Polycyclic compound, pharmaceutical composition thereof, and use thereof

Abstract

Disclosed are a polycyclic compound, a pharmaceutical composition thereof, and a use thereof. Specifically, disclosed are a compound represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof. The polycyclic compound of the present invention has one or more of the following advantages: (1) good inhibitory activity against STAT6; (2) good degradation activity against STAT6; and (3) good pharmacokinetic properties.

Description

Polycyclic compounds, their pharmaceutical compositions and their applications

[0001] This application claims priority to Chinese patent applications filed on March 27, 2025 (2025103754210), September 28, 2025 (2025114023098), January 5, 2026 (2026100067377), March 17, 2026 (2026103302970), and March 20, 2026 (2026). The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention relates to polycyclic 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 and translocating 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 to be solved by this invention is to address the deficiency of insufficient types of STAT6 inhibitors or degraders in the prior art by providing a novel polycyclic compound, its pharmaceutical composition, and its application. The polycyclic compound of this invention has one or more of the following advantages: (1) good inhibitory activity against STAT6; (2) good degradation activity against STAT6; and (3) good pharmacokinetic properties.

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

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

[0012] in,

[0013] Ring A is C 10 -C 20 Aromatic rings, 7-20 membered heteroaromatic rings, saturated or partially unsaturated C9-C 20 Carbon rings, or 9-20 membered heterocycles that are saturated or partially unsaturated; the C 10 -C 20 In the aromatic ring, at least one ring is aromatic or each ring is aromatic; in the 7-20 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, 4, or 5; in the 7-20 membered heteroaromatic ring, at least one ring is aromatic or each ring is aromatic; in the 9-20 membered heteroaromatic ring, 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 9-20 membered heteroaromatic ring, 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

[0014] 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.

[0015] 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.

[0016] R A-1-1 Independently: CyX1 , 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- 4CH(OR A-1-1-1 )2, -(CH2) 0-4 5R 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(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 5(=O)2R A-1-1-1 ,-(CH2) 0-4 5(=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 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 ;

[0017] 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.

[0018] 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 Z1-1 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(=NRZ1-1 )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 ;

[0019] 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 12Cycloalkenyl, 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.

[0020] 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.

[0021] 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, azide, -(CH2) 0-4 N(R Z1-1-1-1 2、-(CH2) 0-4 N(RZ1-1-1-1 )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 N(=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 ;

[0022] R Z1-1-1-1 independently represent -(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 ;

[0023] 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;

[0024] 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)o-2C(=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(RA-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 ;

[0025] R A-1-1-1-1 Independently, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl;

[0026] m can be 0, 1, 2, 3, 4, or 5;

[0027] R A For 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、-S(=NR A-1 )2R A-1 -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(=NR A-1 )R A-1 -NRA-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 -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 ;

[0028] 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.

[0029] R A-2-1 Independently: 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- 4CH(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(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-1-1-1 )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)RA-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 ;

[0030] 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;

[0031] Or L X Independently for -L X1 -L X2 -L X3 -L X4 -;

[0032] 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)-;

[0033] 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)-;

[0034] 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)-;

[0035] L X4It 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)-;

[0036] Where 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.

[0037] R Z Independently for 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, -S(=NR A-1 )2R A-1 , -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(=NR A-1 )OR A-1 , -NR A-1 C(=NR A-1 )R A-1 , -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 ), -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ;

[0038] is

[0039] X 5 and X 6 independently represent a 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)-;

[0040] X 2 For N, CR 2-1 Si-R 2-1 Or P = O;

[0041] It can be a single bond or a double bond;

[0042] 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;

[0043] when When it is a double bond, For -CR A-3 =CR A-3 -;

[0044] 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 14The 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.

[0045] 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.

[0046] R2-1 is 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:

[0047] 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.

[0048] 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;

[0049] 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.

[0050] n1 is 1, 2, 3, or 4; R 3 Substituents on ring E3 or ring E4;

[0051] R 3 It is 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;

[0052] n is 0, 1, 2, 3, 4 or 5;

[0053] 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 ;

[0054] R B-1 -L B -H, -L B -Cy B1’ or -L B -Cy B11 -CyB 2’ ;

[0055] 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

[0056] 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-1-1The 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 membered heteroaryl group is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic.

[0057] 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 arylene 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.

[0058] L A Y and ring B are defined as follows: Scheme 1 or Scheme 2:

[0059] Option 1:

[0060] L A It is a C1-C6 alkylene group, wherein 0, 1, or more 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-4 R A-4 -、-CR A-1 (ORA-1 )-, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0061] R A-4 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.

[0062] Y is hydrogen, halogen, or...

[0063] q can be 0, 1, 2, 3, 4, or 5;

[0064] 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

[0065] 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, 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.

[0066] Option 2:

[0067] -L A -Y does not exist;

[0068] Ring B is C9-C 10 The bicyclic aromatic ring or 8-10 quintile bicyclic heterocyclic aromatic ring, wherein at least one ring of the bicyclic aromatic ring or each ring is aromatic.

[0069] The present invention also provides a compound as shown in formula (I-1), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof:

[0070] in,

[0071] Ring A is a naphthalene ring, a 7-14 membered heteroaryl ring, or a saturated or partially unsaturated C9-C ring. 14 The 7-14 membered heterocyclic ring is a carbon ring, or a saturated or partially unsaturated 9-14 membered heterocyclic ring; in the 7-14 membered heterocyclic ring, 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 7-14 membered heterocyclic ring is monocyclic or polycyclic, and at least one ring is aromatic or each ring is aromatic; in the 9-14 membered heterocyclic ring, 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 9-14 membered heterocyclic ring, 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

[0072] 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.

[0073] 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.

[0074] R A-1-1 Independently: 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- 4CH(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)O-4O(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)0-4 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(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) 0-4 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 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 ;

[0075] 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 ;

[0076] 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;

[0077] m can be 0, 1, 2, 3, 4, or 5;

[0078] R A For 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 ;

[0079] 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.

[0080] R A-2-1 Independently: halogen, -(CH2) 0-4 R A-1-1-1 -(CH2)0-4OR 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- 4CH(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(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(ORA-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 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 =NNN(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 ;

[0081] L A It is a C1-C5 alkylene group, wherein 0, 1, or more 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 )-, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or

[0082] Y is hydrogen, halogen, or...

[0083] q can be 0, 1, 2, 3, 4, or 5;

[0084] 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

[0085] R Z For 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 ;

[0086] 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.

[0087] n is 0, 1, 2, 3, 4 or 5;

[0088] 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 ;

[0089] R B-1 -L B -Cy B1 -H or -L B -Cy B1 -Cy B2 -H;

[0090] 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

[0091] 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.

[0092] 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-1S(=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 )-、

[0093] M can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 independently;

[0094] Or L X Independently for -L X1 -L X2 -L X3 -L X4 -;

[0095] 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)-;

[0096] 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)-;

[0097] 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)-;

[0098] 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)-;

[0099] Where 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.

[0100] for

[0101] X 2 It can be CH or N.

[0102] In certain preferred embodiments of the present invention, certain groups in the compounds represented by formula (I) or formula (I-1), their pharmaceutically acceptable salts, their solvates, or solvates of their pharmaceutically acceptable salts are defined as follows, and groups not mentioned are as described in any embodiment of the present invention (hereinafter referred to as "in one embodiment of the present invention").

[0103] In one aspect of the present invention, in the compound represented by formula (I), ring A is C. 10 -C 20 Bicyclic aromatic ring, C 12 -C 20 The aromatic ring or heterocyclic ring may be a tricyclic aromatic ring, a 9-20 membered bicyclic heterocyclic ring, a 12-20 membered tricyclic heterocyclic ring, a saturated 9-20 bicyclic heterocyclic ring, a saturated 9-20 tricyclic heterocyclic ring, a partially unsaturated 9-20 bicyclic heterocyclic ring, or a partially unsaturated 9-20 tricyclic heterocyclic ring, wherein at least one ring is aromatic or each ring is aromatic. Preferably, the heteroatom in the heterocyclic ring or heterocyclic ring is N and / or O, and the number of heteroatoms is 1, 2, 3, or 4.

[0104] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (For example ), (For example ), (For example ), (For example ), (For example ), (For example ), The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B;

[0105] Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0106] Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S.

[0107] R a1 and R a2 The carbon atoms connected to them together form C4-C6 monocyclic saturated carbon rings, C5-C6 monocyclic saturated carbon rings, and C6-C6 monocyclic saturated carbon rings. 12 Spirocyclic saturated carbon rings, C5-C 12 fused saturated carbon rings, C5-C 12 Bridged ring saturated carbon ring, 4-6 membered monocyclic saturated heterocyclic ring, 5-12 membered spirocyclic saturated heterocyclic ring, 5-12 membered fused ring saturated heterocyclic ring, 5-12 membered bridged ring saturated heterocyclic ring, or In the saturated heterocycle, the heteroatom is selected from one or more of N, O, and S, 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, and S, 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 it is 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 and S. The number of heteroatoms is 1, 2, 3 or 4. It can be monocyclic or polycyclic. When it is polycyclic, at least one ring is aromatic or each ring is aromatic.

[0108] L is a C1-C6 alkylene (e.g., a C1-C6 straight-chain alkylene), wherein in the C1-C6 alkylene, 0, 1, or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -CH=CH-, -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

[0109] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (For example ), (For example ), (For example ), (For example ), The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B;

[0110] Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0111] Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S.

[0112] R a1 and R a2 The carbon atoms connected to them together form C4-C6 monocyclic saturated carbon rings, C6-C6 monocyclic saturated carbon rings, and C6-C6 monocyclic saturated carbon rings. 10 Spirocyclic saturated carbon rings (e.g., C7 spirocyclic saturated carbon rings), 4-6 membered monocyclic saturated heterocycles, 6-10 membered spirocyclic saturated heterocycles (e.g., 7-membered spirocyclic saturated carbon rings), or In the saturated heterocycle, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Cy3 is a C3-C6 cyclic alkene (e.g., a C5 cyclic alkene) or a 3-6 membered heterocyclic alkene (e.g., a 5 membered heterocyclic alkene), wherein the heteroatom in the 3-6 membered heterocyclic alkene is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Cy4 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, and S, and the number of heteroatoms is 1, 2, 3, or 4;

[0113] L is a C1-C4 straight-chain alkylene group (e.g., -CH2- or -(CH2)3-), wherein in the C1-C4 straight-chain alkylene group, 0, 1 or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -C(=O)NH- or -NHC(=O)-.

[0114] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (For example ), (For example ), (For example ), (For example ), (For example ), (For example ), (For example ), (For example ), (For example The end marked with "#" is connected to ring B, and the carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof.

[0115] In a certain embodiment of the invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (For example The carbon atoms marked with "*" have the configuration of R, S, or a mixture thereof, and the end marked with "#" is connected to ring B.

[0116] R a1 and R a2 The carbon atoms connected to them together form a C4-C6 monocyclic saturated carbon ring or a 4-6 member monocyclic saturated heterocycle. In the saturated heterocycle, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0117] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (side view) ), (For example ), (For example ), The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B.

[0118] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... (For example ), (For example ), The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B.

[0119] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B;

[0120] Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0121] Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S.

[0122] R a1 and R a2 The carbon atoms bonded to them together form C4-C6 saturated carbon rings, 4-6 membered saturated heterocycles, or... In the aforementioned 4-6 membered saturated heterocycles, the heteroatom is selected from one or more of N, O, and S, 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, and S, 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 it is 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 and S. The number of heteroatoms is 1, 2, 3 or 4. It can be monocyclic or polycyclic. When it is polycyclic, at least one ring is aromatic or each ring is aromatic.

[0123] L is a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -CH=CH-, -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)NRA-1 -、-OC(=O)NR A-1 -、-NR A-1 OC(=O)-, -CHF-, -CF2-, -S(=O)(=NR A-1 )-or

[0124] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... The end marked with "#" is connected to ring B;

[0125] Ring A2 and ring A4 are each independently a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the heteroaromatic ring is N and the number of heteroatoms is 1;

[0126] Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle or a 5-6 member nitrogen-containing heteroaromatic ring, wherein the number of heteroatoms in the nitrogen-containing saturated heterocycle or nitrogen-containing heteroaromatic ring is 1, and the heteroatom is N;

[0127] R a1 and R a2 The carbon atoms bonded to them together form C4-C6 saturated carbon rings, 4-6 membered saturated heterocycles, or... Cy3 is a C3-C6 cycloalkene, and Cy4 is a benzene ring or a 5-6 membered heteroaromatic ring. In the 5-6 membered heteroaromatic ring, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4.

[0128] L is a C1-C3 alkylene group, wherein 0, 1, or more -CH2- groups are independently replaced by the following groups: -O-, -NH-, or -CH=CH-. In one embodiment of the invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in Scheme 1, ring A is... The end marked with "#" is connected to ring B.

[0129] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When defining ring B as described in Scheme 2, ring A is a naphthalene ring or an 8-10 membered bicyclic heteroaromatic ring.

[0130] In one aspect of the present invention, in the compound represented by formula (I), Y and L A When ring B is defined as described in scheme 2, ring A is...

[0131] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), ring A is a naphthalene ring, a 9-10 membered heteroaryl ring, or a saturated or partially unsaturated C9-C ring. 10 The 9-10 membered heterocycle is a carbon ring, a saturated or partially unsaturated heterocyclic ring, wherein the heteroatom is N, and the number of heteroatoms is 1, 2 or 3.

[0132] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), for The end marked with "#" is connected to ring B.

[0133] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), R A It is hydrogen, halogen, or C1-C6 alkyl.

[0134] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), R A It can be hydrogen, F, or methyl.

[0135] In one embodiment of the present invention, in the compound shown as formula (I) or formula (I-1), m is 0, 1 or 2.

[0136] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), R A It is hydrogen.

[0137] In one aspect of the present invention, in the compound shown as formula (I) or formula (I-1), m is 0 or 1, for example 0.

[0138] In one aspect of the present invention, in the compound represented by formula (I), in aspect 1 or aspect 2, ring B is a 9-membered bicyclic heteroaromatic ring, for example, the heteroatom is N, and the number of heteroatoms is 1, 2 or 3.

[0139] In one embodiment of the present invention, in the compound shown in formula (I-1), ring B is a 9-membered bicyclic heteroaromatic ring, for example, a 9-membered bicyclic heteroaromatic ring with N heteroatom and the number of heteroatoms being 1, 2 or 3.

[0140] In one aspect of the present invention, in the compound represented by formula (I), in either aspect 1 or aspect 2, for The end marked "#1" is connected to L X Connected.

[0141] In one aspect of the present invention, in the compound represented by formula (I-1), for The end marked "#1" is connected to L X Connected.

[0142] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), R B Halogen or -C(=O)N(R) A-1 )2, R A-1 H or C1-C6 alkyl; R B For example, F or -C(=O)N(CH3)2.

[0143] In one aspect of the present invention, in the compound represented by formula (I) or formula (I-1), R B -C(=O)N(R) A-1 )2, for example -C(=O)N(CH3)2.

[0144] In one embodiment of the present invention, in the compound shown as formula (I) or formula (I-1), n ​​is 0, 1 or 2.

[0145] In one embodiment of the present invention, in the compound shown as formula (I) or formula (I-1), n ​​is 0 or 1.

[0146] In one aspect of the present invention, in the compound represented by formula (I), in either aspect 1 or aspect 2, for R B1 and R B2 The definition is the same as R B Preferably, R B1 For halogens, R B2 -C(=O)N(R) A-1 )2, R A-1 It is an H or C1-C6 alkyl group, with the end marked "#1" connected to the L. X Connected.

[0147] In one aspect of the present invention, in the compound represented by formula (I-1), for R B1 and R B2 The definition is the same as R B Preferably, R B1 For halogens, R B2 -C(=O)N(R) A-1 )2, R A-1 It is an H or C1-C6 alkyl group, with the end marked "#1" connected to the L. X Connected.

[0148] In one aspect of the present invention, in the compound represented by formula (I), in either aspect 1 or aspect 2, for The end marked "#1" is connected to L X Connected.

[0149] In one aspect of the present invention, in the compound represented by formula (I-1), for The end marked "#1" is connected to L X Connected.

[0150] In one aspect of the present invention, in the compound represented by formula (I), in either aspect 1 or aspect 2, for The end marked "#1" is connected to L X Connected.

[0151] In one aspect of the present invention, in the compound represented by formula (I-1), for The end marked "#1" is connected to L X Connected.

[0152] In one aspect of the present invention, in the compound represented by formula (I), in either aspect 1 or aspect 2, for The end marked "#1" is connected to L X Connected.

[0153] In one aspect of the present invention, in the compound represented by formula (I-1), for The end marked "#1" is connected to L X Connected.

[0154] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), L A -L A-1 -X 1 - #2 , where L A- 1 It is a C1-C4 alkylene group, X 1 The symbol is -C(=O)-, and the end marked "#2" is connected to ring A.

[0155] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), L A for The end marked "#2" is connected to ring A.

[0156] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), L A for The end marked "#2" is connected to ring A.

[0157] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), Y is hydrogen or

[0158] In one aspect of the present invention, in Scheme 1 of the compound as shown in Formula (I) or in the compound as shown in Formula (I-1), 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.

[0159] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), for

[0160] In one aspect of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), R Z It is hydrogen.

[0161] In one embodiment of the present invention, in Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), q is 0 or 1.

[0162] In one aspect of the present invention, in the compound represented by formula (I) or (I-1), B -L X _ E for The end marked "B" is connected to ring B; the end marked "E" is connected to ring X. Compounds shown in formula (I) or formula (I-1) are compounds shown in formula (I-2).

[0163] in,

[0164] 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.

[0165] R C It is H or halogen;

[0166] p is 0, 1, 2, 3, 4 or 5;

[0167] 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;

[0168] 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 10The 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.

[0169] 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.

[0170] 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)-, -C(R)-. A-1 )2-、-CF2-、-NR A-1 -、-O-、-S- or -S(=O)2-;

[0171] The definitions of the remaining variables are as described in any embodiment of this invention.

[0172] In one aspect of the present invention, for The end marked "#3" is connected to L X5 Connected.

[0173] In one aspect of the present invention, R C It can be hydrogen or F.

[0174] In one embodiment of the present invention, p is 0, 1 or 2.

[0175] In one embodiment of the present invention, p is 0 or 1.

[0176] In one aspect of the present invention, for The end marked "#3" is connected to L X5Connected.

[0177] In one aspect of the present invention, L X5 It is independently 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 one or two.

[0178] In one aspect of the present invention, L X5 for Among them, Cy1 is a saturated 5-6 membered heterocycle, L XA It is a covalent bond or a C1-C5 alkylene group, and the end marked "#11" is connected to ring D.

[0179] In one aspect of the present invention, L X5 for The end marked "#11" is connected to ring D.

[0180] In one aspect of the present invention, L X5 for The end marked "#11" is connected to ring D.

[0181] In one aspect of the present invention, L X5 for The end marked "#11" is connected to ring D.

[0182] 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 an oxo (=O), C1-C6 alkyl, halogen, or C1-C6 alkoxy group.

[0183] 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 an oxo (=O) or C1-C6 alkyl group.

[0184] In one aspect of the present invention, For any of the following situations:

[0185] (1) Where R ZIt 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;

[0186] Ideally, 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;

[0187] (2) Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy;

[0188] (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;

[0189] (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;

[0190] Ideally, 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;

[0191] (5) Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy;

[0192] (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;

[0193] Among them, the end marked "#12" is connected to L. D Connected.

[0194] In one aspect of the present invention, When L is in cases (1), (3), (4) or (6), D It is a covalent bond.

[0195] In one aspect of the present invention, When it is case (2) or (5), L D It is a covalent bond or -NH-.

[0196] In one aspect of the present invention, for Among them, the end marked "#12" is connected to L. D Connected.

[0197] In one aspect of the present invention, for For example, Among them, the end marked "#12" is connected to L. D Connected.

[0198] In one aspect of the present invention, for Among them, the end marked "#12" is connected to L. D Connected.

[0199] In one aspect of the present invention, for Among them, the end marked "#12" is connected to L. D Connected.

[0200] In one aspect of the present invention, L D It is a covalent bond or -NH-.

[0201] In one aspect of the present invention, L D It is a covalent bond.

[0202] In one aspect of the present invention, for At that time, the end marked "#12" was connected to L. D Connected, L D It is a covalent bond.

[0203] In one aspect of the present invention, for At that time, the end marked "#12" was connected to L. D Connected, L D It is a covalent bond or -NH-.

[0204] In one aspect of the present invention, for Among them, X 7 It can be O, CH2, or NH.

[0205] In one aspect of the present invention, for (For example ), Among them, the carbon atoms marked with "*" have the configuration of R, S or a mixture thereof.

[0206] In one aspect of the present invention, for

[0207] In one aspect of the present invention, for (For example ).

[0208] In one aspect of the present invention, for

[0209] In one aspect of the present invention, the compound represented by formula (I) is selected from any one of the following compounds:

[0210] In one embodiment of the present invention, the compound represented by formula (I) is any of the following compounds:

[0211] One of the compounds, wherein, The configuration of the chiral carbon atom and in compound A1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound A1 is... The first-eluting compound was selected under the following conditions: chiral column, Cerule IB 25*250mm, 10μm (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; preferably, the retention time of the first-eluting compound was 1.939min.

[0212] One of the compounds, wherein, The configuration of the chiral carbon atom and in compound A2 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound A2 is... Compounds that elute later under the following conditions: chiral column, Cerule IB 25*250mm, 10μm (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 2.742min;

[0213] One of the compounds, wherein, The configuration of the chiral carbon atom and in compound B1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound B1 is... The first eluting compound was selected under the following conditions: chiral column, Cerule IB 25*250mm, 10µm (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; preferably, the retention time of the first eluting compound was 1.778min.

[0214] One of the compounds, wherein, The configuration of the chiral carbon atom and in compound B2 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound B2 is... Compounds that elute later under the following conditions: chiral column, Cerule IB 25*250mm, 10µm (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 2.245min;

[0215] One of the compounds, in which the compound, The configuration of chiral carbon atoms and in compound C1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound C1 is... The first-eluting compound was selected under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the first-eluting compound was 1.109min.

[0216] One of the compounds, in which the compound, The configuration of chiral carbon atoms and the C2 structure in compounds The chiral carbon atoms have the same configuration (where the carbon atom marked "*1" is the chiral carbon atom), and the compound C2 is... Compounds that elute later under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 1.456min;

[0217] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D1 is... The first-eluting compound was selected under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the first-eluting compound was 1.109min.

[0218] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D2 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D2 is... Compounds that elute later under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 1.456min;

[0219] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D1 is... The first-eluting compound was selected under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the first-eluting compound was 1.109min.

[0220] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D2 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D2 is... Compounds that elute later under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 1.456min;

[0221] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D1 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D1 is... The first-eluting compound was selected under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the first-eluting compound was 1.109min.

[0222] One of the compounds, in which the compound, The configuration of the chiral carbon atom and in compound D2 The chiral carbon atoms have the same configuration (where the carbon atoms marked with "*" are chiral carbon atoms), and the compound D2 is... Compounds that elute later under the following conditions: chiral column OJ-H 30mm*250mm, 5um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=40%; flow rate: 45ml / min; preferably, the retention time of the compound that elutes later is 1.456min.

[0223] The above retention time test conditions are not a limitation on the compound. As long as the above test conditions are used to determine the retention time, and the obtained retention time is the same as or within the error range of the above-described compounds, and the compound is a stereoisomer of the compounds limited by the retention time, then it falls within the protection scope of this invention.

[0224] The present invention also provides a pharmaceutical composition comprising the compound described in 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.

[0225] The present invention also provides the use of the compound described in any of the above embodiments, its pharmaceutically acceptable salt, its solvate, a solvate of its pharmaceutically acceptable salt, or the above pharmaceutical composition in the preparation of a STAT6 inhibitor or degrader.

[0226] The present invention also provides the use of any of the compounds described above, their pharmaceutically acceptable salts, their solvates, solvates of their pharmaceutically acceptable salts, or the pharmaceutical compositions described above in the preparation of medicaments 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 being, for example, atopic dermatitis, sinusitis, or asthma.

[0227] The present invention also provides the use of any of the compounds described above, their pharmaceutically acceptable salts, their solvates, solvates of their pharmaceutically acceptable salts, or the pharmaceutical compositions described above 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, such as atopic dermatitis, sinusitis, or asthma.

[0228] Terminology Explanation

[0229] In this invention, "partially unsaturated carbon ring" refers to a ring with a specified number of ring atoms (e.g., C3-C). 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).

[0230] In this invention, a "partially unsaturated heterocycle" refers to a cyclic group having a specified number of ring atoms (e.g., 3-12 or 3-10), 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 is 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: etc., preferred

[0231] 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 A saturated carbon ring is a ring structure composed solely of carbon atoms, interconnected by single bonds. There are no double or triple bonds or other unsaturated bonds within the ring. Each carbon atom in the ring is bonded to four other atoms, achieving the maximum number of bonds and exhibiting saturation. "Saturated carbon rings" include, but are not limited to:

[0232] In this invention, a "saturated heterocycle" refers to a cyclic group having a specified number of ring atoms (e.g., 3-12 or 3-10), 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.

[0233] In this invention, "aromatic ring" refers to a ring having a specified number of carbon atoms (e.g., C6-C). 10 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.

[0234] 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, or 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 "heteroaromatic ring," at least one ring or each ring is aromatic. The heteroaromatic ring is connected to the rest of the molecule via carbon atoms or heteroatoms; 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 heteroaromatic ring, the number of heteroatoms depends on the number of ring atoms, and the number of heteroatoms is less than the number of ring atoms. "Heteroaromatic rings" include, but are not limited to: Preferred wait.

[0235] In this invention, "halogen" refers to F, Cl, Br or I.

[0236] 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 (Me), 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.

[0237] 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.

[0238] In this invention, "cycloene" refers to a cycloene with a specified number of carbon atoms (e.g., C3-C4). 12An unsaturated monocyclic, bridged, fused, or spirocyclic cyclic group (C5-C6) 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.

[0239] 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.

[0240] 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), 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.

[0241] In this invention, "heterocyclic alkene" refers to a cyclic, unsaturated monocyclic, bridged, fused, or spirocyclic cyclic group having a specified number of ring atoms (e.g., 4-7, 5-6), 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. 2 The 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.

[0242] 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), 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 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.

[0243] In this invention, "alkylene" refers to a divalent group formed by removing two hydrogen atoms from an alkane molecule. It can be a straight-chain alkylene or a branched alkylene, preferably a straight-chain alkylene. "Alkylene" includes, but is not limited to: wait.

[0244] 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.

[0245] 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.

[0246] 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.

[0247] 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.

[0248] 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 10 An 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.

[0249] In this invention, "aneryl" refers to a divalent aryl group.

[0250] 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.

[0251] In this invention, "hybrid aryl" refers to a divalent heteroaryl group.

[0252] In this invention, "alkoxy" refers to the group R X -O-,R X The definition is the same as the term "alkyl".

[0253] 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-.

[0254] 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.

[0255] 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.

[0256] 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.

[0257] 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.

[0258] 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.

[0259] In this invention, "multiple" can be 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0260] 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.

[0261] 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.

[0262] 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.

[0263] 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), Part IV, or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009, Sixth Edition).

[0264] 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.

[0265] In this invention, "prevention" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0266] 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).

[0267] 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.

[0268] The reagents and raw materials used in this invention are all commercially available.

[0269] The positive and progressive effects of this invention are as follows: the polycyclic compounds of this invention have one or more of the following advantages:

[0270] (1) It has good inhibitory activity against STAT6;

[0271] (2) It has good degradation activity against STAT6;

[0272] (3) Good pharmacokinetic properties;

[0273] (4) It has a significant inhibitory effect on IL-4 or IL-13-induced B cell activation;

[0274] (5) It has a significant inhibitory effect on the release of TARC induced by IL-4 or IL-13. Attached Figure Description

[0275] Figure 1 shows the results of the A549 cell degradation selectivity test for compound 10A.

[0276] Figure 2 shows the results of the A549 cell degradation selectivity test for compound 11A.

[0277] Figure 3 shows the results of the A549 cell degradation selectivity test for compound 14.

[0278] Figure 4 shows the degradation results of STAT6 in cynomolgus monkey PBMCs after intravenous administration of compound 14 at a dose of 0.2 mg / kg.

[0279] Figure 5 shows the degradation results of STAT6 in cynomolgus monkey PBMCs after oral administration of compound 14 at a dose of 4 mg / kg.

[0280] Figure 6 shows the degradation results of STAT6 in cynomolgus monkey PBMCs administered with compound 11A via intravenous injection at a dose of 0.2 mg / kg.

[0281] Figure 7 shows the degradation results of STAT6 in cynomolgus monkey PBMCs after oral administration of compound 11A at a dose of 4 mg / kg. Detailed Implementation

[0282] 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.

[0283] The preparation of the compounds of this invention can be referred to WO2025049820A1.

[0284] Example 1: Compound 1 of 4-(4-(3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propyl)piperazin-1-yl)phenyl)-N,N-dimethyl-6-(quinolin-6-yl)-1H-indole-2-carboxamide

[0285] Step 1: 4-(4-(2-(dimethylcarbamoyl)-6-(quinolin-6-yl)-1H-indol-4-yl)phenyl)piperazine-1-carboxylic acid tert-butyl ester 1c

[0286] At room temperature, tert-butyl 4-(4-(6-chloro-2-(dimethylcarbamoyl)-1H-indol-4-yl)phenyl)piperazine-1-carboxylate 1ae (intermediate 1a can be prepared by the method reported in patent WO2025049820A1) (0.15 g, 0.31 mmol), quinoline-6-ylboronic acid 1b (0.064 g, 0.37 mmol), potassium phosphate (0.20 g, 0.93 mmol), and palladium 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]methanesulfonate (0.076 g, 0.093 mmol) were added sequentially to 1,4-dioxane (20 mL) and water (4 mL). Nitrogen gas was exchanged three times, and the reaction mixture was reacted at 85 °C for 6 hours under nitrogen protection. The reaction solution was cooled to room temperature, water (60 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 dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-5%) to give tert-butyl 4-(4-(2-(dimethylcarbamoyl)-6-(quinolin-6-yl)-1H-indol-4-yl)phenyl)piperazine-1-carboxylate 1c (0.10 g, yield 56.0%), as a white solid.

[0287] LCMS: RT=1.14min, m / z=576.2[M+H] + .

[0288] Step 2: N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-6-(quinolin-6-yl)-1H-indole-2-carboxamide 1d

[0289] At room temperature, tert-butyl piperazine-1-carboxylate 1c (0.10 g, 0.17 mmol) was dissolved in dichloromethane (20 mL), followed by the addition of trifluoroacetic acid (5 mL). The reaction mixture was stirred at room temperature for 2 hours. The solvent was concentrated, and the crude product was then dissolved in dichloromethane (100 mL). The dichloromethane phase was washed once with saturated sodium bicarbonate aqueous solution (20 mL), then once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to give product N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-6-(quinoline-6-yl)-1H-indole-2-carboxamide 1d (0.05 g, yield 60.5%) as a yellow solid.

[0290] LCMS: RT=0.89min, m / z=476.2[M+H] + .

[0291] Step 3: Compound 1 of 4-(4-(3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propyl)piperazin-1-yl)phenyl)-N,N-dimethyl-6-(quinolin-6-yl)-1H-indole-2-carboxamide

[0292] At room temperature, N,N-dimethyl-4-(4-(piperazin-1-yl)phenyl)-6-(quinolin-6-yl)-1H-indole-2-carboxamide 1d (30 mg, 0.06 mmol), 3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propionaldehyde 1e (intermediate 1e can be prepared by the method reported in patent WO2025049820A1) (24 mg, 0.08 mmol) were dissolved in dimethyl sulfoxide (1.5 mL) and tetrahydrofuran (1.5 mL), and then sodium triacetylborohydride (27 mg, 0.13 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction was quenched with water (20 mL), then extracted twice with dichloromethane (30 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 the crude product. The crude product was purified by preparative high performance liquid chromatography to obtain compound 1 (7.5 mg, yield 15.4%) of 4-(4-(3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propyl)piperazin-1-yl)phenyl)-N,N-dimethyl-6-(quinolin-6-yl)-1H-indole-2-carboxamide, which was a white solid product.

[0293] LCMS: RT=1.78min, m / z=775.3[M+H] + .

[0294] 1 H NMR (400MHz, MeOH-d4): 8.83 (dd, J=4.4Hz, 1.2Hz, 1H), 8.45 (t, J=7.6Hz, 1H), 8.26 (d, J=1.6Hz, 1H), 8.20 (dd, J= 8.8Hz, 1.6Hz, 1H), 8.15 (d, J=8.8Hz, 1H), 7.79 (s, 1H), 7.67 (d, J=8.4Hz, 2H), 7.57-7.52 (m, 2H), 7.13 (d, J=8.8Hz , 2H), 7.07-7.03 (m, 3H), 7.01-6.97 (m, 2H), 5.32 (dd, J=12.4Hz, 5.2Hz, 1H), 3.69 (s, 3H), 3.47-3.37 (m, 5H), 3.24 -3.10 (m, 4H), 3.05 (t, J=7.6Hz, 2H), 2.95-2.65 (m, 7H), 2.66-2.63 (m, 2H), 2.14-2.00 (m, 1H), 2.00-1.92 (m, 2H).

[0295] Example 2: Compound 2 of 4-(4-(3-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)propyl)piperazin-1-yl)phenyl)-N,N-dimethyl-6-(quinolin-2-yl)-1H-indole-2-carboxamide

[0296] Following the same operating steps as in Example 1, 2-quinoline pinacol boronic acid ester was used instead of quinoline-6-ylboronic acid as the raw material to prepare compound 2 (7.1 mg), which was a white solid product.

[0297] LCMS: RT=1.81min, m / z=775.3[M+H] + .

[0298] 1 H NMR (400MHz, DMSO-d6): 11.89-11.88 (m, 1H), 11.10 (s, 1H), 9.32 (d, J=2.4Hz, 1H), 8.71 (d, J=2.4Hz, 1H), 8.12-8.06 (m, 2H), 7.79-7.75 (m, 2H), 7.71-7.64 (m, 3H), 7.55 (d, J=1.6Hz, 1H), 7.12-7.10 (m, 2H), 6.99- 6.91(m, 4H), 5.39-5.35(m, 1H), 3.60(s, 3H), 3.23-3.20(m, 6H), 2.99-2.95(m, 2H), 2.93-2.84(m, 1H), 2. 75-2.63 (m, 2H), 2.56-2.52 (m, 5H), 2.46-2.40 (m, 3H), 2.00-1.96 (m, 1H), 1.84-1.79 (m, 2H), 1.23 (s, 2H).

[0299] Example 3: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 3

[0300] Step 1: 3-((4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid methyl ester 3b

[0301] At room temperature, methyl 3-aminooxetane-3-carboxylate 3a (3.8 g, 28.98 mmol) was added to a round-bottom flask, followed by acetonitrile (38 mL). Ethyl 4-bromobutyrate (8.48 g, 43.47 mmol), potassium carbonate (12.8 g, 86.94 mmol), and potassium iodide (7.17 g, 43.47 mmol) were then added sequentially. The reaction mixture was heated to 90 °C and stirred for 8 hours. After the reaction was completed, water (40 mL) was added, and the mixture was extracted twice with ethyl acetate (40 mL). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 0%-5%) to give methyl 3-((4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid ester 3b (5.7 g, yield: 80.3%), which was a yellow oil.

[0302] 1 H NMR (400MHz, DMSO-d6) δ4.67 (d, J=6.2Hz, 2H), 4.37 (d, J=6.2Hz, 2H), 4.04 (q, J=7.1Hz, 2H) , 3.71 (s, 3H), 2.84 (s, 1H), 2.40-2.29 (m, 4H), 1.62 (p, J=7.1Hz, 2H), 1.17 (t, J=7.1Hz, 3H).

[0303] Step 2: 3-((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid methyl ester 3c

[0304] Methyl 3-((4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid ester 3b (2.5 g, 10.2 mmol) was dissolved in dichloromethane (25 mL) at room temperature, and sodium bicarbonate (3.4 g, 40.8 mmol) was added. Under nitrogen protection, the mixture was cooled to 10 °C, and benzyl chloroformate (5.2 g, 30.6 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, water (20 mL) was added, and the layers were separated. The aqueous phase was extracted with dichloromethane (20 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%-30%) to give methyl 3-((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid ester 3c (3.5 g, yield: 90.4%) as a yellow oil.

[0305] LCMS: m / z = 380.3[M+1] + .

[0306] Step 3: 5-Benzyl-8-ethyl-9-oxo-2-oxa-5-azaspiro[3.5]nonane-5,8-dicarboxylate 3d

[0307] Methyl 3c of 3-((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)oxetane-3-carboxylic acid ester 3c (3.5 g, 9.22 mmol) was dissolved in tetrahydrofuran (35 mL) at room temperature. The mixture was purged with nitrogen three times, cooled to -78 °C, and a 1 M tetrahydrofuran solution of bis(trimethylsilylamino)lithium (18.45 mL, 18.45 mmol) was added dropwise. The mixture was stirred at -78 °C for 1 hour. After the reaction was complete, a saturated ammonium chloride aqueous solution (35 mL) was added dropwise to quench the reaction. The mixture was extracted twice with ethyl acetate (35 mL), and the combined organic phases were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 3d of 5-benzyl-8-ethyl-9-oxo-2-oxa-5-azaspiro[3.5]nonane-5,8-dicarboxylate ester 3d (3.5 g), a yellow oily crude product.

[0308] LCMS: m / z = 348.3[M+1] + .

[0309] Step 4: Benzyl 9-oxo-2-oxa-5-azaspiro[3.5]nonane-5-carboxylic acid ester 3e

[0310] 3.5 g (10.08 mmol) of 5-benzyl-8-ethyl-9-oxo-2-oxa-5-azaspiro[3.5]nonane-5,8-dicarboxylate 3d was added to a sealing tube at room temperature, followed by dimethyl sulfoxide (35 mL), water (8.75 mL), and lithium chloride (1.3 g, 30.23 mmol). The mixture was heated to 160 °C and stirred for 3 hours. After the reaction was complete, the mixture was cooled to room temperature. Water (30 mL) was added, and the mixture was extracted twice with ethyl acetate (40 mL). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain benzyl-9-oxo-2-oxa-5-azaspiro[3.5]nonane-5-carboxylate 3e (3.3 g), a crude product in the form of a brown oil.

[0311] LCMS: m / z = 276.3 [M+1] + .

[0312] Step 5: Phenyl 9-(((perfluorobutyl)sulfonyl)oxy)-2-oxa-5-azaspiro[3.5]non-8-ene-5-carboxylic acid ester 3f

[0313] Benzyl 9-oxo-2-oxa-5-azaspiro[3.5]nonane-5-carboxylic acid ester 3d (3.3 g, 11.98 mmol) was dissolved in ultra-dry tetrahydrofuran (33 mL) at room temperature. Under nitrogen protection, the temperature was lowered to 0-10 °C, and 1,8-diazabicyclo[5.4.0]undec-7-ene (5.5 g, 35.95 mmol) was added dropwise. After the addition was complete, the mixture was stirred for 10-30 minutes. Perfluorobutylsulfonyl fluoride (10.8 g, 35.95 mmol) was added dropwise at 10-20 °C. After the addition was complete, the mixture was stirred at room temperature for 1 hour. After the reaction was completed, water (30 mL) was added dropwise to quench the reaction. The mixture was extracted twice with ethyl acetate (35 mL). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%-25%) to obtain phenyl 9-(((perfluorobutyl)sulfonyl)oxy)-2-oxa-5-azaspiro[3.5]non-8-ene-5-carboxylic acid ester 3f (2.0 g, yield: 30%), which was a bright yellow oil.

[0314] Step 6: 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-2-oxa-5-azaspiro[3.5]non-8-ene-5-carboxylic acid benzyl ester for 3h

[0315] At room temperature, phenyl 9-(((perfluorobutyl)sulfonyl)oxy)-2-oxa-5-azaspiro[3.5]non-8-en-5-carboxylic acid ester 3f (2.0 g, 3.59 mmol) was dissolved in 1,4-dioxane (20 mL) and water (5 mL), followed by the addition of 4-chloro-7-fluoro-N,N-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole-2-carboxamide (1.3 g, 3.59 mmol), potassium carbonate (990.3 mg, 7.18 mmol), and [1,1′-bis(diphenylphosphine)ferrocene]palladium(II) dichloride (262.7 mg, 0.359 mmol). The mixture was purged with nitrogen three times and stirred at 90 °C for 2 hours. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, and the filtrate was concentrated and the crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%-50%) to obtain 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-2-oxa-5-azaspiro[3.5]non-8-ene-5-carboxylic acid benzyl ester 3h (1.4g, yield: 78.7%), which was a bright yellow solid product.

[0316] Step 7: 4-Chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]nonane-9-yl)-1H-indole-2-carboxamide 3i

[0317] To a methanol / tetrahydrofuran (2 mL / 5 mL) solution of 5-benzyloxycarbonyl-9-(4-chloro-2-(N,N-dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-2-oxa-5-azaspiro[3.5]non-8-en-5-carboxylic acid benzyl ester 3h (100 mg, 0.20 mmol), platinum dioxide (PtO2) (50 mg) was added at room temperature. The mixture was purged with hydrogen three times, and then stirred overnight at room temperature under a hydrogen atmosphere. After the reaction was complete, the solid catalyst was removed by filtration and the mixture was washed with methanol. The combined organic phases were concentrated to give the target product, 4-chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]nonane-9-yl)-1H-indol-2-carboxamide 3i (80 mg, yield: 100%), as a white solid.

[0318] LCMS: m / z = 385.9 [M+H] + .

[0319] Step 8: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 3k

[0320] To a solution of 4-chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]nonane-9-yl)-1H-indole-2-carboxamide 3i (80 mg, 0.22 mmol) and 3-(1H-1,2,3-triazol-1-yl)propionic acid 3j (intermediate 3j can be prepared by the method reported in patent WO2025049820A1) (46 mg, 0.33 mmol) in pyridine (5 mL), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (105 mg, 0.55 mmol) was added at room temperature. The mixture was stirred overnight at 40 °C. After the reaction was complete, the solvent was removed under reduced pressure. The residue was extracted separately with water (30 mL) and ethyl acetate (20 mL). The organic phase was separated, washed successively with 1N hydrochloric acid (5 mL) and saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated to give the crude product. The crude product was purified by column chromatography (dichloromethane / methanol = 0% to 8% gradient elution) to obtain the target compound 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 3k (60 mg, yield 56%), as a white solid.

[0321] LCMS: m / z = 489.0 [M+H] + .

[0322] Step 9: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 3

[0323] Under nitrogen protection, at 25°C, 3l (60 mg, 0.12 mmol) of 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)piperidin-1-yl)phenyl)piperidin-2,6-dione, cesium fluoride (93 mg, 0.61 mmol), and 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa -5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 3k (60 mg, 0.12 mmol) was added to a mixture of dioxane (4 mL) and water (1 mL), along with [2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl]-[2-(2-aminoethyl)phenyl]palladium(II) chloride (21 mg, 0.02 mmol). The mixture was stirred at 85 °C for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude residue. This residue was purified by column chromatography (dichloromethane / methanol = 0% to 10% gradient elution) combined with preparative high performance liquid chromatography to obtain the title compound 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 3 (17.44 mg, yield: 17%), as a white solid.

[0324] LCMS: m / z = 819.3 [M+H] + .

[0325] 1H NMR (400MHz, DMSO-d6): 12.15 (s, 1H), 10.83 (s, 1H), 8.13 (s, 1H), 7.72 (s, 1H), 7.62 (d, J=7.6Hz, 2H), 7.45 (d, J=8.0Hz, 2H), 7.28 (d, J=4.8Hz, 1H), 7.07-6.97 (m, 3H), 6.90 (s, 1H), 7.75 (d, J=6.4Hz, 1H), 4.65 (t, J=6.4Hz, 2H), 4.59 (d, J=7.2 Hz, 1H), 4.45 (d, J. 6.4Hz, 1H), 4.18 (d, J=7.6Hz, 1H), 3.83-3.80 (m, 2H), 3.49 (d, J=10.8Hz, 3H), 3.33-3.02 (m, 9H), 2.8 4-2.66 (m, 5H), 2.31-2.17 (m, 2H), 2.04-1.85 (m, 5H), 1.76 (d, J=12.4Hz, 2H), 1.66 (d, J=12.0Hz, 2H), 1.49-1.40 (m, 1H).

[0326] Example 4: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 4

[0327] Step 1: 4-Chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-1H-indole-2-carboxamide 4b

[0328] At room temperature, 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-2-oxa-5-azaspiro[3.5]non-8-ene-5-carboxylate benzyl ester (350 mg, 0.70 mmol) and sodium methanethiol (320 mg, 4.57 mmol) were sequentially added to an ultradry N,N-dimethylformamide (4 mL) solution. The reaction mixture was stirred at 70 °C for 1 hour. Water (30 mL) was added, and the mixture was extracted three times with ethyl acetate (20 mL). The organic phase was washed once with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to dryness to obtain the crude product. The crude product was slurried with a mixed solvent (ethyl acetate / petroleum ether = 1 / 10, 10 mL) and filtered to obtain 4-chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-1H-indole-2-carboxamide 4b (230 mg, yield: 90%), a yellow solid.

[0329] LCMS: m / z = 364.0 [M+H] + .

[0330] Step 2: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 4d

[0331] At room temperature, 4-chloro-7-fluoro-N,N-dimethyl-6-(2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-1H-indole-2-carboxamide 4b (170 mg, 0.47 mmol), 3-(1H-1,2,3-triazol-1-yl)propionic acid 4c (99 mg, 0.70 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (225 mg, 1.17 mmol) were sequentially added to pyridine (8 mL), and the reaction mixture was reacted at 40 °C for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was dispersed in water (30 mL). The pH was adjusted to <4 with 1N HCl, and the mixture was extracted three times with ethyl acetate (20 mL). The combined organic phases were 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: dichloromethane: methanol = 0%-8%) to obtain 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 4d (160 mg, yield: 70%), as a white solid.

[0332] LCMS: m / z = 486.9 [M+H] + .

[0333] Step 3: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 4

[0334] At room temperature, 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3,5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 4d (20 mg, 0.04 mmol) was dissolved in 1,4-dioxane / water (2 mL / 0.5 mL), followed by the addition of 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-) Dioxaboron-2-yl)phenyl)piperidin-1-yl)phenyl)piperidin-2,6-dione 4e (intermediate 4e can be prepared by the method reported in patent WO2025049820A1) (20 mg, 0.04 mmol), cesium fluoride (31 mg, 0.21 mmol), and [2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl]-[2-(2-aminoethyl)phenyl]palladium(II) chloride (20 mg, 0.02 mmol). The reaction mixture was purged with argon three times and reacted at 85 °C for 2 hours under nitrogen protection. The reaction was detected by LCMS. The reaction solution was cooled to room temperature, water (20 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 with anhydrous sodium sulfate, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: dichloromethane: methanol = 0%-10%) and preparative high performance liquid chromatography to obtain 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 4 (11.05 mg, yield 57%), a white solid.

[0335] LCMS: m / z = 817.2 [M+H] + .

[0336] 1H NMR (400MHz, DMSO-d6): 12.24 (s, 1H), 10.83 (s, 1H), 8.10 (s, 1H), 7.71 (s, 1H), 7.60 (d, J=7.6Hz, 2H) , 7.46 (d, J=8.0Hz, 2H), 7.08-6.95 (m, 4H), 6.91 (s, 1H), 5.71 (s, 1H), 4.69 (d, J=6.4Hz, 2H), 4.64 (t, J =6.8Hz, 2H), 4.50 (d, J = 6.4Hz, 2H), 3.82 (dd, J = 11.6, 4.8Hz, 1H), 3.60 (s, 2H), 3.49 (d, J = 11.2Hz, 2H) , 3.22-3.07 (m, 9H), 2.82 (t, J=10.8Hz, 2H), 2.75-2.62 (m, 2H), 2.26-2.17 (m, 3H), 2.04-1.85 (m, 5H).

[0337] Example 5: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]non-8-en-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 5

[0338] Following the same operating steps as in Examples 3 and 4, methyl 1-aminocyclobutane-1-carboxylate was used instead of methyl 3-aminooxetane-3-carboxylate 3a as the starting material to obtain 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]non-8-en-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 5 (38 mg, yield: 45%), which was a white solid.

[0339] LCMS: RT=2.041min, m / z=815.0[M+H] + .

[0340] 1H NMR (400MHz, DMSO-d6): 12.20 (s, 1H), 10.83 (s, 1H), 8.10 (s, 1H), 7.70 (s, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.4Hz, 2H), 7.09-6.90 (m, 5H), 5.51-5.50 (m, 1H), 4.63 (t, J=6.4Hz, 2H), 3. 84-3.80 (m, 1H), 3.62 (s, 2H), 3.49 (d, J=11.2Hz, 2H), 3.23-3.09 (m, 8H), 2.85-2.63 (m, 5H), 2 .38-2.33(m, 4H), 2.23-2.20(m, 3H), 2.04-1.87(m, 5H), 1.45-1.38(m, 1H), 1.06-0.99(m, 1H).

[0341] Example 6: 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 6A; 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 6B

[0342] Following the same synthetic steps as in the examples, intermediate 3k (180 mg, 0.37 mmol) was subjected to chiral column separation to obtain (R)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 3k-1 (70 mg, yield: 39%) and (S)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 3k-2 (75 mg, yield: 42%).

[0343] Chiral resolution conditions: Instrument: SFC-80; chiral column: Daicel IB 25*250mm, 10um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; column pressure: 100bar; detection wavelength: 214nm; cycle time: 4.2min; sample volume: 180mg sample dissolved in 15mL methanol; injection volume: 2.5mL per injection.

[0344] Compound 3k-1:

[0345] Retention time of chiral column: RT = 1.939 min;

[0346] Compound 3k-2:

[0347] Retention time of chiral column: RT = 2.742 min.

[0348] Then, 3k-1 and 3k-2 were coupled with intermediate 3l to give 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 6A (37 mg) Compound 6B (21 mg, yield: 28%) is a white solid and 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide, which is a white solid.

[0349] Compound 6A:

[0350] LCMS: m / z = 819.0 [M+H] + ;

[0351] 1¹H NMR (400 MHz, DMSO-d₆): 12.15 (s, 1H), 10.84 (s, 1H), 8.13 (s, 1H), 7.72 (s, 1H), 7.62 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 7.28 (d, J=4.4 Hz, 1H), 7.07-6.97 (m, 3H), 6.90 (s, 1H), 4.75 (d, J=6.4 Hz, 1H), 4.65 (t, J=6.4 Hz, 2H), 4.59 (d, J=7.6 Hz, 1H), 4.45 (d, J=6.8 Hz, 1H), 4.19 (d, J=7.6 Hz, 1H), 3.84-3.80 (m, 2H), 3.49 (d, J=10.4 Hz, 3H), 3.33-3.03 (m, 9H), 2.84-2.63 (m, 5H), 2.33-2.16 (m, 2H), 2.03-1.85 (m, 5H), 1.75 (d, J=11.6 Hz, 1H), 1.64 (d, J=11.6 Hz, 1H), 1.43-1.34 (m, 1H).

[0352] Compound 6B:

[0353] LCMS: m / z = 818.8 [M+H] + ;

[0354] 1 ¹H NMR (400 MHz, DMSO-d₆): 12.16 (s, 1H), 10.84 (s, 1H), 8.13 (s, 1H), 7.72 (s, 1H), 7.62 (d, J=8.0 Hz, 2H), 7.45 (d, J=7.6 Hz, 2H), 7.28 (d, J=4.8 Hz, 1H), 7.07-6.97 (m, 3H), 6.90 (s, 1H), 4.75 (d, J=6.4 Hz, 1H), 4.65 (t, J=6.4 Hz, 2H), 4.59 (d, J=7.2 Hz, 1H), 4.45 (d, J=6.0 Hz, 1H), 4.19 (d, J=7.2 Hz, 1H), 3.83-3.80 (m, 2H), 3.49 (d, J=10.8 Hz, 3H), 3.33-3.03 (m, 9H), 2.84-2.62 (m, 5H), 2.31-2.17 (m, 2H), 2.04-1.88 (m, 5H), 1.76 (d, J=10.8 Hz, 1H), 1.66 (d, J=11.2 Hz, 1H), 1.50-1.40 (m, 1H).

[0355] Example 7: 4-(4-(4-(2-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethyl)piperazin-1-yl)phenyl)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 7

[0356] Step 1: 3-(4-(2-(4-(4-bromophenyl)piperazin-1-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7c

[0357] To a solution of 1-(4-bromophenyl)piperazine 7a (200 mg, 0.23 mmol) in 1,2-dichloroethane (10 mL), 2-(1-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)acetaldehyde 7b (502 mg, 1.67 mmol) was added. The mixture was stirred at 50 °C for 1 hour, then cooled to room temperature. Sodium triacetoxyborohydride (353 mg, 1.67 mmol) was added, and the reaction mixture was stirred at 50 °C for another 1 hour. After the reaction was complete, the reaction mixture was poured into water (30 mL) and extracted with dichloromethane (20 mL × 2). The combined organic phases were washed with brine (20 mL), dried over anhydrous sodium sulfate, and concentrated to give the crude product. Purified by column chromatography (silica gel, methanol / dichloromethane gradient 0% to 8%), the compound 3-(4-(2-(4-(4-bromophenyl)piperazin-1-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7c (180 mg, yield: 39%) was given as a yellow solid.

[0358] LCMS: m / z = 562.2 [M+H] + .

[0359] Step 2: 3-(3-methyl-2-oxo-4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenyl)piperazin-1-yl)ethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7d

[0360] To a suspension of 3-(4-(2-(4-(4-bromophenyl)piperazin-1-yl)ethyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7c (130 mg, 0.25 mmol), pinacol diborate (126 mg, 0.50 mmol), and potassium acetate (121 mg, 1.24 mmol) in dioxane (5 mL), [1,1′-bis(diphenylphosphine)ferrocene]palladium dichloride (36 mg, 0.05 mL) was added at 25 °C under nitrogen protection. The mixture was stirred at 95°C for 2 hours. After the reaction was complete, the reaction solution was concentrated under reduced pressure to obtain a crude residue, which was purified by column chromatography (silica gel, methanol / dichloromethane gradient 0% to 10%) to give compound 3-(3-methyl-2-oxo-4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenyl)piperazin-1-yl)ethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7d (90 mg, yield: 63%) as a yellow solid.

[0361] LCMS: RT=1.940min, m / z=574.3[M+H] + .

[0362] Step 3: 4-(4-(4-(2-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethyl)piperazin-1-yl)phenyl)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 7

[0363] 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 4d (90 mg, 0.19 mmol), cesium fluoride (141 mg, 0.93 mmol), and 3-(3-methyl-2-oxo-4-(2-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl) A mixture of dioxane (5 mL) and water (1 mL) of phenyl)piperazin-1-yl)ethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione 7d (106 mg, 0.19 mmol) was added under nitrogen protection at 25 °C to a solution of 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)(2′-amino-1,1′-biphenyl-2-yl)palladium(II) catalyst (47 mg, 0.06 mmol). The mixture was stirred at 85 °C for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude residue, which was purified by column chromatography (silica gel, dichloromethane / methanol gradient 0% to 10%) and preparative high performance liquid chromatography to obtain compound 4-(4-(4-(2-(1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethyl)piperazin-1-yl)phenyl)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 7 (58 mg, yield 35%), as a white solid.

[0364] LCMS: m / z = 449.7 [M / 2 + H] + ;

[0365] 1H NMR (400MHz, DMSO-d6): 12.17 (s, 1H), 11.10 (s, 1H), 8.10 (s, 1H), 7.71 (s, 1H), 7.51 (d, J=8.4 Hz, 2H), 7.09 (d, J=8.4Hz, 2H), 6.99-6.89 (m, 5H), 5.69 (t, J=2.8Hz, 1H), 5.38 (dd, J=12.4, 4. 8Hz, 1H), 4.69 (d, J=6.8Hz, 2H), 4.64 (t, J=6.8Hz, 2H), 4.50 (d, J=6.8Hz, 2H), 3.62-3.60 (m, 5 H), 3.25-3.08(m, 14H), 2.93-2.85(m, 1H), 2.75-2.60(m, 8H), 2.26(s, 2H), 2.02-1.99(m, 1H).

[0366] Example 8: (R)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-7-fluoro-4-(2-methoxyphenyl)-N,N-dimethyl-1H-indole-2-carboxamide compound 8

[0367] Following the same steps as in Example 7, 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide was used instead of 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]non-8-en-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 4d was used as the starting material to obtain the target product (27 mg, yield: 36%), which was a white solid.

[0368] LCMS: RT=1.836min, m / z=895.9[M+H] + ;

[0369] 1H NMR (400MHz, DMSO-d6): 12.14 (s, 1H), 11.11 (s, 1H), 8.10 (s, 1H), 7.71 (s, 1H), 7.50 (d, J= 8.4Hz, 2H), 7.08 (d, J=8.8Hz, 2H), 6.99-6.93 (m, 3H), 6.88-6.87 (m, 2H), 5.49 (s, 1H), 5.4 0-5.36 (m, 1H), 4.63 (t, J=6.8Hz, 2H), 3.62 (s, 5H), 3.25-2.85 (m, 15H), 2.73-2.60 (m, 8H) , 2.46-2.33(m, 4H), 2.23(s, 2H), 2.01-1.99(m, 1H), 1.42-1.40(m, 1H), 1.06-0.98(m, 1H).

[0370] Example 9: Compound 9A of 6-((R)-5-(3-(1H-pyrazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide; Compound 9B of 6-((S)-5-(3-(1H-pyrazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide.

[0371] Intermediate 9a (prepared under the same synthetic conditions as in Example 3) (130 mg, 0.27 mmol) was chirally resolved to obtain 9a-1 and compound 9a-2, respectively.

[0372] Chiral resolution conditions: Instrument: SFC-80; chiral column: Daicel IB 25*250mm, 10um (Regis); column temperature: 35℃; mobile phase: CO2 / [MeOH / ACN]=55 / 45; flow rate: 45ml / min; column pressure: 100bar; detection wavelength: 214nm; cycle time: 3.0min; sample volume: 130mg sample dissolved in 40mL methanol; injection volume: 2.7mL per injection.

[0373] 9a-1: (50 mg, yield: 38%), white solid.

[0374] Retention time of chiral column: RT = 1.778 min;

[0375] 9a-2: (50 mg, yield: 38%), white solid.

[0376] Retention time of chiral column: RT = 2.245 min

[0377] Then, compounds 9a-1 and 9a-2 were coupled with 31, respectively, to obtain 6-((R)-5-(3-(1H-pyrazol-1-yl)propionyl)-2-oxa-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 9A (24 mg, yield 28%), a white solid.

[0378] LCMS: RT=1.971min, m / z=818.0[M+H] + ;

[0379] 1 H NMR (400MHz, DMSO-d6): 12.15 (s, 1H), 10.83 (s, 1H), 7.73 (s, 1H), 7.62 (d, J=7.6Hz, 2H), 7.45 (d, J=7.2Hz, 3H), 7.28 (d, J=4.8Hz, 1H), 7.07-6.97 (m, 3H), 6.89 (s, 1H), 6.22 (s, 1H), 4.74 (d, J=6.4Hz, 1H), 4.59 (d, J=7.2Hz, 1H), 4.44 (d, J=6.4 Hz, 1H), 4.39 (t, J=6.8Hz, 2H), 4.19 (d, J=7.2Hz, 1H), 3.84-3.76 (m, 2H), 3.49 (d, J=10.0Hz, 3H), 3.22-2.89 (m, 9H), 2.8 5-2.62 (m, 5H), 2.33-2.20 (m, 2H), 2.04-1.87 (m, 5H), 1.75 (d, J=11.6Hz, 1H), 1.64 (d, J=12.0Hz, 1H), 1.44-1.34 (m, 1H).

[0380] Compound 9B (27 mg, yield: 32%) is a white solid.

[0381] LCMS: RT=1.981min, m / z=409.7[M / 2+H] + ;

[0382] 1H NMR (400MHz, DMSO-d6): 12.15 (s, 1H), 10.84 (s, 1H), 7.73 (s, 1H), 7.62 (d, J=8.0Hz, 2H), 7.45 (d, J=7.2Hz, 3H), 7.28 (d, J=3.6Hz, 1H), 7.07-6.97 (m, 3H), 6.90 (s, 1H), 6.22 (s, 1H), 4.74 (d, J=6.4Hz, 1H), 4.59 (d, J=7.2Hz, 1H), 4.44 (d, J=6.8 Hz, 1H), 4.39 (t, J=6.8Hz, 2H), 4.19 (d, J=7.2Hz, 1H), 3.83-3.76 (m, 2H), 3.49 (d, J=10.4Hz, 3H), 3.22-2.89 (m, 9H), 2.8 7-2.62 (m, 5H), 2.33-2.17 (m, 2H), 2.04-1.85 (m, 5H), 1.75 (d, J=11.6Hz, 1H), 1.64 (d, J=10.4Hz, 1H), 1.44-1.34 (m, 1H).

[0383] Example 10: Compound 10A of 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide; Compound 10B of 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide.

[0384] Step 1: Methyl 1-((4-ethoxy-4-oxobutyl)amino)cyclobutane carboxylate 10a

[0385] At room temperature, methyl 1-aminocyclobutanecarboxylate (5.0 g, 38.76 mmol) was added to a round-bottom flask, followed by acetonitrile (100 mL). Ethyl 4-bromobutyrate (11.3 g, 58.14 mmol), potassium carbonate (16.0 g, 116.3 mmol), and potassium iodide (9.65 g, 58.14 mmol) were added sequentially. The reaction mixture was heated to 90 °C and stirred for 16 h. After the reaction was complete, water (100 mL) was added, and the mixture was extracted twice with ethyl acetate (200 mL). The combined organic phases were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: methanol: dichloromethane = 0%-20%) to give a yellow oily substance, methyl 1-((4-ethoxy-4-oxobutyl)amino)cyclobutanecarboxylate 10a (6.8 g, yield: 72.2%).

[0386] LCMS: RT=1.783min, m / z=244.2[M+H] + .

[0387] Step 2: 1-(((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)cyclobutanecarboxylate methyl ester 10b

[0388] Methyl 1-((4-ethoxy-4-oxobutyl)amino)cyclobutane carboxylate 10a (6.8 g, 27.98 mmol) was dissolved in dichloromethane (100 mL) at room temperature, and sodium bicarbonate (9.4 g, 111.92 mmol) was added. Under nitrogen protection, the mixture was cooled to 10 °C, and benzyl chloroformate (14.32 g, 83.95 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 2 h. After the reaction was complete, water (100 mL) was added, and the layers were separated. The aqueous phase was extracted with dichloromethane (200 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%–18%) to give a yellow oily substance, methyl 1-(((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)cyclobutane carboxylate 10b (9.0 g, yield: 85.3%).

[0389] LCMS: m / z = 378.0 [M+H] + .

[0390] Step 3: 5-Benzyl-8-ethyl-9-oxo-5-azaspiro[3.5]nonane-5,8-dicarboxylic acid ester 10c

[0391] Methyl 1-(((benzyloxy)carbonyl)(4-ethoxy-4-oxobutyl)amino)cyclobutane carboxylate 10b (6.0 g, 15.9 mmol) was dissolved in tetrahydrofuran (60 mL) at room temperature. The mixture was purged with nitrogen three times, cooled to -78 °C, and a 1 M tetrahydrofuran solution of bis(trimethylsilylamino)lithium (31.8 mL, 31.8 mmol) was added dropwise. The mixture was stirred at -78 °C for 2 h. After the reaction was complete, a saturated ammonium chloride aqueous solution (50 mL) was added dropwise to quench the reaction. The mixture was extracted twice with ethyl acetate (100 mL), and the combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow oily substance, 5-benzyl-8-ethyl-9-oxo-5-azaspiro[3.5]nonane-5,8-dicarboxylic acid ester 10c (5.5 g), which was the crude product.

[0392] LCMS: m / z = 346.0 [M+H] + .

[0393] Step 4: Benzyl-9-oxo-5-azaspiro[3.5]nonane-5-carboxylate 10d

[0394] 10c of 5-benzyl-8-ethyl-9-oxo-5-azaspiro[3.5]nonane-5,8-dicarboxylic acid ester (2.5 g, 7.25 mmol) was added to a sealed container at room temperature, followed by 25 mL of dimethyl sulfoxide and 5 mL of water, and 1.22 g of lithium chloride (29.00 mmol). The mixture was heated to 160 °C and stirred for 4 h. After the reaction was completed, the mixture was cooled to room temperature. 40 mL of water was added, and the mixture was extracted twice with 50 mL of ethyl acetate. The combined organic phases were washed with 50 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain 10d of benzyl-9-oxo-5-azaspiro[3.5]nonane-5-carboxylic acid ester (2.0 g), which was the crude product.

[0395] LCMS: RT=0.880min, m / z=274.1[M+H] + .

[0396] Step 5: 9-(((perfluorobutyl)sulfonyl)oxy)-5-azaspiro[3.5]non-8-ene-5-carboxylic acid benzyl ester 10e

[0397] 10d (2.0 g, 7.33 mmol) of benzyl-9-oxo-5-azaspiro[3.5]nonane-5-carboxylate was dissolved in ultra-dry tetrahydrofuran (30.0 mL) at room temperature. Under nitrogen protection, the temperature was lowered to 0-10 °C, and 1,8-diazabicyclo[5.4.0]undec-7-ene (6.7 g, 43.98 mmol) was added dropwise. After the addition was complete, the mixture was stirred for 10-30 min. Perfluorobutylsulfonyl fluoride (11.1 g, 36.65 mmol) was added dropwise at 10-20 °C. After the addition was complete, the mixture was stirred at room temperature for 16 h. After the reaction was completed, water (50 mL) was added dropwise to quench the reaction. The mixture was extracted twice with ethyl acetate (100 mL). The combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%-8%) to give a bright yellow oily compound phenyl 9-(((perfluorobutyl)sulfonyl)oxy)-5-azaspiro[3.5]non-8-ene-5-carboxylic acid benzyl ester 10e (3.0 g, yield: 75.0%).

[0398] LCMS: RT=1.23min, m / z=556.0[M+H] + .

[0399] Step 6: Benzyl 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-5-azaspiro[3.5]non-8-ene-5-carboxylate 10f

[0400] Benzyl phenyl 9-(((perfluorobutyl)sulfonyl)oxy)-5-azaspiro[3.5]non-8-en-5-carboxylate 10e (3.0 g, 5.40 mmol) was dissolved in 1,4-dioxane (30 mL) and water (5 mL) at room temperature. Then, 4-chloro-7-fluoro-N,N-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-1H-indole-2-carboxamide (1.98 g, 3.40 mmol), potassium carbonate (2.24 g, 16.20 mmol), and [1,1′-bis(diphenylphosphine)ferrocene]palladium(II) dichloride (395.7 mg, 0.54 mmol) were added sequentially. The mixture was purged with nitrogen three times, and the mixture was heated to 90 °C and stirred for 2 h. After the reaction was completed, the reaction solution was filtered with diatomaceous earth, and the filtrate was concentrated and the crude product was purified by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 0%-45%) to obtain a bright yellow solid product benzyl 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-5-azaspiro[3.5]non-8-ene-5-carboxylate 10f (2.4 g, yield: 75.0%).

[0401] LCMS: RT=2.241min, m / z=496.1[M+H]+ .

[0402] Step 7: 10g of 4-chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]non-8-en-9-yl)-1H-indole-2-carboxamide

[0403] 10 f (1.0 g, 2.02 mmol) of 9-(4-chloro-2-(dimethylcarbamoyl)-7-fluoro-1H-indol-6-yl)-5-azaspiro[3.5]non-8-en-5-carboxylate was dissolved in N,N-dimethylformamide (10 mL) and sodium methanethiol (1.12 g, 16.0 mmol) was added. The mixture was heated to 80 °C and stirred for 2 h. After the reaction was completed, the mixture was cooled to room temperature. Water (40 mL) was added, and the mixture was extracted twice with ethyl acetate (50 mL). The combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 10 g (720 mg, yield: 99.0%) of 4-chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]non-8-en-9-yl)-1H-indol-2-carboxamide, a yellow solid.

[0404] LCMS: RT=1.746min, m / z=362.2[M+H] + .

[0405] Step 8: 4-Chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]nonane-9-yl)-1H-indole-2-carboxamide 10h

[0406] 10 g (720 mg, 1.99 mmol) of 4-chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]nonane-8-en-9-yl)-1H-indole-2-carboxamide was dissolved in anhydrous ethanol (30 mL) at room temperature and then added to platinum dioxide (500 mg). The mixture was hydrogenated and stirred at room temperature for 5 h. The solution was filtered through a diatomaceous earth sieve and concentrated under reduced pressure to obtain a yellow solid, 10 h (700 mg), 4-chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]nonane-9-yl)-1H-indole-2-carboxamide.

[0407] LCMS: RT=1.746min, m / z=362.2[M+H] + .

[0408] Step 9: 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i

[0409] At room temperature, chloro-7-fluoro-N,N-dimethyl-6-(5-azaspiro[3.5]nonane-9-yl)-1H-indole-2-carboxamide 10h (700 mg, 1.93 mmol), 3-(1H-pyrazol-1-yl)propionic acid (815 mg, 5.78 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.84 g, 9.65 mmol) were sequentially added to a pyridine (20 mL) solution, and the reaction mixture was stirred at room temperature for 16 hours. Water (50 mL) was added, and the mixture was extracted three times with ethyl acetate (100 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 (eluent: dichloromethane: methanol = 0%-5%) to obtain a yellow solid product 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i (530 mg, yield: 79.2%).

[0410] LCMS: RT=1.937min, m / z=487.2[M+H] + .

[0411] Step 10: (R)-6-[5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl]-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i-1; (S)-6-[5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl]-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i-2

[0412] Chiral resolution of 6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i (530 mg, 1.09 mmol) yielded 10i-1 and 10i-2, respectively.

[0413] Chiral resolution conditions: Instrument: SFC-80; Chiral column OJ-H 30mm*250mm, 5um (Regis); Column temperature: 35℃; Mobile phase: CO2 / [MeOH / ACN]=40%; Flow rate: 45ml / min; Column pressure: 100bar; Detection wavelength: 214nm; Cycle time: 3.0min; Sample volume: 630mg sample dissolved in 60mL methanol; Injection volume: 3.0mL per injection.

[0414] Compound 10i-1: (250 mg, yield: 47%), white solid.

[0415] Retention time of chiral column: RT = 1.109 min;

[0416] Compound 10i-2: (260 mg, yield: 49%), white solid.

[0417] Retention time of chiral column: RT = 1.456 min.

[0418] Step 11: 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 10B

[0419] (S)-6-[5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl]-4-chloro-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide 10i-2 (40 mg, 0.082 mmol), cesium fluoride (125 mg, 0.82 mmol) and 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronacyclopentan-2-yl)phenyl Piperidin-1-yl)phenyl)piperidin-2,6-dione 31 (48 mg, 0.098 mmol) of dioxane 3l (3l is a known intermediate, which can be prepared according to the method reported in patent WO2025 / 49820) (10 mL) was mixed with water (2 mL), and [2-dicyclohexylphosphino-2′,4′,6′-triisopropylbenzyl]-[2-(2-aminoethyl)phenyl]palladium(II) chloride (20 mg) was added. The mixture was stirred at 90 °C for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain a crude residue. This residue was purified by column chromatography (dichloromethane / methanol = 0% to 10% gradient elution) combined with preparative high performance liquid chromatography to obtain compound 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 10B (26 mg, yield: 39%), as a white solid.

[0420] LCMS: RT=2.050min, m / z=817.2[M+H] + ;

[0421] 1 H NMR (400MHz, DMSO-d6): 12.13 (s, 1H), 10.84 (s, 1H), 8.12 (s, 1H), 7.71 (s, 1H), 7.60 (d, J=8.0Hz, 2 H), 7.45 (d, J=8.0Hz, 2H), 7.24 (d, J=5.2Hz, 1H), 7.08-6.97 (m, 3H), 6.89 (s, 1H), 4.63 (s, 2H), 3.8 4-3.80 (m, 1H), 3.65-3.62 (m, 1H), 3.49 (d, J=11.2Hz, 3H), 3.29-2.98 (m, 9H), 2.84-2.62 (m, 5H), 2 .33-2.18(m, 4H), 2.04-1.87(m, 6H), 1.67(d, J=10.0Hz, 2H), 1.39-1.23(m, 3H), 0.45-0.42(m, 1H).

[0422] Compound 10A was obtained using the same synthetic method as compound 10B: (30.56 mg, yield: 45%), as a white solid.

[0423] LCMS: RT=2.045min, m / z=817.2[M+H] + ;

[0424] 1 H NMR (400MHz, DMSO-d6): 12.14 (s, 1H), 10.84 (s, 1H), 8.12 (s, 1H), 7.71 (s, 1H), 7.59 (d, J=8.4H z, 2H), 7.44 (d, J=8.4Hz, 2H), 7.25-7.24 (m, 1H), 7.09-7.06 (m, 2H), 7.00-6.97 (m, 1H), 6.88 (s, 1H), 4.63(s, 2H), 3.84-3.80(m, 1H), 3.68-3.48(m, 4H), 3.06-2.98(m, 9H), 2.82-2.63(m, 5H), 2.49-2.20(m, 5H), 2.04-1.90(m, 6H), 1.69-1.66(m, 2H), 1.40-1.23(m, 2H), 0.46-0.37(m, 1H).

[0425] Example 11: (R)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 11A; 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 11B

[0426] Following the same operating steps as in Example 10, 3-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)piperazin-1-yl)phenyl)piperidin-2,6-dione 11a was used instead of 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)piperidin-1-yl)phenyl)piperidin-2,6-dione 3l to obtain the target product R)-6-(5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3,5]nonane-9-yl)-4-(4-(4- Compound 11A (25.12 mg, yield: 30%) and compound 11B (25.12 mg, yield: 26%) of (4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide were both white solids.

[0427] Compound 11A:

[0428] LCMS: m / z = 800.2[M+H] + ;

[0429] 1H NMR (400MHz, DMSO-d6): 12.07 (s, 1H), 10.80 (s, 1H), 8.11 (s, 1H), 7.71 (s, 1H), 7.53 (d, J=8.4Hz, 2H) ,7.18-7.09(m,5H),6.99(d,J=8.8Hz,2H),6.87(s,1H).4.63(s,2H),3.78-3.74(m,1H),3.66-3.60(m , 1H), 3.53-3.35(m, 5H), 3.31-2.95(m, 13H), 2.70-2.60(m, 2H), 2.49-2.46(m, 1H), 2.42-2.37(m, 2H ), 2.27-2.11(m, 2H), 2.05-1.94(m, 2H), 1.73-1.62(m, 2H), 1.44-1.20(m, 2H), 0.49-0.39(m, 1H)ppm.

[0430] Compound 11B:

[0431] LCMS: m / z = 800.3[M+H] + ;

[0432] 1 H NMR (400MHz, DMSO-d6): 12.08(s, 1H), 10.80(s, 1H), 8.11(s, 1H), 7.71(s, 1 H), 7.53 (d, J=8.8Hz, 2H), 7.18-7.09 (m, 5H), 6.99 (d, J=8.4Hz, 2H), 6.87 (s, 1H).4.62(s, 2H), 3.77-3.65(m, 1H), 3.47-3.21(m, 2H), 3.05-2.98(m, 15H), 2.68-2.61(m, 2H), 2.46-1.99(m, 8H), 1.68-1.24(m, 5H), 0.49-0.40(m, 1H).

[0433] Example 12: 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]non-9-yl)-4-(4-(4-(4-(2,6-dikepiperidin-3-yl)-2-fluorophenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide or 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]non-9-yl)-4-(4-(4-(4-(4-(2,6-dikepiperidin-3-yl)-2-fluorophenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 12

[0434] Following the same operating steps as in Example 10, 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)piperazin-1-yl)phenyl)piperidin-2,6-dione was used instead of 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboron-2-yl)phenyl)piperidin-1-yl)phenyl)piperidin-2,6-dione, and using compound 10i-1 from Example 10 as an intermediate, the target product 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[ [3.5] Non-9-yl)-4-(4-(4-(4-(2,6-dikepiperidin-3-yl)-2-fluorophenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide or 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5] Non-9-yl)-4-(4-(4-(4-(4-(2,6-dikepiperidin-3-yl)-2-fluorophenyl)piperazin-1-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 12 (23.26 mg, yield: 14.7%), is a white solid.

[0435] LCMS: m / z = 819.3 [M+H] + .

[0436] 1H NMR (400MHz, DMSO-d6): δ12.07 (s, 1H), 10.84 (s, 1H), 8.10 (d, J=5.0Hz, 1H), 7.71 (s, 1H), 7.54 (d, J=8.3Hz, 2H), 7.16 (d, J=8 .7Hz, 3H), 7.12-7.04 (m, 2H), 7.00 (dd, J=8.2, 2.0Hz, 1H), 6.88 (dt, J=5.3, 2.7Hz, 1H), 4.62 (d, J=7.3Hz, 4H), 3.83 (dd, J=11. 8, 4.9Hz, 1H), 3.62 (s, 1H), 3.48 (s, 1H), 3.43-3.35 (m, 4H), 3.20 (t, J=4.9Hz, 7H), 3.07 (s, 6H), 2.69-2.61 (m, 1H), 2.33 (s, 2H ), 2.20 (td, J=12.3, 4.3Hz, 2H), 2.02 (dt, J=15.0, 5.4Hz, 2H), 1.67 (s, 2H), 1.39 (s, 1H), 1.26 (d, J=12.4Hz, 1H), 0.44 (s, 1H).

[0437] Example 13: 6-((R)-6-(3-(1H-1,2,3-triazol-1-yl)propionyl)-6-azaspiro[4.5]decane-10-yl)-4-(4-(1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 13A: 6-((S)-6-(3-(1H-1,2,3-triazol-1-yl)propionyl)-6-azaspiro[4.5]decane-10-yl)-4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 13B

[0438] Following the same operating steps as in Example 10, methyl 1-aminocyclopentylcarbamate was used instead of methyl 1-aminocyclobutylcarbamate as the starting material to obtain the target product compound 13A (72.25 mg, yield: 43.5%), a yellow solid, and compound 13B (10.85 mg, yield: 13.3%), a white solid. Intermediates are involved. They are by The compound was obtained by chiral separation under the same conditions as the chiral separation of compound 10i in Example 10.

[0439] Compound 13A:

[0440] LCMS: m / z = 831.2 [M+H] + .

[0441] 1 ¹H NMR (400 MHz, DMSO-d₆): δ 12.07 (s, 1H), 10.83 (s, 1H), 8.10 (s, 1H), 7.70 (s, 1H), 7.57 (d, J = 7.9 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.15-7.03 (m, 3H), 7.01-6.96 (m, 1H), 6.85 (t, J = 2.7 Hz, 1H), 4.61 (t, J = 6.9 Hz, 2H), 3.82 (dd, J = 11.8, 4.9 Hz, 1H), 3.72-3.36 (m, 5H), 3.34-2.90 (m, 8H), 2.88-2.60 (m, 4H), 2.38-2.15 (m, 3H), 2.13-1.67 (m, 10H), 1.64-1.12 (m, 5H), 0.74 (s, 1H).

[0442] Compound 13B:

[0443] LCMS: m / z = 416.3 [M / 2+H] + .

[0444] 1 ¹H NMR (400 MHz, CDCl₃): δ 9.41 (s, 1H), 7.97 (s, 1H), 7.72 (d, J = 1.0 Hz, 1H), 7.66 (d, J = 1.0 Hz, 1H), 7.59-7.52 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 5.9 Hz, 1H), 7.02 (t, J = 8.6 Hz, 1H), 6.98-6.87 (m, 3H), 4.77 (dt, J = 8.2, 4.1 Hz, 2H), 3.80-3.54 (m, 5H), 3.52-3.12 (m, 7H), 3.12-3.02 (m, 1H), 2.98 (m, J = 16.4, 6.0 Hz, 1H), 2.85 (m, J = 13.1 Hz, 2H), 2.81-2.61 (m, 3H), 2.41-2.21 (m, 4H), 2.20-1.98 (m, 7H), 1.98-1.76 (m, 3H), 1.31 (m, J = 41.5 Hz, 2H), 0.86 (m, 2H).

[0445] Example 14: 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(2,6-dioxomorpholin-3-yl)phenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide or 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(4-(2,6-dioxomorpholin-3-yl)phenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 14

[0446] Following the same operating steps as in Example 10, 3-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenyl)piperazin-1-yl)phenyl)piperidin-2,6-dione was used instead of 3-(3-fluoro-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)phenyl)piperidin-1-yl)phenyl)piperidin-2,6-dione was used as an intermediate, and 6-((R)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3] was obtained. [5] Nonane-9-yl)-4-(4-(1-(4-(2,6-dioxomorpholin-3-yl)phenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide or 6-((S)-5-(3-(1H-1,2,3-triazol-1-yl)propionyl)-5-azaspiro[3.5]nonane-9-yl)-4-(4-(1-(4-(4-(2,6-dioxomorpholin-3-yl)phenyl)piperidin-4-yl)phenyl)-7-fluoro-N,N-dimethyl-1H-indole-2-carboxamide compound 14 (23.23 mg, yield: 28.3%), is a white solid.

[0447] LCMS: m / z = 799.3 [M+H] + .

[0448] 1H NMR (400MHz, DMSO-d6): δ12.12 (s, 1H), 10.79 (s, 1H), 8.10 (d, J=6.2Hz, 1H), 7.71 (d, J=1.0Hz, 1H), 7.59 (d, J=7.9Hz, 2H), 7.42 (dd, J=8. 0, 3.7Hz, 2H), 7.23 (d, J = 5.6Hz, 1H), 7.07 (d, J = 8.6Hz, 2H), 6.96 (d, J = 8.8Hz, 2H), 6.87 (d, J = 3.1Hz, 1H), 4.63 (s, 2H), 3.82 (d, J = 11.6Hz, 2H), 3.75 (dt, J=10.9, 5.7Hz, 1H), 3.62 (s, 1H), 3.49 (s, 1H), 3.08 (t, J=46.2Hz, 9H), 2.83-2.71 (m, 3H), 2.68-2.59 (m, 1H), 2.49 (s, 2H), 2 .33 (s, 2H), 2.24-2.09 (m, 2H), 2.07-1.88 (m, 4H), 1.81 (q, J=11.5Hz, 2H), 1.67 (s, 2H), 1.39 (s, 1H), 1.25 (d, J=12.2Hz, 1H), 0.42 (s, 1H).

[0449] Example of effect:

[0450] 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.

[0451] Example 1: Western blot (WB) detection of protein degradation

[0452] Western blotting was used to quantify STAT6 protein degradation and to selectively detect 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 4XLDS Sample Buffer (ThermoFisher, 84788), 10XNuPAGE 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, (D322G) Rabbit mAb, #12640S), Stat4 (Cell Signaling Technologies, (D322G) Rabbit mAb, #12640S) 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)RabbitmAb, #9361S), Vinculin (CellSignalingTechnologies, (E1E9V) RabbitmAb (#13901S), Anti-rabbit IgGHRP-linked Antibody (Cell Signaling Technologies, 7074S). Specific experimental results are shown in Table 1 and Figures 1-3. Figures 1-3 show the degradation results of compounds 10A, 11A, and 14 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) with different proteins (STAT1-STAT6) after 24 h of culture.

[0453] Table 1: Results of protein degradation detection experiments using Western blotting (WB) of the compounds disclosed herein

[0454] The compound of this disclosure, as measured in Example 1 above, exhibits good STAT6 degradation activity.

[0455] Example 2: Degradation Experiment of STAT6-HiBiT A549

[0456] 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 GraphPadPrism software, and a four-parameter nonlinear regression model of inhibitor and response was used to fit the dose-dependent degradation of STAT6. Specific experimental results are shown in Table 2.

[0457] Table 2: Degradation Experiment Results of Compound STAT6-HiBiT A549 of this Disclosure

[0458] The compound disclosed herein, as measured in Example 2, exhibits good STAT6 degradation activity in A549 cells.

[0459] Example 3A: Pharmacokinetic Test in Mice

[0460] 1. Drug preparation

[0461] 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.

[0462] 2. Administration

[0463] ICR mice were fasted for 12 hours before administration, but had free access to water. They were allowed to eat again 4 hours after administration. Intravenous and gavage dosages are shown in Table 3.

[0464] 3. Sampling

[0465] 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 centrifuge tubes were centrifuged at 5000 rpm and 4℃ for 5 min, and the separated plasma was stored at -80℃ for analysis.

[0466] 4. Measurement

[0467] 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.

[0468] 5. Pharmacokinetic Parameter Results

[0469] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 3 below.

[0470] Table 3: Pharmacokinetic parameters of the compounds disclosed in this study in mice

[0471] The above-mentioned pharmacokinetic tests in mice showed that the compound exhibited a high area under the curve, high blood concentration, and good oral bioavailability in mice, demonstrating excellent pharmacokinetic characteristics.

[0472] Example 3B: Rat Pharmacokinetic Test

[0473] 1. Drug preparation

[0474] 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.

[0475] 2. Administration

[0476] 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.

[0477] 3. Sampling

[0478] 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.

[0479] 4. Measurement

[0480] 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.

[0481] 5. Pharmacokinetic Parameter Results

[0482] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 4 below.

[0483] Table 4: Rat pharmacokinetic parameters of the compounds disclosed herein

[0484] The above-mentioned pharmacokinetic tests in rats showed that the compound disclosed herein had a high area under the curve, a high blood concentration, and good oral bioavailability in rats, demonstrating excellent pharmacokinetic characteristics.

[0485] Example 3C: Pharmacokinetic Tests in Crab-Eating Mammals

[0486] 1. Drug preparation

[0487] 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.

[0488] 2. Administration

[0489] The cynomolgus monkeys were fasted for 12 hours before administration, but given free access to water. They resumed eating 4 hours after administration. Intravenous and gavage dosages are shown in Table 5 below.

[0490] 3. Sampling

[0491] 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 cynomolgus monkeys 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.

[0492] 4. Measurement

[0493] 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.

[0494] 5. Pharmacokinetic Parameter Results

[0495] The pharmacokinetic parameters of the compounds disclosed herein are shown in Table 5 below.

[0496] Table 5: Pharmacokinetic parameters of the compounds disclosed in this study in cynomolgus monkeys

[0497] The pharmacokinetic tests conducted on cynomolgus monkeys revealed that the compound exhibited a high area under the plasma concentration-time curve, a high plasma concentration, and good oral bioavailability in male cynomolgus monkeys, demonstrating excellent pharmacokinetic characteristics.

[0498] Example 4: FACS assay to detect the inhibitory effect of the compound on IL-4 or IL-13-induced B cell activation.

[0499] 1. Cell Culture

[0500] hPBMCs were purchased from Rubai Biotechnology Co., Ltd. Cells were cultured in RPMI-1640 (Gibco, 22400089) medium containing 10% inactivated FBS (Gibco, A5256701) at 37°C in a 5% CO2 incubator.

[0501] 2. Experimental Methods

[0502] Resuscitate PBMCs and incubate overnight at 37°C and 5% CO2. Add 100 μL of PBMCs at a rate of 2 × 10⁻⁶ cells / well. 5Cells were added to 96-well U-plates, and serially diluted 10x concentrations of the compound were added to bring the final concentration to 0.1 μM (0.2% DMSO). The cells were then treated at 37°C and 5% CO2 for 24 h. Then, 2 ng / ml of IL-4 (ACRO, #IL4-H4218) or 10 ng / ml of IL-13 (Sino Biological, 10369-HNAC) was added, and the cells were cultured again at 37°C and 5% CO2 for another 24 h. Cells were collected by centrifugation. Fc block (Bio-Legend, 422302) and live / dead (Invitrogen, L10119) were added and incubated at 4°C for 15 min. Then, PE-CD19 (BD, 555413) and FITC-CD23 (Bio-Legend, 338506) antibodies were added and incubated at 4°C for 30 min. Cells were washed with cell staining buffer (Bio-Legend, 420201), resuspended in the staining buffer, and then CD19 was detected by flow cytometry. + The expression level of CD23 in B cells.

[0503] The DMSO orifice stimulated with IL-4 or IL-13 was used as the maximum signal. max The unstimulated DMSO orifice serves as the background signal. min The orifice through which the drug was added and stimulated was used as the signal for the drug-addition group. cpd The inhibition rate is calculated using the following formula: Inhibition rate % = [(Signal cpd -Signal min ) / (Signal max -Signal min )]*100. Data analysis was performed using GraphPadPrism software, and DC50 was calculated by nonlinear regression fitting of four parameters on the dose-dependent CD23 inhibition effect.

[0504] Dupilumab was used as a positive control drug.

[0505] The specific experimental results are shown in Table 6.

[0506] Table 6: Experimental results of the inhibitory effect of the disclosed compounds on IL-4 or IL-13-induced B cell activation.

[0507] The above experiments showed that the compound disclosed herein has a significant inhibitory effect on IL-4 or IL-13-induced B cell activation, which is significantly better than the positive control drug dupilumab.

[0508] Example 5: HTRF assay to detect the inhibitory effect of the compound on IL-4 / IL-13-induced TARC release.

[0509] 1. Cell Culture

[0510] hPBMCs were purchased from Rubai Biotechnology Co., Ltd. Cells were cultured in RPMI-1640 (Gibco, 22400089) medium containing 10% inactivated FBS (Gibco, A5256701) at 37°C in a 5% CO2 incubator.

[0511] 2. Experimental Methods

[0512] Resuscitate PBMCs and incubate overnight at 37°C with 5% CO2. Add 100 μL of PBMCs at 2 × 10⁻⁶ cells / well. 5 Cells were added to 96-well U-plates, and a 10x serially diluted compound was added to bring the final concentration to 0.1 μM (0.2% DMSO). The plates were then incubated at 37°C and 5% CO2 for 24 h. Then, 2 ng / ml of IL-4 (ACRO, #IL4-H4218) or 10 ng / ml of IL-13 (Sino Biological, 10369-HNAC) was added, and the plates were incubated at 37°C and 5% CO2 for another 24 h. The supernatant was collected by centrifugation. Following the instructions of the Human CCL17 TR-FRET Biomarker Assay Kit (BioAuxilium, KIT-CCL17-500), 15 μL of cell supernatant was added to a 384-well microplate (Revvity, 6008280), followed by 5 μL of 4X antibody detection mixture (Eu-Ab1 + FR-Ab2). The plates were covered with a sealing film and incubated at room temperature in the dark for 1 h. The 620nm and 665nm wavelengths were detected using an ELISA reader. TR-FRET data were calculated using a ratio value, as follows: ratio = [(665nm / 620nm) x 1000].

[0513] The DMSO orifice stimulated with IL-4 or IL-13 was used as the maximum signal. max The unstimulated DMSO orifice serves as the background signal. min The orifice through which the drug was added and stimulated was used as the signal for the drug-addition group. cpd The inhibition rate is calculated using the following formula: Inhibition rate % = [(Signal cpd -Signal min ) / (Signal max -Signal min)]*100. Data analysis was performed using GraphPad Prism software, and DC50 was calculated by nonlinear regression fitting of four parameters on the inhibitory effect of dose-dependent TARC release.

[0514] Dupilumab was used as a positive control drug.

[0515] The specific experimental results are shown in Table 7.

[0516] Table 7: Experimental results of the inhibitory effect of the disclosed compounds on IL-4 / IL-13-induced TARC release.

[0517] The above experiments showed that the compound disclosed herein has a significant inhibitory effect on IL-4 or IL-13-induced TARC release, which is significantly better than the positive control drug dupilumab.

[0518] Example 6: Crab-eating monkey PK test

[0519] 1. Drug preparation

[0520] Weigh a certain amount of the drug and prepare the preparation for gavage and intravenous injection (0.2 mg / ml solution for IV and 0.8 mg / ml solution for PO). The solvent for both gavage and intravenous injection is 10% DMA + 10% Solutol HS15 + 80% Saline.

[0521] 2. Administration

[0522] The cynomolgus monkeys were fasted for 12 hours before administration, but allowed free access to water. They resumed eating 4 hours after administration. The intravenous and gavage doses were 0.2 MPa and 4 MPa, respectively.

[0523] 3. Sampling

[0524] At 0.083, 0.25, 0.5, 1, 2, 4, 8, 24, 48, and 72 h after intravenous administration, and at 0.25, 0.5, 1, 2, 4, 8, 24, 48, and 72 h after gavage administration, 1 mL of whole blood was collected from the cephalic vein of the forelimb of cynomolgus monkeys 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.

[0525] 4. Measurement

[0526] 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). Transfer 100 μL of the supernatant to a 96-well plate and perform LC-MS / MS analysis.

[0527] 5. The pharmacokinetic parameters are shown in Table 8.

[0528] Table 8. PK parameters of compounds 11A and 14 after oral gavage in eluted cynomolgus monkeys.

[0529] Example 7: Western blot (WB) detection of STAT6 degradation in cynomolgus monkey PD samples.

[0530] Healthy adult cynomolgus monkeys were selected and administered specific doses of the compound via intravenous injection (0.2 mg / kg) and oral administration (4 mg / kg), respectively. Whole blood (1 ml) was collected from the monkeys before administration and at 1 h, 4 h, 8 h, 24 h, 48 h, and 72 h after administration in anticoagulant tubes. The collected whole blood was diluted with an equal volume of PBS, and then slowly piled onto the surface of a 15 mL centrifuge tube containing 3 mL of Ficoll (Cytiva, 17144002) separation solution. The tube was centrifuged at 400 g for 30 minutes at room temperature. After centrifugation, the supernatant serum was removed, and the PBMC layer in the middle was transferred to a new 15 mL centrifuge tube. The cells were resuspended in at least 3 volumes of PBS, centrifuged at 400 g for 10 minutes at room temperature, and the supernatant was discarded. The PBS washing step was repeated once. Based on the amount of residual red blood cells in the cell pellet, add an appropriate amount of 1× red blood cell lysis buffer (BD, 555899), lyse on ice for 2-5 min, then add 3 volumes of PBS to stop the lysis, gently mix, centrifuge at 500g for 10 min at room temperature and discard the supernatant. If red blood cells remain in the cell pellet, repeat the lysis step. Resuspend the obtained PBMC pellet in PBS, count the cells, centrifuge and discard the supernatant, flash freeze in liquid nitrogen, and store at -80℃. After all time points have been collected, add RIPA lysis buffer (ThermoFisher, 89900) containing 1% protease inhibitor & phosphatase inhibitor (ThermoFisher, 78442) to the cell pellet, lyse on ice for 10 min, and pipette a few times during lysis. Transfer the lysis buffer to a 1.5mL centrifuge tube and centrifuge at 12000rpm for 10 min.

[0531] The supernatant was collected as the total protein lysis buffer and stored at -80°C for later use. The total protein in the lysis buffer was quantified using a BCA protein assay kit (Beyotime, P0012).

[0532] Combine 4X LDS Sample Buffer (ThermoFisher, 84788), 10X NuPAGE TM After mixing the reducing agent (ThermoFisher, NP009) and protein sample, incubate at 95°C for 5 min in a thermostatic mixer to denature the protein. Load 10 μg of protein sample into NuPAGE. 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 until the target protein molecular weight regions were fully separated. 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... TM West Pico PLUS (ThermoFisher, 34577) chemiluminescent substrates were added to the membrane. Chemiluminescence imaging was performed using a chemiluminescence imaging system (ChemiScope 6100). Antibodies used in the experiment included: Stat6 (Cell Signaling Technologies, (D3H4)Rabbit mAb, #5397S), Anti-rabbit IgG HRP-linked Antibody (Cell Signaling Technologies, 7074S), and GAPDH (14C 10)Rabbit mAb (Cell Signaling Technologies, (D3H4)Rabbit mAb, #2118).

[0533] The specific experimental results are shown in Figures 4-7. The above experiments demonstrate that the compound disclosed herein can achieve complete degradation of the STAT6 protein within 24 hours.

Claims

A compound of formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof: in, Ring A is C 10 -C 20 Aromatic rings, 7-20 membered heteroaromatic rings, saturated or partially unsaturated C9-C 20 Carbon rings, or 9-20 membered heterocycles that are saturated or partially unsaturated; the C 10 -C 20 In the aromatic ring, at least one ring is aromatic or each ring is aromatic; in the 7-20 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, 4, or 5; in the 7-20 membered heteroaromatic ring, at least one ring is aromatic or each ring is aromatic; in the 9-20 membered heteroaromatic ring, 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 9-20 membered heteroaromatic ring, 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-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 Independently: 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) 0-4 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(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-1-1-1 )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) 0-4 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, 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, it can be: hydrogen atom, halogen, benzyl, C1-C4 alkyl, -O(CH2). 0-2 Ph, C3-C6 cycloalkyl or 3-6 membered heterocyclic alkyl; m can be 0, 1, 2, 3, 4, or 5; R A is R A-2 , R A-1 , oxo (=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, -S(=NR A-1 )2R A-1 , -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(=NR A-1 )R A-1 , -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 ), -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, 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 A-2-1 Independently: 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) 0-4 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(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-1-1-1 )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 ; 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; 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)-; Where 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. R Z is independently R A-2 , R A-1 , oxo (=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, -S(=NR A-1 )2R A-1 , -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(=NR A-1 )OR A-1 , -NR A-1 C(=NR A-1 )R A-1 , -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 ), -NR A-1 C(=O)N(R A-1 )2 or -NR A-1 S(=O)2R A-1 ； 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 is 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; 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 B-1 -L B -H, -L B -Cy B1’ or -L B -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. 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 arylene 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. L A Y and ring B are defined as follows: Scheme 1 or Scheme 2: Option 1: L A It is a C1-C6 alkylene group, wherein 0, 1, or more 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-4 R A-4 -、-CR A-1 (OR A-1 )-, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or R A-4 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. 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 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, 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. Option 2: -L A -Y does not exist; Ring B is C9-C 10 The bicyclic aromatic ring or 8-10 quintile bicyclic heterocyclic aromatic ring, wherein at least one ring of the bicyclic aromatic ring or each ring is aromatic. A compound of formula (I-1), a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof: in, Ring A is a naphthalene ring, a 7-14 membered heteroaryl ring, or a saturated or partially unsaturated C9-C ring. 14 The 7-14 membered heteroaromatic ring is a carbon ring, or a saturated or partially unsaturated 9-14 membered heterocyclic ring; in the 7-14 membered heteroaromatic ring, 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; in the 9-14 membered heterocyclic ring, 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; the 7-14 membered heteroaromatic ring is a monocyclic or polycyclic ring, and at least one ring is aromatic or each ring is aromatic; in the 9-14 membered heterocyclic ring, 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-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 Independently: 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- 4CH(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) 0-4 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(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-1-1-1 )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; m can be 0, 1, 2, 3, 4, or 5; R A For 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 ; 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 A-2-1 Independently: 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- 4CH(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) 0-4 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(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-1-1-1 )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 ; L A It is a C1-C5 alkylene group, wherein 0, 1, or more 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 )-, -S-, -S(=O)-, -S(=O)2-, -S(=O)(=NR A-1 )-、-CR A-1 =CR A-1 -or 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 Z For 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 ; 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 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 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 arylene 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. 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; 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)-; Where 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. The compound of claim 1, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that, Y, L A When ring B is defined as described in Scheme 1, ring A is... The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B; Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S. R a1 and R a2 The carbon atoms connected to them together form C4-C6 monocyclic saturated carbon rings, C5-C6 monocyclic saturated carbon rings, and C6-C6 monocyclic saturated carbon rings. 12 Spirocyclic saturated carbon rings, C5-C 12 fused saturated carbon rings, C5-C 12 Bridged ring saturated carbon ring, 4-6 membered monocyclic saturated heterocyclic ring, 5-12 membered spirocyclic saturated heterocyclic ring, 5-12 membered fused ring saturated heterocyclic ring, 5-12 membered bridged ring saturated heterocyclic ring, or In the saturated heterocycle, the heteroatom is selected from one or more of N, O, and S, 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, and S, 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 it is 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 and S. The number of heteroatoms is 1, 2, 3 or 4. It can be monocyclic or polycyclic. When it is polycyclic, at least one ring is aromatic or each ring is aromatic. L is a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -CH=CH-, -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 Preferably, Y, L A When ring B is defined as described in Scheme 1, ring A is... The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B; Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S. R a1 and R a2 The carbon atoms connected to them together form C4-C6 monocyclic saturated carbon rings, C6-C6 monocyclic saturated carbon rings, and C6-C6 monocyclic saturated carbon rings. 10 Spirocyclic saturated carbon rings, 4-6 membered monocyclic saturated heterocycles, 6-10 membered spirocyclic saturated heterocycles, or In the saturated heterocycle, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Cy3 is a C3-C6 cycloene 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, and S, and the number of heteroatoms is 1, 2, or 3; Cy4 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, and S, and the number of heteroatoms is 1, 2, 3, or 4; L is a C1-C4 straight-chain alkylene group, wherein 0, 1 or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -C(=O)NH- or -NHC(=O)-; More preferably, Y, L A When ring B is defined as described in Scheme 1, ring A is... The end marked with "#" is connected to ring B, and the carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof. The compound of claim 1, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that, It meets one or more of the following conditions: (1) Y, L A When ring B is defined as described in Scheme 1, ring A is... The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B; R a1 and R a2 The carbon atoms connected to them together form a C4-C6 monocyclic saturated carbon ring or a 4-6 member monocyclic saturated heterocycle. In the saturated heterocycle, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3. Preferably, Y, L A When ring B is defined as described in Scheme 1, ring A is... (For example )、 (For example )、 The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B; (2)R A It is hydrogen, halogen, or C1-C6 alkyl, such as hydrogen, F, or methyl; (3) m is 0, 1 or 2; (4) n is 0, 1 or 2; (5)L A for The end marked "#2" is connected to ring A. The compound of claim 1, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that, Ring A is C 10 -C 20 Bicyclic aromatic ring, C 12 -C 20 The aromatic ring or heterocyclic ring may be a tricyclic aromatic ring, a 9-20 membered bicyclic heterocyclic ring, a 12-20 membered tricyclic heterocyclic ring, a saturated 9-20 bicyclic heterocyclic ring, a saturated 9-20 tricyclic heterocyclic ring, a partially unsaturated 9-20 bicyclic heterocyclic ring, or a partially unsaturated 9-20 tricyclic heterocyclic ring, wherein at least one ring is aromatic or each ring is aromatic; preferably, the heteroatom in the heterocyclic ring or heterocyclic ring is N and / or O, and the number of heteroatoms is 1, 2, 3, or 4. Preferably, Y, L A When ring B is defined as described in scheme 2, ring A is... Preferably, Y, L A When ring B is defined as described in Scheme 1, ring A is... The carbon atom marked with "*" has an R configuration, an S configuration, or a mixture thereof, and the end marked with "#" is connected to ring B; Ring A2 and ring A4 are each independently a C5-C6 cycloene, a 5-6 membered heterocyclic alkene, a benzene ring, or a 5-6 membered heteroaromatic ring. In the heterocyclic alkene or heteroaromatic ring, the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3. Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle, a 5-6 member nitrogen-containing heterocyclic alkene, or a 5-6 member nitrogen-containing heteroaromatic ring. In the nitrogen-containing saturated heterocycle, nitrogen-containing heterocyclic alkene, or nitrogen-containing heteroaromatic ring, the number of heteroatoms is 1, 2, or 3. In addition to containing N, the heteroatoms also contain 0, 1, or more heteroatoms selected from O and S. R a1 and R a2 The carbon atoms bonded to them together form C4-C6 saturated carbon rings, 4-6 membered saturated heterocycles, or... In the aforementioned 4-6 membered saturated heterocycles, the heteroatom is selected from one or more of N, O, and S, 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, and S, 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 it is 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 and S. The number of heteroatoms is 1, 2, 3 or 4. It can be monocyclic or polycyclic. When it is polycyclic, at least one ring is aromatic or each ring is aromatic. L is a C1-C6 alkylene group, wherein in the C1-C6 alkylene group, 0, 1, or more -CH2- groups are independently replaced by the following groups: -O-, -S-, -NH-, -CH=CH-, -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 More preferably, Y, L A When ring B is defined as described in Scheme 1, ring A is... The end marked with "#" is connected to ring B; Ring A2 and ring A4 are each independently a benzene ring or a 5-6 membered heteroaromatic ring, wherein the heteroatom in the heteroaromatic ring is N and the number of heteroatoms is 1; Ring A3 is a 5-6 member nitrogen-containing saturated heterocycle or a 5-6 member nitrogen-containing heteroaromatic ring, wherein the number of heteroatoms in the nitrogen-containing saturated heterocycle or nitrogen-containing heteroaromatic ring is 1, and the heteroatom is N; R a1 and R a2 The carbon atoms bonded to them together form C4-C6 saturated carbon rings or Cy3 is a C3-C6 cycloalkene, and Cy4 is a benzene ring or a 5-6 membered heteroaromatic ring. In the 5-6 membered heteroaromatic ring, the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4. L is a C1-C3 alkylene group, wherein 0, 1 or more -CH2- groups are independently replaced by the following groups: -O-, -NH- or -CH=CH-; For example, Y, L A When ring B is defined as described in Scheme 1, ring A is... The end marked with "#" is connected to ring B. The compound as claimed in claim 1 or 2, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1)R B Halogen or -C(=O)N(R) A-1 )2, R A-1 H or C1-C6 alkyl; R B For example, F or -C(=O)N(CH3)2; (2) for R B1 and R B2 The definition is the same as R B Preferably, R B1 For halogens, R B2 -C(=O)N(R) A-1 )2, R A-1 It is an H or C1-C6 alkyl group, with the "#1" end connected to the L. X Connected; For example, The end marked "#1" is connected to L X Connected. The compound as claimed in claim 1 or 2, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1) Ring A is a naphthalene ring, a 9-10 membered heteroaryl ring, or a saturated or partially unsaturated C9-C ring. 10 The 9-10 membered heterocycle is a carbon ring, saturated or partially unsaturated, wherein the heteroatom is N, and the number of heteroatoms is 1, 2 or 3. (2)R A It is hydrogen; (3) m is 0 or 1; (4) Ring B is a 9-membered bicyclic heteroaromatic ring, for example, a 9-membered bicyclic heteroaromatic ring with N heteroatom and 1, 2 or 3 heteroatoms; For example, The end marked "#1" is connected to L X Connected; (5)R B -C(=O)N(R) A-1 )2, for example -C(=O)N(CH3)2; (6) n is 0 or 1; (7) In Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), L A -L A-1 -X 1 - #2 , where L A-1 It is a C1-C4 alkylene group, X 1 The symbol is -C(=O)-, and the end marked "#2" is connected to ring A; (8) In Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), Y is hydrogen or (9) In Scheme 1 of the compound shown in Formula (I) or in the compound shown in Formula (I-1), 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. (10) In Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), R Z It is hydrogen; (11) In Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), q is 0 or 1. The compound as claimed in claim 1 or 2, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1) for The end marked with "#" is connected to ring B; (2) for The end marked "#1" is connected to L x Connected; (3) In Scheme 1 of the compound as shown in formula (I) or in the compound as shown in formula (I-1), L A for The end marked "#2" is connected to ring A; (4) Scheme 1 of the compound as shown in formula (I) or the compound as shown in formula (I-1), for The compound as claimed in claim 1 or 2, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is 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 X. Compounds of formula (I) or formula (I-1) are compounds of formula (I-2). 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 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)-, -C(R)-. A-1 )2-、-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 1-6. The compound of claim 9, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1) p is 0, 1 or 2; Better place, for The end marked "#3" is connected to L X5 Connected; (2)L X5 for For example The end marked "#11" is connected to ring D; (3) 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 an oxo (=O), C1-C6 alkyl, halogen, or C1-C6 alkoxy group; Better place, For any of the following groups: Group (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; Group (2): Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy; Group (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; Group (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; Ideally, 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; Group (5): Where r is 0, 1, or 2, R Z It is a halogen, a C1-C6 alkyl or a C1-C6 alkoxy; Group (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; Among them, the end marked "#12" is connected to L. D Connected; Even better, When L is group (1), (3), (4) or (6), D It is a covalent bond; When L is group (2) or (5), D It is a covalent bond or -NH-; Better, for Among them, the end marked "#12" is connected to L. D Connected; For example, for Among them, the end marked "#12" is connected to L. D Connected: (4)L D It is a covalent bond or -NH-; (5) for Among them, X 7 It can be O, CH2 or NH; Better place, for (For example )、 Among them, the carbon atoms marked with "*" have the configuration of R, S or a mixture thereof; For example, for The compound of claim 9, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1) for The end marked "#3" is connected to L X5 Connected; (2)R C It is hydrogen or F; (3) p is 0 or 1; (4)L X5 Independently C1-C6 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; (5)L X5 for Among them, Cy1 is a saturated 5-6 membered heterocycle, L XA It is a covalent bond or a C1-C5 alkylene group, with the end marked "#11" connected to ring D; (6) 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 an oxo (=O) or C1-C6 alkyl group; (7)L D It is a covalent bond; (8) for The compound of claim 9, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that... It meets one or more of the following conditions: (1)L X5 for The end marked "#11" is connected to ring D; (2) for 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; Among them, the end marked "#12" is connected to L. D Connected; For example, The compound of claim 1, its pharmaceutically acceptable salt, its solvate, or a solvate of a pharmaceutically acceptable salt thereof, is characterized in that, The compound is selected from any one of the following compounds: A pharmaceutical composition comprising a compound as described 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. The use of a compound 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. The use of a compound 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, wherein the inflammatory diseases are, for example, atopic dermatitis, sinusitis, or asthma. 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 diseases are, for example, atopic dermatitis, sinusitis, or asthma.

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