Bicyclic fused ring containing c-kit kinase inhibitors

Abstract

The present application belongs to the field of biotechnology, and discloses a c-kit kinase inhibitor. Specifically, the present application provides a compound shown in formula I or a pharmaceutically acceptable salt thereof and the use thereof in the preparation of a medicament for treating or preventing a c-kit kinase related disease or disease state. The compound of the present application is a novel and effective c-Kit kinase inhibitor.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a c-kit kinase inhibitor containing a bicyclic fused ring. Background Technology

[0002] c-Kit (also known as CD117 or stem cell factor receptor) is a receptor tyrosine kinase belonging to the type III receptor tyrosine kinase family. c-Kit is activated by binding to its ligand, stem cell factor (SCF), which in turn triggers downstream signaling pathways, including PI3K / AKT, MAPK / ERK, and JAK / STAT. These signaling pathways play crucial roles in cell proliferation, differentiation, survival, and migration.

[0003] c-Kit is widely expressed in hematopoietic stem cells, mast cells, melanocytes, interstitial cells of Cajal (ICC) in the gastrointestinal tract, and germ cells during normal physiological processes, and is crucial for hematopoiesis, pigment production, gastrointestinal motility, and reproductive function. Therefore, abnormal activation or mutation of c-Kit is closely related to a wide variety of tumors and non-tumor diseases.

[0004] Given the crucial role of c-Kit in various diseases, finding a novel and effective c-Kit kinase inhibitor is an important direction in current drug development. However, most approved c-Kit inhibitors are multi-target kinase inhibitors, which present challenges in terms of both clinical efficacy and drug resistance. Some drugs also have low oral bioavailability and short half-lives, requiring frequent dosing. Summary of the Invention

[0005] The present invention aims to develop a novel, highly selective, and bioavailable c-Kit kinase inhibitor.

[0006] On the one hand, the present invention provides a compound of general formula (I) or a pharmaceutically acceptable salt thereof:

[0007]

[0008] in: Each R 1The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl, wherein the C1-C6 alkyl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, wherein the 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl or 6-10 membered aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl; Ring A is a 6-14 quintile bicyclic fused ring; Each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-10 membered cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl group is optionally substituted with one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, and the 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl or C1-C6 alkoxy group is optionally substituted with one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl. R A R B Each is independently selected from C1-C6 alkyl groups; Ring B is a 6-membered aryl or a 5-10-membered heteroaryl; Each R 3 Independently selected from halogens, C1-C6 alkyl groups, 3-10 membered cycloalkyl groups, or C1-C6 alkoxy groups; m and n are each independently selected from 0, 1, 2, 3 or 4; p is selected from 1, 2, 3, or 4.

[0009] In a preferred embodiment of the invention, each R 1The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-10 cycloalkyl, 3-10 heterocycloalkyl, 6-8 aryl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 cycloalkyl, 3-10 heterocycloalkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-10 heterocyclic alkyl, 6-8 aryl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 heterocyclic alkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 The alkyl group is independently selected from halogen, 3-10-membered heterocyclic alkyl, 5-8-membered heteroaryl or C1-C6 alkyl-5-8-membered heteroaryl, wherein the 5-8-membered heteroaryl or C1-C6 alkyl-5-8-membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10-membered heterocyclic alkyl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 Independently selected from halogens, , , , , , , , , , or The , , , , or Optionally substituted with one or more substituents selected from hydroxyl, C1-C3 alkyl, halogenated C1-C3 alkyl, or C1-C3 alkoxy; , , , or Optionally substituted with one or more substituents selected from hydroxyl, halogenated C1-C3 alkyl or C1-C3 alkoxy; Preferably, each R 1 Independently selected from halogens, , , , , , , , , , or The , , , , or Optionally substituted with one or more substituents selected from hydroxy, methyl, difluoromethyl, trifluoromethyl, or methoxy; , , , or Optionally substituted with one or more substituents selected from hydroxy, difluoromethyl, trifluoromethyl or methoxy; More preferably, each R 1 Independently selected from halogens, , , , , , , , , , , , or .

[0010] In a preferred embodiment of the invention, each R 1 Independently selected from fluorine, , , , , , , , , , , , , , , , or .

[0011] In a further preferred embodiment of the invention, each R 1 Independently selected from fluorine, , , , , or .

[0012] In a preferred embodiment of the present invention, ring A is a 6-10 member bicyclic fused ring; preferably a 6-10 member bicyclic fused heterocyclic ring; preferably an 8 member bicyclic fused heterocyclic ring with a 5-membered ring and a 9 member bicyclic fused heterocyclic ring with a 6-membered ring and a 5-membered ring. More preferably , , , , , , , , , , , , , , , , , , , , or ; More preferably , , , , , , , , , or ; More preferably , , , , , , , , , or .

[0013] In a further preferred embodiment of the invention, ring A is , or .

[0014] In a further preferred embodiment of the invention, ring A is .

[0015] In a further preferred embodiment of the invention, ring A is .

[0016] In a further preferred embodiment of the invention, ring A is .

[0017] In a preferred embodiment of the invention, each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-8 membered cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C6 alkyl groups; Preferably, each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-5 membered cycloalkyl groups, 3-5 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C3 alkyl groups; More preferably, each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-5 membered cycloalkyl groups, 3-5 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, , or The C1-C6 alkyl, 3-5 membered heterocyclic alkyl or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or fluorine; More preferably, each R 2Independently selected from fluorine, chlorine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, aziroxy, trifluoromethyl, trifluoroethyl, , , , cyano , or .

[0018] In a further preferred embodiment of the invention, each R 2 Independently selected from fluorine, chlorine, methyl, isobutyl, cyclopropyl, methoxy, trifluoromethyl, , , , , , Or cyano.

[0019] In a further preferred embodiment of the invention, each R 2 Independently selected from fluorine, chlorine, methoxy, trifluoromethyl, , , , , , Or cyano.

[0020] In a further preferred embodiment of the invention, each R 2 It is independently selected from fluorine, chlorine, methoxy, trifluoromethyl or cyano.

[0021] In a preferred embodiment of the present invention, ring B is a 6-membered aryl or a 6-membered heteroaryl; preferably, ring B is... Where X and Y are each independently selected from CH or N; "This indicates that ring B is chemically bonded to the -NH- position;" "" indicates that ring B is chemically bonded to the position of ring A.

[0022] In a further preferred embodiment of the present invention, ring B is ,in" "This indicates that ring B is chemically bonded to the -NH- position;" "" indicates that ring B is chemically bonded to the position of ring A.

[0023] In a preferred embodiment of the invention, each R 3 Independently selected from halogens or C1-C6 alkyl groups; preferably, each R 3 Independently selected from fluorine, chlorine, methyl, ethyl, n-propyl, or isopropyl; more preferably, each R 3It is independently selected from fluorine, chlorine, or methyl.

[0024] In a further preferred embodiment of the invention, each R 3 It is independently selected from fluorine or methyl.

[0025] In a further preferred embodiment of the invention, R 3 It is fluorine.

[0026] In a further preferred embodiment of the invention, R 3 It is methyl.

[0027] In a preferred embodiment of the present invention, m is selected from 0, 1 or 2; preferably, m is selected from 0 or 1.

[0028] In a preferred embodiment of the present invention, n is selected from 0, 1 or 2; preferably, n is selected from 0 or 1.

[0029] In a preferred embodiment of the present invention, p is selected from 1 or 2; preferably, p is 1.

[0030] In a preferred embodiment of the invention, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is further represented as shown in general formula (II): ; Among them, R 1 R 2 R 3 X, Y, m, n, and p are each defined as described above.

[0031] In a preferred embodiment of the invention, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is further represented as shown in general formula (III): ; Among them, R 6 R 7 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl, wherein the C1-C6 alkyl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, wherein the 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl or 6-10 membered aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl; R 8 R 9Each group is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl, C1-C6 alkoxy, hydroxyl, cyano, -P(=O)R A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl group is optionally substituted with one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, and the 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl or C1-C6 alkoxy group is optionally substituted with one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl. R 3A Selected from hydrogen, halogens, or C1-C6 alkyl groups; R 3 The definition is as described above.

[0032] In a preferred embodiment of the present invention, R 6 R 7 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-10 cycloalkyl, 3-10 heterocycloalkyl, 6-8 aryl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 cycloalkyl, 3-10 heterocycloalkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, R 6 R 7 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-10 heterocyclic alkyl, 6-8 aryl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 heterocyclic alkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, R 6 R 7Each of the following is independently selected from hydrogen, halogen, 3-10-membered heterocyclic alkyl, 5-8-membered heteroaryl, or C1-C6 alkyl-5-8-membered heteroaryl, wherein the 5-8-membered heteroaryl or C1-6 alkyl-5-8-membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl, or C1-C6 alkoxy, and wherein the 3-10-membered heterocyclic alkyl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl, or C1-C6 alkoxy.

[0033] In a preferred embodiment of the invention, R 6 Selected from hydrogen or halogen, and R 7 The group is selected from hydrogen, halogen, 3-10-membered heterocyclic alkyl, 5-8-membered heteroaryl or C1-C6 alkyl-5-8-membered heteroaryl, wherein the 5-8-membered heteroaryl or C1-6 alkyl-5-8-membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, and the 3-10-membered heterocyclic alkyl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy.

[0034] In a preferred embodiment of the invention, R 6 R 7 Each is independently selected from hydrogen, halogen, , , , , , , , , , or The , , , , or Optionally, the substituent may be replaced by one or more substituents selected from hydroxyl, C1-C3 alkyl, halogenated C1-C3 alkyl, or C1-C3 alkoxy. , , , or Optionally substituted with one or more substituents selected from hydroxyl, halogenated C1-C3 alkyl or C1-C3 alkoxy; Preferably, R 6 R 7 Each is independently selected from hydrogen, halogen, , , , , , , , , , or The , , , , or Optionally substituted with one or more substituents selected from hydroxy, methyl, difluoromethyl, trifluoromethyl, or methoxy; , , , or Optionally substituted with one or more substituents selected from hydroxy, difluoromethyl, trifluoromethyl or methoxy; More preferably, R 6 R 7 Each is independently selected from hydrogen, halogen, , , , , , , , , , , , or .

[0035] In a further preferred embodiment of the invention, R 6 R 7 Each is independently selected from hydrogen, fluorine, , , , , , , , , , , , , , , , or .

[0036] In a further preferred embodiment of the invention, R 6 R 7 Each is independently selected from hydrogen, fluorine, , , , , or .

[0037] In a further preferred embodiment of the invention, R 6 Selected from hydrogen, fluorine or .

[0038] In a further preferred embodiment of the invention, R 6 Selected from hydrogen or fluorine; hydrogen is preferred.

[0039] In a further preferred embodiment of the invention, R 7 Selected from hydrogen, , , , , or .

[0040] In a further preferred embodiment of the invention, R 7 Selected from hydrogen, or Preferred or .

[0041] In a further preferred embodiment of the invention, R 7 for .

[0042] In a further preferred embodiment of the invention, R 7 for .

[0043] In a further preferred embodiment of the invention, R 3A Selected from hydrogen, fluorine, chlorine, methyl, ethyl, n-propyl, or isopropyl; preferably, R 3A Selected from hydrogen, fluorine, or chlorine; preferably, R 3A It is hydrogen.

[0044] In a preferred embodiment of the present invention, R 8 R 9 Each group is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, C1-C6 alkoxy, hydroxyl, cyano, -P(=O)R A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C6 alkyl groups; Preferably, R 8 R 9 Each element is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, C1-C6 alkoxy, hydroxyl, cyano, -P(=O)R A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C3 alkyl groups; Preferably, R 8 R 9 Each element is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, C1-C6 alkoxy, hydroxyl, cyano. , or The C1-C6 alkyl, 3-5 membered heterocyclic alkyl or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or fluorine; Preferably, R 8 R 9 Each is independently selected from hydrogen, fluorine, chlorine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, aziroxy, trifluoromethyl, trifluoroethyl, , , , cyano , or .

[0045] In a further preferred embodiment of the invention, R 8 R 9 Each is independently selected from hydrogen, fluorine, chlorine, methyl, isobutyl, cyclopropyl, methoxy, trifluoromethyl, , , , , , Or cyano.

[0046] In a further preferred embodiment of the invention, R 8 R 9 Each is independently selected from hydrogen, fluorine, chlorine, methoxy, trifluoromethyl, , , , , , Or cyano.

[0047] In a further preferred embodiment of the present invention, R 8 Selected from hydrogen, fluorine, chlorine, trifluoromethyl, Or cyano; preferably hydrogen or chlorine; more preferably hydrogen.

[0048] In a further preferred embodiment of the invention, R 9 It is selected from hydrogen, fluorine, chlorine, methoxy, trifluoromethyl or cyano; preferably hydrogen or trifluoromethyl; more preferably hydrogen.

[0049] In a preferred embodiment of the invention, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is further represented as shown in general formula (II-1): ; R 2 R 3 R 3A R 6 R 7 The definitions of , n, and ring A are as described above.

[0050] In a further preferred embodiment of the invention, the compound or a pharmaceutically acceptable salt thereof has the following structure: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0051] On the other hand, the present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of any of the above-described compounds or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0052] The pharmaceutical compositions of the present invention can be administered by any suitable route or method, such as oral or parenteral (e.g., intravenous) administration.

[0053] In a preferred embodiment of the invention, the invention also provides the use of any of the foregoing compounds or pharmaceutically acceptable salts thereof or pharmaceutical compositions thereof in the preparation of medicaments for the prevention and / or treatment of c-Kit kinase-related diseases or disease states.

[0054] In a preferred embodiment of the invention, the c-Kit kinase-related disease or disease state is allergic conjunctivitis or chronic sinusitis.

[0055] In a preferred embodiment of the invention, the invention also provides a method for preventing and / or treating c-Kit kinase-related diseases or disease states, comprising administering to an individual in need a compound of the invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention.

[0056] Related definitions Unless otherwise specified, the following terms used in the specification and claims shall have the following meanings: The "compounds" described in this invention include all stereoisomers and tautomers.

[0057] The compounds of this invention may be asymmetric, for example, having one or more stereoisomers. Unless otherwise stated, all stereoisomers are included, such as enantiomers and diastereomers. The compounds of this invention containing asymmetric carbon atoms can be isolated in optically active pure form or in racemic form. The optically active pure form can be resolved from racemic mixtures or synthesized using chiral starting materials or chiral reagents. Racemic, diastereomers, and enantiomers are all included within the scope of this invention.

[0058] The term "isomer" refers to different compounds having the same molecular formula but different atomic arrangements and configurations. Those skilled in the art can separate mixtures of isomers obtainable according to the present invention into individual isomers in known ways.

[0059] In this invention, " "and" "" indicates the absolute configuration of a solid center.

[0060] In this invention, " “ in "" refers to the junction of chemical bonds. When a "" appears in a bicyclic or polycyclic ring... "And if the connection location is uncertain, it means that the connection point is limited to " "Any atom on the single ring, as long as the valence allows."

[0061] The term “optional” or “optionally” means that the event or situation described below may or may not occur, including both the occurrence and non-occurrence of the event or situation.

[0062] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0063] The term "substituted" refers to the replacement of one or more hydrogen atoms on a specific group with a substituent, provided that the valence state of the specific group is normal and the resulting compound is stable. For example, "halogen substituted" means that one or more hydrogen atoms on a specific group are replaced by a halogen, provided that the valence state of the specific group is normal and the resulting compound is stable.

[0064] The numerical ranges used in this article refer to the integers within a given range. For example, "C1-C6" means that the group can have 1, 2, 3, 4, 5, or 6 carbon atoms.

[0065] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, including straight-chain or branched saturated hydrocarbon groups having the indicated number of carbon atoms. For example, the term "C1-C6 alkyl" includes C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl, examples of which include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, n-hexyl, 2-hexyl, 3-hexyl, etc.

[0066] The term "halogenated C1-C6 alkyl" refers to a haloalkyl group containing 1 to 6 carbon atoms, examples of which include, but are not limited to, difluoromethyl, trifluoromethyl, and trifluoroethyl.

[0067] The term "membered ring" refers to the number of skeleton atoms that make up the ring. For example, "3-14 members" means that the number of skeleton atoms in the ring is 3, 5, 7, 9, 11, or 14. Thus, for example, pyridine, piperidine, piperazine, and benzene are six-membered rings, while thiophene and pyrrole are five-membered rings.

[0068] The term "cycloalkyl" refers to a monocyclic saturated hydrocarbon system without heteroatoms or double bonds. The terms "3-14 membered cycloalkyl" contain 3 to 14 ring atoms; "3-10 membered cycloalkyl" contain 3 to 10 ring atoms; and "3-8 membered cycloalkyl" contain 3 to 8 ring atoms. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0069] The term "heterocyclic alkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent. The terms "3-14-membered heterocyclic alkyl" contain 3 to 10 ring atoms; "3-10-membered heterocyclic alkyl" contains 3 to 10 ring atoms; and "3-8-membered heterocyclic alkyl" contains 3 to 8 ring atoms. In the aforementioned "3-14-membered heterocyclic alkyl," "3-10-membered heterocyclic alkyl," and "3-8-membered heterocyclic alkyl," one or more ring atoms are heteroatoms selected from N, O, or S, and the remaining ring atoms are carbon, preferably 1 to 3 of which are heteroatoms.

[0070] The term "aryl" refers to an aromatic ring group consisting of a monocyclic or fused polycyclic aromatic ring with a conjugated π-electron system, obtained by removing a hydrogen atom from a single carbon atom of the parent aromatic ring system. For example, an aryl group can have 6-10 or 6-8 carbon atoms. This includes bicyclic groups comprising an aromatic ring fused with a saturated, partially unsaturated, or aromatic carbon ring. Examples include, but are not limited to, phenyl, naphthyl, anthracene, indene, indane, 1,2-dihydronaphthalene, and 1,2,3,4-tetrahydronaphthalene.

[0071] The term "heteroaryl" refers to an aryl structure comprising at least one heteroatom independently selected from N, O, and S, which substitutes for a portion of a carbon atom to form an aromatic cyclic structure. Heteroaryl groups can be monocyclic or polycyclic fused. Examples of heteroaryl groups include, but are not limited to, pyrroleyl, furanyl, thiopheneyl, pyridinyl, imidazolyl, pyrimidinyl, pyrazinyl, thiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, imidazopyridyl, benzofuranyl, pyridazinyl, and isoyindolyl.

[0072] The term "6-membered heteroaryl" refers to an aryl structure comprising at least one 6-membered ring independently selected from N, O, and S heteroatoms. Examples include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, pyranyl, or thiaranyl; preferably pyridyl or pyrimidinyl.

[0073] The term "C1-C6 alkyl heteroaryl" refers to a heteroaryl structure comprising at least one C1-C6 alkyl substitution, wherein "C1-C6 alkyl" and "heteroaryl" are as defined above. The term "C1-C6 alkyl 5-10-membered heteroaryl" refers to a 5-10-membered heteroaryl structure with C1-C6 alkyl substitution; the term "C1-C6 alkyl 5-8-membered heteroaryl" refers to a 5-8-membered heteroaryl structure with C1-C6 alkyl substitution. Examples include, but are not limited to, , , or .

[0074] The term "alkoxy" refers to an alkyl group linked by an oxygen atom, wherein "alkyl" is as defined above. The term "C1-C6 alkoxy" refers to a group having a C1-C6 alkyl-O- structure. Examples of "C1-C6 alkoxy" include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert-butoxy.

[0075] The term "bicyclic fused ring" refers to a bicyclic compound formed by two ring structures sharing adjacent atoms. This bicyclic structure can be an all-carbon ring (composed entirely of carbon atoms, for example, ...). It can also be a ring containing heteroatoms (such as N, O, or S, etc.) (e.g., ), and can also contain, for example Rings of atomic groups (e.g., "6-14 membered bicyclic fused ring" refers to bicyclic compounds having 6 to 14 ring atoms; "6-10 membered bicyclic fused ring" refers to bicyclic compounds having 6 to 10 ring atoms, including but not limited to: 6-membered bicyclic fused rings with a 5-membered ring and a 3-membered ring, 7-membered bicyclic fused rings with a 5-membered ring and a 4-membered ring, 8-membered bicyclic fused rings with a 5-membered ring and a 5-membered ring, 7-membered bicyclic fused rings with a 6-membered ring and a 3-membered ring, 8-membered bicyclic fused rings with a 6-membered ring and a 4-membered ring, 9-membered bicyclic fused rings with a 6-membered ring and a 5-membered ring, and 10-membered bicyclic fused rings with a 6-membered ring and a 6-membered ring; preferably 8- or 9-membered bicyclic fused rings, these fused alkyl groups can be connected to the rest of the molecule through any one ring atom.

[0076] The term "bicyclic fused heterocycle" refers to a structure consisting of two ring structures that share adjacent atoms and contain heteroatoms (such as N, O, or S) and / or heteroatomic groups (such as...). The bicyclic compound of the present invention. The number of heteroatoms in the "bicyclic fused heterocycle" can be 1, 2, 3, 4, or 5; preferably 1, 2, 3, or 4; more preferably 1, 2, or 3. Including but not limited to: 6-membered bicyclic fused heterocycles with a 5-membered ring and a 3-membered ring (examples include but are not limited to...). ), 7-membered bicyclic fused heterocyclic rings with 5-membered rings and 4-membered rings (examples include, but are not limited to, such as...) ), 8-membered bicyclic fused helical rings with 5-membered rings and 5-membered rings (examples include but are not limited to) ), 7-membered bicyclic fused heterocyclic rings with 6-membered rings and 3-membered rings (examples include, but are not limited to, such as...) ), 8-membered bicyclic fused heterocyclic rings with 6-membered rings and 4-membered rings (examples include but are not limited to) ), 9-membered bicyclic fused helical rings with 6-membered rings and 5-membered rings (examples include but are not limited to) ), 10-membered bicyclic fused heterocyclic rings with 6-membered rings and 6-membered rings (examples include, but are not limited to, such as...) These fused heterocyclic groups can be connected to the rest of the molecule by any suitable ring atom.

[0077] The term "pharmaceutically acceptable" means that a carrier, delivery substance, excipient, diluent, and / or the salt formed therefrom is generally chemically or physically compatible with other components constituting a drug dosage form and physiologically compatible with receptors.

[0078] The term "pharmaceutically acceptable carrier" refers to carriers that do not cause significant irritation to the body and do not impair the biological activity and properties of the active compound. This includes, but is not limited to, any diluents, disintegrants, binders, glidants, and wetting agents approved by the National Medical Products Administration for use in humans or animals.

[0079] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological potency of the free acid or base of a particular compound without any adverse biological effects. Examples include acid (including organic and inorganic acids) addition salts or base addition salts (including organic and inorganic bases), as well as zwitterionic salts and quaternary ammonium salts, such as alkylammonium salts. The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing an acid radical or base using conventional chemical methods. Generally, such salts are prepared by reacting these compounds, in their free acid or base form, with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture of both.

[0080] The term "effective dose" or "therapeutic effective dose" refers to a sufficient amount of a drug or agent that is non-toxic but achieves the desired effect. The precise dosage will vary depending on a variety of factors, such as variables dependent on the subject (e.g., age, immune system health, etc.), the disease or illness, and the treatment administered.

[0081] The term "pharmaceutical composition" means a composition comprising the compounds described in this disclosure or their pharmaceutically acceptable salts, and at least one pharmaceutically acceptable ingredient selected from the following, depending on the manner of administration and the nature of the dosage form: carriers, diluents, adjuvants, excipients, preservatives, fillers, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, flavoring agents, fragrances, antibacterial agents, antifungal agents, lubricants, dispersants, thermosensitive materials, temperature regulators, adhesives, stabilizers, suspending agents, etc.

[0082] The term "treatment" includes suppressing, alleviating, preventing, or eliminating one or more symptoms or side effects associated with the disease, condition, or disorder being treated.

[0083] The abbreviations used in the claims and description have the following meanings: V / V: Volume percentage concentration.

[0084] M: mol / L.

[0085] mM: mmol / L; 1mM = 0.001 mol / L.

[0086] nM: nmol / L; 1 nM = 1×10 -9 mol / L.

[0087] DMSO: Dimethyl sulfoxide.

[0088] DMSO- d6 : Deuterated dimethyl sulfoxide.

[0089] 1 1H NMR: Proton nuclear magnetic resonance spectrum.

[0090] LCMS: Liquid chromatography-mass spectrometry.

[0091] LC-MS / MS: Liquid Chromatography-Tandem Mass Spectrometry.

[0092] m / z: mass-to-charge ratio; rpm: rotational speed; h: hour. Detailed Implementation

[0093] The preparation methods of the compounds of the present invention are described in more detail below, but these specific preparation methods do not constitute any limitation on the scope of the present invention. Furthermore, reaction conditions such as reactants, solvents, bases, amounts of compounds used, reaction temperatures, and reaction times are not limited to the examples below.

[0094] The compounds of the present invention can also be conveniently prepared by combining various synthetic methods described in this specification or known in the art, such combinations being readily performed by those skilled in the art.

[0095] Intermediate 1: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-bromoimidazo[1,2-a]pyridine-3-carboxamide

[0096] a) Preparation of 5-(benzo[d]oxazol-2-yl)-2-methylaniline 2-Chlorobenzo[d]oxazole (230 mg), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)aniline (350 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (123 mg), potassium phosphate (414 mg), 1,4-dioxane (9 mL), and water (1 mL) were added to a reaction flask and stirred at 100 °C for 5 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 445 mg of the title compound.

[0097] b) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-bromoimidazole[1,2-a]pyridine-3-carboxamide 297 mg of 6-bromoimidazole[1,2-a]pyridine-3-carboxylic acid, 246 mg of N-methylimidazole, and 336 mg of N,N,N',N'-tetramethylchlorourea hexafluorophosphate were added to acetonitrile (12 mL), and the mixture was stirred at room temperature for 10 minutes under nitrogen protection. Then, 224 mg of 5-(benzo[d]oxazol-2-yl)-2-methylaniline was added, and the reaction was continued at room temperature for 12 hours under nitrogen. After the reaction was completed, the organic phase was concentrated, a small amount of methanol was added, and the filter cake was collected. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 401 mg of the title compound.

[0098] Example 1: N-(5-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

[0099] a) Preparation of 2-(4-methyl-3-nitrophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole 500 mg of 2-bromo-1-(4-methyl-3-nitrophenyl)ethane-1-one, 701 mg of pyrrolidine-2-imine hydrochloride, 821 mg of sodium carbonate, and 5 mL of N,N-dimethylformamide were added to a reaction flask. The reaction was carried out at 80 °C for 2 hours under a nitrogen atmosphere. The reaction was quenched with water (15 mL) at 25 °C. The precipitated solid was collected by filtration and washed with water to give 410 mg of the title compound.

[0100] b) Preparation of 5-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-2-methylaniline 100 mg of 2-(4-methyl-3-nitrophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole was added to a solution of ethanol (5 mL) and water (0.5 mL), followed by the addition of zinc powder (161 mg) and ammonium chloride (132 mg). The mixture was reacted at 50 °C for 40 minutes. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The filtrate was concentrated to obtain 85 mg of the title compound.

[0101] c) Preparation of N-(5-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide 5-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-yl)-2-methylaniline (80 mg) and imidazo[1,2-a]pyridine-3-carboxylic acid (61 mg) were dissolved in acetonitrile (3 mL), followed by the addition of 1-methylimidazolium (62 mg) and N,N,N',N'-tetramethylchlorourea hexafluorophosphate (116 mg). The reaction was carried out at 50 °C for 2 hours. The reaction was quenched with water at 25 °C, and the mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were then washed with water (2 x 5 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Prep OBDC18 column 30*150 mm, 5 μm; mobile phase A: water (10 mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60 mL / min; gradient (B%): 5%B to 5%B within 1 min, 5%B to 15%B within 2 min, 15% to 30%B within 12 min; wavelength: 254 nm / 220 nm; column temperature: 25°C; retention time (min): 11.6), yielding 10.8 mg of the title compound.

[0102] 1 H NMR (400 MHz, DMSO -d6)δ 9.91 (s, 1H), 9.47 (dt, J = 7.0, 1.2 Hz,1H), 8.56 (s, 1H), 7.77 (dt, J = 9.1, 1.2 Hz, 1H), 7.72 (d, J = 1.8 Hz, 1H),7.56 – 7.48 (m, 3H), 7.24 (d, J = 8.0 Hz, 1H), 7.16 (td, J = 6.9, 1.3 Hz,1H), 3.97 (t, J = 7.0 Hz, 2H), 2.75 (dd, J = 8.2, 6.7 Hz, 2H), 2.56 – 2.51(m, 2H), 2.24(s, 3H). LCMS (ESI) m / z = 358[M+H] + . Example 2: N-(2-methyl-5-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)phenyl)imidazo[1,2-a]pyridin-3-carboxamide

[0103] a) Preparation of 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine-2-amine [1,2,4]triazolo[1,5-a]pyridine-2-amine (402 mg), platinum dioxide (137 mg), and acetic acid (15 mL) were added to a reaction flask and stirred at room temperature for 12 hours under a nitrogen atmosphere. After the reaction was completed, diatomaceous earth was added and the mixture was filtered twice under reduced pressure. The filtrate was then concentrated under reduced pressure to obtain 416 mg of the title compound.

[0104] b) Preparation of 2-bromo-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine 208 mg of 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine-2-amine, 536 mg of cuprous bromide, 1.5 mL of isoamyl nitrite, and 6 mL of acetonitrile were added to a reaction flask and stirred at 70 °C for 12 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 152 mg of the title compound.

[0105] c) Preparation of 2-methyl-5-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)aniline 2-Bromo-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine (152 mg), (3-amino-4-methylphenyl)boronic acid (114 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (62 mg), potassium phosphate (318 mg), 1,4-dioxane (5 mL), and water (1 mL) were added to a reaction flask and stirred at 80 °C for 12 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 81 mg of the title compound.

[0106] d) Preparation of N-(2-methyl-5-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide 2-Methyl-5-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl)aniline (81 mg), imidazole[1,2-A]pyridine-3-carboxylic acid (58 mg), pyridine (140 mg), and phosphorus oxychloride (160 mg) were added to dichloromethane (8 mL), and the mixture was stirred at room temperature under a nitrogen atmosphere for 12 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 9.09 mg of the title compound.

[0107] 1 H NMR (400 MHz, DMSO- d 6) δ 9.94 (s, 1H), 9.47 (d, J = 7.0 Hz, 1H), 8.58(s, 1H), 8.03 (d, J = 1.7 Hz, 1H), 7.81 – 7.75 (m, 2H), 7.54 – 7.50 (m, 1H),7.36 (d, J = 8.0 Hz, 1H), 7.20 – 7.16 (m, 1H), 4.14 (t, J = 5.9 Hz, 2H), 2.86 (t, J = 6.3 Hz, 2H), 2.31 (s, 3H), 2.05 – 2.00 (m, 2H), 1.91 (ddd, J = 10.7, 7.9, 5.1 Hz, 2H). LCMS (ESI) m / z = 373.2 [M+H] + . Example 3: (S)-N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-(1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide a) Preparation of S)-1-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrazol-1-yl)prop-2-ol Pinaryl 4-pyrazoloniate (194 mg), (R)-(-)-epoxypropyl methyl ether (106 mg), and cesium carbonate (326 mg) were added to anhydrous N,N-dimethylformamide (4 mL), and reacted at 100 °C for 3 hours. The solid was filtered off, and the concentrated solvent was used directly in the next step.

[0108] b) Preparation of (S)-N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-(1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (S)-1-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrazol-1-yl)prop-2-ol (42 mg), N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-bromoimidazolo[1,2-a]pyridine-3-carboxamide (67 mg, intermediate 1), sodium carbonate (30 mg), and 1,1-bis(diphenylphosphine)diberberine palladium dichloride (9 mg) were dissolved in 1,4-dioxane (1.6 mL) and water (0.4 mL) and reacted at 100 °C for 3 h. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 26.02 mg of the title compound.

[0109] 1 H NMR (400 MHz, DMSO -d 6) δ 10.05 (s, 1H), 9.66 (t, J = 1.5 Hz, 1H),8.60 (s, 1H), 8.34 (d, J = 1.8 Hz, 1H), 8.23 ​​(d, J = 0.9 Hz, 1H), 8.02 (dd, J =7.9, 1.9 Hz, 1H), 7.93 (d, J= 0.8 Hz, 1H), 7.86 – 7.76 (m, 4H), 7.56 (d, J = 8.1Hz, 1H), 7.49 – 7.38 (m, 2H), 5.19 (d, J = 5.3 Hz, 1H), 4.21 (dd, J = 13.5, 3.9Hz, 1H), 4.07 (dd, J = 13.5, 7.5 Hz, 1H), 4.03 – 3.95 (m, 1H), 3.29 (d, J = 5.2Hz, 2H), 3.28 (s, 3H), 2.42 (s, 3H). LCMS (ESI) m / z = 523.2 [M+H] + ... Example 4: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-((3aR,5r,6aS)-5-hydroxyhexahydrocyclopentan[c]pyrrole-2(1H)-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0110] a) Preparation of 5-(benzo[d]oxazol-2-yl)-2-methylaniline (3-Amino-4-methylphenyl)boronic acid (500 mg), 2-chlorobenzo[d]oxazole (503 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (270 mg), and potassium phosphate (1403 mg) were dissolved in 1,4-dioxane (15 mL) and water (5 mL), and the mixture was reacted at 100 °C for 5 h after nitrogen purging. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give the title compound (768 mg).

[0111] b) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromopyrazolo[1,5-a]pyridine-3-carboxylic acid (467 mg), tetramethylchlorourea hexafluorophosphate (547 mg), and N-methylimidazolium (400 mg) were dissolved in acetonitrile (15 mL) and reacted at room temperature for 5 min. Then, 5-(benzo[d]oxazol-2-yl)-2-methylaniline (364 mg) was added, and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the mixture was filtered, the filtrate was concentrated, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give the title compound (562 mg).

[0112] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-((3aR,5r,6aS)-5-hydroxyhexahydrocyclopentan[c]pyrrole-2(1H)-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (80 mg), (3aR,5r,6aS)-octahydrocyclopentan[c]pyrrole-5-ol hydrochloride (26 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (17 mg), and cesium carbonate (172 mg) were dissolved in 1,4-dioxane (5 mL) solution and reacted at 90 °C for 16 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 6.93 mg of the title compound.

[0113] 1 H NMR (400 MHz, DMSO -d6) δ 9.32 (s, 1H), 8.56 (s, 1H), 8.53 (d, J =7.6 Hz, 1H), 8.41 (d, J = 1.8 Hz, 1H), 7.94 (dd, J = 7.9, 1.9 Hz, 1H), 7.85 –7.76 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.46 – 7.39 (m, 2H), 7.01 (d, J = 2.7Hz, 1H), 6.66 (dd, J = 7.7, 2.7 Hz, 1H), 4.64 (d, J = 4.3 Hz, 1H), 4.16 (s,1H), 3.61 – 3.52 (m, 2H), 3.36 (d, J = 3.7 Hz, 2H), 2.75 (s, 2H), 2.40 (s,3H), 2.14 – 2.02 (m, 2H), 1.45 (dt, J = 12.3, 5.7 Hz, 2H). LCMS (ESI) m / z = 494.2 [M+H] + . Example 5: (S)-N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0114] a) Preparation of (S)-1-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrazol-1-yl)prop-2-ol Dissolve 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)-1H-pyrazole (400 mg), (R)-2-(methoxymethyl)ethylene oxide (218 mg), and cesium carbonate (673 mg) in... N , N The reaction was carried out in a 10 mL solution of dimethylformamide at 100 °C for 3 h. After the reaction was completed, the mixture was filtered and the filtrate was concentrated to obtain the title compound (480 mg).

[0115] b) Preparation of (S)-N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (S)-1-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-pyrazol-1-yl)prop-2-ol (56 mg), N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (90 mg, prepared according to Example 4), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (16 mg), and potassium phosphate (85 mg) were dissolved in 1,4-dioxane (4 mL) and water (1 mL), and reacted at 100 °C for 5 h after nitrogen purging. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 19.20 mg of the title compound.

[0116] 1 H NMR (400 MHz, DMSO- d 6) δ 9.69 (s, 1H), 8.84 (d, J = 7.2 Hz, 1H), 8.77(s, 1H), 8.46 – 8.39 (m, 2H), 8.36 (d, J = 1.9 Hz, 1H), 8.09 (s, 1H), 7.99 (dd, J = 8.0, 1.8 Hz, 1H), 7.86 – 7.76 (m, 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.48 – 7.38(m, 3H), 5.22 (d, J = 5.3 Hz, 1H), 4.23 (dd, J = 13.3, 3.8 Hz, 1H), 4.10 (d, J =7.5 Hz, 1H), 4.07 – 3.99 (m, 1H), 3.32 (s, 2H), 3.30 (d, J = 4.6 Hz, 3H), 2.44 (s, 3H). LCMS (ESI) m / z = 523.2 [M+H] + . Example 6: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0117] a) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (45 mg, prepared according to Example 4), 2-azaspiro[3.3]heptane-6-ol hydrochloride (15 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (9 mg), and cesium carbonate (160 mg) were added to 1,4-dioxane (4 mL), and the mixture was stirred overnight at 80 °C under a nitrogen atmosphere. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 24.28 mg of the title compound.

[0118] 1 H NMR (400 MHz, DMSO -d 6) δ 9.36 (s, 1H), 8.57 (s, 1H), 8.54 (d, J = 7.5Hz, 1H), 8.38 (d, J = 1.8 Hz, 1H), 7.94 (dd, J = 7.9, 1.9 Hz, 1H), 7.81 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.48 – 7.37 (m, 2H), 6.84 (d, J = 2.6 Hz, 1H), 6.38(dd, J = 7.5, 2.6 Hz, 1H), 5.07 (d, J = 6.2 Hz, 1H), 4.02 (m, 1H), 3.94 (d, J =17.5 Hz, 4H), 2.49 – 2.44 (m, 2H), 2.40 (s, 3H), 2.09 – 2.00 (m, 2H). LCMS (ESI) m / z = 480.2[M+H] + . Example 7: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0119] a) Preparation of 5-(benzo[d]oxazol-2-yl)-2-methylaniline 3-Amino-4-methylphenylborate salt (1.48 g), 2-chlorobenzoxazole (1.51 g), potassium carbonate (2.71 g), and 1,1-bis(diphenylphosphine)diferropalladium dichloride (340 mg) were dissolved in 50 mL of 1,4-dioxane and 10 mL of water under a nitrogen atmosphere and reacted at 100 °C for 3 hours. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 1.14 g of the title compound.

[0120] b) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-bromopyrazolo[1,5-a]pyridine-3-carboxamide 6-Bromopyrazolo[1,5-A]pyridine-3-carboxylic acid (289 mg), N,N,N',N'-tetramethylchloromethamidin hexafluorophosphate (336 mg), and N-methylimidazolium (0.6 mL) were dissolved in anhydrous acetonitrile (10 mL) and stirred for 20 min. 5-(benzo[d]oxazol-2-yl)-2-methylaniline (224 mg) was added, and the reaction was carried out overnight at 50 °C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 276 mg of the title compound.

[0121] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-bromopyrazolo[1,5-a]pyridine-3-carboxamide (90 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (30 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (18 mg), and cesium carbonate (326 mg) were added to 1,4-dioxane (5 mL), and the reaction was carried out overnight at 90°C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 14.18 mg of the title compound.

[0122] 1 H NMR (400 MHz, DMSO -d6) δ 9.61 (s, 1H), 8.61 (s, 1H), 8.34 (d, J = 1.8Hz, 1H), 8.09 (d, J = 9.4 Hz, 1H), 7.96 (dd, J = 7.9, 1.9 Hz, 1H), 7.90 (d, J = 2.0Hz, 1H), 7.85 – 7.76 (m, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.48 – 7.37 (m, 2H), 7.02 (dd, J = 9.4, 2.1 Hz, 1H), 5.08 (d, J = 6.3 Hz, 1H), 4.03 (q, J = 6.8 Hz, 1H), 3.82 (d, J = 15.5 Hz, 4H), 2.47 (m, 2H), 2.39 (s, 3H), 2.10 – 1.98 (m, 2H). LCMS (ESI) m / z = 480.2[M+H] + . Example 8: 5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)-N-(2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0123] a) Preparation of 2-((4-methyl-3-nitrobenzyl)amino)-4-(trifluoromethyl)phenol 4-Methyl-3-nitrobenzaldehyde (450 mg) and 2-amino-4-(trifluoromethyl)phenol (482 mg) were dissolved in ethyl acetate (10 mL) solution and reacted at 80 °C for 3 h. After the reaction was completed, the filtrate was concentrated to obtain 900 mg of the title compound.

[0124] b) Preparation of 2-(4-methyl-3-nitrophenyl)-5-(trifluoromethyl)benzo[d]oxazole 2-((4-methyl-3-nitrobenzyl)amino)-4-(trifluoromethyl)phenol (900 mg) and dichlorocyanobenzoquinone (742 mg) were dissolved in dichloromethane (10 mL) and reacted at room temperature for 1 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 4 / 1 (V / V)) to give 810 mg of the title compound.

[0125] c) Preparation of 2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)aniline 2-(4-methyl-3-nitrophenyl)-5-(trifluoromethyl)benzo[d]oxazole (810 mg), iron powder (800 mg), and ammonium chloride (800 mg) were dissolved in ethanol (12 mL) and water (3 mL) and reacted at 80 °C for 3 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 514 mg of the title compound.

[0126] d) Preparation of 5-bromo-N-(2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 150 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid, 175 mg of tetramethylchlorourea hexafluorophosphate, and 129 mg of N-methylimidazolium were dissolved in 15 mL of acetonitrile and reacted at room temperature for 5 min. Then, 152 mg of 2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)aniline was added and reacted at room temperature for 16 h. After the reaction was completed, the mixture was filtered, the filtrate was concentrated, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 206 mg of the title compound.

[0127] e) Preparation of 5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)-N-(2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(2-methyl-5-(5-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (90 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (26 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-yl]dichloro(3-chloropyridine-κN)-palladium (17 mg), and cesium carbonate (172 mg) were dissolved in 1,4-dioxane (5 mL) solution and reacted at 80 °C for 16 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 21.15 mg of the title compound.

[0128] 1 H NMR (400 MHz, DMSO- d 6) δ 9.38 (s, 1H), 8.57 (s, 1H), 8.54 (d, J = 7.5Hz, 1H), 8.43 (d, J = 1.8 Hz, 1H), 8.23 ​​(d, J = 1.7 Hz, 1H), 8.04 (d, J = 8.5 Hz,1H), 7.99 – 7.96 (m, 1H), 7.81 (dd, J = 8.9, 1.8 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 6.84 (d, J = 2.6 Hz, 1H), 6.39 (dd, J = 7.5, 2.6 Hz, 1H), 5.08 (d, J = 6.2 Hz, 1H), 4.02 (q, J = 7.0 Hz, 1H), 3.94 (d, J = 17.9 Hz, 4H), 2.49 – 2.47 (m, 2H), 2.41 (s, 3H), 2.04 (ddd, J = 10.0, 7.6, 2.9 Hz, 2H). LCMS (ESI) m / z = 548.2 [M+H] + . Example 9: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0129] a) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (300 mg, prepared according to Example 4), (1H-pyrazol-4-yl)boronic acid (113 mg), [1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) chloride (44 mg), potassium phosphate (427 mg), 1,4-dioxane (5 mL), and water (1 mL) were added to a reaction flask and reacted at 80 °C for 2 hours under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 120 mg of the title compound.

[0130] b) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (100 mg), 2,2-dimethylethylene oxide (17 mg), potassium carbonate (64 mg), and N,N-dimethylformamide (2 mL) were added to a reaction flask and reacted at 100 °C for 2 hours under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The concentrated filtrate was purified by reversed-phase rapid chromatography under the following conditions (column: Xselect CSH PrepC18, 30*150mm, 5μm; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 40%B to 55%B over 8 minutes; detection wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 9.1), yielding 36.2 mg of the title compound.

[0131] 1 H NMR (400 MHz, DMSO- d 6) d9.67 (s, 1H), 8.83 (dd, J = 7.2, 0.9 Hz, 1H),8.76 (s, 1H), 8.41 (d, J = 1.8 Hz, 1H), 8.36 (d, J = 2.0 Hz, 2H), 8.07 (d, J = 0.8Hz, 1H), 7.98 (dd, J = 8.0, 1.9 Hz, 1H), 7.85 – 7.76 (m, 2H), 7.54 (d, J = 8.1Hz, 1H), 7.47 – 7.37 (m, 3H), 4.77 (s, 1H), 4.07 (s, 2H), 2.43 (s, 3H), 1.10(s, 6H). LCMS (ESI) m / z = 507[M+H] + . Example 10: N-(5-(benzo[d]oxazol-2-yl)-4-fluoro-2-methylphenyl)-5-(6-hydroxy-2-aza[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0132] a) Preparation of 4-fluoro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)aniline 5-Bromo-4-fluoro-2-methylaniline (816 mg), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborane) (1524 mg), tris(dibenzylacetone)dipalladium (366 mg), potassium acetate (784 mg), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (382 mg), 1,4-dioxane (25 mL), and water (5 mL) were added to a reaction flask and stirred at 100 °C for 4 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 3 / 1 (V / V)) to give 870 mg of the title compound.

[0133] b) 4-Fluoro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)aniline (502 mg), 2-chlorobenzo[d]oxazole (306 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (163 mg), potassium carbonate (552 mg), 1,4-dioxane (15 mL), and water (1 mL) were added to a reaction flask and stirred at 100 °C for 4 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 528 mg of the title compound.

[0134] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-4-fluoro-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide 290 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid, 296 mg of N-methylimidazolium, and 403 mg of N,N,N',N'-tetramethylchlorourea hexafluorophosphate were added to acetonitrile (15 mL) and stirred at 50 °C for 10 minutes under a nitrogen atmosphere. 290 mg of 5-(benzo[d]oxazol-2-yl)-4-fluoro-2-methylaniline was added, and the mixture was stirred at 50 °C for 12 hours under a nitrogen atmosphere. After the reaction was complete, the reaction solution was concentrated under reduced pressure. A small amount of methanol was added, and the mixture was filtered to obtain 378 mg of the title compound.

[0135] d) Preparation of N-(5-(benzo[d]oxazol-2-yl)-4-fluoro-2-methylphenyl)-5-(6-hydroxy-2-aza[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-4-fluoro-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (93 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (30 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-yl]dichloro(3-chloropyridine-κN)-palladium (20 mg), cesium carbonate (195 mg), and 1,4-dioxane (3 mL) were added to a reaction flask and stirred at 90 °C for 6 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 34.15 mg of the title compound.

[0136] 1 H NMR (400 MHz, DMSO- d6) δ 9.42 (s, 1H), 8.56 (s, 1H), 8.53 (s, 1H), 8.30 (d, J = 7.0 Hz, 1H), 7.85 (dd, J = 8.6, 6.6 Hz, 2H), 7.50 – 7.43 (m, 3H), 6.83 (d, J = 2.5 Hz, 1H), 6.39 (dd, J = 7.5, 2.6 Hz, 1H), 5.09 (d, J = 6.2 Hz, 1H), 4.02 (d, J = 7.0 Hz, 1H), 3.96 (s, 2H), 3.92 (s, 2H), 2.39 (s, 3H), 2.05 (dd, J =11.8, 7.1 Hz, 4H). LCMS (ESI) m / z = 498.2[M+H] + . Example 11: N-(5-(5-(2-hydroxypropyl-2-yl)benzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide a) Preparation of 2-(4-methyl-3-nitrophenyl)benzo[D]oxazol-5-carboxylic acid ester Methyl 3-amino-4-hydroxybenzoate (1 g), 4-methyl-3-nitrobenzaldehyde (1 g), and ethyl acetate (30 mL) were added to a reaction flask and stirred at 80 °C for 3 hours under a nitrogen atmosphere. After the reaction was complete, the reaction solution was concentrated under reduced pressure, and 2,3-dichloro-5,6-dicyanobenzoquinone (2 g) and dichloromethane (60 mL) were added under a nitrogen atmosphere. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was concentrated under reduced pressure, a small amount of methanol was added, and the mixture was filtered to obtain a filter cake containing 1569 mg of the title compound.

[0137] b) Preparation of methyl 2-(3-amino-4-methylphenyl)benzo[d]oxazol-5-carboxylic acid 2-(4-methyl-3-nitrophenyl)benzo[D]oxazol-5-carboxylic acid ester (936 mg), iron powder (838 mg), ammonium chloride (803 mL), and ethanol / water (4:1) (20 mL) were added to a reaction flask and stirred at 80 °C for 2 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 765 mg of the title compound.

[0138] c) Preparation of 2-(4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)benzo[D]oxazol-5-carboxylic acid ester Pyrazolo[1,5-A]pyridine-3-carboxylic acid (162 mg), N-methylimidazolium (246 mg), and N,N,N',N'-tetramethylchlorourea hexafluorophosphate (336 mg) were added to acetonitrile (15 mL), and the mixture was stirred at 50 °C for 10 minutes under a nitrogen atmosphere. Then, methyl 2-(3-amino-4-methylphenyl)benzo[d]oxazol-5-carboxylic acid (283 mg) was added, and the mixture was stirred at 50 °C for 12 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was concentrated, a small amount of methanol was added, and the mixture was filtered under reduced pressure to obtain a filter cake containing 234 mg of the title compound.

[0139] d) Preparation of N-(5-(5-(2-hydroxypropyl-2-yl)benzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Under a nitrogen atmosphere, methyl magnesium bromide (0.6 mL) was added to anhydrous tetrahydrofuran (5 mL) of 2-(4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)benzo[D]oxazol-5-carboxylic acid ester (128 mg). The mixture was stirred at 50 °C for 2 h. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 39.99 mg of the title compound.

[0140] 1 H NMR (400 MHz, DMSO- d 6) δ 9.78 (s, 1H), 8.87 (d, J = 6.9 Hz, 1H), 8.82(s, 1H), 8.32 (s, 1H), 8.27 (d, J = 8.9 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.86(s, 1H), 7.70 (d, J = 8.6 Hz, 1H), 7.54 (t, J = 8.4 Hz, 3H), 7.15 (t, J = 6.9 Hz,1H), 5.19 (s, 1H), 2.41 (s, 3H), 1.51 (s, 6H). LCMS (ESI) m / z=427[M+H] + . Example 12: N-(5-(6-cyano-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0141] a) Preparation of 2-(3-amino-4-methylphenyl)-1H-benzo[d]imidazol-6-nitrile (3-Amino-4-methylphenyl)boronic acid (300 mg), 2-chloro-1H-benzo[d]imidazolium-6-onitrile (360 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (180 mg), and potassium phosphate (840 mg) were dissolved in 1,4-dioxane (15 mL) and water (3 mL), and reacted at 80 °C for 5 h after nitrogen purging. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give the title compound (480 mg).

[0142] b) Preparation of N-(5-(6-cyano-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Pyrazolo[1,5-a]pyridine-3-carboxylic acid (78 mg), tetramethylchlorourea hexafluorophosphate (135 mg), and N-methylimidazolium (100 mg) were dissolved in acetonitrile (15 mL) and reacted at room temperature for 5 min. Then, 2-(3-amino-4-methylphenyl)-1H-benzo[d]imidazolium-6-onitrile (100 mg) was added, and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the resulting mixture was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 14.68 mg of the title compound.

[0143] 1 H NMR (400 MHz, DMSO- d 6) δ 9.79 (s, 1H), 8.87 (d, J = 7.0 Hz, 1H), 8.82(s, 1H), 8.32 (s, 1H), 8.27 (d, J = 8.9 Hz, 1H), 8.13 (s, 1H), 8.02 (d, J = 8.0Hz, 1H), 7.74 (d, J = 8.3 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.52 (dd, J= 11.4, 7.9 Hz, 2H), 7.14 (t, J = 7.0 Hz, 1H), 2.38 (s, 3H). LCMS (ESI) m / z = 393.2 [M+H] + . Example 13: N-(5-(6-methoxy-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0144] a) Preparation of 5-(6-methoxy-1H-benzo[d]imidazol-2-yl)-2-methylaniline (3-Amino-4-methylphenyl)boronic acid (300 mg), 2-chloro-6-methoxy-1H-benzis[d]imidazole (360 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (180 mg), and potassium phosphate (840 mg) were dissolved in 1,4-dioxane (15 mL) and water (3 mL). The mixture was purged with nitrogen and reacted at 80 °C for 5 h. After the reaction was complete, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give the title compound (373 mg).

[0145] b) Preparation of N-(5-(6-methoxy-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Pyrazolo[1,5-a]pyridine-3-carboxylic acid (78 mg), tetramethylchlorourea hexafluorophosphate (135 mg), and N-methylimidazolium (100 mg) were dissolved in acetonitrile (15 mL) and reacted at room temperature for 5 min. Then, 5-(6-methoxy-1H-benzo[d]imidazol-2-yl)-2-methylaniline (100 mg) was added, and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the resulting mixture was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 17.60 mg of the title compound.

[0146] 1 H NMR (400 MHz, DMSO- d 6) δ 9.85 (s, 1H), 8.89 (d, J = 7.0 Hz, 1H), 8.85(s, 1H), 8.31 (d, J = 1.9 Hz, 1H), 8.26 (d, J= 8.8 Hz, 1H), 7.97 (dd, J = 8.1, 2.0Hz, 1H), 7.71 (d, J = 8.9 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.61 – 7.52 (m, 2H), 7.21 (d, J = 2.3 Hz, 1H), 7.16 (ddd, J = 7.0, 5.7, 1.7 Hz, 2H), 3.90 (s, 3H), 2.44 (s, 3H). LCMS (ESI) m / z = 398.2 [M+H] + . Example 14: N-(5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0147] a) Preparation of 5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylaniline (3-Amino-4-methylphenyl)boronic acid (500 mg), 2,5-dichlorobenzo[d]oxazole (619 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (270 mg), and potassium phosphate (1403 mg) were dissolved in 1,4-dioxane (15 mL) and water (5 mL), and the mixture was reacted at 100 °C for 5 h after nitrogen purging. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 322 mg of the title compound.

[0148] b) Preparation of 5-bromo-N-(5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 150 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid, 175 mg of tetramethylchlorourea hexafluorophosphate, and 129 mg of N-methylimidazolium were dissolved in 15 mL of acetonitrile and reacted at room temperature for 5 min. Then, 152 mg of 5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylaniline was added and reacted at room temperature for 16 h. After the reaction was completed, the mixture was filtered, the filtrate was concentrated, and the residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 134 mg of the title compound.

[0149] c) Preparation of N-(5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (80 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (26 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (17 mg), and cesium carbonate (172 mg) were dissolved in 1,4-dioxane (5 mL) solution and reacted at 80 °C for 2 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 11.11 mg of the title compound.

[0150] 1 H NMR (400 MHz, DMSO- d 6) δ 9.36 (s, 1H), 8.57 (s, 1H), 8.54 (d, J = 7.5Hz, 1H), 8.39 (d, J = 1.8 Hz, 1H), 7.95 (d, J = 1.8 Hz, 1H), 7.93 (d, J = 2.1 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.55 – 7.42 (m, 2H), 6.84 (d, J = 2.5 Hz, 1H), 6.39 (dd, J = 7.5, 2.6 Hz, 1H), 5.09 (d, J = 6.2 Hz, 1H), 4.04 (p, J = 7.1 Hz, 1H), 3.95 (d, J = 17.7 Hz, 4H), 2.49 (s, 2H), 2.41 (s, 3H), 2.05 (ddd, J = 10.0, 7.5, 3.0 Hz, 2H). LCMS (ESI) m / z = 514.2 [M+H] + . Example 15: 5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)-N-(2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0151] a) Preparation of 2-(4-methyl-3-nitrophenyl)-6-(trifluoromethyl)benzo[d]oxazole 2-Hydroxy-4-trifluoromethylaniline (708 mg) and 4-methyl-3-nitrobenzaldehyde (660 mg) were dissolved in ethyl acetate (15 mL) and reacted at 80 °C for 3 hours. The solvent was concentrated, and the crude product was dissolved in dichloromethane (15 mL), and 2,3-dichloro-5,6-dicyanobenzoquinone (908 mg) was added. The reaction was carried out at room temperature under a nitrogen atmosphere for one hour. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 10 / 1 (V / V)) to give 276 mg of the title compound.

[0152] b) Preparation of 2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)aniline 2-(4-methyl-3-nitrophenyl)-6-(trifluoromethyl)benzo[d]oxazole (268 mg) and ammonium chloride (225 mg) were dissolved in an ethanol / water solution of 4:1 (5 mL), and reduced iron powder (232 mg) was added. After nitrogen purging, the mixture was reacted at 85 °C for 24 hours. The solvent was concentrated, and the residue was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 4 / 1 (V / V)) to give 192 mg of the title compound.

[0153] c) Preparation of 5-bromo-N-(2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 129 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid, 149 mg of N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate, and 0.4 mL of N-methylimidazolium were dissolved in anhydrous acetonitrile (15 mL) and stirred for 20 min. 130 mg of 2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)aniline was added, and the mixture was reacted overnight at 50 °C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 120 mg of the title compound.

[0154] d) Preparation of 5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)-N-(2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (51 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (15 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (9 mg) and cesium carbonate (162 mg) were added to 1,4-dioxane (5 mL) and reacted overnight at 90°C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 10.2 mg of the title compound.

[0155] 1 H NMR (400 MHz, DMSO -d 6) δ 9.38 (s, 1H), 8.58 (s, 1H), 8.54 (d, J = 7.5Hz, 1H), 8.44 (d, J = 1.8 Hz, 1H), 8.31 (d, J = 1.6 Hz, 1H), 8.05 – 7.94 (m, 2H), 7.78 (dd, J = 8.4, 1.7 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 2.6 Hz, 1H), 6.39 (dd, J = 7.5, 2.6 Hz, 1H), 5.08 (d, J = 6.2 Hz, 1H), 4.02 (q, J = 7.0 Hz, 1H), 3.94 (d, J = 17.6 Hz, 4H), 2.48 (m, 2H), 2.41 (s, 3H), 2.05 (m, 2H). LCMS (ESI) m / z = 548.2 [M+H] + . Example 16: N-(5-(6-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0156] a) Preparation of 5-(6-chlorobenzo[d]oxazol-2-yl)-2-methylaniline 3-Amino-4-methylphenylborate salt (302 mg), 2,6-dichlorobenzoxazole (376 mg), potassium carbonate (552 mg), and 1,1-bis(diphenylphosphine)diferropalladium dichloride (120 mg) were dissolved in 1,4-dioxane (8 mL) and water (2 mL) under a nitrogen atmosphere and reacted at 100 °C for 3 hours. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 350 mg of the title compound.

[0157] b) Preparation of 5-bromo-N-(5-(6-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 184 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid, 214 mg of N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate, and 0.5 mL of N-methylimidazolium were dissolved in anhydrous acetonitrile (15 mL) and stirred for 20 min. 165 mg of 5-(6-chlorobenzo[d]oxazol-2-yl)-2-methylaniline was added, and the mixture was reacted overnight at 50 °C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 100 mg of the title compound.

[0158] c) Preparation of 5-(6-hydroxy-2-azaspiro[3.3]heptane-2-yl)-N-(2-methyl-5-(6-(trifluoromethyl)benzo[d]oxazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(6-chlorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (100 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (32 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (18 mg), and cesium carbonate (326 mg) were added to 1,4-dioxane (5 mL), and reacted at 80°C for two hours. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloromethane / methanol = 20 / 1 (V / V)) to give 20.69 mg of the title compound.

[0159] 1 H NMR (400 MHz, DMSO -d 6) δ 9.37 (s, 1H), 8.57 (s, 1H), 8.54 (d, J= 7.5Hz, 1H), 8.37 (d, J = 1.8 Hz, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.92 (dd, J = 8.0, 1.9Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.54 – 7.44 (m, 2H), 6.84 (d, J = 2.5 Hz, 1H), 6.38 (dd, J = 7.5, 2.6 Hz, 1H), 5.08 (d, J = 6.2 Hz, 1H), 4.02 (q, J = 6.9 Hz, 1H), 3.94 (d, J = 17.7 Hz, 4H), 2.47 (d, J = 5.7 Hz, 2H), 2.40 (s, 3H), 2.10 – 2.00(m, 2H). LCMS (ESI) m / z = 514.1 [M+H] + . Example 17: N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0160] a) Preparation of 5-fluoro-2-(4-methyl-3-nitrophenyl)benzo[d]oxazole 3 g of 2-amino-4-fluorophenol was added to 30 mL of ethyl acetate and stirred. Then, 4.68 g of 4-methyl-3-nitrobenzaldehyde was added in portions. The resulting mixture was stirred at 80°C for 3 hours. The mixture was concentrated. 5.36 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 70 mL of dichloromethane were added in portions to the mixture at 25°C. The mixture was stirred at 25°C under a nitrogen atmosphere for 1 hour. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (3 x 100 mL). The organic phase was washed with saturated sodium bicarbonate solution (3 x 100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 3.6 g of the title compound.

[0161] b) Preparation of 5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylaniline 440 mg of 5-fluoro-2-(4-methyl-3-nitrophenyl)benzo[d]oxazole was added to a solution of 5 mL of ethanol and 1 mL of water, followed by the addition of zinc powder (634 mg) and ammonium chloride (519 mg). The mixture was reacted at 50 °C for 2 hours. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated to obtain 100 mg of the title compound.

[0162] c) Preparation of 5-bromo-N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 398 mg of 5-bromopyrazolo[1,5-a]pyridine-3-carboxylic acid was dissolved in acetonitrile (40 mL), followed by the addition of 813 mg of 1-methylimidazole and 1529 mg of N,N,N',N'-tetramethylchlorourea hexafluorophosphate. The reaction was carried out at 25 °C for 20 min, followed by the addition of 400 mg of 5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylaniline. The reaction was continued at 80 °C for 16 h. After the reaction was completed, the mixture was quenched with water and extracted with dichloromethane (3 x 30 mL). The organic phase was washed with saturated sodium bicarbonate aqueous solution (3 x 30 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 400 mg of the title compound.

[0163] d) Preparation of N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (300 mg), 2-azaspiro[3.3]hepta-6-ol (73 mg), (SP-4-2)-bromo[dicyclohexyl[3-(1,1-dimethylethoxy)-6-methoxy-2',6'-bis(1-methylethyl)[1,1'-biphenyl]-2 [-k-κC1']phosphine-κP][4-[[2-(trimethylsilyl)ethoxy]carbonyl]phenyl]palladium (61 mg), (3-(tert-butoxy)-2′,6′-diisopropyl-6-methoxy-[1,1′-biphenyl]-2-yl)dicyclohexylphosphine (35 mg), sodium trimethylsilanolate (96 mg), and tetrahydrofuran (3 mL) were added to a reaction flask and reacted at 60 °C for 1 hour under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The concentrated filtrate was purified by reversed-phase rapid chromatography under the following conditions (column: Xselect CSH Prep C18, 30*150mm, 5μm; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 39%B to 55%B over 8 minutes; detection wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 10.43), yielding 60.6 mg of the title compound.

[0164] 1 H NMR (400 MHz, DMSO- d 6) δ 9.36 (s, 1H), 8.59 – 8.51 (m, 2H), 8.39(d, J = 1.8 Hz, 1H), 7.93 (dd, J = 7.9, 1.9 Hz, 1H), 7.85 (dd, J = 8.9, 4.4 Hz, 1H), 7.69 (dd, J = 8.8, 2.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.30 (td, J = 9.3, 2.7 Hz, 1H), 6.84 (d, J = 2.5 Hz, 1H), 6.39 (dd, J = 7.5, 2.6 Hz, 1H), 5.01 (s,1H), 4.03 (p, J = 7.2 Hz, 1H), 3.97 (s, 2H), 3.92 (s, 2H), 2.48 (d,J = 3.1 Hz,2H), 2.40 (s, 3H), 2.05 (ddd, J = 12.5, 6.5, 2.8 Hz, 2H). LCMS (ESI) m / z=498[M+H] + . Example 18: N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0165] a) Preparation of 2-(4-chloro-3-nitrophenyl)benzo[d]oxazole 2-Aminophenol (900 mg) was added to ethyl acetate (20 mL) and stirred, followed by the addition of 4-chloro-3-nitrobenzaldehyde (1.84 g) in portions. The resulting mixture was stirred at 80°C for 3 hours. The mixture was then concentrated. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (1.87 g) and dichloromethane (20 mL) were added in portions to the mixture at 25°C. The mixture was stirred at 25°C under a nitrogen atmosphere for 1 hour. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (3 x 100 mL). The organic phase was washed with saturated sodium bicarbonate solution (3 x 100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 730 mg of the title compound.

[0166] b) Preparation of 5-(benzo[d]oxazol-2-yl)-2-chloroaniline 2-(4-chloro-3-nitrophenyl)benzo[d]oxazole (700 mg) was added to a solution of ethanol (8 mL) and water (1.6 mL), followed by the addition of zinc powder (1 g) and ammonium chloride (818 mg). The mixture was reacted at 50 °C for 2 hours. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated to obtain 700 mg of the title compound.

[0167] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide 5-(benzo[d]oxazol-2-yl)-2-chloroaniline (500 mg) and methyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (625 mg) were dissolved in toluene (10 mL), and under nitrogen protection, trimethylaluminum (1.0 M heptane solution) (4.09 mL) was slowly added at 0 °C. The reaction was carried out at 100 °C for 2 hours. The reaction was quenched with saturated sodium hydroxide solution at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 100 mL), and the combined organic layers were washed with saturated sodium hydroxide solution (3 x 100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 600 mg of the title compound.

[0168] d) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (300 mg), 2-azaspiro[3.3]heptane-6-ol (73 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (54 mg), and cesium carbonate (627 mg) were added to 1,4-dioxane (5 mL), and the mixture was reacted at 80°C for two hours. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated, and the crude product was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Shield RP18OBD, 30*150mm, 5μm; mobile phase A: water (10mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 44%B to 58%B over 11 minutes; wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 10.82), yielding 36.2 mg of the title compound.

[0169] 1 H NMR (400 MHz, DMSO- d 6) δ 9.51 (s, 1H), 8.65 (s, 1H), 8.59 (s, 1H), 8.54 (d, J = 7.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.87 – 7.75 (m, 3H), 7.46 (p, J= 8.6, 8.0 Hz, 2H), 6.83 (s, 1H), 6.40 (d, J = 7.5 Hz, 1H), 5.12 (s, 1H), 4.01– 3.97 (m, 1H), 3.95 (d, J = 17.7 Hz, 4H), 2.46 – 2.40 (m, 2H), 2.09 – 2.00 (m, 2H). LCMS (ESI) m / z=500[M+H] + . Example 19: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-fluoro-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0170] a) Preparation of 1-amino-4-bromo-3-fluoropyridine-1-onium 4-Bromo-3-fluoropyridine (3 g) and amino-2,4,6-trimethylbenzenesulfonate (3.67 g) were dissolved in dichloromethane (30 mL) and stirred at 0 °C for 2 hours. After the reaction was completed, the resulting mixture was concentrated, and the crude product was used directly in the next reaction step.

[0171] b) Preparation of ethyl 5-bromo-6-fluoropyrazolo[1,5-a]pyridine-3-carboxylate 1-Amino-4-bromo-3-fluoropyridine-1-onium (3 g), ethyl propynate (7.66 g), and potassium carbonate (9.72 g) were dissolved in N,N-dimethylformamide (30 mL). The mixture was stirred at 30 °C for 1 hour. The crude product was purified by preparative liquid chromatography under the following conditions (column: Xbridge Phenyl OBD column, 30*150 mm, 5 μm; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; flow rate: 60 mL / min; gradient (B%): from 33%B to 41%B over 10 minutes; detection wavelength: 254 nm / 220 nm; column temperature: 25 °C; retention time (min): 9.80), yielding 100 mg of the title compound.

[0172] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromo-6-fluoropyrazolo[1,5-a]pyridine-3-carboxamide 5-(benzo[d]oxazol-2-yl)-2-methylaniline (13 mg, prepared according to intermediate 1) and ethyl 5-bromo-6-fluoropyrazolo[1,5-a]pyridine-3-carboxylate (80 mg) were dissolved in toluene (1 mL). Under nitrogen protection, trimethylaluminum (1.0 M heptane solution) (0.47 mL) was slowly added at 0 °C. The reaction was carried out at 100 °C for 2 hours. The reaction was quenched with saturated aqueous sodium hydroxide solution at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 20 mL), and the combined organic layers were washed with saturated aqueous sodium hydroxide solution (3 x 20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 20 mg of the title compound.

[0173] d) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-6-fluoro-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromo-6-fluoropyrazolo[1,5-a]pyridine-3-carboxamide (18 mg), 2-azaspiro[3.3]heptane-6-ol (4 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (3 mg), and cesium carbonate (38 mg) were added to 1,4-dioxane (1 mL), and the mixture was reacted at 100°C for two hours. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The concentrated filtrate was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Shield RP18 OBD, 30*150mm, 5μm; mobile phase A: water (10mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 40%B to 55%B over 11 minutes; detection wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 9.47) to obtain 0.7 mg of the title compound.

[0174] 1 H NMR (400 MHz, DMSO- d 6) d 9.46 (s, 1H), 8.96 (d, J = 7.1 Hz, 1H), 8.60(s, 1H), 8.36 (d, J = 1.8 Hz, 1H), 7.95 (dd, J= 7.9, 1.8 Hz, 1H), 7.84 – 7.77(m, 2H), 7.51 (d, J = 8.1 Hz, 1H), 7.48 – 7.38 (m, 2H), 6.95 (d, J = 9.3 Hz, 1H), 5.06 (d, J = 6.2 Hz, 1H), 4.09 – 4.00 (m, 5H), 2.39 (s, 3H), 2.38 – 2.30 (m,2H), 2.08 – 2.01 (m, 2H). LCMS (ESI) m / z=498[M+H] + . Example 20: N-(5-(benzo[d]oxazol-2-yl)-2-fluorophenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0175] a) Preparation of 2-(4-fluoro-3-nitrophenyl)benzo[d]oxazole 2-Aminophenol (900 mg) was added to ethyl acetate (20 mL) and stirred, followed by the addition of 4-fluoro-3-nitrobenzaldehyde (1.67 g) in portions. The resulting mixture was stirred at 80°C for 3 hours. The mixture was then concentrated. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (1.87 g) and dichloromethane (20 mL) were added in portions to the mixture at 25°C. The mixture was stirred at 25°C under a nitrogen atmosphere for 1 hour. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (3 x 100 mL). The organic phase was washed with saturated sodium bicarbonate solution (3 x 100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 600 mg of the title compound.

[0176] b) Preparation of 5-(benzo[d]oxazol-2-yl)-2-fluoroaniline 2-(4-fluoro-3-nitrophenyl)benzo[d]oxazole (500 mg) was added to a solution of ethanol (10 mL) and water (2 mL), followed by the addition of zinc powder (760 mg) and ammonium chloride (621 mg). The mixture was reacted at 50 °C for 2 hours. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated to obtain 400 mg of the title compound.

[0177] c) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-fluorophenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide 5-(benzo[d]oxazol-2-yl)-2-fluoroaniline (180 mg) and methyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (241 mg) were dissolved in toluene (2 mL), and under nitrogen protection, trimethylaluminum (1.0 M heptane solution) (1.6 mL) was slowly added at 0 °C. The reaction was carried out at 100 °C for 2 hours. The reaction was quenched with saturated sodium hydroxide aqueous solution at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL), and the combined organic layers were washed with saturated sodium hydroxide aqueous solution (3 x 30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 120 mg of the title compound.

[0178] d) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-fluorophenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-fluorophenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (100 mg), 2-azaspiro[3,3]heptane-6-ol (25 mg), and (SP-4-2)-bromo[dicyclohexyl[3-(1,1-dimethylethoxy)-6-methoxy-2',6'-bis(1-methylethyl)[1,1'-biphenyl]-2- [κC1']phosphine-κP][4-[[2-(trimethylsilyl)ethoxy]carbonyl]phenyl]palladium (21 mg), (3-(tert-butoxy)-2′,6′-diisopropyl-6-methoxy-[1,1′-biphenyl]-2-yl)dicyclohexylphosphine (12 mg), sodium trimethylsilanolate (99 mg), and tetrahydrofuran (2 mL) were added to a reaction flask, and the reaction was carried out at 60 °C for 1 hour under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated, and the crude product was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Shield RP18 OBD, 30*150mm, 5μm; mobile phase A: water (10mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 41%B to 54%B over 11 min; detection wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 8.52) to obtain 8.4 mg of the title compound.

[0179] 1 H NMR (400 MHz, DMSO- d 6) d 9.68 (s, 1H), 8.74 (dd, J = 7.4, 2.3 Hz, 1H),8.62 (s, 1H), 8.54 (d, J = 7.5 Hz, 1H), 8.01 (m, 1H), 7.86 – 7.80 (m, 2H), 7.54(dd, J = 10.4, 8.6 Hz, 1H), 7.44 (m, 2H), 6.85 (d, J = 2.5 Hz, 1H), 6.40 (dd, J =7.5, 2.6 Hz, 1H), 5.07 (d, J = 6.2 Hz, 1H), 4.03 – 3.98 (m, 5H), 2.46 – 2.40 (m, 2H), 2.10 – 2.05 (m, 2H). LCMS (ESI) m / z = 484[M+H] + . Example 21: N-(5-(5-cyanobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0180] a) Preparation of 2-(4-methyl-3-nitrophenyl)benzo[d]oxazol-5-nitrile 900 mg of 3-amino-4-hydroxybenzonitrile was added to 10 mL of ethyl acetate and stirred. Then, 1330 mg of 4-methyl-3-nitrobenzaldehyde was added in portions. The resulting mixture was stirred at 80°C for 3 hours. The mixture was then concentrated. 1523 mg of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 10 mL of dichloromethane were added in portions to the mixture at 25°C. The mixture was stirred at 25°C under a nitrogen atmosphere for 1 hour. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (3 x 100 mL). The organic phase was washed with saturated sodium bicarbonate solution (3 x 100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 300 mg of the title compound.

[0181] b) Preparation of 2-(3-amino-4-methylphenyl)benzo[d]oxazol-5-nitrile 2-(4-methyl-3-nitrophenyl)benzo[d]oxazol-5-nitrile (280 mg) was added to a solution of ethanol (5 mL) and water (1 mL), followed by the addition of zinc powder (393 mg) and ammonium chloride (322 mg), and the mixture was reacted at 50 °C for 1 hour. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The filtrate was concentrated, yielding 300 mg of the title compound.

[0182] c) Preparation of 5-bromo-N-(5-(5-cyanobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 2-(3-amino-4-methylphenyl)benzo[d]oxazol-5-onitrile (180 mg) and methyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (209 mg) were dissolved in toluene (2 mL), and under nitrogen protection, trimethylaluminum (1.0 M heptane solution) (1.4 mL) was slowly added at 0 °C. The reaction was carried out at 100 °C for 2 hours. The reaction was quenched with saturated aqueous sodium hydroxide solution at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL), and the combined organic layers were washed with saturated aqueous sodium hydroxide solution (3 x 30 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 70 mg of the title compound.

[0183] d) Preparation of N-(5-(5-cyanobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide The following ingredients were added: 5-bromo-N-(5-(5-cyanobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (60 mg), 2-azaspiro[3.3]hepta-6-ol (14 mg), and (SP-4-2)-bromo[dicyclohexyl[3-(1,1-dimethylethoxy)-6-methoxy-2',6'-bis(1-methylethyl)[1,1'-biphenyl]- 2-yl-κC1']phosphine-κP][4-[[2-(trimethylsilyl)ethoxy]carbonyl]phenyl]palladium (12 mg), (3-(tert-butoxy)-2′,6′-diisopropyl-6-methoxy-[1,1′-biphenyl]-2-yl)dicyclohexylphosphine (7 mg), sodium trimethylsilanolate (57 mg), and tetrahydrofuran (2 mL) were added to a reaction flask and reacted at 60 °C for 1 hour under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The concentrated filtrate was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Shield RP18 OBD, 30*150mm, 5μm; mobile phase A: water (10mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 28%B to 45%B over 11 min; detection wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 9.65) to obtain 0.6 mg of the title compound.

[0184] 1 H NMR (400 MHz, DMSO- d 6) d 9.36 (s, 1H), 8.59 – 8.50 (m, 2H), 8.42 (dd, J = 4.1, 1.7 Hz, 2H), 8.04 (d, J = 8.4 Hz, 1H), 7.96 (dd, J = 7.9, 1.9 Hz, 1H), 7.91 (dd, J = 8.5, 1.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 6.84 (d, J = 2.6 Hz, 1H), 6.38 (dd, J = 7.5, 2.6 Hz, 1H), 5.07 (d, J = 6.3 Hz, 1H), 4.02 (m, 1H), 3.94 (d, J= 17.5 Hz, 4H), 2.41 (s, 3H), 2.40 – 2.32 (m, 2H), 2.10 – 2.00 (m, 2H). LCMS (ESI) m / z = 505[M+H] + . Example 22: N-(5-(6-chloro-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0185] a) Preparation of 5-(6-chloro-1H-benzo[d]imidazol-2-yl)-2-methylaniline (3-Amino-4-methylphenyl)boronic acid (378 mg), 2-bromo-6-chloro-1H-benzi[d]imidazole (578 mg), potassium carbonate (690 mg), and 1,1-bis(diphenylphosphine)diberberine palladium dichloride dichloromethane complex (204 mg) were dissolved in 1,4-dioxane (12 mL) and water (3 mL) under a nitrogen atmosphere and reacted at 100 °C for 3 hours. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 266 mg of the title compound.

[0186] b) Preparation of N-(5-(6-chloro-1H-benzo[d]imidazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Pyrazolo[1,5-a]pyridine-3-carboxylic acid (39 mg), N,N,N',N'-tetramethylchloroformamidine hexafluorophosphate (67 mg), and N-methylimidazolium (0.2 mL) were dissolved in anhydrous acetonitrile (10 mL) and stirred for 20 min. Then, 5-(6-chloro-1H-benzo[d]imidazol-2-yl)-2-methylaniline (52 mg) was added, and the mixture was reacted overnight at 50 °C. The solvent was concentrated, and the crude product was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 16.21 mg of the title compound.

[0187] 1 H NMR (400 MHz, DMSO -d 6) δ 13.17 (s, 1H), 9.78 (s, 1H), 8.86 (dd, J =7.0, 1.2 Hz, 1H), 8.82 (s, 1H), 8.26 (dd, J = 8.8, 2.2 Hz, 2H), 7.97 (dd, J=7.9, 1.9 Hz, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.58 – 7.47(m, 2H), 7.28 (dd, J = 8.6, 2.0 Hz, 1H), 7.13 (td, J = 6.9, 1.5 Hz, 1H), 2.37 (s,3H). LCMS (ESI) m / z = 402.1 [M+H] + . Example 23: N-(5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0188] a) Preparation of 5,6-difluoro-2-(4-methyl-3-nitrophenyl)benzo[d]oxazole 2-Amino-4,5-difluorophenol (2 g) was added to ethyl acetate (10 mL) and stirred, followed by the addition of 2.73 g of 4-methyl-3-nitrobenzaldehyde in portions. The resulting mixture was stirred at 80°C for 3 hours. The mixture was then concentrated. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (3.1 g) and dichloromethane (10 mL) were added in portions to the mixture at 25°C. The mixture was stirred at 25°C under a nitrogen atmosphere for 1 hour. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted with dichloromethane (3 x 100 mL). The organic phase was washed with saturated sodium bicarbonate solution (3 x 100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 1.5 g of the title compound.

[0189] b) Preparation of 5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylaniline 1.5 g of 5,6-difluoro-2-(4-methyl-3-nitrophenyl)benzo[d]oxazole was added to a solution of 10 mL of ethanol and 1 mL of water, followed by the addition of 2 g of zinc powder and 1.66 g of ammonium chloride. The mixture was reacted at 50 °C for 1 hour. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated to obtain 750 mg of the title compound.

[0190] c) Preparation of 5-bromo-N-(5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide 100 mg of 5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylaniline was dissolved in 3 mL of tetrahydrofuran, and then 0.8 mL of sodium bis(trimethylsilyl)amino (1 M tetrahydrofuran solution) was added at 0 °C under a nitrogen atmosphere, and the reaction was allowed to proceed for 30 minutes. Next, 3 mL of tetrahydrofuran solution of methyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (147 mg) was added to the mixture at 0 °C. The resulting mixture was stirred at 25 °C for 2 hours. The reaction was quenched with water at 0 °C, and the mixture was then extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with water (3 x 50 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 48 mg of the title compound.

[0191] d) Preparation of N-(5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5,6-difluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (47 mg), 6-(difluoromethyl)-2-azaspiro[3.3]hepta-6-ol (11 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (8 mg) and cesium carbonate (95 mg) were added to 1,4-dioxane (2 mL), and reacted at 100°C for 1 hour. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The concentrated filtrate was purified by reversed-phase rapid chromatography under the following conditions (column: Xselect CSHPrep C18, 30*150mm, 5μm; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 38%B to 50%B over 11 minutes; wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 8.67) to obtain 3 mg of the title compound.

[0192] 1 H NMR (400 MHz, DMSO- d6) δ 9.35 (s, 1H), 8.56 (s, 1H), 8.53 (d, J =7.5 Hz, 1H), 8.37 (d, J = 1.8 Hz, 1H), 8.12 (dd, J = 9.9, 6.9 Hz, 1H), 7.98(dd, J = 10.3, 7.5 Hz, 1H), 7.90 (dd, J = 7.9, 1.9 Hz, 1H), 7.50 (d, J = 8.0Hz, 1H), 6.83 (d, J = 2.5 Hz, 1H), 6.38 (dd, J = 7.5, 2.6 Hz, 1H), 5.07 (d, J= 6.1 Hz, 1H), 4.06 – 3.99 (m, 1H), 3.96 (s, 2H), 3.92 (s, 2H), 2.48 – 2.45 (m, 2H), 2.39 (s, 3H), 2.08 – 2.01 (m, 2H). LCMS (ESI) m / z=516[M+H] + . Example 24: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-(difluoromethyl)-6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0193] a) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(6-(difluoromethyl)-6-hydroxy-2-azaspiro[3.3]hept-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (140 mg, prepared according to Example 4), 6-(difluoromethyl)-2-azaspiro[3.3]hepta-6-ol hydrochloride (62 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (26.3 mg), and cesium carbonate (306 mg) were added to 1,4-dioxane (5 mL), and reacted at 100°C for 1 hour. The resulting mixture was filtered, and the filter cake was washed with acetonitrile. The filtrate was concentrated, and the crude product was purified by reversed-phase rapid chromatography under the following conditions (column: Xselect CSH Prep C18, 30*150mm, 5μm; mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 37%B to 57%B over 8 minutes; wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 8.4), yielding 77.3 mg of the title compound.

[0194] 1 H NMR (400 MHz, DMSO- d 6) δ 9.36 (s, 1H), 8.59 – 8.50 (m, 2H), 8.38(d, J = 1.8 Hz, 1H), 7.94 (dd, J = 7.9, 1.8 Hz, 1H), 7.81 (dt, J = 7.1, 1.5 Hz, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.48 – 7.37 (m, 2H), 6.85 (d, J = 2.6 Hz, 1H), 6.41 (dd, J = 7.5, 2.6 Hz, 1H), 5.91 (s, 1H), 5.83 (t, J = 60 Hz, 1H), 4.01 (s,2H), 3.95 (s, 2H), 2.61 – 2.53 (m, 2H), 2.40 (s, 3H), 2.29 (d, J = 13.6 Hz, 2H). LCMS (ESI) m / z = 530[M+H] + . Example 25: N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0195] a) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromo-N-(5-(5-fluorobenzo[d]oxazol-2-yl)-2-chlorophenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (120 mg, prepared according to Example 18), (1H-pyrazol-4-yl)boronic acid (43 mg), [1,1′-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (17 mg), potassium phosphate (163 mg), 1,4-dioxane (2 mL), and water (0.4 mL) were added to a reaction flask and reacted at 80 °C for 2 hours under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The filtrate was concentrated, and the crude product was purified by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1 / 1 (V / V)) to give 90 mg of the title compound.

[0196] b) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-chlorophenyl)-5-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (850 mg), 2,2-dimethylethylene oxide (13 mg), potassium carbonate (26 mg), and N,N-dimethylformamide (1 mL) were added to a reaction flask and reacted at 100 °C for 16 hours under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with dichloromethane. The filtrate was concentrated, and the crude product was purified by reversed-phase rapid chromatography under the following conditions (column: XBridge Shield RP18OBD, 30*150mm, 5μm; mobile phase A: water (10mmol / L ammonium bicarbonate), mobile phase B: acetonitrile; flow rate: 60mL / min; gradient (B%): 44%B to 59%B over 11 min; wavelength: 254nm / 220nm; column temperature: 25°C; retention time (min): 11.02) to give 24.8 mg of the title compound.

[0197] 1 H NMR (400 MHz, DMSO- d6) 9.86 (s, 1H), 8.84 (dd, J = 7.2, 0.9 Hz, 1H),8.79 (s, 1H), 8.66 (d, J = 2.2 Hz, 1H), 8.37 (t, J = 1.6 Hz, 2H), 8.10 – 8.02 (m,2H), 7.88 – 7.79 (m, 3H), 7.52 – 7.39 (m, 3H), 4.77 (s, 1H), 4.07 (s, 2H), 1.11 (s, 6H). LCMS (ESI) m / z = 527[M+H] + . Example 26: N-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3,3]heptane-2-yl)pyrazolo[1,5-a]pyridin-3-carboxamide

[0198] a) Preparation of 2-bromo-[1,2,4]triazole[1,5-a]pyridine [1,2,4]triazole[1,5-a]pyridine-2-amine (500 mg) and copper bromide (2080 mg) were dissolved in acetonitrile (15 mL), purged with nitrogen, and cooled to 0 °C. Isoamyl nitrite (2 mL) was added, and the mixture was reacted at room temperature for 2 h. After the reaction was complete, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 196 mg of the title compound.

[0199] b) (3-Amino-4-methylphenyl)boronic acid (151 mg), 2-bromo-[1,2,4]triazole[1,5-a]pyridine (196 mg), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (81 mg), and potassium phosphate (424 mg) were dissolved in 1,4-dioxane (15 mL) and water (5 mL), and the mixture was reacted at 100 °C for 5 h after nitrogen purging. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 294 mg of the title compound.

[0200] c) Preparation of N-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide 5-Bromopyrazolo[1,5-a]pyridine-3-carboxylic acid (192 mg), tetramethylchlorourea hexafluorophosphate (225 mg), and N-methylimidazolium (164 mg) were dissolved in acetonitrile (15 mL) and reacted at room temperature for 5 min. Then, 5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-methylaniline (150 mg) was added, and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the mixture was filtered, the filtrate was concentrated, and the residue was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 80 mg of the title compound.

[0201] d) Preparation of N-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-methylphenyl)-5-(6-hydroxy-2-azaspiro[3,3]heptane-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (80 mg), 2-azaspiro[3.3]heptane-6-ol hydrochloride (26 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridin-κN)-palladium (17 mg), and cesium carbonate (172 mg) were dissolved in 1,4-dioxane (5 mL) solution and reacted at 90 °C for 16 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 4.35 mg of the title compound.

[0202] 1 H NMR (400 MHz, DMSO- d 6) δ 9.34 (s, 1H), 9.02 – 8.93 (m, 1H), 8.57 (s, 1H), 8.54 (d, J = 7.5 Hz, 1H), 8.35 (d, J = 1.8 Hz, 1H), 7.95 (dd, J = 7.8, 1.8Hz, 1H), 7.90 – 7.83 (m, 1H), 7.69 (ddd, J = 8.6, 6.9, 1.3 Hz, 1H), 7.42 (d, J =8.0 Hz, 1H), 7.22 (td, J = 6.9, 1.3 Hz, 1H), 6.85 (d,J = 2.6 Hz, 1H), 6.38 (dd, J = 7.5, 2.6 Hz, 1H), 5.08 (s, 1H), 4.03 (t, J = 7.3 Hz, 1H), 3.94 (d, J = 17.8 Hz, 4H), 2.50 (s, 2H), 2.36 (s, 3H), 2.04 (ddd, J = 12.0, 6.4, 2.6 Hz, 2H). LCMS (ESI) m / z = 480.2[M+H] + . Example 27: N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(3-hydroxyazacyclobutane-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0203] a) Preparation of N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-(3-hydroxyazacyclobutane-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide N-(5-(benzo[d]oxazol-2-yl)-2-methylphenyl)-5-bromopyrazolo[1,5-a]pyridine-3-carboxamide (180 mg, prepared according to Example 4), aziridine-3-ol hydrochloride (60 mg), (SP-4-1)-[1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(3-chloropyridine-κN)-palladium (34 mg), and cesium carbonate (340 mg) were dissolved in 1,4-dioxane (5 mL) solution and reacted at 80 °C for 16 h. After the reaction was completed, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (mobile phase: dichloroethane / methanol = 20 / 1 (V / V)) to give 53.28 mg of the title compound.

[0204] 1 H NMR (400 MHz, DMSO- d 6) δ 9.37 (s, 1H), 8.59 (s, 1H), 8.56 (d, J = 7.5Hz, 1H), 8.40 (d, J = 1.8 Hz, 1H), 7.95 (dd, J= 7.9, 1.9 Hz, 1H), 7.86 – 7.78(m, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.47 – 7.38 (m, 2H), 6.88 (d, J = 2.6 Hz, 1H), 6.44 (dd, J = 7.5, 2.6 Hz, 1H), 5.80 (d, J = 6.4 Hz, 1H), 4.63 (d, J = 6.4 Hz, 1H), 4.23 (dd, J = 8.3, 6.5 Hz, 2H), 3.72 (dd, J = 8.5, 4.5 Hz, 2H), 2.41 (s, 3H). LCMS (ESI) m / z = 440.2 [M+H] + . The compounds in Table 1 below were prepared by modifying some of the raw materials, referring to the preparation methods in the above examples.

[0205]

[0206] Experimental Example 1: Method for inhibiting c-KIT kinase activity This invention relates to a method for detecting c-KIT tyrosine kinase activity based on time-resolved fluorescence resonance energy transfer (HTRF) technology. ® The KinEASE TK kit (Cisbio, 62TK0PEJ) was used for detection. The specific implementation steps are as follows: Prepare 2× c-KIT kinase working solution (final concentration 30 nM, Carna, 08-156) using 1× kinase reaction buffer (added with 5 mM MgCl2 (Sigma; M1028) and 1 mM DTT (Sigma; 43816)) from the kit. Add 3 μL of c-KIT kinase working solution to each well of a 384-well plate using a pipette. Add an equal volume of reaction buffer to the blank control group. Centrifuge the plate at 2500 rpm for 30 seconds using a plate centrifuge (Ausun, Mini-p25). Add the test compounds to dimethyl sulfoxide (DMSO) using a compound titrator (Tecan, D300e). Compound concentrations were set as follows: initial concentration 0.1 μM, with 7 concentrations set in a 3-fold gradient; positive compound concentration was set as follows: initial concentration 1... The test plates were prepared with 7 concentrations at a 3-fold gradient, and DMSO (final concentration 0.3%) was added to the negative control group. The plates were centrifuged at 2500 rpm for 30 seconds and then incubated at 25°C for 10 minutes. 4× substrate working solution (final concentration 0.15 μM) and 4× ATP working solution (final concentration: 50 μM, Promega, V915A) were prepared using 1× kinase reaction buffer and premixed at a 1:1 volume ratio. 3 μL of the mixture was added to each well of a 384-well plate using an automated plate washer / dispenser (BioTek, MultiFlo FX). The plates were centrifuged at 2500 rpm for 30 seconds and then incubated at 25°C for 120 minutes. 4× Streptavidin-XL665 working solution (final concentration 9.375 nM) and 0.125× TK were prepared using test buffer. Antibody-Cryptate working solution was mixed at a 1:1 volume ratio, and 6 μL was added to each well of a 384-well plate using an automated dispensing system (BioTek, MultiFlo FX). After centrifugation at 2500 rpm for 30 seconds, the plates were incubated at 25°C for 60 min. Fluorescence intensity was then simultaneously acquired using a microplate reader (Decan, SPARK) at excitation wavelengths of 320 nm and emission wavelengths of 620 nm (donor) and 665 nm (acceptor). The 665 / 620 nm dual-wavelength ratio was calculated to eliminate non-specific interference. A nonlinear regression model (GraphPad Prism software, Log[inhibitor] vs. response - Variable slope) was used to fit the dose-response curve and accurately calculate the half-maximal inhibitory concentration (IC50) of the compound. 50 ).

[0207] Inhibitor (inhibition rate) calculation formula: Inhibition rate (%) = 100[1-( vi - S b ) / ( v o - S b )] ν i : Fluorescence reading ratio of compound group ν o : Fluorescence reading ratio of negative control group S b : Fluorescence reading ratio of blank control group Positive compounds:

[0208] Table 2. Inhibitory activity of the compounds of the present invention against c-KIT kinase

[0209] Experimental Example 2: Phospho-c-Kit (Tyr719) ELISA detection in M-07e cells M-07e cells (CBP60791) were washed once with PBS (BBI, 41403ES76) and the cell suspension density was adjusted to 1×10⁻⁶ cells / mL with phenol red-free 1640 medium (Gibco, C11875500BT). 6Cells / mL, 100 μL per well, were added to 96-well U-bottom cell culture plates (Corning, 3799) and starved at 37 °C and 5% CO2 for 4 h. The compounds prepared in the examples were added using a compound titrator (Tecan, D300e). The initial compound concentration was 0.1 μM, with six concentrations set at 3-fold gradients; the positive control compound (THB001) started at 0.2 μM, with six simultaneous 3-fold gradient concentrations; DMSO (final concentration 0.1%) was added to the blank control and negative control groups. After compound addition, the mixtures were incubated at 37 °C and 5% CO2 for 60 min. Except for the blank control group, which received an equal volume of PBS, all other groups were stimulated with 10 μL of 200 ng / mL SCF (MCE, HY-P70757) and shaken at 25 °C and 450 rpm for 10 min on a constant-temperature shaker (Ausun, MB100-2A). Add 10 μL of 10× lysis buffer (Cell Signaling Technology, 9803S) and 10 μL of 1 mM PMSF (Beyotime, ST507-10mL) to each well. Incubate on ice in a constant-temperature shaker at 600 rpm for 10 min for lysis. Then centrifuge at 4500 rpm for 10 min using a Thermo, ST16R. Transfer 90 μL of the supernatant to a pre-coated ELISA plate and incubate overnight at 4°C. Follow the instructions for the Phospho-c-Kit (Tyr719) kit (CST, 7298) for subsequent assays. Measure the absorbance at 450 nm using a microplate reader (Decan, SPARK). Fit the concentration-inhibition rate curve using a nonlinear regression model (GraphPad Prism software, log[inhibitor] vs. response-variable slope) to calculate the half-maximal inhibitory concentration (IC50) of the compound against phosphorylated c-Kit (Tyr719). 50 ).

[0210] Inhibitor (inhibition rate) calculation formula: Inhibition rate (%) = 100[1-( v i - S b ) / ( v o - S b )] ν i : Absorbance values ​​of compound group ν o : Absorbance value of negative control group S b: Absorbance value of blank control group Table 3. Inhibitory activity of the compounds of the present invention against phosphorylated c-Kit (Tyr719) cells in M-07e cells.

[0211] Experiment 3: Oral PK in mice The test compound was prepared in a solvent of DMSO:(20% sulfobutyl ether β-cyclodextrin saline solution) = 5:95 (v / v). ICR mice (n=3) were administered the drug by single gavage at a dose of 10 mg / kg. Blood samples were collected at 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h post-administration and placed in EDTA-K2 anticoagulant tubes. The plasma was centrifuged at 1500-1600g for 10 min and stored at -20℃. The concentration of the compound in the plasma samples was determined by LC-MS / MS, and pharmacokinetic parameters were calculated using a non-compartmental model in Phoenix WinNonlin 8.3.

[0212] Table 4. Oral p-value data of the compounds of the present invention in mice.

[0213] 0-t: represents the period from 0 hours to 24 hours.

[0214] MRT(0-t) (h): represents the average residence time of drug molecules in the body during mouse pharmacokinetics from time 0 to time t, in hours.

Claims

1. A compound of general formula (I) or a pharmaceutically acceptable salt thereof: in: Each R 1 The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl, wherein the C1-C6 alkyl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, wherein the 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl or 6-10 membered aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl; Ring A is a 6-14 quintile bicyclic fused ring; Each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-10 membered cycloalkyl groups, 3-10 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl group is optionally substituted with one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, and the 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl or C1-C6 alkoxy group is optionally substituted with one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl. R A R B Each is independently selected from C1-C6 alkyl groups; Ring B is a 6-membered aryl or a 5-10-membered heteroaryl; Each R 3 Independently selected from halogens, C1-C6 alkyl groups, 3-10 membered cycloalkyl groups, or C1-C6 alkoxy groups; m and n are each independently selected from 0, 1, 2, 3 or 4; p is selected from 1, 2, 3, or 4.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, Each R 1 The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-10 cycloalkyl, 3-10 heterocycloalkyl, 6-8 aryl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 cycloalkyl, 3-10 heterocycloalkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 The alkyl group is independently selected from halogen, C1-C6 alkyl, 3-10 heterocyclic alkyl, 6-8 aryl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl, wherein the C1-C6 alkyl, 5-8 heteroaryl or C1-C6 alkyl-5-8 heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10 heterocyclic alkyl or 6-8 aryl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 The alkyl group is independently selected from halogen, 3-10-membered heterocyclic alkyl, 5-8-membered heteroaryl or C1-C6 alkyl-5-8-membered heteroaryl, wherein the 5-8-membered heteroaryl or C1-C6 alkyl-5-8-membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogenated C1-C6 alkyl or C1-C6 alkoxy, wherein the 3-10-membered heterocyclic alkyl is optionally substituted by one or more substituents selected from hydroxyl, C1-C6 alkyl, halogenated C1-C6 alkyl or C1-C6 alkoxy; Preferably, each R 1 Independently selected from halogens, , , , , , , , , , or The , , , , or Optionally substituted with one or more substituents selected from hydroxyl, C1-C3 alkyl, halogenated C1-C3 alkyl, or C1-C3 alkoxy; , , , or Optionally substituted with one or more substituents selected from hydroxyl, halogenated C1-C3 alkyl or C1-C3 alkoxy; Preferably, each R 1 Independently selected from halogens, , , , , , , , , , or The , , , , or Optionally substituted with one or more substituents selected from hydroxy, methyl, difluoromethyl, trifluoromethyl, or methoxy; , , , or Optionally substituted with one or more substituents selected from hydroxy, difluoromethyl, trifluoromethyl or methoxy; More preferably, each R 1 Independently selected from halogens, , , , , , , , , , , , or ; More preferably, each R 1 Independently selected from fluorine, , , , , , , , , , , , , , , , or ; More preferably, each R 1 Independently selected from fluorine, , , , , or .

3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, Ring A is a 6-10 fused bicyclic ring; preferably a 6-10 fused bicyclic heterocyclic ring; preferably an 8 fused bicyclic heterocyclic ring with a 5-membered ring and a 9 fused bicyclic heterocyclic ring with a 6-membered ring and a 5-membered ring. More preferably , , , , , , , , , , , , , , , , , , , , or ; More preferably , , , , , , , , , or ; More preferably , , , , , , , , , or ; Further preferably, ring A is , or ; Each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-8 membered cycloalkyl groups, 3-8 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C6 alkyl groups; Preferably, each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-5 membered cycloalkyl groups, 3-5 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, and -P(=O)R groups. A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl, 3-5 membered cycloalkyl, 3-5 membered heterocycloalkyl, or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or halogens, R A R B Each is independently selected from C1-C3 alkyl groups; More preferably, each R 2 Independently selected from halogens, C1-C6 alkyl groups, 3-5 membered cycloalkyl groups, 3-5 membered heterocycloalkyl groups, C1-C6 alkoxy groups, hydroxyl groups, cyano groups, , or The C1-C6 alkyl, 3-5 membered heterocyclic alkyl or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups or fluorine; More preferably, each R 2 Independently selected from fluorine, chlorine, methyl, ethyl, n-propyl, isopropyl, isobutyl, cyclopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, aziroxy, trifluoromethyl, trifluoroethyl, , , , cyano , or ; More preferably, each R 2 Independently selected from fluorine, chlorine, methyl, isobutyl, cyclopropyl, methoxy, trifluoromethyl, , , , , , Or cyano; More preferably, each R 2 Independently selected from fluorine, chlorine, methoxy, trifluoromethyl, , , , , , Or cyano; More preferably, each R 2 It is independently selected from fluorine, chlorine, methoxy, trifluoromethyl or cyano.

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, Ring B is a 6-membered aryl or a 6-membered heteroaryl; preferably, ring B is... Where X and Y are each independently selected from CH or N; "This indicates that ring B is chemically bonded to the -NH- position;" "This indicates that ring B is chemically bonded to the position of ring A; Preferably, ring B is ,in" "This indicates that ring B is chemically bonded to the -NH- position;" "This indicates that ring B is chemically bonded to the position of ring A; Each R 3 Independently selected from halogens or C1-C6 alkyl groups; preferably, each R 3 Independently selected from fluorine, chlorine, methyl, ethyl, n-propyl, or isopropyl; more preferably, each R 3 Independently selected from fluorine, chloro, or methyl; more preferably, each R 3 Independently selected from fluorine or methyl; m is selected from 0, 1, or 2; preferably, m is selected from 0 or 1. n is selected from 0, 1, or 2; preferably, n is selected from 0 or 1. p is selected from 1 or 2; preferably, p is 1.

5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, As shown in general formula (II): ； Among them, R 1 R 2 R 3 X, Y, m, n and p are each defined as described in any one of claims 1 to 4.

6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, As shown in general formula (III): ； Among them, R 6 R 7 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl, wherein the C1-C6 alkyl, 5-10 membered heteroaryl or C1-C6 alkyl-5-10 membered heteroaryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, wherein the 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl or 6-10 membered aryl is optionally substituted by one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl; R 8 R 9 Each group is independently selected from hydrogen, halogen, C1-C6 alkyl, 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl, C1-C6 alkoxy, hydroxyl, cyano, -P(=O)R A R B -S(=O)2R A or -S(=O)(=NH)R A The C1-C6 alkyl group is optionally substituted with one or more substituents selected from hydroxyl, halogen, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl, and the 3-10 membered cycloalkyl, 3-10 membered heterocycloalkyl or C1-C6 alkoxy group is optionally substituted with one or more substituents selected from hydroxyl, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, cyano, 3-8 membered cycloalkyl or 3-8 membered heterocycloalkyl. R 3A Selected from hydrogen, halogens, or C1-C6 alkyl groups; R 3 The definition is as described in any one of claims 1 to 4.

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, As shown in general formula (II-1): ； Among them, R 2 R 3 R 3A R 6 R 7 Each of n and ring A is defined as described in any one of claims 1 to 4.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, It has the following structure: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , or .

9. A pharmaceutical composition comprising a therapeutically effective amount of the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

10. Use of the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of claim 9 in the preparation of a medicament for the prevention and / or treatment of c-Kit kinase-related diseases or disease states; preferably, the c-Kit kinase-related disease or disease state is allergic conjunctivitis or chronic sinusitis.

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