J=5.4Hz,1H),2.72(d,J=5.3Hz,3H).

[0465] Example 98

[0466] 3-Bromo-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 98)

[0467] Example 98 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 98 (35 mg, 67% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ8.21(d,J=9.2Hz,1H),8.13(d,J=1.0Hz,1H),8.07(d,J=8.7Hz,2H),8.03–7.95(m,3H),7.67(s,1H),2.44(s,3H).

[0468] Example 99

[0469] N-Methyl-3-(naphth-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 99)

[0470] Example 99 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with 1-naphthoboronic acid. After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 99 (48 mg, 83% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO-d6) δ8.29(t,J=9.0Hz,2H),8.22(d,J=8.4Hz,2H),8.18(d,J= 8.2Hz,1H),8.12(q,J=3.1Hz,2H),8.05(d,J=8.4Hz,2H),7.99(dd,J=8.9,1.7Hz, 1H),7.92(dd,J=7.1,1.3Hz,1H),7.78(dd,J=8.2,7.0Hz,1H),7.67–7.62(m,1H) ,7.59(ddd,J=8.3,6.8,1.5Hz,1H),7.53(q,J=5.0Hz,1H),2.39(d,J=5.0Hz,3H).

[0471] Example 100

[0472] N-Methyl-3-(thien-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 100)

[0473] Example 100 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with 2-thiopheneboronic acid (Bide, BD9413). After purification by column chromatography (DCM:MeOH = 300:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 100 (36 mg, 69% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ8.60(s,1H),8.21(d,J=9.0Hz,1H),8.12(d,J=8.4Hz,2H),8.02(d,J=8.6Hz,2H),7.97(dd,J=8.9,1.6Hz,1H) ,7.93(dd,J=3.7,1.1Hz,1H),7.81(dd,J=5.1,1.1Hz,1H),7.64(q,J=5.0Hz,1H),7.35(dd,J=5.1,3.6Hz,1H),2.46(d,J=5.0Hz,3H).

[0474] Example 101

[0475] 3-(1-Methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (Compound 101)

[0476] Step 1: Preparation of methyl 3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylate

[0477] Step 1 employs the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 is replaced with methyl 3-bromo-1H-indazole-5-carboxylate. After concentration under reduced pressure, a residue is obtained. This residue is then purified by column chromatography (PE:EA = 30:1) to give the title compound 101-1 (253 mg, 63% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ8.48(dd,J=1.6,0.8Hz,1H),8.21(dd,J=8.9,1.6Hz,1H),7.90–7.80(m,4H),7.78(dd,J=9.0,0.8Hz,1H),4.00(s,3H).

[0478] Step 2: Preparation of methyl 3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylate

[0479] Step 2 uses the same preparation method as Step 2 of Example 71, except that 70-1 in Step 2 of Example 71 is replaced with 101-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (PE:EA = 30:1) to give the title compound 101-2 (49 mg, 25% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ9.31(s,1H),8.21(dd,J=9.0,1.6Hz,1H),7.98–7.81(m,5H),7.79(d,J=8.9Hz,1H),4.14(s,3H),3.99(s,3H).

[0480] Step 3: Preparation of 3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid

[0481] Step 3 uses the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 101-2. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction is performed using DCM (20 mL × 3). The organic layer is washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) is added to the residue, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 101 (29 mg, 66% yield) as a white solid. 1 H NMR (300MHz, DMSO-d6) δ13.14(s,1H),9.14(dd,J=1.6,0.8Hz,1H),8.17(d,J=2.8Hz,1H),8.17–8.1 2(m,2H),8.08(dd,J=9.0,0.9Hz,1H),8.01(d,J=8.6Hz,2H),7.65(s,1H),5.76(s,1H),4.13(s,3H).

[0482] Example 102

[0483] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxylic acid (Compound 102)

[0484] Step 1: Preparation of methyl 3-bromo-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxylate

[0485] Step 1 employs the same preparation method as Step 1 of Example 70, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 70 is replaced with methyl 3-bromo-1H-indazole-5-carboxylate. After concentration under reduced pressure, a residue is obtained. This residue is then purified by column chromatography (PE:EA = 15:1) to give the title compound 102-1 (534 mg, 93% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.41(s,1H),8.09(dd,J=8.9,1.5Hz,1H),7.58(d,J=8.3Hz,2H),7.36–7.29(m,3H),5.62(s,2H),3.96(s,3H).

[0486] Step 2: Preparation of methyl 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxylate

[0487] Step 2 follows the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 102-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (DCM:MeOH = 200:1) to give the title compound 102-2 (64 mg, 77% yield) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ8.65 (s, 1H), 8.10 (s, 1H), 8.06 (d, J = 8.9Hz, 1H), 7.99 (s, 1H), 7.56(d,J=8.1Hz,2H),7.31(d,J=8.9Hz,3H),5.66(s,2H),4.04(s,3H),3.96(s,3H).

[0488] Step 3: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxylic acid

[0489] Step 3 uses the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 102-2. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction is performed using DCM (20 mL × 3). The organic layer is washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) is added to the residue, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 102 (36 mg, 60% yield) as a white solid. 1H NMR(400MHz,DMSO-d6)δ13.04(s,1H),8.58(s,1H),8.44(s,1H),8.02–7.94(m,2H),7.79 (d,J=8.9Hz,1H),7.69(d,J=8.4Hz,2H),7.42(d,J=8.4Hz,2H),5.83(s,2H),3.95(s,3H).

[0490] Example 103

[0491] N-(3-(1-cyclobutyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 103)

[0492] Example 103 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with N-cyclobutyl-pyrazole-4-boronic acid pinacol ester (Bide, BD211291). After purification by column chromatography (DCM:MeOH = 150:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 103 (33 mg, 70% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.74 (s, 1H), 8.47 (d, J = 0.8Hz, 1H), 8.21–7.98 (m, 4H), 7.98–7.82 (m, 3H), 7.49 (dd, J = 9.0, 2.0Hz, 1H), 4. 99(p,J=8.4Hz,1H),3.01(s,3H),2.58(pd,J=9.4,2.6Hz,2H),2.44(qd,J=8.3,3.7Hz,2H),1.83(tdd,J=12.3,8.6,5.6Hz,2H).

[0493] Example 104

[0494] N-(3-(3,5-dimethylisoxazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 104)

[0495] Example 104 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 3,5-dimethylisoxazole-4-boric acid (Leyan, 1022863). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a grayish-white solid was obtained. Diethyl ether (4.0 mL), DCM (0.5 mL), and MeOH (0.1 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 104 (13.6 mg, 30.2% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO) δ9.84 (s, 1H), 8.13–8.03 (m, 3H), 7.97 (d, J = 8.6Hz, 2H), 7.63– 7.57(m,1H),7.49(dd,J=9.1,2.0Hz,1H),2.99(s,3H),2.54(s,3H),2.35(s,3H).

[0496] Example 105

[0497] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indol-5-yl)methanesulfonamide (compound 105)

[0498] Step 1: Preparation of 3-(1-methyl-1H-pyrazol-4-yl)-5-nitro-1-(4-((trifluoromethyl)thio)phenyl)-1H-indole

[0499] Step 1 follows the same preparation method as Step 2 in Example 58, except that 1-iodo-4-(trifluoromethoxy)benzene in Step 2 of Example 58 is replaced with 1-bromo-4-(trifluoromethylthio)benzene. After cooling to room temperature, the reaction solution is poured into water (30 mL), extracted with EA (30 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (PE:EA = 1:1) to obtain the title compound 105-1 (150 mg, 47% yield) as an orange-yellow solid. 1 H NMR (400MHz, CDCl3) δ8.75 (d, J=2.2Hz, 1H), 8.19 (dd, J=9.1, 2.2Hz, 1H), 7.88 (d, J=8 .4Hz,2H),7.83–7.73(m,2H),7.61(dd,J=8.9,2.3Hz,3H),7.56(s,1H),4.05(s,3H).

[0500] Step 2: Preparation of 3-(1-methyl-1H-pyrazol-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indole-5-amine

[0501] Step 2 follows the same preparation method as Step 3 of Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 105-1. The reaction solution is poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (DCM:MeOH = 75:1) to obtain the title compound 105-2 (96 mg, 71% yield) as a light brown solid. 1 H NMR (300MHz, CDCl3) δ7.83–7.74(m,3H),7.65(d,J=0.7Hz,1H),7.60–7.53(m,2H),7.47(dd,J=8.7,0.6H z,1H),7.35(s,1H),7.09(dd,J=2.3,0.6Hz,1H),6.75(dd,J=8.7,2.2Hz,1H),4.00(s,3H),3.66(s,2H).

[0502] Step 3: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indole-5-yl)methanesulfonamide

[0503] Step 3 follows the same preparation method as in Step 3 of Example 1, except that steps 1-2 in Step 3 of Example 1 are replaced with 105-2. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 105 (26 mg, 56% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.49 (s, 1H), 8.03 (d, J = 9.1Hz, 2H), 7.96–7.88 (m, 2H), 7.87–7. 78(m,3H),7.75–7.66(m,2H),7.20(dd,J=8.9,2.1Hz,1H),3.93(s,3H),2.93(s,3H).

[0504] Example 106

[0505] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indol-5-yl)acrylamide (compound 106)

[0506] Example 106 was prepared using the same method as Example 10, except that 10-1 in step 2 of Example 10 was replaced with 105-2. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.5 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 106 (37.5 mg, 85% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ10.20(s,1H),8.32(d,J=1.9Hz,1H),8.01(d,J=14.4Hz,2H),7.96–7.88(m,2H),7.88–7.75(m,3H),7.69(d,J=8.9Hz, 1H), 7.51 (dd, J=9.0, 2.0Hz, 1H), 6.48 (dd, J=16.9, 10.1Hz, 1H), 6.28 (dd, J=17.0, 2.1Hz, 1H), 5.76 (dd, J=10.1, 2.1Hz, 1H), 3.94 (s, 3H).

[0507] Example 107

[0508] N-(3-(cyclohexyl-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 107)

[0509] Example 107 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with cyclohexene-1-ylboric acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 107 (27.3 mg, 63% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO) δ9.72 (s, 1H), 8.06–7.87 (m, 6H), 7.45 (dd, J = 9.1, 2.0Hz, 1H), 6. 61(t,J=3.8Hz,1H),2.97(s,3H),2.63(s,2H),2.37–2.26(m,2H),1.84–1.65(m,4H).

[0510] Example 108

[0511] 3-(cyclopent-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (compound 108)

[0512] Step 1: Preparation of methyl 3-(cyclopenten-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylate

[0513] Step 1 employs the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 101-1, and 1-methyl-1H-pyrazole-4-boric acid is replaced with cyclopenten-1-ylboric acid. After concentration under reduced pressure, crude product 108-1, a yellow solid, is obtained and used directly in the next reaction without purification.

[0514] Step 2: Preparation of 3-(cyclopent-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid

[0515] Step 2 uses the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 108-1. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction is performed using DCM (20 mL × 3). The organic layer is washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) is added to the residue, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 108 (38 mg, 51% yield) as a pale yellow solid. 1 H NMR (300MHz, DMSO) δ13.15(s,1H),8.65(s,1H),8.12–7.91(m,6H),6.75(s,1H),2.93(t,J=6.7Hz,2H),2.65(t,J=6.7Hz,2H),2.01(p,J=7.6Hz,2H).

[0516] Example 109

[0517] 3-(cyclopent-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylic acid (compound 109)

[0518] Step 1: Preparation of methyl 1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylate

[0519] Step 1 follows the same preparation method as Step 1 in Example 54, except that 1-iodo-4-(trifluoromethoxy)benzene in Step 1 of Example 54 is replaced with 4-iodotrifluorotoluene (BYD, BD10289). After cooling to room temperature, the reaction solution is poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (PE:EA = 100:1) to obtain the title compound 109-1 (1356 mg, 85% yield) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ8.46 (dd, J=1.7, 0.7Hz, 1H), 7.96 (dd, J=8.8, 1.6Hz, 1H), 7.86–7.77 (m, 2H), 7. 68–7.61(m,2H),7.61–7.54(m,1H),7.41(d,J=3.4Hz,1H),6.82(dd,J=3.4,0.8Hz,1H),3.95(s,3H).

[0520] Step 2: Preparation of methyl 3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylate

[0521] Step 2 follows the same preparation method as Step 2 in Example 54, except that 54-1 in Step 2 of Example 54 is replaced with 109-1. The reaction solution is poured into water (100 mL), extracted with EA (50 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, DCM (2.0 mL) and n-hexane (10.0 mL) are added to the residue, the mixture is stirred at room temperature for 1 h, and filtered to obtain the title compound 109-2 (1247 mg, 74% yield) as a light pink solid. 1 H NMR (300MHz, CDCl3) δ8.40 (dd, J=1.7, 0.7Hz, 1H), 8.00 (dd, J=8.8, 1.7Hz, 1H), 7.83 (d, J= 8.4Hz,2H),7.62(d,J=8.3Hz,2H),7.55(dd,J=8.8,0.7Hz,1H),7.46(s,1H),3.97(s,3H).

[0522] Step 3: Preparation of methyl 3-(cyclopent-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylate

[0523] Step 3 employs the same preparation method as Step 3 in Example 54, except that 54-2 in Step 3 of Example 54 is replaced with 109-2, and 1-methyl-4-pyrazoleboronic acid pinacol ester is replaced with cyclopenten-1-ylboronic acid. After cooling to room temperature and concentration under reduced pressure, the residue is obtained. The residue is purified by column chromatography (PE:EA = 150:1) to obtain the title compound 109-3 (38.5 mg, 50% yield) as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.72(dd,J=1.7,0.6Hz,1H),7.97(dd,J=8.8,1.7Hz,1H),7.81(d,J=8.3Hz,2H),7.65–7.62(m,2H),7.56(d d,J=8.8,0.7Hz,1H),7.33(s,1H),6.41(p,J=2.1Hz,1H),3.96(s,3H),2.83–2.75(m,2H),2.69–2.62(m,2H),2.09–2.00(m,2H).

[0524] Step 4: Preparation of 3-(cyclopent-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylic acid

[0525] Step 4 uses the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 109-3. After concentration under reduced pressure, a residue is obtained. 1N HCl is added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction is performed using DCM (20 mL × 5). The organic layer is washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) are added to the residue, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 109 (10.7 mg, 29% yield) as a pale yellow solid. 1 H NMR(300MHz,DMSO)δ12.80(s,1H),8.56(d,J=1.6Hz,1H),8.01–7.84(m,6H),7.72(d,J=8 .7Hz,1H),6.29(s,1H),2.80(d,J=6.6Hz,2H),2.66–2.54(m,2H),1.97(p,J=7.6Hz,2H).

[0526] Example 110

[0527] 3-(thiophene-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (compound 110)

[0528] Example 110 was prepared using the same method as Example 108, except that cyclopenten-1-ylboronic acid in step 1 of Example 108 was replaced with thiophene-2-boronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 110 (40.4 mg, 59.5% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ13.24(s,1H),8.76(q,J=1.1Hz,1H),8.20–8.04(m,4H),8.00(d,J=8.5H z,2H),7.92(dd,J=3.7,1.2Hz,1H),7.78(dd,J=5.0,1.0Hz,1H),7.32(dd,J=5.1,3.6Hz,1H).

[0529] Example 111

[0530] 3-(thiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (compound 111)

[0531] Example 111 was prepared using the same method as Example 108, except that thiophene-2-boronic acid in step 1 of Example 108 was replaced with 3-thiopheneboronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 111 (53.8 mg, 74% yield) as a white solid. 1 H NMR (300MHz, DMSO) δ13.17(s,1H),8.78–8.72(m,1H),8.35(dd,J=2.7,1.3Hz,1H),8.17–8.05(m,4H),7.99(d,J=8.6Hz,2H),7.85–7.74(m,2H).

[0532] Example 112

[0533] 3-(thiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylic acid (compound 112)

[0534] Example 112 was prepared using the same method as Example 109, except that cyclopent-1-ene-1-boronic acid in step 3 of Example 109 was replaced with 3-thiopheneboronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 112 (50.4 mg, 45.4% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ12.82(s,1H),8.59(d,J=1.6Hz,1H),8.26(s,1H),7.98(q,J=8.7Hz,4H),7.91(dd,J=8.7,1.6 Hz,1H),7.85(dd,J=2.8,1.3Hz,1H),7.80–7.75(m,1H),7.72(dd,J=5.0,2.8Hz,1H),7.60(dd,J=5.0,1.3Hz,1H).

[0535] Example 113

[0536] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indol-5-yl)methanesulfonamide (compound 113)

[0537] Example 113 was prepared using the same method as Example 58, except that in step 1 of Example 58, 1-methyl-4-pyrazoloniate pinacol ester was replaced with thiophene-2-boric acid, and in step 2, 1-iodo-4-(trifluoromethoxy)benzene was replaced with 4-iodotrifluorotoluene. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 113 (19.8 mg, 12% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO) δ9.63 (s, 1H), 8.18 (s, 1H), 8.01–7.87 (m, 5H), 7.71 (d, J = 8.9Hz, 1H), 7.55(dd,J=5.1,1.2Hz,1H),7.42(dd,J=3.5,1.2Hz,1H),7.27–7.17(m,2H),2.94(s,3H).

[0538] Example 114

[0539] N-(3-(cyclohexyl-1-en-1-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-yl)methanesulfonamide (compound 114)

[0540] Example 114 was prepared using the same method as Example 58, except that 1-methyl-4-pyrazolone pinacol ester in step 1 of Example 58 was replaced with cyclohexene-1-boronic acid. After purification by column chromatography (PE:EA = 5:1), a crude product in the form of a light pink solid was obtained. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 114 (96.2 mg, 30.5% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.42(s,1H),7.79(d,J=2.1Hz,1H),7.77–7.67(m,3H),7.62–7.51(m,3H),7.15(dd,J=8.8,2.1Hz,1H),6.21(t,J=1.8Hz ,1H),2.90(s,3H),2.45(t,J=4.9Hz,2H),2.25(td,J=5.7,3.3Hz,2H),1.75(ddt,J=9.0,6.8,3.6Hz,2H),1.66(ddd,J=11.2,7.7,5.0Hz,2H).

[0541] Example 115

[0542] N-(1-(cyclopenten-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 115)

[0543] Example 115 was prepared using the same method as Example 1, except that 3-bromo-5-nitro-1H-indazole in step 1 of Example 1 was replaced with 3-bromo-6-nitro-1H-indazole, 4-trifluoromethylphenylboronic acid was replaced with cyclopenten-1-ylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 115 (55.2 mg, 65.5% yield) in the form of a creamy white solid. 1H NMR (300MHz, DMSO) δ10.11(s,1H),8.20(d,J=8.1Hz,2H),8.13(d,J=8.8Hz,1H),7.89(d,J=8.2Hz,2H),7.78(d,J=1.7H z,1H),7.24(dd,J=8.8,1.8Hz,1H),6.01–5.94(m,1H),3.08(s,5H),2.63(td,J=7.7,2.5Hz,2H),2.06(p,J=7.6Hz,2H).

[0544] Example 116

[0545] N-(1-(cyclohexyl-1-en-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 116)

[0546] Example 116 was prepared using the same method as Example 1, except that 3-bromo-5-nitro-1H-indazole in step 1 of Example 1 was replaced with 3-bromo-6-nitro-1H-indazole, 4-trifluoromethylphenylboronic acid was replaced with cyclohexen-1-ylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (PE:EA = 5:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 116 (55.1 mg, 63% yield) in the form of a creamy white solid. 1 H NMR (300MHz, DMSO) δ10.02(s,1H),8.19(d,J=8.1Hz,2H),8.11(d,J=8.8Hz,1H),7.87(d,J=8.2Hz,2H),7.61(d,J=1.7Hz,1H),7.22(dd, J=8.8,1.8Hz,1H),6.11(t,J=3.9Hz,1H),3.06(s,3H),2.70–2.61(m,2H),2.31(d,J=3.5Hz,2H),1.90–1.79(m,2H),1.77–1.65(m,2H).

[0547] Example 117

[0548] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylic acid (Compound 117)

[0549] Step 1: Preparation of methyl 3-bromo-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylate

[0550] To a mixture of methyl 3-bromo-1H-indazole-5-carboxylate (225 mg, 1.0 mmol), 1-bromo-4-(trifluoromethylthio)benzene (180 μL, 1.2 mmol), CuI (95 mg, 0.5 mmol), and K₂CO₃ (277 mg, 2.0 mmol) dissolved in dry DMF (5.0 mL), N,N'-dimethylethylenediamine (110 μL, 1.0 mmol) was added, and the mixture was heated and stirred at 120 °C for 10 h. TLC (PE:EA = 4:1, R f =0.8) indicates that a small amount of the starting material remains and a new spot was detected. After cooling to room temperature, the reaction solution was poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer was washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product 117-1 that is brownish-black and gelatinous. It was used directly in the next reaction without purification.

[0551] Step 2: Preparation of methyl 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylate

[0552] Step 2 follows the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 117-1. After concentration under reduced pressure, a residue is obtained. This residue is then purified by column chromatography (DCM:MeOH = 100:1) to give the title compound 117-2 (60.6 mg, 22.5% two-step yield) as a yellowish-gray solid. 1 HNMR(400MHz, CDCl3)δ8.70(dd,J=1.6,0.8Hz,1H),8.20–8.14(m,2H),8.05(s, 1H),7.90–7.83(m,4H),7.80(dd,J=8.9,0.8Hz,1H),4.06(s,3H),4.00(s,3H).

[0553] Step 3: Preparation of 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylic acid

[0554] Step 3 follows the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 is replaced with 117-2. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 117 (28.8 mg, 50% yield) as a white solid. 1 H NMR (300MHz, DMSO) δ13.14(s,1H),8.65(s,1H),8.59(s,1H),8.16–7.99(m,5H),7.99–7.91(m,2H),3.99(s,3H).

[0555] Example 118

[0556] 3-(thiophene-3-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylic acid (compound 118)

[0557] Example 118 was prepared using the same method as Example 117, except that 1-methyl-1H-pyrazole-4-boric acid in step 2 of Example 117 was replaced with thiophene-3-boric acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 118 (34.5 mg, 47.5% yield) as a white solid. 1 H NMR (300MHz, DMSO) δ13.21(s,1H),8.74(t,J=1.1Hz,1H),8.34(dd,J=2.8,1.4Hz,1H),8.18–8.02(m,4H),7.97(d,J=8.6Hz,2H),7.85–7.74(m,2H).

[0558] Example 119

[0559] 3-(thiophene-2-yl)-1-(4-((trifluoromethyl)thio)phenyl)-1H-indazole-5-carboxylic acid (compound 119)

[0560] Example 119 was prepared using the same method as Example 117, except that 1-methyl-1H-pyrazole-4-boric acid in step 2 of Example 117 was replaced with thiophene-2-boric acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (5.0 mL) and n-hexane (0.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 119 (26.2 mg, 39% yield) as a white solid. 1 H NMR(300MHz,DMSO)δ13.21(s,1H),8.81–8.72(m,1H),8.15(dd,J=9.0,1.5Hz,1H),8.11–8.01(m,3H),7.9 7(d,J=8.7Hz,2H),7.92(dd,J=3.7,1.1Hz,1H),7.78(dd,J=5.1,1.1Hz,1H),7.31(dd,J=5.1,3.6Hz,1H).

[0561] Example 120

[0562] N-(1-(1-methyl-1H-pyrazole-4-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-yl)methanesulfonamide (compound 120)

[0563] Example 120 was prepared using the same method as Example 7, except that the 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 4-iodo-1-methyl-1H-pyrazole (Bide, BD59498). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow gel was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 120 (24 mg, 55% yield) in the form of a pale yellow solid. 1 H NMR (300MHz, DMSO) δ10.10(s,1H),8.33(d,J=0.8Hz,1H),8.23(d,J=8.1Hz,2H),8.16(d,J=8.8Hz,1 H),7.98–7.85(m,3H),7.51(d,J=1.7Hz,1H),7.23(dd,J=8.8,1.8Hz,1H),3.97(s,3H),3.08(s,3H).

[0564] Example 121

[0565] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide (compound 121)

[0566] Example 121 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with thiophene-3-boric acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 121 (49.4 mg, 60% yield) in the form of a pale yellow solid. 1 H NMR(300MHz, CDCl3)δ8.58(s,1H),7.97–7.86(m,3H),7.84–7.70(m,4H),7.49(td,J=6.1,3.8Hz ,3H),6.52(dd,J=16.8,1.3Hz,1H),6.31(dd,J=16.8,10.1Hz,1H),5.84(dd,J=10.1,1.3Hz,1H).

[0567] Example 122

[0568] N-(ethylsulfonyl)-N-(3-(thiophen-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)ethanesulfonamide (compound 122)

[0569] Example 122 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with thiophene-3-boric acid, and acryloyl chloride in step 2 was replaced with ethylsulfonyl chloride. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.5 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 122 (7.4 mg, 6.6% yield) in the form of a pale yellow solid. 1 H NMR(400MHz, CDCl3)δ8.05(d,J=2.0Hz,1H),7.95–7.87(m,3H),7.83(dd,J=8.8,2.8Hz,3H), 7.72(dd,J=5.1,1.3Hz,1H),7.56–7.47(m,2H),3.67(q,J=7.4Hz,4H),1.51(t,J=7.4Hz,6H).

[0570] Example 123

[0571] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide (compound 123)

[0572] Example 123 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with thiophene-2-boric acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a creamy white solid was obtained. Diethyl ether (5.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 123 (53.8 mg, 65% yield) in the form of a white solid. 1 H NMR (300MHz, CDCl3) δ8.61(s,1H),7.92(d,J=8.4Hz,2H),7.86–7.65(m,4H),7.61–7.45(m,2H),7.42(d,J=5.0Hz ,1H),7.19(dd,J=5.1,3.6Hz,1H),6.52(d,J=16.8Hz,1H),6.31(dd,J=16.8,10.1Hz,1H),5.84(d,J=10.1Hz,1H).

[0573] Example 124

[0574] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)acrylamide (compound 124)

[0575] Example 124 was prepared using the same method as Example 10, except that 1-2 in step 1 of Example 10 was replaced with 5-2 prepared in step 2 of Example 5, and 1-methyl-1H-pyrazole-4-boric acid was replaced with thiophene-3-boric acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellowish-brown solid was obtained. Diethyl ether (5.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 124 (73.2 mg, 57% yield) in the form of a creamy-white solid. 1 H NMR (300MHz, CDCl3) δ8.57(s,1H),7.90(dd,J=2.9,1.3Hz,1H),7.84–7.71(m,3H),7.67(d,J=9.0Hz,1H),7. 56–7.33(m,5H),6.51(dd,J=16.8,1.4Hz,1H),6.30(dd,J=16.8,10.1Hz,1H),5.83(dd,J=10.0,1.3Hz,1H).

[0576] Example 125

[0577] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)acrylamide (compound 125)

[0578] Example 125 was prepared using the same method as Example 10, except that 1-2 in step 1 of Example 10 was replaced with 5-2 prepared in step 2 of Example 5, and 1-methyl-1H-pyrazole-4-boric acid was replaced with thiophene-2-boric acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (5.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 125 (70.8 mg, 82.5% yield) in the form of a white solid. 1 H NMR (300MHz, CDCl3) δ8.58(d,J=1.9Hz,1H),7.88–7.75(m,2H),7.72(dd,J=3.6,1.1Hz,1H),7.66(d,J=9.0Hz,1H),7.50(dd,J=9.1,1.9Hz,2H ),7.45–7.32(m,3H),7.18(dd,J=5.1,3.6Hz,1H),6.52(dd,J=16.8,1.3Hz,1H),6.31(dd,J=16.8,10.1Hz,1H),5.83(dd,J=10.1,1.3Hz,1H).

[0579] Example 126

[0580] N-(3-(furan-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 126)

[0581] Example 126 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 3-furanboric acid (Leyan, 1035787). After purification by column chromatography (PE:EA = 3:1), a crude product in the form of a creamy white solid was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 126 (27.4 mg, 41% yield) in the form of a white solid. 1H NMR(400MHz, DMSO)δ9.76(s,1H),8.42(dd,J=1.5,0.8Hz,1H),8.13–8.05(m,2H),8.03(dd,J=9.0,0.7Hz,1H),7.99–7.94(m,2 H),7.93(t,J=1.7Hz,1H),7.88(dd,J=2.0,0.7Hz,1H),7.49(dd,J=9.1,2.0Hz,1H),7.07(dd,J=1.9,0.8Hz,1H),3.02(s,3H).

[0582] Example 127

[0583] N-(3-(furan-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)acrylamide (compound 127)

[0584] Example 127 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with 2-furanboric acid (Leyan, 1020048). After purification by column chromatography (PE:EA = 3:1), a crude product in the form of a creamy white solid was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 127 (29.4 mg, 62% yield) in the form of a creamy white solid. 1 H NMR (400MHz, CDCl3) δ8.55(s,1H),7.90(d,J=8.3Hz,2H),7.79(d,J=8.5Hz,2H),7.71(d,J=9.0Hz,1H),7.63(dd,J=1.9,0.8Hz,2H),7.54(s,1H),7 .05(dd,J=3.4,0.8Hz,1H), 6.59(dd,J=3.4,1.8Hz,1H), 6.51(dd,J=16.9,1.3Hz,1H), 6.32(dd,J=16.8,10.2Hz,1H), 5.83(dd,J=10.2,1.2Hz,1H).

[0585] Example 128

[0586] 1-(cyclohexyl-1-en-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (compound 128)

[0587] Step 1: Preparation of methyl 3-bromo-1-(cyclohex-1-en-1-yl)-1H-indazole-6-carboxylate

[0588] Step 1 employs the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 is replaced with methyl 3-bromo-1H-indazole-6-carboxylate, and 4-trifluoromethylphenylboronic acid is replaced with cyclohexen-1-ylboronic acid. After concentration under reduced pressure, a residue is obtained, which is then purified by column chromatography (PE:EA = 50:1) to give the title compound 128-1 (143.6 mg, 86% yield) as a pale yellow oil. 1 H NMR (400MHz, CDCl3) δ8.31(t,J=1.1Hz,1H),7.87(dd,J=8.5,1.3Hz,1H),7.65(dd,J=8.5,0.8Hz,1H),6.06(td,J=4.0,1.9Hz,1H),3 .98(s,3H),2.63(dddd,J=8.8,4.3,3.3,1.9Hz,2H),2.34(dddd,J=8.8,6.3,4.1,2.6Hz,2H),1.94–1.85(m,2H),1.81–1.73(m,2H).

[0589] Step 2: Preparation of methyl 1-(cyclohexyl-1-en-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylate

[0590] Step 2 uses the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 is replaced with 128-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (PE:EA = 75:1) to give the title compound 128-2 (127.3 mg, 76% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ8.39(t,J=1.1Hz,1H),8.10(d,J=8.1Hz,2H),8.03(dd,J=8.6,0.8Hz,1H),7.91(dd,J=8.6,1.3Hz,1H),7.76(d,J=8.1Hz,2H),6. 15(tt,J=4.1,1.7Hz,1H),4.00(s,3H),2.78–2.66(m,2H),2.39(ddt,J=8.5 ,6.5,2.8Hz,2H),1.94(qd,J=6.0,2.4Hz,2H),1.81(qd,J=5.8,2.3Hz,2H).

[0591] Step 3: Preparation of 1-(cyclohexyl-1-en-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid

[0592] Step 3 followed the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 was replaced with 128-2. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.5 mL) and n-hexane (2.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 128 (103 mg, 85% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ13.31(s,1H),8.30(t,J=1.0Hz,1H),8.28–8.17(m,3H),7.97–7.79(m,3H),6.19(dq,J=3. 9,2.0Hz,1H),2.66(tq,J=4.2,2.1Hz,2H),2.36(tt,J=6.3,2.8Hz,2H),1.93–1.82(m,2H),1.79–1.68(m,2H).

[0593] Example 129

[0594] 1-(cyclopent-1-en-1-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (compound 129)

[0595] Example 129 was prepared using the same method as Example 128, except that cyclohexen-1-ylboronic acid in step 1 of Example 128 was replaced with cyclopenten-1-ylboronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.5 mL) and n-hexane (2.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 129 (88.1 mg, 79.5% yield) as a white solid. 1 H NMR(400MHz,DMSO)δ13.35(s,1H),8.42(t,J=1.1Hz,1H),8.30–8.17(m,3H),7.97–7.85(m,3H) ,6.14(t,J=2.3Hz,1H),3.10(tt,J=7.7,2.3Hz,2H),2.71–2.61(m,2H),2.08(p,J=7.5Hz,2H).

[0596] Example 130

[0597] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)ethanesulfonamide (compound 130)

[0598] Example 130 was prepared using the same method as Example 10, except that 1-2 in step 1 of Example 10 was replaced with 5-2 prepared in step 2 of Example 5, 1-methyl-1H-pyrazole-4-boric acid was replaced with 3-thiopheneboric acid, and acryloyl chloride in step 2 was replaced with ethylsulfonyl chloride. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a light brown gel was obtained. Diethyl ether (2.0 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 130 (33.8 mg, 36% yield) in the form of a light yellow solid. 1 H NMR(300MHz,C6D6)δ9.86(s,1H),8.08(dd,J=2.9,1.3Hz,1H),8.01–7.89(m,4H),7.81(dd,J=5.0,2.8Hz,1H),7.70( dd,J=5.0,1.3Hz,1H),7.66–7.56(m,2H),7.46(dd,J=9.1,2.0Hz,1H),3.11(q,J=7.3Hz,2H),1.22(t,J=7.3Hz,3H).

[0599] Example 131

[0600] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)ethanesulfonamide (compound 131)

[0601] Example 131 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boric acid in step 1 of Example 10 was replaced with 3-thiopheneboric acid, and acryloyl chloride in step 2 was replaced with ethylsulfonyl chloride. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a light brown solid was obtained. Diethyl ether (1.0 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 131 (13.8 mg, 30.6% yield) in the form of a light brown solid. 1H NMR (300MHz, DMSO) δ9.91(s,1H),8.17–8.06(m,3H),8.03(d,J=9.1Hz,1H),8.00–7.91(m,3H),7.82(dd,J=5.0,2 .8Hz,1H),7.72(dd,J=5.0,1.3Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),3.12(q,J=7.3Hz,2H),1.22(t,J=7.3Hz,3H).

[0602] Example 132

[0603] N-(1-(thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 132)

[0604] Example 132 was prepared using the same method as Example 7, except that the 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 2-iodothiophene (Adamas, 01063602). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 132 (45.3 mg, 69% yield) in the form of a pale yellow solid. 1 H NMR (300MHz, DMSO) δ10.22(s,1H),8.31–8.13(m,3H),7.92(d,J=8.2Hz,2H),7.75(d,J=1.7Hz,1H),7.55(dd,J=5. 5,1.4Hz,1H),7.42(dd,J=3.8,1.4Hz,1H),7.28(dd,J=8.8,1.8Hz,1H),7.21(dd,J=5.5,3.8Hz,1H),3.10(s,3H).

[0605] Example 133

[0606] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 133)

[0607] Example 133 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 3-thiopheneboric acid. After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 133 (35 mg, 67% yield) in the form of a white solid. 1 H NMR(300MHz, DMSO-d6)δ9.82(s,1H),8.15(dd,J=2.9,1.3Hz,1H),8.11(d,J=8.4Hz,2H),8.05(d,J=9.1Hz,1H),8.0 1–7.94(m,3H),7.83(dd,J=5.0,2.9Hz,1H),7.74(dd,J=5.0,1.3Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),3.02(s,3H).

[0608] Example 134

[0609] N-(3-(4-methylthiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 134)

[0610] Example 134 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 4-methyl-2-thiopheneboric acid (Bide, BD2775). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 134 (44 mg, 81% yield) in the form of a white solid. 1 H NMR (300MHz, DMSO-d6) δ9.85 (s, 1H), 8.06 (t, J = 7.4Hz, 3H), 8.03 (d, J = 1.7Hz, 1H), 7.97 (d, J = 8.6Hz, 2H),7.60(d,J=1.4Hz,1H),7.52(dd,J=9.1,1.9Hz,1H),7.35–7.30(m,1H),3.02(s,3H),2.34(s,3H).

[0611] Example 135

[0612] N-(3-(5-formylthiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 135)

[0613] Example 135 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-aldehydethiophene-4-boric acid (Bide, BD8087). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a brown solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 135 (45 mg, 81% yield) in the form of a brown solid. 1 H NMR (300MHz, DMSO-d6) δ10.10(d,J=1.2Hz,1H),9.84(s,1H),8.69(t,J=1.4Hz,1H),8.62(d,J=1.5Hz,1H),8 .12(d,J=8.4Hz,2H),8.07(d,J=9.1Hz,1H),7.99(d,J=8.7Hz,3H),7.52(dd,J=9.1,2.0Hz,1H),3.04(s,3H).

[0614] Example 136

[0615] N-(3-(2-chlorothiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 136)

[0616] Example 136 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-chlorothiophene-3-boric acid (Bide, BD8051). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 136 (40 mg, 71% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO) δ9.83 (s, 1H), 8.15–8.08 (m, 2H), 8.06 (dd, J = 9.1, 0.7Hz, 1 H),7.97(d,J=8.6Hz,2H),7.79–7.71(m,2H),7.53–7.44(m,2H),2.99(s,3H).

[0617] Example 137

[0618] N-(1-(thiophen-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 137)

[0619] Example 137 was prepared using the same method as Example 7, except that the 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 3-iodothiophene (Bide, BD87557). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 137 (53 mg, 61% yield) in the form of a white solid. 1 ¹H NMR (400MHz, DMSO) δ 10.13 (s, 1H), 8.30–8.23 (m, 2H), 8.18 (dd, J = 8.8, 0.6Hz, 1H), 7.95–7.87 (m, 3H), 7.86 (dd, J = 5.1, 3.1Hz, 1H), 7.71 (dd, J = 1.8, 0.7Hz, 1H), 7.61 (dd, J = 5.1, 1.5Hz, 1H), 7.26 (dd, J = 8.8, 1.9Hz, 1H), 3.10 (s, 3H). Example 138

[0620] N-(3-(4-methylthiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 138)

[0621] Example 138 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 4-methyl-3-thiopheneboric acid (Bide, BD98883). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 138 (39 mg, 72% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.75 (s, 1H), 8.09 (t, J = 9.5Hz, 3H), 8.02-7.94 (m, 3H), 7.83 (d, J = 1 .5Hz,1H),7.50(dd,J=8.7,1.8Hz,1H),7.45(d,J=2.5Hz,1H),3.00(s,3H),2.47(s,3H).

[0622] Example 139

[0623] N-(3-(2-methylthiophen-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 139)

[0624] Example 139 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-methyl-3-thiopheneboric acid (BYD, BD161868). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 139 (35 mg, 65% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.81(s,1H),8.11(d,J=8.4Hz,2H),8.06(d,J=9.0Hz,1H),7.97(d,J=8.6Hz,2H),7.75(d,J= 2.0Hz,1H),7.58(d,J=5.3Hz,1H),7.49(dd,J=9.1,2.0Hz,1H),7.46(d,J=5.3Hz,1H),2.99(s,3H),2.69(s,3H).

[0625] Example 140

[0626] N-(3-(2-formylthiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 140)

[0627] Example 140 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-aldehydethiophene-3-boric acid (Bide, BD2643). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a yellow solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 140 (40 mg, 72% yield) in the form of a yellow solid. 1 H NMR (400MHz, DMSO) δ10.38-10.29(m,1H),9.90(s,1H),8.39(d,J=3.8Hz,1H),8.14(d,J=8.4Hz,2H),8.09(d,J=9.1H z,1H),8.00(d,J=8.5Hz,2H),7.85(d,J=2.0Hz,1H),7.83(d,J=5.0Hz,1H),7.53(dd,J=9.0,2.0Hz,1H),3.02(s,3H).

[0628] Example 141

[0629] N-(3-(2,5-dimethylthiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 141)

[0630] Example 141 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2,5-dimethylthiophene-3-boric acid (Bide, BD260481). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 141 (30 mg, 54% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.78 (s, 1H), 8.09 (d, J = 8.4Hz, 2H), 8.05 (d, J = 9.0Hz, 1H), 7.96 (d, J = 8.6Hz, 2H) ,7.74(d,J=1.9Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),7.13(d,J=1.3Hz,1H),2.98(s,3H),2.60(s,3H).

[0631] Example 142

[0632] N-(3-(benzo[b]thiophene-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 142)

[0633] Example 142 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with benzothiophene-2-boric acid (Bide, BD6032). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 142 (37 mg, 64% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.89 (s, 1H), 8.21-8.11 (m, 3H), 8.08 (dd, J = 11.7, 2.5Hz, 3H) ,8.04-7.97(m,3H),7.56(dd,J=9.1,2.0Hz,1H),7.51-7.41(m,2H),3.06(s,3H).

[0634] Example 143

[0635] N-(3-(3-methylthiophen-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 143)

[0636] Example 143 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 3-methylthiophene-2-boric acid (Bide, BD2774). After purification by column chromatography (DCM:MeOH = 500:1), a crude product in the form of a white solid was obtained. Diethyl ether (5.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 143 (33 mg, 61% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.90(s,1H),8.10(d,J=8.4Hz,2H),8.07(d,J=9.0Hz,1H),7.98(d,J=8.6Hz,2H),7.92(d,J= 1.9Hz,1H),7.72(d,J=5.1Hz,1H),7.50(dd,J=9.1,2.1Hz,1H),7.18(d,J=5.0Hz,1H),2.99(s,3H),2.52(s,3H).

[0637] Example 144

[0638] N-(3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide (compound 144)

[0639] Example 144 was prepared using the same method as Example 8, except that step 1-2 in Example 8 was replaced with step 2 of Example 12-2. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (PE:EA = 4:1) to obtain a crude product as a pale yellow solid. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 144 (18.7 mg, 44% yield) as a creamy white solid. 1 H NMR(300MHz, CDCl3)δ8.65(s,1H),8.58(d,J=2.4Hz,1H),8.35–8.24(m,2H),7.55(s,1H),7.37(d,J=8 .7Hz,2H),6.55(dd,J=16.8,1.2Hz,1H),6.33(dd,J=16.8,10.2Hz,1H),5.89(dd,J=10.1,1.2Hz,1H).

[0640] Example 145

[0641] N-(3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide (compound 145)

[0642] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-b]pyridine

[0643] Step 1 employed the same preparation method as Step 1 of Example 1, except that the 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 was replaced with 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine. After concentration under reduced pressure, a residue was obtained. This residue was purified by column chromatography (PE:EA = 50:1) to give the title compound 145-1 (176 mg, 18% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ9.55(d,J=2.4Hz,1H),8.94(d,J=2.4Hz,1H),8.48(d,J=8.5Hz,2H),7.83(d,J=8.6Hz,2H).

[0644] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-b]pyridine-5-amine

[0645] Step 2 uses the same preparation method as step 3 in Example 58, except that 58-2 in step 3 of Example 58 is replaced with 145-1. After concentration under reduced pressure, crude product 145-2, which is a yellow solid, is obtained and used directly in the next reaction without purification.

[0646] Step 3: Preparation of N-(3-bromo-1-(4-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide

[0647] Step 3 follows the same preparation method as Step 1 of Example 8, except that 1-2 in Step 1 of Example 8 is replaced with 145-2. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (PE:EA = 4:1) to obtain a crude product that is a pale yellow solid. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 145 (22.4 mg, 36.5% yield) as a creamy white solid. 1H NMR (300MHz, CDCl3) δ8.67(s,1H),8.60(d,J=2.5Hz,1H),8.47(d,J=8.5Hz,2H),7.77(d,J=8.6Hz,2H), 7.56(s,1H),6.55(dd,J=16.9,1.2Hz,1H),6.33(dd,J=16.8,10.2Hz,1H),5.90(dd,J=10.3,1.2Hz,1H).

[0648] Example 146

[0649] N-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylamide (compound 146)

[0650] Step 1: Preparation of 5-nitro-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

[0651] Step 1 was prepared using the same method as Step 1 of Example 145, except that 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine in Step 1 of Example 145 was replaced with 5-nitro-1H-pyrrolo[2,3-b]pyridine (Bide, BD104973), 4-trifluoromethylphenylboronic acid was replaced with 4-trifluoromethoxyphenylboronic acid, and Py was replaced with DBU. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (PE:EA = 40:1) to give the title compound 146-1 (221 mg, 68.5% yield) as a yellow solid. 1 H NMR(400MHz, CDCl3) δ9.26(d,J=2.4Hz,1H),8.85(d,J=2.5Hz,1H),7.83–7.76(m ,2H),7.67(d,J=3.7Hz,1H),7.43(dq,J=7.8,1.0Hz,2H),6.87(d,J=3.7Hz,1H).

[0652] Step 2: Preparation of 1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-amine

[0653] Step 2 uses the same preparation method as Step 2 of Example 145, except that 145-1 in Step 2 of Example 145 is replaced with 146-1. After concentration under reduced pressure, crude product 146-2, which is brownish-black and oily, is obtained and used directly in the next reaction without purification.

[0654] Step 3: Preparation of N-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylamide

[0655] Step 3 follows the same preparation method as Step 3 of Example 145, except that 145-2 in Step 3 of Example 145 is replaced with 146-2. After concentration under reduced pressure, a residue is obtained. The residue is purified by column chromatography (PE:EA = 3:1) to obtain a crude product as a white solid. Diethyl ether (1.0 mL) and n-hexane (2.5 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 146 (82.8 mg, 70% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ8.56(d,J=2.3Hz,1H),8.27(d,J=2.4Hz,1H),7.87–7.73(m,2H),7.50(d,J=3.8Hz,2H),7.37(d,J= 8.5Hz,2H),6.64(d,J=3.7Hz,1H),6.49(dd,J=16.9,1.4Hz,1H),6.31(dd,J=16.8,10.1Hz,1H),5.82(d,J=10.1Hz,1H).

[0656] Example 147

[0657] N-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methanesulfonamide (compound 147)

[0658] Example 147 was prepared using the same method as Example 11, except that step 1 of Example 11, 9-2, was replaced with 146-2 prepared in step 2 of Example 146. After concentration under reduced pressure, a residue was obtained. This residue was purified by column chromatography (PE:EA = 2:1) to obtain a crude product as a pale yellow solid. Diethyl ether (1.0 mL) and n-hexane (2.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 147 (100 mg, 79% yield) as a white solid. 1 H NMR (300MHz, CDCl3) δ8.24(d,J=2.4Hz,1H),8.03(d,J=2.4Hz,1H),7.84–7.74(m,2H),7. 56(d,J=3.7Hz,1H),7.44–7.34(m,2H),6.68(d,J=3.7Hz,1H),6.50(s,1H),3.01(s,3H).

[0659] Example 148

[0660] N-(3-(1-methyl-1H-pyrrolo-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 148)

[0661] Example 148 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with N-methylpyrrole-3-boronic acid pinacol ester (Bide, BD219651). After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a creamy white solid was obtained. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 148 (69 mg, 79.5% yield) in the form of a pale yellow solid. 1 H NMR (300MHz, DMSO) δ14.48(s,1H),12.82(d,J=8.4Hz,2H),12.76(d,J=9.0Hz,1H),12.68(dd,J=5.4,3.3Hz ,3H),12.26–12.15(m,2H),11.68(t,J=2.4Hz,1H),11.36(dd,J=2.7,1.7Hz,1H),8.51(s,3H),7.75(s,3H).

[0662] Example 149

[0663] 1-(thiophene-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (compound 149)

[0664] Step 1: Preparation of methyl 3-bromo-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

[0665] Step 1 followed the same preparation method as Step 1 in Example 54, except that methyl 1H-indole-5-carboxylate was replaced with methyl 3-bromo-1H-indazole-6-carboxylate, and 1-iodo-4-(trifluoromethoxy)benzene was replaced with 3-iodothiophene. After cooling to room temperature, the reaction solution was poured into water (100 mL), extracted with EA (50 mL × 3), and the organic layer was washed with saturated brine (30 mL × 2). After drying with anhydrous sodium sulfate and concentrating under reduced pressure, the residue was obtained. The residue was purified by column chromatography (PE:EA = 30:1) to give the title compound 149-1 (60.6 mg, 8.5% yield) as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.41(dt,J=7.2,1.0Hz,1H),7.95(ddd,J=8.5,2.4,1.2Hz,1H),7.66(ddd,J=53.5,8.5,0.8Hz,1H),7.55–7.48(m,3H),3.98(s,3H).

[0666] Step 2: Preparation of methyl 1-(thiophene-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylate

[0667] Step 2 employs the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 149-1, and 1-methyl-1H-pyrazole-4-boric acid is replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (PE:EA = 40:1), the title compound 149-2 (45.4 mg, 67% yield) was obtained as a pale yellow gel. 1 H NMR(300MHz, CDCl3) δ8.49(s,1H),8.13(dd,J=15.7,8.2Hz,3H),7.99(dd,J=8.6,1.3Hz, 1H),7.80(d,J=8.1Hz,2H),7.65–7.57(m,2H),7.54(dd,J=5.3,3.0Hz,1H),4.00(s,3H).

[0668] Step 3: Preparation of 1-(thiophene-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid

[0669] Step 3 followed the same preparation method as in Example 14, except that compound 13 in step 1 of Example 14 was replaced with 149-2. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (1.5 mL) and n-hexane (2.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 149 (32.3 mg, 74% yield) as a white solid. 1 H NMR (300MHz, DMSO) δ13.34(s,1H),8.39(d,J=1.2Hz,1H),8.31(t,J=7.7Hz,3H),8.06(dd,J=3.1, 1.5Hz, 1H), 7.93 (dd, J=8.5, 1.2Hz, 3H), 7.87 (dd, J=5.2, 3.1Hz, 1H), 7.66 (dd, J=5.2, 1.5Hz, 1H).

[0670] Example 150

[0671] 1-(thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (Compound 150)

[0672] Example 150 was prepared using the same method as Example 149, except that 3-iodothiophene in step 1 of Example 149 was replaced with 2-iodothiophene. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 150 (33.4 mg, 75% yield) as a yellow solid. 1 H NMR (300MHz, DMSO) δ13.36 (s, 1H), 8.42–8.22 (m, 4H), 8.01–7.89 (m, 3H), 7.66–7.55 (m, 2H), 7.23 (dd, J = 5.4, 3.8Hz, 1H).

[0673] Example 151

[0674] N-(3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylamide (compound 151)

[0675] Step 1: Preparation of 3-bromo-5-nitro-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

[0676] Step 1 was prepared using the same method as Step 1 of Example 146, except that the 5-nitro-1H-pyrrolo[2,3-b]pyridine in Step 1 of Example 146 was replaced with 3-bromo-5-nitro-1H-pyrrolo[2,3-b]pyridine (Bide, BD561411). After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (PE:EA = 50:1) to give the title compound 151-1 (303 mg, 37.7% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ9.28 (d, J = 2.4Hz, 1H), 8.81 (d, J = 2.5Hz, 1H), 7.79–7.73 (m, 2H), 7.72 (s, 1H), 7.43 (dt, J = 7.9, 1.0Hz, 2H).

[0677] Step 2: Preparation of 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-amine

[0678] Step 2 uses the same preparation method as Step 2 of Example 146, except that 146-1 in Step 2 of Example 146 is replaced with 151-1. After concentration under reduced pressure, crude product 151-2, which is a pale yellow solid, is obtained and used directly in the next reaction without purification.

[0679] Step 3: Preparation of N-(3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylamide

[0680] Step 3 follows the same preparation method as Step 3 of Example 146, except that 146-2 in Step 3 of Example 146 is replaced with 151-2. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (PE:EA = 3:1) to obtain a crude product as a white solid. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 151 (52 mg, 81.5% yield) as a white solid. 1 H NMR(300MHz, CDCl3)δ8.45(d,J=2.0Hz,1H),8.34(d,J=2.4Hz,1H),7.80–7.69(m,2H),7.53(s,2H),7.42 –7.32(m,2H),6.51(dd,J=16.9,1.4Hz,1H),6.32(dd,J=16.8,10.1Hz,1H),5.84(dd,J=10.1,1.3Hz,1H).

[0681] Example 152

[0682] N-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)acrylamide (compound 152)

[0683] Example 152 was prepared using the same method as Example 145, except that 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine in step 1 of Example 145 was replaced with 5-nitro-1H-pyrazolo[3,4-b]pyridine, and 4-trifluoromethylphenylboronic acid was replaced with 4-trifluoromethoxyphenylboronic acid. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (PE:EA = 3:1) to obtain a crude product as a white solid. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 152 (59.4 mg, 85% yield) as a white solid. 1H NMR (300MHz, CDCl3) δ8.77(d,J=1.5Hz,1H),8.52(d,J=2.4Hz,1H),8.41–8.28(m,2H),8.19(s,1H),7.53(s,1H) ,7.43–7.32(m,2H),6.53(dd,J=16.8,1.3Hz,1H),6.32(dd,J=16.8,10.2Hz,1H),5.87(dd,J=10.2,1.3Hz,1H).

[0684] Example 153

[0685] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methanesulfonamide (compound 153)

[0686] Example 153 was prepared using the same method as Example 1, except that step 3 of Example 1, 1-2, was replaced with 151-2 prepared in step 2 of Example 151. After purification by column chromatography (DCM:MeOH = 80:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (0.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 153 (21 mg, 32% yield) in the form of a pale yellow solid. 1 H NMR (300MHz, DMSO) δ9.69(s,1H),8.29(s,1H),8.27(d,J=2.3Hz,1H),8.15(d,J=0.8Hz,1H ),8.13–8.05(m,3H),7.87(d,J=0.8Hz,1H),7.63–7.55(m,2H),3.93(s,3H),3.00(s,3H).

[0687] Example 154

[0688] N-(3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)acrylamide (compound 154)

[0689] Example 154 was prepared using the same method as Example 10, except that 1-methyl-1H-pyrazole-4-boronic acid in step 1 of Example 10 was replaced with 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a light brown oil was obtained. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 154 (70.7 mg, 55.4% yield) as a light yellow solid. 1 H NMR (300MHz, DMSO) δ10.40 (s, 1H), 8.59–8.51 (m, 1H), 8.40 (d, J = 0.8Hz, 1H) ,8.09(d,J=8.4Hz,2H),8.05–7.98(m,2H),7.94(d,J=8.6Hz,2H),7.76(dd,J =9.1,2.0Hz,1H),6.49(dd,J=17.0,10.0Hz,1H),6.31(dd,J=16.9,2.2Hz,1H ), 5.80 (dd, J=9.9, 2.2Hz, 1H), 4.28 (q, J=7.3Hz, 2H), 1.47 (t, J=7.3Hz, 3H).

[0690] Example 155

[0691] 3-(1-Ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (Compound 155)

[0692] Example 155 was prepared using the same method as Example 108, except that cyclopenten-1-ylboronic acid in step 1 of Example 108 was replaced with 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 155 (71.3 mg, 85% yield) as a white solid. 1 H NMR(300MHz,DMSO)δ13.14(s,1H),8.67(dd,J=1.5,0.8Hz,1H),8.63(d,J=0.8Hz,1H), 8.20–8.02(m,5H),7.98(d,J=8.6Hz,2H),4.29(q,J=7.3Hz,2H),1.46(t,J=7.3Hz,3H).

[0693] Example 156

[0694] 3-(1-Cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (Compound 156)

[0695] Example 156 was prepared using the same method as Example 108, except that cyclopenten-1-ylboronic acid in step 1 of Example 108 was replaced with pinacol 1-cyclopropylpyrazole-4-boronic acid (Bide, BD210594). After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 156 (82.5 mg, 92.7% yield) as a white solid. 1 H NMR(300MHz,DMSO)δ13.11(s,1H),8.66(dd,J=9.0,1.1Hz,2H),8.20–8.02(m,5H),7.9 7(d,J=8.6Hz,2H),3.91(tt,J=7.5,3.8Hz,1H),1.24–1.16(m,2H),1.09–0.98(m,2H).

[0696] Example 157

[0697] N-(1-(2,4-bis(trifluoromethyl)phenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 157)

[0698] Example 157 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 2,4-bis(trifluoromethyl)phenylboronic acid (BYD, BD27613). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.5 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 157 (36 mg, 48% yield) in the form of a white solid. 1H NMR (300MHz, DMSO) δ9.71(s,1H),8.37(s,1H),8.31(d,J=6.6Hz,2H),8.05(d,J=8.3Hz,1H),7.96(d,J=0.8H z,1H),7.88(d,J=1.8Hz,1H),7.49(d,J=8.9Hz,1H),7.39(dd,J=8.9,1.9Hz,1H),3.97(s,3H),3.01(s,3H).

[0699] Example 158

[0700] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-yl)acrylamide (compound 158)

[0701] Step 1: Preparation of 5-nitro-3-(thiophen-2-yl)-1H-indole

[0702] Step 1 was performed using the same preparation method as Step 1 of Example 58, except that 1-methyl-4-pyrazoleboronic acid pinacol ester in Step 1 of Example 58 was replaced with 2-thiopheneboronic acid. After cooling to room temperature and concentration under reduced pressure, the residue was obtained. The residue was purified by column chromatography (PE:EA = 4:1) to give the title compound 158-1 (390.8 mg, 53.4% ​​yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ8.86 (d, J = 2.2Hz, 1H), 8.57 (d, J = 2.2Hz, 1H), 8.17 (dd, J = 9. 0,2.2Hz,1H),7.55–7.50(m,2H),7.50–7.44(m,2H),7.40(dd,J=5.0,1.3Hz,1H).

[0703] Step 2: Preparation of 5-nitro-3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole

[0704] Step 2 uses the same preparation method as Step 2 of Example 58, except that 58-1 in Step 2 of Example 58 is replaced with 158-1. After cooling to room temperature, the reaction solution is poured into water (30 mL), extracted with EA (30 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 158-2, which is yellow-orange gelatinous and used directly in the next reaction without purification.

[0705] Step 3: Preparation of 3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-amine

[0706] Step 3 uses the same preparation method as Step 3 in Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 158-2. The reaction solution is poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain crude product 158-3, which is yellow-black oily and used directly in the next reaction without purification.

[0707] Step 4: Preparation of N-(3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-yl)acrylamide

[0708] Step 4 follows the same preparation method as in Example 10, except that 10-1 in step 2 of Example 10 is replaced with 158-3. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 158 (41 mg, 55.5% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.32(s,1H),7.59–7.52(m,2H),7.51(s,1H),7.42(dd,J=23.5,6.8Hz,5H),7.35–7.31(m,1H),7.26–7. 24(m,1H),7.13(dd,J=5.2,3.5Hz,1H),6.48(dd,J=16.8,1.4Hz,1H),6.29(dd,J=16.8,10.2Hz,1H),5.78(d,J=10.1Hz,1H).

[0709] Example 159

[0710] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(pentafluoro-λ) 6 (-Thioalkyl)phenyl)-1H-indazole-5-yl)acrylamide (compound 159)

[0711] Step 1: 3-Bromo-5-nitro-1-(4-(pentafluoro-λ) 6 Preparation of thioalkyl)phenyl)-1H-indazole

[0712] Step 1 employed the same preparation method as Step 1 in Example 7, except that 3-bromo-6-nitro-1H-indazole in Step 1 of Example 7 was replaced with 3-bromo-5-nitro-1H-indazole, and 4-iodo-1-methylimidazole was replaced with 4-iodobenzenepentafluoride (Adamas, 014159623). After concentration under reduced pressure, a residue was obtained, which was purified by column chromatography (PE:EA = 75:1) to give the title compound 159-1 (151.8 mg, 68.5% yield) as a creamy white solid. 1 H NMR (300MHz, CDCl3) δ8.71 (dd, J=2.2, 0.6Hz, 1H), 8.43 (dd, J=9.3, 2.2Hz, 1H), 8.03–7.95 (m, 2H), 7.90–7.80 (m, 3H).

[0713] Step 2: 3-Bromo-1-(4-(pentafluoro-λ) 6 Preparation of 5-thioalkyl)phenyl)-1H-indazole-5-amine

[0714] Step 2 uses the same preparation method as Step 2 of Example 145, except that 145-1 in Step 2 of Example 145 is replaced with 159-1. After concentration under reduced pressure, crude product 159-2, which is a pale yellow solid, is obtained and used directly in the next reaction without purification.

[0715] Step 3: 3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(pentafluoro-λ) 6 Preparation of 5-thioalkyl)phenyl)-1H-indazole-5-amine

[0716] Step 3 uses the same preparation method as step 1 of Example 10, except that 1-2 in step 1 of Example 10 is replaced with 159-2. After concentration under reduced pressure, crude product 159-3, which is a pale yellowish-brown gel, is obtained and used directly in the next reaction without purification.

[0717] Step 4: N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(pentafluoro-λ) 6 Preparation of thioalkyl)phenyl)-1H-indazole-5-yl)acrylamide

[0718] Step 4 follows the same preparation method as step 2 in Example 10. The 10-1 in step 2 of Example 10 is replaced with 159-3. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid is obtained. Diethyl ether (1.5 mL) and n-hexane (2.5 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 159 (47.3 mg, 59% yield) in the form of a creamy white solid. 1H NMR (300MHz, DMSO) δ10.41(s,1H),8.56(s,1H),8.37(s,1H),8.05(d,J=20.6Hz,6H),7.75(d,J=9.2 Hz,1H),6.49(dd,J=16.9,10.0Hz,1H),6.31(d,J=16.9Hz,1H),5.81(d,J=10.0Hz,1H),3.99(s,3H).

[0719] Example 160

[0720] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(pentafluoro-λ) 6 (-Thioalkyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 160)

[0721] Step 1: N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(pentafluoro-λ) 6 Preparation of 1-thioalkyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0722] Step 1 follows the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 159-3 prepared in Step 3 of Example 159. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a pale yellow solid. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 160 (56.7 mg, 68% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO) δ9.75(s,1H),8.38(d,J=0.8Hz,1H),8.14–8.00(m,6H),7.93–7.88(m,1H),7.49(dd,J=9.0,2.0Hz,1H),3.98(s,3H),3.01(s,3H).

[0723] Example 161

[0724] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-yl)acrylamide (compound 161)

[0725] Example 161 was prepared using the same method as Example 158, except that 2-thiopheneboronic acid in step 1 of Example 158 was replaced with 3-thiopheneboronic acid. After purification by column chromatography (PE:EA = 5:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (2.0 mL) and n-hexane (3.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 161 (102 mg, 82.5% yield) as a creamy white solid. 1 H NMR(400MHz, CDCl3) δ8.32(d,J=1.9Hz,1H),7.60–7.53(m,2H),7.52(dt,J=3.0,1.4Hz,1H),7.48(t,J=4.4Hz ,2H),7.45–7.29(m,6H),6.47(dd,J=16.8,1.3Hz,1H),6.29(dd,J=16.8,10.2Hz,1H),5.78(d,J=10.0Hz,1H).

[0726] Example 162

[0727] N-(1-(thiazolyl-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 162)

[0728] Example 162 was prepared using the same method as Example 7, except that 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 2-bromothiazole (Bide, BD2057). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 162 (73.5 mg, 84% yield) in the form of a creamy white solid. 1 H NMR (400MHz, DMSO) δ10.32(s,1H),8.58(d,J=1.8Hz,1H),8.27(d,J=8.0Hz,2H),8.19(d,J=8.8Hz,1H),7.9 5(d,J=8.3Hz,2H),7.78(d,J=3.5Hz,1H),7.57(d,J=3.5Hz,1H),7.37(dd,J=8.8,2.0Hz,1H),3.10(s,3H).

[0729] Example 163

[0730] N-(1-(thiazolyl-4-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 163)

[0731] Example 163 was prepared using the same method as Example 7, except that 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 4-bromothiazole (Bide, BD20327). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a creamy white solid was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 163 (54.4 mg, 62% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ10.17 (s, 1H), 9.35 (d, J = 2.3Hz, 1H), 8.41–8.37 (m, 1H), 8.32–8.26 (m, 2H), 8.17 (dd, J=8.9,0.6Hz,1H),7.93(d,J=8.3Hz,2H),7.89(d,J=2.3Hz,1H),7.30(dd,J=8.8,1.9Hz,1H),3.07(s,3H).

[0732] Example 164

[0733] 1-(thiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (Compound 164)

[0734] Example 164 was prepared using the same method as Example 149, except that 3-iodothiophene in step 1 of Example 149 was replaced with 2-bromothiazole. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 164 (50.4 mg, 68% yield) as a creamy white solid. 1 H NMR (400MHz, DMSO) δ13.42(s,1H),9.28–9.21(m,1H),8.33(dd,J=8.6,0.8Hz,1H),8.30(d,J=8.1Hz, 2H),8.02(dd,J=8.5,1.5Hz,1H),7.97(d,J=8.3Hz,2H),7.83(d,J=3.5Hz,1H),7.62(d,J=3.5Hz,1H).

[0735] Example 165

[0736] 1-(thiazol-4-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (Compound 165)

[0737] Example 165 was prepared using the same method as Example 149, except that 3-iodothiophene in step 1 of Example 149 was replaced with 4-bromothiazole. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) was added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 165 (56.2 mg, 72% yield) as a pale pink solid. 1 H NMR (400MHz, DMSO) δ13.31(s,1H),9.40(d,J=2.3Hz,1H),9.11(t,J=1.1Hz,1H),8.32(t,J=7.9Hz,3H),7.99(d,J=2.3Hz,1H),7.98–7.93(m,3H).

[0738] Example 166

[0739] 1-(thiazol-5-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxylic acid (compound 166)

[0740] Example 166 was prepared using the same method as Example 149, except that 3-iodothiophene in step 1 of Example 149 was replaced with 5-bromothiazole (Bide, BD20089). After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (3.0 mL) and n-hexane (0.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 166 (16.6 mg, 43% yield) as a creamy white solid. 1 H NMR (400MHz, DMSO) δ13.45(s,1H),9.17(d,J=0.8Hz,1H),8.46(d,J=0.8Hz,1H),8.36(t,J=1.1H z,1H),8.34(d,J=8.6Hz,1H),8.31–8.26(m,2H),7.98(dd,J=8.6,1.3Hz,1H),7.97–7.93(m,2H).

[0741] Example 167

[0742] N-(3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylamide (compound 167)

[0743] Example 167 was prepared using the same method as Example 10, except that step 1-2 in Example 10 was replaced with 151-2 prepared in step 2 of Example 151. After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (2.0 mL) and n-hexane (3.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 167 (19.4 mg, 15% yield) as a creamy white solid. 1 H NMR (400MHz, DMSO) δ10.42(s,1H),8.69(d,J=2.3Hz,1H),8.50(d,J=2.3Hz,1H),8.26(s,1H),8.11(dd,J=8.7,1.7Hz,3H),7.86(d,J=0 .8Hz,1H),7.61–7.56(m,2H),6.49(dd,J=17.0,10.1Hz,1H),6.31(dd,J=17.0,2.0Hz,1H),5.81(dd,J=10.1,2.1Hz,1H),3.94(s,3H).

[0744] Example 168

[0745] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-7-yl)methanesulfonamide (compound 168)

[0746] Example 168 was prepared using the same method as Example 1, except that 3-bromo-5-nitro-1H-indazole in step 1 of Example 1 was replaced with 3-bromo-7-nitro-1H-indazole (BYD, BD85266). After purification by column chromatography (PE:EA = 1:2), a crude product in the form of a light brown gel was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 168 (56 mg, 77% yield) as a light yellow solid. 1H NMR (400MHz, DMSO) δ9.36(s,1H),8.50(d,J=0.8Hz,1H),8.12(dd,J=8.0,1.1Hz,1H),8.06(d,J=0.8Hz,1H),7.85( d,J=8.6Hz,2H),7.77–7.70(m,2H),7.44(dd,J=7.4,1.1Hz,1H),7.37(t,J=7.7Hz,1H),3.96(s,3H),2.74(s,3H).

[0747] Example 169

[0748] N-(3-(1-cyclopentyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 169)

[0749] Example 169 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pinacol 1-cyclopentyl-1H-pyrazole-4-boronic acid (Adamas, 011146197). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) and DCM (0.1 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 169 (44 mg, 60% yield) in the form of a creamy white solid. 1 H NMR (400MHz, DMSO) δ9.75 (s, 1H), 8.40 (d, J = 0.8Hz, 1H), 8.11–8.05 (m, 2H), 8.04(d,J=0.7Hz,1H),8.04–8.00(m,1H),7.95(d,J=8.7Hz,2H),7.90(d,J=2 .0Hz,1H),7.48(dd,J=9.0,2.0Hz,1H),4.85(p,J=7.1Hz,1H),3.01(s,3H), 2.21–2.10(m,2H),2.07–1.97(m,2H),1.91–1.80(m,2H),1.74–1.63(m,2H).

[0750] Example 170

[0751] N-(3-(1,5-dimethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 170)

[0752] Example 170 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pinacol 1,5-dimethyl-1H-pyrazole-4-boric acid (Bide, BD213101). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a white solid was obtained. Diethyl ether (2.5 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 170 (46 mg, 68% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO)δ9.76(s,1H),8.08(d,J=8.5Hz,2H),8.03(dd,J=9.0,0.7Hz,1H),7.95(d,J=8.7Hz,2H),7 .90(s,1H),7.83(dd,J=2.0,0.7Hz,1H),7.47(dd,J=9.0,2.0Hz,1H),3.87(s,3H),2.99(s,3H),2.59(s,3H).

[0753] Example 171

[0754] N-(3-(1-propyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 171)

[0755] Example 171 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pinacol 1-propyl-1H-pyrazole-4-boronic acid (Adamas, 013565401). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow oil was obtained. Diethyl ether (2.5 mL) and DCM (0.1 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 171 (45 mg, 65% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.74(s,1H),8.41(d,J=0.8Hz,1H),8.07(d,J=8.4Hz,2H),8.04(d,J=0.7Hz,1H),8.02(dd,J=9.0,0.7Hz,1H),7.95(d,J=8 .5Hz,2H),7.90(d,J=1.9Hz,1H),7.48(dd,J=9.0,2.0Hz,1H),4.20(t,J=7.0Hz,2H),3.01(s,3H),1.88(h,J=7.3Hz,2H),0.89(t,J=7.4Hz,3H).

[0756] Example 172

[0757] N-(3-(1-phenyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 172)

[0758] Example 172 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol 1-phenyl-1H-pyrazole-4-boronic acid (Adamas, 013652405). After purification by column chromatography (DCM:MeOH = 200:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 172 (59.4 mg, 80% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.75 (s, 1H), 9.15 (s, 1H), 8.36 (s, 1H), 8.12 (d, J = 8.4Hz, 2H), 8.08–8.01 (m, 3H), 8.01 –7.98(m,2H),7.96(s,1H),7.62–7.54(m,2H),7.52(dd,J=9.0,2.0Hz,1H),7.43–7.36(m,1H),3.03(s,3H).

[0759] Example 173

[0760] N-(3-(4,4-difluorocyclohexyl-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 173)

[0761] Example 173 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with 4,4-difluorocyclohexene-1-boronic acid pinacol ester (Adamas, 011092823). After purification by column chromatography (PE:EA = 3:1), a crude product in the form of a white solid was obtained. Diethyl ether (1.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 173 (59.4 mg, 84% yield) in the form of a white solid. 1H NMR (400MHz, DMSO) δ9.74(s,1H),8.04(d,J=8.5Hz,2H),8.02–7.97(m,1H),7.94(d,J=8.7Hz,2H),7.90(d,J=2.0 Hz,1H),7.47(dd,J=9.0,2.0Hz,1H),6.48(s,1H),2.98(s,3H),2.96–2.85(m,4H),2.26(tt,J=14.0,6.6Hz,2H).

[0762] Example 174

[0763] N-(3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 174)

[0764] Example 174 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-(tetrahydropyran-4-yl)-1H-pyrazole-4-boronic acid pinacol ester (Bide, BD210595). After purification by column chromatography (DCM:MeOH = 50:1), a white gel-like crude product was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 174 (61 mg, 80.5% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.74(s,1H),8.46(d,J=0.8Hz,1H),8.11–8.05(m,3H),8.05–8.00(m,1H),7.95(d,J=8.6Hz,2H),7.92–7.89(m,1H),7.49( dd,J=9.1,2.0Hz,1H),4.62–4.52(m,1H),4.01(dt,J=11.4,3.4Hz,2H),3.50(tdd,J=12.4,7.2,3.7Hz,2H),3.01(s,3H),2.06(h,J=4.0Hz,4H).

[0765] Example 175

[0766] N-(3-(1-(difluoromethyl)-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 175)

[0767] Example 175 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with 1-(difluoromethyl)-1H-pyrazole-4-boronic acid pinacol ester (Adamas, 011146182). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a white solid was obtained. Diethyl ether (4.0 mL) and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 175 (50 mg, 71% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.76 (s, 1H), 8.93 (d, J = 0.8Hz, 1H), 8.40 (d, J = 0.6Hz, 1H), 8.13–7.82 (m, 7H), 7.51 (dd, J = 9.0, 2.0Hz, 1H), 3.02 (s, 3H).

[0768] Example 176

[0769] N-(3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 176)

[0770] Example 176 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-methyl-3-trifluoromethyl-1H-pyrazole-5-boronic acid pinacol ester (Adamas, 013553880). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a light pink solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 176 (32.2 mg, 42.7% yield) in the form of a light pink solid. 1 H NMR (400MHz, DMSO) δ9.84(s,1H),8.14(d,J=8.4Hz,2H),8.09(d,J=9.1Hz,1H),8.00(d,J=8.6H z,2H),7.87–7.83(m,1H),7.56(dd,J=9.1,2.0Hz,1H),7.37(s,1H),4.27(s,3H),3.02(s,3H).

[0771] Example 177

[0772] N-(3-(1-(trifluoromethyl)-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 177)

[0773] Example 177 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol 1-trifluoromethyl-1H-pyrazole-4-boronic acid (Bide, BD01488893). After purification by column chromatography (DCM:MeOH = 200:1), a crude product in the form of a white solid was obtained. Diethyl ether (2.5 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 177 (50 mg, 68% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.76 (s, 1H), 9.18 (s, 1H), 8.57 (t, J = 0.9Hz, 1H), 8.10 (d, J = 8.4Hz, 2H),8.05(d,J=9.0Hz,1H),8.01–7.94(m,3H),7.52(dd,J=9.1,2.0Hz,1H),3.03(s,3H).

[0774] Example 178

[0775] N-(1-(isothiazo-4-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (compound 178)

[0776] Example 178 was prepared using the same method as Example 7, except that 4-iodo-1-methylimidazole in step 1 of Example 7 was replaced with 4-bromoisothiazol (Adamas, 013650314). After purification by column chromatography (PE:EA = 2:1), a pale yellow crude solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 178 (47.7 mg, 54.5% yield) as a creamy white solid. 1 H NMR (300MHz, DMSO) δ10.20(s,1H),9.42(s,1H),9.13(s,1H),8.33–8.24(m,2H),8.21(d,J=8.8 Hz,1H),7.93(d,J=8.2Hz,2H),7.67(d,J=1.7Hz,1H),7.28(dd,J=8.8,1.8Hz,1H),3.12(s,3H).

[0777] Example 179

[0778] N-(5-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-yl)methanesulfonamide (compound 179)

[0779] Step 1: Preparation of 5-bromo-3-nitro-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0780] Step 1 uses the same preparation method as Step 1 of Example 1, except that 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 is replaced with 5-bromo-3-nitro-1H-indazole (BYD, BD00798336). After concentration under reduced pressure, crude product 179-1, which is a yellow-green solid, is obtained and used directly in the next reaction without purification.

[0781] Step 2: Preparation of 5-bromo-1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-amine

[0782] Step 2 follows the same preparation method as Step 3 of Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 179-1. After concentration under reduced pressure, a residue is obtained. This residue is then purified by column chromatography (PE:EA = 7.5:1) to give the title compound 179-2 (228.6 g, 32% two-step yield) as a light brownish-black solid. 1 H NMR (400MHz, CDCl3) δ8.14(d,J=1.0Hz,1H),7.86(d,J=8.5Hz,2H),7.79(d,J=8.6Hz,2H),7.45(d,J=8.9Hz,1H),7.05(dd,J=8.9,1.0Hz,1H),4.65(s,2H).

[0783] Step 3: Preparation of 5-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-amine

[0784] Step 3 uses the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 179-2. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (DCM:MeOH = 75:1) to give the title compound 179-3 (135 mg, 100% yield) as a pale yellow colloidal substance. 1 H NMR (300MHz, CDCl3) δ8.19(d,J=0.9Hz,1H),7.90(d,J=8.4Hz,2H),7.79(d,J=8.6Hz,2H),7.69 (s,1H),7.57(s,1H),7.51–7.45(m,1H),7.19(dd,J=8.6,0.9Hz,1H),4.34(s,2H),4.00(s,3H).

[0785] Step 4: Preparation of N-(5-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-yl)methanesulfonamide

[0786] Step 4 follows the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 179-3. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a white solid. Diethyl ether (2.0 mL) is added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtration yields the title compound 179 (16 mg, 36.5% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.66(s,1H),8.47(d,J=0.9Hz,1H),8.19(s,1H),8.07(d,J= 8.4Hz,2H),8.00–7.90(m,4H),7.71(d,J=8.8Hz,1H),3.91(s,3H),2.85(s,3H).

[0787] Example 180

[0788] N-(5-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-yl)acrylamide (compound 180)

[0789] Example 180 was prepared using the same method as Example 8, except that step 1-2 in Example 8 was replaced with 179-3 prepared in step 3 of Example 179. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a white solid. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 180 (40 mg, 49% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ10.15(s,1H),8.14(s,1H),8.07(d,J=8.4Hz,2H),8.00(s,1H),7.96(d,J=8.6Hz,2H),7.91(d,J=8.9Hz,1H),7.73 (s,1H),7.70(d,J=8.8Hz,1H),6.63(dd,J=17.1,10.2Hz,1H),6.32(dd,J=17.0,2.0Hz,1H),5.84(dd,J=10.1,2.2Hz,1H),3.89(s,3H).

[0790] Example 181

[0791] N-(3-(2-acetylthiophene-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 181)

[0792] Example 181 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 2-acetyl-3-thiopheneboric acid (Bide, BD250313). After purification by column chromatography (DCM:MeOH = 200:1), a crude product in the form of a white solid was obtained. Diethyl ether (2.5 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 181 (50 mg, 68% yield) in the form of a white solid. 1 H NMR (400MHz, CDCl3) δ9.83 (s, 1H), 8.14 (d, J = 5.1Hz, 1H), 8.10 (d, J = 8.5Hz, 2H), 8.07 (d, J = 9.6Hz ,1H),7.96(d,J=8.5Hz,2H),7.52(d,J=5.0Hz,1H),7.50–7.45(m,2H),2.98(s,3H),2.33(s,3H).

[0793] Example 182

[0794] N-(1-(methanesulfonyl)-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)acrylamide (compound 182)

[0795] Step 1: Preparation of 3-bromo-1-(methanesulfonyl)-6-nitro-1H-indazole

[0796] Under ice bath conditions, Et3N (280 μL, 2.0 mmol) and methanesulfonyl chloride (120 μL, 1.5 mmol) were added dropwise to a solution of 3-bromo-6-nitro-1H-indazole (242 mg, 1.0 mmol) dissolved in DCM (2.0 mL), and the mixture was stirred at room temperature for 1 h. TLC (PE:EA = 10:1, R f =0.1) indicates complete consumption of the starting material and detection of a new spot. Concentration under reduced pressure to remove the solvent yielded a residue, which was purified by column chromatography (PE:EA = 5:1) to give the title compound 182-1 (238 mg, 75% yield) as a pale yellow solid. 1 H NMR (300MHz, CDCl3) δ8.98(dd,J=2.0,0.7Hz,1H),8.31(dd,J=8.8,1.9Hz,1H),7.85(dd,J=8.8,0.7Hz,1H),3.43(s,3H).

[0797] Step 2: Preparation of 3-bromo-1-(methanesulfonyl)-1H-indazole-6-amine

[0798] Step 2 uses the same preparation method as Step 3 of Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 182-1. After concentration under reduced pressure, a residue is obtained. The residue is then purified by column chromatography (PE:EA = 4:1) to obtain 182-2 (123 g, 57% yield), a pale yellow-brown solid. 1 H NMR (400MHz, CDCl3) δ7.39(d,J=8.7Hz,1H),7.19(d,J=1.9Hz,1H),6.75(dd,J=8.6,1.9Hz,1H),4.19(s,2H),3.22(s,3H).

[0799] Step 3: Preparation of 1-(methanesulfonyl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-amine

[0800] Step 3 uses the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 is replaced with 182-2. After concentration under reduced pressure, crude product 182-3, which is a yellow solid, is obtained and used directly in the next reaction without purification.

[0801] Step 4: Preparation of N-(1-(methanesulfonyl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-yl)acrylamide

[0802] Step 4 follows the same preparation method as Step 1 in Example 8, except that 1-2 in Step 1 of Example 8 is replaced with 182-3. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (PE:EA = 2:1) to obtain a crude product that is a pale yellow oil. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 182 (4.4 mg, 9% two-step yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.34(d,J=1.8Hz,1H),8.13–8.07(m,2H),7.93(d,J=8.8Hz,1H),7.84(dd,J=8.8,1.8Hz,1H),7.80(d,J=8 .1Hz,2H),7.62(s,1H),6.52(dd,J=16.8,1.1Hz,1H),6.30(dd,J=16.8,10.2Hz,1H),5.86(dd,J=10.2,1.1Hz,1H),3.34(s,3H).

[0803] Example 183

[0804] N-(1-Phenylacetyl-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (Compound 183)

[0805] Example 183 was prepared using the same method as Example 1, except that 3-bromo-5-nitro-1H-indazole in step 1 of Example 1 was replaced with 3-bromo-6-nitro-1H-indazole, 4-trifluoromethylphenylboronic acid was replaced with phenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 4-trifluoromethylphenylboronic acid. After purification by column chromatography (PE:EA = 3:1), a crude product in the form of a light brown solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 183 (30.4 mg, 38% yield) in the form of a light brown solid. 1 H NMR (400MHz, CDCl3) δ8.16–8.11(m,2H),8.03(dd,J=8.7,0.7Hz,1H),7.83–7.74(m,4H),7.72(dd,J=1.9,0.7H z,1H),7.63–7.55(m,2H),7.46–7.40(m,1H),7.13(dd,J=8.7,1.9Hz,1H),6.67(d,J=12.4Hz,1H),3.06(s,3H).

[0806] Example 184

[0807] N-(1-Methyl-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide (Compound 184)

[0808] Step 1: Preparation of 3-bromo-1-methyl-6-nitro-1H-indazole

[0809] Under ice bath conditions, KOH (84 mg, 1.5 mmol) was added to a solution of 3-bromo-6-nitro-1H-indazole (242 mg, 1.0 mmol) dissolved in acetone (5 mL), followed by dropwise addition of iodomethane (94 μL, 1.5 mmol). The mixture was stirred at room temperature for 1 h. TLC (PE:EA = 10:1, RL) was then performed. f =0.3) indicates complete consumption of the starting material and detection of a new spot. Concentration under reduced pressure to remove the solvent yielded a residue, which was purified by column chromatography (PE:EA = 30:1) to give the title compound 184-1 (151 mg, 59% yield) as a pale yellow solid. 1H NMR (300MHz, CDCl3) δ8.38(dd,J=1.9,0.7Hz,1H),8.07(dd,J=8.9,1.8Hz,1H),7.74(dd,J=8.9,0.7Hz,1H),4.17(s,3H).

[0810] Step 2: Preparation of 3-bromo-1-methyl-1H-indazole-6-amine

[0811] Step 2 follows the same preparation method as Step 3 in Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 184-1. The reaction solution is poured into water (30 mL), extracted with DCM (20 mL × 3), the organic layer is washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound 184-2 as a yellow solid. The crude product is used directly in the next reaction without purification.

[0812] Step 3: Preparation of 1-methyl-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-amine

[0813] Step 3 uses the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 is replaced with 184-2. After concentration under reduced pressure, crude product 184-3, which is brownish-black and gelatinous, is obtained and used directly in the next reaction without purification.

[0814] Step 4: Preparation of N-(1-methyl-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)methanesulfonamide

[0815] Step 4 follows the same preparation method as Step 3 of Example 1, except that 1-2 in Step 3 of Example 1 is replaced with 184-3. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (PE:EA = 2:1) to obtain a crude product that is a pale yellow solid. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) are added to the crude product, and the mixture is stirred at room temperature for 1 h. Filtering yields the title compound 184 (41.5 mg, 19% three-step yield) as a pale brown solid. 1 H NMR (400MHz, CDCl3) δ8.08–8.01(m,2H),7.95(d,J=8.6Hz,1H),7.75(d,J=8.2Hz,2H),7.44(d ,J=1.8Hz,1H),6.98(dd,J=8.6,1.9Hz,1H),6.79(d,J=5.8Hz,1H),4.13(s,3H),3.08(s,3H).

[0816] Example 185

[0817] N-(1-Methyl-3-(4-(trifluoromethyl)phenyl)-1H-indazol-6-yl)acrylamide (compound 185)

[0818] Example 185 was prepared using the same method as Example 8, except that step 1-2 in Example 8 was replaced with 184-3 prepared in step 3 of Example 184. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (PE:EA = 2.5:1) to obtain a crude product as a light brown solid. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 185 (34.5 mg, 45% yield) as a light brown solid. 1 H NMR(400MHz, CDCl3)δ8.36(s,1H),8.11–8.01(m,2H),7.89(dd,J=8.7,0.7Hz,1H),7.77–7.70(m,2H),7.54(s,1H),6.95(dd ,J=8.7,1.8Hz,1H),6.51(dd,J=16.8,1.2Hz,1H),6.31(dd,J=16.8,10.2Hz,1H),5.84(dd,J=10.1,1.2Hz,1H),4.12(s,3H).

[0819] Example 186

[0820] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)cyclopropanesulfonamide (compound 186)

[0821] Step 1: Preparation of N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)cyclopropanesulfonamide

[0822] To a solution of 10⁻¹ (54 mg, 0.15 mmol) prepared in step 1 of Example 10, dissolved in DCM (3.0 mL), Py (30 μL, 0.375 mmol) and cyclopropylsulfonyl chloride (16 μL, 0.15 mmol; Biotin, BD31865) were added dropwise, and the mixture was heated and stirred at 50 °C for 8 h. TLC (DCM:MeOH = 75:1, R f=0.3) showed complete consumption of 10⁻¹ and a new spot was detected. After concentration under reduced pressure, the residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 75:1) to give a crude product as a pale yellow solid. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 186 (57.7 mg, 83.5% yield) as a pale brownish-yellow solid. 1 H NMR (400MHz, DMSO) δ9.75(s,1H),8.37(s,1H),8.07(d,J=8.4Hz,2H),8.01(t,J=4.5Hz,2H),7.94(d,J=8.5Hz,2H),7.9 1(d,J=1.9Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),3.98(s,3H),2.65(tt,J=7.7,5.1Hz,1H),0.91(tt,J=7.4,2.5Hz,4H).

[0823] Example 187

[0824] N-(3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)propane-2-sulfonamide (Compound 187)

[0825] Example 187 was prepared using the same method as Example 186, except that the cyclopropyl sulfonyl chloride in step 1 of Example 186 was replaced with isopropyl sulfonyl chloride (BYD, BD40123). After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a light brown solid. Diethyl ether (1.5 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The residue was then filtered to obtain the title compound 187 (48.6 mg, 70% yield) as a light brown solid. 1 H NMR (400MHz, DMSO) δ9.83(s,1H),8.34(s,1H),8.06(d,J=8.5Hz,2H),8.02–7.97(m,2H),7.94(d,J=8.6Hz,2H) ,7.89(d,J=2.0Hz,1H),7.50(dd,J=9.1,2.0Hz,1H),3.98(s,3H),3.25(p,J=6.8Hz,1H),1.27(d,J=6.8Hz,6H).

[0826] Example 188

[0827] 3-(cyclohexyl-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (Compound 188)

[0828] Example 188 was prepared using the same method as Example 108, except that cyclopent-1-ene-1-boric acid in step 1 of Example 108 was replaced with cyclohex-1-ene-1-boric acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.5 mL) and n-hexane (2.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 188 (81.8 mg, 85% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ13.05(s,1H),8.65–8.59(m,1H),8.10–7.98(m,4H),7.95(d,J=8.7Hz,2H),6.71(tt,J=4.0,1.7H z,1H),2.64(tq,J=6.4,2.3Hz,2H),2.34(ddq,J=5.8,4.0,2.5Hz,2H),1.84–1.75(m,2H),1.71(dp,J=8.4,2.5Hz,2H).

[0829] Example 189

[0830] 3-(cyclohexyl-1-en-1-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indole-5-carboxylic acid (compound 189)

[0831] Example 189 was prepared using the same method as Example 109, except that cyclopent-1-ene-1-boric acid in step 3 of Example 109 was replaced with cyclohex-1-ene-1-boric acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (2.0 mL) and n-hexane (2.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 189 (32.4 mg, 60% yield) as a creamy white solid. 1H NMR (400MHz, DMSO) δ12.67(s,1H),8.53(d,J=1.5Hz,1H),7.95(d,J=8.6Hz,2H),7.91–7.82(m,4H),7.70(d,J =8.7Hz,1H),6.34–6.26(m,1H),2.29(td,J=6.1,3.5Hz,2H),1.78(qd,J=7.9,4.1Hz,2H),1.73–1.64(m,2H).

[0832] Example 190

[0833] N-(3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethanesulfonamide (compound 190)

[0834] Step 1: Preparation of 3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0835] Step 1 employs the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 1-2 prepared in Step 2 of Example 1, and 1-methyl-1H-pyrazole-4-boric acid is replaced with 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester. After concentration under reduced pressure, a crude product 190-1, which is a yellow-black oil, is obtained and used directly in the next reaction without purification.

[0836] Step 2: Preparation of N-(3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethanesulfonamide

[0837] Step 2 followed the same preparation method as in Example 186, except that 10-1 in Step 1 of Example 186 was replaced with 190-1, and cyclopropylsulfonyl chloride was replaced with ethylsulfonyl chloride. After concentration under reduced pressure, a residue was obtained. This residue was purified by column chromatography (DCM:MeOH = 100:1) to obtain a crude product that was a light brown gel. Diethyl ether (2.5 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 190 (101.5 mg, 88% yield) as a light pink solid. 1H NMR (400MHz, DMSO) δ9.82(s,1H),8.38(d,J=0.8Hz,1H),8.11–8.04(m,2H),8.01(dd,J=8.2,0.7Hz,2H),7.94(d,J=8.6Hz,2H),7.91– 7.87(m,1H),7.49(dd,J=9.1,2.0Hz,1H),4.28(q,J=7.3Hz,2H),3.11(q,J=7.3Hz,2H),1.47(t,J=7.3Hz,3H),1.23(t,J=7.4Hz,3H).

[0838] Example 191

[0839] N-(3-(1-ethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)cyclopropanesulfonamide (compound 191)

[0840] Example 191 was prepared using the same method as Example 186, except that 10-1 in step 1 of Example 186 was replaced with 190-1 prepared in step 1 of Example 190. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product as a light brown solid. Diethyl ether (2.5 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 191 (131.2 mg, 83% yield) as a light pink solid. 1 H NMR (400MHz, DMSO) δ9.75 (s, 1H), 8.40 (d, J = 0.8Hz, 1H), 8.11–8.04 (m, 2H), 8.04–7.98 (m, 2H), 7.94 (d, J = 8.7Hz, 2H), 7.92 (dd, J = 2.0, 0.7Hz, 1H), 7.51 (dd, J=9.0, 2.0Hz, 1H), 4.28 (q, J=7.3Hz, 2H), 2.65 (tt, J=7.6, 5.1Hz, 1H), 1.47 (t, J=7.3Hz, 3H), 0.97–0.85 (m, 4H).

[0841] Example 192

[0842] N-(3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 192)

[0843] Step 1: Preparation of 1-methyl-4-(tributyltin)-1H-imidazolium

[0844] Under an argon atmosphere and at -10°C, a solution of isopropyl magnesium chloride-lithium chloride complex (1.16 mL, 1.5 mmol, 1.3 min THF; Anage, W4201411000) was added dropwise to a solution of 4-iodo-1-methylimidazole (208 mg, 1.0 mmol) dissolved in dry THF, and stirred for 1 h to obtain a white suspension. Then, under the same conditions, tributyltin chloride (300 μL, 1.1 mmol; Adamas, 01024600) was added dropwise, and stirred at room temperature for 12 h to obtain a pale yellow solution. The reaction was quenched by adding 2.0 mL of saturated NH4Cl aqueous solution. The reaction solution was poured into water (20 mL), extracted with EA (20 mL × 3), washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound 192-1, a pale yellow oil. The crude product was used directly in the next reaction without purification.

[0845] Step 2: Preparation of N-(3-(1-methyl-1H-imidazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0846] To the mixture of 1-3 (65 mg, 0.15 mmol), 192-1 (112 mg, 0.225 mmol), Na2CO3 (48 mg, 0.45 mmol), and Pd(dppf)Cl2·DCM (12 mg, 0.015 mmol; Leyan, 1047232) prepared in step 3 of Example 1, 1,4-Dioxane (1 mL) and water (0.25 mL) were added, and the mixture was heated and stirred at 80 °C for 4 h under an argon atmosphere. TLC (DCM:MeOH = 75:1, R f =0.05) showed that 1-3 were completely consumed and a new spot was detected. After cooling to room temperature, the residue was concentrated under reduced pressure. The residue was purified by column chromatography (DCM:MeOH = 75:1) to give a crude product as a white solid. Diethyl ether (2.5 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 192 (55.1 mg, 84.5% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.72(s,1H),8.42(d,J=2.1Hz,1H),8.06(d,J=8.5Hz,2H),7.98(d,J=9.0Hz,1H),7.94(d,J= 8.5Hz,2H),7.84(d,J=1.3Hz,1H),7.78(d,J=1.3Hz,1H),7.47(dd,J=9.0,2.2Hz,1H),3.78(s,3H),2.96(s,3H).

[0847] Example 193

[0848] N-(3-(1-methyl-1H-pyrazole-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 193)

[0849] Example 193 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with pinacol 1-methylpyrazole-3-boronic acid (Bide, BD206181). After purification by column chromatography (DCM:MeOH = 150:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 193 (46.8 mg, 72% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.79(s,1H),8.33(d,J=2.0Hz,1H),8.09(d,J=8.5Hz,2H),8.00(d,J=9.0Hz,1H),7.95(d,J= 8.5Hz,2H),7.88(d,J=2.3Hz,1H),7.51(dd,J=9.1,2.2Hz,1H),6.83(d,J=2.2Hz,1H),4.00(s,3H),2.98(s,3H).

[0850] Example 194

[0851] N-(3-(thiazolyl-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 194)

[0852] Example 194 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol thiazol-5-boronic acid (Bide, BD208153). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 194 (13.5 mg, 20.5% yield) in the form of a creamy white solid. 1H NMR (400MHz, DMSO) δ9.88(s,1H),9.28(s,1H),8.57(s,1H),8.08(d,J=8.4Hz,2H),8.05(d,J=9. 1Hz, 1H), 8.01 (d, J = 2.0Hz, 1H), 7.98 (d, J = 8.5Hz, 2H), 7.53 (dd, J = 9.1, 2.0Hz, 1H), 3.05 (s, 3H).

[0853] Example 195

[0854] N-(3-(1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 195)

[0855] Example 195 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol pyrazole-4-boronic acid (Leyan, 1027953). After purification by column chromatography (DCM:MeOH = 20:1), a crude product in the form of a light pink solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 195 (22.6 mg, 54% yield) in the form of a light pink solid. 1 H NMR (400MHz, DMSO) δ13.27 (s, 1H), 9.74 (s, 1H), 8.24 (s, 2H), 8.08 (d, J = 8.5Hz, 2H), 8.02(d,J=9.0Hz,1H),7.98–7.89(m,3H),7.48(dd,J=9.1,2.0Hz,1H),3.01(s,3H).

[0856] Example 196

[0857] N-(3-(5-methylfuran-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (Compound 196)

[0858] Example 196 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 5-methyl-2-furanboronic acid pinacol ester (Bide, BD77254). After purification by column chromatography (DCM:MeOH = 1:0), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 196 (49 mg, 75% yield) in the form of a white solid. 1H NMR (400MHz, DMSO) δ9.84 (s, 1H), 8.08 (d, J = 8.4Hz, 2H), 8.04 (d, J = 2.0Hz, 1H), 8.02 (d, J = 9.1Hz, 1H), 7.95 (d, J = 8.5Hz, 2H),7.51(dd,J=9.1,2.1Hz,1H),6.99(d,J=3.2Hz,1H),6.38(dd,J=3.3,1.2Hz,1H),3.01(s,3H),2.45(d,J=1.0Hz,3H).

[0859] Example 197

[0860] N-(3-(1H-pyrrolo-3-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 197)

[0861] Example 197 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol pyrrole-3-boronic acid (Bide, BD88977). After purification by column chromatography (DCM:MeOH = 20:1), a crude product in the form of a light pink solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 197 (42.2 mg, 50% yield) in the form of a light pink solid. 1 H NMR (400MHz, DMSO) δ13.32(s,1H),9.74(s,1H),8.39(s,1H),8.27–7.57(m,8H),7.48(dd,J=9.0,2.0Hz,1H),3.01(s,3H).

[0862] Example 198

[0863] N-(3-(cyclopenten-1-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indole-5-yl)methanesulfonamide (compound 198)

[0864] Example 198 was prepared using the same method as Example 58, except that 1-methyl-4-pyrazolone pinacol ester in step 1 of Example 58 was replaced with cyclopentene-1-boronic acid. After purification by column chromatography (PE:EA = 4:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 198 (105.6 mg, 40% yield) in the form of a white solid. 1H NMR (400MHz, DMSO) δ9.47(s,1H),7.83(d,J=2.0Hz,1H),7.78–7.70(m,3H),7.57(t,J=9.0Hz,3H),7.17(dd,J=8 .8,2.1Hz,1H),6.15(t,J=2.2Hz,1H),2.91(s,3H),2.79–2.71(m,2H),2.61–2.54(m,2H),1.95(p,J=7.5Hz,2H).

[0865] Example 199

[0866] N-(3-(1-methyl-1H-pyrrolo-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (Compound 199)

[0867] Example 199 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boronic acid in step 4 of Example 1 was replaced with pinacol 1-methyl-2-pyrroloboronic acid (Adamas, 013558572). After purification by column chromatography (DCM:MeOH = 1:0), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 199 (44.8 mg, 69% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.78(s,1H),8.13–8.07(m,2H),8.07–8.02(m,1H),7.95(d,J=8.6Hz,2H),7.92–7.87(m,1H),7.49(dd,J=9 .0,2.0Hz,1H),7.05(dd,J=2.6,1.7Hz,1H),6.70(dd,J=3.7,1.7Hz,1H),6.25(dd,J=3.8,2.6Hz,1H),3.98(s,3H),2.99(s,3H).

[0868] Example 200

[0869] 3-(1-Methyl-1H-pyrazole-4-yl)-1-(4-(pentafluoro-λ) 6 (-Thioalkyl)phenyl)-1H-indazole-5-carboxylic acid (Compound 200)

[0870] Example 200 was prepared using the same method as Example 117, except that 1-bromo-4-(trifluoromethylthio)benzene in step 1 of Example 117 was replaced with 4-iodobenzenepentafluoride. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (10 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (10 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (1.5 mL) and n-hexane (0.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 200 (22.7 mg, 71% yield) as a pale gray solid. 1 H NMR (400MHz, DMSO) δ13.14(s,1H),8.69–8.64(m,1H),8.59(s,1H),8.17–8.05(m,7H),3.99(s,3H).

[0871] Example 201

[0872] 1-(4-(pentafluoro-λ) 6 (-Thioalkyl)phenyl)-3-(thiophen-3-yl)-1H-indazole-5-carboxylic acid (Compound 201)

[0873] Example 201 was prepared using the same method as Example 117, except that 1-bromo-4-(trifluoromethylthio)benzene in step 1 of Example 117 was replaced with 4-iodobenzenepentafluoride, and 1-methyl-1H-pyrazole-4-boric acid in step 2 was replaced with thiophene-3-boric acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (10 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (10 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 201 (23.1 mg, 72% yield) as a pale gray solid. 1 H NMR(400MHz,DMSO)δ13.14(s,1H),8.78–8.70(m,1H),8.35(dd,J=2.9,1.3Hz,1 H),8.21–8.05(m,6H),7.81(dd,J=5.0,2.8Hz,1H),7.77(dd,J=5.1,1.3Hz,1H).

[0874] Example 202

[0875] 3-(cyclopent-1-en-1-yl)-1-(4-(pentafluoro-λ) 6(-Thioalkyl)phenyl)-1H-indazole-5-carboxylic acid (compound 202)

[0876] Example 202 was prepared using the same method as Example 117, except that 1-bromo-4-(trifluoromethylthio)benzene in step 1 of Example 117 was replaced with 4-iodobenzenepentafluoride, and 1-methyl-1H-pyrazole-4-boronic acid in step 2 was replaced with cyclopenten-1-ylboronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (10 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (10 mL × 5). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue. Diethyl ether (1.5 mL) and n-hexane (1.0 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 202 (17.7 mg, 57% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ13.10(s,1H),8.66(d,J=1.5Hz,1H),8.22–7.96(m,6H),6.78(t,J=2.2H z,1H),2.94(tt,J=6.7,1.9Hz,2H),2.67(ddq,J=9.7,5.0,2.4Hz,2H),2.02(p,J=7.6Hz,2H).

[0877] Example 203

[0878] N-(3-(2-methyl-2H-tetrazole-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 203)

[0879] Step 1: Preparation of N-(3-cyano-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide

[0880] Dry DMA (6 mL) was added to a mixture of 1-3 (346 mg, 0.8 mmol), Zn(CN)₂ (66 mg, 0.56 mmol; Adamas, 013580251), Pd(t-Bu₃P)₂ (50 mg, 0.6 mmol; Adamas, 014369225), and Zn powder (12 mg, 0.04 mmol) prepared in Example 1, and the mixture was heated and stirred at 100 °C for 8 h under an argon atmosphere. TLC (PE:EA = 2:1, R f=0.15) showed 1-3 basic consumption and a new point was detected. After cooling to room temperature, the mixture was vacuum-sealed, and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (PE:EA = 3:1) to give the title compound 203-1 (87.3 mg, 29% yield) as a pale pinkish-gray solid. 1 H NMR (400MHz, CDCl3) δ7.89–7.77(m,7H),7.53(dd,J=9.1,2.0Hz,1H),3.10(s,3H).

[0881] Step 2: Preparation of N-(3-(2H-tetrazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0882] Dry DMF (1.2 mL) was added to a mixture of 203-1 (76 mg, 0.2 mmol), NaN3 (39 mg, 0.6 mmol), and NH4Cl (32 mg, 0.6 mmol), and the mixture was heated and stirred at 130 °C for 12 h under an argon atmosphere. TLC (DCM:MeOH = 20:1, R) was performed. f =0.05) showed that 203-1 was completely consumed and a new spot was detected. After cooling to room temperature, the reaction solution was poured into EA (20 mL), washed successively with water (20 mL × 2) and saturated brine (20 mL × 2), the organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, which was purified by column chromatography (DCM:MeOH = 15:1) to give the title compound 203-2 (54.3 mg, 64% yield) as a pale brownish-gray gel. 1 H NMR (400MHz, DMSO) δ9.99 (s, 1H), 8.35 (d, J = 2.0Hz, 1H), 8.14 (d, J = 8.4Hz, 2H), 8.0 7(d,J=9.1Hz,1H),8.04(d,J=8.6Hz,2H),7.57(dd,J=9.1,2.1Hz,1H),3.02(s,3H).

[0883] Step 3: Preparation of N-(3-(2-methyl-2H-tetrazol-5-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0884] Iodimethane (12 μL, 0.191 mmol) was added dropwise to a solution of 203-2 (54 mg, 0.1275 mmol) and K2CO3 (35 mg, 0.255 mmol) in MeCN (1.0 mL), and the mixture was stirred at room temperature for 2 h. TLC (DCM:MeOH = 100:1, RL) was performed. f=0.2) indicates that 203-2 was completely consumed and a new spot was detected. The residue was concentrated under reduced pressure and purified by column chromatography (DCM:MeOH = 150:1) to obtain a white, gel-like crude product. Diethyl ether (1.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 203 (5.9 mg, 10.6% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO) δ10.01(s,1H),8.36(d,J=2.0Hz,1H),8.19(d,J=8.4Hz,2H),8.12(d,J =9.2Hz,1H),8.03(d,J=8.5Hz,2H),7.59(dd,J=9.1,2.1Hz,1H),4.52(s,3H),3.02(s,3H).

[0885] Example 204

[0886] N-(3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethanesulfonamide (compound 204)

[0887] Step 1: Preparation of 3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0888] Step 1 uses the same preparation method as Step 4 of Example 1, except that 1-3 in Step 4 of Example 1 is replaced with 1-2 prepared in Step 2 of Example 1, and 1-methyl-1H-pyrazole-4-boric acid is replaced with pinacol ester of 1-cyclopropyl-1H-pyrazole-4-boronic acid (Bide, BD210594). After concentration under reduced pressure, crude product 204-1, which is yellow-black oil, is obtained and used directly in the next reaction without purification.

[0889] Step 2: Preparation of N-(3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)ethanesulfonamide

[0890] Step 2 followed the same preparation method as in Example 186, except that 10-1 in Step 1 of Example 186 was replaced with 204-1, and cyclopropylsulfonyl chloride was replaced with ethylsulfonyl chloride. After concentration under reduced pressure, a residue was obtained. This residue was purified by column chromatography (DCM:MeOH = 100:1) to obtain a crude product that was a light brown gel. Diethyl ether (3.0 mL), DCM (0.5 mL), and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 204 (110 mg, 92.5% yield) as a creamy white solid. 1H NMR (400MHz, DMSO) δ9.83(s,1H),8.40(d,J=0.8Hz,1H),8.06(d,J=8.4Hz,2H),8.03–7.98(m,2H),7.94(d,J=8.5Hz,2H),7.88(d,J=2.0Hz,1H) ,7.49(dd,J=9.1,2.0Hz,1H),3.89(tt,J=7.4,3.9Hz,1H),3.11(q,J=7.3Hz,2H),1.22(t,J=7.3Hz,3H),1.19–1.13(m,2H),1.08–1.01(m,2H).

[0891] Example 205

[0892] N-(3-(1-cyclopropyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)cyclopropanesulfonamide (compound 205)

[0893] Example 205 was prepared using the same method as Example 186, except that 10-1 in step 1 of Example 186 was replaced with 204-1 prepared in step 1 of Example 204. After concentration under reduced pressure, a residue was obtained. The residue was purified by column chromatography (DCM:MeOH = 100:1) to obtain a crude product as a light brown solid. Diethyl ether (3.0 mL), DCM (0.5 mL), and n-hexane (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 205 (95.2 mg, 78% yield) as a light pink solid. 1 H NMR (400MHz, DMSO) δ9.75(s,1H),8.42(d,J=0.8Hz,1H),8.07(d,J=8.4Hz,2H),8.04–7.98(m,2H),7.98–7.88(m,3H),7.51(dd,J=9.0,2 .0Hz,1H),3.89(tt,J=7.5,3.9Hz,1H),2.66(tt,J=7.6,5.1Hz,1H),1.21–1.14(m,2H),1.08–1.00(m,2H),0.91(tt,J=7.2,2.6Hz,4H).

[0894] Example 206

[0895] 3-(1,5-Dimethyl-1H-pyrazole-4-yl)-N-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-sulfonamide (Compound 206)

[0896] Example 206 was prepared using the same method as Example 4, except that 4-methoxyphenylboronic acid in step 1 of Example 4 was replaced with 4-trifluoromethylphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 5 was replaced with pinacol 1,5-dimethyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (1.5 mL) and n-hexane (1.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 206 (53.3 mg, 79% yield) in the form of a pale yellow solid. 1 H NMR (400MHz, DMSO) δ8.40(d,J=1.6Hz,1H),8.19(d,J=8.9Hz,1H),8.12(d,J=8.5Hz,2H),8.06(s,1H),7.99(d,J= 8.5Hz,2H),7.93(dd,J=9.0,1.7Hz,1H),7.57(q,J=5.1Hz,1H),3.88(s,3H),2.61(s,3H),2.42(d,J=5.0Hz,3H).

[0897] Example 207

[0898] N-(3-(1-methyl-1H-indol-2-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 207)

[0899] Example 207 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with N-methylindole-2-boric acid (Adamas, 013521375). After purification by column chromatography (DCM:MeOH = 1:0), a crude product in the form of a pale gray solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 207 (80.7 mg, 83% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.84(s,1H),8.16(d,J=8.5Hz,2H),8.09(d,J=9.1Hz,1H),8.04–7.95(m,3H),7.71(d,J=7.9Hz,1H),7.62(d,J=8.3Hz ,1H),7.55(dd,J=9.1,2.0Hz,1H),7.29(ddd,J=8.3,7.0,1.2Hz,1H),7.15(td,J=7.3,1.0Hz,1H),7.10(s,1H),4.13(s,3H),3.01(s,3H).

[0900] Example 208

[0901] N-(1-(4-cyanophenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 208)

[0902] Example 208 was prepared using the same method as Example 7, except that 3-bromo-6-nitro-1H-indazole in step 1 of Example 7 was replaced with 3-bromo-5-nitro-1H-indazole, 4-iodo-1-methylimidazolium was replaced with 4-bromobenzonitrile (BYD, BD34361), and 4-trifluoromethylphenylboronic acid in step 4 was replaced with 1-methyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 50:1), a crude product in the form of a light brown solid was obtained. Diethyl ether (2.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 208 (19.2 mg, 43% yield) in the form of a light gray solid. 1 H NMR (400MHz, DMSO) δ9.75(s,1H),8.39(s,1H),8.08–8.01(m,6H),7.89(d,J=2.0Hz,1H),7.48(dd,J=9.0,2.0Hz,1H),3.98(s,3H),3.01(s,3H).

[0903] Example 209

[0904] N-(3-(thiophen-2-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 209)

[0905] Example 209 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 2-thiopheneboronic acid. After purification by column chromatography (PE:EA = 2.5:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 209 (87.2 mg, 96% yield) in the form of a pale pink solid. 1H NMR (400MHz, DMSO) δ9.82 (s, 1H), 8.02 (d, J = 1.9Hz, 1H), 7.98–7.90 (m, 3H), 7.77–7.70 (m, 2H ),7.65–7.58(m,2H),7.48(dd,J=9.0,2.0Hz,1H),7.30(dd,J=5.1,3.6Hz,1H),3.01(s,3H).

[0906] Example 210

[0907] N-(3-(thiophen-3-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 210)

[0908] Example 210 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 3-thiopheneboronic acid. After purification by column chromatography (PE:EA = 2.5:1), a crude product in the form of a brown solid was obtained. Diethyl ether (3.0 mL) and DCM (0.5 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 210 (67.1 mg, 74% yield) in the form of a light gray solid. 1 H NMR(400MHz, DMSO)δ9.75(s,1H),8.11(dd,J=2.9,1.3Hz,1H),8.00–7.95(m,3H),7.93(d,J=9.0Hz,1H),7.80(d d,J=5.0,2.9Hz,1H),7.72(dd,J=5.0,1.3Hz,1H),7.65–7.58(m,2H),7.46(dd,J=9.1,2.0Hz,1H),3.01(s,3H).

[0909] Example 211

[0910] N-(3-(cyclopenten-1-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 211)

[0911] Example 211 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 1-cyclopentenylboronic acid. After purification by column chromatography (PE:EA = 2.5:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.5 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 211 (82.3 mg, 94% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.72(s,1H),7.92(d,J=2.0Hz,1H),7.89(dd,J=9.1,7.1Hz,3H),7.63–7.55(m,2H),7.43(dd,J=9.1,2.0Hz,1H ), 6.56 (p, J = 2.4Hz, 1H), 2.98 (s, 3H), 2.91 (ddd, J = 9.8, 6.3, 2.2Hz, 2H), 2.65 (ddd, J = 9.9, 5.6, 2.0Hz, 2H), 2.00 (p, J = 7.6Hz, 2H).

[0912] Example 212

[0913] N-(3-(cyclohexyl-1-en-1-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazol-5-yl)methanesulfonamide (compound 212)

[0914] Example 212 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with 1-cyclohexenylboronic acid. After purification by column chromatography (PE:EA = 2.5:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (4.0 mL) was added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 212 (79.5 mg, 88% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO)δ9.66(s,1H),7.92–7.83(m,4H),7.61–7.54(m,2H),7.42(dd,J=9.0,2.0Hz,1H),6.61–6.55(m,1H) ,2.96(s,3H),2.62(q,J=4.8Hz,2H),2.32(qd,J=6.4,2.7Hz,2H),1.82–1.74(m,2H),1.70(dtd,J=9.1,5.8,2.6Hz,2H).

[0915] Example 213

[0916] N-(3-(1,5-dimethyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethoxy)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 213)

[0917] Example 213 was prepared using the same method as Example 1, except that 4-trifluoromethylphenylboronic acid in step 1 of Example 1 was replaced with 4-trifluoromethoxyphenylboronic acid, and 1-methyl-1H-pyrazole-4-boronic acid in step 4 was replaced with pinacol 1,5-dimethyl-1H-pyrazole-4-boronic acid. After purification by column chromatography (DCM:MeOH = 50:1), a crude product in the form of a white solid was obtained. Diethyl ether (3.0 mL), DCM (0.5 mL), and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 213 (81.2 mg, 87% yield) in the form of a white solid. 1 H NMR(400MHz,DMSO)δ9.71(s,1H),7.98–7.90(m,3H),7.88(s,1H),7.81(dd,J=2.1,0.7Hz,1 H),7.63–7.57(m,2H),7.44(dd,J=9.0,2.0Hz,1H),3.86(s,3H),2.98(s,3H),2.58(s,3H).

[0918] Example 214

[0919] N-(1-(4-(bromodifluoromethoxy)phenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide (compound 214)

[0920] Step 1: Preparation of 1-(bromodifluoromethoxy)-4-iodobenzene

[0921] Dry NMP (20 mL) was added to cuprous bromide (2869 mg, 20 mmol; BD122223) and 140681-55-6 (2835 mg, 8 mmol; 1021061), and the mixture was stirred at room temperature for 5 min under argon atmosphere. Then, (bromodifluoromethyl)trimethylsilane (2436 mg, 12 mmol; BD303257) was added, and the mixture was stirred at room temperature for 5 min. Finally, 4-iodophenol (880 mg, 4.0 mmol; Adamas, 01085495) was added, and the mixture was stirred at room temperature for 12 h. TLC (PE:EA = 100:1, R f=0.15) showed that 4-iodophenol was almost completely consumed and a new spot was detected. The reaction was quenched by adding saturated NH4Cl aqueous solution (30 mL), extracted with EA (30 mL × 3), the organic layer was washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain the residue, and purified by column chromatography (PE:EA = 1:0) to give the title compound 214-1 (209 mg, 60% yield) as a colorless oil: 1 H NMR (400MHz, CDCl3) δ7.78–7.69(m,2H),7.04–6.97(m,2H).

[0922] Step 2: Preparation of 3-bromo-1-(4-(bromodifluoromethoxy)phenyl)-5-nitro-1H-indazole

[0923] Step 2 employs the same preparation method as Step 1 in Example 7, except that 3-bromo-6-nitro-1H-indazole in Step 1 of Example 7 is replaced with 3-bromo-5-nitro-1H-indazole, and 4-iodo-1-methylimidazole is replaced with 214-1. After concentration under reduced pressure, the residue was obtained and purified by column chromatography (PE:EA = 75:1) to give the title compound 214-2 (64.2 mg, 23% yield) as a pale yellow gel. 1 H NMR (400MHz, CDCl3) δ8.64 (ddd, J=52.1, 2.1, 0.6Hz, 1H), 8.44–8.36 (m, 1H), 7.82–7.71 (m, 3H), 7.48 (dt, J=8.8, 1.0Hz, 2H).

[0924] Step 3: Preparation of 3-bromo-1-(4-(bromodifluoromethoxy)phenyl)-1H-indazole-5-amine

[0925] Step 3 uses the same preparation method as step 3 in Example 58, except that 58-2 in step 3 of Example 58 is replaced with 214-2. After concentration under reduced pressure, crude product 214-3, which is light brown and oily, is obtained and used directly in the next reaction without purification.

[0926] Step 4: N-(3-bromo-1-(4-(bromodifluoromethoxy)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0927] Step 4 uses the same preparation method as step 3 of Example 1, except that steps 1-2 in step 3 of Example 1 are replaced with 214-3. After purification by column chromatography (PE:EA = 2:1), the title compound 214-4 (28.2 mg, 29% two-step yield) was obtained as a yellow solid.

[0928] Step 5: Preparation of N-(1-(4-(bromodifluoromethoxy)phenyl)-3-(1-methyl-1H-pyrazole-4-yl)-1H-indazole-5-yl)methanesulfonamide

[0929] Step 5 follows the same preparation method as step 4 of Example 1, except that 1-3 in step 4 of Example 1 are replaced with 214-4. After concentration under reduced pressure, a residue is obtained. This residue is purified by column chromatography (DCM:MeOH = 75:1) to obtain a crude product that is a pale brownish-yellow solid. Diethyl ether (2.0 mL), DCM (0.5 mL), and n-hexane (1.0 mL) are added to the crude product. The mixture is stirred at room temperature for 1 h, and then filtered to obtain the title compound 214 (15.6 mg, 55% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO) δ9.70 (s, 1H), 8.36 (s, 1H), 8.00 (d, J = 0.8Hz, 1H), 7.98–7.89 (m, 3H), 7.8 8(d,J=1.9Hz,1H),7.62–7.53(m,2H),7.45(dd,J=9.0,2.0Hz,1H),3.98(s,3H),3.00(s,3H).

[0930] Example 215

[0931] N-(3-(1-(tert-butyl)-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 215)

[0932] Example 215 was prepared using the same method as Example 1, except that 1-methyl-1H-pyrazole-4-boric acid in step 4 of Example 1 was replaced with 1-tert-butylpyrazole-4-boronic acid pyrrolyl ester (Bide, BD231235). After purification by column chromatography (DCM:MeOH = 100:1), a pale yellow gel-like crude product was obtained. DCM (1.0 mL) and n-hexane (2.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 215 (84.4 mg, 88% yield) as a creamy white solid. 1 H NMR(400MHz, DMSO)δ9.75(s,1H),8.39(d,J=0.8Hz,1H),8.09(s,1H),8.08–8.05(m,2H),8.02(d,J=9.0Hz ,1H),7.94(d,J=8.6Hz,2H),7.92(d,J=1.9Hz,1H),7.50(dd,J=9.0,2.0Hz,1H),3.01(s,3H),1.63(s,9H).

[0933] Example 216

[0934] N-(4-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 216)

[0935] Step 1: Preparation of 3-bromo-4-methyl-5-nitro-1H-indazole

[0936] Under ice bath conditions, NBS (214 mg, 1.2 mmol) was added in portions to a solution of 4-methyl-5-nitro-1H-indazole (177 mg, 1.0 mmol; BD219869) dissolved in DMF (5.0 mL), and the mixture was stirred at room temperature for 0.5 h. TLC (PE:EA = 5:1, R f =0.15) indicates that the starting material was completely consumed and a new spot was detected. Water (30 mL) was slowly added dropwise to the reaction solution, and the mixture was filtered to give the title compound 216-1 (239 mg, 93% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO) δ13.97(s,1H),7.93(d,J=9.1Hz,1H),7.57(d,J=9.1Hz,1H),2.92(s,3H).

[0937] Step 2: Preparation of 3-bromo-4-methyl-5-nitro-1-(4-(trifluoromethyl)phenyl)-1H-indazole

[0938] Step 2 employed the same preparation method as Step 1 of Example 1, except that the 3-bromo-5-nitro-1H-indazole in Step 1 of Example 1 was replaced with 216-1. The residue was purified by column chromatography (PE:EA = 50:1) to give the title compound 216-2 (159 mg, 80% yield) as a pale yellow solid. 1 H NMR (400MHz, CDCl3) δ8.01(d,J=9.2Hz,1H),7.88–7.78(m,4H),7.61(d,J=9.2Hz,1H),3.09(s,3H).

[0939] Step 3: Preparation of 3-bromo-4-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-amine

[0940] Step 3 uses the same preparation method as Step 3 of Example 58, except that 58-2 in Step 3 of Example 58 is replaced with 216-2. The reaction solution is poured into water (50 mL), extracted with DCM (30 mL × 3), the organic layer is washed with saturated brine (30 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the title compound 216-3, which is a pale yellow solid. The crude product is used directly in the next reaction without purification.

[0941] Step 4: Preparation of N-(3-bromo-4-methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0942] Step 4 uses the same preparation method as step 3 of Example 1, except that steps 1-2 in step 3 of Example 1 are replaced with 216-3. After concentration under reduced pressure, the title compound 216-4, a pale yellow solid, is obtained. The crude product is used directly in the next reaction without purification.

[0943] Step 5: Preparation of N-(4-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazol-5-yl)methanesulfonamide

[0944] Step 5 follows the same preparation method as step 4 of Example 1, except that steps 1-3 in step 4 of Example 1 are replaced with 216-4. After purification by column chromatography (DCM:MeOH = 75:1), a pale yellow gel-like crude product was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 216 (60.3 mg, 67% yield) as a white solid. 1 H NMR (400MHz, DMSO) δ9.21 (s, 1H), 8.15–8.10 (m, 1H), 8.03 (d, J = 8.5Hz, 2H), 7.95 (d, J = 8.7Hz, 2H), 7.81 (d,J=8.9Hz,1H),7.77(d,J=0.8Hz,1H),7.46(d,J=9.0Hz,1H),3.95(s,3H),2.97(s,3H),2.49(s,3H).

[0945] Example 217

[0946] N-(6-methyl-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 217)

[0947] Example 217 was prepared using the same method as Example 216, except that 4-methyl-5-nitro-1H-indazole in step 1 of Example 216 was replaced with 6-methyl-5-nitro-1H-indazole (Bide, BD105022). After purification by column chromatography (DCM:MeOH = 75:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 217 (74.5 mg, 83% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.23(s,1H),8.44(s,1H),8.12–8.03(m,3H),7.94(dd,J=7.6,5.6Hz,4H),3.98(s,3H),3.07(s,3H),2.52(s,3H).

[0948] Example 218

[0949] N-(6-chloro-3-(1-methyl-1H-pyrazole-4-yl)-1-(4-(trifluoromethyl)phenyl)-1H-indazole-5-yl)methanesulfonamide (compound 218)

[0950] Example 218 was prepared using the same method as Example 216, except that 4-methyl-5-nitro-1H-indazole in step 1 of Example 216 was replaced with 6-chloro-5-nitro-1H-indazole (Bide, BD248314). After purification by column chromatography (DCM:MeOH = 100:1), a crude product in the form of a pale yellow solid was obtained. Diethyl ether (3.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 218 (64.2 mg, 68% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ9.65 (s, 1H), 8.51 (s, 1H), 8.19 (s, 1H), 8.13–8.04 (m, 4H), 7.95 (d, J = 8.5Hz, 2H), 3.98 (s, 3H), 3.08 (s, 3H).

[0951] Example 219

[0952] N-Methyl-1-(thiophen-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxamide (Compound 219)

[0953] Example 219 was prepared using the same method as Example 18, except that compound 17 in step 1 of Example 18 was replaced with compound 149. After purification by column chromatography (PE:EA = 2:1), a crude product in the form of a white solid was obtained. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. The product was then filtered to obtain the title compound 219 (19.2 mg, 32% yield) in the form of a white solid. 1 H NMR(400MHz, DMSO)δ8.75(q,J=4.5Hz,1H),8.33(dd,J=3.2,2.0Hz,2H),8.31–8.27(m,2H),8.07(dd,J=3.2 ,1.5Hz,1H),7.93(d,J=8.2Hz,2H),7.89–7.83(m,2H),7.71(dd,J=5.2,1.5Hz,1H),2.85(d,J=4.5Hz,3H).

[0954] Example 220

[0955] N-Isopropyl-1-(thiophen-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-6-carboxamide (Compound 220)

[0956] Example 220 was prepared using the same method as Example 18, except that compound 17 in step 1 of Example 18 was replaced with compound 149, and MeNH2·HCl was replaced with isopropylamine (Adamas, 01112080). After purification by column chromatography (PE:EA = 3:1), a crude product in the form of a white solid was obtained. Diethyl ether (1.0 mL) and n-hexane (1.0 mL) were added to the crude product, and the mixture was stirred at room temperature for 1 h. Filtering yielded the title compound 220 (21.9 mg, 34% yield) in the form of a white solid. 1 H NMR (400MHz, DMSO) δ8.54(d,J=7.7Hz,1H),8.35–8.24(m,4H),8.08(dd,J=3.1,1.4Hz,1H),7.93(d,J=8.2H z,2H),7.90–7.83(m,2H),7.71(dd,J=5.1,1.5Hz,1H),4.23–4.10(m,J=6.7Hz,1H),1.22(d,J=6.6Hz,6H).

[0957] Example 221

[0958] 1-(thiophene-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1H-indazole-6-carboxylic acid (compound 221)

[0959] Example 221 was prepared using the same method as Example 149, except that 4-trifluoromethylphenylboronic acid in step 2 of Example 149 was replaced with 4-trifluoromethoxyphenylboronic acid. After concentration under reduced pressure, a residue was obtained. 1N HCl was added dropwise to the residue solution dissolved in water (20 mL) to adjust the pH to approximately 1. Extraction was performed using DCM (20 mL × 3). The organic layer was washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the residue. Diethyl ether (4.0 mL) and n-hexane (0.5 mL) were added to the residue, and the mixture was stirred at room temperature for 1 h. Filtration yielded the title compound 221 (53.2 mg, 66% yield) as a pale yellow solid. 1 H NMR (400MHz, DMSO) δ13.32(s,1H),8.38(t,J=1.0Hz,1H),8.29(d,J=8.6Hz,1H),8.23–8.16(m,2H),8.03(dd,J=3.1, 1.4Hz, 1H), 7.91 (dd, J=8.6, 1.4Hz, 1H), 7.86 (dd, J=5.2, 3.1Hz, 1H), 7.65 (dd, J=5.2, 1.4Hz, 1H), 7.61–7.54 (m, 2H).

[0960] Example 222

[0961] 1-(thiophene-3-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indazole-5-carboxylic acid (com...

Claims

1. A bicyclic compound of formula (I) or a pharmaceutically acceptable salt thereof: in, X is selected from CR a Or N, the R a Selected from H or halogens; Y is selected from CH or N; Ring A is selected from C 6-10 Aryl, 5-10 heteroaryl or C 3-6 Cycloalkenyl, wherein the 5- to 10-membered heteroaryl group comprises 1 to 4 heteroatoms independently selected from N, O, or S; Each R 1 They may be the same or different, and each is independently selected from H, D, halogen, -CN, -NO2, -NH2, -OR b1 -SR b2 -SF5, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl and phenyl groups are optionally substituted by 0 to 3 substituents independently selected from -OH, halogen, -CN, -NO2 or -NH2; Ring B is selected from C 6-10 Aryl, 5-10 heteroaryl or C 3-6 Cycloalkenyl, wherein the 5- to 10-membered heteroaryl group comprises 1 to 4 heteroatoms independently selected from N, O, or S; Each R 2 They may be the same or different, and each is independently selected from H, D, halogen, -CN, -NO2, -NH2, -OR b1 -SR b2 C, whether substituted or not 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl and phenyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH, halogen or -CN; R b1 and R b2 Each time, the same or different, and each independently selected from H, D, substituted or unsubstituted C, are used. 1-6 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl and phenyl groups are optionally substituted with 0 to 3 substituents independently selected from halogens, -CN, -NH2 or -OH; R 3 Selected from R 4 and R 5 Each time it may be the same or different, and each is independently selected from H, D, -OH, substituted or unsubstituted C. 1-6 Alkyl, substituted or unsubstituted C 3-6 Cycloalkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 Alkyl, C 3-6 The cycloalkyl group and phenyl group are optionally separated by 0 to 3 independently selected from halogen, -OR f or -NR f R g Substituents; R f and R g Each time the same or different, and each independently selected from H and C 1-6 Alkyl or C 3-6 cycloalkyl; R c R d and R e Each time it may be the same or different, and each is independently selected from H, D, halogen, -CN, -OH or C. 1-6 Halogenated or non-halogenated alkyl groups; m is selected from any integer from 0 to 3; n is any integer from 0 to 3.

2. The bicyclic compound or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, The ring A is specifically selected from any of the following structural segments: Each R 1 Same or different, and each independently selected from H, halogen, -OR b1 -SR b2 -SF5 or substituted or unsubstituted C 1-4 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-4 The alkyl and phenyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH or halogens; R b1 and R b2 Each time, the same or different, and each independently selected from H, D, substituted or unsubstituted C, are used. 1-6 Alkyl, or substituted or unsubstituted phenyl, wherein the substituted C 1-6 The alkyl and phenyl groups are optionally substituted with 0 to 3 substituents independently selected from halogens, -CN, -NH2 or -OH.

3. The bicyclic compound or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that ring B is specifically selected from any one of the following structural segments: Each R 2 Same or different, and each independently selected from halogen, -OR b1 -SR b2 C, either substituted or unsubstituted 1-3 Alkyl, wherein, The replaced C 1-3 The alkyl groups are optionally substituted by 0 to 3 independent substituents selected from -OH or halogens; R b1 and R b2 Each time, the same or different, and each independently selected from H, or substituted or unsubstituted C. 1-3 Alkyl, wherein the substituted C 1-3 The alkyl group is optionally substituted by 0 to 3 independent substituents selected from halogens.

4. The bicyclic compound or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, The R 3 Choose from any of the following structural fragments: R 4 and R 5 Each time, the same or different, and each independently selected from H, or substituted or unsubstituted C. 1-3 Alkyl, wherein the substituted C 1-3 The alkyl groups are optionally substituted by 0 to 3 independent substituents selected from halogens. R c R d and R e Each time it may be the same or different, and each is independently selected from H, halogen or C. 1-3 Halogenated or non-halogenated alkyl groups; m is selected from any integer from 0 to 2; n is any integer from 0 to 2.

5. The bicyclic compound of claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The bicyclic compounds also include any one of their tautomers, meso compounds, racemates, stereoisomers, metabolites, metabolic precursors, prodrugs, chelates, non-covalent complexes, or solvates.

6. The bicyclic compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, characterized in that, The bicyclic compound or its pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate is selected from any of the following compounds:

7. The use of a bicyclic compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate thereof, in the preparation of a TEAD inhibitor.

8. Use of any one of the bicyclic compounds of claims 1 to 5, or a pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate thereof, in the preparation of a medicament for the prevention or treatment of TEAD-mediated, YAP / TAZ-mediated, or YAP / TAZ-TEAD-mediated diseases.

9. The application according to claim 8, characterized in that, The diseases mediated by TEAD, YAP / TAZ, or by the interaction between YAP / TAZ and TEAD include any one of cancer, organ fibrosis, metabolic diseases, or inflammatory diseases.

10. A pharmaceutical composition for the prevention or treatment of diseases mediated by TEAD, YAP / TAZ, or mediated by the interaction between YAP / TAZ and TEAD, characterized in that, The composition comprises a bicyclic compound as described in any one of claims 1 to 5, or a pharmaceutically acceptable salt, ester, stereoisomer, deuterated compound, or solvate thereof, and a pharmaceutically acceptable carrier. The bicyclic compound further comprises a pharmaceutically acceptable salt, tautomer, meso compound, racemic compound, stereoisomer, metabolite, metabolic precursor, prodrug, chelate, non-covalent complex, or solvate thereof as an active ingredient and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition according to claim 10, characterized in that, The pharmaceutical composition is preferably in the form of capsules, powders, tablets, granules, pills, injections, syrups, oral liquids, inhalers, ointments, suppositories, or patches.

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