K-Ras mutant protein inhibitors

Abstract

The present invention relates to a K-Ras mutant protein inhibitor represented by formula (I), a composition comprising the inhibitor and its use. #imgabs0#

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to the following applications: PCT / CN2022 / 114762, filed on August 25, 2022; PCT / CN2022 / 115089, filed on August 26, 2022; PCT / CN2022 / 120586, filed on September 22, 2022; PCT / CN2022 / 120995, filed on September 23, 2022; PCT / CN2022 / 121656, filed on September 24, 2022; PCT / CN2022 / 125529, filed on September 27, 2022; PCT / CN2022 / 125529, filed on October 14, 2022; PCT / CN2022 / 125684, filed on October 17, 2022; PCT / CN2022 / 127167, filed on October 25, 2022; and PCT / CN2023 / 072571, filed on January 17, 2023, all priorities are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention relates to compounds that inhibit the activities of various forms of K-Ras proteins, including wild-type K-Ras and mutant K-Ras, compositions containing the compounds, and methods of use thereof. Background Art

[0004] Kirsten rat sarcoma 2 viral oncogene homolog ("K-Ras") is a small GTPase and a member of the RAS oncogene family. K-Ras acts as a molecular switch that cycles between inactive (GDP-bound) and active (GTP-bound) states, transducing upstream cellular signals received from a variety of tyrosine kinases to downstream effectors to regulate a variety of processes, including cell proliferation. Aberrant expression of K-Ras accounts for approximately 20% of all cancers and oncogenic K-Ras mutations, and oncogenic K-Ras mutations that stabilize GTP binding lead to constitutive activation of K-Ras. K-Ras mutations at codons 12, 13, 61, and other positions in the K-Ras primary amino acid sequence are present in 88% of all pancreatic adenocarcinoma patients, 50% of all colorectal adenocarcinoma patients, and 32% of lung adenocarcinoma patients. A recent publication also suggests that wild-type K-Ras inhibition may be a viable therapeutic strategy for treating K-Ras wild-type dependent cancers.

[0005] Allele-specific K-Ras G12C inhibitors, such as sotorasib (AMG510) or adagrasib (MRTX849), are currently changing the treatment paradigm for patients with K-RasG12C mutant non-small cell lung cancer and colorectal cancer. The success in addressing previously elusive K-Ras alleles has boosted drug discovery efforts for all K-Ras mutants. Multiple K-Ras inhibitors have the potential to address a broad range of patient populations, including cancers with K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-RasG12R, K-RasG12S, K-RasG12A, K-RasQ61H mutants, and K-Ras wild-type amplification.

[0006] Therefore, there is an unmet need to develop new and diverse K-Ras inhibitors to treat K-Ras-mediated cancers. Summary of the invention

[0007] The present invention provides a compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a conjugated form thereof:

[0008]

[0009] The definitions of the variables are as follows.

[0010] The present application also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as defined herein; and a pharmaceutically acceptable excipient.

[0011] The present application also provides a method for treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof, or a pharmaceutical composition as defined herein.

[0012] The present application also provides a method for treating cancer in a subject in need thereof, the method comprising (a) determining whether the cancer is associated with K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-Ras G12R, K-RasG12S, K-Ras G12A, K-Ras Q61H mutations and / or K-Ras wild-type amplification; (b) if so, administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or formula (II) as defined herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof, or a pharmaceutical composition.

[0013] The present application also provides a compound of formula (I) or formula (II) as defined herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof, or a pharmaceutical composition for use in treatment.

[0014] The present application also provides a compound of formula (I) or formula (II) as defined herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof, or a pharmaceutical composition for use as a drug.

[0015] The present application also provides a compound of formula (I) or formula (II) as defined herein, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof, or a pharmaceutical composition for use in a method for treating cancer.

[0016] The present application also provides the use of a compound of formula (I) or formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof or a pharmaceutical composition as defined in the present application for treating cancer.

[0017] The present application also provides the use of a compound of formula (I) or formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, a PROTAC molecule thereof or a pharmaceutical composition as defined in the present application for preparing a drug for treating cancer.

[0018] Detailed description

[0019] This application provides the following disclosure:

[0020] [1]. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof:

[0021]

[0022] in,

[0023] X1, at each occurrence, is independently selected from a bond, -C(R X11 )(R X12 )-、-NR X13 -, -O-, -S-, -S(=O)-, or -S(=O)2-;

[0024] R X11 or R X12 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0025] Optionally, R X11 and R X12 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R SX1 replace;

[0026] R X13 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2、-P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)ORD 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0027] R X2 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0028] X2 is independently selected at each occurrence from N or CR1;

[0029] R1 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1A )2.-OR 1A 、-SR 1A 、-S(=O)R 1B 、-S(=O)2R 1B 、-C(=O)R 1B 、-C(=O)OR 1A 、-OC(=O)R 1B 、-C(=O)N(R 1A )2.-NR 1A C(=O)R 1B 、-OC(=O)OR 1A 、-NR 1A C(=O)OR 1A 、-NR 1A C(=S)OR 1A 、-OC(=O)N(R 1A )2.-NR 1A C(=O)N(R 1A )2, -S(=O)OR 1A 、-OS(=O)R 1B 、-S(=O)N(R 1A )2.-NR 1A S(=O)R 1B 、-S(=O)2OR 1A 、-OS(=O)2R 1B 、-S(=O)2N(R 1A )2.-NR 1A S(=O)2R 1B 、-OS(=O)2OR 1A 、-NR 1A S(=O)2OR 1A 、-OS(=O)2N(R 1A )2.-NR 1A S(=O)2N(R 1A )2. -P(R 1A )2. -P(=O)(R 1B)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1C )2.-OR 1C 、-SR 1C 、-S(=O)R 1D 、-S(=O)2R 1D 、-C(=O)R 1D 、-C(=O)OR 1D 、-OC(=O)R 1D 、-C(=O)N(R 1C )2.-NR 1C C(=O)R 1D 、-OC(=O)OR 1C 、-NR 1C C(=O)OR 1C 、-NR 1C C(=S)OR 1C 、-OC(=O)N(R 1C )2.-NR 1C C(=O)N(R 1C )2, -S(=O)OR 1C 、-OS(=O)R 1D 、-S(=O)N(R 1C )2.-NR 1C S(=O)R 1D 、-S(=O)2OR 1C 、-OS(=O)2R 1D 、-S(=O)2N(R 1C )2.-NR 1CS(=O)2R 1D 、-OS(=O)2OR 1C 、-NR 1C S(=O)2OR 1C 、-OS(=O)2N(R 1C )2.-NR 1C S(=O)2N(R 1C )2. -P(R 1C )2、-P(=O)(R 1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0030] Ring A is selected from a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring;

[0031] R S1 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S1A )2.-OR S1A 、-SR S1A 、-S(=O)R S1B 、-S(=O)2R S1B 、-C(=O)R S1B 、-C(=O)OR S1A 、-OC(=O)R S1B 、-C(=O)N(R S1A )2. -N S1A C(=O)R S1B 、-OC(=O)OR S1A 、-N S1A C(=O)OR S1A 、-NR S1A C(=S)O S1A 、-OC(=O)N(R S1A )2.-NR S1A C(=O)N(R S1A )2, -S(=O)OR S1A 、-OS(=O)R S1B 、-S(=O)N(R S1A )2.-NR S1A S(=O)R S1B、-S(=O)2OR S1A 、-OS(=O)2R S1B 、-S(=O)2N(R S1A )2.-NR S1A S(=O)2R S1B 、-OS(=O)2OR S1A 、-NR S1A S(=O)2OR S1A 、-OS(=O)2N(R S1A )2.-NR S1A S(=O)2N(R S1A )2. -P(R S1A )2. -P(=O)(R S1B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S1C )2.-OR S1C 、-SR S1C 、-S(=O)R S1D 、-S(=O)2R S1D 、-C(=O)R S1D 、-C(=O)OR S1C 、-OC(=O)R S1D 、-C(=O)N(R S1C )2.-NR S1C C(=O)R S1D 、-OC(=O)OR S1C 、-NR S1C C(=O)OR S1C 、-NRS1C C(=S)OR S1C 、-OC(=O)N(R S1C )2.-NR S1C C(=O)N(R S1C )2, -S(=O)OR S1C 、-OS(=O)R S1D 、-S(=O)N(R S1C )2.-NR S1C S(=O)R S1D 、-S(=O)2OR S1C 、-OS(=O)2R S1D 、-S(=O)2N(R S1C )2.-NR S1C S(=O)2R S1D 、-OS(=O)2OR S1C 、-NR S1C S(=O)2OR S1C 、-OS(=O)2N(R S1C )2.-NR S1C S(=O)2N(R S1C )2. -P(R S1C )2、-P(=O)(R S1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0032] Optionally, two R S1 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S11 replace;

[0033] Optionally, two adjacent R S1 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S12 replace;

[0034] Optionally, two non-adjacent R S1 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S13 replace;

[0035] m1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9;

[0036] Y1 is a bond, O, S, S(=O), S(=O)2 or NR Y11 ;

[0037] R Y11 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2、-P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)RD 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2、-P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0038] R3 is selected from

[0039] R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 38 , R 39 , R 310 and R 311 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SRA 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C)2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0040] Optionally, R 31 and R 32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S33 replace;

[0041] Optionally, R 33 and R 34 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S34 replace;

[0042] Optionally, R 35 and R 36 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S35 replace;

[0043] Optionally, R 38 and R 39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S310 replace;

[0044] Optionally, R 310 and R 311 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S316 replace;

[0045] n2 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0046] n3 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0047] n4 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0048] n5 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0049] n6 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0050] Ring B is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0051] Ring C is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0052] Ring D is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring;

[0053] Ring I is a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring, comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0054] Ring J is a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0055] Ring K is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring, containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0056] R S31 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31A )2.-OR S31A 、-SR S31A 、-S(=O)R S31B 、-S(=O)2R S31B 、-C(=O)R S31B 、-C(=O)OR S31A 、-OC(=O)R S31B 、-C(=O)N(R S31A )2.-NR S31A C(=O)R S31B 、-OC(=O)OR S31A 、-NR S31A C(=O)OR S31A 、-NR S31A C(=S)OR S31A 、-OC(=O)N(R S31A )2.-NR S31A C(=O)N(R S31A )2, -S(=O)OR S31A 、-OS(=O)R S31B 、-S(=O)N(R S31A )2.-NR S31A S(=O)R S31B 、-S(=O)2OR S31A 、-OS(=O)2R S31B 、-S(=O)2N(R S31A )2.-NR S31A S(=O)2R S31B 、-OS(=O)2OR S31A 、-NR S31A S(=O)2OR S31A 、-OS(=O)2N(R S31A )2.-NR S31A S(=O)2N(R S31A )2. -P(R S31A )2、-P(=O)(R S31B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31C )2.-OR S31C 、-SR S31C 、-S(=O)R S31D 、-S(=O)2R S31D 、-C(=O)R S31D 、-C(=O)OR S31C 、-OC(=O)R S31D 、-C(=O)N(R S31C )2.-NR S31C C(=O)R S31D 、-OC(=O)OR S31C 、-NR S31C C(=O)OR S31C 、-NR S31C C(=S)OR S31C 、-OC(=O)N(R S31C )2.-NR S31C C(=O)N(R S31C )2, -S(=O)OR S31C 、-OS(=O)R S31D 、-S(=O)N(R S31C )2.-NR S31C S(=O)R S31D 、-S(=O)2OR S31C 、-OS(=O)2R S31D 、-S(=O)2N(R S31C )2.-NR S31C S(=O)2R S31D 、-OS(=O)2OR S31C 、-NR S31C S(=O)2OR S31C 、-OS(=O)2N(R S31C )2.-NR S31C S(=O)2N(R S31C )2. -P(RS31C )2. -P(=O)(R S31D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0057] Optionally, two R S31 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S311 replace;

[0058] Optionally, two adjacent R S31 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S312 replace;

[0059] Optionally, two non-adjacent R S31 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S313 replace;

[0060] m3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0061] R S32 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32A )2.-OR S32A 、-SR S32A 、-S(=O)R S32B 、-S(=O)2R S32B 、-C(=O)R S32B 、-C(=O)OR S32A 、-OC(=O)R S32B 、-C(=O)N(R S32A )2.-NRS32A C(=O)R S32B 、-OC(=O)OR S32A 、-NR S32A C(=O)OR S32A 、-NR S32A C(=S)OR S32A 、-OC(=O)N(R S32A )2.-NR S32A C(=O)N(R S32A )2, -S(=O)OR S32A 、-OS(=O)R S32B 、-S(=O)N(R S32A )2.-NR S32A S(=O)R S32B 、-S(=O)2OR S32A 、-OS(=O)2R S32B 、-S(=O)2N(R S32A )2.-NR S32A S(=O)2R S32B 、-OS(=O)2OR S32A 、-NR S32A S(=O)2OR S32A 、-OS(=O)2N(R S32A )2.-NR S32A S(=O)2N(R S32A )2. -P(R S32A )2. -P(=O)(R S32B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32C )2.-OR S32C 、-SR S32C 、-S(=O)R S32C 、-S(=O)2R S32D 、-C(=O)R S32D 、-C(=O)OR S32C 、-OC(=O)R S32D 、-C(=O)N(R S32C )2.-NR S32C C(=O)R S32D 、-OC(=O)OR S32C 、-NR S32C C(=O)OR S32C 、-NR S32C C(=S)OR S32C 、-OC(=O)N(R S32C )2.-NR S32C C(=O)N(R S32C )2, -S(=O)OR S32C 、-OS(=O)R S32C 、-S(=O)N(R S32C )2.-NR S32C S(=O)R S32D 、-S(=O)2OR S32C 、-OS(=O)2R S32D 、-S(=O)2N(R S32C )2.-NR S32C S(=O)2R S32D 、-OS(=O)2OR S32C 、-NR S32C S(=O)2OR S32C 、-OS(=O)2N(R S32C )2.-NR S32C S(=O)2N(R S32C )2. -P(R S32C )2、-P(=O)(R S32D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0062] Optionally, two R S32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S321 replace;

[0063] Optionally, two adjacent R S32 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S322 replace;

[0064] Optionally, two non-adjacent R S32 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S323 replace;

[0065] m4 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0066] R 37 Selected from -N(R 37A ) a 2- or 3-10-membered heterocyclic ring, wherein the 3-10-membered heterocyclic ring is optionally independently replaced by one or more R S37 replace;

[0067] R S38 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38A )2.-OR S38A 、-SR S38A 、-S(=O)R S38B 、-S(=O)2R S38B 、-C(=O)R S38B 、-C(=O)OR S38A 、-OC(=O)R S38B 、-C(=O)N(R S38A )2.-NR S38A C(=O)R S38B 、-OC(=O)OR S38A 、-NR S38A C(=O)OR S38A 、-NR S38A C(=S)OR S38A 、-OC(=O)N(R S38A )2.-NRS38A C(=O)N(R S38A )2, -S(=O)OR S38A 、-OS(=O)R S38B 、-S(=O)N(R S38A )2.-NR S38A S(=O)R S38B 、-S(=O)2OR S38A 、-OS(=O)2R S38B 、-S(=O)2N(R S38A )2.-NR S38A S(=O)2R S38B 、-OS(=O)2OR S38A 、-NR S38A S(=O)2OR S38A 、-OS(=O)2N(R S38A )2.-NR S38A S(=O)2N(R S38A )2. -P(R S38A )2、-P(=O)(R S38B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocycle, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocycle, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38C )2.-OR S38C 、-SR S38C 、-S(=O)R S38D 、-S(=O)2R S38D 、-C(=O)R S38D 、-C(=O)OR S38C 、-OC(=O)R S38D、-C(=O)N(R S38C )2.-NR S38C C(=O)R S38D 、-OC(=O)OR S38C 、-NR S38C C(=O)OR S38C 、-NR S38C C(=S)OR S38C 、-OC(=O)N(R S38C )2.-NR S38C C(=O)N(R S38C )2, -S(=O)OR S38C 、-OS(=O)R S38D 、-S(=O)N(R S38C )2.-NR S38C S(=O)R S38D 、-S(=O)2OR S38C 、-OS(=O)2R S38D 、-S(=O)2N(R S38C )2.-NR S38C S(=O)2R S38D 、-OS(=O)2OR S38C 、-NR S38C S(=O)2OR S38C 、-OS(=O)2N(R S38C )2.-NR S38C S(=O)2N(R S38C )2. -P(R S38C )2. -P(=O)(R S38D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0068] Optionally, two R S38 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S381 replace;

[0069] Optionally, two adjacent R S38 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S382 replace;

[0070] Optionally, two non-adjacent RS38 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S383 replace;

[0071] m8 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0072] R S39 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39A )2.-OR S39A 、-SR S39A 、-S(=O)R S39B 、-S(=O)2R S39B 、-C(=O)R S39B 、-C(=O)OR S39A 、-OC(=O)R S39B 、-C(=O)N(R S39A )2.-NR S39A C(=O)R S39B 、-OC(=O)OR S39A 、-NR S39A C(=O)OR S39A 、-NR S39A C(=S)OR S39A 、-OC(=O)N(R S39A )2.-NR S39A C(=O)N(R S39A )2, -S(=O)OR S39A 、-OS(=O)R S39B 、-S(=O)N(R S39A )2.-NR S39A S(=O)R S39B 、-S(=O)2OR S39A 、-OS(=O)2R S39B 、-S(=O)2N(R S39A )2.-NR S39A S(=O)2R S39B 、-OS(=O)2ORS39A 、-NR S39A S(=O)2OR S39A 、-OS(=O)2N(R S39A )2.-NR S39A S(=O)2N(R S39A )2. -P(R S39A )2、-P(=O)(R S39B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39C )2.-OR S39C 、-SR S39C 、-S(=O)R S39C 、-S(=O)2R S39D 、-C(=O)R S39D 、-C(=O)OR S39C 、-OC(=O)R S39D 、-C(=O)N(R S39C )2.-NR S39C C(=O)R S39D 、-OC(=O)OR S39C 、-NR S39C C(=O)OR S39C 、-NR S39C C(=S)OR S39C 、-OC(=O)N(R S39C )2.-NR S39C C(=O)N(R S39C )2, -S(=O)OR S39C 、-OS(=O)RS39C 、-S(=O)N(R S39C )2.-NR S39C S(=O)R S39D 、-S(=O)2OR S39C 、-OS(=O)2R S39D 、-S(=O)2N(R S39C )2.-NR S39C S(=O)2R S39D 、-OS(=O)2OR S39C 、-NR S39C S(=O)2OR S39C 、-OS(=O)2N(R S39C )2.-NR S39C S(=O)2N(R S39C )2. -P(R S39C )2、-P(=O)(R S39D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0073] Optionally, two R S39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S391 replace;

[0074] Optionally, two adjacent R S39 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S392 replace;

[0075] Optionally, two non-adjacent R S39 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S393 replace;

[0076] m9 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0077] R S315 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315A )2.-OR S315A 、-SR S315A 、-S(=O)R S315B 、-S(=O)2R S315B 、-C(=O)R S315B 、-C(=O)OR S315A 、-OC(=O)R S315B 、-C(=O)N(R S315A )2.-NR S315A C(=O)R S315B 、-OC(=O)OR S315A 、-NR S315A C(=O)OR S315A 、-NR S315A C(=S)OR S315A 、-OC(=O)N(R S315A )2.-NR S315A C(=O)N(R S315A )2, -S(=O)OR S315A 、-OS(=O)R S315B 、-S(=O)N(R S315A )2.-NR S315A S(=O)R S315B 、-S(=O)2OR S315A 、-OS(=O)2R S315B 、-S(=O)2N(R S315A )2.-NR S315A S(=O)2R S315B 、-OS(=O)2OR S315A 、-NR S315A S(=O)2OR S315A 、-OS(=O)2N(R S315A )2.-NR S315A S(=O)2N(R S315A )2. -P(R S315A )2. -P(=O)(R S315B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315C )2.-OR S315C 、-SR S315C 、-S(=O)R S315C 、-S(=O)2R S315D 、-C(=O)R S315D 、-C(=O)OR S315C 、-OC(=O)R S315D 、-C(=O)N(R S315C )2.-NR S315C C(=O)R S315D 、-OC(=O)OR S315C 、-NR S315C C(=O)OR S315C 、-NR S315C C(=S)OR S315C 、-OC(=O)N(R S315C )2.-NR S315C C(=O)N(R S315C )2, -S(=O)OR S315C 、-OS(=O)R S315C 、-S(=O)N(R S315C )2.-NR S315C S(=O)R S315D 、-S(=O)2OR S315C 、-OS(=O)2R S315D 、-S(=O)2N(R S315C )2.-NR S315C S(=O)2R S315D 、-OS(=O)2OR S315C 、-NR S315C S(=O)2OR S315C 、-OS(=O)2N(R S315C )2.-NRS315C S(=O)2N(R S315C )2. -P(R S315C )2、-P(=O)(R S315D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0078] Optionally, two R S315 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S3151 replace;

[0079] Optionally, two adjacent R S315 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S3152 replace;

[0080] Optionally, two non-adjacent R S315 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S3153 replace;

[0081] m 10 Selected from 0, 1, 2, 3, 4, 5 or 6;

[0082] R4 is selected from 6-10 membered aryl, 5-10 membered heteroaryl, wherein the 6-10 membered aryl, 5-10 membered heteroaryl, are independently unsubstituted or substituted with one or more R S4 replace;

[0083] Each occurrence of Z is independently selected from or N;

[0084] When Z is selected from C, each occurrence of Ring E is independently selected from a 6-membered aryl ring or a 5-6-membered heteroaryl ring, and each occurrence of Ring F is independently selected from a 3-10-membered carbocyclic ring or a 3-10-membered heterocyclic ring;

[0085] When Z is selected from N, each occurrence of Ring E is selected from a 5-6 membered heteroaryl ring, and each occurrence of Ring F is selected from a 3-10 membered heterocyclic ring;

[0086] RS4 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4A )2.-OR S4A 、-SR S4A 、-S(=O)R S4B 、-S(=O)2R S4B 、-C(=O)R S4B 、-C(=O)OR S4A 、-OC(=O)R S4B 、-C(=O)N(R S4A )2.-NR S4A C(=O)R S4B 、-OC(=O)OR S4A 、-NR S4A C(=O)OR S4A 、-NR S4A C(=S)OR S4A 、-OC(=O)N(R S4A )2.-NR S4A C(=O)N(R S4A )2, -S(=O)OR S4A 、-OS(=O)R S4B 、-S(=O)N(R S4A )2.-NR S4A S(=O)R S4B 、-S(=O)2OR S4A 、-OS(=O)2R S4B 、-S(=O)2N(R S4A )2.-NR S4A S(=O)2R S4B 、-OS(=O)2OR S4A 、-NR S4A S(=O)2OR S4A 、-OS(=O)2N(R S4A )2.-NR S4A S(=O)2N(R S4A )2. -P(R S4A )2. -P(=O)(R S4B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4C )2.-OR S4C 、-SR S4C 、-S(=O)R S4D 、-S(=O)2R S4D 、-C(=O)R S4D 、-C(=O)OR S4D 、-OC(=O)R S4D 、-C(=O)N(R S4C )2.-NR S4C C(=O)R S4D 、-OC(=O)OR S4C 、-NR S4C C(=O)OR S4C 、-NR S4C C(=S)OR S4C 、-OC(=O)N(R S4C )2.-NR S4C C(=O)N(R S4C )2, -S(=O)OR S4C 、-OS(=O)R S4D 、-S(=O)N(R S4C )2.-NR S4C S(=O)R S4D 、-S(=O)2OR S4C 、-OS(=O)2R S4D 、-S(=O)2N(R S4C )2.-NR S4C S(=O)2R S4D 、-OS(=O)2OR S4C 、-NR S4CS(=O)2OR S4C 、-OS(=O)2N(R S4C )2.-NR S4C S(=O)2N(R S4C )2. -P(R S4C )2. -P(=O)(R S4D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0087] R5 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5A )2.-OR 5A 、-SR 5A 、-S(=O)R 5B 、-S(=O)2R 5B 、-C(=O)R 5B 、-C(=O)OR 5A 、-OC(=O)R 5B 、-C(=O)N(R 5A )2.-NR 5A C(=O)R 5B 、-OC(=O)OR 5A 、-NR 5A C(=O)OR 5A 、-NR 5A C(=S)OR 5A 、-OC(=O)N(R 5A )2.-NR 5A C(=O)N(R 5A )2, -S(=O)OR 5A 、-OS(=O)R 5B 、-S(=O)N(R 5A )2.-NR 5A S(=O)R 5B 、-S(=O)2OR 5A 、-OS(=O)2R 5B 、-S(=O)2N(R 5A )2.-NR 5A S(=O)2R 5B 、-OS(=O)2OR 5A 、-NR5A S(=O)2OR 5A 、-OS(=O)2N(R 5A )2.-NR 5A S(=O)2N(R 5A )2. -P(R 5A )2. -P(=O)(R 5B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5C )2.-OR 5C 、-SR 5C 、-S(=O)R 5D 、-S(=O)2R 5D 、-C(=O)R 5D 、-C(=O)OR 5D 、-OC(=O)R 5D 、-C(=O)N(R 5C )2.-NR 5C C(=O)R 5D 、-OC(=O)OR 5C 、-NR 5C C(=O)OR 5C 、-NR 5C C(=S)OR 5C 、-OC(=O)N(R 5C )2.-NR 5C C(=O)N(R 5C )2, -S(=O)OR 5C 、-OS(=O)R 5D、-S(=O)N(R 5C )2.-NR 5C S(=O)R 5D 、-S(=O)2OR 5C 、-OS(=O)2R 5D 、-S(=O)2N(R 5C )2.-NR 5C S(=O)2R 5D 、-OS(=O)2OR 5C 、-NR 5C S(=O)2OR 5C 、-OS(=O)2N(R 5C )2.-NR 5C S(=O)2N(R 5C )2. -P(R 5C )2、-P(=O)(R 5D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0088] R 1A , R 1C , R S1A , R S1C , R S31A , R S31C , R S32A , R S32C , R 37A , R S38A , R S38C , R S39A , R S39C , R S315A , R S315C , R S4A , R S4C , R 5A and R 5C are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B)2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0089] Optionally, (two R 1A , two R 1C , two R S1A , two R S1C , two R S31A , two R S31C , two R S32A , two R S32C , two R 37A , two R S38A , two R S38C , two R S39A , two R S39C , two R S315A , two R S315C , two R S4A , two R S4C , two R 5A and two R 5C ) and the nitrogen atom to which it is connected together form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring, wherein the 3-10 membered heterocyclic ring or the 5-10 membered heteroaromatic ring is independently unsubstituted or substituted with one or more R SS replace;

[0090] R 1B , R 1D , R S1B , R S1D , R S31B , R S31D , R S32B , R S32D , R S38B , R S38D , R S39B , R S39D , R S315B , R S315D , R S4B , R S4D , R 5B and R 5D Each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C2-6 Alkynyl, -N(R A )2.-OR A 、-SR A , 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0091] R A , R B , R C and R D Each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are independently unsubstituted or substituted with one or more R SA replace;

[0092] R SX1 , R S11 , R S12 , R S13 , R S33 , R S34 , R S35 , R S316 , R S311 , R S312 , R S313 , R S321 , R S322 , R S323 , R S37 , R S310 , R S381 , R S382 , R S383 , R S391 , R S392 , R S393 , R S3151 , RS3152 , R S3153 , R SS and R SA are each independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -OC(=O)O(C 1-6 alkyl), -NHC(=O)(OC 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(OC 1-6 alkyl), -OC(=O)NH(C 1-6 alkyl), -OC(=O)N(C 1-6 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH2, -N(C 1-6 alkyl)C(=O)NH(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)N(C 1-6 Alkyl)2, -S(=O)(OC 1-6 alkyl), -OS(=O)(C 1-6 alkyl), -S(=O)NH2, -S(=O)NH(C 1-6 alkyl), -S(=O)N(C1-6 Alkyl)2, -NHS(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)(C 1-6 Alkyl), -S(=O)2(OC 1-6 alkyl), -OS(=O)2(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), -OS(=O)2O(C 1-6 alkyl), -NHS(=O)2O(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2O(C 1-6 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 alkyl), -OS(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 alkyl), -NHS(=O)2N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)S(=O)2NH2, -N(C 1-6 Alkyl)S(=O)2NH(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)2N(C 1-6 Alkyl)2, -PH(C 1-6 Alkyl), -P(C 1-6 Alkyl)2, -P(=O)H(C 1-6 alkyl), -P(=O)(C 1-6 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-3Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy, -C 2-3 Alkenyl, -C 2-3 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -OH, -O(C 1-3 alkyl), -SH, -S(C 1-3 alkyl), -S(=O)(C 1-3 alkyl), -S(=O)2(C 1-3 alkyl), -C(=O)(C 1-3 alkyl), -C(=O)OH-C(=O)(OC 1-3 alkyl), -OC(=O)(C 1-3 alkyl), -C(=O)NH2, -C(=O)NH(C 1-3 alkyl), -C(=O)N(C 1-3 Alkyl)2, -NHC(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(C 1-3 alkyl), -OC(=O)O(C 1-3 alkyl), -NHC(=O)(OC 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(OC 1-3 alkyl), -OC(=O)NH(C 1-3 alkyl), -OC(=O)N(C 1-3 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-3 alkyl), -NHC(=O)N(C 1-3 Alkyl)2, -N(C 1-3 alkyl)C(=O)NH2, -N(C 1-3 alkyl)C(=O)NH(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)N(C 1-3 Alkyl)2, -S(=O)(OC 1-3 alkyl), -OS(=O)(C 1-3 alkyl), -S(=O)NH2, -S(=O)NH(C 1-3 alkyl), -S(=O)N(C 1-3 Alkyl)2, -NHS(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)(C 1-3Alkyl), -S(=O)2(OC 1-3 alkyl), -OS(=O)2(C 1-3 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-3 alkyl), -S(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2(C 1-3 alkyl), -OS(=O)2O(C 1-3 alkyl), -NHS(=O)2O(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2O(C 1-3 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-3 alkyl), -OS(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-3 alkyl), -NHS(=O)2N(C 1-3 Alkyl)2, -N(C 1-3 Alkyl)S(=O)2NH2, -N(C 1-3 Alkyl)S(=O)2NH(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)2N(C 1-3 Alkyl)2, -PH(C 1-3 Alkyl), -P(C 1-3 Alkyl)2, -P(=O)H(C 1-3 alkyl), -P(=O)(C 1-3 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0093] Each occurrence of heterocyclyl or heterocycle independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S(=O) or S(=O)2;

[0094] Each occurrence of heteroaryl independently contains 1, 2, 3 or 4 heteroatoms selected from N, O or S.

[0095] [2] The compound of formula (I) described in [1], its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein the compound is selected from any one of the following formulas:

[0096]

[0097] [3] The compound of formula (I) described in [1] to [2], its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein:

[0098] X1 is independently selected at each occurrence from -C(R X11 )(R X12 )-、-NR X13 -, -O-, or -S-;

[0099] R X11 or R X12 are independently selected from hydrogen, deuterium, halogen or -C 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl;

[0100] R X13 Selected from hydrogen, deuterium or -C 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, --NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl.

[0101] [4]. A compound of formula (I) as described in any one of [1] to [3], a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein X1 is selected from -O-, -S-, -NH-, -N(CH3)-, -CH2- or -CHF-.

[0102] [5]. The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to [4], wherein R X2 Selected from hydrogen, deuterium or -C 1-6 alkyl;

[0103] Preferably, R X2 is selected from hydrogen, deuterium or methyl.

[0104] [6]. A compound of formula (I) as described in any one of [1] to [5], a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein Ring A is selected from a 5-6 membered carbocyclic ring or a 5-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O.

[0105] [7]. The compound of formula (I) as described in any one of [1] to [6], its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein the compound is selected from any one of the following formulas:

[0106]

[0107]

[0108] [8]. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to [7], wherein m1 is selected from 0, 1 or 2.

[0109] [9]. The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of [1] to [8], wherein:

[0110] R S1 Selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl;

[0111] Preferably, R S1 Selected from -F, -CH3 or -OH.

[0112]

[10] . A compound of formula (I) as described in any one of [1] to [9], a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein the compound is selected from any one of the following formulas in Table A:

[0113] Table A

[0114]

[0115]

[0116]

[0117] Preferably, the compound is selected from any one of the formulas in Table B below:

[0118] Table B

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132]

[0133]

[0134]

[0135]

[11] . A compound of formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof:

[0136]

[0137] in,

[0138] Each occurrence of X1 is independently selected from a single bond, -C(R X11 )(R X12 )-、-NR X13 -, -O-, -S-, -S(=O)-, or -S(=O)2-;

[0139] R X11 or R X12 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2、-P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2、-P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0140] Optionally, R X11 and R X12 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R SX1 replace;

[0141] R X13 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 aAlkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)ORD 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2、-P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl3-10;

[0142] Each occurrence of X2 is independently selected from N or CR1;

[0143] R1 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1A )2.-OR 1A 、-SR 1A 、-S(=O)R 1B 、-S(=O)2R 1B 、-C(=O)R 1B 、-C(=O)OR 1A 、-OC(=O)R 1B 、-C(=O)N(R 1A )2.-NR 1A C(=O)R 1B 、-OC(=O)OR 1A 、-NR1A C(=O)OR 1A 、-NR 1A C(=S)OR 1A 、-OC(=O)N(R 1A )2.-NR 1A C(=O)N(R 1A )2, -S(=O)OR 1A 、-OS(=O)R 1B 、-S(=O)N(R 1A )2.-NR 1A S(=O)R 1B 、-S(=O)2OR 1A 、-OS(=O)2R 1B 、-S(=O)2N(R 1A )2.-NR 1A S(=O)2R 1B 、-OS(=O)2OR 1A 、-NR 1A S(=O)2OR 1A 、-OS(=O)2N(R 1A )2.-NR 1A S(=O)2N(R 1A )2. -P(R 1A )2、-P(=O)(R 1B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1C )2.-OR 1C 、-SR 1C、-S(=O)R 1D 、-S(=O)2R 1D 、-C(=O)R 1D 、-C(=O)OR 1D 、-OC(=O)R 1D 、-C(=O)N(R 1C )2.-NR 1C C(=O)R 1D 、-OC(=O)OR 1C 、-NR 1C C(=O)OR 1C 、-NR 1C C(=S)OR 1C 、-OC(=O)N(R 1C )2.-NR 1C C(=O)N(R 1C )2, -S(=O)OR 1C 、-OS(=O)R 1D 、-S(=O)N(R 1C )2.-NR 1C S(=O)R 1D 、-S(=O)2OR 1C 、-OS(=O)2R 1D 、-S(=O)2N(R 1C )2.-NR 1C S(=O)2R 1D 、-OS(=O)2OR 1C 、-NR 1C S(=O)2OR 1C 、-OS(=O)2N(R 1C )2.-NR 1C S(=O)2N(R 1C )2. -P(R 1C )2、-P(=O)(R 1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0144] Ring A is selected from a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S=O or S(=O)2, a benzene ring, or a 5-6 membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from N, O or S;

[0145] R 81 and R 82 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R 8A )2.-OR 8A 、-SR 8A 、-S(=O)R 8B 、-S(=O)2R 8B 、-C(=O)R 8B 、-C(=O)OR 8B 、-C(=O)N(R 8B )2, -S(=O)OR 8B 、-S(=O)N(R 8B )2, -S(=O)2OR 8B 、-S(=O)2N(R 8B )2、-P(=O)(R 8B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 8C )2.-OR 8C 、-SR 8C 、-S(=O)R 8D 、-S(=O)2R 8D 、-C(=O)R 8D 、-C(=O)OR 8C 、-OC(=O)R 8D 、-C(=O)N(R 8C )2.-NR 8C C(=O)R 8D 、-OC(=O)OR 8C 、-NR 8C C(=O)OR 8D、-OC(=O)N(R 8C )2.-NR 8C C(=O)N(R 8C )2, -S(=O)OR 8C 、-OS(=O)R 8D 、-S(=O)N(R 8C )2.-NR 8C S(=O)R 8D 、-S(=O)2OR 8C 、-OS(=O)2R 8D 、-S(=O)2N(R 8C )2.-NR 8C S(=O)2R 8D 、-OS(=O)2OR 8C 、-NR 8C S(=O)2OR 8C 、-OS(=O)2NR 8C 、-NR 8C S(=O)2N(R 8C )2. -P(R 8C )2、-P(=O)(R 8D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0146] Optionally, R 81 and R 82 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S81 replace;

[0147] Optional, R 81 and R 82 Together with the carbon atoms to which they are commonly attached, they form a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring; wherein the 3-10 membered carbocyclic ring or the 3-10 membered heterocyclic ring are each independently unsubstituted or substituted by one or more R S82 replace;

[0148] n7 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0149] Ring M is selected from a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from N, O or S;

[0150] R S8 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N, oxo, -N(R S8A )2.-OR S8A 、-SR S8A 、-S(=O)R S8B 、-S(=O)2R S8B 、-C(=O)R S8B 、-C(=O)OR S8A 、-OC(=O)R S8B 、-C(=O)N(R S8A )2.-NR S8A C(=O)R S8B 、-OC(=O)OR S8A 、-NR S8A C(=O)OR S8A 、-NR S8A C(=S)OR S8A 、-OC(=O)N(R S8A )2.-NR S8A C(=O)N(R S8A )2, -S(=O)OR S8A 、-OS(=O)R S8B 、-S(=O)N(R S8A )2.-NR S8A S(=O)R S8B 、-S(=O)2OR S8A 、-OS(=O)2R S8B 、-S(=O)2N(R S8A )2.-NR S8A S(=O)2R S8B 、-OS(=O)2OR S8A 、-NR S8A S(=O)2OR S8A 、-OS(=O)2N(R S8A )2.-NR S8A S(=O)2N(R S8A )2. -P(R S8A )2、-P(=O)(R S8B )2, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N, oxo, -N(R S8C )2.-OR S8C 、-SR S8C 、-S(=O)R S8D 、-S(=O)2R S8D 、-C(=O)R S8D 、-C(=O)OR S8C 、-OC(=O)R S8D 、-C(=O)N(R S8C )2.-NR S8C C(=O)R S8D 、-OC(=O)OR S8C 、-NR S8C C(=O)OR S8C 、-NR S8C C(=S)OR S8C 、-OC(=O)N(R S8C )2.-NR S8C C(=O)N(R S8C )2, -S(=O)OR S8C 、-OS(=O)R S8D 、-S(=O)N(R S8C )2.-NR S8C S(=O)R S8D 、-S(=O)2OR S8C 、-OS(=O)2R S8D 、-S(=O)2N(R S8C )2.-NR S8C S(=O)2R S8D 、-OS(=O)2OR S8C 、-NR S8C S(=O)2OR S8C 、-OS(=O)2N(R S8C )2.-NRS8C S(=O)2N(R S8C )2. -P(R S8C )2. -P(=O)(R S8D )2, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl;

[0151] n8 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0152] R S2 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S2A )2.-OR S2A 、-SR S2A 、-S(=O)R S2B 、-S(=O)2R S2B 、-C(=O)R S2B 、-C(=O)OR S2A 、-OC(=O)R S2B 、-C(=O)N(R S2A )2.-NR S2A C(=O)R S2B 、-OC(=O)OR S2A 、-NR S2A C(=O)OR S2A 、-NR S2A C(=S)OR S2A 、-OC(=O)N(R S2A )2.-NR S2A C(=O)N(R S2A )2, -S(=O)OR S2A 、-OS(=O)R S2B 、-S(=O)N(R S2A )2.-NR S2A S(=O)R S2B 、-S(=O)2OR S2A 、-OS(=O)2R S2B 、-S(=O)2N(R S2A )2.-NR S2A S(=O)2R S2B 、-OS(=O)2OR S2A 、-NRS2A S(=O)2OR S2A 、-OS(=O)2N(R S2A )2.-NR S2A S(=O)2N(R S2A )2. -P(R S2A )2、-P(=O)(R S2B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S2C )2.-OR S2C 、-SR S2C 、-S(=O)R S2D 、-S(=O)2R S2D 、-C(=O)R S2D 、-C(=O)OR S2D 、-OC(=O)R S2D 、-C(=O)N(R S2C )2.-NR S2C C(=O)R S2D 、-OC(=O)OR S2C 、-NR S2C C(=O)OR S2C 、-NR S2C C(=S)OR S2C 、-OC(=O)N(R S2C )2.-NR S2C C(=O)N(R S2C )2, -S(=O)OR S2C 、-OS(=O)R S2D、-S(=O)N(R S2C )2.-NR S2C S(=O)R S2D 、-S(=O)2OR S2C 、-OS(=O)2R S2D 、-S(=O)2N(R S2C )2.-NR S2C S(=O)2R S2D 、-OS(=O)2OR S2C 、-NR S2C S(=O)2OR S2C 、-OS(=O)2N(R S2C )2.-NR S2C S(=O)2N(R S2C )2. -P(R S2C )2、-P(=O)(R S2D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0153] Optionally, two R S2 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S21 replace;

[0154] Optionally, two adjacent R S2 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S22 replace;

[0155] Optionally, two non-adjacent R S2 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S23 replace;

[0156] m2 is selected from 0, 1, 2, 3, 4 or 5;

[0157] Y1 is a bond, O, S, S(=O), S(=O)2 or NR Y11 ;

[0158] R Y11Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)ORC 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0159] R3 is selected from

[0160] R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 38 , R 39 , R 310 and R 311 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR A 、-C(=O)N(R A )2, -S(=O)OR A 、-S(=O)N(RA )2, -S(=O)2OR A 、-S(=O)2N(R A )2、-P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2、-P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0161] Optionally, R 31 and R 32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S33 replace;

[0162] Optionally, R 33 and R 34 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S34 replace;

[0163] Optionally, R 35 and R 36 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S35 replace;

[0164] Optionally, R 38 and R 39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S310 replace;

[0165] Optionally, R 310 and R 311 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S316 replace;

[0166] n2 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0167] n3 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0168] n4 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0169] n5 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0170] n6 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0171] Ring B is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0172] Ring C is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0173] Ring D is selected from a 3- to 10-membered carbocyclic ring or a 3- to 10-membered heterocyclic ring.

[0174] Ring I is a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0175] Ring J is a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0176] Ring K is selected from a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2;

[0177] R S31 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31A )2.-OR S31A 、-SR S31A 、-S(=O)RS31B 、-S(=O)2R S31B 、-C(=O)R S31B 、-C(=O)OR S31A 、-OC(=O)R S31B 、-C(=O)N(R S31A )2.-NR S31A C(=O)R S31B 、-OC(=O)OR S31A 、-NR S31A C(=O)OR S31A 、-NR S31A C(=S)OR S31A 、-OC(=O)N(R S31A )2.-NR S31A C(=O)N(R S31A )2, -S(=O)OR S31A 、-OS(=O)R S31B 、-S(=O)N(R S31A )2.-NR S31A S(=O)R S31B 、-S(=O)2OR S31A 、-OS(=O)2R S31B 、-S(=O)2N(R S31A )2.-NR S31A S(=O)2R S31B 、-OS(=O)2OR S31A 、-NR S31A S(=O)2OR S31A 、-OS(=O)2N(R S31A )2.-NR S31A S(=O)2N(R S31A )2. -P(R S31A )2. -P(=O)(R S31B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31C )2.-OR S31C 、-SR S31C 、-S(=O)R S31D 、-S(=O)2R S31D 、-C(=O)R S31D 、-C(=O)OR S31C 、-OC(=O)R S31D 、-C(=O)N(R S31C )2.-NR S31C C(=O)R S31D 、-OC(=O)OR S31C 、-NR S31C C(=O)OR S31C 、-NR S31C C(=S)OR S31C 、-OC(=O)N(R S31C )2.-NR S31C C(=O)N(R S31C )2, -S(=O)OR S31C 、-OS(=O)R S31D 、-S(=O)N(R S31C )2.-NR S31C S(=O)R S31D 、-S(=O)2OR S31C 、-OS(=O)2R S31D 、-S(=O)2N(R S31C )2.-NR S31C S(=O)2R S31D 、-OS(=O)2OR S31C 、-NR S31C S(=O)2OR S31C 、-OS(=O)2N(R S31C )2.-NR S31C S(=O)2N(R S31C )2. -P(R S31C )2、-P(=O)(R S31D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0178] Optionally, two RS31 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S311 replace;

[0179] Optionally, two adjacent R S31 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S312 replace;

[0180] Optionally, two non-adjacent R S31 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S313 replace;

[0181] m3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0182] R S32 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32A )2.-OR S32A 、-SR S32A 、-S(=O)R S32B 、-S(=O)2R S32B 、-C(=O)R S32B 、-C(=O)OR S32A 、-OC(=O)R S32B 、-C(=O)N(R S32A )2.-NR S32A C(=O)R S32B 、-OC(=O)OR S32A 、-NR S32A C(=O)OR S32A 、-NR S32A C(=S)OR S32A、-OC(=O)N(R S32A )2.-NR S32A C(=O)N(R S32A )2, -S(=O)OR S32A 、-OS(=O)R S32B 、-S(=O)N(R S32A )2.-NR S32A S(=O)R S32B 、-S(=O)2OR S32A 、-OS(=O)2R S32B 、-S(=O)2N(R S32A )2.-NR S32A S(=O)2R S32B 、-OS(=O)2OR S32A 、-NR S32A S(=O)2OR S32A 、-OS(=O)2N(R S32A )2.-NR S32A S(=O)2N(R S32A )2. -P(R S32A )2、-P(=O)(R S32B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32C )2.-OR S32C 、-SR S32C 、-S(=O)R S32C 、-S(=O)2R S32D 、-C(=O)R S32D、-C(=O)OR S32C 、-OC(=O)R S32D 、-C(=O)N(R S32C )2.-NR S32C C(=O)R S32D 、-OC(=O)OR S32C 、-NR S32C C(=O)OR S32C 、-NR S32C C(=S)OR S32C 、-OC(=O)N(R S32C )2.-NR S32C C(=O)N(R S32C )2, -S(=O)OR S32C 、-OS(=O)R S32C 、-S(=O)N(R S32C )2.-NR S32C S(=O)R S32D 、-S(=O)2OR S32C 、-OS(=O)2R S32D 、-S(=O)2N(R S32C )2.-NR S32C S(=O)2R S32D 、-OS(=O)2OR S32C 、-NR S32C S(=O)2OR S32C 、-OS(=O)2N(R S32C )2.-NR S32C S(=O)2N(R S32C )2. -P(R S32C )2、-P(=O)(R S32D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0183] Optionally, two R S32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S321 replace;

[0184] Optionally, two adjacent R S32 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S322 replace;

[0185] Optionally, two non-adjacent R S32 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S323 replace;

[0186] m4 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0187] R 37 Selected from -N(R 37A ) 2 or 3-10 membered heterocyclic group, wherein the 3-10 membered heterocyclic group is optionally independently replaced by one or more R S37 replace;

[0188] R S38 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38A )2.-OR S38A 、-SR S38A 、-S(=O)R S38B 、-S(=O)2R S38B 、-C(=O)R S38B 、-C(=O)OR S38A 、-OC(=O)R S38B 、-C(=O)N(R S38A )2.-NR S38A C(=O)R S38B 、-OC(=O)OR S38A 、-NR S38A C(=O)OR S38A 、-NR S38A C(=S)OR S38A 、-OC(=O)N(R S38A )2.-NR S38A C(=O)N(R S38A )2, -S(=O)OR S38A 、-OS(=O)R S38B 、-S(=O)N(R S38A )2.-NR S38A S(=O)RS38B 、-S(=O)2OR S38A 、-OS(=O)2R S38B 、-S(=O)2N(R S38A )2.-NR S38A S(=O)2R S38B 、-OS(=O)2OR S38A 、-NR S38A S(=O)2OR S38A 、-OS(=O)2N(R S38A )2.-NR S38A S(=O)2N(R S38A )2. -P(R S38A )2、-P(=O)(R S38B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38C )2.-OR S38C 、-SR S38C 、-S(=O)R S38D 、-S(=O)2R S38D 、-C(=O)R S38D 、-C(=O)OR S38C 、-OC(=O)R S38D 、-C(=O)N(R S38C )2.-NR S38C C(=O)R S38D 、-OC(=O)OR S38C 、-NR S38C C(=O)OR S38C、-NR S38C C(=S)OR S38C 、-OC(=O)N(R S38C )2.-NR S38C C(=O)N(R S38C )2, -S(=O)OR S38C 、-OS(=O)R S38D 、-S(=O)N(R S38C )2.-NR S38C S(=O)R S38D 、-S(=O)2OR S38C 、-OS(=O)2R S38D 、-S(=O)2N(R S38C )2.-NR S38C S(=O)2R S38D 、-OS(=O)2OR S38C 、-NR S38C S(=O)2OR S38C 、-OS(=O)2N(R S38C )2.-NR S38C S(=O)2N(R S38C )2. -P(R S38C )2、-P(=O)(R S38D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0189] Optionally, two R S38 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S381 replace;

[0190] Optionally, two adjacent R S38 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S382 replace;

[0191] Optionally, two non-adjacent R S38 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S383replace;

[0192] m8 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0193] R S39 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39A )2.-OR S39A 、-SR S39A 、-S(=O)R S39B 、-S(=O)2R S39B 、-C(=O)R S39B 、-C(=O)OR S39A 、-OC(=O)R S39B 、-C(=O)N(R S39A )2.-NR S39A C(=O)R S39B 、-OC(=O)OR S39A 、-NR S39A C(=O)OR S39A 、-NR S39A C(=S)OR S39A 、-OC(=O)N(R S39A )2.-NR S39A C(=O)N(R S39A )2, -S(=O)OR S39A 、-OS(=O)R S39B 、-S(=O)N(R S39A )2.-NR S39A S(=O)R S39B 、-S(=O)2OR S39A 、-OS(=O)2R S39B 、-S(=O)2N(R S39A )2.-NR S39A S(=O)2R S39B 、-OS(=O)2OR S39A 、-NR S39A S(=O)2OR S39A 、-OS(=O)2N(R S39A )2.-NR S39A S(=O)2N(R S39A )2. -P(R S39A)2. -P(=O)(R S39B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39C )2.-OR S39C 、-SR S39C 、-S(=O)R S39C 、-S(=O)2R S39D 、-C(=O)R S39D 、-C(=O)OR S39C 、-OC(=O)R S39D 、-C(=O)N(R S39C )2.-NR S39C C(=O)R S39D 、-OC(=O)OR S39C 、-NR S39C C(=O)OR S39C 、-NR S39C C(=S)OR S39C 、-OC(=O)N(R S39C )2.-NR S39C C(=O)N(R S39C )2, -S(=O)OR S39C 、-OS(=O)R S39C 、-S(=O)N(R S39C )2.-NR S39C S(=O)R S39D 、-S(=O)2OR S39C 、-OS(=O)2R S39D 、-S(=O)2N(RS39C )2.-NR S39C S(=O)2R S39D 、-OS(=O)2OR S39C 、-NR S39C S(=O)2OR S39C 、-OS(=O)2N(R S39C )2.-NR S39C S(=O)2N(R S39C )2. -P(R S39C )2. -P(=O)(R S39D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0194] Optionally, two R S39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S391 replace;

[0195] Optionally, two adjacent R S39 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S392 replace;

[0196] Optionally, two non-adjacent R S39 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S393 replace;

[0197] m9 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0198] R S315 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315A )2.-ORS315A 、-SR S315A 、-S(=O)R S315B 、-S(=O)2R S315B 、-C(=O)R S315B 、-C(=O)OR S315A 、-OC(=O)R S315B 、-C(=O)N(R S315A )2.-NR S315A C(=O)R S315B 、-OC(=O)OR S315A 、-NR S315A C(=O)OR S315A 、-NR S315A C(=S)OR S315A 、-OC(=O)N(R S315A )2.-NR S315A C(=O)N(R S315A )2, -S(=O)OR S315A 、-OS(=O)R S315B 、-S(=O)N(R S315A )2.-NR S315A S(=O)R S315B 、-S(=O)2OR S315A 、-OS(=O)2R S315B 、-S(=O)2N(R S315A )2.-NR S315A S(=O)2R S315B 、-OS(=O)2OR S315A 、-NR S315A S(=O)2OR S315A 、-OS(=O)2N(R S315A )2.-NR S315A S(=O)2N(R S315A )2. -P(R S315A )2. -P(=O)(R S315B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315C )2.-OR S315C 、-SR S315C 、-S(=O)R S315C 、-S(=O)2R S315D 、-C(=O)R S315D 、-C(=O)OR S315C 、-OC(=O)R S315D 、-C(=O)N(R S315C )2.-NR S315C C(=O)R S315D 、-OC(=O)OR S315C 、-NR S315C C(=O)OR S315C 、-NR S315C C(=S)OR S315C 、-OC(=O)N(R S315C )2.-NR S315C C(=O)N(R S315C )2, -S(=O)OR S315C 、-OS(=O)R S315C 、-S(=O)N(R S315C )2.-NR S315C S(=O)R S315D 、-S(=O)2OR S315C 、-OS(=O)2R S315D 、-S(=O)2N(R S315C )2.-NR S315C S(=O)2R S315D 、-OS(=O)2OR S315C 、-NR S315C S(=O)2OR S315C 、-OS(=O)2N(R S315C )2.-NR S315C S(=O)2N(R S315C )2. -P(R S315C )2、-P(=O)(RS315D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0199] Optionally, two R S315 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S3151 replace;

[0200] Optionally, two adjacent R S315 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S3152 replace;

[0201] Optionally, two non-adjacent R S315 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S3153 replace;

[0202] m 10 Selected from 0, 1, 2, 3, 4, 5 or 6;

[0203] R4 is selected from 6-10 membered aryl, 5-10 membered heteroaryl, wherein the 6-10 membered aryl, 5-10 membered heteroaryl, are independently unsubstituted or substituted with one or more R S4 replace;

[0204] Each occurrence of Z is independently selected from C or N;

[0205] When Z is selected from C, each occurrence of Ring E is independently selected from a 6-membered aryl ring or a 5-6-membered heteroaryl ring, and each occurrence of Ring F is a 3-10-membered carbocyclic ring or a 3-10-membered heterocyclic ring;

[0206] When Z is selected from N, each occurrence of Ring E is independently selected from a 5-6 membered heteroaryl ring, and each occurrence of Ring F is a 3-10 membered heterocyclic ring;

[0207] R S4 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4A )2.-OR S4A 、-SR S4A 、-S(=O)R S4B 、-S(=O)2R S4B 、-C(=O)R S4B 、-C(=O)OR S4A 、-OC(=O)R S4B 、-C(=O)N(R S4A )2.-NR S4A C(=O)R S4B 、-OC(=O)OR S4A 、-NR S4A C(=O)OR S4A 、-NR S4A C(=S)OR S4A 、-OC(=O)N(R S4A )2.-NR S4A C(=O)N(R S4A )2, -S(=O)OR S4A 、-OS(=O)R S4B 、-S(=O)N(R S4A )2.-NR S4A S(=O)R S4B 、-S(=O)2OR S4A 、-OS(=O)2R S4B 、-S(=O)2N(R S4A )2.-NR S4A S(=O)2R S4B 、-OS(=O)2OR S4A 、-NR S4A S(=O)2OR S4A 、-OS(=O)2N(R S4A )2.-NR S4A S(=O)2N(R S4A )2. -P(R S4A )2. -P(=O)(R S4B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4C )2.-OR S4C 、-SR S4C 、-S(=O)R S4D 、-S(=O)2R S4D 、-C(=O)R S4D 、-C(=O)OR S4D 、-OC(=O)R S4D 、-C(=O)N(R S4C )2.-NR S4C C(=O)R S4D 、-OC(=O)OR S4C 、-NR S4C C(=O)OR S4C 、-NR S4C C(=S)OR S4C 、-OC(=O)N(R S4C )2.-NR S4C C(=O)N(R S4C )2, -S(=O)OR S4C 、-OS(=O)R S4D 、-S(=O)N(R S4C )2.-NR S4C S(=O)R S4D 、-S(=O)2OR S4C 、-OS(=O)2R S4D 、-S(=O)2N(R S4C )2.-NR S4C S(=O)2R S4D 、-OS(=O)2OR S4C 、-NR S4C S(=O)2OR S4C 、-OS(=O)2N(R S4C )2.-NRS4C S(=O)2N(R S4C )2. -P(R S4C )2、-P(=O)(R S4D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0208] R5 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5A )2.-OR 5A 、-SR 5A 、-S(=O)R 5B 、-S(=O)2R 5B 、-C(=O)R 5B 、-C(=O)OR 5A 、-OC(=O)R 5B 、-C(=O)N(R 5A )2.-NR 5A C(=O)R 5B 、-OC(=O)OR 5A 、-NR 5A C(=O)OR 5A 、-NR 5A C(=S)OR 5A 、-OC(=O)N(R 5A )2.-NR 5A C(=O)N(R 5A )2, -S(=O)OR 5A 、-OS(=O)R 5B 、-S(=O)N(R 5A )2.-NR 5A S(=O)R 5B 、-S(=O)2OR 5A 、-OS(=O)2R 5B 、-S(=O)2N(R 5A )2.-NR 5A S(=O)2R 5B 、-OS(=O)2OR 5A 、-NR 5A S(=O)2OR 5A 、-OS(=O)2N(R 5A)2.-NR 5A S(=O)2N(R 5A )2. -P(R 5A )2. -P(=O)(R 5B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5C )2.-OR 5C 、-SR 5C 、-S(=O)R 5D 、-S(=O)2R 5D 、-C(=O)R 5D 、-C(=O)OR 5D 、-OC(=O)R 5D 、-C(=O)N(R 5C )2.-NR 5C C(=O)R 5D 、-OC(=O)OR 5C 、-NR 5C C(=O)OR 5C 、-NR 5C C(=S)OR 5C 、-OC(=O)N(R 5C )2.-NR 5C C(=O)N(R 5C )2, -S(=O)OR 5C 、-OS(=O)R 5D 、-S(=O)N(R 5C )2.-NR 5C S(=O)R 5D、-S(=O)2OR 5C 、-OS(=O)2R 5D 、-S(=O)2N(R 5C )2.-NR 5C S(=O)2R 5D 、-OS(=O)2OR 5C 、-NR 5C S(=O)2OR 5C 、-OS(=O)2N(R 5C )2.-NR 5C S(=O)2N(R 5C )2. -P(R 5C )2、-P(=O)(R 5D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0209] R 1A , R 1C , R S2A , R S2C , R S31A , R S31C , R S32A , R S32C , R 37A , R S38A , R S38C , R S39A , R S39C , R S315A , R S315C , R S4A , R S4C , R 5A , R 5C , R 8A , R 8C , R S8A and R S8C are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B)2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C、-NR C S(=O)2N(R C )2. -P(R C )2、-P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0210] Optionally, (two R 1A , two R 1C , two R S2A , two R S2C , two R S31A , two R S31C , two R S32A , two R S32C , two R 37A , two R S38A , two R S38C , two R S39A , two R S39C , two R S315A , two R S315C , two R S4A , two R S4C , two R 5A , two R 5C , two R 8A , two R 8C , two R S8A and two R S8C ) and the nitrogen atom to which it is connected together form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring, wherein the 3-10 membered heterocyclic ring or the 5-10 membered heteroaromatic ring is independently unsubstituted or substituted with one or more R SS replace;

[0211] R 1B , R 1D , R S2B , R S2D , R S31B , R S31D , R S32B , R S32D , R S38B , R S38D , R S39B , R S315B , R S315D , R S39D , R S4B , R S4D , R 5B , R 5D , R 8B , R 8D , R S8B and R S8DEach independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A , 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2ORC 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2. -P(R C )2. -P(=O)(R D )2, substituted by a 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl substituent;

[0212] (R A , R B , R C and R D ) are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are independently unsubstituted or substituted with one or more R SA replace;

[0213] R SX1 , R S21 , R S22 , R S23 , R S33 , R S34 , R S35 , R S37 , R S310 , R S316 , R S311 , R S312 , R S313 , R S321 , R S322, R S323 , R S381 , R S382 , R S383 , R S391 , R S392 , R S393 , R S3151 , R S3152 , R S3153 , R S81 , R S82 , R SS and R SA are each independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -OC(=O)O(C 1-6 alkyl), -NHC(=O)(OC 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(OC 1-6 alkyl), -OC(=O)NH(C 1-6 alkyl), -OC(=O)N(C 1-6 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH2, -N(C 1-6 alkyl)C(=O)NH(C 1-6Alkyl), -N(C 1-6 alkyl)C(=O)N(C 1-6 Alkyl)2, -S(=O)(OC 1-6 alkyl), -OS(=O)(C 1-6 alkyl), -S(=O)NH2, -S(=O)NH(C 1-6 alkyl), -S(=O)N(C 1-6 Alkyl)2, -NHS(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)(C 1-6 Alkyl), -S(=O)2(OC 1-6 alkyl), -OS(=O)2(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), -OS(=O)2O(C 1-6 alkyl), -NHS(=O)2O(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2O(C 1-6 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 alkyl), -OS(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 alkyl), -NHS(=O)2N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)S(=O)2NH2, -N(C 1-6 Alkyl)S(=O)2NH(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)2N(C 1-6 Alkyl)2, -PH(C 1-6 Alkyl), -P(C 1-6 Alkyl)2, -P(=O)H(C 1-6 alkyl), -P(=O)(C 1-6 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more selected from deuterium, halogen, -C 1-3 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy, -C 2-3 Alkenyl, -C 2-3 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -OH, -O(C 1-3 alkyl), -SH, -S(C 1-3 alkyl), -S(=O)(C 1-3 alkyl), -S(=O)2(C 1-3 alkyl), -C(=O)(C 1-3 alkyl), -C(=O)OH, -C(=O)(OC 1-3 alkyl), -OC(=O)(C 1-3 alkyl), -C(=O)NH2, -C(=O)NH(C 1-3 alkyl), -C(=O)N(C 1-3 Alkyl)2, -NHC(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(C 1-3 alkyl), -OC(=O)O(C 1-3 alkyl), -NHC(=O)(OC 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(OC 1-3 alkyl), -OC(=O)NH(C 1-3 alkyl), -OC(=O)N(C 1-3 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-3 alkyl), -NHC(=O)N(C 1-3 Alkyl)2, -N(C 1-3 alkyl)C(=O)NH2, -N(C 1-3 alkyl)C(=O)NH(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)N(C 1-3 Alkyl)2, -S(=O)(OC 1-3 alkyl), -OS(=O)(C 1-3alkyl), -S(=O)NH2, -S(=O)NH(C 1-3 alkyl), -S(=O)N(C 1-3 Alkyl)2, -NHS(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)(C 1-3 Alkyl), -S(=O)2(OC 1-3 alkyl), -OS(=O)2(C 1-3 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-3 alkyl), -S(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2(C 1-3 alkyl), -OS(=O)2O(C 1-3 alkyl), -NHS(=O)2O(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2O(C 1-3 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-3 alkyl), -OS(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-3 alkyl), -NHS(=O)2N(C 1-3 Alkyl)2, -N(C 1-3 Alkyl)S(=O)2NH2, -N(C 1-3 Alkyl)S(=O)2NH(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)2N(C 1-3 Alkyl)2, -PH(C 1-3 Alkyl), -P(C 1-3 Alkyl)2, -P(=O)H(C 1-3 alkyl), -P(=O)(C 1-3 alkyl), 3-10-membered cycloalkyl, 3-10-membered cycloalkenyl, 3-10-membered cycloalkynyl, 3-10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl;

[0214] Each occurrence of heterocyclyl or heterocycle independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S(=O) or S(=O)2;

[0215] Each occurrence of heteroaryl independently contains 1, 2, 3 or 4 heteroatoms selected from N, O or S.

[0216]

[12] . The compound of formula (I) described in

[11] , its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein the compound is selected from any of the following formulas:

[0217]

[0218]

[0219]

[13] . The compound of formula (I) described in

[12] , its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein R 81 and R 82 Selected from hydrogen, deuterium, -C 1-6 Alkyl, or 3-6 membered cycloalkyl;

[0220] Preferably, R 81 is selected from hydrogen or deuterium; R 82 Selected from methyl or cyclopropyl.

[0221] Ring M is selected from a 5-membered heteroaryl group containing 1, 2, 3 or 4 heteroatoms selected from N, O or S, or a 6-membered heteroaryl group containing 1 or 2 heteroatoms selected from N.

[0222] Preferably, ring M is a 6-membered heteroaryl group containing 1 or 2 heteroatoms selected from N, and the 6-membered heteroaryl group is substituted by one -NH2 or -OH, and may also be optionally substituted by one or more R S8 replace.

[0223] In some embodiments, the group Selected from

[0224] wherein n9 is selected from 0, 1, 2, 3 or 4;

[0225] R S8 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with an alkyl substituent.

[0226] Preferably, R S8 Selected from -NHCH3.

[0227] n8 is selected from 0 or 1, or n9 is selected from 0 or 1.

[0228] In some embodiments, the group Selected from

[0229]

[14] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[13] , wherein Y1 is selected from O.

[0230]

[15] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] , wherein R 31 , R 32 , R 33 , R 34 , R 35 and R 36 are each independently selected from hydrogen or deuterium.

[0231]

[16] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[15] , wherein n2 is selected from 1.

[0232]

[17] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[16] , wherein n3 is selected from 1 and n4 is selected from 1.

[0233]

[18] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of [1] to

[17] , wherein:

[0234] R3 is selected from

[0235] Ring B or Ring C is a 4-6 membered heterocyclic ring, which optionally further contains 1 or 2 heteroatoms selected from N or O;

[0236] Ring D is a 3-membered carbon ring;

[0237] R 37 Selected from -N(R 37A ) a 2- or 6-membered heterocyclic group, wherein the 3- to 6-membered heterocyclic group is optionally independently substituted by 1, 2 or 3 R S37 replace.

[0238] R 37A Selected from hydrogen, deuterium or -C 1-6 alkyl.

[0239]

[19] . The compound of formula (I) as described in any one of [1] to

[18] , its stereoisomer, its atropisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its pharmaceutically acceptable salt of its atropisomer, its prodrug, its deuterated molecule or its conjugated form, wherein:

[0240] Group for

[0241] Wherein, X3 is selected from CH2, NH, O, S, S(=O) or S(=O)2; when X3 is selected from CH2 or NH, the hydrogen in CH2 or NH is optionally replaced by one or more R S37 replace.

[0242] R 37A Selected from hydrogen, deuterium or -C 1-3 alkyl.

[0243]

[20] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of [1] to

[19] , wherein:

[0244] Group Selected from

[0245]

[21] . The compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[20] , wherein:

[0246] Group Selected from

[0247]

[22] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of [1] to

[21] , wherein:

[0248] Group for

[0249] Group for

[0250] Group for

[0251] Group for

[0252]

[23] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to

[14] , wherein R 38 and R 39 are each independently selected from hydrogen or deuterium.

[0253]

[24] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] , wherein n5 is selected from 1.

[0254]

[25] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[24] , wherein Ring I is a 4-6 membered cycloalkyl ring.

[0255]

[26] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[25] , wherein ring J is a 4-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O or S.

[0256]

[27] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[26] , wherein:

[0257] Group Selected from

[0258] Among them, R S381 Selected from hydrogen or R S38 ;

[0259] m 81 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8.

[0260]

[28] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[27] , wherein:

[0261] R S381 Selected from hydrogen, deuterium, -C 1-6 alkyl or 3-6 membered cycloalkyl, wherein the -C 1-6 The alkyl or 3-6 membered cycloalkyl is independently unsubstituted or 1, 2 or 3 are selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2-NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with a substituent.

[0262]

[29] . A compound of formula (I) as described in any one of [1] to

[14] and

[23] to

[28] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein R S381 is selected from hydrogen, deuterium, -CH3, -CH2CH3 or cyclopropyl.

[0263]

[30] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[29] , wherein m 81 Select from 0.

[0264]

[31] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[30] , wherein:

[0265] m9 is selected from 0, 1 or 2.

[0266]

[32] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[31] , wherein:

[0267] m9 is selected from 0.

[0268]

[33] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[32] , wherein:

[0269] m9 is selected from 1.

[0270]

[34] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[33] , wherein:

[0271] Group Selected from

[0272]

[0273] Among them, R S394 Selected from hydrogen or R S391 .

[0274]

[35] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[34] , wherein:

[0275] R S39 is selected from halogen;

[0276] Preferably, R S39 Select from -F.

[0277]

[36] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[23] to

[35] , wherein:

[0278] R S391 Selected from hydrogen, deuterium, halogen or -C 1-6 Alkyl; wherein the -C1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2-OH or -OC 1-6 Substitution of alkyl groups;

[0279] Preferably, R S391 is selected from hydrogen, deuterium, -F or -CH3.

[0280]

[37] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[36] , wherein:

[0281] Group Selected from

[0282]

[38] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[23] to

[37] , wherein:

[0283] Group Selected from

[0284]

[39] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of [1] to

[14] , wherein:

[0285] Ring B is a 4-6 membered heterocyclic ring containing a fused nitrogen atom.

[0286]

[40] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[39] , wherein:

[0287] Ring C is a 4-6 membered heterocyclic ring containing a fused nitrogen atom.

[0288]

[41] A compound of formula (I) as described in any one of [1] to

[14] ,

[39] to

[40] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, wherein:

[0289] Group Selected from

[0290]

[42] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[41] , wherein m3 is selected from 0, 1, 2, 3 or 4.

[0291]

[43] . A compound of formula (I) as described in any one of [1] to

[14] and

[39] to

[42] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein R S31 Selected from deuterium or -F;

[0292] Optionally, two R S31 Together with the carbon atoms to which they are attached, they form Or cyclopropyl; wherein said or cyclopropyl is independently unsubstituted or substituted with 1, 2 or 3 R S311 replace; or

[0293] Optionally, two adjacent R S31 Together with the carbon atoms to which they are attached, they form a 5-10 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, or a 5-10 membered heteroaromatic ring containing 1 or 2 heteroatoms selected from N, O or S, wherein each ring is independently unsubstituted or substituted with 1, 2 or 3 R S312 replace.

[0294]

[44] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[39] to

[43] , wherein:

[0295] Group Selected from

[0296] in,

[0297] Ring G is selected from a 5-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, a 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S;

[0298] Ring H is selected from a 5-10 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, a 5-10 membered heteroaryl containing 1 or 2 heteroatoms selected from N, O or S;

[0299] R S36 Definition and R S31 same;

[0300] R S314 Selected from hydrogen or R S311 ;

[0301] m 31 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0302] m 32 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0303] m 33 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0304] m 34 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0305] m5 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0306] m6 is selected from 0, 1, 2, 3, 4, 5 or 6.

[0307] 45. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[44] , wherein:

[0308] Group Selected from

[0309]

[0310] in,

[0311] m 31 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0312] m 32 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8;

[0313] m 33 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

[0314] m 34 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0315] m5 is selected from 0, 1, 2, 3, 4, 5 or 6;

[0316] m6 is selected from 0, 1, 2, 3, 4, 5 or 6.

[0317]

[46] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[39] to

[45] , wherein:

[0318] R S311 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Substitution of alkyl groups;

[0319] R S312 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with a substituent.

[0320] R S314 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with a substituent.

[0321]

[47] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[39] to

[46] , wherein:

[0322] R S311 Independently selected from deuterium, -F or -OCH3;

[0323] R S312 Independently selected from deuterium, -F, -OCH3 or -CH2OCH3;

[0324] R S314 Independently selected from hydrogen, deuterium, -F, -CH3, -CH2OCH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2CH(CH3)2.

[0325]

[48] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[49] , wherein:

[0326] R S36 Selected from deuterium or -F.

[0327]

[49] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[48] , wherein:

[0328] m 31 Select from 0 or 1;

[0329] m 32Select from 0 or 1;

[0330] m 33 Select from 0 or 1;

[0331] m 34 Select from 0 or 1;

[0332] m5 is selected from 0 or 1;

[0333] m6 is selected from 0 or 1.

[0334]

[50] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[49] , wherein:

[0335] Group Selected from

[0336]

[51] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[39] to

[50] , wherein:

[0337] Group Selected from

[0338]

[52] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to

[14] , wherein R 310 and R 311 are each independently selected from hydrogen or deuterium.

[0339]

[53] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[14] or

[52] , wherein n6 is selected from 1 or 2.

[0340]

[54] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] ,

[52] or

[53] , wherein:

[0341] Ring K is a 4- to 10-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O atoms.

[0342]

[55] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[52] to

[54] , wherein:

[0343] Group Selected from

[0344] Wherein, ring L is selected from a 4-6 membered heterocyclic ring, which optionally further contains 1 or 2 heteroatoms selected from N or O.

[0345]

[56] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[52] to

[55] , wherein:

[0346] Group Selected from

[0347]

[57] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[52] to

[56] , wherein:

[0348] R S315 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl.

[0349]

[58] . A compound of formula (I) as described in any one of [1] to

[14] ,

[52] to

[57] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein R S315 Independently selected from -F or -CH3.

[0350]

[59] . A compound of formula (I) as described in any one of [1] to

[14] ,

[52] to

[58] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein m 10 Selected from 0, 1, 2 or 3.

[0351]

[60] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as described in any one of [1] to

[14] and

[52] to

[59] , wherein:

[0352] Group Selected from

[0353]

[61] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[14] and

[52] to

[60] , wherein:

[0354] Group Selected from

[0355]

[62] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to

[14] , wherein: Select from Table C below:

[0356] Table C

[0357]

[0358]

[0359]

[0360]

[0361]

[0362]

[0363]

[0364]

[0365]

[63] . A compound of formula (I) according to any one of claims [1] to

[62] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, wherein R4 is selected from phenyl, pyridyl, naphthyl, quinolyl, isoquinolyl, indazolyl, benzothienyl, or benzothiazolyl, and the phenyl, pyridyl, naphthyl, quinolyl, isoquinolyl, indazolyl, benzothienyl, or benzothiazolyl is unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 R S4 replace.

[0366]

[64] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to

[63] , wherein:

[0367] R4 is selected from

[0368]

[0369] m7 is selected from 0, 1, 2 or 3;

[0370] R S4a Selected from -OH or -NH2;

[0371] R S4b Selected from hydrogen, deuterium, and halogen;

[0372] R S4c Selected from hydrogen, deuterium, -C 1-3 Alkyl, -C 2-3 Alkenyl or -C 2-3 Alkynyl;

[0373] R S4d is selected from hydrogen, deuterium or halogen;

[0374] R S4e Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0375] R S4f Selected from -OH or -NH2;

[0376] R S4g Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0377] R S4h Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0378] R S4i Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0379] R S4j Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl;

[0380] R S4k Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl;

[0381] R S4l Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl;

[0382] R S4m Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl;

[0383] R S4n Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0384] R S4o Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0385] R S4p Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl.

[0386]

[65] . The compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of [1] to

[64] , wherein:

[0387] m7 is selected from 0;

[0388] R S4a Selected from -OH or -NH2;

[0389] R S4b Select from -F;

[0390] R S4c is selected from ethyl, vinyl or ethynyl;

[0391] R S4d is selected from hydrogen, or -F;

[0392] R S4e Select from -F;

[0393] R S4f Selected from -NH2;

[0394] R S4g is selected from hydrogen, -F, or methyl;

[0395] R S4h is selected from hydrogen, -F or methyl;

[0396] R S4i Selected from -I or -CF3;

[0397] R S4j Selected from -CN;

[0398] R S4k Selected from hydrogen;

[0399] R S4l Selected from methyl;

[0400] R S4m Selected from -CF3, -OCF2Cl, -OCF3 or -CF2H;

[0401] R S4n is selected from hydrogen, -F or methyl;

[0402] R S4o is selected from hydrogen, -F or methyl;

[0403] R S4p is selected from hydrogen, -F or methyl.

[0404]

[66] . The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule as described in any one of [1] to

[65] , wherein R4 is selected from Table D:

[0405] Table D

[0406]

[0407]

[0408]

[67] . The compound of formula (I) as described in any one of [1] to

[66] , its stereoisomer, its atropisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its pharmaceutically acceptable salt of its atropisomer, its prodrug, its deuterated molecule or its conjugated form, wherein the prodrug is selected from the following formula:

[0409]

[0410] R 4a Selected from

[0411] R 4c Selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace;

[0412] R 4d and R 4e are each independently selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C(=O)C 1-6 Alkyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace;

[0413] R 4f and R 4g are each independently selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C(=O)C 1-6 Alkyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace;

[0414] R 4h , R 4i , R 4m , R 4n and R 4p are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are optionally substituted by one or more selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;

[0415] Optionally, R 4f and R 4gTogether with the atoms to which they are attached, they form a 4-10 membered heterocyclyl ring, which optionally further contains 1 or 2 heteroatoms selected from N, O, S, S(=O) or S(=O)2, and is optionally replaced by one or more R 4j replace;

[0416] Optionally, R 4f and R 4h Together with the atoms to which they are attached, they form a 4-10 membered heterocyclyl ring, which optionally further contains 1 or 2 heteroatoms selected from N, O, S, S(=O) or S(=O)2, and is optionally replaced by one or more R 4j replace.

[0417] Each occurrence of R 4j are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, oxo, -NO2, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl, wherein the -C1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently optionally substituted by 1, 2 or 3 groups selected from halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -CN, oxo, -OH, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2; -OC 1-6 Alkyl is substituted with a substituent; or -C 1-6 The alkyl group is replaced by 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, -CN, -OH, -NH2, -NH(C 1-6 Alkyl), N(C 1-6 Alkyl)2 or -OC 1-6 Substitution of alkyl groups;

[0418] The other variable definitions are the same as above;

[0419] Preferably, R 4a Selected from Table E below:

[0420] Table E

[0421]

[0422]

[0423]

[0424]

[68] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[67] , wherein R5 is selected from halogen.

[0425]

[69] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[68] , wherein R5 is selected from -F.

[0426]

[70] . A compound of formula (I) as described in any one of [1] to

[69] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, wherein the compound is selected from the following Table F:

[0427] Table F

[0428]

[0429]

[0430]

[0431]

[0432]

[0433]

[0434]

[0435]

[0436]

[0437]

[0438]

[0439]

[0440]

[0441]

[0442]

[0443]

[0444]

[0445]

[0446]

[0447]

[0448]

[0449]

[0450]

[0451]

[0452]

[0453]

[0454]

[0455]

[0456]

[0457]

[0458]

[0459]

[0460]

[0461]

[0462]

[0463]

[0464]

[0465]

[0466]

[0467]

[0468]

[0469]

[0470]

[0471]

[0472]

[0473]

[0474]

[0475]

[0476]

[0477]

[0478]

[0479]

[0480]

[0481]

[0482]

[0483]

[0484]

[0485]

[0486]

[0487]

[0488]

[0489]

[0490]

[0491]

[0492]

[0493]

[0494]

[0495]

[0496]

[0497]

[0498]

[0499]

[0500]

[0501]

[0502]

[0503]

[0504]

[0505]

[0506]

[0507]

[0508]

[0509]

[0510]

[0511]

[0512]

[0513]

[0514]

[0515]

[0516]

[0517]

[0518]

[0519]

[0520]

[0521]

[0522]

[0523]

[0524]

[0525]

[0526]

[0527]

[0528]

[0529]

[0530]

[0531]

[0532]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538]

[0539]

[0540]

[0541]

[0542]

[0543]

[0544]

[0545]

[0546]

[0547]

[0548]

[0549]

[0550]

[0551]

[0552]

[0553]

[0554]

[0555]

[0556]

[0557]

[0558]

[0559]

[0560]

[0561]

[0562]

[0563]

[0564]

[0565]

[0566]

[0567]

[0568]

[0569]

[0570]

[0571]

[0572]

[0573]

[0574]

[0575]

[0576]

[0577]

[0578]

[0579]

[0580]

[0581]

[0582]

[0583]

[0584]

[0585]

[0586]

[0587]

[0588]

[0589]

[0590]

[0591]

[0592]

[0593]

[0594]

[0595]

[0596]

[0597]

[0598]

[0599]

[0600]

[0601]

[0602]

[0603]

[0604]

[0605]

[0606]

[0607]

[0608]

[0609]

[0610]

[0611]

[0612]

[0613]

[0614]

[0615]

[0616]

[0617]

[0618]

[0619]

[0620]

[0621]

[0622]

[0623]

[0624]

[0625]

[0626]

[0627]

[0628]

[0629]

[0630]

[0631]

[0632]

[0633]

[0634]

[0635]

[0636]

[0637]

[0638]

[0639]

[0640]

[0641]

[0642]

[71] . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) as described in any one of [1] to

[81] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof and a pharmaceutically acceptable excipient.

[0643]

[72] . A method for treating cancer in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) as described in any one of [1] to

[81] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition as described in

[71] .

[0644]

[73] . A method for treating cancer in a subject in need thereof, the method comprising:

[0645] (a) determining whether a cancer is associated with K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-RasG12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutations and / or K-Ras wild-type amplification; and

[0646] (b) if yes, administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) described in any one of [1] to

[81] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition described in

[71] .

[0647]

[74] . A compound of formula (I) as described in any one of [1] to

[81] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition as described in

[71] for use in treatment.

[0648]

[75] . A compound of formula (I) as described in any one of [1] to

[81] , a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition as described in

[71] for use as a medicament.

[0649]

[76] . A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof as described in any one of [1] to

[81] , or a pharmaceutical composition as described in

[71] for use in a method for treating cancer.

[0650]

[77] . Use of the compound of formula (I) described in any one of [1] to

[81] , its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of a stereoisomer, its prodrug, its deuterated molecule or its conjugated form, or the pharmaceutical composition described in

[71] for treating cancer.

[0651]

[78] . Use of the compound of formula (I) described in any one of [1] to

[81] , its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of a stereoisomer, its prodrug, its deuterated molecule or PROTAC molecule, or the pharmaceutical composition described in

[71] in the preparation of a medicament for treating cancer.

[0652]

[79] . The method for treating cancer described in

[71] , the method for treating cancer described in

[76] , the use for treating cancer described in

[77] , or the use for preparing a medicament for treating cancer described in

[78] , wherein the cancer is selected from pancreatic cancer, colorectal cancer, lung cancer (such as non-small cell lung cancer), breast cancer, colon cancer, gastric cancer, endometrial cancer, esophageal cancer or gastroesophageal junction cancer.

[0653]

[80] . The method for treating cancer described in

[71] or

[79] , the method for treating cancer described in

[76] or

[79] , the use for treating cancer described in

[77] or

[79] , or the use of a medicament for treating cancer described in

[78] or

[79] , wherein the cancer is associated with at least one of K-Ras G12C, K-Ras G12D, K Ras G12V, K Ras G13D, K Rasg G12R, KRass G12S, K Rash G12A, K RasQ61H mutations and / or K-Ras wild-type amplification.

[0654]

[81] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G12C-related cancer

[0655]

[82] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G12D-related cancer.

[0656]

[84] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G13D-related cancer.

[0657]

[85] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G12R-related cancer.

[0658]

[86] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G12S-related cancer.

[0659]

[87] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a K-Ras G12A-related cancer.

[0660]

[88] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use of

[78] ,

[79] or

[80] for preparing a medicament for treating cancer, wherein the cancer is a K-Ras Q61H-related cancer.

[0661]

[89] . The method for treating cancer described in

[71] ,

[79] or

[80] , the method for treating cancer described in

[76] ,

[79] or

[80] , the use for treating cancer described in

[77] ,

[79] or

[80] , or the use for preparing a medicament for treating cancer described in

[78] ,

[79] or

[80] , wherein the cancer is a cancer associated with wild-type amplification of K-Ras.

[0662] definition

[0663] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. All patents, patent applications, and publications cited in this application are incorporated by reference.

[0664] Unless otherwise indicated, the terms "halogen" or "halo" are used interchangeably herein to refer to fluorine, chlorine, bromine or iodine. Preferred halogen groups include -F, -Cl and -Br.

[0665] Unless otherwise specified, the term "alkyl" used in this application includes a saturated monovalent hydrocarbon group having a straight chain or a branched chain. 1-6Alkyl includes methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, n-hexyl, 2-hexyl and 2-methylpentyl. Similarly, C 1-3 C in the alkyl group 1-3 It is defined to mean a group having 1, 2, 3, 4, 5 or 6 carbon atoms in a straight or branched chain arrangement.

[0666] Unless otherwise indicated, the term "haloalkyl" (e.g., -C 1-6 Haloalkyl, -C 1-4 Haloalkyl or -C 1-3 Haloalkyl) refers to an alkyl chain as defined herein (e.g., -C 1-6 Alkyl, -C 1-4 Alkyl or -C 1-3 One or more (e.g., one, two, or three) hydrogen atoms in the alkyl group are replaced by halogen, such as trifluoromethyl, difluoromethyl, and fluoromethyl.

[0667] The term "alkylene" refers to a difunctional group derived from an alkyl group as defined above by removing a hydrogen atom, for example, methylene (i.e., -CH2-), ethylene (i.e., -CH2-CH2- or -CH(CH3)-), and propylene (i.e., -CH2-CH2-CH2-, -CH(-CH2-)CH3)- or -CH2-CH(CH3)-).

[0668] The term "alkenyl" refers to a straight or branched chain hydrocarbon group containing one or more double bonds, typically 2 to 20 carbon atoms in length. 2-6 The term "alkenyl" refers to a group consisting of 2 to 6 carbon atoms. Alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, 2-methyl-2-buten-1-yl, heptenyl, octenyl, and the like.

[0669] The term "alkynyl" includes straight or branched chain hydrocarbon groups containing one or more triple bonds and generally having a length of 2 to 20 carbon atoms. 2-6 "Alkynyl" contains 2 to 6 carbon atoms. Representative alkynyl groups include, but are not limited to, for example, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octynyl, and the like.

[0670] The term "alkoxy" radical is an oxygen ether formed from the alkyl groups described above.

[0671] Unless otherwise indicated, the term "aryl" as used herein refers to an unsubstituted or substituted monocyclic or polycyclic aromatic ring system containing carbon ring atoms. Preferred aryl groups are monocyclic or bicyclic 6-10 membered aromatic ring systems. Preferred aryl groups are phenyl and naphthyl.

[0672] Unless otherwise specified, the term "heterocycle" as used in this application refers to an unsubstituted and substituted monocyclic or polycyclic non-aromatic ring system containing one or more heteroatoms, including monocyclic heterocycles, bicyclic heterocycles, bridged heterocycles, fused heterocycles or ortho heterocycles. Preferred heteroatoms include N, O and S, including N-oxides, sulfur oxides and dioxides. Preferably, the ring is a three- to ten-membered ring, and is fully saturated or has one or more degrees of unsaturation. Multiple degrees of substitution are included in this definition, preferably one, two or three substitutions. Examples of such heterocyclic groups include, but are not limited to, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, oxoazepanyl, azepanyl, tetrahydrofuranyl, dioxolanyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone and oxadiazolyl.

[0673] Unless otherwise indicated, the term "heteroaryl" as used herein means an aromatic ring system containing carbon and at least one heteroatom. The heteroaryl group may be monocyclic or polycyclic, substituted or unsubstituted. Monocyclic heteroaryl groups may contain 1 to 4 heteroatoms in the ring, while polycyclic heteroaryl groups may contain 1 to 10 heteroatoms. Polycyclic heteroaryl rings may contain fused, spiro or bridged ring connections, for example, bicyclic heteroaryl groups are polycyclic heteroaryl groups. Bicyclic heteroaryl rings may contain 8 to 12 member atoms. Monocyclic heteroaryl rings may contain 5 to 8 member atoms (carbon atoms and heteroatoms). Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, triazolyl, pyridinyl, pyridazinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, benzoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyladeninyl, quinolinyl, or isoquinolinyl.

[0674] The term "carbocycle" refers to a substituted or unsubstituted non-aromatic ring system containing only carbon atoms, such as monocyclic, bicyclic, bridged, fused, silyl, etc. Exemplary "cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0675] The term "oxo" refers to an oxygen atom and a carbon atom to which it is attached to form a radical

[0676] The term "composition" as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product resulting directly or indirectly from combination of the specified ingredients in the specified amounts. Thus, a pharmaceutical composition containing a compound of the invention as an active ingredient and a method for preparing the composition.

[0677] The term "pharmaceutically acceptable salt" refers to a salt prepared from a pharmaceutically acceptable non-toxic base or acid. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from a pharmaceutically acceptable non-toxic base including an inorganic base and an organic base. When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from a pharmaceutically acceptable non-toxic acid including an inorganic acid and an organic acid. Since the compounds of the present invention are intended for pharmaceutical use, they are preferably provided in a substantially pure form, for example at least 60% pure, more suitably at least 75% pure, and especially at least 98% pure (% by weight).

[0678] The present invention includes within its scope prodrugs of the compounds of the present invention. Typically, such prodrugs are functional derivatives of compounds that are easily converted into desired compounds in vivo. Therefore, in the therapeutic methods of the present invention, the term "administering" should include treating various described disorders with a specifically disclosed compound or with a compound that may not be specifically disclosed but is converted into a specific compound in vivo after administration to a subject. Conventional procedures for selecting and preparing suitable prodrug derivatives are described in, for example, "Prodrug Design" ("Design of Prodrugs", ed. 25 H. Bundgaard, Elsevier, 1985).

[0679] The definition of any substituent or variable at a particular position in a molecule is intended to be independent of the definitions of substituents or variables at other positions in the molecule. It should be understood that one of ordinary skill in the art can select substituents and substitution patterns on the compounds of the invention to yield chemically stable compounds and can be readily synthesized by techniques known in the art as well as the methods illustrated in this application.

[0680] The present invention includes the compounds, which may contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention includes all such possible diastereomers and racemic mixtures thereof, their substantially pure resolved enantiomers, all possible geometric isomers and pharmaceutically acceptable salts thereof.

[0681] The present invention includes all stereoisomers of the compounds and pharmaceutically acceptable salts thereof. In addition, mixtures of stereoisomers and isolated specific stereoisomers are also included. In the process of synthetic steps for preparing these compounds, or in the process of steps using racemization or epimerization methods known to those skilled in the art, the products of these steps may be mixtures of stereoisomers.

[0682] The term "stereoisomer" used in the present invention refers to isomers in which atoms or atomic groups in a molecule are connected to each other in the same order but have different spatial arrangements, including configurational isomers and conformational isomers. Configurational isomers include geometrical isomers and optical isomers, and optical isomers mainly include enantiomers and diastereomers. The present invention includes all possible stereoisomers of compounds.

[0683] Certain compounds provided herein may exist as atropisomers, which are conformational stereoisomers resulting from single bond rotation in the molecule being prevented or significantly slowed due to spatial interactions with other parts of the molecule. The compounds provided herein include all atropisomers, including both pure single atropisomer preparations, respective enriched preparations, or respective non-specific mixtures. When the single bond rotation barrier is high enough and the mutual conversion between conformations is slow enough, separation and isolation of isomeric species can be allowed.

[0684] The present invention is intended to include all isotopes of atoms occurring in the compounds of the present invention. Isotopes include atoms having the same atomic number but different mass numbers. As a general example and not limitation, isotopes of hydrogen include deuterium and tritium. Isotopes of hydrogen can be represented by 1H (hydrogen), 2 H (deuterium) and 3 H (tritium). They are also commonly expressed as D (deuterium) and T (tritium). In this application, CD3 means that all hydrogen atoms are deuterated methyl. Carbon isotopes include 13 C and 14 C. Isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically labeled reagent in place of a non-labeled reagent.

[0685] Unless otherwise specifically indicated, when the compound of the present invention exists in tautomerism, the present invention includes any possible tautomers and pharmaceutically acceptable salts thereof and mixtures thereof.

[0686] When the compound of the present invention and its pharmaceutically acceptable salt exist in the form of solvate or polymorph, the present invention includes any possible solvate and polymorph. The type of solvent forming the solvate is not particularly limited as long as the solvent is pharmaceutically acceptable.

[0687] The pharmaceutical composition of the present invention comprises the compounds of the present invention (or its pharmaceutically acceptable salt) as active ingredient, pharmaceutically acceptable carrier and optional other therapeutic ingredients or adjuvant. Although the most suitable approach in any given case will depend on the specific host, and the nature and severity of the disease (the active ingredient is being used for the treatment of the disease), the composition includes compositions suitable for oral, rectal, local and parenteral (including subcutaneous, intramuscular and intravenous) administration. The pharmaceutical composition can be conveniently present in unit dosage form and prepared by any method well-known in the pharmaceutical field.

[0688] In practice, according to conventional pharmaceutical formulation techniques, the compound of formula (I) as defined in the present application, its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of a stereoisomer, its prodrug, its deuterated molecule or its conjugated form as an active ingredient can be combined with a pharmaceutical carrier into a close mixture. Depending on the dosage form required for the route of administration, such as oral or parenteral (including intravenous), the carrier can take a variety of forms. Therefore, the pharmaceutical composition of the present invention can exist as discrete units suitable for oral administration, such as capsules, cachets or tablets, each containing a predetermined amount of active ingredients. In addition, the composition can exist as a powder form, a granular form, a solution form, a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion or an oil-in-water emulsion. In addition to the above-mentioned common dosage forms, the compound of the present invention or its pharmaceutically acceptable salt can also be administered by controlled release and / or delivery device. The composition can be prepared by any pharmaceutical method. Generally, such a method includes the step of combining the active ingredient with a carrier constituting one or more essential ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product is then conveniently shaped into the desired presentation.

[0689] Therefore, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt thereof. The compound of formula I or a pharmaceutically acceptable salt thereof may also be included in a pharmaceutical composition in combination with one or more other therapeutically active compounds.

[0690] The pharmaceutical carrier used can be, for example, solid, liquid or gas. Examples of solid carriers include lactose, gypsum, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers are syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In the preparation of compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethylene glycol, oil, alcohol, flavoring agents, preservatives, colorants, etc. can be used to form oral liquid preparations such as suspensions, elixirs and solutions; and carriers such as starch, sugar, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrants, etc. can be used to form oral solid preparations such as powders, capsules and tablets. Tablets and capsules are preferred oral dosage units due to ease of administration, which use solid pharmaceutical carriers. Alternatively, tablets can be coated by standard aqueous or non-aqueous techniques.

[0691] Tablets containing the compositions of the present invention can be prepared by compressing or molding with one or more auxiliary ingredients or adjuvants, optionally. Compressed tablets can be prepared by compressing the active ingredient in a free-flowing form such as powder or granules (optionally mixed with a binder, lubricant, inert diluent, surfactant or dispersant) in a suitable machine. Molded tablets can be prepared by molding a mixture of powdered compounds moistened with an inert liquid diluent in a suitable machine. Molded tablets can be prepared by molding a mixture of powdered compounds moistened with an inert liquid diluent in a suitable machine. Each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each capsule or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a preparation for oral administration can contain about 0.5 mg to about 5 g of active agent, and mixed with a suitable and convenient amount of carrier material, which can account for about 0.05% to about 95% of the total composition. Dosage unit forms generally contain from about 0.01 mg to about 2 g of active ingredient, typically 0.01 mg, 0.02 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, 1000 mg, 1500 mg or 2000 mg.

[0692] The pharmaceutical composition of the present invention suitable for parenteral administration can be prepared as a solution or suspension of the active compound in water. Suitable surfactants, such as hydroxypropylcellulose, can be included. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and mixtures thereof in oil. In addition, preservatives can be included to prevent the harmful growth of microorganisms.

[0693] The pharmaceutical composition of the present invention suitable for injection includes sterile aqueous solution or dispersion. In addition, the composition can be in the form of sterile powder for the temporary preparation of such sterile injectable solution or dispersion. In all cases, the final injection dosage form must be sterile and must be an effective fluid. The pharmaceutical composition must be stable under manufacturing and storage conditions; therefore, it is preferably stored to prevent the contamination of microorganisms such as bacteria and fungi. The carrier can be a solvent or a dispersion medium, including, for example, water, ethanol, polyols (such as glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils and suitable mixtures thereof.

[0694] The pharmaceutical composition of the present invention can be in a form suitable for topical use, such as an aerosol, cream, ointment, lotion, powder, etc. In addition, the composition can be in a form suitable for use in a transdermal device. These preparations can be prepared by conventional processing methods using the compounds of the present invention or their pharmaceutically acceptable salts. As an example, a cream or ointment is prepared by mixing a hydrophilic material and water with about 0.05wt% to about 10wt% of the compound to produce a cream or ointment with a desired consistency.

[0695] The pharmaceutical composition of the present invention can be in a form suitable for rectal administration, wherein the carrier is a solid. Preferably, the mixture forms a unit dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be easily formed by first mixing the composition with a softened or melted carrier, then cooling and molding in a mold.

[0696] In addition to the above-mentioned carrier components, if appropriate, the above-mentioned pharmaceutical preparations may also include one or more additional carrier components, such as diluents, buffers, flavoring agents, adhesives, surfactants, thickeners, lubricants, preservatives (including antioxidants) and the like. In addition, other adjuvants may be included to make the preparation isotonic with the blood of the intended recipient. Compositions containing the compound described in Formula I or its pharmaceutically acceptable salt may also be prepared in the form of powders or liquid concentrates.

[0697] Typically, dosage levels of about 0.001 mg / kg to about 150 mg / kg of body weight per day are useful for treating the above conditions, or about 0.05 mg to about 7 g per patient per day. For example, inflammation, cancer, psoriasis, allergies / asthma, immune system diseases and disorders, central nervous system (CNS) diseases and disorders may be effectively treated by administering about 0.001 to 50 mg of the compound per kilogram of body weight per day, or about 0.05 mg to about 3.5 g per patient per day.

[0698] However, it should be understood that the specific dosage level for any particular patient will depend on a variety of factors including age, weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease being treated.

[0699] These and other aspects will become apparent from the following written description of the invention.

[0700] It will be appreciated that, if any prior art publication is referred to in this application; such reference does not constitute an admission that the publication forms part of the common general knowledge in the art in any country.

[0701] The disclosures of all publications, patents, patent applications, and published patent applications cited in this application by identification are hereby incorporated by reference in their entirety.

[0702] Although the foregoing invention has been described in detail by way of illustration and example for ease of understanding, it is obvious that some minor changes and modifications may be made by those skilled in the art. Therefore, the description and example should not be interpreted as limiting the scope of the invention.

[0703] The compounds of the present invention can be synthesized from commercially available reagents using the synthetic methods and reaction schemes described herein. The examples outlining specific synthetic routes are intended to provide guidance to synthetic chemists in the art, who will readily appreciate that solvents, concentrations, reagents, protecting groups, the sequence of synthetic steps, times, temperatures, etc. can be modified as needed within the skill and judgment of those skilled in the art. Example

[0704] The compounds of the present invention can be synthesized and tested for activity according to pharmacological experiments.

[0705] DMF N,N-Dimethylformamide EA Ethyl acetate <![CDATA[CH3CN / MeCN]]> Acetonitrile DCM Dichloromethane NaH Sodium hydride THF Tetrahydrofuran <![CDATA[Na2SO4]]> Sodium sulfate <![CDATA[Cs2CO3]]> Cesium carbonate TFA 2,2,2-Trifluoroacetic acid <![CDATA[POCl3]]> Phosphorus oxychloride <![CDATA[NaHCO3]]> Sodium bicarbonate DMSO Dimethyl sulfoxide DIPEA / DIEA N,N-Diisopropylethylamine Cf Cesium fluoride Dabco 1,4-diazobicyclo(2.2.2)octane sat. Saturated h / hrs Hour(s)

[0706] Intermediate 1 (INT 1)

[0707]

[0708] According to the procedure of WO2021041671, INT 1 was synthesized using 2-(4-fluorophenyl)acetic acid as the starting material.

[0709] Intermediate 2 (INT 2)

[0710]

[0711] 2,6-Dichloropyridin-4-amine (35.7 g, 219.0 mmol) and 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane ditetrafluoroborate (93.1 g, 262.8 mmol) were dissolved in DMF (357 mL) and CH3CN (357 mL), and the mixture was stirred at 80°C for 6 hours. The reaction solution was quenched with water (400 mL), extracted with DCM (400 mL×3), and the organic layers were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column (eluent petroleum ether:EtOAc=30:1, v / v) to give INT 2-1 (12.6 g, purity about 50%), MS (ESI, m / z): 181 [M+H] + .

[0712] A mixture of INT 2-1 (2.0 g, 11.05 mmol), NIS (2.98 g, 13.26 mmol) and p-toluenesulfonic acid monohydrate (105 mg, 0.55 mmol) was stirred at 70 ° C for 4 hours in CH3CN (8.4 mL) under a nitrogen atmosphere. The reaction mixture was quenched with water (20 mL), extracted with EtOAc (20 mL × 3), the organic layers were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column (eluted with petroleum ether: EtOAc = 50: 1 to 20: 1, v / v) to give INT 2-2 (3.6 g). MS (ESI, m / z): 307 [M + H] + .

[0713] A mixture of INT 2-2 (1.0 g, 3.26 mmol), Pd(PPh3)2Cl2 (229 mg, 0.33 mmol) and Et3N (1.19 g, 11.77 mmol) was stirred in a sealed tube under a carbon monoxide atmosphere (1.5 MPa) at 80 ° C for 20 hours in EtOH (17.0 mL). The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column to give INT2-3 (1.2 g). MS (ESI, m / z): 253 [M+H] + .

[0714] A mixture of INT 2-3 (800 mg, 3.16 mmol) and trichloroacetyl isocyanate (714 mg, 3.79 mmol) was stirred in THF (8 mL) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was triturated with MTBE to give INT2-4 (880 mg).

[0715] A mixture of INT 2-4 (780 mg, 1.77 mmol), NH3 / MeOH (1.26 mL, 7 M, 8.85 mmol) and MeOH (7.8 mL) was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was triturated with MTBE to give INT 2-5 (550 mg). MS (ESI, m / z): 250 [M+H] + .

[0716] A mixture of INT 2-5 (375 mg, 1.50 mmol), DIPEA (595 mg, 4.60 mmol) and POCl3 (15 mL) was stirred at 105°C for 17 hours. The reaction mixture was concentrated under reduced pressure. The residue was diluted with 1,4-dioxane (5 mL), and the resulting solution was added dropwise to a K2CO3 aqueous solution (20%, 30 mL). The mixture was stirred at room temperature for 2 hours, the pH was adjusted to 2-3, and the filter cake was collected by filtration and dried to give INT 2 (344 mg). MS (ESI, m / z): 268 [M+H] + .

[0717] Intermediate 3 (INT 3)

[0718]

[0719] A mixture of INT 2-3 (4.53 g, 17.90 mmol), NaOH (2.99 g, 74.76 mmol) in EtOH (50 mL) and water (10 mL) was stirred at 50 ° C for 4 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in water (40 mL) and extracted with EtOAc (2×30 mL). The pH value of the aqueous phase was adjusted to 2, extracted with EtOAc (2×30 mL), and the organic layers were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give INT 3-1 (2.68 g, 11.91 mmol, yield 66.54%). MS: m / z 225 [M+H] + .

[0720] A mixture of INT 3-1 (2.44 g, 10.84 mmol) and (SOCl2 15 mL) was stirred at 70 ° C for 2 hours. The mixture was concentrated under reduced pressure. A solution of the obtained residue in CH3CN (10 mL) was added dropwise to a mixture of ammonium thiocyanate (2.22 g, 29.16 mmol) in CH3CN (40 mL), and then stirred for 1.5 hours. The reaction mixture was filtered, the filter cake was collected, and dried to give INT 3-2 (2.21 g, 8.31 mmol, yield 76.59%). MS: m / z 264 (MH) - .

[0721] To a mixture of INT 3-2 (2.01 g, 7.55 mmol), NaOH (0.1 M aqueous solution, 150 mL) and MeOH (150 mL) was added CH3I (2.22 g, 15.64 mmol). The mixture was stirred at room temperature for 0.5 h. The aqueous phase was adjusted to pH 3 with hydrochloric acid, extracted with EtOAc (1×200 mL, 1×100 mL), and the organic layers were combined and concentrated under reduced pressure. The residue was triturated with water (20 mL) to give INT3 (1.88 g, 6.71 mmol, yield 88.85%). MS: m / z 278 (MH) - .

[0722] Intermediate 4 (INT 4)

[0723]

[0724] To a mixture of cis-cyclopentane-1,2-diamine (500 mg, 2.9 mmol, HCl salt) in DCM (20 mL) was added TEA (1.2 g, 11.6 mmol) at 0 ° C. The resulting mixture was stirred for 15 minutes, and then Boc2O (1.5 g, 6.96 mmol) was added. After completion, the reaction mixture was diluted with DCM, washed with citric acid (saturated 10% aqueous solution) and salt, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with petroleum ether: EtOAc = 10: 1 to 5: 1, v / v) to give INT4-1 (77 mg). MS m / z: 301 [M + H] + .

[0725] INT4-1 (370 mg, 1.23 mmol) was dissolved in DMF (12.3 mL) and stirred at 0 ° C under a nitrogen atmosphere. NaH (147.6 mg, 3.69 mmol, 60%) and CH3I (523.8 mg, 3.69 mmol) were added and stirred at 0 ° C for 1 hour. The reaction mixture was diluted with water, extracted with EtOAc, and the organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with petroleum ether: EtOAc = 10: 1 to 5: 1, v / v) to give INT4-2 (330 mg). MS m / z: 329 [M + H] + .

[0726] A mixture of INT 4-2 (300 mg, 0.91 mmol) and TFA (1.5 mL) was stirred in DCM (3 mL) at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to give INT 4 (480 mg, crude). MS m / z: 129 [M+H] + .

[0727] Intermediate 5 (INT 5)

[0728]

[0729] A mixture of INT 5-3 (1.4 g, 19.41 mmol), NaOH (5N aqueous solution, 3.9 g), 1,4-dioxane (14 mL) and Boc2O (2.84 g, 13.01 mmol) was stirred at room temperature. After completion, the mixture was extracted with DCM, and the organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with petroleum ether: EtOAc = 5: 1, v / v) to give INT 5-4 (2.5 g). LCMS: 273 [M + H] + .

[0730] A mixture of INT 5-4 (2.5 g, 9.18 mmol) in DMF (83 mL) was stirred at 0 ° C under a nitrogen atmosphere. NaH (1.1 g, 27.54 mmol, 60%) and CH3I (3.9 g, 27.54 mmol) were added and the resulting mixture was stirred at 0 ° C. The reaction mixture was diluted with water (100 mL), extracted with EtOAc, and the organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with petroleum ether: EtOAc = 5: 1, v / v) to give INT 5-5 (750 mg). LCMS: 301 [M + H] + .

[0731] To a solution of INT 5-5 (566.6 mg, 1.89 mmol) in CH3CN (10 mL) was added HCl / 1,4-dioxane (3 mL, 4 M). The reaction mixture was stirred at room temperature for 4 hours. After completion, the reaction mixture was concentrated under reduced pressure to give INT 5 (466 mg, crude product). LCMS: 101 [M+H] + .

[0732] Example 1

[0733]

[0734] Phosphorus oxychloride (0.5 mL) was added to a toluene (10 mL) solution of INT 3 (209 mg, 0.75 mmol) and DIEA (0.5 mL) under a nitrogen atmosphere and stirred at 80 ° C for 4 hours. After completion, the mixture was concentrated under reduced pressure. The residue was diluted with DCM (5 mL), and DIEA (1.5 mL) and INT 4 (386 mg, crude product) were added. The reaction mixture was stirred at room temperature for 3 hours. After completion, the mixture was diluted with DCM (60 mL), water (30 mL) and separated. The collected organic layer was concentrated under reduced pressure to give compound 1-1 (crude product), which can be used directly in the next step without purification. MS: m / z 390 [M+H] + .

[0735] DIEA (1 mL) was added to a CH3CN (10 mL) solution of compound 1-1 (crude product) and stirred at 60°C for 6 hours. After completion, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (eluted with Hex:EtOAc=3:1, v / v) to give compound 1-2 (149 mg, 0.42 mmol). MS: m / z 354 [M+H] + .

[0736] 3-Chlorobenzoic acid (76.7 mg, 0.44 mmol) was added to a solution of compound 1-2 (131.5 mg, 0.37 mmol) in DCM (15 mL) at 0°C and stirred for 1 hour. After completion, the residue was diluted with DCM (30 mL) and water (30 mL), and the mixture was adjusted to pH = 8 to 9 with saturated NaHCO3. The separated organic layer was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: DCM: MeOH = 40: 1, v / v) to give compound 1-3 (115 mg, 0.31 mmol). MS: m / z 370 [M+H] + .

[0737] To a solution of compound 1-3 (103.9 mg, 0.45 mmol) and ((2R, 7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methanol (150 mg, 0.94 mmol) in THF (15 mL) was added t-BuONa (133 mg, 1.38 mmol) at 40°C. The mixture was stirred for 30 minutes. The mixture was diluted with EtOAc (30 mL) and water (30 mL) and the organic layer was separated. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give compound 1-4 (108 mg, crude product). MS: m / z 465 [M+H] + .

[0738] To a solution of compound 1-4 (108 mg, crude), INT 2 (256 mg, 0.50 mmol) and Cs2CO3 (346 mg, 1.06 mmol) in toluene (15 mL) and water (3 mL) was added methanesulfonic acid [(di(1-adamantyl)-n-butylphosphine)-2-(2'-amino-1,1'-biphenyl)] palladium (II) (25 mg, 0.034 mmol) and the mixture was purged with nitrogen and stirred at 100°C for 16 hours. After completion, the mixture was concentrated under reduced pressure and the residue was diluted with EtOAc (40 mL) and water (30 mL). The organic layer was separated and concentrated under reduced pressure. The residue was purified by Pre-TLC (DCM: MeOH = 30: 1, v / v) to give compound 1-5 (30 mg, 0.037 mmol). MS: m / z 815 [M+1] + .

[0739] HCl / 1,4-dioxane (2 mL, 4 M) was added to a solution of compound 1-5 (30 mg, 0.037 mmol) in CH3CN (5 mL). The reaction mixture was stirred at room temperature for 1 hour. After completion, the reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc (30 mL) and water (20 mL) and adjusted to pH = 8 to 9 with saturated NaHCO3. The organic layer was separated and concentrated under reduced pressure to give compound 1-6 (50 mg, crude product). MS: m / z 771 [M+H] + .

[0740] CsF (106 mg, 0.70 mmol) was added to a mixture of compound 1-6 (50 mg, crude) in DMF (5 mL). The mixture was stirred at room temperature for 6 hours. After completion, the mixture was diluted with EtOAc (40 mL) and water (30 mL), and adjusted to pH = 8 to 9 with saturated NaHCO3. The organic layer was separated and concentrated under reduced pressure. The residue was purified by Pre-HPLC (C18 column, A: 0.05% NH3·H2O aqueous solution, B: CH3CN, gradient: B from 30% to 85% in 60 minutes, flow rate of 40 mL / min, 232 nm) and the product fraction was lyophilized to obtain compound 1 (4.3 mg, 0.007 mmol). MS: m / z 615 [M+H] + .

[0741] Example 2

[0742]

[0743] Phosphorus oxychloride (1 mL) was added to a toluene (15 mL) solution of INT 7 (512 mg, 1.83 mmol) and DIEA (0.5 mL) under a nitrogen atmosphere and stirred at 80 ° C for 4 hours. After completion, the mixture was concentrated under reduced pressure. The residue was diluted with DCM (20 mL), and DIEA (1.5 mL) and INT 10 (466 mg, crude product) were then added, and the reaction mixture was stirred at room temperature for 16 hours. After completion, the residue was diluted with DCM (30 mL) and water (30 mL) and separated. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with Hex: EtOAc = 2: 1, v / v) to obtain compound 2-1 (276 mg, 0.85 mmol). MS: m / z 326 [M + H] + .

[0744] To a solution of compound 2-1 (263.4 mg, 0.81 mmol) in DCM (15 mL) was added 3-chloroperoxybenzoic acid (177 mg, 1.03 mmol) at 0°C and stirred for 3 hours. After completion, the residue was diluted with DCM (30 mL) and water (30 mL), and the mixture was adjusted to pH = 8 to 9 with saturated NaHCO3. The organic layer was separated and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with Hex: EtOAc = 1: 1, v / v) to give compound 2-2 (171 mg, 0.50 mmol). MS: m / z 342 [M+H] + .

[0745] To a solution of compound 2-2 (153.2 mg, 0.45 mmol) and ((2R, 7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methanol (150 mg, 0.94 mmol) in THF (15 mL) was added t-BuONa (133 mg, 1.38 mmol) at room temperature. The mixture was stirred for 10 minutes and then diluted with EtOAc (30 mL) and water (30 mL). The organic layer was separated, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by Pre-TLC (eluted with DCM:MeOH=20:1, v / v) to give compound 2-3 (123 mg, 0.28 mmol). MS: m / z437[M+H] + .

[0746] Compound 2-3 (123 mg, 0.28 mmol), INT 2 (311 mg, 0.61 mmol) and Cs2CO3 (409 mg, 1.26 mmol) were dissolved in toluene (20 mL) and water (5 mL), and methanesulfonic acid [(di(1-adamantyl)-n-butylphosphine)-2-(2'-amino-1,1'-biphenyl)] palladium (II) (31 mg, 0.043 mmol) was added. The mixture was purged with nitrogen and stirred at 100°C for 16 hours. After the reaction was completed, the mixture was concentrated under reduced pressure, and the residue was diluted with EtOAc (40 mL) and water (30 mL). The organic layer was separated and concentrated under reduced pressure. The residue was subjected to Pre-TLC (DCM: MeOH = 20: 1, v / v elution) to give compound 2-4 (107 mg, 0.14 mmol). MS: m / z 787 [M+1] + .

[0747] HCl / 1,4-dioxane (2 mL, 4 M) was added to a solution of compound 2-4 (107 mg, 0.14 mmol) in CH3CN (5 mL). The reaction mixture was stirred at room temperature for 1 hour. After completion, the reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc (30 mL) and water (20 mL), and the pH was adjusted to 8 to 9 with saturated NaHCO3. The organic layer was separated and concentrated under reduced pressure to give compound 2-5 (104 mg, crude product). MS: m / z 743 [M+H] + .

[0748] CsF (319 mg, 2.10 mmol) was added to a mixture of compound 2-5 (104 mg, crude product) in DMF (5 mL). The mixture was stirred at room temperature for 16 hours. After completion, the mixture was diluted with EtOAc (30 mL) and water (20 mL). The pH value of the mixture was adjusted to 8 to 9 with saturated NaHCO3. The organic layer was separated and concentrated under reduced pressure. The residue was purified by Pre-HPLC (C18 column, A: 0.1% TFA aqueous solution, B: CH3CN, gradient: from 15% B to 50% B in 47 minutes, flow rate of 60 mL / min, 285 nm), and the product fractions were lyophilized to give compound 2 (64.5 mg, 0.092 mmol) as a TFA salt. MS: m / z587[M+H] + .

[0749] Example 3

[0750]

[0751] DIEA (3.82 g, 29.56 mmol) was added to a solution of cis-tetrahydrofuran-3,4-diamine dihydrochloride (2.04 g, 11.65 mmol) in ethyl formate (24 mL) at room temperature. The mixture was stirred at 57°C overnight. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain compound 3-1 (4.32 g, 27.32 mmol, yield 234.40%, crude product).

[0752] LiAlH4 (1.35 g, 35.57 mmol) was added in batches to a solution of compound 3-1 (3.78 g, 23.90 mmol) in THF (30 mL) at 0 ° C under a nitrogen atmosphere. The mixture was stirred at 51 ° C for 7 hours. The reaction mixture was quenched with water (1.5 mL), saturated NaOH (1.5 mL) aqueous solution and water (3 mL). The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with DCM: MeOH = 50: 1 to 10: 1, v / v) to give compound 3-2 (380 mg, 2.92 mmol, yield 12.21%). MS m / z: 131 [M + H] + .

[0753] To a solution of INT 3 (151 mg, 0.539 mmol) in toluene (5 mL) was added DIEA (0.6 mL) and POCl3 (0.5 mL). The mixture was stirred at 81 ° C for 2 hours and then concentrated under reduced pressure. A DCM solution of the residue was added to a solution of compound 3-2 (80 mg, 0.615 mmol) and DIEA (0.7 mL) in DCM (3 mL) at 0 ° C. The mixture was stirred at room temperature for 0.5 hours. The mixture was diluted with water, extracted with DCM (20 mL×3), and dried over Na2SO4. The combined organic layers were concentrated under reduced pressure to give compound 3-3 (220 mg, 0.561 mmol, yield 91.26%). MS m / z: 392 [M+H] + .

[0754] DIEA (0.6 mL) was added to a solution of compound 3-3 (220 mg, 0.561 mmol) in acetonitrile (6 mL). The mixture was stirred at 81 ° C for 4 hours. The reaction mixture was diluted with water, extracted with EtOAc (30 mL), and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by Pre-TLC (Hex: EtOAc = 2: 1, v / v) to give compound 3-4 (90 mg, 0.253 mmol, yield 45.10%). MS m / z: 356 [M + H] + .

[0755] To a solution of compound 3-4 (90 mg, 0.253 mmol) in DCM (5 mL) was slowly added m-CPBA (63 mg, 0.310 mmol, 85% wt) at 0°C under a nitrogen atmosphere. The mixture was stirred at 0°C for 2 hours. The reaction mixture was quenched with saturated Na2S2O3 aqueous solution (2 mL), and the separated organic layer was washed with saturated NaHCO3 aqueous solution (10 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by Pre-TLC (DCM: MeOH = 20: 1, v / v) to give compound 3-5 (104 mg, 0.280 mmol, yield 110.58%). MS m / z: 372 [M+H] + .

[0756] Under nitrogen atmosphere, t-BuONa (51 mg, 0.531 mmol) was added to a solution of ((2R, 7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methanol (64 mg, 0.402 mmol) in THF (4 mL) at 0°C. Then a solution of compound 3-5 (104 mg, 0.280 mmol) in THF (2 mL) was added, and the mixture was stirred at room temperature for 0.5 hours. The mixture was quenched with water and extracted with EtOAc (30 mL). The organic layer was washed with brine (30 mL×2), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by Pre-TLC (DCM: MeOH=15:1, v / v) to give compound 3-6 (40 mg, 0.086 mmol, yield 30.62%). MS m / z: 467 [M+H] + .

[0757] Cs2CO3 (80 mg, 0.246 mmol) and cataCXium A Pd G3 (11 mg, 0.015 mmol) were added to a solution of compound 3-6 (40 mg, 0.086 mmol) and INT 1 (60 mg, 0.117 mmol) in toluene (10 mL) and water (2 mL). The reaction mixture was stirred at 100 ° C overnight under a nitrogen atmosphere. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by pre-thin layer chromatography (DCM: MeOH = 20: 1, v / v) to give compound 3-7 (55 mg, 0.067 mmol, yield 78.57%). MSm / z: 817 [M + H] + .

[0758] A solution of compound 3-7 (55 mg, 0.067 mmol) and HCl (0.5 mL, 4M dioxane solution) in acetonitrile (5 mL) was stirred at room temperature for 2 hours. The solution was diluted with saturated NaHCO3 aqueous solution (20 mL) and extracted with EtOAc (30 mL). The organic layer was washed with brine (30 mL), dried over Na2SO4, and concentrated under reduced pressure to give compound 3-8 (52 mg, 0.067 mmol, yield 99.93%). MS m / z: 773 [M+H] + .

[0759] Compound 3-8 (52 mg, 0.067 mmol) was dissolved in DMF (3 mL) solution, CsF (0.14 g, 0.922 mmol) was added, stirred at 40 ° C for 2 hours under nitrogen protection, diluted with water (10 mL), extracted with EtOAc (20 mL), dried the organic layer with Na2SO4, and concentrated under reduced pressure. The residue was purified by Prep-HPLC (Agela Durashell C18, 30 mm × 250 mm, 10 um; A: 0.05% NH3·H2O aqueous solution, B: CH3CN, gradient: B increased from 25% to 60% in 60 minutes, flow rate 40 mL / min, 230 nm) and then lyophilized to obtain off-white solid compound 3 (19.0 mg, 0.140 mmol, yield 45.80%). MS m / z: 617 [M+H] + .

[0760] The isomers were separated by Prep-HPLC-Gilson, and the separation conditions were as follows: chromatographic column, CHIRAL ARTCellulose-SA column (2cm×25cm, 5um); mobile phase, Hex (0.2% isopropylamine) / EtOH (55:45); flow rate: 20mL / min. Compound 3A (2.9mg, off-white solid, first eluting isomer, retention time: 3.802 minutes); compound 3B (6.5mg, off-white solid, a mixture of the second eluting isomer and the third eluting isomer, retention time: 4.14 minutes); and compound 3C (2.6mg, off-white solid, fourth eluting isomer, retention time: 6.121 minutes) were obtained.

[0761] Example 4

[0762]

[0763] Compound 4-1 (0.096 g, 280.87 μmol) was dissolved in DCM (0.006 L) and cooled in an ice ethanol bath. Then m-CPBA (62 mg, 305.39 μmol) was added and stirred at the same temperature for 1.5 h. The mixture was then purified by Pre-TLC to obtain compound 4-2 (47 mg, 131.36 μmol, yield 46.7%). MS (ESI, m / z): 358 [M+H] + .

[0764] ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methanol (0.02g, 125.62μmol) was dissolved in THF (2mL) and cooled with an ice ethanol bath. Then t-BuONa (0.02g, 208.10μmol) was added and stirred for 10 minutes, and then a solution of compound 4-2 (47mg, 131.36μmol) in THF (4mL) was added. The reaction mixture was stirred for 20 minutes. The mixture was then quenched with water and extracted with EA. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by Pre-TLC (DCM:MeOH=15:1, v / v) to give compound 4-3 (24mg, 52.99μmol, yield 40.3%). MS (ESI, m / z): 453[M+H] + .

[0765] Compound 4-3 (24 mg, 52.99 μmol), ((2-fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane (0.038 g, 74.14 μmol), cataCXium A Pd G3 (0.02 g, 27.46 μmol), Cs2CO3 (0.053 g, 162.66 μmol) were dissolved in toluene (4 mL) and water (1 mL) and stirred at 100 ° C for 16 hours under a nitrogen atmosphere. The reactant was extracted with EA. The organic layer was concentrated in vacuo. The residue was purified by Pre-TLC (DCM: MeOH = 15: 1, v / v) to give compound 4-4 (22 mg, 27.39 μmol, yield 51.6%). MS (ESI, m / z): 803 [M+H] + .

[0766] To a solution of compound 4-4 (22 mg, 27.39 μmol) in CH3CN (3 mL) was added HCl (4M 1,4-dioxane solution, 0.5 mL). The reaction mixture was stirred at room temperature for 3 hours. The mixture was quenched with aqueous NaHCO3 solution and extracted with EA. The organic layer was concentrated under vacuum to give compound 4-5 (39 mg, 51.38 μmol, yield 187.5%). MS (ESI, m / z): 759 [M+H] + .

[0767] CsF (0.06 g, 394.98 μmol) was added to a DMF (3 mL) solution of compound 4-5 (39 mg, 51.38 μmol). The reaction mixture was stirred at 44 ° C for 1 h. The mixture was then extracted with EA. The organic layer was concentrated in vacuo. The residue was purified by Prep-HPLC (Agela Durashell C18, 30 mm × 250 mm, 10 um, phase A: 0.1% TFA aqueous solution, phase B: CH3CN, gradient: from 10% B to 35% B in 37 minutes, flow rate 40 mL / min, 250 nm) and freeze-dried to give compound 4 (0.0091 g, 12.69 μmol, TFA salt, yield 24.7%). MS (ESI, m / z): 603 [M + H] + .

[0768] Example 5

[0769]

[0770] A solution of compound 5-1 (0.053 g, 113.51 μmol), N-(6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)-5-((triisopropylsilyl)ethynyl)naphthalene-2-yl)-1,1-diphenylmethanimine (0.098 g, 155.13 μmol), cataCXium A Pd G3 (0.023 g, 35.58 μmol), Cs2CO3 (0.102 g, 313.05 μmol) in toluene (6 mL) and water (1.5 mL) was stirred at 100 ° C for 16 hours under a nitrogen atmosphere. The reaction solution was extracted with EA. The organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by Pre-TLC (DCM: MeOH = 15: 1, v / v) to give compound 5-2 (98 mg, 104.67 μmol, yield 92.2%). MS (ESI, m / z): 936 [M+H] + .

[0771] Compound 5-2 (0.098 g, 104.67 μmol) was dissolved in dichloromethane (2 mL), and HCl (4 M in 1,4-dioxane, 0.6 mL) was added. The reaction mixture was stirred at room temperature for 1.5 hours, and HCl (4 M in 1,4-dioxane, 0.2 mL) was added again, stirred at room temperature for 1.5 hours and concentrated under reduced pressure to give crude compound 5-3 (0.10 g, 129.53 μmol, yield 123.7%). MS (ESI, m / z): 772 [M+H] + .

[0772] Compound 5-3 (0.1 g, 129.53 μmol) was dissolved in DMF (3 mL) and CsF (0.24 g, 1.58 mmol) was added. The reaction mixture was stirred at 44 ° C for 1.5 h. The reaction solution was extracted with EA. The organic layer was dried over Na2SO4 and concentrated under vacuum. The residue was purified by Prep-HPLC (Daisogel-C18, 50 mm × 250 mm, 10 um, phase A: 0.1% TFA aqueous solution, phase B: CH3CN, gradient: from 10% B to 40% B in 46 minutes, flow rate 60 mL / min, 230 nm) and lyophilized to give compound 5 (0.0425 g, 58.24 μmol, TFA salt, yield 44.9%). MS (ESI, m / z): 616 [M + H] + .

[0773] Pharmacological experiments

[0774] 1. SOS1-catalyzed nucleotide exchange experiments

[0775] In the presence of 10 nM GDP, HIS-KRAS (G12V, aa 1-169) preloaded with GDP was preincubated with the compounds in 384-well plates (Greiner) for 15 min, followed by the addition of purified SOS1 ExD (Flag tag, aa 564-1049), BODIPY TM FL GTP (Invitrogen) and MAb (monoclonal antibody) Anti 6HIS-Tb cryptate Gold (Cisbio) were added to the test wells (final concentrations: 10-15nM GDP-loaded HIS-KRAS (G12V), 5nM GDP, 0.5μM SOS1 ExD, 80nM BODIPY TMFL GTP, 52.5ng / mL MAb Anti6HIS-Tb cryptate Gold) and incubated at 25°C for 4 hours. Wells containing the same percentage of DMSO were used as blank controls, and wells without KRAS were used as negative controls. TR-FRET signals were measured using a Tecan Spark multi-mode microplate reader. The detection parameters were F486: excitation wavelength 340nm, absorption wavelength 486nm, delay time 100μs, integration time 200μs; F520: excitation wavelength 340nm, absorption wavelength 520nm, delay time 100μs, integration time 200μs. The TR-FRET ratio of each well was calculated, TR-FRET ratio = (F520 signal / F486 signal) * 10000. The percentage of activity of the wells with added compounds was normalized between the blank control group and the negative control group (activity % = (TR-FRET ratio 添加化合物 –TR-FRET ratio 阴性对照组 ) / (TR-FRET ratio 空白对照组 –TR-FRET ratio 阴性对照组 )*100%). IC was then calculated by 4-parameter logistic model fitting or by Excel statistics. 50 value.

[0776] Table 1

[0777]

Claims

1. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof: in, X1, at each occurrence, is independently selected from a bond, -C(R X11 )(R X12 )-、-NR X13 -, -O-, -S-, -S(=O)-, or -S(=O)2-; R X11 or R X12 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R X11 and R X12 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R SX1 replace; R X13 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R X2 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; X2 is independently selected at each occurrence from N or CR1; R1 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1A )2.-OR 1A 、-SR 1A 、-S(=O)R 1B 、-S(=O)2R 1B 、-C(=O)R 1B 、-C(=O)OR 1A 、-OC(=O)R 1B 、-C(=O)N(R 1A )2.-NR 1A C(=O)R 1B 、-OC(=O)OR 1A 、-NR 1A C(=O)OR 1A 、-NR 1A C(=S)OR 1A 、-OC(=O)N(R 1A )2.-NR 1A C(=O)N(R 1A )2, -S(=O)OR 1A 、-OS(=O)R 1B 、-S(=O)N(R 1A )2.-NR 1A S(=O)R 1B 、-S(=O)2OR 1A 、-OS(=O)2R 1B 、-S(=O)2N(R 1A )2.-NR 1A S(=O)2R 1B 、-OS(=O)2OR 1A 、-NR 1A S(=O)2OR 1A 、-OS(=O)2N(R 1A )2.-NR 1A S(=O)2N(R 1A )2.-P(R 1A )2. -P(=O)(R 1B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1C )2.-OR 1C 、-SR 1C 、-S(=O)R 1D 、-S(=O)2R 1D 、-C(=O)R 1D 、-C(=O)OR 1D 、-OC(=O)R 1D 、-C(=O)N(R 1C )2.-NR 1C C(=O)R 1D 、-OC(=O)OR 1C 、-NR 1C C(=O)OR 1C 、-NR 1C C(=S)OR 1C 、-OC(=O)N(R 1C )2.-NR 1C C(=O)N(R 1C )2, -S(=O)OR 1C 、-OS(=O)R 1D 、-S(=O)N(R 1C )2.-NR 1C S(=O)R 1D 、-S(=O)2OR 1C 、-OS(=O)2R 1D 、-S(=O)2N(R 1C )2.-NR 1C S(=O)2R 1D 、-OS(=O)2OR 1C 、-NR 1C S(=O)2OR 1C 、-OS(=O)2N(R 1C )2.-NR 1C S(=O)2N(R 1C )2.-P(R 1C )2. -P(=O)(R 1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Ring A is selected from a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring; R S1 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S1A )2.-OR S1A 、-SR S1A 、-S(=O)R S1B 、-S(=O)2R S1B 、-C(=O)R S1B 、-C(=O)OR S1A 、-OC(=O)R S1B 、-C(=O)N(R S1A )2. -N S1A C(=O)R S1B 、-OC(=O)OR S1A 、-N S1A C(=O)OR S1A 、-NR S1A C(=S)O S1A 、-OC(=O)N(R S1A )2.-NR S1A C(=O)N(R S1A )2, -S(=O)OR S1A 、-OS(=O)R S1B 、-S(=O)N(R S1A )2.-NR S1A S(=O)R S1B 、-S(=O)2OR S1A 、-OS(=O)2R S1B 、-S(=O)2N(R S1A )2.-NR S1A S(=O)2R S1B 、-OS(=O)2OR S1A 、-NR S1A S(=O)2OR S1A 、-OS(=O)2N(R S1A )2.-NR S1A S(=O)2N(R S1A )2.-P(R S1A )2. -P(=O)(R S1B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S1C )2.-OR S1C 、-SR S1C 、-S(=O)R S1D 、-S(=O)2R S1D 、-C(=O)R S1D 、-C(=O)OR S1C 、-OC(=O)R S1D 、-C(=O)N(R S1C )2.-NR S1C C(=O)R S1D 、-OC(=O)OR S1C 、-NR S1C C(=O)OR S1C 、-NR S1C C(=S)OR S1C 、-OC(=O)N(R S1C )2.-NR S1C C(=O)N(R S1C )2, -S(=O)OR S1C 、-OS(=O)R S1D 、-S(=O)N(R S1C )2.-NR S1C S(=O)R S1D 、-S(=O)2OR S1C 、-OS(=O)2R S1D 、-S(=O)2N(R S1C )2.-NR S1C S(=O)2R S1D 、-OS(=O)2OR S1C 、-NR S1C S(=O)2OR S1C 、-OS(=O)2N(R S1C )2.-NR S1C S(=O)2N(R S1C )2.-P(R S1C )2. -P(=O)(R S1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S1 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S11 replace; Optionally, two adjacent R S1 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S12 replace; Optionally, two non-adjacent R S1 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S13 replace; m1 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9; Y1 is a bond, O, S, S(=O), S(=O)2 or NR Y11 ; R Y11 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R3 is selected from R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 38 , R 39 , R 310 and R 311 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R 31 and R 32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S33 replace; Optionally, R 33 and R 34 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S34 replace; Optionally, R 35 and R 36 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S35 replace; Optionally, R 38 and R 39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S310 replace; Optionally, R 310 and R 311 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S316 replace; n2 is selected from 0, 1, 2, 3, 4, 5 or 6; n3 is selected from 0, 1, 2, 3, 4, 5 or 6; n4 is selected from 0, 1, 2, 3, 4, 5 or 6; n5 is selected from 0, 1, 2, 3, 4, 5 or 6; n6 is selected from 0, 1, 2, 3, 4, 5 or 6; Ring B is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring C is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring D is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring; Ring I is a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring, comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring J is a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring K is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring, containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; R S31 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31A )2.-OR S31A 、-SR S31A 、-S(=O)R S31B 、-S(=O)2R S31B 、-C(=O)R S31B 、-C(=O)OR S31A 、-OC(=O)R S31B 、-C(=O)N(R S31A )2.-NR S31A C(=O)R S31B 、-OC(=O)OR S31A 、-NR S31A C(=O)OR S31A 、-NR S31A C(=S)OR S31A 、-OC(=O)N(R S31A )2.-NR S31A C(=O)N(R S31A )2, -S(=O)OR S31A 、-OS(=O)R S31B 、-S(=O)N(R S31A )2.-NR S31A S(=O)R S31B 、-S(=O)2OR S31A 、-OS(=O)2R S31B 、-S(=O)2N(R S31A )2.-NR S31A S(=O)2R S31B 、-OS(=O)2OR S31A 、-NR S31A S(=O)2OR S31A 、-OS(=O)2N(R S31A )2.-NR S31A S(=O)2N(R S31A )2.-P(R S31A )2. -P(=O)(R S31B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31C )2.-OR S31C 、-SR S31C 、-S(=O)R S31D 、-S(=O)2R S31D 、-C(=O)R S31D 、-C(=O)OR S31C 、-OC(=O)R S31D 、-C(=O)N(R S31C )2.-NR S31C C(=O)R S31D 、-OC(=O)OR S31C 、-NR S31C C(=O)OR S31C 、-NR S31C C(=S)OR S31C 、-OC(=O)N(R S31C )2.-NR S31C C(=O)N(R S31C )2, -S(=O)OR S31C 、-OS(=O)R S31D 、-S(=O)N(R S31C )2.-NR S31C S(=O)R S31D 、-S(=O)2OR S31C 、-OS(=O)2R S31D 、-S(=O)2N(R S31C )2.-NR S31C S(=O)2R S31D 、-OS(=O)2OR S31C 、-NR S31C S(=O)2OR S31C 、-OS(=O)2N(R S31C )2.-NR S31C S(=O)2N(R S31C )2.-P(R S31C )2. -P(=O)(R S31D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S31 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S311 replace; Optionally, two adjacent R S31 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S312 replace; Optionally, two non-adjacent R S31 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S313 replace; m3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; R S32 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32A )2.-OR S32A 、-SR S32A 、-S(=O)R S32B 、-S(=O)2R S32B 、-C(=O)R S32B 、-C(=O)OR S32A 、-OC(=O)R S32B 、-C(=O)N(R S32A )2.-NR S32A C(=O)R S32B 、-OC(=O)OR S32A 、-NR S32A C(=O)OR S32A 、-NR S32A C(=S)OR S32A 、-OC(=O)N(R S32A )2.-NR S32A C(=O)N(R S32A )2, -S(=O)OR S32A 、-OS(=O)R S32B 、-S(=O)N(R S32A )2.-NR S32A S(=O)R S32B 、-S(=O)2OR S32A 、-OS(=O)2R S32B 、-S(=O)2N(R S32A )2.-NR S32A S(=O)2R S32B 、-OS(=O)2OR S32A 、-NR S32A S(=O)2OR S32A 、-OS(=O)2N(R S32A )2.-NR S32A S(=O)2N(R S32A )2.-P(R S32A )2. -P(=O)(R S32B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32C )2.-OR S32C 、-SR S32C 、-S(=O)R S32C 、-S(=O)2R S32D 、-C(=O)R S32D 、-C(=O)OR S32C 、-OC(=O)R S32D 、-C(=O)N(R S32C )2.-NR S32C C(=O)R S32D 、-OC(=O)OR S32C 、-NR S32C C(=O)OR S32C 、-NR S32C C(=S)OR S32C 、-OC(=O)N(R S32C )2.-NR S32C C(=O)N(R S32C )2, -S(=O)OR S32C 、-OS(=O)R S32C 、-S(=O)N(R S32C )2.-NR S32C S(=O)R S32D 、-S(=O)2OR S32C 、-OS(=O)2R S32D 、-S(=O)2N(R S32C )2.-NR S32C S(=O)2R S32D 、-OS(=O)2OR S32C 、-NR S32C S(=O)2OR S32C 、-OS(=O)2N(R S32C )2.-NR S32C S(=O)2N(R S32C )2.-P(R S32C )2. -P(=O)(R S32D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S321 replace; Optionally, two adjacent R S32 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S322 replace; Optionally, two non-adjacent R S32 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S323 replace; m4 is selected from 0, 1, 2, 3, 4, 5 or 6; R 37 Selected from -N(R 37A ) a 2- or 3-10-membered heterocyclic ring, wherein the 3-10-membered heterocyclic ring is optionally independently replaced by one or more R S37 replace; R S38 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38A )2.-OR S38A 、-SR S38A 、-S(=O)R S38B 、-S(=O)2R S38B 、-C(=O)R S38B 、-C(=O)OR S38A 、-OC(=O)R S38B 、-C(=O)N(R S38A )2.-NR S38A C(=O)R S38B 、-OC(=O)OR S38A 、-NR S38A C(=O)OR S38A 、-NR S38A C(=S)OR S38A 、-OC(=O)N(R S38A )2.-NR S38A C(=O)N(R S38A )2, -S(=O)OR S38A 、-OS(=O)R S38B 、-S(=O)N(R S38A )2.-NR S38A S(=O)R S38B 、-S(=O)2OR S38A 、-OS(=O)2R S38B 、-S(=O)2N(R S38A )2.-NR S38A S(=O)2R S38B 、-OS(=O)2OR S38A 、-NR S38A S(=O)2OR S38A 、-OS(=O)2N(R S38A )2.-NR S38A S(=O)2N(R S38A )2.-P(R S38A )2. -P(=O)(R S38B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocycle, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocycle, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38C )2.-OR S38C 、-SR S38C 、-S(=O)R S38D 、-S(=O)2R S38D 、-C(=O)R S38D 、-C(=O)OR S38C 、-OC(=O)R S38D 、-C(=O)N(R S38C )2.-NR S38C C(=O)R S38D 、-OC(=O)OR S38C 、-NR S38C C(=O)OR S38C 、-NR S38C C(=S)OR S38C 、-OC(=O)N(R S38C )2.-NR S38C C(=O)N(R S38C )2, -S(=O)OR S38C 、-OS(=O)R S38D 、-S(=O)N(R S38C )2.-NR S38C S(=O)R S38D 、-S(=O)2OR S38C 、-OS(=O)2R S38D 、-S(=O)2N(R S38C )2.-NR S38C S(=O)2R S38D 、-OS(=O)2OR S38C 、-NR S38C S(=O)2OR S38C 、-OS(=O)2N(R S38C )2.-NR S38C S(=O)2N(R S38C )2.-P(R S38C )2. -P(=O)(R S38D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S38 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S381 replace; Optionally, two adjacent R S38 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S382 replace; Optionally, two non-adjacent R S38 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S383 replace; m8 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; R S39 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39A )2.-OR S39A 、-SR S39A 、-S(=O)R S39B 、-S(=O)2R S39B 、-C(=O)R S39B 、-C(=O)OR S39A 、-OC(=O)R S39B 、-C(=O)N(R S39A )2.-NR S39A C(=O)R S39B 、-OC(=O)OR S39A 、-NR S39A C(=O)OR S39A 、-NR S39A C(=S)OR S39A 、-OC(=O)N(R S39A )2.-NR S39A C(=O)N(R S39A )2, -S(=O)OR S39A 、-OS(=O)R S39B 、-S(=O)N(R S39A )2.-NR S39A S(=O)R S39B 、-S(=O)2OR S39A 、-OS(=O)2R S39B 、-S(=O)2N(R S39A )2.-NR S39A S(=O)2R S39B 、-OS(=O)2OR S39A 、-NR S39A S(=O)2OR S39A 、-OS(=O)2N(R S39A )2.-NR S39A S(=O)2N(R S39A )2.-P(R S39A )2. -P(=O)(R S39B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39C )2.-OR S39C 、-SR S39C 、-S(=O)R S39C 、-S(=O)2R S39D 、-C(=O)R S39D 、-C(=O)OR S39C 、-OC(=O)R S39D 、-C(=O)N(R S39C )2.-NR S39C C(=O)R S39D 、-OC(=O)OR S39C 、-NR S39C C(=O)OR S39C 、-NR S39C C(=S)OR S39C 、-OC(=O)N(R S39C )2.-NR S39C C(=O)N(R S39C )2, -S(=O)OR S39C 、-OS(=O)R S39C 、-S(=O)N(R S39C )2.-NR S39C S(=O)R S39D 、-S(=O)2OR S39C 、-OS(=O)2R S39D 、-S(=O)2N(R S39C )2.-NR S39C S(=O)2R S39D 、-OS(=O)2OR S39C 、-NR S39C S(=O)2OR S39C 、-OS(=O)2N(R S39C )2.-NR S39C S(=O)2N(R S39C )2.-P(R S39C )2. -P(=O)(R S39D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S391 replace; Optionally, two adjacent R S39 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S392 replace; Optionally, two non-adjacent R S39 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S393 replace; m9 is selected from 0, 1, 2, 3, 4, 5 or 6; R S315 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315A )2.-OR S315A 、-SR S315A 、-S(=O)R S315B 、-S(=O)2R S315B 、-C(=O)R S315B 、-C(=O)OR S315A 、-OC(=O)R S315B 、-C(=O)N(R S315A )2.-NR S315A C(=O)R S315B 、-OC(=O)OR S315A 、-NR S315A C(=O)OR S315A 、-NR S315A C(=S)OR S315A 、-OC(=O)N(R S315A )2.-NR S315A C(=O)N(R S315A )2, -S(=O)OR S315A 、-OS(=O)R S315B 、-S(=O)N(R S315A )2.-NR S315A S(=O)R S315B 、-S(=O)2OR S315A 、-OS(=O)2R S315B 、-S(=O)2N(R S315A )2.-NR S315A S(=O)2R S315B 、-OS(=O)2OR S315A 、-NR S315A S(=O)2OR S315A 、-OS(=O)2N(R S315A )2.-NR S315A S(=O)2N(R S315A )2.-P(R S315A )2. -P(=O)(R S315B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315C )2.-OR S315C 、-SR S315C 、-S(=O)R S315C 、-S(=O)2R S315D 、-C(=O)R S315D 、-C(=O)OR S315C 、-OC(=O)R S315D 、-C(=O)N(R S315C )2.-NR S315C C(=O)R S315D 、-OC(=O)OR S315C 、-NR S315C C(=O)OR S315C 、-NR S315C C(=S)OR S315C 、-OC(=O)N(R S315C )2.-NR S315C C(=O)N(R S315C )2, -S(=O)OR S315C 、-OS(=O)R S315C 、-S(=O)N(R S315C )2.-NR S315C S(=O)R S315D 、-S(=O)2OR S315C 、-OS(=O)2R S315D 、-S(=O)2N(R S315C )2.-NR S315C S(=O)2R S315D 、-OS(=O)2OR S315C 、-NR S315C S(=O)2OR S315C 、-OS(=O)2N(R S315C )2.-NR S315C S(=O)2N(R S315C )2.-P(R S315C )2. -P(=O)(R S315D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S315 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S3151 replace; Optionally, two adjacent R S315 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S3152 replace; Optionally, two non-adjacent R S315 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S3153 replace; m 10 Selected from 0, 1, 2, 3, 4, 5 or 6; R4 is selected from 6-10 membered aryl, 5-10 membered heteroaryl, wherein the 6-10 membered aryl, 5-10 membered heteroaryl, are independently unsubstituted or substituted with one or more R S4 replace; Each occurrence of Z is independently selected from or N; When Z is selected from C, each occurrence of Ring E is independently selected from a 6-membered aryl ring or a 5-6-membered heteroaryl ring, and each occurrence of Ring F is independently selected from a 3-10-membered carbocyclic ring or a 3-10-membered heterocyclic ring; When Z is selected from N, each occurrence of Ring E is selected from a 5-6 membered heteroaryl ring, and each occurrence of Ring F is selected from a 3-10 membered heterocyclic ring; R S4 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4A )2.-OR S4A 、-SR S4A 、-S(=O)R S4B 、-S(=O)2R S4B 、-C(=O)R S4B 、-C(=O)OR S4A 、-OC(=O)R S4B 、-C(=O)N(R S4A )2.-NR S4A C(=O)R S4B 、-OC(=O)OR S4A 、-NR S4A C(=O)OR S4A 、-NR S4A C(=S)OR S4A 、-OC(=O)N(R S4A )2.-NR S4A C(=O)N(R S4A )2, -S(=O)OR S4A 、-OS(=O)R S4B 、-S(=O)N(R S4A )2.-NR S4A S(=O)R S4B 、-S(=O)2OR S4A 、-OS(=O)2R S4B 、-S(=O)2N(R S4A )2.-NR S4A S(=O)2R S4B 、-OS(=O)2OR S4A 、-NR S4A S(=O)2OR S4A 、-OS(=O)2N(R S4A )2.-NR S4A S(=O)2N(R S4A )2.-P(R S4A )2. -P(=O)(R S4B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4C )2.-OR S4C 、-SR S4C 、-S(=O)R S4D 、-S(=O)2R S4D 、-C(=O)R S4D 、-C(=O)OR S4D 、-OC(=O)R S4D 、-C(=O)N(R S4C )2.-NR S4C C(=O)R S4D 、-OC(=O)OR S4C 、-NR S4C C(=O)OR S4C 、-NR S4C C(=S)OR S4C 、-OC(=O)N(R S4C )2.-NR S4C C(=O)N(R S4C )2, -S(=O)OR S4C 、-OS(=O)R S4D 、-S(=O)N(R S4C )2.-NR S4C S(=O)R S4D 、-S(=O)2OR S4C 、-OS(=O)2R S4D 、-S(=O)2N(R S4C )2.-NR S4C S(=O)2R S4D 、-OS(=O)2OR S4C 、-NR S4C S(=O)2OR S4C 、-OS(=O)2N(R S4C )2.-NR S4C S(=O)2N(R S4C )2.-P(R S4C )2. -P(=O)(R S4D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R5 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5A )2.-OR 5A 、-SR 5A 、-S(=O)R 5B 、-S(=O)2R 5B 、-C(=O)R 5B 、-C(=O)OR 5A 、-OC(=O)R 5B 、-C(=O)N(R 5A )2.-NR 5A C(=O)R 5B 、-OC(=O)OR 5A 、-NR 5A C(=O)OR 5A 、-NR 5A C(=S)OR 5A 、-OC(=O)N(R 5A )2.-NR 5A C(=O)N(R 5A )2, -S(=O)OR 5A 、-OS(=O)R 5B 、-S(=O)N(R 5A )2.-NR 5A S(=O)R 5B 、-S(=O)2OR 5A 、-OS(=O)2R 5B 、-S(=O)2N(R 5A )2.-NR 5A S(=O)2R 5B 、-OS(=O)2OR 5A 、-NR 5A S(=O)2OR 5A 、-OS(=O)2N(R 5A )2.-NR 5A S(=O)2N(R 5A )2.-P(R 5A )2. -P(=O)(R 5B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5C )2.-OR 5C 、-SR 5C 、-S(=O)R 5D 、-S(=O)2R 5D 、-C(=O)R 5D 、-C(=O)OR 5D 、-OC(=O)R 5D 、-C(=O)N(R 5C )2.-NR 5C C(=O)R 5D 、-OC(=O)OR 5C 、-NR 5C C(=O)OR 5C 、-NR 5C C(=S)OR 5C 、-OC(=O)N(R 5C )2.-NR 5C C(=O)N(R 5C )2, -S(=O)OR 5C 、-OS(=O)R 5D 、-S(=O)N(R 5C )2.-NR 5C S(=O)R 5D 、-S(=O)2OR 5C 、-OS(=O)2R 5D 、-S(=O)2N(R 5C )2.-NR 5C S(=O)2R 5D 、-OS(=O)2OR 5C 、-NR 5C S(=O)2OR 5C 、-OS(=O)2N(R 5C )2.-NR 5C S(=O)2N(R 5C )2.-P(R 5C )2. -P(=O)(R 5D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R 1A , R 1C , R S1A , R S1C , R S31A , R S31C , R S32A , R S32C , R 37A , R S38A , R S38C , R S39A , R S39C , R S315A , R S315C , R S4A , R S4C , R 5A and R 5C are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, (two R 1A , two R 1C , two R S1A , two R S1C , two R S31A , two R S31C , two R S32A , two R S32C , two R 37A , two R S38A , two R S38C , two R S39A , two R S39C , two R S315A , two R S315C , two R S4A , two R S4C , two R 5A and two R 5C ) and the nitrogen atom to which it is connected together form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring, wherein the 3-10 membered heterocyclic ring or the 5-10 membered heteroaromatic ring is independently unsubstituted or substituted with one or more R SS replace; R 1B , R 1D , R S1B , R S1D , R S31B , R S31D , R S32B , R S32D , R S38B , R S38D , R S39B , R S39D , R S315B , R S315D , R S4B , R S4D , R 5B and R 5D Each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A , 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R A , R B , R C and R D Each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are independently unsubstituted or substituted with one or more R SA replace; R SX1 , R S11 , R S12 , R S13 , R S33 , R S34 , R S35 , R S316 , R S311 , R S312 , R S313 , R S321 , R S322 , R S323 , R S37 , R S310 , R S381 , R S382 , R S383 , R S391 , R S392 , R S393 , R S3151 , R S3152 , R S3153 , R SS and R SA are each independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -OC(=O)O(C 1-6 alkyl), -NHC(=O)(OC 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(OC 1-6 alkyl), -OC(=O)NH(C 1-6 alkyl), -OC(=O)N(C 1-6 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH2, -N(C 1-6 alkyl)C(=O)NH(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)N(C 1-6 Alkyl)2, -S(=O)(OC 1-6 alkyl), -OS(=O)(C 1-6 alkyl), -S(=O)NH2, -S(=O)NH(C 1-6 alkyl), -S(=O)N(C 1-6 Alkyl)2, -NHS(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)(C 1-6 Alkyl), -S(=O)2(OC 1-6 alkyl), -OS(=O)2(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), -OS(=O)2O(C 1-6 alkyl), -NHS(=O)2O(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2O(C 1-6 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 alkyl), -OS(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 alkyl), -NHS(=O)2N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)S(=O)2NH2, -N(C 1-6 Alkyl)S(=O)2NH(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)2N(C 1-6 Alkyl)2, -PH(C 1-6 Alkyl), -P(C 1-6 Alkyl)2, -P(=O)H(C 1-6 alkyl), -P(=O)(C 1-6 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-3 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy, -C 2-3 Alkenyl, -C 2-3 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -OH, -O(C 1-3 alkyl), -SH, -S(C 1-3 alkyl), -S(=O)(C 1-3 alkyl), -S(=O)2(C 1-3 alkyl), -C(=O)(C 1-3 alkyl), -C(=O)OH-C(=O)(OC 1-3 alkyl), -OC(=O)(C 1-3 alkyl), -C(=O)NH2, -C(=O)NH(C 1-3 alkyl), -C(=O)N(C 1-3 Alkyl)2, -NHC(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(C 1-3 alkyl), -OC(=O)O(C 1-3 alkyl), -NHC(=O)(OC 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(OC 1-3 alkyl), -OC(=O)NH(C 1-3 alkyl), -OC(=O)N(C 1-3 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-3 alkyl), -NHC(=O)N(C 1-3 Alkyl)2, -N(C 1-3 alkyl)C(=O)NH2, -N(C 1-3 alkyl)C(=O)NH(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)N(C 1-3 Alkyl)2, -S(=O)(OC 1-3 alkyl), -OS(=O)(C 1-3 alkyl), -S(=O)NH2, -S(=O)NH(C 1-3 alkyl), -S(=O)N(C 1-3 Alkyl)2, -NHS(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)(C 1-3 Alkyl), -S(=O)2(OC 1-3 alkyl), -OS(=O)2(C 1-3 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-3 alkyl), -S(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2(C 1-3 alkyl), -OS(=O)2O(C 1-3 alkyl), -NHS(=O)2O(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2O(C 1-3 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-3 alkyl), -OS(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-3 alkyl), -NHS(=O)2N(C 1-3 Alkyl)2, -N(C 1-3 Alkyl)S(=O)2NH2, -N(C 1-3 Alkyl)S(=O)2NH(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)2N(C 1-3 Alkyl)2, -PH(C 1-3 Alkyl), -P(C 1-3 Alkyl)2, -P(=O)H(C 1-3 alkyl), -P(=O)(C 1-3 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Each occurrence of heterocyclyl or heterocycle independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S(=O) or S(=O)2; Each occurrence of heteroaryl independently contains 1, 2, 3 or 4 heteroatoms selected from N, O or S.

2. The compound of formula (I) according to claim 1, its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of a stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein the compound is selected from any one of the following formulas:

3. A compound of formula (I) according to claim 1 or 2, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, wherein: X1 is independently selected at each occurrence from -C(R X11 )(R X12 )-、-NR X13 -, -O-, or -S-; R X11 or R X12 are independently selected from hydrogen, deuterium, halogen or -C 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl; R X13 Selected from hydrogen, deuterium or -C 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, --NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl.

4. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 3, wherein X1 is selected from -O-, -S-, -NH-, -N(CH3)-, -CH2- or -CHF-.

5. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 4, wherein R X2 Selected from hydrogen, deuterium or -C 1-6 alkyl; Preferably, R X2 is selected from hydrogen, deuterium or methyl.

6. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 5, wherein: Ring A is selected from a 5-6 membered carbocyclic ring or a 5-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O.

7. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 6, wherein The compound is selected from any of the following formulas:

8. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 7, wherein m1 is selected from 0, 1 or 2.

9. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 8, wherein: R S1 Selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl; Preferably, R S1 Selected from -F, -CH3 or -OH.

10. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof as claimed in any one of claims 1 to 9, wherein The compound is selected from any formula in Table A in the specification; preferably, the compound is selected from any formula in Table B in the specification.

11. A compound of formula (II), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof: in, Each occurrence of X1 is independently selected from a single bond, -C(R X11 )(R X12 )-、-NR X13 -, -O-, -S-, -S(=O)-, or -S(=O)2-; R X11 or R X12 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R X11 and R X12 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R SX1 replace; R X13 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 aAlkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl3-10; Each occurrence of X2 is independently selected from N or CR1; R1 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1A )2.-OR 1A 、-SR 1A 、-S(=O)R 1B 、-S(=O)2R 1B 、-C(=O)R 1B 、-C(=O)OR 1A 、-OC(=O)R 1B 、-C(=O)N(R 1A )2.-NR 1A C(=O)R 1B 、-OC(=O)OR 1A 、-NR 1A C(=O)OR 1A 、-NR 1A C(=S)OR 1A 、-OC(=O)N(R 1A )2.-NR 1A C(=O)N(R 1A )2, -S(=O)OR 1A 、-OS(=O)R 1B 、-S(=O)N(R 1A )2.-NR 1A S(=O)R 1B 、-S(=O)2OR 1A 、-OS(=O)2R 1B 、-S(=O)2N(R 1A )2.-NR 1A S(=O)2R 1B 、-OS(=O)2OR 1A 、-NR 1A S(=O)2OR 1A 、-OS(=O)2N(R 1A )2.-NR 1A S(=O)2N(R 1A )2.-P(R 1A )2. -P(=O)(R 1B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 1C )2.-OR 1C 、-SR 1C 、-S(=O)R 1D 、-S(=O)2R 1D 、-C(=O)R 1D 、-C(=O)OR 1D 、-OC(=O)R 1D 、-C(=O)N(R 1C )2.-NR 1C C(=O)R 1D 、-OC(=O)OR 1C 、-NR 1C C(=O)OR 1C 、-NR 1C C(=S)OR 1C 、-OC(=O)N(R 1C )2.-NR 1C C(=O)N(R 1C )2, -S(=O)OR 1C 、-OS(=O)R 1D 、-S(=O)N(R 1C )2.-NR 1C S(=O)R 1D 、-S(=O)2OR 1C 、-OS(=O)2R 1D 、-S(=O)2N(R 1C )2.-NR 1C S(=O)2R 1D 、-OS(=O)2OR 1C 、-NR 1C S(=O)2OR 1C 、-OS(=O)2N(R 1C )2.-NR 1C S(=O)2N(R 1C )2.-P(R 1C )2. -P(=O)(R 1D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Ring A is selected from a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S=O or S(=O)2, a benzene ring, or a 5-6 membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from N, O or S; R 81 and R 82 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R 8A )2.-OR 8A 、-SR 8A 、-S(=O)R 8B 、-S(=O)2R 8B 、-C(=O)R 8B 、-C(=O)OR 8B 、-C(=O)N(R 8B )2, -S(=O)OR 8B 、-S(=O)N(R 8B )2, -S(=O)2OR 8B 、-S(=O)2N(R 8B )2. -P(=O)(R 8B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 8C )2.-OR 8C 、-SR 8C 、-S(=O)R 8D 、-S(=O)2R 8D 、-C(=O)R 8D 、-C(=O)OR 8C 、-OC(=O)R 8D 、-C(=O)N(R 8C )2.-NR 8C C(=O)R 8D 、-OC(=O)OR 8C 、-NR 8C C(=O)OR 8D 、-OC(=O)N(R 8C )2.-NR 8C C(=O)N(R 8C )2, -S(=O)OR 8C 、-OS(=O)R 8D 、-S(=O)N(R 8C )2.-NR 8C S(=O)R 8D 、-S(=O)2OR 8C 、-OS(=O)2R 8D 、-S(=O)2N(R 8C )2.-NR 8C S(=O)2R 8D 、-OS(=O)2OR 8C 、-NR 8C S(=O)2OR 8C 、-OS(=O)2NR 8C 、-NR 8C S(=O)2N(R 8C )2.-P(R 8C )2. -P(=O)(R 8D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R 81 and R 82 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S81 replace; Optional, R 81 and R 82 Together with the carbon atoms to which they are commonly attached, they form a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring; wherein the 3-10 membered carbocyclic ring or the 3-10 membered heterocyclic ring are each independently unsubstituted or substituted by one or more R S82 replace; n7 is selected from 0, 1, 2, 3, 4, 5 or 6; Ring M is selected from a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms selected from N, O or S; R S8 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N, oxo, -N(R S8A )2.-OR S8A 、-SR S8A 、-S(=O)R S8B 、-S(=O)2R S8B 、-C(=O)R S8B 、-C(=O)OR S8A 、-OC(=O)R S8B 、-C(=O)N(R S8A )2.-NR S8A C(=O)R S8B 、-OC(=O)OR S8A 、-NR S8A C(=O)OR S8A 、-NR S8A C(=S)OR S8A 、-OC(=O)N(R S8A )2.-NR S8A C(=O)N(R S8A )2, -S(=O)OR S8A 、-OS(=O)R S8B 、-S(=O)N(R S8A )2.-NR S8A S(=O)R S8B 、-S(=O)2OR S8A 、-OS(=O)2R S8B 、-S(=O)2N(R S8A )2.-NR S8A S(=O)2R S8B 、-OS(=O)2OR S8A 、-NR S8A S(=O)2OR S8A 、-OS(=O)2N(R S8A )2.-NR S8A S(=O)2N(R S8A )2.-P(R S8A )2. -P(=O)(R S8B )2, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N, oxo, -N(R S8C )2.-OR S8C 、-SR S8C 、-S(=O)R S8D 、-S(=O)2R S8D 、-C(=O)R S8D 、-C(=O)OR S8C 、-OC(=O)R S8D 、-C(=O)N(R S8C )2.-NR S8C C(=O)R S8D 、-OC(=O)OR S8C 、-NR S8C C(=O)OR S8C 、-NR S8C C(=S)OR S8C 、-OC(=O)N(R S8C )2.-NR S8C C(=O)N(R S8C )2, -S(=O)OR S8C 、-OS(=O)R S8D 、-S(=O)N(R S8C )2.-NR S8C S(=O)R S8D 、-S(=O)2OR S8C 、-OS(=O)2R S8D 、-S(=O)2N(R S8C )2.-NR S8C S(=O)2R S8D 、-OS(=O)2OR S8C 、-NR S8C S(=O)2OR S8C 、-OS(=O)2N(R S8C )2.-NR S8C S(=O)2N(R S8C )2.-P(R S8C )2. -P(=O)(R S8D )2, -10-membered cycloalkyl, -10-membered cycloalkenyl, -10-membered cycloalkynyl, -10-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl; n8 is selected from 0, 1, 2, 3, 4, 5 or 6; R S2 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S2A )2.-OR S2A 、-SR S2A 、-S(=O)R S2B 、-S(=O)2R S2B 、-C(=O)R S2B 、-C(=O)OR S2A 、-OC(=O)R S2B 、-C(=O)N(R S2A )2.-NR S2A C(=O)R S2B 、-OC(=O)OR S2A 、-NR S2A C(=O)OR S2A 、-NR S2A C(=S)OR S2A 、-OC(=O)N(R S2A )2.-NR S2A C(=O)N(R S2A )2, -S(=O)OR S2A 、-OS(=O)R S2B 、-S(=O)N(R S2A )2.-NR S2A S(=O)R S2B 、-S(=O)2OR S2A 、-OS(=O)2R S2B 、-S(=O)2N(R S2A )2.-NR S2A S(=O)2R S2B 、-OS(=O)2OR S2A 、-NR S2A S(=O)2OR S2A 、-OS(=O)2N(R S2A )2.-NR S2A S(=O)2N(R S2A )2.-P(R S2A )2. -P(=O)(R S2B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S2C )2.-OR S2C 、-SR S2C 、-S(=O)R S2D 、-S(=O)2R S2D 、-C(=O)R S2D 、-C(=O)OR S2D 、-OC(=O)R S2D 、-C(=O)N(R S2C )2.-NR S2C C(=O)R S2D 、-OC(=O)OR S2C 、-NR S2C C(=O)OR S2C 、-NR S2C C(=S)OR S2C 、-OC(=O)N(R S2C )2.-NR S2C C(=O)N(R S2C )2, -S(=O)OR S2C 、-OS(=O)R S2D 、-S(=O)N(R S2C )2.-NR S2C S(=O)R S2D 、-S(=O)2OR S2C 、-OS(=O)2R S2D 、-S(=O)2N(R S2C )2.-NR S2C S(=O)2R S2D 、-OS(=O)2OR S2C 、-NR S2C S(=O)2OR S2C 、-OS(=O)2N(R S2C )2.-NR S2C S(=O)2N(R S2C )2.-P(R S2C )2. -P(=O)(R S2D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S2 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S21 replace; Optionally, two adjacent R S2 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S22 replace; Optionally, two non-adjacent R S2 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S23 replace; m2 is selected from 0, 1, 2, 3, 4 or 5; Y1 is a bond, O, S, S(=O), S(=O)2 or NR Y11 ; R Y11 Selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R3 is selected from R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 38 , R 39 , R 310 and R 311 are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A 、-S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR A 、-C(=O)N(R A )2, -S(=O)OR A 、-S(=O)N(R A )2, -S(=O)2OR A 、-S(=O)2N(R A )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R 31 and R 32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S33 replace; Optionally, R 33 and R 34 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S34 replace; Optionally, R 35 and R 36 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S35 replace; Optionally, R 38 and R 39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S310 replace; Optionally, R 310 and R 311 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S316 replace; n2 is selected from 0, 1, 2, 3, 4, 5 or 6; n3 is selected from 0, 1, 2, 3, 4, 5 or 6; n4 is selected from 0, 1, 2, 3, 4, 5 or 6; n5 is selected from 0, 1, 2, 3, 4, 5 or 6; n6 is selected from 0, 1, 2, 3, 4, 5 or 6; Ring B is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring C is a 3-10 membered heterocyclic ring, optionally further comprising 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring D is selected from a 3-10 membered carbocyclic ring or a 3-10 membered heterocyclic ring; Ring I is a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring J is a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; Ring K is a 3-10 membered carbocyclic ring, or a 3-10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O, S, S(═O) or S(═O)2; R S31 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31A )2.-OR S31A 、-SR S31A 、-S(=O)R S31B 、-S(=O)2R S31B 、-C(=O)R S31B 、-C(=O)OR S31A 、-OC(=O)R S31B 、-C(=O)N(R S31A )2.-NR S31A C(=O)R S31B 、-OC(=O)OR S31A 、-NR S31A C(=O)OR S31A 、-NR S31A C(=S)OR S31A 、-OC(=O)N(R S31A )2.-NR S31A C(=O)N(R S31A )2, -S(=O)OR S31A 、-OS(=O)R S31B 、-S(=O)N(R S31A )2.-NR S31A S(=O)R S31B 、-S(=O)2OR S31A 、-OS(=O)2R S31B 、-S(=O)2N(R S31A )2.-NR S31A S(=O)2R S31B 、-OS(=O)2OR S31A 、-NR S31A S(=O)2OR S31A 、-OS(=O)2N(R S31A )2.-NR S31A S(=O)2N(R S31A )2.-P(R S31A )2. -P(=O)(R S31B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S31C )2.-OR S31C 、-SR S31C 、-S(=O)R S31D 、-S(=O)2R S31D 、-C(=O)R S31D 、-C(=O)OR S31C 、-OC(=O)R S31D 、-C(=O)N(R S31C )2.-NR S31C C(=O)R S31D 、-OC(=O)OR S31C 、-NR S31C C(=O)OR S31C 、-NR S31C C(=S)OR S31C 、-OC(=O)N(R S31C )2.-NR S31C C(=O)N(R S31C )2, -S(=O)OR S31C 、-OS(=O)R S31D 、-S(=O)N(R S31C )2.-NR S31C S(=O)R S31D 、-S(=O)2OR S31C 、-OS(=O)2R S31D 、-S(=O)2N(R S31C )2.-NR S31C S(=O)2R S31D 、-OS(=O)2OR S31C 、-NR S31C S(=O)2OR S31C 、-OS(=O)2N(R S31C )2.-NR S31C S(=O)2N(R S31C )2.-P(R S31C )2. -P(=O)(R S31D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S31 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S311 replace; Optionally, two adjacent R S31 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S312 replace; Optionally, two non-adjacent R S31 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S313 replace; m3 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; R S32 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32A )2.-OR S32A 、-SR S32A 、-S(=O)R S32B 、-S(=O)2R S32B 、-C(=O)R S32B 、-C(=O)OR S32A 、-OC(=O)R S32B 、-C(=O)N(R S32A )2.-NR S32A C(=O)R S32B 、-OC(=O)OR S32A 、-NR S32A C(=O)OR S32A 、-NR S32A C(=S)OR S32A 、-OC(=O)N(R S32A )2.-NR S32A C(=O)N(R S32A )2, -S(=O)OR S32A 、-OS(=O)R S32B 、-S(=O)N(R S32A )2.-NR S32A S(=O)R S32B 、-S(=O)2OR S32A 、-OS(=O)2R S32B 、-S(=O)2N(R S32A )2.-NR S32A S(=O)2R S32B 、-OS(=O)2OR S32A 、-NR S32A S(=O)2OR S32A 、-OS(=O)2N(R S32A )2.-NR S32A S(=O)2N(R S32A )2.-P(R S32A )2. -P(=O)(R S32B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S32C )2.-OR S32C 、-SR S32C 、-S(=O)R S32C 、-S(=O)2R S32D 、-C(=O)R S32D 、-C(=O)OR S32C 、-OC(=O)R S32D 、-C(=O)N(R S32C )2.-NR S32C C(=O)R S32D 、-OC(=O)OR S32C 、-NR S32C C(=O)OR S32C 、-NR S32C C(=S)OR S32C 、-OC(=O)N(R S32C )2.-NR S32C C(=O)N(R S32C )2, -S(=O)OR S32C 、-OS(=O)R S32C 、-S(=O)N(R S32C )2.-NR S32C S(=O)R S32D 、-S(=O)2OR S32C 、-OS(=O)2R S32D 、-S(=O)2N(R S32C )2.-NR S32C S(=O)2R S32D 、-OS(=O)2OR S32C 、-NR S32C S(=O)2OR S32C 、-OS(=O)2N(R S32C )2.-NR S32C S(=O)2N(R S32C )2.-P(R S32C )2. -P(=O)(R S32D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-1 membered aryl or 5-10 membered heteroaryl; Optionally, two R S32 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S321 replace; Optionally, two adjacent R S32 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S322 replace; Optionally, two non-adjacent R S32 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S323 replace; m4 is selected from 0, 1, 2, 3, 4, 5 or 6; R 37 Selected from -N(R 37A ) 2 or 3-10 membered heterocyclic group, wherein the 3-10 membered heterocyclic group is optionally independently replaced by one or more R S37 replace; R S38 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38A )2.-OR S38A 、-SR S38A 、-S(=O)R S38B 、-S(=O)2R S38B 、-C(=O)R S38B 、-C(=O)OR S38A 、-OC(=O)R S38B 、-C(=O)N(R S38A )2.-NR S38A C(=O)R S38B 、-OC(=O)OR S38A 、-NR S38A C(=O)OR S38A 、-NR S38A C(=S)OR S38A 、-OC(=O)N(R S38A )2.-NR S38A C(=O)N(R S38A )2, -S(=O)OR S38A 、-OS(=O)R S38B 、-S(=O)N(R S38A )2.-NR S38A S(=O)R S38B 、-S(=O)2OR S38A 、-OS(=O)2R S38B 、-S(=O)2N(R S38A )2.-NR S38A S(=O)2R S38B 、-OS(=O)2OR S38A 、-NR S38A S(=O)2OR S38A 、-OS(=O)2N(R S38A )2.-NR S38A S(=O)2N(R S38A )2.-P(R S38A )2. -P(=O)(R S38B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S38C )2.-OR S38C 、-SR S38C 、-S(=O)R S38D 、-S(=O)2R S38D 、-C(=O)R S38D 、-C(=O)OR S38C 、-OC(=O)R S38D 、-C(=O)N(R S38C )2.-NR S38C C(=O)R S38D 、-OC(=O)OR S38C 、-NR S38C C(=O)OR S38C 、-NR S38C C(=S)OR S38C 、-OC(=O)N(R S38C )2.-NR S38C C(=O)N(R S38C )2, -S(=O)OR S38C 、-OS(=O)R S38D 、-S(=O)N(R S38C )2.-NR S38C S(=O)R S38D 、-S(=O)2OR S38C 、-OS(=O)2R S38D 、-S(=O)2N(R S38C )2.-NR S38C S(=O)2R S38D 、-OS(=O)2OR S38C 、-NR S38C S(=O)2OR S38C 、-OS(=O)2N(R S38C )2.-NR S38C S(=O)2N(R S38C )2.-P(R S38C )2. -P(=O)(R S38D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S38 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S381 replace; Optionally, two adjacent R S38 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S382 replace; Optionally, two non-adjacent R S38 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S383 replace; m8 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; R S39 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39A )2.-OR S39A 、-SR S39A 、-S(=O)R S39B 、-S(=O)2R S39B 、-C(=O)R S39B 、-C(=O)OR S39A 、-OC(=O)R S39B 、-C(=O)N(R S39A )2.-NR S39A C(=O)R S39B 、-OC(=O)OR S39A 、-NR S39A C(=O)OR S39A 、-NR S39A C(=S)OR S39A 、-OC(=O)N(R S39A )2.-NR S39A C(=O)N(R S39A )2, -S(=O)OR S39A 、-OS(=O)R S39B 、-S(=O)N(R S39A )2.-NR S39A S(=O)R S39B 、-S(=O)2OR S39A 、-OS(=O)2R S39B 、-S(=O)2N(R S39A )2.-NR S39A S(=O)2R S39B 、-OS(=O)2OR S39A 、-NR S39A S(=O)2OR S39A 、-OS(=O)2N(R S39A )2.-NR S39A S(=O)2N(R S39A )2.-P(R S39A )2. -P(=O)(R S39B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S39C )2.-OR S39C 、-SR S39C 、-S(=O)R S39C 、-S(=O)2R S39D 、-C(=O)R S39D 、-C(=O)OR S39C 、-OC(=O)R S39D 、-C(=O)N(R S39C )2.-NR S39C C(=O)R S39D 、-OC(=O)OR S39C 、-NR S39C C(=O)OR S39C 、-NR S39C C(=S)OR S39C 、-OC(=O)N(R S39C )2.-NR S39C C(=O)N(R S39C )2, -S(=O)OR S39C 、-OS(=O)R S39C 、-S(=O)N(R S39C )2.-NR S39C S(=O)R S39D 、-S(=O)2OR S39C 、-OS(=O)2R S39D 、-S(=O)2N(R S39C )2.-NR S39C S(=O)2R S39D 、-OS(=O)2OR S39C 、-NR S39C S(=O)2OR S39C 、-OS(=O)2N(R S39C )2.-NR S39C S(=O)2N(R S39C )2.-P(R S39C )2. -P(=O)(R S39D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S39 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S391 replace; Optionally, two adjacent R S39 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S392 replace; Optionally, two non-adjacent R S39 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S393 replace; m9 is selected from 0, 1, 2, 3, 4, 5 or 6; R S315 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315A )2.-OR S315A 、-SR S315A 、-S(=O)R S315B 、-S(=O)2R S315B 、-C(=O)R S315B 、-C(=O)OR S315A 、-OC(=O)R S315B 、-C(=O)N(R S315A )2.-NR S315A C(=O)R S315B 、-OC(=O)OR S315A 、-NR S315A C(=O)OR S315A 、-NR S315A C(=S)OR S315A 、-OC(=O)N(R S315A )2.-NR S315A C(=O)N(R S315A )2, -S(=O)OR S315A 、-OS(=O)R S315B 、-S(=O)N(R S315A )2.-NR S315A S(=O)R S315B 、-S(=O)2OR S315A 、-OS(=O)2R S315B 、-S(=O)2N(R S315A )2.-NR S315A S(=O)2R S315B 、-OS(=O)2OR S315A 、-NR S315A S(=O)2OR S315A 、-OS(=O)2N(R S315A )2.-NR S315A S(=O)2N(R S315A )2.-P(R S315A )2. -P(=O)(R S315B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S315C )2.-OR S315C 、-SR S315C 、-S(=O)R S315C 、-S(=O)2R S315D 、-C(=O)R S315D 、-C(=O)OR S315C 、-OC(=O)R S315D 、-C(=O)N(R S315C )2.-NR S315C C(=O)R S315D 、-OC(=O)OR S315C 、-NR S315C C(=O)OR S315C 、-NR S315C C(=S)OR S315C 、-OC(=O)N(R S315C )2.-NR S315C C(=O)N(R S315C )2, -S(=O)OR S315C 、-OS(=O)R S315C 、-S(=O)N(R S315C )2.-NR S315C S(=O)R S315D 、-S(=O)2OR S315C 、-OS(=O)2R S315D 、-S(=O)2N(R S315C )2.-NR S315C S(=O)2R S315D 、-OS(=O)2OR S315C 、-NR S315C S(=O)2OR S315C 、-OS(=O)2N(R S315C )2.-NR S315C S(=O)2N(R S315C )2.-P(R S315C )2. -P(=O)(R S315D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, two R S315 Together with the carbon atoms to which they are attached, they form 3-10 membered carbocyclic ring or 3-10 membered heterocyclic ring; wherein The 3- to 10-membered carbocyclic ring or the 3- to 10-membered heterocyclic ring are each independently unsubstituted or substituted with one or more R S3151 replace; Optionally, two adjacent R S315 Together with the atoms to which they are attached, they form a 3-10 membered carbocyclic ring, a 3-10 membered heterocyclic ring, a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein each ring is independently unsubstituted or substituted with one or more R S3152 replace; Optionally, two non-adjacent R S315 connected to form a bridge comprising 0, 1, 2, 3, 4, 5 or 6 carbon atoms, wherein each carbon atom in the bridge is independently unsubstituted or substituted by 1 or 2 heteroatoms selected from N, O, S, S=O or S(=O)2; each hydrogen on a carbon atom or N atom in the bridge is independently unsubstituted or substituted by R S3153 replace; m 10 Selected from 0, 1, 2, 3, 4, 5 or 6; R4 is selected from 6-10 membered aryl, 5-10 membered heteroaryl, wherein the 6-10 membered aryl, 5-10 membered heteroaryl, are independently unsubstituted or substituted with one or more R S4 replace; Each occurrence of Z is independently selected from C or N; When Z is selected from C, each occurrence of Ring E is independently selected from a 6-membered aryl ring or a 5-6-membered heteroaryl ring, and each occurrence of Ring F is a 3-10-membered carbocyclic ring or a 3-10-membered heterocyclic ring; When Z is selected from N, each occurrence of Ring E is independently selected from a 5-6 membered heteroaryl ring, and each occurrence of Ring F is a 3-10 membered heterocyclic ring; R S4 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4A )2.-OR S4A 、-SR S4A 、-S(=O)R S4B 、-S(=O)2R S4B 、-C(=O)R S4B 、-C(=O)OR S4A 、-OC(=O)R S4B 、-C(=O)N(R S4A )2.-NR S4A C(=O)R S4B 、-OC(=O)OR S4A 、-NR S4A C(=O)OR S4A 、-NR S4A C(=S)OR S4A 、-OC(=O)N(R S4A )2.-NR S4A C(=O)N(R S4A )2, -S(=O)OR S4A 、-OS(=O)R S4B 、-S(=O)N(R S4A )2.-NR S4A S(=O)R S4B 、-S(=O)2OR S4A 、-OS(=O)2R S4B 、-S(=O)2N(R S4A )2.-NR S4A S(=O)2R S4B 、-OS(=O)2OR S4A 、-NR S4A S(=O)2OR S4A 、-OS(=O)2N(R S4A )2.-NR S4A S(=O)2N(R S4A )2.-P(R S4A )2. -P(=O)(R S4B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R S4C )2.-OR S4C 、-SR S4C 、-S(=O)R S4D 、-S(=O)2R S4D 、-C(=O)R S4D 、-C(=O)OR S4D 、-OC(=O)R S4D 、-C(=O)N(R S4C )2.-NR S4C C(=O)R S4D 、-OC(=O)OR S4C 、-NR S4C C(=O)OR S4C 、-NR S4C C(=S)OR S4C 、-OC(=O)N(R S4C )2.-NR S4C C(=O)N(R S4C )2, -S(=O)OR S4C 、-OS(=O)R S4D 、-S(=O)N(R S4C )2.-NR S4C S(=O)R S4D 、-S(=O)2OR S4C 、-OS(=O)2R S4D 、-S(=O)2N(R S4C )2.-NR S4C S(=O)2R S4D 、-OS(=O)2OR S4C 、-NR S4C S(=O)2OR S4C 、-OS(=O)2N(R S4C )2.-NR S4C S(=O)2N(R S4C )2.-P(R S4C )2. -P(=O)(R S4D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R5 is selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5A )2.-OR 5A 、-SR 5A 、-S(=O)R 5B 、-S(=O)2R 5B 、-C(=O)R 5B 、-C(=O)OR 5A 、-OC(=O)R 5B 、-C(=O)N(R 5A )2.-NR 5A C(=O)R 5B 、-OC(=O)OR 5A 、-NR 5A C(=O)OR 5A 、-NR 5A C(=S)OR 5A 、-OC(=O)N(R 5A )2.-NR 5A C(=O)N(R 5A )2, -S(=O)OR 5A 、-OS(=O)R 5B 、-S(=O)N(R 5A )2.-NR 5A S(=O)R 5B 、-S(=O)2OR 5A 、-OS(=O)2R 5B 、-S(=O)2N(R 5A )2.-NR 5A S(=O)2R 5B 、-OS(=O)2OR 5A 、-NR 5A S(=O)2OR 5A 、-OS(=O)2N(R 5A )2.-NR 5A S(=O)2N(R 5A )2.-P(R 5A )2. -P(=O)(R 5B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R 5C )2.-OR 5C 、-SR 5C 、-S(=O)R 5D 、-S(=O)2R 5D 、-C(=O)R 5D 、-C(=O)OR 5D 、-OC(=O)R 5D 、-C(=O)N(R 5C )2.-NR 5C C(=O)R 5D 、-OC(=O)OR 5C 、-NR 5C C(=O)OR 5C 、-NR 5C C(=S)OR 5C 、-OC(=O)N(R 5C )2.-NR 5C C(=O)N(R 5C )2, -S(=O)OR 5C 、-OS(=O)R 5D 、-S(=O)N(R 5C )2.-NR 5C S(=O)R 5D 、-S(=O)2OR 5C 、-OS(=O)2R 5D 、-S(=O)2N(R 5C )2.-NR 5C S(=O)2R 5D 、-OS(=O)2OR 5C 、-NR 5C S(=O)2OR 5C 、-OS(=O)2N(R 5C )2.-NR 5C S(=O)2N(R 5C )2.-P(R 5C )2. -P(=O)(R 5D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; R 1A , R 1C , R S2A , R S2C , R S31A , R S31C , R S32A , R S32C , R 37A , R S38A , R S38C , R S39A , R S39C , R S315A , R S315C , R S4A , R S4C , R 5A , R 5C , R 8A , R 8C , R S8A and R S8C are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -S(=O)R B 、-S(=O)2R B 、-C(=O)R B 、-C(=O)OR B 、-C(=O)N(R B )2, -S(=O)OR B 、-S(=O)N(R B )2, -S(=O)2OR B 、-S(=O)2N(R B )2. -P(=O)(R B )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optional, (two R 1A , two R 1C , two R S2A , two R S2C , two R S31A , two R S31C , two R S32A , two R S32C , two R 37A , two R S38A , two R S38C , two R S39A , two R S39C , two R S315A , two R S315C , two R S4A , two R S4C , two R 5A , two R 5C , two R 8A , two R 8C , two R S8A and two R S8C ) and the nitrogen atom to which it is connected together form a 3-10 membered heterocyclic ring or a 5-10 membered heteroaromatic ring, wherein the 3-10 membered heterocyclic ring or the 5-10 membered heteroaromatic ring is independently unsubstituted or substituted with one or more R SS replace; R 1B , R 1D , R S2B , R S2D , R S31B , R S31D , R S32B , R S32D , R S38B , R S38D , R S39B , R S315B , R S315D , R S39D , R S4B , R S4D , R 5B , R 5D , R 8B , R 8D , R S8B and R S8D Each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, halogenated C 2-6 Alkenyl, -C 2-6 Alkynyl, halo C 2-6 Alkynyl, -N(R A )2.-OR A 、-SR A , 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -N(R C )2.-OR C 、-SR C 、-S(=O)R D 、-S(=O)2R D 、-C(=O)R D 、-C(=O)OR C 、-OC(=O)R D 、-C(=O)N(R C )2.-NR C C(=O)R D 、-OC(=O)OR C 、-NR C C(=O)OR D 、-OC(=O)N(R C )2.-NR C C(=O)N(R C )2, -S(=O)OR C 、-OS(=O)R D 、-S(=O)N(R C )2.-NR C S(=O)R D 、-S(=O)2OR C 、-OS(=O)2R D 、-S(=O)2N(R C )2.-NR C S(=O)2R D 、-OS(=O)2OR C 、-NR C S(=O)2OR C 、-OS(=O)2NR C 、-NR C S(=O)2N(R C )2.-P(R C )2. -P(=O)(R D )2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; (R A , R B , R C and R D ) are each independently selected from hydrogen, deuterium, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are independently unsubstituted or substituted with one or more R SA replace; R SX1 , R S21 , R S22 , R S23 , R S33 , R S34 , R S35 , R S37 , R S310 , R S316 , R S311 , R S312 , R S313 , R S321 , R S322 , R S323 , R S381 , R S382 , R S383 , R S391 , R S392 , R S393 , R S3151 , R S3152 , R S3153 , R S81 , R S82 , R SS and R SA are each independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -OC(=O)O(C 1-6 alkyl), -NHC(=O)(OC 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(OC 1-6 alkyl), -OC(=O)NH(C 1-6 alkyl), -OC(=O)N(C 1-6 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-6 alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH2, -N(C 1-6 alkyl)C(=O)NH(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)N(C 1-6 Alkyl)2, -S(=O)(OC 1-6 alkyl), -OS(=O)(C 1-6 alkyl), -S(=O)NH2, -S(=O)NH(C 1-6 alkyl), -S(=O)N(C 1-6 Alkyl)2, -NHS(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)(C 1-6 Alkyl), -S(=O)2(OC 1-6 alkyl), -OS(=O)2(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), -OS(=O)2O(C 1-6 alkyl), -NHS(=O)2O(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2O(C 1-6 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 alkyl), -OS(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 alkyl), -NHS(=O)2N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)S(=O)2NH2, -N(C 1-6 Alkyl)S(=O)2NH(C 1-6 Alkyl), -N(C 1-6 alkyl)S(=O)2N(C 1-6 Alkyl)2, -PH(C 1-6 Alkyl), -P(C 1-6 Alkyl)2, -P(=O)H(C 1-6 alkyl), -P(=O)(C 1-6 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently unsubstituted or substituted with one or more substituents selected from deuterium, halogen, -C 1-3 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy, -C 2-3 Alkenyl, -C 2-3 Alkynyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C 1-3 Alkyl), -N(C 1-3 Alkyl)2, -OH, -O(C 1-3 alkyl), -SH, -S(C 1-3 alkyl), -S(=O)(C 1-3 alkyl), -S(=O)2(C 1-3 alkyl), -C(=O)(C 1-3 alkyl), -C(=O)OH, -C(=O)(OC 1-3 alkyl), -OC(=O)(C 1-3 alkyl), -C(=O)NH2, -C(=O)NH(C 1-3 alkyl), -C(=O)N(C 1-3 Alkyl)2, -NHC(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(C 1-3 alkyl), -OC(=O)O(C 1-3 alkyl), -NHC(=O)(OC 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)(OC 1-3 alkyl), -OC(=O)NH(C 1-3 alkyl), -OC(=O)N(C 1-3 alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-3 alkyl), -NHC(=O)N(C 1-3 Alkyl)2, -N(C 1-3 alkyl)C(=O)NH2, -N(C 1-3 alkyl)C(=O)NH(C 1-3 Alkyl), -N(C 1-3 alkyl)C(=O)N(C 1-3 Alkyl)2, -S(=O)(OC 1-3 alkyl), -OS(=O)(C 1-3 alkyl), -S(=O)NH2, -S(=O)NH(C 1-3 alkyl), -S(=O)N(C 1-3 Alkyl)2, -NHS(=O)(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)(C 1-3 Alkyl), -S(=O)2(OC 1-3 alkyl), -OS(=O)2(C 1-3 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-3 alkyl), -S(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2(C 1-3 alkyl), -OS(=O)2O(C 1-3 alkyl), -NHS(=O)2O(C 1-3 Alkyl), -N(C 1-3 Alkyl)S(=O)2O(C 1-3 alkyl), -OS(=O)2NH2, -OS(=O)2NH(C 1-3 alkyl), -OS(=O)2N(C 1-3 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-3 alkyl), -NHS(=O)2N(C 1-3 Alkyl)2, -N(C 1-3 Alkyl)S(=O)2NH2, -N(C 1-3 Alkyl)S(=O)2NH(C 1-3 Alkyl), -N(C 1-3 alkyl)S(=O)2N(C 1-3 Alkyl)2, -PH(C 1-3 Alkyl), -P(C 1-3 Alkyl)2, -P(=O)H(C 1-3 alkyl), -P(=O)(C 1-3 alkyl)2, 3-10 membered cycloalkyl, 3-10 membered cycloalkenyl, 3-10 membered cycloalkynyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Each occurrence of heterocyclyl or heterocycle independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, S, S(=O) or S(=O)2; Each occurrence of heteroaryl independently contains 1, 2, 3 or 4 heteroatoms selected from N, O or S.

12. The compound of formula (I) according to claim 11, its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of its stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein: The compound is selected from any of the following formulas:

13. The compound of formula (I) according to claim 12, its stereoisomer, its pharmaceutically acceptable salt, its pharmaceutically acceptable salt of the stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule, wherein: R 81 and R 82 Selected from hydrogen, deuterium, -C 1-6 Alkyl, or 3-6 membered cycloalkyl; Preferably, R 81 is selected from hydrogen or deuterium; R 82 is selected from methyl or cyclopropyl; Ring M is selected from a 5-membered heteroaryl group containing 1, 2, 3 or 4 heteroatoms selected from N, O or S, or a 6-membered heteroaryl group containing 1 or 2 heteroatoms selected from N; Preferably, ring M is a 6-membered heteroaryl group containing 1 or 2 heteroatoms selected from N, and the 6-membered heteroaryl group is substituted by one -NH2 or -OH, and may also be optionally substituted by one or more R S8 replace; In some embodiments, the group Selected from wherein n9 is selected from 0, 1, 2, 3 or 4; R S8 Selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 substituted by an alkyl substituent; Preferably, R S8 Selected from -NHCH3; n8 is selected from 0 or 1, or n9 is selected from 0 or 1; In some embodiments, the group Selected from 14. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 13, wherein: Y1 is selected from O.

15. The compound of formula (I), its stereoisomer, its pharmaceutically acceptable salt, the pharmaceutically acceptable salt of the stereoisomer, its prodrug, its deuterated molecule or its PROTAC molecule according to any one of claims 1 to 14, wherein: R 31 , R 32 , R 33 , R 34 , R 35 and R 36 are each independently selected from hydrogen or deuterium.

16. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 15, wherein: n2 is selected from 1.

17. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 16, wherein: n3 is selected from 1, and n4 is selected from 1.

18. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 17, wherein: R3 is selected from Ring B or Ring C is a 4-6 membered heterocyclic ring, which optionally further contains 1 or 2 heteroatoms selected from N or O; Ring D is a 3-membered carbon ring; R 37 Selected from -N(R 37A ) a 2- or 6-membered heterocyclic group, wherein the 3- to 6-membered heterocyclic group is optionally independently substituted by 1, 2 or 3 R S37 replace; R 37A Selected from hydrogen, deuterium or -C 1-6 alkyl.

19. The compound of formula (I) according to any one of claims 1 to 18, its stereoisomer, its atropisomer, its pharmaceutically acceptable salt, the pharmaceutically acceptable salt of the stereoisomer, the pharmaceutically acceptable salt of the atropisomer, its prodrug, its deuterated molecule or its conjugated form, wherein: Group for Wherein, X3 is selected from CH2, NH, O, S, S(=O) or S(=O)2; when X3 is selected from CH2 or NH, the hydrogen in CH2 or NH is optionally replaced by one or more R S37 replace; R 37A Selected from hydrogen, deuterium or -C 1-3 alkyl.

20. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 19, wherein: Group Selected from 21. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 20, wherein: Group Selected from 22. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 21, wherein: Group for Group for Group for Group for 23. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, wherein: R 38 and R 39 are each independently selected from hydrogen or deuterium.

24. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claim 23, wherein: n5 is selected from 1.

25. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, 23 and 24, wherein: Ring I is a 4-6 membered cycloalkyl ring.

26. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 25, wherein: Ring J is a 4-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O or S.

27. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 26, wherein: Group Selected from Among them, R S381 Selected from hydrogen or R S38 ; m 81 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8.

28. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 27, wherein: R S381 Selected from hydrogen, deuterium, -C 1-6 alkyl or 3-6 membered cycloalkyl, wherein the -C 1-6 The alkyl or 3-6 membered cycloalkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy-CN, -NH2-NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with a substituent.

29. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 28, wherein: R S381 is selected from hydrogen, deuterium, -CH3, -CH2CH3 or cyclopropyl.

30. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 29, wherein: m 81 Select from 0.

31. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 30, wherein: m9 is selected from 0, 1 or 2.

32. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 31, wherein: m9 is selected from 0.

33. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 32, wherein: m9 is selected from 1.

34. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 33, wherein: Group Selected from Among them, R S394 Selected from hydrogen or R S391 .

35. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 34, wherein: R S39 is selected from halogen; Preferably, R S39 Select from -F.

36. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 35, wherein: R S391 Selected from hydrogen, deuterium, halogen or -C 1-6 Alkyl; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Substitution of alkyl groups; Preferably, R S391 is selected from hydrogen, deuterium, -F or -CH3.

37. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 36, wherein: Group Selected from 38. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 23 to 37, wherein: Group Selected from 39. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, wherein: Ring B is a 4-6 membered heterocyclic ring containing a fused nitrogen atom.

40. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claim 39, wherein: Ring C is a 4-6 membered heterocyclic ring containing a fused nitrogen atom.

41. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, 39 and 40, wherein: Group Selected from 42. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 41, wherein: m3 is selected from 0, 1, 2, 3 or 4.

43. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 42, wherein: R S31 Selected from deuterium or -F; Optionally, two R S31 Together with the carbon atoms to which they are attached, they form Or cyclopropyl; wherein said or cyclopropyl is independently unsubstituted or substituted with 1, 2 or 3 R S311 replace; or Optionally, two adjacent R S31 Together with the carbon atoms to which they are attached, they form a 5-10 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, or a 5-10 membered heteroaromatic ring containing 1 or 2 heteroatoms selected from N, O or S, wherein each ring is independently unsubstituted or substituted with 1, 2 or 3 R S312 replace.

44. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 43, wherein: Group Selected from in, Ring G is selected from a 5-6 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, a 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O or S; Ring H is selected from a 5-10 membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O, a benzene ring, a 5-10 membered heteroaryl containing 1 or 2 heteroatoms selected from N, O or S; R S36 Definition and R S31 same; R S314 Selected from hydrogen or R S311 ; m 31 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; m 32 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8; m 33 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; m 34 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; m5 is selected from 0, 1, 2, 3, 4, 5 or 6; m6 is selected from 0, 1, 2, 3, 4, 5 or 6.

45. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 44, wherein: Group Selected from in, m 31 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; m 32 Selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8; m 33 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; m 34 Selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; m5 is selected from 0, 1, 2, 3, 4, 5 or 6; m6 is selected from 0, 1, 2, 3, 4, 5 or 6.

46. ​​A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 45, wherein: R S311 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Substitution of alkyl groups; R S312 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 Substitution of alkyl groups; R S314 are independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 groups selected from deuterium, halogen, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 The alkyl group is substituted with a substituent.

47. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 46, wherein: R S311 Independently selected from deuterium, -F or -OCH3; R S312 Independently selected from deuterium, -F, -OCH3 or -CH2OCH3; R S314 Independently selected from hydrogen, deuterium, -F, -CH3, -CH2OCH3, -CH2CH2CH3, -CH(CH3)2, -CHF2, -CH2CH(CH3)2.

48. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 49, wherein: R S36 Selected from deuterium or -F.

49. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 48, wherein: m 31 Select from 0 or 1; m 32 Select from 0 or 1; m 33 Select from 0 or 1; m 34 Select from 0 or 1; m5 is selected from 0 or 1; m6 is selected from 0 or 1.

50. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 49, wherein: Group Selected from 51. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 39 to 50, wherein: Group Selected from 52. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, wherein R 310 and R 311 are each independently selected from hydrogen or deuterium.

53. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 or claim 52, wherein, n6 is selected from 1 or 2.

54. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, claim 52 or claim 53, wherein: Ring K is a 4- to 10-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N or O atoms.

55. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 54, wherein: Group Selected from Wherein, ring L is selected from a 4-6 membered heterocyclic ring, which optionally further contains 1 or 2 heteroatoms selected from N or O.

56. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 55, wherein: Group Selected from 57. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 56, wherein: R S315 are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NH(C 1-6 Alkyl) or -N(C 1-6 Alkyl)2; wherein the -C 1-6 The alkyl groups are independently unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of deuterium, halogen, halo 1-6 Alkyl, halogenated C 1-6 Alkoxy, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH or -OC 1-6 alkyl.

58. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 57, wherein: R S315 Independently selected from -F or -CH3.

59. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 58, wherein: m 10 Selected from 0, 1, 2 or 3.

60. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 59, wherein: Group Selected from 61. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14 and claims 52 to 60, wherein: Group Selected from 62. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 14, wherein: Selected from Table C in the specification.

63. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 62, wherein R4 is selected from phenyl, pyridyl, naphthyl, quinolyl, isoquinolyl, indazolyl, benzothienyl or benzothiazolyl, wherein the phenyl, pyridyl, naphthyl, quinolyl, isoquinolyl, indazolyl, benzothienyl or benzothiazolyl is unsubstituted or substituted by 1, 2, 3, 4, 5 or 6 R S4 replace.

64. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 63, wherein R4 is selected from m7 is selected from 0, 1, 2 or 3; R S4a Selected from -OH or -NH2; R S4b Selected from hydrogen, deuterium, and halogen; R S4c Selected from hydrogen, deuterium, -C 1-3 Alkyl, -C 2-3 Alkenyl or -C 2-3 Alkynyl; R S4d is selected from hydrogen, deuterium or halogen; R S4e Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4f Selected from -OH or -NH2; R S4g Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4h Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4i Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4j Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl; R S4k Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl; R S4l Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl; R S4m Selected from hydrogen, deuterium, halogen, -CN, -C 1-3 Alkyl, halogenated gC 1-3 Alkyl or -O haloC 1-3 alkyl; R S4n Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4o Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl; R S4p Selected from hydrogen, deuterium, halogen, -C 1-3 Alkyl or halogenated C 1-3 alkyl.

65. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 64, wherein: m7 is selected from 0; R S4a Selected from -OH or -NH2; R S4b Select from -F; R S4c is selected from ethyl, vinyl or ethynyl; R S4d is selected from hydrogen or -F; R S4e Select from -F; R S4f Selected from -NH2; R S4g is selected from hydrogen, -F, or methyl; R S4h is selected from hydrogen, -F or methyl; R S4i Selected from -I or -CF3; R S4j Selected from -CN; R S4k Selected from hydrogen; R S4l Selected from methyl; R S4m Selected from -CF3, -OCF2Cl, -OCF3 or -CF2H; R S4n is selected from hydrogen, -F or methyl; R S4o is selected from hydrogen, -F or methyl; R S4p is selected from hydrogen, -F or methyl.

66. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof according to any one of claims 1 to 65, wherein R4 is selected from Table D in the specification.

67. A compound of formula (I), a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a pharmaceutically acceptable salt of the atropisomer, a prodrug thereof, a deuterated molecule thereof, or a conjugated form thereof according to any one of claims 1 to 66, wherein: The prodrug is selected from the following formula: R 4a Selected from R 4c Selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace; R 4d and R 4e are each independently selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C(=O)C 1-6 Alkyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace; R 4f and R 4g are each independently selected from hydrogen, -C 1-30 Alkyl, -C 2-30 Alkenyl, -C 2-30 Alkynyl, -C(=O)C 1-6 Alkyl, -C 0-6 Alkylene-(3-20 membered carbocyclic group), -C 0-6 Alkylene-(3-20 membered heterocyclic group), -C 0-6 Alkylene-(6-10 membered aryl) or -C 0-6 Alkylene-(5-10 membered heteroaryl), each of which is independently substituted by one or more R 4j replace; R 4h , R 4i , R 4m , R 4n and R 4p are each independently selected from hydrogen, deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; wherein the -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are optionally substituted with one or more substituents selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 alkyl)2, oxo, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl; Optionally, R 4f and R 4g Together with the atoms to which they are attached, they form a 4-10 membered heterocyclyl ring, which optionally further contains 1 or 2 heteroatoms selected from N, O, S, S(=O) or S(=O)2, and is optionally replaced by one or more R 4j replace; Optionally, R 4f and R 4h Together with the atoms to which they are attached, they form a 4-10 membered heterocyclyl ring, which optionally further contains 1 or 2 heteroatoms selected from N, O, S, S(=O) or S(=O)2, and is optionally replaced by one or more R 4j replace; Each occurrence of R 4j are independently selected from deuterium, halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -CN, oxo, -NO2, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -S(halogenated C 1-6 alkyl), -S(=O)(C 1-6 alkyl), -S(=O)2(C 1-6 alkyl), -C(=O)(C 1-6 alkyl), -C(=O)OH, -C(=O)(OC 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -C(=O)NH2, -C(=O)NH(C 1-6 alkyl), -C(=O)N(C 1-6 Alkyl)2, -NHC(=O)(C 1-6 Alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 alkyl), -S(=O)2NH2, -S(=O)2NH(C 1-6 alkyl), -S(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2(C 1-6 Alkyl), -N(C 1-6 Alkyl)S(=O)2(C 1-6 alkyl), 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl, wherein the -C 1-6 Alkyl, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, -C 2-6 Alkenyl, -C 2-6 The alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl are each independently optionally substituted by 1, 2 or 3 substituents selected from the group consisting of halogen, -C 1-6 Alkyl, halogenated C 1-6 Alkyl, -CN, oxo, -OH, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, -OC 1-6 Alkyl; or 1, 2 or 3 selected from deuterium, halogen, halogenated C 1-6 Alkyl, -CN, -OH, -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2 or -OC 1-6 Alkyl-substituted-C 1-6 alkyl; The definitions of other variables are the same as above; Preferably, R 4a Selected from Table E in the specification.

68. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTA molecule thereof according to any one of claims 1 to 67, wherein R5 is selected from halogen.

69. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTA molecule thereof according to any one of claims 1 to 68, wherein R5 is selected from -F.

70. A compound of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTA molecule thereof according to any one of claims 1 to 69, wherein The compound is selected from Table F in the specification.

71. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, and a pharmaceutically acceptable excipient.

72. A method for treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) as described in any one of claims 1-81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition as described in claim 71.

73. A method for treating cancer in a subject in need thereof, the method comprising: (a) determining whether the cancer is associated with K-Ras G12C, K-Ras G12D, K-Ras G12V, K-Ras G13D, K-RasG12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutations and / or K-Ras wild-type amplification; (b) if so, administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) as described in any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof, or a PROTAC molecule thereof, or a pharmaceutical composition as described in claim 71.

74. A compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition according to claim 71 for use in treatment.

75. A compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition according to claim 71, for use as a medicament.

76. A compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition according to claim 71, for use in a method of treating cancer.

77. Use of a compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof or a conjugated form thereof, or a pharmaceutical composition according to claim 71 in the treatment of cancer.

78. Use of a compound of formula (I) according to any one of claims 1 to 81, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof, or a pharmaceutical composition according to claim 71 in the preparation of a medicament for treating cancer.

79. The method for treating cancer according to claim 71, the use in a method for treating cancer according to claim 76, the use for treating cancer according to claim 77, or the use for preparing a medicament for treating cancer according to claim 78, wherein: The cancer is selected from pancreatic cancer, colorectal cancer, lung cancer (such as non-small cell lung cancer), breast cancer, colon cancer, gastric cancer, endometrial cancer, esophageal cancer or gastroesophageal junction cancer.

80. The method for treating cancer according to claim 71 or 79, the use for a method for treating cancer according to claim 76 or 79, the use for treating cancer according to claim 77 or 79, or the use for preparing a medicament for treating cancer according to claim 78 or 79, wherein: The cancer is associated with at least one of K-Ras G12C, K-Ras G12D, K-Ras G12V, K-RasG13D, K-Ras G12R, K-Ras G12S, K-Ras G12A, K-Ras Q61H mutations and / or K-Ras wild-type amplification.

81. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein: The cancer is a K-Ras G12C-associated cancer.

82. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein: The cancer is a K-Ras G12D-associated cancer.

83. The method for treating cancer according to claim 71, 79 or 80, the use in a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a K-Ras G12V-associated cancer.

84. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein: The cancer is a K-Ras G13D-associated cancer.

85. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a K-Ras G12R-related cancer.

86. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a K-Ras G12S-related cancer.

87. The method for treating cancer according to claim 71, 79 or 80, the use in a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a K-Ras G12A-associated cancer.

88. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a K-Ras Q61H-associated cancer.

89. The method for treating cancer according to claim 71, 79 or 80, the use for a method for treating cancer according to claim 76, 79 or 80, the use for treating cancer according to claim 77, 79 or 80, or the use for preparing a medicament for treating cancer according to claim 78, 79 or 80, wherein The cancer is a cancer associated with wild-type amplification of K-Ras.

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