Novel substituted heterocyclic compound as stats-targeting degradation agent

Abstract

Disclosed in the present invention is a novel substituted heterocyclic compound having STATs degradation activity, and specifically disclosed is a compound having the structure of formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, isotopically substituted substance or isomer thereof as a STAT6 degradation agent. The compound can be used for preventing or treating diseases related to STATs targets or signaling pathways.

Description

Novel substituted heterocyclic compounds as STAT target degraders

[0001] This application requests the following:

[0002] Priority rights to the earlier application filed with the China National Intellectual Property Administration on March 19, 2025, with patent application number 202510328603.2 and entitled "Novel Substituted Heterocyclic Compounds as STAT Target Degrading Agents";

[0003] Priority rights to the earlier application filed with the China National Intellectual Property Administration on March 4, 2026, with patent application number 2026102604297 and title "Novel Substituted Heterocyclic Compounds as STAT Target Degrading Agents";

[0004] The full text of the prior application is incorporated herein by reference. Technical Field

[0005] This invention belongs to the field of pharmaceutical chemistry, specifically including novel substituted heterocyclic compounds with dual-target degradation activity of STATs, compositions containing such compounds, and methods for applying such compounds to prepare medicaments for treating or preventing diseases related to STAT signaling pathways. Background Technology

[0006] Signal transducer and activator of transcription (STATs) are a unique family of proteins that bind to DNA. They contain SH2 and SH3 domains and can bind to specific phosphorylated tyrosine peptides. When STATs are phosphorylated, they polymerize into homodimers or heterodimers, becoming activated transcription activators that enter the cell nucleus and bind to specific sites on the promoter sequences of target genes, promoting transcription. Currently, four JAKs (JAK13 and Tyk2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) have been successfully cloned. These seven STAT proteins can be structurally divided into the following functional regions: 1) The conserved N-terminal sequence, which is the domain for STAT dimerization and STAT dimer interaction; 2) The coil-and-coil domain, which is the domain for STAT interaction with other transcription factors already bound to the target promoter region; 3) The DNA-binding domain, located between 400 and 500 amino acid residues; 4) The LD domain (connector domain), mainly involved in transcriptional regulation; 5) The SH2 domain, located between 600 and 700 amino acid residues, which is highly conserved; 6) The C-terminal transcriptional activity domain, which also contains serine phosphorylation sites. The SH2 domain is the most conserved and functionally most important region. The Arg residues in this core sequence can directly bind to phosphotyrosine residues on another molecule, thereby mediating the connection between the two molecules. When STAT is phosphorylated, it polymerizes into an activated transcription activator, enters the nucleus, binds to target genes, and promotes their transcription. It plays a crucial role in signal transduction and transcriptional activation.

[0007] The JAK-STAT pathway is one of the most important signaling pathways in mammalian physiology and pathology, mainly composed of four parts: (1) extracellular signaling factors, (2) receptors, (3) JAK kinases, and (4) signal transduction and transcriptional activating proteins (STATs). JAK-STAT is the most important signaling pathway besides the second messenger system. From the perspective of gain-of-function expression or mutation analysis, different JAKs are associated with hematologic malignancies. Mutations or overactivation of the JAK-STAT pathway ultimately lead to: cell proliferation, resistance to apoptosis, and promotion of angiogenesis, which eventually induces cancer.

[0008] The JAK / STAT signaling pathway has become a highly promising drug target. Several drugs targeting JAK have already been approved for marketing. Ruxolitinib, originally developed by Incyte, is a small molecule kinase inhibitor of JAK1 / JAK2. It received FDA approval in November 2011 for the treatment of intermediate- to high-risk myelofibrosis (MF). In 2014, it was further approved for polycythemia vera (PCV). Pfizer's selective JAK3 inhibitor, tofacitinib, received FDA approval in November 2012 for rheumatoid arthritis (RA). Although JAK has become a validated drug target, due to its important physiological functions, most drugs in clinical trials and already on the market have serious toxic side effects, limiting its development and widespread application. STAT targets, as important downstream signaling relays of JAK-STAT, are mechanistically more promising in terms of safety than JAK. Currently, several drugs targeting the STAT family have entered clinical trials, but none have yet been approved for marketing. Therefore, there is an urgent need to develop drugs targeting the STAT family, especially selective inhibitors of the STAT family.

[0009] STAT6 (Signal Transducer and Activator of Transcription 6) is an important member of the signal transducer and activator of transcription (STAT) family, playing a crucial role in the immune system. STAT6 is a transcription factor with dual functions of signal transduction and transcriptional activation. It is activated by phosphorylation of Janus kinase (JAK) after binding to cytokine receptors, forming homodimers or heterodimers and translocating into the nucleus to regulate the expression of specific genes. STAT6 plays an important role in allergic diseases such as asthma and atopic dermatitis. Its aberrant activation can lead to an overactive Th2 immune response, triggering inflammation. STAT6 also plays a key role in certain tumors. For example, in solitary fibromas, STAT6 fuses with the NAB2 gene, leading to its aberrant activation and translocation to the nucleus. Aberrant activation or dysfunction of STAT6 may be associated with autoimmune diseases.

[0010] STAT6, as an important target in various inflammations, autoimmune diseases, and tumors, has become a research hotspot. Although a few inhibitors, such as KP-723 being developed by Johnson & Johnson and a small-molecule STAT6 inhibitor being developed by Gilead in collaboration with LEO Pharma, show promise for treating inflammatory diseases such as asthma, atopic dermatitis, and chronic obstructive pulmonary disease, these molecules suffer from numerous drug-like limitations, urgently requiring the development of new therapeutic strategies with better drug-like properties. Summary of the Invention

[0011] The object of this invention is to provide compounds of formula (I) or pharmaceutically acceptable salts, solvates, enantiomers and isotopic substitutes thereof.

[0012] in,

[0013] A, B, C, D, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0014] "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N;

[0015] L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 );

[0016] X4 is arbitrarily and independently selected from C(R3) or N;

[0017] Q1 can be arbitrarily and independently selected from C(R0) or N;

[0018] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R)d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0019] Y is independently selected from O, S, or =NR0;

[0020] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution;

[0021] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0022] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0023] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C 3-10 Heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0024] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0025] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0026] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0027] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0028] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0029] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0030] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0031] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0032] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0033] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0034] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0035] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0036] v is any integer selected from 0, 1, 2, and 3.

[0037] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has the structure of formula (IA).

[0038] in,

[0039] A, B, C, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0040] "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N;

[0041] L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 );

[0042] X4 is arbitrarily and independently selected from C(R3) or N;

[0043] Q1, Q2, and Q3 can be independently selected from C(R0) or N;

[0044] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1(R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0045] Y is independently selected from O, S, or =NR0;

[0046] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution;

[0047] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0048] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0049] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0050] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0051] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0052] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0053] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0054] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0055] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0056] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0057] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0058] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0059] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0060] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0061] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0062] v is any integer selected from 0, 1, 2, and 3.

[0063] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has the structure of formula (IB).

[0064] in,

[0065] A, B, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0066] "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N;

[0067] L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 );

[0068] X4 is arbitrarily and independently selected from C(R3) or N;

[0069] Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0070] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(Rd1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0071] Y is independently selected from O, S, or =NR0;

[0072] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C1-3 Alkyl substitution;

[0073] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0074] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0075] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0076] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0077] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0078] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0079] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0080] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0081] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0082] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0083] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0084] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0085] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0086] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0087] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0088] v is any integer selected from 0, 1, 2, and 3.

[0089] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IC).

[0090] in,

[0091] A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0092] Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C;

[0093] X4 is arbitrarily and independently selected from C(R3) or N;

[0094] L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 );

[0095] Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0096] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1(R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0097] Y is independently selected from O, S, or =NR0;

[0098] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C1-3 Alkyl substitution;

[0099] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0100] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0101] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0102] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0103] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0104] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0105] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0106] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0107] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0108] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0109] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0110] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0111] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0112] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0113] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0114] v is any integer selected from 0, 1, 2, and 3.

[0115] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (ID).

[0116] in,

[0117] A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0118] Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C;

[0119] X4 is arbitrarily and independently selected from C(R3) or N;

[0120] Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0121] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(Rd1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0122] Y is independently selected from O, S, or =NR0;

[0123] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution;

[0124] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0125] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0126] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0127] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0128] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0129] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0130] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0131] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0132] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0133] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0134] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0135] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0136] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0137] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0138] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0139] v is any integer selected from 0, 1, 2, and 3.

[0140] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has the structure of formula (IE).

[0141] in,

[0142] A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0143] Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C;

[0144] Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0145] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(Rd1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0146] Y is independently selected from O, S, or =NR0;

[0147] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution;

[0148] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0149] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0150] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0151] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0152] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0153] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0154] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0155] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0156] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0157] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0158] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0159] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0160] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0161] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0162] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0163] v is any integer selected from 0, 1, 2, and 3.

[0164] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IF).

[0165] in,

[0166] A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures.

[0167] Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C;

[0168] Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0169] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(Rd1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0170] Y is independently selected from O, S, or =NR0;

[0171] Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution;

[0172] Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0173] Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0174] Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0175] Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl groups are substituted.

[0176] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0177] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0178] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0179] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0180] m is an integer arbitrarily selected from 0, 1, 2, 3, and 4;

[0181] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0182] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0183] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0184] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0185] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0186] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0187] v is any integer selected from 0, 1, 2, and 3.

[0188] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IG-1) to (IG-8).

[0189] Wherein, F is preferably a triazole ring or a pyrazole ring;

[0190] Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C;

[0191] Each X2 can be the same or different, and is preferably selected from O or NR;

[0192] Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N;

[0193] Q1, Q2, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0194] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(Rd1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0195] Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 alkyl;

[0196] Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 alkyl;

[0197] Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 alkyl;

[0198] Each R a They can be the same or different, and each can be arbitrarily and independently selected from C. 1-20 Alkoxy, C 1-20 Alkylthio, C 1-20 alkylamine group, C 1-20 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, 3-8 membered saturated or partially saturated cycloalkyl, and 3-8 membered saturated or partially saturated heterocyclic groups; wherein R a The hydrogen atom is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-20 The alkyl group may be optionally separated by 1 to 10 O atoms;

[0199] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0200] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0201] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0202] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0203] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0204] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0205] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0206] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0207] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0208] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0209] v is any integer selected from 0, 1, 2, and 3.

[0210] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IH-1) to (IH-8).

[0211] Wherein, F is preferably a triazole ring or a pyrazole ring;

[0212] Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C;

[0213] Each X2 and X6 can be the same or different, and is preferably selected from O or NR;

[0214] Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N;

[0215] Q1, Q2, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0216] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0217] Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 alkyl;

[0218] Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 alkyl;

[0219] Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 alkyl;

[0220] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0221] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0222] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0223] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0224] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0225] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0226] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0227] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0228] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0229] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0230] v is any integer selected from 0, 1, 2, and 3.

[0231] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (II).

[0232] in,

[0233] Ring F is preferably absent, a triazole ring, or a pyrazole ring;

[0234] The ring G can be arbitrarily and independently selected from the following structures: in This represents the connection site with X4;

[0235] Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C;

[0236] Z is arbitrarily and independently selected from CH=CH, S, S=O, or SO2; G is not a CH=CH bond if and only if it is a CH=CH bond.

[0237] Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N;

[0238] Q1 and Q2 are arbitrarily and independently selected from C(R0) or N;

[0239] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0240] Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0241] Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0242] Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C.1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0243] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy group, -C(=O)NR d8 R d9 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is optionally substituted by one or more substituents, wherein the substituents are arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0244] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0245] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0246] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0247] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0248] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0249] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0250] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0251] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0252] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0253] v is any integer selected from 0, 1, 2, and 3.

[0254] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IIA-1) to (IIA-4).

[0255] Ring F is preferably absent, a triazole ring, or a pyrazole ring;

[0256] The ring G can be arbitrarily and independently selected from the following structures: in This represents the connection site with X4;

[0257] Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C;

[0258] Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N;

[0259] Q1, Q2, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N;

[0260] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1(R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0261] Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0262] Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0263] Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0264] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0265] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0266] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0267] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0268] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0269] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0270] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0271] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0272] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0273] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0274] v is any integer selected from 0, 1, 2, and 3.

[0275] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (IIB-1) to (IIB-20).

[0276] Ring F is preferably absent, a triazole ring, or a pyrazole ring;

[0277] Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C;

[0278] Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N;

[0279] L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups;

[0280] Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C.1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0281] Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0282] Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups;

[0283] Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH.

[0284] Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution;

[0285] The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P.

[0286] The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes;

[0287] n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5;

[0288] f is any integer selected from 0, 1, 2, 3, 4, and 5;

[0289] p is any integer selected from 0, 1, 2, 3, 4, and 5;

[0290] q is any integer selected from 0, 1, 2, 3, 4, and 5;

[0291] s is any integer selected from 0, 1, 2, 3, 4, and 5;

[0292] t is any integer selected from 0, 1, 2, 3, 4, and 5;

[0293] v is any integer selected from 0, 1, 2, and 3.

[0294] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure of formula (III).

[0295] Among them, rings G, R, R1, R5, R6, n, q and v have the definitions described above independently of each other;

[0296] Ring G is selected from 5-6 membered heteroaryl and 9-10 membered heteroaryl;

[0297] R is selected from H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy;

[0298] R1 is selected from hydrogen or methyl;

[0299] R5 is selected from F or hydrogen;

[0300] R6 is selected from H or methyl;

[0301] n, q, and v are selected from 0, 1, 2, or 3.

[0302] According to an embodiment of the present invention, ring G is selected from benzofuranyl, indolyl, thienyl, benzodihydrofuranyl, and dihydroindolyl;

[0303] According to an embodiment of the present invention, ring G is selected from...

[0304] According to an embodiment of the present invention, ring G is selected from... Among them, *end and connect;

[0305] According to an embodiment of the present invention, R is selected from F, methyl, or methoxy.

[0306] According to an embodiment of the present invention, Selected from

[0307] According to an embodiment of the present invention, Selected from Among them, *end and connect;

[0308] According to an embodiment of the present invention, Selected from

[0309] In one embodiment of the invention, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has a structure shown in formula (III-1) or (III-2).

[0310] Among them, rings G, R, R1, R5, R6, n, q, and v independently have the definitions described above.

[0311] In one aspect of the present invention, the above-mentioned compound or its pharmaceutically acceptable salt, or its corresponding isomer or isotopic substitute, is a novel compound selected from the structures disclosed in the examples.

[0312] The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of at least one of the compound represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate, an enantiomer, and an isotopic substitute.

[0313] According to embodiments of the present invention, the pharmaceutical composition is formulated for administration via a route selected from the following: oral, injection, rectal, nasal, pulmonary, local, oral and sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural.

[0314] According to an embodiment of the present invention, the pharmaceutical composition is preferably administered orally.

[0315] The oral dosage form is not particularly limited and can be any oral dosage form known in the art, preferably including tablets, capsules, suspensions or oral solutions and other oral dosage forms known in the art.

[0316] According to embodiments of the present invention, the pharmaceutical composition may further comprise pharmaceutically acceptable excipients selected from at least one of the following: fillers, disintegrants, binders, lubricants, surfactants, flavoring agents, humectants, pH adjusters, solubilizers or co-solvents, and osmotic pressure regulators. Those skilled in the art can readily determine how to select the appropriate excipients and their corresponding amounts based on the specific dosage form requirements.

[0317] According to embodiments of the present invention, the pharmaceutical composition may further contain one or more additional therapeutic agents.

[0318] Another object of the present invention is to provide the use of the above-mentioned compounds, their pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutes in the preparation of medicaments for the prevention and / or treatment of diseases related to the STAT signaling pathway. These STAT signaling pathway-related diseases include, but are not limited to, cancer, metabolic diseases, autoimmune diseases, and inflammatory diseases.

[0319] Another object of the present invention is to provide the above-described compounds, their pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutes, and the use of said pharmaceutical compositions in the preparation of medicaments for the prevention and / or treatment of STAT-related or mediated diseases. The STAT-related or mediated diseases include, but are not limited to, cancer, metabolic diseases, autoimmune diseases, inflammatory diseases, etc.

[0320] The present invention also provides the above-described compounds, their pharmaceutically acceptable salts, solvates, enantiomers and isotopic substitutes, and the use of the pharmaceutical compositions in the degradation of STATs.

[0321] The present invention also provides the above-described compounds, their pharmaceutically acceptable salts, solvates, enantiomers and isotopic substitutes, and the use of the pharmaceutical compositions in the preparation of medicaments for the degradation of STATs.

[0322] This invention also provides compounds of formula (I), pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutes thereof, and the use of said pharmaceutical compositions in the prevention and / or treatment of diseases related to the STAT signaling pathway. These STAT signaling pathway-related diseases include, but are not limited to, cancer, metabolic diseases, autoimmune diseases, and inflammatory diseases.

[0323] The present invention also provides the above-described compounds, their pharmaceutically acceptable salts, solvates, enantiomers, and isotopic substitutes, and the use of said pharmaceutical compositions in the prevention and / or treatment of STATs-related or mediated diseases. The STATs-related or mediated diseases have the definitions described above.

[0324] The present invention also provides a method for preventing and / or treating diseases related to the STAT signaling pathway, comprising administering to a patient a preventive or therapeutically effective amount of at least one of a compound of formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, an enantiomer thereof, and an isotopic substitute thereof, or administering to a patient a preventive or therapeutically effective amount of the aforementioned pharmaceutical composition. The STAT signaling pathway-related diseases have the definitions described above.

[0325] The present invention also provides a method for preventing and / or treating STATs-related or mediated diseases, comprising administering to a patient a preventive or therapeutically effective amount of at least one of the above-described compounds, pharmaceutically acceptable salts thereof, solvates, enantiomers, and isotopic substitutes thereof, or administering to a patient a preventive or therapeutically effective amount of the above-described pharmaceutical composition. The STATs-related or mediated diseases described herein have the definitions presented above.

[0326] In some implementations, the STATs are preferably STAT6.

[0327] In some implementations, the patient is a mammal, preferably a human. Beneficial effects

[0328] The heterocyclic compounds of this invention were unexpectedly discovered to be not only potent degraders of STAT targets but also exhibit good selectivity. They are expected to have a larger safety window, thus making them more suitable as drug candidates for the prevention or treatment of diseases related to STAT target signaling pathways.

[0329] Definitions and explanations:

[0330] C 1-10 Selected from C1, C2, C3, C4, C5, C6, C7, C8, C9 and C 10 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 ;

[0331] As used in this article, the term "alkyl" should be understood to refer to a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms, also denoted as "C". 1-20 Alkyl group. For example, "C 1-10 "Alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. 1-8 "Alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. 1-6"Alkyl" means a straight-chain or branched alkyl group 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 their isomers.

[0332] The term "alkylene" as used in this article refers to the formula -(CH2). n - A straight-chain or branched divalent hydrocarbon group. Non-limiting examples include ethylene and propylene.

[0333] The term "one or more" as used in this article refers to more than one, such as one, two, three, four, five or more.

[0334] The term "monocyclic or polycyclic structure with 3 to 18 carbon atoms" encompasses various monocyclic or polycyclic structures having 3 to 18 carbon atoms (and may also contain other heteroatoms). The number of carbon atoms in the monocyclic or polycyclic structure can be selected from 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or any combination of these values. The monocyclic or polycyclic structure can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, fused rings, spirocyclic rings, or bridged ring structures; wherein aromatic rings, heteroaromatic rings, aliphatic rings, heterocyclic rings, fused rings, spirocyclic rings, or bridged rings are defined as follows.

[0335] The term "alkenyl" should be understood to refer to a linear or branched hydrocarbon group containing one or more double bonds and having 2 to 20 carbon atoms, preferably "C". 2-10 "Alkenyl". "C" 2-10 "Alkenyl" should be understood to preferably represent a linear or branched hydrocarbon group containing one or more double bonds and having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, more preferably "C 2-8 "Alkenyl". "C" 2-10 "Alkenyl" should be understood to preferably represent a linear or branched hydrocarbon group containing one or more double bonds and having 2, 3, 4, 5, 6, 7 or 8 carbon atoms, for example, having 2, 3, 4, 5 or 6 carbon atoms (i.e., C... 2-6 alkenyl), having 2 or 3 carbon atoms (i.e., C24, C34, C4 ... 2-3Alkenyl). It should be understood that when the alkenyl group contains more than one double bond, the double bonds may be separable or conjugated. The alkenyl group is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)- Pentyl-1-enyl, (Z)-pentyl-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl 2-Methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1-methyl But-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl.

[0336] The term "alkynyl" should be understood to refer to a straight or branched hydrocarbon group containing one or more triple bonds and having 2 to 20 carbon atoms, preferably "C". 2-10 "Alkyne group". The term "C" 2-10 "Alkyne" should be understood to preferably represent a linear or branched hydrocarbon group containing one or more triple bonds and having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, for example, having 2, 3, 4, 5, 6, 7, or 8 carbon atoms (i.e., "C"). 2-8 "Alkyne group" has 2, 3, 4, 5 or 6 carbon atoms (i.e., "C"). 2-6 The alkynyl group ("C") has 2 or 3 carbon atoms ("C") 2-3The alkynyl group is, for example, ethynyl, prop-1-alkynyl, prop-2-alkynyl, but-1-alkynyl, but-2-alkynyl, but-3-alkynyl, pent-1-alkynyl, pent-2-alkynyl, pent-3-alkynyl, pent-4-alkynyl, hex-1-alkynyl, hex-2-alkynyl, hex-3-alkynyl, hex-4-alkynyl, hex-5-alkynyl, 1-methylprop-2-alkynyl, 2-methylbut-3-alkynyl, 1-methylbut-3-alkynyl, 1-methylbut-2-alkynyl, 3-methylbut-1-alkynyl, 1-ethylprop-2-alkynyl, 3-methylpent-4-alkynyl, 2-methylpent-4-alkynyl, 1-methylpent-4-alkynyl -Alynyl, 2-methylpentan-3-ynyl, 1-methylpentan-3-ynyl, 4-methylpentan-2-ynyl, 1-methylpentan-2-ynyl, 4-methylpentan-1-ynyl, 3-methylpentan-1-ynyl, 2-ethylbutan-3-ynyl, 1-ethylbutan-3-ynyl, 1-ethylbutan-2-ynyl, 1-propylpropan-2-ynyl, 1-isopropylpropan-2-ynyl, 2,2-dimethylbutan-3-ynyl, 1,1-dimethylbutan-3-ynyl, 1,1-dimethylbutan-2-ynyl, or 3,3-dimethylbutan-1-ynyl. In particular, the ynyl group is ethynyl, propan-1-ynyl, or propan-2-ynyl.

[0337] The term "heteroalkyl" refers to a saturated or partially unsaturated group consisting of 1 to 20 carbon atoms and at least one heteroatom or heterogroup. In some embodiments, the heteroatom is selected from O, N, S, or P and their isotopes, wherein the N, S, or P atom is optionally oxidized and the nitrogen heteroatom is optionally quaternized. In other embodiments, the heterogroup is selected from -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O), -S(=O)2-, -C(=O)N(H)-, -N(H)-, -C(=NH)-, -S(=O)2N(H)-, and -S(=O)N(H)-. In some embodiments, the heteroalkyl group is C 1-10 Heteroalkyl, C 1-6Heteroalkyl. Heteroatoms or heteroatomic groups can be located at any internal position of a heteroalkyl group, including the position where the alkyl group is attached to the rest of the molecule, such as alkoxy, alkathio, alkamino, or ether. Examples of heteroalkyl groups include, but are not limited to, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH2(CH3)2, -CH2-CH2-O-CH3, -NHCH3, -N(CH3)2, -NHCH2CH3, -N(CH3)(CH2CH3), -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH2(CH3)2, -CH2-S-CH2-CH3, -CH2-CH2, -S(=O)-CH3, -CH2-CH2-S(=O)2-CH3, and at most two heteroatoms can be consecutive, such as -CH2-NH-OCH3.

[0338] The terms "alicylic ring," "carbocyclic (group)," or "cycloalkyl" refer to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon group, wherein the carbocyclic ring may contain 3 to 20 carbon atoms, preferably C14. 3-12 Cycloalkyl groups, comprising 3 to 12 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, more preferably comprising 3 to 6 carbon atoms (C 3-6 (Cycloalkyl). The carbocyclic ring can be monocyclic or polycyclic, and it can be a saturated cycloalkyl group or optionally contain one, two or more double bonds and / or triple bonds on its ring, thereby forming so-called cycloalkenyl or cycloynyl groups. In the case of multiple rings, these rings can form spirocyclic, fused, and bridged ring structures. For example, non-limiting examples of monocyclic carbocyclic rings include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, cyclooctyl, cyclooctatetraenyl, etc.; non-limiting examples of polycyclic carbocyclic rings include decahydronaphthyl or isobornyl.

[0339] The term "aryl" or "aromatic ring" refers to, preferably, a monocyclic, bicyclic (e.g., fused, bridged, or spirocyclic), or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a monoaromatic ring or a polyaromatic ring fused together. Preferably, "C" indicates a single aromatic ring or a partially aromatic ring. 6-14 "Aromatic". The term "C" 6- 14 "Aryl" should be understood to preferably represent a monovalent aromatic or partially aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring ("C") having 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms. 6-14Aryl), particularly a ring with 6 carbon atoms (“C6 aryl”), such as phenyl; or biphenyl, or a ring with 9 carbon atoms (“C9 aryl”), such as indenyl or indenyl, or a ring with 10 carbon atoms (“C9 aryl”). 10 Aryl groups, such as tetrahydronaphthyl, dihydronaphthyl, or naphthyl, or rings with 13 carbon atoms (“C”). 13 Aryl groups, such as fluorene groups, or rings with 14 carbon atoms (“C”). 14 Aryl), for example, anthracene. When the C 6-20 When the aryl group is substituted, it can be monosubstituted or polysubstituted. Furthermore, there are no restrictions on the substitution site; for example, it can be ortho, para, or meta substituted.

[0340] The term "spirocyclic" refers to a ring system in which two rings share a single cyclic atom, and it may contain aliphatic rings, heterocyclic rings, aromatic rings, or heteroaromatic rings as described above.

[0341] The term "fused ring" refers to a ring system in which two rings share two cyclic atoms, and it may contain aliphatic rings, heterocyclic rings, aromatic rings or heteroaromatic rings as described above.

[0342] The term "bridged ring" refers to a ring system in which two rings share three or more cyclic atoms, and it may contain aliphatic rings, heterocyclic rings, aromatic rings or heteroaromatic rings as described above.

[0343] The term "heterocyclic (group)" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent comprising 3 to 20 ring atoms, wherein one or more ring atoms are heteroatoms or groups selected from N, O, NH, S, S(O) or S(O)2, but excluding ring portions of -OO-, -OS-, or -SS-, and the remaining ring atoms are carbon. Preferably, 3-12 membered heterocyclic groups comprising 3 to 12 ring atoms, wherein 1 to 4 are heteroatoms (e.g., 1, 2, 3, and 4); more preferably, 3-6 membered heterocyclic groups comprising 3 to 6 ring atoms (e.g., 3, 4, 5, and 6). The heterocyclic group can be connected to the rest of the molecule via any one of the carbon atoms, or a nitrogen atom (if present), or an oxygen or sulfur atom (especially in the case of forming ononium salts). The heterocyclic group can include fused or bridged rings and / or spirocyclic rings. Non-limiting examples of monocyclic heterocyclic groups include azirrobutyl, oxacyclobutyl, pyrrolyl, imidazoalkyl, tetrahydrofuranyl, tetrahydrothiophenyl, dihydroimidazoyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, dioxacyclopentenyl, tetrahydropyranyl, pyrrolinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dithiaalkyl, trithiaalkyl, homopiperazinyl, diazacycloheptyl, etc., preferably piperidinyl or pyrrolyl. Polycyclic heterocyclic groups include spirocyclic, fused-ring, and bridged-ring heterocyclic groups, and may also be benzofused heterocyclic groups such as dihydroisoquinolinyl. The heterocyclic group may be bicyclic, and non-limiting examples include hexahydrocyclopenta[c]pyrrolo-2(1H)-yl and hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl. Heterocyclic groups can also be partially unsaturated, meaning they can contain one or more double bonds. Non-limiting examples include dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrroleyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl, or 4H-[1,4]thiazinyl.

[0344] The heterocyclic group may be optionally substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo, carboxyl, or carboxylic acid ester group.

[0345] In this document, the term "heteroaryl / heteroary ring" refers to a heteroaryl system comprising 1 to 4 heteroatoms and 5 to 20 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, nitrogen, and phosphorus. The heteroaryl group is preferably 5 to 10-membered (e.g., 5, 6, 7, 8, 9, or 10-membered), more preferably 5-membered or 6-membered. Non-limiting examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrroleyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, and their benzo[a] derivatives, such as benzofuranyl, benzothienyl, benzooxazolyl, benzoisooxazolyl, benzoimidazolyl, benzotriazolyl, indazole, and indolyl. Isoindolyl, etc.; or pyridyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and their benzo[derivatives], such as quinolinyl, quinazolinyl, isoquinolinyl, etc.; or acrylonitrileyl, inazinyl, purineyl, etc., and their benzo[derivatives]; or terpineyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphridinyl, pteridinyl, carbazoyl, acridineyl, phenazinyl, phenothiazinyl and / or phenotoxazinyl, etc.

[0346] The heteroaryl / heteroaryl ring can 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, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0347] Unless otherwise stated, heterocyclic groups, heteroaryl groups, or heteroaromatic rings include all possible isomers, such as their positional isomers. Thus, for some illustrative, non-limiting examples, forms may include those in which one, two, or more of the following positions (if present) are substituted or bonded to other groups, including pyridin-2-yl, pyridinoid-2-yl, pyridinoid-3-yl, pyridinoid-3-yl, pyridinoid-4-yl, and pyridinoid-4-yl; thiophene groups or thiophene groups include thiophene-2-yl, thiophene-2-yl, thiophene-3-yl, and thiophene-3-yl; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, etc.

[0348] The term “pharmaceutically acceptable” as used herein refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0349] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of this invention, prepared by reacting a compound having specific substituents discovered in this invention with a relatively non-toxic acid or base. When the compounds of this invention contain relatively acidic functional groups, base addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of base in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amine, or magnesium salts or similar salts. When the compounds of this invention contain relatively basic functional groups, acid addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of acid in a pure solution or 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, hydrogen sulfate, hydroiodic acid, phosphorous acid, etc.; and organic acid salts, such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, octanoic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, tartaric acid, and methanesulfonic acid; as well as salts of amino acids (such as arginine), and salts of organic acids such as glucuronic acid (see Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 66:1-19 (1977)). Certain compounds of the present invention contain both basic and acidic functional groups, and thus can be converted into either a base or an acid addition salt.

[0350] Preferably, the salt is contacted with a base or acid in a conventional manner, and then the parent compound is separated, thereby regenerating the neutral form of the compound. The parent form of the compound differs from its various salt forms in certain physical properties, such as different solubilities in polar solvents.

[0351] The term "pharmaceutically acceptable salt" as used herein refers to derivatives of the compounds of this invention, wherein the parent compound is modified by salting with an acid or a base. 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 anions such as carboxylic acids, etc. Pharmaceutically acceptable salts include conventional non-toxic salts such as sodium salts, potassium salts, amine salts, quaternary ammonium salts of the parent compound, etc. Conventional non-toxic salts include, but are not limited to, salts 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, edetate, ethanedisulfonic acid, ethanesulfonic acid, fumaric acid, glucohepose, gluconic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, hydroiodide, hydroxyl, hydroxynaphthalene, etc. The inorganic and organic bases mentioned above, such as hydroxyethanesulfonic acid, lactic acid, lactose, dodecyl sulfonic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, nitric acid, oxalic acid, dihydroxynaphthyl acid, pantothenic acid, phenylacetic acid, phosphoric acid, polygalacturonic acid, propionic acid, salicylic acid, stearic acid, acetic acid, succinic acid, aminosulfonic acid, p-aminobenzenesulfonic acid, sulfuric acid, tannin, tartaric acid, and p-toluenesulfonic acid, are selected from Na, potassium, magnesium, calcium, etc., or amines, diethylamine, triethylamine, ethanolamine, etc.

[0352] 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 these compounds in free acid or base form with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture of both. Generally, non-aqueous media such as ethers, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred.

[0353] In addition to the salt form, the compounds provided by this invention also exist in prodrug form. The prodrugs of the compounds described herein readily undergo chemical changes under physiological conditions to be converted into the compounds of this invention. Furthermore, the prodrugs can be converted into the compounds of this invention in the in vivo environment via chemical or biochemical methods.

[0354] Some compounds of the present invention may exist in non-solventized or solvated forms, including hydrated forms. Generally, solvated and non-solventized forms are equivalent and both are included within the scope of the present invention. Some compounds of the present invention may exist in polycrystalline or amorphous forms.

[0355] In this document, the term "solvate" refers to an association formed by one or more solvent molecules with the compounds 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. Therefore, the term "hydrate" refers to an association formed by solvent molecules that are water.

[0356] Some compounds of this invention may have asymmetric carbon atoms (optical centers) or double bonds. Racemates, diastereomers, geometric isomers, and single isomers are all included within the scope of this invention.

[0357] The illustrations of racemic, ambiscalemic and scalemic, or enantiomerically pure compounds in this document are derived from Maehr, J. Chem. Ed. 1985, 62: 114-120. Unless otherwise specified, wedge-shaped and dashed lines denote the absolute configuration of a stereocenter. When the compounds described herein contain alkene double bonds or other geometrically asymmetric centers, they include E and Z geometric isomers unless otherwise specified. Similarly, all tautomers are included within the scope of this invention.

[0358] The compounds of this invention can exist in specific geometric or stereoisomeric forms. This invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)- enantiomers, (R)- and (S)- enantiomers, diastereomers, (D)- isomers, (L)- isomers, and racemic mixtures thereof, as well as other mixtures, such as mixtures enriched with enantiomers or diastereomers, all of which are within the scope of this invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included within the scope of this invention.

[0359] Optically active (R)- and (S)- isomers, as well as D- and L- isomers, can be prepared by chiral synthesis, chiral reagents, or other conventional techniques. To obtain an enantiomer of a compound of the present invention, 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 desired enantiomer in pure form. 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 salt of the diastereomeric isomer is formed with a suitable optically active acid or base, followed by diastereomeric resolution by fractional crystallization or chromatography known in the art, and then the pure enantiomer is recovered. Furthermore, the separation of enantiomers and diastereomeric isomers is typically accomplished by chromatography using a chiral stationary phase, optionally combined with chemical derivatization (e.g., from amines to carbamates).

[0360] The compounds of this invention may contain atomic isotopes in non-natural proportions on one or more atoms constituting 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, regardless of radioactivity, are included within the scope of the present invention.

[0361] The term "pharmaceutically acceptable carrier" refers to any formulation or carrier medium capable of delivering an effective amount of the active substance of this invention without interfering with the biological activity of the active substance and without toxic side effects on the host or patient. Representative carriers include water, oil, vegetables and minerals, ointment bases, lotion bases, and ointment bases. These bases include suspending agents, thickeners, transdermal penetration enhancers, etc. Their formulations are well known to those skilled in the art of cosmetics or topical pharmaceuticals. For further information on carriers, see Remington: The Science and Practice of Pharmacy, 21st Ed., Lippincott, Williams & Wilkins (2005), the contents of which are incorporated herein by reference.

[0362] When any variable (e.g., R) appears more than once in the composition or structure of a compound, its definition is independent in each case. Thus, for example, if a group is substituted by 0-2 Rs, the group can optionally be substituted by at most two Rs, and the Rs in each case have independent options. Furthermore, combinations of substituents and / or their variants are only permitted if such combinations produce a stable compound.

[0363] When a substituent can be cross-bonded to two atoms on a ring, it can bond to any atom on that ring. When a listed substituent does not specify which atom it is attached to in a compound included but not specifically mentioned in the general chemical formula, it can bond to any atom of that substituent. Combinations of substituents and / or their variants are permitted only if such combinations produce stable compounds.

[0364] The term "halogen" or "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0365] The present invention is now 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 field of organic synthesis. The embodiments of the present invention can be synthesized using the methods described below, as well as synthetic methods known in the field of organic synthetic chemistry, or by modifications thereof. Preferred methods include, but are not limited to, the methods described below.

[0366] Unless otherwise specified, all solvents used in this invention are commercially available and require no further purification. Reactions are typically carried out in an anhydrous solvent under an inert nitrogen atmosphere. Nuclear magnetic resonance (NMR) spectra were determined using a Bruker-Avance-400 (400 MHz) spectrometer, and chemical shifts are reported in δ (ppm). Mass spectrometry was performed using an Agilent 1200 series (plus 6110 / and 1956A) LC / MS or a Shimadzu MS (DAD:SPD-M20A(LC)) and a Shimadzu Micromass 2020 detector. The mass spectrometer was equipped with an electrospray ionization (ESI) source operating in both positive and negative modes.

[0367] The abbreviations used are as follows: aq for aqueous solution; TLC for thin-layer chromatography; RT for room temperature; MeOH for methanol; EtOH for ethanol; EtOAc for ethyl acetate; THF for tetrahydrofuran; equivalent (eq); CDI for carbonyl diimidazole; DCM for dichloromethane; PE for petroleum ether; DIAD for diisopropyl azodicarbonate; DMF for N,N-dimethylformamide; DMSO for dimethyl sulfoxide; CBz for benzyloxycarbonyl; BOC for tert-butyl... Butyl carbonyl; HOAc is acetic acid; Ms is methanesulfonyl; NMP is N-methylpyrrolidone; DMAP is 4-(dimethylamino)pyridine; Boc2O is di-tert-butyl dicarbonate; TFA is trifluoroacetic acid; DIPEA is diisopropylethylamine; SOCl2 is thionyl chloride; CS2 is carbon disulfide; TsOH is 4-toluenesulfonic acid; MTBE is tert-butyl methyl ether; FA is formic acid; ACN is acetonitrile; i-PrOH is 2-propanol.

[0368] Compounds can be named manually or using... The reaction should be named accordingly; if it is a commercially purchased product, the supplier's catalog name can also be used. TLC or LC-MS is typically used to determine whether the reaction is complete. Detailed Implementation

[0369] To illustrate the invention in more detail, the following examples are given, but the scope of the invention is not limited thereto.

[0370] Example 1: Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(3-(1-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)ureo)piperidin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound 1):

[0371] 1) Synthesis of 5-fluoro-7-nitro-2,3-dihydrobenzofuran

[0372] 5-Fluoro-2,3-dihydrobenzofuran (9 g, 65.15 mmol) was dissolved in nitric acid (80 mL) and stirred at -10 °C for 0.5 h. The mixture was then quenched dropwise with water (125 mL) at -10 °C and extracted with ethyl acetate (3 × 100 mL). The combined organic phases were dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to give 5-fluoro-7-nitro-2,3-dihydrobenzofuran (11.9 g, 65.03 mmol, yield: 99.8%).

[0373] 1 H NMR (400MHz, DMSO-d6) δ7.71-7.68(m,1H),7.63-7.61(m,1H),4.81(t,J=8.0Hz,2H),3.32-3.30(m,2H).

[0374] 2) Synthesis of 5-fluoro-2,3-dihydrobenzofuran-7-amine

[0375] To a solution of ethyl acetate (100 mL) containing 11.9 g (65.03 mmol) of 5-fluoro-2,3-dihydrobenzofuran, Pd and C (15.3 g, 10% content) were added, and the mixture was stirred at 25 °C under a hydrogen atmosphere for 12 hours. The reaction mixture was filtered, and the filtrate was collected and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent PE: EA = 0%–50%, R...). f =0.5) Purification yielded 5-fluoro-2,3-dihydrobenzofuran-7-amine (7.5 g, 49.02 mmol, yield: 75.4%).

[0376] 1 H NMR (400MHz, DMSO-d6) δ6.24-6.20(m,2H),4.90(s,2H),4.47(t,J=8.0Hz,2H),3.09(t,J=8.0Hz,2H).

[0377] 3) Synthesis of 4-bromo-5-fluoro-2,3-dihydrobenzofuran-7-amine

[0378] Under nitrogen protection, NBS (0.27 g, 1.567 mmol) was added to 30 mL of DMF containing 0.3 g (1.959 mmol) of 5-fluoro-2,3-dihydrobenzofuran-7-amine. The mixture was stirred at 0 °C for 1 hour under nitrogen protection. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (30 mL × 3). The combined organic residues were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (eluent PE: EA = 0%–50%) to give 4-bromo-5-fluoro-2,3-dihydrobenzofuran-7-amine (347 mg, 1.496 mmol, yield: 76.3%).

[0379] 1 H NMR (400MHz, DMSO-d6) δ6.40(d,J=8.0Hz,1H),5.10(s,2H),4.55(t,J=8.0Hz,2H),3.13(t,J=8.0Hz,2H).

[0380] 4) Synthesis of 4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-amine

[0381] Under nitrogen protection, a mixture of 4-bromo-5-fluoro-2,3-dihydrobenzofuran-7-amine (2.5 g, 10.78 mmol) dissolved in 1,4-dioxane (102 mL) and water (17 mL) was added, followed by the addition of 2,6-bisbenzyloxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)pyridine (5.4 g, 12.93 mmol), Pd(dppf)Cl2 (0.78 g, 1.078 mmol), and Na2CO3 (3.43 g, 32.33 mmol). The mixture was heated to 80 °C and stirred for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water (130 mL) and extracted with ethyl acetate (60 mL × 3). The combined organic phases were dried, filtered, and concentrated to dryness. The crude compound was subjected to normal-phase column chromatography (eluent PE: EA = 0%–50%) to give a yellow solid 4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-amine (4.04 g, 9.14 mmol, yield: 84.8%). LCMS m / z: 443 [M+H] + .

[0382] 5) Synthesis of 2,6-bisbenzyloxy-3-(5-fluoro-7-iodo-2,3-dihydrobenzofuran-4-yl)pyridine

[0383] At 0°C, a mixed solution of MeCN (10 mL), HCl (12 M, 2 M), and water (10 mL) containing 4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-amine (4.04 g, 9.14 mmol) was added to a solution of water (2 mL) containing NaNO2 (820 mg, 11.88 mmol). The mixture was stirred at 0°C for 1 hour under nitrogen protection. Then, an aqueous solution of potassium iodide (3.03 g, 18.28 mmol) (5 mL) was added dropwise to the above mixed solution, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (30 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting PE: EA = 0%–30%) to 2,6-bisbenzyloxy-3-(5-fluoro-7-iodo-2,3-dihydrobenzofuran-4-yl)pyridine (3.4 g, 6.15 mmol, yield: 67.3%), LCMS m / z: 554 [M+H]. + .

[0384] 6) Synthesis of tert-butyl carbamate (1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)carbamate

[0385] To a toluene (28 mL) solution containing 2,6-bisbenzyloxy-3-(5-fluoro-7-iodo-2,3-dihydrobenzofuran-4-yl)pyridine (500 mg, 0.904 mmol), tert-butyl aziridine-3-ylcarbamate (778 mg, 4.518 mmol), BINAP (56.3 mg, 0.09 mmol), Pd2(dba)3 (82.8 mg, 0.09 mmol), and t-BuONa (174 mg, 1.808 mmol) were added, and the mixture was heated to 120 °C and stirred for 18 hours. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (30 mL c×3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent PE: EA = 0%–10%) to give tert-butyl 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)carbamate (238 mg, 0.398 mmol, yield: 44.0%).

[0386] 1H NMR (400MHz, DMSO-d6) δ7.59-7.57(m,1H),7.55-7.47(m,3H),7.43-7.40(m,2H),7.38-7.28(m,5H),6.50(d,J=8.0Hz,1H),6.1 4(d,J=12Hz,1H),5.36-5.34(m,4H),4.44-4.28(m,3H),4.09-4.02(m,2H),3.66-3.56(m,2H),3.01-2.75(m,2H),1.39(s,9H).

[0387] 7) Synthesis of tert-butyl carbamate (1-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)carbamate

[0388] To a solution of 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)carbamate (200 mg, 0.335 mmol) in ethyl acetate (50 mL), Pd / C (356 mg) and Pd(OH)₂ (470.4 mg) were added. The mixture was heated at 40 °C and stirred for 8 hours under a hydrogen atmosphere. The reaction mixture was filtered and concentrated under reduced pressure to obtain 1-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)carbamate (133 mg, 0.317 mmol, yield: 94.7%), LCMS m / z: 420 [M+H].

[0389] 8) Preparation of 3-(7-(3-aminoazacyclobutane-1-yl)-5-fluoro-2,3-dihydrobenzofuran-4-yl)piperidine-2,6-dione

[0390] To a solution of 133 mg (0.317 mmol) of tert-butyl carbamate in dichloromethane (16 mL), 2,2,2-trifluoroacetic acid (5 mL) was added. The reaction mixture was stirred at 25 °C for 1 hour. The reaction mixture was concentrated to give a yellow solid 3,7-(3-aminoazacyclobutane-1-yl)-5-fluoro-2,3-dihydrobenzofuran-4-yl)piperidin-2,6-dione (101 mg, 0.317 mmol, yield: 100%). LCMS m / z: 320 [M+H] + .

[0391] 9) Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(3-(1-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)ureo)piperidin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide:

[0392] To a solution of 1,4-dioxane (20 mL) containing 3-(7-(3-aminoazacyclobutane-1-yl)-5-fluoro-2,3-dihydrobenzofuran-4-yl)piperidin-2,6-dione (101 mg, 0.317 mmol), add (1-(4-(6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(dimethylaminoyl)-1H-indol-4-yl)phenyl)piperidin-4-yl)phenyl carboxylate (217.5 mg, 0.317 mmol) and DMAP (46.4 mg, 0.380 mmol), heat to 90 °C and stir for 2 hours. Dilute the mixture with water (30 mL) and extract with ethyl acetate (30 mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then subjected to preparative high-performance liquid chromatography (HPLC) (system: Waters 3767 / Qda; column: Sunfire C18, 19*250mm, 10µm; mobile phase A: H₂O, mobile phase B: ACN; flow rate: 20mL / min; gradient: 46-56%, retention time: 9.6-10.5min). Purification for 16 min yielded 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(3-(1-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydrobenzofuran-7-yl)azacyclobutane-3-yl)ureo)piperidin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (127 mg, yield: 45%), LCMS: m / z: 912 [M+H] + .

[0393] Example 2: Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound 2) and its isomers (compounds 2-1 and 2-2):

[0394] 1) Synthesis of 2,6-bis(benzyloxy)-3-(4-bromo-5-fluorobenzofuran-7-yl)pyridine

[0395] Under nitrogen protection, Pd(dppf)Cl2 (10.72 g, 14.66 mmol, 0.1 eq) was added to a mixed solution of 4-bromo-5-fluoro-7-iodobenzofuran (50 g, 146.6 mmol, 1.0 eq), 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxopentaborane-2-yl)pyridine (91.72 g, 219.9 mmol, 1.5 eq) and K2CO3 (60.70 g, 439.9 mmol, 3.0 eq) in dioxane / water (1400 mL / 140 mL). After thorough stirring, the reaction mixture was heated to 100 °C and stirred for approximately 16 h. Cool to room temperature, quench with water (1000 mL), extract with ethyl acetate (500 mL × 3), combine organic phases, back-extract with saturated brine (500 mL), dry to anhydrous Na₂SO₄, filter and concentrate under reduced pressure. The residue is purified by silica gel column chromatography (PE / EA = 10 / 1 elution) to give 2,6-bis(benzyloxy)-3-(4-bromo-5-fluorobenzofuran-7-yl)pyridine (50.5 g, 68.3% yield). LC-MS M / Z: 506 [M+H] + .

[0396] 2) Synthesis of 2,6-bis(benzyloxy)-3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)pyridine:

[0397] Under nitrogen protection, PdCl2APhOS (7.02 g, 9.92 mmol, 0.1 eq) was added to a toluene / water (500 mL / 50 mL) mixture of 2,6-bis(benzyloxy)-3-(4-bromo-5-fluorobenzofuran-7-yl)pyridine (50 g, 99.21 mmol, 1.0 eq), trifluoro(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-14-boron potassium salt (35.12 g, 148.81 mmol, 1.5 eq), and Cs2CO3 (96.73 g, 297.62 mmol, 3.0 eq) and stirred until homogeneous. The reaction mixture was then heated to 100 °C. oThe reaction was stirred at C for approximately 16 hours. After cooling to room temperature, water (300 mL) was added to quench the reaction, followed by extraction with ethyl acetate (300 mL × 3). The combined organic phases were back-extracted with saturated brine (300 mL), dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE / EA = 10 / 1 elution) to give 2,6-bis(benzyloxy)-3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)pyridine (20 g, yield 36.4%). LC-MS M / Z: 555 [M+H] + .

[0398] 3) Synthesis of 3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)piperidine-2,6-dione:

[0399] Under nitrogen protection, Pd / C (800 mg) and Pd(OH)₂ (800 mg) were added to a THF (320 mL) solution of 2,6-bis(benzyloxy)-3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)pyridine (8 g, 15.87 mmol, 1.0 eq). After stirring until homogeneous, the mixture was purged with hydrogen and heated to 40 °C with stirring for approximately 16 h. The mixture was then filtered and concentrated under reduced pressure to obtain 4.8 g of crude 3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)piperidin-2,6-dione. LC-MS M / Z: 393 [M+18] + .

[0400] 4) Synthesis of 3-(5-fluoro-4-(2-hydroxyethyl)benzofuran-7-yl)piperidine-2,6-dione:

[0401] To a THF (50 mL) solution of 4.8 g of the obtained above-prepared 3-(5-fluoro-4-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzofuran-7-yl)piperidin-2,6-dione (5 mL), 6N HCl aqueous solution (5 mL) was added. The reaction mixture was stirred at room temperature for about 6 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (100 mL × 3). The organic phases were combined, back-extracted with saturated brine (100 mL), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to give 3-(5-fluoro-4-(2-hydroxyethyl)benzofuran-7-yl)piperidin-2,6-dione (3.1 g crude product). LC-MS M / Z: 309.2 [M+18] + .

[0402] 5) Synthesis of 2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)acetaldehyde:

[0403] At room temperature, IBX (5.77 g, 20.62 mmol, 2.0 eq) was added to a MeCN (150 mL) solution of 3-(5-fluoro-4-(2-hydroxyethyl)benzofuran-7-yl)piperidin-2,6-dione (3 g, 10.31 mmol, 1.0 eq). After stirring, the reaction mixture was heated to 70 °C and stirred for about 2 h. After cooling to room temperature, water (150 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (150 mL x 3). The organic phases were combined, back-extracted with saturated brine (100 mL), dried over anhydrous Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure to give 2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)acetaldehyde (3 g crude). LC-MS: m / z = 307.2 [M+18] + .

[0404] 6) Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide)

[0405] Under 0°C ice bath conditions, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxamide trifluoroacetate (11.76 g, approximately 20.62 mmol, 1 eq) and AcOH (1 mL) were added to a MeOH solution of 2-(7-(2,6-dioxadiazin-3-yl)-5-fluorobenzofuran-4-yl)acetaldehyde (13 g crude, approximately 20.62 mmol, 1 eq). After thorough stirring, NaBH3CN (2.60 g, 41.22 mmol, 2.0 eq) was added to the reaction mixture. The mixture was allowed to rise naturally to room temperature, and the reaction was continued with stirring for approximately 16 h. Water (150 mL) was added to the reaction mixture, and the mixture was extracted with DCM (300 mL x 3). The organic phases were combined, back-extracted with saturated brine (300 mL), dried over anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM:MeOH 10:1 elution) to give 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (5.2 g, approximately 30% yield). LC-MS: m / z: 844.4 [M+H] + .

[0406] 7) Resolution of the two isomers of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide:

[0407] 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(7-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-4-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (5.2 g, 6.161 mmol) was purified by chiral column chromatography (using K-Prep). The LAB100G system was used, with a REGIS(S,S)WHELK-O1 column (250*40mm, 10μm particle size); mobile phase A was ACN, and mobile phase B was MeOH (A:B = 10:90); detection wavelength was 214nm; flow rate was 100mL / min; column temperature was RT; back pressure was 100bar; injection volume was 30mL; and circulation time was 26min to obtain the crude product. This crude product was further purified by preparative high-performance liquid chromatography (Waters 2767 / Qda system, XBridge C18 column (19*250mm, 10μm); mobile phase A was 10mmol / L NH4HCO3 / H2O, and mobile phase B was ACN; flow rate was 20mL / min; gradient elution: 41-41%; retention time within 20min: 11.20-13.10min). Two isomers were obtained:

[0408] Compound 2-1: Peak 1. Chiral HPLC: 24.363 min; (544.55 mg, 0.645 mmol, yield 10.47%). LC-MS M / Z: 844.6 [M+H] + .

[0409] 1 H NMR (400MHz, DMSO-d6): δ12.15-12.08(m,1H),10.93(s,1H),8.11(d,J=11.2Hz,1H),8.04(d,J=2.0Hz,1H),7.68(d,J=11.6Hz 1H),7.56-7.49(m,2H),7.14(d,J=2.0Hz,1H),7.10-7.13(m,3H),7.02-6.90 (m,1H),6.87-6.84(m,1H),6.18-6.11(m,1H),4.67-4.56(m,2H),4.42-4.30 (m,2H),4.24(dd,J=12.4,4.8Hz,1H),3,70-3.55(m,2H),3.28-2.94(m,14H) ,2.86-2.72(m,1H),2.72-2.51(m,7H),2.48-2.23(m,3H),2.11-2.01(m,1H).

[0410] 19 F NMR (377MHz, DMSO-d6): δ-127.318,-136.638,-136.819

[0411] Compound 2-2: Peak 2. Chiral HPLC: 37.605 min; (230.21 mg, 0.273 mmol, yield 4.43%). LC-MS M / Z: 844.6 [M+H] + .

[0412] 1 H NMR (400MHz, DMSO-d6): δ12.15-12.08(m,1H),10.93(s,1H),8.11(d,J=11.2Hz,1H),8.04(d,J=2.0Hz,1H),7.68(d,J=11.6Hz 1H),7.56-7.49(m,2H),7.14(d,J=2.0Hz,1H),7.10-7.13(m,3H),7.02-6.90 (m,1H),6.87-6.84(m,1H),6.18-6.11(m,1H),4.67-4.56(m,2H),4.42-4.30 (m,2H),4.24(dd,J=12.4,4.8Hz,1H),3,70-3.55(m,2H),3.28-2.94(m,14H) ,2.86-2.72(m,1H),2.72-2.51(m,7H),2.48-2.23(m,3H),2.11-2.01(m,1H).

[0413] 19 F NMR (377MHz, DMSO-d6): δ-127.318, -136.638, -136.819.

[0414] Example 3: Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound 3) and its R / S isomers (compound 3-1 and compound 3-2):

[0415] 1) Synthesis of (E)-4-bromo-7-(2-ethoxyvinyl)-5-fluorobenzofuran:

[0416] Under nitrogen protection, K3PO4 (37 g, 175.95 mmol, 3.0 eq), RuPhos (2.7 g, 5.87 mmol, 0.1 eq), compound 2 (23 g, 117.3 mmol, 2.0 eq), and Pd(OAc)2 (1.3 g, 5.87 mmol, 0.1 eq) were added sequentially to a solution of 4-bromo-5-fluoro-7-iodobenzofuran (20 g, 58.65 mmol, 1.0 eq) in i-PrOH (1000 mL). After thorough stirring, the mixture was heated to 60 °C and stirred for approximately 16 h. After cooling to room temperature, the mixture was diluted with water (500 mL) and extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE elution) to give (E)-4-bromo-7-(2-ethoxyvinyl)-5-fluorobenzofuran (10.3 g, 36.14 mmol, 61.7% yield).

[0417] 1 H NMR (400MHz, CDCl3) δ7.62(d,J=2.2Hz,1H),7.47(d,J=12.9Hz,1H),6.82(d,J=10.2Hz,1H), 6.73(d,J=2.2Hz,1H), 5.83(d,J=12.9Hz,1H), 3.91(q,J=7.0Hz,2H), 1.30(t,J=7.0Hz,3H).

[0418] 2) Synthesis of 2-(4-bromo-5-fluorobenzofuran-7-yl)acetaldehyde:

[0419] At room temperature, a 6N HCl aqueous solution (50 mL) was added to a THF (50 mL) solution of (E)-4-bromo-7-(2-ethoxyvinyl)-5-fluorobenzofuran (9.2 g, 32.28 mmol, 1.0 eq). After stirring until homogeneous, the reaction mixture was heated to 45 °C and stirred for 1 h under nitrogen protection. The reaction mixture was diluted with water (300 mL) and extracted with ethyl acetate (300 mL × 3). The combined organic phases were dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to give 2-(4-bromo-5-fluorobenzofuran-7-yl)acetaldehyde (8.5 g crude product).

[0420] 3) Synthesis of 2-(4-bromo-5-fluorobenzofuran-7-yl)ethyl-1-ol:

[0421] Under ice bath conditions at 0°C, NaBH4 (2.5 g, 66.14 mmol, 2.5 eq) was added to a MeOH (100 mL) solution of 8.5 g of 2-(4-bromo-5-fluorobenzofuran-7-yl)acetaldehyde. The mixture was then allowed to rise naturally to room temperature and stirred for about 1 h. The reaction was quenched with 300 mL of saturated NH4Cl aqueous solution and extracted with ethyl acetate (300 mL × 3). The combined organic phases were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE / EA = 2 / 1 elution) to give 2-(4-bromo-5-fluorobenzofuran-7-yl)ethyl-1-ol (6.9 g, approximately 80.6% yield).

[0422] 1 H NMR (400MHz, DMSO-d6) δ8.19(s,1H),7.25(d,J=10.2Hz,1H),6.97(s,1H),4.80(t,J=5.3Hz,1H),3.75(dd,J=12.2,6.7Hz,2H),3.00(t,J=6.7Hz,2H).

[0423] 4) Synthesis of (2-(4-bromo-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane:

[0424] Under ice bath conditions at 0°C, imidazole (3.0 g, 43.44 mmol, 1.1 eq) and TBSCl (4.8 g, 31.86 mmol, 1.5 eq) were added to a DCM (200 mL) solution of 2-(4-bromo-5-fluorobenzofuran-7-yl)ethyl-1-ol (7.5 g, 28.96 mmol, 1.0 eq). After stirring, the mixture was reacted at room temperature for approximately 2 h. The reaction mixture was diluted with water (300 mL) and extracted with ethyl acetate (300 mL × 3). The organic phases were combined and dried over anhydrous Na₂SO₄. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE / EA = 10:1 elution) to give (2-(4-bromo-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane (10 g, approximately 93% yield).

[0425] 1 H NMR (400MHz, DMSO-d6) δ8.29(d,J=2.2Hz,1H),7.34(d,J=10.2Hz,1H),7.07(d,J=2.2Hz,1H), 4.01(t,J=6.4Hz,2H),3.14(t,J=6.4Hz,2H),1.30(t,J=7.1Hz,1H),0.87(s,9H),0.00(s,6H).

[0426] 5) Synthesis of (2-(4-(3,5-bis(benzyloxy)phenyl)-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane:

[0427] Under nitrogen protection, Na₂CO₃ (5.7 g, 53.63 mmol, 2.5 eq), 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)pyridine (1.3 g, 32.18 mmol, 1.5 eq), and Pd(dppf)Cl₂ (1.6 g, 2.15 mmol, 0.1 eq) were added to a dioxane / water (300 mL / 30 mL) mixture of (2-(4-bromo-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane (8 g, 21.45 mmol, 1.0 eq) (300 mL / 30 mL) under dioxane / water mixture. After stirring until homogeneous, the reaction mixture was heated to 80 °C and stirred for approximately 16 h under nitrogen protection. After cooling to room temperature, the reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE / EA = 10:1 elution) to give (2-(4-(3,5-bis(benzyloxy)phenyl)-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane (9 g, 72% yield). LCMS: m / z = 584.3 [M+H] + .

[0428] 6) Synthesis of 3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5-fluorobenzofuran-4-yl)piperidine-2,6-dione:

[0429] Under nitrogen protection, Pd / C (0.5 g, 50% aqueous solution) and Pd(OH)₂ (500 mg, 50% aqueous solution) were added to a THF (500 mL) solution of (2-(4-(3,5-bis(benzyloxy)phenyl)-5-fluorobenzofuran-7-yl)ethoxy)(tert-butyl)dimethylsilane (5 g, 8.58 mmol, 1.0 eq). After stirring until homogeneous, the mixture was heated to 50 °C and stirred for approximately 16 h under nitrogen protection. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give 3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5-fluorobenzofuran-4-yl)piperidin-2,6-dione. LC-MS: m / z: 406.3 [M+H] + .

[0430] 1H NMR (400MHz, DMSO-d6) δ11.00(s,1H),8.12(d,J=2.0Hz,1H),7.13(d,J=9.6Hz,1H),7.08(d,J=2.4Hz,1H),4.42(dd,J=12.8,4.8Hz,1H),3.97 (t,J=6.8Hz,2H),3.10(t,J=6.6Hz,2H),2.95-2.80(m,1H),2.81-2.50 (m1H),2.44-2.22(m,1H),2.10-2.02(m,1H),0.86(s,9H),0.00(s,6H).

[0431] 7) Synthesis of 3-(5-fluoro-7-(2-hydroxyethyl)benzofuran-4-yl)piperidine-2,6-dione:

[0432] Under nitrogen protection at room temperature, TBAF (3.5 g, 13.31 mmol, 1.5 eq) was added to a THF (70 mL) solution of 3-(7-(2-((tert-butyldimethylsilyl)oxy)ethyl)-5-fluorobenzofuran-4-yl)piperidin-2,6-dione (3.6 g, 8.87 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for approximately 16 h. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (200 mL × 3). The organic phases were combined and dried over anhydrous Na₂SO₄. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (PE / EA = 1 / 3 elution) to give 3-(5-fluoro-7-(2-hydroxyethyl)benzofuran-4-yl)piperidin-2,6-dione (780 mg, 2.68 mmol). LC-MS: m / z: 309.2 [M+18] + .

[0433] 8) Synthesis of 2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)acetaldehyde:

[0434] At room temperature, IBX (3755 mg, 13.41 mmol, 3.0 eq) was added to a MeCN (50 mL) solution of 3-(5-fluoro-7-(2-hydroxyethyl)benzofuran-4-yl)piperidin-2,6-dione (1300 mg, 4.47 mmol, 1.0 eq). After stirring until homogeneous, the reaction mixture was heated to 70 °C and stirred for approximately 16 h. After cooling to room temperature, a saturated NaHCO3 solution (100 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL x 3). The organic phases were combined, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure to give 2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)acetaldehyde (2 mg crude). LC-MS: m / z = 307.2 [M+18] + .

[0435] 9) Synthesis of 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid:

[0436] At room temperature, LiOH·H₂O (29.32 g, 732.90 mmol, 5.0 eq) was added to a THF / H₂O (1000 mL / 250 mL) mixture of methyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid (45.00 g, 146.58 mmol, 1.0 eq) and methyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid (40.00 g, approximately 93% yield). After stirring thoroughly, the reaction mixture was heated to 50 °C and stirred for approximately 2 h. The pH was adjusted to 5-6 with concentrated hydrochloric acid, resulting in the precipitation of a large amount of solid. The mixture was filtered, and the filter cake was washed with water (200 mL). After drying under reduced pressure, 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid was obtained. LC-MS: m / z: 291.8 [M+H] +

[0437] 10) Synthesis of 6-bromo-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide:

[0438] At room temperature, T4P (140.55 g, 195.21 mmol, 1.5 eq, containing 50% EA) and DIEA (33.58 g, 260.28 mmol, 2.0 eq) were added sequentially to THF (1000 mL) containing 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid (38.00 g, 130.14 mmol, 1.0 eq) and dimethylamine hydrochloride (5.33 g, 65.07 mmol, 1.0 eq). The reaction mixture was stirred for approximately 16 h. A saturated NaHCO3 solution (300 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (200 mL × 2). The organic phases were combined, back-extracted with saturated brine (200 mL), and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the mixture was slurried with ethyl acetate (200 mL), filtered, and the filter cake was dried to give 6-bromo-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (40.00 g, 31.25 mmol, yield 96.0%). LC-MS: m / z: 320.8 [M+H] +

[0439] 11) Synthesis of 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxoboronan-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)propane-1-one:

[0440] Under nitrogen protection at room temperature, NMI (37 g, 453.92 mmol, 4.0 eq), TCFH (63.8 g, 226.96 mmol, 2.0 eq), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentan-2-yl)-1,2,3,6-tetrahydropyridine (23.7 g, 113.48 mmol, 1.0 eq) were added to a MeCN (1000 mL) solution of 3-(1H-1,2,3-triazol-1-yl)propionic acid (16 g, 113.48 mmol, 1.0 eq). The reaction mixture was stirred for approximately 2 h while maintaining the reaction conditions. The reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (500 mL × 3). The organic phases were combined, dissolved in anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM / MeOH = 20 / 1 elution) to give 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxoboronan-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)propane-1-one (24.7 g, 74.40 mmol, yield 65.56%). LC-MS: m / z = 333.3 [M+H] + .

[0441] 12) Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide:

[0442] Under nitrogen protection at room temperature, K₂CO₃ (14.6 g, 105.48 mmol, 2.5 eq), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)propane-1-one (15.4 g, 46.41 mmol, 1.1 eq), and Pd(dppf)Cl₂ (3.1 g, 4.22 mmol, 0.1 eq) were added to a dioxane / water (400 mL / 40 mL) mixed solution of 6-bromo-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (13.5 g, 42.19 mmol, 1.0 eq) at room temperature, 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)propane-1-one (15.4 g, 46.41 mmol, 1.1 eq) and 1-(dppf)Cl₂ (3.1 g, 4.22 mmol, 0.1 eq) after stirring. The reaction mixture was then heated to 80 °C and stirred for approximately 16 h. Cool to room temperature, dilute with water (500 mL), and extract with ethyl acetate (500 mL × 3). Combine the organic phases, dry over anhydrous Na₂SO₄, filter, concentrate the filtrate under reduced pressure, and purify the residue by silica gel column chromatography (DCM / MeOH = 20 / 1 elution) to give 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (13 g, 29.21 mmol, yield 69.51%). LC-MS: m / z: 445.3 [M+H] + .

[0443] 13) Synthesis of tert-butyl piperazine-1-carboxylate:

[0444] Under nitrogen protection at room temperature, 4-(4-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (20 g, 45.05 mmol, 1.0 eq) tert-butyl piperazine-1-carboxylate (21 g, 54.05 mmol, 1.2 eq), Pd(dppf)Cl2 (3.30 g, 4.51 mmol, 0.1 eq) and K2CO3 (18.65 g, 135.15 mmol, 3.0 eq) were added to a mixed solution of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (300 mL / 30 mL) in dioxane / water (300 mL / 30 mL). After stirring thoroughly, the mixture was heated to 100℃ and stirred for approximately 3 hours. After cooling to room temperature, it was diluted with water (200 mL) and extracted with ethyl acetate (100 mL). The organic phase was back-extracted with saturated brine (200 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (DCM / MeOH = 10 / 1 elution) to give tert-butyl 4-(4-(6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(dimethylaminoyl)-7-fluoro-1H-indol-4-yl)phenyl)piperazine-1-carboxylate (21.0 g, yield 69.6%). LC-MS: m / z: 671 [M+H] + .

[0445] 14) Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxamide:

[0446] At room temperature, 50 mL of TFA was added to a solution of 21 g (45.05 mmol, 1.0 eq) of tert-butyl piperazine-1-carboxylate in DCM. The reaction was stirred for approximately 3 h. Concentration under reduced pressure yielded 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxamide trifluoroacetate (20.0 g, yield 98.48%). LC-MS: m / z: 571.3 [M+H] + .

[0447] 15) Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide:

[0448] Under 0°C ice bath conditions, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxamide trifluoroacetate (4345 mg, 7.61 mmol, 1.1 eq) and AcOH (1 mL) were added to a MeOH solution containing 2-(4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxamide trifluoroacetate (4345 mg, 7.61 mmol, 1.1 eq) and AcOH (1 mL). After stirring for about 30 min, NaBH3CN (1090 mg, 17.3 mmol, 2.5 eq) was added to the reaction mixture. The mixture was allowed to rise naturally to room temperature and the reaction was continued with stirring for about 3 h. Add 200 mL of saturated NH4Cl aqueous solution to the reaction mixture and extract with ethyl acetate (200 mL x 3). Combine the organic phases, remove anhydrous Na2SO4, filter, concentrate the filtrate under reduced pressure, and purify the residue by silica gel column chromatography (elution with DCM:MeOH from 100:1 to 20:1) to give 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (1800 mg, 2.13 mmol, yield 30.8%). LC-MS: m / z: 844.4 [M+H] + .

[0449] 16) Resolution of the R / S isomers of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide:

[0450] The obtained 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (4.2 g, 4.976 mmol) was purified by chiral chromatography (using a YMC K-prep 100 system, Regis column). WHELK-O1(S,S) type, specification 250*40mm, particle size 10μm; mobile phase A:ACN, B:EtOH, A:B = 30:70; detection wavelength 214nm; flow rate 80mL / min; column temperature RT; back pressure 100bar; injection volume 1.5mL; cycle time 7min, to obtain crude product. This crude product was further purified by prep-HPLC (Waters 3767 / QDA, column: Green ODS, 30*150mm, 5μm; mobile phase A: 0.1% FA / H2O, B:ACN; flow rate 20mL / min; gradient: 25-45%; retention time 8-10min within 18min). Purification yielded two isomers:

[0451] Compound 3-1: Peak 1 chiral HPLC: 28.047 min; (712.85 mg, 0.845 mmol, yield 16.97%). M / Z = 844.6 [M+H]+.

[0452] 1 H NMR (400MHz, DMSO-d6): δ12.14-12.08(m,1H),10.94(s,1H),8.15-8.08(m,1H),8.06(d,J=2.4Hz,1H),7.71-7.66(m,1H),7.52(dd,J=8.8,2.4H,z 2H),7.13(d,J=11.2Hz,1H),7.06(d,J=4.8Hz,2H),7.02(d,J=2.4Hz,1 H),7.02-6.90(m,1H),6.84-6.83(m,1H),6.18-6.11(m,1H),4.67-4.58 (m,2H),4.42-4.30(m,3H),3.70-3.55(m,2H),3.28-2.94(m,14H),2.86 -2.64(m,7H),2.61-2.51(m,1H),2.40-2.21(m,3H),2.06-1.96(m,1H).

[0453] 19F NMR (377MHz, DMSO-d6): δ-124.213,-136.638,-136.819

[0454] Compound 3-2: Peak 2 chiral HPLC: 38.479 min; (714.92 mg, 0.837 mmol, yield 17.02%). M / Z = 844.6 [M+H] + .

[0455] 1 H NMR (400MHz, DMSO-d6): δ12.14-12.08(m,1H),10.94(s,1H),8.15-8.08(m,1H),8.06(d,J=2.4Hz,1H),7.71-7.66(m,1H),7.52(dd,J=8.8,2.4H,z 2H),7.13(d,J=11.2Hz,1H),7.06(d,J=4.8Hz,2H),7.02(d,J=2.4Hz,1 H),7.02-6.90(m,1H),6.84-6.83(m,1H),6.18-6.11(m,1H),4.67-4.58 (m,2H),4.42-4.30(m,3H),3.70-3.55(m,2H),3.28-2.94(m,14H),2.86 -2.64(m,7H),2.61-2.51(m,1H),2.40-2.21(m,3H),2.06-1.96(m,1H).

[0456] 19 F NMR (377MHz, DMSO-d6): δ-124.200,-136.637,-136.821

[0457] Example 4: Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-1H-indole-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide (compound 4):

[0458] Following steps similar to those in Examples 1-3, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-1H-indol-7-yl)ethyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indol-2-carboxamide (compound 4) was obtained. LC-MS M / Z: 843.5 [M+H] + .

[0459] Example 5: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-1H-indol-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indol-2-carboxamide (Compound 5)

[0460] Following steps similar to Examples 1-4, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluoro-1H-indol-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indol-2-carboxamide (compound 5) was obtained. LC-MS M / Z: 825.3 [M+H] + .

[0461] Example 6: Synthesis of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperazin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound 6):

[0462] Following steps similar to those in Examples 1-4, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperazin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound 6) was obtained. LC-MS M / Z: 826.5 [M+H] + .

[0463] Example 7: Synthesis of 6-((R)-1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-6-methyl-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound 7):

[0464] Following steps similar to those in Examples 1-6, 6-((R)-1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-6-methyl-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)-5-fluorobenzofuran-7-yl)ethyl)piperazin-1-yl)phenyl)-N,N-dimethyl-1H-indole-2-carboxamide (compound 7) was obtained. LC-MS M / Z: 840.4 [M+H] + .

[0465] Example 8: Synthesis of the following compound:

[0466] Following the synthesis steps of Examples 1-7 above, the compounds were obtained as shown in Tables A, B, and C below:

[0467] Table A

[0468] Table B

[0469] Table C

[0470] Test Example 1: Detection of the test substance's degradation activity against the target protein

[0471] 1. Experimental Objective

[0472] Using 293T-STAT6-HiBiT-KI cells, the degradation activity of the test substance on the target ATAT6 protein was evaluated by the HiBiT method based on changes in the fluorescence signal intensity of the intracellular target abundance.

[0473] 2. Experimental Materials

[0474] HiBiT Lytic Detection System, DMEM, FBS, FBS, 96-well cell plate.

[0475] 3. Experimental Procedure

[0476] All cell lines were cultured in complete medium at 37°C and 5% CO2. Cells in the logarithmic growth phase were harvested and counted using a platelet counter. Cell viability was assessed using the trypan blue rejection assay to ensure it was above 90%. Cell density was adjusted with complete medium and then seeded into 96-well cell culture plates at 90 μL per well, for a total of 10,000 cells. Cells in the 96-well plates were cultured overnight at 37°C and 5% CO2. Tenfold drug solutions were prepared: the working concentration of the test compound was 1000 nM, with 10 concentrations and 3-fold dilutions; the working concentration of the positive control compound DR023-174 was 1000 nM, with 10 concentrations and 3-fold dilutions. 10 μL of each serially diluted compound was then transferred to the corresponding wells of the 96-well cell culture plate, with three replicates for each drug concentration. Cells in the drug-treated 96-well plates were cultured for another 48 hours at 37°C and 5% CO2, followed by target protein degradation analysis. Equilibrate the cell plate to room temperature for 30 minutes using the HiBiT Lytic Detection System reagent. Take a new 50 mL sterile tube and use an appropriate volume of room temperature reagent. HiBiT Lytic Buffer diluted LgBiT Protein (1:100) and Mix HiBiT Lytic Substrate (1:50) by inverting the container. Add 100 μL of the prepared solution to each well. In a light-protected environment, use the HiBiT lysis reagent and shake at 300 rpm on a track-mounted shaker for 5 minutes to lyse the cells. Incubate the cell plate at room temperature for 20 minutes to stabilize the light signal. Use a multi-functional microplate reader (Microplate Reader). Plus, BMG) reads signal values ​​and collects data in Luminescence mode.

[0477] 4. Data Analysis:

[0478] Data was analyzed using GraphPad Prism 7.0 software. A nonlinear S-curve regression was used to fit the data to derive the dose-response curve, and the dose-response ratio (DC) was calculated from this curve. 50 value.

[0479] Hibit signal:%of Control=(Lum 待测药 -Lum 培养液对照 ) / (Lum 溶剂对照 -Lum 培养液对照 )×100%.

[0480] Degradation efficiency: Degradation% = 100 - (Lum) 待测药 -Lum 培养液对照 ) / (Lum 溶剂对照 -Lum 培养液对照 )×100%.

[0481] Test Example 2: Detection of the test substance's degradation activity against the target protein

[0482] The HiBiT method was used to test the degradation activity of the compound against the STAT-6 target in Jurkat-STAT6-HiBiT-KI cells.

[0483] 2-1. Reagents and Consumables

[0484] Table 2-1

[0485] 2-2. Instruments and Equipment

[0486] Table 2-2

[0487] 2-3. Experimental Procedure

[0488] Cell culture conditions: RPMI 1640 medium, 10% FBS, 1% PS, cultured in a 37℃ & 5% CO2 incubator.

[0489] Aisipu constructed a Jurkat-STAT6-HiBiT-KI monoclonal cell line with a HiBiT tag inserted at the C-terminus of the STAT6 cell line for compound degradation activity testing. Cells were seeded in 384-well plates (Corning, 33764) at 10,000 cells / 40 μL RPMI 1640 medium (Hyclone, SH30809.01) containing 10% fetal bovine serum (Avantor, 76294-180) and 1% penicillin / streptomycin (Gibco, 15140-122). Serially diluted compounds were then added to the 384-well cell culture plates (40 nL to 40 μL) using an ECHO 665 ultrasonic pipetting system (Labcyte) to bring the final DMSO concentration to 0.1%. The plates were incubated at 37°C and 5% CO2 for 24 h. Before detection, remove the plate and allow it to equilibrate at room temperature for 10 minutes. Add 20 μL of the prepared Nano-Glo HiBiT Lytic assay reagent (Promega, N3040) to the 384-well plate. Shake in the dark for 3 minutes and then use a microplate reader (BMG, PHERAstar FSX) to detect the luminescence intensity.

[0490] 2-4. Data Processing and Analysis

[0491] The degradation rate is calculated using the following formula:

[0492] Degradation rate % = (Ave_H - Sample) / Ave_H * 100%, where Ave_H is the average value of the DMSO wells and Sample is the reading from the compound-treated wells. DC was calculated using 4-parameter fitting with Xlfit data analysis software. 50 The results are shown in the table below:

[0493] Table 2-3 Degradation activities of representative compounds against STAT-6 target

[0494] Reference molecular structure is The synthetic route is as described in patent WO2025049820.

[0495] The results above show that, compared with the reference molecule, some of the representative compounds of this invention have higher target degradation activity.

[0496] Test Example 3: Rat PK test to evaluate the pharmacokinetic characteristics of representative compounds.

[0497] The test compound was dissolved in the drug delivery solvent (IV: 5% DMSO + 5% Solutol + 90% Saline; PO: 5% DMSO + 5% Solutol + 90% Saline) to prepare a stock solution.

[0498] Drug administration and blood collection:

[0499] This experiment used male SD rats, with 3 rats in each group, and administered the drugs at a dose of 1 mg / kg IV and 10 mg / kg PO. The animals in the oral administration group were fasted overnight but had free access to water the day before administration.

[0500] Plasma samples were collected after drug administration at the following time points: 0.083 h, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 h after IV administration; and 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after PO administration. (Blood was collected via the jugular vein or other suitable vein, 0.2 mL / time point, anticoagulated with K2-EDTA. Plasma was obtained by centrifugation within 1 h after blood sample collection (centrifugation conditions: 6800 g, 6 min, 2-8℃). Samples were stored at -80℃ before analysis.)

[0501] Biological sample analysis

[0502] The drug concentration in plasma was determined using LC-MS / MS. Pharmacokinetic parameters, such as AUC(0-t), T1 / 2, Cmax, Tmax, and MRT, were calculated using WinNonlin based on plasma drug concentration data at different time points.

[0503] Results Summary and Analysis

[0504] The mean pharmacokinetic parameters of representative compounds in rats are shown in the table below:

[0505] Table 3-1 Mean pharmacokinetic parameters of representative compounds in rats

[0506] Note: Data in the table are averages; MPK: mg / kg; IV: intravenous injection; PO: oral administration.

[0507] The above results indicate that the representative novel compounds of this invention not only possess superior target degradation activity but also exhibit excellent PK characteristics. They also demonstrate relatively high exposure rates and considerable bioavailability when taken orally, and therefore can be developed as oral drugs for disease prevention and treatment in animals or humans.

[0508] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

Compounds of formula (I), their pharmaceutically acceptable salts, solvates, enantiomers, or isotopic substitutes, in, A, B, C, D, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N; L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 ); X4 is arbitrarily and independently selected from C(R3) or N; Q1 can be arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C 3-10 Heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "hybrid" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. The compound according to claim 1, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute, is characterized in that, It has a (IA) structure. in, A, B, C, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N; L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 ); X4 is arbitrarily and independently selected from C(R3) or N; Q1, Q2, and Q3 can be independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having the structure of formula (IB). in, A, B, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. "Any" represents a single or double bond, and when When it is a single bond, X1, X2, and X3 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 )P(=Y)–, -OS(=Y)-, -S(=O)2-; and when When it is a double bond, X1, X2, and X3 are arbitrarily and independently selected from C(R) d1 ) or N; L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 ); X4 is arbitrarily and independently selected from C(R3) or N; Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-10 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. The compound, pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute according to claim 1 or 2, is characterized in that, It has a (IC) structure. in, A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C; X4 is arbitrarily and independently selected from C(R3) or N; L can be arbitrarily and independently selected from non-existent, single bond, O, S, or N (R) d7 ); Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having a structure of formula (ID). in, A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C; X4 is arbitrarily and independently selected from C(R3) or N; Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. The compound, pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute according to any one of claims 1-3, is characterized in that, It has an IE structure. in, A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C; Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having a structure of formula (IF). in, A, E, and F are arbitrarily and independently selected from monocyclic or polycyclic structures that are absent, have single bonds, or have 3 to 18 carbon atoms. The monocyclic or polycyclic structures can be arbitrarily selected from aromatic rings, heteroaromatic rings, aliphatic rings, heterocycles, fused rings, spirocycles, or bridged ring structures. Each can independently represent a single bond or a double bond: when When it is a single bond, X3, X1, and X2 are arbitrarily and independently selected from -C(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-, -O-, -S-, -C(=O)O-, -OC(=O)-, -OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-C(=O)-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), -C(=S)-, -S(=O)–, -(R d4 P(=Y)–, -OS(=Y)-, -S(=O)2-, X5 and X6 are arbitrarily and independently selected from C(R3) or N; when When it is a double bond, X3, X1, and X2 are arbitrarily and independently selected from C(R) d1 () or N, X5 and X6 are selected from C; Q1, Q2, Q3, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Y is independently selected from O, S, or =NR0; Each R can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 3-8 membered saturated or partially saturated cycloalkyl and 3-8 membered saturated or partially saturated heterocyclic groups; wherein the hydrogen on R is optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl substitution; Each R0 can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, aminoacyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C 1-10 Alkyl, C 1-10 Halogenated alkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R1 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, -CN, pentafluoride sulfide, -OH, -SH, -NH2, -COOH, or 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 groups, C 3-10 Saturated or partially saturated heterocyclic alkyl groups, C 3-10 cycloalkyl or C 3-10 Heterocyclic alkyl-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 group or carboxyl substitute; wherein the hydrogen on R1 is optionally preferably selected from one or more groups selected from H, deuterium, halogen, OCH3, carboxyl, OH, CN and NR. d8 R d9 Substituents may be used to replace the aryl group; or any two adjacent R1 groups together with their attached atoms may form a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen atom on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R2 may be the same or different, and can be independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, 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 Cycloalkylamine, C3-10 heterocyclic alkylamino, C 3-10 Cycloalkoxy, C 3-10 Cycloalkyl acyl, C 3-10 Cycloalkoxyacetyl, C 3-10 Cycloalkylsulfonyl and C 3-10 cycloalkylsulfinyl group; wherein the hydrogen on R2 is optionally replaced by one or more groups selected from hydrogen, deuterium, halogen, -CN, sulfonium pentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, hydroxyl groups, and saturated or partially saturated C4 groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally further surrounded by one or more atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3 and saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R3 may be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogen, CN, sulfide pentafluoride, OH, SH, NH2, -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 Cyclic hydrocarbon group, C 3-10 Heterocyclic hydrocarbon groups, composed of C 3-10 Cyclic hydrocarbon group or C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Alkyl groups, and those composed of C 3-10 Cyclic hydrocarbon group, C 3-10 C-substituted heterocyclic hydrocarbon groups 1-10 Heteroalkyl; wherein the hydrogen on R3 is optionally replaced by one to a plurality of atoms selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 The group is substituted with a saturated or partially saturated cycloalkyl or heterocyclic group; or any two adjacent R3s together with their attached atoms form a 5-6 membered heteroaryl, a 3-8 membered saturated or partially saturated cycloalkyl, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl, saturated or partially saturated cycloalkyl, or heterocyclic alkyl group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; 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; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. The compound, pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute according to any one of claims 1-4, is characterized in that, It has the structure of formulas (IG-1) to (IG-8). in, F is preferably absent, or contains a triazole ring or a pyrazole ring; Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C; Each X2 can be the same or different, and is preferably selected from O or NR; Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N; Q1, Q2, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 alkyl; Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 alkyl; Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 alkyl; Each R a They can be the same or different, and each can be arbitrarily and independently selected from C. 1-20 Alkoxy, C 1-20 Alkylthio, C 1-20 alkylamine group, C 1-20 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, 3-8 membered saturated or partially saturated cycloalkyl, and 3-8 membered saturated or partially saturated heterocyclic groups; wherein R a The hydrogen atom is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-20 The alkyl group may be optionally separated by 1 to 10 O atoms; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having a structure of formula (IH-1) to (IH-8). in, F is preferably absent, or contains a triazole ring or a pyrazole ring; Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C; Each X2 and X6 can be the same or different, and is preferably selected from O or NR; Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N; Q1, Q2, Q4, and Q5 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 alkyl; Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 alkyl; Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 alkyl; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. Compounds of formula (II), their pharmaceutically acceptable salts, solvates, enantiomers, or isotopic substitutes, in, Ring F is preferably absent, a triazole ring, or a pyrazole ring; The ring G can be arbitrarily and independently selected from the following structures: in This represents the connection site with X4; Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C; Z can be arbitrarily and independently selected from S, S=O, or SO2; Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N; Q1 and Q2 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having a structure of formula (IIA-1) to (IIA-4). Ring F is preferably absent, a triazole ring, or a pyrazole ring; The ring G can be arbitrarily and independently selected from the following structures: in This represents the connection site with X4; Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C; Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N; Q1 and Q2 are arbitrarily and independently selected from C(R0) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3; Preferably, the compound, its pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substituted derivative is characterized by having a structure of formula (IIB-1) to (IIB-18). Ring F is preferably absent, a triazole ring, or a pyrazole ring; Each can independently represent a single bond or a double bond: when When it is a single bond, X5 can be arbitrarily and independently selected from C(R1) or N; when When it is a double bond, X5 is selected from C; Each X4 can be the same or different, and can be arbitrarily and independently selected from C(R3) or N; L1, L2, L3, L4, L5, and L6 are independently selected from non-existent, single bonds, and -C(R) d1 (R) d2 )-、-OC(R d1 (R) d2 )-、-C(R d1 (R) d2 )O-、-OC(R d1 (R) d2 )-、-C(=O)N(R d3 )-、-N(R d3 )C(=O)-、-N(R d4 )-、-C(=NR d5 )-、-S(=O)2N(R d6 )-、-N(R d7 )-、-N(R d7 )C(R d1 (R) d2 -, -O-, -S-, -N(R) d3 )C(=O)-, -C(=O)O-, -OC(=O)-, -C(=O)-, -C(=S)-, -S(=O)–-(R d4 )P(=O)–, -OS(=Y)-, -S(=O)2-, -C(R d1 (R) d2 )C(R d1 (R) d2 )-、-C(R d1 (R) d2 )C(=O)-、(=O)C(R d1 (R) d2 ), olefinic bonds, alkyneic bonds, 6-10 aryl groups, 5-8 heteroaryl groups, 3-18 saturated or partially saturated cycloalkyl groups and 3-18 saturated or partially saturated heterocyclic groups; Each R can be the same or different, and is preferably hydrogen, deuterium, halogen, or C. 1-10 Alkoxy, C 1-10 Alkylamine, -CN, C 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R1 can be the same or different, and is preferably hydrogen, deuterium, halogen, -CN, -OH, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R3 may be the same or different, and each can be arbitrarily and independently selected from hydrogen, deuterium, halogen, or C. 1-10 Alkyl groups, 3-18 membered saturated or partially saturated cycloalkyl groups, and 3-18 membered saturated or partially saturated heterocyclic groups; Each R4, R6, R5, and R7 may be the same or different, and each may be arbitrarily and independently selected from hydrogen, deuterium, halogen, amino acyl, amide, hydroxyl, mercapto, amino, C 1-10 Alkoxy, C 1-10 Alkylthio, C 1-10 Alkylamine, -CN, sulfide pentafluoride, C 1-10 Alkyl, C 2-10 alkenyl, C 2-10 alkynyl group, C 1-10 Alkoxy, -C(=O)NRd8Rd9, 6-10 aryl, 5-8 heteroaryl, 3-8 saturated or partially saturated cycloalkyl, and 3-8 saturated or partially saturated heterocyclic groups; wherein the hydrogen on R0 is further optionally substituted by one or more substituents, said substituents being arbitrarily selected from hydrogen, deuterium, halogen, C1-10 alkyl, C1-10 haloalkyl, cyano, cyanoethyl, O=, OH, C 1-3 Alkyl, C 1-3 Alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group, wherein the C 1-3 Alkyl, C 1-3 The alkoxy, saturated or partially saturated cycloalkyl, or saturated or partially saturated heterocyclic group may be optionally substituted with 1 to 3 substituents selected from H, deuterium, halogen, haloalkyl, cyano, OCH3, and OH. Each R d1 R d2 R d3 R d4 R d5 R d6 R d7 R d8 R d9 They can be the same or different, and can be arbitrarily and independently selected from hydrogen, deuterium, halogens, CN, OH, SH, NH2, -COOH, C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3- 10 Heterocyclic group; wherein the C 1-10 Alkyl, C 2-10 alkynyl or C 1-10 Alkoxy, C 1-10 Alkyl acyl, C 1-10 alkylsulfonyl, C 2-10 Heteroalkyl, C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl, via C 3-10 C-substituted cyclic hydrocarbon groups 1-10 Alkyl or C 3-10 cycloalkyl, C 3-10 Heterocyclic alkyl-substituted C 3-10 The heterocyclic group is optionally surrounded by one or more radicals selected from hydrogen, deuterium, halogen, oxo, CN, OH and C. 3-10 Saturated or partially substituted groups; saturated cycloalkyl or heterocyclic substituents; or R d8 R d9 Together with the atoms attached thereto, it forms a 5-6 membered heteroaryl group, a 3-8 membered saturated or partially saturated cycloalkyl group, or a 3-8 membered saturated or partially saturated heterocyclic group, wherein the hydrogen on the aryl group, saturated or partially saturated cycloalkyl group, or heterocyclic group is optionally selected from hydrogen, deuterium, halogen, -CN, sulfopentafluoride, -OH, CF3, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl groups, =O, and saturated or partially saturated C groups 3-6 Cycloalkyl substitution, and C 1-6 Alkyl and C 1-6 The alkoxy group is optionally surrounded by one or more carbon atoms selected from hydrogen, deuterium, halogen, oxometalate, CN, CF3, OH, OCH3, OCH2CH3, saturated or partially saturated C atoms. 3-6 Cycloalkyl group substitution; The term "heteroatom" refers to any heteroatom and its isotopes that are independently selected from O, N, S, and P. The halogens mentioned are arbitrarily and independently selected from F, Cl, Br, I and their isotopes; n is an integer arbitrarily selected from 0, 1, 2, 3, 4, and 5; f is any integer selected from 0, 1, 2, 3, 4, and 5; p is any integer selected from 0, 1, 2, 3, 4, and 5; q is any integer selected from 0, 1, 2, 3, 4, and 5; s is any integer selected from 0, 1, 2, 3, 4, and 5; t is any integer selected from 0, 1, 2, 3, 4, and 5; v is any integer selected from 0, 1, 2, and 3. The compound, pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute according to any one of claims 1-6, is characterized in that, It has the structure of formula (III), Among them, rings G, R, R1, R5, R6, n, q and v have the definitions described above independently of each other; Ring G is selected from 5-6 membered heteroaryl and 9-10 membered heteroaryl; R is selected from H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy; R1 is selected from hydrogen or methyl; R5 is selected from F or hydrogen; R6 is selected from H or methyl; n, q, and v are selected from 0, 1, 2, or 3; Preferably, ring G is selected from benzofuranyl, indolyl, thienyl, benzodihydrofuranyl, and dihydroindolyl; Preferably, ring G is selected from Preferably, ring G is selected from Among them, *end and connect; Preferably, R is selected from F, methyl, or methoxy; Preferably, Selected from Preferably, Selected from Among them, *end and connect; Preferably, Selected from Preferably, the compound or its pharmaceutically acceptable salt, isotopic substitute or isomer has the structure shown in formula (III-1) or (III-2). Among them, rings G, R and v independently have the definitions described in any one of claims 1-7. The compound, pharmaceutically acceptable salt, solvate, enantiomer, or isotopic substitute according to any one of claims 1-7, is characterized in that, The compound is selected from novel compounds with structures disclosed in this specification. A pharmaceutical composition comprising a therapeutically effective amount of at least one of the compounds of any one of claims 1-8, a pharmaceutically acceptable salt thereof, a solvate thereof, an enantiomer thereof, or an isotopic substitute thereof. The use of the compound of any one of claims 1-8, its pharmaceutically acceptable salt, solvate, enantiomer or isotopic substitute, or the pharmaceutical composition of claim 9 in the preparation of a medicament for the prevention and / or treatment of diseases related to the STATs signaling pathway; preferably, the diseases related to the STATs signaling pathway include, but are not limited to, cancers such as lung cancer, stomach cancer, liver cancer, brain cancer, inflammation, autoimmune diseases, and Alzheimer's disease.

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