Cyclic compound, pharmaceutical composition thereof and use thereof

Abstract

Disclosed in the present invention is a cyclic compound, a pharmaceutical composition thereof and the use thereof. Specifically disclosed in the present invention is a compound as represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof. The compound of the present invention has a new structure and a good inhibitory activity or degradation activity against STAT6.

Description

Cyclic compounds, their pharmaceutical compositions and their applications

[0001] This application claims priority to Chinese patent applications 2025103511238 (filed March 24, 2025), 2025110573544 (filed July 30, 2025), 2025114127330 (filed September 29, 2025), 2026102168762 (filed February 14, 2026), and 2026103300833 (filed March 17, 2026). The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention relates to cyclic compounds, pharmaceutical compositions thereof, and their applications. Background Technology

[0003] Proteolysis-targeting chimeric molecule (PROTAC) is a novel class of drugs that can degrade various proteins associated with human diseases. It offers advantages such as high efficiency, high selectivity, and targeting of "undruggable" proteins. PROTAC technology can be used to target multiple cancer targets, including different targets in solid tumors and hematologic malignancies, and exhibits highly efficient killing of certain tumor cells in a target-dependent manner. Scientists have discovered more than 600 E3 ligases in the human genome. The main E3 ligases used in PROTACs are CRBN, VHL, cIAP, and MDM2, with CRBN and VHL being the most effective and frequently used.

[0004] The signal transducer and activator of transcription (STAT) protein family consists of transcription factors that play important roles in the regulation of cellular processes such as proliferation, differentiation, apoptosis, and angiogenesis. Seven STAT genes have been identified in the human genome: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

[0005] STAT6 has received particular attention, and recent studies have shown that STAT6 signaling is crucial for IL-4 and IL-13-induced epithelial-mesenchymal transition (EMT) and the invasiveness of colorectal cancer cells (CRC). STAT6 (Signal transducer and activator of transcription 6) is involved in intracellular signaling of IL-4 and IL-13. It has been reported that STAT6 deficiency prevents Thrp cells from differentiating into Th2 cells (immunity, 4, 313-319, 1996), and in a mouse model of asthma with STAT6 deficiency, IgE production, increased airway responsiveness, and suppressed eosinophil infiltration of the airways and lungs are observed (J. Exp. Med, 187, 9, 1537-1542, 1998), suggesting that STAT6 is associated with inflammatory respiratory diseases such as asthma.

[0006] Furthermore, reports indicate that administering antigens to patients with allergic rhinitis increases the levels of STAT6 and IL-4 mRNA in the nasal mucosa (Clin. Exp. Allergy 30, 86-93, 1709-1716, 2000). Additionally, overexpression of IL-4 in mice induces dermatitis symptoms such as inflammatory cell infiltration of the skin (J. Invest. Dermatol. 117.4, 977-983 (2001)), suggesting a link between STAT6 and allergic rhinitis and dermatitis. STAT6 binds to the GYKXF motif of the IL-4 receptor α chain (IL-4Ra), a component of both the IL-4 and IL-13 receptors (Science 165, 1265-1267, 1994). These receptors also bind to JAK family kinases. When IL-4 or IL-13 binds to its receptor, STAT6 undergoes tyrosine phosphorylation via JAK family kinases, forming a dimer that translocates to the nucleus to function as a transcription factor (Science 165, 1265-1267, 1994). Therefore, inhibiting any of these processes, such as tyrosine phosphorylation of STAT6, would suppress its function as a transcription factor, potentially offering therapeutic potential for various diseases associated with the aforementioned IL-4 and IL-13.

[0007] STAT6 is involved in multiple aspects of inflammatory diseases and other related conditions. Given its role in the regulation of cellular processes, regulating one or more STAT proteins, specifically the activity of STAT6, is a key area of ​​research for the treatment of cancer, inflammatory conditions, and other therapeutic needs, such as atopic dermatitis, sinusitis, asthma, esophageal diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and peripheral nervous system diseases.

[0008] Published patent applications for STAT6 inhibitors or degraders include: WO2023192960A1, WO2023250058A1, WO2024030628A1, WO2024064080A1, WO2025049820A1 and WO2025049821A1. Summary of the Invention

[0009] The technical problem this invention aims to solve is to address the deficiency in the variety of STAT6 inhibitors or degraders in existing technologies by providing a novel cyclic compound, its pharmaceutical composition, and its applications. The cyclic compound of this invention exhibits good inhibitory or degradative activity against STAT6.

[0010] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0011] This invention provides a compound as shown in formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof:

[0012] Ring B is a saturated or partially unsaturated C3-C ring. 18 Carbon rings, saturated or partially unsaturated 3-18 membered heterocycles, C6-C 18 Aromatic rings or 5-18 membered heteroaromatic rings; in the 3-18 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-18 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 18 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-18 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0013] n is 0, 1, 2, 3, 4 or 5;

[0014] R B Independently for R A-2 R B-1 Hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 =S, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1-S(=O)(=NR) A-1 )R A-1 -S(=NR) A-1 )2R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A- 1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A- 1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=NR A-1 OR A-1 -NR A-1 C(=O)R A-1 NR A-1 C(=NR A-1 )R A-1 -NR A-1 C(=O)N(R A-1 )2、-NR A- 1 C(=NR A-1 )N(R A-1 )2、-NR A-1 C(=NOR A-1 )N(R A-1 )2、-NR A-1 C(=NR A-1 )NH(OR A-1 ) or -NR A-1 S(=O)2R A-1 ;

[0015] R A-2 Independently for C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0016] R B-1 -L B -H, -L B -Cy B1’ or -LB-Cy B11 -Cy B2’ ;

[0017] L B Independently C1-C4 alkylene groups, wherein 0, 1, 2, 3, or 4 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0018] Cy B1’ and Cy B2’ Each independently constitutes C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C3-C 12 cycloalkyl, C3-C12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0019] R A-1 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0020] Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0021] R A-1-1 and R A-2-1 Each independently is: Cy X1 Halogen, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A- 1-1-1 -(CH2) 0-4 CH(OR A-1-1-1 2、-(CH2) 0-4 SR A-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0-1 Ph、-(CH2) 0-4 Py, =(CH2) 0-4 O(CH2)0-1Py, -CH=CHPh, nitro, cyano, azide, =(CH2) 0-4 N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )C(=S)R A-1-1-1 -(CH2) 0- 4N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )C(=S)N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1-1 )C(=O)R A- 1-1-1 -N(R) A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 -(CH2)0-4 C(=O)R A-1-1-1 、-C(=S)R A-1-1-1 、-(CH2) 0-4 -C(=O)OR A-1-1-1 、-(CH2) 0-4 -C(=O)SR A-1-1-1 、-(CH2) 0-4 -C(=O)OSi(R A-1-1-1 )3、-(CH2) 0-4 OC(=O)R A-1-1-1 、-OC(=O)(CH2) 0- 4SR A-1-1-1 、-(CH2) 0-4 SC(=O)R A-1-1-1 、-(CH2) 0-4 C(=O)N(R A-1-1-1 )2、-C(=S)N(R A-1-1-1 )2、-C(=S)SR A-1-1-1 、-SC(=S)SR A-1-1-1 、-(CH2) 0- 4OC(=O)N(R A-1-1-1 )2、-C(=O)N(OR A-1-1-1 )R A-1-1-1 、-C(=O)C(=O)R A-1-1-1 、-C(=O)CH2C(=O)R A-1-1-1 、-C(=NOR A-1-1-1 )R A-1-1-1 、-(CH2) 0-4 SSR A-1-1-1 、-(CH2) 0-4 S(=O)2R A-1-1-1 、-(CH2) 0-4 S(=O)2OR A-1-1-1 、-(CH2) 0-4 OS(=O)2OR A-1-1-1 、-S(=O)2N(R A-1-1-1 )2、-(CH2) 0- 4S(=O)R A-1-1-1 、-N(R A-1-1-1 )S(=O)2N(R A-1-1-1 )2、-N(R A-1-1-1 )S(=O)2R A-1-1-1 、-N(OR A-1-1-1 )R A-1-1-1 、-C(=NH)N(R A-1-1-1 )2、-(CH2) 0- 4P(=O)(R A-1-1-12、-(CH2) 0-4 OP(=O)(R A-1-1-1 2、-(CH2) 0-4 OP(=O)(OR A-1-1-1 )2、-Si(R A-1-1-1 3. -(CH=CH) 0-4 ON(R A-1-1-1 2. -(CH=CH) 0-4 C(=O)ON(R A-1-1-1 )2、=O、=S、=NR A-1-1-1 =NN(R) A-1-1-1 )2、=NNHC(=O)R A-1-1-1 =NNHC(=O)OR A-1-1-1 =NNHS(=O)2R A-1-1-1 =NR A-1-1-1 or = NOR A-1-1-1 ;

[0022] Cy X1 Independently for C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl, 5-14 heteroaryl, optionally bounded by one or more R Z1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0023] R Z1 Independently for R Z1-1 Oxygenation (=O), =NR Z1-1 =S, hydrogen, halogen, cyano, nitro, -OR Z1-1 -SR Z1-1 -N(R) Z1-1 )2、-Si(R Z1-13. -S(=O)R Z1-1 -S(=O)2R Z1-1 -S(=O)(=NR) Z1-1 )R Z1-1 -S(=O)2N(R) Z1-1 )2、-S(=NR Z1-1 )2R Z1-1 -C(=O)R Z1-1 -C(=O)OR Z1-1 -C(=O)N(R) Z1-1 )2、-C(=O)N(R Z1-1 OR Z1-1 -OC(=O)R Z1-1 -OC(=O)N(R) Z1-1 )2、-P(=O)(R Z1-1 )2、-P(=O)(OR Z1-1 )2、-OP(=O)(R Z1- 1 )2、-OP(=O)(OR Z1-1 )2、-NR Z1-1 C(=O)OR Z1-1 -NR Z1-1 C(=O)R Z1-1 -NR Z1-1 C(=NR Z1-1 OR Z1-1 -NR Z1-1 C(=NR Z1-1 )R Z1-1 -NR Z1- 1 C(=NR Z1-1 )N(R Z1-1 )2、-NR Z1-1 C(=NOR Z1-1 )N(R Z1-1 )2、-NR Z1-1 C(=NR Z1-1 )NH(OR Z1-1 -NR Z1-1 C(=O)N(R Z1-1 )2 or -NR Z1- 1 S(=O)2R Z1-1 ;

[0024] R Z1-1 Independently hydrogen, C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. Z1-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0025] Alternatively, two R atoms on the same atom or two adjacent atoms Z1-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R Z1-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0026] R Z1-1-1 Independently halogenated, -(CH2) 0-4 R Z1-1-1-1 -(CH2) 0-4 OR Z1-1-1-1 -O(CH2) 0-4 R Z1-1-1-1 -O(CH2) 0-4 -C(=O)OR Z1-1-1-1 -(CH2) 0- 4CH(OR Z1-1-1-1 2、-(CH2) 0-4 SR Z1-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0-1 Ph、-(CH2)0-4 Py, -(CH2) 0-4 O(CH2) 0-1 Py, -CH=CHPh, nitro, cyano, azido, -(CH2) 0-4 N(R Z1-1-1-1 )2, -(CH2) 0-4 N(R Z1-1-1-1 )C(=O)R Z1-1-1-1 , -N(R Z1-1-1-1 )C(=S)R Z1-1-1-1 , -(CH2) 0-4 N(R Z1- 1-1-1 )C(=O)N(R Z1-1-1-1 )2, -N(R Z1-1-1-1 )C(=S)N(R Z1-1-1-1 )2, -(CH2) 0-4 N(R Z1-1-1-1 )C(=O)OR Z1-1-1-1 , -N(R Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)R Z1- 1-1-1 , -N(R Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)N(R Z1-1-1-1 )2, -N(R Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)OR Z1-1-1-1 , -(CH2) 0-4 C(=O)R Z1-1-1-1 , -C(=S)R Z1-1- 1-1 , -(CH2) 0-4 -C(=O)OR Z1-1-1-1 , -(CH2) 0-4 -C(=O)SR Z1-1-1-1 , -(CH2) 0-4 -C(=O)OSi(R Z1-1-1-1 )3, -(CH2) 0-4 OC(=O)R Z1-1-1-1 , -OC(=O)(CH2) 0-4 SR Z1-1-1-1 , -(CH2) 0-4 SC(=O)R Z1-1-1-1 , -(CH2) 0-4 C(=O)N(R Z1-1-1-1 )2, -C(=S)N(R Z1-1-1-1 )2, -C(=S)SR Z1-1-1-1 , -SC(=S)SR Z1-1-1-1, -(CH2) 0-4 OC(=O)N(R Z1-1-1-1 )2, -C(=O)N(OR Z1-1-1-1 )R Z1-1-1-1 , -C(=O)C(=O)R Z1-1-1-1 , -C(=O)CH2C(=O)R Z1-1-1- 1 , -C(=NOR Z1-1-1-1 )R Z1-1-1-1 , -(CH2) 0-4 SSR Z1-1-1-1 , -(CH2) 0-4 S(=O)2R Z1-1-1-1 , -(CH2) 0-4 S(=O)2OR Z1-1-1-1 , -(CH2) 0-4 OS(=O)2OR Z1- 1-1-1 , -S(=O)2N(R Z1-1-1-1 )2, -(CH2) 0-4 S(=O)R Z1-1-1-1 , -N(R Z1-1-1-1 )S(=O)2N(R Z1-1-1-1 )2, -N(R Z1-1-1-1 )S(=O)2R Z1-1-1-1 , -N(OR Z1-1-1- 1 )R Z1-1-1-1 , -C(=NH)N(R Z1-1-1-1 )2, -(CH2) 0-4 P(=O)(R Z1-1-1-1 )2, -(CH2) 0-4 OP(=O)(R Z1-1-1-1 )2, -(CH2) 0-4 OP(=O)(OR Z1-1-1-1 )2, -Si(R Z1- 1-1-1 )3, -(CH=CH) 0-4 O-N(R Z1-1-1-1 )2, -(CH=CH) 0-4 C(=O)O-N(R Z1-1-1-1 )2, =O, =S, =NR Z1-1-1-1 , =NN(R Z1-1-1-1 )2, =NNHC(=O)R Z1- 1-1-1 , =NNHC(=O)OR Z1-1-1-1 , =NNHS(=O)2R Z1-1-1-1 , =NR Z1-1-1-1 or =NOR Z1-1-1-1 ;

[0027] R Z1-1-1-1 Independently -(CH2) 0-2 R Z1-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR Z1-1-1-1-1 -(CH2) 0-2 CH(OR Z1-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R Z1-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR Z1-1-1-1-1 -(CH2) 0-2 SR Z1-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR Z1-1-1-1-1 -(CH2) 0-2 N(R Z1-1-1-1-1 )2、-Si(R Z1-1-1-1-1 3. -C(=O)SR Z1-1-1-1-1 -(CH=CH) 0-4 C(=O)OR Z1-1-1-1-1 or -SSR Z1-1- 1-1-1 ;

[0028] R Z1-1-1-1-1 Independently constitutes a hydrogen atom, halogen, benzyl, C1-C6 alkyl, or -O(CH2). 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl; wherein the heteroatom in the 3-6 membered heterocyclic alkyl is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2 or 3;

[0029] R A-1-1-1 Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)ORA-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1-1 ;

[0030] R A-1-1-1-1 Independently hydrogen, halogen, benzyl, C1-C6 alkyl, -O(CH2) 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl; wherein the heteroatom in the 3-6 membered heterocyclic alkyl is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2 or 3;

[0031] Cy B11 Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0032] Ring A is a saturated or partially unsaturated C3-C ring. 20 Carbon rings, saturated or partially unsaturated 3-20 membered heterocycles, C6-C20 Aromatic rings or 5-20 membered heteroaromatic rings; in the 3-20 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-20 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 20 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-20 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-20 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A- 1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0033] m can be 0, 1, 2, 3, 4, or 5;

[0034] Y is hydrogen, halogen, or...

[0035] q can be 0, 1, 2, 3, 4, or 5;

[0036] Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0037] R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=NR) A-1 )2R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1)2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=NR A-1 OR A-1 -NR A-1 C(=O)R A-1 NR A-1 C(=NR A-1 )R A-1 -NR A-1 C(=O)N(R A- 1 )2、-NR A-1 C(=NR A-1 )N(R A-1 )2、-NR A-1 C(=NOR A-1 )N(R A-1 )2、-NR A-1 C(=NR A-1 )NH(OR A-1 ) or -NR A-1 S(=O)2R A-1 ;

[0038] L A It is a C1-C6 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A- 1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0039] Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0040] L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B;

[0041] L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A-1 The substituted 3-16-membered heterocyclic alkyl or 3-16-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; the 6-membered heteroaryl group has heteroatoms selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3.

[0042] L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0043] L c For covalent bonds, -O-, -S-, or -NL 11 -;

[0044] L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1 -、-OC(=O)NR A-1 -、-NR A-1OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-、 M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently;

[0045] -L a -L b -L c -with L X Connect any point on the [structure / structure];

[0046] L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E;

[0047] Or L X Independently for -L X1 -L X2 -L X3 -L X4 -;

[0048] L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)′-OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0049] L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)′-OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2′-NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0050] L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0051] L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0052] Cy is independently saturated or partially unsaturated C3-C 12Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0053] for

[0054] X 5 and X 6 Independently covalent bond, -C(R) A-3 )2-, -SO2-, -S(=O)′-P(=O)R A-3 -、-P(=O)OR A-3 -、-P(=O)N(R A-3 -, -C(=O)- or -C(=S)-;

[0055] X 2 For N, CR 2-1 Si-R 2-1 Or P = O;

[0056] It can be a single bond or a double bond;

[0057] when When it is a single bond, X 3 and X 4 Independently covalent bond, -C(R) A-3 -2-, -CF2-, -O-, or -S-; X 3 When it is a covalent bond, X 2 and X 4 Directly connected; X 4 When it is a covalent bond, X 3 and X 5 Directly connected; X 3 When both X and X4 are covalent bonds, X 2 and X 5 Directly connected;

[0058] when When it is a double bond, For -CR A-3 CR A-3 -;

[0059] R A-3 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0060] Alternatively, two R atoms on the same atom or two adjacent atoms A-3 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0061] R 2-1 Independently hydrogen, -OR A-1 -SR A-1 -S(=O)R A-1 -SO2R A-1 -N(R) A-1 2. Or optionally by one or more R A-1-1 Replacement C1-C 12 alkyl;

[0062] Or R 2-1 and R A-3 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0063] Ring E3 is a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the 5-6 membered heteroaromatic ring is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3;

[0064] Cycle E4 is a C4-C7 cycloene or a 4-7 membered heterocyclic alkene, wherein the heteroatom in the 4-7 membered heterocyclic alkene is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3 or 4.

[0065] n1 is 1, 2, 3, or 4; R 3 Substituents on ring E3 or ring E4;

[0066] R 3 It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, C1-C6 alkyl substituted with one or more halogens, or C1-C6 alkoxy substituted with one or more halogens.

[0067] In certain preferred embodiments of the present invention, certain groups of the compound represented by formula (I), its pharmaceutically acceptable salt, its solvate or its pharmaceutically acceptable salt are defined as follows, and groups not mentioned are as described in any embodiment of the present invention (hereinafter referred to as "in a certain embodiment of the present invention").

[0068] In one aspect of the present invention,

[0069] Ring B is a saturated or partially unsaturated C3-C ring. 18 Carbon rings, saturated or partially unsaturated 3-18 membered heterocycles, C6-C 18Aromatic rings or 5-18 membered heteroaromatic rings; in the 3-18 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-18 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 18 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-18 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0070] n is 0, 1, 2, 3, 4 or 5;

[0071] R B Independently for R A-2 R B-1 Hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 =S, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A- 1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A- 1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ;

[0072] R A-2 Independently for C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0073] R B-1 -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 -H;

[0074] L B Independently C1-C3 alkylene groups, wherein 0, 1, 2 or 3 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or

[0075] R A-1Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0076] Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0077] R A-1-1 and R A-2-1 Each can be independently classified as: halogen, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A-1-1- 1 -(CH2) 0-4 CH(OR A-1-1-1 2、-(CH2) 0-4 SR A-1-1-1, -(CH2) 0-4 Ph, -(CH2) 0-4 O(CH2) 0-1 Ph, -(CH2) 0-4 Py, -(CH2) 0-4 O(CH2) 0-1 Py, -CH=CHPh, nitro, cyano, azido, -(CH2) 0-4 N(R A-1-1-1 )2, -(CH2) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 , -N(R A-1-1-1 )C(=S)R A-1-1-1 , -(CH2) 0-4 N(R A-1-1- 1 )C(=O)N(R A-1-1-1 )2, -N(R A-1-1-1 )C(=S)N(R A-1-1-1 )2, -(CH2) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 , -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)R A-1-1-1 , -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2, -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 , -(CH2) 0-4 C(=O)R A-1-1-1 , -C(=S)R A-1-1-1 , -(CH2) 0- 4-C(=O)OR A-1-1-1 , -(CH2) 0-4 -C(=O)SR A-1-1-1 , -(CH2) 0-4 -C(=O)OSi(R A-1-1-1 )3, -(CH2) 0-4 OC(=O)R A-1-1-1 , -OC(=O)(CH2) 0-4 SR A-1- 1-1 , -(CH2) 0-4 SC(=O)R A-1-1-1 , -(CH2) 0-4 C(=O)N(R A-1-1-1 )2, -C(=S)N(RA-1-1-1 )₂, -C(=S)SR A-1-1-1 , -SC(=S)SR A-1-1-1 , -(CH₂) 0- ₄OC(=O)N(R A-1-1-1 )₂, -C(=O)N(OR A-1-1-1 )R A-1-1-1 , -C(=O)C(=O)R A-1-1-1 , -C(=O)CH₂C(=O)R A-1-1-1 , -C(=NOR A-1-1-1 )R A-1-1-1 , -(CH₂) 0-4 SSR A-1-1-1 , -(CH₂) 0-4 S(=O)₂R A-1-1-1 , -(CH₂) 0-4 S(=O)₂OR A-1-1-1 , -(CH₂) 0-4 OS(=O)₂OR A-1-1-1 , -S(=O)₂N(R A-1-1-1 )₂, -(CH₂) 0- ₄S(=O)R A-1-1-1 , -N(R A-1-1-1 )S(=O)₂N(R A-1-1-1 )₂, -N(R A-1-1-1 )S(=O)₂R A-1-1-1 , -N(OR A-1-1-1 )R A-1-1-1 , -C(=NH)N(R A-1-1-1 )₂, -(CH₂) 0- ₄P(=O)(R A-1-1-1 )₂, -(CH₂) 0-4 OP(=O)(R A-1-1-1 )₂, -(CH₂) 0-4 OP(=O)(OR A-1-1-1 )₂, -Si(R A-1-1-1 )₃, -(CH=CH) 0-4 O-N(R A-1-1-1 )₂, -(CH=CH) 0-4 C(=O)O-N(R A-1-1-1 )₂, =O, =S, =NR A-1-1-1 , =NN(R A-1-1-1 )₂, =NNHC(=O)R A-1-1-1 , =NNHC(=O)OR A-1-1-1 , =NNHS(=O)₂R A-1-1-1 , =NR A-1-1-1 or =NOR A-1-1-1 ;

[0078] R A-1-1-1 Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR A-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1-1 ;

[0079] R A-1-1-1-1 Independently, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C5-C6 cycloalkyl or 5-6 membered heterocyclic alkyl;

[0080] Cy B1 and Cy B2 Each independently constitutes C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0081] Ring A is a saturated or partially unsaturated C3-C ring. 14 Carbon rings, saturated or partially unsaturated 3-14 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-14 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)′-OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A- 1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 ′-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0082] m can be 0, 1, 2, 3, 4, or 5;

[0083] Y is hydrogen, halogen, or...

[0084] q can be 0, 1, 2, 3, 4, or 5;

[0085] Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0086] R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR)A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ;

[0087] L A It is a C1-C5 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A- 1 )-、-CF2′-CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0088] Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0089] L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B;

[0090] L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A-1 The substituted 3-16-membered heterocyclic alkyl or 3-16-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; the 6-membered heteroaryl group has heteroatoms selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3.

[0091] L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0092] L x For covalent bonds, -O-, -S-, or -NL 11 -;

[0093] L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C)R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NRA-1 )-、

[0094] -L a -L b -L c -with L X Connect any point on the [structure / structure];

[0095] L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E;

[0096] M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently;

[0097] Or L X Independently for -L X1 -L X2 -L X3 -L X4 -;

[0098] L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0099] L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0100] L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0101] L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0102] Cy is independently saturated or partially unsaturated C3-C 12Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0103] for

[0104] X 5 and X 6 Independently covalent bond, -C(R) A-1 )2-, -SO2-, -S(=O)-, -P(=O)R A-1 -、-P(=O)OR A-1 -、-P(=O)N(R A-1 -, -C(=O)- or -C(=S)-;

[0105] X 2 For N, CR 2-1 Si-R 2-1 Or P = O;

[0106] R 2-1 Independently hydrogen, halogen, cyano, -OR A-1 -SR A-1 -S(=O)R A-1 -SO2R A-1 -N(R) A-1 2. Or optionally by one or more R A-1-1 Replacement C1-C 12 alkyl;

[0107] Or R 2-1 and R A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0108] It can be a single bond or a double bond;

[0109] when When it is a single bond, X 3 and X 4 Independently covalent bond, -C(R) A-1 -2-, -CF2-, -O-, or -S-; X 3 When it is a covalent bond, X 2 and X 4 Directly connected; X 4 When it is a covalent bond, X 3 and X 5 Directly connected; X 3 and X 4 When all are covalent bonds, X 2 and X 5 Directly connected;

[0110] when When it is a double bond, For -CR A-1 =CR A-1 -;

[0111] Ring E3 is a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the 5-6 membered heteroaromatic ring is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3;

[0112] Cycloethylene E4 is a 4-7 membered heterocyclic alkene, wherein the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3 or 4.

[0113] n1 is 1, 2, 3, or 4; R 3 Substituents on ring E3 or ring E4;

[0114] R 3 It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, C1-C6 alkyl substituted with one or more halogens, or C1-C6 alkoxy substituted with one or more halogens.

[0115] In one aspect of the present invention,

[0116] Ring B is a saturated or partially unsaturated C3-C ring. 12Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0117] n is 0, 1, 2, 3, 4 or 5;

[0118] R B Independently for R A-2 R B-1 Hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 =S, -oR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A- 1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A- 1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2RA-1 ;

[0119] R A-2 Independently for C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2 - 1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0120] R B-1 -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 -H;

[0121] L B Independently C1-C3 alkylene groups, wherein 0, 1, 2 or 3 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or

[0122] R A-1 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0123] Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5.

[0124] R A-1-1 and R A-2-1 Each can be independently classified as: halogen, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A-1-1- 1 -(CH2) 0-4 CH(OR A-1-1-1)₂, -(CH₂) 0-4 SR A-1-1-1 , -(CH₂) 0-4 Ph, -(CH₂) 0-4 O(CH₂) 0-1 Ph, -(CH₂) 0-4 Py, -(CH₂) 0-4 O(CH₂) 0-1 Py, -CH=CHPh, nitro, cyano, azido, -(CH₂) 0-4 N(R A-1-1-1 )₂, -(CH₂) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 , -N(R A-1-1-1 )C(=S)R A-1-1-1 , -(CH₂) 0-4 N(R A-1-1- 1 )C(=O)N(R A-1-1-1 )₂, -N(R A-1-1-1 )C(=S)N(R A-1-1-1 )₂, -(CH₂) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 , -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)R A-1-1-1 , -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )₂, -N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 , -(CH₂) 0-4 C(=O)R A-1-1-1 , -C(=S)R A-1 = 1-1 , =(CH₂) 0- 4-C(=O)OR A-1-1-1 , =(CH₂) 0-4 -C(=O)SR A-1-1-1 , -(CH₂) 0-4 -C(=O)OSi(R A-1-1-1 )₃, -(CH₂)₀₋₄OC(=O)R A-1-1-1 , -OC(=O)(CH₂)₀₋₄SR A-1- 1-1 , -(CH₂)₀₋₄SC(=O)R A-1-1-1 , -(CH₂)₀₋₄C(=O)N(R A-1-1-1)₂, -C(=S)N(R A-1-1-1 )₂, -C(=S)SR A-1-1-1 , -SC(=S)SR A-1-1-1 , -(CH₂) 0- ₄OC(=O)N(R A-1-1-1 )₂, -C(=O)N(OR A-1-1-1 )R A-1-1-1 , -C(=O)C(=O)R A-1-1-1 , -C(=O)CH₂C(=O)R A-1-1-1 , -C(=NOR A-1-1-1 )R A-1-1-1 , -(CH₂) 0-4 SSR A-1-1-1 , -(CH₂)₀₋₄S(=O)₂R A-1-1-1 , -(CH₂)₀₋₄S(=O)₂OR A-1-1-1 , -(CH₂)₀₋₄OS(=O)₂OR A-1-1-1 , -S(=O)₂N(R A-1-1-1 )₂, -(CH₂) 0- ₄S(=O)R A-1-1-1 , -N(R A-1-1-1 )S(=O)₂N(R A-1-1-1 )₂, -N(R A-1-1-1 )S(=O)₂R A-1-1-1 , -N(OR A-1-1-1 )R A-1-1-1 , -C(=NH)N(R A-1-1-1 )₂, -(CH₂) 0- ₄P(=O)(R A-1-1-1 )₂, -(CH₂)₀₋₄OP(=O)(R A-1-1-1 )₂, -(CH₂)₀₋₄OP(=O)(OR A-1-1-1 )₂, -Si(R A-1-1-1 )₃, =(CH=CH) 0-4 O-N(R A-1-1-1 )₂, -(CH=CH) 0-4 C(=O)O-N(R A-1-1-1 )₂, =O, =S, =NR A-1-1-1 , =NN(R A-1-1-1 )₂, =NNHC(=O)R A-1-1-1 , =NNHC(=O)OR A-1-1-1 , =NNHS(=O)₂R A-1-1-1 , =NR A-1-1-1 or =NOR A-1-1-1 ;

[0125] R A-1-1-1Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR A-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1-1 ;

[0126] R A-1-1-1-1 Independently, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C5-C6 cycloalkyl or 5-6 membered heterocyclic alkyl;

[0127] Cy B1 and Cy B2 Each independently constitutes C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0128] Ring A is a saturated or partially unsaturated C3-C ring. 14 Carbon rings, saturated or partially unsaturated 3-14 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-14 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0129] m can be 0, 1, 2, 3, 4, or 5;

[0130] Y is hydrogen, halogen, or...

[0131] q can be 0, 1, 2, 3, 4, or 5;

[0132] Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A- 1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0133] R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )RA-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ;

[0134] L A It is a C1-C5 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A- 1 )-、-CF2′-CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0135] Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0136] L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B;

[0137] L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A-1 The substituted 3-16-membered heterocyclic alkyl or 3-16-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; the 6-membered heteroaryl group has heteroatoms selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0138] L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0139] L c For covalent bonds, -O-, -S-, or -NL 11 -;

[0140] L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C)R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-、

[0141] -L a -L b -L c -with L X Connect any point on the [structure / structure];

[0142] L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E;

[0143] M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently;

[0144] Or L X Independently for -L X1 -L X2 -L X3 -L X4 -;

[0145] L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0146] L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NRA-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0147] L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0148] L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -or-NR A-1 OC(=O)-;

[0149] Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0150] for

[0151] X 2 It can be CH or N.

[0152] In one embodiment of the present invention, ring B is C6-C. 14 Aromatic rings or 5-14 heterocyclic aromatic rings, such as C6-C 10 A 9-10 membered heteroaromatic ring, where the aromatic ring or heteroatom is N and the number of heteroatoms is one or two; another example is a 9-10 membered heteroaromatic ring, where the heteroatom is N and the number of heteroatoms is one or two, wherein the 9-10 membered heteroaromatic ring or C6-C 10 In an aromatic ring, at least one ring is aromatic or every ring is aromatic.

[0153] In one aspect of the present invention, for Ring B1 is a 5-membered heteroaromatic ring or 5-membered heterocyclic alkene with N as the heteroatom and one or two heteroatoms. Preferably, ring B1 is a 5-membered heteroaromatic ring with N as the heteroatom and one heteroatom. The end marked with "#" is connected to ring A, and the end marked with "#1" is connected to L. X Connected, the end marked "#2" is connected to L a Connected.

[0154] In one aspect of the present invention, for For example, The end marked with "#" is connected to ring A, and the end marked with "#1" is connected to L. X Connected, the end marked "#2" is connected to L a Connected.

[0155] In one aspect of the present invention, n is 0, 1, or 2; for example, 0 or 1, and more specifically, 0.

[0156] In one aspect of the present invention, R B Independently halogenated, oxo-(=O) or -C(=O)N(R) A-1 )2, R A-1 It is hydrogen or C1-C6 alkyl.

[0157] In one aspect of the present invention, R B Independently, it is F, oxo(=O) or -C(=O)N(CH3)2, for example, F.

[0158] In one aspect of the present invention, for For example, The end marked with "#" is connected to ring A, and the end marked with "#1" is connected to L. X Connected, the end marked "#2" is connected to L a The carbon atoms connected by an asterisk (*) have the configuration of R, S, or a mixture thereof; For example,

[0159] In one aspect of the present invention, for The end marked with "#" is connected to ring A, and the end marked with "#1" is connected to L. X Connected, the end marked "#2" is connected to L a Connected.

[0160] In one embodiment of the present invention, ring A is a saturated or partially unsaturated 3-6 member monocyclic heterocyclic ring, a saturated or partially unsaturated 8-12 member spirocyclic heterocyclic ring, a 5-6 member monocyclic heteroaromatic ring, a 12-20 member bicyclic heteroaromatic ring, or a 12-20 member tricyclic heteroaromatic ring. In the 12-20 member bicyclic heteroaromatic ring or the 12-20 member tricyclic heteroaromatic ring, one ring is aromatic, and the remaining rings are saturated or partially unsaturated. Preferably, in the heterocyclic ring or the heteroaromatic ring, the heteroatom is N, and the number of heteroatoms is 1.

[0161] In one embodiment of the present invention, ring A is a saturated or partially unsaturated 3-10 membered heterocycle, for example, a saturated or partially unsaturated 5-6 membered heterocycle with N heteroatoms and one or two heteroatoms.

[0162] In one aspect of the present invention, for Among them, ring A1 is a 5-6 membered heterocycle with N heteroatom, consisting of 1 or 2 heteroatoms, and is either saturated or partially unsaturated. Ra1 and R a2 Independently, it is H or R. a1 and R a2 The carbon atoms bonded to them together form C3-C6 saturated carbon rings, 3-6 membered saturated heterocycles, or... In the aforementioned 3-6 membered saturated heterocycles, the heteroatom is selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, or 3; the cyclic Cy3 is a C3-C6 cyclic alkene or a 3-6 membered heterocyclic alkene, wherein the heteroatom in the 3-6 membered heterocyclic alkene is selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, or 3; the cyclic Cy4 is a C6-C... 10 Aromatic rings or 5-10 quinone heteroaryl rings, the C6-C 10 The aromatic ring can be monocyclic or polycyclic. When polycyclic, at least one ring is aromatic or each ring is aromatic. In the 5-10 membered heteroaromatic ring, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, or 4. It can be monocyclic or polycyclic; when polycyclic, at least one ring is aromatic or each ring is aromatic. R a1 and R a2 For example, H is a ring labeled "#4" connected to ring B.

[0163] In one aspect of the present invention, for Wherein, ring A is a saturated or partially unsaturated 5-6 membered heterocycle with N heteroatom and one or two heteroatoms, and the end marked "#4" is connected to ring B; ring A is preferably an unsaturated 5-6 membered heterocycle with one heteroatom.

[0164] In one aspect of the present invention, for In this case, ring A is a saturated or partially unsaturated 6-membered heterocycle with N as the heteroatom and a heteroatom number of 1.

[0165] In one aspect of the present invention, for For example, The end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof; R a1 and R a2 Independently, it is H or R. a1 and R a2 The carbon atoms bonded to them together form C3-C6 saturated carbon rings, 3-6 membered saturated heterocycles, or... Cy3 is a C3-C6 cycloene, and Cy4 is a C6-C6 cycloene. 10 Aromatic ring.

[0166] In one aspect of the present invention, for Among them, the end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof.

[0167] In one aspect of the present invention, for For example, Among them, the end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof.

[0168] In one aspect of the present invention, for For example, In this configuration, the end marked "#4" is connected to ring B, and the carbon atoms marked "*" have an R configuration, an S configuration, or a mixture thereof. For example,

[0169] In one aspect of the present invention, R A It is hydrogen or halogen; for example, it is hydrogen.

[0170] In one embodiment of the present invention, m is 0 or 1.

[0171] In one aspect of the present invention, for Among them, the end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof.

[0172] In one aspect of the present invention, L A It is a C1-C5 alkylene (e.g., a C1-C5 straight-chain alkylene), wherein 0, 1 or more methylene groups are independently replaced by -C(=O)-.

[0173] In one embodiment of the present invention, LA is... L A-1 For connecting bonds or C1-C5 alkylene groups (e.g., C1-C5 straight-chain alkylene groups), the end marked "#5" is connected to ring A.

[0174] In one embodiment of the present invention, LA is... The end marked "#5" is connected to ring A.

[0175] In one embodiment of the present invention, LA is... The end marked "#5" is connected to ring A.

[0176] In one embodiment of the present invention, Y is hydrogen or... For example,

[0177] In one aspect of the present invention, ring Z is a 5-14 membered heteroaromatic ring, for example, a 5-6 membered monocyclic heteroaromatic ring with N heteroatom and 1, 2 or 3 heteroatoms, or more specifically, a 5 membered heteroaromatic ring with N heteroatom and 1, 2 or 3 heteroatoms.

[0178] In one aspect of the present invention, for For example,

[0179] In one aspect of the present invention, R Z It is hydrogen.

[0180] In one embodiment of the present invention, q is 0 or 1.

[0181] In one aspect of the present invention, L a For covalent bonds, -NL 11 -or L 11 It is hydrogen or C1-C6 alkyl, and the end marked "a" is connected to ring B.

[0182] In one aspect of the present invention, L a for L 11 It is a C1-C6 alkyl group, and the end marked "a" is connected to ring B.

[0183] In one aspect of the present invention, L a for The end marked "a" is connected to ring B.

[0184] In one aspect of the present invention, L b For C1-C 10 Alkylene (e.g., C1-C) 10 (linear alkylene), the C1-C 10 Zero, one, or more methylene groups in the alkylene group are independently... -NR B -、-O-、-S-、-CR B =CR B -、C6-C 14 Aromatic rings or 5-14 quinone heterocyclic aromatic rings are substituted.

[0185] In one aspect of the present invention, L bIt is a C4-C7 alkylene (e.g., a C4-C7 straight-chain alkylene), wherein 0, 1, 2, or 3 methylene groups in the C4-C7 alkylene are independently separated. -NH-, -O-, -N(C1-C6 alkyl)-, -CH=CH-, 5-6 membered heteroaromatic rings or benzene ring substitution.

[0186] In one aspect of the present invention, L b It is a C4-C7 alkylene (e.g., a C4-C7 straight-chain alkylene, further such as a C4 straight-chain alkylene, a C5 straight-chain alkylene, a C6 straight-chain alkylene, or a C7 straight-chain alkylene), wherein 0 or 1 methylene groups in the C4-C7 alkylene are independently replaced by -O- or -CH=CH-.

[0187] In one aspect of the present invention, L b It is a C4-C7 alkylene (e.g., a C4-C7 straight-chain alkylene), wherein one methylene group in the C4-C7 alkylene is converted to a -CR group. B =CR B -replace.

[0188] In one aspect of the present invention, L b for The end marked "#7" is connected to L c Connected, It is a double bond, which has a Z configuration or an E configuration.

[0189] In one aspect of the present invention, L b for The end marked "#7" is connected to L c Connected, It is a double bond, which has a Z configuration or an E configuration.

[0190] In one aspect of the present invention, L b for For example, The end marked "#7" is connected to L c Connected, It is a double bond, which has a Z configuration or an E configuration.

[0191] In one aspect of the present invention, L b for The end marked "#7" is connected to L c Connected, It is a double bond, which has a Z configuration or an E configuration.

[0192] In one aspect of the present invention, L b for The end marked "#7" is connected to L c Connected, It is a double bond, which is either Z-configuration or E-configuration, with Z-configuration being preferred.

[0193] In one aspect of the present invention, L c It is a covalent bond or -O-.

[0194] In one aspect of the present invention, L c It is -O-.

[0195] In one aspect of the present invention, a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, which has a Z configuration or an E configuration.

[0196] In one aspect of the present invention, a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, which is either Z-configuration or E-configuration, with Z-configuration being preferred.

[0197] In one aspect of the present invention, a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, which has a Z configuration or an E configuration.

[0198] In one aspect of the present invention, a -L a -L b -L c for For example, The end marked "a" is connected to ring B. It is a double bond, which has a Z configuration or an E configuration.

[0199] In one aspect of the present invention, a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, which has a Z configuration or an E configuration.

[0200] In one aspect of the present invention, B -L X_E For C1-C 20 Alkylene (e.g., C1-C) 20 (linear alkylene), the C1-C 20 In the alkylene group, 0, 1, 2, 3, 4, 5, 6, 7, or 8 methylene groups are independently replaced by the following groups: -Cy-, C(=O)-, -C(=S)-, -CR A-1 2-, -CF2-, -NR A-1 -、-O-、-S- or -S(=O)2-, the end marked "B" is connected to ring B, and the end marked "E" is connected to ring E.

[0201] In one aspect of the present invention, B -L X-E for The end marked "B" is connected to ring B; the end marked "E" is connected to ring E; -L a -L b -L c -with L X The ring C is connected in the middle, and the compound shown in formula (I) is the same as the compound shown in formula (I-1):

[0202] in,

[0203] Ring C is C6-C 10 An aromatic ring or a 5-10 membered heteroaromatic ring, wherein the heteroatom in the 5-10 membered heteroaromatic ring is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0204] R C It is H or halogen;

[0205] p is 0, 1, 2, 3, 4 or 5;

[0206] L X5Covalent bond or C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -, -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、-P(=O)OR A-1 -、-P(=O)R A-1 -、-P(=O)N(R A-1 )2-、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-、

[0207] M is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0208] Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10 quinone heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-10 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0209] Ring D is a saturated or partially unsaturated C3-C ring. 12Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10 quinone heteroaryl rings, wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-10 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0210] L D It is a covalent bond or a C1-C3 alkylene group, wherein in the C1-C3 alkylene group, 0, 1, 2 or 3 methylene groups are independently replaced by the following groups: -C(=O)′-C(=S)-, -CR2-, -CF2-, -NR A-1 -、-O-、-S- or -S(=O)2-;

[0211] The definitions of the remaining variables are as described in any embodiment of this invention.

[0212] In one embodiment of the present invention, ring C is C6-C. 10 Aromatic rings, such as benzene rings.

[0213] In one aspect of the present invention, for The end marked "#8" is connected to ring B; the end marked "#9" is connected to L. c Connected; the end marked "#10" is connected to L. X5 Connected.

[0214] In one aspect of the present invention, R C It can be hydrogen or F; for example, H.

[0215] In one embodiment of the present invention, p is 0 or 1.

[0216] In one aspect of the present invention, for The end marked "#8" is connected to ring B; the end marked "#9" is connected to L. c Connected; the end marked "#10" is connected to L. X5 Connected.

[0217] In one aspect of the present invention, for The end marked "#8" is connected to ring B; the end marked "#9" is connected to L. c Connected; the end marked "#10" is connected to L. X5 Connected.

[0218] In one aspect of the present invention, L X5 Independently C1-C6 alkylene (e.g., C1-C6 straight-chain alkylene), wherein one, two, or three methylene groups in the C1-C6 alkylene are independently replaced by -Cy- or -C(=O)-, Cy is a saturated 5-6 membered heterocycle, wherein the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is one or two.

[0219] In one aspect of the present invention, L X5 Independently C1-C6 alkylene (e.g., C1-C6 straight-chain alkylene), wherein one methylene group in the C1-C6 alkylene is independently replaced by -Cy-, where Cy is a saturated 5-6 membered heterocycle, and the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is one or two.

[0220] In one aspect of the present invention, L X5 for Among them, cycloyl is a saturated 5-6 membered heterocycle, L XA It is a covalent bond or a C1-C5 alkylene (e.g., a C1-C5 straight-chain alkylene), wherein 0, 1, or 2 methylene groups in the C1-C5 alkylene are independently replaced by -Cy- or -C(=O)-, Cy is a saturated 5-6 membered heterocycle, wherein the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is 1 or 2; the end marked "#11" is connected to ring D.

[0221] In one aspect of the present invention, L X5 for Among them, cycloyl is a saturated 5-6 membered heterocycle, L XA For covalent bonds or C1-C5 alkylene groups (e.g., C1-C5 straight-chain alkylene groups), the end marked "#11" is connected to ring D.

[0222] In one aspect of the present invention, L XA It is a C1-C5 alkylene (e.g., a C1-C5 straight-chain alkylene, further for example, a C3 straight-chain alkyl).

[0223] In one aspect of the present invention, L X5 for The end marked "#11" is connected to ring D.

[0224] In one aspect of the present invention, L X5 for The end marked "#11" is connected to ring D.

[0225] In one aspect of the present invention, L X5 for For example, For example, The end marked "#11" is connected to ring D.

[0226] In one embodiment of the present invention, ring D is C6-C. 10 Aromatic rings or 5-10 quinone heteroaryl rings, the C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z Replaced by, R Z It is oxo (=O), halogen, C1-C6 alkyl, or C1-C6 alkoxy; preferably, R Z It is an oxo (=O), halogen, or C1-C6 alkyl group.

[0227] In one aspect of the present invention, It is any of the following:

[0228] (1) Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 1 or 2 heteroatoms;

[0229] For example, R Z It is a C1-C6 alkyl group, r is 1, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 2 heteroatoms;

[0230] (2) Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy, such as a halogen or a C1-C6 alkyl;

[0231] (3) Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and ring E2 is a 5-6 membered heteroaromatic ring with N heteroatom and 1 or 2 heteroatoms, wherein the 5-6 membered heteroaromatic ring is aromatic;

[0232] (4) Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 1 or 2 heteroatoms;

[0233] For example, R Z It is a C1-C6 alkyl group, r is 1, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 2 heteroatoms;

[0234] (5) Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy;

[0235] (6) Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and ring E2 is a 5-6 membered heteroaromatic ring with N heteroatom and 1 or 2 heteroatoms, wherein the 5-6 membered heteroaromatic ring is aromatic;

[0236] Among them, the end marked "#12" is connected to L. D Connected.

[0237] In one aspect of the present invention, for Among them, the end marked "#12" is connected to L. D Connected.

[0238] In one aspect of the present invention, for For example, For example, Among them, the end marked "#12" is connected to L. D Connected.

[0239] In one aspect of the present invention, for

[0240] In one aspect of the present invention, L D It is a covalent bond, -C(=O)-, -NH- or -C(=O)NH-; for example, a covalent bond or -NH-; and also, for example, a covalent bond.

[0241] In one aspect of the present invention, for The end marked "T1" is connected to ring E.

[0242] In one aspect of the present invention, for Among them, X 7 It can be O, CH2, or NH.

[0243] In one aspect of the present invention, for For example,

[0244] In one aspect of the present invention, the compound represented by formula (I) is a compound represented by formula (I-2):

[0245] The definitions of each variable are as described in any embodiment of this invention.

[0246] In one aspect of the present invention, the compound represented by formula (I) is selected from any of the following compounds:

[0247] Among them, including In the structure, It is a carbon-carbon double bond, which has a Z configuration or an E configuration.

[0248] The present invention also provides a pharmaceutical composition comprising a compound as shown in formula (I) of any of the above embodiments, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0249] The present invention also provides the use of a compound of formula (I) as described in any of the above embodiments, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of a pharmaceutically acceptable salt thereof, or the above pharmaceutical composition in the preparation of a STAT6 inhibitor or degrader.

[0250] The present invention also provides the use of a compound of formula (I) as described in any of the above embodiments, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of a pharmaceutically acceptable salt thereof, or the above pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of STAT6-mediated diseases, preferably, the STAT6-mediated diseases being cancer, inflammatory diseases, esophageal diseases, chronic obstructive pulmonary disease, Alzheimer's disease, or peripheral nervous system diseases; the inflammatory diseases may be atopic dermatitis, sinusitis, or asthma.

[0251] The present invention also provides the use of any of the above-described compounds as shown in formula (I), pharmaceutically acceptable salts thereof, solvates thereof, solvates of pharmaceutically acceptable salts thereof, or the above-described pharmaceutical compositions in the preparation of medicaments for the prevention and / or treatment of cancer, inflammatory diseases, esophageal diseases, chronic obstructive pulmonary disease, Alzheimer's disease, or peripheral nervous system diseases; wherein the inflammatory disease may be atopic dermatitis, sinusitis, or asthma.

[0252] Terminology Explanation

[0253] In this invention, "partially unsaturated carbon rings" refers to rings with a specified number of ring atoms (e.g., 3-18 membered heterocycles, C3-C4). 12 Or C3-C 10 The ring atom has only a ring structure composed of carbon atoms, which contains at least one double or triple bond, but is not completely unsaturated (i.e. does not satisfy the aromaticity condition).

[0254] In this invention, a "partially unsaturated heterocycle" refers to a cyclic group having a specified number of ring atoms (e.g., 3-12, 3-10, 3-14, 3-18, 3-20, 3-6, 8-12, or 5-6), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (1, 2, or 3 of N, O, S, P, and Si), containing at least one double or triple bond, but not completely unsaturated (i.e., not satisfying the aromaticity condition). In the partially unsaturated heterocycle, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms must be less than the number of ring atoms. For example, when the number of ring atoms in the heterocycle is 3, the number of heteroatoms is at most two. "Partially unsaturated heterocycles" include, but are not limited to: For example, wait.

[0255] In this invention, "saturated carbon ring" refers to a ring with a specified number of ring atoms (e.g., C3-C). 12 Or C3-C 10 Ring atoms are composed only of carbon atoms in a ring structure. The carbon atoms are connected to each other by single bonds. There are no double bonds, triple bonds or other unsaturated bonds in the ring. Each carbon atom in the ring is connected to four atoms, which reaches the maximum number of bonds and has saturation.

[0256] In this invention, a "saturated heterocycle" refers to a cyclic group having a specified number of ring atoms (e.g., 3-12, 3-10, 3-14, 3-18, 3-20, 3-6, 8-12, or 5-6), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (1, 2, or 3 of N, O, S, P, and Si). All atoms within the ring are connected by single bonds, and there are no double or triple bonds or other unsaturated bonds, thus exhibiting saturation. In the saturated heterocycle, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms must be less than the number of ring atoms. For example, when the number of ring atoms in the heterocycle is 3, the number of heteroatoms is at most two. "Saturated heterocycles" include, but are not limited to: wait.

[0257] In this invention, In the case of a cyclop- ...

[0258] In this invention, "aromatic ring" refers to a ring having a specified number of carbon atoms (e.g., C6-C). 10 C6-C 18 C6-C 20 Or C6-C 14 An aromatic ring is an unsaturated ring, which is monocyclic or polycyclic (e.g., one or two). When polycyclic, the monocyclic rings share two atoms and one bond. In the "aromatic ring", at least one ring or each ring is aromatic. The aromatic ring is connected to the rest of the molecule through an aromatic or non-aromatic ring and satisfies any of the following conditions: (1) it is connected to the rest of the molecule through two or more single bonds; (2) it shares two atoms and one bond with the rest of the molecule. An "aromatic ring" includes, but is not limited to: wait.

[0259] In this invention, a "heteroaromatic ring" refers to an unsaturated cyclic group having a specified number of ring atoms (e.g., 5-14, 5-10, 5-6, 5-18, 5-20, 9-10, or 12-20), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (one or more of N, O, and S). It can be a monocyclic or polycyclic ring, with the monocyclic rings sharing two atoms and one bond. In the "heteroaromatic ring," at least one ring or each ring is aromatic. The heteroaromatic ring is connected to the rest of the molecule via a carbon atom or a heteroatom; the heteroaromatic ring is connected to the rest of the molecule via a ring with or without heteroatoms; the heteroaromatic ring is connected to the rest of the molecule via an aromatic ring or a non-aromatic ring, and it satisfies any of the following conditions: (1) it is connected to the rest of the molecule via two or more single bonds; (2) it shares two atoms and one bond with the rest of the molecule. In the aforementioned heteroaromatic ring, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms must be less than the number of ring atoms. "Hyperaromatic ring" includes, but is not limited to: wait.

[0260] In this invention, "halogen" refers to F, Cl, Br or I.

[0261] In this invention, "alkyl" refers to a straight-chain or branched chain composed of a specified carbon atom (e.g., C1-C1). 12 () forms a monovalent saturated hydrocarbon group. For example, C1-C 12 Includes C 1-10 C 1- 9. C 1-8 C 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-4 C 10 C8, C7, C6, and C5 alkyl groups, etc. Examples of alkyl groups include, but are not limited to, methyl (M... e ), ethyl (Ft), propyl (including n-propyl and isopropyl), butyl (including n-butyl, isobutyl, s-butyl and t-butyl), pentyl (including n-pentyl, isopentyl and neopentyl), hexyl, heptyl, octyl, etc.

[0262] In this invention, "alkenyl" refers to an unsaturated monovalent hydrocarbon group consisting of a specified carbon atom (e.g., C2-C6) whether straight-chain or branched; it has one or more (e.g., 1, 2, or 3) carbon-carbon sp groups. 2 Double bond.

[0263] In this invention, "alkynyl" refers to an unsaturated monovalent hydrocarbon group consisting of a specified carbon atom (e.g., C2-C6) that is either straight-chain or branched; it has one or more (e.g., 1, 2 or 3) carbon-carbon sp triple bonds.

[0264] In this invention, "cycloalkyl" refers to a ring with a specified number of carbon atoms (e.g., C3-C4). 12 ), saturated monovalent monocyclic, bridged, fused, or spirocyclic groups whose ring atoms consist only of carbon atoms.

[0265] In this invention, "cycloalkenyl" refers to a group having a specified number of carbon atoms (e.g., C3-C4). 12 Unsaturated monovalent monocyclic, bridged, fused, or spirocyclic cyclic groups consisting only of carbon atoms, having one or more (e.g., 1, 2, or 3) carbon-carbon sp atoms. 2 It has a double bond and is not aromatic.

[0266] 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.

[0267] In this invention, "heterocyclic alkyl" refers to a saturated monovalent monocyclic, bridged, fused, or spirocyclic group having a specified number of ring atoms (e.g., 3-12, 3-6, 5-6, 3-16), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (1, 2, or 3 of N, O, S, P, and Si). In the heterocyclic alkyl group, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms is less than the number of ring atoms. "Heterocyclic alkyl" includes, but is not limited to, […]. wait.

[0268] In this invention, "heterocyclic alkenyl" refers to a cyclic, unsaturated monovalent monocyclic, bridged, fused, or spirocyclic group having a specified number of ring atoms (e.g., 3-12, 5-6, 3-16), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified heteroatom type (one or more of N, O, S, P, and Si), and having one or more (e.g., 1, 2, or 3) carbon-carbon sp groups. 2The double bond is non-aromatic. In the heterocyclic alkenyl group, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms is less than the number of ring atoms.

[0269] In this invention, "alkylene" refers to a divalent group formed by removing two hydrogen atoms from an alkane molecule. "alkylene" can be a straight-chain alkylene or a branched-chain alkylene. "alkylene" includes, but is not limited to: For example, wait.

[0270] In this invention, "cycloalkylene" refers to a saturated divalent monocyclic, fused, bridged, or spirocyclic group having a specified number of ring atoms and consisting only of carbon atoms.

[0271] In this invention, "cycloene group" refers to a group having a specified number of carbon atoms (e.g., C3-C4). 12 An unsaturated divalent monocyclic, bridged, fused, or spirocyclic cyclic group consisting only of carbon atoms, having one or more (e.g., 1, 2, or 3) carbon-carbon sp atoms. 2 It has a double bond and is not aromatic.

[0272] In this invention, "heterocyclic alkyl group" refers to a saturated divalent monocyclic, bridged, fused, or spirocyclic group having a specified number of ring atoms (e.g., 3-12), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (1, 2, or 3 of N, O, S, P, and Si). In the heterocyclic alkyl group, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms is less than the number of ring atoms.

[0273] In this invention, "heterocyclic alkenyl" refers to a cyclic, unsaturated divalent monocyclic, bridged, fused, or spirocyclic group having a specified number of ring atoms (e.g., 3-12), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified heteroatom type (one or more of N, O, S, P, and Si), and having one or more (e.g., 1, 2, or 3) carbon-carbon sp... 2 The double bond is non-aromatic. In the described heterocyclic alkenyl group, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms is lower than the number of ring atoms.

[0274] In this invention, "aryl" refers to an aryl group having a specified number of carbon atoms (e.g., C6-C). 14 Furthermore, for example, C6-C 10An aryl group is a cyclic, unsaturated monovalent hydrocarbon group, which may be monocyclic or polycyclic (e.g., two or three). When polycyclic, the monocyclic rings share two atoms and one bond. In this aryl group, at least one ring or each ring is aromatic. The aryl group is attached to the rest of the molecule through an aromatic or non-aromatic ring.

[0275] In this invention, "aneryl" refers to a divalent aryl group.

[0276] In this invention, "heteroaryl" refers to a cyclic, unsaturated monovalent group having a specified number of ring atoms (e.g., 5-14, more specifically 5-10, and even more specifically 5-6), a specified number of heteroatoms (e.g., 1, 2, 3, 4, or 5), and a specified type of heteroatom (one or more of N, O, and S). It can be monocyclic or polycyclic, with the monocyclic rings sharing two atoms and one bond. In the heteroaryl group, at least one ring or each ring is aromatic. The number of heteroatoms in the heteroaryl group depends on the number of ring atoms, and the number of heteroatoms is less than the number of ring atoms.

[0277] In this invention, "hybrid aryl" refers to a divalent heteroaryl group.

[0278] In this invention, "alkenyl" refers to a straight-chain or branched divalent hydrocarbon group having a specified number of carbon atoms and at least one carbon-carbon double bond, wherein the carbon-carbon double bond can be located at any position within the alkenyl group. "Alkenyl" includes, but is not limited to: For example, wait.

[0279] In this invention, "alkoxy" refers to the group R X -O-,R X The definition is the same as the term "alkyl".

[0280] In this invention, a "covalent bond" refers to a structure on both sides of a covalent bond that is directly connected by a single bond, such as -ABC-. ​​When B is a covalent bond, -ABC- is equivalent to -AC-.

[0281] In this invention, "optional" or "optionally" means that the event or condition described below may occur but is not required, and the description includes both cases where said event or condition occurs and cases where said event or condition does not occur. For example, the term "optionally replaced" means that it may or may not be replaced.

[0282] Those skilled in the art will understand that, according to conventions used in the art, the structural formulas of the groups described in this invention are... This refers to the fact that the corresponding group is connected to other fragments or groups in the compound through this site.

[0283] In this invention, a single dash "-" can be added before the substituent used to indicate that the named substituent is connected to the parent part by a single bond.

[0284] In this invention, an "=" can be added before the substituent to indicate that the named substituent is connected to the parent part by a double bond.

[0285] In this invention, when a variable is defined as an alkylene group substituted by one or more R groups, the R group can be a substituent at any site in the alkylene group. If the methylene group in the alkylene group can be replaced by other groups, the R group can also be a substituent on the replaced group.

[0286] In this invention, "multiple" can be 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0287] In this invention, "pharmaceutically acceptable salt" refers to the salt of the compounds of this invention, prepared by reacting a compound with a specific substituent discovered in this invention with a relatively non-toxic acid or base. When the compounds of this invention contain relatively acidic functional groups, a base addition salt can be obtained by contacting the neutral form of such compounds with a sufficient amount of base in a pure solution or a suitable inert solvent. When the compounds of this invention contain relatively basic functional groups, an acid addition salt can be obtained by contacting the neutral form of such compounds with a sufficient amount of acid in a pure solution or a suitable inert solvent.

[0288] In this invention, "solvate" refers to a substance formed by combining the compound of this invention with a stoichiometric or non-stoichiometric solvent. Solvent molecules in a solvate can exist in an ordered or disordered arrangement.

[0289] In this invention, "pharmaceutical-acceptable salt" and "solvent" in "pharmaceutical-acceptable salt solvate" refer to substances formed by combining the compound of this invention with 1, a substance prepared with a relatively non-toxic, pharmaceutically acceptable acid or base, or a stoichiometric or non-stoichiometric solvent, as described above.

[0290] In this invention, "pharmaceuticalally acceptable excipients" refers to excipients and additives used in the production of pharmaceuticals and the dispensing of prescriptions; these are all substances included in pharmaceutical preparations, excluding the active ingredient. See the Pharmacopoeia of the People's Republic of China (2020 Edition), Volume IV, or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009, Sixth Edition).

[0291] In this invention, “treatment” refers to a therapeutic therapy. When a specific condition is involved, treatment means: (1) alleviating one or more biological manifestations of the disease or condition, (2) interfering with (a) one or more points in a biological cascade that causes or induces the condition or (b) one or more biological manifestations of the condition, (3) improving one or more symptoms, effects or side effects associated with the condition, or one or more symptoms, effects or side effects associated with the condition or its treatment, or (4) slowing the development of the condition or one or more biological manifestations of the condition.

[0292] In this invention, "prevention" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0293] In this invention, "STAT6-mediated diseases" refer to diseases directly or indirectly caused by abnormal activation or dysfunction of signal transduction and transcription activator 6 (STAT6).

[0294] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0295] The reagents and raw materials used in this invention are all commercially available.

[0296] The positive and progressive effects of this invention are that the cyclic compounds of this invention have good inhibitory or degradation activity against STAT6. Attached Figure Description

[0297] Figure 1 shows the A549 cell degradation selectivity of compound 3A. Detailed Implementation

[0298] The present invention will be described in detail below with reference to embodiments, but this does not imply any adverse limitation on the invention. The present invention has been described in detail, and specific embodiments thereof have been disclosed. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of the present invention without departing from the concept and scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product specification.

[0299] The preparation of the compounds of this invention can be referred to WO2025049820A1, wherein the -L in the compound structure a -L b -L c - Some of them can be synthesized using conventional synthesis methods in this field.

[0300] In the embodiments, including In the structure, It is a carbon-carbon double bond, which has a Z configuration or an E configuration.

[0301] Example 1: 3-[4-(3-{4-[(1 2 Z, 6E)-1 6 -(1-{3-(1-hydro-1,2,3-triazol-1-yl)propionyl}-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecan-6-ene-2 4 [-yl]piperazin-1-yl]propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl]piperidine-2,6-dione compound 1

[0302] Step 1: Methyl 4-(4-(4-tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-6-chloro-1-hydro-indole-2-carboxylate 1c

[0303] At room temperature, methyl 4-bromo-6-chloro-1-hydro-indole-2-carboxylate 1a (intermediate 1a can be prepared by the method reported in patent WO2025049820A1) (0.45 g, 1.56 mmol), tert-butyl 4-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)piperazine-1-carboxylate 1b (0.69 g, 1.64 mmol), potassium carbonate (0.65 g, 4.68 mmol), and dichloro[1,1′-bis(diphenylphosphine)ferrocene]palladium (0.114 g, 0.16 mmol) were added sequentially to 1,4-dioxane (20 mL) and water (4 mL). The reaction mixture was purged with nitrogen three times and reacted at 85 °C for 8 hours under nitrogen protection. The reaction solution was cooled to room temperature, water (150 mL) was added, and the mixture was extracted once with ethyl acetate (150 mL). The organic phase was washed once with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 20-50%, v / v) to give 1c (0.70 g, yield: 89.94%), a white solid.

[0304] LCMS: m / z = 500.1 [M+H] + .

[0305] Step 2: Methyl 6-chloro-4-(2-hydroxy-4-(piperazin-1-yl)phenyl)-1-hydro-indole-2-carboxylate 1d

[0306] Methyl 4-(4-(4-tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-6-chloro-1-hydro-indole-2-carboxylate 1c (0.68 g, 1.36 mmol) was dissolved in dichloromethane (50 mL) at room temperature, then cooled to 0 °C, and a solution of boron tribromide in dichloromethane (17% wt, 6.0 g, 4.08 mmol) was added dropwise. After the addition was complete, the mixture was stirred at 0 °C for 1 hour, and then stirred at room temperature for 16 hours. The reaction mixture was quenched with water (70 mL), adjusted to alkalinity with saturated sodium bicarbonate solution, and then extracted once with dichloromethane (150 mL). The organic phase was washed once with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to give 1d (0.50 g, yield: 95.5%) as a yellow solid.

[0307] LCMS: m / z = 386.1 [M+H] + .

[0308] Step 3: Methyl 4-[2-((tert-butoxycarbonyl)oxy)-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-hydro-indole-2-carboxylic acid 1e

[0309] At room temperature, methyl 6-chloro-4-(2-hydroxy-4-(piperazin-1-yl)phenyl)-1-hydro-indole-2-carboxylate 1d (0.50 g, 1.30 mmol), triethylamine (0.39 g, 3.89 mmol), and di-tert-butyl dicarbonate (0.62 g, 2.85 mmol) were sequentially added to dichloromethane (50 mL). The reaction mixture was stirred at room temperature for 16 hours. Water (50 mL) was added to the reaction mixture, and the mixture was extracted once with dichloromethane (50 mL). The organic phase was washed once with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%–10%) to give 1e (0.45 g, yield: 95.9%) as a yellow solid.

[0310] LCMS: m / z = 586.2 [M+H] + .

[0311] Step 4: 4-[2-((tert-butoxycarbonyl)oxy)-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-(trimethylsilyl)ethoxy)methyl]-1-hydro-indole-2-carboxylic acid methyl ester 1f

[0312] Methyl 4-[2-((tert-butoxycarbonyl)oxy)-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1H-indole-2-carboxylate 1e (0.45 g, 0.77 mmol) was dissolved in N,N-dimethylformamide (40 mL) at room temperature, cooled to 0 °C, and sodium hydrogen (0.08 g, 1.92 mmol, 60% wt) was added. The reaction mixture was stirred at 0 °C for 20 minutes, and 2-(trimethylsilyl)ethoxymethyl chloride (0.38 g, 2.30 mmol) was added, followed by stirring at 0 °C for 8 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted once with dichloromethane (150 mL). The organic phase was washed once with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-5%) to obtain 1f (0.50 g, yield: 91.0%), which was a white solid.

[0313] LCMS: m / z = 716.3 [M+H] + .

[0314] Step 5: 1g of methyl 4-[4-(4-tert-butyloxycarbonylpiperazin-1-yl)-2-hydroxyphenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylate

[0315] At room temperature, methyl 4-[2-((tert-butoxycarbonyl)oxy)-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-(trimethylsilyl)ethoxy)methyl]-1H-indole-2-carboxylate 1f (0.50 g, 0.70 mmol) and potassium carbonate (0.29 g, 2.10 mmol) were added sequentially to methanol (30 mL). The reaction mixture was stirred at room temperature for 6 hours. Water (60 mL) was added to the reaction mixture, and the mixture was extracted once with dichloromethane (150 mL). The organic phase was washed once with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%–10%) to obtain 1 g (0.38 g, yield: 88.3%) as a white solid.

[0316] LCMS: m / z = 615.1 [M+H] + .

[0317] Step 6: Methyl 4-[2-but-3-en-1-yloxy-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylic acid 1i

[0318] At room temperature, 1 g (0.15 g, 0.24 mmol) of methyl 4-[4-(4-tert-butoxycarbonylpiperazin-1-yl)-2-hydroxyphenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylate, 0.10 g (0.73 mmol) of potassium carbonate, and 0.091 g (0.29 mmol) of 4-bromobut-1-ene were sequentially added to 20 mL of N,N-dimethylformamide. The reaction mixture was stirred at 50 °C for 16 hours. The reaction mixture was cooled to room temperature, 40 mL of water was added, and the mixture was extracted once with 100 mL of dichloromethane. The organic phase was washed once with 80 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-10%) to obtain 1i (0.14 g, yield: 85.8%), which was a white solid.

[0319] LCMS: m / z = 670.3 [M+H] + .

[0320] Step 7: 1g of 4-[2-but-3-en-1-yloxy-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylic acid

[0321] At room temperature, methyl 4-[2-but-3-en-1-yloxy-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylate 1i (0.14 g, 0.21 mmol) and sodium hydroxide (0.036 g, 0.90 mmol) were added sequentially to methanol (20 mL) and water (10 mL). The reaction mixture was stirred at 50 °C for 5 hours. The reaction mixture was cooled to room temperature, the pH was adjusted to 5 with 1 N hydrochloric acid, and the mixture was extracted twice with dichloromethane (70 mL). The organic phase was washed once with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-10%) to obtain 1g (0.13g, yield: 95.1%), which was a white solid.

[0322] LCMS: m / z = 656.1 [M+H] + .

[0323] Step 8: 4-[4-(2-allyl(methyl)carbamoyl-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indol-4-yl)-3-but-3-en-1-yloxyphenyl]piperazine-1-carboxylic acid tert-butyl ester 11

[0324] At room temperature, 1 g (0.13 g, 0.20 mmol) of 4-[2-but-3-en-1-yloxy-4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl]-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1-hydro-indole-2-carboxylic acid, 1 kJ (0.017 g, 0.24 mmol) of N-methylprop-2-en-1-amine, 0.23 g (0.59 mmol) of 2-(7-azabenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate, and 0.08 g (0.80 mmol) were added sequentially to 50 mL of dichloromethane. The reaction mixture was stirred at room temperature for 4 hours. Add water (40 mL) to the reaction solution, extract once with dichloromethane (100 mL), wash the organic phase once with saturated brine (60 mL), dry the organic phase with anhydrous sodium sulfate, filter, and concentrate under reduced pressure to dryness to obtain the crude product. The crude product is purified by silica gel column chromatography (dichloromethane:methanol = 0%-10%) to obtain white solid 11 (0.11 g, yield: 78.3%).

[0325] LCMS: m / z = 709.1 [M+H] + .

[0326] Step 9: tert-butyl 4-[4-(2-(allylmethylcarbamoyl)-6-chloro-1-hydro-indole-4-yl)-3-(3-butenoxy)phenyl]piperazine-1-carboxylate 1m

[0327] At room temperature, 0.40 g (1.08 mmol) of tert-butyl 4-[4-(2-allyl(methyl)carbamoyl-6-chloro-1-[(2-trimethylsilylethoxy)methyl]-1H-indol-4-yl)-3-but-3-en-1-yloxyphenyl]piperazine-1-carboxylate 11 was dissolved in tetrabutylammonium fluoride-tetrahydrofuran solution (1 mol / mL, 20 mL). The reaction mixture was stirred at 50 °C for 16 hours. The reaction mixture was cooled to room temperature, and water (40 mL) was added. The mixture was extracted once with dichloromethane (100 mL), and the organic phase was washed once with saturated brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-10%) to obtain 1 M (0.05 g, yield 68.2%) as a white solid.

[0328] LCMS: m / z = 579.2 [M+H] + .

[0329] Step 10: tert-butyl 4-[(1 2 Z,6E)-16-chloro-9-methyl-10-oxo-1 1Hydrogen-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecane-6-ene-2 4 [-yl]piperazine-1-carboxylic acid ester 1n

[0330] At room temperature, 1 m (0.045 g, 0.08 mmol) of tert-butyl 4-[4-(2-(allylmethylcarbamoyl)-6-chloro-1H-indol-4-yl)-3-(3-butenoxy)phenyl]piperazine-1-carboxylate and 1,3-bis(2,4,6-trimethylphenyl)-2-(imidazolidinediyl)(dichlorobenzylmethyl)(tricyclohexylphosphine)ruthenium (0.013 g, 0.02 mmol) were added sequentially to 10 mL of dichloromethane. The mixture was exchanged with nitrogen three times and stirred at 50 °C for 2 hours under nitrogen protection. The reaction mixture was cooled to room temperature, 40 mL of water was added, and the mixture was extracted once with 100 mL of dichloromethane. The organic phase was washed once with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-15%) to obtain 1n (0.04 g, yield 93.5%), which was a yellow solid.

[0331] LCMS: m / z = 551.1 [M+H] + .

[0332] Step 11: tert-butyl 4-[(1 2 Z,6E)-16-(1-(3-(1-hydro-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-10-oxo-1 1 Hydrogen-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecane-6-ene-2 4 [-yl]piperazine-1-carboxylate 1p

[0333] At room temperature, tert-butyl4-[(1 2 Z,6E)-16-chloro-9-methyl-10-oxo-1 1 Hydrogen-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecane-6-ene-2 4[-yl]piperazine-1-carboxylate 1n (0.035 g, 0.06 mmol), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1-hydro-1,2,3-triazol-1-yl)propane-1-one 1o (intermediate 1o can be obtained by the method reported in patent WO2025049820A1) The following reagents were prepared: 0.032 g (0.10 mmol), potassium phosphate (0.04 g, 0.19 mmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium methanesulfonate (0.005 g, 0.006 mmol) were added sequentially to 1,4-dioxane (4 mL) and water (1 mL). The mixture was exchanged with nitrogen three times and stirred at 100 °C for 2 hours under nitrogen protection. The reaction solution was cooled to room temperature, 20 mL of water was added, and the mixture was extracted once with dichloromethane (80 mL). The organic phase was washed once with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 0%-8%) to obtain 1p (0.02g, yield 43.6%), which was a yellow solid.

[0334] LCMS: m / z = 721.1 [M+H] + .

[0335] Step 12: (1) 2 Z,6E)-16-(1-(3-(1-hydro-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-2 4 -(piperazine-1-yl)-1 1 H-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecane-6-en-10-one 1q

[0336] At room temperature, tert-butyl4-[(1 2 Z,6E)-16-(1-(3-(1-hydro-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-10-oxo-1 1 Hydrogen-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecane-6-ene-2 4[-yl]piperazine-1-carboxylic acid ester 1p (0.02 g, 0.03 mmol) was dissolved in dichloromethane (3 mL), and then trifluoroacetic acid (0.5 mL) was added. The reaction mixture was stirred at room temperature for 1 hour. The solvent was concentrated off, and then the crude product was dissolved in dichloromethane (100 mL). The dichloromethane phase was washed once with saturated sodium bicarbonate aqueous solution (20 mL), then washed once with saturated brine (20 mL), and then dried over anhydrous sodium sulfate. The product was filtered and concentrated under reduced pressure to dryness to give product 1q (0.017 g, yield 98.7%) as a yellow solid.

[0337] LCMS: m / z = 621.1 [M+H] + .

[0338] Step 13: 3-[4-(3-{4-[(1) 2 Z, 6E)-1 6 -(1-{3-(1-hydro-1,2,3-triazol-1-yl)propionyl}-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecan-6-ene-2 4 [-yl]piperazin-1-yl]propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl]piperidine-2,6-dione compound 1

[0339] At room temperature, (1) 2 Z,6E)-16-(1-(3-(1-hydro-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-9-methyl-2 4 -(piperazine-1-yl)-1 1H-3-oxa-9-aza-1(4,2)-indolo-2(1,2)-benzocyclodecan-6-en-10-one 1q (0.017 g, 0.03 mmol), 3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1-hydro-benzo[d]imidazol-4-yl)propionaldehyde 1r (intermediate 1r can be prepared by the method reported in patent WO2025049820A1) (0.010 g, 0.03 mmol) were added sequentially to dimethyl sulfoxide (1.5 mL) and tetrahydrofuran (1.5 mL), followed by sodium triacetylborohydride (0.011 g, 0.05 mmol). The reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with water (20 mL), then extracted twice with dichloromethane (40 mL), the combined dichloromethane phases were washed once with saturated brine (30 mL), dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain crude product. The crude product was purified by high performance liquid chromatography to obtain product compound 1 (1.4 mg, yield: 5.5%), which was a white solid.

[0340] LCMS: m / z = 920.1 [M+H] + .

[0341] 1 H NMR (400MHz, MeOH-d4): 8.02 (d, J=7.2Hz, 1H), 7.69 (d, J=9.2Hz, 1H), 7.37 (d, J=8.0Hz, 1H), 7.25 (dd, J=8.4Hz, 3.6Hz, 1H), 7.07-6.95 (m, 5H), 6.73 (s, 1H), 6.60 (d, J=8.4Hz, 1H), 6.29-6.25 (m, 1H), 5.86-5.84 (m, 1H), 5.71-5.69 (m, 1H), 5. 35-5.30 (m, 1H), 4.53-4.49 (m, 3H), 3.73-3.62 (m, 5H), 3.26-3.20 (m, 3H), 3.18-3.12 (m, 5H), 3.05 (t, J=7.6Hz, 2H), 2. 91-2.56 (m, 8H), 2.58 (t, J=7.2Hz, 2H), 2.37-2.32 (m, 4H), 2.19-2.13 (m, 2H), 2.12-1.90 (m, 4H), 1.60 (t, J=7.6Hz, 2H).

[0342] High performance liquid chromatography (HPLC) conditions: Column: Ultimate Prep C18 10μm 21.2×250mm; Mobile phase: A: water (10mM ammonium bicarbonate) B: acetonitrile; Gradient: 34-64% B in 8min, end time: 16min; Flow rate (ml / min): 30; Retention time (min): 11.4; Wavelength (nm): 214 / 254.

[0343] Example 2: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperazin-1-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione compound 2

[0344] Step 1: methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-1H-indole-2-carboxylic acid 2c

[0345] At room temperature, methyl 4-(4-(4-tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-6-chloro-1H-indole-2-carboxylate 2a (3.50 g, 7.00 mmol), 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl) 2b of acetone-1-one (3.49 g, 10.50 mmol), cesium fluoride (3.72 g, 24.50 mmol), and palladium methanesulfonate (0.59 g, 0.70 mmol) of 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]methanesulfonate were added sequentially to 1,4-dioxane (50 mL) and water (15 mL). The reaction mixture was purged with nitrogen three times and reacted at 100 °C for 18 hours under nitrogen protection. The reaction mixture was cooled to room temperature, and water (100 mL) was added. The mixture was extracted twice with dichloromethane (150 mL), washed once with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to give methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-1H-indole-2-carboxylate 2c (3.3 g, yield 70.4%), as a yellow solid.

[0346] LCMS: m / z = 670.3 [M+H] + .

[0347] Step 2: methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-hydroxy-4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxylate 2d

[0348] At room temperature, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-methoxyphenyl)-1H-indole-2-carboxylate 2c (3.20 g, 4.78 mmol) was dissolved in dichloromethane (50 mL), then cooled to 0 °C, and a solution of boron tribromide in dichloromethane (17% wt, 47 mL, 47.0 mmol) was added dropwise. After the addition was complete, the mixture was stirred at 0 °C for 1 hour, and then stirred at room temperature for 16 hours. Add boron tribromide dichloromethane solution (17% wt, 10 mL, 10.0 mmol) dropwise at room temperature, then stir at room temperature for 5 hours. Quench the reaction solution with methanol (70 mL) in an ice-water bath, concentrate by rotary evaporation to remove methanol, adjust the base with saturated sodium bicarbonate aqueous solution, and then extract once with dichloromethane (350 mL). Dry the organic phase with anhydrous sodium sulfate, filter, and concentrate under reduced pressure to dryness to obtain crude methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-hydroxy-4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxylate 2d (2.5 g, yield: 94.3%) as a yellow solid.

[0349] LCMS: m / z = 556.1 [M+H] + .

[0350] Step 3: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-hydroxyphenyl)-1H-indole-2-carboxylic acid methyl ester 2e

[0351] At room temperature, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-hydroxy-4-(piperazin-1-yl)phenyl)-1H-indole-2-carboxylate 2d (2.50 g, 4.50 mmol), triethylamine (1.37 g, 13.51 mmol), and di-tert-butyl dicarbonate (0.98 g, 4.50 mmol) were sequentially added to dichloromethane (80 mL). The reaction mixture was stirred at room temperature for 16 hours. Water (100 mL) was added to the reaction mixture, and the mixture was extracted once with dichloromethane (100 mL). The organic phase was washed once with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-10%) to give methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-hydroxyphenyl)-1H-indole-2-carboxylate 2e (2.00 g, yield: 67.8%), as a yellow solid.

[0352] LCMS: m / z = 656.3 [M+H] + .

[0353] Step 4: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylic acid methyl ester 2f

[0354] At room temperature, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(tert-butyloxycarbonyl)piperazin-1-yl)-2-hydroxyphenyl)-1H-indole-2-carboxylate 2e (0.42 g, 0.64 mmol), potassium carbonate (0.27 g, 1.92 mmol), and 4-bromobut-1-ene 2 g (0.17 g, 1.28 mmol) were sequentially added to N,N-dimethylformamide (10 mL). The reaction mixture was stirred at 80 °C for 18 hours. The reaction mixture was cooled to room temperature, water (50 mL) was added, and the mixture was extracted twice with dichloromethane (100 mL). The organic phase was washed once with saturated brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-10%) to give methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylate 2f (0.23 g, yield: 50.6%), as a yellow solid.

[0355] LCMS: m / z = 710.2[M+H] + .

[0356] Step 5: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylic acid 2h

[0357] At room temperature, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylate 2f (0.23 g, 0.32 mmol) and sodium hydroxide (0.05 g, 1.30 mmol) were added sequentially to methanol (25 mL) and water (10 mL). The reaction mixture was stirred at 50 °C for 5 hours. The reaction mixture was cooled to room temperature, the pH was adjusted to 5 with 1 N hydrochloric acid, and the mixture was extracted twice with dichloromethane (60 mL). The organic phase was washed once with saturated brine (45 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-10%) to obtain crude 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylic acid 2h (0.20 g, yield: 88.7%), as a yellow solid.

[0358] LCMS: m / z = 696.2 [M+H] + .

[0359] Step 6: 4-(4-(6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(but-3-en-1-yl(methyl)carbamoyl)-1H-indol-4-yl)-3-(but-3-cyclo-1-yloxy)phenyl)piperazine-1-carboxylic acid tert-butyl ester 2j

[0360] At room temperature, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(2-(but-3-en-1-yloxy)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-1H-indole-2-carboxylic acid 2h (0.20 g, 0.29 mmol), 2-(2-(methylamino)ethoxy)ethane-1-ol 2i (0.04 g, 0.32 mmol), 2-(7-azabenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (0.16 g, 0.43 mmol), and N,N-diisopropylethylamine (0.11 g, 0.86 mmol) were dissolved in dichloromethane (40 mL). The reaction mixture was stirred at room temperature for 18 hours. The reaction solution was added to water (50 mL), extracted once with dichloromethane (100 mL), the organic phase was washed once with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-10%) to obtain 2j (0.10 g, yield 45.6%) of tert-butyl piperazine-1-carboxylate, a yellow solid.

[0361] LCMS: m / z = 763.4 [M+H] + .

[0362] Step 7: 4-((1) 2 Z,6Z)-16-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2-(1,2)-benzocycloundecane-6-ene-2 4 2kJ / (2kJ)piperazine-1-carboxylic acid tert-butyl ester

[0363] At room temperature, 4-(4-(6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2-(but-3-en-1-yl(methyl)carbamoyl)-1H-indol-4-yl)-3-(but-3-cyclo-1-yloxy)phenyl)piperazine-1-carboxylic acid tert-butyl ester 2j (0.10 g, 0.13 mmol) and 1,3-bis(2,4,6-trimethylphenyl)-2-(imidazolidinediyl)(dichlorobenzylmethyl)(tricyclohexylphosphine)ruthenium (0.022 g, 0.03 mmol) were sequentially added to dichloromethane (10 mL). The mixture was exchanged with nitrogen three times and stirred at 50 °C for 3 hours under nitrogen protection. The reaction solution was cooled to room temperature, water (30 mL) was added, and the mixture was extracted once with dichloromethane (80 mL). The organic phase was washed once with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-15%) to give 2k (0.075 g, yield 77.8%) as a yellow solid.

[0364] LCMS: m / z = 735.3 [M+H] + .

[0365] Step 8: (1) 2 Z,6Z)-16-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-2 4 -(piperazine-1-yl)-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-en-11-one 21

[0366] At room temperature, 4-((1) 2 Z,6Z)-16-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2-(1,2)-benzocycloundecane-6-ene-2 42kJ of tert-butyl piperazine-1-carboxylate (0.075 g, 0.10 mmol) was dissolved in dichloromethane (10 mL), and then trifluoroacetic acid (5 mL) was added. The reaction mixture was stirred at room temperature for 2 hours. The solvent was concentrated off, and then the crude product was dissolved in dichloromethane (100 mL). The dichloromethane phase was washed once with saturated sodium bicarbonate aqueous solution (20 mL), then washed once with saturated brine (20 mL), and then dried over anhydrous sodium sulfate. The product was filtered, concentrated under reduced pressure to dryness to give 21 (0.05 g, yield 80.1%), a brown solid.

[0367] LCMS: m / z = 635.1 [M+H] + .

[0368] Step 9: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperazin-1-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione compound 2

[0369] At room temperature, (1) 2 Z,6Z)-16-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-24 - (piperazine-1-yl)-1 1 H-3-oxa-10-aza-1(4,2)-indol-2(1,2)-benzocycloundecane-6-en-11-one 21 (50 mg, 0.08 mmol), 3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propionaldehyde 1m (intermediate 1m can be prepared by the method reported in patent WO2025049820A1) (30 mg, 0.09 mmol) was dissolved in dimethyl sulfoxide (1.5 mL) and tetrahydrofuran (1.5 mL), and then sodium triacetylborohydride (33 mg, 0.16 mmol) was added. The reaction solution was stirred at room temperature for 3 hours. The reaction was quenched with water (20 mL), then extracted twice with dichloromethane (40 mL). The combined dichloromethane phases were washed once with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was purified by preparative high-performance liquid chromatography to obtain (Z)-3-(4-(4-(16 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 Compound 2 (11 mg, yield 14.9%) of 1-(1-yl)piperazine-1-yl)propyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione was a white solid product.

[0370] LCMS: m / z = 934.3 [M+H] + .

[0371] 1 H NMR (400MHz, DMSO-d6): 11.34-11.29 (m, 1H), 11.10 (s, 1H), 8.12 (d, J=5.2Hz, 1H), 7. 69(d, J=12.4Hz, 1H), 7.64-7.61(m, 1H), 7.35(s, 1H), 7.19-7.06(m, 2H), 6.98-6.55(m , 8H), 5.39-5.35 (m, 3H), 4.66-4.43 (m, 2H), 3.71-3.58 (m, 6H), 3.29-3.16 (m, 6H), 3.0 4(s, 3H), 2.97-2.84(m, 3H), 2.75-2.54(m, 7H), 2.45-2.21(m, 7H), 2.08-1.79(m, 6H).

[0372] Example 3: 3-((4-(4-((1) 2 Z, 6E)-1 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 ,2 3 -difluoro-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundeceno-6-ene-2 4 -yl)piperazine-1-yl)-5-fluoro-2-methoxyphenyl)amino)piperidine-2,6-dione compound 3A; 3-((4-[4-((1 2 Z,7Z)-1 6 -[1-(3-(1H-pyrazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-1 7 ,2 3-difluoro-11-methyl-12-oxo-1 1 H-3-oxa-11-aza[1(4,2)-indole-2(1,2-benzene]cyclododecano-7-ene-2 4 [-yl)piperazin-1-yl]-5-fluoro-2-methoxyphenyl)amino)piperidine-2,6-dione compound 3B

[0373] Step 1: 1-Bromo-3-fluoro-4-iodo-2-(pent-4-en-1-oxy)benzene 3b

[0374] At room temperature, 6-bromo-2-fluoro-3-iodophenol (5.00 g, 15.82 mmol) was dissolved in N,N-dimethylformamide (40 mL), followed by the addition of 5-bromo-1-pentene (7.02 g, 47.46 mmol), cesium carbonate (15.40 g, 47.46 mmol), and potassium iodide (263 mg, 1.58 mmol). The reaction mixture was exchanged with nitrogen three times and reacted at 80 °C for 3 hours under nitrogen protection. The reaction was monitored by TCL until completion. The reaction mixture was cooled to room temperature, and water (100 mL) was added. The mixture was extracted three times with ethyl acetate (100 mL), and the organic phase was washed three times with saturated brine (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to give the product 1-bromo-3-fluoro-4-iodo-2-(pent-4-en-1-oxy)benzene 3b (6.00 g, yield: 99%), which was a yellow oil.

[0375] 1 H NMR (400MHz, DMSO-d6): 7.52-7.48(m, 1H), 7.29-7.26(m, 1H), 5.91-5.81(m, 1H), 5.09- 4.98 (m, 2H), 4.05 (t, J=6.4Hz, 2H), 2.23 (dd, J=14.4Hz, 7.2Hz, 2H), 1.84-1.78 (m, 2H).

[0376] Step 2: Tert-butyl 4-(4-bromo-2-fluoro-3-(pent-4-en-1-oxy)phenyl)piperazine-1-carboxylic acid ester 3c

[0377] At room temperature, 1-bromo-3-fluoro-4-iodo-2-(pent-4-ene-1-hydroxy)benzene 3b (88 mg, 0.23 mmol) was dissolved in anhydrous 1,4-dioxane (6 mL), followed by the addition of tert-butylpiperazine-1-carboxylate (47 mg, 0.25 mmol), tris(dibenzylacetone)dipalladium (21 mg, 0.02 mmol), 9-dimethyloxanthracene (13 mg, 0.02 mmol), and cesium carbonate (112 mg, 0.34 mmol). The reaction mixture was subjected to three nitrogen exchanges and reacted at 80°C for 6 hours under nitrogen protection. The reaction solution was cooled to room temperature and concentrated to dryness under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 0%-7%) to obtain crude tert-butyl 4-(4-bromo-2-fluoro-3-(pent-4-en-1-oxy)phenyl)piperazine-1-carboxylic acid ester 3c (56 mg, purity: 82%, yield 44.5%), which was a yellow solid.

[0378] LCMS: m / z: 443.2 [M+H] + .

[0379] Step 3: 1-(4-bromo-2-fluoro-3-(pent-4-en-1-yloxy)phenyl)piperazine 3d

[0380] At room temperature, 2 mL of trifluoroacetic acid was added to a solution of tert-butyl 4-(4-bromo-2-fluoro-3-(pent-4-en-1-oxy)phenyl)piperazine-1-carboxylic acid ester 3c (56 mg, 0.13 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated directly to dryness under reduced pressure to give crude product 1-(4-bromo-2-fluoro-3-(pent-4-en-1-yloxy)phenyl)piperazine 3d (95 mg), a light brown oil. The crude product was not further purified and was used directly in the next step.

[0381] LCMS: m / z: 343.2 [M+H] + .

[0382] Step 4: 1-(4-bromo-2-fluoro-3-(penta-4-en-1-yloxy)phenyl)-4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazine 3e

[0383] At room temperature, N,N-diisopropylethylamine (128 mg, 0.99 mmol) and 1,2-difluoro-4-methoxy-5-nitrobenzene (26 mg, 0.14 mmol) were added to a solution of crude product 1-(4-bromo-2-fluoro-3-(pent-4-en-1-yloxy)phenyl)piperazine 3d (95 mg, 0.28 mmol) in N,N-dimethylformamide (4 mL). The reaction solution was reacted at 80 °C for 5 hours. The reaction solution was cooled to room temperature, water (10 mL) was added, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phase was washed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 0%-11%) to give 1-(4-bromo-2-fluoro-3-(penta-4-en-1-yloxy)phenyl)-4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazine 3e (40 mg, two-step yield: 57%), as an orange-red solid.

[0384] LCMS: m / z: 511.8 [M+H] + .

[0385] 1 H NMR (400MHz, DMSO-d6): 7.88 (d, J=13.2Hz, 1H), 7.35 (d, J=8.8Hz, 1H), 6.82 (t, J=8.8Hz, 1H), 6.75 (d, J=7.6Hz, 1H), 5.92-5.81 (m, 1H), 5.07 ( d, J=16.8Hz, 1H), 5.00 (d, J=10.0Hz, 1H), 4.04 (t, J=6.4Hz, 2H), 3.96( s, 3H), 3.46 (s, 4H), 3.18 (s, 4H), 2.27-2.21 (m, 2H), 1.85-1.78 (m, 2H).

[0386] Step 5: Methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-1H-indole-2-carboxylic acid ester 3h

[0387] At room temperature, 3f of methyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylate (434 mg, 1.31 mmol) was dissolved in 1,4-dioxane / water (20 mL / 5 mL), followed by the addition of 3g of 3-(1H-pyrazol-1-yl)-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)-5,6-dihydropyridin-1(2H)-yl)propane-1-one (400 mg, 1.31 mmol), potassium carbonate (362 mg, 2.62 mmol), and 1,1′-bis(diphenylphosphino)ferrocene palladium(II) dichloride (107 mg, 0.13 mmol). The reaction mixture was purged with nitrogen three times and reacted at 80 °C for 2 hours under nitrogen protection. The reaction was detected by LCMS. The crude product was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to give methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-1H-indole-2-carboxylic acid ester 3h (320 mg, yield: 57%), as a yellow solid.

[0388] LCMS: m / z = 431.2[M+H] + .

[0389] Step 6: Methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxazolidine-2-yl)-1H-indole-2-carboxylic acid ester 3i

[0390] At room temperature, methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-1H-indole-2-carboxylic acid ester (100 mg, 0.19 mmol) was dissolved in 1,4-dioxane (5 mL) and thiohexane. Then, pinacol diboronate (354 mg, 1.40 mmol), potassium acetate (205 mg, 2.10 mmol), and methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (59 mg, 0.07 mmol) were added sequentially. The reaction mixture was purged with nitrogen three times and reacted at 80 °C for 2 hours under nitrogen protection. The reaction was detected by LCMS. The crude product was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to obtain methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxazolidine-2-yl)-1H-indole-2-carboxylic acid ester 3i (270 mg, yield: 74%), as a yellow solid.

[0391] 1 H NMR (400MHz, DMSO-d6): 12.52 (d, J=6.8Hz, 1H), 7.72 (dd, J=12.4Hz, 2.0Hz, 1H), 7.43-7.37 (m, 3H), 6.18-6.21 (m, 1H) , 6.06 (s, 1H), 4.39-4.23 (m, 4H), 3.90 (s, 3H), 3.66-3.56 (m, 2H), 3.00-2.92 (m, 2H), 2.33-2.26 (m, 2H), 1.34 (s, 12H).

[0392] Step 7: Methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid ester 3j

[0393] At room temperature, methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxazolidine-2-yl)-1H-indole-2-carboxylic acid ester 3i (100 mg, 0.19 mmol) was dissolved in 1,4-dioxane / water (5 mL / 1 mL), and 1-(4-bromo-2-fluoro-3-yl) was added sequentially. -(penta-4-en-1-yloxy)phenyl)-4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazine 3e (95 mg, 0.19 mmol), potassium phosphate (81 mg, 0.38 mmol), and methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (32 mg, 0.04 mmol). The reaction mixture was refluxed under nitrogen for 2 hours after three nitrogen exchanges. The reaction was monitored by LCMS until completion. The solvent was concentrated under reduced pressure to obtain the crude product, which was dispersed in water (15 mL) and ethyl acetate (15 mL). The pH of the reaction mixture was adjusted to less than 5 with 1 N hydrochloric acid. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (15 mL). The combined organic phases were washed twice with saturated brine (15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid ester 3j (190 mg, crude product), as a yellow solid.

[0394] LCMS: m / z = 827.8 [M+H] + .

[0395] Step 8: 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid 3k

[0396] At room temperature, lithium hydroxide (97 mg, 2.30 mmol) was added to a methanol (4 mL) solution of 3j (190 mg) of the crude product methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid ester. The reaction mixture was stirred overnight. The reaction was completed by LCMS, and the solvent was concentrated under reduced pressure to obtain the crude product, which was dispersed in water (15 mL) and ethyl acetate (15 mL). The pH of the reaction mixture was adjusted to less than 5 with 1 N hydrochloric acid. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (15 mL). The combined organic phases were washed twice with saturated brine (15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid 3k (200 mg, crude product), as a yellow solid.

[0397] LCMS: m / z = 813.7 [M+H] + .

[0398] Step 9: 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-N-methyl-1H-indole-2-carboxamide 31

[0399] At room temperature, N,N-dimethylformamide (N,N'-dimethylformamide) containing 150 mg (crude) of 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-1H-indole-2-carboxylic acid 3j) was dissolved. In a 10 mL solution, N-methylbut-3-ene-1-amine hydrochloride (27 mg, 0.22 mmol), N,N-diisopropylethylamine (119 mg, 0.92 mmol), 1-hydroxybenzotriazole (30 mg, 0.22 mmol), and 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (84 mg, 0.22 mmol) were added sequentially. The reaction mixture was stirred for 2 hours under nitrogen protection. After the reaction was complete as detected by LCMS, the reaction mixture was poured into ice water (30 mL) and extracted twice with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine (15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to give 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-N-methyl-1H-indole-2-carboxamide 31 (100 mg, total yield of three steps: 66%), as a yellow solid.

[0400] LCMS: m / z = 441.4 [M / 2 + H] + .

[0401] Step 10: (1) 2 Z, 6Z)-1 6 -[1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl]-1 7 ,2 3 -Difluoro-2 4 -[4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl]-10-methyl-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-en-11-one and (1 2 Z,7Z)-1 6 -[1-[3-(1H-pyrazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-1 7 ,2 3-Difluoro-24-[4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl]-1 1 -Methyl-1 1 H-3-Oza-1 1 -aza[1(4,2)-indole-2(1,2-benzene]cyclododecano-7-en-12-one 3m

[0402] At room temperature, 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-4-(3-fluoro-4-(4-(2-fluoro-5-methoxy-4-nitrophenyl)piperazin-1-yl)-2-(pent-4-en-1-yloxy)phenyl)-N-methyl-1H-indole-2-carboxamide 31 (110 mg, 0.13 mmol) and 1,3-bis(2,4,6-trimethylphenyl)-2-(imidazolidinediyl)(dichlorobenzylmethyl)(tricyclohexylphosphine)ruthenium (30 mg) were added sequentially to dichloromethane (30 mL). The mixture was exchanged three times with argon gas, and the reaction solution was refluxed for 1 hour under argon protection. The reaction solution was cooled to room temperature, and the dichloromethane was concentrated under reduced pressure to remove the impurities. The remaining mixture was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to give 3m (75 mg, yield: 70%), a cyclic mixture, as a yellow solid.

[0403] LCMS: m / z = 852.7 [M+H] + .

[0404] Step 11: (1) 2 Z, 6Z)-1 6 -[1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl]-1 7 ,2 3 -Difluoro-2 4 -[4-(4-amino-2-fluoro-5-methoxyphenyl)piperazin-1-yl]-10-methyl-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-en-11-one and (1 2 Z,7Z)-1 6 -[1-[3-(1H-pyrazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-2 4 -[4-(4-amino-2-fluoro-5-methoxyphenyl)piperazin-1-yl]-1 7 ,2 3 -Difluoro-11-methyl-1 1 H-3-Oza-11 -Aza[1(4,2)-indole-2(1,2)-benzene]cyclododecane-7-en-12-one 3n

[0405] At room temperature, 3m (90 mg, 0.11 mmol), iron powder (59 mg, 1.06 mmol), and ammonium chloride (57 mg, 1.06 mmol) were added sequentially to ethanol (5 mL) and water (2 mL). The reaction mixture was subjected to three argon gas exchanges and reacted at 80 °C for 3 hours under argon protection. The reaction mixture was cooled to room temperature, and water (20 mL) was added. The mixture was extracted twice with ethyl acetate (15 mL), and the organic phase was washed once with saturated brine (15 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%–5%) to obtain 3n (60 mg, yield: 69%), a cyclic mixture, as a yellow solid.

[0406] LCMS: m / z = 822.8 [M+H] + .

[0407] Step 12: 3-((4-(4-((1) 2 Z, 6Z)-1 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 ,2 3 -difluoro-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperazine-1-yl)-5-fluoro-2-methoxyphenyl)amino)piperidine-2,6-dione compound 3A; 3-((4-[4-((1 2 Z,7Z)-1 6 -[1-(3-(1H-pyrazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-1 7 ,2 3 -difluoro-11-methyl-12-oxo-1 1 H-3-oxa-11-aza[1(4,2)-indole-2(1,2-benzene]cyclododecane-7-ene-2 4 [-yl)piperazin-1-yl]-5-fluoro-2-methoxyphenyl)amino)piperidine-2,6-dione compound 3B

[0408] At room temperature, 3n (60 mg, 0.07 mmol), sodium bicarbonate (61 mg, 0.73 mmol), and 3-bromopiperidine-2,6-dione (28 mg, 0.15 mmol) were added sequentially to DMF (4 mL). The mixture was subjected to three argon gas exchanges, and the reaction was carried out at 80 °C for 12 hours under argon protection. During the reaction, 3-bromopiperidine-2,6-dione (56 mg, 0.29 mmol) was added in three separate portions. After the reaction was complete, the reaction mixture was cooled to room temperature. The DMF was concentrated under reduced pressure to remove the precipitate. The remaining mixture was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 0%-10%) to obtain the crude product. The crude product was purified by high-performance liquid chromatography (HPLC) to give compound 3A (0.73 mg, yield: 1%) as a white solid and compound 3B (0.86 mg, yield: 1%) as a yellow solid.

[0409] Compound 3A: LCMS: m / z = 920.2 [M+H] + ;

[0410] 1 ¹H NMR (400 MHz, dimethyl sulfoxide-d6): 12.05–12.03 (m, 1H), 10.86 (s, 1H), 7.73–7.71 (m, 1H), 7.43–7.37 (m, 1H), 7.14–7.12 (m, 1H), 6.92–6.57 (m, 5H), 6.20–6.15 (m, 2H), 5.48–5.38 (m, 2H), 5.14 (d, J = 6.8 Hz, 1H), 4.37–4.25 (m, 5H), 3.82–3.56 (m, 8H), 3.28–2.67 (m, 15H), 2.33–1.80 (m, 9H).

[0411] Compound 3B: LCMS: m / z = 934.2 [M+H] + .

[0412] Example 4:

[0413] 3-((4-((1 2 Z, 6Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-5-ene-2 4 -yl)piperidin-1-yl)-3-fluorophenyl)amino)piperidin-2,6-dione compound 4A; 3-((4-((1 2 Z, 6Z)-16 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperidin-1-yl)-3-fluorophenyl)amino)piperidin-2,6-dione compound 4B

[0414] Step 1: 6-Bromo-N-(But-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4b

[0415] At room temperature, 11.0 g (37.61 mmol) of 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid 4a was dissolved in N,N-dimethylformamide (110 mL), followed by the addition of N-methylbut-3-ene-1-amine hydrochloride (4.57 g, 37.61 mmol), N,N-diisopropylethylamine (14.55 g, 112.82 mmol), and 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (15.72 g, 41.37 mmol). The reaction mixture was stirred for 2 hours under nitrogen protection. The reaction was monitored by LCMS until complete. The reaction mixture was then poured into ice water (500 mL) and extracted twice with ethyl acetate (100 mL). The combined organic phases were washed twice with saturated brine (150 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 6-bromo-N-(but-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4b (8.8 g, yield: 65.1%), a brown solid.

[0416] LCMS: m / z = 359.2 [M+H] + .

[0417] Step 2: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4d

[0418] At room temperature, 6-bromo-N-(but-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4b (8.8 g, 24.47 mmol) was dissolved in 1,4-dioxane (100 mL) and water (10 mL), followed by the addition of 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)-3,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)propane-1-one 4c (8.13 g, 24.47 mmol), potassium carbonate (10.13 g, 73.41 mmol), and [1,1′-bis(diphenylphosphine)ferrocene]palladium(II) dichloride (1.79 g, 2.45 mmol). The reaction was purged with nitrogen three times, and the mixture was heated to 90°C and stirred for 16 hours. After the reaction was completed, the reaction solution was filtered with diatomaceous earth. The filtrate was concentrated and the crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 0%-70%) to obtain 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4d (9.5 g, yield: 80.1%), as a brown solid product.

[0419] LCMS: m / z = 485.3 [M+H] + .

[0420] Step 3: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentan-2-yl)-1H-indole-2-carboxamide 4e

[0421] At room temperature, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-4-chloro-7-fluoro-N-methyl-1H-indole-2-carboxamide 4d (7.5 g, 15.47 mmol) was dissolved in 1,4-dioxane (100 mL), followed by the addition of pinacol diboronate (7.85 g, 30.93 mmol), potassium acetate (4.53 g, 46.2 mmol), and methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (1.31 g, 1.55 mmol). The reaction mixture was exchanged with nitrogen three times and reacted at 80°C for 16 hours under nitrogen protection. The reaction was completed by LCMS. The solvent was concentrated under reduced pressure to obtain the crude product, which was then purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 0%-70%) to give methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)-1H-indole-2-carboxamide 4e (5.7 g, yield: 63.9%), as a white solid.

[0422] LCMS: m / z = 577.4 [M+H] + .

[0423] Step 4: 4g of 4-(3-(3-buten-1-yloxy)-4-chlorophenyl)-1-(2-fluoro-4-nitrophenyl)piperidine

[0424] At room temperature, 4-(3-(but-3-en-1-oxy)-4-chlorophenyl)piperidine 4f (200 mg, 0.752 mmol) and 3,4-difluoronitrobenzene (143.6 mg, 0.903 mmol) were dissolved in acetonitrile (2 mL), and potassium carbonate (208 mg, 1.51 mmol) was added. The mixture was exchanged three times with nitrogen, and the reaction solution was stirred at 80 °C for 16 hours under nitrogen protection. The reaction was completed as detected by LCMS. The reaction solution was cooled to room temperature, water (5 mL) was added, and the mixture was extracted three times with ethyl acetate (10 mL). The organic phase was washed three times with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5%) to give 4 g (180 mg, yield: 59.1%) of 4-(3-(3-buten-1-yloxy)-4-chlorophenyl)-1-(2-fluoro-4-nitrophenyl)piperidine as a yellow solid.

[0425] LCMS: m / z = 405.1 [M+H] + .

[0426] Step 5: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(3-buten-1-yl)-4-(2-(3-buten-1-yloxy)-4-(1-(2-fluoro-4-nitrophenyl)piperidin-4-yl)phenyl)-7-fluoro-N-methyl-1H-indole-2-carboxamide 4h

[0427] At room temperature, 4 g (180 mg, 0.444 mmol) of 4-(3-(3-buten-1-yloxy)-4-chlorophenyl)-1-(2-fluoro-4-nitrophenyl)piperidine and 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(but-3-en-1-yl)-7-fluoro-N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole-2- Formamide 4e (307 mg, 0.533 mmol) was dissolved in a mixed solvent of dioxane (2 mL) and water (0.4 mL). Methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-tris-isopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (37.6 mg, 0.044 mmol) and potassium phosphate (283 mg, 1.33 mmol) were added sequentially. Nitrogen exchange was performed three times, and the reaction mixture was stirred at 70 °C for 2 hours under nitrogen protection. The reaction was completed as detected by LCMS. The reaction solution was cooled to room temperature, water (5 mL) was added, and the mixture was extracted three times with ethyl acetate (10 mL). The organic phase was washed three times with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 10%) to give 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(3-buten-1-yl)-4-(2-(3-buten-1-yloxy)-4-(1-(2-fluoro-4-nitrophenyl)piperidin-4-yl)phenyl)-7-fluoro-N-methyl-1H-indole-2-carboxamide 4h (190 mg, yield: 27.5%), as a yellow solid.

[0428] LCMS: m / z = 819.4 [M+H] + .

[0429] Step 6: (1) 2 Z)-1 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluorine-2 4 -(1-(2-fluoro-4-nitrophenyl)piperidin-4-yl)-9-methyl-1 1 H-3-O-9-N-1(4,2)-Indole-2(1,2)-Benzocyclodecane-5-en-10-one and (1 2 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluorine-2 4 -(1-(2-fluoro-4-nitrophenyl)piperidin-4-yl)-10-methyl-1 1 H-3-O-10-N-1(4,2)-Indole-2(1,2)-Benzocycloundecane-6-en-11-one 4i

[0430] At room temperature, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-N-(3-buten-1-yl)-4-(2-(3-buten-1-yloxy)-4-(1-(2-fluoro-4-nitrophenyl)piperidin-4-yl)phenyl)-7-fluoro-N-methyl-1H-indole-2-carboxamide (100 mg, 0.122 mmol) was dissolved in dichloromethane (1 mL) and 1,3-bis(2,4,6-trimethylphenyl)-2-(imidazolidinediyl)(dichlorobenzylmethyl)(tricyclohexylphosphine)ruthenium (20.7 mg, 0.024 mmol) was added. The reaction mixture was stirred at room temperature for 12 hours under nitrogen protection after three nitrogen exchanges. The reaction was completed by LCMS. The reaction mixture was then concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 10%) to give 4i (62 mg, yield: 64.2%), which was a cyclized mixture.

[0431] LCMS: m / z = 791.4 [M+H] + ;

[0432] Step 7: (1) 2 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluorine-2 4 -(1-(2-fluoro-4-aminophenyl)piperidin-4-yl)-9-methyl-1 1H-3-O-9-N-1(4,2)-Indole-2(1,2)-Benzocyclodecan-5-en-10-one and (1 2 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluorine-2 4 -(1-(2-fluoro-4-aminophenyl)piperidin-4-yl)-10-methyl-1 1 H-3-O-10-N-1(4,2)-Indole-2(1,2)-Benzocycloundecane-6-en-11-one 4j

[0433] At room temperature, mixture 4i (58 mg, 0.073 mmol), iron powder (40.96 mg, 0.733 mmol), and ammonium chloride (39.2 mg, 0.733 mmol) were added sequentially to ethanol (1 mL) and water (1 mL). The reaction mixture was purged with nitrogen three times and reacted at 80 °C for 2 hours under nitrogen protection. The reaction mixture was cooled to room temperature, water (5 mL) was added, and the mixture was extracted twice with ethyl acetate (10 mL). The organic phase was washed once with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%–5%) to give mixture 4j (35 mg, yield: 62.7%) as a white solid.

[0434] LCMS: m / z = 761.3 [M+H] + .

[0435] Step 8: 3-((4-((1) 2 Z, 6Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-5-ene-2 4 -yl)piperidin-1-yl)-3-fluorophenyl)amino)piperidin-2,6-dione compound 4A; 3-((4-((1 2 Z, 6Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-10-methyl-11-oxo-1 1H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperidin-1-yl)-3-fluorophenyl)amino)piperidin-2,6-dione compound 4B

[0436] At room temperature, mixture 4j (35 mg, 0.046 mmol), sodium bicarbonate (38.6 mg, 0.46 mmol), and 3-bromopiperidine-2,6-dione (44 mg, 0.23 mmol) were sequentially added to N,N-dimethylformamide (1 mL). The mixture was exchanged with nitrogen three times, and the reaction was carried out at 80 °C for 12 hours under nitrogen protection. During the reaction, 3-bromopiperidine-2,6-dione (17.66 mg, 0.092 mmol) was added in three portions. After the reaction was complete, the reaction solution was cooled to room temperature. The mixture was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 0%-10%) to obtain the crude product. The crude product was further purified by high-performance liquid chromatography (HPLC) to give compound 4A (0.64 mg, yield: 1.62%) as a yellow solid and compound 4B (0.84 mg, yield: 2.09%) as a yellow solid.

[0437] Compound 4A: LCMS: RT = 1.818 min, m / z = 858.7 [M+H] + ;

[0438] Compound 4B: LCMS: RT = 1.865 min, m / z = 872.8 [M+H] + .

[0439] High performance liquid chromatography preparation conditions: Column: YMC-Actus Triart C18, 150*20mm, 5um; Mobile phase: A: water (0.1% NH4HCO3) B: acetonitrile; Gradient: 37-57% in 11min, stop at 10.6min; Flow rate: 20ml / min.

[0440] Example 5: 3-((4-(4-((1) 2 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-5-ene-2 4 -yl)piperidin-1-yl)-5-fluoro-2-methoxyphenyl)amino)piperidin-2,6-dione compound 5A; 3-((4-(4-((12 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxo-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-6-ene-2 4 -yl)piperidin-1-yl)-5-fluoro-2-methoxyphenyl)amino)piperidin-2,6-dione compound 5B; 3-((4-((1 2 Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-10-methyl-11-oxo-1 1 H-3-oxa-10-aza-1(4,2)-indole-2(1,2)-benzocycloundecane-6-ene-2 4 -yl)piperidin-1-yl)-5-fluoro-2-methoxyphenyl)amino)piperidin-2,6-dione compound 5C

[0441] Following the same experimental procedures as in Example 4, 1,2-difluoro-4-methoxy-5-nitrobenzene was used instead of 3,4-difluoronitrobenzene as the starting material to obtain compound 5A (2.14 mg, yield: 2.07%), a white solid; compound 5B (2.17 mg, yield: 2.10%), a yellow solid; and compound 5C (2.12 mg, yield: 2.02%), a yellow solid.

[0442] Compound 5A: LCMS: RT = 1.818 min, m / z = 888.8 [M+H] + ;

[0443] Compound 5B: LCMS: RT = 1.865 min, m / z = 888.8 [M+H] + ;

[0444] Compound 5C: LCMS: RT = 1.921 min, m / z = 902.8 [M+H] + .

[0445] High performance liquid chromatography preparation conditions: Column: YMC-Actus Triart C18, 150*20mm, 5um; Mobile phase: A: water (0.1% NH4HCO3) B: acetonitrile; Gradient: 38-58% in 17.1min, stop at 18min; Flow rate: 20ml / min.

[0446] Example 6: (Z)-3-[4-[4-[1 6 -(1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzenecyclodecane-24-yl]piperidin-1-yl]-3-fluorophenyl]piperidin-2,6-dione compound 6

[0447] Step 1: 6-Bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid tert-butyl ester 6b

[0448] At room temperature, 1,1-di-tert-butoxy-N,N-dimethylmethylamine (1.26 g, 6.19 mmol) was added dropwise to a suspension of 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid 6a (450 mg, 1.55 mmol) in toluene (15 mL). The mixture was refluxed for 2 hours. After the reaction was complete, the solvent was removed, and the crude product was purified by silica gel column chromatography (eluting with a gradient of ethyl acetate / dichloromethane from 0% to 10%) to give tert-butyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylic acid 6b (350 mg, 65% yield) as a white solid.

[0449] 1 H NMR (400MHz, DMSO-d6): 12.90 (s, 1H), 7.46 (d, J=4.8Hz, 1H), 7.08 (s, 1H), 1.58 (s, 9H).

[0450] Step 2: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-1H-indole-2-carboxylic acid tert-butyl ester 6c

[0451] At room temperature, 1,1-bis(diphenylphosphine)ferrocene palladium dichloride (74 mg, 0.10 mmol) was added to a mixture of tert-butyl 6-bromo-4-chloro-7-fluoro-1H-indole-2-carboxylate 6b (350 mg, 1.01 mmol), potassium carbonate (278 mg, 2.02 mmol), and 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-5,6-dihydropyridin-1(2H)-yl)-3-(1H-1,2,3-triazol-1-yl)prop-1-one (335 mg, 1.01 mmol) dioxane (10 mL) and water (2 mL) under nitrogen protection. The reaction mixture was stirred at 90 °C for 3 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain the crude residue. The crude product was purified by silica gel column chromatography (eluting with a gradient of methanol / dichloromethane from 0% to 8%) to obtain 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-chloro-7-fluoro-1H-indole-2-carboxylic acid tert-butyl ester 6c (350 mg, yield: 73%), as a yellow solid.

[0452] LCMS: m / z = 445.2 [M+H] + .

[0453] Step 3: {2-[2-(2-bromo-5-iodophenoxy)ethoxy]ethyl} tert-butyl methylcarbamate 6e

[0454] Under ice bath conditions, diisopropyl azodicarbonate (1.52 mg, 7.54 mmol) was slowly added to a solution of tert-butyl (2-(2-hydroxyethoxy)ethyl)(methyl)carbamate (0.83 g, 3.77 mmol), 2-bromo-5-iodophenol (1.35 g, 4.52 mmol) 6d, and triphenylphosphine (1.98 g, 7.54 mmol) in tetrahydrofuran (20 mL). The reaction mixture was then stirred at room temperature for 16 hours. After the starting materials were completely reacted as determined by LCMS, the reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 × 30 mL). After combining the organic phases, the product was washed with brine (3 × 30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Finally, it was purified by column chromatography (dichloromethane / methanol = 10%) to obtain the target product {2-[2-(2-bromo-5-iodophenoxy)ethoxy]ethyl} tert-butyl methylcarbamate 6e (1.60 g, yield: 82%) as a colorless oil.

[0455] LCMS: m / z = 516.0 [M+H] + .

[0456] Step 4: 6g of 8-(4-chloro-2-fluorophenyl)-1,4-dioxa-8-azaspiro[4.5]decane

[0457] At room temperature, sodium tert-butoxide (3.69 g, 38.46 mmol) was added in portions to a mixed solution of 1-bromo-4-chloro-2-fluorobenzene 6f (4 g, 19.23 mmol), 1,4-dioxa-8-azaspiro[4.5]decane (3.02 g, 21.15 mmol), tris(dibenzylacetone)dipalladium (880 mg, 0.96 mmol), and 2,2′-bis(diphenylphosphine)-1,1′-binaphthyl (597 mg, 0.96 mmol) in toluene (40 mL), and the mixture was purged three times with argon. The mixture was then stirred at 95 °C for 5 hours under argon protection. After the reaction was completed, the mixture was concentrated under reduced pressure using a rotary evaporator. The crude product was purified by silica gel column chromatography (eluting with a gradient of 0% to 10% ethyl acetate / petroleum ether) to obtain 6 g (3.00 g, yield: 58%) of compound 8-(4-chloro-2-fluorophenyl)-1,4-dioxa-8-azaspiro

[0045] decane, which was a yellow oil.

[0458] LCMS: m / z = 272.0 [M+H] + .

[0459] Step 5: 1-(4-chloro-2-fluorophenyl)piperidin-4-one for 6 hours

[0460] To a solution of 6 g (4.00 g, 14.76 mmol) of 8-(4-chloro-2-fluorophenyl)-1,4-dioxa-8-azaspiro[4.5]decane in 15 mL of formic acid, 2 mL of concentrated hydrochloric acid was added at room temperature. The mixture was stirred at 70 °C for 3 h. After the reaction was complete, the solvent was removed. The residue was dissolved in ethyl acetate (30 mL) and neutralized with aqueous potassium carbonate solution to pH > 9. The organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (30 mL × 2). The organic phases were combined and concentrated to give 1-(4-chloro-2-fluorophenyl)piperidin-4-one 6 h (3.00 g, yield: 90%) as a yellow oil.

[0461] LCMS: m / z = 228.3 [M+H] + .

[0462] Step 6: 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-one 6i

[0463] Under nitrogen protection and at room temperature, 149 mg (0.18 mmol) of dioxane (10 mL) and water (2 mL) containing 1-(4-chloro-2-fluorophenyl)piperidin-4-one (500 mg, 2.20 mmol), potassium carbonate (608 mg, 4.41 mmol), and 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)pyridine (918 mg, 2.20 mmol) were added to a mixed solution of methanesulfonic acid (2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)(2-amino-1,1-biphenyl-2-yl)palladium(II) (2-amino-1,1-biphenyl-2-yl)). The reaction mixture was then stirred at 95 °C for 5 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to give a crude residue. The crude product was subjected to silica gel column chromatography (eluting with a gradient of ethyl acetate / petroleum ether from 0% to 25%) to give compound 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-one 6i (580 mg, yield: 55%) as a yellow solid.

[0464] LCMS: m / z = 483.0 [M+H] + .

[0465] Step 7: 1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yltrifluoromethanesulfonate 6j

[0466] At -78 °C, a solution of 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-one 6i (900 mg, 1.87 mmol) dissolved in THF (2 mL) was added dropwise to a tetrahydrofuran (6 mL) solution containing sodium bis(trimethylsilyl)amino (2 mol / L, 1.40 mL, 2.80 mmol). The mixture was stirred at this low temperature for 1 hour, and then N-phenylbis(trifluoromethanesulfonyl)imide (1.00 g, 2.80 mmol) was added at this temperature. After the reaction was complete, the reaction mixture was diluted with ethyl acetate (30 mL) and washed successively with saturated ammonium chloride solution (15 mL) and saturated brine (25 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate / petroleum ether at a gradient of 0% to 13%) to give compound 1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yltrifluoromethanesulfonate 6j (850 mg, yield: 74%), as a yellow oil.

[0467] LCMS: m / z = 615.0 [M+H] + .

[0468] Step 8: 2,6-Bis(benzyloxy)-3-[3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-5,6-dihydropyridin-1(2H)-yl)phenyl]pyridine 6k was added to a suspension of 1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl trifluoromethanesulfonate 6j (1.70 g, 2.77 mmol), pinacol diboronate (2.11 g, 8.31 mL), and potassium acetate (1.36 g, 13.84 mmol) in dioxane (20 mL) at room temperature under nitrogen protection, along with bis(1,1′-diphenylphosphine-ferrocene)palladium (202 mg, 0.27 mmol). The mixture was then heated under reflux for 2 hours. After the reaction was complete, the mixture was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (eluting with a gradient of ethyl acetate / petroleum ether from 0% to 13%) to give 2,6-bis(benzyloxy)-3-[3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-5,6-dihydropyridin-1(2H)-yl)phenyl]pyridine 6k (1.20 g, yield: 73%) as a yellow solid.

[0469] LCMS: m / z = 593.4 [M+H] + .

[0470] Step 9: tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-bromophenoxy]ethoxy]ethyl](methyl)carbamate 61

[0471] Under nitrogen protection at room temperature, dichlorobis(1,1′-diphenylphosphine-ferrocene)palladium (44 mg, 0.06 mmol) was added to a mixed solution containing tert-butyl-2-[2-(2-bromo-5-iodophenoxy)ethoxy]ethylcarbamate 6e (300 mg, 0.60 mmol), potassium carbonate (249 mg, 1.80 mmol), and 2,6-bis(benzyloxy)-3-[3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-5,6-dihydropyridin-1(2H)-yl)phenyl]pyridine 6k (356 mg, 0.60 mmol) in tetrahydrofuran (10 mL) and water (2 mL). The reaction mixture was then stirred at 70 °C for 3 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to give a crude residue. The crude product was purified by silica gel column chromatography (eluting with a gradient of ethyl acetate / petroleum ether from 0% to 22%) to give tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-bromophenoxy]ethoxy]ethyl](methyl)carbamate 61 (220 mg, yield: 44%), as a yellow oil.

[0472] LCMS: m / z = 838.0 [M+H] + .

[0473] Step 10: tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate 6m

[0474] Under nitrogen protection at room temperature, dichlorobis(1,1′-diphenylphosphine-ferrocene)palladium (35 mg, 0.05 mmol) was added to a suspension of dioxane (5 mL) containing tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-bromophenoxy]ethoxy]ethyl](methyl)carbamate 61 (220 mg, 0.26 mmol), pinacol diboronate (Pin2B2) (134 mg, 0.53 mmol), and potassium acetate (129 mg, 1.31 mmol). The mixture was then stirred at 95 °C for 2 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluting with a gradient of 0% to 34% ethyl acetate / petroleum ether) to give tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate 6m (210 mg, yield: 90%), as a yellow oil.

[0475] LCMS: m / z = 886.2 [M+H] + .

[0476] Step 11: tert-butyl[2-[2-[5-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate 6n

[0477] At room temperature, palladium on carbon (150 mg) was added to a solution of tetrahydrofuran (10 mL) containing tert-butyl[2-[2-[5-[1-[4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl]-1,2,3,6-tetrahydropyridin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate (210 mg, 0.24 mmol). The mixture was then stirred at room temperature for 5 hours under a hydrogen atmosphere. After the reaction was complete, the reaction solution was filtered to remove the solid catalyst, and the filter cake was washed with tetrahydrofuran. After concentration, the combined organic phases of 6m yielded tert-butyl[2-[2-[5-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate 6n (210 mg, crude product), which was a colorless oil.

[0478] LCMS: m / z = 709.9 [M+H] + .

[0479] Step 12: tert-butyl 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[2-[2-[2-[[(tert-butoxycarbonyl)(methyl)amino]ethoxy]ethoxy]-4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]phenyl]-7-fluoro-1H-indole-2-carboxylic acid ester 6o

[0480] Under nitrogen protection at room temperature, cesium fluoride (225 mg, 1.48 mmol) was added to a methyl carbamate 6n containing tert-butyl[2-[2-[5-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenoxy]ethoxy]ethyl](methyl)carbamate 6n (210 mg, crude), cesium fluoride (225 mg, 1.48 mmol), and tert-butyl6-[1-[3-(1H-1,2,3-tri] A mixture of dioxane (10 mL) and water (2 mL) of [[azazol-1-yl]propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-chloro-7-fluoro-1H-indole-2-carboxylic acid ester 6c (140 mg, 0.30 mmol) was added to methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (25 mg, 0.03 mmol). The reaction mixture was then stirred at 90 °C for 3 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to give the crude product. The crude product was subjected to silica gel column chromatography (eluting with a gradient of methanol / dichloromethane from 0% to 7%) to give the title compound tert-butyl 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[2-[2-[2-[[(tert-butoxycarbonyl)(methyl)amino]ethoxy]ethoxy]-4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]phenyl]-7-fluoro-1H-indole-2-carboxylic acid ester 6o (100 mg, yield: 33%), as a yellow oil.

[0481] LCMS: m / z = 1020.8 [M+H] + .

[0482] Step 13: 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-[2-[2-(methylamino)ethoxy]ethoxy]phenyl]-7-fluoro-1H-indole-2-carboxylic acid 6p

[0483] To a solution of tert-butyl 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[2-[2-[2-[[(tert-butoxycarbonyl)(methyl)amino]ethoxy]ethoxy]-4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]phenyl]-7-fluoro-1H-indole-2-carboxylic acid ester 6O (100 mg, 0.10 mmol), 2 mL of trifluoroacetic acid was added. The mixture was then stirred and reacted at room temperature for 2 hours. After the reaction was complete, the solvent was removed by vacuum distillation. The residue was dissolved in dichloromethane (10 mL) and concentrated again to give crude product 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-[2-[2-(2-(methylamino)ethoxy]ethoxy]phenyl]-7-fluoro-1H-indole-2-carboxylic acid 6p (100 mg, crude product), which is a yellow oil.

[0484] LCMS: RT=0.601min, m / z=864.8[M+H] + .

[0485] Step 14: (Z)-3-[4-[4-[1 6 -(1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzenecyclodecane-2 4 [-yl]piperidin-1-yl]-3-fluorophenyl]piperidin-2,6-dione compound 6

[0486] To a solution of N,N-dimethylformamide (5 mL) containing 6-[1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl]-4-[4-[1-[4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl]piperidin-4-yl]-2-[2-[2-(methylamino)ethoxy]ethoxy]phenyl]-7-fluoro-1H-indole-2-carboxylic acid 6p (100 mg, crude), N,N-diisopropylethylamine (75 mg, 0.58 mmol) and 1-hydroxybenzotriazole (100 mg), 2-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethylurea hexafluorophosphate (88 mg, 0.23 mmol) was added in portions at room temperature. After stirring the mixture for 1 hour, it was poured into water (20 mL). Extraction was performed twice with ethyl acetate (30 mL). The combined organic phases were washed with saturated brine (15 mL x 2), dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by preparative high-performance liquid chromatography to obtain the final product (Z)-3-[4-[4-[1 6 -(1-[3-(1H-1,2,3-triazol-1-yl)propionyl]-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-1 0 -Oxyto-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzenecyclodecane-2 4 [-yl]piperidin-1-yl]-3-fluorophenyl]piperidin-2,6-dione compound 6 (36 mg, yield: 43%) is a white solid.

[0487] LCMS: m / z = 847.0 [M+H] + ;

[0488] 1H NMR (400MHz, DMSO-d6): 11.88 (d, J=10.8Hz, 1H), 10.84 (s, 1H), 8.11 (d, J=12.0Hz, 1H), 7.69 (d, J=12.0Hz, 1H), 7.35-7.32 (m, 1H), 7.08-6.84 (m, 7H), 6.14 (d, J=10.4Hz, 1H), 4.65-4.59 (m, 2H), 4.38-4.24 (m, 4H), 3.82 (dd, J=11.6, 4.4Hz, 1H), 3.71-3.58 (m, 7H), 3.50-3.47 (m, 4 H), 3.12-3.07(m, 2H), 2.97(s, 3H), 2.80-2.62(m, 4H), 2.35-2.17(m, 3H), 2.04-1.88(m, 5H).

[0489] Example 7: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 7 (-yl)piperidin-1-yl)-3-fluorophenyl)piperidin-2,6-dione compound

[0490] Step 1: 2-Chloro-5-(4-piperidinyl)phenol hydrochloride 7b

[0491] At room temperature, tert-butyl 4-(4-chloro-3-hydroxyphenyl)piperidin-1-carboxylate 7a (10.0 g, 32.07 mmol) was dissolved in dichloromethane (100 mL). The solution was cooled to 0 °C, and 1,4-dioxane hydrochloride solution (100 mL, 4 M) was added dropwise. After the addition was complete, the reaction was carried out at 20 °C for 2 hours. The reaction was confirmed to be complete by LCMS. The solution was concentrated to dryness under reduced pressure. The crude product was slurried with methyl tert-butyl ether (100 mL) to give product 2-chloro-5-(4-piperidinyl)phenol hydrochloride 7b (6.6 g, crude product), a white solid.

[0492] LCMS: m / z = 212.2[M+H] + .

[0493] Step 2: Benzyl 4-(4-chloro-3-hydroxyphenyl)piperidine-1-carboxylate 7c

[0494] At room temperature, 2-chloro-5-(4-piperidinyl)phenol hydrochloride 7b (6.6 g, 26.72 mmol) was dissolved in a mixture of tetrahydrofuran (50 mL) and water (50 mL). The solution was cooled to 0 °C, and sodium hydroxide (4.0 g, 100.00 mmol) and benzyl chloroformate (5.0 g, 29.39 mmol) were added sequentially. The reaction mixture was heated to 25 °C and stirred for 3 hours. The reaction was complete as determined by LC-MS, and the pH of the reaction mixture was adjusted to 3-4 with dilute hydrochloric acid (1 M). The aqueous phase was extracted three times with ethyl acetate (100 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 3:1) to obtain 4-(4-chloro-3-hydroxyphenyl)piperidin-1-carboxylate 7c (7.5 g, two-step yield: 67.4%), which was a yellow oil.

[0495] LCMS: m / z = 346.2 [M+H] + .

[0496] Step 3: 4-(3-(2-(((tert-butoxycarbonyl)(methyl)amino)ethoxy)ethoxy)-4-chlorophenyl)piperidine-1-carboxylic acid benzyl ester 7d

[0497] At room temperature, 6.5 g (18.80 mmol) of benzyl 4-(4-chloro-3-hydroxyphenyl)piperidin-1-carboxylate 7c, 4.5 g (20.68 mmol) of (2-(2-hydroxyethoxy)ethyl)(methyl)carbamate tert-butyl ester (4.5 g (20.68 mmol) and 5.7 g (28.19 mmol) of tri-n-butylphosphine (5.7 g (28.19 mmol)) were dissolved in tetrahydrofuran (65 mL). The reaction solution was cooled to 0 °C in an ice-water bath, and a tetrahydrofuran solution of N,N,N′,N′-tetramethylazodicarbonamide (4.9 g, 28.19 mmol, 20 mL) was added dropwise. After the addition was complete, the reaction was carried out at 20 °C for 2 hours. The reaction was detected as complete by LCMS. The reaction solution was quenched with water (100 mL), extracted three times with ethyl acetate (100 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 5:1) to obtain 7d (7.5 g, yield: 67.4%) of 4-(3-(2-(((tert-butoxycarbonyl)(methyl)amino)ethoxy)ethoxy)-4-chlorophenyl)piperidine-1-carboxylic acid benzyl ester, a yellow oil.

[0498] LCMS: m / z = 569.2 [M + Na] + .

[0499] Step 4: (2-(2-chloro-5-(piperidin-4-yl)phenoxy)ethoxy)ethyl)(methyl)carbamate tert-butyl ester 7e

[0500] At room temperature, 8.1 g (14.81 mmol) of benzyl 4-(3-(2-(((tert-butoxycarbonyl)(methyl)amino)ethoxy)ethoxy)-4-chlorophenyl)piperidin-1-carboxylate 7d was dissolved in ethyl acetate (80 mL), and palladium on carbon (10 wt%, 1.5 g) was added, purging with hydrogen three times. The reaction mixture was stirred at 25 °C for 16 hours. The reaction was completed by LCMS, filtered, and the filter cake was washed with tetrahydrofuran (150 mL). The mother liquor was concentrated under reduced pressure to give 5.5 g (90.0% yield) of tert-butyl (2-(2-chloro-5-(piperidin-4-yl)phenoxy)ethoxy)ethyl)(methyl)carbamate 7e, a brown oil.

[0501] LCMS: m / z = 413.1 [M+H] + ;

[0502] Step 5: 7g of (2-(2-(5-(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-yl)-2-chlorophenoxy)ethoxy)ethyl)(methyl)carbamate tert-butyl ester

[0503] At room temperature, tert-butyl (2-(2-chloro-5-(piperidin-4-yl)phenoxy)ethoxy)ethyl)(methyl)carbamate 7e (5.4 g, 13.08 mmol) was dissolved in toluene (54 mL), followed by the sequential addition of 2,6-bis(benzyloxy)-3-(4-bromo-3-fluorophenyl)pyridine (5.4 g, 11.66 mmol), tris(dibenzylacetone)palladium (1.0 g, 1.09 mmol), 2-dicyclohexylphosphine-2′,4′,6′-triisopropylbiphenyl (1.1 g, 2.33 mmol), and cesium carbonate (11.5 g, 35.06 mmol), purging with nitrogen three times. The reaction mixture was stirred at 100 °C for 6 hours. The reaction was monitored by LCMS until complete. The reaction mixture was quenched with water (100 mL), extracted three times with ethyl acetate (100 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 5:1) to obtain 7 g (3.9 g, yield 42.1%) of (2-(2-(5-(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-yl)-2-chlorophenoxy)ethoxy)ethyl)(methyl)carbamate tert-butyl ester, as a yellow oil.

[0504] LCMS: m / z = 796.2 [M+H] + .

[0505] Step 6: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-((tert-butoxycarbonyl(methyl)amino)ethoxy)ethoxyoxy)phenyl)-7-fluoro-1H-indole-2-carboxylic acid methyl ester 7h

[0506] At room temperature, 7 g (2.3 g, 2.89 mmol) of (2-(2-(2-(5-(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperidin-4-yl)-2-chlorophenoxy)ethoxy)ethyl)(methyl)carbamate tert-butyl ester was dissolved in a mixture of 1,4-dioxane (20 mL) and water (2 mL), followed by the addition of 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4, Methyl 5,5-tetramethyl-1,3,2-dioxaboron-2-yl)-1H-indole-2-carboxylate 71 (intermediate 71 was obtained according to the experimental procedure of intermediate 3i in Example 3) (2.0 g, 3.75 mmol) methane, sulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (244.3 mg, 288.81 μmol) and potassium phosphate (1.8 g, 8.49 mmol), purged with nitrogen three times. The reaction solution was stirred at 80 °C for 16 hours. The reaction was completed by LCMS and then cooled to room temperature. The reaction solution was quenched with water (50 mL), extracted three times with ethyl acetate (50 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 1:1) to give methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-((tert-butoxycarbonyl(methyl)amino)ethoxy)ethoxyoxy)phenyl)-7-fluoro-1H-indole-2-carboxylic acid 7h (2.1 g, yield 62.8%), as a yellow solid.

[0507] LCMS: m / z = 1157.7 [M+H] + .

[0508] Step 7: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid methyl ester 7i

[0509] Methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-((tert-butoxycarbonyl(methyl)amino)ethoxy)ethoxyoxy)phenyl)-7-fluoro-1H-indole-2-carboxylic acid 7h (2.1 g, 1.81 mmol)) was dissolved in dichloromethane (20 mL) at room temperature. Trifluoroacetic acid (4 mL) was added dropwise at 10 °C, and the reaction was maintained at this temperature for 2 hours. The reaction was confirmed by LCMS. The reaction solution was concentrated under reduced pressure. The crude product was slurried with methyl tert-butyl ether (50 mL) to obtain methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid methyl ester 7i (1.5 g, yield: 78.2%), a yellow solid.

[0510] LCMS: m / z: 1057.4 [M+H] + .

[0511] Step 8: 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid 7j

[0512] At room temperature, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid ester 7i (1.5 g, 1.42 mmol) was dissolved in a mixture of tetrahydrofuran (20 mL), methanol (20 mL), and water (4 mL), followed by the addition of sodium hydroxide (283.8 mg, 7.09 mmol). The reaction mixture was reacted at 50 °C for 16 hours. The reaction was monitored by LCMS until completion, and the reaction mixture was then cooled to 0 °C. The pH of the reaction solution was adjusted to 3 with dilute hydrochloric acid (2M), and the reaction solution was purified by reversed-phase column chromatography (0.1% HCl / MeOH) to give 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid 7j (900 mg, yield: 60.8%), as a yellow solid.

[0513] LCMS: m / z: 1043.3 [M+H] + .

[0514] Step 9: (Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-ylpropionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2 4 -(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-1 7 -Fluoro-9-methyl-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecan-10-one 7k

[0515] At room temperature, 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-2-(2-(methylamino)ethoxy)ethoxyphenyl)-7-fluoro-1H-indole-2-carboxylic acid 7i (400.0 mg, 383.45 μmol) was dissolved in dichloromethane (40 mL), followed by the sequential addition of 2-(7-azobenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (219.9 mg, 575.17 μmol) and N,N-diisopropylethylamine (197.9 mg, 1.53 mmol). The reaction solution was reacted at 25 °C for 2 hours. The reaction was confirmed by LCMS. The reaction solution was quenched with water (20 mL), extracted twice with dichloromethane (20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 1:4) to obtain (Z)-1. 6 -(1-(3-(1H-1,2,3-triazol-1-ylpropionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2 4 -(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-1 7 -Fluoro-9-methyl-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodeca-10-one 7k (200.0 mg, yield: 50.9%) is a yellow solid.

[0516] LCMS: m / z: 1025.2 [M+H] + .

[0517] Step 10: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 7 (-yl)piperidin-1-yl)-3-fluorophenyl)piperidin-2,6-dione compound

[0518] At room temperature, (Z)-1 6 -(1-(3-(1H-1,2,3-triazol-1-ylpropionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2 4-(1-(4-(2,6-bis(benzyloxy)pyridin-3-yl-2-fluorophenyl)piperidin-4-yl)-1 7 -Fluoro-9-methyl-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecan-10-one 7k (50.0 mg, 48.77 μmol) was dissolved in tetrahydrofuran (5 mL), and palladium on carbon (10 wt%, 100 mg) and palladium hydroxide on carbon (10%, 100 mg) were added sequentially. Hydrogen gas was purged three times, and the mixture was heated to 50 °C and stirred for 3 hours. The reaction was monitored by LCMS until complete. The mixture was filtered, and the filter cake was washed with tetrahydrofuran (50 mL). The mother liquor was concentrated under reduced pressure and purified by high-performance liquid chromatography to obtain (Z)-3-(4-(4-(1 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocycloalkyl-2 4 (-yl)piperidin-1-yl)-3-fluorophenyl)piperidin-2,6-dione compound 7 (1.93 mg, yield: 4.66%, white solid).

[0519] LCMS: m / z = 849.8 [M+H] + ;

[0520] 1 H-NMR (400MHz, DMSO-D6) δ11.77 (s, 1H), 10.82 (s, 1H), 8.11 (d, J = 11.6Hz, 1H), 7.69 (d, J = 10.4Hz, 1H), 7.35-7.28 (m, 1H), 7.11- 7.01 (m, 3H), 7.01-6.95 (m, 2H), 6.94-6.89 (m, 1H), 6.88-6.81 (m, 1H), 4.61 (q, J=6.8Hz, 2H), 4.54-4.44 (m, 1H), 4.24 (s, 2H), 3. 95-3.86 (m, 1H), 3.82 (dd, J=12.0, 4.8Hz, 1H), 3.76-3.59 (m, 4H), 3.48 (d, J=10.8Hz, 4H), 3.27-3.21 (m, 1H), 3.13-3.01 (m, 3H), 2.96 (s, 3H), 2.86-2.58 (m, 6H), 2.28-2.14 (m, 1H), 2.08-1.99 (m, 1H), 1.98-1.84 (m, 6H), 1.81-1.71 (m, 1H), 1.58-1.42 (m, 1H).

[0521] Example 8: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3,6-dioxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 8 (-yl)piperidin-1-yl)-3-fluorophenyl)piperidin-2,6-dione compound

[0522] Following the same procedure as in Example 7, intermediate 3i was substituted for methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole-2-carboxylate 71 to give the target product compound 8 (14.96 mg, yield: 23%), a white solid.

[0523] LCMS: RT=1.940min, m / z=846.0[M+H] + ;

[0524] 1 H NMR (400MHz, DMSO-d6): 11.88 (d, J=10.8Hz, 1H), 10.83 (s, 1H), 7.72 (d, J=10.4Hz, 1H), 7.43-7.32 (m, 2H), 7.09-6.85 (m, 7H), 6.21-6.12 (m, 2H), 4.37-4.24(m, 6H), 3.82(dd, J=11.6, 4.8Hz, 1H), 3.70-3.47(m, 11H), 3.0 0-2.97 (m, 5H), 2.80-2.62 (m, 4H), 2.32-2.19 (m, 3H), 2.04-1.93 (m, 5H).

[0525] Example 9: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indole-2-(1,2)-benzocyclodecane-2 4 9)-(1-yl)-3-fluorophenyl)piperazine-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0526] Step 1: tert-butyl (5-(5-bromo-2-chlorophenoxy)pentyl)(methyl)carbamate 9b

[0527] At room temperature, 5-bromo-2-chlorophenol 9a (2.8 g, 13.53 mmol), tert-butyl(5-hydroxypentyl)(methyl)carbamate (3.0 g, 13.53 mmol), and triphenylphosphine (5.3 g, 20.30 mmol) were dissolved in tetrahydrofuran (30 mL). The reaction solution was cooled to 0 °C in an ice-water bath, and a tetrahydrofuran solution of diisopropyl azodicarbonate (4.1 g, 20.30 mmol, 20 mL) was added dropwise. After the addition was complete, the reaction was carried out at 20 °C for 2 hours. The reaction was detected as complete by LCMS. The reaction solution was quenched with water (100 mL), extracted three times with ethyl acetate (100 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 5:1) to give tert-butyl (5-(5-bromo-2-chlorophenoxy)pentyl)(methyl)carbamate 9b (3.3 g, yield: 59.9%), as a yellow oil.

[0528] LCMS: m / z = 406.2 [M+H] + .

[0529] Step 2: Benzyl 4-(3-((5-(((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)-4-chlorophenyl)piperazine-1-carboxylic acid ester 9c

[0530] At room temperature, tert-butyl(5-(5-bromo-2-chlorophenoxy)pentyl)(methyl)carbamate 9b (2.7 g, 6.63 mmol) was dissolved in 1,4-dioxane (54 mL), followed by the sequential addition of benzylpiperazine-1-carboxylate (1.5 g, 6.63 mmol), tris(dibenzylacetone)dipalladium (604 mg, 0.66 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (763 mg, 1.32 mmol), and cesium carbonate (4.4 g, 13.36 mmol), purging with nitrogen three times. The reaction mixture was stirred at 100 °C for 16 hours. The reaction was confirmed to be complete by LCMS. The reaction mixture was quenched with water (100 mL), extracted three times with ethyl acetate (100 mL), and the combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 4:1) to give benzyl 4-(3-((5-((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)-4-chlorophenyl)piperazine-1-carboxylic acid ester 9c (2.1 g, yield: 58.1%), as a yellow oil.

[0531] LCMS: m / z = 546.1 [M+H] + .

[0532] Step 3: Tert-butyl(5-(2-chloro-5-(piperazin-1-yl)phenoxy)pentyl)(methyl)carbamate 9d

[0533] At room temperature, 2.1 g (3.85 mmol) of 4-(3-((5-((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)-4-chlorophenyl)piperazine-1-carboxylic acid ester 9c was dissolved in ethyl acetate (40 mL), and palladium on carbon (10 wt%, 1.0 g) was added, purging with hydrogen three times. The reaction mixture was stirred at 25 °C for 16 hours. The reaction was completed by LCMS, filtered, and the filter cake was washed with tetrahydrofuran (100 mL). The mother liquor was concentrated under reduced pressure to give tert-butyl(5-(2-chloro-5-(piperazine-1-yl)phenoxy)pentyl)(methyl)carbamate 9d (1.5 g, yield 94.9%) as a brown oil.

[0534] LCMS: m / z = 412.1 [M+H] + .

[0535] Step 4: (5-(5-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-chlorophenoxy)pentyl)(methyl)tert-butyl carbamate 9e

[0536] At room temperature, tert-butyl(5-(2-chloro-5-(piperazin-1-yl)phenoxy)pentyl)(methyl)carbamate 9d (1.8 g, 4.38 mmol) was dissolved in toluene (36 mL), followed by the sequential addition of 2,6-bis(benzyloxy)-3-(4-bromo-3-fluorophenyl)pyridine (2.1 g, 4.38 mmol), tris(dibenzylacetone)palladium (403 mg, 0.44 mmol), 2-dicyclohexylphosphine-2′,4′,6′-triisopropylbiphenyl (419 mg, 0.88 mmol), and cesium carbonate (11.5 g, 8.76 mmol), purging with nitrogen three times. The reaction mixture was stirred at 100 °C for 6 hours. The reaction was monitored by LCMS until complete. The reaction mixture was quenched with water (100 mL), extracted three times with ethyl acetate (100 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 4:1) to give (5-(5-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-chlorophenoxy)pentyl)(methyl)carbamate 9e (1.9 g, yield: 54.6%), as a yellow oil.

[0537] LCMS: m / z = 795.3 [M+H]+ .

[0538] Step 5: Methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester 9f

[0539] At room temperature, 9e (1.9 g, 2.39 mmol) of (5-(5-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-chlorophenoxy)pentyl)(methyl)carbamate tert-butyl ester 9e was dissolved in a mixture of 1,4-dioxane (20 mL) and water (2 mL), followed by the addition of methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7- Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxoboropentane-2-yl)-1H-indole-2-carboxylic acid ester 3i (1.3 g, 2.39 mmol), methanesulfonic acid (2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) (203 mg, 239.0 μmol), and potassium phosphate (1.6 g, 7.17 mmol) were added, with nitrogen purging three times. The reaction mixture was stirred at 80 °C for 16 hours. The reaction was monitored by LCMS until completion, and then cooled to room temperature. The reaction mixture was quenched with water (50 mL), extracted three times with ethyl acetate (50 mL), and the combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 1:3) to give methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester 9f (1.8 g, yield: 65.3%), as a yellow solid.

[0540] LCMS: m / z = 1155.5 [M+H] + .

[0541] Step 6: 9g of methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester

[0542] At room temperature, methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-((tert-butoxycarbonyl)(methyl)amino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester 9f (1.8 g, 1.56 mmol) was dissolved in dichloromethane (20 mL). Trifluoroacetic acid (4 mL) was added dropwise at 10 °C, and the reaction was maintained at this temperature for 2 hours. The reaction was confirmed by LCMS. The reaction solution was concentrated under reduced pressure. The crude product was slurried with methyl tert-butyl ether (40 mL) to obtain 9 g (1.5 g, yield: 910%) of methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester.

[0543] LCMS: m / z: 1055.4 [M+H] + .

[0544] Step 7: 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid 9h

[0545] At room temperature, 9 g (1.5 g, 1.42 mmol) of methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid ester was dissolved in a mixture of tetrahydrofuran (15 mL), methanol (15 mL), and water (4 mL). Sodium hydroxide (170 mg, 4.26 mmol) was then added, and the reaction mixture was reacted at 50 °C for 16 hours. The reaction was monitored by LCMS until completion, and the reaction mixture was then cooled to 0 °C. The pH of the reaction solution was adjusted to 3 with dilute hydrochloric acid (2M), and the reaction solution was purified by reversed-phase column chromatography (0.1% HCl / MeOH) to give 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid 9h (870 mg, yield: 59.1%), as a yellow solid.

[0546] LCMS: m / z: 1041.3 [M+H] + .

[0547] Step 8: (Z)-1 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-2 4 -(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-1 7 -Fluoro-9-methyl-1 1 H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecan-10-one 9i

[0548] At room temperature, 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-4-(4-(4-(4-(2,6-di(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-2-((5-(methylamino)pentyl)oxo)phenyl)-7-fluoro-1H-indole-2-carboxylic acid 9h (870 mg, 836.53 μmol) was dissolved in dichloromethane (20 mL), and then 2-(72-azobenzotriazole)-N,N,N′,N′-tetramethylurea hexafluorophosphate (475 mg, 1.25 mmol) and N,N-diisopropylethylamine (322 mg, 2.50 mmol) were added sequentially. The reaction solution was reacted at 25 °C for 2 hours. The reaction was confirmed by LCMS. The reaction solution was quenched with water (20 mL), extracted twice with dichloromethane (20 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: tetrahydrofuran = 1:5) to give 9i (540 mg, yield: 62.6%) as a yellow solid.

[0549] LCMS: m / z: 1023.4 [M+H] + .

[0550] Step 9: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxa-9-aza-1(4,2)-indole-2-(1,2)-benzocyclodecane-2 4 9)-(1-yl)-3-fluorophenyl)piperazine-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0551] Compound 9 (150.0 mg, 0.14 mmol) was dissolved in tetrahydrofuran (15 mL) at room temperature, and palladium on carbon (10 wt%, 150 mg) was added sequentially. Hydrogen gas was purged three times, and the mixture was heated to 50 °C and stirred for 4 hours. The reaction was monitored by LCMS until complete. The mixture was filtered, and the filter cake was washed with tetrahydrofuran (50 mL). The mother liquor was concentrated under reduced pressure and purified by high-performance liquid chromatography to give compound 9 (19.91 mg, yield: 16.9%) as a white solid.

[0552] LCMS: m / z = 845.3 [M+H] + ;

[0553] 1H-NMR (400MHz, DMSO-D6) δ11.93 (d, J=9.6Hz, 1H), 10.81 (s, 1H), 7.70-7.67 (m, 1H), 7.37 (d, J=22.3Hz, 1H), 7.18 (q, J=4.3Hz, 1H), 7.07-7.02 ( m, 2H), 6.98 (d, J=8.2Hz, 1H), 6.79 (dd, J=19.4, 6.2Hz, 1H), 6.73 (s, 1H), 6.63 (d, J=8.2Hz, 1H), 6.41 (s, 1H), 6.18-6.14 (m, 1H), 6.09 (d, J=9.3 Hz, 1H), 4.36-4.27 (m, 4H), 4.07 (s, 2H), 3.80 (dd, J=12.0, 4.8Hz, 1H), 3.58 (dt, J=26.5, 5.8Hz, 2H), 3.39-3.33 (m, 4H), 3.18-3.12 (m, 5H), 2.9 6-2.88(m, 6H), 2.68-2.59(m, 2H), 2.30(s, 2H), 2.23-2.17(m, 2H), 2.0 4-1.96 (m, 1H), 1.75 (d, J=22.3Hz, 2H), 1.52 (s, 1H), 1.46-1.23 (m, 2H).

[0554] Example 10: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 ,2 5 -Difluoro-9-methyl-10-one-1 1 H-3-O-9-NO-1(4,2)-Indole-2(1,2)-Benzocyclodecane-2 4 10 (-yl)piperazin-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0555] Following the same procedure as in Example 9, 5-bromo-2-chloro-4-fluorophenol was used instead of 5-bromo-2-chlorophenol 9a to prepare compound 10 (25.12 mg), which was a white solid.

[0556] LCMS: m / z = 863.2 [M+H] + ;

[0557] 1 H-NMR (400MHz, DMSO-D6) δ12.01 (s, 1H), 10.81 (s, 1H), 7.69 (dd, J=10.0, 2.0Hz, 1H),

[0558] 7.37(dd, J=22.0, 1.2Hz, 1H), 7.16-7.13(m, 1H), 7.07-6.96(m, 3H), 6.88-6.79(m , 2H), 6.41 (s, 1H), 6.18-6.11 (m, 2H), 4.34-4.30 (m, 4H), 4.13 (s, 1H), 3.82-3.78 (m, 1H), 3.62-43.53 (m, 2H), 3.26-3.18 (m, 10H), 2.96-2.89 (m, 5H), 2.64-2.59 (m , 1H), 2.30-2.14(m, 4H), 2.04-1.95(m, 1H), 1.78-1.72(m, 2H), 1.50-1.15(m, 5H).

[0559] Example 11: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 -H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 11 (-yl)piperazin-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0560] Following the same procedure as in Example 9, methyl 6-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole-2-carboxylate 71 was substituted for methyl 6-(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)-1H-indole-2-carboxylate 3i to prepare compound 11 (12.96 mg), which was a white solid.

[0561] LCMS: m / z = 846.60 [M+H] + ;

[0562] 1H-NMR (400MHz, DMSO-d6) δ11.95 (d, J=8.4Hz, 1H), 10.83 (s, 1H), 8.11 (d, J=11.2Hz, 1H), 7.68 (d, J=11.6Hz, 1H), 7.25-7.16 (m, 1 H), 7.11-6.98(m, 3H), 6.90-6.72(m, 2H), 6.66(d, J=8.0Hz, 1H), 6.43(s, 1H), 6.18-6.10(m, 1H), 4.68-4.58(m, 2H), 6.40-6.30(m , 2H), 4.28-4.00 (m, 2H), 3.82 (dd, J=6.0, 11.6Hz, 1H), 3.70-3.56 (m, 2H), 3.46-3.33 (m, 5H), 3.26-3.12 (m, 5H), 3.12-3.05 (m, 2H) ), 2.98(s, 3H), 2.70-3.60(m, 1H), 2.48-2.14(m, 3H), 2.05-1.96(m, 1H), 1.95-1.72(m, 3H), 1.70-1.45(m, 2H), 1.45-1.32(m, 2H).

[0563] Example 12: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 -H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 12 (-yl)piperazin-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0564] At room temperature, (Z)-16-(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-24-(4-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-2-fluorophenyl)piperazin-1-yl)-17-fluoro-9-methyl-11H-3-oxo-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-10-one 12a (starting material 12a can be prepared according to the same route as in Example 9) (140 mg, 136.70 μmol) was dissolved in tetrahydrofuran (10 mL), and palladium on carbon (70 mg) and platinum dioxide (30 mg) were added, purging with hydrogen three times. The reaction solution was reacted at 20 °C for 5 hours. The reaction was confirmed by LCMS. After filtration, the filter cake was washed with tetrahydrofuran (20 mL). The filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by high performance liquid chromatography to give compound 12 (16.85 mg, yield: 14.5%) as a pale yellow solid.

[0565] LCMS: m / z = 848.70 [M+H] + ;

[0566] 1 H-NMR (400MHz, DMSO-d6) δ11.87 (s, 1H), 10.83 (s, 1H), 8.11 (d, J = 11.6Hz, 1H), 7.68 (d, J = 10.4Hz, 1H), 7.25-6.98 (m, 4 H), 6.86-6.67(m, 3H), 6.43(s, 1H), 4.68-4.58(m, 2H), 6.55-6.42(m, 1H), 4.40-4.30(m, 1H), 4.20-4.00(m, 2H), 3.98- 3.80(m, 2H), 3.68-3.58(m, 1H), 3.46-3.32(m, 5H), 3.33-3.29(m, 1H), 3.28-3.12(m, 4H), 3.12-3.05(m, 3H), 2.98(s, 3 H), 2.85-2.71(m, 1H), 2.70-2.58(m, 1H), 2.40-2.12(m, 2H), 2.05-1.72(m, 6H), 1.70-1.43(m, 2H), 1.43-1.30(m, 2H).

[0567] Example 13: 3-(4-(4-((Z)-1 6 -((R)-1-(3-(1H-pyrazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 13 (-yl)piperazin-1-yl)-3-fluorophenyl)piperidine-2,6-dione compound

[0568] Compound 13 (19 mg) was prepared as a white solid by following similar experimental procedures as in Examples 9 and 12.

[0569] LCMS: m / z = 847.4 [M+H] + ;

[0570] 1 HNMR (400MHz, DMSO-d6) δ11.87 (d, J=4.7Hz, 1H), 10.84 (s, 1H), 7.72 (dd, J=10.4, 2.2Hz, 1H), 7.42 (dd, J=15.3, 1.8Hz, 1H), 7.20 (dd, J=8.3, 4.0Hz, 1H), 7.12-7.04 (m, 2H), 7.01 (d, J=8.2Hz, 1H), 6.85 (dd, J=5.9, 2.6Hz, 1H), 6.79 (s, 1H), 6.69 (d, J=8.5Hz, 1H), 6.43 (d , J=3.1Hz, 1H), 6.20 (dt, J=10.1, 2.1Hz, 1H), 5.11 (s, 8H), 4.51 (d, J=11.3Hz, 1H), 4.35 (q, J=7.2Hz, 2H), 4.09 (s, 1H), 3.943.77 (m, 2 H), 3.43-3.32 (m, 4H), 3.25-3.17 (m, 4H), 2.95 (d, J=22.6Hz, 6H), 2.81-2.57 (m, 2H), 2.22 (dd, J=12.3, 4.1Hz, 2H), 2.06-1.65 (m, 7H).

[0571] Example 14: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 H-3-oxo-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 14 Compounds of 1-yl)piperazine-1-yl)phenyl)piperidine-2,6-dione

[0572] Compound 14 (8.54 mg) was prepared as a white solid by following similar experimental procedures as in Examples 9 and 12.

[0573] LCMS: rn / z = 830.7 [M+H] + ;

[0574] 1 H-NMR (400MHz, DMSO-d6) δ11.85 (d, J=14.6Hz, 1H), 10.78 (d, J=8.2Hz, 1H), 8.08 (d, J=11.3Hz, 1H), 7.66 (d, J=10.4Hz, 1H), 7.20-7.14 (m, 1H), 7 ... m, 2H), 4.47 (s, 1H), 4.33 (d, J=24.5Hz, 1H), 4.08 (s, 2H), 3.90 (d, J=12.6Hz, 1H), 3.73 (dd, J=11.1, 5.1Hz, 1H), 3.59 (d, J=22.3Hz, 1H), 3.39-3. 33(m, 4H), 3.27(s, 4H), 3.04(dt, J=23.9, 6.4Hz, 3H), 2.95(s, 3H), 2.77 -2.58(m, 2H), 2.30-2.08(m, 2H), 2.02-1.73(m, 7H), 1.59-1.33(m, 5H).

[0575] Example 15: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 ,2 5 -Difluoro-9-methyl-10-oxo-1 1 -H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 15 compounds of 1-yl)piperazine-1-yl)-3-fluorophenyl)piperidine-2,6-dione

[0576] Compound 15 (23.17 mg) was prepared as a white solid by following similar experimental procedures as in Examples 9 and 12.

[0577] LCMS: m / z = 866.7 [M+H] +;

[0578] 1 H-NMR (400MHz, DMSO-d6) δ1H-NMR (400MHz, DMSO-D6) δ8.08 (d, J=11.0Hz, 1H), 7.66 (d, J=11.0Hz, 1H), 7.13- 7.03 (m, 3H), 6.97 (d, J=8.2Hz, 1H), 6.89 (t, J=4.8Hz, 1H), 6.80 (d, J=7.7Hz, 1H), 6.41 (s, 1H), 4.58 (q, J=7. 1Hz, 2H), 4.46 (d, J=12.1Hz, 1H), 4.09 (s, 2H), 3.90-3.78 (m, 2H), 3.21 (d, J=29.1Hz, 8H), 3.07-2.98 (m, 4H) , 2.95(s, 3H), 2.80-2.54(m, 2H), 2.48-2.52(3H), 2.30-2.17(m, 1H), 2.04-1.72(m, 6H), 1.52-1.27(m, 5H).

[0579] Example 16: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-8-methyl-9-oxo-1 1 -H-3-oxa-8-aza-1(4,2)-indole-2(1,2)-benzocyclononane-2 4 16 (-yl)piperidin-1-yl)phenyl)piperidin-2,6-dione compound

[0580] Following similar experimental procedures as in Example 9, compound 16 (29.1 mg) was prepared as a white solid.

[0581] LCMS: rn / z = 813.60 [M+H] + ;

[0582] 1H-NMR (400MHz, DMSO-d6) δ11.98-11.90 (m, 1H), 10.78 (s, 1H), 8.10 (d, J=11.6Hz, 1H), 7.68 (d, J=10.8Hz, 1H), 7.50-7.40 (m, 1H), 7.06 (d, J=8. 8Hz, 3H), 6.96 (t, J=6.0Hz, 3H), 6.92-6.83 (m, 1H), 6.77 (s, 1H), 6.16- 6.08(m, 1H), 4.68-4.58(m, 2H), 4.40-4.30(m, 2H), 4.12-4.02(m, 2H), 3 .82(d, J=11.2Hz, 2H), 3.78-3.72(m, 1H), 3.68-3.55(m, 2H), 3.12-3.0 5(m, 2H), 3.02(s, 3H), 2.82-2.70(m, 4H), 2.70-3.58(m, 1H), 2.48-2.42 (m, 1H), 2.30-2.22 (m, 1H), 2.22-2.10 (m, 1H), 2.06-2.02 (m, 1H), 2.00 -1.97 (m, 1H), 1.95-1.72 (m, 5H), 1.70-1.58 (m, 2H), 1.58-1.48 (m, 2H).

[0583] Example 17: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-pyrazol-1-yl)propionyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 7 -Fluoro-9-methyl-10-oxo-1 1 -H-3-oxa-9-aza-1(4,2)-indole-2(1,2)-benzocyclodecane-2 4 17 Compounds of 1-yl)piperidin-1-yl)phenyl)piperidin-2,6-dione

[0584] Following similar experimental procedures as in Example 9, compound 17 (16.3 mg) was prepared as a white solid.

[0585] LCMS: m / z = 826.70 [M+H] + ;

[0586] 1H-NMR (400MHz, DMSO-d6) δ7.72 (d, J=11.6Hz, 1H), 7.40 (d, J=22.8Hz, 1H), 7.29 (q, J=4.0Hz, 1H), 7.07 (d, J=8.2Hz, 3H), 6.96 (d, J=8.6Hz, 3H), 6.87 (dd, J=22.4, 6.0Hz, 1H), 6.43 (d, J=3.2Hz, 1H), 6.18 (d, J=13.6Hz, 1H), 6.13 (d, J=10.0Hz, 1H), 6.05 (s, 1H), 4.37-4.30 (m, 4H), 4.20-4.0 5 (m, 1H), 3.82 (d, J = 11.8Hz, 2H), 3.74 (dd, J = 11.0, 4.8Hz, 1H), 3.60 (dt, J = 26.6, 5.4Hz, 2H), 3.00-2.94 (m, 5H), 2.80-2.70 (m, 3H), 2.70-2.60 (m, 2H), 2.49-2.43 (m, 1H), 2.35-2.22 (m, 2H), 2.20-2.00 (m, 3H), 2.00 -1.90 (m, 2H), 1.90-1.74 (m, 5H), 1.65-1.40 (m, 2H), 1.40-1.28 (m, 2H).

[0587] Example 18: (Z)-3-(4-(4-(1) 6 -(1-(3-(1H-1,2,3-triazol-1-yl)propionyl)piperidin-3-yl)-1 7 -Fluoro-8-methyl-9-oxo-1 1 -H-3-oxa-8-aza-1(4,2)-indolole-2(1,2)-benzocyclononane-2 4 18 (-yl)piperidin-1-yl)phenyl)piperidin-2,6-dione compound

[0588] Compound 18 (22.05 mg) was prepared as a white solid by following similar experimental procedures as in Examples 9 and 12.

[0589] LCMS: m / z = 815.70 [M+H] + ;

[0590] 1H-NMR (400MHz, DMSO-D6) δ11.83 (s, 1H), 10.78 (s, 1H), 8.10 (d, J = 12.4Hz, 1H), 7.68 (d, J = 12.0Hz, 1H), 7.42 (d, J = 6.3Hz, 1H), 7. 07 (d, J=8.8Hz, 3H), 7.00-6.90 (m, 4H), 6.75 (s, 1H), 4.60 (dd, J=15.8, 7.2Hz, 2H), 4.49 (d, J=12.8Hz, 1H), 4.08 (s, 2H), 3.94-3.8 7 (m, 1H), 3.82 (d, J=12.0Hz, 2H), 3.74 (dd, J=11.0, 4.8Hz, 1H), 3.29-3.23 (m, 2H), 3.11-2.97 (m, 7H), 2.79-2.70 (m, 3H), 2.70-2. 58 (m, 2H), 2.502.43 (m, 1H), 2.19-2.09 (m, 1H), 2.07-2.00 (m, 1H), 1.95-1.82 (m, 6H), 1.77 (d, J=14.6Hz, 1H), 1.70-1.42 (m, 5H).

[0591] Example of effect:

[0592] Cell culture: MV411, Jurkat, and A549 were purchased from Beyotime Biotechnology Co., Ltd., and hPBMCs were purchased from Rubai Biotechnology Co., Ltd. Cells were cultured in RPMI-1640 (Gibco, 22400089) medium containing 10% FBS (Gibco, 10091-148) at 37°C in a 5% CO2 incubator.

[0593] Example 1: Western blot (WB) detection of protein degradation

[0594] Western blotting was used to quantify the degradation of STAT6 protein and to detect the selectivity of STAT1, 2, 3, 4, and 5 proteins. 400,000 cells were seeded into 24-well plates and cultured overnight. A compound concentration gradient was prepared, starting at 10 μM and diluted 1:3. The serially diluted compounds were added to the cell wells and incubated at 37°C in a 5% CO2 incubator for 24 h. Cells were centrifuged and washed once with PBS. RIPA lysis buffer (ThermoFisher, 89900) containing 1% protease inhibitor & phosphatase inhibitor (ThermoFisher, 78442) was added to the cell pellet, and the plate was placed on ice for 10 min. The lysis buffer was transferred to 1.5 mL centrifuge tubes by pipetting several times, centrifuged at 12,000 rpm for 10 min, and the supernatant was transferred to a new 1.5 mL centrifuge tube and stored at -80°C. Total protein was quantified using a BCA protein assay kit (Beyotime, P0012). Combine 4X LDS Sample Buffer (ThermoFisher, 84788), 10X NuPAGE TM After mixing the reducing agent (ThermoFisher, NP009) with the protein sample, incubate at 95°C for 5 minutes in a thermostatic mixer to denature the protein. Load 20-40 μg of protein onto a NuPAGE plate. TM 4-12% Bis-Tris Gel (Invitrogen) TM NuPAGE (NP0336BOX) was added to the electrophoresis tank. TM MOPSSDS electrophoresis buffer (Novex, NP001) was used for electrophoresis at a constant voltage of 100V. After protein separation, iBlot was used. TM 2. Transfer apparatus (Invitrogen) TM (IB21001) using the iBlot2 dry blotting system (Invitrogen) TM The membrane was transferred using IB23001. After transfer, it was blocked at room temperature for 1 hour with Quick Block blocking buffer (Beyotime, P0231). Primary antibody was added, and the membrane was incubated overnight at 4°C with gentle shaking. The membrane was washed three times for 5 minutes each with Western blotting buffer (Beyotime, P0023C-1L). The corresponding secondary antibody was added, and the membrane was incubated at room temperature for 1 hour with gentle shaking. The membrane was washed five times for 5 minutes each with Western blotting buffer. The SuperSignal... TMWest Pico PLUS (ThermoFisher, 34577) chemiluminescent substrates were applied to the membrane. Chemiluminescence imaging was performed using a chemiluminescence imaging system (ChemiScope 6100). Antibodies used in the experiment: Statl (Cell Signaling Technologies, (D1K9Y) Rabbit mAb, #14994S), Stat2 (Cell Signaling Technologies, (D9J7L) Rabbit mAb, #72604S), Stat3 (Cell Signaling Technologies, (D3Z2G) Rabbit mAb, #12640S), Stat4 (Cell Signaling Technologies, (C46B10) Rabbit mAb, #2653S), Stat5 (Cell Signaling Technologies, (D2O6Y) Rabbit mAb, #94205S), phospho-Stat5 (Cell Signaling Technologies, (Tyr694, D47E7) Rabbit mAb, #4322S), Stat6 (Cell Signaling Technologies, (D3H4) Rabbit mAb, #5397S), phospho-Stat6 (Cell Signaling Technologies, (Tyr641)Rabbit mAb, #9361S), Vinculin (Cell Signaling Technologies, (E1E9V) Rabbit mAb, #13901S), Anti-rabbit IgG HRP-linked Antibody (Cell Signaling Technologies, 7074S).

[0595] The test results are shown in Table 1.

[0596] Table 1: Results of protein degradation detection experiments using Western blotting (WB) of the compounds disclosed herein

[0597] Western blot (WB) results showed that the disclosed compound specifically degraded Stat6 protein, but had virtually no degradation on STAT1, 2, 3, 4, and 5 proteins. Figure 1 shows the protein degradation results of compound 3A at different concentrations (100 nM, 33.333 nM, 11.111 nM, 3.7037 nM, 1.2346 nM, 0.4115 nM, 0.1372 nM, 0.0457 nM, 0.0152 nM, 0.0051 nM) after incubation with different proteins (STAT1, 2, 3, 4, 5, and 6 proteins) for 24 hours.

[0598] Example 2: Degradation experiment of STAT6-HiBiT A549

[0599] A HiBiT tag was knocked into the C-terminus of the A549 STAT6 gene using CRISPR / Cas9 technology (refer to WO2025049820A1). The degradation of endogenous STAT6 in STAT6-HiBiT A549 cells was quantified using the Nano-Glo HiBiT Lytic Detection System (Promega, 3040). A549 (STAT6-HiBiT) cells were seeded at a density of 1250 cells (20 μL) per well in 384-well plates. The compound was added to the detection plate at a working concentration of 10 μM, with 4-fold serial dilutions for a total of 10 dose gradients. The detection plate was then incubated at 37°C and 5% CO2 for 24 hours. At the endpoint, 20 μL of Nano-Glo HiBiT lysis reagent was added to each well, and the plate was shaken at 300 rpm for 10 minutes at room temperature. The luminescence values ​​were read using a Tecan microplate reader. Data were analyzed using GraphPad Prism software, and a four-parameter nonlinear regression model of inhibitor and response was used to fit the dose-dependent degradation of STAT6.

[0600] Table 2: Degradation Experiment Results of Compound STAT6-HiBiT A549 of this Disclosure

[0601] The compound disclosed herein exhibits good STAT6 degradation activity, as determined by the above-mentioned Effect Example 1 and Effect Example 2.

[0602] Example 3: Pharmacokinetic Test in Mice

[0603] 1. Drug preparation

[0604] Weigh a certain amount of the drug and prepare the preparation for gavage and intravenous injection (0.2 mg / ml solution for IV and 0.3 mg / ml solution for PO). The solvent for both gavage and intravenous injection is 10% DMA + 10% Solutol HS15 + 80% Saline.

[0605] 2. Administration

[0606] ICR mice were fasted for 12 hours before administration, but had free access to water. The intravenous dose was 1 mg / kg, and the oral dose was 2 mg / kg or 5 mg / kg. Mice were allowed to resume eating 4 hours after administration.

[0607] 3. Sampling

[0608] At 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 h after intravenous administration, and at 0.25, 0.5, 1, 2, 4, 8, and 24 h after gavage administration, 30 μL of whole blood was collected from the submandibular vein of mice and placed in anticoagulant centrifuge tubes containing EDTA-K2. The tubes were centrifuged at 5000 rpm and 4°C for 5 min. The separated plasma was then stored at -80°C for analysis.

[0609] 4. Measurement

[0610] Take 10 μL of plasma sample and add 200 μL of MeOH / Acetonitrile (1:1, v / v) containing internal standards (50 nM terfenadine and 500 nM tolbutamide) for protein precipitation (vortex for 10 min, then centrifuge at 4000 rpm for 10 min). Take 100 μL of supernatant and transfer it to a 96-well plate for LC-MS / MS analysis.

[0611] 5. Pharmacokinetic Parameter Results

[0612] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 3 below.

[0613] Table 3: Pharmacokinetic parameters of the compounds disclosed herein

[0614] The disclosed compound exhibits a high area under the curve, high plasma concentration, and good oral bioavailability in mice, demonstrating excellent pharmacokinetic characteristics.

[0615] Example 4: Rat Pharmacokinetic Test

[0616] 1. Drug preparation

[0617] Weigh a certain amount of the drug and prepare the preparation for gavage and intravenous injection (0.2 mg / ml solution for IV and 1.0 mg / ml solution for PO). The solvent for both the gavage and intravenous injection preparations is 10% DMA + 10% Solutol HS15 + 80% Saline.

[0618] 2. Administration

[0619] SD rats were fasted for 12 hours before administration, but had free access to water. They were reintroduced to food 4 hours after administration. The intravenous and gavage doses were 1 MPa and 10 MPa, respectively.

[0620] 3. Sampling

[0621] At 0.083, 0.25, 0.5, 1, 2, 4, 8 and 24 h after intravenous administration, and at 0.25, 0.5, 1, 2, 4, 8 and 24 h after gavage administration, 200 μL of whole blood was collected from the jugular vein of rats and placed in anticoagulant centrifuge tubes containing EDTA-K2. The centrifuge tubes were centrifuged at 5000 rpm and 4℃ for 5 min, and the separated plasma was stored at -80℃ for analysis.

[0622] 4. Measurement

[0623] Take 10 μL of plasma sample and add 200 μL of MeOH / Acetonitrile (1:1, v / v) containing internal standards (50 nM terfenadine and 500 nM tolbutamide) for protein precipitation (vortex for 10 min, then centrifuge at 4000 rpm for 10 min). Take 100 μL of supernatant and transfer it to a 96-well plate for LC-MS / MS analysis.

[0624] 5. Pharmacokinetic Parameter Results

[0625] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 4 below.

[0626] Table 4: Pharmacokinetic parameters of the compounds disclosed herein

[0627] The disclosed compound exhibits a high area under the curve, high plasma concentration, and good oral bioavailability in rats, demonstrating excellent pharmacokinetic characteristics.

[0628] Example 5: Pharmacokinetic Test in Beagle Dogs

[0629] 1. Drug preparation

[0630] Weigh a certain amount of the drug and prepare the preparation for gavage and intravenous injection (0.5 mg / ml solution for IV and 0.4 mg / ml solution for PO). The solvent for both the gavage and intravenous injection preparations is 10% DMA + 10% Solutol HS15 + 80% Saline.

[0631] 2. Administration

[0632] Beagles should be fasted for 12 hours before administration, with free access to water. They should resume eating 4 hours after administration. The intravenous and gavage doses are 0.5 MPa and 2 MPa, respectively.

[0633] 3. Sampling

[0634] At 0.083, 0.25, 0.5, 1, 2, 4, 8 and 24 h after intravenous administration, and at 0.25, 0.5, 1, 2, 4, 8 and 24 h after gavage administration, 1 mL of whole blood was collected from the cephalic vein of the forelimb of a beagle dog and placed in an anticoagulant centrifuge tube containing EDTA-K2. The centrifuge tube was centrifuged at 5000 rpm and 4℃ for 5 min. The separated plasma was then stored at -80℃ for analysis.

[0635] 4. Measurement

[0636] Take 10 μL of plasma sample and add 200 μL of MeOH / Acetonitrile (1:1, v / v) containing internal standards (50 nM terfenadine and 500 nM tolbutamide) for protein precipitation (vortex for 10 min, then centrifuge at 4000 rpm for 10 min). Take 100 μL of supernatant and transfer it to a 96-well plate for LC-MS / MS analysis.

[0637] 5. Pharmacokinetic Parameter Results

[0638] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 5 below.

[0639] Table 5

[0640] The disclosed compound exhibits a high area under the curve, high plasma concentration, and good oral bioavailability in beagle dogs, demonstrating excellent pharmacokinetic characteristics.

Claims

1. A compound of formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, Ring B is a saturated or partially unsaturated C3-C ring. 18 Carbon rings, saturated or partially unsaturated 3-18 membered heterocycles, C6-C 18 Aromatic rings or 5-18 membered heteroaromatic rings; in the 3-18 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-18 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 18 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-18 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. n is 0, 1, 2, 3, 4 or 5; R B independently represents R A-2 , R B-1 , hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 , =S, -OR A-1 , -SR A-1 , -N(R A-1 )2, -Si(R A-1 )3, -S(=O)R A-1 , -S(=O)2R A-1 , -S(=O)(=NR A-1 )R A-1 , -S(=NR A-1 )2R A-1 , -S(=O)2N(R A-1 )2, -C(=O)R A-1 , -C(=O)OR A-1 , -C(=O)N(R A- 1 )2, -C(=O)N(R A-1 )OR A-1 , -OC(=O)R A-1 , -OC(=O)N(R A-1 )2, -P(=O)(R A-1 )2, -P(=O)(OR A-1 )2, -OP(=O)(R A-1 )2, -OP(=O)(OR A- 1 )2, -NR A-1 C(=O)OR A-1 , -NR A-1 C(=NR A-1 )OR A-1 , -NR A-1 C(=O)R A-1 , NR A-1 C(=NR A-1 )R A-1 , -NR A-1 C(=O)N(R A-1 )2, -NR A- 1 C(=NR A-1 )N(R A-1 )2, -NR A-1 C(=NOR A-1 )N(R A-1 )2, -NR A-1 C(=NR A-1 )NH(OR A-1 ) or -NR A-1 S(=O)2R A-1 ； R A-2 Independently for C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R B-1 is -L B -H, -L B -Cy B1’ or -LB-Cy B11 -Cy B2’ ; L B Independently C1-C4 alkylene groups, wherein 0, 1, 2, 3, or 4 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A- 1 )-、-CR A-1 =CR A-1 -or Cy B1’ and Cy B2’ Each independently constitutes C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R A-1 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. R A-1-1 and R A-2-1 Each independently is: Cy X1 Halogen, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A- 1-1-1 -(CH2) 0-4 CH(OR A-1-1-1 2、-(CH2) 0-4 SR A-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0-1 Ph、-(CH2) 0-4 Py, -(CH2) 0-4 O(CH2) 0-1 Py, -CH=CHPh, nitro, cyano, azide, -(CH2) 0-4 N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )C(=S)R A-1-1-1 -(CH2) 0- 4N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )C(=S)N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1- 1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 -(CH2) 0-4 C(=O)R A-1-1-1 -C(=S)R A-1-1-1 -(CH2) 0-4 -C(=O)OR A-1-1-1 、-(CH2) 0-4 -C(=O)SR A-1-1-1 、-(CH2) 0-4 -C(=O)OSi(R A-1-1-1 )3、-(CH2) 0-4 OC(=O)R A-1-1-1 、-OC(=O)(CH2) 0-4 SR A-1-1-1 、-(CH2) 0-4 SC(=O)R A-1-1-1 、-(CH2) 0- 4C(=O)N(R A-1-1-1 )2、-C(=S)N(R A-1-1-1 )2、-C(=S)SR A-1-1-1 、-SC(=S)SR A-1-1-1 、-(CH2) 0-4 OC(=O)N(R A-1-1-1 )2、-C(=O)N(OR A-1-1-1 )R A-1-1-1 、-C(=O)C(=O)R A-1-1-1 、-C(=O)CH2C(=O)R A-1-1-1 、-C(=NOR A-1-1-1 )R A-1-1-1 、-(CH2) 0-4 SSR A-1-1-1 、-(CH2) 0-4 S(=O)2R A-1-1-1 、-(CH2) 0-4 S(=O)2OR A-1-1-1 、-(CH2) 0-4 OS(=O)2OR A-1-1-1 、-S(=O)2N(R A-1-1-1 )2、-(CH2) 0-4 S(=O)R A-1-1-1 、-N(R A-1-1-1 )S(=O)2N(R A-1-1-1 )2、-N(R A-1-1-1 )S(=O)2R A-1-1-1 、-N(OR A-1-1-1 )R A-1-1-1 、-C(=NH)N(R A-1-1-1 )2、-(CH2) 0-4 P(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(OR A-1-1-1 )₂, -Si(R A-1-1-1 )₃, -(CH=CH) 0-4 o-N(R A-1-1-1 )₂, -(CH=CH) 0-4 C(=O)O-N(R A-1-1-1 )₂, =O, =S, =NR A-1-1-1 , =NN(R A-1-1-1 )₂, =NNHC(=O)R A-1-1-1 , =NNHC(=O)OR A-1-1-1 , =NNHS(=O)₂R A-1-1-1 , =NR A-1-1-1 or =NOR A-1-1-1 ; Cy X1 Independently for C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl, 5-14 heteroaryl, optionally bounded by one or more R Z1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R Z1 independently R Z1-1 , oxo (=O), =NR Z1-1 , =S, hydrogen, halogen, cyano, nitro, -OR Z1-1 , -SR Z1-1 , -N(R Z1-1 )2, -Si(R Z1-1 )3, -S(=O)R Z1-1 , -S(=O)2R Z1-1 , -S(=O)(=NR Z1-1 )R Z1-1 , -S(=O)2N(R Z1-1 )2, -S(=NR Z1-1 )2R Z1-1 , -C(=O)R Z1-1 , -C(=O)OR Z1-1 , -C(=O)N(R Z1-1 )2, -C(=O)N(R Z1-1 )OR Z1-1 , -OC(=O)R Z1-1 , -OC(=O)N(R Z1-1 )2, -P(=O)(R Z1-1 )2, -P(=O)(OR Z1-1 )2, -OP(=O)(R Z1- 1 )2, -OP(=O)(OR Z1-1 )2, -NR Z1-1 C(=O)OR Z1-1 , -NR Z1-1 C(=O)R Z1-1 , -NR Z1-1 C(=NR Z1-1 )OR Z1-1 , -NR Z1-1 C(=NR Z1-1 )R Z1-1 , -NR Z1- 1 C(=NR Z1-1 )N(R Z1-1 )2, -NR Z1-1 C(=NOR Z1-1 )N(R Z1-1 )2, -NR Z1-1 C(=NR Z1-1 )NH(OR Z1-1 ), -NR Z1-1 C(=O)N(R Z1-1 )2 or -NR Z1- 1 S(=O)2R Z1-1 ; R Z1-1 Independently hydrogen, C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. Z1-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Alternatively, two R atoms on the same atom or two adjacent atoms Z1-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R Z1-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. R Z1-1-1 Independently halogenated, -(CH2) 0- 4R Z1-1-1-1 -(CH2) 0-4 OR Z1-1-1-1 -O(CH2) 0-4 R Z1-1-1-1 -O(CH2) 0-4 -C(=O)OR Z1-1-1-1 -(CH2) 0- 4CH(OR Z1-1-1-1 2、-(CH2) 0-4 SR Z1-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0- 1Ph、-(CH2) 0-4 Py, -(CH2) 0-4 O(CH2) 0- 1Py, -CH=CHPh, nitro, cyano, azide, -(CH2) 0-4 N(R Z1-1-1-1 2、-(CH2) 0-4 N(R Z1-1-1-1 )C(=O)R Z1-1-1-1 -N(R) Z1-1-1-1 )C(=S)R Z1-1-1-1 -(CH2) 0-4 N(R Z1- 1-1-1 )C(=O)N(R Z1-1-1-1 )2、-N(R Z1-1-1-1 )C(=S)N(R Z1-1-1-1 2、-(CH2) 0-4 N(R Z1-1-1-1 )C(=O)OR Z1-1-1-1 -N(R) Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)R Z1- 1-1-1 -N(R) Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)N(R Z1-1-1-1 )2、-N(R Z1-1-1-1 )N(R Z1-1-1-1 )C(=O)OR Z1-1-1-1 -(CH2) 0-4 C(=O)R Z1-1-1-1 -C(=S)R Z1- 1-1-1 -(CH2) 0-4 -C(=O)OR Z1-1-1-1 -(CH2) 0-4 -C(=O)SR Z1-1-1-1 、-(CH2) 0-4 -C(=O)OSi(R Z1-1-1-1 )3、-(CH2) 0-4 OC(=O)R Z1-1-1-1 、-OC(=O)(CH2) 0-4 SR Z1-1-1-1 、-(CH2) 0-4 SC(=O)R Z1-1-1-1 、-(CH2) 0-4 C(=O)N(R Z1-1-1-1 )2、-C(=S)N(R Z1-1-1-1 )2、-C(=S)SR Z1-1-1-1 、-SC(=S)SR Z1-1-1-1 、-(CH2) 0-4 OC(=O)N(R Z1-1-1-1 )2、-C(=O)N(OR Z1-1-1-1 )R Z1-1-1-1 、-C(=O)C(=O)R Z1-1-1-1 、-C(=O)CH2C(=O)R Z1- 1-1-1 、-C(=NOR Z1-1-1-1 )R Z1-1-1-1 、-(CH2) 0-4 SSR Z1-1-1-1 、-(CH2) 0-4 S(=O)2R Z1-1-1-1 、-(CH2) 0-4 S(=O)2OR Z1-1-1-1 、-(CH2) 0-4 OS(=O)2OR Z1- 1-1-1 、-S(=O)2N(R Z1-1-1-1 )2、-(CH2) 0-4 S(=O)R Z1-1-1-1 、-N(R Z1-1-1-1 )S(=O)2N(R Z1-1-1-1 )2、-N(R Z1-1-1-1 )S(=O)2R Z1-1-1-1 、-N(OR Z1-1- 1-1 )R Z1-1-1-1 、-C(=NH)N(R Z1-1-1-1 )2、-(CH2) 0-4 P(=O)(R Z1-1-1-1 )2、-(CH2) 0-4 OP(=O)(R Z1-1-1-1 )2、-(CH2) 0-4 OP(=O)(OR Z1-1-1-1 )2, -Si(R Z1-1-1-1 )3, -(CH=CH) 0-4 O-N(R Z1-1-1-1 )2, -(CH=CH) 0-4 C(=O)O-N(R Z1-1-1-1 )2, =O, =S, =NR Z1-1-1-1 , =NN(R Z1-1-1-1 )2, =NNHC(=O)R Z1-1-1-1 , =NNHC(=O)OR Z1-1-1-1 , =NNHS(=O)2R Z1-1-1-1 , =NR Z1-1-1-1 or =NOR Z1-1-1-1 ; R Z1-1-1-1 Independently -(CH2) 0-2 R Z1-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR Z1-1-1-1-1 -(CH2) 0-2 CH(OR Z1-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R Z1-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR Z1-1-1-1-1 -(CH2) 0-2 SR Z1-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0- 2NH2、-(CH2) 0-2 NHR Z1-1-1-1-1 -(CH2) 0-2 N(R Z1-1-1-1-1 )2、-Si(R Z1-1-1-1-1 3. -C(=O)SR Z1-1-1-1-1 -(CH=CH) 0-4 C(=O)OR Z1-1-1-1-1 or -SSR Z1-1-1-1-1 ; R Z1-1-1-1-1 Independently constitutes a hydrogen atom, halogen, benzyl, C1-C6 alkyl, or -O(CH2). 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl; wherein the heteroatom in the 3-6 membered heterocyclic alkyl is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2 or 3; R A-1-1-1 Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR A-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1- 1 ; R A-1-1-1-1 Independently hydrogen, halogen, benzyl, C1-C6 alkyl, -O(CH2) 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl; wherein the heteroatom in the 3-6 membered heterocyclic alkyl is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2 or 3; Cy B11 Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Ring A is a saturated or partially unsaturated C3-C ring. 20 Carbon rings, saturated or partially unsaturated 3-20 membered heterocycles, C6-C 20 Aromatic rings or 5-20 membered heteroaromatic rings; in the 3-20 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-20 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 20 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-20 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-20 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or m can be 0, 1, 2, 3, 4, or 5; Y is hydrogen, halogen, or... q can be 0, 1, 2, 3, 4, or 5; Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=NR) A-1 )2R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A- 1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A- 1 )2、-OP(=O)(OR A-1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=NR A -)OR A-1 -NR A-1 C(=O)R A-1 NR A-1 C(=NR A-1 )R A-1 -NR A- 1 C(=O)N(R A-1 )2、-NR A-1 C(=NR A-1 )N(R A-1 )2、-NR A-1 C(=NOR A-1 )N(R A-1 )2、-NR A-1 C(=NR A-1 )NH(OR A-1 ) or -NR A-1 S(=O)2R A-1 ; L A It is a C1-C6 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B; L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A-1 The substituted 3-16-membered heterocyclic alkyl or 3-16-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; the 6-membered heteroaryl group has heteroatoms selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3. L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L c For covalent bonds, -O-, -S-, or -NL 11 -; L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-、-OC(=O)-、-C(=O)O-、-S(=O)-、-S(=O)2-、-NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-、-CHF-、-CF2-、-S(=O)(=NR A-1 )-、 M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently; -L a -L b -L c -with L X Connect any point on the [structure / structure]; L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E; Or L X Independently for -L X1 -L X2 -L X3 -L X4 -; L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A- 1-, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)₂-, -NR A-1 S(=O)₂-, -S(=O)₂NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. for X 5 and X 6 Independently covalent bond, -C(R) A-3 )2-, -SO2-, -S(=O)-, -P(=O)R A-3 -、-P(=O)OR A-3 -、-P(=O)N(R A-3 -, -C(=O)- or -C(=S)-; X 2 For N, CR 2-1 Si-R 2-1 Or P = O; It can be a single bond or a double bond; when When it is a single bond, X 3 and X 4 Independently covalent bond, -C(R) A-3 -2-, -CF2-, -O-, or -S-; X 3 When it is a covalent bond, X 2 and X 4 Directly connected; X 4 When it is a covalent bond, X 3 and X 5 Directly connected; X 3 and X 4 When all are covalent bonds, X 2 and X 5 Directly connected; when When it is a double bond, is -CR A-3 CR A-3 -; R A-3 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Alternatively, two R atoms on the same atom or two adjacent atoms A-3 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. R 2-1 Independently hydrogen, -OR A-1 -SR A-1 -S(=O)R A-1 -SO2R A-1 -N(R) A-1 2. Or optionally by one or more R A-1-1 Replacement C1-C 12 alkyl; Or R 2-1 and R A-3 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. Ring E3 is a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the 5-6 membered heteroaromatic ring is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3; Cycle E4 is a C4-C7 cycloene or a 4-7 membered heterocyclic alkene, wherein the heteroatom in the 4-7 membered heterocyclic alkene is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3 or 4. n1 is 1, 2, 3, or 4; R 3 Substituents on ring E3 or ring E4; R 3 It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, C1-C6 alkyl substituted with one or more halogens, or C1-C6 alkoxy substituted with one or more halogens.

2. The compound of formula (I) as claimed in claim 1, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, Ring B is a saturated or partially unsaturated C3-C ring. 18 Carbon rings, saturated or partially unsaturated 3-18 membered heterocycles, C6-C 18 Aromatic rings or 5-18 membered heteroaromatic rings; in the 3-18 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-18 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 18 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-18 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. n is 0, 1, 2, 3, 4 or 5; R B Independently for R A-2 R B-1 Hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 =S, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A- 1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A- 1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ; R A-2 Independently for C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R B-1 is -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 -H; LB is independently a C1-C3 alkylene group, wherein 0, 1, 2 or 3 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or R A-1 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. R A-1-1 and R A-2-1 Each can be independently classified as: halogen, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A- 1-1-1 -(CH2) 0-4 CH(OR A-1-1-1 2、-(CH2) 0-4 SR A-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0-1 Ph、-(CH2) 0-4 Py, -(CH2) 0-4 O(CH2) 0-1 Py, -CH=CHPh, nitro, cyano, azide, -(CH2) 0-4 N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )C(=S)R A-1-1-1 -(CH2) 0- 4N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )C(=S)N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1- 1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 -(CH2) 0-4 C(=O)R A-1-1-1 -C(=S)R A-1-1-1 -(CH2) 0-4 -C(=O)OR A-1-1-1 、-(CH2) 0-4 -C(=O)SR A-1-1-1 、-(CH2) 0-4 -C(=O)OSi(R A-1-1-1 )3、-(CH2) 0-4 OC(=O)R A-1-1-1 、-OC(=O)(CH2) 0-4 SR A-1-1-1 、-(CH2) 0-4 SC(=O)R A-1-1-1 、-(CH2) 0-4 C(=O)N(R A-1-1-1 )2、-C(=S)N(R A-1-1-1 )2、-C(=S)SR A-1-1-1 、-SC(=S)SR A-1-1-1 、-(CH2) 0-4 OC(=O)N(R A-1-1-1 )2、-C(=O)N(OR A-1-1-1 )R A-1-1-1 、-C(=O)C(=O)R A-1-1-1 、-C(=O)CH2C(=O)R A-1-1-1 、-C(=NOR A-1-1-1 )R A-1-1-1 、-(CH2) 0-4 SSR A-1-1-1 、-(CH2) 0-4 S(=O)2R A-1-1-1 、-(CH2) 0-4 S(=O)2OR A-1-1-1 、-(CH2) 0-4 OS(=O)2OR A-1-1-1 、-S(=O)2N(R A-1-1-1 )2、-(CH2) 0-4 S(=O)R A-1-1-1 、-N(R A-1-1-1 )S(=O)2N(R A-1-1-1 )2、-N(R A-1-1-1 )S(=O)2R A-1-1-1 、-N(OR A-1-1-1 )R A-1-1-1 、-C(=NH)N(R A-1-1-1 )2、-(CH2) 0-4 P(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(OR A-1-1-1 )2、-Si(R A-1-1-1 )3, -(CH=CH) 0-4 O-N(R A-1-1-1 )2, -(CH=CH) 0-4 C(=O)O-N(R A-1-1-1 )2, =O, =S, =NR A-1-1-1 , =NN(R A-1-1-1 )2, =NNHC(=O)R A-1-1-1 , =NNHC(=O)OR A-1-1-1 , =NNHS(=O)2R A-1-1-1 , =NR A-1-1-1 or =NOR A-1-1-1 ; R A-1-1-1 Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR A-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1- 1 ; R A-1-1-1-1 Independently, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C5-C6 cycloalkyl or 5-6 membered heterocyclic alkyl; Cy B1 and Cy B2 Each independently constitutes C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Ring A is a saturated or partially unsaturated C3-C ring. 14 Carbon rings, saturated or partially unsaturated 3-14 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-14 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or m can be 0, 1, 2, 3, 4, or 5; Y is hydrogen, halogen, or... q can be 0, 1, 2, 3, 4, or 5; Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A- 1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ; L A It is a C1-C5 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B; L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A-1 The substituted 3-16-membered heterocyclic alkyl or 3-16-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; the 6-membered heteroaryl group has heteroatoms selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3. L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L c For covalent bonds, -O-, -S-, or -NL 11 -; L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-、-OC(=O)-、-C(=O)O-、-S(=O)-、-S(=O)2-、-NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-、-CHF-、-CF2-、-S(=O)(=NR A-1 )-、 -L a -L b -L c -with L X Connect any point on the [structure / structure]; L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E; M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently; Or L X Independently for -L X1 -L X2 -L X3 -L X4 -; L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)₂-, -NR A-1 S(=O)₂-, -S(=O)₂NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. for X 5 and X 6 Independently covalent bond, -C(R) A-1 )2-, -SO2-, -S(=O)-, -P(=O)R A-1 -、-P(=O)OR A-1 -、-P(=O)N(R A-1 -, -C(=O)- or -C(=S)-; X 2 For N, CR 2-1 S1-R 2-1 Or P = O; R 2-1 Independently hydrogen, halogen, cyano, -OR A-1 -SR A-1 -S(=O)R A-1 -SO2R A-1 -N(R) A-1 2. Or optionally by one or more R A-1-1 Replacement C1-C 12 alkyl; Or R 2-1 and R A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. It can be a single bond or a double bond; when When it is a single bond, X 3 and X 4 Independently covalent bond, -C(R) A-1 -2-, -CF2-, -O-, or -S-; X 3 When it is a covalent bond, X 2 and X 4 Directly connected; X 4 When it is a covalent bond, X 3 and X 5 Directly connected; X 3 and X 4 When all are covalent bonds, X 2 and X 5 Directly connected; when When it is a double bond, is -CR A-1 =CR A-1 -; Ring E3 is a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the 5-6 membered heteroaromatic ring is selected from one or more of N, O, S and Se, and the number of heteroatoms is 1, 2 or 3; Cycloethylene E4 is a 4-7 membered heterocyclic alkene, wherein the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3 or 4. n1 is 1, 2, 3, or 4; R 3 Substituents on ring E1 or ring E2; R 3 It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, C1-C6 alkyl substituted with one or more halogens, or C1-C6 alkoxy substituted with one or more halogens.

3. The compound of formula (I) as claimed in claim 2, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, Ring B is a saturated or partially unsaturated C3-C ring. 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, Si, and P, and the number of heteroatoms is 1, 2, 3, 4, or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. n is 0, 1, 2, 3, 4 or 5; R B Independently for R A-2 R B-1 Hydrogen, halogen, cyano, nitro, oxo (=O), =NR A-1 =S, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A- 1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A-1 )2、-NR A- 1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ; R A-2 Independently for C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-2-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R B-1 is -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 -H; L B Independently C1-C3 alkylene groups, wherein 0, 1, 2 or 3 methylene groups are independently replaced by the following groups: -O-, -C(=O)-, -C(=S)-, -C(=NR)-. A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or R A-1 Independently hydrogen, C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 Aryl or 5-14 heteroaryl; wherein the C1-C 12 Alkyl, C3-C 12 cycloalkyl, C3-C 12 Cycloalkenyl, 3-12 membered heterocyclic alkyl, 3-12 membered heterocyclic alkenyl, C6-C 14 aryl or 5-14 heteroaryl groups are optionally surrounded by one or more R groups. A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Alternatively, two R atoms on the same atom or two adjacent atoms A-1 Together with the atoms bonded to them, they form saturated or partially unsaturated C3-C atoms. 12 Carbon rings, or saturated or partially unsaturated 3-12 membered heterocycles; wherein the C3-C 12 The carbon ring or 3-12 membered heterocycle is optionally separated by one or more R A-1-1 The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5. R A-1-1 and R A-2- 1. Independently, they are: halogens, -(CH2) 0-4 R A-1-1-1 -(CH2) 0-4 OR A-1-1-1 -O(CH2) 0-4 R A-1-1-1 -O(CH2) 0-4 -C(=O)OR A- 1-1-1 -(CH2) 0-4 CH(OR A-1-1-1 2、-(CH2) 0-4 SR A-1-1-1 -(CH2) 0-4 Ph、-(CH2) 0-4 O(CH2) 0- 1Ph、-(CH2) 0-4 Py, -(CH2) 0-4 O(CH2) 0-1 Py, -CH=CHPh, nitro, cyano, azide, -(CH2) 0-4 N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )C(=S)R A-1-1-1 -(CH2) 0- 4N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )C(=S)N(R A-1-1-1 2、-(CH2) 0-4 N(R A-1-1-1 )C(=O)OR A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1- 1 )C(=O)R A-1-1-1 -N(R) A-1-1-1 )N(R A-1-1-1 )C(=O)N(R A-1-1-1 )2、-N(R A-1-1-1 )N(R A-1-1-1 )C(=O)OR A-1-1-1 -(CH2) 0-4 C(=O)R A-1-1-1 -C(=S)R A-1-1-1 -(CH2) 0-4 -C(=O)OR A-1-1-1 、-(CH2) 0-4 -C(=O)SR A-1-1-1 、-(CH2) 0-4 -C(=O)OSi(R A-1-1-1 )3、-(CH2) 0-4 OC(=O)R A-1-1-1 、-OC(=O)(CH2) 0-4 SR A-1-1-1 、-(CH2) 0-4 SC(=O)R A-1-1-1 、-(CH2) 0-4 C(=O)N(R A-1-1-1 )2、-C(=S)N(R A-1-1-1 )2、-C(=S)SR A-1-1-1 、-SC(=S)SR A-1-1-1 、-(CH2) 0-4 OC(=O)N(R A-1-1-1 )2、-C(=O)N(OR A-1-1-1 )R A-1-1-1 、-C(=O)C(=O)R A-1-1-1 、-C(=O)CH2C(=O)R A-1-1-1 、-C(=NOR A-1-1-1 )R A-1-1-1 、-(CH2) 0-4 SSR A-1-1-1 、-(CH2) 0-4 S(=O)2R A-1-1-1 、-(CH2) 0-4 S(=O)2OR A-1-1-1 、-(CH2) 0-4 OS(=O)2OR A-1-1-1 、-S(=O)2N(R A-1-1-1 )2、-(CH2) 0-4 S(=O)R A-1-1-1 、-N(R A-1-1-1 )S(=O)2N(R A-1-1-1 )2、-N(R A-1-1-1 )S(=O)2R A-1-1-1 、-N(OR A-1-1-1 )R A-1-1-1 、-C(=NH)N(R A-1-1-1 )2、-(CH2) 0-4 P(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(R A-1-1-1 )2、-(CH2) 0-4 OP(=O)(OR A-1-1-1 )2、-Si(R A-1-1-1 )₃, -(CH=CH) 0-4 O-N(R A-1-1-1 )₂, -(CH=CH) 0-4 C(=O)O-N(R A-1-1-1 )₂, =O, =S, =NR A-1-1-1 , =NN(R A-1-1-1 )₂, =NNHC(=O)R A-1-1-1 , =NNHC(=O)OR A-1-1-1 , =NNHS(=O)₂R A-1-1-1 , =NR A-1-1-1 or =NOR A-1-1-1 ; R A-1-1-1 Independently: -(CH2) 0-2 R A-1-1-1-1 -(CH2) 0-2 OH, -(CH2) 0-2 OR A-1-1-1-1 -(CH2) 0-2 CH(OR A-1-1-1-1 2. Cyano, azide, nitro, -(CH2) 0-2 C(=O)R A-1-1-1-1 -(CH2) 0-2 C(=O)OH, -(CH2) 0-2 C(=O)OR A-1-1-1-1 -(CH2) 0-2 SR A-1-1-1-1 -(CH2) 0-2 SH, -(CH2) 0-2 NH2、-(CH2) 0-2 NHR A-1-1-1-1 -(CH2) 0-2 N(R A-1-1-1-1 )2、-Si(R A-1-1-1-1 3. -C(=O)SR A-1-1-1-1 -(CH=CH) 0-4 C(=O)OR A-1-1-1-1 or -SSR A-1-1-1- 1 ; R A-1-1-1-1 Independently, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C5-C6 cycloalkyl or 5-6 membered heterocyclic alkyl; Cy B1 and Cy B2 Each independently constitutes C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 heteroarylene, optionally enclosed by one or more R A-1-1 The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Ring A is a saturated or partially unsaturated C3-C ring. 14 Carbon rings, saturated or partially unsaturated 3-14 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-14 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A -1)-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or m can be 0, 1, 2, 3, 4, or 5; Y is hydrogen, halogen, or... q can be 0, 1, 2, 3, 4, or 5; Ring Z is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaromatic rings; in the 3-12 membered heterocycles, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 5-14 membered heteroaromatic rings, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4 or 5; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 3-12 membered heterocycle, 0, 1, or more -CH2- groups on the ring are independently replaced by the following groups: -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -, -NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )- or R A and R Z Each independently as R A-2 R A-1 Oxygenation (=O), =NR A-1 =S, hydrogen, halogen, cyano, nitro, -OR A-1 -SR A-1 -N(R) A-1 )2、-Si(R A-1 3. -S(=O)R A-1 -S(=O)2R A-1 -S(=O)(=NR) A-1 )R A-1 -S(=O)2N(R) A-1 )2、-C(=O)R A-1 -C(=O)OR A-1 -C(=O)N(R) A-1 )2、-C(=O)N(R A-1 OR A-1 -OC(=O)R A-1 -OC(=O)N(R) A-1 )2、-P(=O)(R A-1 )2、-P(=O)(OR A-1 )2、-OP(=O)(R A-1 )2、-OP(=O)(OR A- 1 )2、-NR A-1 C(=O)OR A-1 -NR A-1 C(=O)R A-1 -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ; L A It is a C1-C5 alkylene group, wherein 0, 1, or more methylene groups are independently replaced by the following groups: -Cy X -, -O-, -C(=O)-, -C(=S)-, -C(=NR A-1 -, -CF2-, -CR A-1 F-、-CR A-1 R A-1 -、-CR A-1 (OR A-1 )-、-NR A-1 -, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A- 1 =CR A-1 -or Cy X Independently for C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene or 5-14 quinone heteroarylene; wherein the C3-C 12 Cycloalkylene, C3-C 12 Cycloalkenyl, 3-12-membered heterocyclic alkyl, 3-12-membered heterocyclic alkenyl, C6-C 14 arylene, 5-14 arylene heteroarylene, optionally enclosed by one or more R Z The substituted 3-12-membered heterocyclic alkyl or 3-12-membered heterocyclic alkenyl groups have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14-membered heteroaryl groups have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 14 The aryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 member heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L a For covalent bonds, -NL 11 -、 The end marked "a" is connected to ring B; L 11 and L 12 H or C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16 membered heterocyclic alkenyl, phenyl or 6 membered heteroaryl, wherein the C1-C6 alkyl, C3-C 16 Cycloalkyl, 3-16 membered heterocycloalkyl, C3-C 16 Cycloalkenyl, 3-16-membered heterocyclic alkenyl, phenyl or 6-membered heteroaryl, optionally separated by one or more R A -1 is substituted; in the 3-16 membered heterocyclic alkyl or 3-16 membered heterocyclic alkenyl groups, the heteroatom is selected from one or more of N, O, S, P and Si, and the number of heteroatoms is 1, 2, 3, 4 or 5; in the 6 membered heteroaryl group, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; L b For C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by... -NR B -、-O-、-S-、 -CR B =CR B -、 Saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C1-C 15 Alkylene, C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R B The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5. The 5-14 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5. The C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L c For covalent bonds, -O-, -S-, or -NL 11 -; L X Covalent bond or C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-、-OC(=O)-、-C(=O)O-、-S(=O)-、-S(=O)2-、-NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A-1 )-、-Si(=NR A-1 )-、 -P(=O)R A-1 -、 -NR A-1 C(=O)-、-C(=O)NR A- 1-、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-、-CHF-、-CF2-、-S(=O)(=NR A-1 )-、 -L a -L b -L c -with L X Connect any point on the [structure / structure]; L X When it is a covalent bond, -L a -L b -L c - Connect to any point on ring E; M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently; Or L X Independently for -L X1 -L X2 -L X3 -L X4 -; L X1 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)₂-, -NR A-1 S(=O)₂-, -S(=O)₂NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; L X2 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 -or -NR A-1 OC(=O)-; L X3 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)₂-, -NR A-1 S(=O)₂-, -S(=O)₂NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; L X4 It is a covalent bond or a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or 2 methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -、-C(R A-1 )2-、-CR A-1 =CR A-1 -、 -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-, -S(=O)2NR A-1 -, -NR A-1 C(=O)-, -C(=O)NR A-1 -, -OC(=O)NR A-1 - or -NR A-1 OC(=O)-; Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14 membered heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 14 Aromatic rings or 5-14-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles are selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-14 membered heteroaromatic rings are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; the C6-C 14 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-14 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. for X 2 It can be CH or N.

4. The compound of formula (I) as described in at least one of claims 1-3, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) Ring B is C6-C 14 Aromatic rings or 5-14 heterocyclic aromatic rings, such as C6-C 10 A 9-10 membered heteroaromatic ring, where the aromatic ring or heteroatom is N and the number of heteroatoms is one or two; another example is a 9-10 membered heteroaromatic ring, where the heteroatom is N and the number of heteroatoms is one or two, wherein the 9-10 membered heteroaromatic ring or C6-C 10 In an aromatic ring, at least one ring is aromatic or every ring is aromatic; (2) n is 0, 1, or 2; for example, it is 0. (3)R B Independently halogenated, oxo-(=O) or -C(=O)N(R) A-1 )2, R A-1 It is hydrogen or C1-C6 alkyl; (4) Ring A is a saturated or partially unsaturated 3-6 member monocyclic heterocyclic ring, a saturated or partially unsaturated 8-12 member spirocyclic heterocyclic ring, a 5-6 member monocyclic heteroaromatic ring, a 12-20 member bicyclic heteroaromatic ring, or a 12-20 member tricyclic heteroaromatic ring. In the 12-20 member bicyclic heteroaromatic ring or the 12-20 member tricyclic heteroaromatic ring, one ring is aromatic and the other rings are saturated or partially unsaturated. Preferably, in the heterocyclic ring or the heteroaromatic ring, the heteroatom is N and the number of heteroatoms is 1. Preferably, ring A is a saturated or partially unsaturated 3-10 membered heterocycle, for example, a saturated or partially unsaturated 5-6 membered heterocycle with N heteroatoms and one or two heteroatoms. (5)R A It is hydrogen or halogen; for example, it is hydrogen. (6) m is 0 or 1; (7)L A It is a C1-C5 alkylene group, wherein 0, 1 or more methylene groups are independently replaced by -C(=O)-; (8) Y is hydrogen or For example, (9)R Z It is hydrogen; (10) q is 0 or 1; (11) Ring Z is a 5-14 membered heteroaromatic ring, such as a 5-6 membered monocyclic heteroaromatic ring with N heteroatom and 1, 2 or 3 heteroatoms; (12)L a For covalent bonds, -NL 11 -or L 11 It is hydrogen or C1-C6 alkyl, and the end marked "a" is connected to ring B; (13)L b For C1-C 10 Alkylene, the C1-C 10 Zero, one, or more methylene groups in the alkylene group are independently... -NR B -、-O-、-S-、-CR B =CR B -、C6-C 14 Aromatic rings or 5-14 quinone heterocyclic aromatic rings are substituted; (14)L c It is a covalent bond or -O-, for example -O-; (15) B -L X - E For C1-C 20 Alkylene, the C1-C 20 In the alkylene group, 0, 1, 2, 3, 4, 5, 6, 7, or 8 methylene groups are independently replaced by the following groups: -Cy-, C(=O)-, -C(=S)-, -CR A-1 2-, -CF2-, -NR A-1 -、-O-、-S- or -S(=O)2-, the end marked "B" is connected to ring B, and the end marked "E" is connected to ring E; (16) for Among them, X 7 It can be O, CH2 or NH; For example, For example, 5. The compound of formula (I) as described in at least one of claims 1-3, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) for Ring B1 is a 5-membered heteroaromatic ring or 5-membered heterocyclic alkene with N as the heteroatom and one or two heteroatoms. Preferably, ring B1 is a 5-membered heteroaromatic ring with N as the heteroatom and one heteroatom. The end marked with "#" is connected to ring A, and the end marked with "#1" is connected to L. X Connected, the end marked "#2" is connected to L a Connected; (2)R B It can be independently F, oxo (=O) or -C (=O)N(CH3)2; (3) for Among them, ring A1 is a 5-6 membered heterocycle with N heteroatom, consisting of 1 or 2 heteroatoms, and is either saturated or partially unsaturated. R a1 and R a2 Independently, it is H or R. a1 and R a2 The carbon atoms bonded to them together form C3-C6 saturated carbon rings, 3-6 membered saturated heterocycles, or... In the aforementioned 3-6 membered saturated heterocycles, the heteroatom is selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, or 3; the cyclic Cy3 is a C3-C6 cyclic alkene or a 3-6 membered heterocyclic alkene, wherein the heteroatom in the 3-6 membered heterocyclic alkene is selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, or 3; the cyclic Cy4 is a C6-C... 10 Aromatic rings or 5-10 quinone heteroaryl rings, the C6-C 10 The aromatic ring can be monocyclic or polycyclic. When polycyclic, at least one ring is aromatic or each ring is aromatic. In the 5-10 membered heteroaromatic ring, the heteroatom is selected from one or more of N, O, S, and Se, and the number of heteroatoms is 1, 2, 3, or 4. It can be monocyclic or polycyclic; when polycyclic, at least one ring is aromatic or each ring is aromatic. R a1 and R a2 For example, H; the end marked "#4" is connected to ring B; Better place, for Wherein, ring A is a saturated or partially unsaturated 5-6 membered heterocycle with N heteroatoms, and the number of heteroatoms is 1 or 2; the end marked "#4" is connected to ring B; ring A is preferably an unsaturated 5-6 membered heterocycle with 1 heteroatom. (4)L A for L A-1 It is a linking bond or a C1-C5 alkylene group; the end marked "#5" is connected to ring A; Ideally, L A for For example, The end marked "#5" is connected to ring A; (5) for For example, (6)L b It is a C4-C7 alkylene group, wherein 0, 1, 2, or 3 methylene groups in the C4-C7 alkylene group are independently separated. -NH-, -O-, -N(C1-C6 alkyl)-, -CH=CH-, 5-6 membered heteroaromatic rings or benzene ring substitution; Ideally, L b It is a C4-C7 alkylene group, wherein one methylene group in the C4-C7 alkylene group is coated with -CR B =CR B -replace; (7)L a for L 11 It is a C1-C6 alkyl group, with the end marked "a" connected to ring B; preferably, L a for The end marked "a" is connected to ring B.

6. The compound of formula (I) as described in at least one of claims 1-3, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) for For example, The end marked "#" is connected to ring A, and the end marked "#1" is connected to L. X Connected, the end marked "#2" is connected to L a Connected; (2) for For example, The end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof; R a1 and R a2 Independently, it is H or R. a1 and R a2 The carbon atoms bonded to them together form C3-C6 saturated carbon rings, 3-6 membered saturated heterocycles, or... Cy3 is a C3-C6 cycloene, and Cy4 is a C6-C6 cycloene. 10 Aromatic rings; Better place, For any of the following schemes: Option 1: For example, For example, For example, In this configuration, the end marked "#4" is connected to ring B, and the carbon atoms marked "*" have an R configuration, an S configuration, or a mixture thereof. For example, Option 2: Among them, the end marked "#4" is connected to ring B, and the carbon atom marked "*" has the configuration of R configuration, S configuration or a mixture thereof; (3)L b For any of the following schemes: Option 1: L b for The end marked "#7" is connected to L c Connected, It is a double bond, and it has either a Z configuration or an E configuration; Option 2: L b for The end marked "#7" is connected to L c Connected, It is a double bond, and it has either a Z configuration or an E configuration; Option 3: L b for For example, The end marked "#7" is connected to L c Connected, It is a double bond, and it has either a Z configuration or an E configuration; Option 4: L b for The end marked "#7" is connected to L c Connected, It is a double bond, which has a Z configuration or an E configuration.

7. The compound of formula (I) as described in at least one of claims 1-3, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) for For example, The end marked "#" is connected to ring A, and the end marked "#1" is connected to L. X Connected, the end marked "#2" is connected to L a The carbon atoms connected by an asterisk (*) have the configuration of R, S, or a mixture thereof; For example, (2) a -L a -L b -L c For any of the following schemes: Option 1: a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, and it has either a Z configuration or an E configuration; Option 2: a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, and it has either a Z configuration or an E configuration; Option 3: a -L a -L b -L c for For example, The end marked "a" is connected to ring B. It is a double bond, and it has either a Z configuration or an E configuration; Option 4: a -L a -L b -L c for The end marked "a" is connected to ring B. It is a double bond, and it has either a Z configuration or an E configuration; (3) for Among them, the end marked "#4" is connected to ring B, and the carbon atom marked "*" has an R configuration, an S configuration, or a mixture thereof.

8. The compound of formula (I) as claimed in at least one of claims 1-7, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, B -L X - E for The end marked "B" is connected to ring B; the end marked "E" is connected to ring E; -L a -L b -L c -with L X The ring C is connected in the middle, and the compound shown in formula (I) is the same as the compound shown in formula (I-1): in, Ring C is C6-C 10 An aromatic ring or a 5-10 membered heteroaromatic ring, wherein the heteroatom in the 5-10 membered heteroaromatic ring is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. R C It is H or halogen; p is 0, 1, 2, 3, 4 or 5; L X5 Covalent bond or C1-C 15 Alkylene, the C1-C 15 In the alkylene group, 0, 1, or more methylene groups are independently replaced by the following groups: -Cy-, -O-, -S-, -NR. A-1 -, -C(=O)-, -OC(=O)-, -C(=O)O-, -S(=O)-, -S(=O)2-, -NR A-1 S(=O)2-、-S(=O)2NR A-1 -、-C(=S)-、-C(=NR A- 1 )-、-Si(=NR A-1 )-、-P(=O)OR A-1 -、-P(=O)R A-1 -、-P(=O)N(R A-1 )2-、-NR A-1 C(=O)-、-C(=O)NR A-1 -、-OC(=O)NR A-1 -、-NR A- 1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-、 M is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Cy is independently saturated or partially unsaturated C3-C 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10 quinone heteroaryl rings; wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-10 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. Ring D is a saturated or partially unsaturated C3-C ring. 12 Carbon rings, saturated or partially unsaturated 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10 quinone heteroaryl rings, wherein the C3-C 12 Carbon rings, 3-12 membered heterocycles, C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z The substituted 3-12 membered heterocycles have heteroatoms selected from one or more of N, O, S, P, and Si, and the number of heteroatoms is 1, 2, 3, 4, or 5; the 5-10 membered heteroaromatic rings have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, 4, or 5; the C6-C 10 The aromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; the 5-10 membered heteroaromatic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic. L D It is a covalently bonded or C1-C3 alkylene group, wherein in the C1-C3 alkylene group, 0, 1, 2, or 3 methylene groups are independently replaced by the following groups: -C(=O)-, -C(=S)-, -CR2-, -CF2-, -NR. A-1 -、-O-、-S- or -S(=O)2-; The definitions of the remaining variables are as described in at least one of claims 1-7.

9. The compound of formula (I) as claimed in claim 8, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) Ring C is C6-C 10 Aromatic rings, such as benzene rings; (2)R C It can be hydrogen or F; for example, H; (3) p is 0 or 1; (4)L X5 Independently C1-C6 alkylene, wherein 1, 2 or 3 methylene groups in the C1-C6 alkylene are independently replaced by -Cy- or -C(=O)-, Cy is a saturated 5-6 membered heterocycle, wherein the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is 1 or 2; Ideally, L X5 It is a C1-C6 alkylene group, wherein one methylene group in the C1-C6 alkylene group is independently replaced by -Cy-, where Cy is a saturated 5-6 membered heterocycle, and the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is 1 or 2; (5) Ring D is C6-C 10 Aromatic rings or 5-10 quinone heteroaryl rings, the C6-C 10 Aromatic rings or 5-10-membered heteroaryl rings are optionally surrounded by one or more R Z Replaced by, R Z It is oxo (=O), halogen, C1-C6 alkyl, or C1-C6 alkoxy; preferably, R Z It is an oxo (=O), halogen, or C1-C6 alkyl group; (6)L D It is a covalent bond, -C(=O)-, -NH- or -C(=O)NH-; for example, a covalent bond or -NH-; and also, for example, a covalent bond.

10. The compound of formula (I) as claimed in claim 8, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or more of the following conditions: (1) for: The end marked "#8" is connected to ring B; the end marked "#9" is connected to L. c Connected; the end marked "#10" is connected to L. X5 Connected; Better place, for Preferred The end marked "#8" is connected to ring B; the end marked "#9" is connected to L. c Connected; the end marked "#10" is connected to L. XS Connected; (2)L X5 for Among them, Cy1 and L XA The definition satisfies any of the following schemes: Option 1: Cy1 is a saturated 5-6 membered heterocyclic ring. L XA It is a covalent bond or a C1-C5 alkylene bond, for example, a C1-C5 alkylene bond, with the end marked "#11" connected to ring D; Option 2: Cy1 is a saturated 5-6 membered heterocyclic ring. L XA It is a covalent bond or a C1-C5 alkylene group, wherein 0, 1, or 2 methylene groups in the C1-C5 alkylene group are independently replaced by -Cy- or -C(=O)-, Cy is a saturated 5-6 membered heterocycle, wherein the heteroatom in the 5-6 membered heterocycle is N, and the number of heteroatoms is 1 or 2; the end marked "#11" is connected to ring D; (3) For any of the following schemes: Option 1: Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 1 or 2 heteroatoms; For example, R Z It is a C1-C6 alkyl group, r is 1, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 2 heteroatoms; Option 2: Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy, such as a halogen or a C1-C6 alkyl; Option 3: Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and ring E2 is a 5-6 membered heteroaromatic ring with N heteroatom and 1 or 2 heteroatoms, wherein the 5-6 membered heteroaromatic ring is aromatic; Option 4: Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 1 or 2 heteroatoms; For example, R Z It is a C1-C6 alkyl group, r is 1, and the ring E1 is a 5-6 membered heterocyclic alkene with N heteroatom and 2 heteroatoms; Option 5: Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy; Option 6: Where R Z It is a C1-C6 alkyl group; r is 0, 1 or 2, and ring E2 is a 5-6 membered heteroaromatic ring with N heteroatom and 1 or 2 heteroatoms, wherein the 5-6 membered heteroaromatic ring is aromatic; Among them, the end marked "#12" is connected to L. D Connected.

11. The compound of formula (I) as claimed in claim 8, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, It meets one or two of the following conditions: (1)L X5 for For example, For example, For example, The end marked "#11" is connected to ring D; (2) for For example, For example, Furthermore, for example, The end marked "#12" is connected to LD.

12. The compound of formula (I) as described in at least one of claims 8-11, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, The compound shown in formula (I) is the same as the compound shown in formula (I-2): The definitions of each variable are as described in at least one of claims 8-11; Better place, for The end marked "T1" is connected to ring E.

13. The compound of formula (I) as described in at least one of claims 1-3, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, characterized in that, The compound represented by formula (I) is selected from any of the following compounds: Among them, including In the structure, It is a carbon-carbon double bond, which has a Z configuration or an E configuration.

14. A pharmaceutical composition comprising a compound of formula (I) as claimed in at least one of claims 1-13, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

15. The use of a compound of formula (I) as described in at least one of claims 1-13, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 14 in the preparation of a STAT6 inhibitor or degrader.

16. The use of a compound of formula (I) as described in at least one of claims 1-13, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 14 in the preparation of a medicament for the prevention and / or treatment of STAT6-mediated diseases, preferably, wherein the STAT6-mediated diseases are cancer, inflammatory diseases, esophageal diseases, chronic obstructive pulmonary disease, Alzheimer's disease, or peripheral nervous system diseases; the inflammatory diseases may be atopic dermatitis, sinusitis, or asthma.

17. The use of a compound of formula (I) as described in at least one of claims 1-13, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 14 in the preparation of a medicament for the prevention and / or treatment of cancer, inflammatory diseases, esophageal diseases, chronic obstructive pulmonary disease, Alzheimer's disease, or peripheral nervous system diseases; wherein the inflammatory disease may be atopic dermatitis, sinusitis, or asthma.

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