Novel heterocyclic compound as CDKs inhibitor and application of novel heterocyclic compound

Abstract

The invention discloses a novel heterocycle compound with CDKs target inhibition activity, and particularly discloses a compound which is used as a CDKs target inhibitor and has a structure shown in a formula (I) or pharmaceutically acceptable salt, solvate, hydrate, isotope substitute or isomer of the compound.

Description

Novel heterocyclic compounds as CDKs inhibitors and their applications

[0001] The present invention claims:

[0002] Priority to the prior application, patent application number 202311074460.4, filed with the State Intellectual Property Office of China on August 24, 2023, entitled “Novel heterocyclic compounds as CDKs inhibitors and their applications”;

[0003] Priority to the prior application PCT / CN2023 / 138273, filed with the State Intellectual Property Office of China on December 12, 2023, entitled “Novel heterocyclic compounds as CDKs inhibitors and their applications”;

[0004] Priority to the prior application, patent application number 202411135464.3, filed with the State Intellectual Property Office of China on August 16, 2024, entitled “Novel heterocyclic compounds as CDKs inhibitors and their applications”;

[0005] The entire contents of said prior application are incorporated herein by reference. Technical Field

[0006] The present invention belongs to the field of medicinal chemistry and specifically discloses novel heterocyclic compounds with CDKs target inhibitory activity, compositions containing such compounds, and methods for using such compounds to prepare drugs for treating or preventing diseases related to CDKs targets. Background Art

[0007] Cyclin-dependent kinases (CDKs) belong to the serine / threonine protein kinase family. Twenty-one CDKs have been discovered, and most require binding to cyclins to form active heterodimeric complexes. This active heterodimeric complex phosphorylates the corresponding substrates, driving various stages of the cell cycle and regulating cell growth and proliferation. Among all CDKs, CDK1 / 2 / 4 / 6 primarily function by regulating the cell cycle, while CDK7 / 8 / 9 / 10 / 11 simultaneously participate in cell cycle and transcriptional regulation to exert their biological functions.

[0008] Studies have shown that the occurrence and progression of many malignant tumors are associated with cell cycle dysregulation, with overactivation of CDKs being one of the most important causes. CDKs play an important role in both tumor cell proliferation and apoptosis. Therefore, selective inhibition of CDKs can have a positive therapeutic effect in the treatment of tumors. Currently, inhibitors targeting CDK4 / 6, such as palbociclib, ribociclib, abemaciclib, and dalcili, are available on the market and have demonstrated excellent efficacy in the treatment of breast cancer. CDK7, a key member of the CDK family, primarily forms a CDK-activating kinase complex (CAK) with cyclin H and MAT1. The CAK complex can phosphorylate other cell cycle kinases, promoting the normal progression of the cell cycle. Furthermore, the CAK complex can phosphorylate RNA polymerase II, participating in the transcriptional regulation of related genes.

[0009] Studies have shown that CDK7 is overexpressed in numerous malignancies, including liver cancer, gastric cancer, cervical cancer, breast cancer, pancreatic cancer, colorectal cancer, neuroblastoma, prostate cancer, non-small cell lung cancer, and acute myeloid leukemia, and is associated with aggressive clinical pathology and poor prognosis. Due to the high homology among members of the CDK family and the varying mechanisms of action across different tumor types, non-selective CDK7 inhibitors have been associated with adverse reactions due to off-target effects in clinical trials. Currently, there are no selective CDK7 inhibitors available. However, numerous preclinical and clinical trials have demonstrated that highly selective CDK7 inhibitors have significant potential therapeutic value in a variety of difficult-to-treat tumors.

[0010] Technical Effects

[0011] The inventors unexpectedly discovered that some of the novel heterocyclic compounds of formula (I) of the present invention not only have significant CDK7 inhibitory activity, but also have higher activity, better selectivity, pharmacokinetic and bioavailability compared to clinical reference compounds with known structures such as THZ2, Samuraciclib, CYC-202, etc., and are expected to have better human PK properties and efficacy, and are more suitable for development as candidate drugs for the prevention or treatment of diseases related to CDKs targets or signaling pathways.

[0012] Summary of the Invention

[0013] The object of the present invention is to provide a compound represented by formula (I) or a pharmaceutically acceptable salt, solvate, enantiomer and isotope-substituted product thereof.

[0014] in,

[0015] Any independently selected from a single bond or a double bond;

[0016] R0 is independently selected from or selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0017] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0018] Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a fused ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, fused ring, spirocyclic ring or bridged ring structure can contain 0 or more unsaturated olefinic bonds;

[0019] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0020] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(Rd1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-、-O-、-S-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O) 、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(Rd1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0021] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3)C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0022] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0023] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally best replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Substitution by alkoxy, carboxyl, OH, or CN;

[0024] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, said monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and said aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Halogenated alkyl, C 1-10 Substitution by alkoxy, carboxyl, OH, or CN;

[0025] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C1-10 Alkyl, C 1-10 Halogenated alkyl, C 1-10 Substitution by alkoxy, carboxyl, OH, or CN;

[0026] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, said monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and said aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Halogenated alkyl, C 1-10 Substitution by alkoxy, carboxyl, OH, or CN;

[0027] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, OH, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Halogenated alkyl, C 1-10 Alkoxy group substitution;

[0028] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0029] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0030] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0031] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0032] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4.

[0033] The object of the present invention is to provide a compound represented by formula (I-1) or a pharmaceutically acceptable salt, solvate, enantiomer and isotope-substituted product thereof.

[0034] in,

[0035] Any independently selected from a single bond or a double bond;

[0036] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0037] Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a fused ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, fused ring, spirocyclic ring or bridged ring structure can contain 0 or more unsaturated olefinic bonds;

[0038] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0039] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(Rd1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-;

[0040] L3 is independently selected from being absent, a single bond, or -C(R d1 )(R d2)-, -C(R d1 )=C(R d2 )-, alkynyl, -OC(R d1 )(R d2 )-, -C(R d1 )(R d2 )O-, -C(=O)N(R d3 )-, -C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )-, -S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2)C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0041] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0042] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0043] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0044] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0045] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0046] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0047] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0048] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0049] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0050] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0051] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (I-1A),

[0052] in,

[0053] Any independently selected from a single bond or a double bond;

[0054] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0055] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0056] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(Rd2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-、-O-、-S-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(Rd1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0057] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(Rd3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0058] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0059] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0060] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0061] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0062] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C1-10 alkyloxy, C 1-10 Alkylsulfonyl, C1- 10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0063] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0064] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0065] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0066] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0067] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0068] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (I-1B),

[0069] in,

[0070] Any independently selected from a single bond or a double bond;

[0071] X, Y, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0072] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0073] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2)-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0074] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d )1(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(Rd1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0075] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0076] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0077] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0078] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0079] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0080] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0081] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0082] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0083] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0084] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0085] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (I-1C),

[0086] in,

[0087] Any independently selected from a single bond or a double bond;

[0088] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0089] Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a fused ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, fused ring, spirocyclic ring or bridged ring structure can contain 0 or more unsaturated olefinic bonds;

[0090] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0091] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2)C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0092] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-;

[0093] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0094] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0095] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0096] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0097] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0098] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0099] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0100] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0101] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0102] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0103] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (I-1D),

[0104] in,

[0105] Any independently selected from a single bond or a double bond;

[0106] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0107] Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a fused ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, fused ring, spirocyclic ring or bridged ring structure can contain 0 or more unsaturated olefinic bonds;

[0108] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain 0 or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0109] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3) -, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 ) -, -OC(R d1 )(R d2 )C(R d1 )(R d2 ) -, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 ) -, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 ) -, -C(R d1 )(R d2 )C(=NR d3 ) -, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 ) -, -C(R d1 )(R d2 )S(=O)2 N(R d3 ) -, -N(R d3 )C(R d1 )(R d2 ) -, -OC(R d1 )(R d2 ) -, -SC(R d1 )(R d2 ) -, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 ) -, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 ) - or -C(R d1 )(R d2 )S(=O)2-;

[0110] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(Rd1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0111] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0112] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0113] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0114] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0115] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C1-10 alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two Rd1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0116] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0117] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0118] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0119] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0120] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4.

[0121] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (I-1E),

[0122] in,

[0123] Any independently selected from a single bond or a double bond;

[0124] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0125] Ring B and Ring C are arbitrarily and independently selected from non-existent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from aromatic, heteroaromatic, aliphatic, heterocyclic, fused, spiro, or bridged ring structures; and the aliphatic, heterocyclic, fused, spiro, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B or Ring C is absent, R1 or R3 may be absent or may be directly connected to L2 or L3;

[0126] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(Rd2 )-, alkyne bond, -OC(R d1 )(R d2 )-, -C(R d1 )(R d2 )O-, -C(=O)N(R d3 )-, -N(R d3 )-, -C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )-, -S(=O)2N(R d3 )-, -N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2 N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(Rd1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0127] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NRd3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0128] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0129] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0130] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0131] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N, N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0132] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C1-10 alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0133] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0134] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0135] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0136] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0137] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0138] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (II):

[0139] in,

[0140] Any independently selected from a single bond or a double bond;

[0141] X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0142] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0143] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(Rd3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0144] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0145] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2)O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(Rd2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0146] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0147] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0148] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are attached on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0149] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0150] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0151] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0152] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0153] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0154] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0155] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0156] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (IIA),

[0157] in,

[0158] Any independently selected from a single bond or a double bond;

[0159] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0160] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0161] L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、 -C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(Rd2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0162] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0163] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1)(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(Rd1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0164] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0165] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0166] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0167] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0168] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0169] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0170] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0171] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0172] m is an integer arbitrarily selected from 2, 3 and 4;

[0173] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0174] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (IIB),

[0175] in,

[0176] Any independently selected from a single bond or a double bond;

[0177] X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0178] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0179] L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(Rd3 )C(R d1 )(R d2 )-、-C(Rd1)(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0180] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0181] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(Rd3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2)C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0182] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0183] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0184] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0185] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0186] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0187] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0188] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0189] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0190] m is an integer arbitrarily selected from 2, 3 and 4;

[0191] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5.

[0192] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (IIC),

[0193] in,

[0194] X is arbitrarily and independently selected from N, CR;

[0195] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0196] L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(Rd3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0197] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0198] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2)O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(Rd2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0199] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0200] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0201] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0202] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0203] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0204] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0205] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0206] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0207] m is an integer arbitrarily selected from 2, 3 and 4;

[0208] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0209] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0210] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (IID),

[0211] in,

[0212] X is arbitrarily and independently selected from N, CR;

[0213] X7 is arbitrarily and independently selected from -C(R d1)(R d2 )-, -C(R d1 )=C(R d2 )-, alkyne bond, -OC(R d1 )(R d2 )-, -C(R d1 )(R d2 )O-, -C(=O)N(R d3 )-, -N(R d3 )-, -C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )-, -S(=O)2N(R d3 )-, -N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2 N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(Rd1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-; and the hydrogen on X7 is preferably optionally substituted by 1 to more R3;

[0214] L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1)(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0215] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0216] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(Rd2 )-、- C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0217] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0218] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0219] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0220] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0221] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0222] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0223] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0224] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0225] m is an integer arbitrarily selected from 2, 3 and 4;

[0226] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0227] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0228] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (IIE),

[0229] in,

[0230] X is arbitrarily and independently selected from N, CR;

[0231] L and L1 are each independently selected from -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2)S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0232] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0233] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2)(R d3 )-、-S(=O)2)(R d3 )-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(Rd1)(R d2 )S(=O)2)(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2)S(=O)2-;

[0234] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0235] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0236] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0237] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0238] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0239] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0240] R5, R6 and R7 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the hydrogen on R5, R6 and R7 is preferably optionally replaced by 1 to more selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C1-6 Alkoxy, -NH2, -NHC 1- 6-alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3- 6 cycloalkyl groups; or any two of R5, R6 and R7 can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which they are attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0241] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0242] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0243] m is an integer arbitrarily selected from 2, 3 and 4;

[0244] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0245] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4.

[0246] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has the structure of formula (IIF),

[0247] in,

[0248] X is arbitrarily and independently selected from N, CR;

[0249] L and L1 are each independently selected from -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(Rd2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-、-O-、-S-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(Rd1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0250] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0251] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1)(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0252] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0253] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0254] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0255] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0256] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0257] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0258] R5, R6 and R7 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the hydrogen on R5, R6 and R7 is preferably optionally replaced by 1 to more selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1- 6-alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 cycloalkyl groups; or any two of R5, R6 and R7 can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which they are attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0259] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0260] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0261] m is an integer arbitrarily selected from 2, 3 and 4;

[0262] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5;

[0263] t is an integer arbitrarily selected from 0, 1, 2, 3 and 4.

[0264] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (IIIA),

[0265] in,

[0266] Any independently selected from a single bond or a double bond;

[0267] X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0268] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0269] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1)(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-、-O-、-S-、-C(=O)O-、-OC(=O)-、-C(=O)-、-C(=S)-、-S(=O)-、-C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d 2)N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2 N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2)C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0270] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0271] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(Rd2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0272] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0273] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0274] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0275] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0276] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0277] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0278] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0279] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0280] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0281] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5.

[0282] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (IIIB),

[0283] in,

[0284] Any independently selected from a single bond or a double bond;

[0285] X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR;

[0286] Ring B is arbitrarily and independently selected from the group consisting of absent, single-bonded, or monocyclic or polycyclic structures of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring, or a bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring, or bridged ring structure may contain zero or more unsaturated olefinic bonds; and when Ring B is absent, R3 may be absent or may be directly attached to L2;

[0287] L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(Rd2 )-, -C(R d1 )=C(R d2 )-, alkyne bond, -OC(R d1 )(R d2 )-, -C(R d1 )(R d2 )O-, -C(=O)N(R d3 )-, -N(R d3 )-, -C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )-, -S(=O)2N(R d3 )-, -N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2 N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(Rd1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-;

[0288] R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally best replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxyamino, OCH3, carboxyl, OH, CN substituents are further substituted;

[0289] L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2)C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-;

[0290] Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; further, Q is preferably substituted with 1 or more R1 substituents;

[0291] Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0292] Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms to which they are connected on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN;

[0293] Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by one or more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkoxy;

[0294] Each R3 may be the same or different and is independently selected from the group consisting of absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2- 10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups;

[0295] Every R d1 、R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1- 10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by one or more alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further substituted by one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl group substitution; or any two R d1 、R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted with 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3;

[0296] The heteroatom represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof;

[0297] The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof;

[0298] m is an integer arbitrarily selected from 0, 1, 2, 3 and 4;

[0299] n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5.

[0300] In one embodiment of the present invention, the compound or its pharmaceutically acceptable salt, isotope-substituted product or isomer thereof has a structure of formula (IV):

[0301] wherein X is selected from N or CH;

[0302] R is selected from C 1-6 Alkyl or C 3-8 Cycloalkyl;

[0303] R0 is selected from C 1-6 Alkyl, C 3-8 Cycloalkyl, halogenated C 1-6 Alkoxy, 5-10 membered heterocyclic group, 5-10 membered heteroaryl, C 1-6 Alkoxy-5-10 membered heteroaryl;

[0304] L3 is selected from NH, O, -CH2NH-;

[0305] Not present or selected from C 1-6 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group;

[0306] R1 is selected from hydroxy, oxo (=O), C 1-6 Alkyl, C 1-6 Alkoxy; t is selected from 0, 1 or 2;

[0307] L1 is selected from NH, O, -CH2NH-;

[0308] L2 is selected from -C(O)NH-, -C(O)O-, -C(O)OCH2-;

[0309] Ring A is selected from 5-8 membered heterocyclic group, C 6-10 aryl;

[0310] Ring B is selected from the group consisting of unsubstituted or optionally substituted with 1, 2 or more halogen, C 1-6 Alkyl or C 1-6 Alkoxy substituted groups: C 6-10 Aryl, 3-8 membered heterocyclic group;

[0311] R2 is selected from H, C 1-6 Alkyl, C 1-6 alkoxy;

[0312] R3 is selected from unsubstituted or optionally substituted with 1, 2 or more halogen, C 1-6 Alkyl, C 1-6 Alkoxy, hydroxy C 1-6 Alkyl substituted groups: C 2-6 Alkenyl-C(O)NH-, C 2-6 Alkynyl-C(O)-, C 1-6 Alkyl-NH-C 2-6 Alkenyl-C(O)-, (C 1-6 Alkyl)2-NC 2-6 Alkenyl-C(O)-, 5-6 membered heterocyclyl-NH-C 2-6 alkenyl-C(O)-;

[0313] m is selected from 0, 1 or 2; n is selected from 0, 1 or 2.

[0314] According to an embodiment of the present invention, R is selected from C 1-3 Alkyl or C 3-6 Cycloalkyl;

[0315] According to an embodiment of the present invention, R is selected from ethyl, isopropyl, cyclopropyl.

[0316] According to an embodiment of the present invention, R0 is selected from C 1-3 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-3 Alkoxy, 5-6 membered heterocyclic group, 5-6 membered heteroaryl, C1-6 Alkoxy-5-6 membered heteroaryl;

[0317] According to an embodiment of the present invention, R0 is selected from methyl, cyclopropyl, difluoromethoxy, trifluoroethoxy, pyridyl, pyrimidinyl,

[0318] According to an embodiment of the present invention, R0 is selected from ).

[0319] According to an embodiment of the present invention, Not present or selected from C 1-6 Alkyl, C 3-6 Cycloalkyl, 5-6 membered heterocyclic group;

[0320] According to an embodiment of the present invention, Absent or selected from propyl, butyl, piperidinyl, tetrahydropyranyl, tetrahydrofuranyl, cyclobutyl,

[0321] According to an embodiment of the present invention, is absent or selected from isopropyl, isobutyl, cyclobutyl,

[0322] According to an embodiment of the present invention, R1 is selected from hydroxy, methyl, oxo (=O), and methoxy.

[0323] According to an embodiment of the present invention, ring A is selected from phenyl, piperidinyl,

[0324] According to an embodiment of the present invention, ring A is selected from

[0325] According to an embodiment of the present invention, ring B is selected from the following groups which are unsubstituted or optionally substituted with 1, 2 or more F or methyl groups: phenyl, 4-6 membered heterocyclyl;

[0326] According to an embodiment of the present invention, ring B is selected from phenyl, N-heterocyclobutane, tetrahydropyrrolyl, According to an embodiment of the present invention, ring B is selected from

[0327] According to an embodiment of the present invention, R3 is selected from the following groups which are unsubstituted or optionally substituted by 1, 2 or more F, methyl, isopropyl, methoxy, hydroxymethyl: C 2-6 Alkenyl-C(O)NH-, C 2-6 Alkynyl-C(O)-, C 1-6Alkyl-NH-C 2-6 Alkenyl-C(O)-, (C 1-6 Alkyl)2-NC 2-6 Alkenyl-C(O)-, 5-6 membered heterocyclyl-NH-C 2-6 alkenyl-C(O)-;

[0328] According to an embodiment of the present invention, R3 is selected from

[0329] In certain embodiments, wherein: Preferably selected from the following structures:

[0330] In one embodiment of the present invention, the above-mentioned compound or a pharmaceutically acceptable salt thereof, or a corresponding isomer or isotope substituted product thereof is a novel compound selected from the compounds disclosed in the Examples.

[0331] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of at least one of the compound represented by formula (I), its pharmaceutically acceptable salts, solvates, enantiomers and isotope substitutions.

[0332] According to the present invention, the pharmaceutical composition further comprises pharmaceutically acceptable adjuvants, carriers or excipients.

[0333] According to an embodiment of the present invention, the pharmaceutical composition is formulated for administration by a route selected from the group consisting of oral, parenteral, rectal, nasal, pulmonary, topical, buccal and sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural.

[0334] According to an embodiment of the present invention, the pharmaceutical composition is preferably administered orally.

[0335] The oral dosage form is not particularly limited and can be any oral dosage form known in the art, preferably tablets, capsules, suspensions or oral solutions, etc. When used as an oral dosage form, the dosage standard used is, for example, 1-1500 mg / day.

[0336] According to an embodiment of the present invention, the pharmaceutically acceptable excipient, carrier or vehicle is selected from at least one of the following, including but not limited to: a filler, a disintegrant, a binder, a lubricant, a surfactant, a flavoring agent, a wetting agent, a pH regulator, a solubilizer or cosolvent, and an osmotic pressure regulator. Those skilled in the art can easily determine how to select the corresponding excipient and its corresponding dosage according to the needs of the specific dosage form.

[0337] According to an embodiment of the present invention, the pharmaceutical composition may further contain one or more additional therapeutic agents.

[0338] Another object of the present invention is to provide the use of the above-mentioned compound in the preparation of a drug for preventing and / or treating CDKs target-related diseases including tumors, inflammation, autoimmune diseases (such as lupus erythematosus, psoriasis, psoriasis) and the like.

[0339] The present invention also provides the compound represented by formula (I), its pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutions, and the use of the pharmaceutical composition in preventing and / or treating diseases related to the CDKs signaling pathway. The diseases related to the CDKs signaling pathway have the definitions described above.

[0340] The present invention also provides a method for preventing and / or treating diseases associated with the CDKs signaling pathway, comprising administering to a patient a preventively or therapeutically effective amount of at least one of the compounds of formula (I), pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutions thereof, or administering to a patient a preventively or therapeutically effective amount of the pharmaceutical composition described above. The diseases associated with the CDKs signaling pathway are as defined above.

[0341] In some embodiments, the patient is a mammal, preferably a human.

[0342] Definition and Explanation:

[0343] C 1-20 Selected from C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 、C 11 、C 12 、C 13 、C 14 、C 15 、C 16 、C 17 、C 18 、C 19 and C 20 ; C 2-10 Selected from C2, C3, C4, C5, C6, C7, C8, C9 and C 10 ; C 3-10 Selected from C3, C4, C5, C6, C7, C8, C9 and C 10 ;

[0344] As used herein, the term "alkyl" is understood to mean a linear or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms, also referred to as "C 1-20 Alkyl". For example, "C 1-10"Alkyl" means straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, "C 1-8 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, "C 1-6 The term "alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, or the like or isomers thereof.

[0345] As used herein, the term "alkylene" refers to a group of the formula -(CH2) n -a linear or branched divalent hydrocarbon group. Non-limiting examples include ethylene and propylene.

[0346] As used herein, the term "1 to a plurality of" means more than one, for example, 1, 2, 3, 4, 5 or more.

[0347] The term "aliphatic ring", "carbocycle" or "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group, which may contain 3 to 20 carbon atoms, preferably 3 to 12 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, more preferably 3 to 6 carbon atoms. The carbocycle may be monocyclic or polycyclic, and may be a saturated cycloalkyl or may optionally contain one, two or more double bonds and / or triple bonds on its ring, thereby forming a so-called cycloalkenyl or cycloalkynyl group. In the case of a carbocycle having multiple rings, these rings may form spirocyclic, fused ring and bridged ring structures. For example, non-limiting examples of monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclooctatetraenyl, and the like; and non-limiting examples of polycyclic carbocycles include decalinyl or isobornyl.

[0348] The term "heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 20 ring atoms, one or more of which is a heteroatom or atomic group selected from N, O, NH, S, S(O) or S(O)2, but excluding the ring portion of -OO-, -OS- or -SS-, and the remaining ring atoms are carbon. Preferably, it contains 3 to 12 ring atoms, 1-4 of which are heteroatoms (e.g., 1, 2, 3, and 4); more preferably, it contains 3 to 6 ring atoms (e.g., 3, 4, 5, 6). The heterocyclic group can be connected to the rest of the molecule through any one of the carbon atoms or a nitrogen atom (if present) or an oxygen or sulfur atom (particularly in the case of forming an onium salt). The heterocyclic group can include fused or bridged rings and / or spirocyclic rings. The limiting examples of monocyclic heterocyclic radical include azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, dioxolyl, tetrahydropyranyl, pyrrolinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dithianyl, trithianyl, homopiperazinyl, diazepanyl etc., preferably piperidinyl, pyrrolidinyl.Polycyclic heterocyclic radical includes the heterocyclic radical of spirocycle, condensed ring and bridged ring, and can also be the heterocyclic radical such as dihydroisoquinolinyl of benzo fusion.Described heterocyclic radical can be bicyclic, and its limiting examples include hexahydrocyclopenta [c] pyrrole -2 (1H) -base, hexahydro pyrrolo [1,2-a] pyrazine -2 (1H) -base. The heterocyclyl group may also be partially unsaturated, i.e. it may contain one or more double bonds, non-limiting examples of which include dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrrolyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl.

[0349] The heterocyclyl group may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl or carboxylate.

[0350] As used herein, the term "heteroaryl / heteroaromatic ring" refers to a heteroaromatic system comprising 1 to 4 heteroatoms, 5 to 20 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, nitrogen and phosphorus. Heteroaryl is preferably 5 to 10 yuan (e.g., 5, 6, 7, 8, 9 or 10 yuan), more preferably 5 yuan or 6 yuan. Non-limiting examples of heteroaryl include, but are not limited to, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, etc. and their benzo derivatives, such as benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzotriazolyl, indazolyl, indolyl, , isoindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and benzo derivatives thereof, such as quinolyl, quinazolinyl, isoquinolyl, etc.; or acinyl, indolizinyl, purinyl, etc. and benzo derivatives thereof; or cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl and / or phenoxazinyl, etc.

[0351] The heteroaryl group / heteroaromatic ring may be optionally substituted or unsubstituted. When substituted, the substituents are preferably one, two or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylate.

[0352] Unless otherwise specified, heterocyclic groups, heteroaryls, or heteroaromatic rings include all possible isomeric forms thereof, such as positional isomers thereof. Thus, for some illustrative, non-limiting examples, substituted or bonded to other groups at one, two, or more positions of the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-positions, etc. (if present) may include pyridin-2-yl, pyridin-2-ylene, pyridin-3-yl, pyridin-3-ylene, pyridin-4-ylene, and pyridin-4-ylene; thienyl or thienylene include thien-2-yl, thien-2-ylene, thien-3-ylene, and thien-3-ylene; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, and pyrazol-5-yl.

[0353] The term "aryl" or "aromatic ring" means: It should be understood that it preferably refers to a monovalent aromatic or partially aromatic monocyclic, bicyclic (such as fused, bridged, spiro) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a single aromatic ring or a polyaromatic ring fused together, preferably "C 6-14 Aryl". The term "C 6-14"Aryl" is understood to mean preferably a monovalent aromatic or partially aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring ("C 6-14 or a ring having 9 carbon atoms ("C9 aryl"), for example indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl) such as tetrahydronaphthyl, dihydronaphthyl or naphthyl, or a ring having 13 carbon atoms ("C 13 aryl), such as fluorenyl, or a ring having 14 carbon atoms ("C 14 aryl”), such as anthracenyl. When the C 6-20 When the aryl group is substituted, it may be monosubstituted or polysubstituted. Furthermore, there is no limitation on the position of substitution, and for example, substitution may be at the ortho, para or meta position.

[0354] The term "spirocyclic" refers to a ring system in which two rings share one ring atom, which may contain an aliphatic ring, a heterocyclic ring, an aromatic ring or a heteroaromatic ring as described above.

[0355] The term "paracyclic" refers to a ring system in which two rings share two ring atoms, and may contain an aliphatic ring, a heterocyclic ring, an aromatic ring or a heteroaromatic ring as described above.

[0356] The term "bridged ring" refers to a ring system in which two rings share three or more ring atoms, and may contain an aliphatic ring, a heterocyclic ring, an aromatic ring or a heteroaromatic ring as described above.

[0357] The term "pharmaceutically acceptable" as used herein refers to those compounds, materials, compositions and / or dosage forms which, within the scope of sound medical judgment, are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0358] The term "pharmaceutically acceptable salt" refers to salts of the compounds of the present invention, prepared by reacting the compounds of the present invention with relatively nontoxic acids or bases. When the compounds of the present invention contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of base in neat solution or in a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino or magnesium salts, or similar salts. When the compounds of the present invention contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of acid in neat solution or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, bicarbonate, phosphoric acid, monohydrogen phosphate, dihydrogen phosphate, sulfuric acid, bisulfate, hydroiodic acid, phosphorous acid, and the like; and organic acid salts such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid, and methanesulfonic acid; and salts of amino acids such as arginine, and organic acids such as glucuronic acid (see Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functional groups and can be converted into either base or acid addition salts.

[0359] Preferably, the neutral form of the compound is regenerated by contacting the salt with a base or acid in a conventional manner and isolating the parent compound. The parent form of the compound differs from its various salt forms in certain physical properties, such as solubility in polar solvents.

[0360] As used herein, "pharmaceutically acceptable salts" are derivatives of the compounds of the present invention, wherein the parent compound is modified by salification with an acid or alkali. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of bases such as amines, alkali metal or organic salts of acid radicals such as carboxylic acids, and the like. Pharmaceutically acceptable salts include conventional non-toxic salts such as sodium salts, potassium salts, amine salts, quaternary ammonium salts of the parent compound, and the like. Conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids, inorganic and organic bases, wherein the inorganic or organic acid is selected from 2-acetoxybenzoic acid, 2-hydroxyethanesulfonic acid, acetic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, bicarbonate, carbonic acid, citric acid, edetic acid, ethanedisulfonic acid, ethanesulfonic acid, fumaric acid, glucoheptose, gluconic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, hydroiodide, hydroxyl, hydroxynaphthalene The inorganic base and organic base described in the following examples are selected from sodium, potassium, magnesium, calcium, etc. or amines, diethylamine, triethylamine, ethanolamine, etc.

[0361] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing acid radicals or bases by conventional chemical methods. Generally, such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of an appropriate base or acid in water or an organic solvent, or a mixture of the two. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred.

[0362] In addition to the form of salts, the compounds provided by the present invention also exist in prodrug form. The prodrugs of the compounds described herein easily undergo chemical changes under physiological conditions to be converted into the compounds of the present invention. In addition, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an in vivo environment.

[0363] Some compounds of the present invention may exist in unsolvated or solvated forms, including hydrate forms. Generally speaking, solvated forms are comparable to unsolvated forms and are included within the scope of the present invention. Some compounds of the present invention may exist in polycrystalline or amorphous forms.

[0364] As used herein, the term "solvate" refers to an association formed between one or more solvent molecules and a compound of the present invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. Thus, the term "hydrate" refers to an association formed when the solvent molecule is water.

[0365] Certain compounds of the present invention may have asymmetric carbon atoms (optical centers) or double bonds. Racemates, diastereomers, geometric isomers and individual isomers are all within the scope of the present invention.

[0366] The diagrammatic representations of racemic, ambiscalemic, scalemic, or enantiomerically pure compounds herein are adapted from Maehr, J. Chem. Ed. 1985, 62:114-120. Unless otherwise indicated, wedge-shaped and dashed bonds are used to represent the absolute configuration at a stereocenter. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, they are intended to include both E and Z geometric isomers unless otherwise specified. Likewise, all tautomeric forms are intended to be encompassed within the scope of this invention.

[0367] The compounds of the present invention may exist in specific geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and trans-isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers, (D)-isomers, (L)-isomers, and racemic mixtures and other mixtures thereof, such as enantiomerically or diastereomerically enriched mixtures, all of which are within the scope of the present invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are encompassed within the scope of the present invention.

[0368] Optically active (R)- and (S)-isomers, as well as D and L isomers, can be prepared by chiral synthesis or chiral reagents or other conventional techniques. If one enantiomer of a compound of the present invention is desired, it can be prepared by asymmetric synthesis or derivatization with a chiral auxiliary, wherein the resulting diastereomeric mixture is separated and the auxiliary group is cleaved to provide the pure desired enantiomer. Alternatively, when the molecule contains a basic functional group (such as an amino group) or an acidic functional group (such as a carboxyl group), a diastereomeric salt is formed with an appropriate optically active acid or base, and then the diastereoisomers are separated by fractional crystallization or chromatography as is known in the art, and then the pure enantiomer is recovered. In addition, the separation of enantiomers and diastereomers is typically accomplished by using chromatography, which employs a chiral stationary phase and is optionally combined with a chemical derivatization method (e.g., carbamate formation from an amine).

[0369] The compounds of the present invention may contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute the compound. For example, the compounds may be labeled with radioactive isotopes, such as tritium ( 3 H), iodine-125( 125 I) or C-14( 14C) All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0370] The term "pharmaceutically acceptable carrier" refers to any formulation or carrier medium that can deliver an effective amount of the active substance of the present invention, does not interfere with the biological activity of the active substance, and has no toxic side effects on the host or patient. Representative carriers include water, oils, vegetables and minerals, cream bases, lotion bases, ointment bases, etc. These bases include suspending agents, viscosity increasing agents, transdermal enhancers, etc. Their preparation is well known to those skilled in the art of cosmetics or topical medicine. For additional information on carriers, reference can be made to Remington: The Science and Practice of Pharmacy, 21st Ed., Lippincott, Williams & Wilkins (2005), the contents of which are incorporated herein by reference.

[0371] When any variable (e.g., R) occurs more than once in a compound's composition or structure, its definition at each occurrence is independent. Thus, for example, if a group is substituted with 0-2 Rs, the group may be optionally substituted with up to two Rs, with each occurrence of R being an independent choice. Furthermore, combinations of substituents and / or their variants are permissible only if such combinations result in stable compounds.

[0372] When a substituent's bond crosses two atoms in a ring, such substituent may be bonded to any atom in the ring. When a substituent is listed without specifying the atom through which it is bonded to a compound included in the general chemical formula but not specifically mentioned, such substituent may be bonded to any atom therein. Combinations of substituents and / or variants thereof are permissible only if such combinations result in stable compounds.

[0373] The term "halo" or "halogen" refers to fluorine, chlorine, bromine and iodine.

[0374] The present invention will now be further described by way of examples. The examples given below are for illustrative purposes only and are not intended to limit the scope of this invention. The compounds of the present invention can be prepared using many methods known in the art of organic synthesis. The examples of the present invention can be synthesized using the methods described below, as well as synthetic methods known in the art of synthetic organic chemistry, or by methods modified therefrom. Preferred methods include, but are not limited to, the methods described below.

[0375] Unless otherwise specified, all solvents used in the present invention are commercially available and do not require further purification when used. The reaction is usually carried out using anhydrous solvents under an inert atmosphere of nitrogen. The nuclear magnetic resonance spectrum is measured on a Bruker-Avance-400 (400 MHz) spectrometer, and the chemical shift is reported in the form of δ (ppm). Mass spectrometry is performed using an Agilent 1200 series (plus 6110 / and 1956A) LC / MS or Shimadzu MS (DAD: SPD-M20A (LC)) and Shimadzu Micromass 2020 detector. The mass spectrometer is equipped with an electrospray ionization source (ESI) operating in positive and negative modes.

[0376] The present invention uses the following abbreviations: aq represents water; DCM represents dichloromethane; PE represents petroleum ether; DMF represents N,N-dimethylformamide; DMSO represents dimethyl sulfoxide; EtOAc represents ethyl acetate; EtOH represents ethanol; MeOH represents methanol; Cbz represents benzyloxycarbonyl, an amine protecting group; Boc represents tert-butyloxycarbonyl, an amine protecting group; HOAc represents acetic acid; NaBH(OAc)3 represents sodium triacetoxyborohydride; r.t represents room temperature; THF represents tetrahydrofuran; Boc2O represents di-tert-butyl dicarbonate; TFA represents trifluoroacetic acid; DIPEA represents diisopropylethylamine; Pd(dppf)Cl2 represents [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride; POCl3 represents phosphorus oxychloride; NaH represents sodium hydride; LAH represents lithium aluminum hydride; Pd(OAc)2 represents palladium(II) acetate; Pd2(dba)3 represents tris(dibenzylideneacetone)dipalladium; Pd(PPh3)4 represents tetrakis(triphenylphosphine)palladium; Et3SiH represents triethylsilane; PPh3 represents triphenylphosphine; Xantphos represents 4,5-bis(diphenylphosphino)-9,9-dimethyl; MeSO3H represents methanesulfonic acid; Xphos represents 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl; Lawesson's reagent represents 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphane-2,4-disulfide; NBS represents Table N-bromosuccinimide; t-BuOK represents potassium tert-butoxide; DIPEA is diisopropylethylamine; SOCl2 is thionyl chloride; CS2 is carbon disulfide; TsOH is 4-toluenesulfonic acid; MTBE is tert-butyl methyl ether; i-PrOH is 2-propanol; DAST is diethylaminosulfur trifluoride; DIAD is diisopropyl azodicarboxylate; DEAD is diethyl azodicarboxylate; DBAD is di-tert-butyl azodicarboxylate; TES is triethylsilane; LDA Lithium diisopropylamide; NBS is N-bromosuccinimide; NIS is N-iodosuccinimide; NCS is N-chlorosuccinimide; DMP is DMP reagent; DMF-DMA is 1,1-dimethoxy-N,N-dimethylmethanamine; TMP is 2,2,6,6-tetramethylpiperidine; NMO is N-methylmorpholine N-oxide; TBSC1 is tert-butyldimethylsilyl chloride; SEMC1 is 2-(trimethylsilyl)ethoxymethyl chloride; NFSI is N-fluorobenzenesulfonamide; AIBN is azobisisobutyronitrile; EDCI is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; HOBT is hydroxybenzotriazole; TBAF is tetra-n-butylammonium fluoride; HATU is 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolyl[4,5-b]pyridinium trioxide hexafluorophosphate; Xphos is 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl; cataCXium A is n-butyl-bis(1-adamantyl)phosphine; DPPP is 1,3-bis(diphenylphosphino)propane; DPPF is 1,1′-bis(diphenylphosphino)ferrocene; HMTA is 1,3,5,7-tetraazaadamantane; PMBC1 is p-methoxybenzyl chloride; HEPES is 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; EGTA is ethylene glycol bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid.

[0377] Compounds can be named manually or using The product is named after the manufacturer. If purchased commercially, the supplier's catalog name can also be used. TLC or LC-MS is usually used to determine whether the reaction is complete.

[0378] Specific embodiment

[0379] In order to illustrate the present invention in more detail, the following examples are given, but the scope of the present invention is not limited thereto.

[0380] Example 1. Synthesis of 2,2,2-trifluoroacetate of 3-acrylamide-N-(3-((2-(((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)benzamide (Compound C1-1):

[0381] 1) Synthesis of 8-isopropyl-2-(methylthio)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine:

[0382] A mixed solution (10.0 mL) of 4-chloro-8-isopropyl-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine (500.0 mg, 2.06 mmol), 3-nitrobenzylamine (376.8 mg, 2.48 mmol), and N,N-diisopropylethylamine (799.6 mg, 6.20 mmol) in isopropyl alcohol was heated to 80° C. and stirred for 2 hours. After cooling, the resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water (containing 0.1% aqueous ammonia), gradient: 5%-95%) to give 8-isopropyl-2-(methylthio)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine (650 mg, 1.82 mmol, yield: 88%).

[0383] LC-MS m / z:359[M+H] + .

[0384] 2) Synthesis of 8-isopropyl-2-(methylsulfonyl)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine:

[0385] A toluene solution (15.0 mL) containing 8-isopropyl-2-(methylthio)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine (650.0 mg, 1.82 mmol) and m-chloroperbenzoic acid (1837 mg, 9.08 mmol, purity: 85%) was stirred at room temperature overnight. After the reaction, the resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile containing 0.1% formic acid and water containing 0.1% formic acid, gradient: 5%-95%) to give 8-isopropyl-2-(methylsulfonyl)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine (400 mg, 1.02 mmol, yield: 56%). LC-MS: m / z = 391 [M+H]. + .

[0386] 3) Synthesis of tert-butyl (3R, 4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrobenzyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate:

[0387] A solution of 8-isopropyl-2-(methylsulfonyl)-N-(3-nitrobenzyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine (400.0 mg, 1.02 mmol) and tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate (283.1 mg, 1.23 mmol) in dioxane (10.0 mL) was heated to 140° C. and reacted overnight. After cooling, the resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give tert-butyl (3R,4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrobenzyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate (300 mg, 0.56 mmol, yield: 55%). LC-MS: m / z=541 [M+H] + .

[0388] 4) Synthesis of tert-butyl (3R, 4R)-4-((4-((3-aminobenzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0389] At room temperature, saturated ammonium chloride solution (1 mL) was added dropwise to a solution of tert-butyl (3R,4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrobenzyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate (300.0 mg, 0.56 mmol) and iron powder (155.6 mg, 2.78 mmol) in ethanol (4 mL). After the addition was complete, the temperature was raised to 70°C and the reaction was allowed to react for 2 hours. After cooling, the reaction solution was directly filtered through celite, and the filter cake was washed three times with methanol (3 × 10 mL). The resulting filtrate was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give the target compound, tert-butyl (3R,4R)-4-((4-((3-aminobenzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (120 mg, 0.24 mmol, yield: 42%). LC-MS: m / z = 511 [M+H] + .

[0390] 5) Synthesis of tert-butyl (3R, 4R)-4-((4-((3-(3-acrylamidobenzamide)benzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0391] A mixed solution of (3R,4R)-4-((4-((3-aminobenzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (120.0 mg, 0.24 mmol), 3-acrylamidobenzoic acid (53.9 mg, 0.28 mmol), N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (134.4 mg, 0.48 mmol) and N-methylimidazole (78.7 mg, 0.96 mmol) in N,N-dimethylformamide (5.0 mL) was stirred at 30°C for 2 hours. After the reaction was completed, the reaction solution was directly purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain tert-butyl (3R,4R)-4-((4-((3-(3-acrylamidobenzamido)benzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (60 mg, 0.09 mmol, yield: 36%). LC-MS: m / z = 684 [M+H] + .

[0392] 6) Synthesis of 2,2,2-trifluoroacetate of 3-acrylamide-N-(3-((2-(((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)benzamide (Compound C1-1):

[0393] To a solution of tert-butyl (3R,4R)-4-((4-((3-(3-acrylamidobenzamide)benzyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (60 mg, 0.09 mmol) in dichloromethane (3 mL) was added dropwise trifluoroacetic acid (1 mL) and the mixture was reacted at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain the target compound 3-acrylamide-N-(3-((2-((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)methyl)phenyl)benzamide trifluoroacetate (26.5 mg, 0.038 mmol, yield: 42%). LC-MS: m / z = 584 [M+H]. + .

[0394] 1 H NMR (400MHz, MeOD_d4): 8.39 (s, 1H), 7.93 (d, J=2.4Hz, 2H), 7.67-7.61 (m, 2H), 7.48 (t , J=8Hz, 2H), 7.38 (t, J=8Hz, 1H), 7.23 (d, J=8Hz, 1H), 6.46-6.38 (m, 2H), 5.82 (d, J=8H z, 1H), 4.86 (s, 2H), 3.83 (s, 1H), 3.64 (s, 2H), 3.07-3.00 (m, 1H), 2.86 (t, J=8Hz, 1H), 2.73 (t, J=8Hz, 1H), 1.98-1.94 (m, 2H), 1.45 (s, 1H), 1.29 (d, J=4Hz, 6H), 1.14 (s, 2H).

[0395] Example 2, Synthesis of 3-acrylamido-N-(3-((3R,4R)-3-hydroxypiperidin-4-yl)methylamino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)benzamide (Compound C1-2):

[0396] 1) Synthesis of 8-isopropyl-2-(methylthio)-N-(3-nitrophenyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine:

[0397] A mixed solution (20.0 mL) of 4-chloro-8-isopropyl-2-(methylthio)pyrazolo[1,5-a][1,3,5]triazine (1 g, 4.13 mmol), 3-nitroaniline (742 mg, 5.37 mmol), and N,N-diisopropylethylamine (1.6 g, 12.39 mmol) in acetonitrile was heated at 80°C for 4 hours. After cooling, water (40 mL) was added to the reaction solution, and the mixture was extracted three times with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (30 mL x 1), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to afford the target compound, 8-isopropyl-2-(methylthio)-N-(3-nitrophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine (1.2 g, 3.48 mmol, yield: 84%). LC-MS: m / z = 345 [M+H] + .

[0398] 2) Synthesis of 8-isopropyl-2-(methylsulfonyl)-N-(3-nitrophenyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine:

[0399] A solution of 8-isopropyl-2-(methylthio)-N-(3-nitrophenyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine (1 g, 2.91 mmol) and m-chloroperbenzoic acid (885 mg, 4.36 mmol, purity: 85%) in dichloromethane (15.0 mL) was stirred at room temperature for 2 hours. After the reaction, the resulting mixture was concentrated in vacuo to remove the solvent to obtain the crude product, which was used directly in the next reaction. LC-MS: m / z = 377 [M+H] + .

[0400] 3) Synthesis of tert-butyl (3R, 4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrophenyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate:

[0401] A solution of 8-isopropyl-2-(methylsulfonyl)-N-(3-nitrophenyl)pyrazolo[1,5-a][1,3,5]triazine-4-amine (800 mg, 2.12 mmol) and tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate (587 mg, 2.55 mmol) in dioxane (10.0 mL) was heated to 100°C and allowed to react overnight. After cooling, water (20 mL) was added to the reaction system, and the mixture was extracted three times with ethyl acetate (20 mL x 3). The organic phases were combined, washed with saturated brine (30 mL x 1), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give the target compound, tert-butyl (3R,4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrophenyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate (600 mg, 1.13 mmol, yield: 53%). LC-MS: m / z = 527 [M+H] + .

[0402] 4) Synthesis of tert-butyl (3R, 4R)-4-((4-((3-aminophenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0403] At room temperature, saturated ammonium chloride solution (0.5 mL) was added dropwise to a solution of tert-butyl (3R,4R)-3-hydroxy-4-((8-isopropyl-4-((3-nitrophenyl)amino)pyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)piperidine-1-carboxylate (50 mg, 0.095 mmol) and iron powder (Fe) (26.7 mg, 0.047 mmol) in ethanol (2 mL). After the addition was complete, the temperature was raised to 70°C and the reaction was allowed to react for 2 hours. After cooling, the reaction solution was directly filtered through celite, and the filter cake was washed three times with methanol (10 mL x 3). The resulting filtrate was concentrated in vacuo to remove the solvent to yield the target compound, tert-butyl (3R,4R)-4-((4-((3-aminophenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (30.0 mg, 0.06 mmol, 63% yield). LC-MS: m / z = 497 [M+H] + .

[0404] 5) Synthesis of tert-butyl (3R, 4R)-4-((4-((3-(3-acrylamidobenzamide)phenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0405] To a solution of tert-butyl (3R,4R)-4-((4-((3-aminophenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (200 mg, 0.40 mmol) and 3-acrylamidobenzoic acid (116 mg, 0.60 mmol) in N,N-dimethylformamide (3 mL) were added 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (201 mg, 0.53 mmol) and N,N-diisopropylethylamine (69 mg, 0.53 mmol). The mixture was reacted at room temperature under nitrogen for 2 hours. After the reaction was completed, water (10 mL) was added to the reaction solution, and the mixture was extracted three times with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine (30 mL x 1), dried over anhydrous sodium sulfate, filtered, and concentrated to give a crude product. The crude product was purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to give tert-butyl (3R,4R)-4-((4-((3-(3-acrylamidobenzylamide)phenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (130 mg, 0.19 mmol, yield: 48%). LC-MS: m / z = 670 [M+H] + .

[0406] 6) Synthesis of 3-acrylamido-N-(3-((3R,4R)-3-hydroxypiperidin-4-yl)methylamino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)benzamide (Compound C1-2):

[0407] To a solution of tert-butyl (3R,4R)-4-((4-((3-(3-acrylamidobenzamide)phenyl)amino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-2-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (60 mg, 0.089 mmol) in dichloromethane (1.5 mL) was added dropwise trifluoroacetic acid (0.3 mL) and the reaction was carried out at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia water, gradient: 5%-95%) to give 3-acrylamido-N-(3-((3R,4R)-3-hydroxypiperidin-4-yl)methylamino)-8-isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)benzamide (compound 2) (40 mg, 0.07 mmol, yield: 78%).

[0408] LC-MS: m / z=570[M+H] + ;

[0409] 1H NMR (400MHz, MeOD) δ8.40 (m, 3H), 8.23 ​​(s, 1H), 7.70 (s, 1H), 7.60 (d, J=8.0Hz, 2H), 7.41 (t, J=7.7Hz, 2H ), 7.31 (m, 2H), 6.36 (dt, J = 21.3, 12.3Hz, 2H), 5.73 (d, J = 9.2Hz, 1H), 3.78 (m, 2H), 3.54 (m, 2H), 3.38 (sm 1H), 3.03(m, 1H), 2.93(m, 1H), 2.70(m 1H), 1.93 (d, J=8.7Hz, 1H), 1.73 (m, 1H), 1.57 (m, 1H), 1.20 (d, J=6.8Hz, 6H).

[0410] Example 3. Synthesis of 3-acrylamide-N-(3-((5-((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)benzamide (Compound C1-3):

[0411] 1) Synthesis of 5-chloro-3-isopropyl-N-(3-nitrobenzyl)pyrazolo[1,5-a]pyrimidin-7-amine:

[0412] A solution of 5,7-dichloro-3-isopropylpyrazolo[1,5-a]pyrimidine (300.0 mg, 1.30 mmol), 3-nitrobenzylamine (218 mg, 1.43 mmol), and triethylamine (144 mg, 1.43 mmol) in isopropanol (4.0 mL) was heated to 80°C and reacted for 2 hours. After cooling, the resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give 5-chloro-3-isopropyl-N-(3-nitrobenzyl)pyrazolo[1,5-a]pyrimidin-7-amine (250 mg, 0.72 mmol, 56% yield). LC-MS: m / z = 345.8 [M+H] + .

[0413] 2) Synthesis of tert-butyl (5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl) (3-nitrobenzyl)carbamate:

[0414] A solution of 5-chloro-3-isopropyl-N-(3-nitrobenzyl)pyrazolo[1,5-a]pyrimidin-7-amine (250.0 mg, 0.72 mmol), di-tert-butyl dicarbonate (205 mg, 0.94 mmol), 4-dimethylaminopyridine (40 mg, 0.33 mmol), and triethylamine (146 mg, 1.45 mmol) in tetrahydrofuran (2.0 mL) was heated to 50° C. and reacted overnight. The resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give tert-butyl ((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)(3-nitrobenzyl)carbamate (158 mg, 0.35 mmol, yield: 49%). LC-MS: m / z=446 [M+H] + .

[0415] 3) Synthesis of tert-butyl (3R, 4R)-4-((7-((tert-butoxycarbonyl)(3-nitrobenzyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0416] A solution of tert-butyl (5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)(3-nitrobenzyl)carbamate (50.0 mg, 0.11 mmol), butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate (31 mg, 0.13 mmol), (SP-4-1)-[1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(2-methylpyridine)palladium (8.4 mg, 0.01 mmol), and cesium carbonate (110 mg, 0.34 mmol) in dioxane (2 mL) was heated to 90°C and reacted overnight. After cooling, the resulting mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and 0.1% ammonia in water, gradient: 5%-95%) to give the target compound, tert-butyl (3R,4R)-4-((7-((tert-butoxycarbonyl)(3-nitrobenzyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (38.8 mg, 0.06 mmol, yield: 54%). LC-MS: m / z = 640 [M+H] + .

[0417] 4) Synthesis of tert-butyl (3R, 4R)-4-((7-((3-aminobenzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0418] To a solution of tert-butyl (3R,4R)-4-((7-(tert-butyloxycarbonyl)(3-nitrobenzyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (38.8 mg, 0.06 mmol) and iron powder (17 mg, 0.3 mmol) in ethanol (2 mL) was added dropwise a saturated ammonium chloride solution (0.5 mL). After the addition was complete, the temperature was raised to 70°C and the reaction was allowed to react for 2 hours. After cooling, the reaction solution was directly filtered through celite, and the filter cake was washed three times with methanol (10 mL x 3). The resulting filtrate was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and 0.1% ammonia water, gradient: 5%-95%) to give the target compound (3R,4R)-4-((7-((3-aminobenzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (30 mg, 0.05 mmol, yield: 81%). LC-MS: m / z=610 [M+H] + .

[0419] 5) Synthesis of tert-butyl (3R, 4R)-4-((7-((3-(3-acrylamidobenzamido)benzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate:

[0420] To a solution of tert-butyl (3R,4R)-4-((7-((3-aminobenzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (30.0 mg, 0.05 mmol) and 3-acrylamidobenzoic acid (12 mg, 0.06 mmol) in N,N-dimethylformamide (3 mL) were added 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (28 mg, 0.07 mmol) and N,N-diisopropylethylamine (19 mg, 0.15 mmol), the temperature was raised to 30°C, and the reaction was carried out for 2 hours. The reaction mixture was filtered and purified by C18 column chromatography (mobile phase: acetonitrile and 0.1% ammonia in water, gradient: 5%-95%) to obtain the target compound, tert-butyl (3R,4R)-4-((7-((3-(3-acrylamidobenzamido)benzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (30 mg, 0.039 mmol, yield: 78%). LC-MS: m / z = 783 [M+H]. + .

[0421] 6) Synthesis of 3-acrylamide-N-(3-((5-((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)benzamide:

[0422] To a dichloromethane solution (3 mL) of tert-butyl (3R,4R)-4-((7-((3-(3-acrylamidobenzamido)benzyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (30 mg, 0.039 mmol) was added dropwise trifluoroacetic acid (1 mL) and the mixture was reacted at room temperature for 2 hours. After the reaction was completed, the reaction solution was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to obtain the target compound 3-acrylamide-N-(3-((5-((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)methyl)phenyl)benzamide (Compound C1-3) (15.08 mg, 0.026 mmol, yield: 66%). LC-MS: m / z = 583 [M+H] + .

[0423] 1 H NMR (400MHz, MeOD): δ8.37 (s, 1H), 7.89 (s, 2H), 7.77-7.54 (m, 2H), 7.51-7.40 (m, 3H), 7.22 (d, J=7.4 Hz, 1H), 6.58-6.32 (m, 2H), 5.82 (dd, J=9.4, 2.1Hz, 1H), 5.45 (s, 1H), 4.74 (s, 2H), 3.97-3.43 (m, 5H), 3.43-3.25 (m, 1H), 3.09- 2.96 (m, 1H), 2.84 (dt, J=22.7, 10.6Hz, 1H), 2.02 (d, J=12.1Hz, 1H), 1.84 (s, 1H), 1.52 (d, J=11.7Hz, 1H), 1.30 (d, J=6.9Hz, 6H).

[0424] Example 4. Synthesis of (R)-3-acrylamido-N-(3-((3-isopropyl-5-(piperidin-3-oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)phenyl)benzamide (Compound C1-4):

[0425] 1) Synthesis of 5-chloro-3-isopropyl-N-(3-nitrophenyl)pyrazolo[1,5-a]pyrimidin-7-amine:

[0426] To a solution of 3-nitroaniline (180 mg, 1.31 mmol) in N,N-dimethylformamide (4 mL) was added sodium hydride (160 mg, 3.93 mmol, 60% purity, dispersed in kerosene) at 0°C. The mixture was stirred at 0°C for 0.5 hours. Then, 5,7-dichloro-3-isopropylpyrazolo[1,5-a]pyrimidine (300 mg, 1.31 mmol) was added, and the temperature was raised to 90°C for 16 hours. After the reaction was complete, the mixture was cooled to room temperature and methanol (2 mL) was added. The resulting mixture was filtered and directly purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain the target compound, 5-chloro-3-isopropyl-N-(3-nitrophenyl)pyrazolo[1,5-a]pyrimidin-7-amine (380 mg, 1.14 mmol, yield: 87%). LC-MS: m / z=332[M+H] + .

[0427] 2) Synthesis of tert-butyl (5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)(3-nitrophenyl)carbamate:

[0428] 4-Dimethylaminopyridine (254 mg, 2.08 mmol) was added to a solution of 5-chloro-3-isopropyl-N-(3-nitrophenyl)pyrazolo[1,5-a]pyrimidin-7-amine (300 mg, 0.90 mmol) and di-tert-butyl dicarbonate (300 mg, 1.37 mmol) in tetrahydrofuran (2.0 mL). The mixture was stirred at room temperature for 4 hours. After the reaction, the mixture was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain the target compound, tert-butyl 5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)(3-nitrophenyl)carbamate (320 mg, 0.74 mmol, yield: 82%). LC-MS: m / z = 432 [M+H]. + .

[0429] 3) Synthesis of tert-butyl (R)-3-((7-((tert-butyloxycarbonyl)(3-nitrophenyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate:

[0430] To a solution of tert-butyl (R)-3-hydroxypiperidine-1-carboxylate (154 mg, 0.76 mmol) in N,N-dimethylformamide (2 mL) was added sodium hydride (60 mg, 1.52 mmol, 60% purity, dispersed in kerosene) at 0°C, and the mixture was stirred at room temperature for 30 minutes. Then, a solution of tert-butyl 5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)(3-nitrophenyl)carbamate (220 mg, 0.51 mmol) in tetrahydrofuran (2 mL) was added at room temperature, and the reaction was continued by stirring at room temperature for 4 hours. After the reaction, a small amount of methanol was added to the reaction system to quench the sodium hydrogen. The reaction solution was then filtered and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain the target compound (R)-tert-butyl 3-((7-(tert-butyloxycarbonyl)(3-nitrophenyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (80 mg, 0.13 mmol, yield: 26.3%). LC-MS: m / z = 597 [M+H] + .

[0431] 4) Synthesis of tert-butyl (R)-3-((7-((3-aminophenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate:

[0432] To a solution of tert-butyl (R)-3-((7-(tert-butyloxycarbonyl)(3-nitrophenyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (120 mg, 0.20 mmol) and iron powder (57 mg, 1.0 mmol) in ethanol (4 mL) was added a saturated ammonium chloride solution (1 mL). After the addition was complete, the mixture was heated to 70°C and stirred for 2 hours. After cooling, the reaction solution was directly filtered through celite, and the filter cake was washed three times with methanol (10 mL x 3). The resulting filtrate was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to give (R)-tert-butyl 3-((7-((3-aminophenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (100 mg, 0.17 mmol, yield: 85%). LC-MS: m / z = 567 [M+H] + .

[0433] 5) Synthesis of tert-butyl (R)-3-((7-((3-(3-acrylamidobenzamido)phenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate:

[0434] To a solution of tert-butyl (R)-3-((7-((3-aminophenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (100 mg, 0.17 mmol) and 3-acrylamidobenzoic acid (40 mg, 0.21 mmol) in N,N-dimethylformamide (2 mL) were added 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (100 mg, 0.26 mmol) and N,N-diisopropylethylamine (34 mg, 0.26 mmol), and the mixture was reacted at room temperature under nitrogen protection for 3 hours. The reaction mixture was filtered and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% aqueous ammonia, gradient: 5%-95%) to obtain tert-butyl (R)-3-((7-((3-(3-acrylamidobenzamido)phenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (30 mg, 0.04 mmol, yield: 23%). LC-MS: m / z = 740 [M+H]. + .

[0435] 6) Synthesis of (R)-3-acrylamido-N-(3-((3-isopropyl-5-(piperidin-3-oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)phenyl)benzamide:

[0436] To a solution of tert-butyl (R)-3-((7-((3-(3-acrylamidobenzamido)phenyl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (40 mg, 0.054 mmol) in dichloromethane (2.0 mL) was added trifluoroacetic acid (0.5 mL), and the mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated in vacuo to remove the solvent and purified by C18 column chromatography (mobile phase: acetonitrile and water containing 0.1% ammonia, gradient: 5%-95%) to obtain (R)-3-acrylamido-N-(3-((3-isopropyl-5-(piperidin-3-oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)phenyl)benzamide (Compound C1-4) (20 mg, 0.037 mmol, yield: 68%). LC-MS: m / z=540[M+H] + ;

[0437] 1H NMR (400MHz, DMSO) δ10.47 (s, 1H), 10.42 (s, 1H), 8.20 (s, 1H), 7.94 (d, J=11.5Hz, 2H), 7.87 (s, 1H), 7.73-7.62 (m, 2H), 7.50 (t, J=7.9Hz, 1H), 7.42 (t, J=7.9Hz, 1H), 7.16 (d, J=8.1Hz, 1H), 6.47 (dd, J=16.8, 9.8Hz, 1H), 6.3 0 (d, J=16.7Hz, 1H), 5.79 (d, J=10.3Hz, 1H), 5.66 (s, 1H), 5.07 (s, 1H), 3.19 (d, J=9.7Hz, 1H), 3.07 (d, J=7.2Hz , 1H), 2.79 (m, 1H), 2.73 (m, 1H), 2.66 (m, J=12.9Hz, 1H), 2.01 (s, 1H), 1.76-1.44 (m, 4H), 1.32 (d, J=6.8Hz, 6H).

[0438] Example 5. Synthesis of 1-(2-fluoroacryloyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo-11,5-a]pyrimidin-7-yl)amino)-2-azaspiro-13,3]heptane-2-carboxylate (Compound C2-5):

[0439] 1) Synthesis of tert-butyl 6-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[13.3]heptane-2-carboxylate:

[0440] To a solution of tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate (839 mg, 3.95 mmol) in tetrahydrofuran (5 mL) at 0°C was added sodium hydride (158 mg, 3.95 mmol, content: 60%) and stirred at 0°C for 0.5 hours. A solution of 5,7-dichloro-3-isopropylpyrazolo[1,5-a]pyrimidine (1.09 g, 4.76 mmol) in tetrahydrofuran (1 mL) was then added dropwise to the reaction mixture, and the resulting mixture was stirred at room temperature for 3 hours. LCMS confirmed the reaction was complete. The mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic phases were washed with saturated brine (1 × 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 0-50% elution) to give tert-butyl 6-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (1.5 g, yield: 93.7%), LC-MS m / z: 406 [M+H] + ;

[0441] 2) Synthesis of tert-butyl 6-((tert-butyloxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate:

[0442] A solution of tert-butyl 6-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (1.4 g, 3.46 mmol), di-tert-butyl dicarbonate (905 mg, 4.15 mmol), 4-dimethylaminopyridine (633 mg, 5.19 mmol), and N,N-diisopropylethylamine (2.2 g, 17.3 mmol) in dichloromethane (7 mL) was heated at 40°C with stirring for 16 hours. The reaction was complete by LCMS. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 20-65% elution) to give tert-butyl 6-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (749 mg, yield: 44%), LC-MS m / z: 506 [M+H] + ;

[0443] 3) Synthesis of tert-butyl 6-((tert-butyloxycarbonyl)(3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3,3-heptane-2-carboxylate

[0444] A solution of tert-butyl 6-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (701 mg, 1.38 mmol), tetrahydro-2H-pyran-4-amine (169 mg, 1.67 mmol), (SP-4-1)-[1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(2-methylpyridine)palladium (117 mg, 0.139 mmol), and cesium carbonate (1.36 g, 4.16 mmol) in 1,4-dioxane (3 mL) was heated at 100° C. and stirred for 16 hours. The resulting mixed reaction solution was heated at 100° C. and stirred for 16 hours under argon protection. The reaction was complete by LCMS. After cooling, the resulting mixed reaction solution was diluted with water (20 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic phase was washed with brine (1 × 30 mL) and dried over anhydrous sodium sulfate. The crude product (923 mg) was filtered and concentrated under reduced pressure and used directly in the next step without further purification. LC-MS M / z: 571 [M+H] + ;

[0445] 4) 3-isopropyl-N 7 -(2-azaspiro[3.3]heptane-6-yl)-N 5 Synthesis of -(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine-5,7-diamine:

[0446] A mixture of tert-butyl 6-((tert-butyloxycarbonyl)(3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (923 mg, 1.62 mmol) in dichloromethane (3 mL) and 2,2,2-trifluoroacetic acid (1 mL) was stirred at room temperature for 2 hours. LCMS confirmed the reaction was complete. The resulting mixture was concentrated under reduced pressure to give a crude product (2 g), which was used directly in the next step without further purification. LC-MS m / z: 371 [M+H] + ;

[0447] 5) Synthesis of 1-(tert-butyloxycarbonyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate:

[0448] To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (514 mg, 2.97 mmol) in dichloromethane (2 mL) was added triethylamine (1.1 g, 10.8 mmol) and bis(trichloromethyl) carbonate (440 mg, 1.485 mmol) at 0°C, and the mixture was stirred at 0°C for 0.5 hours. 7 -(2-azaspiro[3.3]heptane-6-yl)-N 5 1-(Tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine-5,7-diamine (1 g, 2.7 mmol) in dichloromethane (2 mL) was added to the above reaction mixture. The resulting mixture was stirred for 16 hours. LCMS confirmed the reaction was complete. The resulting mixture was quenched by adding saturated aqueous ammonium chloride (10 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic phase was washed with brine (1 × 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography to give 1-(tert-butoxycarbonyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (188 mg, yield: 12.3%), LC-MS m / z: 570 [M+H] + ;

[0449] 6) Synthesis of 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylic acid azetidin-3-yl ester:

[0450] A mixed solution of 1-(tert-butyloxycarbonyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (188 mg, 0.33 mmol) in 2,2,2-trifluoroacetic acid (0.4 mL) and dichloromethane (1.2 mL) was stirred at room temperature for 2 hours. The residue was detected by LCMS to be complete. The crude product (308 mg) of the obtained mixed reaction solution was concentrated under reduced pressure and used directly in the next step without further purification (308 mg), LC-MS m / z: 470 [M+H] + ;

[0451] 7) Synthesis of 1-(2-fluoroacryloyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate:

[0452] A solution of 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylic acid azetidin-3-yl ester (100 mg, 0.213 mmol), 2-fluoroacrylic acid (29 mg, 0.32 mmol), N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (119 mg, 0.42 mmol) and N-methylimidazole (70 mg, 0.852 mmol) in N,N-dimethylformamide (2 mL) was stirred at room temperature for 2 hours. The reaction was complete by LCMS. The mixed reaction solution was purified by preparative high performance liquid chromatography to give 1-(2-fluoroacryloyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (5 mg, yield: 4.3%), LC-MS m / z: 542 [M+H] + ;

[0453] 1 H NMR (400MHz, MeOD-d4): δ7.88 (s, 1H), 5.61 (d, J=3.5Hz, 1H), 5.49 (d, J=3.5Hz, 1H), 5.38 (s, 1H), 5.21 ( dd, J=16.1, 3.5Hz, 1H), 5.16 (d, J=4.1Hz, 1H), 4.73 (s, 1H), 4.34 (t, J=29.2Hz, 5H), 4.00 (d, J=11.3Hz, 5H), 3.60 (t, J=10.6Hz, 2H), 3.09 (dd, J=15.7, 9.2Hz, 1H), 2.84-2.71 (m, 2H), 2.52 -2.41 (m, 2H), 2.02 (d, J = 10.7Hz, 2H), 1.64 (d, J = 9.0Hz, 2H), 1.30 (d, J = 6.9Hz, 6H).

[0454] Example 6. Synthesis of (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate (Compound 6):

[0455] A solution of 6-((3-isopropyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyrazolo[1,5-a]pyrimidin-7-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate azetidin-3-yl ester (100 mg, 0.113 mmol), (E)-4-(dimethylamino)but-2-enoic acid (53 mg, 0.32 mmol), N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (119 mg, 0.426 mmol) and N-methylimidazole (70 mg, 0.852 mmol) in N,N-dimethylformamide (2 mL) was stirred at room temperature for 2 hours. LCMS confirmed the reaction was complete. The mixed reaction solution was purified by preparative HPLC to give (5 mg, yield: 4.1%), LC-MS m / z: 581 [M+H]+;

[0456] 1H NMR (400MHz, MeOD-d4): δ7.60 (s, 1H), 6.85-6.71 (m, 1H), 6.17 (d, J=15.6Hz, 1 H), 5.15 (d, J=7.8Hz, 2H), 4.58 (d, J=11.6Hz, 2H), 4.37-3.89 (m, 12H), 3.56 (t , J=10.7Hz, 3H), 3.19-2.98(m, 3H), 2.83-2.68(m, 2H), 2.29(d, J=16.5Hz, 8H) , 2.02 (d, J = 12.4Hz, 2H), 1.53 (td, J = 15.3, 4.2Hz, 2H), 1.28 (d, J = 6.9Hz, 6H).

[0457] Example 7. Synthesis of (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 7)

[0458] 1) Synthesis of (R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0459] To a solution of (R)-benzyl 3-hydroxypyrrolidine-1-carboxylate (470 mg, 2.12 mmol) and triethylamine (430 mg, 4.25 mmol) in dichloromethane (2.5 mL) was added bis(trichloromethyl) carbonate (126 mg, 0.42 mmol) in portions at 0°C. The resulting mixed reaction solution was stirred at 0°C for 30 minutes. 5-Chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (250 mg, 0.85 mmol) was then added in portions at 0°C. The resulting mixed reaction solution was stirred at room temperature for 2.5 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH3·H2O = 50-70% elution) to give (R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (443 mg, yield: 96.0%), LC-MS m / z: 541 [M+H] + ;

[0460] 2) Synthesis of tert-butyl (3R, 4R)-4-(((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate

[0461] A solution of (R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (300 mg, 0.56 mmol), tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate (192 mg, 0.83 mmol), (SP-4-1)-[1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(2-methylpyridine)palladium (93 mg, 0.11 mmol) and cesium carbonate (543 mg, 1.66 mmol) in 1,4-hexacyclopentane (5 mL) was heated at 100° C. and stirred overnight under nitrogen protection. After cooling, the mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% formic acid = 60-80% elution) to give (3R,4R)-4-(((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (85 mg, yield: 21%), LC-MS m / z: 735 [M+H]. + ;

[0462] 3) Synthesis of tert-butyl (3R, 4R)-3-hydroxy-4-(((3-isopropyl-7-((1-((((((R)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)piperidine-1-carboxylate

[0463] A solution of tert-butyl (3R,4R)-4-(((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (371 mg, 0.50 mmol) and palladium on carbon (185 mg) in 2,2,2-trifluoroethanol (4 mL) was heated at 50° C. under a hydrogen atmosphere and stirred for 16 hours. After cooling, the resulting mixed reaction solution was dissolved in dichloromethane and filtered. The collected filtrate was concentrated under reduced pressure to give a crude product, which was used directly in the next step without further purification. LC-MS m / z: 601 [M+H] + ;

[0464] 4) Synthesis of tert-butyl (3R, 4R)-4-(((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate

[0465] A solution of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride (86 mg, 0.52 mmol), triethylamine (177 mg, 1.75 mmol) and 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (200 mg, 0.52 mmol) in dichloromethane (3 mL) was stirred at room temperature for 10 minutes. Then, tert-butyl (3R,4R)-3-hydroxy-4-(((3-isopropyl-7-((1-((((((R)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)piperidine-1-carboxylate (210 mg, 0.35 mmol) was added at room temperature. The resulting mixed reaction solution was stirred at room temperature for 1 hour. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% The reaction mixture was purified by eluting with NH4HCO3 in pure water (eluted with 60-80% NH4HCO3) to give (3R,4R)-4-(((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (160 mg, yield: 64%), LC-MS m / z: 712 [M+H]. + ;

[0466] 5) Synthesis of (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0467] A solution of tert-butyl (3R,4R)-4-(((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (160 mg, 0.22 mmol) in dichloromethane (3 mL) and 2,2,2-trifluoroacetic acid (1 mL) was stirred at room temperature for 3 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile: pure water containing 0.1% NH4HCO3 = 30-70% elution) to give the product (30 mg, yield: 22%). LC-MS m / z: 612 [M+H] + ;

[0468] 1 H NMR (400MHz, MeOD): δ7.86 (s, 1H), 6.81-6.73 (m, 2H), 5.70 (s, 1H), 5.34-5.26 (m , 1H), 4.17(s, 2H), 3.98-3.87(m, 4H), 3.83-3.67(m, 5H), 3.55-3.37(m, 4H), 3.06 -3.02(m, 4H), 2.91(s, 6H), 2.81(t, J=8.0Hz, 1H), 2.31-2.23(m, 1H), 2.20-2.13( m, 2H), 2.08 (s, 2H), 1.95-1.91 (m, 1H), 1.68-1.63 (m, 3H), 1.29 (d, J=4.0Hz, 6H).

[0469] Example 8. Synthesis of (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 8)

[0470] 1) Synthesis of 5-chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine

[0471] To a solution of tert-butyl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (500 mg, 1.27 mmol) in dichloromethane (6 mL) was added 2,2,2-trifluoroacetic acid (2 mL) dropwise. The resulting mixed reaction solution was stirred at room temperature for 2 hours. The resulting mixed reaction solution was concentrated under reduced pressure to obtain a crude product, which was used directly in the next step without further purification. LC-MS m / z: 294 [M+H] + ;

[0472] 2) Synthesis of (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0473] To a solution of (S)-benzyl 3-hydroxypyrrolidine-1-carboxylate (302 mg, 1.37 mmol) and triethylamine (276 mg, 2.74 mmol) in tetrahydrofuran (15 mL) was added bis(trichloromethyl) carbonate (252 mg, 0.86 mmol) in portions at 0°C. The resulting mixed reaction solution was stirred at 0°C for 30 minutes. 5-Chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (500 mg, 1.71 mmol) was then added in portions at room temperature. The resulting mixed reaction solution was stirred at room temperature overnight. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH3·H2O = 5-95% elution) to give (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (350 mg, yield: 47.4%), LC-MS m / z: 541 [M+H] + ;

[0474] 3) Synthesis of tert-butyl (3R, 4R)-4-(((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate

[0475] A solution of (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (350 mg, 0.65 mmol), tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate (179 mg, 0.78 mmol), (SP-4-1)-[1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(2-methylpyridine)palladium (59 mg, 0.07 mmol), and cesium carbonate (634 mg, 1.95 mmol) in dioxane (4 mL) was heated at 100° C. and stirred overnight. After cooling, the resulting reaction mixture was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH3·H2O = 5-95% elution) to give tert-butyl (3R,4R)-4-(((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (180 mg, yield: 38%), LC-MS m / z: 735 [M+H]. + ;

[0476] 4) Synthesis of tert-butyl (3R, 4R)-3-hydroxy-4-(((3-isopropyl-7-((1-((((((S)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)piperidine-1-carboxylate

[0477] A solution of (3R,4R)-tert-butyl 4-(((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (180 mg, 0.25 mmol) and palladium on carbon (60 mg) in 2,2,2-trifluoroethanol (5 mL) was stirred under a hydrogen atmosphere for 4 hours. The mixed reaction solution was filtered, and the filtrate was collected and concentrated under reduced pressure to give a crude product, which was used directly in the next step without further purification. LC-MS: m / z: 601 [M+H] + ;

[0478] 5) Synthesis of tert-butyl (3R, 4R)-4-(((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate

[0479] A mixture of tert-butyl (3R,4R)-3-hydroxy-4-(((3-isopropyl-7-((1-((((((S)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)piperidine-1-carboxylate (130 mg, 0.22 mmol), (E)-4-(dimethylamino)but-2-enoic acid (34 mg, 0.26 mmol), 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (126 mg, 0.33 mmol) and triethylamine (67 mg, 0.66 mmol) was added. 1) in dichloromethane (2.5 mL) was stirred at room temperature overnight. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile: pure water containing 0.1% NH3H2O ​​= 5-95% elution) to give (3R, 4R)-4-(((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (60 mg, yield: 39%), LC-MS m / z: 712 [M+H] + ;

[0480] 6) Synthesis of (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0481] To a solution of tert-butyl (3R,4R)-4-(((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate (60 mg, 0.084 mmol) in dichloromethane (1.2 mmol) was added dropwise 2,2,2-trifluoroacetic acid (0.4 mL). The resulting mixed reaction solution was stirred at room temperature. The reaction mixture was concentrated under reduced pressure for 2 hours. The residue was purified by C18 column chromatography (acetonitrile: pure water containing 0.1% NH3·H2O = 5-95% elution) to give (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((((3R,4R)-3-hydroxypiperidin-4-yl)methyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (8.1 mg, yield: 31.8%), LC-MS m / z: 612 [M+H]. + ;

[0482] 1 H NMR (400MHz, MeOD-d4): δ7.77 (s, 1H), 6.78-6.73 (m, 2H), 5.55 (s, 1H), 5.29 (d, J=16.0Hz, 1H), 4.13 (s, 2H), 3.95 (t, J=5.6Hz, 2H), 3.91-3.78 (m, 3H), 3.75-3.71 (m, 2H), 3.67-3.48 (m, 3H), 3.45-3.37 (m, 2H), 3.10-3.03 (m, 3H), 2.99-2.96 (m, 1H), 2.90 (s, 6H), 2.81 (t, J=11.2Hz, 1H), 2.30-2.17 (m, 2 H), 2.09-2.03(m, 3H), 1.84(s, 1H), 1.72-1.62(m, 3H), 1.29(d, J=2.8Hz, 3H), 1.27(d, J=2.8Hz, 3H).

[0483] Example 9. Synthesis of 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 9)

[0484] 1) Synthesis of tert-butyl 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0485] To a solution of tert-butyl 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (1.0 g, 1.85 mmol), triethylamine (56 mg, 0.56 mmol), and di-tert-butyl dicarbonate (604 mg, 2.77 mmol) in tetrahydrofuran (10 mL) was added 4-diaminopyridine (22 mg, 0.185 mmol). The resulting mixed reaction solution was stirred at room temperature for 1 hour. The mixed reaction solution was diluted with water (20 mL) and extracted with 50 mL (3 × 50 mL). The combined organic phase was washed with saturated brine (1 × 50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluted with ethyl acetate:petroleum ether = 0-30%) to give tert-butyl 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (0.92 g, yield: 78%), LC-MS m / z: 641 [M+H]. + ;

[0486] 2) Synthesis of 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-(((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0487] To a solution of tert-butyl 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (1.0 g, 1.56 mmol), (SP-4-1)-[1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichloro(2-methylpyridine)palladium (0.13 mg, 0.16 mmol), and cesium carbonate (0.51 g, 1.56 mmol) in 1,4-dioxane (10 mL) at 0°C under nitrogen was added (S)-6,6-dimethylpiperidin-3-amine (0.24 g, 1.87 mmol). The resulting mixed reaction mixture was heated at 110° C. and stirred for 16 hours under nitrogen protection. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×30 mL). The combined organic phase was washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether = 15-50% elution) to give 4-((tert-butoxycarbonyl)(5-(((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester (0.23 g, yield: 21%), LC-MS m / z 733 [M+H] + ;

[0488] 3) Synthesis of tert-butyl (5S)-5-((7-((1-((1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate

[0489] To a solution of 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-(((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (0.4 g, 0.55 mmol), 4-dimethylaminopyridine (6.7 mg, 0.06 mmol), and triethylamine (0.17 g, 1.65 mmol) in tetrahydrofuran (4 mL) was added portionwise di-tert-butyl dicarbonate (3.47 g, 86.82 mmol) at 0°C. The resulting reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with water at 0°C and extracted with ethyl acetate (1×30 mL). The combined organic phases were washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:dichloromethane = 0-10% elution) to give (5S)-5-((7-((1-((1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylic acid tert-butyl ester (0.16 g, yield: 35%), LC-MS m / z: 833 [M+H]. + ;

[0490] 4) Synthesis of tert-butyl (5S)-5-((7-((tert-butoxycarbonyl)(1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate

[0491] A solution of tert-butyl (5S)-5-((7-((1-((1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)(tert-butoxycarbonyl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate (0.26 g, 0.312 mmol) and palladium on carbon (26 mg, 10% content) in ethyl acetate (2 mL) was heated at 50° C. under a hydrogen atmosphere (1 atm) and stirred for 4 hours. The mixed reaction solution was filtered, and the filter cake was washed with ethyl acetate (3×20 mL). The filtrate was collected and concentrated under reduced pressure to give tert-butyl (5S)-5-((7-(tert-butoxycarbonyl)(1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate (0.15 g, yield: 68.8%), LC-MS m / z: 699 [M+H] + ;

[0492] 5) Synthesis of tert-butyl (5S)-5-((7-((tert-butoxycarbonyl)(1-((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate

[0493] A solution of (E)-4-(dimethylamino)but-2-enoic acid (33 mg, 0.258 mmol), 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.196 g, 0.515 mmol), and N,N-diisopropylethylamine (0.132 g, 1.03 mmol) in N,N-dimethylformamide (2 mL) was stirred at room temperature for 0.5 hour. Then, tert-butyl (5S)-5-((7-((tert-butoxycarbonyl)(1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate (0.15 g, 0.215 mmol) was added to the reaction mixture, and the resulting mixture was stirred at room temperature for 2 hours. The resulting mixed reaction solution was diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic phase was washed with saturated brine (1×10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:dichloromethane = 0-10% elution) to give (5S)-5-((7-((tert-butyloxycarbonyl)(1-((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylic acid tert-butyl ester (0.05 g, yield: 28.7%), LC-MS m / z: 810 [M+H]. + ;

[0494] 6) Synthesis of 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0495] A solution of tert-butyl (5S)-5-((7-(tert-butoxycarbonyl)(1-((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)amino)-2,2-dimethylpiperidine-1-carboxylate (50 mg, 0.0617 mmol) in 2,2,2-trifluoroacetic acid (0.5 mL) and dichloromethane (2 mL) was stirred at room temperature for 1 hour. The mixed reaction solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:dichloromethane = 0-10% elution) to give 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-((((S)-6,6-dimethylpiperidin-3-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (20 mg, yield: 53.1%), LC-MS m / z: 610 [M+H] + ;

[0496] 1 H NMR (400MHz, MeOH-d4): δ7.61 (s, 1H), 6.90-6.76 (m, 1H), 6.45 (dd, J=27.2, 15.6Hz, 1H), 5.33 (s, 1H), 5.27 ( d, J=18.4Hz, 1H), 4.07 (s, 2H), 3.96 (s, 1H), 3.90-3.79 (m, 1H), 3.70 (dt, J=13.2, 12.0Hz, 4H), 3.22 (s, 1H), 3 .14 ​​(dd, J=19.6, 8.8Hz, 5H), 2.80-2.73 (m, 1H), 2.27 (s, 6H), 2.22 (s, 1H), 2.15 (s, 1H), 2.08 (d, J=14.0Hz, 2H ), 1.97 (d, J = 10.4Hz, 1H), 1.70 (d, J = 12.0Hz, 2H), 1.58 (s, 3H), 1.28 (d, J = 6.8Hz, 6H), 1.22 (d, J = 6.0Hz, 6H).

[0497] Example 10. Synthesis of (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo-11,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 10)

[0498] 1) Synthesis of tert-butyl (R)-3-((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0499] A solution of (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (200 mg, 0.37 mmol), (R)-tert-butyl 3-hydroxypiperidine-1-carboxylate (186 mg, 0.93 mmol), Pd2(dba)3 (34 mg, 0.037 mmol), (R)-(-)-1-[(S)-2-(dicyclohexylphosphino)ferrocene]ethyldi-tert-butylphosphine (42 mg, 0.076 mmol), and cesium carbonate (362 mg, 1.11 mmol) in toluene (3 mL) was heated in a microwave at 140°C for 2 hours under nitrogen protection. After cooling, the resulting reaction mixture was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% formic acid = 5-95% elution) to give (R)-tert-butyl 3-((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (160 mg, yield: 61.3%), LC-MS m / z: 706 [M+H]. + ;

[0500] 2) Synthesis of tert-butyl (R)-3-((7-((tert-butoxycarbonyl)(1-(((((S)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0501] A solution of (R)-tert-butyl 3-((7-((1-((((S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (160 mg, 22.70 mmol) and palladium on carbon (30 mg) in 2,2,2-trifluoroethanol (2 mL) was stirred at room temperature for 4 hours under a hydrogen atmosphere. The resulting mixed reaction solution was filtered and the filter cake was washed with 2,2,2-trifluoroethanol (2×3 mL). The crude product obtained by concentrating the mixed reaction solution under reduced pressure was used directly in the next step without further purification. LC-MS m / z: 572 [M+H] + ;

[0502] 3) Synthesis of tert-butyl (R)-3-((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0503] (R)-tert-butyl 3-((7-((tert-butoxycarbonyl)(1-(((((S)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (100 mg, 0.175 mmol), (E)-4-(dimethylamino)but-2-enoic acid (44 mg, 0.265 mmol) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (43 mg, 0.174 mmol) were dissolved in dichloromethane ( 4 mL) solution was stirred at room temperature for 8 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile: pure water containing 0.1% formic acid = 5-95% elution) to give (R)-3-((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylic acid tert-butyl ester (60 mg, yield: 50.1%), LC-MS m / z: 683 [M+H] + ;

[0504] 4) Synthesis of (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0505] To a solution of (R)-tert-butyl 3-((7-((1-(((((S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (60 mg, 0.088 mmol) in dichloromethane (1.2 mL) was added dropwise 2,2,2-trifluoroacetic acid (0.4 mL) at room temperature. The resulting mixture was stirred at room temperature for 4 hours. The residue was purified by C18 column chromatography (acetonitrile:pure water containing 0.1% formic acid = 5-95% elution) to give (S)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (12 mg, yield: 23.4%), LC-MS m / z: 583 [M+H] + ;

[0506] 1 H NMR (400MHz, MeOD-d4): δ7.77(s, 1H), 6.83-6.77(m, 1H), 6.67-6.57(m, 1H), 5.64(s, 1H) ), 5.50 (s, 1H), 5.29 (d, J = 16.8Hz, 1H), 4.10 (s, 2H), 3.92-3.70 (m, 5H), 3.61-3.49 (m, 4 H), 3.43 (d, J=12.8Hz, 1H), 3.29 (s, 1H), 3.17-3.06 (m, 4H), 2.62 (s, 6H), 2.29-2.24 (m, 1H), 2.16-1.97(m, 6H), 1.86-1.83(m, 1H), 1.61(d, J=8.4Hz, 2H), 1.32(d, J=6.8Hz, 6H).

[0507] Example 11. Synthesis of 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 11)

[0508] 1) Synthesis of tert-butyl (3R)-3-((7-((1-(((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0509] A solution of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride (56 mg, 0.34 mmol), triethylamine (113 mg, 1.12 mmol), and 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (128 mg, 0.34 mmol) in dichloromethane (3 mL) was stirred at room temperature for 10 minutes. Then, tert-butyl (3R)-3-((3-isopropyl-7-((1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (128 mg, 0.22 mmol) was added to the reaction mixture. The resulting reaction mixture was stirred at room temperature for 1 hour. The resulting reaction mixture was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH4HCO3 = 50-70% elution) to give tert-butyl (3R)-3-((7-((1-(((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (79 mg, yield: 52%), LC-MS m / z: 683 [M+H]. + ;

[0510] 2) Synthesis of 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0511] A solution of tert-butyl (3R)-3-((7-((1-(((1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (79 mg, 0.12 mmol) in dichloromethane (3 mL) and 2,2,2-trifluoroacetic acid (1 mL) was stirred at room temperature for 3 hours. The resulting reaction mixture was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH4HCO3 = 30-70% elution) to give 1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (20 mg, yield: 22%), LC-MS m / z: 583 [M+H] + ;

[0512] 1H NMR (400MHz, MeOD): δ7.74 (s, 1H), 6.88-6.78 (m, 1H), 6.47-6.43 (m, 1H), 5. 59(s, 1H), 5.32-5.18(m, 2H), 4.09(s, 2H), 3.89-3.79(m, 1H), 3.79-3.47(m , 5H), 3.24-3.18(m, 3H), 3.10-3.06(m, 3H), 2.89-2.85(m, 3H), 2.27(s, 6H) , 2.15 (s, 1H), 2.07 (s, 3H), 1.89 (s, 2H), 1.60 (s, 3H), 1.31 (d, J=8.0Hz, 6H).

[0513] Example 12. Synthesis of (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 12)

[0514] 1) Synthesis of (S)-(4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester

[0515] To a solution of (S)-3-hydroxypyrrolidine-1-carboxylic acid benzyl ester (641 mg, 2.90 mmol) and triethylamine (879 mg, 8.70 mmol) in dichloromethane (10 mL) was added triphosgene (345 mg, 1.16 mmol) in portions at 0°C. The resulting mixed reaction solution was stirred for 1 hour. 5-Chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (850 mg, 2.90 mmol) was then added at room temperature. The resulting mixed reaction solution was stirred for 1 hour at room temperature. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give (S)-4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester (800 mg, yield: 51.1%), LC-MS m / z: 541 [M+H] + ;

[0516] 2) Synthesis of (S)-4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester

[0517] To a solution of (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl-4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (800 mg, 1.48 mmol) and di-tert-butyl dicarbonate (646 mg, 2.96 mmol) in tetrahydrofuran (8 mL) was added 4-dimethylaminopyridine (90 mg, 0.74 mmol) at room temperature. The resulting mixed reaction solution was heated at 50°C and stirred for 2 hours. After cooling, the mixed reaction solution was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with saturated brine (1 x 30 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (700 mg, yield: 73.8%), LC-MS m / z: 641 [M+H] + ;

[0518] 3) Synthesis of (S)-4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester

[0519] (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (700 mg, 1.09 mmol) and potassium cyclopropyltrifluoroborate (243 mg, 1.64 mmol) were added to a pre-stirred solution of Pd(dppf)Cl2 (80 mg, 0.11 mmol) and cesium carbonate (1069 mg, 3.28 mmol) in 1,4-dioxane (8 mL) in a microwave vial. The reaction vessel was sealed and heated in a microwave at 110°C for 2 hours. The resulting mixture was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with brine (1 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give (S)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (600 mg, yield: 85%), LC-MS m / z: 647 [M+H] + ;

[0520] 4) Synthesis of (S)-4-((tert-butyloxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid pyrrolidin-3-yl ester

[0521] A solution of (S)-4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-((benzyloxy)carbonyl)pyrrolidin-3-yl ester (600 mg, 0.93 mmol) and palladium hydroxide (520 mg, 3.72 mmol) in methanol (6 mL) was stirred at room temperature for 2 hours under hydrogen protection. The mixed reaction liquid was filtered and the filter cake was washed with methanol. The filtrate was collected and concentrated under reduced pressure to give (S)-4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid pyrrolidin-3-yl ester (500 mg, crude product), LC-MS m / z: 513 [M+H] + ;

[0522] 5) Synthesis of (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0523] To a solution of (S)-pyrrolidin-3-yl-4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (100 mg, 0.20 mmol) and (E)-4-(dimethylamino)but-2-enoic acid (30 mg, 0.23 mmol) in acetonitrile (2 mL) was added 1-methylimidazole (110 mg, 0.39 mmol) and N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (220 mg, 0.78 mmol) at room temperature. The resulting mixture was stirred at room temperature for 2 hours. After cooling, the mixture was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (60 mg, yield: 49%), LC-MS m / z: 624 [M+H] + ;

[0524] 6) Synthesis of (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0525] A solution of (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (60 mg, 0.10 mmol) in dichloromethane (2 mL) and 2,2,2-trifluoroacetic acid (0.5 mL) was stirred at room temperature for 2 hours. The resulting reaction mixture was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with saturated brine (1 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give (S)-4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (S,E)-1-(4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl ester (20 mg, yield: 39.7%), LC-MS m / z: 524 [M+H]+ ;

[0526] 1 H NMR (400MHz, MeOD): δ7.83 (s, 1H), 6.85-6.66 (m, 2H), 5.98 (s, 1H), 5.35-5.29 (m, 1H), 4.13 (s, 2H), 3.99-3.62(m, 7H), 3.29-3.08(m, 3H), 2.86(d, J=1.2Hz, 6H), 2.32-2.29(m, 1H), 2.20( m, 1H), 2.11-2.04 (m, 3H), 1.66-1.60 (m, 2H), 1.34 (d, J=6.8Hz, 6H), 1.12-1.00 (m, 4H).

[0527] Example 13. Synthesis of (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 13)

[0528] 1) Synthesis of 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0529] At 0 ° C, bis(trichloromethyl)carbonate (2129 mg, 7.17 mmol) was added in batches to a solution of 3-hydroxyazetidine-1-carboxylic acid benzyl ester (1780 mg, 8.60 mmol) and triethylamine (2172 mg, 21.50 mmol) in dichloromethane (20 mL), and stirred at room temperature for 1 hour. At room temperature, 5-chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (2100 mg, 7.17 mmol) was added in batches to the above mixed reaction solution. The resulting mixed reaction solution was stirred at room temperature for 1 hour. The mixed reaction solution was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phase was washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (pure water containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (2000 mg, yield: 53%), LC-MS m / z: 527 [M+H] + ;

[0530] 2) Synthesis of 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0531] To a solution of 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (2000 mg, 3.80 mmol) and di-tert-butyl dicarbonate (995 mg, 4.56 mmol) in tetrahydrofuran (20 mL) was added 4-dimethylaminopyridine (1392 mg, 11.41 mmol) at room temperature. The resulting mixed reaction solution was heated at 50°C and stirred for 2 hours. After cooling, the resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phase was washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (pure water containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (1200 mg, yield: 50%), LC-MS m / z: 627 [M+H] + ;

[0532] 3) Synthesis of 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0533] 4-((tert-Butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate 1-((benzyloxy)carbonyl)azetidin-3-yl ester (1200 mg, 1.92 mmol) and potassium cyclopropyltrifluoroborate (340 mg, 2.30 mmol) were added to a deoxygenated, stirred solution of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride (140 mg, 0.19 mmol) and cesium carbonate (1875 mg, 5.75 mmol) in 1,4-dioxane (12 mL) and water (3 ml) in a microwave tube. The microwave tube was sealed and heated at 110° C. under microwave conditions with stirring for 2 hours. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 reverse-phase column chromatography (purified water containing 0.1% formic acid: purified water containing 0.1% formic acid = 25%-65% elution) to afford 1-((benzyloxy)carbonyl)azetidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (500 mg, yield: 41%). LC-MS m / z: 633 [M+H]. + ;

[0534] 4) Synthesis of 4-((tert-butyloxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate azetidin-3-yl ester

[0535] A solution of 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-((benzyloxy)carbonyl)azetidin-3-yl ester (500 mg, 0.79 mmol) and palladium carbon (222 mg) in methanol (6 mL) was stirred at room temperature for 2 hours under a hydrogen atmosphere. The mixed reaction liquid was filtered and the filter cake was washed with methanol. The filtrate was collected and concentrated under reduced pressure to give 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid azetidin-3-yl ester (330 mg, yield: 84%), LC-MS m / z: 499 [M+H] + ;

[0536] 5) Synthesis of (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((tert-butyloxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0537] To a solution of 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate azetidin-3-yl ester (110 mg, 0.22 mmol) and (E)-4-(dimethylamino)but-2-enoic acid (34 mg, 0.27 mmol) in acetonitrile (2 mL) at room temperature were added 1-methyl-1H-imidazole (72 mg, 0.88 mmol) and N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (124 mg, 0.44 mmol). The resulting mixed reaction solution was stirred at room temperature for 2 hours. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phase was washed with saturated brine (1×30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (pure water containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((tert-butoxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (60 mg, yield: 44%), LC-MS m / z: 610 [M+H] + ;

[0538] 6) Synthesis of (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0539] A solution of (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((tert-butyloxycarbonyl)(5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (60 mg, 0.10 mmol) in dichloromethane (2 mL) and 2,2,2-trifluoroacetic acid (0.5 mL) was stirred at room temperature for 2 hours. The resulting reaction mixture was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with saturated brine (1 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (pure water containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give (E)-1-(4-(dimethylamino)but-2-enoyl)azetidin-3-yl 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (20 mg, yield: 40%), LC-MS m / z: 510 [M+H]+ ;

[0540] 1 H NMR (400MHz, MeOD): δ8.11 (s, 1H), 6.79-6.72 (m, 1H), 6.51 (d, J=15.2Hz, 1H), 6.05 (s, 1H), 5.22-5.21(m, 1H), 4.72-4.64(m, 1H), 4.45-4.40m, 1H), 4.34-4.16(m, 4H), 4.08-4.06(m, 1 H), 3.96 (d, J=7.2Hz, 2H), 3.29-3.24 (m, 1H), 3.15-3.10 (m, 2H), 2.92 (s, 6H), 2.29-2.20 (m , 1H), 2.05 (d, J=10.8Hz, 2H), 1.78-1.75 (m, 2H), 1.37 (d, J=7.2Hz, 8H), 1.30-1.29 (m, 2H).

[0541] Example 14. Synthesis of 1-(2-fluoroacryloyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 14)

[0542] 1) Synthesis of tert-butyl (3R)-3-((7-(1-(((1-(2-fluoroacryloyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0543] A solution of tert-butyl (3R)-3-((3-isopropyl-7-(1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (140 mg, 0.26 mmol), 2-fluoroacrylic acid (44 mg, 0.49 mmol), 1-methyl-1H-imidazole (80 mg, 0.980 mmol), and N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (137 mg, 0.49 mmol) in N,N-dimethylformamide (3 mL) was stirred at room temperature for 16 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (acetonitrile:purified water containing 0.1% NH4HCO3 = 50-70% elution) to give tert-butyl (3R)-3-((7-(1-(((1-(2-fluoroacryloyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (91.70 mg, yield: 58.1%), LC-MS m / z: 644 [M+H]. + ;

[0544] 2) Synthesis of 1-(2-fluoroacryloyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0545] A solution of tert-butyl (3R)-3-((7-(1-(((1-(2-fluoroacryloyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (80 mg, 0.12 mmol) in dichloromethane (3 mL) and 2,2,2-trifluoroacetic acid (1 mL) was stirred at room temperature for 3 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (acetonitrile:purified water containing 0.1% NH4HCO3 = 30-70% elution) to give 1-(2-fluoroacryloyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (16 mg, yield: 23.6%), LC-MS m / z: 544 [M+H] + ;

[0546] 1H NMR (400MHz, MeOD): δ7.77 (s, 1H), 5.54-5.40 (m, 2H), 5.28-5.23 (m, 2H), 4.10 (s, 2H) , 3.92-3.90 (m, 1H), 3.82 (dd, J=13.4, 5.7Hz, 1H), 3.78-3.68 (m, 3H), 3.63-3.54 (m, 2H ), 3.45-3.41(m, 1H), 3.33(s, 1H), 3.18-3.04(m, 4H), 2.25-2.21(m, 1H), 2.18-2.05(m , 5H), 2.03-1.97 (m, 1H), 1.88-1.81 (m, 1H), 1.63-1.60 (m, 2H), 1.32 (d, J=6.9Hz, 6H).

[0547] Example 15. Synthesis of (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 15)

[0548] 1) Synthesis of tert-butyl (R)-3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0549] A solution of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride (0.087 g, 0.52 mmol), triethylamine (0.177 g, 1.75 mmol) and 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluranium hexafluorophosphate (0.20 g, 0.52 mmol) in dichloromethane (3 mL) was stirred at 0° C. for 10 minutes, and then (R)-3-((3-isopropyl-7-((1-(((((R)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidin -1-carboxylic acid tert-butyl ester (198 mg, 0.35 mmol) was added to the above mixed reaction solution. The obtained mixed reaction solution was stirred at room temperature for 3 hours. The mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile pure water = 5-95% elution) to give (R)-3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylic acid tert-butyl ester (140 mg, yield: 59%), LC-MS m / z: 683 [M+H] + ;

[0550] 2) Synthesis of (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0551] (R)-tert-butyl 3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (140 mg, 0.21 mol) and 2,2,2-trifluoroacetic acid (1 mL) were dissolved in dichloromethane (3 mL). ) solution and stirred at room temperature for 3 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by preparative HPLC to give (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-isopropyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (62 mg, yield: 52%), LC-MS m / z: 583 [M+H] + ;

[0552] 1H NMR (400MHz, MeOD-d4): δ7.77 (s, 1H), 6.77 (s, 1H), 6.72 (t, J=12.0Hz, 1H), 5.65 (s, 1H), 5.50 (s, 1H), 5.29 (d, J=12.0Hz, 1H), 4.10 (s, 2H), 3.95-3.91 (m, 2H), 3.79-3.72 (m, 4H), 3.65-3.4 6(m, 2H), 3.47-3.41(m, 1H), 3.33(s, 1H), 3.18(s, 1H), 3.10-3.06(m, 4H), 2.88(s, 6H), 2.31- 2.22 (m, 1H), 2.21-2.01 (m, 6H), 1.89-1.83 (m, 1H), 1.64-1.58 (m, 2H), 1.32 (d, J=8.0Hz, 6H).

[0553] Example 16. Synthesis of 1-(But-2-ynyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-(but-2-ynyl)pyrrolidin-3-yl ester (Compound 16)

[0554] 1) Synthesis of tert-butyl (3R)-3-((7-(1-(((1-(but-2-ynyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0555] A solution of tert-butyl (3R)-3-((3-isopropyl-7-(1-((pyrrolidin-3-yloxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (180 mg, 0.315 mmol), but-2-ynoic acid (40 mg, 0.48 mmol), 1-methyl-1H-imidazole (111 mg, 1.35 mmol), and N,N,N′,N′-tetramethylchloroformamidine hexafluorophosphate (177 mg, 0.630 mmol) in N,N-dimethylformamide (3 mL) was stirred at room temperature for 16 hours. The resulting reaction mixture was concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (MeCN:H2O (0.1% NH4HCO3) = 50-70% elution) to give (3R)-3-((7-(1-(((1-(but-2-ynyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylic acid tert-butyl ester (91.70 mg, yield: 45.6%), LC-MS m / z: 638 [M+H]+ ;

[0556] 2) Synthesis of 1-(but-2-ynyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-(but-2-ynyl)pyrrolidin-3-yl ester

[0557] A solution of tert-butyl (3R)-3-((7-(1-(((1-(but-2-ynyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (104 mg, 0.163 mmol) in dichloromethane (3 mL) and 2,2,2-trifluoroacetic acid (1 mL) was stirred at room temperature for 3 hours. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 reverse phase column chromatography (CH3CN:H2O (0.1% FA) = 30-70% elution) to give 1-(but-2-ynyl)pyrrolidin-3-yl 4-((3-isopropyl-5-((((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid 1-(but-2-ynyl)pyrrolidin-3-yl ester (35 mg, yield: 40.0%), LC-MS m / z: 538 [M+H] + ;

[0558] 1 H NMR (400MHz, MeOD): δ7.78 (s, 1H), 5.50 (s, 1H), 5.27-5.25 (m, 1H), 4.13-4.10 ( m, 2H), 3.88-3.85 (m, 3H), 3.76-3.72 (m, 3H), 3.65-3.61 (m, 1H), 3.45-3.41 (m, 2H), 3.19-3.13(m, 4H), 2.23-2.18(m, 2H), 2.16-2.14(m, 1H), 2.11(s, 3H), 2.1 0-2.01(m, 4H), 1.88-1.85(m, 1H), 1.66-1.61(m, 2H), 1.33(s, 3H), 1.31(s, 3H).

[0559] Example 17. Synthesis of (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-ethyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (Compound 17)

[0560] 1) Synthesis of tert-butyl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0561] To a solution of 5,7-dichloro-3-ethylpyrazolo[1,5-a]pyrimidine (500 mg, 2.33 mmol) and tert-butyl 4-aminopiperidine-1-carboxylate (560 mg, 2.79 mmol) in isopropanol (7 mL) was added N,N-diisopropylethylamine (900 mg, 6.98 mmol) at room temperature. The resulting mixed reaction solution was heated at 70°C and stirred for 2 hours. After cooling, the mixed reaction solution was diluted with water and extracted with ethyl acetate (3 × 200 mL). The combined organic phases were washed with saturated brine (1 × 50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give tert-butyl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (560 mg, yield: 63.5%), LC-MS m / z: 380 [M+H] + ;

[0562] 2) Synthesis of 5-chloro-3-ethyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine

[0563] To a solution of tert-butyl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (560 mg, 1.48 mmol) in dichloromethane (3 mL) at room temperature was added 2,2,2-trifluoroacetic acid (1 mL) dropwise. The resulting mixed reaction solution was stirred at room temperature for 1 hour. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3 x 200 mL). The combined organic phases were washed with saturated brine (1 x 50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give 5-chloro-3-ethyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (350 mg, yield: 84.9%), LC-MS m / z: 280 [M+H] + ;

[0564] 3) Synthesis of 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0565] To a solution of benzyl 3-hydroxypyrrolidine-1-carboxylate (333 mg, 1.51 mmol) and triethylamine (380 mg, 3.76 mmol) in tetrahydrofuran (2 mL) was added triphosgene (186 mg, 0.63 mmol) in portions at 0°C. The resulting mixed reaction solution was stirred at 0°C for 30 minutes. 5-Chloro-3-ethyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (350 mg, 1.25 mmol) was added to the mixed reaction solution at room temperature. The resulting mixed reaction solution was stirred at room temperature overnight. The resulting mixed reaction solution was concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% NH3·H2O = 5-95% elution) to give 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (200 mg, yield: 30.3%), LC-MS m / z: 527 [M+H] + ;

[0566] 4) Synthesis of tert-butyl (R)-3-((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0567] Tris(dibenzylideneacetone)dipalladium (35 mg, 0.038 mmol) and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocene]ethyldi-tert-butylphosphine (42 mg, 0.076 mmol) were added to a deoxygenated and pre-stirred toluene solution (2 mL) of 1-(benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-ethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (200 mg, 0.380 mmol), tert-butyl (R)-3-hydroxypiperidine-1-carboxylate (92 mg, 0.46 mmol), and cesium carbonate (371 mg, 1.14 mmol). The microwave tube was sealed and heated at 140°C in a microwave for 2 hours. The resulting reaction mixture was diluted with brine / water (10 mL, 1:1) and extracted with diethyl ether (3 x 50 mL). The combined organic phases were washed with brine / water (4×10 mL, 1:1), dried, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile:purified water containing 0.1% formic acid = 25-95% elution) to give (R)-3-((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo(H,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylic acid tert-butyl ester (90 mg, yield: 34.3%), LC-MS m / z: 692 [M+H]. + ;

[0568] 5) Synthesis of tert-butyl (R)-3-((3-ethyl-7-((1-(((((R)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0569] To a solution of (R)-tert-butyl 3-((7-((1-(((((R)-1-((benzyloxy)carbonyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (90 mg, 0.130 mmol) in methanol (5 mL) was added palladium on carbon (28 mg). The resulting mixed reaction solution was stirred at room temperature overnight under a hydrogen atmosphere. The mixed reaction solution was filtered, and the filter cake was washed with methanol (3×20 mL). The filtrate was collected and concentrated under reduced pressure to give the crude product, which was used directly in the next step without further purification. LC-MS m / z: 558 [M+H] + ;

[0570] 6) Synthesis of tert-butyl (R)-3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate

[0571] To a solution of tert-butyl (R)-3-((3-ethyl-7-((1-(((((R)-pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (60 mg, 0.11 mmol) and (E)-4-(dimethylamino)but-2-enoic acid (17 mg, 0.13 mmol) in dichloromethane (2 mL) was added 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (49.1 mg, 0.13 mmol) and N,N-diisopropylethylamine (42 mg, 0.323 mmol) at room temperature. The resulting reaction mixture was stirred at room temperature for 2 min. hours. The mixed reaction solution was diluted with water and extracted with ethyl acetate (3×80 mL). The combined organic phase was washed with saturated brine (1×20 mL), dried over anhydrous sulfuric acid, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give (R)-3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylic acid tert-butyl ester (50 mg, yield: 69.5%), LC-MS m / z: 669 [M+H] + ;

[0572] 7) Synthesis of (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-ethyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0573] To a solution of tert-butyl (R)-3-((7-((1-(((((R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl)oxy)carbonyl)piperidin-4-yl)amino)-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl)oxy)piperidine-1-carboxylate (50 mg, 0.075 mmol) in dichloromethane (1.2 mL) was added dropwise 2,2,2-trifluoroacetic acid (0.3 mL). The resulting mixed reaction solution was stirred at room temperature for 2 hours. The resulting mixed reaction solution was diluted with water and extracted with ethyl acetate (3×30 mL). The combined organic phase was washed with saturated brine (1×10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by C18 column chromatography (acetonitrile containing 0.1% formic acid: pure water containing 0.1% formic acid = 25%-65% elution) to give (R)-1-((E)-4-(dimethylamino)but-2-enoyl)pyrrolidin-3-yl 4-((3-ethyl-5-(((R)-piperidin-3-yl)oxy)pyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (15 mg, yield: 35.3%), LC-MS m / z: 569 [M+H] + ;

[0574] 1 H NMR (400MHz, MeOD-d4): δ7.79 (s, 1H), 6.84-6.72 (m, 2H), 5.54 (s, 1H), 5.34-5.30 ( m, 1H), 4.13-4.11 (m, 2H), 3.99-3.97 (m, 2H), 3.83-3.73 (m, 4H), 3.62-3.53 (m, 2H) , 3.47-3.43(m, 1H), 3.2-3.09(m, 4H), 2.93(s, 6H), 2.69-2.63(m, 2H), 2.32-2.29( m, 1H), 2.20-2.02 (m, 6H), 1.89-1.85 (m, 1H), 1.64-1.62 (m, 2H), 1.29-1.25 (m, 3H).

[0575] Example 18, 4-((5-cyclopropyl-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylic acid-1-(2-fluoroacryloyl)pyrrolidin-3-yl ester or enantiomer (Compounds 18A and B)

[0576] 1) Synthesis of 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0577] To a solution of benzyl 3-hydroxypyrrolidine-1-carboxylate (641 mg, 2.90 mmol) and triethylamine (879 mg, 8.70 mmol) in dichloromethane (10 mL) at 0°C, bis(trichloromethyl)carbonate (345 mg, 1.16 mmol) was added portionwise and stirred at room temperature for 1 hour. 5-Chloro-3-isopropyl-N-(piperidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (850 mg, 2.90 mmol) was added to the reaction mixture at room temperature. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with saturated brine (1 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase chromatography on a C18 column (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (800 mg, yield: 51%), LC-MS m / z: 541 [M+H] + ;

[0578] 2) Synthesis of 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate

[0579] To a solution of 1-(benzyloxy)carbonyl)pyrrolidin-3-yl 4-((5-chloro-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)amino)piperidine-1-carboxylate (800 mg, 1.48 mmol) and di-tert-butyl dicarbonate (646 mg, 2.96 mmol) in tetrahydrofuran (8 mL) was added 4-dimethylaminopyridine (90 mg, 0.74 mmol) at room temperature. The resulting mixed reaction solution was heated at 50°C and stirred for 2 hours. After cooling, the resulting mixture was diluted with water and extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed with saturated brine (1 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase chromatography on a C18 column (acetonitrile containing 0.1% formic acid:purified water containing 0.1% formic acid = 25%-65% elution) to give 1-((benzyloxy)carbonyl)pyrrolidin-3-yl 4-((tert-butoxycarbonyl)(5-chloro-3-isopropylpyrazolo[...

Claims

1. A compound represented by formula (I) or a pharmaceutically acceptable salt, solvate, enantiomer or isotope thereof; in, Any independently selected from a single bond or a double bond; R0 is independently selected from or selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally preferably replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Substitution of alkoxycarboxyl, OH, and CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 or any two R1s and the carbon atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to more unsaturated olefinic bonds and 0 to more heteroatoms; furthermore, the hydrogen on R1 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Substitution of alkoxy, carboxyl, OH, and CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 or any two R2 and the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Substitution of alkoxy, carboxyl, OH, and CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 or any two R3 and the carbon atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to more unsaturated olefinic bonds; further, the hydrogen on R3 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Substitution of alkoxy, carboxyl, OH, and CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 The cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups may be optionally substituted with one or more alkyl radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH, C 1-10 Alkylamino, di(C 1-10 Alkyl)amino, C 1-10 Alkyl, C 1-10 Alkoxy group substitution; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is arbitrarily selected from an integer of 0, 1, 2, 3 and 4.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has the structure of formula (I-1), in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, fused rings, spiro rings or bridged ring structures; further R2 The hydrogen on the atom is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, and CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is arbitrarily selected from an integer of 0, 1, 2, 3 and 4.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has the structure of formula (I-1A), in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、 -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has a structure of formula (I-1B), in, Any independently selected from a single bond or a double bond; X, Y, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has the structure of formula (I-1C), in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; Ring B and Ring C are arbitrarily independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the alicyclic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or It can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 ), -C(R d1 )(R d2 )(R)C(=O)O-, -OC(=O)C(R d1 )(R d2 ), -C(R d1 )(R d2 )(R)C(=O)-, -C(R d1 )(R d2 )(R)C(=S)-, -S(=O)C(R d1 )(R d2 ), - or -C(R d1 )(R d2 )(R)S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to more unsaturated olefinic bonds and 0 to more heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to more Substitution with a group selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is arbitrarily selected from an integer of 0, 1, 2, 3 and 4.

4. A compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has a structure of formula (I-1D): in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring A is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 or more unsaturated olefinic bonds; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two Each R1 and the carbon atom connected to it on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to more unsaturated olefinic bonds and 0 to more heteroatoms; furthermore, the hydrogen on R1 is optionally substituted with 1 to more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has the structure of formula (I-1E): in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring B and Ring C are arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B or Ring C is non-existent, R1 or R3 can be non-existent or can also be directly connected to L2 or L3; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R2 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally substituted with one or more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2- 10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R3 and the carbon atoms connected to them on the ring together form a 3-18-membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; further, the hydrogen on R3 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and Saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the carbon to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is arbitrarily selected from an integer of 0, 1, 2, 3 and 4.

5. The compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has the structure of formula (II): in, Any independently selected from a single bond or a double bond; X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily and independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, A heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5.

6. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has the structure of formula (IIA): in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 or any two R1s and the carbon atoms to which they are connected on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can be Contains 0 to more unsaturated olefinic bonds and 0 to more heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; Preferably, the compound or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has a structure of formula (IIB), in, Any independently selected from a single bond or a double bond; X, X1, X2, X3, X4, X5 and X6 are arbitrarily independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; Preferably, the compound or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has a structure of formula (IIC), in, X is arbitrarily and independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 The cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyl ... Multiple substitutions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has the structure of formula (IID): in, X is arbitrarily and independently selected from N, CR; X7 is independently selected from -C(R d1 )(R d2 )-, -C(R d1 )=C(R d2 )-, alkynyl, -OC(R d1 )(R d2 )-, -C(R d1 )(R d2 )O-, -C(=O)N(R d3 )-, -N(R d3 )-, -C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )-, -S(=O)2N(R d3 )-, -N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )O-, -C(R d1 )(R d2 )C(=O)N(R d3 )-, -C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-, -C(R d1 )(R d2 )C(=NR d3 )-, -C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-, -C(R d1 )(R d2 )S(=O)2N(R d3 )-, -N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)O-、-OC(=O)C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(=O)-、-C(R d1 )(R d2 )C(=S)-、-S(=O)C(R d1 )(R d2 )-or-C(R d1 )(R d2 )S(=O)2-; and the hydrogen on X7 is preferably optionally substituted by 1 to more R3; L, L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-, -OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further Q is preferably substituted with 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has the structure of formula (IIE): in, X is arbitrarily and independently selected from N, CR; L and L1 are each independently selected from -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, Alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbuteneamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; R5, R6 and R7 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2- 10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the hydrogen on R5, R6 and R7 is preferably optionally replaced by 1 to more selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1- The 6-alkoxy group is optionally further substituted with 1 to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 or any two of R5, R6 and R7 can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which they are attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl are optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; Preferably, the compound or its pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof has the structure of formula (IIF): in, X is arbitrarily and independently selected from N, CR; L and L1 are each independently selected from -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 alkyl Oxygen, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; R5, R6 and R7 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2- 10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the hydrogen on R5, R6 and R7 is preferably optionally replaced by 1 to more selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1- The 6-alkoxy group is optionally further substituted with 1 to more substituted ions selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 or any two of R5, R6 and R7 can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which they are attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl are optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; t is an integer arbitrarily selected from 0, 1, 2, 3 and 4; 7. The compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt, solvate, hydrate, isotope-substituted product or isomer thereof, which has a structure of formula (IIIA): in, Any independently selected from a single bond or a double bond; X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily and independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R1 and the carbon atoms connected to the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic The alicyclic, heterocyclic, cyclic, spirocyclic or bridged ring structure may contain 0 to more unsaturated olefinic bonds and 0 to more heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to more substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; Preferably, it has the structure of formula (IIIB): in, Any independently selected from a single bond or a double bond; X, X0, X1, X2, X3, X4, X5 and X6 are arbitrarily and independently selected from N, CR; Ring B is arbitrarily and independently selected from non-existent, single bond or monocyclic or polycyclic structure of 3 to 18 carbon atoms, and the monocyclic or polycyclic structure can be arbitrarily selected from aromatic ring, heteroaromatic ring, aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure; and the aliphatic ring, heterocyclic ring, cyclic ring, spirocyclic ring or bridged ring structure can contain 0 to more unsaturated olefinic bonds; and when Ring B is non-existent, R3 can be non-existent or can also be directly connected to L2; L1 and L2 are each independently selected from the group consisting of absence, a single bond, -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-、-N(R d3 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-, -SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; R0 is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkoxy or -L3-Q; and the hydrogen on R0 is optionally replaced by 1 to more selected from H, deuterium, halogen, C 1- 10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Substituents of alkoxyamino, OCH3, carboxyl, OH, and CN are further substituted; L3 is independently selected from absence, a single bond or -C(R d1 )(R d2 )-、-C(R d1 )=C(R d2 )-, acetylenic bond, -OC(R d1 )(R d2 )-、-C(R d1 )(R d2 )O-、-C(=O)N(R d3 )-、-C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )-、-S(=O)2N(R d3 )-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)-, -C(R d1 )(R d2 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )O-、-C(R d1 )(R d2 )C(=O)N(R d3 )-、-C(R d1 )(R d2 )C(R d1 )(R d2 )N(R d3 )-、-C(R d1 )(R d2 )C(=NR d3 )-、-C(R d1 )(R d2 )N(R d3 )C(R d1 )(R d2 )-、-C(R d1 )(R d2 )S(=O)2N(R d3 )-、-N(R d3 )C(R d1 )(R d2 )-、-OC(R d1 )(R d2 )-、-SC(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)O-, -OC(=O)C(R d1 )(R d2 )-, -C(R d1 )(R d2 )C(=O)-, -C(R d1 )(R d2 )C(=S)-, -S(=O)C(R d1 )(R d2 )- or -C(R d1 )(R d2 )S(=O)2-; Q is arbitrarily and independently selected from a monocyclic or polycyclic structure of 3 to 18 carbon atoms, wherein the monocyclic or polycyclic structure may be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an alicyclic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the alicyclic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure may contain 0 to more unsaturated olefinic bonds; further, Q is preferably substituted by 1 to more R1 substituents; Each R may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; and the hydrogen on R is preferably 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R1 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, -COOH, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, dialkylphosphinoyl, alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl-substituted carboxyl or carboxyl substitute; or any two R1 together with the carbon atoms connected to them on the ring form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spirocyclic rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; further, the hydrogen on R1 is optionally substituted with 1 to multiple substituents selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN; Each R2 may be the same or different and is independently selected from hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, dialkylphosphinoyl, alkylsulfonyl, -COOH, acrylamide, N,N-dimethylbutenamide, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3- 10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 alkyl substituted carboxyl or carboxyl substitute; or any two R2 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, wherein the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; further, the hydrogen on R2 is optionally replaced by 1 to more selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4- 10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy; Each R3 may be the same or different and is independently selected from absence, hydrogen, deuterium, halogen, -CN, -OH, -SH and -NH2, CH=O, dialkylphosphinoyl, alkylsulfonyl, acrylamide, N,N-dimethylbutenamide, -COOH or selected from C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Alkoxy, C 2-10 Heteroalkyl, C 3-10 Saturated or partially saturated cycloalkyl, aryl, heteroaryl, C 3-10 Saturated or partially saturated heterocyclic group, C 3-10 Cycloalkyl or C 3-10 Heterocycloalkyl substituted C 1-10 Alkyl, C 3-10 Cycloalkyl substituted C 2-10 Heteroalkyl, C 3-10 Heterocyclic group, C 1-10 Alkyl substituted carboxyl or carboxyl substitute; or any two R3 and the atoms connected to them on the ring together form a 3-18 membered monocyclic or polycyclic structure, the monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures; and the aliphatic rings, heterocyclic rings, cyclic rings, spiro rings or bridged ring structures can contain 0 to multiple unsaturated olefinic bonds; furthermore, the hydrogen on R3 is optionally replaced by 1 to multiple selected from H, deuterium, halogen, amino, OCH3, carboxyl, OH, CN, C 1-10 Alkyl, C 3-10 Cycloalkyl, C 4-10 Heterocyclic group, C 2-10 Alkenyl, C 2-10 Alkynyl or C 1-10 Substitution of alkoxy groups; Every R d1 , R d2 and R d3 may be the same or different and are independently selected from hydrogen, deuterium, halogen, cyano, amino, hydroxyl, C 1-10 Alkyl, C 2-10 Alkenyl, C 2-10 Alkynyl, C 1-10 Alkylamino, N,N-di(C 1-10 Alkyl)amino, C 1-10 Alkyloxy, C 1-10 Alkyl acyl, C 1-10 Alkyloxy, C 1-10 Alkylsulfonyl, C 1-10 Alkylsulfinyl, C 3-10 Cycloalkylamino, C3-10 heterocycloalkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 Cycloalkylsulfinyl, aryl, heteroaryl; and the alkyl, alkenyl, alkynyl, aryl, saturated or partially saturated cycloalkyl, heterocycloalkyl is optionally substituted by 1 to more substituted alkyl radicals selected from hydrogen, deuterium, halogen, -CN, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 alkyl)2, oxy, and saturated or partially saturated C 3-6 Cycloalkyl substituted, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further substituted with one to more radicals selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C 3-6 Cycloalkyl radical substitution; or any two R d1 , R d2 or R d3 It can form a 3-18 membered monocyclic or polycyclic structure together with the atoms to which it is attached, wherein the monocyclic or polycyclic structure can be arbitrarily selected from an aromatic ring, a heteroaromatic ring, an aliphatic ring, a heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure; and the aliphatic ring, heterocyclic ring, a cyclic ring, a spirocyclic ring or a bridged ring structure can contain 0 to multiple unsaturated olefinic bonds and 0 to multiple heteroatoms; wherein the cycloalkyl, heterocycloalkyl, aryl, heteroaryl group is optionally substituted by 1 to multiple groups selected from hydrogen, deuterium, halogen, oxo, CN, CF3, OH, OCH3, OCH2CH3; The hetero represents an atom or group independently selected from O, N, S, S=O, S(=O)2, P and isotopes thereof; The halogen is arbitrarily and independently selected from F, Cl, Br, I and isotopes thereof; m is an integer arbitrarily selected from 0, 1, 2, 3 and 4; n is an integer arbitrarily selected from 0, 1, 2, 3, 4 and 5; Preferably, it has the structure of formula (IV): wherein X is selected from N or CH; R is selected from C 1-6 Alkyl or C 3-8 Cycloalkyl; R0 is selected from C 1-6 Alkyl, C 3-8 Cycloalkyl, halogenated C 1-6 Alkoxy, 5-10 membered heterocyclic, 5-10 membered heteroaryl, C 1-6 Alkoxy-5-10 membered heteroaryl; L3 is selected from NH, O, -CH2NH-; Not present or selected from C 1-6 Alkyl, C 3-8 Cycloalkyl, 3-8 membered heterocyclic group; R1 is selected from hydroxy, oxo (=O), C 1-6 Alkyl, C 1-6 Alkoxy; t is selected from 0, 1 or 2; L1 is selected from NH, O, -CH2NH-; L2 is selected from -C(O)NH-, -C(O)O-, -C(O)OCH2-; Ring A is selected from 5-8 membered heterocyclic group, C 6-10 Aryl; Ring B is selected from unsubstituted or optionally substituted with 1, 2 or more halogen, C 1-6 Alkyl or C 1-6 Alkoxy-substituted groups: C 6-10 Aryl, 3-8 membered heterocyclic group; R2 is selected from H, C 1-6 Alkyl, C 1-6 Alkoxy; R3 is selected from unsubstituted or optionally substituted with 1, 2 or more halogen, C 1-6 Alkyl, C 1-6 Alkoxy, hydroxyl C 1-6 Alkyl substituted groups: C 2-6 Alkenyl-C(O)NH-, C 2-6 Alkynyl-C(O)-, C 1-6 Alkyl-NH-C 2-6 Alkenyl-C(O)-, (C 1-6 Alkyl)2-NC 2-6 Alkenyl-C(O)-, 5-6 membered heterocyclic-NH-C 2-6 alkenyl-C(O)-; m is selected from 0, 1 or 2; n is selected from 0, 1 or 2; Preferably, R is selected from C 1-3 Alkyl or C 3-6 Cycloalkyl; Preferably, R is selected from ethyl, isopropyl, cyclopropyl; Preferably, R0 is selected from C 1-3 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-3 Alkoxy, 5-6 membered heterocyclic group, 5-6 membered heteroaryl, C 1-6 Alkoxy-5-6 membered heteroaryl; Preferably, R0 is selected from methyl, cyclopropyl, difluoromethoxy, trifluoroethoxy, pyridyl, pyrimidinyl, Preferably, R0 is selected from Preferably, Not present or selected from C 1-6 Alkyl, C 3-6 Cycloalkyl, 5-6 membered heterocyclic group; Preferably, is absent or selected from propyl, butyl, piperidinyl, tetrahydropyranyl, tetrahydrofuranyl, cyclobutyl, Preferably, is absent or selected from isopropyl, isobutyl, cyclobutyl, Preferably, R1 is selected from hydroxy, methyl, oxo (=O), methoxy; Preferably, ring A is selected from phenyl, piperidinyl, Preferably, ring A is selected from Preferably, ring B is selected from the following groups which are unsubstituted or optionally substituted with 1, 2 or more F or methyl: phenyl, 4-6 membered heterocyclyl; Preferably, ring B is selected from phenyl, N-heterocyclobutane, tetrahydropyrrolyl, Preferably, ring B is selected from (like )、 Preferably, R3 is selected from the following groups which are unsubstituted or optionally substituted with 1, 2 or more F, methyl, isopropyl, methoxy, hydroxymethyl: C 2-6 Alkenyl-C(O)NH-, C 2-6 Alkynyl-C(O)-, C 1-6 Alkyl-NH-C 2-6 Alkenyl-C(O)-, (C 1-6 Alkyl)2-NC 2-6 Alkenyl-C(O)-, 5-6 membered heterocyclic-NH-C 2-6 alkenyl-C(O)-; Preferably, R3 is selected from Preferably, Preferred is selected from the following structures: R is as described in any one of claims 1-6.

8. The compound, isomer or isotope substitute or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, which is a new compound selected from the examples of the present invention.

9. Use of the compound according to any one of claims 1 to 8 or its pharmaceutically acceptable salt, solvate, hydrate or isotope isomer for the preparation of a medicament for preventing and / or treating the CDKs target-related diseases discussed herein, including tumors, inflammation, autoimmune diseases (such as lupus erythematosus, psoriasis, psoriasis) and the like.

10. A pharmaceutical composition, wherein the main active ingredient is the compound according to any one of claims 1 to 8 or its pharmaceutically acceptable salt, solvate, hydrate or isotope isomer, and some other auxiliary ingredients, so that it can be suitable for use in various forms of pharmaceutical dosage forms such as liquid preparations (including oral liquids, injections, eye drops, etc.), solid preparations (including tablets, capsules, pills, granules, etc.), and the pharmaceutical composition can be used to prepare drugs for preventing and / or treating the CDKs target-related diseases discussed herein, including tumors, inflammation, autoimmune diseases (such as lupus erythematosus, psoriasis, psoriasis) and other diseases.

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