Azaindazole macrocyclic compounds and their use

Abstract

The present application relates to azaindazole macrocycle compounds having the structure of Formula I, which have the effect of inhibiting the activity of multiple protein kinases, including, for example, HPK1, FLT3, and KDR. JPEG2024533563000206.jpg43158

Description

[Technical Field] 【0001】 The present invention relates to macrocyclic azindazole derivatives, particularly macrocyclic azindazole derivatives having multi-target kinase inhibitory activity, and pharmaceutical compositions, and also to the use of such compounds and drug combinations in the improvement or treatment of protein kinase-mediated diseases, such as cancer. [Background technology] 【0002】 Cancer, or malignant tumors, are a serious disease that threatens human health and life, and the incidence and mortality rates of cancer continue to show a significant upward trend. The proliferation, metastasis, and apoptosis of tumor cells are closely related to abnormalities in a series of signaling pathways, and immune evasion by tumor cells and the decline or suppression of the body's immune function are also important causes of cancer development and progression. Therefore, by suppressing the activity of crucial kinases in the signaling pathways of tumor cells and simultaneously activating immune cells, the body's own immunity to the tumor can be increased, effectively suppressing the proliferation and metastasis of tumor cells, offering promising prospects for the treatment of cancer patients. 【0003】 Hematopoietic progenitor kinase 1 (HPK1) is a serine / threonine kinase that was first obtained by cloning from hematopoietic progenitor cells (Hu, MC et al., Genes Dev. 1996;10:2251-2264; Keifer, F. et al., The EMBO Journal 1996;15:7013-7025), and belongs to the mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K) family. HPK1 is mainly distributed in lymphoid organs or tissues such as bone marrow, lymph nodes, and the thymus, and is primarily expressed in immune cells (T cells, B cells, dendritic cells) (Hu, MC et al., Genes Dev. 1996;10:2251-2264). 【0004】 Recent studies have shown that HPK1 is a negative regulatory protein in the T cell acceptor (TCR) signaling pathway. TCR signaling activates HPK1, and activated HPK1 phosphorylates the Ser376 residue of SLP-76, promoting the binding of SLP-76 to the 14-3-3 protein (Di Bartolo, V. et al., J. Exp. Med. 2007; 204: 681-691; Shui, J. et al., Nature Immuno. 2007; 8: 84-91). The interaction between SLP-76 and 14-3-3 downregulates ERK signaling and calcium ion flow, leading to ubiquitination of SLP-76 and degradation of the SLP-76 complex, thereby inhibiting the TCR activation pathway and suppressing T cell function (Lasserre, R. et al., J. Cell Biol. 2011;195:839-853). 【0005】 In vivo experiments have shown that HPK1 knockout mice exhibit enhanced T cell function and increased production of cytokines such as IL-2 and IFN-γ in response to antigen stimulation (Shui, J. et al., Nature Immuno. 2007; 8: 84-91; Alzabin, S. et al., J. Immunol. 2009; 182: 6187-6194; Alzabin, S. et al., Cancer Immunol. Immunother. 2010; 59: 419-429). Further studies have revealed that the negative control of immune cells by HPK1 depends on the activity of its kinase. Compared to wild-type mice, mice with blocked HPK1 kinase activity exhibited enhanced CD8+ T cell function, faster clearance of chronic lymphocytic meningitis virus, and better suppression of tumor growth (Hernandez, S. et al., Cell Reports 2018;25:80-94). In a Lewis lung cancer (LLC) model, mice transfected with HPK1- / - T cells showed enhanced antitumor immune responses compared to wild-type mice (Sawasdikosol, S. et al., Immunol.Res.2012;54:262-265). Studies have revealed that the immunosuppressive effects of HPK1 on B cells (Sauer, K. et al., J. Biol. Chem. 2001; 276: 45207-45216; Tsuji, S. et al., J. Exp. Med. 2001; 194: 529-539; Wang, X. et al., J. Biol. Chem. 2012; 287: 34091-34100; Konigsberger, S. et al., PLo One, 2010; 5: e12468), dendritic cells (Alzabin, S. et al., J. Immunol. 2009; 182: 6187-6194), NK cells, and Treg cells are derived from the activity of its kinase (Liu, J. et al., PLo One). One, 2019;14:e0212670). 【0006】 Clinical studies have shown that, compared to healthy controls, patients with systemic lupus erythematosus (Zhang, Q. et al., J. Autoimmun., 2011;37:180-189) and psoriatic arthritis (Stoeckman, AK et al., Genes Immun. 2006;7:583-591; Baltiwalla, FM et al., Mol. Med. 2005;11:21-29) exhibit significantly downregulated levels of HPK1 in their tissues, suggesting that HPK1 downregulation contributes to the enhancement of the autoimmune response. On the other hand, upregulation of HPK1 levels was observed in various cancers, such as acute granulocytic leukemia (Chen-Deutsch, X. et al., Leuk.Res. 2012;36:884-888; Chen-Deutsch, X. et al., Cell Cycle 2012;11:1364-1373), urothelial carcinoma of the bladder (Wang. Y et al., Mol.Med.Rep. 2012;5:260-265), extramammary Paget's disease (Qian, Y et al., Am J.Dermatopathol. 2011;33:681-686), and colon cancer (Yang, HS et al., Mol.Cell Biol. 2006;26:1297-1306). 【0007】 For this reason, HPK1 is a promising potential target for the treatment of tumors and viral diseases, and the development of small molecule inhibitors of HPK1 kinase is of great clinical interest. FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed in hematopoietic progenitor cells and stem cells, and plays a crucial role in the survival, proliferation, and differentiation of hematopoietic cells. Mutations or abnormal expression of FLT3 can cause blood disorders such as leukemia (Gilliland, DG et al., Blood, 2002;100:1532-1542; Stirewalt, DL et al., Nat. Rev. Cancer, 2003;3:650-665). Mutations in the FLT3 gene are present in approximately 30% of adult patients with acute myeloid leukemia (AML) (Nakao, MS et al., Leukemia, 1996;10:1911-1918; Kottaridis PD, Blood, 2001;98:1742-1759), and are the most common gene mutation and poor prognostic factor in patients (Abu-Duhier FM et al., British Journal of Haematology, 2000;111:190-195; Meshinchi S. et al., Clin. Cancer Res., 2009;15:4263-4269). Therefore, FLT3 is a crucial target for the development of small molecule drugs for the treatment of such tumors. 【0008】 In 2017, Midostaurin, a small molecule drug and the first FLT3 inhibitor developed by Novartis in the United States, received marketing authorization and is being used in combination therapy for FLT3-positive AML patients receiving drug treatment for the first time. Since then, Gilteritinib, developed by Astellas, and Quizartinib, developed by Daiichi Sankyo, have successively received marketing authorization and are being used in monotherapy or combination therapy for AML with FLT3 abnormal expression or mutations. Although there are several commercially available small molecule FLT3 inhibitors, many problems remain as a treatment option for AML, such as a short duration of clinical effect, which can lead to drug resistance. At the same time, clinical data suggest that FLT3 inhibitor drugs can efficiently remove primitive cells in the peripheral blood of patients, but have a weak effect on the bone marrow (Bortheakur, G. et al., Haematologica, Jan. 2011;96:62-68). One possible cause of these problems is the presence of a signaling pathway instead of FLT3. Therefore, to meet existing clinical needs, there is a need to develop a new generation of FLT3 inhibitors, particularly small molecule compounds that can simultaneously inhibit multiple signaling pathways. 【0009】 Vascular endothelial growth factor receptors (VEGFRs) belong to the type III receptor tyrosine kinase family. Among these, VEGFR2 (KDR) is also known as a kinase insert domain receptor (KDR) and is widely distributed in vascular endothelial cells, playing a very important role in inducing the growth, proliferation, and migration of neothelial cells around tumors. 【0010】 Currently, several types of VEGFR2 inhibitors have received approval for use in the treatment of related tumors. In 2006, Sunitinib, a small molecule drug and VEGFR inhibitor developed by Novartis in the United States, received marketing approval and is used in the treatment of gastrointestinal stromal tumors and metastatic renal cell carcinoma. As a multi-target inhibitor, Sunitinib effectively suppresses VEGFR activity and also inhibits various kinases such as PDGFR and c-Kit. Because of its multi-target inhibitory effect, this drug can be applied to a variety of indications and can also reduce drug resistance caused by activation of signaling pathways other than VEGFR. Since then, many other multi-target small molecule inhibitors, such as Sorafenib, Cabozantininb, and Lenvatininb, have received approval and achieved great success. 【0011】 While numerous patent applications for HPK1 small molecule inhibitors have been disclosed to date, such as WO2018049191, WO2018049200, WO2018102366, WO2018183964, WO2019090198, WO2019206049, WO2019238067, and WO2020092528, no HPK1-targeting drugs are currently commercially available. In particular, small molecule drugs that simultaneously inhibit HPK1 and other kinase targets are rare. Such small molecule compounds directly inhibit the growth of tumor cells and simultaneously stimulate autoimmune functions to eliminate tumor cells. Therefore, there is an urgent need for the clinical development of novel small molecule HPK1 inhibitors with such high activity. [Overview of the project] 【0012】 This application relates to a azindazole macrocyclic compound having the structure of formula I, [ka] Alternatively, the present invention provides isomers thereof, pharmaceutically acceptable salts, crystalline polymorphs, isotope-labeled compounds, active metabolites, or prodrugs. 【0013】 Among them, the structure and atomic numbering of the azaindazole ring are shown in formula (Ia). [Chemical Formula] In the structure of formula I, X is selected from CR , 11 or N, where R x is independently selected from H or halogen; R 1 is 1) hydrogen, halogen, cyano, -C(=O)OR a1 , -C(=O)NR a1 R b1 , -OR a1 , -NR a1 R b1 , -NR e1 C(=O)R a1 , -NR e1 C(=O)NR a1 R b1 , -SR a1 , -S(=O)R a1 and S(=O)2R a1 ; or 2) C 11 alkyl, C 1-6 alkenyl, C 2-4 alkynyl, C 2-4 cyclic alkyl and 3-8 member aliphatic heterocyclic group, optionally substituted with 0, 1, 2, 3 or 4 R 3-8 11 Here, R a1 , R b1 and R e1 are independently selected from the following: 1) hydrogen; or 2) C 11 alkyl, C 1-6 monocyclic cyclic alkyl and a 3-6 member monocyclic aliphatic heterocyclic group, optionally substituted with 0, 1, 2, 3 or 4 R 3-6 ; Alternatively, R a1 and R b1 bonded to the same nitrogen atom form a 4-6 member aliphatic heterocyclic group optionally substituted with 0, 1, 2, 3 or 4 R 11 together with the nitrogen atom to which they are attached;​ Among them, R 11 The group is an oxo group, halogen, hydroxy, amino, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylamino, C 3-6 Cyclylalkyl and C 3-6 Selected from the group consisting of cycloalkoxy groups. 【0014】 L 1 The following can be selected: 1) Single bond; or 2) A 6-10 membered aryl group or a 5-10 membered heteroaryl group, wherein the aryl group or heteroaryl group is bonded by a single bond to the 3-position and A ring of the azindazole ring, respectively; in addition to being bonded to the 3-position and A ring of the azindazole ring, the aryl group or heteroaryl group may have 0, 1, 2, 3, 4, 5, or 6 R members. 4 It is replaced by; Ring A is selected from a 3-12 membered cyclic hydrocarbon group or a 3-12 membered heterocyclic group having a monocyclic or bicyclic ring, and is composed of two different atoms, L 1 and L 2 They are bonded to each other; also, ring A is L 1 and L 2 In addition to being coupled, there are arbitrarily m R 2 It has been replaced with. 【0015】 The B ring is selected from a 6-12 membered cyclic hydrocarbon group or a 5-12 membered heterocyclic group having a monocyclic or bicyclic ring, and is composed of two different atoms, L 2 And it is bound to the 5-position of the azaindazole ring, respectively. Here, 1) If the B ring is a monocyclic hydrocarbon group or a monocyclic heterocyclic group, L 2 The shortest distance between the atoms of the two B rings linked to the 5-position of the azindazole ring is 1, 2, or 3 chemical bonds; 2) If the B ring is a bicyclocyclic hydrocarbon group or a bicycloheterocyclic group, L 2The shortest distance between the atoms of the two B rings, each of which is connected to the 5-position of the azaindazole ring, is 1, 2, 3, 4, or 5 chemical bonds. Among them, the B ring is L 2 In addition to being bonded to the 5-position of the azaindazole ring, it is optionally substituted with n Rs 3 【0016】 R 2 is independently selected from the following respectively: 1) oxo group, halogen, cyano, -C(=O)R a2 , -C(=O)OR a2 , -C(=O)NR a2 R b2 , -C(=NR d2 )(NR a2 R b2 , -OR a2 , -OC(=O)R a2 , -OC(=O)OR c2 , -OC(=O)NR a2 R b2 , -SR a2 , -S(=O)R c2 , -S(=O)2R c2 , sulfonic acid group, -S(=O)NR a2 R b2 , -S(=O)2NR a2 R b2 , -S(=O)(=NR d2 )(R c2 , -NR a2 R b2 , -NR a2 C(=O)R b2 , -NR a2 C(=O)OR c2 , -NR e2 C(=O)NR a2 R b2 , -NR e2 C(=NR d2 )(NR a2 R b2 , -NR a2 S(=O)2R c2 , -NR e2 S(=O)2NR a2 R b2 , nitro, -PR c2 R​f2 -P(=O)R c2 R f2 and phosphonic acid groups; or 2) optionally 0, 1, 2, 3, 4, 5 or 6 R 22 substituted, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, 5-10 member heteroaryl group, C 3-12 cyclic alkyl and 3-12 member aliphatic heterocyclic group; 3) optionally 0, 1, 2, 3, 4, 5 or 6 R 22 substituted and linked to two different ring-constituting atoms of the A ring, a divalent bridging C 1-5 alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group; alternatively, two R 2 each bonded to one or two ring-constituting atoms of the A ring, together with the said one or two ring-constituting atoms, optionally 0, 1, 2, 3, 4 or 5 R 22 substituted, form a C 5-12 alicyclic hydrocarbon group or 5-12 member aliphatic heterocyclic group. 【0017】 Here, R a2 , R[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​c2 and R f2 Each of these independently has any number of R values: 0, 1, 2, 3, 4, or 5. 22 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Selected from the group consisting of cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; or R bonded to the same phosphorus atom c2 and R f2 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 22 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0019】 R d2 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 22 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. R 22 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a22 , -C(=O)OR a22 -C(=O)NR a22 R b22 -C(=NR d22 )NR a22 R b22 , -OR a22 -OC(=O)R a22 , -OC(=O)OR c22 -OC(=O)NR a22 R b22 , -SR a22 -S(=O)R c22 -S(=O)2R c22 , sulfonic acid group, -S(=O)NR a22 Rb22 -S(=O)2NR a22 R b22 -S(=O)(=NR d22 )R c22 , -NR a22 R b22 , -NR a22 C(=O)R b22 , -NR a22 C(=O)OR c22 , -NR e22 C(=O)NR a22 R b22 , -NR e22 C(=NR d22 )NR a22 R b22 , -NR a22 S(=O)2R c22 , -NR e22 S(=O)2NR a22 R b22 , Nitro, -PR c22 R f22 ,-P(=O)R c22 R f22 , phosphonic acid group and =NR d22 ; or 2) 0, 1, 2, 3, 4 or 5 R 23 C is arbitrarily replaced by 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R a22 , R b22 and R e22 Each of these is independently selected from the following: 1) Hydro; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a22and R b22 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 23 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0020】 R c22 and R f22 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl and 3-10 membered aliphatic heterocyclic groups; or R bonded to the same phosphorus atom c22 and R f22 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 23 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with; R d22 teeth, 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Selected from the group consisting of cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. 【0021】 R 23 teeth, 1) Oxo group, halogen, cyano, -C(=O)R a23 , -C(=O)OR a23 -C(=O)NR a23 R b23 -C(=NR d23 )NR a23 R b23 , -OR a23 -OC(=O)R a23 , -OC(=O)OR c23 -OC(=O)NRa23 R b23 , -SR a23 -S(=O)R c23 -S(=O)2R c23 , sulfonic acid group, -S(=O)NR a23 R b23 -S(=O)2NR a23 R b23 -S(=O)(=NR d23 )R c23 , -NR a23 R b23 , -NR a23 C(=O)R b23 , -NR a23 C(=O)OR c23 , -NR e23 C(=O)NR a23 R b23 , -NR e23 C(=NR d23 )NR a23 R b23 , -NR a23 S(=O)2R c23 , -NR e23 S(=O)2NR a23 R b23 , Nitro, -PR c23 R f23 ,-P(=O)R c23 R f23 , phosphonic acid group and =NR d23 ; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Selected from the group consisting of cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a23 , R b23 and R e23 Each of these is independently selected from the following: 1) Hydro; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a23 and R b23 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0022】 R c23 and R f23 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R G It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c23 and R f23 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0023】 R d23 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups, 3- to 8-membered aliphatic heterocyclic groups. R 3 Each of these is independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a3 , -C(=O)OR a3 -C(=O)NRa3 R b3 , -C(=N Rd3 )NR a3 R b3 , -OR a3 -OC(=O)R a3 , -OC(=O)OR c3 -OC(=O)NR a3 R b3 , -SR a3 -S(=O)R c3 -S(=O)2R c3 , sulfonic acid group, -S(=O)NR a3 R b3 -S(=O)2NR a3 R b3 -S(=O)(=N Rd3 )R c3 , -NR a3 R b3 , -NR a3 C(=O)R b3 , -NR a3 C(=O)OR c3 , -NR e3 C(=O)NR a3 R b3 , -NR e3 C(=N Rd3 )NR a3 R b3 , -NR a3 S(=O)2R c3 , -NR e3 S(=O)2NR a3 R b3 , Nitro, -PR c3 R f3 ,-P(=O)R c3 R f3 and phosphonic acid group; or 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 32 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 6-10 membered aryl group, 5-10 membered heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; 3) Divalent bridge C linked to two different ring-constituting atoms of ring B 1-6 Alkylidene group. Alternatively, two R atoms bonded to one or two ring-forming atoms of the B ring, respectively. 3 The substituents, along with the one or two ring constituent atoms, may optionally consist of 0, 1, 2, 3, 4, or 5 R atoms. 32 C is replaced by 5-12 It forms an alicyclic hydrocarbon group or a 5-12 membered aliphatic heterocyclic group. 【0024】 Here, R a3 , R b3 and R e3 Each of these is independently selected from the following: 1) Hydro; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a3 and R b3 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 32 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0025】 R c3 and R f3 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. Alternatively, R bonded to the same phosphorus atom c3 and R f3 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 32 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0026】 R d3 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; R 32 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a32 , -C(=O)OR a32 -C(=O)NR a32 R b32 , -C(=N Rd32 )NR a32 R b32 , -OR a32 -OC(=O)R a32 , -OC(=O)OR c32 -OC(=O)NR a32 R b32 , -SR a32 -S(=O)R c32 -S(=O)2R c32 , sulfonic acid group, -S(=O)NR a32 R b32 -S(=O)2NR a32 R b32 -S(=O)(=N Rd32 )R c32 , -NR a32 R b32 , -NR a32 C(=O)R b32 , -NR a32 C(=O)OR c32 , -NR e32 C(=O)NR a32 R b32 , -NR e32 C(=N Rd32 )NR a32 R b32 , -NR a32 S(=O)2R c32 , -NR e32 S(=O)2NRa32 R b32 , Nitro, -PR c32 R f32 ,-P(=O)R c32 R f32 , phosphonic acid group and =NR d32 ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R a32 , R b32 and R e32 Each of these is independently selected from the following: 1) Hydro; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. Alternatively, R bonded to the same nitrogen atom a32 and R b32 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 33 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0027】 R c32 and R f32 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atomc32 and R f32 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 33 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0028】 R d32 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R 33 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a33 , -C(=O)OR a33 -C(=O)NR a33 R b33 , -C(=N Rd33 )NR a33 R b33 , -OR a33 -OC(=O)R a33 , -OC(=O)OR c33 -OC(=O)NR a33 R b33 , -SR a33 -S(=O)R c33 -S(=O)2R c33 , sulfonic acid group, -S(=O)NR a33 R b33 -S(=O)2NR a33 R b33 -S(=O)(=N Rd33 )R c33 , -NR a33 R b33 , -NR a33 C(=O)R b33 , -NR a33 C(=O)OR c33 , -NR e33 C(=O)NR a33 Rb33 , -NR e33 C(=N Rd33 )NR a33 R b33 , -NR a33 S(=O)2R c33 , -NR e33 S(=O)2NR a33 R b33 , Nitro, -PR c33 R f33 ,-P(=O)R c33 R f33 , phosphonic acid group and =NR d33 ; 2) Arbitrarily R G Substituted with 0, 1, 2, 3, or 4 substituents independently selected from C 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a33 , R b33 and R e33 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a33 and R b33 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0029】 R c33 and R f33 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R G It is replaced with C 1-4Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c33 and R f33 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0030】 R d33 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; R 4 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a4 , -C(=O)OR a4 -C(=O)NR a4 R b4 -C(=NR d4 )NR a4 R b4 , -OR a4 -OC(=O)R a4 , -OC(=O)OR c4 -OC(=O)NR a4 R b4 , -SR a4 -S(=O)R c4 -S(=O)2R c4 -S(=O)NR a4 R b4 -S(=O)2NR a4 R b4 -S(=O)(=NR d4 )R c4 , -NR a4 Rb4 , -NR a4 C(=O)R b4 , -NR a4 C(=O)OR c4 , -NR e4 C(=O)NR a4 R b4 , -NR e4 C(=NR d4 )NR a4 R b4 , -NR a4 S(=O)2R c4 and -NR e4 S(=O)2NR a4 R b4 ; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 42 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-10 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, L 1 Two R atoms bonded to two ring-forming atoms of the ring. 4 is the aforementioned L 1 Along with the two ring-forming atoms of the ring, there are arbitrarily 0, 1, 2, 3, 4, 5, or 6 R atoms. 42 It is replaced with C 5-12 It forms an alicyclic hydrocarbon group or a 5-12 membered aliphatic heterocyclic group. 【0031】 R a4 , R b4 and R e4 Each of these is independently selected from the following: 1) Hydro; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a4 and Rb4 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 42 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0032】 R c4 and R f4 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. R d4 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. R 42 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a42 , -C(=O)OR a42 -C(=O)NR a42 R b42 -C(=NR d42 )NR a42 R b42 , -OR a42 -OC(=O)R a42 , -OC(=O)OR c42 -OC(=O)NR a42 R b42 , -SR a42 -S(=O)R c42 -S(=O)2R c42 -S(=O)NR a42 R b42 -S(=O)2NR a42 Rb42 -S(=O)(=NR d42 )R c42 , -NR a42 R b42 , -NR a42 C(=O)R b42 , -NR a42 C(=O)OR c42 , -NR e42 C(=O)NR a42 R b42 , -NR e42 C(=NR d42 )NR a42 R b42 , -NR a42 S(=O)2R c42 , -NR e42 S(=O)2NR a42 R b42 and =NR d42 ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R a42 , R b42 and R e42 Each of these is independently selected from the following: 1) Hydro; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. Alternatively, R bonded to the same nitrogen atom a42 and R b42 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 43 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0033】 R c42 and R f42 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R d42 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R 43 teeth, 1) Oxo group, halogen, cyano, -C(=O)R a43 , -C(=O)OR a43 -C(=O)NR a43 R b43 -C(=NR d43 )NR a43 R b43 , -OR a43 -OC(=O)R a43 , -OC(=O)OR c43 -OC(=O)NR a43 R b43 , -SR a43 -S(=O)R c43 -S(=O)2R c43 -S(=O)NR a43 R b43 -S(=O)2NR a43 R b43 -S(=O)(=NR d43 )R c43 , -NR a43 R b43 , -NR a43 C(=O)R b43, -NR a43 C(=O)OR c43 , -NR e43 C(=O)NR a43 R b43 , -NR e43 C(=NR d43 )NR a43 R b43 , -NR a43 S(=O)2R c43 , -NR e43 S(=O)2NR a43 R b43 and =NR d43 ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a43 , R b43 and R e43 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a43 and R b43 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0034】 R c43 and R f43 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R G It is replaced with C 1-4 Alkyl, C2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R d43 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups, 3- to 8-membered aliphatic heterocyclic groups. L 2 Each of these is independently selected from -CH2-, -NH-, -O-, and -S-, where each L 2 R is independently 0, 1, or 2 5 Substituted by; within the limits of the valence, two adjacent L 2 p L molecules are linked to each other by single, double, or triple bonds. 2 However, it forms a linking group that connects ring A and ring B; L at both ends 2 It is bonded to ring A and ring B by single bonds, respectively. 【0035】 R 5 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a5 , -C(=O)OR a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 , -OR a5 -OC(=O)R a5 , -OC(=O)OR c5 -OC(=O)NR a5 R b5 -OP(=O)(R G1 )2, -SR a5 -S(=O)R c5-S(=O)2R c5 , sulfonic acid group, -S(=O)NR a5 R b5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR a5 C(=O)OR c5 , -NR e5 C(=O)NR a5 R b5 , -NR e5 C(=NR d5 )NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2, -P(=O)R c5 R f5 -P(=O)(R G1 )2 and =NR d5 ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) The same L 2 , or two adjacent L 2 Two R's that are joined together 5 The one or two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It is replaced with C 3-6 It forms an alicyclic hydrocarbon group or a 3-6 membered aliphatic heterocyclic group; or 4) Two non-adjacent L 2 Two R's are connected to each other. 5The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms an alicyclic hydrocarbon group or a 3-6 membered aliphatic heterocyclic group. 【0036】 R a5 , R b5 and R e5 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with [a specific compound]. R c5 and R f5 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c5 and R f5 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with [a specific compound]. 【0037】 R d5 The following can be selected: 1) Hydro, hydroxy, C 1-4 Alkoxy, cyano, nitro, and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups. R 52 The following can be selected: 1) Oxo group, halogen, cyano; 2)-C(=O)R G1 -C(=O)R G2 -C(=NRG3)N(R G2 )2, -OC(=O)R G2 -OP(=O)(R G1 )2, -S(=O)R G2 -S(=O)2R G2 , sulfonic acid group, -S(=O)N(R G2 )2, -S(=O)2N(R G2 )2, -S(=O)(=NRG3)R G2 , -N(R G2 )C(=O)R G1 , -N(R G2 )C(=O)R G2 , -N(R G2 )C(=NRG3)N(R G2 )2, -N(R G2 )S(=O)2R G2 , -N(R G2 )S(=O)2N(R G2 )2, -N(R G2 )P(=O)(R G1 )2, -P(=O)(R G2 )2, -P(=O)(R G1 )2, =NR G3 and R G1 ; 3) R G2 ; R G The following can be selected: 1) Halogen, oxo group, cyano, carboxy, hydroxy, C1-4 Alkoxy, amino, C 1-4 Alkylamino, C 1-4 Alkylsulfoxide group, C 1-4 Alkylsulfone group and C 1-4 Alkylaminosulfonyl; 2) C optionally substituted with 0, 1, 2, 3 or 4 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cyclrylalkyl and 3-8 member aliphatic heterocyclic group, and the substituents are independently oxo group, halogen, hydroxy, methylol, carboxy, cyano, C 1-3 Alkoxy, amino or C 1-3 Selected from the group consisting of alkylamino. R G1 is -OR G2 and -N(R G2 )2. 【0038】 R G2 is selected from the following: 1) Hydro; 2) C optionally substituted with 0, 1, 2 or 3 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 3-6 Cyclrylalkyl, 3-6 member aliphatic heterocyclic group and phenyl, and the substituents are independently oxo group, halogen, hydroxy, methylol, carboxy, cyano, C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylamino; 3) Two Rs bonded to the same nitrogen atom G2 form a 3-6 member aliphatic heterocyclic group together with the nitrogen atom, and the 3-6 member aliphatic heterocyclic group is optionally substituted with 0, 1, 2 or 3 substituents, and the substituents are independently oxo group, halogen, hydroxy, methylol, carboxy, cyano, C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylamino. 【0039】 R G3 These are hydro, cyano, nitro, -OR G2 -S(=O)2R G2 and R G2 Selected from. p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. m is 0, 1, 2, 3, 4, 5, or 6. n is 0, 1, 2, 3, 4, 5, or 6. 【0040】 One aspect of the present invention provides a pharmaceutical composition comprising the compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer or prodrug thereof, and a pharmaceutically acceptable carrier. 【0041】 One aspect of the present invention further provides the use of the compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer or prodrug thereof, or the pharmaceutical composition thereof, in the prevention or treatment of a protein kinase-mediated disease. 【0042】 One aspect of the present invention further provides the use of a compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer or prodrug thereof, or a pharmaceutical composition thereof, in the manufacture of a pharmaceutical for the prevention or treatment of a disease mediated by a protein kinase, wherein the disease includes one or more types of tumors. 【0043】 One aspect of the present invention further provides the use of a compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer or prodrug thereof, or a pharmaceutical composition thereof, in the treatment or improvement of a disease, wherein the disease includes one or more types of tumors. 【0044】 One aspect of the present invention further provides a method for inhibiting HPK1 kinase activity, comprising administering to an individual a compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer, or prodrug thereof. 【0045】 One aspect of the present invention provides a method for simultaneously inhibiting the activity of multiple protein kinases, further comprising administering to an individual a compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer, or prodrug thereof. The protein kinases include HPK1, FLT3, and KDR. 【0046】 One aspect of the present invention further provides a method for treating a patient's disease or illness, comprising administering to the patient a therapeutically effective amount of the compound of formula (I) of this application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer, or prodrug thereof. 【0047】 In one aspect of the present invention, the compound of formula (I) of this application has the effect of inhibiting the activity of multiple protein kinases. The protein kinases include HPK1, FLT3, and KDR. [Modes for carrying out the invention] 【0048】 Next, the present invention will be described more specifically by reference to examples. These examples will make the features and advantages of the present invention clearer and more obvious. 【0049】 Here, the term “exemplary” means “used as an example, embodiment, or description.” Embodiments described as “exemplary” are not intended to be superior to or better than other embodiments. Furthermore, the technical features of the different embodiments of this application described below can be combined with each other, insofar as they do not contradict each other. 【0050】 Definition and Explanation of Terms In the present invention, unless otherwise specified, the description or mention of a certain group, whether used alone or in combination with other terms, applies to all groups containing that group. For example, the description of an alkyl group applies to C 1-6 alkyl, C 1-3 alkyl, etc., and applies to C 1-6 The description or mention of an alkyl group applies to " 1-6 alkoxy", etc. The following definitions apply to the scope of the claims and the specification. 【0051】 Among them, when there are multiple substituents represented by the same symbol in the structure, the types of these substituents may be the same or different. For example, the group of the B ring contains 2 R 3 substituents. In this case, these two R 3 may both be methoxy, or one may be methoxy and the other may be methyl. 【0052】 The term "halogen atom or halogen" includes fluoro, chloro, bromide, and iodo. The term "C m-n " group (where m and n are integers) indicates a range including the endpoints, indicating that the corresponding group contains m - n carbon atoms. For example, C 1-6 alkyl indicates an alkyl containing 1 - 6 carbon atoms, and C 2-6 alkenyl indicates an alkenyl containing 2 - 6 carbon atoms. 【0053】 The term "n-member ring structure" (where n is an integer) generally represents the number of ring-constituting atoms in a certain part, and the number of ring-constituting atoms is n. "m - n-member" indicates a range including the endpoints, indicating that the corresponding ring structure contains m - n ring-constituting atoms. For example, piperidinyl is an example of a 6-member heterocyclic group, and pyrazolyl is an example of a 5-member heteroaromatic ring group. 【0054】 The term "substituted" refers to the formal substitution of hydrogen atoms by an atom or group of atoms as a "substituent" bonded to another group. Unless otherwise specified, "substituted" means any degree of substitution, as long as such substitution is permissible. The choice of substituent is independent, and substitution is possible at any chemically accessible position. As should be understood, substitution at a given atom is limited by its valence. As should be understood, substitution at a given atom produces a chemically stable molecule. A single divalent substituent (e.g., oxo) can substitute for two hydrogen atoms. 【0055】 The "remainder of the compound" refers to the complete molecular structure portion other than the "substituents." The residue of the compound is linked to the substituents by one or more unsaturated valencies. The residue of the compound may contain one or more "linking points," and two or more "linking points" may be located on the same atom or on different atoms. 【0056】 The term "alkyl" refers to a linear or branched saturated hydrocarbon group. Alkyl groups are the remaining atomic groups after removing one hydrogen atom from an alkane. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-propyl, isopropyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, and 1,2,2-trimethylpropyl. 【0057】 The term "alkenyl" refers to a linear or branched hydrocarbon group having one or more carbon-carbon double bonds. An alkenyl is the remaining atomic group after removing one hydrogen atom from an alkene. Examples of alkenyls include ethyleneyl, 1-propenyl, 2-propenyl, allyl, 1-butenyl, 2-butenyl, (E)-buto-2-en-1-yl, (Z)-buto-2-en-1-yl, 2-methyl-prop-1-en-1-yl, 1,3-butadien-1-yl, and 1,3-butadien-2-yl. 【0058】 The term "alkynyl" refers to a linear or branched hydrocarbon group having one or more carbon-carbon triple bonds. Alkynnyls are the remaining atomic group after removing one hydrogen atom from an alkyne. Examples of alkynyls include ethynyl, 1-propynyl, propargyl, 1-butynyl, buta-2-in-1-yl, buta-3-in-1-yl, buta-3-en-1-inyl, and 3-methylpen-2-en-4-in-1-yl. 【0059】 The term "alkylidene group" refers to a divalent group formed by simultaneously removing two hydrogen atoms from the same carbon atom of an alkane, where the two free valencies are either on the same atom or on two atoms. The two free valencies are either on the same atom in the remainder of the compound or on two atoms in the remainder of the compound. Examples include the methylene group (-CH2- or =CH2), 1,1-ethylidene (-CH(CH3)- or =CH-CH3), 1,2-ethylidene (-CH2CH2-), butane-1,4-diyl, butane-1,3-diyl, and 2,2-dimethylprop-1,3-diyl. 【0060】 The term "n-membered oxoalkylidene group" refers to a divalent group in which one or more carbon atoms in the main chain of an n-membered alkylidene group are substituted with oxygen atoms, and the two free valencies are located on the same atom in the remainder of the compound, or on two atoms in the remainder of the compound. For example, an example of a 3-membered oxoalkylidene group is 2-oxa-1,3-propylidene (-CH2OCH2-), and an example of a 4-membered oxoalkylidene group is 2-oxa-1,4-butylidene (-CH2OCH2CH2-). Alkylidene groups in which only the side-chain carbon atoms are substituted with oxygen atoms should not be considered "oxoalkylidene groups." For example, the group obtained by substituting the methyl side chain of 2-methyl-1,3-propylidene with oxygen (-CH2CH(OH)CH2-) should be considered as 1,3-propylidene substituted with 2-hydroxyl. 【0061】 The term "n-membered azaalkylidene group" refers to a divalent group in which one or more carbon atoms in the main chain of an n-membered alkylidene group are substituted with nitrogen atoms, and its two free valencies are located on the same atom in the remainder of the compound, or on two atoms in the remainder of the compound. For example, an example of a three-membered azidoalkylidene group is 2-aza-1,3-propylidene (-CH2NHCH2-), and an example of a two-membered azidoalkylidene group is aza-1,2-ethylidene (-CH2NH-). Alkylidene groups in which only the side-chain carbon atoms are substituted with nitrogen atoms should not be considered "azidoalkylidene groups." For example, the group obtained by substituting the methyl side chain of 2-methyl-1,3-propylidene with nitrogen (-CH2CH(NH2)CH2-) should be considered as 1,3-propylidene substituted with 2-amino. 【0062】 The term "alkoxy" refers to a group having the formula "-O-alkyl," where alkyl is defined as described above. Examples include methoxy, ethoxy, n-propyloxy, isopropoxy, n-butyloxy, tert-butyloxy, and n-hexyloxy. 【0063】 The term "alkylthio group" refers to a group having the formula "-S-alkyl," where alkyl is defined as described above. Examples include methylthio group, ethylthio group, n-propylthio group, isopropylthio group, n-butylthio group, tert-butylthio group, and n-hexylthio group. 【0064】 The term "alkylamino" includes groups of the formula "-NH-alkyl" and groups of the formula "-N(alkyl)2", where alkyl is defined as above. Examples of groups of the formula "-NH-alkyl" include methylamino, ethylamino, isopropylamino, and n-hexylamino, while examples of groups of the formula "-N(alkyl)2" include dimethylamino, diethylamino, methylethylamino, methylisopropylamino, and ethyl n-hexylamino. 【0065】 The term "alkyl sulfoxide group" refers to a group with the formula "-S(=O)-alkyl," where alkyl is defined as described above. Examples include methyl sulfoxide group, ethyl sulfoxide group, and isopropyl sulfoxide group. 【0066】 The term "alkyl sulfone group" refers to a group with the formula "-S(=O)2-alkyl," where alkyl is defined as described above. Examples include methyl sulfone group, ethyl sulfone group, and isopropyl sulfone group. 【0067】 The term "alkylaminosulfinyl" includes groups of the formula "-S(=O)-NH-alkyl" and groups of the formula "-S(=O)-N(alkyl)2", where alkyl is defined as above. Examples of groups of the formula "-S(=O)-NH-alkyl" include methylaminosulfinyl, ethylaminosulfinyl, isopropyl aminosulfinyl, and tert-butylaminosulfinyl. Examples of groups of the formula "-S(=O)-N(alkyl)2" include dimethylaminosulfinyl, diethylaminosulfinyl, methylethylaminosulfinyl, and ethylisobutylaminosulfinyl. 【0068】 The term "alkylaminosulfonyl" includes groups of the formula "-S(=O)2-NH-alkyl" and groups of the formula "-S(=O)2-N(alkyl)2", where alkyl is defined as above. Examples of groups of the formula "-S(=O)2-NH-alkyl" include methylaminosulfonyl, ethylaminosulfonyl, isopropyl aminosulfonyl, and tert-butylaminosulfonyl. Examples of groups of the formula "-S(=O)2-NH-alkyl" include dimethylaminosulfonyl, diethylaminosulfonyl, methylisopropyl aminosulfonyl, and ethyl tert-butylaminosulfonyl. 【0069】 The term "carbonyl" refers to the group of the formula -(C=O)-, which can also be written as -C(O)-. The term "cyano" refers to the base of the equation -C≡N, which can also be written as -CN. The term "methylol" refers to the group with the formula -CH2OH. 【0070】 The term "oxo" refers to an oxygen atom as a divalent substituent. When this oxygen atom is bonded to a carbon atom, it forms a carbonyl group, and when it is bonded to a heteroatom, it forms a sulfoxide, sulfone, or N-epoxide group, etc. In some examples, the cyclylalkyl and heterocyclic groups may be optionally substituted with one or two oxo atoms. 【0071】 The term "imidoyl" or the notation "=NR" refers to an amino group in the form of a divalent substituent, wherein the same nitrogen atom forms a double bond with one of the remaining atoms of the compound, which is arbitrarily selected, due to its two valencies, and the nitrogen atom is bonded to an R group as defined in the context, due to its third valency. When the nitrogen atom is bonded to a carbon atom, it forms imides, amidines, or guanidyls, and when it is bonded to a heteroatom, it forms sulfoxideimides, etc. 【0072】 The term "cyclic hydrocarbon group" includes monocyclic or polycyclic alicyclic hydrocarbon groups and aromatic hydrocarbon groups. A monocyclic alicyclic hydrocarbon group has one hydrocarbon ring and includes cyclized alkyl and alkenyl compounds. A polycyclic alicyclic hydrocarbon group has two or more hydrocarbon rings, of which at least one is an alicyclic hydrocarbon ring (including cyclized alkyl and alkenyl compounds), and the other rings may be alicyclic hydrocarbon rings and / or aromatic hydrocarbon rings; of which, one of the rings is bonded to at least one of the other rings by becoming a spiro ring (two rings sharing one ring-forming atom) or a bridging ring (two rings sharing two or more ring-forming atoms). Polycyclic hydrocarbon groups are linked to the remainder of the compound by the ring-forming carbon atoms of the hydrocarbon rings. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclylhexadienyl, bicyclo[3.1.0]pentyl, norbornyl group, norbornyl, bicyclo[1.1.1]propyl, 1H-inden-1-yl, and 2,3-dihydro-1H-inden-2-yl. When any of the rings in a cyclic hydrocarbon group are saturated, such a cyclic hydrocarbon group is a saturated cyclic hydrocarbon group and is also called a "cyclylalkyl". 【0073】 A "cyclic hydrocarbon alkylidene group" containing a cyclic hydrocarbon group is characterized in that the two valencies of the cyclic hydrocarbon group are bonded to two linkage points in the remainder of the compound, and these two valencies may be on the same carbon atom of the cyclic hydrocarbon alkylidene group or on two separate carbon atoms of the cyclic hydrocarbon alkylidene group; and these two linkage points may be on the same atom in the remainder of the compound or on two separate atoms in the remainder of the compound. Examples include 1,1-cyclobutylidene and 1,3-cyclobutylidene. The term "arylate" refers to a monocyclic or polycyclic aromatic hydrocarbon group. Examples include phenyl and naphthyl. 【0074】 The term "heterocyclic group" refers to a monocyclic or polycyclic group having at least one heteroatom selected from oxygen, nitrogen, sulfur, and phosphorus as a ring component. A polycyclic heterocyclic group comprises two or more ring structures, at least one of which has at least one heteroatom selected from oxygen, nitrogen, sulfur, and phosphorus as a ring component, while the other ring structure may or may not have heteroatoms as ring components; in this case, one of the rings is bonded to at least one other ring by becoming a spiroring (two rings sharing one ring component atom) or a bridging ring (two rings sharing two or more ring component atoms). The heterocyclic group may be linked to the remainder of the compound by an optionally selected ring component carbon atom, or is linked to the remainder of the compound by an optionally selected ring component heteroatom. In one embodiment, any of the ring component carbon atoms of the heterocyclic group may be substituted with an oxo atom to form a carbonyl group. In one embodiment, any of the ring component nitrogen atoms of the heterocyclic group may be an N-epoxide. In one embodiment, any of the ring-constituting nitrogen atoms of the heterocyclic group may be a quaternary ammonium ion. 【0075】 Aromatic heterocyclic groups (i.e., "heteroaryl") and "aliphatic heterocyclic groups" containing heterocyclic groups. "Heteroaryl" refers to a monocyclic or polycyclic aromatic heterocyclic group having at least one heteroatom selected from oxygen, nitrogen, and sulfur as a ring component. Within the range permitted by the valence of such carbon or heteroatom, the heteroaryl may be linked to the remainder of the compound by an optionally selected carbon atom, or be linked to the remainder of the compound by an optionally selected heteroatom. In one embodiment, any of the ring-constituting carbon atoms of the heteroaryl moiety may be substituted with an oxo to form a carbonyl group. In one embodiment, any of the ring-constituting nitrogen atoms of the heteroaryl moiety may be an N-epoxide. In one embodiment, any of the ring-constituting nitrogen atoms of the heteroaryl moiety may be a quaternary ammonium ion. Examples include pyrrolyl groups (including pyrrole-1-yl, pyrrole-2-yl, and pyrrole-3-yl), pyrazolyl, imidazolyl, oxazolylyl, isoxazoyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyridine-2(1H)-on-1-yl, pyridine-4(1H)-on-1-yl, pyrazinyl, pyrimidinyl, pyridadinyl, pyrazine-3(2H)-on-2-yl, 1,2,4-triazinyl, 1,3,5-triazinyl, indolyl, benzofuranyl, benzothiinyl, indazolyl, benzimidazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, naphthilidinyl, imidazo[1,2-b]thiazolyl, and prinyl. 【0076】 "Aliphatic heterocyclic groups" include monocyclic or polycyclic aliphatic heterocyclic groups. Monocyclic aliphatic heterocyclic groups do not necessarily contain ring-forming double bonds, or they may contain one or more ring-forming double bonds. Polycyclic aliphatic heterocyclic groups contain at least one alicyclic structure, and the other rings may be alicyclic or aromatic rings; in polycyclic aliphatic heterocyclic groups, none of the ring structures necessarily contain ring-forming double bonds, or they may contain one or more ring-forming double bonds. Examples include azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranil, 2-oxoxazolidinyl, piperidinyl, 3-oxopiperidinyl, piperazinyl, morpholinyl, azecycloheptyl, 2-oxa-6-azapyrro[3,3]heptyl, and 1,2,3,4-tetrahydroquinolinyl. 【0077】 The heterocyclic group includes a heterocyclic alkylene group, that is, the heterocyclic group is bonded by two valencies to two linkages in the remainder of the compound, the two valencies being on the same ring-constituting atom of the heterocyclic alkylene group or on two ring-constituting atoms of the heterocyclic alkylene group; the two linkages being on the same atom in the remainder of the compound or on two atoms in the remainder of the compound, respectively. Examples include 1,1-(3-oxacyclobutylidene) and 1,3-(2-azacyclopentylidene). 【0078】 The term "isomer" refers to an isomer that arises from a difference in the spatial arrangement of atoms within a molecule. In the context of the present invention, "stereoisomers" refer to all stereoisomers. For example, if an asymmetric carbon atom is present in such a compound, enantiomers and diastereomers are formed; if a carbon-carbon double bond, carbon-nitrogen double bond, or ring structure is present in such a compound, cis-trans isomers are formed. Unless otherwise specified, the compounds of the present invention include all isomers, such as optically active isomers, geometric isomers, rotational isomers, tautomers, and stabilizable conformers; and may exist as mixtures of isomers or as isolated isomers. Methods for preparing optically active products from optically inert starting materials are known in the art, for example, by racemic separation or stereoisomerization. 【0079】 The separation of racemic mixtures of compounds can be carried out by any of the many methods known to the art. One method involves the stepwise recrystallization of chiral dividing acids of optically active salt-forming organic acids. Suitable dividing agents for stepwise recrystallization may be optically active acids, such as D-tartaric acid, L-tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, L-camphor sulfonic acid, etc. Other dividing agents suitable for fractional recrystallization include, for example, stereoisomerized α-methylbenzylamine, 2-phenylglycinol, cyclohexylethylamine, etc. 【0080】 The separation of a racemic mixture can be carried out, for example, by reacting it with a suitable optically active substance (e.g., a chiral alcohol or Mosher's acid chloride) to convert it to a diastereomer, separating the diastereomer, and converting it back to the corresponding single optical isomer (e.g., by hydrolysis). Alternatively, it can be carried out by eluting it with a column packed with an optically active resolution agent. The composition of a suitable column and elution solvent can be determined by those skilled in the art. 【0081】 The term "isotope-labeled compound" refers to a compound of the present invention in which one or more of the constituent atoms are replaced with atoms of a specific isotope. For example, the isotopes in the compound of the present invention include various isotopes of elements such as H, C, N, O, F, P, S, Cl, and I, for example. 2 H, 3 H, 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 30 P, 32 P, 35 S, 36 S, 123 I, 124 I and 125Examples include I. The present invention includes various compounds labeled with isotopes as defined. For example, among them are radioactive isotopes ( 3 H and 14 Compounds containing (such as C), or containing non-radioactive isotopes ( 2 H and 13 These are compounds containing isotopes (such as C). Such isotope-labeled compounds are used in metabolic studies. 14 Using C); reaction kinetics research (for example, 2 H or 3 It uses H; includes detection or imaging techniques such as positron emission tomography (PET) or single-photon emission tomography (SPECT), and analysis of the tissue distribution of drugs or substrates; and is suitable for radiation therapy of patients. 【0082】 in particular, 18 Compound F is particularly suitable for PET or SPECT studies. Isotope-labeled compounds of formula (I) can generally be prepared by means of common techniques known to those skilled in the art, or by methods similar to those described in the attached embodiments and preparations, using appropriate isotope-labeled reagents instead of conventionally used unlabeled reagents. Also, heavier isotopes, especially deuterium ( 2 Substitution with H or D is preferable in some cases because it provides therapeutic benefits resulting from greater metabolic stability, such as an increased in vivo half-life, reduced dosage needs, or improved therapeutic indicators. 【0083】 The term "pharmaceutically acceptable" means, within the bounds of sound medical judgment, that the compound, material, composition and / or dosage form is suitable for use in contact with human and animal tissues and is free from excessive toxicity, irritation, allergic reactions or other problems or complications, and that the benefit / risk ratio is reasonable. 【0084】 A "pharmaceutically acceptable salt" refers to a salt that retains the biological potency and properties of the compound of the present invention and does not typically exhibit any undesirable biological or otherwise harmful effects. In many cases, the compounds of the present invention can form acid addition salts and / or alkali addition salts in the presence of amino and / or carboxyl or similar groups. 【0085】 Pharmaceutically usable acid addition salts can be formed from inorganic and organic acids. Inorganic acids include, for example (but not limited to), hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids include, for example (but not limited to), acetic acid, propionic acid, glycolic acid, oxalic acid, malonic acid, butanediic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methylsulfinic acid, ethylsulfinic acid, benzenesulfinic acid, p-toluenesulfonic acid, ethanedisulfonic acid, sulfosalicylic acid, aspartic acid, and glutamic acid. 【0086】 Pharmaceutically usable alkali addition salts can be formed from inorganic and organic bases. Inorganic bases include, but are not limited to, basic compounds of sodium, potassium, ammonia, calcium, magnesium, iron, silver, zinc, and copper; among these, suitable salts include ammonia salts, potassium salts, sodium salts, calcium salts, and magnesium salts. Organic bases include primary amines, secondary and tertiary amines, substituted amines (including naturally occurring substituted amines), cyclic amines, and alkali ion exchange resins; for example (but are not limited to), isopropylamine, benzylamine, choline, diethanolamine, diethylamine, dicyclohexylamine, lysine, arginine, meglumine, piperazine, and aminobutanetriol. 【0087】 All compounds and their pharmaceutically acceptable salts may be found together with other substances (including, for example, water and other solvents, or as hydrates and solvates) or isolated. The compounds and salts described in this application may exist in various forms, including hydrates and solvates, when in a solid state. The hydrates and solvates of the compounds and salts described in this application include hydrates and solvates in which the water and solvent may be replaced with isotopes, such as D2O, methanol-d3, methanol-d4, acetone-d6, and DMSO-d6. The presence of hydrates and solvates can be identified by means such as nuclear magnetic resonance (NMR) by those skilled in the art. 【0088】 The term "crystalline polymorphism" refers to the compounds of the present invention that exist in different crystalline lattice forms or in an amorphous form. The crystalline polymorphisms of the compounds of the present invention and their salts include mixtures of various crystalline lattice forms, as well as mixtures of one or more crystalline lattice forms and amorphous forms. The presence of crystalline polymorphism can be identified by means such as X-ray diffraction by those skilled in the art. Unless otherwise explicitly stated, compounds and their salts as used herein are understood to include all solid forms of the compounds. The term "active metabolite" refers to an active derivative of a compound that is formed when the compound is metabolized. 【0089】 A "pharmaceutically acceptable prodrug" means any pharmaceutically acceptable ester, ester salt, amide, or other derivative of the compound of the present invention that, when administered to a receptor, can directly or indirectly deliver the compound of the present invention or its pharmaceutically active metabolites or residues. Particularly preferred derivatives or prodrugs, when administered to a patient, can enhance the bioavailability of the compound of the present application (for example, by making orally administered compounds more readily absorbed into the bloodstream) or facilitate the delivery of the parent compound to a biological organ or site of action. 【0090】 The term "pharmaceutical composition" refers to any biologically active compound mixed with at least one pharmaceutically acceptable chemical component or reagent, the pharmaceutically acceptable chemical component or reagent being a "carrier" that contributes to the introduction of the compound into cells or tissues, and such carriers include, but are not limited to, stabilizers, diluents, suspensions, thickeners and / or excipients. Pharmaceutical compositions include, but are not limited to, the following forms: tablets, pills, powders, lozenges, small drug pouches, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (solid or dissolved in liquid solvents), ointments, soft and hard gelatin capsules, suppositories, transdermal patches, sterile injections and sterile packaged powders, etc. 【0091】 The term “pharmaceutically acceptable carrier” includes any or all solvents, dispersions, coatings, surfactants, antioxidants, preservatives (e.g., antimicrobials, antifungals), isotonic agents, absorption retarders, salts, antiseptics, drug stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavorings, dyes, and combinations thereof, as known to those skilled in the art. This includes use in therapeutic and pharmaceutical compositions of any ordinary carrier, provided it is not incompatible with the active ingredient. 【0092】 The term “administer” or “give” refers to the route by which the compound and its pharmaceutical composition are introduced to a subject in order to achieve the intended role. The route of administration is determined by whether the treatment is local or systemic and by the site of treatment. Examples of possible routes of administration include injection (including subcutaneous, intravenous, intra-arterial, extra-enterogastrointestinal, intraperitoneal, subarachnoid and other local injections), topical (including transdermal, epidermal, ocular and mucous membrane delivery, and intranasal, vaginal and rectal delivery), oral, inhalation or inhalation (intra-airway or intranasal, e.g., inhalation or inhalation of powders or aerosols, including by atomizers), and injectable administration may be done in single pushes or by infusion (e.g.) using a continuous infusion pump. 【0093】 "Therapeutic dose" refers to the amount of the compound of the present invention that induces a biological or medical response in an individual, such response as reduction of enzyme or protein activity, improvement of symptoms, remission of symptoms, delay or slowing of disease progression, or prevention of disease. 【0094】 "Individual" or "patient" refers to mammals and non-mammals that are individuals suffering from a disease, illness, or illness. Examples of mammals include, but are not limited to, all members of the mammalian species: humans; non-human primates (e.g., chimpanzees, other apes and monkeys); livestock, e.g., cattle, horses, sheep, goats, and pigs; other domestic animals, e.g., rabbits, dogs and cats; and laboratory animals, including rodents such as rats, mice and guinea pigs. Examples of non-mammals include, but are not limited to, birds and fish. 【0095】 compound On the other hand, this application provides a azindazole macrocyclic compound having the structure of formula I, or its isomers, pharmaceutically acceptable salts, crystalline polymorphs, isotope-labeled compounds, active metabolites, or prodrugs. [ka] The structure and atomic numbering of the azindazole ring are shown in formula (Ia): [ka] ; In the structure of equation I, X is CR x Or selected from N, where R x Each of these is independently selected from H or halogen; R 1 The following can be selected: 1) Hydro, halogen, cyano, -C(=O)OR a1 -C(=O)NR a1 R b1 , -OR a1 , -NR a1 R b1 , -NR e1 C(=O)R a1 , -NRe1 C(=O)NR a1 R b1 、 -SR a1 、 -S(=O)R a1 and S(=O)2R a1 ; or 2) optionally 0, 1, 2, 3 or 4 R 11 substituted, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkylalkyl and 3 - 8 member aliphatic heterocyclic group. Here, R a1 、R b1 and R e1 are each independently selected from: 1) hydro; or 2) optionally 0, 1, 2, 3 or 4 R 11 substituted, C 1-6 alkyl, C 3-6 monocyclic cycloalkylalkyl and 3 - 6 member monocyclic aliphatic heterocyclic group; or, R a1 and R b1 bonded to the same nitrogen atom, together with the nitrogen atom to which they are bonded, form a 4 - 6 member aliphatic heterocyclic group optionally substituted with 0, 1, 2, 3 or 4 R 11 ; Among them, R 11 is selected from the group consisting of an oxo group, halogen, hydroxy, amino, cyano, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylamino, C 3-6 cycloalkylalkyl and C 3-6 cycloalkoxy group. 【0096】 L 1 is selected from: 1) a single bond; or 2) A 6-10 membered aryl group or a 5-10 membered heteroaryl group, wherein the aryl group or heteroaryl group is bonded by a single bond to the 3-position and A ring of the azindazole ring, respectively; in addition to being bonded to the 3-position and A ring of the azindazole ring, the aryl group or heteroaryl group may have 0, 1, 2, 3, 4, 5, or 6 R members. 4 It is replaced by; Ring A is selected from a 3-12 membered cyclic hydrocarbon group or a 3-12 membered heterocyclic group having a monocyclic or bicyclic ring, and is composed of two different atoms, L 1 and L 2 They are bonded to each other; also, ring A is L 1 and L 2 In addition to being coupled, there are arbitrarily m R 2 It has been replaced with. 【0097】 The B ring is selected from a 6-12 membered cyclic hydrocarbon group or a 5-12 membered heterocyclic group having a monocyclic or bicyclic ring, and is composed of two different atoms, L 2 And it is bound to the 5-position of the azaindazole ring, respectively. Here, 1) If the B ring is a monocyclic hydrocarbon group or a monocyclic heterocyclic group, L 2 The shortest distance between the atoms of the two B rings linked to the 5-position of the azindazole ring is 1, 2, or 3 chemical bonds; 2) If the B ring is a bicyclocyclic hydrocarbon group or a bicycloheterocyclic group, L 2 The shortest distance between the atoms of the two B rings linked to the 5-position of the azindazole ring is 1, 2, 3, 4, or 5 chemical bonds. Among them, ring B is L 2 In addition to being bonded to the 5-position of the azaindazole ring, n R 3 It is arbitrarily replaced. 【0098】 R 2 Each of these is independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a2 , -C(=O)OR a2 -C(=O)NRa2 R b2 -C(=NR d2 )NR a2 R b2 , -OR a2 -OC(=O)R a2 , -OC(=O)OR c2 -OC(=O)NR a2 R b2 , -SR a2 -S(=O)R c2 -S(=O)2R c2 , sulfonic acid group, -S(=O)NR a2 R b2 -S(=O)2NR a2 R b2 -S(=O)(=NR d2 )R c2 , -NR a2 R b2 , -NR a2 C(=O)R b2 , -NR a2 C(=O)OR c2 , -NR e2 C(=O)NR a2 R b2 , -NR e2 C(=NR d2 )NR a2 R b2 , -NR a2 S(=O)2R c2 , -NR e2 S(=O)2NR a2 R b2 , Nitro, -PR c2 R f2 ,-P(=O)R c2 R f2 and phosphonic acid group; or 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 22 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-10 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; 3) Any 0, 1, 2, 3, 4, 5, or 6 R 22 A divalent bridge C is substituted and linked to two different ring-forming atoms of the A ring.1-5 alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group; Alternatively, two R atoms bonded to one or two ring-forming atoms of the A ring, respectively. 2 Along with the one or two ring-forming atoms, optionally 0, 1, 2, 3, 4, or 5 R 22 C is replaced by 5-12 It forms an alicyclic hydrocarbon group or a 5-12 membered aliphatic heterocyclic group. 【0099】 Here, R a2 , R b2 and R e2 Each of these is independently selected from the following: 1) Hydro; or 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 22 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a2 and R b2 Along with the nitrogen atom, there are 0, 1, 2, 3, 4 or 5 R 22 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0100】 R c2 and R f2 Each of these independently has any number of R values: 0, 1, 2, 3, 4, or 5. 22 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Selected from the group consisting of cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; or R bonded to the same phosphorus atom c2 and R f2 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 22It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0101】 R d2 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 22 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. R 22 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a22 , -C(=O)OR a22 -C(=O)NR a22 R b22 -C(=NR d22 )NR a22 R b22 , -OR a22 -OC(=O)R a22 , -OC(=O)OR c22 -OC(=O)NR a22 R b22 , -SR a22 -S(=O)R c22 -S(=O)2R c22 , sulfonic acid group, -S(=O)NR a22 R b22 -S(=O)2NR a22 R b22 -S(=O)(=NR d22 )R c22 , -NR a22 R b22 , -NR a22 C(=O)R b22 , -NR a22 C(=O)OR c22 , -NR e22 C(=O)NR a22 R b22 , -NR e22 C(=NR d22 )NR a22 Rb22 , -NR a22 S(=O)2R c22 , -NR e22 S(=O)2NR a22 R b22 , Nitro, -PR c22 R f22 ,-P(=O)R c22 R f22 , phosphonic acid group and =NR d22 ; or 2) 0, 1, 2, 3, 4 or 5 R 23 C is arbitrarily replaced by 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; R a22 , R b22 and R e22 Each of these is independently selected from the following: 1) Hydro; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a22 and R b22 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 23 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0102】 R c22 and R f22 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C3-10 Cyclylalkyl and 3-10 membered aliphatic heterocyclic groups; or R bonded to the same phosphorus atom c22 and R f22 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 23 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with; R d22 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Choose any 0, 1, 2, 3, 4 or 5 R 23 C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R 23 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a23 , -C(=O)OR a23 -C(=O)NR a23 R b23 -C(=NR d23 )NR a23 R b23 , -OR a23 -OC(=O)R a23 , -OC(=O)OR c23 -OC(=O)NR a23 R b23 , -SR a23 -S(=O)R c23 -S(=O)2R c23 , sulfonic acid group, -S(=O)NR a23 R b23 -S(=O)2NR a23 R b23 -S(=O)(=NR d23 )R c23 , -NR a23 R b23 , -NR a23 C(=O)R b23 , -NR a23 C(=O)OR c23 , -NRe23 C(=O)NR a23 R b23 , -NR e23 C(=NR d23 )NR a23 R b23 , -NR a23 S(=O)2R c23 , -NR e23 S(=O)2NR a23 R b23 , Nitro, -PR c23 R f23 ,-P(=O)R c23 R f23 , phosphonic acid group and =NR d23 ; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a23 , R b23 and R e23 Each of these is independently selected from the following: 1) Hydro; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a23 and R b23 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0103】 R c23 and R f23 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R GIt is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c23 and R f23 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0104】 R d23 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; or 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups, 3- to 8-membered aliphatic heterocyclic groups. R 3 Each of these is independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a3 , -C(=O)OR a3 -C(=O)NR a3 R b3 , -C(=N Rd3 )NR a3 R b3 , -OR a3 -OC(=O)R a3 , -OC(=O)OR c3 -OC(=O)NR a3 R b3 , -SR a3 -S(=O)R c3 -S(=O)2R c3 , sulfonic acid group, -S(=O)NR a3 R b3 -S(=O)2NR a3 R b3 -S(=O)(=N Rd3)R c3 , -NR a3 R b3 , -NR a3 C(=O)R b3 , -NR a3 C(=O)OR c3 , -NR e3 C(=O)NR a3 R b3 , -NR e3 C(=N Rd3 )NR a3 R b3 , -NR a3 S(=O)2R c3 , -NR e3 S(=O)2NR a3 R b3 , Nitro, -PR c3 R f3 ,-P(=O)R c3 R f3 and phosphonic acid group; or 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 32 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 6-10 membered aryl group, 5-10 membered heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; 3) Divalent bridge C linked to two different ring-constituting atoms of ring B 1-6 Alkylidene group. Alternatively, two R atoms bonded to one or two ring-forming atoms of the B ring, respectively. 3 The substituents, along with the one or two ring constituent atoms, may optionally consist of 0, 1, 2, 3, 4, or 5 R atoms. 32 C is replaced by 5-12 It forms an alicyclic hydrocarbon group or a 5-12 membered aliphatic heterocyclic group. 【0105】 Here, R a3 , R b3 and R e3 Each of these is independently selected from the following: 1) Hydro; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 32 It is replaced with C1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a3 and R b3 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 32 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0106】 R c3 and R f3 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. Alternatively, R bonded to the same phosphorus atom c3 and R f3 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 32 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0107】 R d3 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; R 32 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a32, -C(=O)OR a32 -C(=O)NR a32 R b32 , -C(=N Rd32 )NR a32 R b32 , -OR a32 -OC(=O)R a32 , -OC(=O)OR c32 -OC(=O)NR a32 R b32 , -SR a32 -S(=O)R c32 -S(=O)2R c32 , sulfonic acid group, -S(=O)NR a32 R b32 -S(=O)2NR a32 R b32 -S(=O)(=N Rd32 )R c32 , -NR a32 R b32 , -NR a32 C(=O)R b32 , -NR a32 C(=O)OR c32 , -NR e32 C(=O)NR a32 R b32 , -NR e32 C(=N Rd32 )NR a32 R b32 , -NR a32 S(=O)2R c32 , -NR e32 S(=O)2NR a32 R b32 , Nitro, -PR c32 R f32 ,-P(=O)R c32 R f32 , phosphonic acid group and =NR d32 ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. Ra32 , R b32 and R e32 Each of these is independently selected from the following: 1) Hydro; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a32 and R b32 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 33 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0108】 R c32 and R f32 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c32 and R f32 Along with the phosphorus atom, optionally 0, 1, 2, 3, 4, or 5 R 33 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0109】 R d32 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 33 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R 33 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a33 , -C(=O)OR a33 -C(=O)NR a33 R b33 , -C(=N Rd33 )NR a33 R b33 , -OR a33 -OC(=O)R a33 , -OC(=O)OR c33 -OC(=O)NR a33 R b33 , -SR a33 -S(=O)R c33 -S(=O)2R c33 , sulfonic acid group, -S(=O)NR a33 R b33 -S(=O)2NR a33 R b33 -S(=O)(=N Rd33 )R c33 , -NR a33 R b33 , -NR a33 C(=O)R b33 , -NR a33 C(=O)OR c33 , -NR e33 C(=O)NR a33 R b33 , -NR e33 C(=N Rd33 )NR a33 R b33 , -NR a33 S(=O)2R c33 , -NR e33 S(=O)2NR a33 R b33 , Nitro, -PR c33 R f33 ,-P(=O)R c33 R f33 , phosphonic acid group and =NR d33 ; 2) Arbitrarily R GSubstituted with 0, 1, 2, 3, or 4 substituents independently selected from C 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a33 , R b33 and R e33 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a33 and R b33 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0110】 R c33 and R f33 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R G It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c33 and R f33 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0111】 R d33The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R 4 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a4 , -C(=O)OR a4 -C(=O)NR a4 R b4 -C(=NR d4 )NR a4 R b4 , -OR a4 -OC(=O)R a4 , -OC(=O)OR c4 -OC(=O)NR a4 R b4 , -SR a4 -S(=O)R c4 -S(=O)2R c4 -S(=O)NR a4 R b4 -S(=O)2NR a4 R b4 -S(=O)(=NR d4 )R c4 , -NR a4 R b4 , -NR a4 C(=O)R b4 , -NR a4 C(=O)OR c4 , -NR e4 C(=O)NR a4 R b4 , -NR e4 C(=NR d4 )NR a4 R b4 , -NR a4 S(=O)2R c4 and -NR e4 S(=O)2NR a4 Rb4 ; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 42 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-10 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Or, L 1 Two R atoms bonded to each of the two ring-forming atoms of the ring. 4 is the aforementioned L 1 Along with the two ring-forming atoms of the ring, there are arbitrarily 0, 1, 2, 3, 4, 5, or 6 R atoms. 42 It is replaced with C 5-12 It forms an alicyclic hydrocarbon group or a 5-12 membered aliphatic heterocyclic group. 【0112】 R a4 , R b4 and R e4 Each of these is independently selected from the following: 1) Hydro; 2) Arbitrarily 0, 1, 2, 3, 4, 5, or 6 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a4 and R b4 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 42 It forms a 3- to 12-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0113】 R c4 and R f4 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups. R d4 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-12 Cyclylalkyl groups and 3-12 membered aliphatic heterocyclic groups; R 42 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a42 , -C(=O)OR a42 -C(=O)NR a42 R b42 -C(=NR d42 )NR a42 R b42 , -OR a42 -OC(=O)R a42 , -OC(=O)OR c42 -OC(=O)NR a42 R b42 , -SR a42 -S(=O)R c42 -S(=O)2R c42 -S(=O)NR a42 R b42 -S(=O)2NR a42 R b42 -S(=O)(=NR d42 )R c42 , -NR a42 R b42 , -NR a42 C(=O)R b42 , -NR a42 C(=O)OR c42 , -NR e42 C(=O)NR a42 R b42 , -NR e42 C(=NR d42 )NR a42 Rb42 , -NR a42 S(=O)2R c42 , -NR e42 S(=O)2NR a42 R b42 and =NR d42 ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-6 Alkyl, C 1-6 Alkylidene group, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R a42 , R b42 and R e42 Each of these is independently selected from the following: 1) Hydro; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a42 and R b42 Along with the nitrogen atom, optionally 0, 1, 2, 3, 4, or 5 R 43 It forms a 3- to 10-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0114】 R c42 and R f42 Each is independently selected from the following: any 0, 1, 2, 3, 4, or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R d42 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Choose any 0, 1, 2, 3, 4 or 5 R 43 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-10 Cyclylalkyl groups and 3-10 membered aliphatic heterocyclic groups. R 43 The following can be selected: 1) Oxo group, halogen, cyano, -C(=O)R a43 , -C(=O)OR a43 -C(=O)NR a43 R b43 -C(=NR d43 )NR a43 R b43 , -OR a43 -OC(=O)R a43 , -OC(=O)OR c43 -OC(=O)NR a43 R b43 , -SR a43 -S(=O)R c43 -S(=O)2R c43 -S(=O)NR a43 R b43 -S(=O)2NR a43 R b43 -S(=O)(=NR d43 )R c43 , -NR a43 R b43 , -NR a43 C(=O)R b43 , -NR a43 C(=O)OR c43 , -NR e43 C(=O)NR a43 R b43 , -NR e43 C(=NR d43 )NR a43 R b43 , -NR a43 S(=O)2R c43 , -NR e43 S(=O)2NR a43 R b43 and =NRd43 ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R a43 , R b43 and R e43 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a43 and R b43 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 3- to 8-membered aliphatic heterocyclic group that is substituted with [a specific component]. 【0115】 R c43 and R f43 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R G It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. R d43 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 G C is replaced by 1-4 Alkyl, C2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-8 Cyclylalkyl groups, 3- to 8-membered aliphatic heterocyclic groups. L 2 Each of these is independently selected from -CH2-, -NH-, -O-, and -S-, where each L 2 R is independently 0, 1, or 2 5 Substituted by; within the limits of the valence, two adjacent L 2 p L molecules are linked to each other by single, double, or triple bonds. 2 However, it forms a linking group that connects ring A and ring B; L at both ends 2 It is bonded to ring A and ring B by single bonds, respectively. 【0116】 R 5 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a5 , -C(=O)OR a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 , -OR a5 -OC(=O)R a5 , -OC(=O)OR c5 -OC(=O)NR a5 R b5 -OP(=O)(R G1 )2, -SR a5 -S(=O)R c5 -S(=O)2R c5 , sulfonic acid group, -S(=O)NR a5 R b5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR a5 C(=O)OR c5 , -NRe5 C(=O)NR a5 R b5 , -NR e5 C(=NR d5 )NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2, -P(=O)R c5 R f5 -P(=O)(R G1 )2 and =NR d5 ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) The same L 2 , or two adjacent L 2 Two R's that are joined together 5 The one or two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It is replaced with C 3-6 It forms an alicyclic hydrocarbon group or a 3-6 membered aliphatic heterocyclic group; or 4) Two non-adjacent L 2 Two R's are connected to each other. 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms an alicyclic hydrocarbon group or a 3-6 membered aliphatic heterocyclic group. 【0117】 R a5 , R b5 and R e5Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with [a specific compound]. 【0118】 R c5 and R f5 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same phosphorus atom c5 and R f5 Along with the phosphorus atom, optionally 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with [a specific compound]. 【0119】 R d5 The following can be selected: 1) Hydro, hydroxy, C 1-4 Alkoxy, cyano, nitro, and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups. R 52 The following can be selected: 1) Oxo group, halogen, cyano; 2)-C(=O)R G1 -C(=O)R G2 -C(=NRG3)N(R G2 )2, -OC(=O)R G2 -OP(=O)(R G1 )2, -S(=O)R G2 -S(=O)2R G2 , sulfonic acid group, -S(=O)N(R G2 )2, -S(=O)2N(R G2 )2, -S(=O)(=NRG3)R G2 , -N(R G2 )C(=O)R G1 , -N(R G2 )C(=O)R G2 , -N(R G2 )C(=NRG3)N(R G2 )2, -N(R G2 )S(=O)2R G2 , -N(R G2 )S(=O)2N(R G2 )2, -N(R G2 )P(=O)(R G1 )2, -P(=O)(R G2 )2, -P(=O)(R G1 )2, =NR G3 and R G1 ; 3) R G2 ; R G The following can be selected: 1) Halogen, oxo group, cyano, carboxy, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkylamino, C 1-4 Alkyl sulfoxide group, C 1-4 Alkyl sulfone group and C 1-4 Alkylaminosulfonyl; 2) C which is optionally substituted with 0, 1, 2, 3 or 4 substituents. 1-4 Alkyl, C 1-4 Alkylidene group, C2-4 Alkenil, C 2-4 Alkinyl, C 3-6 The substituents are cycloalkyl groups and 3- to 8-membered aliphatic heterocyclic groups, and the substituents are independently oxo, halogen, hydroxy, methylol, carboxy, cyano, and C 1-3 Alkoxy, amino, or C 1-3 Selected from the group consisting of alkylaminos. R G1 is -OR G2 and -N(R G2 ) Selected from 2. 【0120】 R G2 The following can be selected: 1) Hydro; 2) C which is optionally substituted with 0, 1, 2, or 3 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 3-6 The substituents are a cyclylalkyl group, a 3-6 membered aliphatic heterocyclic group, and a phenyl group, and the substituents are independently an oxo group, halogen, hydroxyl, methylol, carboxyl, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos; 3) Two R atoms bonded to the same nitrogen atom G2 The nitrogen atom forms a 3-6 membered aliphatic heterocyclic group with the nitrogen atom, and the 3-6 membered aliphatic heterocyclic group is optionally substituted with 0, 1, 2, or 3 substituents, and the substituents are independently oxo, halogen, hydroxy, methylol, carboxy, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos. 【0121】 R G3 These are hydro, cyano, nitro, -OR G2 -S(=O)2R G2 and R G2 Selected from. p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. m is 0, 1, 2, 3, 4, 5, or 6. n is 0, 1, 2, 3, 4, 5, or 6. In one embodiment, X is selected from CH or N. In one embodiment, X is selected from CH. In one embodiment, X is selected from CF. In one embodiment, X is selected from N. 【0122】 In one embodiment, R 1 The following can be selected: 1) Hydro, halogen atom, cyano, -C(=O)NR a1 R b1 , -OR a1 and NR a1 R b1 ; 2) Any number of R values: 0, 1, 2, 3, or 4 11 It is replaced with C 1-6 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-8 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups. In one embodiment, R 1 The following can be selected: 1) Hydro, halogen atoms, cyano, acetylene yl and OR a1 and NR a1 R b1 ; 2) Any number of R values: 0, 1, 2, 3, or 4 11 It is replaced with C 1-4 Alkyl groups, C3-5 monocyclic cyclylalkyl groups, and 4-5 membered monocyclic aliphatic heterocyclic groups. In one embodiment, R 1 Hydro, fluoro, cyano, C 1-4 Alkyl, C 3-4 Cyclylalkyl groups, 3-4 membered aliphatic heterocyclic groups, and OR a1 Selected from the group consisting of . 【0123】 In one embodiment, R 1The group is selected from the group consisting of hydro, fluoro, cyano, methyl, ethyl, 1-propyl, isopropyl, cyclopropyl, methoxy, ethoxy, cyclopropyloxy, and isopropoxy groups. In one embodiment, R 1 It is a hydro. 【0124】 In one embodiment, R a1 , R b1 and R e1 These are, independently, hydro and C. 1-3 Alkyl and C 3-4 Selected from the group consisting of cyclylalkyl groups; Alternatively, R bonded to the same nitrogen atom a1 and R b1 However, together with the nitrogen atom to which they are bonded, they form an unsubstituted 4-6 membered aliphatic heterocyclic group. In one embodiment, R a1 , R b1 and R e1 Each of these is independently selected from the group consisting of hydro, methyl, ethyl, and cyclopropyl. 【0125】 In one embodiment, R 11 The group is an oxo group, halogen, hydroxy, amino, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylamino, C 3-6 Cyclylalkyl and C 3-6 Selected from the group consisting of cycloalkoxy groups. In one embodiment, R 11 is a halogen atom, hydroxyl, cyano, C 1-3 Alkoxy, cyclopropyl oxy, C 1-3 Selected from the group consisting of alkyl and cyclopropyl. In one embodiment, R 11 The compound is selected from the group consisting of fluoro, hydroxy, cyano, methoxy, ethoxy, cyclopropyloxy, methyl, ethyl, and cyclopropyl. 【0126】 One embodiment, L 1 It is a single bond. One embodiment, L 1 The group is selected from the group consisting of a 6-10 membered aryl group or a 5-10 membered heteroaryl group, and the aryl group or heteroaryl group is simultaneously bonded to the 3-position and A ring of the azindazole ring; in addition to being bonded to the azindazole ring and the A ring, the aryl group or heteroaryl may optionally have 0, 1, 2, 3, 4, 5, or 6 R 4 It has been replaced with. One embodiment, L 1 The group is selected from the group consisting of phenyl, a 5-6 membered heteroaryl group, or a 9-10 membered bicycloheteraryl group, wherein the aryl group or heteroaryl group is simultaneously bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms; in addition to being bonded to the azindazole ring and the A ring, the aryl group or heteroaryl may optionally have 0, 1, 2, 3, 4, 5, or 6 R atoms. 4 It has been replaced with. One embodiment, L 1 The group is selected from the group consisting of phenyl or a 5-6 membered heteroaryl group, wherein the aryl group or heteroaryl group is simultaneously bonded to the 3-position and A ring of the azindazole ring; in addition to the aryl group or heteroaryl being bonded to the azindazole ring and the A ring, it may optionally have 0, 1, 2 or 3 R 4 It has been replaced with. 【0127】 One embodiment, L 1 The A ring is not a single bond, and the A ring is selected from a C3-12 cyclic hydrocarbon group or a 3-12 membered heterocyclic group having a single or biring ring, and the L ring is formed by two different ring constituent atoms. 1 and L 2 They are connected to each other: 1) The monocyclic or bicyclic structure does not contain an aromatic ring; 2) The monocyclic or bicyclic hydrocarbon group or heterocyclic group contains at least one aromatic ring. 【0128】 One embodiment, L 1 The A ring is not a single bond, and the A ring is selected from a C5-11 cyclic hydrocarbon group or a 5-11 membered heterocyclic group having a single or biring ring, and is composed of two different ring constituent atoms, L 1 and L 2 They are connected to each other: 1) The monocyclic or bicyclic structure does not contain an aromatic ring; 2) The monocyclic or bicyclic hydrocarbon group or heterocyclic group contains at least one aromatic ring. 【0129】 One embodiment, L 1 The A ring is not a single bond, and the A ring is selected from C5, C6, C7, C8, C9 cyclic hydrocarbon groups or 5-membered, 6-membered, 7-membered, 8-membered, 9-membered heterocyclic groups that have a single or double ring, and is composed of two different ring constituent atoms, L 1 and L 2 They are connected to each other: 1) The monocyclic or bicyclic structure does not contain an aromatic ring; 2) The monocyclic or bicyclic hydrocarbon group or heterocyclic group contains at least one aromatic ring. 【0130】 One embodiment, L 1 The A ring is not a single bond, and the A ring is selected from monocyclic or bicyclic alicyclic hydrocarbon groups of C5, C6, C7, C8, C9 or 5-membered, 6-membered, 7-membered, 8-membered, or 9-membered aliphatic heterocyclic groups, and is formed by two different ring constituent atoms, L 1 and L 2 Each of these is bonded to the other, and the monocyclic or bicyclic structure does not contain an aromatic ring. 【0131】 One embodiment, L 1 It is not a single bond, and the A ring is selected from a benzene ring or a 5-6 membered monocyclic heteroaryl ring, and also by two different ring constituent atoms, L 1 and L 2 They are each connected to the other. 【0132】 One embodiment, L 1 It is not a single bond, and ring A is C 6-11Selected from bicyclocyclic hydrocarbon groups or 6-11 membered bicycloheterocyclic groups, and also by two different ring constituent atoms, L 1 and L 2 Each of these is bonded to the other, and the bicyclic structure contains at least one aromatic ring. 【0133】 In one embodiment, the B ring is selected from phenyl, naphthyl, a 5-6 member monocyclic heteroaryl, or a 9-10 member bicycloheteraryl, and the L ring is composed of two different ring constituent atoms. 2 They are bonded to the 5-position of the azindazole ring, respectively: 1) When the B ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, the shortest distance between the two ring constituent atoms is 1, 2, or 3 chemical bonds; preferably, the shortest distance between the two ring constituent atoms is 1 or 2 chemical bonds; 2) When the B ring is selected from naphthyl or 9-10 membered bicycloheteroaryl, the shortest distance between the two ring constituent atoms is 1, 2, 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring constituent atoms is 1, 2, 3, or 4 chemical bonds. 【0134】 In one embodiment, the B ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, and the L ring is composed of two different ring constituent atoms. 2 The atoms are bonded to the 5-position of the azindazole ring, and the shortest distance between the two ring-constituting atoms is 1, 2, or 3 chemical bonds; preferably, the shortest distance between the two ring-constituting atoms is 1 or 2 chemical bonds. 【0135】 In one embodiment, the B ring is selected from naphthyl or 9-10 membered bicycloheteroaryl, and the L ring is composed of two different ring constituent atoms. 2 The atoms are bonded to the 5-position of the azindazole ring, and the shortest distance between the two ring-constituting atoms is 1, 2, 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-constituting atoms is 1, 2, 3, or 4 chemical bonds. 【0136】 In one embodiment, the B ring is selected from naphthyl or 9-10 membered bicycloheteroaryl, and the L ring is composed of two different ring constituent atoms. 2 They are bonded to the 5-position of the azaindazole ring, and here, L 1 and L 2 The ring-forming atoms linked together all belong to the same monocyclic arylate, and the shortest distance between the two ring-forming atoms is 1, 2, or 3 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 1 or 2 chemical bonds. 【0137】 In one embodiment, the B ring is selected from naphthyl or 9-10 membered bicycloheteroaryl, and the L ring is composed of two different ring constituent atoms. 2 They are bonded to the 5-position of the azaindazole ring, and here, L 1 and L 2 Each of the ring-forming atoms linked to the ring belongs to one of two monocyclic arylates, and the shortest distance between the two ring-forming atoms is 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 3 or 4 chemical bonds. 【0138】 In one embodiment, ring B is a fused ring C consisting of one monocyclic arylate and one monocyclic alicyclic group. 9-12 Selected from bicyclocyclic hydrocarbon groups or fused ring 8-12 membered bicycloheterocyclic groups, and also by two different ring constituent atoms, L 2 The monocyclic arylate is bonded to the 5-position of the azindazole ring, respectively; the monocyclic alicyclic group is selected from the group consisting of phenyl or a 5-6 membered heteroaryl group, and the monocyclic alicyclic group is C 5-7 Selected from a monocyclic hydrocarbon group or a 5-7 membered monocyclic heteroalicyclic group; where the ring constituent atom linked to the 5-position of the azindazole ring belongs to the monocyclic arylate, L 2 The ring-forming atoms linked thereto belong to the monocyclic alicyclic group, and the shortest distance between the two ring-forming atoms is 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 3 or 4 chemical bonds. 【0139】 In one embodiment, the B ring is selected from phenyl or pyridyl, and the L ring is composed of two different ring constituent atoms. 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and the two ring-constituting atoms constitute an ortho, meta, or para positional relationship; preferably, the two ring-constituting atoms are in an ortho or meta positional relationship. 【0140】 In one embodiment, the B ring is selected from phenyl or pyridyl, and the L ring is composed of two different ring constituent atoms. 2 They are bonded to the 5-position of the azindazole ring, and the two ring-constituting atoms are in an ortho-positional relationship. 【0141】 In one embodiment, the B ring is selected from phenyl, and by two different ring constituent atoms, L 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and the two ring-constituting atoms constitute an ortho, meta, or para positional relationship; preferably, the two ring-constituting atoms are in an ortho or meta positional relationship. 【0142】 In one embodiment, the B ring is selected from phenyl, and by two different ring constituent atoms, L 2 They are bonded to the 5-position of the azindazole ring, and the two ring-constituting atoms are in an ortho-positional relationship. 【0143】 One embodiment, L 1 It is a single bond; therefore, the compound of this application has the structural formula of formula II. [ka] Among these, ring A is selected from a 3-12 membered cyclic hydrocarbon group or a 3-12 membered heterocyclic group having a monocyclic or bicyclic ring, and two different atoms are used to form the 3-position and L of the azindazole ring. 2 They are bonded to each other, and here, ring A is bonded to the 3-position of the azindazole ring and L 2 In addition to being coupled, there are arbitrarily m R 2 It is replaced by; X, B ring, R2 , R 3 , L 2 The definitions of p, m, and n are as described above. 【0144】 In one embodiment, ring A has a monoring or biring C 6-12 Selected from cyclic hydrocarbon groups or 5-12 membered heterocyclic groups, and also, by two different ring constituent atoms, the 3-position and L of the azindazole ring. 2 Each of these is bonded to the other, and the monocycle directly linked to the 3-position of the azindazole ring is an aromatic ring, and among them, 1) If the A ring is phenyl or monocyclic heteroaryl, then the 3-position of the azindazole ring of the A ring and L 2 The shortest distance between the two atoms linked to each other is one, two, or three chemical bonds; preferably, the shortest distance between the two atoms is one or two chemical bonds; 2) If ring A is a bicyclocyclic hydrocarbon group or a bicycloheterocyclic group, then the 3-position of the azindazole ring of ring A and L 2 The shortest distance between the two atoms linked to each other is 1, 2, 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two atoms is 1, 2, 3, or 4 chemical bonds. 【0145】 In one embodiment, the B ring is selected from phenyl, naphthyl, 5-6 member monocyclic heteroaryl, or 9-10 member bicycloheteraryl, and is composed of two different ring constituent atoms. 2 They are bound to the 5-position of the azaindazole ring, respectively, and among them, 1) If the B ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, then the 5-position of the azindazole ring of the B ring and L 2 The shortest distance between the two ring-forming atoms linked to each other is one, two, or three chemical bonds; 2) If the B ring is selected from naphthyl or 9-10 membered bicycloheteroaryl, the 5-position of the azindazole ring of the B ring and L 2 The shortest distance between the two ring-forming atoms linked to each other is 1, 2, 3, 4, or 5 chemical bonds. 【0146】 In one embodiment, the B ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, and the L ring is composed of two different ring constituent atoms. 2 The atoms are bonded to the 5-position of the azindazole ring, and the shortest distance between the two ring-constituting atoms is 1, 2, or 3 chemical bonds. 【0147】 In one embodiment, R 2 These are independently selected from the following: 1) Halogen, cyano, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkanamine group or C 1-3 Alkyl sulfone group; 2) Any number of R values: 0, 1, 2, 3, or 4 22 It is replaced with C 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; 3) Any 0, 1, 2, 3, or 4 R 22 It is replaced with C 1-5 Alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group. R 22 These are independently selected from the following: 1) Oxo group, halogen, cyano, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkanamine group, C 1-3 Alkyl sulfone group or carboxyl group; 2) C which is optionally substituted with 0, 1, 2, 3 or 4 substituents. 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 The substituents are cycloalkyl groups and 3- to 8-membered aliphatic heterocyclic groups, and the substituents are independently oxo groups, halogens, hydroxyl groups, and hydroxyl groups. 1-3 Alkyl, C 1-3 Alkoxy-C 1-3Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Selected from the group consisting of alkyl groups; 3) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-5 The substituents are alkylidene group, 3-6 membered oxoalkylidene group, and 2-6 membered azaalkylidene group, and the substituents are independently oxo group, halogen, hydroxy, and hydroxy-C 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Selected from the group consisting of alkyl groups. 【0148】 In one embodiment, R 3 These are independently selected from the following: 1) Halogen, cyanoacrylate, -C(=O)NR a3 R b3 and OR a3 ; 2) Any number of R values: 0, 1, 2, 3, or 4 32 It is replaced with C 1-3 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Here, R a3 and R b3 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 32 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a3 and R b3Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 32 It forms a 4- to 6-membered aliphatic heterocyclic group that is substituted with [a specific compound]. R 32 These are independently selected from the following: 1) Oxo group, halogen, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamino; 2) C which is arbitrarily substituted with 0, 1, or 2 substituents 1-4 Alkyl, C 3-6 The substituents are cycloalkyl groups and 3-6 membered aliphatic heterocyclic groups, and the substituents are independently oxo, halogen, hydroxy, methylol, cyano, and C 1-3 Alkoxy, amino, or C 1-3 Selected from alkylaminos. 【0149】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, where each L 2 R is independently 0, 1, or 2 5 It is replaced by; two adjacent L 2 Each of them is connected to the others by a single bond, and there are p Ls linked to each other. 2 However, it forms a linking group that connects ring A and ring B; L 2 If it is -CH2-, then its substituent R 5 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 , -OR a5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NRa5 R b5 , -NR G2 P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) The same L 2 Two R's that are joined together 5 The substituent is L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,1-cyclopropyl, 1,1-cyclobutyl, 1,1-cyclopentyl, 1,1-cyclohexyl, 3,3-oxetanyl, 3,3-azetidinyl, 3,3-tetrahydrofuranyl, 3,3-tetrahydropyrrolyl, 3,3-tetrahydropyranyl group, 4,4-tetrahydropyranyl group, 3,3-piperidinyl and 4,4-piperidinyl; 4) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 A cyclic group is formed by substitution with, the cyclic group being selected from: 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclopentyl, 1,2-cyclohexyl, 3,4-tetrahydrofuranyl, 3,4-tetrahydropyrrolyl, 3,4-tetrahydropyranyl, and 3,4-piperidinyl; 5) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52A cyclic group is formed by substitution with the following, the cyclic group being selected from: 1,3-cyclobutyl, 1,3-cyclopentyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 2,5-tetrahydrofuranyl, 2,5-tetrahydropyrrolyl, 2,6-tetrahydropyranyl group, 3,5-tetrahydropyranyl group, 2,6-piperidinyl, 3,5-piperidinyl, 2,6-morpholinyl, 2,5-morpholinyl, 3,5-morpholinyl, 2,6-piperazinyl and 2,5-piperazinyl; L 2 If it is -NH-, then its substituent R 5 The following are selected independently: 1)-C(=O)R a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 and P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,2-azecyclopropyl, 1,2-azetidinyl, 1,2-tetrahydropyrrolyl, 1,2-piperidinyl, 3,4-morpholinyl, and 1,2-piperidinyl; 4) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,3-azetidinyl, 1,3-tetrahydropyrrolyl, 1,3-piperidinyl, 1,4-piperidinyl, and 1,4-piperazinyl; L 2 If R is -S-, 5 It is independently selected from the oxo group. 【0150】 Here, R a5 , R b5 and R e5 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-3 Alkyl, C 3-6 Cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydropyranyl group, and piperidinyl; Alternatively, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms morpholinil with 1-azetidinyl, 1-tetrahydropyrrolyl, 1-piperidinyl, and 1-piperazinyl, which are substituted with; R c5 These are independently of any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-3 Alkyl, C 3-6 Selected from the group consisting of cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranil, tetrahydropyrrolyl, tetrahydropyranil, and piperidinyl. 【0151】 R d5 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2-(C 1-3 Alkyl); 2) C 1-3Alkyl and cyclopropyl; R 52 The following are selected: oxo group, fluoro, cyano, hydroxy, C 1-3 Alkoxy, cyclopropyl oxy, C 1-3 Alkyl, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, amino and C 1-3 Alkylamino; R G1 is -OR G2 and -N(R G2 ) Selected from 2. 【0152】 R G2 The following can be selected: 1) Hydro; 2) C which is optionally substituted with 0, 1, 2, or 3 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 3-6 The substituents are a cyclylalkyl group, a 3-6 membered aliphatic heterocyclic group, and a phenyl group, and the substituents are independently an oxo group, halogen, hydroxyl, methylol, carboxyl, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos. 3) Two R atoms bonded to the same nitrogen atom G2 The nitrogen atom forms a 3-6 membered aliphatic heterocyclic group with the nitrogen atom, and the 3-6 membered aliphatic heterocyclic group is optionally substituted with 0, 1, 2, or 3 substituents, and the substituents are independently oxo, halogen, hydroxy, methylol, carboxy, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos. 【0153】 R G3 The following are selected: hydro, cyano, nitro, -OR G2 -S(=O)2R G2 and R G2 . One embodiment, L 1It is a single bond, and the compound has the structural formula of formula IIa, [ka] X is either CH or N; Ring A is selected from a benzene ring or a 5-6 membered aromatic heterocycle, and the 3-position and L of the azindazole ring are determined by two different ring constituent atoms. 2 They are bonded to each other; also, the A ring is bonded to the 3-position of the azindazole ring and L 2 In addition to being coupled, there are arbitrarily m R 2 It is replaced by; The B ring is composed of two different ring-forming atoms, L 2 It is bonded to the 5-position of the azaindazole ring, and the shortest distance between the two ring constituent atoms is 1, 2, or 3 chemical bonds, where Y 1 , Y 2 and Y 3 Each is independently selected from CR3 or N, and Y 1 , Y 2 and Y 3 In this case, N can be at most two; m is selected from 0, 1, 2, 3, or 4. n is selected from 0, 1, 2, or 3. R 2 , R 3 , L 2 The definition of p is as described above. 【0154】 In one embodiment, the compound has the structural formula of formula IIb, [ka] Here, X is either CH or N; A 2 Ring and A 3 The ring forms a fused ring system, where: A 2 The ring is selected from a benzene ring or a 5-6 membered aromatic heterocycle, and is bonded to the 3-position of the azindazole ring by one of the ring constituent atoms, A 3The ring is selected from a C5, C6, or C7 monocyclic hydrocarbon group or a 5-membered, 6-membered, or 7-membered monoheterocyclic group, and one of the ring constituent atoms is L 2 It is connected to; A 2 In addition to being bonded to the 3-position of the azaindazole ring, the ring also has an optional m1 R 2 It is replaced with A 3 The ring is L 2 In addition to being bound, there are unsubstituted or optionally m2 R 2 It is replaced by; The B ring is composed of two different ring-forming atoms, L 2 It is bonded to the 5-position of the azaindazole ring, and the shortest distance between the two ring constituent atoms is 1, 2, or 3 chemical bonds, where Y 1 , Y 2 and Y 3 Each is independently selected from CR3 or N, and Y 1 , Y 2 and Y 3 In this case, N can be at most two; m1 and m2 are integers between 0 and 4, and the sum of m1 and m2 is m, which can be selected from 0, 1, 2, 3, or 4. n is selected from 0, 1, 2, or 3. R 2 , R 3 , L 2 The definition of p is as described above. 【0155】 In one embodiment, the compound has the structural formula of formula IIc, [ka] Among them, ring A, R 2 , R 3 , L 2 The definitions of p, m, and n are as described above. 【0156】 In one embodiment, in the structural formulas of formulas IIa and IIc, ring A is selected from phenyl or a 5-6 membered monocyclic heteroaryl, and the 3-position and L of the azindazole ring are determined by two different ring constituent atoms. 2Each is bonded to the other, and the shortest distance between the two ring-forming atoms is one or two chemical bonds; preferably, two chemical bonds. 【0157】 In one embodiment, in the structural formulas of formulas IIa and IIc, ring A is selected from naphthyl or 9-10 membered bicycloheteroaryl, and is composed of two different ring constituent atoms, L 1 and L 2 Each is bonded to the other, and the shortest distance between the two ring-forming atoms is 1, 2, 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 1, 2, 3, or 4 chemical bonds. 【0158】 In one embodiment, in the structural formulas of formulas IIa and IIc, ring A is selected from naphthyl or 9-10 membered bicycloheteroaryl, and is composed of two different ring constituent atoms, L 1 and L 2 They are joined to each other, and here, L 1 and L 2 The ring-forming atoms linked together all belong to the same monocyclic arylate, and the shortest distance between the two ring-forming atoms is 1, 2, or 3 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 1 or 2 chemical bonds. 【0159】 In one embodiment, in the structural formulas of formulas IIa and IIc, ring A is a fused ring C consisting of one monocyclic arylate and one monocyclic alicyclic group. 9-12 Selected from bicyclocyclic hydrocarbon groups or fused ring 8-12 membered bicycloheterocyclic groups, and also by two different ring constituent atoms, L 1 and L 2 Each is bonded to; the monocyclic arylate is selected from the group consisting of phenyl or a 5-6 membered heteroaryl group, and the monocyclic alicyclic group is selected from a C5-7 monocyclic hydrocarbon group or a 5-7 membered monocyclic heteroalicyclic group; where L 1 and L 2The ring-forming atoms linked thereto both belong to the monocyclic arylate, and the shortest distance between the two ring-forming atoms is 1, 2, or 3 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 1 or 2 chemical bonds. 【0160】 In some embodiments, in the structural formulas of formulas IIa and IIc, the A ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, and the 3-position and L of the azindazole ring are determined by two different ring constituent atoms. 2 Each is bonded to the other, and the shortest distance between the two ring-forming atoms is one or two chemical bonds; preferably, two chemical bonds. Ring B is a benzene ring, Y 1 , Y 2 and Y 3 Each is independently selected from CR3; and the B ring is composed of two different ring-forming atoms, L 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and these two ring-constituting atoms form an ortho, meta, or para positional relationship. 【0161】 In some embodiments, in the structural formula of formula IIb, A 2 Ring and A 3 The fused ring system consisting of rings is selected from the group consisting of naphthyl or 9-10 membered bicycloheteroaryl, among which A 2 The ring is bonded to the 3-position of the azindazole ring by one ring-forming atom, A 3 The ring is formed by one of the ring-constituting atoms L 2 It is connected to; A 2 In addition to being bonded to the 3-position of the azaindazole ring, the ring may have an optional m1 independent R 2 Replaced with A 3 The ring is L 2 In addition to being bound, there are unsubstituted or optionally m2 independent R 2 Substituted by; the shortest distance between the two ring-forming atoms is 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 3 or 4 chemical bonds. 【0162】 In some embodiments, in the structural formula of formula IIb, A 2 The ring is selected from a benzene ring or a 5-6 membered aromatic heterocycle, and is bonded to the 3-position of the azindazole ring by one of the ring-forming atoms; A 3 The ring is selected from a C5, C6, or C7 monocyclic hydrocarbon group or a 5-membered, 6-membered, or 7-membered monoheterocyclic group, and one of the ring constituent atoms is L 2 Bonded to the two ring-forming atoms; the shortest distance between the two ring-forming atoms is 3, 4, or 5 chemical bonds; preferably, the shortest distance between the two ring-forming atoms is 3 or 4 chemical bonds. 【0163】 In some embodiments, in the structural formula of formula IIb, A 2 The ring is selected from a benzene ring or a 5-6 membered aromatic heterocycle, and is bonded to the 3-position of the azindazole ring by one of the ring-forming atoms; A 3 The ring is selected from a C5, C6, or C7 monocyclic hydrocarbon group or a 5-membered, 6-membered, or 7-membered monoheterocyclic group, and one of the ring constituent atoms is L 2 It is connected to; A 2 In addition to the ring being bonded to the 3-position of the azaindazole ring, there are optionally m1 independent R 2 Replaced with A 3 The ring is L 2 In addition to being bound, there are unsubstituted or optionally m2 independent R 2 It will be replaced with. 【0164】 In some embodiments, in the structural formulas of formulas IIa and IIb, the B ring is a benzene ring, and Y 1 , Y 2 and Y 3 Each is independently selected from CR3; and the B ring is composed of two different ring-forming atoms, L 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and these two ring-constituting atoms form an ortho, meta, or para positional relationship. In some embodiments, ring A is one of the following structures: [ka] In these structural formulas, the asterisk (*) at the end of a chemical bond indicates that the bond is attached to the 3-position of the azindazole ring, and the ** at the end of a chemical bond indicates that the bond is L 2 This indicates that it is connected; W 1 and W 2 These are selected independently from CH and N. The ring-forming carbon atoms and / or ring-forming nitrogen atoms in these structural formulas may be arbitrarily 0, 1, 2, 3, or 4 R atoms. 2 It has been replaced with. 【0165】 In some embodiments, ring A is a monoring selected from the group consisting of the following structures: [ka] In these structural formulas, the asterisk (*) at the end of a chemical bond indicates that the bond is attached to the 3-position of the azindazole ring, and the ** at the end of a chemical bond indicates that the bond is L 2 This indicates that it is connected; The ring-forming carbon atoms in these structural formulas may be arbitrarily 0, 1, or 2 R atoms. 2 It has been replaced with. 【0166】 Some embodiments include A 2 Ring and A 3 The fused ring systems consisting of rings are selected from the following group of structures: [ka] In these structural formulas, the asterisk (*) at the end of a chemical bond indicates that the bond is attached to the 3-position of the azindazole ring, and the ** at the end of a chemical bond indicates that the bond is L 2 This indicates that it is connected; W 1 and W 2 These are selected independently from CH and N. The ring-forming carbon atoms and / or ring-forming nitrogen atoms in these structural formulas may be arbitrarily 0, 1, 2, 3, or 4 R atoms. 2 It has been replaced with. In some embodiments, the B ring is a benzene ring or a six-membered heteroaryl group. 【0167】 In one embodiment, the compound has a structural formula of formula IIIb, [ka] Here, X is selected from N and CH. Ring A is selected from phenyl or pyridyl, and ring A is formed by two different ring constituent atoms at the 3-position and L of the azindazole ring. 2 Each is bonded to the other, and the shortest distance between the two ring-forming atoms is one or two chemical bonds; preferably, two chemical bonds. The B ring is a benzene ring, and the B ring is composed of two different ring-forming atoms. 2 The two ring constituent atoms are bonded to the 5-position of the azaindazole ring, respectively, and are in an ortho-positional and meta-positional relationship, preferably in an ortho-positional relationship; R 2 , L 2 The definitions of p and m are as described above. 【0168】 Some embodiments include R 2 Each of these is independently selected from the following: 1) Oxo group, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl, carboxy; 2) One of the following aliphatic heterocyclic groups, where the asterisk (*) at the end of a chemical bond in the structural formula indicates that the bond is more closely attached to the A ring: [ka] Among these, the aliphatic heterocyclic group may optionally have 0, 1, 2, or 3 substituents R 221 It is substituted with substituent R 221 The following are independently selected: oxo group, fluoro, chloro, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cyclylalkyl, C3-C6 oxocycloalkyl, -C(=O)-C1-C6 alkyl, -S(=O)2-C1-C6 alkyl; 3) Ethylidene group, propyridene group, butyridene group, pentylene group, oxapropyridene group, oxabutylidene group, oxapentylene group, azapropyridene group, azabutylidene group, or azapentylene group, which are optionally substituted with 0, 1, or 2 substituents selected from fluoro, hydroxy, or methyl; 4) 0, 1, 2, or 3 substituents R 221 Phenyl, pyridyl, pyrimidinyl, imidazolyl, pyrazolyl, or thiazolyl are substituted with substituent R 221 The following are independently selected: oxo group, fluoro, chloro, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cyclylalkyl, C3-C6 oxocycloalkyl; m is 0, 1, or 2. 【0169】 In one embodiment, in the structural formula of formula IIIb, R 2 Each of these is independently selected from the following: 1) Fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl; 2) One of the following aliphatic heterocyclic groups, where the asterisk (*) at the end of a chemical bond in the structural formula indicates that the bond is more closely attached to the A ring: [ka] Among these, the aliphatic heterocyclic group may optionally have 0, 1, 2, or 3 substituents R 221 It is substituted with substituent R 221 The following are independently selected: oxo group, fluoro, chloro, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cyclylalkyl, C3-C6 oxocycloalkyl, -C(=O)-C1-C6 alkyl, -S(=O)2-C1-C6 alkyl. 【0170】 In one embodiment, in the structural formula of formula IIIb, R 221 Each of these groups is independently selected from the following: oxo group, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, dimethylamino, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, difluoroethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl, oxetanyl, or tetrahydropyranyl group. 【0171】 In one embodiment, the compound has a structural formula of general formula (IIIa), [ka] Here: X is either CH or N; L 1 The aryl group is selected from the group consisting of phenyl, a 5-6 membered heteroaryl group, or a 9-10 membered bicycloheteraryl group, wherein the aryl group or heteroaryl group is simultaneously bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms; in addition to being bonded to the azindazole ring and the A ring, the aryl group or heteroaryl may optionally have 0, 1, 2, 3, or 4 R atoms. 4 It is replaced by; Ring A is selected from monocyclic or bicyclic alicyclic hydrocarbon groups of C5, C6, C7, C8, and C9, or from 5-membered, 6-membered, 7-membered, 8-membered, and 9-membered aliphatic heterocyclic groups, and is composed of two different ring constituent atoms, L 1 and L 2 Each of these is bonded to the other, and the monocyclic or bicyclic structure does not contain an aromatic ring; The B ring is composed of two different ring-forming atoms, L 2 It is bonded to the 5-position of the azaindazole ring, and the shortest distance between the two ring constituent atoms is 1, 2, or 3 chemical bonds, where Y 1 , Y 2 and Y 3 Each is independently selected from CR3 or N, and Y 1 , Y 2 and Y 3 In this case, N can be at most two; R 2 These are independently selected from the following: 1) Halogen, cyano, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkanamine group or C 1-3 Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 1-5 alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group, C 2-4Alkenil, C 2-4 Alkinyl, C 3-6 A cyclylalkyl group and a 3- to 8-membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen, hydroxyl, hydroxyl-C 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 alkyl; R 4 These are independently selected from the following: 1) Halogen, cyano, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkanamine group or C 1-3 Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, 3 or 4 substituents. 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 The substituents are cycloalkyl groups and 3- to 8-membered aliphatic heterocyclic groups, and the substituents are independently oxo groups, halogens, hydroxyl groups, and hydroxyl groups. 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Selected from the group consisting of alkyl groups. 3) Arbitrarily 0, 1, 2, or 3 R 42 A phenyl or 5-6 member heteroaryl group substituted with; Among them, R 42 These are independently selected from the following: 1) Halogen, cyano, hydroxy, C 1-3 Alkoxy, amino, C 1-3 Alkanamine group and C 1-3Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, or 3 substituents 1-3 Alkyl, C 2-4 Alkinyl, C 3-6 The substituents are cyclylalkyl and 3-6 membered aliphatic heterocyclic groups, and the substituents are independently halogen, hydroxyl, methylol, cyano, and C 1-3 Alkoxy, amino, or C 1-3 Selected from the group consisting of alkylaminos; L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, where each L 2 R is independently 0, 1, or 2 5 It is replaced by; two adjacent L 2 Each of them is connected to the others by a single bond, and there are p Ls linked to each other. 2 However, it forms a linking group that connects ring A and ring B; L 2 If it is -CH2-, then its substituent R 5 These are independently selected from the following: 1) Oxo group, halogen, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 , -OR a5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) The same L2 Two R's that are joined together 5 The substituent is L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,1-cyclopropyl, 1,1-cyclobutyl, 1,1-cyclopentyl, 1,1-cyclohexyl, 3,3-oxetanyl, 3,3-azetidinyl, 3,3-tetrahydrofuranyl, 3,3-tetrahydropyrrolyl, 3,3-tetrahydropyranyl group, 4,4-tetrahydropyranyl group, 3,3-piperidinyl and 4,4-piperidinyl; 4) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 A cyclic group is formed by substitution with, the cyclic group being selected from: 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclopentyl, 1,2-cyclohexyl, 3,4-tetrahydrofuranyl, 3,4-tetrahydropyrrolyl, 3,4-tetrahydropyranyl, and 3,4-piperidinyl; 5) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 A cyclic group is formed by substitution with the following, the cyclic group being selected from: 1,3-cyclobutyl, 1,3-cyclopentyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 2,5-tetrahydrofuranyl, 2,5-tetrahydropyrrolyl, 2,6-tetrahydropyranyl group, 3,5-tetrahydropyranyl group, 2,6-piperidinyl, 3,5-piperidinyl, 2,6-morpholinyl, 2,5-morpholinyl, 3,5-morpholinyl, 2,6-piperazinyl and 2,5-piperazinyl; L 2 If it is -NH-, then its substituent R 5 The following are selected independently: 1)-C(=O)R a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 and P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,2-azecyclopropyl, 1,2-azetidinyl, 1,2-tetrahydropyrrolyl, 1,2-piperidinyl, 3,4-morpholinyl, and 1,2-piperidinyl; 4) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a cyclic group substituted with, the cyclic group being selected from: 1,3-azetidinyl, 1,3-tetrahydropyrrolyl, 1,3-piperidinyl, 1,4-piperidinyl, and 1,4-piperazinyl; L 2 If R is -S-, 5 It is independently selected from the oxo group. 【0172】 Here, R a5 , R b5 and R e5Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-3 Alkyl, C 3-6 Cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydropyranyl group, and piperidinyl; Alternatively, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms morpholinil with 1-azetidinyl, 1-tetrahydropyrrolyl, 1-piperidinyl, and 1-piperazinyl, which are substituted with; R c5 These are independently of any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-3 Alkyl, C 3-6 Selected from the group consisting of cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranil, tetrahydropyrrolyl, tetrahydropyranil, and piperidinyl. 【0173】 R d5 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2-(C 1-3 Alkyl); 2) C 1-3 Alkyl and cyclopropyl; R 52 The following are selected: oxo group, fluoro, cyano, hydroxy, C 1-3 Alkoxy, cyclopropyl oxy, C 1-3 Alkyl, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, amino and C 1-3 Alkylamino. R G1 is -OR G2 and -N(R G2 ) Selected from 2. 【0174】 R G2 The following can be selected: 1) Hydro; 2) C which is optionally substituted with 0, 1, 2, or 3 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 3-6 The substituents are a cyclylalkyl group, a 3-6 membered aliphatic heterocyclic group, and a phenyl group, and the substituents are independently an oxo group, halogen, hydroxyl, methylol, carboxyl, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos. 3) Two R atoms bonded to the same nitrogen atom G2 The nitrogen atom forms a 3-6 membered aliphatic heterocyclic group with the nitrogen atom, and the 3-6 membered aliphatic heterocyclic group is optionally substituted with 0, 1, 2, or 3 substituents, and the substituents are independently oxo, halogen, hydroxy, methylol, carboxy, cyano, and C 1-3 Alkoxy, amino, C 1-3 Selected from the group consisting of alkylaminos. 【0175】 R G3 These are hydro, cyano, nitro, -OR G2 -S(=O)2R G2 and R G2 Selected from. m is 0, 1, 2, 3, 4, 5, or 6. p is selected from 2, 3, 4, 5, 6, 7, 8, or 9. n is selected from 0, 1, 2, or 3. R 3 The definition is as stated above. 【0176】 In some embodiments, the compound is the compound of general formula (IIIa), or its isomers, pharmaceutically acceptable salts, crystalline polymorphs, isotope-labeled compounds, active metabolites, or prodrugs, where: L 1 The following can be selected: 1) Phenyl, thiynyl, or pyridyl; 2) A five-membered or six-membered monocyclic heteroaryl containing two ring-forming heteroatoms, where one ring-forming heteroatom is a nitrogen atom, and the other ring-forming heteroatom is selected from nitrogen, oxygen, and sulfur, where L 1 It is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms; L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, 2, or 3 R rings. 4 It has been replaced with. 【0177】 In some embodiments, among the compounds of general formula (IIIa), L 1 The following can be selected: 1) Phenyl, thiynyl, or pyridyl; 2) A five-membered or six-membered monocyclic heteroaryl containing two ring-forming heteroatoms, where one ring-forming heteroatom is a nitrogen atom, and the other ring-forming heteroatom is arbitrarily selected from nitrogen, oxygen, and sulfur, where L 1 It is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms; L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, or 2 R rings. 4 It is replaced by; 3) Quinolinyl, isoquinolinyl, indolyl, indazolyl, benzimidazolyl, benzothiazolyl, or benzisothiazolyl, where L 1 It is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms, and both of these ring-forming atoms are located on the benzene ring; L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, 2, or 3 R rings. 4 It has been replaced with. 【0178】 In some embodiments, the compound of general formula (IIIa) is L 1 The following can be selected: 1) Phenyl, thiynyl, or pyridyl; 2) A five-membered or six-membered monocyclic heteroaryl containing two ring-forming heteroatoms, where one ring-forming heteroatom is a nitrogen atom, and the other ring-forming heteroatom is arbitrarily selected from nitrogen, oxygen, and sulfur, where L 1 It is bonded to the 3-position and A ring of the azindazole ring by two adjacent ring-forming atoms; L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, or 2 R rings. 4 It has been replaced with. 【0179】 In some embodiments, the compound is the compound of general formula (IIIa), or its isomers, pharmaceutically acceptable salts, crystalline polymorphs, isotope-labeled compounds, active metabolites, or prodrugs, where, L 1 The group is selected from the group consisting of naphthyl or a 9-10 membered heteroaryl group, wherein the naphthyl or heteroaryl is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms, respectively; the heteroaryl group contains at least one ring-forming nitrogen atom and no other ring-forming heteroatoms, or contains one or two ring-forming heteroatoms selected from nitrogen, oxygen, and sulfur; in addition to being bonded to the azindazole ring and the A ring, the naphthyl or heteroaryl may optionally have 0, 1, 2, 3, or 4 R 4 It has been replaced with. 【0180】 In some embodiments, the compound of general formula (IIIa) is as follows: L 1The group is selected from the group consisting of naphthyl or a 9-10 membered heteroaryl group, wherein the 9-10 membered heteroaryl group contains at least one benzene ring; the naphthyl or heteroaryl is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms, and both of these ring-forming atoms are located on the benzene ring; the heteroaryl group contains at least one ring-forming nitrogen atom and no other ring-forming heteroatoms, or contains one or two ring-forming heteroatoms selected from nitrogen, oxygen, and sulfur; in addition to being bonded to the azindazole ring and the A ring, the naphthyl or heteroaryl may optionally have 0, 1, 2, 3, or 4 R atoms. 4 It has been replaced with. 【0181】 In some embodiments, the compound of general formula (IIIa) is as follows: L 1 The L is selected from the group consisting of quinolinyl, isoquinolinyl, indolyl, indazolyl, benzimidazolyl, benzothiazolyl, or benzisothiazolyl; 1 It is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms, and both of these ring-forming atoms are located on the benzene ring; the L 1 In addition to being bound to the azaindazole ring and the A ring, it has unsubstituted or 1, 2, or 3 independently R 4 Substituted with a substituent selected from; 【0182】 In some embodiments, the compound of general formula (IIIa) is L 1 The L is selected from the group consisting of quinolinyl, isoquinolinyl, indolyl, indazolyl, benzimidazolyl, benzothiazolyl, or benzisothiazolyl; 1 It is bonded to the 3-position and A ring of the azindazole ring by two non-adjacent ring-forming atoms, and both of these ring-forming atoms are located on the benzene ring; the L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, or 2 R rings. 4It has been replaced with. 【0183】 In some embodiments, the compound of general formula (IIIa) is L 1 It is one selected from the group consisting of the following structures, where "*" at the end of a chemical bond in the structural formula indicates that the bond is attached to the 3-position of the azindazole ring, and "**" at the end of a chemical bond in the structural formula indicates that the bond is attached to the A ring: [ka] Also, L 1 In addition to being bound to the azaindazole ring and the A ring, it optionally has 0, 1, or 2 R rings. 4 It has been replaced with. 【0184】 In one embodiment, in the compound of general formula (IIIa), the B ring is selected from phenyl or a 6-membered heteroaryl group, where Y 1 , Y 2 and Y 3 Each is independently selected from CR3 or N, and Y 1 , Y 2 and Y 3 In this case, N can be at most two. 【0185】 In one embodiment, in the compound of general formula (IIIa), Y 1 , Y 2 and Y 3 Each of them operates independently, CR 3 Selected from. In one embodiment, in the compound of general formula (IIIa), Y 1 is selected from N, Y 2 and Y 3 Each of them operates independently, CR 3 Selected from. In one embodiment, in the compound of general formula (IIIa), Y 2 is selected from N, Y 1 and Y 3 Each of them operates independently, CR 3 Selected from. 【0186】 In one embodiment, in the compound of general formula (IIIa), Y 3 is selected from N, Y 1 and Y 2 Each of them operates independently, CR 3 Selected from. In one embodiment, in the compound of general formula (IIIa), Y 1 and Y 2 is selected from N, Y 3 CR 3 Selected from. In one embodiment, in the compound of general formula (IIIa), Y 2 and Y 3 is selected from N, Y 1 CR 3 Selected from. 【0187】 In one embodiment, ring A is selected from monocyclic or bicyclic alicyclic hydrocarbon groups of C5, C6, C7, C8, and C9, or from 5-membered, 6-membered, 7-membered, 8-membered, and 9-membered aliphatic heterocyclic groups, and is composed of two different ring constituent atoms, L 1 and L 2 Each of these is bonded to the other, and the monocyclic or bicyclic structure does not contain an aromatic ring. 【0188】 In one embodiment, ring A is one of the following structures, where "*" at the end of a chemical bond in the structural formula indicates that the bond is attached to L1, and "**" at the end of a chemical bond in the structural formula indicates that the bond is attached to L1. 2 This indicates that it is connected: [ka] Also, ring A is L 1 and L 2 In addition to being coupled, there are optionally 0, 1, or 2 R 2 It has been replaced with. 【0189】 In one embodiment, R 2 Each of these is independently selected from the following: 1) Oxo group, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl and N,N-dimethyl-2-amino-2-propyl, carboxy; 2) 0, 1, 2, or 3 substituents R 22 The substituted groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, tetrahydropyrrolyl, piperidinyl, piperazinyl and morpholinyl, and substituent R 221 The following are independently selected: oxo group, fluoro, chloro, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C3-C6 cyclylalkyl, C3-C6 oxocycloalkyl; 3) Ethylidene group, propyridene group, butyridene group, pentylene group, oxapropyridene group, oxabutylidene group, oxapentylene group, azapropyridene group, azabutylidene group, or azapentylene group, which are optionally substituted with 0, 1, or 2 substituents selected from fluoro, hydroxy, or methyl; m is 0, 1, or 2. 【0190】 In one embodiment, R 221Each of these groups is independently selected from the following: oxo group, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, dimethylamino, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, difluoroethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl, oxetanyl, tetrahydropyranyl group. 【0191】 In one embodiment, R 3 These are independently fluoro, chloro, cyano, and C 1-3 Alkoxy, difluoromethoxy, trifluoromethoxy, cyclopropyloxy, C 1-3 Selected from the group consisting of alkyl, difluoromethyl, trifluoromethyl, and cyclopropyl, and at least one R 3 However, in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring. 3 The element is selected from the group consisting of fluoro, chloro, methoxy, methyl, or ethyl. n is 1, 2, or 3. 【0192】 In one embodiment, R 3 These are independently selected from the group consisting of fluoro, chloro, cyano, methoxy, methyl, and ethyl, and also include at least one R 3 However, in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring. 3 The element is selected from the group consisting of fluoro, chloro, methoxy, methyl, or ethyl. n is either 1 or 2. 【0193】 In one embodiment, R 3The following are independently selected from the group consisting of fluoro, chloro, cyano, and methoxy. Also, at least one R 3 However, in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and in the B ring, the R is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring. 3 The compound is selected from the group consisting of fluoro, chlor, or methoxy; preferably fluoro; n is selected from 1 or 2. Preferably, it is 1. 【0194】 In one embodiment, R 3 The following are independently selected from fluoro and methoxy; and at least one R 3 However, in the B ring, it is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, preferably the R 3 is fluoro; n is selected from 1 or 2. Preferably, it is 1. 【0195】 In one embodiment, the B ring is selected from a phenyl or a 6-membered heteroaryl group, and the L ring is composed of two different ring constituent atoms. 2 Y is bonded to the 5-position of the azaindazole ring, and the shortest distance between the two ring-constituting atoms is 1, 2, or 3 chemical bonds; where Y 1 , Y 2 and Y 3 Each is independently selected from CR3 or N, and Y 1 , Y 2 and Y 3 In this case, N can be at most two. 【0196】 In one embodiment, ring B is a benzene ring, and Y 1 , Y 2 and Y 3 Each is independently selected from CR3; and the B ring is formed by two different ring constituent atoms, L 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and these two ring-constituting atoms form an ortho, meta, or para positional relationship. 【0197】 In one embodiment, R 2 These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a2 R b2 , -OR a2 -S(=O)R c2 -S(=O)2R c2 -S(=O)2NR a2 R b2 , -NR a2 R b2 , -NR a2 C(=O)R b2 , -NR e2 C(=O)NR a2 R b2 , -NR a2 S(=O)2R c2 and -NR e2 S(=O)2NR a2 R b2 ; 2) Any number of R values: 0, 1, 2, 3, or 4 22 It is replaced with C 1-4 Alkyl, C 1-5 alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Here, R a2 , R b2 and R e2 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 22 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a2 and R b2 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 22 It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R c2 R can be any 0, 1, 2, 3 or 4 22 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Selected from cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; R 22 The following are selected independently: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamine group; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino. 【0198】 In one embodiment, R 2 These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a2 R b2 , -OR a2 -S(=O)R c2 -S(=O)2R c2 -S(=O)2NR a2 R b2 , -NR a2 R b2 , -NR a2 C(=O)R b2 , -NR e2 C(=O)NR a2 R b2 , -NR a2 S(=O)2R c2 and -NR e2 S(=O)2NR a2 R b2 ; 2) Any number of R values: 0, 1, 2, 3, or 4 GIt is replaced with C 1-4 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Here, R a2 , R b2 and R e2 Each of these is independently selected from the following: 1) Hydro; 2) Non-substitutive or optionally R G A C substituted with 1, 2, 3, or 4 substituents, independently selected from the above. 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; or, R bonded to the same nitrogen atom a2 and R b2 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R c2 R can be any 0, 1, 2, 3 or 4 G C is replaced by 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Selected from cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups. 【0199】 In one embodiment, R 2 The following are selected independently: Two R atoms bonded to each of the two ring-forming atoms of ring A. 2 The substituents, along with the two ring-forming atoms, can be any 0, 1, 2, 3, or 4 R atoms. 22 C is replaced by 5-6 It forms an alicyclic hydrocarbon group or a 5-6 membered aliphatic heterocyclic group. 【0200】 In one embodiment, R 2 These are independently selected from the following: 1) Halogen atom, cyano, hydroxy, C 1-4Alkoxy, amino, C 1-4 Alkanamine group or C 1-3 Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 1-5 alkylidene group, 3-6 member oxoalkylidene group, 2-6 member azaalkylidene group, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 A cyclylalkyl group and a 3- to 8-membered aliphatic heterocyclic group, wherein the substituents are independently selected from: an oxo group, a halogen atom, hydroxyl, and hydroxyl-C. 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Alkyl. 【0201】 In one embodiment, R 2 These are independently selected from the following: Fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl, carboxy. 【0202】 In one embodiment, R 2 The group is independently selected from the group consisting of 3 to 8-membered aliphatic heterocyclic groups, the aliphatic heterocyclic group containing 1 or 2 ring-forming heteroatoms, the ring-forming heteroatoms selected from N, O, and S, the aliphatic heterocyclic group is optionally substituted with 0, 1, 2, or 3 substituents, the substituents independently selected from: oxo group, halogen atom, hydroxyl, hydroxyl-C 1-3Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Alkyl. 【0203】 In one embodiment, R 2 Each of these is independently selected from the following: an ethylidene group, propylidene group, butylidene group, pentylene group, oxapropylidene group, oxabutylidene group, oxapentylene group, azapropylidene group, azabutylidene group, or azapentylene group, which are optionally substituted with 0, 1, or 2 substituents, wherein the substituents are selected from fluoro, hydroxy, or methyl. 【0204】 In one embodiment, R 221 Each of these groups is independently selected from the following: oxo group, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy group, cyclopropyloxy, dimethylamino, methyl, ethyl, 1-propyl, isopropyl group, cyclopropyl, difluoromethyl, trifluoromethyl, difluoroethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, N,N-dimethyl-2-amino-2-propyl, oxetanyl, or tetrahydropyranyl group. 【0205】 In one embodiment, R 3 These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a3 R b3 , -OR a3 -S(=O)R c3 -S(=O)2R c3 -S(=O)2NR a3 R b3 , -NR a3 R b3 , -NR a3 C(=O)Rb3 , -NR e3 C(=O)NR a3 R b3 , -NR a3 S(=O)2R c3 and -NR e3 S(=O)2NR a3 R b3 ; 2) Any number of R values: 0, 1, 2, 3, or 4 32 It is replaced with C 1-4 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; 3) Two R atoms bonded to each of the two ring-constituting atoms of the B ring 3 The substituents, along with the two ring-forming atoms, can be any 0, 1, 2, 3, or 4 R atoms. 32 C is replaced by 5-6 It forms an alicyclic hydrocarbon group or a 5-6 membered aliphatic heterocyclic group; Here, R a3 , R b3 and R e3 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 32 C is replaced by 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; or, R bonded to the same nitrogen atom a3 and R b3 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 32 It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R c3 R can be any 0, 1, 2, 3 or 4 32 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Selected from cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; R 32These are independently selected from the following: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamino; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino. 【0206】 In one embodiment, R 3 These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a3 R b3 and OR a3 ; 2) Any number of R values: 0, 1, 2, 3, or 4 32 It is replaced with C 1-3 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; Here, R a3 and R b3 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 32 It is replaced with C 1-4 Alkyl, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; or, R bonded to the same nitrogen atom a3 and R b3 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 32 It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R 32 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamino; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino. 【0207】 In one embodiment, R 3 These are independently selected from the following: Two R atoms bonded to two ring-forming atoms of the B ring, respectively. 3 The substituents, along with the two ring-forming atoms, can be any 0, 1, 2, 3, or 4 R atoms. 32 C is replaced by 5-6 It forms an alicyclic hydrocarbon group or a 5-6 membered aliphatic heterocyclic group. 【0208】 In one embodiment, R 32 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamino; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino. 【0209】 In one embodiment, R 3 These are independently fluoro, chloro, cyano, and C1-3 Alkoxy, difluoromethoxy, trifluoromethoxy, cyclopropyloxy, C 1-3 Selected from the group consisting of alkyl, difluoromethyl, trifluoromethyl, and cyclopropyl; also, at least one R 3 However, in the B ring, it is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and the R 3 However, it is selected from the group consisting of fluoro, chloro, methoxy, methyl, or ethyl. 【0210】 In one embodiment, R 3 The following are independently selected from the group consisting of fluoro, chloro, cyano, methoxy, methyl, and ethyl; and at least one R 3 However, in the B ring, it is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and the R 3 The element is selected from the group consisting of fluoro, chloro, methoxy, methyl, or ethyl. 【0211】 In one embodiment, R 3 The following are independently selected from the group consisting of fluoro, chloro, cyano, and methoxy. Also, at least one R 3 However, in the B ring, it is located in the ortho position of the ring constituent atom linked to the 5-position of the azindazole ring, and the R 3 The element is selected from the group consisting of fluoro, chlor, or methoxy. 【0212】 In one embodiment, R 3 The following are independently selected from fluoro and methoxy; and at least one R 3 However, in the B ring, it is located in the ortho position of the ring-forming atom linked to the 5-position of the azindazole ring. In one embodiment, R 3 The fluorine atom is selected from fluorocarbons, and the fluorine atom is located in the ortho position of the ring-forming atom linked to the 5-position of the azindazole ring in the B ring. 【0213】 In one embodiment, R 4These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a4 R b4 , -OR a4 -S(=O)R c4 -S(=O)2R c4 -S(=O)2NR a4 R b4 , -NR a4 R b4 , -NR a4 C(=O)R b4 , -NR e4 C(=O)NR a4 R b4 , -NR a4 S(=O)2R c4 and -NR e4 S(=O)2NR a4 R b4 ; 2) Any number of R values: 0, 1, 2, 3, or 4 42 It is replaced with C 1-4 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; 3) L 1 Two R atoms bonded to each of the two ring-forming atoms of the ring. 4 The substituents, along with the two ring-forming atoms, can be any 0, 1, 2, 3, or 4 R atoms. 42 C is replaced by 5-6 It forms an alicyclic hydrocarbon group or a 5-6 membered aliphatic heterocyclic group; Here, R a4 , R b4 and R e4 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 42 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; Alternatively, R bonded to the same nitrogen atom a4 and R b4Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 42 It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R c4 R can be any 0, 1, 2, 3 or 4 42 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Selected from cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; Here, R 42 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino and C 1-4 Alkanamine group; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: oxo group, halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino. 【0214】 In one embodiment, R 4 These are independently selected from the following: 1) Halogen atom, cyano, -C(=O)NR a4 R b4 , -OR a4 -S(=O)R c4 -S(=O)2R c4 -S(=O)2NR a4 R b4 , -NR a4 R b4 , -NR a4 C(=O)R b4 , -NR e4 C(=O)NR a4 R b4 , -NR a4 S(=O)2R c4 and -NRe4 S(=O)2NR a4 R b4 ; 2) Any number of R values: 0, 1, 2, 3, or 4 G It is replaced with C 1-4 Alkyl, C 2-4 Alkynyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3- to 8-membered aliphatic heterocyclic groups; Here, R a4 , R b4 and R e4 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 G It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; or, R bonded to the same nitrogen atom a4 and R b4 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R G It forms a 4-6 member aliphatic heterocyclic group that is substituted with; R c4 R can be any 0, 1, 2, 3 or 4 G It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Selected from cyclylalkyl groups and 4-6 membered aliphatic heterocyclic groups; 【0215】 In one embodiment, R 4 These are independently selected from the following: L 1 Two R atoms bonded to each of the two ring-forming atoms of the ring. 4 The substituents, along with the two ring-forming atoms, can be any 0, 1, 2, 3, or 4 R atoms. 42 C is replaced by 5-6 It forms an alicyclic hydrocarbon group or a 5-6 membered aliphatic heterocyclic group. 【0216】 In one embodiment, R 4 These are independently selected from the following: 1) Halogen atom, cyano, hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkanamine group or C 1-3 Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, 3 or 4 substituents. 1-4 Alkyl, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 A cyclylalkyl group and a 3- to 8-membered aliphatic heterocyclic group, wherein the substituents are independently selected from: an oxo group, a halogen atom, hydroxyl, and hydroxyl-C. 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Alkyl. 【0217】 In one embodiment, R 4 Independently, any 0, 1, 2, or 3 R 42 Substituted with, selected from phenyl or 5-6 member heteroaryl groups: Here, R 42 These are independently selected from the following: 1) Halogen atom, cyano, hydroxy, C 1-3 Alkoxy, amino, C 1-3 Alkanamine group and C 1-3 Alkyl sulfone group; 2) C which is optionally substituted with 0, 1, 2, or 3 substituents 1-3 Alkyl, C 2-4 Alkinyl, C 3-6 A cycloalkyl group and a 3-6 membered aliphatic heterocyclic group, wherein the substituent is independently selected from: halogen atom, hydroxyl, methylol, cyano, C 1-3 Alkoxy, amino, or C1-3 Alkylamino. 【0218】 In one embodiment, R 4 These are independently selected from: fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy groups, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl groups, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, and N,N-dimethyl-2-amino-2-propyl. 【0219】 In one embodiment, R 4 The group is selected from the group consisting of 3-8 membered aliphatic heterocyclic groups, the aliphatic heterocyclic group contains 1 or 2 ring-forming heteroatoms, the ring-forming heteroatoms are selected from N, O, and S, the aliphatic heterocyclic group is unsubstituted or substituted with 1, 2, or 3 substituents, the substituents independently being an oxo group, a halogen atom, a hydroxyl group, or a hydroxyl group. 1-3 Alkyl, C 1-3 Alkoxy-C 1-3 Alkyl, cyano, C 1-3 Alkoxy, amino, C 1-3 Alkylamino, Amino-C 1-3 Alkyl or C 1-3 Alkylamino-C 1-3 Selected from alkyl groups. 【0220】 In one embodiment, R 4 It is one selected from the group consisting of the following aliphatic heterocyclic groups, and the "*" at the end of a chemical bond in the structural formula indicates that the bond is L 1 Showing that it is bonded to the ring: [ka] Among these, the aliphatic heterocyclic group is optionally substituted with 0, 1, 2, or 3 substituents, the substituents independently selected from: oxo, fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, 2-amino-2-propyl, N-methyl-2-amino-2-propyl, and N,N-dimethyl-2-amino-2-propyl. 【0221】 In one embodiment, R 4 Independently, any 0, 1, or 2 R 42 Selected from the group consisting of phenyl, pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, or thiazolyl, which are substituted with: Here, R 42 These are independently selected from the following: fluoro, chloro, cyano, hydroxy, methoxy, ethoxy, isopropoxy groups, cyclopropyloxy, methyl, ethyl, 1-propyl, isopropyl groups, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, amino, methylamino, dimethylamino, and diethylamineyl. 【0222】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It has been replaced with. One embodiment, L 2 Each of these is independently selected from the group consisting of -CH2-, -NH-, or O-. 【0223】 One embodiment, L 2 Each of these is independently selected from -CH2- or O-. One embodiment, L 2Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; two adjacent L 2 If both are carbon, then the two L 2 They are bonded together by a triple bond. 【0224】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; two adjacent L 2 In the case where one is carbon and the other is nitrogen, the two L 2 These are joined by a double bond, and the double bond is either a Z-form or an E-form. 【0225】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; two adjacent L 2 If both are nitrogen, then the two L 2 These are joined by a double bond, and the double bond is either a Z-form or an E-form. 【0226】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; two adjacent L 2 They are all connected to each other by single bonds. 【0227】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, or O-, L 2Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; two adjacent L 2 They are all connected to each other by single bonds. 【0228】 One embodiment, L 2 If it is -CH2-, then L 2 Each time it appears, there are arbitrarily 0, 1, or 2 R 5 It has been replaced with. One embodiment, L 2 If it is -NH-, then L 2 Each time it appears, arbitrarily 0 or 1 R 5 It has been replaced with. One embodiment, L 2 If it is -S-, then L 2 Each time it appears, it is arbitrarily replaced by 0, 1, or 2 oxos. 【0229】 One embodiment, L 2 If L is -CH2-, then L 2 substituent R 5 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 , -OR a5 -OP(=O)(R G1 )2, -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR e5 C(=NR d5 )NR a5 R b5 , -NRa5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2, -P(=O)R c5 R f5 -P(=O)(R G1 )2 and =NR d5 ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-6 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) The same L 2 , or two adjacent L 2 Two R's that are joined together 5 The substituents are the 1 or 2 L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms an alicyclic hydrocarbon group or a 3- to 6-membered aliphatic heterocyclic group; 4) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms an alicyclic hydrocarbon group or a 3-6 membered aliphatic heterocyclic group. 【0230】 One embodiment, L 2 If L is -NH-, 2 substituent R 5 These are independently selected from the following: 1)-C(=O)R a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 -S(=O)2Rc5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 ,-P(=O)R c5 R f5 and P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-6 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; 3) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with; 4) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with; R a5 , R b5 and R e5 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; or, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms a 3- to 6-membered aliphatic heterocyclic group that is substituted with; Rc5 and R f5 Each is independently selected from the following: any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; or, R bonded to the same phosphorus atom c5 and R f5 This is formed together with the nitrogen atom by any 0, 1, 2, 3, or 4 R 52 A 3- to 6-membered aliphatic heterocyclic group substituted with; R d5 The following can be selected: 1) Hydro, hydroxy, C 1-4 Alkoxy, cyano, nitro, and S(=O)2R G ; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, phenyl, 5-6 member heteroaryl group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups; R 52 The following can be selected: 1) Oxo group, halogen atom, cyano; 2) R G2 ; 3) R G1 -C(=O)R G1 -C(=O)R G2 -OP(=O)(R G1 )2, -S(=O)2R G2 -S(=O)2N(R G2 )2, -S(=O)(=NRG3)R G2 , -N(R G2 )C(=O)R G1 , -N(R G2 )C(=O)R G2 , -N(R G2 )S(=O)2R G2 , -N(R G2 )S(=O)2N(R G2 )2, -N(R G2 )P(=O)(RG1 )2, -P(=O)(R G2 )2, -P(=O)(R G1 )2 and =NR G3 . 【0231】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by; L 2 If is -S-, then L 2 substituent R 5 These are independently selected from the following: oxo and =NR d5 ; R d5 The following are selected: hydro, cyano, nitro, and S(=O)2R G . 【0232】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced by;R 5 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 , -OR a5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2P(=O)(R G1 )2, -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 and P(=O)(R G1 )2; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-4 Alkyl, C 2-5 Alkylidene group, C 3-6 Cyclylalkyl groups and 3-6 membered aliphatic heterocyclic groups. 【0233】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, or O-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced with R 5 These are independently selected from the following: 1) Oxo group, halogen atom, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 , -OR a5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2, -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 and P(=O)(R G1 )2; 2) C 1-4 Alkyl, C 2-5 Alkylidene group, C 3-6 Cyclylalkyl and 3-6 membered aliphatic heterocyclic groups, optionally 0, 1, 2, 3, or 4 R 52 It has been replaced with. 【0234】 One embodiment, L 2 Each of these is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-: 1) L 2 If L is -CH2-, then L 2 substituent R 5 The following are independently selected: oxo group, halogen atom, cyano, -C(=O)R a5 carboxy, -C(=O)NR a5 R b5 , -OR a5 , -NR a5 R b5 , -NR a5 C(=O)R b5 , -NR e5 C(=O)NR a5 R b5 , -NR a5 S(=O)2R c5 , -NR e5 S(=O)2NR a5 R b5 , -NR G2 P(=O)(R G1 )2; 2) L 2 If L is -NH-, 2 substituent R 5 It is independently selected from the following: -C(=O)R a5 -C(=O)NR a5 R b5 -C(=NR d5 )NR a5 R b5 -S(=O)2R c5 -S(=O)2NR a5 R b5 -S(=O)(=NR d5 )R c5 and P(=O)(R G1 )2; 3) L2 If is -CH2- or NH-, then L 2 substituent R 5 It is independently selected from the following: C 1-4 Alkyl, C 3-6 Cyclylalkyl and 3-6 membered aliphatic heterocyclic groups, optionally 0, 1, 2, 3, or 4 R 52 It is replaced by; 4) L 2 If R is -S-, 5 It is independently selected from the oxo group. Here, R a5 , R b5 and R e5 Each of these is independently selected from the following: 1) Hydro; 2) Any number of R values: 0, 1, 2, 3, or 4 52 It is replaced with C 1-3 Alkyl, C 3-6 Cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydropyranyl group, and piperidinyl; Alternatively, R bonded to the same nitrogen atom a5 and R b5 Along with the nitrogen atom, optionally 0, 1, 2, 3, or 4 R 52 It forms morpholinil with 1-azetidinyl, 1-tetrahydropyrrolyl, 1-piperidinyl, and 1-piperazinyl, which are substituted with; R c5 These are independently selected from the following: any 0, 1, 2, 3, or 4 R 52 It is replaced with C 1-3 Alkyl, C 3-6 Cyclylalkyl, 3-oxetanyl, 3-azetidinyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydropyranyl group, and piperidinyl; R d5 The following can be selected: 1) Hydro, cyano, nitro and S(=O)2-(C 1-3 Alkyl); 2) C 1-3 Alkyl and cyclopropyl; R 52 The following are selected: oxo group, fluoro, cyano, hydroxy, C 1-3 Alkoxy, cyclopropyl oxy, C 1-3 Alkyl, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, amino and C 1-3 Alkylamino. 【0235】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced with R 5 The following are selected independently: 1) The same L 2 , or two adjacent L 2 Two R's that are joined together 5 The substituents are the 1 or 2 L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms a subalicyclic hydrocarbon group or a 3-6 membered subaliphatic heterocyclic group; 2) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 C is replaced by 3-6 It forms a subalicyclic hydrocarbon group or a 3-6 membered subaliphatic heterocyclic group. 【0236】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It has been replaced with, L2 If R is -CH2-, 5 These are independently selected from the following: 1) The same L 2 Two R's that are joined together 5 The substituent is L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 Substituted with 1,1-cyclopropyl, 1,1-cyclobutyl, 1,1-cyclopentyl, 1,1-cyclohexyl, 3,3-oxetanyl, 3,3-azetidinyl, 3,3-tetrahydrofuranyl, 3,3-tetrahydropyrrolyl, 3,3-tetrahydropyranyl group, 4,4-tetrahydropyranyl group, 3,3-piperidinyl and 4,4-piperidinyl; 2) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 Substituted with 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclopentyl, 1,2-cyclohexyl, 3,4-tetrahydrofuranyl, 3,4-tetrahydropyrrolyl, 3,4-tetrahydropyranyl groups and 3,4-piperidinyl; 3) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 All other L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 These molecules form 1,3-cyclobutyl, 1,3-cyclopentyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 2,5-tetrahydrofuranyl, 2,5-tetrahydropyrrolyl, 2,6-tetrahydropyranyl group, 3,5-tetrahydropyranyl group, 2,6-piperidinyl, 3,5-piperidinyl, 2,6-morpholinyl, 2,5-morpholinyl, 3,5-morpholinyl, 2,6-piperazinyl, and 2,5-piperazinyl. 【0237】 One embodiment, L2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2 Each of these can independently have any number of R values: 0, 1, or 2. 5 It has been replaced with, L 2 If R is -NH-, 5 These are independently selected from the following: 1) Two adjacent L 2 Two R's that are joined together 5 The substituents are the two L 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 Substituted with 1,2-azecyclopropyl, 1,2-azetidinyl, 1,2-tetrahydropyrrolyl, 1,2-piperidinyl, 3,4-morpholinyl, and 1,2-piperidinyl; 2) Two non-adjacent L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atoms, and the two L 2 Other L between 2 Along with the atom, any 0, 1, 2, 3, or 4 R 52 These molecules form 1,3-azetidinyl, 1,3-tetrahydropyrrolyl, 1,3-piperidinyl, 1,4-piperidinyl, and 1,4-piperazinyl, which are substituted with . 【0238】 In one embodiment, R 52 The following are selected: oxo group, fluoro, cyano, hydroxy, C 1-3 Alkoxy, cyclopropyl oxy, C 1-3 Alkyl, cyclopropyl, difluoromethyl, trifluoromethyl, methylol, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, amino and C 1-3 Alkylamino. 【0239】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, or S-, L 2Each of these can independently have any number of R values: 0, 1, or 2. 5 It is replaced with R 5 The following are selected independently: 1) Oxo group, halogen atom, cyano, hydroxy, C 1-3 Alkoxy, amino, C 1-3 Alkanamino or C 1-3 alkyl; 2) L 2 If it is carbon, then the same L 2 Two R's that are joined together 5 The substituent is L 2 It forms a C3, C4, or C5 cycloalkylene group with an atom, and the cycloalkylene group may optionally have 0, 1, 2, 3, or 4 R atoms. 52 It is replaced by; 3) Two adjacent L 2 If carbon or nitrogen, then the two L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Together with atoms, it forms a C4, C5, C6 cycloalkylene group or a 4, 5, and 6-membered heterocyclic alkylene group, and the cycloalkylene group and heterocyclic alkyl group optionally have 0, 1, 2, 3, or 4 R 52 It is replaced by; 4) Two non-adjacent L 2 If carbon or nitrogen, then the two L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atom and the two L 2 All other L between atoms 2 Together with atoms, it forms a C4, C5, C6 cycloalkylene group or a 4, 5, and 6-membered heterocyclic alkylene group, and the cycloalkylene group and heterocyclic alkylene group may optionally have 0, 1, 2, 3, or 4 R 52 It is replaced by; Here, R 52 The following are selected: halogen atoms, cyano, hydroxy, C 1-3 Alkoxy or C 1-3 Alkyl. 【0240】 One embodiment, L 2 Each of these is independently selected from the following: 1)-CH2-,-CF2-,-CH(C 1-3 Alkyl)-,-C(1,1-cyclopropyl)-,-C(C 1-3 Alkyl)2-, -CH(OH)-, -CH(C 1-3 -alkoxy)-, -CH(CN)-, -C(=O)-, -CH(NH2)-, -CH(NHC) 1-3 Alkyl)-,-CH(N(C 1-3 Alkyl)2)-,-NH-,-N(C 1-3 Alkyl)-, -N(cyclopropyl)-, -N(CH2CH2OH)-, -N(C(=O)C 1-3 Alkyl)-, -N(C(=O)cyclopropyl)-, -N(C(=O)CH2OH)-, -N(C(=O)CH2N(C 1-3 Alkyl)2)-,-N(S(=O)2C 1-3 Alkyl)-, -N(S(=O)2-cyclopropyl)-, -O-, -S(=O)- or S(=O)2-; 2) Each of these is independently substituted with any 0, 1, 2, or 3 substituents -CH(C 1-3 Alkyl)-, -C(C 1-3 The substituent is alkyl)2-, -C(1,1-clopropylidene)-, or C(1,1-cyclobutylidene)-, and the substituent is selected from fluoro, hydroxy, cyano, or methoxy; 3) Two adjacent L 2 It is simultaneously a carbon and is linked by a single methylene group to form 1,2-clopropylidene (each independently substituted with any 0, 1, 2, or 3 substituents selected from the group consisting of fluoro, hydroxy, cyano, or methoxy); 4) Three consecutive L 2 It is simultaneously a carbon atom, and the carbon atoms at both ends are linked by a single methylene group to form 1,3-cyclobutylidene (each independently substituted with 0, 1, 2, or 3 substituents selected from the group consisting of fluoro, hydroxy, cyano, or methoxy atoms). 【0241】 In one embodiment, R G The following can be selected: 1) Halogen atom, cyano, hydroxy, C 1-3 Alkoxy, amino, or C 1-3 Alkylamino; 2) C which is optionally substituted with 0, 1, 2, 3, or 4 substituents 1-4 Alkyl, C 1-4 Alkylidene group, C 2-4 Alkenil, C 2-4 Alkinyl, C 3-6 The substituents are cycloalkyl groups and 3- to 8-membered aliphatic heterocyclic groups, and the substituents are independently oxo groups, halogen atoms, hydroxyl, methylol, carboxyl, cyano, and C 1-3 Alkoxy, amino, or C 1-3 Selected from alkylaminos. 【0242】 In one embodiment, the B ring is selected from phenyl or a 5-6 membered monocyclic heteroaryl, and the L ring is composed of two different ring constituent atoms. 2 The atoms are bonded to the 5-position of the azindazole ring, and the shortest distance between the two ring-constituting atoms is 1, 2, or 3 chemical bonds. 【0243】 In one embodiment, the B ring is a benzene ring, and the B ring is composed of two different ring-forming atoms, L 2 The two ring-constituting atoms are bonded to the 5-position of the azindazole ring, respectively, and these two ring-constituting atoms form an ortho, meta, or para positional relationship. 【0244】 One embodiment, L 2 Each is independently selected from the group consisting of -CH2-, -NH-, -O-, and -S-, where each L 2 R is independently 0, 1, or 2 5 Substituted by; within the limits of the valence, two adjacent L 2 p L atoms are connected to each other by single, double, or triple bonds. 2However, it forms a linking group that connects ring A and ring B; L at both ends 2 They are bonded to ring A and ring B by single bonds, respectively; R 5 These are independently selected from the following: 1) Oxo group, halogen, cyano, hydroxy, C 1-3 Alkoxy, amino, C 1-3 Alkanamino or C 1-3 alkyl; 2) L 2 If it is carbon, then the same L 2 Two R's that are joined together 5 The substituent is L 2 It forms a C3, C4, or C5 cycloalkylene group with an atom, and the C3, C4, or C5 cycloalkylene group may have 0, 1, 2, 3, or 4 R atoms. 52 It is replaced by; 3) Two adjacent L 2 If carbon or nitrogen, then the two L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Together with atoms, they form C4, C5, C6 cycloalkylene groups or 4, 5, and 6-membered heterocyclic alkylene groups, and the cycloalkylene group and heterocyclic alkyl group optionally have 0, 1, 2, 3, or 4 R 52 It is replaced by; 4) Two non-adjacent L 2 If carbon or nitrogen, then the two L 2 Two Rs that are connected to each other 5 The substituents are the two L 2 Atom and the two L 2 All other L between atoms 2 Together with atoms, it forms a C4, C5, C6 cycloalkylene group or a 4, 5, and 6-membered heterocyclic alkylene group, and the cycloalkylene group and heterocyclic alkylene group may optionally have 0, 1, 2, 3, or 4 R 52 It is replaced by; Among them, R 52 The following are selected: halogen, cyano, hydroxy, C 1-3 Alkoxy or C 1-3 Alkyl. 【0245】 In one embodiment, p is selected from 2, 3, 4, 5, 6, 7, 8, or 9. In one embodiment, p is selected from 2, 3, 4, 5, 6, 7, or 8. In one embodiment, p is selected from 4, 5, 6, 7, or 8. In one embodiment, p is selected from 5, 6, or 7. In one embodiment, p is selected from 1, 2, 3, or 4. In one embodiment, p is selected from 2, 3, or 4. 【0246】 In one embodiment, the sum of m1 and m2 is m. In one embodiment, m is 0, 1, 2, 3, 4, 5, or 6. In one embodiment, m is selected from 0, 1, 2, 3, or 4. In one embodiment, m is selected from 0, 1, or 2. In one embodiment, m is selected from 0 or 1. 【0247】 In one embodiment, n is 0, 1, 2, 3, 4, 5, or 6. In one embodiment, n is selected from 0, 1, 2, or 3. In one embodiment, n is selected from 1 or 2. In one embodiment, n is selected from 0 or 1. In one embodiment, n is selected from 1. 【0248】 In one embodiment, the compound is selected from the group consisting of the following compounds: [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] 【0249】 In one embodiment, the compound is selected from the group consisting of the following compounds: [Table 12] [Table 13] [Table 14] [Table 15] [Table 16] 【0250】 In one embodiment, the compound is selected from the group consisting of the following compounds: [Table 17] [Table 18] [Table 19] [Table 20] 【0251】 In one embodiment, the compound is selected from the group consisting of the following compounds: [Table 21] [Table 22] 【0252】 Composition and Uses One aspect of the present invention provides a pharmaceutical composition comprising the compound described in the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer, or prodrug thereof, and a pharmaceutically acceptable carrier. 【0253】 The aforementioned pharmaceutical composition can be prepared by methods well known in the pharmaceutical field and can be administered by various routes. The mode of administration may be topical (including transdermal, epidermal, ocular and mucous membrane delivery, and including intranasal, vaginal and rectal delivery), transpulmonary (intra-airway or intranasal, for example, by inhalation or blowing of powder or aerosol, including by atomizer), oral, or non-enteral. 【0254】 In one embodiment, the composition is suitable for non-enteral administration. This includes intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, and other local injections or infusions; or intracranial, e.g., subarachnoid or intraventricular administration. Non-enteral administration may be performed with a single push per dose, or (for example) by continuous infusion pump. 【0255】 In one embodiment, the composition is suitable for topical administration. Pharmaceutical compositions and formulations for topical administration include transdermal patches, ointments, detergents, creams, jellies, drops, suppositories, sprays, liquids, and powders. Conventional drug delivery systems, aqueous, powder, or oily matrices, thickeners, etc., may be essential or present as needed. 【0256】 One aspect of the present invention provides the use of the compound of the present application or its pharmaceutically acceptable salts, hydrates, solvates, active metabolites, crystalline polymorphs, isotope-labeled forms, isomers, or prodrugs, and the pharmaceutical composition thereof, in the prevention or treatment of diseases mediated by protein kinases. 【0257】 One aspect of the present invention provides the use of the compound of the present application or its pharmaceutically acceptable salts, hydrates, solvates, active metabolites, crystalline polymorphs, isotope-labeled forms, isomers, or prodrugs, and the pharmaceutical composition thereof, in the prevention or treatment of HPK1-mediated diseases. 【0258】 One embodiment of the present invention provides a method for modulating (e.g., inhibiting) HPK1 activity, and includes administering to a patient a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer or prodrug thereof, and the pharmaceutical composition thereof, in order to stimulate and / or enhance the immune response occurring in cancer. 【0259】 One embodiment of the present invention provides a method for simultaneously regulating (e.g., inhibiting) the activity of multiple rothein kinase targets (e.g., FLT3, KDR, etc.), and includes administering to a patient the compound of the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer, or prodrug thereof, and the pharmaceutical composition thereof, in order to inhibit the growth of tumor cells. 【0260】 One embodiment of the present invention provides a method for simultaneously modulating (e.g., inhibiting) the activity of HPK1 and several other rhodochrotine kinase targets (e.g., FLT3, KDR, etc.), and for stimulating and / or enhancing the immune response occurring in cancer to inhibit the growth of tumor cells, the present invention includes administering to a patient the compound of the present invention or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer or prodrug thereof, and the pharmaceutical composition thereof. In one embodiment of the present invention, a method for preventing, improving or treating a disease mediated by HPK1 is provided, comprising administering to a patient suffering from a disease mediated by HPK1 a therapeutically effective amount of the compound of the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer or prodrug thereof, and the pharmaceutical composition thereof. 【0261】 In one aspect of the present invention, a method is provided for preventing, improving or treating a tumor (including benign and malignant tumors), comprising administering to a patient suffering from a tumor a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer, or prodrug thereof, and the pharmaceutical composition thereof. 【0262】 In one aspect of the present invention, a method for preventing, improving or treating a virus-induced disease is provided, comprising administering to a patient suffering from a tumor a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer, or prodrug thereof, and the pharmaceutical composition thereof. 【0263】 In one embodiment of the present invention, a method for preventing, improving or treating myelodysplastic syndrome is provided, comprising administering to a patient suffering from a tumor a therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer, or prodrug thereof, and the pharmaceutical composition thereof. 【0264】 In one aspect of the present invention, the use of the compound described herein or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer or prodrug thereof, and the pharmaceutical composition thereof, in the treatment or improvement of a particular disease, wherein the disease includes one or more selected from the group consisting of tumors, myelodysplastic syndromes and virus-induced diseases. 【0265】 In one aspect of the present invention, the use of the compound described herein or its pharmaceutically acceptable salts, hydrates, solvates, active metabolites, crystalline polymorphs, isotope-labeled compounds, isomers, or prodrugs, and the pharmaceutical composition thereof, in the treatment or improvement of tumors is provided. 【0266】 In one aspect of the present invention, the use of the compound described herein or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled compound, isomer, or prodrug thereof, and the pharmaceutical composition thereof, in the treatment or improvement of a virus-induced disease is provided. 【0267】 In one aspect of the present invention, the use of the compound of the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled, isomer or prodrug thereof, or a pharmaceutical composition thereof, for preparing a drug for use in the treatment or improvement of a specific disease, wherein the disease includes one or more selected from the group consisting of tumors, myelodysplastic syndromes and virus-induced diseases. 【0268】 One aspect of the present invention provides the use of the compound of the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer or prodrug thereof, or a pharmaceutical composition thereof, for preparing a drug used for the treatment or improvement of tumors. One aspect of the present invention provides the use of the compound of the present application or a pharmaceutically acceptable salt, hydrate, solvate, active metabolite, crystalline polymorph, isotope-labeled form, isomer or prodrug thereof, or a pharmaceutical composition thereof, for preparing a drug for use in the treatment or improvement of a virus-induced disease. 【0269】 In one embodiment, the tumor includes one or more types selected from the group consisting of chronic or acute leukemia, lymphoma, primary CNS lymphoma, multiple myeloma, lung cancer, hepatocellular carcinoma, cholangiocarcinoma, gallbladder cancer, gastric cancer, colorectal cancer, small intestinal leiomyosarcoma, breast cancer, triple-negative breast cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, vaginal cancer, vulvar cancer, malignant teratoma, pancreatic cancer, pancreatic ductal adenocarcinoma, nasopharyngeal cancer, oral cancer, laryngeal cancer, hypopharyngeal cancer, esophageal squamous cell carcinoma, esophageal adenocarcinoma, thyroid cancer, kidney cancer, bladder cancer, malignant brain tumor, rhabdomyosarcoma, osteosarcoma, chondrosarcoma, osteofibrosarcoma, Ewing's sarcoma, myxoid polyp, malignant thymocyte, malignant peripheral nerve sheath tumor, prostate cancer, testicular cancer, penile cancer, urethral cancer, and cutaneous malignancies (including squamous cell carcinoma, basal cell carcinoma, malignant melanoma, etc.). 【0270】 In one embodiment, the virus causing the disease includes one or more viruses selected from the group consisting of hepatitis viruses, human immunodeficiency viruses, human papillomaviruses, herpes simplex viruses, measles viruses, noroviruses, bocca viruses, coxsackieviruses, Ebola viruses, enteroviruses, lymphocytic meningitis viruses, influenza viruses, SARS viruses, and novel coronaviruses. 【0271】 synthesis The compounds of the present invention and their salts can be prepared by known organic synthesis techniques and can be prepared according to any one of numerous possible synthetic routes (for example, those described in the following protocols). 【0272】 The reactions used to prepare the compounds of the present invention can be carried out in a suitable solvent. A suitable solvent can be substantially inactive with the starting materials (reactants), intermediates, or products at the temperature in which the reaction is carried out (for example, a temperature range from the solidification temperature of the solvent to the boiling temperature of the solvent). A given reaction can be carried out in one solvent or a mixture of various solvents. Depending on the specific reaction step, a person skilled in the art can select a suitable solvent to use for that particular reaction step. 【0273】 The preparation of the compounds of the present invention may involve the protection and deprotection of various chemical groups. Those skilled in the art can easily determine whether protection and deprotection are necessary and select appropriate protecting groups. The following provides a general guide to the preparation of the compounds of the present invention. As those skilled in the art should understand, the methods shown in the protocol can be modified or optimized using general knowledge of organic chemistry to prepare the various compounds of this application. 【0274】 The aforementioned compound can be prepared according to the method shown in the following protocol. Unless otherwise explicitly stated, all methods described herein may be performed in any suitable order, provided that such order does not appear to be inconsistent with the context. The use of any examples or illustrative expressions provided herein (e.g., "like...") is intended solely to better illustrate the invention and not to limit the scope of the invention as otherwise claimed. [Examples] 【0275】 The preparation and properties of a compound of formula (I) according to one embodiment of the present invention will be described in detail below based on examples. The starting materials used are known and commercially available, or can be synthesized using or in accordance with methods known in the art. 【0276】 Unless otherwise specified, all reactions in the examples are carried out by continuous magnetic stirring, and the reaction temperature is measured in degrees Celsius. The reaction can be monitored by any suitable method known in the art, such as nuclear magnetic resonance spectroscopy (NMR), infrared absorption spectroscopy (IR), spectroscopy (e.g., ultraviolet-visible spectroscopy), liquid chromatography-mass spectroscopy (LC-MS), mass spectroscopy, high-performance liquid chromatography, or thin-layer chromatography (or thin-layer chromatography). The product can be purified by any suitable method known in the art, such as column chromatography (normal-phase or reversed-phase), preparative thin-layer chromatography, pulping, or recrystallization. Typically, for normal-phase column chromatography, Qingdao Ocean (Paihao) 100-200 mesh silica gel is used as the support. For thin-layer chromatography (TLC), Merck's Silica gel 60 F254 silica gel plates are used, and for preparative thin-layer chromatography (pre-TLC), silica gel plates are prepared using Anhui Liangchen Silica Source (liangchen guiyuan) GF254. 【0277】 The structures of the compounds in embodiments of the present invention are detected by nuclear magnetic resonance spectroscopy (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). Nuclear magnetic resonance spectra are measured using a Bruker AVANCE-400 nuclear magnetic resonance spectrometer, with deuterated dimethyl sulfoxide (DMSO-d6) or deuterated chloroform (CDCl3) as the measurement solvent. NMR chemical shifts (δ) are expressed in parts per million (ppm), with tetramethylsilane (TMS) as the internal standard. Liquid mass chromatography is performed using an Agilent 1100 series liquid-phase chromatograph and a Bruker HCT-Ultra ion-trap mass spectrometer. 【0278】 Abbreviation [Table 23] 【0279】 Example 1. Compound 3:1 2 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] 【0280】 Step 1: Preparation of 3-(3-(benzyloxy)propoxy)-2-bromopyridine [ka] 2-bromo-3-hydroxypyridine (7.50 g, 43.1 mmol) and 3-benzyloxy-1-bromidehydrin (11.85 g, 51.72 mmol) were mixed with DMF (45 mL), then potassium iodide (716 mg, 4.31 mmol) and potassium carbonate (11.92 g, 86.21 mmol) were added, and the mixture was stirred in an 80°C oil bath for 2 hours. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate (20 mL x 4). The filtrates were combined and concentrated under reduced pressure to dryness. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1) to obtain the title product (13.08 g, yellow solid) in 94.2% yield. ESI-MS:322.1, [M+H] + . 【0281】 Step 2: Preparation of 1-(3-(3-(benzyloxy)propoxy)pyridine-2-yl)-4-methylpiperazine [ka] 3-(3-(benzyloxy)propoxy)-2-bromopyridine (4.50 g, 13.97 mmol), 1-methylpiperazine (7.35 mL, 69.8 mmol), BINAP (1.30 g, 2.09 mmol), and tert-butoxy potassium (3.41 g, 27.9 mmol) were mixed with toluene (45 mL), stirred at room temperature under a nitrogen atmosphere, and then tri(disabenzylacetone)dipalladium (1.28 g, 1.40 mmol) was added. The mixture was then placed in an oil bath at 110°C and stirred for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, concentrated to dry, and the residue was purified by column chromatography (dichloromethane / anhydrous methanol: 20 / 1) to obtain the title product (4.660 g, orange oily substance) in a yield of 97.7%. ESI-MS:342.2, [M+H] + . 【0282】 Step 3: Preparation of 1-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)-4-methylpiperazine [ka] 1-(3-(3-(benzyloxy)propoxy)pyridine-2-yl)-4-methylpiperazine (4.460 g, 13.06 mmol) was added to dichloromethane (27 mL), and the mixture was stirred at 0°C under a nitrogen atmosphere. Then, a solution of N-bromosuccinimide (2.560 g, 14.37 mmol) in dry acetonitrile (27 mL) was added dropwise. After the addition was complete, the reaction was incubated for 2 hours. After the reaction was complete, saturated sodium bisulfite (2 mL) aqueous solution was added to quench the mixture, and 5% sodium carbonate aqueous solution (100 mL) was added to dichloromethane (100 mL x 4). The organic phases were combined, and the mixture was concentrated under reduced pressure to dryness. The residue was purified by column chromatography (dichloromethane / anhydrous methanol: 300 / 1-200 / 1) to obtain the title product (5.090 g, orange solid) in yield of 92.7%. ESI-MS:420.2, [M+H] + . 【0283】 Step 4: Preparation of 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborkane-2-yl)pyridine-2-yl)-4-methylpiperazine [ka] 1-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)-4-methylpiperazine (1,000 g, 2.38 mmol), bis(pinacolato)borate (1.21 g, 4.76 mmol), and potassium acetate (0.700 g, 7.14 mmol) are mixed with dioxane (12 mL), stirred under a nitrogen atmosphere at room temperature, then Pd(dppf)Cl2 (174 mg, 0.24 mmol) is added, and the mixture is stirred in a 90°C oil bath for 22 hours. After the reaction is complete, the mixture is cooled to room temperature, filtered, washed with dioxane (5 mL x 4) on the filter cake, the filtrates are combined, and concentrated under reduced pressure to dryness to obtain the crude title product (2,000 g, brown oily substance), which is used directly in the next reaction. ESI-MS: 468.3, [M+H] + . 【0284】 Step 5: Preparation of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine [ka] 5-Bromo-3-iodo-1-(((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine (800 mg, 1.76 mmol), 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)-4-methylpiperazine (1.070 g, 2.29 mmol) and potassium carbonate (730 mg, 5.28 mmol) are mixed with dioxane (8 mL) and water (2 mL), stirred under a nitrogen atmosphere at room temperature, and then Pd(dppf)Cl2 (129 mg, 0.18 mmol) is added. The reaction was further complicated by adding mmol of the methyl dichloromethane and stirring in an 80°C oil bath for 4 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to dryness, and the residue was purified by column chromatography (dichloromethane / anhydrous methanol / triethylamine: 150 / 1 / 0.3) to obtain the title product (503 mg, brown oily substance) in a yield of 42.8%. ESI-MS:667.2, [M+H] + . 【0285】 Step 6: Preparation of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine [ka] 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine (500 mg, 0.75 mmol) is added to a tetrahydrofuran (5 mL) and tetrahydrofuranil solution of tetrabutylammonium fluoride (1 M, 3.74 mL, 3.74 mmol), and the mixture is stirred at 60°C under a nitrogen atmosphere for 16 hours. After the reaction is complete, the reaction solution is concentrated under reduced pressure to dryness. The residue is diluted with water (10 mL) and saturated sodium carbonate solution (5 mL), extracted with dichloromethane (20 mL x 4), the organic phases are combined, concentrated under reduced pressure to dryness, and the residue is purified by column chromatography (dichloromethane / anhydrous methanol / triethylamine: 100 / 1 / 0.2 to 30 / 1 / 0.1) to obtain the title product (180 mg, yellow oily substance) with a yield of 44.7%. ESI-MS: 537.2, [M+H] + . 【0286】 Step 7: Preparation of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine [ka] To a solution of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine (180 mg, 0.34 mmol) in 1,2-dichloroethane (9 mL), N,N-diisopropylethylamine (166 μL, 1.01 mmol) and p-toluenesulfonyl chloride (128 mg, 0.67 mmol) were added, and the mixture was stirred in an oil bath at 45°C under a nitrogen atmosphere for 15 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to dryness, and the residue was purified by column chromatography (dichloromethane / anhydrous methanol / triethylamine: 1000 / 5 / 3~800 / 10 / 3) to obtain the title product (180 mg, yellow solid) in yield of 86.3%. ESI-MS:691.1, [M+H] + . 【0287】 Step 8: Preparation of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-(4-methylpiperazine-1-yl)pyridin-3-yl)oxypropanol [ka] In a reaction bottle fitted with a calcium chloride drying tube, 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine (200 mg, 0.29 mmol) and dichloromethane (6 mL) were added and stirred at 0°C. Then, a dichloromethane solution of trichloride bore (1 M, 0.87 mL, 0.87 mmol) was added and the mixture was stirred at room temperature for 5 hours until a solid precipitated. After the reaction was complete, methyl tert-butyl ether (10 mL) was added, the mixture was filtered, and the filter cake was dried under vacuum to obtain the crude hydrochloride salt of the title product (219 mg, brown solid). ESI-MS:601.1, [M+H] + . 【0288】 Step 9: Preparation of 3-fluoro-2-(3-(5-(3-(hydroxypropoxy))-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol [ka] 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol (200 mg, 0.33 mmol), 2-fluoro-6-hydroxyphenylboronic acid (78 mg, 0.50 mmol), and potassium phosphate (212 mg, 1.00 mmol) are mixed with dioxane (8 mL) and water (2 mL), and the mixture is stirred at room temperature under a nitrogen atmosphere. Then XPhos-Pd-G2 (13 mg, 0.02 mmol) is added, and the mixture is stirred in a 90°C oil bath for 40 minutes. After the reaction is complete, the reaction mixture is cooled to room temperature, diluted with 5% sodium chloride aqueous solution (30 mL), and then mixed with dichloromethane (50 mL). Extraction was performed using 4 mL of cellulose sulfate, the organic phase was combined, and the mixture was concentrated under reduced pressure to dryness. The residue was purified by column chromatography (dichloromethane / anhydrous methanol / triethylamine: 40 / 1 / 0.1-30 / 1 / 0.1) to obtain the crude solid. Dichloromethane (200 mL) was added to the solid to dissolve it, washed with saturated sodium carbonate (50 mL), washed with purified water (50 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to dryness to obtain the title product (133 mg, yellow solid), with a yield of 63.2%. ESI-MS:633.2, [M+H] + . 【0289】 Step 10:1 2 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] To a solution of 3-fluoro-2-(3-(5-(3-(hydroxypropoxy))-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol (80 mg, 0.13 mmol) in dry tetrahydrofuran (10 mL), add triphenylphosphine (166 mg, 0.63 mmol), and stir in an oil bath at 40°C under a nitrogen atmosphere. Then, add a solution of diisopropyl azodicarboxylate (125 μL, 0.63 mmol) in dry tetrahydrofuran (2 mL) dropwise, and stir at 40°C for 3 hours after the addition is complete. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to dryness, and the residue was purified by column chromatography (dichloromethane / anhydrous methanol / triethylamine: 50 / 1 / 0.1) to obtain the crude product. The crude product was purified by thin-layer chromatography (dichloromethane / anhydrous methanol: 10 / 1) to obtain the title product (49 mg, yellow solid), with a yield of 63.0%. ESI-MS:615.2, [M+H] + . 【0290】 Step 11:1 2 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] 1 2 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6-Fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane (49 mg, 0.08 mmol) was dissolved in methanol (3 mL), and then methanol solution of sodium hydroxide (1 M, 1.5 mL) was added, and the mixture was stirred at room temperature for 20 minutes. After the reaction was complete, the mixture was purified by thin-layer chromatography (dichloromethane / anhydrous methanol: 10 / 1) to obtain the title product (31 mg, pale yellow solid) in yield of 84.5%. ESI-MS:461.2, [M+H] + . 1 H NMR(DMSO-d6,400 MHz)δ13.70(s,1H),9.11(s,1H),8.71(s,1H),8.36(d,J=1.6 Hz,1H),8.07(s,1H),7.44-7.36(m,1H),7.02-6.93(m,2H),4.62-4.51(m,2H),4.17 -4.04(m,2H),3.56-3.37(m,4H),2.49-2.41(m,4H),2.39-2.31(m,2H),2.24(s,3H). 【0291】 Example 4. Compound 4:1 2 -(4-morpholinyl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] 【0292】 Step 1: Preparation of 4-(3-(3-(benzyloxy)propoxy)pyridine-2-yl)morpholinium [ka] 3-(3-(benzyloxy)propoxy)-2-bromopyridine (4.50 g, 14.0 mmol), morpholinium (6.08 mL, 69.8 mmol), BINAP (1.30 g, 2.09 mmol), and tert-butoxy potassium (3.41 g, 27.9 mmol) are mixed with toluene (45 mL), stirred at room temperature under a nitrogen atmosphere, then tri(disabenzylacetone)dipalladium (1.28 g, 1.40 mmol) is added, and the mixture is stirred in an oil bath at 110°C for 12 hours. After the reaction was complete, the temperature was lowered to 0°C, and 200 mL of saturated ammonium chloride aqueous solution was added to quench the mixture. The mixture was extracted with ethyl acetate (200 mL x 2), washed with saturated brine (200 mL), and the organic phase was concentrated under reduced pressure to dryness. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1-3 / 1) to obtain the title product (3.730 g, brown oily substance) in yield of 81.3%. ESI-MS:329.2, [M+H] + . 【0293】 Step 2: Preparation of 4-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)morpholinium [ka] 4-(3-(3-(benzyloxy)propoxy)pyridine-2-yl)morpholinium (3.53 g, 10.8 mmol) was dissolved in dichloromethane (21 mL), stirred under a nitrogen atmosphere at 0°C, and then a solution of N-bromosuccinimide (1.91 g, 10.75 mmol) in dry acetonitrile (21 mL) was added dropwise. After the addition was complete, the reaction was incubated for 0.5 hours. After the reaction was complete, saturated sodium bisulfite (1 mL) was added to quench the reaction mixture, and the reaction solution was concentrated under reduced pressure to dryness. The residue was diluted with 5% aqueous sodium carbonate (100 mL), extracted with dichloromethane (100 mL x 3), the organic phases were combined, and the mixture was concentrated under reduced pressure to dryness. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1) to obtain the title product (3.60 g, yellow oily liquid) in yield of 82.3%. ESI-MS:407.3 / 409.3, [M+H] + . 【0294】 Step 3: Preparation of 4-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborakane-2-yl)pyridine-2-yl)morpholinium [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)morpholinium as a starting material, in accordance with the process of Example 1 (step 4), instead of 1-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)-4-methylpiperazine. The crude product is used directly in the next reaction. ESI-MS: 455.3, [M+H] + . 【0295】 Step 4: Preparation of 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-ylpyridine-2-ylmorpholinium [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)morpholinium as a starting material, instead of 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxabouralkane-2-yl)pyridine-2-yl)morpholinium, following the process of Example 1 (step 5), with respect to 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxabouralkane-2-yl)pyridine-2-yl)morpholinium. The yield is 56.0%. ESI-MS: 654.2, [M+H] + . 【0296】 Step 5: Preparation of 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1H-pyrazolo[3,4-c]pyridine-3-yl)pyridine-2-yl)morpholinium [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-ylpyridine-2-ylmorpholinium as a starting material, instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-ylpyridine-2-ylmorpholinium, according to the process of Example 1 (step 6). The yield is 62.6%. ESI-MS:524.1, [M+H] + . 【0297】 Step 6: Preparation of 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)pyridine-2-yl)morpholinium [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1H-pyrazolo[3,4-c]pyridine-3-yl)pyridine-2-yl)morpholinium as a starting material, instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine. The yield is 91.3%. ESI-MS:678.1, [M+H] + . 【0298】 Step 7: Preparation of 3-((5-(5-(5-bromo-1-cresylyl-1H-pyrazolo[3,4-c]pyridine-3-yl]-2-morpholinopyridine-3-yl)oxy)propanol [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)pyridine-2-yl)morpholinium as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine, following the process of Step 8 of Example 1. After the reaction is complete, the mixture is concentrated under reduced pressure at 30°C until dry. Water (20 mL) is added to the residue, and it is diluted with saturated sodium carbonate aqueous solution (10 mL). The mixture is extracted twice with dichloromethane (50 mL), the organic phases are combined, and the mixture is concentrated under reduced pressure until dry. The residue is purified by column chromatography (eluent: ethyl acetate) to obtain the title product as a yellow solid, with a yield of 83.0%. ESI-MS:588.1, [M+H] + . 【0299】 Step 8: Preparation of 3-fluoro-2-(3-(5-(3-(hydroxypropoxy))-6-morpholinopyridine-3-yl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol [ka] The compound is prepared using 3-((5-(5-(5-bromo-1-crezylyl-1H-pyrazolo[3,4-c]pyridine-3-yl]-2-morpholinopyridine-3-yl)oxy)propanol as a starting material instead of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol, following the process of Step 9 of Example 1. The yield is 74.5%. ESI-MS:620.2, [M+H] + . 【0300】 Step 9:1 2 -(4-morpholinyl)-2 1 -Benzenesulfonyl-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] The compound is prepared using 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol as a starting material, in place of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazole[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol, according to the process of Example 1 (step 10). The yield is 28.2%. ESI-MS:602.1, [M+H] + . 【0301】 Step 10:1 2 -(4-morpholinyl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane [ka] The compound was prepared according to the process of Example 1 (step 11): 2 -(4-morpholinyl)-2 1 -Benzenesulfonyl-3 6 Using -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane, 2 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 It is prepared as a starting material instead of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane. The yield is 80.6%. ESI-MS:448.2, [M+H] + . 1 H NMR(DMSO-d6,400 MHz)δ13.74(s,1H),9.11(s,1H),8.71(s,1H),8.38(d,J=1.4 Hz,1H),8.09(s,1H),7.45-7.31(m,1H),7.06-6.84(m,2H),4.67-4.50(m,2H) ,4.19-4.03(m,2H),3.82-3.67(m,4H),3.52-3.40(m,4H),2.39-2.28(m,2H). 【0302】 Example 5. Compound 5:1 6 -(4-morpholinyl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] 【0303】 Step 1: Preparation of 1-(3-(benzyloxy)propoxy)-2-bromobenzene [ka] The compound is prepared using 2-bromophenol as a starting material instead of 2-bromo-3-hydroxypyridine, following the process of Example 1 (Step 1). The resulting crude compound is used directly in the next reaction without purification. ESI-MS:321.0, [M+H] + . 【0304】 Step 2: Preparation of 4-(2-(3-(benzyloxy)propoxy)phenyl)morpholinium [ka] The compound is prepared using 1-(3-(benzyloxy)propoxy)-2-bromobenzene as a starting material instead of 3-(3-(benzyloxy)propoxy)-2-bromopyridine, following the process of Example 1 (Step 2). The resulting crude compound is used directly in the next reaction without purification. The yield for both steps is 72.8%. ESI-MS:328.2, [M+H] + . 【0305】 Step 3: Preparation of 4-(2-(3-(benzyloxy)propoxy)-4-bromophenyl)morpholinium [ka] The compound is prepared using 4-(2-(3-(benzyloxy)propoxy)phenyl)morpholinium as a starting material in place of 1-(3-(3-(benzyloxy)propoxy)pyridine-2-yl)-4-methylpiperazine, following the process of Example 1 (step 3). The resulting crude compound is used directly in the next reaction without purification. ESI-MS:406.1, [M+H] + . 【0306】 Step 4: Preparation of 4-(2-(3-(benzyloxy)propoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborakane-2-yl)phenyl)morpholinium [ka] The compound is prepared using 4-(2-(3-(benzyloxy)propoxy)-4-bromophenyl)morpholinium as a starting material instead of 1-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)-4-methylpiperazine, following the process of Example 1 (step 4). The resulting crude compound is used directly in the next reaction without purification. ESI-MS: 454.3, [M+H] + . 【0307】 Step 5: Preparation of 4-(2-(3-(benzyloxy)propoxy)-4-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)morpholinium [ka] The compound is prepared using 4-(2-(3-(benzyloxy)propoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxabouralkane-2-yl)phenyl)morpholinium as a starting material instead of 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)-4-methylpiperazine, following the process of Example 1 (step 5). The yield of the three-step reaction is 41.4%. ESI-MS:653.2, [M+H] + . 【0308】 Step 6: Preparation of 4-{2-[3-(benzyloxy)propoxy]-4-{5-bromo-1H-pyrazolo[3,4-c]pyridine-3-yl}phenyl}morpholinium [ka] The compound is prepared using 4-(3-(3-(benzyloxy)propoxy)-5-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-ylpyridine-2-ylmorpholinium as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine according to the process of Example 1 (step 6), with respect to 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine as a starting material. The yield is 91.1%. ESI-MS:523.1, [M+H] + . 【0309】 Step 7: Preparation of 4-(2-(3-(benzyloxy)propoxy)-4-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)morpholinium [ka] The compound is prepared using 4-{2-[3-(benzyloxy)propoxy]-4-{5-bromo-1H-pyrazolo[3,4-c]pyridine-3-yl}phenyl}morpholinium as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine, following the process of Example 1 (step 7). The yield is 90.6%. ESI-MS:677.1, [M+H] + . 【0310】 Step 8: Preparation of 3-(5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-morpholiniumphenoxy)-1-propanol [ka] The compound is prepared using 4-(2-(3-(benzyloxy)propoxy)-4-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)morpholinium as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine, according to the process of Example 4 (step 7), with respect to 4-(2-(3-(benzyloxy)propoxy)-4-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine). The yield is 53.6%. ESI-MS:587.1, [M+H] + . 【0311】 Step 9: Preparation of 3-fluoro-2-(3-(3-(3-hydroxypropoxy)-4-morpholinophenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol [ka] The compound is prepared by using 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-morpholiniumphenoxy)-1-propanol as a starting material instead of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-(4-methylpiperazine-1-yl)pyridin-3-yl)oxypropanol) in accordance with the process of Example 1 (step 9). The yield is 93.9%. ESI-MS:619.2, [M+H] + . 【0312】 Step 10:1 6 -(4-morpholinyl)-2 1 -Benzenesulfonyl-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] The compound is prepared by using 3-fluoro-2-(3-(3-(3-hydroxypropoxy)-4-morpholinophenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol as a starting material in place of 3-fluoro-2-(3-(5-(3-hydroxypropoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol, following the process of Example 1 (step 10). The crude product of the resulting compound is used in the following reaction. ESI-MS:601.2, [M+H] + . 【0313】 Step 11:1 6 -(4-morpholinyl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] The compound was prepared according to the process of Example 1 (step 11): 6 -(4-morpholinyl)-2 1 -Benzenesulfonyl-3 6 -Fluoro-4,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane 2 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 It is prepared as a starting material instead of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane. The yield for both steps is 28.6%. ESI-MS: 447.2, [M+H] + . 1H NMR(DMSO-d6,400 MHz)δ13.62(s,1H),9.09(s,1H),8.76(s,1H),7.87(d,J=0.8 Hz,1H),7.50(dd,J=8.0,1.2 Hz,1H),7.44-7.36(m,1H),7.04(d,J=8.4 Hz,1H),7.01-6.95(m,2H),4.60-4.52(m,2H),4.15-4.07(m,2H),3.79-3.72(m,4H),3.10-3.03(m,4H),3.38-3.28(m,2H). 【0314】 Example 6. Compound 6:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] 【0315】 Step 1: Preparation of 3-(3-(3-(benzyloxy)propoxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine [ka] The compound is prepared using 3-(3-(3-(benzyloxy)propoxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1H-pyrazolo[3,4-c]pyridine as a starting material, in place of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine, according to the process of Example 1 (step 7). The yield is 97%. ESI-MS:690.1, [M+H] + . 【0316】 Step 2: Preparation of 3-(5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)phenoxy)-1-propanol [ka] The compound is prepared by following the process of Example 1 (step 8), using 3-(3-(3-(benzyloxy)propoxy)-4-(4-methylpiperazine-1-yl)phenyl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine. The hydrochloride salt of the title molecule is obtained. The yield is 99%. ESI-MS:600.1, [M+H] + . 【0317】 Step 3: Preparation of 3-fluoro-2-(3-(3-(3-hydroxypropoxy)-4-(4-methylpiperazine-1-yl)phenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol [ka] The compound is prepared using 3-(5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)phenoxy)-1-propanol as a starting material instead of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol) as a starting material according to the process of Example 1 (step 9). The yield is 36.8%. ESI-MS:632.2, [M+H] + . 【0318】 Step 4:16 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] The compound is prepared using 3-fluoro-2-(3-(3-(3-hydroxypropoxy)-4-(4-methylpiperazine-1-yl)phenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol as a starting material in place of 3-fluoro-2-(3-(5-(3-hydroxypropoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol, according to the process of Example 1 (step 10). The yield is 39%. ESI-MS:614.2, [M+H] + . 【0319】 Step 5:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] The compound was prepared according to the process of Example 1 (step 11): 6 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 -Fluoro-4,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane 2 -(4-methylpiperazine-1-yl)-2 1-Benzenesulfonyl-3 6 It is prepared as a starting material instead of -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane. The yield for both steps is 62%. ESI-MS:460.2, [M+H] + . 1 H NMR(DMSO-d6,400 MHz)δ13.62(s,1H),9.09(s,1H),8.75(s,1H),7.85(d,J=0.8 Hz,1H),7.47(dd,J=8.4,1.6 Hz,1H),7.44-7.36(m,1H),7.02(d,J=8.0 Hz,1H),7.00-6.93(m,2H),4.62-4.51(m,2H),4.17-4.04(m,2H),3.14-3.00(m,4H),2.49-2.41(m,4H),2.39-2.31(m,2H),2.24(s,3H). 【0320】 Example 7. Compound 7:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0321】 Step 1: Preparation of 1-(4-(benzyloxy)butyloxy)-2-bromobenzene [ka] At room temperature, dissolve (4-bromide-butyloxy)methylbenzene (5.218 g, 21.46 mmol) and 2-bromophenol (3.898 g, 23.61 mmol) in DMF (50 mL), add anhydrous potassium carbonate (8.156 g, 59.0 mmol), and stir overnight at room temperature. Quench the reaction by adding the reaction mixture to a semi-saturated aqueous sodium bicarbonate solution (500 mL), extract with ethyl acetate (200 mL x 2), wash the organic phase with water (400 mL) and saturated brine (400 mL), dry over anhydrous sodium sulfate, filter by suction, and evaporate by rotary evaporation to dryness. The resulting crude product of the title compound is purified and used directly in the next reaction. ESI-MS:335.0, [M+H] + . 【0322】 Step 2: Preparation of 1-(2-(4-(benzyloxy)butyloxy)phenyl)-4-methylpiperazine [ka] The compound was prepared according to the process of Example 1 (Step 2), using 1-(4-(benzyloxy)butyloxy)-2-bromobenzene as a starting material instead of 3-(3-(benzyloxy)propoxy)-2-bromopyridine, and using a cresil solution of tert-pentanol potassium instead of tert-butoxy potassium. The yield for both steps was 79.7%. ESI-MS:355.2, [M+H] + . 【0323】 Step 3: Preparation of 1-(2-(4-(benzyloxy)butyloxy)-4-bromophenyl)-4-methylpiperazine [ka] Compound 1-(2-(4-(benzyloxy)butyloxy)phenyl)-4-methylpiperazine (6.064 g, 17.11 mmol) is dissolved in acetic acid (78 mL), and a solution of liquid bromine (967 μL, 17.62 mmol) in acetic acid (20 mL) is slowly added dropwise at room temperature, stirring continuously at room temperature for 2 hours. After the reaction is complete, the reaction mixture is concentrated under vacuum, the resulting residue is diluted with water (200 mL), the pH is adjusted to 12 with 2N NaOH aqueous solution, extracted with ethyl acetate (100 mL x 2), the organic phase is washed with saturated brine (200 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated by rotary evaporation to dryness. The resulting crude product of the title compound is used directly in the next reaction without purification. ESI-MS:433.1, [M+H] + . 【0324】 Step 4: Preparation of 1-(2-(4-(benzyloxy)butyloxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxyboalkane-2-yl)phenyl)-4-methylpiperazine [ka] The compound is prepared using 1-(2-(4-(benzyloxy)butyloxy)-4-bromophenyl)-4-methylpiperazine as a starting material instead of 1-(3-(3-(benzyloxy)propoxy)-5-bromopyridine-2-yl)-4-methylpiperazine, following the process of Example 1 (step 4). The resulting crude compound is used directly in the next reaction without purification. ESI-MS:481.3, [M+H] + . 【0325】 Step 5: Preparation of 3-(3-(4-(benzyloxy)butyloxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine [ka] The compound is prepared by using 1-(2-(4-(benzyloxy)butyloxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxyboalkane-2-yl)phenyl)-4-methylpiperazine as a starting material instead of 1-(3-(3-(benzyloxy)propoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)-4-methylpiperazine according to the process of Example 1 (step 5). The yield of the three-step reaction is 28%. ESI-MS:680.2, [M+H] + . 【0326】 Step 6: Preparation of 3-(3-(4-(benzyloxy)butyloxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1H-pyrazolo[3,4-c]pyridine [ka] The compound is prepared using 1-{2-[4-(benzyloxy)butyloxy]-4-(5-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl}-4-methylpiperazine as a starting material instead of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazine-1-yl)pyridine-3-yl)-5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine, according to the process of Example 1 (step 6). The yield is 50.7%. ESI-MS:550.1, [M+H] + . 【0327】 Step 7: Preparation of 3-(3-(4-(benzyloxy)butyloxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine [ka] The compound is prepared using 3-(3-(4-(benzyloxy)butyloxy)-4-(4-methylpiperazin-1-yl)phenyl)-5-bromo-1H-pyrazolo[3,4-c]pyridine as a starting material in place of 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1H-pyrazolo[3,4-c]pyridine, according to the process of Example 1 (step 7). ESI-MS:704.2, [M+H] + . 【0328】 Step 8: Preparation of 4-(5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)phenoxy)-1-butanol [ka] The compound is prepared using 3-(5-(3-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine as the starting material, instead of 3-(3-(4-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine, according to the process of Example 1 (step 8), with 3-(3-(4-(benzyloxy)butyloxy)-4-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine as the starting material, instead of 3-(3-(4-(benzyloxy)propoxy)-6-(4-methylpiperazin-1-yl)pyridine-3-yl)-5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine. The yield for both steps is 79.7%. ESI-MS:614.1, [M+H] + . 【0329】 Step 9: Preparation of 3-fluoro-2-(3-(3-(4-hydroxybutyloxy)-4-(4-methylpiperazine-1-yl)phenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol [ka] The compound is prepared using 4-(5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-(4-methylpiperazine-1-yl)phenoxy)-1-butanol as a starting material instead of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-(4-methylpiperazine-1-yl)pyridin-3-yl)oxypropanol, according to the process of Example 1 (step 9). ESI-MS:646.2, [M+H] + . 【0330】 Step 10:1 6 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 Preparation of -fluoro-4,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] The compound is prepared using 3-fluoro-2-(3-(3-(4-hydroxybutyloxy)-4-(4-methylpiperazine-1-yl)phenyl)-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol as a starting material instead of 3-((5-(5-bromo-1-toluenesulfonyl-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(4-methylpiperazine-1-yl)pyridine-3-yl)oxypropanol, following the process of Example 1 (step 10). The crude product of the resulting compound is used in the following reaction. ESI-MS:628.2, [M+H] + . 【0331】 Step 11:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6Preparation of -fluoro-4,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] The compound was prepared according to the process of Example 1 (step 11): 6 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 Using -fluoro-4,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterononane, 2 -(4-methylpiperazine-1-yl)-2 1 -Benzenesulfonyl-3 6 It is prepared using -fluoro-4,8-dioxa-1(3,5)-pyridine hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane as a starting material. The yield for both steps is 61.5%. ESI-MS: 474.2, [M+H] + . 1 H NMR(DMSO-d6,400 MHz)δ13.76(s,1H),9.14(s,1H),8.13(s,1H),7.40-7.35(m,1H),7.28(dd,J=8.4,1.6 Hz,1H),7.22(d,J=0.8 Hz,1H),7.09(d,J=8.1 Hz,1H),6.98(d,J=8.5 Hz,1H),6.88(dd,J=10.0,8.7 Hz,1H),4.30-4.22(m,2H),4.15-4.07(m,2H),3.50-2.80(m,8H),2.65(br,3H),2.28-2.14(m,4H),1.84-1.72(m,2H). 【0332】 The following compounds in the examples are synthesized via appropriate intermediates following a method similar to that in Example 1: [Table 24] [Table 25] [Table 26] [Table 27] [Table 28] [Table 29] 【0333】 Example 9. Compound 9:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] 【0334】 Step 1: Preparation of 2-(2-bromo-3-fluorobenzyloxy)ethanol [ka] Under a nitrogen atmosphere and at 0°C, ethanediol (1.758 g, 28.37 mmol) is added dropwise to a suspension of sodium hydride (82 mg, 2.05 mmol) in dry tetrahydrofuran (5 mL), and the mixture is stirred at the same temperature for 30 minutes. The temperature is then raised to room temperature, and 2-bromo-3-fluorobenzyl bromide (500 mg, 1.87 mmol) is added. The mixture is stirred at room temperature for 2 hours, then raised to 50°C and stirred for 2 hours. The system temperature is cooled to 0°C, the mixture is quenched with water (50 mL), extracted with ethyl acetate (50 mL x 2), the organic phase is washed once each with water (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The title product (417 mg, colorless oily) is obtained in 90% yield. ESI-MS:250.2, [M+H] + . 【0335】 Step 2: Preparation of 2-(2-(2-bromo-3-fluorobenzyl)oxy)ethoxy)tetrahydro-2H-pyran [ka] To a solution of 2-(2-bromo-3-fluorobenzyloxy)ethanol (417 mg, 1.67 mmol) in dichloromethane (5 mL), 3,4-dihydro-2H-pyran (169 mg, 2.01 mmol) and 4-methylbenzenesulfinate pyridine salt (84 mg, 0.34 mmol) were added and the mixture was stirred at room temperature for 14 hours. Then, sodium carbonate solution (40 mL) was added and the mixture was extracted with dichloromethane (40 mL). The organic phase was washed once each with water (40 mL) and saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 10 / 1) to obtain the title product (506 mg, colorless oily substance) in yield of 90.8%. ESI-MS:334.2, [M+H] + . 【0336】 Step 3: Preparation of 2-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ka] In a dry ice ethanol bath under a nitrogen atmosphere, a solution of 2-(2-(2-bromo-3-fluorobenzyl)oxy)ethoxy)tetrahydro-2H-pyran (386 mg, 1.16 mmol) in dried tetrahydrofuran (4 mL) was cooled to -70°C. Then, a solution of n-butyllithium in n-hexane (2.5 M, 0.56 mL, 1.39 mmol) was slowly added dropwise, maintaining the internal temperature below -60°C. After the addition was complete, the mixture was stirred at -65°C for 1 hour. Then, isopyropanol pinacol borate (259 mg, 1.39 mmol) was slowly added dropwise to the reaction system, stirred at -65°C for 1 hour, and then the temperature was raised to 0°C and stirred for 1 hour. The reaction was cooled to -10°C, quenched with ammonium chloride solution (40 mL), extracted with ethyl acetate (40 mL x 2), the organic phase was washed once each with water (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The title compound (352 mg, pale yellow oily substance) was obtained in a yield of 80%. ESI-MS:398.2, [M+NH4]+. 【0337】 Step 4: Preparation of tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate [ka] Under a nitrogen atmosphere, a solution of 2-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (300 mg, 0.46 mmol), tert-butyl 4-(2-acetoxy-4-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate (352 mg, 0.93 mmol), sodium carbonate (148 mg, 1.39 mmol), and Xphos-Pd-G2 (37 mg, 0.05 mmol) in 1,4-dioxane (5 mL) and water (1 mL) is heated to 80°C and stirred for 4 hours. The solution was cooled to room temperature, diluted with water (60 mL), extracted with ethyl acetate (50 mL x 2), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and evaporated to dryness by suction filtration. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1-2 / 1) to obtain the title product (322 mg, yellow solid) with a yield of 84%. ESI-MS:820.4, [M+H] + . 【0338】 Step 5: Preparation of tert-butyl 4-(4-(5-(2-fluoro-6-((2-hydroxyethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate [ka] At 0°C, a solution of tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate (322 mg, 0.39 mmol) in methanol (5 mL) is mixed with an aqueous lithium hydroxide solution (3M, 1.0 mL), and the mixture is stirred at the same temperature for 1 hour. After the reaction is complete, the pH is adjusted to 7 with a 5% citric acid solution, extracted with ethyl acetate (50 mL x 2), the organic phase is washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness to obtain a crude product (286 mg). The resulting crude product (286 mg, 0.37 mmol) is dissolved in anhydrous methanol (5 mL), and p-tosylic acid monohydrate (70 mg, 0.37 mmol) is added at room temperature. The mixture is then heated to 40°C and stirred for 14 hours. The reaction system is evaporated by rotary evaporation to dryness, the residue is dissolved in dichloromethane (50 mL), and then washed with sodium bicarbonate solution (30 mL), water (30 mL), and saturated brine (30 mL) in that order. The mixture is dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue is purified by column chromatography (dichloromethane / methanol: 15 / 1) to obtain the title compound (250 mg, pale yellow solid) in 92% yield. ESI-MS: 694.4, [M+H] + . 【0339】 Step 6:1 6 -(4-tert-butoxycarbonylpiperazine-1-yl)-2 1 -((2-trimethylsilylethyl)oxymethyl)-3 6 Preparation of -fluoro-5,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] Under a nitrogen atmosphere and at room temperature, tributylphosphine (186 mg, 0.92 mmol) is added dropwise to a solution of TMAD (159 mg, 0.92 mmol) in dry tetrahydrofuran (20 mL), and after stirring for 5 minutes, a solution of tert-butyl 4-(4-(5-(2-fluoro-6-((2-hydroxyethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate (160 mg, 0.23 mmol) in tetrahydrofuran (5 mL) is added dropwise. After the addition is complete, the mixture is stirred at room temperature for 1 hour. Water (50 mL) is added to quench the mixture, and the organic phase is extracted with ethyl acetate (50 mL x 2). The organic phase is washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography (petroleum ether / ethyl acetate: 5 / 1-1 / 1) to obtain the title compound (64 mg, white solid) in a yield of 48%. ESI-MS: 676.3, [M+H] + . 【0340】 Step 7:1 6 -(1-piperazinyl)-2 1 H-3 6 Preparation of -fluoro-5,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] At 0℃, 1 6 -(4-tert-butoxycarbonylpiperazine-1-yl)-2 1 -((2-trimethylsilylethyl)oxymethyl)-3 6To a solution of -fluoro-5,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterooctane (50 mg, 0.07 mmol) in dichloromethane (5 mL), trifluoroacetic acid (1.0 mL) is added dropwise, and the mixture is stirred at room temperature for 14 hours. The reaction system is swiftly evaporated to dryness, dissolved in dichloromethane (20 mL), sodium carbonate solution (20 mL) is added, and the mixture is extracted with a dichloromethane / isopyropanol mixed solvent (1 / 4, 20 mL x 3). The extracts are combined and swiftly evaporated to dryness to obtain the crude product. The crude product is further dissolved in acetonitrile (5 mL), and ammonia water (0.5 mL) is added, and the mixture is stirred for 30 minutes. Add water (30 mL), extract with a mixed solvent of dichloromethane / isopyropanol (1 / 4, 20 mL x 3), combine the organic phases, wash once with saturated saline solution (20 mL), dry over anhydrous sodium sulfate, filter by suction, and evaporate to dryness. The title compound (33 mg, white solid) is obtained in 100% yield. ESI-MS:446.2, [M+H] + . 【0341】 Step 8:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] At room temperature, 1 6 -(1-piperazinyl)-2 1 H-3 6To a dichloromethane / methanol mixed solvent system (1 / 1, 4 mL) containing -fluoro-5,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane (33 mg, 0.07 mmol), 1H-benzotriazole-1-methanol (14 mg, 0.09 mmol), sodium acetate (12 mg, 0.14 mmol), and sodium triacetoxyborohydride (31 mg, 0.14 mmol), the mixture is stirred at room temperature for 12 hours. The reaction is quenched with sodium bicarbonate solution (30 mL), extracted with dichloromethane / isopyropanol mixed solvent (4 / 1, 20 mL x 3), the organic phases are combined and washed once with saturated saline solution (30 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by thin-layer chromatography (dichloromethane / methanol: 7 / 1) to obtain the title product (18 mg, white solid) in a yield of 53%. ESI-MS:460.2, [M+H] + . 1 H NMR(DMSO-d6,400MHz)δ13.76(s,1H),9.15(s,1H),9.00(s,1H),7.96(d,J=1.5 Hz,1H),7.62(dd,J=8.2,1.6 Hz,1H),7.49-7.44(m,2H),7.38-7.33(m,1H),7.03(d,J=8.4 Hz,1H),4.51(br,2H),4.41(s,2H),4.08(s,2H),3.05(s,4H),2.55-2.45(m,4H),2.24(m,3H). 【0342】 Example 10. Compound 10:1 6 -(1-piperazinyl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0343】 Step 1: Preparation of 3-(2-bromo-3-fluorobenzyloxy)-1-propanol [ka] The compound is prepared using 1,3-propanediol instead of ethanediol as a starting material, following the process of Example 9 (Step 1). The yield is 100%. ESI-MS:262.9, [M+H] + . 【0344】 Step 2: Preparation of 2-(3-((2-bromo-3-fluorobenzyl)oxy)propoxy)tetrahydro-2H-pyran [ka] The compound is prepared using 3-(2-bromo-3-fluorobenzyloxy)-1-propanol as a starting material instead of 2-(2-bromo-3-fluorobenzyloxy)ethanol, following the process of Example 9 (Step 2). The yield is 93.1%. ESI-MS: 346.9, [M+H] + . 【0345】 Step 3: Preparation of 2-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ka] The compound is prepared according to the process of Example 9 (step 3), using 2-(3-((2-bromo-3-fluorobenzyl)oxy)propoxy)tetrahydro-2H-pyran as a starting material instead of 2-(2-(2-bromo-3-fluorobenzyl)oxy)ethoxy)tetrahydro-2H-pyran. The yield is 93.1%. ESI-MS:412.2, [M+H] + . 【0346】 Step 4: Preparation of tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate [ka] The compound is prepared by using 2-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as a starting material instead of 2-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane) according to the process of Example 9 (step 4), with 2-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane) as a starting material in place of 2-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane). The yield is 95%. ESI-MS:834.4, [M+H] + . 【0347】 Step 5: Preparation of tert-butyl 4-(4-(5-(2-fluoro-6-((3-hydroxypropoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate [ka] The compound is prepared using tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate as a starting material instead of tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate according to the process of Example 9 (step 5), with tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate as a starting material in place of tert-butyl 4-(2-acetoxy-4-(5-(2-fluoro-6-((2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate. The yield is 88%. ESI-MS:708.3, [M+H] + . 【0348】 Step 6:1 6 -(4-tert-butoxycarbonylpiperazine-1-yl)-2 1 -((2-trimethylsilylethyl)oxymethyl)-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] The compound is prepared by using tert-butyl 4-(4-(5-(2-fluoro-6-((3-hydroxypropoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate as a starting material instead of tert-butyl 4-(4-(5-(2-fluoro-6-((2-hydroxyethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate according to the process of Example 9 (step 6), with tert-butyl 4-(4-(5-(2-fluoro-6-((2-hydroxyethoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)piperazine-1-carboxylate as a starting material. The yield is 77%. ESI-MS:690.3, [M+H] + . 【0349】 Step 7:1 6 -(1-piperazinyl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] The compound was prepared according to the process of Example 9 (step 7), 6 -(4-tert-butoxycarbonylpiperazine-1-yl)-2 1 -((2-trimethylsilylethyl)oxymethyl)-3 6 Using -fluoro-5,9-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheteronanane 1 6 -(4-tert-butoxycarbonylpiperazine-1-yl)-2 1 -((2-trimethylsilylethyl)oxymethyl)-3 6It is prepared as a starting material instead of -fluoro-5,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane. The yield is 100%. ESI-MS:460.3, [M+H] + . 【0350】 Example 11. Compound 11:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] The compound was prepared according to the process of Example 9 (step 8), 6 -(1-piperazinyl)-2 1 H-3 6 Using -fluoro-5,9-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheteronanane 1 6 -(1-piperazinyl)-2 1 H-3 6 It is prepared as a starting material instead of -fluoro-5,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterooctane. The yield is 54%. ESI-MS: 474.2, [M+H] + . 1H NMR(DMSO-d6,400 MHz)δ13.76(s,1H),9.14(d,J=0.8 Hz,1H),8.47(s,1H),7.70(d,J=1.6 Hz,1H),7.54-7.50(m,1H),7.50-7.45(m,1H),7.43-7.38(m,1H),7.36-7.29(m,1H),7.03(d,J=8.0 Hz,1H),4.40(t,J=6.4 Hz,2H),4.33(s,2H),3.76-3.66(m,2H),3.05(s,4H),2.54-2.44(m,4H),2.24(s,3H),2.12-2.02(m,2H). 【0351】 Example 12. Compound 12:1 6 -(4-(2-hydroxyethyl)piperazin-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0352】 Step 1:1 6 -(4-(2-(tert-butyldimethylsilyloxy)ethyl)piperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] At room temperature, 1 6 -(1-piperazinyl)-2 1 H-3 6To a mixture of -fluoro-5,9-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclononane (20 mg, 0.04 mmol) in dichloromethane (1 mL) and anhydrous methanol (1 mL), (tert-butyldimethylsilyloxy)acetaldehyde (16 mg, 0.09 mmol) was added and the mixture was stirred for 1 hour. Sodium triacetoxyburohydride (28 mg, 0.13 mmol) was then added and the mixture was stirred at room temperature for 12 hours. The reaction was quenched with sodium bicarbonate solution (10 mL), extracted with a mixed solvent of dichloromethane / isopyropanol (1 / 4, 20 mL x 2), the organic phases were combined and washed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by thin-layer chromatography (dichloromethane / methanol: 10 / 1) to obtain the title compound (12 mg, white solid), with a yield of 44%. ESI-MS: 618.5, [M+H] + . 【0353】 Step 2:1 6 -(4-(2-hydroxyethyl)piperazin-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] At 0℃, 1 6 -(4-(2-(tert-butyldimethylsilyloxy)ethyl)piperazine-1-yl)-2 1 H-3 6To a solution of -fluoro-5,9-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclononane (12 mg, 0.02 mmol) in tetrahydrofuran (1 mL), a solution of 1 M tetrabutylammonium fluoride in tetrahydrofuranil (60 μL, 0.06 mmol) was added dropwise, and the mixture was stirred at room temperature for 14 hours. The reaction was quenched with water (10 mL), extracted with a mixed solvent of dichloromethane / isopyropanol (4 / 1, 10 mL x 3), the organic phases were combined and washed once with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered by suction and evaporated to dryness, and the residue was purified by thin-layer chromatography (dichloromethane / methanol: 7 / 1) to obtain the title product (5 mg, white solid), with a yield of 51%. ESI-MS:504.3, [M+H] + . 【0354】 The following compounds in the examples are synthesized via appropriate intermediates following a method similar to that in Example 9: [Table 30] [Table 31] [Table 32] 【0355】 Example 17. Compound 17:1 6 -(3,3,4-trimethylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0356】 Step 1: Preparation of tert-butyl(4-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)aminocarboxylate (intermediate 17-1) [ka] Under a nitrogen atmosphere, a mixture of 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine (454 mg, 1.00 mmol), tert-butyl(2-((tert-butyloxy group carbonyl)oxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxygen boroheterocyclopentan-2-yl)phenyl)aminocarboxylate (435 mg, 1.00 mmol), Pd(dppf)Cl2 (73 mg, 0.10 mmol), potassium phosphate (637 mg, 3.0 mmol), 1,4-dioxane (10 mL), and water (2 mL) was stirred at 80°C for 14 hours. The solution was cooled to room temperature, diluted with water (60 mL), extracted with ethyl acetate (50 mL x 2), the organic phase was washed with saturated saline solution (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 5:1-3:1 to obtain the title compound (227 mg, white solid) with a yield of 42.4%. ESI-MS:635.2, [M+H] + . 【0357】 Step 2: Preparation of tert-butyl(4-(5-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-1-((2-(trimethylsilyl)))ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-hydroxyphenyl)aminocarboxylate (intermediate 17-2) [ka] Under a nitrogen atmosphere, a solution of 2-(2-fluoro-6-((3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)methyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxyboalkane (1.450 g, 2.62 mmol), intermediate 17-1 (2.062 g, 5.23 mmol), sodium carbonate (831 mg, 7.85 mmol), and Xphos-Pd-G2 (206 mg, 0.26 mmol) in 1,4-dioxane (30 mL) and water (6 mL) is heated and stirred at 80°C for 2 hours. After cooling to room temperature, the solution is diluted with water (120 mL), extracted with ethyl acetate (80 mL x 2), the organic phase is washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 10:1-2:1 to obtain the title compound (1.576 g, brown oily substance) in a yield of 80.5%. ESI-MS:723.4, [M+H] + . 【0358】 Step 3: Preparation of tert-butyl(4-(5-(2-fluoro-6-((3-hydroxypropoxy)methyl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c))]pyridine-3-yl)-2-hydroxyphenyl)aminocarboxylate (intermediate 17-3) [ka] To a solution of intermediate 17-2 (1.576 g, 2.18 mmol) in anhydrous methanol (25 mL), p-tosylic acid monohydrate (435 mg, 2.29 mmol) is added, and the mixture is heated to 40°C and stirred for 1.5 hours. Most of the methanol is removed by rotary evaporation, the residue is dissolved in dichloromethane (100 mL), washed with sodium bicarbonate solution (50 mL) and saturated brine (50 mL) in sequence, dried over anhydrous sodium sulfate, filtered by suction and evaporated to dryness, and the residue is purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 5:1-1:1 to obtain the title compound (1.055 g, white solid) in a yield of 75.9%. ESI-MS:639.3, [M+H] + . 【0359】 Step 4: 16-(tert-butoxycarbonylamino)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 17-4) [ka] Under a nitrogen atmosphere and at room temperature, tributylphosphine (1.668 g, 8.26 mmol) is added dropwise to a solution of TMAD (1.419 g, 8.26 mmol) in dry tetrahydrofuran (25 mL), and after stirring for 5 minutes, dry tetrahydrofuran (50 mL) is added. Then, the temperature is raised to 50°C, and a solution of intermediate 17-3 (1.055 mg, 1.65 mmol) in tetrahydrofuran (25 mL) is added dropwise. After the addition is complete, the mixture is stirred for 0.5 hours. Water (300 mL) is added to quench the mixture, and it is extracted with ethyl acetate (10 mL x 2). The organic phase is washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 10:1-1:1 to obtain the title compound (880 mg, white solid) with a yield of 85.8%. ESI-MS:621.3, [M+H] + . 【0360】 Step 5: 16-Amino-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 17-5) [ka] At room temperature, p-tosylic acid monohydrate (630 mg, 3.31 mmol) is added to a solution of intermediate 17-4 (823 mg, 1.33 mmol) in anhydrous methanol (15 mL), and the temperature is raised to 60°C and the mixture is stirred for 6 hours. The reaction system is swiftly evaporated to remove most of the methanol, and the residue is dissolved in dichloromethane (80 mL). The mixture is then washed sequentially with sodium bicarbonate solution (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue is purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 5:1-2:1 to obtain the title compound (640 mg, white solid) in a yield of 93.6%. ESI-MS:521.3, [M+H] + . 【0361】 Step 6: 16-Bromo-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 17-6) [ka] Under a nitrogen atmosphere, p-tosylic acid monohydrate (415 mg, 2.18 mmol) and tert-butylnitrile (146 mg, 1.42 mmol) are added to a 15 mL solution of intermediate 17-5 (568 mg, 1.09 mmol) in acetonitrile, and the mixture is stirred at room temperature for 20 minutes. Then, copper bromide (61 mg, 0.27 mmol) and tetrabutylammonium bromide (1.406 g, 4.36 mmol) are added, and the mixture is heated to 70°C under a nitrogen atmosphere and stirred for 2 hours. The mixture is cooled to room temperature, water (100 mL) is added to quench the reaction, and the organic phase is extracted with ethyl acetate (60 mL x 2). The organic phase is washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by column chromatography and gradient eluted with petroleum ether / ethyl acetate = 7:1-2:1 to obtain the title compound (425 mg, white solid) in a yield of 66%. ESI-MS: 584.3, [M+H] + . 【0362】 Step 7:1 6 -(4-tert-butoxyoxoacyl-3,3-dimethylpiperazine-1-yl)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 17-7) [ka] Under a nitrogen atmosphere, a toluene (2 mL) solution of intermediate 17-6 (50 mg, 0.09 mmol), 1-tert-butoxyoxoacyl-2,2-dimethylpiperazine (55 mg, 0.26 mmol), palladium acetate (2 mg, 0.009 mmol), BINAP (11 mg, 0.017 mmol), and cesium carbonate (84 mg, 0.26 mmol) is heated to 100°C and stirred for 14 hours. After cooling to room temperature, water (20 mL) is added to the reaction system and extracted with ethyl acetate (20 mL x 2). The organic phases are combined, washed once each with water (20 mL) and saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by preparative chromatography and eluted with dichloromethane / methanol = 10:1 to obtain the title compound (33 mg, colorless oily substance) in a yield of 54%. ESI-MS:717.4, [M+H] + . 【0363】 Step 8:1 6 -(3,3-dimethylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-5,9-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 17-8) [ka] At 0°C, trifluoroacetic acid (0.5 mL) is added dropwise to a solution of intermediate 17-7 (33 mg, 0.05 mmol) in dichloromethane (3 mL), and the mixture is stirred at room temperature for 14 hours. The reaction mixture is evaporated by rotary evaporation to dryness, the residue is dissolved in acetonitrile (2 mL), aqueous ammonia (0.1 mL) is added, and the mixture is stirred for 30 minutes and evaporated to dryness. Water (30 mL) is added, and the mixture is extracted with dichloromethane:isopyropanol = 4:1 (30 mL × 3). The organic phases are combined and washed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. Crude product of the title compound (27 mg, yellow solid) is obtained, with a yield of 100%. ESI-MS:488.3, ​​[M+H] + . 【0364】 Step 9: Preparation of Compound 17 [ka] At room temperature, to a system of intermediate 17-8 (27 mg, 0.05 mmol) in dichloromethane:methanol = 1:1 (3 mL), 1H-benzotriazole-1-methanol (12 mg, 0.08 mmol), sodium acetate (14 mg, 0.17 mmol), and sodium triacetoxyborohydride (35 mg, 0.17 mmol) were added, and the mixture was stirred at room temperature for 5 hours. The reaction was quenched with sodium bicarbonate solution (20 mL), extracted with dichloromethane:isopyropanol = 4:1 (20 mL x 2), the organic phases were combined and washed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered by suction, and evaporated to dryness. The residue was purified by preparative chromatography and eluted with dichloromethane / methanol = 7:1 to obtain the title product (14 mg, white solid) in 50% yield. ESI-MS:502.3, [M+H] + . 1 H NMR(DMSO-d6,400 MHz)δ13.81(s,1H),9.15(s,1H),8.48(s,1H),7.72(s,1H),7.54(m,1H),7.45-7.51(m,1H),7.41(m,1H),7.30-7.35(m,1H),7.04(d,J=7.6 Hz,1H),4.39(t,J=6.4 Hz,2H),4.34(s,2H),3.72(d,J=4.8 Hz,2H),3.15(m,4H),2.86(m,2H),2.6(m,3H),2.07(dd,J=7.0,3.1 Hz, 2H), 1.24(m, 6H). 【0365】 The following compounds in the examples are synthesized via appropriate intermediates following a method similar to that in Example 17: [Table 33] [Table 34] [Table 35] [Table 36] [Table 37] 【0366】 Example 94. Compound 94:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of -fluoro-4-oxa-8-aza-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0367】 Step 1: Preparation of benzyl 4-(4-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(((tert-butoxycarbonyl))(3-hydroxypropyl)amino)methyl)phenyl)piperazine-1-carboxylate (intermediate 94-1) [ka] Under a nitrogen atmosphere, benzyl 4-(2-(((tert-butoxycarbonyl)(3-hydroxypropyl)amino)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxygenboreheterocyclopentan-2-yl)phenyl)piperazine-1-carboxylate (1.32 g, 2.17 mmol) is dissolved in dioxane / water (20 / 2 mL), and 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine (984 mg, 2.17 mmol), Pd(dppf)Cl2 (161 mg, 0.22 mmol), and potassium phosphate (1.38 g, 6.51 mmol) are added, and the mixture is heated to 80°C and reacted for 18 hours. The mixture was quenched with water (20 mL), extracted with ethyl acetate (50 mL x 3), washed with saturated saline solution (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain 1.45 g of the title compound, a yellow oily substance, with a yield of 82.6%. ESI-MS:809.3, [M+H] + . 【0368】 Step 2: Preparation of benzyl 4-(2-(((tert-butyloxy carbonyl)(3-hydroxypropyl)amino)methyl)-4-(5-(2-fluoro-6-hydroxyphenyl)-1-((2-(trimethylsilyl)ethoxy)methyl))-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate (intermediate 94-2) [ka] Under a nitrogen atmosphere, intermediate 94-1 (1.45 g, 1.79 mmol) is dissolved in dioxane / water (20 / 2 mL), and 2-fluoro-6-hydroxyphenylboronic acid (335 mg, 2.15 mmol), Xphos-Pd-G2 (704 mg, 0.89 mmol), and potassium phosphate (1.14 g, 5.37 mmol) are added. The mixture is heated to 100°C and reacted for 3 hours. Water (30 mL) is added to quench the reaction, and the solution is extracted with ethyl acetate (100 mL x 3). The mixture is washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain 1.42 g of the title compound, a yellow oily substance, with a yield of 94.3%. ESI-MS:841.1, [M+H] + . 【0369】 Step 3: Preparation of benzyl 4-(2-(((tert-butyloxy carbonyl)(3-bromidopropyl)amino)methyl)-4-(5-(2-fluoro-6-hydroxyphenyl)-1-((2-(trimethylsilyl)ethoxy)methyl))-1H-pyrazolo[3,4-c]pyridine-3-yl)phenyl)piperazine-1-carboxylate (intermediate 94-3) [ka] Under a nitrogen atmosphere, intermediate 94-2 (1.20 g, 1.43 mmol) is dissolved in dichloromethane (20 mL), triphenylphosphine (487 mg, 1.86 mmol) is added, and N-bromosuccinimide (330 mg, 1.86 mmol) is added at 0°C. The reaction is carried out at room temperature for 18 hours. Water (50 mL) is added to quench the reaction, and the mixture is extracted with dichloromethane (50 mL x 3). The mixture is washed with saturated saline solution (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified by silica gel column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain 1.13 g of the title compound, a yellow oily substance, with a yield of 87.5%. ESI-MS:903.3, [M+H] + . 【0370】 Step 4:1 6 -(4-benzyloxycarbonylpiperazine-1-yl)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-8-tert-butoxyoxoacyl-4-oxa-8-aza-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 94-4) [ka] Under a nitrogen atmosphere, intermediate 94-3 (1.10 g, 1.22 mmol) is dissolved in DMF (80 mL), cesium carbonate (1.19 g, 3.66 mmol) and sodium iodide (183 mg, 1.22 mmol) are added, and the mixture is heated to 100°C and reacted for 3 hours. Water (30 mL) is added to quench the reaction, and the mixture is extracted with ethyl acetate (100 mL x 3). The mixture is washed with saturated saline solution (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product is purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain 796 mg of the title compound, a yellow oily substance, with a yield of 79.6%. ESI-MS:823.4, [M+H] + . 【0371】 Step 5: 16-(piperazine-1-yl)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-8-tert-butoxyoxoacyl-4-oxa-8-aza-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 94-5) [ka] Intermediate 94-4 (796 mg, 0.97 mmol) is dissolved in methanol (20 mL), Pd / C (80 mg) is added, and the reaction is carried out at room temperature for 18 hours under a hydrogen atmosphere. The mixture is filtered and concentrated to obtain a crude product of the title compound, 712 mg of a yellow oily substance. ESI-MS: 689.4, [M+H] + . 【0372】 Step 6:1 6 -(4-methylpiperazine-1-yl)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-8-tert-butoxyoxoacyl-4-oxa-8-aza-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane (intermediate 94-6) [ka] Under a nitrogen atmosphere, intermediate 94-5 (712 mg, 1.03 mmol) is dissolved in dichloromethane (20 mL), 1H-benzotriazole-1-methanol (230 mg, 1.55 mmol) is added, and sodium triacetoxyborohydride (437 mg, 2.06 mmol) is added at 0°C. The reaction is carried out at room temperature for 3 hours. Water (50 mL) is added to quench the mixture, and it is extracted with dichloromethane (50 mL x 3). The mixture is washed with saturated saline solution (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to obtain 715 mg of the title compound, a yellow oily substance, with a yield of 98.7%. ESI-MS:703.4, [M+H] + . 【0373】 Step 7: Preparation of Compound 94 [ka] Under a nitrogen atmosphere, intermediate 94-6 (49 mg, 0.07 mmol) is dissolved in dichloromethane (5 mL), trifluoroacetic acid (1 mL) is added at 0°C, and the reaction is carried out at room temperature for 18 hours. The mixture is concentrated under reduced pressure, acetonitrile (5 mL) and aqueous ammonia (1 mL) are added, and the mixture is stirred at room temperature for 30 minutes. The organic phases are combined by extraction (10 mL x 3) with (dichloromethane:isopyropanol = 5:1), washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and purified by thin-layer preparative chromatography (dichloromethane:methanol = 5:1) to obtain 15.47 mg of the title compound as a white solid, with a yield of 46.9%. ESI-MS: 473.3, [M+H] + . 1 H NMR (DMSO-d6,400 MHz)δ13.70(s,1H),9.12(d,J=1.2 Hz,1H),8.16(d,J=1.3 Hz,1H),7.85(d,J=2.1 Hz,1H),7.62(dd,J=8.1,2.0 Hz,1H),7.38-7.32(m,1H),7.23(d,J=8.2 Hz,1H),6.97(d,J=8.5 Hz,1H),6.86(dd,J=10.2,8.3 Hz,1H),4.15(t,J=4.9 Hz,2H),3.93(s,2H),3.01(t,J=7.6 Hz,2H),2.90(t,J=4.7 Hz,4H),2.56-2.51(m,4H),2.25(s,3H),2.00(s,2H). 【0374】 Example 95. Compound 95:1 6 -(4-methylpiperazine-1-yl)-2 1 H-3 6 Preparation of fluoro-8-methyl-4-oxa-8-aza-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclononane [ka] 【0375】 Step 1: Preparation of Compound 95 Under a nitrogen atmosphere, compound 94 (51 mg, 0.11 mmol) is dissolved in dichloromethane (8 mL), 1H-benzotriazole-1-methanol (33 mg, 0.22 mmol) is added, and sodium triacetoxyborohydride (70 mg, 0.33 mmol) is added at 0°C. The reaction is carried out at room temperature for 3 hours. The reaction system is quenched with saturated sodium bicarbonate solution (10 mL), extracted with dichloromethane (20 mL x 3), washed with saturated saline solution (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and purified by thin-layer preparative chromatography (dichloromethane:methanol = 5:1) to obtain 19 mg of the title compound as a white solid. The yield is 36.5%. E SI-MS:487.3, [M+H] + . 1 H NMR (DMSO-d6,400 MHz)δ13.66(s,1H),9.12(d,J=1.1 Hz,1H),8.17(d,J=1.2 Hz,1H),7.72(d,J=2.2 Hz,1H),7.61(dd,J=8.2,2.0 Hz,1H),7.38-7.32(m,1H),7.25(d,J=8.2 Hz,1H),6.96(d,J=8.4 Hz,1H),6.88(dd,J=10.5,8.3 Hz,1H),4.11(t,J=4.9 Hz, 2H), 3.67 (s, 2H), 2.98-2.84 (m, 6H), 2.60-2.52 (m, 4H), 2.39 (s, 3H), 2.26 (s, 3H), 2.04 (s, 2H). 【0376】 The following compounds in the examples are synthesized from compound 94 by selecting appropriate starting materials: [Table 38] [Table 39] 【0377】 Example 119. Compound 119:(R)-1 6-((R)-Hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-yl)-2 1 H-3 6 Preparation of -fluoro-6-hydroxy-4,8-dioxa-1(1,3)-benzenehetero-2(3,5)-(6-azindazolyl)hetero-3(1,2)-benzeneheterocyclooctane [ka] 【0378】 Step 1: Preparation of (R)-8-(4-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-((R)-ethyleneoxide-2-ylmethoxy)phenyl)octahydropyrazino[2,1-c][1,4]oxazine (intermediate 119-1) [ka] Under a nitrogen atmosphere, (R)-5-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-(hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-yl)phenol (200 mg, 0.36 mmol) is dissolved in acetonitrile (10 mL), potassium carbonate (148 mg, 1.08 mmol), (R)-p-glycidyl tosylate (164 mg, 0.72 mmol), and sodium iodide (52 mg, 0.36 mmol) are added, and the mixture is heated to 75°C and reacted for 18 hours. The mixture was quenched with water (10 mL), extracted with ethyl acetate (20 mL x 3), washed with saturated saline solution (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography (methanol:dichloromethane = 1:20) to obtain 112 mg of the title compound as a yellow oily substance, with a yield of 50%. ESI-MS:616.2, [M+H] + . 【0379】 Step 2: Preparation of 3-fluoro-2-(3-(4-((R)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl)-3-((R)-ethyleneoxide-2-yl)methoxy)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine-5-yl)phenol (intermediate 119-2) [ka] Under a nitrogen atmosphere, intermediate 119-1 (112 mg, 0.18 mmol) is dissolved in dioxane / water (10 / 2 mL), and 2-fluoro-6-hydroxyphenylboronic acid (34 mg, 0.22 mmol), Xphos-Pd-G2 (15 mg, 0.02 mmol), and potassium phosphate (115 mg, 0.54 mmol) are added. The mixture is heated to 85°C and reacted for 3 hours. Water (30 mL) is added to quench the reaction, and the mixture is extracted with ethyl acetate (20 mL x 3). The mixture is washed with saturated saline solution (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product is purified by silica gel column chromatography (methanol:ethyl acetate = 1:50) to obtain 43 mg of the title compound, a yellow oily substance, with a yield of 37%. ESI-MS: 648.2, [M+H] + . 【0380】 Step 3: (R)-1 6 -((R)-Hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-yl)-2 1 H-2 1 -((2-(trimethylsilyl)ethoxy)methyl)-3 6 Preparation of -fluoro-6-hydroxy-4,8-dioxa-1(1,3)-benzene hetero-2(3,5)-(6-azindazolyl) hetero-3(1,2)-benzene heterocyclooctane (intermediate 119-3) [ka] Under a nitrogen atmosphere, intermediate 119-2 (43 mg, 0.07 mmol) is dissolved in acetonitrile (5 mL), cesium carbonate (65 mg, 0.20 mmol) is added, and the mixture is heated to 80°C and reacted for 3 hours. Water (10 mL) is added to quench the reaction, and the mixture is extracted with ethyl acetate (20 mL x 3). The mixture is washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product is purified by thin-layer preparative chromatography (methanol:ethyl acetate = 1:50) to obtain 17 mg of the title compound as a white solid. The yield is 39.5%. ESI-MS: 648.2, [M+H] + . 【0381】 Step 4: Preparation of Compound 119 [ka] Under a nitrogen atmosphere, intermediate 119-3 (17 mg, 0.03 mmol) is dissolved in dichloromethane (5 mL), trifluoroacetic acid (1 mL) is added at 0°C, and the reaction is carried out at room temperature for 18 hours. The mixture is concentrated under reduced pressure, acetonitrile (5 mL) and aqueous ammonia (1 mL) are added, and the mixture is stirred at room temperature for 30 minutes. Extraction is performed with (dichloromethane:isopyropanol = 5:1) for (10 mL x 3), the organic phases are combined, washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and purified by thin-layer preparative chromatography (dichloromethane:methanol = 10:1) to obtain 5.34 mg of the title compound as a white solid, with a yield of 39%. ESI-MS:518.2, [M+H] + . 1H NMR(DMSO-d6,400 MHz)δ13.62(s,1H),9.09(s,1H),8.68(s,1H),7.74(s,1H),7.59-7.24(m,2H),7.24- 6.83(m,3H),5.78-5.47(m,1H),4.74-4.70(m,1H),4.35-4.26(m,2H),4.04(t,J=9.4 Hz,1H),3.92-3.86(m,1H),3.82-3.75(m,1H),3.75-3.43(m,3H),3.38-3.35(m, 1H), 3.21-3.15(m, 1H), 2.83-2.74(m, 2H), 2.72-2.64(m, 1H), 2.46-2.20(m, 4H). 【0382】 The following compounds in the examples are synthesized via appropriate intermediates following a method similar to that in Example 119: [Table 40] 【0383】 Methods and results for detecting biological activity: 1. HPK1 kinase activity test The kinase activity of HPK1 is expressed as autophosphorylation activity and downstream substrate phosphorylation activity. In the autophosphorylation process, it consumes ATP to produce ADP without requiring additional substrates, and the kinase's activity is reflected in the amount of product detected by ADP-Glo ​​reagent and luminescence spectroscopy. 【0384】 Test substance: A compound prepared according to the embodiment of the present invention. Preparation of the compound storage solution: Dissolve the test compound in 100% DMSO to prepare a 10 mM storage solution; [Table 41] [Table 42] [Table 43] 【0385】 Exam steps: Dilute the stock solution of the test compound fivefold with 100% DMSO, then perform a fourfold dilution in a 96-well dilution plate. Take 1 μL of the compound and add it to 49 μL of kinase reaction buffer, then shake in a microplate shaker for 20 minutes. Transfer 2 μL of 2× HPK1 kinase solution to a 384 reaction plate, add 1 μL of the test compound to the 384 reaction plate (Greiner, Cat#784075), centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 10 minutes. Transfer 1 μL of 4× ATP mixture to a 384 reaction plate, centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 60 minutes. In all reaction systems, the final concentration of DMSO is 0.5%. Transfer 4 μL of ADP-Glo ​​to a 384 reaction plate, centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 40 minutes. Transfer 8 μL of the detection solution to a 384 reaction plate, centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 40 minutes. Read the fluorescence signal with a Biotek multifunction plate reader and determine the IC50 (50% inhibitory concentration) of the compound using the four-coefficient nonlinear curve fitting formula. 【0386】 The compounds shown in the examples exhibited IC50 values ​​within the following ranges: ++++ = IC50 ≤ 5 nM, +++ = 5 nM <IC50≦50 nM、++=50 nM<IC50≦500 nM、+=IC50> 500 nM. [Table 44] [Table 45] The data in Tables 44-45 demonstrates that the compounds of the embodiments of the present invention exhibit a strong inhibitory effect on HPK1 kinase activity. 【0387】 2. Activity test of FLT3 kinase Test substance: A compound prepared according to the embodiment of the present invention. Preparation of compound storage solution: Dissolve the test compound in 100% DMSO to make a 10 mM storage solution; Dilute the test compound storage solution fivefold with 100% DMSO, then perform a fourfold 1:1 dilution in a 96-well dilution plate, take 1 μL of the compound, add it to 39 μL of kinase reaction buffer (1× kinase buffer, 5 mM MgCl2, 1 mM DTT), and shake in a microplate shaker for 20 minutes. 4× positive control (4 μL of positive drug added to 196 μL of kinase buffer at the first concentration point) and 4× negative control (4 μL of 100% DMSO added to 196 μL of kinase buffer). 【0388】 Exam steps: (1) Prepare a 2.5× FLT3 kinase solution (160 pM) using 1× enzyme reaction buffer, transfer 2 μL of the kinase solution to a 384 reaction plate, add 1 μL of the test compound at a gradient concentration to the 384 reaction plate (Greiner, 784075), centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 10 minutes. (2) Prepare 2.5× TK-substrate-biotin (2.5 μM) and 2.5× ATP (2.5 μM) using 1× enzyme reaction buffer, mix well, then add 2 μL of the TK-substrate-biotin / ATP mixture to a 384 reaction plate, centrifuge for 30 seconds (1000 rpm), and incubate at 25°C for 40 minutes. (3) Prepare 2× Sa-XL 665 (125 nM) and 1× TK-antibody-Cryptate using HTRF assay buffer. Add 5 μL of the Sa-XL 665 and TK-antibody-Cryptate mixture to each well, centrifuge for 30 seconds (1000 rpm), and react at room temperature for 1 hour. (4) Read the fluorescence signal using a Biotek multifunction plate reader and determine the IC50 (50% inhibitory concentration) of the compound using the four-coefficient nonlinear curve fitting formula. 【0389】 The compounds shown in the examples exhibited IC50 values ​​within the following ranges: ++++ = IC50 ≤ 5 nM, +++ = 5 nM <IC50≦50 nM、++=50 nM<IC50≦500 nM、+=IC50> 500 nM. [Table 46] The data in Table 46 shows that the compounds of the embodiments of the present invention exhibit a strong inhibitory effect on the activity of FLT3 kinase. 【0390】 3. Activity testing of KDR kinase Test substance: A compound prepared according to the embodiment of the present invention. Preparation of compound storage solution: Dissolve the test compound in 100% DMSO to make a 10 mM storage solution; dilute the test compound storage solution fivefold with 100% DMSO, then perform a fourfold 1:1 dilution in a 96-well dilution plate, take 1 μL of the compound, add it to 39 μL of kinase reaction buffer (1× kinase buffer, 5 mM MgCl2, 1 mM DTT), and shake in a microplate shaker for 20 minutes. Prepare 4× positive control (4 μL of positive drug added to 196 μL of kinase buffer at the first concentration point) and 4× negative control (4 μL of 100% DMSO added to 196 μL of kinase buffer). 【0391】 Exam steps: (1) Prepare a 2.5× KDR kinase solution (250 pM) using 1× enzyme reaction buffer, transfer 2 μL of the kinase solution to a 384 reaction plate, add 1 μL of the test compound at a gradient concentration to the 384 reaction plate (Greiner, Cat#784075), centrifuge for 1 minute (1000 rpm), and incubate at 25°C for 10 minutes. (2) Prepare 2.5× TK-substrate-biotin (2.5 μM) and 2.5× ATP (12.5 μM) using 1× enzyme reaction buffer, mix well, then add 2 μL of the TK-substrate-biotin / ATP mixture to a 384 reaction plate, centrifuge for 30 seconds (1000 rpm), and incubate at 25°C for 40 minutes. (3) Prepare 2× Sa-XL 665 (125 nM) and 1× TK-antibody-Cryptate using HTRF assay buffer. Add 5 μL of the Sa-XL 665 and TK-antibody-Cryptate mixture to each well, centrifuge for 30 seconds (1000 rpm), and react at room temperature for 1 hour. (4) Read the fluorescence signal using a Biotek multifunction plate reader and determine the IC50 (50% inhibitory concentration) of the compound using the four-coefficient nonlinear curve fitting formula. 【0392】 The compounds shown in the examples exhibited IC50 values ​​within the following ranges: ++++ = IC50 ≤ 5 nM, +++ = 5 nM <IC50≦50 nM、++=50 nM<IC50≦500 nM、+=IC50> 500 nM. [Table 47] 【0393】 4. ELISA test for IL-2 secretion by Jurkat cells Test substance: A compound prepared according to the embodiment of the present invention. 【0394】 Exam steps: Different concentrations of the test compound are incubated with human Jurkat-E6-1 cells for 30 minutes in a humidified incubator at 37°C with 5% CO2. The cells are transferred to a cell culture plate pre-coated with anti-human CD3 antibody, then soluble anti-human CD28 antibody is added, and the cells are stimulated for 24 hours in a humidified incubator at 37°C with 5% CO2. The cell culture medium is collected by centrifugation and transferred to a 96-well transparent microplate (Thermo) pre-coated with anti-human IL-2 antibody. The microplate is incubated at room temperature for 2 hours, gently shaken, and washed four times with washing buffer. The OD values ​​are then read using a microplate reader (Molecular Device, i3X) according to the operating procedure of the ELISA MAX Deluxe Set Human IL-2 (BioLegend, Cat#431804) kit. The optimal standard curve is selected using the microplate reader's application software, and the corresponding concentration is calculated from the OD values ​​of the sample. The results are shown as a percentage (%) of the amount of IL-2 secreted from cells treated with the compound / DMSO. [Table 48] ...

Claims

[Claim 1] A azindazole macrocyclic compound represented by formula I, or its stereoisomers, pharmaceutically acceptable salts, hydrates, or solvates, The structure and atomic numbering of the azindazole ring are shown in formula (Ia). In the structure of formula I, X is either CH or N; R １ H is, L １ It is a single bond; Ring A is selected from one of the following structures: In these structural formulas, the asterisk (*) at the end of a chemical bond indicates that the bond is attached to the 3-position of the azindazole ring, and the double asterisk (**) at the end of a chemical bond indicates that the bond is attached to the L-position. ２ This indicates that they are bound together. In these structural formulas, the ring-forming carbon atoms are one R ２ Replaced by, The B ring is phenyl, and also L is formed by two different atoms. ２ They are bound to the 5-position of the azaindazole ring, respectively. Here, ring B is L ２ The shortest distance between the two B ring atoms linked to the 5-position of the azindazole ring is a single chemical bond. Among them, ring B is bonded to L ２ and in addition to being bonded to the 5-position of the azaindazole ring, it is optionally substituted with n R ３ where R ３ is fluorine, Furthermore, it is located adjacent to the ring-forming atom bonded at the 5-position of the azindazole ring on the B ring, R ２ Each is independently selected from the following aliphatic heterocyclic groups, The asterisk (*) at the end of a chemical bond in the structural formula indicates that the bond is attached to ring A. Among these, the aliphatic heterocyclic group may optionally have 0, 1, 2, or 3 substituents R ２２１ It is substituted with substituent R ２２１ These are independently oxo, fluoro, cyano, hydroxy, and C groups. １ -C ６ Alkoxy, C １ -C ６ Alkylamino, C １ -C ６ Alkyl, C １ -C ６ Fluoroalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C ３ -C ６ Cyclylalkyl, C ３ -C ６ Selected from oxocycloalkyl, L ２ Each of them is independent of -CH ２ Selected from the group consisting of - and -O-, where each L ２ These are independently substituted with 0 or 1 -OH, and two adjacent L ２ The p Ls are connected by single bonds and are linked to each other. ２ However, it forms a linking group that connects ring A and ring B, and L at both ends ２ These are bonded to ring A and ring B by single bonds, respectively. p is 4, 5, or 6. m is 1, A azindazole macrocyclic compound characterized in that n is 0 or 1, or its stereoisomers, pharmaceutically acceptable salts, hydrates, or solvates. [Claim 2] The aforementioned compound is represented by formula IIIb, Here, X is CH, Ring A is selected from one of the following structures: In these structural formulas, the asterisk (*) at the end of a chemical bond indicates that the bond is attached to the 3-position of the azindazole ring, and the double asterisk (**) at the end of a chemical bond indicates that the bond is attached to the L-position. ２ This indicates that they are bound together. In these structural formulas, the para position of the carbon atom indicated by "*" contains one R ２ Replaced by, The B ring is phenyl, and the B ring is L through two different ring-forming atoms. ２ And bonded to the 5-position of the azaindole ring, respectively, and the two ring-forming atoms are located adjacent to each other. R ２ Each is independently selected from the following aliphatic heterocyclic groups, The asterisk (*) at the end of a chemical bond in the structural formula indicates that the bond is attached to ring A. Among these, the aliphatic heterocyclic group may optionally have 0, 1, 2, or 3 substituents R ２２１ It is substituted with substituent R ２２１ These are independently selected from oxo, fluoro, hydroxy, methoxy, ethoxy, isopropoxy, cyclopropoxy, dimethylamino, methyl, ethyl, 1-propyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, oxacyclobutyl, and tetrahydropyranyl. p is 4, 5, or 6. The azaindazole macrocyclic compound according to claim 1, characterized in that m is 1, or its stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate. [Claim 3] The azaindazole macrocyclic compound according to claim 1, characterized in that X is CH, or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof. [Claim 4] A azindazole macrocyclic compound selected from the group consisting of the following compounds, or its stereoisomers, pharmaceutically acceptable salts, hydrates, or solvates. [Claim 5] A pharmaceutical composition comprising an azaindazole macrocyclic compound according to any one of claims 1 to 4, or a stereoisomer thereof, a pharmaceutically acceptable salt, hydrate, or solvate thereof, and a pharmaceutically acceptable carrier. [Claim 6] Use of an azaindazole macrocyclic compound according to any one of claims 1-4, or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, for the preparation of a medicament for the prevention, improvement, or treatment of a disease mediated by HPK1 or other protein kinases, The other protein kinases mentioned above are FLT3 kinase and / or KDR kinase. The use is characterized in that the disease includes one or more diseases selected from the group consisting of tumors, myelodysplastic syndromes, and virus-induced diseases. [Claim 7] Use of the pharmaceutical composition according to claim 5 for the preparation of a pharmaceutical for the prevention, improvement or treatment of a disease mediated by HPK1 or other protein kinases, The other protein kinases mentioned above are FLT3 kinase and / or KDR kinase. The use is characterized in that the disease includes one or more diseases selected from the group consisting of tumors, myelodysplastic syndromes, and virus-induced diseases. [Claim 8] The aforementioned tumors include chronic or acute leukemia, lymphoma, primary CNS lymphoma, multiple myeloma, myeloproliferative neoplasm, lung cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, gallbladder cancer, bile duct cancer, gastric cancer, colorectal cancer, small intestinal leiomyosarcoma, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, vaginal cancer, vulvar cancer, malignant teratoma, pancreatic cancer, neuroendocrine tumor, nasopharyngeal cancer, oral cancer, laryngeal cancer, hypopharyngeal cancer, esophageal cancer, and esophageal stool tumor. One or more types selected from the group consisting of cancer, thyroid cancer, pheochromocytoma, pancreatic endocrine tumor, renal cancer, bladder cancer, malignant brain tumor, rhabdomyosarcoma, osteosarcoma, chondrosarcoma, osteofibrosarcoma, Ewing's sarcoma, myxoid polyps, malignant thymoma, malignant peripheral nerve schwannoma, prostate cancer, testicular cancer, penile cancer, urethral cancer, and benign or malignant tumors of the skin (including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma). The use according to claim 6, characterized in that the virus is one or more viruses selected from the group consisting of hepatitis viruses, human immunodeficiency viruses, human papillomaviruses, herpes simplex viruses, measles viruses, noroviruses, bocca viruses, coxsackieviruses, Ebola viruses, enteroviruses, lymphocytic meningitis viruses, influenza viruses, SARS viruses, and novel coronaviruses. [Claim 9] A pharmaceutical composition according to claim 5 for the prevention, improvement, or treatment of a disease mediated by HPK1 or other protein kinases, The pharmaceutical composition is characterized in that the disease comprises one or more diseases selected from the group consisting of tumors, myelodysplastic syndromes, and virus-induced diseases.

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